WO2025003957A1

WO2025003957A1 - Substance delivery controlled inside mammals

Info

Publication number: WO2025003957A1
Application number: PCT/IB2024/056281
Authority: WO
Inventors: Daniel Smyth; Wolfram Frederik DUECK
Original assignee: Cochlear Ltd
Current assignee: Cochlear Ltd
Priority date: 2023-06-30
Filing date: 2024-06-27
Publication date: 2025-01-02
Anticipated expiration: 2025-12-30

Abstract

An apparatus including a reservoir and a therapeutic substance located in the reservoir, wherein the apparatus is an implantable therapeutic substance delivery apparatus, and the apparatus is configured to deliver the therapeutic substance to a recipient thereof by diffusion controlled release. In an exemplary embodiment, the apparatus is also a cochlear implant.

Description

SUBSTANCE DELIVERY CONTROLLED INSIDE MAMMALS

CROSS-REFERENCE TO RELATED APPLICATIONS

[oooi] This application claims priority to U.S. Provisional Application No. 63/524,327, entitled SUBSTANCE DELIVERY CONTROLLED INSIDE MAMMALS, filed on June 30, 2023, naming Daniel SMYTH as an inventor, the entire contents of that application being incorporated herein by reference in its entirety.

BACKGROUND

[0002] Medical devices have provided a wide range of therapeutic benefits to recipients over recent decades. Medical devices can include internal or implantable components/devices, external or wearable components/devices, or combinations thereof (e.g., a device having an external component communicating with an implantable component). Medical devices, such as traditional hearing aids, partially or fully-implantable hearing prostheses (e.g., bone conduction devices, mechanical stimulators, cochlear implants, etc.), pacemakers, defibrillators, functional electrical stimulation devices, and other medical devices, have been successful in performing lifesaving and/or lifestyle enhancement functions and/or recipient monitoring for a number of years.

[0003] The types of medical devices and the ranges of functions performed thereby have increased over the years. For example, many medical devices, sometimes referred to as “implantable medical devices,” now often include one or more instruments, apparatus, sensors, processors, controllers or other functional mechanical or electrical components that are permanently or temporarily implanted in a recipient. These functional devices are typically used to diagnose, prevent, monitor, treat, or manage a disease/injury or symptom thereof, or to investigate, replace or modify the anatomy or a physiological process. Many of these functional devices utilize power and/or data received from external devices that are part of, or operate in conjunction with, implantable components.

SUMMARY

[0004] In an exemplary embodiment, there is an apparatus, comprising: a reservoir; and a therapeutic substance located in the reservoir, wherein the apparatus is an implantable therapeutic substance delivery apparatus, and the apparatus is configured to deliver the therapeutic substance to a recipient thereof by diffusion controlled release. [0005] In an exemplary embodiment, there is an apparatus, comprising: a cistern; and a delivery tube device, wherein the apparatus is an implantable therapeutic substance delivery apparatus, the delivery tube device is a diffusion delivery tube device, and the apparatus is configured so that therapeutic substance located in the cistern travels to the delivery tube for delivery to a human implanted with the device.

[0006] In an exemplary embodiment, there is a method, comprising: accessing an interior of a human; and treating an ailment of the human by controllably delivering a therapeutic substance delivered from an implantable therapeutic substance delivery device, wherein the action of controllably delivering the therapeutic substance is executed passively.

[0007] In an exemplary embodiment, there is an apparatus, comprising: a first at least partially bounded volume; a second at least partially bounded volume; and at least one apparatus outlet at the second bounded volume, wherein the apparatus is an implantable therapeutic substance delivery apparatus, and the apparatus delivers the therapeutic substance to a recipient thereof effectively entirely due to a concentration gradient.

[0008] In an exemplary embodiment, there is a method, comprising: accessing an interior of a human; and treating an ailment of a human by controllably delivering a therapeutic substance delivered from an implantable therapeutic substance delivery device, wherein the action of controllably delivering the therapeutic substance is executed effectively without a net movement of solvent in which the therapeutic substance is present from a therapeutic substance containing volume of the device to the ambient environment outside the device.

[0009] In an exemplary embodiment, there is an implantable therapeutic substance delivery apparatus, comprising a cistern and a delivery tube device, wherein the delivery tube device includes a tubular apparatus that includes a first lumen and a second lumen distinctly different from the first lumen, the delivery tube device is a diffusion delivery tube device, the first lumen is in fluid communication with the cistern and the second lumen is in fluid communication with the first lumen, and the apparatus is configured so that the therapeutic substance located in the cistern travels to the delivery tube device for delivery to a human implanted with the device.

BRIEF DESCRIPTION OF THE DRAWINGS

[ooio] Embodiments are described below with reference to the attached drawings, in which:

[0011] FIG. 1A is a perspective view of an exemplary hearing prosthesis in which at least some of the teachings detailed herein are applicable; [0012] FIGs. 1B-1D are quasi functional diagrams of an exemplary device to which some embodiments may be applicable;

[0013] FIGs IE and 2A and 2B and 2C and IF present some schematics related to base technologies associated with some embodiments;

[0014] FIGs. 3 and 4 show other exemplary medical devices to which at least some of the teachings herein are applicable;

[0015] FIG. 5 shows a top view of an exemplary implantable portion of a cochlear implant according to an embodiment;

[0016] FIGs. 6 and 7 and 7A and 40 and 41 and 42 show some details of a portion of an exemplary implantable portion of a cochlear implant according to an embodiment;

[0017] FIG. 8 shows a side view of an ear for reference purposes;

[0018] FIG. 9 shows some details of some portions of an exemplary implantable portion of a cochlear implant according to an embodiment;

[0019] FIG. 10 is a functional diagram;

[0020] FIGs 11-19 show some exemplary design data;

[0021] FIGs. 20-21 and 22-26 and 27-31 and 32-37 and 39A show some exemplary performance, etc., data; and

[0022] FIGs. 38-39 show exemplary flowcharts.

DETAILED DESCRIPTION

[0023] Merely for ease of description, the techniques presented herein are primarily described herein with reference to an illustrative medical device, namely a hearing prosthesis. First introduced is a cochlear implant. The techniques presented herein may also be used with a variety of other medical devices that, while providing a wide range of therapeutic benefits to recipients, patients, or other users, may benefit from the teachings herein used in other medical devices. For example, any techniques presented herein described for one type of hearing prosthesis, such as a cochlear implant, corresponds to a disclosure of another embodiment of using such teaching with, at least in conjunction with, another hearing prosthesis, including bone conduction devices (percutaneous, active transcutaneous and/or passive transcutaneous), middle ear auditory prostheses, direct acoustic stimulators, and also utilizing such with other electrically simulating auditory prostheses (e.g., auditory brain stimulators), etc. The techniques presented herein can be used with implantable / implanted microphones, whether or not used as part of a hearing prosthesis (e.g., a body noise or other monitor, whether or not it is part of a hearing prosthesis) and/or external microphones. The techniques presented herein can also be used with vestibular devices (e.g., vestibular implants), sensors, seizure devices (e.g., devices for monitoring and/or treating epileptic events, where applicable), sleep apnea devices, retinal implants, electroporation, etc., and thus any disclosure herein is a disclosure of utilizing such devices with the teachings herein, providing that the art enables such.

[0024] Note also embodiments include the application of the teachings herein to a medical device that is a non-implanted medical device, such as a minimally invasive probe used by medical personnel.

[0025] By way of example, any of the technologies detailed herein which are associated with components that are implanted in a recipient can be combined with information delivery technologies disclosed herein, such as for example, devices that evoke a hearing percept, to convey information to the recipient. By way of example only and not by way of limitation, a sleep apnea implanted device can be combined with a device that can evoke a hearing percept so as to provide information to a recipient, such as status information, etc. In this regard, the various sensors detailed herein and the various output devices detailed herein can be combined with such a non-sensory prosthesis or any other nonsensory prosthesis that includes implantable components so as to enable a user interface, as will be described herein, that enables information to be conveyed to the recipient, which information is associated with the implant.

[0026] While the teachings detailed herein will be described for the most part with respect to hearing prostheses, in keeping with the above, it is noted that any disclosure herein with respect to a hearing prosthesis corresponds to a disclosure of another embodiment of utilizing the associated teachings with respect to any of the other prostheses noted herein, whether a species of a hearing prosthesis, or a species of a sensory prosthesis.

[0027] The techniques presented herein are also described with reference by way of background to another illustrative medical device, namely a retinal implant. As noted above, the techniques presented herein are also applicable to the technology of vestibular devices (e.g., vestibular implants), visual devices (i.e., bionic eyes), as well as sensors, pacemakers, drug delivery systems, defibrillators, functional electrical stimulation devices, catheters, seizure devices (e.g., devices for monitoring and/or treating epileptic events), sleep apnea devices, electroporation, etc.

[0028] Any reference to one of the above-noted sensory prostheses corresponds to an alternate disclosure using one of the other above-noted sensory prostheses unless otherwise noted providing that the art enables such.

[0029] FIG. 1A is perspective view of an implantable portion of a cochlear implant 100, implanted in a recipient. The implantable portion of the cochlear implant 100 is part of a partially implantable cochlear implant system 10 that can include external component s), as will be detailed below.

[0030] The recipient has an outer ear 101, a middle ear 105, and an inner ear 107. Components of outer ear 101, middle ear 105, and inner ear 107 are described below, followed by a description of implant 100.

[0031] In a fully functional ear, outer ear 101 comprises an auricle 110 and an ear canal 102. An acoustic pressure or sound wave 103 is collected by auricle 110 and channeled into and through ear canal 102. Disposed across the distal end of ear canal 102 is a tympanic membrane 104 which vibrates in response to sound wave 103. This vibration is coupled to oval window or fenestra ovalis 112 through three bones of middle ear 105, collectively referred to as the ossicles 106 and comprising the malleus 108, the incus 109, and the stapes 111. Bones 108, 109, and 111 of middle ear 105 serve to filter and amplify sound wave 103, causing oval window 112 to articulate, or vibrate in response to vibration of tympanic membrane 104. This vibration sets up waves of fluid motion of the perilymph within cochlea 140. Such fluid motion, in turn, activates tiny hair cells (not shown) inside of cochlea 140. Activation of the hair cells causes appropriate nerve impulses to be generated and transferred through the spiral ganglion cells (not shown) and auditory nerve 114 to the brain (also not shown) where they are perceived as sound.

[0032] As shown, implantable portion of cochlear implant 100 comprises one or more components which are temporarily or permanently implanted in the recipient. Implant 100 is shown in FIG. 1A with an external device 142, that is part of system 10 (along with implantable portion of the cochlear implant 100), which, as described below, is configured to provide power to the implant.

[0033] In the illustrative arrangement of FIG. 1A, external device 142 may comprise a power source (not shown) disposed in a Behind-The-Ear (BTE) unit 126. External device 142 also includes components of a transcutaneous energy transfer link, referred to as an external energy transfer assembly. The transcutaneous energy transfer link is used to transfer power and/or data to implant 100. Various types of energy transfer, such as infrared (IR), electromagnetic, capacitive, and inductive transfer, may be used to transfer the power and/or data from external device 142 to implant 100. In the illustrative embodiments of FIG. 1A, the external energy transfer assembly comprises an external coil 130 that forms part of an inductive radio communication link. External coil 130 is typically a wire antenna coil comprised of multiple turns of electrically insulated single-strand or multi-strand platinum or gold wire. External device 142 also includes a magnet (not shown) positioned within the turns of wire of external coil 130. It should be appreciated that the external device shown in FIG. 1A is merely illustrative, and other external devices may be used with embodiments of the present invention.

[0034] Implantable portion of the cochlear implant 100 comprises an internal energy transfer assembly 132 which may be positioned in a recess of the temporal bone adjacent auricle 110 of the recipient. As detailed below, internal energy transfer assembly 132 is a component of the transcutaneous energy transfer link and receives power and/or data from external device 142. In the illustrative embodiment, the energy transfer link comprises an inductive RF link, and internal energy transfer assembly 132 comprises a primary internal coil 136. Internal coil 136 is typically a wire antenna coil comprised of multiple turns of electrically insulated single-strand or multi-strand platinum or gold wire.

[0035] The implantable portion of the cochlear implant 100 further comprises a main implantable component 120 and an elongate stimulating assembly 118. In embodiments of the present invention, internal energy transfer assembly 132 and main implantable component 120 are hermetically sealed within a biocompatible housing. In embodiments of the present invention, main implantable component 120 includes a sound processing unit (not shown) to convert the sound signals received by the implantable microphone in internal energy transfer assembly 132 to data signals. Main implantable component 120 further includes a stimulator unit (also not shown) which generates electrical stimulation signals based on the data signals. The electrical stimulation signals are delivered to the recipient via elongate stimulating assembly 118.

[0036] Elongate stimulating assembly 118 has a proximal end connected to main implantable component 120, and a distal end implanted in cochlea 140. Stimulating assembly 118 extends from main implantable component 120 to cochlea 140 through mastoid bone 119. In some embodiments stimulating assembly 118 may be implanted at least in basal region 116, and sometimes further. For example, stimulating assembly 118 may extend towards apical end of cochlea 140, referred to as cochlea apex 134. In certain circumstances, stimulating assembly 118 may be inserted into cochlea 140 via a cochleostomy 122. In other circumstances, a cochleostomy may be formed through round window 121, oval window 112, the promontory 123 or through an apical turn 147 of cochlea 140.

[0037] Stimulating assembly 118 comprises a longitudinally aligned and distally extending array 146 of electrodes 148, disposed along a length thereof. As noted, a stimulator unit generates stimulation signals which are applied by stimulating contacts 148, which, in an exemplary embodiment, are electrodes, to cochlea 140, thereby stimulating auditory nerve 114. In an exemplary embodiment, stimulation contacts can be any type of component that stimulates the cochlea (e.g., mechanical components, such as piezoelectric devices that move or vibrate, thus stimulating the cochlea (e.g., by inducing movement of the fluid in the cochlea), electrodes that apply current to the cochlea, etc.). Embodiments detailed herein will generally be described in terms of an electrode assembly 118 utilizing electrodes as elements 148. It is noted that alternate embodiments can utilize other types of stimulating devices. Any device, system, or method of stimulating the cochlea via a device that is located in the cochlea can be utilized in at least some embodiments. In this regard, any implantable array that stimulates tissue, such as a retinal implant array, or a spinal array, or a pacemaker array, etc., is encompassed within the teachings herein unless otherwise noted.

[0038] As noted, the implantable portion 100 comprises a partially implantable prosthesis, as contrasted to a totally implantable prosthesis that is capable of operating, at least for a period of time, without the need for external device 142. Therefore, implantable portion of cochlear implant 100 does not comprise a rechargeable power source that stores power received from external device 142, as contrasted to an embodiment where there is an implantable rechargeable power source (e.g., a rechargeable battery). During operation of implant 100, the power is transferred from the external component to the implanted component via the link, and distributed to the various other implanted components as needed.

[0039] It is noted that the teachings detailed herein and/or variations thereof can be utilized with a totally implantable prosthesis. That is, in an alternate embodiment of the cochlear implants or other hearing prostheses detailed herein, the prostheses are totally implantable prostheses, such as where there is an implanted microphone and sound processor and battery. [0040] FIG. IB provides a schematic of an exemplary conceptual sleep apnea system 1991. Here, this exemplary sleep apnea system utilizes a microphone 12 (represented conceptually) to capture a person’s breathing or otherwise the sounds made by a person while sleeping. The microphone transduces the captured sound into an electrical signal which is provided via electrical leads 198 to the main unit 197, which includes a processor unit that can evaluate the signal from leads 198 or, in another arrangement, unit 197 is configured to provide that signal to a remote processing location via the Internet or the like, where the signal was evaluated. Upon an evaluation that an action should be taken or otherwise can be utilitarian taken by the sleep apnea system 1991, the unit 197 activates to implement sleep apnea countermeasures, which countermeasures are conducted by a hose 1902 sleep apnea mask 195. By way of example only and not by way of limitation, pressure variations can be used to treat the sleep apnea upon an indication of such an occurrence.

[0041] In an exemplary embodiment, the advanced implantation methods and devices detailed herein can be utilized to treat sleep apnea / in a device that can be used to treat. Specifically, the electrodes of the implant disclosed below can be utilized in place of the electrodes 194 (placed accordingly, of course), and the implant can be of a configuration to treat sleep apnea. In this regard, in an exemplary embodiment, the implantable components detailed herein can be located at locations to treat sleep apnea in accordance with the teachings herein, with the requisite modification if necessary or otherwise utilitarian to implement such.

[0042] FIGs. 1C and ID provide another exemplary schematic of another exemplary conceptual sleep apnea system 1992. Here, the sleep apnea system is different from that of figure IB in that electrodes 194 (which can be implanted in some embodiments) are utilized to provide stimulation to the human who is experiencing a sleep apnea scenario. FIG. 1C illustrates an external unit, and FIG. ID illustrates the external unit 120 and an implanted unit 110 in signal communication via an inductance coil 707 of the external unit and a corresponding implanted inductance coil (not shown) of the implanted unit, according to which the teachings herein can be applicable. Implanted unit 110, can be configured for implantation in a recipient, in a location that permits it to modulate nerves of the recipient 100 via electrodes 194. In treating sleep apnea, implant unit 110 and/or the electrodes thereof can be located on a genioglossus muscle of a patient. Such a location is suitable for modulation of the hypoglossal nerve, branches of which run inside the genioglossus muscle. [0043] External unit 120 can be configured for location external to a patient, either directly contacting, or close to the skin of the recipient. External unit 120 may be configured to be affixed to the patient, for example, by adhering to the skin of the patient, or through a band or other device configured to hold external unit 120 in place. Adherence to the skin of external unit 120 may occur such that it is in the vicinity of the location of implant unit 110 so that, for example, the external unit 120 can be in signal communication with the implant unit 110 as conceptually shown, which communication can be via an inductive link or an RF link or any link that can enable treatment of sleep apnea using the implant unit and the external unit. External unit 120 can include a processor unit 198 that is configured to control the stimulation executed by the implant unit 110. In this regard, processor unit 198 can be in signal communication with microphone 12, via electrical leads, such as in an arrangement where the external unit 120 is a modularized component, or via a wireless system, such as conceptually represented in FIG. ID.

[0044] A common feature of both of these sleep apnea treatment systems is the utilization of the microphone to capture sound, and the utilization of that captured sound to implement one or more features of the sleep apnea system. In some embodiments, the teachings herein are used with the sleep apnea device just detailed.

[0045] FIG. 3 presents an exemplary embodiment of a neural prosthesis in general, and a retinal prosthesis and an environment of use thereof, in particular, the components of which can be used in whole or in part, with some of the teachings herein. In some embodiments of a retinal prosthesis, a retinal prosthesis sensor-stimulator 10801 is positioned proximate the retina 11001. In an exemplary embodiment, photons entering the eye are absorbed by a microelectronic array of the sensor-stimulator 10801 that is hybridized to a glass piece 11201 containing, for example, an embedded array of microwires. The glass can have a curved surface that conforms to the inner radius of the retina. The sensor-stimulator 108 can include a microelectronic imaging device that can be made of thin silicone containing integrated circuitry that convert the incident photons to an electronic charge.

[0046] An image processor 10201 is in signal communication with the sensor-stimulator 10801 via cable 10401 which extends through surgical incision 00601 through the eye wall (although in other embodiments, the image processor 10201 is in wireless communication with the sensor-stimulator 10801). The image processor 10201 processes the input into the sensor-stimulator 10801 and provides control signals back to the sensor-stimulator 10801 so the device can provide processed output to the optic nerve. That said, in an alternate embodiment, the processing is executed by a component proximate with or integrated with the sensor-stimulator 10801. The electric charge resulting from the conversion of the incident photons is converted to a proportional amount of electronic current which is input to a nearby retinal cell layer. The cells fire and a signal is sent to the optic nerve, thus inducing a sight perception.

[0047] The retinal prosthesis can include an external device disposed in a Behind-The-Ear (BTE) unit or in a pair of eyeglasses, or any other type of component that can have utilitarian value. The retinal prosthesis can include an external light / image capture device (e.g., located in / on a BTE device or a pair of glasses, etc.), while, as noted above, in some embodiments, the sensor-stimulator 10801 captures light / images, which sensor-stimulator is implanted in the recipient.

[0048] In the interests of compact disclosure, any disclosure herein of a microphone or sound capture device corresponds to an analogous disclosure of a light / image capture device, such as a charge-coupled device. Corollary to this is that any disclosure herein of a stimulator unit which generates electrical stimulation signals or otherwise imparts energy to tissue to evoke a hearing percept corresponds to an analogous disclosure of a stimulator device for a retinal prosthesis. Any disclosure herein of a sound processor or processing of captured sounds or the like corresponds to an analogous disclosure of a light processor / image processor that has analogous functionality for a retinal prosthesis, and the processing of captured images in an analogous manner. Indeed, any disclosure herein of a device for a hearing prosthesis corresponds to a disclosure of a device for a retinal prosthesis having analogous functionality for a retinal prosthesis. Any disclosure herein of fitting a hearing prosthesis corresponds to a disclosure of fitting a retinal prosthesis using analogous actions. Any disclosure herein of a method of using or operating or otherwise working with a hearing prosthesis herein corresponds to a disclosure of using or operating or otherwise working with a retinal prosthesis in an analogous manner.

[0049] Figure 4 depicts an exemplary vestibular implant 400 according to one example. Some specific features are described utilizing the above-noted cochlear implant of figure 1 in contacts for the various elements. In this regard, some features of a cochlear implant are utilized with vestibular implants. In the interest of textual and pictorial economy, various elements of the vestibular implant that generally correspond to the elements of the cochlear implant above are referenced utilizing the same numerals. Still, it is noted that some features of the vestibular implant 400 will be different from that of the cochlear implant above. By way of example only and not by way of limitation, there may not be a microphone on the behind-the-ear device 126. Alternatively, sensors that have utilitarian value in the vestibular implant can be contained in the BTE device 126. By way of example only and not by way of limitation, motion sensors can be located in BTE device 126. There also may not be a sound processor in the BTE device. Conversely, other types of processors, such as those that process data obtained from the sensors, will be present in the BTE device 126. Power sources, such as a battery, will also be included in the BTE device 126. Consistent with the BTE device of the cochlear implant of figure 1, a transmitter / transceiver will be located in the BTE device or otherwise in signal communication therewith. Any one or more of the teachings herein can be used with the arrangement of FIG. 4.

[0050] The implantable component includes a receiver-stimulator in a manner concomitant with the above cochlear implant. Here, the vestibular stimulator comprises a main implantable component 120 and an elongate electrode assembly 14188 (where the elongate electrode assembly 14188 has some different features from the elongate electrode assembly 118 of the cochlear implant, some of which will be described shortly). In some embodiments, internal energy transfer assembly 132 and main implantable component 120 are hermetically sealed within a biocompatible housing. In some embodiments, main implantable component 120 includes a processing unit (not shown) to convert data obtained by sensors, which could be on board sensors implanted in the recipient, into data signals.

[0051] Main implantable component 120 further includes a stimulator unit (also not shown) which generates electrical stimulation signals based on the data signals. The electrical stimulation signals are delivered to the recipient via elongate electrode assembly 14188.

[0052] It is briefly noted that while the embodiment shown in figure 4 represents a partially implantable vestibular implant, embodiments can include a totally implantable vestibular implant, such as, where, for example, the motion sensors are located in the implantable portion, in a manner analogous to a cochlear implant.

[0053] Elongate electrode assembly 14188 has a proximal end connected to main implantable component 120, and extends through a hole in the mastoid 119, in a manner analogous to the elongate electrode assembly 118 of the cochlear implant, and includes a distal end that extends to the inner ear. In some embodiments, the distal portion of the electrode assembly 14188 includes a plurality of leads 410 that branch out away from the main body of the electrode assembly 118 to electrodes 420. Electrodes 420 can be placed at the base of the semicircular ducts as shown in figure 4. In an exemplary embodiment, one or more of these electrodes are placed in the vicinity of the vestibular nerve branches innervating the semicircular canals. In some embodiments, the electrodes are located external to the inner ear, while in other embodiments, the electrodes are inserted into the inner ear. Note also while this embodiment does not include an electrode array located in the cochlea, in other embodiments, one or more electrodes are located in the cochlea in a manner analogous to that of a cochlear implant.

[0054] Returning back to hearing prosthesis devices, and in particular a cochlear implant, FIG. IE is a side view of the internal component (implantable component) of cochlear implant 100 without the other components of system 10 (e.g., the external components). The implantable portion of cochlear implant 100 comprises a receiver/stimulator 180 (combination of main implantable component 120 and internal energy transfer assembly 132) and a stimulating assembly or lead 118. Stimulating assembly 118 includes a helix region 182, a transition region 184, a proximal region 186, and an intra-cochlear region 188. Proximal region 186 and intra-cochlear region 188 form an electrode array assembly 190. In an exemplary embodiment, proximal region 186 is located in the middle-ear cavity of the recipient after implantation of the intra-cochlear region 188 into the cochlea. Thus, proximal region 186 corresponds to a middle-ear cavity sub-section of the electrode array assembly 190. Electrode array assembly 190, and in particular, intra-cochlear region 188 of electrode array assembly 190, supports a plurality of electrode contacts 148. These electrode contacts 148 are each connected to a respective conductive pathway, such as wires, PCB traces, etc. (not shown) which are connected through lead 118 to receiver/stimulator 180, through which respective stimulating electrical signals for each electrode contact 148 travel.

[0055] FIG. 2A is a side view of electrode array assembly 190 in a curled orientation, as it would be when inserted in a recipient's cochlea, with electrode contacts 148 located on the inside of the curve. FIG. 2A depicts the electrode array of FIG. IB in situ in a patient's cochlea 140.

[0056] FIG. 2B depicts a side view of a device 390 corresponding to a cochlear implant electrode array assembly that can include some or all of the features of electrode array assembly 190 of FIG. IE. More specifically, in an exemplary embodiment, stimulating assembly 118 includes electrode array assembly 390 instead of electrode array assembly 190 (i.e., 190 is replaced with 390). [0057] Electrode array assembly 390 includes a cochlear implant electrode array componentry of the 190 assembly above. Note also element 310, which is a quasi-handle like device utilized with utilitarian value vis-a-vis inserting the 188 section into a cochlea. By way of example only and not by way of limitation, element 310, which is a silicone body that extends laterally away from the longitudinal axis of the electrode array assembly 390, and has a thickness that is less than that of the main body of the assembly (the portion through which the electrical leads that extend to the electrodes extend to the elongate lead assembly 302). The thickness combined with the material structure is sufficient so that the handle can be gripped at least by a tweezers or the like during implantation and by application of a force on to the tweezers, the force can be transferred into the electrode array assembly 390 so that section 188 can be inserted into the cochlea.

[0058] FIG. 2C presents additional details of an external component assembly 242, corresponding to external component 142 above. It is noted that in a modified form, this device can be used with the other prostheses herein (e.g., some such embodiments might not have the ear piece 250).

[0059] External assembly 242 typically comprises a sound transducer 220 for detecting sound, and for generating an electrical audio signal, typically an analog audio signal. In this illustrative arrangement, sound transducer 220 is a microphone. In alternative arrangements, sound transducer 220 can be any device now or later developed that can detect sound and generate electrical signals representative of such sound. An exemplary alternate location of sound transducer 220 will be detailed below. As will be detailed below, a sound transducer can also be located in an ear piece, which can utilize the “funneling” features of the pinna for more natural sound capture (more on this below).

[0060] External assembly 242 also comprises a signal processing unit, a power source (not shown), and an external transmitter unit. External transmitter unit 206 (sometimes herein referred to as a headpiece) comprises an external coil 208 and, a magnet (not shown) secured directly or indirectly to the external coil 208. The signal processing unit processes the output of microphone 220 that is positioned, in the depicted arrangement, by outer ear 201 of the recipient. The signal processing unit generates coded signals using a signal processing apparatus (sometimes referred to herein as a sound processing apparatus), which can be circuitry (often a chip) configured to process received signals - because element 230 contains this circuitry, the entire component 230 is often called a sound processing unit or a signal processing unit. These coded signals can be referred to herein as a stimulation data signals, which are provided to external transmitter unit 206 via a cable 247. In this exemplary arrangement of figure ID, cable 247 includes connector jack 221 which is bayonet fitted into receptacle 219 of the signal processing unit 230 (an opening is present in the dorsal spine, which receives the bayonet connector, in which includes electrical contacts to place the external transmitter unit into signal communication with the signal processor 230). It is also noted that in alternative arrangements, the external transmitter unit is hardwired to the signal processor subassembly 230. That is, cable 247 is in signal communication via hardwiring, with the signal processor subassembly. (The device of course could be disassembled, but that is different than the arrangement shown in figure ID that utilizes the bayonet connector.) Conversely, in some embodiments, there is no cable 247. Instead, there is a wireless transmitter and/or transceiver in the housing of component 230 and/or attached to the housing (e.g., a transmitter / transceiver can be attached to the receptacle 219) and the headpiece can include a receiver and/or transceiver, and can be in signal communication with the transmitter / transceiver of / associated with element 230.

[0061] FIG. IF provides additional details of an exemplary in-the-ear (ITE) component 250. The overall component containing the signal processing unit is, in this illustration, constructed and arranged so that it can fit behind outer ear 201 in a BTE (behind-the-ear) configuration, but may also be worn on different parts of the recipient's body or clothing.

[0062] In some arrangements, the signal processor (also referred to as the sound processor) may produce electrical stimulations alone, without generation of any acoustic stimulation beyond those that naturally enter the ear. While in still further arrangements, two signal processors may be used. One signal processor is used for generating electrical stimulations in conjunction with a second speech processor used for producing acoustic stimulations.

[0063] As shown in FIG. IF, an ITE component 250 is connected to the spine of the BTE (a general term used to describe the part to which the battery 270 attaches, which contains the signal (sound) processor and supports various components, such as the microphone - more on this below) through cable 252 (and thus connected to the sound processor / signal processor thereby). ITE component 250 includes a housing 256, which can be a molding shaped to the recipient. Inside ITE component 250 there is provided a sound transducer 220 that can be located on element 250 so that the natural wonders of the human ear can be utilized to funnel sound in a more natural manner to the sound transducer of the external component. In an exemplary arrangement, sound transducer 242 is in signal communication with remainder of the BTE unit via cable 252, as is schematically depicted in figure IF via the sub cable extending from sound transducer 242 to cable 252. Shown in dashed lines are leads 21324 that extend from transducer 220 to cable 252. Not shown is an air vent that extends from the left side of the housing 256 to the right side of the housing (at or near the tip on the right side) to balance air pressure “behind” the housing 256 and the ambient atmosphere when the housing 256 is in an ear canal.

[0064] Also, FIG. 2C shows a removable power component 270 (sometimes battery back, or battery for short) directly attached to the base of the body / spine 230 of the BTE device. As seen, the BTE device in some embodiments includes control buttons 274. The BTE device may have an indicator light 276 on the earhook to indicate operational status of signal processor. Examples of status indications include a flicker when receiving incoming sounds, low rate flashing when power source is low or high rate flashing for other problems.

[0065] In one arrangement, external coil 130 transmits electrical signals to the internal coil via an inductance communication link. The internal coil is typically a wire antenna coil comprised of at least one, or two or three or more turns of electrically insulated single-strand or multi-strand platinum or gold wire. The electrical insulation of the internal coil is provided by a flexible silicone molding (not shown). In use, internal receiver unit may be positioned in a recess of the temporal bone adjacent to outer ear 101 of the recipient.

[0066] With the above as a primer (the above should be considered base technologies from which we build upon, and are not part of the invention, but the teachings below can use any one or more of these features in some embodiments, providing that the art enables such), embodiments are directed to cochlear implants and other implants that, in some embodiments, utilize one or more of the teachings above, albeit modified in at least some instances, to practice the teachings herein.

[0067] FIG. 5 shows an implantable portion 500 of the cochlear implant, corresponding to portion 100 of figure 1A detailed above. In this regard, the features detailed above with respect to the cochlear implants are included in this embodiment. Element 181 corresponds to the RF antenna that receives transcutaneous magnetic inductive signals from the external component. The antenna 181 is in signal communication with electronics located in housing 185. Housing 185 is a hermetically sealed titanium housing that includes componentry of the cochlear implant that is configured to receive signals from the antenna 181 and, based on those signals, output signals to the electrodes of the electrode assembly 590, which can correspond to the electrode assembly 190 detailed above. Collectively, the electronics in the housing 185 and the antenna 181 establish a receiver-stimulator assembly 580, which can correspond to the receiver-stimulator assembly 180 detailed above. The antenna 181 and the housing 185 are located within a silicone body 183 that has been molded about those components. The electrode assembly 590 is in signal communication with the electronics of the housing 185 via lead assembly 589. The lead assembly can be a silicone body that is molded about electrical leads that run from the electrodes to a feedthrough that interfaces with the housing 185 to enable signal communication from the electronics in the housing to the electrical leads and thus to the electrodes. The electrode assembly, and in particular, the silicone body thereof, can be made separate from the silicone body that envelops the housing 185. In this regard, in an exemplary embodiment, the lead assembly 589 along with the electrode array assembly 590 is connected to the housing 185, or more accurately, the lead wires of the lead assembly 589 are first attached to a feedthrough that interfaces with the housing 185, thus placing the lead assembly into electrical signal communication with the receiver-stimulator assembly 580, which lead wires are supported by the silicone body that envelops the lead wires of the lead assembly 589. Then, silicone is molded about the housing 185 to form the silicone body 183, which silicone body traps or otherwise adheres the lead assembly 589 to the silicone body.

[0068] This embodiment further has a feature of a therapeutic substance delivery subsystem. In this regard, the embodiment of figure 5 is configured to deliver a therapeutic substance from outside the cochlea to inside the cochlea when the electrode array 590 is located in the cochlea. In this regard, the implantable portion includes a therapeutic substance delivery subsystem as just noted. This subsystem includes a cistern 510, as seen in figure 5, that forms part of a reservoir fill assembly (additional details of this will be described below). Fig. 6 shows additional details of the therapeutic substance delivery subsystem. In particular, the cistern 510 is shown in fluid communication with a conduit that includes a first portion 512 that leads to a second portion 514. Here, the cistern 512 is supported by the silicone body 183 that envelops the housing. In some embodiments, the cistern is completely subsumed within the silicone body 183, while in other embodiments, a portion of the cistern extends out of or otherwise is flush with a surface of the silicone body 183. The cistern 510 can be made out of titanium or a polymer that is stable with the therapeutic substance that will be placed into the cistern. The cistern 510 can include a septum at a top portion thereof, that can enable the cistern to be charged with a therapeutic substance. Some additional details of this will be describe below. [0069] The conduit can be a polymer tube or be established by a polymer tube that is stable with the therapeutic substance. The tube interfaces with the cistern in any manner that can enable fluid to transfer from the cistern to the tube (an interference fit of a male outlet of the cistern over the tube can be used, for example). The tube runs from the cistern 510 into the silicone body 516 that envelops the electrical leads 592 that run from the electrodes. (Electrical leads could be located in the tube, while in other embodiments, the tube is “parallel” to and adjacent to the leads.) Note further that in an embodiment, the tube(s) could be located outside the silicone body 516 and run parallel with the silicone body (connected along the length, such as by straps or some connector that holds the tube(s) against the body along the length thereof) or loose so that the tube can be moved away from the silicone body, where the end of the tube then meets the electrode array (roughly analogous to how the old Chesapeake Bay Bridge Tunnel operated - bridges were separate from each other, but the bridges joined each other / met at the tunnels - here, the tube and the body could meet at the array, so that there is only one opening into the cochlea). In this regard, in an exemplary embodiment, the cistern 510 and the portion of the tube 512 that extends out of the silicone body 516 can be molded in the silicone body 183 during the molding process of the silicone body 183 about the housing 185. Portion 514 of the tube and at least some of the portion 512 of the tube can be placed with the electrical leads 592 and then silicone can be molded around both at the same time to establish the body 516. In an embodiment, there is no definitive structural tube per se, but instead a conduit within the silicone, that is a hollow space therein. For example, the hollow space can be a hollow space left over from removing a mandrel about which the lead is molded around. In an embodiment, silicone can be removed by hogging out a hollow space for example. Any device, system and/or method that can enable a passageway within the implant to be established that can enable the teachings herein can be used in some embodiments providing that the art enables the process and/or the end result. Thus, in an embodiment, the implant is “tubeless” vis-a-vis the therapeutic substance deliver system, in whole or in part (e.g., portion 514 and/or 518 could be tubeless, but portion 512 could be a tube for example. Any portion can be tubeless or be established by a tube.

[0070] Concomitant with the embodiments above, the electrode assembly 590 is located at the end of the lead assembly 589. The tube extends into the electrode array portion shown. The portion 518 of the tube that extends into the electrode array portion extends to the tip of the electrode array 590. Collectively, the portions 518, 514, 512 and the cistern form an implantable therapeutic substance reservoir. In an embodiment, portion 518 is configured to be flexible. In an embodiment, all portions or a majority of the portions of the therapeutic substance delivery system that are located intracochlearly when fully implanted are flexible. In an embodiment, the portions located intracochlearly are at least as flexible as the electrode array would be without the portion 518. Thus, in some embodiments, the portion 518 is even more flexible than the electrode array without the portion 518.

[0071] A plug 530 is located at the end of the tube (interference fitted inside the tube, for example, or bonded to the tube). The plug provides a bacterial seal at the tube portion 518 and thus the reservoir assembly, but enables the therapeutic substance in the reservoir to pass through, and thus into the cochlea. Additional details of this will be described below.

[0072] In view of the above, in an embodiment, there is an apparatus, such as an implantable portion of a cochlear implant, which includes an array of electrodes, and an implantable therapeutic substance reservoir. The apparatus is configured so that the therapeutic substance reservoir extends from a location behind an ear canal of a human between a mastoid bone and skin of the human to the cochlea when the apparatus is fully implanted in a recipient. In this regard, as noted above, the cistern, which is part of the reservoir, is adjacent the receiverstimulator 580. When the implant is implanted in a head of a human, the cistern 510 is located behind and/or above the ear canal, or at least a portion thereof is so located. In an embodiment, at least 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100% of the overall area subsumed by the cistern (when looking down at the coil) is so located. Note further that in an embodiment, when looking directly at the side of the head (90 degrees from the front), with respect to a 50 percentile human factors engineering human of 60 years of age bom in the United States, the implantable portion is configured so that any one or more of the aforementioned features vis-a-vis the cistem 510 is also applicable an area that is not overshadowed by the pinna of that human (for example 100% is not overshadowed, or at least 20% is not overshadowed). Note that this is not a subjective feature with respect to a given human. This is an objective feature that relates to a qualifiable fact relating to the aforementioned 50 percentile human. That said, in an exemplary embodiment, this can be a subjective value for a given person.

[0073] With respect to FIG. 8, there is a quadrant system presented that is centered about the ear canal 106 of the recipient. As can be seen, it is established by a vertical line 99 and a horizontal line 98 centered at the center of the ear canal 106. These lines establish four quadrants about the ear canal: QI, Q2, Q3, and Q4. As will be understood, these quadrants generally follow the 12 hour clock, with quadrant 1 falling between the 12 o’clock position and the 3 o’clock position, quadrant 2 falling between the 3 o’clock position and the 6 o’clock position, quadrant 3 falling between the 6 o’clock position and the 9 o’clock position, and quadrant 4 falling between the 9 o’clock position and the 12 o’clock position. In an embodiment, the cistern falls completely within quadrant Q4. Accordingly, in an exemplary embodiment, there is a hearing prosthesis device that includes a reservoir that has a portion that falls within quadrant 4. The quadrants are established by the outermost opening of the ear canal 106, when looking directly at the side of the human (90 degrees from the front). These are established at the outermost portion where ear canal establishes a closed circle or oval, etc., in cross-section.

[0074] Note that there can be alternate quadrants. In an exemplary embodiment, quadrants can be established by lines 94/96, which are the topmost and back most tangent lines of the ear canal 106 (the opening of the ear canal), lines 99 and 98 as just detailed which correspond to the center of the opening of the ear canal), and lines 95 and 97 which correspond to the forward most and bottom most tangent lines of the ear canal (again, vis-a-vis the opening). The just noted features can be applicable to any of the quadrants established by any of these lines. (Quadrants can include a quadrant based on line 97 and line 94 - all lines can be mixed and matched.)

[0075] Note further that in an exemplary embodiment, there can be quadrants that are based on lines parallel to any one or more of the lines shown in figure 8, wherein the lines are 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, or 6 cm or any value or range of values therebetween in 1 mm increments to the left or right or above or below a given line. Any of the aforementioned features can be applicable to such a quadrant.

[0076] In an embodiment, at least 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95%, or more, or any value or range of values therebetween in 1% increments (e.g., 33%, 54%, 31 to 94%, etc.) of the total volume of the reservoir can be located behind (where the face of the human is the front) and/or above (where the feet of the human are below) any one or more of the just noted lines.

[0077] In an embodiment, the reservoir is completely integrated in the implantable portion of the cochlear implant. For example, as detailed above, the cistern 510 is located within the silicone body that envelops the housing 185, and the tube portions 512, 514, and 518 and the plug 530 are all within the boundary that establishes the lead assembly with the electrode assembly. [0078] In an exemplary embodiment, of the total outer surface area of the components that make up the reservoir (e.g., cistern and tubes and plug, if present), at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100% of that surface area is in direct contact with silicone that establishes the silicone body that encases the housing and the silicone body of the lead assembly, including the electrode assembly. Some portions of the cistern, such as the septum that enables the reservoir to be filled, can be located proud of the silicone body that encases the housing or otherwise flush with the surrounding body of silicone.

[0079] Figure 7 shows a lead assembly 789 prior to connection of that lead assembly to the receiver-stimulator of the cochlear implant. In an exemplary embodiment, this lead assembly is manufactured separately from the receiver-stimulator. As seen on the right end of the lead assembly 789, there is a T-shaped component 777. It is noted that some embodiments do not utilize the T 777.

[0080] Figure 7 also shows a non-mutually exclusive feature associated with the tubing of the lead assembly. In particular, two different tubes are utilized. Here, there is a first tube that has portions 714 and 712, which tube is a silicone tube. This tube can be easily bent or deformed so as to establish the portions 714 and 712 without permanently kinking the tube or otherwise creating a detrimental effect to the flow of the therapeutic substance therein.

[0081] In an embodiment, the carrier member 146 of the electrode array is molded about the tube 718 by itself or with tube 718 connected to tube 714. In an embodiment, the carrier member 146 of the electrode array is molded about portion 518. Subsequently, the silicone body 516 of the lead assembly is molded about tube 714 (and/or portion of tube 718 depending on the length of tube 718) / about portion 714. That said, in an embodiment, the carrier member is established with the silicone body 516 and thus those portions are monolithic with each other.

[0082] In an embodiment there is an electrode array that includes tube 718 and/or portion 518. FIG. 7A shows the tubes, or more accurately, the lumens and the reservoir without the silicone of the lead body / silicone body (in some embodiments, the lumens are established by distinct tubes that are the coated with silicone of the silicone body / where the silicone body is moulded over the tubes, and in other embodmients, the lumens are made within the silicone body. Also, this shows an embodiment without plug 530 (embodiments can include a closure device and can not have a closure device). [0083] We now distinguish between the lead assembly and the lead portion of the implantable component. The lead assembly is the component that is attached to the housing and the receiver-stimulator during manufacturing, and can be identified after manufacturing, as would a bracket welded to a pressure vessel can be distinguished from the pressure vessel afterwards. Corollary to this is that the implantable component has a lead portion after manufacture of the implantable component or otherwise the completed implantable component that is obtained by doctors or surgeons or healthcare professionals for implantation (the surgeons do not attach the lead assembly to the receiver-stimulator; the components are delivered as one single apparatus in a completed form ready for implantation). The lead portion is the portion of the external component that extends from the feedthrough of housing 185 (the feedthrough to which the electrical leads are attached) to the most distal end of the electrode assembly 590, and this can take on portions of the silicone body that for example encases the electrical leads, and, in this embodiment, the cistern 510 and the portion of the tube 712 for example. In an exemplary embodiment, such as where the feedthrough is located on the left side of the housing 185 directly facing the lead assembly

589 (as opposed to being on the bottom or top or side of the housing), the lead portion of the implantable component would be the portion to the left of reference line 599. This would thus include a portion of the silicone body 183 that encases the housing 185 (which would also encase portions of the electrical leads for example) if the leads extended from the silicone body of the lead assembly prior to the establishment of the silicone body 183. And there are some embodiments where the feedthrough is located on the bottom or the top of the housing 185 or on the sides of the housing (side relative to the side facing the electrode array

590 in the arrangement of figure 5). Thus, the lead portion of the implantable component could extend to the right of the reference line 599 (as opposed to ending there) but in a potentially narrow channel (which may or may not be distinct) encompassing the wire leads of the lead assembly 589. Indeed, in an embodiment, there can be a channel in the bottom of the housing 185 that provides room for the electrical leads. The lead portion would be the electrical leads in that channel and the portion of the silicone body that fills at least a portion of the channel to secure the lead relative to the housing 185 between the feedthrough and the silicone body of the lead assembly 589. Thus, when looking on the side, there could have a dog leg sub portion that extends downward from the front of the housing 185 (from the left side of reference 599) and then underneath the housing 185. Note that in these embodiments, the lead portion would include everything to the left of reference 599. [0084] Embodiments thus include a reservoir assembly that is completely located, relative to the embodiment of figure 5, to the left of line 599, which line represents the leftmost portion of the housing 185. In an exemplary embodiment, with respect to the total interior volume of the reservoir, at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% of that volume or any value or range of values therebetween in 1% increments is located to the left of line 599, and thus to the left of the leftmost portion of the housing 185.

[0085] By leftmost portion of the housing 185, with reference to figure 5, this is the portion that extends in the direction of the longitudinal axis of the implantable portion (the horizontal of figure 5) opposite the antenna 181.

[0086] By rough analogy, the portions of the silicone body 185 at issue that are part of the lead portion can be considered akin to the mounting portion of an antenna. The base of the antenna that includes a fixture so that the antenna can be attached to say the fuselage of an aircraft for example, would still be considered to be an antenna portion for example.

[0087] And it is again noted that portions of the silicone body 183 can overlap with the silicone body of the lead assembly 589.

[0088] Thus, we see embodiments where the reservoir is completely integrated into a lead portion of the cochlear implant, the lead portion including the array of electrodes.

[0089] In an embodiment, the reservoir has a volume of less than, greater than and/or equal to (all-inclusive or non-inclusive) 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100, 110, 120, 130, 140 or 150 microliters, or any value or range of values therebetween in 0.01 microliter increments (e.g., 9.03, 22.22, 5.01 to 19.31 microliters, etc.) Thus, in an embodiment, the reservoir has a volume of no more than any one of those values (e.g., no more than 20 microliters, no more than 10 microliters, no more than 0.73 microliters, etc.). By “no more than,” that includes a volume that is less. The specification is that the volume does not exceed that amount. And the volume corresponds to the volume that can receive therapeutic substance.

[0090] In an embodiment, the cistern has an interior volume (fluid capacity) that is less than, greater than and/or equal to 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100, 110, 120, 130, 140 or 145 microliters or any value or range of values therebetween in 0.005 microliter increments. In an embodiment, the tube 714 (alone or including portion 712) has an interior volume (fluid capacity) of 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6. 3.7,

3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55 or 60 microliters or any value or range of values therebetween in 0.005 microliter increments. In an embodiment, the tube 718 has an interior volume (fluid capacity) of 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, .30, .35, .4, .5, .6, .7, .8, .9, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8. 8.5, 9, 9.5, 10, 11, 12, 13, 14, 15, 16, 17,1 8, 19 or 20 microliters, or any value or range of values therebetween in 0.001 microliter increments, or any of the values that can be calculated using the data herein. In an embodiment, the length of tube 718 is less than greater than and/or equal to 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 or 40 mm, or any value or range of values therebetween in 0.1 mm increments, or any of the values that can be calculated using the data herein. In an embodiment, the length of tube 714 (alone or including portion 712) is less than greater than and/or equal to 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180 190 or 200 mm, or any value or range of values therebetween in 0.1 mm increments. The outer diameter of the cistern can be less than, greater than and/or equal to 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7,

1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, or 7 mm, or any value or range of values therebetween in 0.05 mm increments. In an embodiment, the inner diameter of tube 718 is less than, greater than and/or equal to 0.01, 0.015, 0.2, 0.25, 0.3, 0.35, 0.4, 0.045, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, or 0.2 mm, or any value or range of values therebetween in 0.001 mm increments. In an embodiment, the inner diameter of tube 714 and/or portion 712 is less than, greater than and/or equal to 0.1, .15, 0.2, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, 0.3, 0.31, 0.32, 0.33, 0.34, 0.35, 0.36, 0.37, 0.38, 0.39, 0.4, 0.41, 0.42, 0.43, 0.44, 0.45 mm, or any value or range of values therebetween in 0.001 mm increments.

[0091] An embodiment is such that the apparatus includes an integrated septum configured to receive a termination of a syringe to enable a therapeutic substance to be delivered to the reservoir, which integrated septum provides a bacterial seal between the reservoir and an outside environment of the apparatus after the termination is removed. FIG. 9 shows an exemplary embodiment of such, which is a view with respect to section 9-9 of FIG. 5. Here, additional details of an exemplary cistern according to an exemplary embodiment are described. The cistern 510 includes a titanium housing wall 912 to which is attached support fixture 920 that is a titanium ring that is welded to the top of the cylindrical wall 912 of the cistern.

[0092] The support fixture holds a septum 930. The material of the septum is clamped in between portions of the titanium ring 920 or otherwise bonded to the interior side walls of the ring 920.

[0093] Embodiments can include the utilization of a self-healing septum. The septum 930 is configured to permit at least one puncturing (and in some embodiments repeated puncturing) and subsequent healing by a termination of a syringe. The termination can be inserted through the septum so that a therapeutic substance can be injected into the cistern, and thus “charge” or otherwise convey the substance into the reservoir. That said, in an embodiment, the septum can be a one time use / single use septum. And in this regard, in an exemplary embodiment, the reservoir or otherwise a therapeutic substance delivery system is a one time use system. In an embodiment, it is utilized for some chronic diseases or otherwise some chronic ailments.

[0094] And while embodiments above have focused on the utilization of a charging device or a fill device or otherwise filling the reservoir just before implantation, in another embodiment, the therapeutic substance can be located in the reservoir while the therapeutic substance is located in the packaging and otherwise sterilely sealed in the packaging.

[0095] Indeed, embodiments include selecting a specific type of therapeutic substance to be delivered by the implantable portion, and then charging the implantable portion within the affirmation time periods herein. Note further that embodiments can include packaging two or more different types of therapeutic substances instead of just one single therapeutic substance. In this exemplary embodiment, this can enable the healthcare professional to choose which therapeutic substance to utilize just prior to implantation. Further, a plurality of the same therapeutic substance can be provided at different strengths to allow the healthcare provider to choose the strength to be delivered. Corollary to this is that in some embodiments, the therapeutic substance can be such that the substance itself determines the diffusion rate. For example, the same therapeutic substance could be provided in a mixture that diffuses more slowly relative to that same therapeutic substance provided in another mixture. All of this can be chosen just prior to implantation.

[0096] Still, embodiments include shipping together the therapeutic substance and the implantable portion, whether in the same packaging or in separate packages but shipped together.

[0097] The septum seals the top of the cistern and otherwise establishes a barrier between the reservoir and the tissue above the mastoid bone / the internal portion of the human proximate the proximal portion of the lead portion of the implantable component. In an exemplary embodiment, septum 930 is configured to receive and otherwise permit a termination of a syringe, such as that of a hypodermic syringe, to pass therethrough in a manner analogous to or otherwise the same as liquid medical containers that include septums (self-healing septums) that enables the termination of the syringe to pass therethrough to access the liquid therapeutic substance in the container. In at least some exemplary embodiments, any device, system, and/or method that will enable repeated sealingly access from outside the external component (whether implanted in some embodiments or not implanted in others (and the two need not be mutually exclusive, but can be so) - as will be described below, the septum can be used prior to implantation to enable the reservoir to be charged) can be utilized in some embodiments.

[0098] In view of the above, in an exemplary embodiment, there is an apparatus, comprising an implantable therapeutic substance reservoir, a plurality of electrodes (e.g., electrodes 148), a silicone carrier body (e.g., carrier 146) supporting the plurality of electrodes. Further, the apparatus includes a stimulator assembly including a housing and stimulation electronics. In this embodiment, the apparatus can include a receiver-stimulator such as receiver-stimulator 580 noted above, or only a stimulator, or some other componentry in addition to a stimulator. The point is this apparatus requires only a stimulator. And as noted above, embodiments can be applicable to pacemakers or the like where for example, there may not be a receiver component thereof. In this regard, any disclosure related to a receiver-stimulator corresponds to a disclosure of an alternate embodiment of a stimulator and/or a receiver unless otherwise noted providing that the art enables such. Put another way, any reference to a receiverstimulator includes an alternate embodiment where there is only a receiver or only a stimulator, or a stimulator and some other components or additional components plural but no receiver. Corollary to this is that a receiver-stimulator or a receiver can include an assembly that has additional functionality beyond a receiver-stimulator, providing that there is functionality of the receiver-stimulator.

[0099] In this embodiment, the apparatus includes a fill port (e.g., the septum) in fluid communication with the reservoir configured to enable therapeutic substance delivery to the reservoir (e.g., such as by a termination of a syringe piercing the septum), and the fill port is between the housing and the plurality of electrodes. In an embodiment, the “between” is based on relative position relative to a longitudinal axis of the apparatus (in FIG. 5, the longitudinal axis is horizontal to the view thereof).

[ooioo] Embodiments include arrangements that provide a desired release rate of drug molecules from one or more openings of a drug solution filled, elongated lumen into body fluid of a target organ (such as the cochlea by way of example and not by way of limitation). Embodiments can achieve this by providing an apparatus with specific lumen dimensions, such as, for example, the overall lumen length and the cross-sectional area over its length. Embodiments include geometry controlled passive diffusion local drug release. Embodiments include an arrangement that provides a controlled release of drug molecules from an implanted cistern through a tube device into a distant location in the body of a patient (e.g., the scala tympani) by concentration-gradient driven passive diffusion of drug molecules through a solvent (such as water). Embodiments include no net movement of the solvent / effectively no net movement of the solvent / substantially no net movement of solvent. The desired (targeted / design) release rate of drug molecules from the device at the distant location such as the cochlea, can be adjusted (design adjusted, as opposed to real-time adjustment for example) by the drug molecular size, the concentration of the drug solution used to fill the device and/or the geometrical factors of the device including length and/or inner diameters of the tubes.

[ooioi] In an embodiment, of the total amount of solvent contained in the reservoir upon completion of charging and/or at the time that the outlet interfaces with the body fluid and/or at the completion of the implantation (e.g., after closure), no more than 30, 25, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1% of the solvent is transferred from the reservoir into the environment. In an embodiment, the just noted diffusion qualifiers occur after 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours after the outlet first comes into contact with the body fluid and/or after the completion of recharging. [00102] In one implementation, the lumen device (sometimes herein referred to as a delivery tube device) containing the drug solution can be made of a series of lumens of different length and/or cross-sectional areas as shown in FIG. 7. Here, there are 2 lumens, lumen 7144 and lumen 7188, which are established by tubes 714 and 718 respectively. Lumen 7144 is connected to “lumen” 5100, which is established by cistern 510. Briefly, the phrase length of a lumen/lumen length will be used herein, and this refers to the distance that the therapeutic substance molecules take when traveling from the cistern to the outlet. The length is an extrapolated length or otherwise a length that would exist if the lumens and the cistern, etc., were positioned in a linear fashion. By way of example, if the lumen was shaped in a U shape, the length would be the length that results if the U was flattened into a straight shape or otherwise the distance from the top of the U at the left side to the top of the U at the right side. The ramifications of this will be described below. Indeed, the lumens will very well likely not be straight. For example, there will be an arcuate shape with respect to extension from the portion on the outside of the mastoid bone between the skin to the middle ear cavity (through the portion of bone removed to access the middle ear in the case of a cochlear implant). The global geometry of the lumen can have any shape that can have utilitarian value. Also, it could be that the tube defining the lumen must be “bunched up” or coiled or snaked or helical, such as, for example, if the total global length of the device cannot exceed a certain number for anatomical reasons, the tube could be coiled. Moreover, even with a “straight” tube, the internal lumen could be helixed to be much longer than the tube to meet a desired diffusion rate / performance. For example, say that the length of the tube 714 is X mm. The lumen inside the tube could be equal to or greater than 1.5, 2, 2.5, 3, 3.5, 4, 4.5 or 5 times X or more to achieve a different desired diffusion rate / performance feature beyond that which would be the case if the lumen and the length of the tube had a traditional 1 to 1 relationship.

[00103] Figure 10 depicts an exemplary functional arrangement of the various lumens, and here, treats the cistern 510 (or more accurately, the volume established by cistern 510) as a short and wide lumen 5100 for purposes of analysis (by rough analogy, this can be like treating the structure between mounts of a jet engine on an aircraft as being incompressible / having a rigidity / strength very high (unrealistically so) in a finite element analysis of the flexure of the wing during flight). In reality, the cistern would be arranged so that the axial direction extends normal or relatively normal to the direction of extension of tube 714, as shown in the figures referenced above (the cylindrical shape corresponding to the interior volume of the cistern). Still, in this example, there is a cistern 510, which is relatively short but has a relatively large cross-sectional area and therefore internal volume. The volume and otherwise the lumen established by cistern 510 has a diameter ID 30 as shown in figure 10. Attached to the cistern 510 is a tube 714, often referred to as tube 1 or the first tube. Thus, lumen 7144 is attached to “lumen” 5100 as seen in FIG. 10. Lumen 7144 has a smaller inner diameter ID 10 relative to ID 30, more on this below.

[00104] Attached to tube 714 is a second tube 718, as noted above. This is often referred to as tube 2 or the second tube. Tube 714 has lumen 7188, which has an inner diameter ID 20, which can be the same or different than ID 10. Note that the tubes could overlap with respect to the longitudinal direction thereof. In this regard, as seen in figure 7, a portion of tube 718 is actually located inside tube 714 (the tube 714 can be interference fitted into tube 718 in an exemplary embodiment where the outer diameter of tube 714 is slightly larger than ID 10). But note that in alternative embodiments, tube 714 ends where tube 718 begins. So in this regard, the length of the lumen 7144 would be less than the full length of the lumen because a portion of that length (again where the length refers to the path of therapeutic substance travel) is taken up by lumen 7188.

[00105] In an exemplary embodiment, the end of tube 718 is in fluidic communication with the target, here perilymph of scala tympani in a human cochlea. In an exemplary embodiment, there can be a filter at the outlet of tube 718. More on this below. In an embodiment, there is no filter at the outlet, or anywhere for that matter.

[00106] In an embodiment, the outlet has a cross-sectional area lying on a plane normal to a longitudinal direction of extension of the lumen 7188 that is the same as the mean, median and/or mode of the cross-sectional area lying on planes normal to that longitudinal direction, and/or the same as the largest or smallest area, and in some embodiments, the cross-sectional area is constant along the length of lumen 7188 or does not change more than 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14 or 15% from the maximum along at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100% of the length. (Note that these values can be the case for the lumen 7144 as well, where the “outlet” would be the part into which the tube 714 is located in some embodiments.)

[00107] In an exemplary embodiment, the tube 718 can be changed out or otherwise a tube 718 can be selected for use with the apparatus. By way of example only and not by way limitation, the tube 718 can be attached to tube 714 shortly before implantation and/or during the surgical procedure implanting the apparatus. In an exemplary embodiment, tube 718 can be interference fitted into tube 714. In an exemplary embodiment, there is a method of selecting the tube 718 from a plurality of tubes available to the surgeon or otherwise the healthcare professional and attaching the tube 718 that is selected to tube 714 so that the performance features associated with that tube will be achieved, which performance features are disclosed herein. Accordingly, if a higher release rate is desired for example, a tube with a cross-section and/or a length that will achieve the desired release rate is selected and attached to tube 714 so that after implantation, the desirable results are achieved. In an exemplary embodiment, the tubes can be color-coded or otherwise placed in different containers so that the tubes can be differentiated from each other and/or otherwise so that the performance features of a given tube can be determined without having to measure the dimensions of the tube. In an embodiment, instead of tube 718 being located inside the carrier or otherwise the 2^nd lumen being located in the carrier, the tube 718 can be attached to an outlet on the carrier and then the tube 718 would co-extend with the electrode array by way of example. This would facilitate the “changing out” or otherwise the attachment of the desired tube 718 to tube 714.

[00108] In an exemplary embodiment, the lumen 7188 could be oversized or otherwise dimensioned to this largest dimension’s detailed herein, at least with respect to cross- sectional area, and an exemplary embodiment includes putting in a “filler material” into the lumen to reduce the cross-sectional area. By way of example only and not by way of limitation, a cylindrical body could be fit into the opening and extended down into the lumen 7188. The cylindrical body could have a cross-sectional area itself that is precisely controlled, which cross-sectional area reduces the effective cross-sectional area of the lumen 7188. This can be a way to have a standardized apparatus that can be modified for unique or otherwise specific performance features, which modification can be executed in the field or at least at a distribution site in at least some exemplary embodiments.

[00109] The entire lumen formed by the cistern lumen, the tube 1 lumen and the tube 2 lumen can be initially filled with a solution containing a drug (a solution containing an API - active pharmaceutical ingredient) at a certain concentration. When the tip of tube 2 is brought in contact with perilymph for example, a fluidic bridge between the API containing fluid contained in lumen 2 and perilymph is formed. This can allow API molecules to diffuse out of the apparatus and into perilymph following the concertation gradient from a high concentration inside the apparatus to a lower concentration outside the apparatus. In an exemplary embodiment, at the beginning of therapeutic substance delivery, the highest API release rate occurs. Over time the API release rate reduces unit the rate stabilizes at a moderate release rate due to an only relatively slowly changing concertation gradient inside the apparatus. From then, the concentration gradient inside the apparatus is only relatively slowly changing due to the sustained supply of API molecules from the cistern into tube 714.

[oono] The change of release rate over time (dn/dt) depends on the API molecules diffusion coefficient D, the cross-sectional area of the lumen(s) and the concentration gradient over length dc/dx. By adjusting the design combination of drug molecule and design of the apparatus, a desired drug release rate over time can be achieved in the resulting implantable apparatus.

[oom] In an embodiment, API movement from location x to location y over a distance z can be controlled (design controlled) by one or more of the following factors: concentration gradient between x and y (driving force); the distance between x and y, the cross-sectional area defined by the drug-impermeable boundaries between x and y, the solvent (diffusion medium) that fills the volume in between x and y (solvent can be water, hydrogel, or a polymer for example), the drug molecule; the size and polarity of the molecule defining its diffusion coefficient and/or adding a diffusion limiting component in the diffusion path between x and y.

[00112] Figs 11 to 15 show exemplary design data for exemplary apparatuses according to exemplary embodiments. Here, the Y axis is logarithmic and the X axis is linear. In an exemplary embodiment, the cross-section of the lumen of tube 1 and the cross-section of the lumen of tube 2 is circular although in other embodiments, other shapes can be utilized. The cross-section of the volume established by the cistern can be considered for convenience as a cross-section that is constant over a distance, here, 4 mm or 8 mm as various shown by way of example only and not by way of limitation. The lumens of tube 1 and tube 2 can be considered geometries that drive the performance, providing that the internal volume of the cistern is sufficiently large. The distance (X axis) is the above-noted linearized length of the reservoir, from the furthest part of the cistern from the outlet, to the outlet.

[00113] FIGs. 16-19 show exemplary design data for exemplary apparatuses according to exemplary embodiments, where the cross-sectional area of the lumen of tube 2 is different for different designs, where the cross-section of the lumen of tube 1 is held constant. Briefly, it is noted that the graphs provided are exemplary and embodiments include the data shown in the graphs (these and others) plus or minus the value represented by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25%, or any value or range of values therebetween in 0.1% increments (e.g., 4.1%, 19.5%, 7.7% to 23.3%, etc.), this provided in the interests of textual economy. FIG. 20 shows exemplary release rates from the apparatus to the human over a period of days for various cross-sections of the lumen of tube 2 for a constant length thereof and for a constant distance and cross-section of the lumen of tube 1 (e.g., one or more of those discussed above and/or below, such as, for example, a lumen length for tube 2 of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 mm or any value or range of values therebetween in 0.1 mm increments, a lumen length for tube 1 of 50, 60, 70, 80, 90, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129 or 130 mm, or any value or range of values therebetween in 0.1 mm increments, a lumen cross-sectional area for tube 1 of 0.15, 0.14, 0.13, 0.12, 0.11, 0.10, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, 0.03, 0.02, 0.01, 0.0009, 0.0008, 0.0007, 0.006, 0.0005, 0.0004, 0.0003, 0.0002, 0.0001 mm², or any value or range of values therebetween in 0.00001 mm² increments), where the values for the curves are keyed to values of cross-sectional area (mm²) of lumen 2. Shown in the graphs is an exemplary dexamethasone release rate over time from an apparatus with constant cistern dimensions, constant tube 1 dimensions and a tube 2 with constant length but varying inner diameter.

[00114] FIG. 21 shows concentration gradients along the path for some of the exemplary embodiments above. The unlabeled curves correspond to the areas in order of FIG. 20 in between those shown on the graph. This figure shows exemplary concentration gradients within the cistern (beginning first 4 mm), tube 1 and then tube 2 (the transition occurring at the dashed line) that has been established after seven (7) days of therapeutic substance delivery to the human for varying inner diameters of tube 2, where the y axis shows dexamethasone concentration of the fluid inside the lumens in mg/mL. In an embodiment, the cross-sectional area of the lumen of tube 2 is circular.

[00115] Embodiments can include a lumen for the second tube having any of the values below or any range of values therebetween as a cross-sectional area in mm² (lying on a plane normal to a longitudinal axis of the lumen / the direction of the lumen), and these can be for the full length of the second lumen or the average (mean, median and/or mode) over the full length and/or the value or the average for less than, greater than and/or equal to 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100%, or any value or range of values therebetween in 1% increments and can be any of the values therebetween or any range of values therebetween (the percentage differences):

0.000005 0.00003 0.00008 0.00159 0.00503 0.01039 0.01767 0.02688 0.03801 0.05107

0.00001 0.00004 0.00010 0.00166 0.00515 0.01057 0.01791 0.02717 0.03836 0.05147

0.00002 0.00006 0.00011 0.00173 0.00528 0.01075 0.01815 0.02746 0.03871 0.05187

0.00003 0.00007 0.00013 0.00181 0.00541 0.01094 0.01839 0.02776 0.03906 0.05228

0.00004 0.00009 0.00015 0.00189 0.00554 0.01112 0.01863 0.02806 0.03941 0.05269

0.00005 0.00010 0.00018 0.00196 0.00567 0.01131 0.01887 0.02835 0.03976 0.05309

0.00006 0.00012 0.00020 0.00204 0.00581 0.01150 0.01911 0.02865 0.04011 0.05350

0.00008 0.00014 0.00023 0.00212 0.00594 0.01169 0.01936 0.02895 0.04047 0.05391

0.00010 0.00017 0.00025 0.00221 0.00608 0.01188 0.01961 0.02926 0.04083 0.05433

0.00011 0.00019 0.00028 0.00229 0.00622 0.01208 0.01986 0.02956 0.04119 0.05474

0.00013 0.00021 0.00031 0.00238 0.00636 0.01227 0.02011 0.02986 0.04155 0.05515

0.00015 0.00024 0.00035 0.00246 0.00650 0.01247 0.02036 0.03017 0.04191 0.05557

0.00018 0.00027 0.00038 0.00255 0.00665 0.01267 0.02061 0.03048 0.04227 0.05599

0.00020 0.00030 0.00042 0.00264 0.00679 0.01287 0.02087 0.03079 0.04264 0.05641

0.00023 0.00033 0.00045 0.00273 0.00694 0.01307 0.02112 0.03110 0.04301 0.05683

0.00025 0.00036 0.00049 0.00283 0.00709 0.01327 0.02138 0.03142 0.04337 0.05726

0.00028 0.00040 0.00053 0.00292 0.00724 0.01348 0.02164 0.03173 0.04374 0.05768

0.00031 0.00043 0.00057 0.00302 0.00739 0.01368 0.02190 0.03205 0.04412 0.05811

0.00035 0.00047 0.00062 0.00312 0.00754 0.01389 0.02217 0.03237 0.04449 0.05853

0.00038 0.00051 0.00066 0.00322 0.00770 0.01410 0.02243 0.03269 0.04486 0.05896

0.00042 0.00055 0.00071 0.00332 0.00785 0.01431 0.02270 0.03301 0.04524 0.05940

0.00045 0.00059 0.00075 0.00342 0.00801 0.01453 0.02297 0.03333 0.04562 0.05983

0.00049 0.00064 0.00080 0.00353 0.00817 0.01474 0.02324 0.03365 0.04600 0.06026

0.00053 0.00068 0.00086 0.00363 0.00833 0.01496 0.02351 0.03398 0.04638 0.06070

0.00057 0.00073 0.00091 0.00374 0.00849 0.01517 0.02378 0.03431 0.04676 0.06114

0.00062 0.00078 0.00096 0.00385 0.00866 0.01539 0.02405 0.03464 0.04714 0.06158

0.00066 0.00083 0.00102 0.00396 0.00882 0.01561 0.02433 0.03497 0.04753 0.06202

0.00071 0.00088 0.00108 0.00407 0.00899 0.01584 0.02461 0.03530 0.04792 0.06246

0.00075 0.00093 0.00113 0.00419 0.00916 0.01606 0.02488 0.03563 0.04831 0.06290

0.00080 0.00099 0.00119 0.00430 0.00933 0.01629 0.02516 0.03597 0.04870 0.06335

0.00086 0.00105 0.00126 0.00442 0.00950 0.01651 0.02545 0.03631 0.04909 0.06379 0.07992 0.09842 0.11885 0.14120 0.16547 0.19167 0.21979 0.24983 0.28180

0.08042 0.09898 0.11946 0.14186 0.16619 0.19244 0.22062 0.25072 0.28274

0.08093 0.09954 0.12007 0.14253 0.16691 0.19322 0.22145 0.25161 0.28369

0.08143 0.10010 0.12069 0.14320 0.16764 0.19400 0.22229 0.25250 0.28463

0.08194 0.10066 0.12130 0.14387 0.16836 0.19478 0.22312 0.25339 0.28558

0.08245 0.10122 0.12192 0.14455 0.16909 0.19556 0.22396 0.25428 0.28653

[00116] Note that embodiments can have different cross-sectional areas than those above (larger or smaller). Embodiments also include variations of the length of the lumen of tube 2. FIGs. 22-24 show exemplary design data for exemplary apparatuses according to exemplary embodiments, where the length of the lumen of tube 2 is different for different designs, where the cross-sections of the lumen of tube 1 and the lumen of tube 2 is held constant, but the length of the lumen of tube 1 takes up the difference in the length of the overall lumen when the length of the lumen of tube 2 is shortened. Briefly, it is noted that the graphs provided are exemplary and embodiments include the data shown in the graphs (these and others) plus or minus the value represented by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25%, or any value or range of values therebetween in 0.1% increments, this provided in the interests of textual economy. FIG. 25 shows exemplary release rates from the apparatus to the human over a period of days for various lengths of the lumen of tube 2 for a constant cross-sectional area thereof and for a constant cross-section of the lumen of tube 1, but a length of the lumen of tube 1 that changes as noted above with different lengths of lumen 2 (e.g., one or more of those discussed herein), where the values for the curves are presented as keyed to lumen 2 length in mm.

[00117] FIG. 26 shows concentration gradients along the path for some of the exemplary embodiments above. The unlabeled curves correspond to the lengths in 5 mm increments between those shown on the graph.

[00118] Embodiments can include a lumen for the second tube having any of the values below or any range of values therebetween as a length in mm or can be larger or smaller by 5, 10,

15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100% or any value or range of values therebetween in 1% increments and can be any of the values therebetween or any range of values therebetween (the percentage differences).

1 4.5 8 11.5 15 18.5 22 25.5 29 32.5 36 40 44 48 52 56 60.1 4.6 8.1 11.6 15.1 18.6 22.1 25.6 29.1 32.6 36.1 40.1 44.1 48.1 52.1 56.1 60.1.2 4.7 8.2 11.7 15.2 18.7 22.2 25.7 29.2 32.7 36.2 40.2 44.2 48.2 52.2 56.2 60.2 .3 4.8 8.3 11.8 15.3 18.8 22.3 25.8 29.3 32.8 36.3 40.3 44.3 48.3 52.3 56.3 60.3.4 4.9 8.4 11.9 15.4 18.9 22.4 25.9 29.4 32.9 36.4 40.4 44.4 48.4 52.4 56.4 60.4.5 5 8.5 12 15.5 19 22.5 26 29.5 33 36.5 40.5 44.5 48.5 52.5 56.5 60.5.6 5.1 8.6 12.1 15.6 19.1 22.6 26.1 29.6 33.1 36.6 40.6 44.6 48.6 52.6 56.6 60.6.7 5.2 8.7 12.2 15.7 19.2 22.7 26.2 29.7 33.2 36.7 40.7 44.7 48.7 52.7 56.7 60.7.8 5.3 8.8 12.3 15.8 19.3 22.8 26.3 29.8 33.3 36.8 40.8 44.8 48.8 52.8 56.8 60.8.9 5.4 8.9 12.4 15.9 19.4 22.9 26.4 29.9 33.4 36.9 40.9 44.9 48.9 52.9 56.9 60.9

2 5.5 9 12.5 16 19.5 23 26.5 30 33.5 37 41 45 49 53 57 61.1 5.6 9.1 12.6 16.1 19.6 23.1 26.6 30.1 33.6 37.1 41.1 45.1 49.1 53.1 57.1 61.1.2 5.7 9.2 12.7 16.2 19.7 23.2 26.7 30.2 33.7 37.2 41.2 45.2 49.2 53.2 57.2 61.2.3 5.8 9.3 12.8 16.3 19.8 23.3 26.8 30.3 33.8 37.3 41.3 45.3 49.3 53.3 57.3 61.3.4 5.9 9.4 12.9 16.4 19.9 23.4 26.9 30.4 33.9 37.4 41.4 45.4 49.4 53.4 57.4 61.4.5 6 9.5 13 16.5 20 23.5 27 30.5 34 37.5 41.5 45.5 49.5 53.5 57.5 61.5.6 6.1 9.6 13.1 16.6 20.1 23.6 27.1 30.6 34.1 37.6 41.6 45.6 49.6 53.6 57.6 61.6.7 6.2 9.7 13.2 16.7 20.2 23.7 27.2 30.7 34.2 37.7 41.7 45.7 49.7 53.7 57.7 61.7.8 6.3 9.8 13.3 16.8 20.3 23.8 27.3 30.8 34.3 37.8 41.8 45.8 49.8 53.8 57.8 61.8.9 6.4 9.9 13.4 16.9 20.4 23.9 27.4 30.9 34.4 37.9 41.9 45.9 49.9 53.9 57.9 61.9

3 6.5 10 13.5 17 20.5 24 27.5 31 34.5 38 42 46 50 54 58 62.1 6.6 10.1 13.6 17.1 20.6 24.1 27.6 31.1 34.6 38.1 42.1 46.1 50.1 54.1 58.1 62.1.2 6.7 10.2 13.7 17.2 20.7 24.2 27.7 31.2 34.7 38.2 42.2 46.2 50.2 54.2 58.2 62.2.3 6.8 10.3 13.8 17.3 20.8 24.3 27.8 31.3 34.8 38.3 42.3 46.3 50.3 54.3 58.3 62.3.4 6.9 10.4 13.9 17.4 20.9 24.4 27.9 31.4 34.9 38.4 42.4 46.4 50.4 54.4 58.4 62.4.5 7 10.5 14 17.5 21 24.5 28 31.5 35 38.5 42.5 46.5 50.5 54.5 58.5 62.5.6 7.1 10.6 14.1 17.6 21.1 24.6 28.1 31.6 35.1 38.6 42.6 46.6 50.6 54.6 58.6 62.6.7 7.2 10.7 14.2 17.7 21.2 24.7 28.2 31.7 35.2 38.7 42.7 46.7 50.7 54.7 58.7 62.7.8 7.3 10.8 14.3 17.8 21.3 24.8 28.3 31.8 35.3 38.8 42.8 46.8 50.8 54.8 58.8 62.8.9 7.4 10.9 14.4 17.9 21.4 24.9 28.4 31.9 35.4 38.9 42.9 46.9 50.9 54.9 58.9 62.9

4 7.5 11 14.5 18 21.5 25 28.5 32 35.5 39 43 47 51 55 59 63.1 7.6 11.1 14.6 18.1 21.6 25.1 28.6 32.1 35.6 39.1 43.1 47.1 51.1 55.1 59.1 63.1.2 7.7 11.2 14.7 18.2 21.7 25.2 28.7 32.2 35.7 39.2 43.2 47.2 51.2 55.2 59.2 63.2.3 7.8 11.3 14.8 18.3 21.8 25.3 28.8 32.3 35.8 39.3 43.3 47.3 51.3 55.3 59.3 63.3.4 7.9 11.4 14.9 18.4 21.9 25.4 28.9 32.4 35.9 39.4 43.4 47.4 51.4 55.4 59.4 63.4

[00119] Note that embodiments can have lengths different than those above (larger or smaller). FIGs. 27-29 show exemplary design data for exemplary apparatuses according to exemplary embodiments, where the cross-sectional area of the lumen of tube 1 is different for different designs, where the cross-section of the lumen of tube 2 is held constant. Briefly, it is noted that the graphs provided are exemplary and embodiments include the data shown in the graphs (these and others) plus or minus the value represented by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25%, or any value or range of values therebetween in 0.1% increments (e.g., 4.1%, 19.5%, 7.7% to 23.3%, etc.), this provided in the interests of textual economy.

[00120] FIG. 31 shows exemplary release rates from the apparatus to the human over a period of days for various cross-sections of the lumen of tube 1 for a constant length thereof and for a constant distance and cross-section of the lumen of tube 2 (e.g., one or more of those discussed above, such as, for example, a lumen length for tube 2 of 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 mm or any value or range of values therebetween in 0.1 mm increments, a lumen length for tube 1 of 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, or 130 mm, or any value or range of values therebetween in 0.1 mm increments, a lumen cross- sectional area for tube 2 of 0.15, 0.14, 0.13, 0.12, 0.11, 0.10, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, 0.03, 0.02, 0.01, 0.0009, 0.0008, 0.0007, 0.006, 0.0005, 0.0004, 0.0003, 0.0002, 0.0001 mm², or any value or range of values therebetween in 0.00001 mm² increments), where the values for the curves are keyed to values of cross-sectional area (mm²) of lumen 1. Shown in the graphs is an exemplary dexamethasone release rate over time from an apparatus with constant cistern dimensions, constant tube 2 dimensions and a tube 1 with constant length but varying inner diameter.

[00121] FIG. 30 shows concentration gradients along the path for some of the exemplary embodiments above. The unlabeled curves correspond to diameters of a circular cross- sectional area of lumen in decrements of 0.1 mm. This figure shows exemplary concentration gradients within the cistern (beginning first 4 mm), tube 1 and then tube 2 (the transition occurring at the dashed line) that has been established after seven (7) days of therapeutic substance delivery to the human for varying inner diameters of tube 2, where the y axis shows dexamethasone concentration of the fluid inside the lumens in mg/mL. In an embodiment, the cross-sectional area of the lumen of tube 2 is circular and as noted, the lumen of tube 1 is circular.

[00122] Embodiments can include a lumen for the first tube having any of the values noted above for the lumen of the second tube (in the interests of textual economy - the values need not be the same, again, this is simply textual economy) or any range of values therebetween as a cross-sectional area in mm² (lying on a plane normal to a longitudinal axis of the lumen / the direction of the lumen), and these can be for the full length of the first lumen or the average (mean, median and/or mode) over the full length and/or the value or the average for less than, greater than and/or equal to 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100%, or any value or range of values therebetween in 1% increments and can be any of the values therebetween or any range of values therebetween (the percentage differences).

0.28748 0.32170 0.35785 0.39592 0.43592 0.47784 0.52168 0.56745 0.61514 0.66476

0.28843 0.32271 0.35891 0.39704 0.43709 0.47906 0.52296 0.56879 0.61653 0.66621

0.28938 0.32371 0.35997 0.39815 0.43826 0.48029 0.52424 0.57012 0.61793 0.66765

0.29033 0.32472 0.36103 0.39927 0.43943 0.48152 0.52553 0.57146 0.61932 0.66910

0.29129 0.32573 0.36210 0.40039 0.44061 0.48275 0.52681 0.57280 0.62072 0.67055

0.29225 0.32675 0.36317 0.40152 0.44179 0.48398 0.52810 0.57415 0.62211 0.67201

0.29321 0.32776 0.36424 0.40264 0.44297 0.48522 0.52939 0.57549 0.62351 0.67346

0.29417 0.32877 0.36531 0.40376 0.44415 0.48645 0.53068 0.57683 0.62491 0.67492

0.29513 0.32979 0.36638 0.40489 0.44533 0.48769 0.53197 0.57818 0.62631 0.67637

0.29609 0.33081 0.36745 0.40602 0.44651 0.48893 0.53327 0.57953 0.62772 0.67783

0.29706 0.33183 0.36853 0.40715 0.44770 0.49017 0.53456 0.58088 0.62912 0.67929

0.29802 0.33285 0.36961 0.40828 0.44888 0.49141 0.53586 0.58223 0.63053 0.68075

0.29899 0.33388 0.37068 0.40942 0.45007 0.49265 0.53716 0.58359 0.63194 0.68222

0.29996 0.33490 0.37176 0.41055 0.45126 0.49390 0.53846 0.58494 0.63335 0.68368

0.30093 0.33593 0.37284 0.41169 0.45245 0.49514 0.53976 0.58630 0.63476 0.68515

0.30191 0.33696 0.37393 0.41282 0.45365 0.49639 0.54106 0.58765 0.63617 0.68661

0.30288 0.33799 0.37501 0.41396 0.45484 0.49764 0.54237 0.58901 0.63759 0.68808

0.30386 0.33902 0.37610 0.41511 0.45604 0.49889 0.54367 0.59038 0.63900 0.68956

0.30484 0.34005 0.37719 0.41625 0.45723 0.50014 0.54498 0.59174 0.64042 0.69103

0.30582 0.34108 0.37828 0.41739 0.45843 0.50140 0.54629 0.59310 0.64184 0.69250

0.30680 0.34212 0.37937 0.41854 0.45963 0.50265 0.54760 0.59447 0.64326 0.69398

0.30778 0.34316 0.38046 0.41969 0.46084 0.50391 0.54891 0.59584 0.64468 0.69546

0.30876 0.34420 0.38155 0.42084 0.46204 0.50517 0.55023 0.59720 0.64611 0.69693

0.30975 0.34524 0.38265 0.42199 0.46325 0.50643 0.55154 0.59857 0.64753 0.69841

0.31074 0.34628 0.38375 0.42314 0.46445 0.50769 0.55286 0.59995 0.64896 0.69990

0.31172 0.34732 0.38485 0.42429 0.46566 0.50896 0.55418 0.60132 0.65039 0.70138

0.31271 0.34837 0.38595 0.42545 0.46687 0.51022 0.55550 0.60270 0.65182 0.70287

0.31371 0.34941 0.38705 0.42660 0.46808 0.51149 0.55682 0.60407 0.65325 0.70435

0.31470 0.35046 0.38815 0.42776 0.46930 0.51276 0.55814 0.60545 0.65468 0.70584

0.31570 0.35151 0.38926 0.42892 0.47051 0.51403 0.55947 0.60683 0.65612 0.70733

0.31669 0.35257 0.39036 0.43008 0.47173 0.51530 0.56079 0.60821 0.65755 0.70882 0.31769 0.35362 0.39147 0.43125 0.47295 0.51657 0.56212 0.60960 0.65899 0.71031

0.31869 0.35467 0.39258 0.43241 0.47417 0.51785 0.56345 0.61098 0.66043 0.71181

0.31969 0.35573 0.39369 0.43358 0.47539 0.51912 0.56478 0.61237 0.66187 0.71331

0.32069 0.35679 0.39480 0.43475 0.47661 0.52040 0.56612 0.61375 0.66332 0.71480

[00123] Note that embodiments can have different cross-sectional areas than those above

(larger or smaller). And note that in some embodiments, the values just listed above can be for the lumen of tube 1. Embodiments can have a wall thickness (the body forming the lumen, e.g., tube 1) of less than, greater than and/or equal to 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50% or more or any value or range of values therbetween in 0.1% increments of the diameter or the radius of the lumen.

[00124] Embodiments also include variations of the length of the lumen of tube 1. FIGs. 32- 34 show exemplary design data for exemplary apparatuses according to exemplary embodiments, where the length of the lumen of tube 1 is different for different designs, where the cross-sections of the lumen of tube 1 and the lumen of tube 2 is held constant, and the length of the lumen of tube 2 is constant. Briefly, it is noted that the graphs provided are exemplary and embodiments include the data shown in the graphs (these and others) plus or minus the value represented by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25%, or any value or range of values therebetween in 0.1% increments, this provided in the interests of textual economy. FIG. 35 shows exemplary release rates from the apparatus to the human over a period of days for various lengths of the lumen of tube 1 for a constant cross-sectional area thereof and for a constant cross-section of the lumen of tube 2, and the length of the lumen of tube 2 being constant.

[00125] FIG. 36 shows concentration gradients along the path for some of the exemplary embodiments above. The lengths correspond to the lengths of FIGs. 34-36.

[00126] Embodiments can include a lumen for the first tube having any of the values noted above for the lumen of the second tube (in the interests of textual economy - the values need not be the same, again, this is simply textual economy) or any of the below values or any range of values therebetween as a length in mm or can be larger or smaller by 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100%, or any value or range of values therebetween in 1% increments and can be any of the values therebetween or any range of values therebetween (the percentage differences).

64 68 72 76 80 84 88 92 96 100 104 108 112 116 120

64.1 68.1 72.1 76.1 80.1 84.1 88.1 92.1 96.1 100.1 104.1 108.1 112.1 116.1 120.1 .2 72.2 76.2 80.2 84.2 88.2 92.2 96.2 100.2 104.2 108.2 112.2 116.2 120.2.3 72.3 76.3 80.3 84.3 88.3 92.3 96.3 100.3 104.3 108.3 112.3 116.3 120.3.4 72.4 76.4 80.4 84.4 88.4 92.4 96.4 100.4 104.4 108.4 112.4 116.4 120.4.5 72.5 76.5 80.5 84.5 88.5 92.5 96.5 100.5 104.5 108.5 112.5 116.5 120.5.6 72.6 76.6 80.6 84.6 88.6 92.6 96.6 100.6 104.6 108.6 112.6 116.6 120.6.7 72.7 76.7 80.7 84.7 88.7 92.7 96.7 100.7 104.7 108.7 112.7 116.7 120.7.8 72.8 76.8 80.8 84.8 88.8 92.8 96.8 100.8 104.8 108.8 112.8 116.8 120.8.9 72.9 76.9 80.9 84.9 88.9 92.9 96.9 100.9 104.9 108.9 112.9 116.9 120.9 69 73 77 81 85 89 93 97 101 105 109 113 117 121.1 73.1 77.1 81.1 85.1 89.1 93.1 97.1 101.1 105.1 109.1 113.1 117.1 121.1.2 73.2 77.2 81.2 85.2 89.2 93.2 97.2 101.2 105.2 109.2 113.2 117.2 121.2.3 73.3 77.3 81.3 85.3 89.3 93.3 97.3 101.3 105.3 109.3 113.3 117.3 121.3.4 73.4 77.4 81.4 85.4 89.4 93.4 97.4 101.4 105.4 109.4 113.4 117.4 121.4.5 73.5 77.5 81.5 85.5 89.5 93.5 97.5 101.5 105.5 109.5 113.5 117.5 121.5.6 73.6 77.6 81.6 85.6 89.6 93.6 97.6 101.6 105.6 109.6 113.6 117.6 121.6.7 73.7 77.7 81.7 85.7 89.7 93.7 97.7 101.7 105.7 109.7 113.7 117.7 121.7.8 73.8 77.8 81.8 85.8 89.8 93.8 97.8 101.8 105.8 109.8 113.8 117.8 121.8.9 73.9 77.9 81.9 85.9 89.9 93.9 97.9 101.9 105.9 109.9 113.9 117.9 121.9 70 74 78 82 86 90 94 98 102 106 110 114 118 122.1 74.1 78.1 82.1 86.1 90.1 94.1 98.1 102.1 106.1 110.1 114.1 118.1 122.1.2 74.2 78.2 82.2 86.2 90.2 94.2 98.2 102.2 106.2 110.2 114.2 118.2 122.2.3 74.3 78.3 82.3 86.3 90.3 94.3 98.3 102.3 106.3 110.3 114.3 118.3 122.3.4 74.4 78.4 82.4 86.4 90.4 94.4 98.4 102.4 106.4 110.4 114.4 118.4 122.4.5 74.5 78.5 82.5 86.5 90.5 94.5 98.5 102.5 106.5 110.5 114.5 118.5 122.5.6 74.6 78.6 82.6 86.6 90.6 94.6 98.6 102.6 106.6 110.6 114.6 118.6 122.6.7 74.7 78.7 82.7 86.7 90.7 94.7 98.7 102.7 106.7 110.7 114.7 118.7 122.7.8 74.8 78.8 82.8 86.8 90.8 94.8 98.8 102.8 106.8 110.8 114.8 118.8 122.8.9 74.9 78.9 82.9 86.9 90.9 94.9 98.9 102.9 106.9 110.9 114.9 118.9 122.9 71 75 79 83 87 91 95 99 103 107 111 115 119 123.1 75.1 79.1 83.1 87.1 91.1 95.1 99.1 103.1 107.1 111.1 115.1 119.1 123.1.2 75.2 79.2 83.2 87.2 91.2 95.2 99.2 103.2 107.2 111.2 115.2 119.2 123.2.3 75.3 79.3 83.3 87.3 91.3 95.3 99.3 103.3 107.3 111.3 115.3 119.3 123.3.4 75.4 79.4 83.4 87.4 91.4 95.4 99.4 103.4 107.4 111.4 115.4 119.4 123.4 128 132 136 140 144 148 152 156 160 164 168 172 124.1 128.1 132.1 136.1 140.1 144.1 148.1 152.1 156.1 160.1 164.1 168.1 172.1

124.2 128.2 132.2 136.2 140.2 144.2 148.2 152.2 156.2 160.2 164.2 168.2 172.2

124.3 128.3 132.3 136.3 140.3 144.3 148.3 152.3 156.3 160.3 164.3 168.3 172.3

124.4 128.4 132.4 136.4 140.4 144.4 148.4 152.4 156.4 160.4 164.4 168.4 172.4

124.5 128.5 132.5 136.5 140.5 144.5 148.5 152.5 156.5 160.5 164.5 168.5 172.5

124.6 128.6 132.6 136.6 140.6 144.6 148.6 152.6 156.6 160.6 164.6 168.6 172.6

124.7 128.7 132.7 136.7 140.7 144.7 148.7 152.7 156.7 160.7 164.7 168.7 172.7

124.8 128.8 132.8 136.8 140.8 144.8 148.8 152.8 156.8 160.8 164.8 168.8 172.8

124.9 128.9 132.9 136.9 140.9 144.9 148.9 152.9 156.9 160.9 164.9 168.9 172.9

125 129 133 137 141 145 149 153 157 161 165 169 173

125.1 129.1 133.1 137.1 141.1 145.1 149.1 153.1 157.1 161.1 165.1 169.1 173.1

125.2 129.2 133.2 137.2 141.2 145.2 149.2 153.2 157.2 161.2 165.2 169.2 173.2

125.3 129.3 133.3 137.3 141.3 145.3 149.3 153.3 157.3 161.3 165.3 169.3 173.3

125.4 129.4 133.4 137.4 141.4 145.4 149.4 153.4 157.4 161.4 165.4 169.4 173.4

125.5 129.5 133.5 137.5 141.5 145.5 149.5 153.5 157.5 161.5 165.5 169.5 173.5

125.6 129.6 133.6 137.6 141.6 145.6 149.6 153.6 157.6 161.6 165.6 169.6 173.6

125.7 129.7 133.7 137.7 141.7 145.7 149.7 153.7 157.7 161.7 165.7 169.7 173.7

125.8 129.8 133.8 137.8 141.8 145.8 149.8 153.8 157.8 161.8 165.8 169.8 173.8

125.9 129.9 133.9 137.9 141.9 145.9 149.9 153.9 157.9 161.9 165.9 169.9 173.9

126 130 134 138 142 146 150 154 158 162 166 170 174

126.1 130.1 134.1 138.1 142.1 146.1 150.1 154.1 158.1 162.1 166.1 170.1 174.1

126.2 130.2 134.2 138.2 142.2 146.2 150.2 154.2 158.2 162.2 166.2 170.2 174.2

126.3 130.3 134.3 138.3 142.3 146.3 150.3 154.3 158.3 162.3 166.3 170.3 174.3

126.4 130.4 134.4 138.4 142.4 146.4 150.4 154.4 158.4 162.4 166.4 170.4 174.4

126.5 130.5 134.5 138.5 142.5 146.5 150.5 154.5 158.5 162.5 166.5 170.5 174.5

126.6 130.6 134.6 138.6 142.6 146.6 150.6 154.6 158.6 162.6 166.6 170.6 174.6

126.7 130.7 134.7 138.7 142.7 146.7 150.7 154.7 158.7 162.7 166.7 170.7 174.7

126.8 130.8 134.8 138.8 142.8 146.8 150.8 154.8 158.8 162.8 166.8 170.8 174.8

126.9 130.9 134.9 138.9 142.9 146.9 150.9 154.9 158.9 162.9 166.9 170.9 174.9

127 131 135 139 143 147 151 155 159 163 167 171 175

127.1 131.1 135.1 139.1 143.1 147.1 151.1 155.1 159.1 163.1 167.1 171.1 175.1

127.2 131.2 135.2 139.2 143.2 147.2 151.2 155.2 159.2 163.2 167.2 171.2 175.2

127.3 131.3 135.3 139.3 143.3 147.3 151.3 155.3 159.3 163.3 167.3 171.3 175.3

127.4 131.4 135.4 139.4 143.4 147.4 151.4 155.4 159.4 163.4 167.4 171.4 175.4

[00127] Note that embodiments can have lengths than those above (larger or smaller).

[00128] In view of the above, it can be seen that in an exemplary embodiment, there is an apparatus, such as the above-noted therapeutic substance delivery device, alone or in combination with the cochlear implant electrode array or some other medical device, such as any of those detailed herein, that includes a reservoir, and, in some embodiments, the therapeutic substance located in the volume. In this exemplary embodiment, the reservoir can correspond to, for example, the cistern plus one or more of the tubes detailed above. In an embodiment, the apparatus is configured to deliver the therapeutic substance to a recipient thereof by diffusion controlled release (controlled because the dimensions of the reservoir are precisely implemented to provide precise control (passive control)).

[00129] Embodiments do not elute the drug or therapeutic substance, or more accurately, that is not the principle of drug delivery (more on this in a moment), but instead can diffuse the substance, through a barrier or without a barrier (in some embodiments, the opening corresponds to the diameter of the lumen of the second tube). That is, in some embodiments, the outlet could be open. But with respect to outlet(s) that have barriers, the barrier has pores allowing direct fluidic connection between the liquid inside (drug solution) and the liquid outside (perilymph for example) the therapeutic substance delivery system. This allows free diffusion of the therapeutic substance molecules from inside the device to outside across the barrier following a concentration gradient. That is, the therapeutic substance molecules do not need to dissolve or absorb or adsorb into a third matrix (considering the therapeutic substance solvent inside the device as a first matrix and perilymph (or other bodily fluids) as the second matrix). The barrier, if present, can be utilized to prevent pathogens such as virus, bacterium, protozoan, prion, viroid, and/or fungus to exit and enter the device (e.g., a bacterial filter of 0.22 micrometer pore size or smaller is used in some embodiments). The barrier also provides, in some embodiments, a mechanical mechanism to increase the flow resistance between the lumen inside the apparatus and the outside environment (i.e., perilymph in the implanted state). This can enable containment of the therapeutic substance solution inside the device after initial priming (filling) during handling and implanting the implant. In the implanted state the barrier’s flow resistance helps to avoid significant amounts of liquid to exit or enter the delivery system in the event of pressure changes inside or outside the device from, for example, body movement or impact, or simply handling of the device during implantation.

[00130] In an embodiment, there could be some de minimus diffusion and/or elution of the therapeutic substance through the tubes and/or through the silicone body of the lead assembly (as opposed to leaving the apparatus through the outlet). In at least some exemplary embodiments, this is unwanted, but because of the limited amounts at play, does not present a problem. In an exemplary embodiment, of the therapeutic substance that is used to charge or fill the reservoir, no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5, 0.25, or .1%, or any value or range of values therebetween in 0.1% increments of the therapeutic substance diffuses and/or elutes through the tubes and/or the silicone bodies. It is noted that some of the aforementioned values may not be desired or tolerable, while in other embodiments they may be tolerable. In an exemplary embodiment, the rate of delivery is at least substantially based on diffusion through the outlet (whether or not there is a distinct barrier in the outlet). In an exemplary embodiment, of the therapeutic substance that leaves the reservoir and enters the body, at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100%, or any value or range of values therebetween in 0.1% increments of such is a result of diffusion, including diffusion through the distinct barrier, within any one or more of the timeframes detailed herein (or in total).

[00131] In an embodiment, the therapeutic substance is water-based, and the therapeutic substance diffuses out while the water remains in the delivery system and salts, etc., diffuses into the reservoir to address the concentration gradient. In an embodiment, net water movement into the device (osmosis) is avoided. In embodiments, a therapeutic solution that is isotonic to match the osmolarity of perilymph to avoid osmosis is utilized.

[00132] This is contrasted to, for example, the operation of a membrane across the opening, where the therapeutic substance or otherwise the active ingredient, actually comes out of the water, and then passes into the membrane, and then passes back into the water of the cochlea for example. Embodiments according to the teachings detailed herein are such that the therapeutic substance does not leave the water that is located in the reservoir at the time of charging with the therapeutic substance. The diffusion is a diffusion of the therapeutic substance, as opposed to the principle of operation of the membrane. In an embodiment, there is no semi-permeable membrane that is used in / bounding the reservoir. In an embodiment, there is a 100 micrometer thick membrane, which membrane does not impact the release rate, or reduces the rate by at most 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1% or any value or range of values therebetween in 0.1% increments from the rate that would be present in the absence of the membrane. Indeed, in an embodiment, the apparatus is completely free of hydrogel. In an embodiment, at least 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% of all therapeutic substance delivered to the human by the apparatus (by mass and/or by volume) is delivered to the human without the use of hydrogel.

[00133] Embodiments include sound pressure wave mitigation and/or prevention. In an embodiment, there is utilitarian value in avoiding a scenario where sound energy that travels through the skin and impinges upon the tubes and/or sound energy that creates movements or otherwise waves of fluid motion of the perilymph within the cochlea creates pressure waves within the reservoir of the therapeutic substance delivery apparatus. In an embodiment, there can thus be a pressure dampening device at the outlet or proximate the outlet or somewhere along the length of the tube device by way of example. That said, in an exemplary embodiment, a pressure gradient could be applied to the reservoir, which pressure gradient is sufficiently large to overwhelm the effects of any pressure resulting from soundwaves by way of example.

[00134] In some embodiments, there still is exchange of the same amount of water molecules in and out across the outlet, but to make up for the drug diffusing out (outflux) into perilymph, it can be assumed that it is not water molecules moving in but solutes from perilymph such as sodium and chloride diffusing in (influx) to keep the osmolarity the same. Accordingly, in an embodiment, the therapeutic substance solution is water-based, and the therapeutic substance stays dissolved in water, and diffuses out of the reservoir into perilymph (outflux) following a gradient of a higher therapeutic substance concentration in the water-based therapeutic substance solution to a lower therapeutic substance concentration in the water-based perilymph.

[00135] In an embodiment, a total water amount of the therapeutic substance delivery system at the time of implantation is within 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, or 0.5%, or any value or range of values therebetween in 0.05% increments of the value of water amount at the point when 80, 85, 90, or 95% of the therapeutic substance has diffused out of the system into the body.

[00136] In an embodiment, there is no pressure gradient that causes the therapeutic substance to diffuse or otherwise leave the reservoir, at least after the implantable component is implanted in a human. In an exemplary embodiment, the systems are configured to avoid an overpressure (or under pressure) by any one or more of the amounts detailed herein. As briefly noted above, in some embodiments, the pressure of the initial charging will cause the therapeutic substance to be out or otherwise leave the barriers, and this can be utilized to determine whether or not the reservoir is full or otherwise that the therapeutic substance has reached the tip of the electrode array, but after the charging process, the pressure inside the reservoir should be approximately room pressure or whatever is the local ambient pressure. That is, the reservoir is not a pressurized system. The principle of operation of therapeutic substance delivery occurs from the concentration gradient that exists inside the reservoir with respect to the therapeutic substance relative to the therapeutic substance outside the reservoir, specifically, the cochlea in the embodiment where the device is a cochlear implant electrode array. In this regard, initially, such as within minutes of insertion of the electrode array into the cochlea, the outlet will be in fluidic contact with the perilymph of the cochlea or other bodily fluid with respect to another body cavity. Thus, there will be a gradient between the outside the reservoir inside of the reservoir relative to the outlet. Over time, this gradient will fall to a 1 to 1 ratio or substantially a 1 to 1 ratio, owing to the “desire” of the system to balance the chemical state inside the reservoir to the outside of the reservoir. In an exemplary embodiment, within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, 500, 550, 600, 700, 800, 900, 1000, 1250, 1500, 1750, 2000, 2250, 2500, 3000, 3500, 4000, 4500, or 5000 hours after first entering the cochlea / the outlet coming into contact with the perilymph or pertinent body fluid, at least and/or no more than 50, 55, 60, 65, 70, 75, 80, 85, 90, 91, 92, 93, 94, or 95%, or any value or range of values in 1% increments of the therapeutic substance that was in the reservoir at the time that the outlet (whether with a barrier or not, and if more outlets, from when the first and/or last outlet) came into contact with the body fluid remains in the reservoir owing to diffusion through the distinct barrier into the cochlea or pertinent body cavity or body space. In an embodiment, any barrier that is present does not control the release rate. In an embodiment, any barrier that is present reduces the flow rate by at most 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1% or any value or range of values therebetween in 0.1% increments relative to that which would exist int eh absence of the barrier. In an embodiment, the barriers are invisible barriers.

[00137] Still, in some embodiments, there is no barrier at the end of tube 2, and in some embodiments the fluid is retained therein by capillary forces / actions.

[00138] In an embodiment, the filters can be considered a third tube, which third tube has the lowest cross-sectional area. Indeed, in an embodiment, the effective cross-sectional area of the barrier is at most 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1% or any value or range of values therebetween in 0.1% increments of the cross-sectional area of the second lumen.

[00139] Note also that in some embodiments, the barrier is a flow restrictor, as opposed to something that controls diffusion. Indeed, the filters have little to nothing to do with controlling delivery rate. [00140] In an exemplary embodiment, the therapeutic substance delivery system is a valveless system and/or a flow restrictor less system (save for the substantial barrier(s) to the extent they are considered flow restrictors).

[00141] In an exemplary embodiment, no portion of the lead assembly is saturated and/or no portion of the implantable portion is saturated with a therapeutic substance, with the possible exception of a barrier if present or at least a portion of the barrier in at least some exemplary embodiments.

[00142] In an embodiment, the silicone of the lead assembly and/or any of the tubes, or otherwise the material of the tubes, is not porous and/or is not aerated.

[00143] As seen above, in some embodiments, the reservoir and the lead assembly are part of a single unit. Also as seen, in an embodiment, the electrode array and the reservoir are part of a single unit.

[00144] Consistent with the teachings above, in an embodiment, the reservoir of the apparatus includes a first sub-reservoir and a second sub-reservoir, the second sub-reservoir being constricting relative to the first sub-reservoir and molecules of the therapeutic substance move from the first sub-reservoir to the second sub-reservoir during delivery of the therapeutic substance to the recipient. In an embodiment, the first sub-reservoir can be the cistern and the second sub-reservoir can be the first tube or the second tube. In an embodiment, the first sub- reservoir can be the first tube in the second sub-reservoir can be the second tube. However, in this embodiment, the cross-sectional area of the lumen of the second tube cannot be the same as or larger than the cross-sectional area of the lumen of the first tube, otherwise the second sub- reservoir would not be a constricting sub- reservoir. The phrase sub-reservoirs means that they are distinct from one another, either by for example dimension or by structural differentiation. This as opposed to a single tube that is arbitrarily divided into sections which would only be a single sub-reservoir. In an embodiment, the reservoir includes a third sub-reservoir, and the third sub-reservoir is constructing relative to the second sub-reservoir, and molecules of the therapeutic substance move from the first subreservoir to the second sub-reservoir to the third sub-reservoir during delivery of the therapeutic substance to the recipient. In an embodiment, there are 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more, or any value or range of values therebetween in 1 increments sub-reservoirs and at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more, or any value or range of values therebetween in 1 increments are constricting relative to an “upstream” sub-reservoir. [00145] In an embodiment, the reservoir is established by at least a cistern and a conduit device (e.g., tubes 714 and 718 collectively). In an embodiment, the conduit device includes a first conduit section having a first cross-sectional area normal to a direction of extension of the first conduit section (or normal to the direction of molecule movement during delivery to the recipient) that is larger than a second cross-sectional area of a second conduit section normal to a direction of extension of the second conduit section (or normal to the direction of molecule movement during delivery to the recipient). In an embodiment, the cross-sectional area of the second conduit section is such that a release rate of the therapeutic substance from the apparatus at and/or after Y days of release into the recipient (the “at” is the Y day mark (e.g., 7 days - it must meet the requirements at the 7 day mark), the “after” is the Y day and later (e.g., 7, 8, 9, 10, 11, 12 days, and so on - it must meet the requirement on a day at or after the Y day, whether that is the 7^th day or the 10^th day is covered)) is less than X% of that which would exist if the first cross-sectional area was the same as the second cross-sectional area, all other things being equal, where Y is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, or 100, or any value or range of values therebetween in 1 increment, and X is 70, 65, 60, 55, 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19.5, 19, 18.5, 18, 17.5, 17, 16.5, 16, 15.5, 15, 14.5, 14, 13.5, 13, 12.5, 12, 11.5, 11, 10.5, 10, 9.75, 9.5, 9.25, 9.0, 8.75, 8.5, 8.25, 8.0, 7.75, 7.5, 7.25, 7.0, 6.75, 6.5, 6.25, 6.0, 5.75, 5.5, 5.25, 5.0, 4.9, 4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, 3.0, 2.9, 2.8, 2.7, 2.6., 2.5, 2.4, 2.3, 2.2, 2.1, 2.0, 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1, 1.0, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or 0.1, or any value or range of values therebetween in 0.01 increments. In this regard, for example, if the length of the first and second conduit sections is constant (they can be different consistent with the teachings above), and the cross-sectional area of the first conduit section is constant, and the type of therapeutic substance in the reservoir is the same, and there is no pressure gradient or pressure change relative to that which is the case for the comparison, and there is no temperature change, etc., the above-noted release rates will be obtained for the different second cross-sectional area relative to that which would be the case if the second cross-sectional area is the same as the first cross-sectional area.

[00146] In an embodiment where the first conduit section has a first cross-sectional area normal to a direction of extension (molecule movement) that is at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, or 100, or any value or range of values therebetween in 1 increment times larger than a second cross-sectional area of a second conduit section, and the first conduit section has a first length that is larger than a second length of the second conduit section, the length of the second conduit section is such that a release rate of the therapeutic substance from the apparatus after Y days of release into a human is less than 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19.5, 19,

18.5, 18, 17.5, 17, 16.5, 16, 15.5, 15, 14.5, 14, 13.5, 13, 12.5, 12, 11.5, 11, 10.5, 10, 9.75, 9.5, 9.25, 9.0, 8.75, 8.5, 8.25, 8.0, 7.75, 7.5, 7.25, 7.0, 6.75, 6.5, 6.25, 6.0, 5.75, 5.5, 5.25, 5.0, 4.9, 4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, or 3.0, or any value or range of values therebetween in 0.01 increments of that which would be the case if the first length was 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30, or any value or range of values therebetween in 1 increment times the second length, all other things being equal.

[00147] In an embodiment, there is an apparatus that includes a cistern and a delivery tube device. Again, the apparatus is an implantable therapeutic substance delivery apparatus. In an embodiment, the delivery tube device is a diffusion delivery tube device. The apparatus is configured so that therapeutic substance located in the cistern travels to the delivery tube for delivery to a human implanted with the device.

[00148] In an embodiment, the cistern has an internal volume of at least an order of magnitude larger than that of the delivery tube.

[00149] In an embodiment, the delivery tube device has a first section having a first cross- sectional area normal to a direction of extension of the first section that is larger than a second cross-sectional area of a second section of the delivery tube device, the second cross- sectional area being normal to a direction of extension of the second section. In an embodiment, the first cross-sectional area is such that a release rate of the therapeutic substance from the apparatus after Y days of release into a human is at least 1.1, 1.2, 1.3, 1.4,

1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.5, 4, 4.5, or 5 times, or any value or range of values therebetween in 0.01 increments that which would be the case if the first cross-sectional area was the same as the second cross-sectional area and/or no more than 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.5, 4, 4.5, 5,

5.5, or 6 times, or any value or range of values therebetween in 0.01 increments that which would be the case if the first cross-sectional area was the same as the second cross-sectional area, all other things being equal. [00150] In an embodiment, the first cross-sectional area is such that a release rate of the therapeutic substance from the apparatus after Y days of release into a human is within 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30% or any value or range of values therebetween in 0.1% increments that which would be the case if the first cross-sectional area was the same as the second cross-sectional area, all other things being equal.

[00151] In an embodiment, the delivery tube device has a first section having a first length that is larger than a second length of a second section of the delivery tube device, and the first section has a first cross-sectional area normal to a direction of extension of the first section that is at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90 or 100 or any value or range of values therebetween in 1 increment times larger than a second cross-sectional area of the second section of the delivery tube device normal to a direction of extension of the second section. The length of the first section is at least four times larger than the length of the second section, and the length of the first section is such that a release rate of the therapeutic substance from the apparatus after seven days of release into a human is within 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1% or any value or range of values therebetween in 0.1% increments of that which would exist if the length of the first section was at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 or any value or range of values therebetween in 1 increment times larger than the length of the second section, all other things being equal.

[00152] In an embodiment, the delivery tube device has a first section having a first length that is larger than a second length of a second section of the delivery tube device. Again, as noted above with respect to some embodiments, the first section has a first cross-sectional area normal to a direction of extension of the first section that is larger than a second cross- sectional area of the second section of the delivery tube device normal to a direction of extension of the second section. Here, the second cross-sectional area is such that a release rate of the therapeutic substance at and/or after 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours of release into a human of the therapeutic substance from the apparatus is less than X% of that which would exist if the first cross-sectional area was the same as the second cross-sectional area. In an embodiment, the second cross-sectional area is such that a release rate of the therapeutic substance at and/or after 12 hours of release into the human of the therapeutic substance from the apparatus is within X% of that which would exist if the second cross-sectional area was at least one of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 times smaller or 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 times larger.

[00153] Embodiments include an apparatus, such as any of those described herein, or otherwise an implantable medical device, that comprises a first at least partially bounded volume (e.g., lumen of tube 1 or the cistern, etc.) and a second at least partially bounded volume (e.g., the lumen of the second tube). In an embodiment, there is at least one apparatus outlet at the second bounded volume (e.g., the outlet at the end of the second tube). Again, consistent with the teachings herein the apparatus is an implantable therapeutic substance delivery apparatus. In this embodiment, the apparatus delivers the therapeutic substance to a recipient thereof effectively entirely due to a concentration gradient. This as opposed to pressurized delivery, etc.

[00154] In an embodiment, the apparatus provides for passive diffusion local therapeutic substance release entirely controlled by geometry, such as the geometries detailed above. And note that this control is passive control. The geometry is designed and then set when the apparatus is manufactured or otherwise assembled (more on this below). This is not an active control for example where, for example, an outlet diameter is varied after the apparatus is implanted in the recipient after say a day or two or three or four of therapeutic substance delivery. In an embodiment, the control is “controlled” or maintained or otherwise unchanged for at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 500, 600, 700, 800, 900, 1000, 1250, 1500, 2000, 2500, 3000, 3500, 4000 or more days, or any value or range of values therebetween in 1 day increments. That is, in an exemplary embodiment, the control is unchanged or otherwise maintained for the life of the implant or otherwise for as long as the implant is providing therapeutic substance.

[00155] Consistent with the embodiment above where there are two tubes, an embodiment has a third at least partially bounded volume, wherein the third at least partially bounded volume is substance movement located between the first volume and the second volume. By “substance movement located,” it is meant along the direction of travel of molecules of the therapeutic substance during delivery, which can be over the course of days or weeks or months. For example, this is movement from the cistern to the outlet. This would be the opposite of movement of the salts or the other molecules that move into the reservoir to balance out the molecules that have moved out of the reservoir. [00156] Briefly, while embodiments often focus on a single outlet, instead of a single exit point, there can be multiple exit points. The exit points may have different cross-sectional areas to account for the changing concentration inside the device. For example, the cross- sectional area of the outlets can increase increase with increasing distance from the cistern to achieve an even or a quasi even drug release. This can be utilitarian as a concentration gradient across the exit can decreasing with increasing distance from the reservoir. FIGs. 40- 42 discussed below show exemplary embodiments of multiple outlet arrangements. In an embodiment, the outlets can be located radially as well. In an embodiment, the outlets are sized and dimensioned to take into account that the concentration gradient changes along the length of the tube 718 for example, and the outlets provide a release rate that is within 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14,

13, 12, 11, 10, 8, 8, 7, 6, 5, 4, 3, 2, or 1%, or any value or range of values there between in 0.1 % increments between 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 outlets or at least 50 or 60 or 70 or 80 or 90% of the outlets or all of the outlets that are axially spaced out from one another / provide for delivery at a given location that is the same for a comparable number of other locations (e.g., there could be two outlets at length 119 mm for example, and they could be different - the collective release rate can be used for that location and compared to the collective release rate at another location). Averaging can be used mean/median and/or mode for locations that are spaced apparat from each other in 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.5, or 5 mm, or any value or range of values therebetween in 0.01 mm increments, and the averages comparted to each other. The just noted flow rates can be for any of the temporal values herein, such as at and/or after 7 days of delivery.

[00157] In an embodiment, a volume of the first volume is at least Z times the volume of the third volume and the third volume is at least AA times the volume of the second volume (and the values of Z need not be the same), where Z can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,

14, 15, 16, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, or 400, or any value or range of values therebetween in 1 increments, and AA can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 500, 600, 700, 800, 900, 1000, 1250, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500, 6000, 7000, 8000, 9000, 10000, or any value or range of values therebetween in 1 increment. [00158] In an embodiment, a first cross-sectional area of the first volume lying on a plane normal to a direction of substance movement from the first volume to the second volume is at least AA and/or AA times 10 times a second cross-sectional area of the third volume lying on a plane normal to the direction of substance movement from the first volume to the second volume. Also, a third cross-sectional area of the second volume lying on a plane normal to the direction of substance movement from the first volume to the second volume is at least Z or Z times 10 times smaller than the second cross-sectional area.

[00159] In an embodiment, the second at least partially bounded volume is a lumen having a diameter, and a release rate at and/or after seven days or any of the temporal periods detailed herein of releasing therapeutic substance into a human such that the release rate increases by an amount between any value of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450 or 500 times or any value or range of values therebetween in 1 increment (e.g., between 8 and 15, between 5 and 67, between 22 and 122, etc.) with an increase in diameter of between any value of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, or 500 times, or any value or range of values therebetween in 1 increment, all other things being equal. In an embodiment, the release rate decreases by any of the ranges just noted with an increase in length of the second at least partially bounded volume of any of the just noted ranges.

[00160] Embodiments include methods. FIG. 38 shows an exemplary flowchart for an exemplary method, method 3800, which includes action 3810, which includes accessing an interior of a human, such as a cavity in a human. In an embodiment, this can be a cochlea as noted above, or the semicircular canals, etc. Note that this does not require an affirmative action of opening a passage into the cavity, or moving a device into the cavity, such as the end of tube 2. This can be met by, for example, by having the outlet present in the cavity (another actor could place the outlet in the cavity). If for example the outlet is in the cavity, and the therapeutic substance can move through the outlet, action 3810 is met. Method 3800 includes method action 3820, which includes the action of treating an ailment of a human by controllably delivering a therapeutic substance delivered from an implantable therapeutic substance delivery device, wherein the action of controllably delivering the therapeutic substance is executed passively. In an embodiment, the control is controlled according to the dimensions and/or the selection of the size of the therapeutic substance, etc. There is no metering or pressure variation or valving, etc., that is utilized to control the delivery of the therapeutic substance. In an embodiment, the control is based entirely on any one or more of the features detailed herein that enables the control.

[00161] In an exemplary embodiment, a fluidic bridge between the therapeutic substance and a body fluid of the human is present. In an exemplary embodiment, this is a result of method action 3810. Indeed, in an exemplary embodiment, there can be a method action of establishing the fluidic bridge. In an exemplary embodiment, this bridge allows molecules of the therapeutic substance to diffuse from the therapeutic substance delivery device into the body of the human. Consistent with the teachings above, the body fluid can be perilymph, but could be another type of body fluid, such as, for example, the fluid that is in the semicircular canals, etc.

[00162] In an exemplary embodiment, after an initial temporal period where the therapeutic substance release rate steadily reduces from a relatively higher rate, the therapeutic substance release rate quasi-stabilizes at a lower rate. In an embodiment, this can correspond to the performance associated with the release rates detailed above.

[00163] In an embodiment, there is a first period of release and a second period of release. The first period of release can be where there is a reduction of greater than and/or equal to 30, 31, 32, 33, 34, 35, 36, 37, 38, 38, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, or 96%, or any value or range of values therebetween in 0.1% increments from the initial release amount (max and/or the average (mean, median and/or mode)) over a specific time, such as 1, 2 or 3 hours from initial implantation, and there could be an initial gap from implantation (wait 1 hour for example). In an embodiment, the second period can be such that the release rate does not change by an amount more than 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1%, or any value or range of values therebetween in 0.1% increments. In an embodiment, the initial temporal period and/or the first period is less than and/or equal to 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 45, or 50 hours or any value or range of values therebetween in 0.1 hr increments. In an embodiment, the second temporal period and/or the quasi stabilized period is greater than and/or equal to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 45, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200 days or more, or any value or range of values therebetween in 1 hour increments. Note that the first temporal period can be contiguous with the second temporal period, or may not be contiguous. Note that the first temporal period need not be the same as the initial temporal period noted above, and the second temporal period need not be the same as the quasi-stabilized period.

[00164] In an embodiment, the quasi-stabilized release rate is due to a slowly changing concentration gradient of the substance within the device. In an embodiment, the slowly changing concentration gradient is due to a sustained supply of molecules of the therapeutic substance from a large volume area to a smaller volume area of the device. In an embodiment, the action of controllably delivering the therapeutic substance is governed by Fick’s Law.

[00165] In an embodiment, the quasi-stabilized release rate and/or the second temporal period is such that the change in concentration gradient is no more than and/or equal to 50, 45, 40, 35, 30, 25, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1%, or any value or range of values therebetween in 0.1% increments. In an embodiment, the first temporal period and/or the reduced period is such that the change in concentration gradient is greater than and/or equal to 70, 65, 60, 55, 50, 45, 40, 35, or 30%, or any value or range of values therebetween in 0.1% increments.

[00166] An embodiment includes a method represented by the flowchart of FIG. 39. Here, there is a method, method 3900, which includes method action 3910, which entails accessing an interior of a human. This has been detailed above. Method 3900 also includes method action 3920, which includes treating an ailment of a human by controllably delivering a therapeutic substance delivered from an implantable therapeutic substance delivery device, wherein the action of controllably delivering the therapeutic substance is executed effectively without a net movement of solvent in which the therapeutic substance is present from a therapeutic substance containing volume of the device to the ambient environment outside the device. As detailed above, in some embodiments, there is a filter or a plug at the outlet, while in other embodiments, there is no such filter plug at the outlet. Embodiments include practicing this method with or without the filter or plug at the outlet.

[00167] In an embodiment, there is only a single media.

[00168] In an embodiment, the second lumen is the limiting factor on performance. In an exemplary embodiment, changing a length and/or cross-sectional area by 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350 or 400% or any value or range of values therebetween in 1% increments, of the second lumen will change the performance (e.g., rate or concentration gradient) more than changing the comparable value by that amount for lumen 1 and/or by 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175 or 200% more than the amount that was changed (e.g., if the change was 20%, the change on lumen 1 would be 20% plus 20% or 100% or 150% of the 20%).

[00169] Note that in an embodiment, any of the values herein can be maximum values.

[00170] For example, even though no diffusion controlling element is needed in at least some embodiments, there can be utilitarian value to using a flow restrictor (sometimes herein referred to as a filter or plug - it need not be a flow restrictor) at the tip / end of tube 2. In an embodiment, this can have utilitarian value in reducing / avoiding the scenario of direct pressure translation from the reservoir (e.g., the cistern) into the cochlea during refill or in the event of impact. Also, risks can be mediated by a porous material between the reservoir and the tubing which provides flow resistance. This can be achieved by choosing the cross- sectional area, pore size, density and/or length. The pores can be small enough to also act as a bacterial filter (e.g., 0.22um or smaller in some embodiments. Thus, a filter can be located at the outlet of the cistern and/or in/at the end of tube 1 where it connects to the cistern (thus arguably making the cistern a closed volume - without the filter, the volume would be a partially closed / enclosed volume).

[00171] In an embodiment, the volume has a total distance extending from an outlet of the volume into the human to a location furthest therefrom, the volume is sized and dimensioned so that a concentration gradient of molecules of therapeutic substance at and/or after seven days of substance delivery is such that the concentration varies by no more than 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19.5, 19, 18.5, 18,

17.5, 17, 16.5, 16, 15.5, 15, 14.5, 14, 13.5, 13, 12.5, 12, 11.5, 11, 10.5, 10, 9.75, 9.5, 9.25, 9.0, 8.75, 8.5, 8.25, 8.0, 7.75, 7.5, 7.25, 7.0, 6.75, 6.5, 6.25, 6.0, 5.75, 5.5, 5.25, 5.0, 4.9, 4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, 3.0, 2.9, 2.8, 2.7, 2.6., 2.5, 2.4, 2.3, 2.2, 2.1, 2.0, 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1, or 1% or any value or range of values there between in 0.1% increments from a maximum for at least a first section of the total distance along the volume, the first section having a distance of at least 75, 70, 65, 60, 55, 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20,

19.5, 19, 18.5, 18, 17.5, 17, 16.5, 16, 15.5, 15, 14.5, 14, 13.5, 13, 12.5, 12, 11.5, 11, 10.5, 10, 9.75, 9.5, 9.25, 9.0, 8.75, 8.5, 8.25, 8.0, 7.75, 7.5, 7.25, 7.0, 6.75, 6.5, 6.25, 6.0, 5.75, 5.5, 5.25, 5.0%, or any value or range of values there between in 0.1% increments of the total distance. In an embodiment, the volume is sized and dimensioned so that a concentration gradient of molecules of therapeutic substance at and/or after seven days or any of the temporal periods herein of substance delivery is such that the concentration is effectively constant and/or substantially constant for the noted distance.

[00172] In an embodiment, the volume is sized and dimensioned so that the concentration gradient of molecules of therapeutic substance at and/or after seven days of substance delivery (or any of the temporal periods noted herein) is such that the concentration reduces by an amount of at least 75, 70, 65, 60, 55, 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30,

29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19.5, 19, 18.5, 18, 17.5, 17, 16.5, 16, 15.5, 15, 14.5, 14, 13.5, 13, 12.5, 12, 11.5, 11, 10.5, 10, 9.75, 9.5, 9.25, 9.0, 8.75, 8.5, 8.25, 8.0, 7.75, 7.5, 7.25, 7.0, 6.75, 6.5, 6.25, 6.0, 5.75, 5.5, 5.25, 5.0 %, or any value or range of values there between in 0.1% increments over a second section of the total distance along the volume, the second section having a distance of 75, 70, 65, 60, 55, 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31,

30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19.5, 19, 18.5, 18, 17.5, 17, 16.5, 16, 15.5, 15, 14.5, 14, 13.5, 13, 12.5, 12, 11.5, 11, 10.5, 10, 9.75, 9.5, 9.25, 9.0, 8.75, 8.5, 8.25, 8.0, 7.75, 7.5,

7.25, 7.0, 6.75, 6.5, 6.25, 6.0, 5.75, 5.5, 5.25, 5.0 %, or any value or range of values there between in 0.1% increments of the total distance, the second section being contiguous with the first section.

[00173] In an embodiment, a release rate over a 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 day period within 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 or 35 days of a beginning of delivering the therapeutic substance is less than 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19.5, 19, 18.5, 18, 17.5, 17, 16.5, 16, 15.5, 15, 14.5, 14, 13.5, 13, 12.5, 12, 11.5, 11, 10.5, 10, 9.75, 9.5, 9.25, 9.0, 8.75, 8.5,

8.25, 8.0, 7.75, 7.5, 7.25, 7.0, 6.75, 6.5, 6.25, 6.0, 5.75, 5.5, 5.25, 5.0, 4.9, 4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, 3.0, 2.9, 2.8, 2.7, 2.6., 2.5, 2.4, 2.3, 2.2, 2.1, 2.0, 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1, or 1%, or any value or range of values there between in 0.1% increments of a maximum release rate.

[00174] The graphs of FIGs. 20 and 21 are for a lumen of tube 2 of 15 mm and a length of the equivalent lumen of the cistern of 4 mm and the lumen of tube 1 taking up the difference of the total length (the total length can be 134 mm) and the cross-sectional area of the lumen of tube 1 is that of a circular cross-sectional area that is 0.3 mm over the entire length of the lumen of tube 1. The graphs of FIGs. 30 and 31 have lumens of the same lengths as just noted, where the cross-sectional areas of the lumen of tube 1 changes from that of a circular diameter of 0.5 mm to 0.1 mm in 0.1 mm decrements (the bottom curves are for the 0.1 mm diameter). The graphs of FIGs. 35 and 36 are for a lumen of tube 2 of 15 mm and a length of the equivalent lumen of the cistern of 4 mm and the lumen of tube 1 being 60, 80, 100, 114, or 131 mm or any value or range of values therebetween in 1 mm increment, with the cross- sectional area of the lumen of tube 1 being that of a circular cross-sectional area that is 0.3 mm over the entire length of the lumen of tube 1.

[00175] In an embodiment, the apparatus is configured so that a release rate at and/or after 7 days or any of the temporal periods detailed herein of releasing the therapeutic substance decreases by at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, or 500%, or any value or range of values therebetween in 1% increments for an increase of formula weight by at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, or 500, or any value or range of values therebetween in 1 increment times, all other things being equal.

[00176] FIG. 37 presents a graph of release at various times per molecule size, for an exemplary embodiment disclosed above. Below is a table of various release rates at and/or after 7 days of delivery and/or any of the temporal parts herein according to an exemplary embodiment for an embodiment herein. Embodiments can include an apparatus that delivers per these release rates having any of the values below or any range of values therebetween as a value of ng/hr and/or can be larger or smaller by 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100%, or any value or range of values therebetween in 1% increments and can be any of the values therebetween or any range of values therebetween (the percentage differences).

98 97.8 97.6 97.4 97.2 97 96.8 96.6 96.4 96.2 96

96 95.8 95.6 95.4 95.2 95 94.8 94.6 94.4 94.2 94

94 93.8 93.6 93.4 93.2 93 92.8 92.6 92.4 92.2 92

92 91.8 91.6 91.4 91.2 91 90.8 90.6 90.4 90.2 90

90 89.8 89.6 89.4 89.2 89 88.8 88.6 88.4 88.2 88

88 87.8 87.6 87.4 87.2 87 86.8 86.6 86.4 86.2 86

86 85.8 85.6 85.4 85.2 85 84.8 84.6 84.4 84.2 84

84 83.8 83.6 83.4 83.2 83 82.8 82.6 82.4 82.2 82

82 81.8 81.6 81.4 81.2 81 80.8 80.6 80.4 80.2 80

80 79.8 79.6 79.4 79.2 79 78.8 78.6 78.4 78.2 78

78 77.8 77.6 77.4 77.2 77 76.8 76.6 76.4 76.2 76 76 75.8 75.6 75.4 75.2 75 74.8 74.6 74.4 74.2 74

74 73.8 73.6 73.4 73.2 73 72.8 72.6 72.4 72.2 72

72 71.8 71.6 71.4 71.2 71 70.8 70.6 70.4 70.2 70

70 69.8 69.6 69.4 69.2 69 68.8 68.6 68.4 68.2 68

68 67.8 67.6 67.4 67.2 67 66.8 66.6 66.4 66.2 66

66 65.8 65.6 65.4 65.2 65 64.8 64.6 64.4 64.2 64

64 63.8 63.6 63.4 63.2 63 62.8 62.6 62.4 62.2 62

62 61.8 61.6 61.4 61.2 61 60.8 60.6 60.4 60.2 60

60 59.8 59.6 59.4 59.2 59 58.8 58.6 58.4 58.2 58

58 57.8 57.6 57.4 57.2 57 56.8 56.6 56.4 56.2 56

56 55.8 55.6 55.4 55.2 55 54.8 54.6 54.4 54.2 54

54 53.8 53.6 53.4 53.2 53 52.8 52.6 52.4 52.2 52

52 51.8 51.6 51.4 51.2 51 50.8 50.6 50.4 50.2 50

50 49.8 49.6 49.4 49.2 49 48.8 48.6 48.4 48.2 48

48 47.8 47.6 47.4 47.2 47 46.8 46.6 46.4 46.2 46 44.9 44.8 44.7 44.6 44.5 44.4 44.3 44.2 44.1 44 43.9 43.8 43.7 43.6 43.5 43.4 43.3 43.2

42.9 42.8 42.7 42.6 42.5 42.4 42.3 42.2 42.1 42 41.9 41.8 41.7 41.6 41.5 41.4 41.3 41.2 40.9 40.8 40.7 40.6 40.5 40.4 40.3 40.2 40.1 40 39.9 39.8 39.7 39.6 39.5 39.4 39.3 39.2 38.9 38.8 38.7 38.6 38.5 38.4 38.3 38.2 38.1 38 37.9 37.8 37.7 37.6 37.5 37.4 37.3 37.2 36.9 36.8 36.7 36.6 36.5 36.4 36.3 36.2 36.1 36 35.9 35.8 35.7 35.6 35.5 35.4 35.3 35.2 34.9 34.8 34.7 34.6 34.5 34.4 34.3 34.2 34.1 34 33.9 33.8 33.7 33.6 33.5 33.4 33.3 33.2 32.9 32.8 32.7 32.6 32.5 32.4 32.3 32.2 32.1 32 31.9 31.8 31.7 31.6 31.5 31.4 31.3 31.2 30.9 30.8 30.7 30.6 30.5 30.4 30.3 30.2 30.1 30 29.9 29.8 29.7 29.6 29.5 29.4 29.3 29.2 28.9 28.8 28.7 28.6 28.5 28.4 28.3 28.2 28.1 28 27.9 27.8 27.7 27.6 27.5 27.4 27.3 27.2 26.9 26.8 26.7 26.6 26.5 26.4 26.3 26.2 26.1 26 25.9 25.8 25.7 25.6 25.5 25.4 25.3 25.2 24.9 24.8 24.7 24.6 24.5 24.4 24.3 24.2 24.1 24 23.9 23.8 23.7 23.6 23.5 23.4 23.3 23.2 22.9 22.8 22.7 22.6 22.5 22.4 22.3 22.2 22.1 22 21.9 21.8 21.7 21.6 21.5 21.4 21.3 21.2 20.9 20.8 20.7 20.6 20.5 20.4 20.3 20.2 20.1 20 19.9 19.8 19.7 19.6 19.5 19.4 19.3 19.2 18.9 18.8 18.7 18.6 18.5 18.4 18.3 18.2 18.1 18 17.9 17.8 17.7 17.6 17.5 17.4 17.3 17.2 16.9 16.8 16.7 16.6 16.5 16.4 16.3 16.2 16.1 16 15.9 15.8 15.7 15.6 15.5 15.4 15.3 15.2 14.9 14.8 14.7 14.6 14.5 14.4 14.3 14.2 14.1 14 13.9 13.8 13.7 13.6 13.5 13.4 13.3 13.2 12.9 12.8 12.7 12.6 12.5 12.4 12.3 12.2 12.1 12 11.9 11.8 11.7 11.6 11.5 11.4 11.3 11.2 10.9 10.8 10.7 10.6 10.5 10.4 10.3 10.2 10.1 10 9.9 9.8 9.7 9.6 9.5 9.4 9.3 9.2 8.9 8.8 8.7 8.6 8.5 8.4 8.3 8.2 8.1 8 7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6 5.9 5.8 5.7 5.6 5.5 5.4 5.3 5.2 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1

3 2.99 2.98 2.97 2.96 2.95 2.94 2.93 2.92 2.91

2.9 2.89 2.88 2.87 2.86 2.85 2.84 2.83 2.82 2.81

2.8 2.79 2.78 2.77 2.76 2.75 2.74 2.73 2.72 2.71

2.7 2.69 2.68 2.67 2.66 2.65 2.64 2.63 2.62 2.61

2.6 2.59 2.58 2.57 2.56 2.55 2.54 2.53 2.52 2.51

2.5 2.49 2.48 2.47 2.46 2.45 2.44 2.43 2.42 2.41

2.4 2.39 2.38 2.37 2.36 2.35 2.34 2.33 2.32 2.31

2.3 2.29 2.28 2.27 2.26 2.25 2.24 2.23 2.22 2.21

2.2 2.19 2.18 2.17 2.16 2.15 2.14 2.13 2.12 2.11

2.1 2.09 2.08 2.07 2.06 2.05 2.04 2.03 2.02 2.01

2 1.99 1.98 1.97 1.96 1.95 1.94 1.93 1.92 1.91

1.9 1.89 1.88 1.87 1.86 1.85 1.84 1.83 1.82 1.81

1.8 1.79 1.78 1.77 1.76 1.75 1.74 1.73 1.72 1.71

1.7 1.69 1.68 1.67 1.66 1.65 1.64 1.63 1.62 1.61

1.6 1.59 1.58 1.57 1.56 1.55 1.54 1.53 1.52 1.51

1.5 1.49 1.48 1.47 1.46 1.45 1.44 1.43 1.42 1.41

1.4 1.39 1.38 1.37 1.36 1.35 1.34 1.33 1.32 1.31

1.3 1.29 1.28 1.27 1.26 1.25 1.24 1.23 1.22 1.21

1.2 1.19 1.18 1.17 1.16 1.15 1.14 1.13 1.12 1.11

1.1 1.09 1.08 1.07 1.06 1.05 1.04 1.03 1.02 1.01

1 0.99 0.98 0.97 0.96 0.95 0.94 0.93 0.92 0.91

0.9 0.89 0.88 0.87 0.86 0.85 0.84 0.83 0.82 0.81

0.8 0.79 0.78 0.77 0.76 0.75 0.74 0.73 0.72 0.71

0.7 0.69 0.68 0.67 0.66 0.65 0.64 0.63 0.62 0.61

0.6 0.59 0.58 0.57 0.56 0.55 0.54 0.53 0.52 0.51

0.5 0.49 0.48 0.47 0.46 0.45 0.44 0.43 0.42 0.41

0.4 0.39 0.38 0.37 0.36 0.35 0.34 0.33 0.32 0.31

0.3 0.29 0.28 0.27 0.26 0.25 0.24 0.23 0.22 0.21

[00177] Note that embodiments can have values different than those above (larger or smaller).

[00178] In an embodiment BDNF MW (molecular weight in grams / mol) is 28,109. Some values herein assume a 10,000 ug/mL application concentration. In an embodiment, 24% of Dex release rate can be achieved (on a weight basis, 4% on a molar basis). In an embodiment, dexamethasone disodium phospahe (as can be used in a lOmg/mL injection solution) has a MW of 516g/mol. Accordingly, it is much smaller which would result in reduced diffusivity of BDNF compared to Dex which in turn can result in a smaller / lower release rate. When comparing the released BDNF mass over time, it can be 24% of the mass of dex released in the same time, or when considering the number of BDNF molecules released, it can be 4% of the number of dex molecules release over the same time. This is when keeping the dimension, temperature, solvent and diffusion time constant.

[00179] In an embodiment, release rate vs FW can be linear, decreasing from 30 ng/hr to 3 ng/hr from between 100 to 500 Da or any value or range of values therebetween in 0.1 Da increments (e.g., a 200 Da molecule could have a release rate of 20 ng) to 10000 to 500000 Da or any value or range of values therebetween in 0.1 Da increments.

[00180] Embodiments can include lumens and cisterns that can establish a concentration gradient along the direction of movement as noted in the FIGs. above. By way of example, concentration gradients can change from a unitized value and/or a real value shown below along the length thereof tracking the curves presented above, and can be different from any value shown below and/or can be any value different from those below or in between and including those values by 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100%, or any value or range of values therebetween in 1% increments and can be any of the values therebetween or any range of values therebetween (the percentage differences).

10000 7000 4000 1000

9900 6900 3900 950

9800 6800 3800 900

9700 6700 3700 850

9600 6600 3600 800

9500 6500 3500 750

9400 6400 3400 700

9300 6300 3300 650

9200 6200 3200 600

9100 6100 3100 550

9000 6000 3000 500

8900 5900 2900 450

8800 5800 2800 400 8700 5700 2700 350

8600 5600 2600 300

8500 5500 2500 250

8400 5400 2400 200

8300 5300 2300 150

8200 5200 2200 100

8100 5100 2100 50

8000 5000 2000 0

7900 4900 1900

7800 4800 1800

7700 4700 1700

7600 4600 1600

7500 4500 1500

7400 4400 1400

7300 4300 1300

7200 4200 1200

7100 4100 1100

[00181] Note that the graphs presented herein have a precision that will end at some point, consistent with any printed graph. In this regard, embodiments include designs that have values / performance features that correspond to “about” those presented in the graphs. That is, by way of example only, with reference to FIG. 20, which shows release rates per time, the curve for the area of 0.00785 mm² represents a disclosure of a release rate at 7 days of about 11 ng/hr.

[00182] Corollary to this is that values have been given for design features and performance features as noted above. These values can correspond to values along the graphs for purposes of precision. By way of example, we disclose above 11.5 ng/hr release rate. This can correspond to a value on the curve for the 0.00785 mm² of FIG. 20 if precision is desired.

[00183] FIG. 39A shows a performance chart for passive diffusion based local drug delivery for a small molecule, such as dexamethasone, in an exemplary embodiment having any one or more of the features disclosed herein. Note that embodiments include using the teachings herein for large molecule (e.g., brain derived neurotrophic factor - BDNF) drugs which can be dissolved in aqueous or other solvents. The graph of FIG. 39A shows exemplary performance data for dexamethasone phosphate release rate into physiological saline at 37 deg Celsius over time using a device having one or more of the features detailed above. [00184] The graphs presented herein are for some exemplary embodiments and other embodiments can have other values from those presented in the graphs. In this regard, embodiments include values that are less than greater than and/or equal to 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% of the values presented on the graphs or any value or range of values therebetween in 1% increments. Also, embodiments include values that are less than greater than and/or equal to 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 700, 800, 900, 1000, 1250, 1500, 1750, 2000 % of the values presented on the graphs or any value or range of values therebetween in 1% increments.

[00185] Note that the values above are presented for Dex pharmaceutical (e.g., dexamethasone phosphate) unless otherwise noted, and in the concentrations noted above.

[00186] In an embodiment, the teachings herein are used with any one or more of the teachings of U.S. patent application serial number 63/399613, filed on August 19, 2022, entitled Substance Delivery Inside Mammals, naming Daniel Smyth as an inventor. In an embodiment, any one or more of the design features and/or performance features detailed therein are used in any one or more apparatuses detailed herein providing that the art enables such. In an embodiment, any one or more of the method actions and/or method results and/or method prerequisites / qualifiers detailed therein are used in any one or more methods detailed herein providing that the art enables such. Indeed, an embodiment includes taking the entire implantable apparatus disclosed therein and providing a lumen having one or more of the features thereof disclosed herein. In an embodiment, any one or more of the packaging and/or charging arrangements disclosed therein are used with the device disclosed herein.

[00187] In an exemplary embodiment, at least 60, 65, 70, 75, 80, 85, 90, 91, 92, 93, 94, or 95% or, any value or range of values therebetween in 1% increments of the total internal volume of the reservoir (the volume that receives the therapeutic substance) is located no more than 1.5, 1.4, 1.3, 1.2, 1.1, 1, 0.9, 0.8, 0.7, 0.6, or 0.5 cm from reference line 599 or otherwise from the leftmost portion of the housing 185 and/or the interior volume of the reservoir according to any one or more of the percentages detailed above is located to the left of reference 599. [00188] Concomitant with the teachings of the septum above, the fill port includes a resealable septum configured to receive a termination of a syringe, wherein the septum is configured provide a barrier to bacteria upon removal of the syringe from the septum after delivery of the therapeutic substance to the reservoir.

[00189] And note that in an exemplary embodiment, the therapeutic substance might “squirt” out the opening of the tube 718 when the reservoir is full. In an exemplary embodiment, the pressure buildup during the charging and filling could be such that once full, continued attempted transfer of the therapeutic substance in the reservoir will cause a pressure buildup so that the fluid at least beads out of the outlet. This can give an indication to the healthcare professional that the reservoir is full. Further, this can provide a safeguard mechanism to avoid “bursting” or otherwise damaging the reservoir.

[00190] And, in some embodiments where there is a plug in the outlet, the plug 530 can be configured to be sufficiently porous that the increased pressure will result in therapeutic substance “leaking” out of the plug. Indeed, in an exemplary embodiment, this can be how the healthcare provider determines that the reservoir is full. In an exemplary embodiment of this embodiment, there might have to be some care taken to avoid increasing the pressure to the point where the leakage cannot keep up with the increase in pressure.

[00191] Thus, in an embodiment, there is an assembly that includes an implantable portion and includes a reservoir fill assembly in fluid communication with the reservoir via the fill port, wherein the reservoir fill assembly is configured to be at least substantially filled with a therapeutic substance to fill the reservoir, and the reservoir fill assembly is removable from the fill port so that the apparatus can be implanted without the reservoir fill assembly. In an embodiment, upon the removal of the reservoir fill assembly from the fill port, the implantable portion is ready to be implanted in the recipient at least with respect to actions related to closing the fill port, because in this embodiment, the fill port is self-sealing and/or self-closing. That said, in an alternate embodiment, the fill port could be “filled” with another substance, such as a quick curing silicone or an adhesive, or otherwise such substance could be injected or otherwise placed into the passageway, to further enhance the sealing fixtures. In an embodiment, the another substance used to fill the port does not permit the substance to diffuse, unlike the diffusion port material for the outlet. To the extend that there is diffusion, it is far lower than the diffusion of the diffusion port material for the outlet. [00192] In an embodiment, compression can be applied after the termination is removed or otherwise a component can be located in the silicone body, such as a spring or the like, that will permit the termination to open the passageway when the termination is pressed towards the tube, but then once the termination is removed, the component will compress the silicone to close the passageway. That said, the spring or the like need not necessarily be present. Instead, a C-shaped body that is relatively rigid or solid could be located on either side of the passageway, where the simple fact that the silicone fills the interior of the seal is sufficient to result in the self-healing or otherwise closure the passageway when the termination is removed. That is, the termination will compress the silicone against the sides of the C- shaped body (the interior of the C-shaped body), thus opening up the passageway, and then when removed, the silicone will expand back to its original status, and thus close the passageway.

[00193] In an exemplary embodiment, the action of charging the reservoir as detailed herein occurs within 24, 18, 12, 6, 5, 4, 3, 2, or 1 hour, or any value or range of value therebetween in one minute increments prior to placing at least a portion of the implantable portion inside the body of a recipient through an artificially created opening in the skin of the recipient. In an embodiment, the action of charging the reservoir as detailed herein occurs within 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 minutes or any value or range of value therebetween in 1 second increments prior to placing at least a portion of the implantable portion inside the body of a recipient through an artificially created opening in the skin of the recipient. In an exemplary embodiment, the portion that can be placed into the recipient could be the receiver-stimulator when it is placed over the mastoid bone through the incision of the skin of the head over the mastoid bone.

[00194] Embodiments include the action of implanting the implantable portion in a human after providing the therapeutic substance. In an embodiment, no more therapeutic substance is provided to the therapeutic substance delivery system after the action of providing therapeutic substance. In this exemplary embodiment, this can correspond to a one time charging, where, after implantation, no more additional therapeutic substance is provided to the reservoir otherwise the implantable portion. That said, as noted above, embodiments can include, after implantation, utilizing a termination of a syringe to pierce the skin over the septum of the implantable cistern to recharge the therapeutic substance or to provide a different therapeutic substance after a certain amount of time. [00195] Corollary to this is that embodiments include, prior to charging or otherwise filling the reservoir, selecting a particular type of therapeutic substance to be delivered by the implantable portion or otherwise to be placed into the reservoir. Embodiments thus can enable a wide variety of therapeutic substances to be selected at the time of surgery or within any of the after mentioned times associated with the first portion of the implant being located in the human. For example, therapeutic substance A could be selected for some patients and therapeutic substance B could be selected for other patients, all which could be selected at or during the surgical procedure. In an embodiment, the therapeutic substance is dexamethasone. But it is noted that other types of therapeutic substance can be used / contained in the reservoir, for example, systemic steroids, anticoagulants, clot busters, antifibrotics, antiproliferatives or NSAIDs. Therapeutic substances include drugs, but also include nondrug substances. In an exemplary embodiment, therapeutic substances include steroids (as just noted and/or biologies). Therapeutic substances can also include minerals and the like. Any disclosure herein of drug or the containment of drug or the delivery of drug also corresponds to another embodiment that corresponds to an embodiment that is directed towards a therapeutic substance. That is, typically, the word drug used herein is shorthand for therapeutic substance. Accordingly, embodiments include the present disclosure where the word drug is replaced by the word therapeutic substance, unless otherwise specified.

[00196] The therapeutic substance may be a corticosteroid such as betamethasone, clobetasol, diflorasone, fluocinolone, triamcinolone, salt, ester, or combination thereof.

[00197] In an embodiment, there is an apparatus, such as the implantable portion of the cochlear implant, or the lead assembly thereof, which includes an implantable electrode array including a plurality of electrodes supported by a silicone body. In this exemplary embodiment, the electrode array includes a therapeutic substance delivery channel (e.g., tube portion 518 or tube 718) including at least one port (e.g., the distal end portion of portion 581 or tube 718). In an exemplary embodiment, the port includes a distinct barrier made of a material that maintains a bacterial barrier prior to charging the channel with a water-based substance. In an exemplary embodiment, the barrier is plug 530.

[00198] Figure 40 presents an alternate exemplary embodiment of the distinct barrier with respect to electrode array 1890. Here, element 1830 is a cap that fits over the distal end of the tube 718 (instead of in the tube as with the plug). In this exemplary embodiment, tube 718 extends outward a tiny amount so that the cap can fit over the tube. In the embodiment shown in figure 18A, the cap 1830 is a forward surface of the array. In some embodiments, the cap protrudes somewhat from the silicone body that is the silicone carrier 146 that envelops tube 718. Conversely, figure 41 shows an exemplary electrode array 1990 where the material of the carrier 146 extends past the cap 1830. This can have utilitarian value with respect to protecting the cap otherwise providing that the most forward surface is the relatively flexible and soft silicone of the body that establishes the carrier 146. Any arrangement that can enable the teachings detailed herein can be utilized in at least some exemplary embodiments.

[00199] In an embodiment, the distinct barrier has pores. For example, the pores of the distinct barrier are no greater than 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.09, 0.08, 0.07, 0.06, 0.05 microns, or any value or range of values therebetween in 0.005 micron increments (but note that some of these might not establish a bacterial barrier - some embodiments do not establish a bacterial barrier).

[00200] The barrier can be PVDF. Note that micropores or millipores can be used depending on the embodiment.

[00201] By distinct barrier, it is meant that the barrier is a different component in material and /or dimension and/or arrangement from the other components immediately adjacent the barrier. For example, the barrier is a different component in material and dimensioned from the silicone that establishes the carrier. The barrier is also different in material and dimension from the tube 718. In an embodiment, a rolled silicone filter could be used, or a porous silicone could be used.

[00202] In an exemplary embodiment, the distinct barrier is entirely made of polyvinylidene fluoride and can be made of Durapore®.

[00203] In an embodiment, the distinct barrier is configured to diffuse dexamethasone at a rate of no more than 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9.5, 9, 8.5, 8, 7.5, 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.75, 1.5, 1.25, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, or 0.2 nanograms / hour (mean, median, and/or mode and/or maximum rate over any one or more of the time periods detailed herein) or any value or range of values therebetween in 0.05 nanogram /hour increments after implantation into a body, such as a body cavity, such as a human cochlea, at a pressure of 1 atmosphere plus or minus 0.1 atmosphere and/or at a pressure in the reservoir that results from implantation in the human after the surgery is completed, where the reservoir was charged at 1 atmosphere. (This does not mean that the charging must be done at 1 atmosphere. This means that when done at 1 atmosphere, this is what happens.) In an embodiment, the therapeutic substance diffuses through the barrier and is replaced with NaCL. As the concentration of the therapeutic substance decreases over time, so will the release rate.

[00204] In an embodiment, the distinct barrier is also configured so that an over-pressure in the channel relative to an outside environment will cause dexamethasone to be driven out the plug while maintaining the plug for subsequent use as a diffusion distinct barrier. In an exemplary embodiment, the over-pressure can be 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350 or 400% or more or any value or range of values there between in 1% increments where the denominator is the pressure prior to the overpressure. This can have utilitarian value with respect to a scenario where an overpressure exists during the charging operation the reservoir. The idea being that it is utilitarian for the cap or plug to not “pop” off or rupture. In an embodiment, the tube(s) of the reservoir also are configured so that an overpressure in the reservoir maintains the reservoir for subsequent use when implanted in a human. In an embodiment, there is a valve that is configured to eject substance upon overpressure. This can be located along the lead and/or at the cistern. This can be located away from the electrode array / portions that are located / to be located in the cochlea upon full implantation. In an embodiment, there can be a poppet that pops out upon over pressurization. The poppet can be configured so that it must be replaced or a new one is placed at the location of the old one. Spare poppets can be provided with the implant in the packaging. In an embodiment, the valve / poppet ensures or otherwise reduces the likelihood of damage to the substance delivery system via over pressurization. In a sense, the poppet can be a sacrificial component.

[00205] In an embodiment, there is little to no mass transfer when the therapeutic substance is delivered to the recipient. All delivery or substantially all delivery or effectively all is executed by diffusion. In an embodiment, at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% or any value or range of values therebetween in 0.1 % increments of the delivery is by diffusion. In an embodiment, the just noted diffusion qualifiers occur after 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours after the outlet first comes into contact with the body fluid and/or after the completion of recharging (to take into account the fact that there could be some amount of mass transfer for example during the implantation process and/or the surgical process or the recharging process, owing to, for example, the application of pressure onto the cistern during implantation by way of example). [00206] While the embodiments above have focused on a single outlet for the therapeutic substance, embodiments include reservoirs that have multiple outlets. In this regard, figure 42 shows an exemplary electrode array 2888 that includes outlets located on the lateral wall facing side of the electrode array. Each of the outlets includes plugs 2030 in this embodiment, which may not be present ion other embodiments, which can correspond to the plugs detailed above. Also shown is the various placement of the plugs. As can be seen, some of the plugs can be located in board of the most outboard portions of the outlet, and some of plugs can extend into the tube 718. Providing that the therapeutic substance can transfer from the tube to the ambient environment after implantation, any arrangement can be utilized. It is also noted that the outlets can have various sizes and/or dimensions and they can be different from one another. In an exemplary embodiment, the plugs 2030 are adhesively bonded to the tube 718 and/or to the silicone body that establishes the carrier. In this embodiment, the tube 718 has orifices located along the length thereof, and the plugs 2030 fill the orifices. In an embodiment, the plugs interference fit with the orifices two maintain the plugs in the orifices. In an embodiment, again adhesive or some other bonding technique is utilized.

[00207] In an exemplary embodiment, the reservoir is a non-expandable reservoir. By way of example only and not by way of limitation, in an exemplary embodiment, the reservoir is might be made out of an elastomeric material, but the reservoir is structured so that the elasticity is de minimus. In an exemplary embodiment, in a 1 atm pressurize state, the reservoir establishes a first interior volume. When subjected to a pressurization such as any one or more of the pressurization’s above by way of example, depending on the pressurization, the reservoir establishes a second interior volume that is no more than 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1% larger than the first interior volume.

[00208] It is noted that the phrase “filled” as used herein is not an absolute term. This refers to the action of placing the substance into the reservoir from a location outside of the reservoir. The reservoir need not be filled to capacity. Although embodiments do include filling the reservoir to capacity.

[00209] Some embodiments of the therapeutic substance can be a drug. Thus, embodiments are directed towards a drug delivery system. Therapeutic substances include drugs, but also include nondrug substances. In an exemplary embodiment, therapeutic substances include steroids and biologies. Therapeutic substances can also include minerals and the like. [00210] In an exemplary embodiment, the barriers described above serve a dual function as a flow restrictor and bacterial barrier.

[00211] In view of the above, as can be seen, in an exemplary embodiment, there is an apparatus, comprising, by way of example, a cochlear implant electrode array, and an implantable drug reservoir. In this exemplary embodiment, the apparatus is configured such that the drug reservoir is part of the electrode array, and the drug reservoir is at least substantially located outside of the middle ear space and outside of the inner ear space when the cochlear implant electrode array is fully implanted in a recipient. (Note that reservoir is a relative term. Because of the relative de minimis size of the cistern, the tubing of the lead assembly including the electrode array is considered a reservoir. Conversely, if the cistern was much larger than at least some of the exemplary embodiments disclosed herein, the tubes of the lead assembly would not be considered reservoirs.) In the embodiments above, the cistern is totally located outside the middle ear and the inner ear when the cochlear implant electrode array is fully implanted in a recipient, both in the relaxed state and in the fully operational expanded state. In at least some embodiments, the cistern is an inelastic enclosure aside from the septum or a totally inelastic enclosure.

[00212] In an exemplary embodiment, in a 1 atm pressurize state, the cistern establishes a first interior volume. When subjected to a pressurization such as any one or more of the pressurization’s above by way of example, depending on the pressurization, the reservoir establishes a second interior volume that is no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1% larger than the first interior volume. In an embodiment, if the septum is rigidly retrained to avoid expansion, the reservoir establishes a second interior volume that is no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1% larger than the first interior volume.

[00213] In some embodiments, the teachings detailed herein enable an apparatus that is configured to deliver, on a first temporal period average, less than and/or equal to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, or 60 nanograms per hour or any value or range of values therebetween in 0.05 nanogram increments per hour of therapeutic substance during a first temporal period over a second temporal period without recharging. In an exemplary embodiment, the first temporal period is 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, or 60 hours, or days, or any value or range of values therebetween in one hour or day increments, and the second temporal period is 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300 hours, or days, or any value or range of values therebetween in one hour or day increments. In an embodiment, the distinct barrier is both a bacterial filter and controls the rate of delivery / determines the rate of delivery of the therapeutic substance. Different barrier configurations (e.g., porosities) can be selected to obtain different diffusion rates. In an embodiment the barrier is of a design so that the barrier is relatively thin, sufficiently thin, so that it has relatively little impact on the diffusion rate. Other barriers may be more amenable to rate control in other embodiments. In an embodiment, to change / control a rate of delivery, a concentration in the reservoir can be changed / adjusted. For example, a high concentration can equate to a faster diffusion, at least initially, and visa-versa. Alternative and/or in addition to this, the cross-sectional area of the lengthy tubes (tubes 718 and/or 714) can be changed / modified to achieve a desired rate, at least approximately.

[00214] Also, in some embodiments, as detailed, the apparatus is configured such that the reservoir can be refilled or recharged without surgery.

[00215] In an exemplary embodiment, the pressure under which the drug is located is a pressure that is no more than 1.01, 1.02, 1.03, 1.04, 1.05, 1,06, 1.07, 1.08, 1.09, 1.1, 1.12, 1.14, 1.16, 1.18, or 1.2 times greater than the ambient pressure inside the cochlea and/or the statistical average atmospheric pressure at sea level in Washington, D.C. for the calendar year 2021 based on data at Dulles Airport and/or 1 atmosphere or any value or range of values therebetween in increments of 0.01 times, all other things being equal. In this embodiment, the distinct barrier can be configured to prevent pressures above any one or more of the aforementioned pressures.

[00216] Any arrangement disclosed herein can be an arrangement that is refillable and/or rechargeable, unless otherwise specified. And again, other embodiments include implantable portions that cannot be re-filled or recharged, at least after implantation.

[00217] Embodiments include a device that is configured to be fully charged or otherwise primed in a time that is no more than 10, nine, eight, seven, six, five, four, three, two, one minutes or any value or range of values therebetween in one second increments.

[00218] It is noted that any disclosure with respect to one or more embodiments detailed herein can be practiced in combination with any other disclosure with respect to one or more other embodiments detailed herein. That is, some exemplary embodiments include any one or more of the teachings detailed herein combined with any one or more of the other teachings detailed herein, unless otherwise stated such, providing that the art enables such. It is also noted that any disclosure herein of any feature corresponds to a disclosure of an exemplary embodiment that explicitly excludes that given feature from utilization with any one or more other features detailed herein unless otherwise specified providing that the art enables such.

[00219] It is noted that any disclosure herein of any method action corresponds to a disclosure of a device and/or system that enables that method action. It is noted that any disclosure herein of any method of manufacturing or otherwise developing or making a device disclosed herein corresponds to a disclosure of the resulting device that results from that method. It is noted that any disclosure herein of any apparatus and/or system corresponds to a disclosure of providing and/or making that apparatus and/or system. It is noted that any disclosure herein of any functionality corresponds to a device and/or system is configured to provide that functionality. It is noted that any disclosure of any device and/or system herein corresponds to a disclosure of a method of utilizing that device and/or system.

[00220] In this regard, it is noted that any disclosure of a device and/or system herein also corresponds to a disclosure of utilizing the device and/or system detailed herein, at least in a manner to exploit the functionality thereof. Further, it is noted that any disclosure of a method of manufacturing corresponds to a disclosure of a device and/or system resulting from that method of manufacturing. It is also noted that any disclosure of a device and/or system herein corresponds to a disclosure of manufacturing that device and/or system.

[00221] While various embodiments have been described above, it should be understood that they have been presented by way of example only, and not limitation. It will be apparent to persons skilled in the relevant art that various changes in form and detail can be made therein without departing from the spirit and scope of the invention. Thus, the breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents.

Claims

CLAIMS What is claimed is:

1. An apparatus, comprising: a reservoir; and a therapeutic substance located in the reservoir, wherein the apparatus is an implantable therapeutic substance delivery apparatus, and the apparatus is configured to deliver the therapeutic substance to a recipient thereof by diffusion controlled release.

2. The apparatus of claim 1, wherein: the reservoir includes a first sub-reservoir and a second sub-reservoir, the second subreservoir being constricting relative to the first sub-reservoir; and molecules of the therapeutic substance move from the first sub-reservoir to the second sub-reservoir during delivery of the therapeutic substance to the recipient.

3. The apparatus of claim 1, wherein: the reservoir includes a first sub-reservoir, a second sub-reservoir, and a third subreservoir the second sub-reservoir being constricting relative to the first sub-reservoir and the third sub-reservoir being constricting relative to the second sub-reservoir; molecules of the therapeutic substance move from the first sub-reservoir to the second sub-reservoir to the third sub-reservoir during delivery of the therapeutic substance to the recipient.

4. The apparatus of claims 1, 2 or 3, wherein: the reservoir is established by at least a cistern and a conduit device; the conduit device includes a first conduit section having a first cross-sectional area normal to a direction of extension of the first conduit section that is larger than a second cross-sectional area of a second conduit section normal to a direction of extension of the second conduit section; and the cross-sectional area of the second conduit section is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into the recipient is less than l/3^rd of that which would exist if the first cross-sectional area was the same as the second cross-sectional area, all other things being equal.

5. The apparatus of claims 1, 2 or 3, wherein: the reservoir is established by at least a cistern and a conduit device; the conduit device includes a first conduit section having a first cross-sectional area normal to a direction of extension of the first conduit section that is larger than a second cross-sectional area of a second conduit section normal to a direction of extension of the second conduit section; and the cross-sectional area of the second conduit section is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into a human is less than 10% of that which would be the case if the first cross-sectional area was the same as the second cross-sectional area, all other things being equal.

6. The apparatus of claims 1, 2 or 3, wherein: the reservoir is established by at least a cistern and a conduit device; the conduit device includes a first conduit section having a first cross-sectional area normal to a direction of extension of the first conduit section that is at least five times larger than a second cross-sectional area of a second conduit section normal to a direction of extension of the second conduit section; the first conduit section has a first length that is larger than a second length of the second conduit section; and the length of the second conduit section is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into a human is less than 50% of that which would be the case if the first length was 25 times the second length, all other things being equal.

7. The apparatus of claims 1, 2 or 3, wherein: the reservoir is established by at least a cistern and a conduit device; the conduit device includes a first conduit section having a first cross-sectional area normal to a direction of extension of the first conduit section that is at least five times larger than a second cross-sectional area of a second conduit section normal to a direction of extension of the second conduit section; the first conduit section has a first length that is larger than a second length of the second conduit section; and the length of the second conduit section is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into a human is less than 70% of that which would be the case if the length of the second section was 25 times the second length, all other things being equal.

8. An apparatus, comprising: a cistern; and a delivery tube device, wherein the apparatus is an implantable therapeutic substance delivery apparatus, the delivery tube device is a diffusion delivery tube device, and the apparatus is configured so that therapeutic substance located in the cistern travels to the delivery tube device for delivery to a human implanted with the device.

9. The apparatus of claim 8, wherein: the cistern has an internal volume of at least an order of magnitude larger than that of the delivery tube.

10. The apparatus of claims 8 or 9, wherein: the delivery tube device has a first section having a first cross-sectional area normal to a direction of extension of the first section that is larger than a second cross-sectional area of a second section of the delivery tube device, the second cross-sectional area being normal to a direction of extension of the second section; and the first cross-sectional area is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into a human is at least twice that which would be the case if the first cross-sectional area was the same as the second cross- sectional area, all other things being equal.

11. The apparatus of claims 8 or 9, wherein: the delivery tube device has a first section having a first cross-sectional area normal to a direction of extension of the first section that is larger than a second cross-sectional area of a second section of the delivery tube device, the second cross-sectional area being normal to a direction of extension of the second section; and the first cross-sectional area is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into a human is within 20% of that which would be the case if the first cross-sectional area was the same as the second cross- sectional area, all other things being equal.

12. The apparatus of claims 8 or 9, wherein: the delivery tube device has a first section having a first length that is larger than a second length of a second section of the delivery tube device; the first section has a first cross-sectional area normal to a direction of extension of the first section that is at least five times larger than a second cross-sectional area of the second section of the delivery tube device normal to a direction of extension of the second section; and the length of the first section is at least four times larger than the length of the second section, and the length of the first section is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into a human is within 10% of that which would exist if the length of the first section was at least 6 times larger than the length of the second section, all other things being equal.

13. The apparatus of claims 8 or 9, wherein: the delivery tube has a first section having a first length that is larger than a second length of a section of the delivery tube; the first section has a first cross-sectional area normal to a direction of extension of the first section that is at least five times larger than a second cross-sectional area of the second section of the delivery tube device normal to a direction of extension of the second section; and the length of the first section is at least four times larger than the length of the second section, and the length of the first section is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into a human is within 10% of that which would exist if the length of the first section was at least 8 times larger than the length of the second section, all other things being equal.

14. The apparatus of claims 8 or 9, wherein: the delivery tube device has a first section having a first length that is larger than a second length of a second section of the delivery tube device; the first section has a first cross-sectional area normal to a direction of extension of the first section that is larger than a second cross-sectional area of the second section of the delivery tube device normal to a direction of extension of the second section; and the second cross-sectional area is such that a release rate of the therapeutic substance at and/or after 12 hours of release into a human of the therapeutic substance from the apparatus is less than 60% of that which would exist if the second cross-sectional area was the same as the second cross-sectional area; and the second cross-sectional area is such that a release rate of the therapeutic substance at and/or after 12 hours of release into the human of the therapeutic substance from the apparatus is within 10% of that which would exist if the second cross-sectional area was at least one of 10 times smaller or 10 times larger.

15. A method, comprising: accessing an interior of a human; and treating an ailment of the human by controllably delivering a therapeutic substance delivered from an implantable therapeutic substance delivery device, wherein the action of controllably delivering the therapeutic substance is executed passively.

16. The method of claim 15, wherein: a fluidic bridge between the therapeutic substance and a body fluid in the human is present.

17. The method of claim 16, wherein: the bridge allows molecules of the therapeutic substance to diffuse from the device into the interior of the human.

18. The method of claims 15, 16 or 17, wherein: the body fluid is perilymph.

19. The method of claims 15, 16, 17 or 18, wherein: after an initial temporal period where therapeutic substance release rate steadily reduces from a relatively higher rate, the therapeutic substance release rate quasi-stabilizes at a lower rate.

20. The method of claim 19, wherein: the quasi-stabilized release rate is due to a slowly changing concentration gradient of the substance within the device.

21. The method of claim 20, wherein: the slowly changing concentration gradient is due to a sustained supply of molecules of the therapeutic substance from a large volume area to a smaller volume area of the device.

22. The method of claims 15, 16, 17, 18, 19, 20 or 21, wherein: the action of controllably delivering the therapeutic substance is governed by Fick’s Law.

23. An apparatus, comprising: a first at least partially bounded volume; a second at least partially bounded volume; and at least one apparatus outlet at the second bounded volume, wherein the apparatus is an implantable therapeutic substance delivery apparatus, and the apparatus delivers the therapeutic substance to a recipient thereof effectively entirely due to a concentration gradient.

24. The apparatus of claim 23, wherein: the apparatus provides for passive diffusion local therapeutic substance release entirely controlled by geometry.

25. The apparatus of claims 23 or 24, further comprising: a third at least partially bounded volume, wherein the third at least partially bounded volume is substance movement located between the first volume and the second volume, a volume of the first volume is at least 5 times the volume of the third volume and the volume of the third volume is at least 5 times the volume of the second volume.

26. The apparatus of claims 23 or 24, further comprising: a third at least partially bounded volume, wherein the third at least partially bounded volume is substance movement located between the first volume and the second volume, a first cross-sectional area of the first volume lying on a plane normal to a direction of substance movement from the first volume to the second volume is at least 8 times a second cross-sectional area of the third volume lying on a plane normal to the direction of substance movement from the first volume to the second volume, and a third cross-sectional area of the second volume lying on a plane normal to the direction of substance movement from the first volume to the second volume is at least 6 times smaller than the second cross-sectional area.

27. The apparatus of claims 23 or 24, further comprising: a third at least partially bounded volume, wherein the third at least partially bounded volume is substance movement located between the first volume and the second volume, the second at least partially bounded volume is a lumen having a diameter, and a release rate at and/or after seven days of releasing therapeutic substance into a human such that the release rate increases by an amount between 8 and 15 times with an increase in diameter of between 2 and 5 times, all other things being equal.

28. The apparatus of claims 23 or 24, further comprising: a third at least partially bounded volume, wherein the third at least partially bounded volume is substance movement located between the first volume and the second volume, the second at least partially bounded volume is a lumen having a length and a release rate at and/or after seven days of releasing therapeutic substance into a human such that the release rate decreases by an amount between 2 and 5 times with an increase in length of between 4 and 8 times, all other things being equal.

29. The apparatus of claims 23, 24, 25, 26, 27 or 28, further comprising: the apparatus is configured so that a release rate at and/or after 7 days of releasing the therapeutic substance decreases by at least 70% for an increase of formula weight by at least 100 times, all other things being equal.

30. A method, comprising: accessing an interior of a human; and treating an ailment of a human by controllably delivering a therapeutic substance delivered from an implantable therapeutic substance delivery device, wherein the action of controllably delivering the therapeutic substance is executed effectively without a net movement of solvent in which the therapeutic substance is present from a therapeutic substance containing volume of the device to the ambient environment outside the device

31. The method of claim 30, wherein: the volume has a total distance extending from an outlet of the volume into the human to a location furthest therefrom, the volume is sized and dimensioned so that a concentration gradient of molecules of therapeutic substance at and/or after seven days of substance delivery is such that the concentration varies by no more than 5% from a maximum for at least a first section of the total distance along the volume, the first section having a distance of at least l/3^rd of the total distance.

32. The method of claims 30 or 31, wherein: the volume is sized and dimensioned so that the concentration gradient of molecules of therapeutic substance at and/or after seven days of substance delivery is such that the concentration reduces by an amount of at least 20% over a second section of the total distance along the volume, the second section having a distance of Yi of the total distance, the second section being contiguous with the first section.

33. The method of claims 30 or 31, wherein: the volume is sized and dimensioned so that the concentration gradient of molecules of therapeutic substance at and/or after seven days of substance delivery is such that the concentration reduces by an amount of no more than 20% over a second section of the total distance along the volume, the second section having a distance of l/3^rd of the total distance, the second section being contiguous with the first section.

34. The method of claims 30 or 31, wherein: the volume is sized and dimensioned so that the concentration gradient of molecules of therapeutic substance at and/or after seven days of substance delivery is such that the concentration reduces by an amount of no more than 20% over a second section of the total distance along the volume, the second section having a distance of 1/2 of the total distance, the second section being contiguous with the first section.

35. The method of claims 30, 31, 32, 33 or 34, wherein: a release rate over a 5 day period within 8 days of a beginning of delivering the therapeutic substance is less than 20% of a maximum release rate.

36. The method of claims 30, 31, 32, 33 or 34, wherein: a release rate over a 5 day period within 8 days of a beginning of delivering the therapeutic substance is less than 10% of a maximum release rate.

37. The method of claims 30, 31, 32, 33 or 34, wherein: a release rate over a 5 day period within 8 days of a beginning of delivering the therapeutic substance is less than 5% of a maximum release rate.

38. An implantable therapeutic substance delivery apparatus, comprising: a cistern; and a delivery tube device, wherein the delivery tube device includes a tubular apparatus that includes a first lumen and a second lumen distinctly different from the first lumen, the delivery tube device is a diffusion delivery tube device, the first lumen is in fluid communication with the cistern and the second lumen is in fluid communication with the first lumen, and the apparatus is configured so that the therapeutic substance located in the cistern travels to the delivery tube device for delivery to a human implanted with the device.

39. An apparatus, wherein at least one of: the apparatus includes a reservoir; the apparatus includes a therapeutic substance located in the reservoir; the apparatus is an implantable therapeutic substance delivery apparatus; the apparatus is configured to deliver the therapeutic substance to a recipient thereof by diffusion controlled release; the reservoir includes a first sub-reservoir and a second sub-reservoir, the second subreservoir being constricting relative to the first sub-reservoir; molecules of the therapeutic substance move from the first sub-reservoir to the second sub-reservoir during delivery of the therapeutic substance to the recipient; the reservoir includes a first sub-reservoir, a second sub-reservoir, and a third subreservoir the second sub-reservoir being constricting relative to the first sub-reservoir and the third sub-reservoir being constricting relative to the second sub-reservoir; molecules of the therapeutic substance move from the first sub-reservoir to the second sub-reservoir to the third sub-reservoir during delivery of the therapeutic substance to the recipient; the reservoir is established by at least a cistern and a conduit device; the conduit device includes a first conduit section having a first cross-sectional area normal to a direction of extension of the first conduit section that is larger than a second cross-sectional area of a second conduit section normal to a direction of extension of the second conduit section; the cross-sectional area of the second conduit section is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into the recipient is less than l/3^rd of that which would exist if the first cross-sectional area was the same as the second cross-sectional area, all other things being equal; the reservoir is established by at least a cistern and a conduit device; the conduit device includes a first conduit section having a first cross-sectional area normal to a direction of extension of the first conduit section that is larger than a second cross-sectional area of a second conduit section normal to a direction of extension of the second conduit section; the cross-sectional area of the second conduit section is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into a human is less than 10% of that which would be the case if the first cross-sectional area was the same as the second cross-sectional area, all other things being equal; the reservoir is established by at least a cistern and a conduit device; the conduit device includes a first conduit section having a first cross-sectional area normal to a direction of extension of the first conduit section that is at least five times larger than a second cross-sectional area of a second conduit section normal to a direction of extension of the second conduit section; the first conduit section has a first length that is larger than a second length of the second conduit section; the length of the second conduit section is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into a human is less than 50% of that which would be the case if the first length was 25 times the second length, all other things being equal; the reservoir is established by at least a cistern and a conduit device; the conduit device includes a first conduit section having a first cross-sectional area normal to a direction of extension of the first conduit section that is at least five times larger than a second cross-sectional area of a second conduit section normal to a direction of extension of the second conduit section; the first conduit section has a first length that is larger than a second length of the second conduit section; the length of the second conduit section is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into a human is less than 70% of that which would be the case if the length of the second section was 25 times the second length, all other things being equal; a cistern; and a delivery tube device; the apparatus is an implantable therapeutic substance delivery apparatus; the delivery tube device is a diffusion delivery tube device; the apparatus is configured so that therapeutic substance located in the cistern travels to the delivery tube for delivery to a human implanted with the device; the cistern has an internal volume of at least an order of magnitude larger than that of the delivery tube; the delivery tube device has a first section having a first cross-sectional area normal to a direction of extension of the first section that is larger than a second cross-sectional area of a second section of the delivery tube device, the second cross-sectional area being normal to a direction of extension of the second section; the first cross-sectional area is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into a human is at least twice that which would be the case if the first cross-sectional area was the same as the second cross- sectional area, all other things being equal; the delivery tube device has a first section having a first cross-sectional area normal to a direction of extension of the first section that is larger than a second cross-sectional area of a second section of the delivery tube device, the second cross-sectional area being normal to a direction of extension of the second section; the first cross-sectional area is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into a human is within 20% of that which would be the case if the first cross-sectional area was the same as the second cross- sectional area, all other things being equal; the delivery tube device has a first section having a first length that is larger than a second length of a second section of the delivery tube device; the first section has a first cross-sectional area normal to a direction of extension of the first section that is at least five times larger than a second cross-sectional area of the second section of the delivery tube device normal to a direction of extension of the second section; and the length of the first section is at least four times larger than the length of the second section, and the length of the first section is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into a human is within 10% of that which would exist if the length of the first section was at least 6 times larger than the length of the second section, all other things being equal; the delivery tube has a first section having a first length that is larger than a second length of a section of the delivery tube; the first section has a first cross-sectional area normal to a direction of extension of the first section that is at least five times larger than a second cross-sectional area of the second section of the delivery tube device normal to a direction of extension of the second section; the length of the first section is at least four times larger than the length of the second section, and the length of the first section is such that a release rate of the therapeutic substance from the apparatus at and/or after seven days of release into a human is within 10% of that which would exist if the length of the first section was at least 8 times larger than the length of the second section, all other things being equal; the delivery tube device has a first section having a first length that is larger than a second length of a second section of the delivery tube device; the first section has a first cross-sectional area normal to a direction of extension of the first section that is larger than a second cross-sectional area of the second section of the delivery tube device normal to a direction of extension of the second section; the second cross-sectional area is such that a release rate of the therapeutic substance at and/or after 12 hours of release into a human of the therapeutic substance from the apparatus is less than 60% of that which would exist if the second cross-sectional area was the same as the second cross-sectional area; the second cross-sectional area is such that a release rate of the therapeutic substance at and/or after 12 hours of release into the human of the therapeutic substance from the apparatus is within 10% of that which would exist if the second cross-sectional area was at least one of 10 times smaller or 10 times larger; the apparatus is configured to execute an action of treating an ailment of the human by controllably delivering a therapeutic substance delivered from an implantable therapeutic substance delivery device, wherein the action of controllably delivering the therapeutic substance is executed passively; a fluidic bridge between the therapeutic substance and a body fluid in the human is present; the bridge allows molecules of the therapeutic substance to diffuse from the device into the interior of the human; the body fluid is perilymph; after an initial temporal period where therapeutic substance release rate steadily reduces from a relatively higher rate, the therapeutic substance release rate quasi-stabilizes at a lower rate; the quasi-stabilized release rate is due to a slowly changing concentration gradient of the substance within the device; the slowly changing concentration gradient is due to a sustained supply of molecules of the therapeutic substance from a large volume area to a smaller volume area of the device; the action of controllably delivering the therapeutic substance is governed by Fick’s Law; the apparatus includes a first at least partially bounded volume; the apparatus includes a second at least partially bounded volume; the apparatus includes at least one apparatus outlet at the second bounded volume; the apparatus is an implantable therapeutic substance delivery apparatus; the apparatus delivers the therapeutic substance to a recipient thereof effectively entirely due to a concentration gradient; the apparatus provides for passive diffusion local therapeutic substance release entirely controlled by geometry; the apparatus includes a third at least partially bounded volume, wherein the third at least partially bounded volume is substance movement located between the first volume and the second volume; a volume of the first volume is at least 5 times the volume of the third volume and the volume of the third volume is at least 5 times the volume of the second volume; the apparatus includes a third at least partially bounded volume; the third at least partially bounded volume is substance movement located between the first volume and the second volume; a first cross-sectional area of the first volume lying on a plane normal to a direction of substance movement from the first volume to the second volume is at least 8 times a second cross-sectional area of the third volume lying on a plane normal to the direction of substance movement from the first volume to the second volume; a third cross-sectional area of the second volume lying on a plane normal to the direction of substance movement from the first volume to the second volume is at least 6 times smaller than the second cross-sectional area; the third at least partially bounded volume is substance movement located between the first volume and the second volume; the second at least partially bounded volume is a lumen having a diameter, and a release rate at and/or after seven days of releasing therapeutic substance into a human such that the release rate increases by an amount between 8 and 15 times with an increase in diameter of between 2 and 5 times, all other things being equal; the third at least partially bounded volume is substance movement located between the first volume and the second volume; the second at least partially bounded volume is a lumen having a length and a release rate at and/or after seven days of releasing therapeutic substance into a human such that the release rate decreases by an amount between 2 and 5 times with an increase in length of between 4 and 8 times, all other things being equal; the apparatus is configured so that a release rate at and/or after 7 days of releasing the therapeutic substance decreases by at least 70% for an increase of formula weight by at least 100 times, all other things being equal; the apparatus is configured to execute the action of treating an ailment of a human by controllably delivering a therapeutic substance delivered from an implantable therapeutic substance delivery device; the action of controllably delivering the therapeutic substance is executed effectively without a net movement of solvent in which the therapeutic substance is present from a therapeutic substance containing volume of the device to the ambient environment outside the device; the volume has a total distance extending from an outlet of the volume into the human to a location furthest therefrom, the volume is sized and dimensioned so that a concentration gradient of molecules of therapeutic substance at and/or after seven days of substance delivery is such that the concentration varies by no more than 5% from a maximum for at least a first section of the total distance along the volume, the first section having a distance of at least l/3^rd of the total distance; the volume is sized and dimensioned so that the concentration gradient of molecules of therapeutic substance at and/or after seven days of substance delivery is such that the concentration reduces by an amount of at least 20% over a second section of the total distance along the volume, the second section having a distance of Yi of the total distance, the second section being contiguous with the first section; the volume is sized and dimensioned so that the concentration gradient of molecules of therapeutic substance at and/or after seven days of substance delivery is such that the concentration reduces by an amount of no more than 20% over a second section of the total distance along the volume, the second section having a distance of l/3^rd of the total distance, the second section being contiguous with the first section; the volume is sized and dimensioned so that the concentration gradient of molecules of therapeutic substance at and/or after seven days of substance delivery is such that the concentration reduces by an amount of no more than 20% over a second section of the total distance along the volume, the second section having a distance of 1/2 of the total distance, the second section being contiguous with the first section; a release rate over a 5 day period within 8 days of a beginning of delivering the therapeutic substance is less than 20% of a maximum release rate; a release rate over a 5 day period within 8 days of a beginning of delivering the therapeutic substance is less than 10% of a maximum release rate; a release rate over a 5 day period within 8 days of a beginning of delivering the therapeutic substance is less than 5% of a maximum release rate; the apparatus includes a first tube and a second tube, wherein the second tube is interference fitted into the first tube; the apparatus includes a tube, wherein an end of tube is in fluidic communication with a target; the target is perilymph of scala tympani in a human cochlea; the apparatus includes a filter at the outlet of tube; the outlet has a cross-sectional area lying on a plane normal to a longitudinal direction of extension of the lumen that is the same as the mean, median and/or mode of the cross- sectional area lying on planes normal to that longitudinal direction, and/or the same as the largest or smallest area, and/or the cross-sectional area is constant along the length of lumen and/or does not change more than 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14 or 15% from the maximum along at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100% of the length; the tube can be changed out or otherwise a tube 718 can be selected for use with the apparatus; the apparatus is configured so that one tube can be attached to another tube shortly before implantation and/or during the surgical procedure implanting the apparatus to select the delivery regime; the apparatus is configured so that if a higher release rate is desired, a tube with a cross-section and/or a length that will achieve the desired release rate is selected and attached to the other tube so that after implantation, the desirable results are achieved; the tubes are color-coded; a lumen length for tube 2 is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 mm or any value or range of values therebetween in 0.1 mm increments; a lumen length for tube 1 is 50, 60, 70, 80, 90, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129 or 130 mm, or any value or range of values therebetween in 0.1 mm increments; a lumen cross-sectional area for tube 1 is 0.15, 0.14, 0.13, 0.12, 0.11, 0.10, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, 0.03, 0.02, 0.01, 0.0009, 0.0008, 0.0007, 0.006, 0.0005, 0.0004, 0.0003, 0.0002, 0.0001 mm², or any value or range of values therebetween in 0.00001 mm² increments; a lumen cross-sectional area for tube 2 is 0.15, 0.14, 0.13, 0.12, 0.11, 0.10, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, 0.03, 0.02, 0.01, 0.0009, 0.0008, 0.0007, 0.006, 0.0005, 0.0004, 0.0003, 0.0002, 0.0001 mm², or any value or range of values therebetween in 0.00001 mm² increments; the lumen for the second tube can have any of the values above or any range of values therebetween as a cross-sectional area in mm² (lying on a plane normal to a longitudinal axis of the lumen / the direction of the lumen), and these can be for the full length of the second lumen or the average (mean, median and/or mode) over the full length and/or the value or the average for less than, greater than and/or equal to 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100%, or any value or range of values therebetween in 1% increments and can be any of the values therebetween or any range of values therebetween (the percentage differences); the apparatus does not elute the drug or therapeutic substance; a principle of drug delivery of the apparatus is not elution; a principle of drug delivery is that the apparatus diffusese the substance, through a barrier or without a barrier (in some embodiments, the opening corresponds to the diameter of the lumen of the second tube); the outlet of the apparatus is open; the outlet of the apparatus includes a filter; the outlet has a barrier; the barrier has pores allowing direct fluidic connection between the liquid inside (drug solution) and the liquid outside (perilymph for example) the therapeutic substance delivery system; the apparatus has free diffusion of the therapeutic substance molecules from inside the device to outside across the barrier following a concentration gradient; the apparatus is configured so that the therapeutic substance molecules do not need to dissolve or absorb or adsorb into a third matrix (considering the therapeutic substance solvent inside the device as a first matrix and perilymph (or other bodily fluids) as the second matrix); the barrier, if present, can be utilized to prevent pathogens such as virus, bacterium, protozoan, prion, viroid, and/or fungus to exit and enter the apparatus; the apparatus includes a bacterial filter of 0.22 micrometer pore size or smaller; the barrier also provides a mechanical mechanism to increase the flow resistance between the lumen inside the apparatus and the outside environment; the barrier provides containment of the therapeutic substance solution inside the apparatus after initial priming (filling) during handling and implanting the implant; the barrier, in the implanted state increases avoidance of significant amounts of liquid to exit or enter the delivery system in the event of pressure changes inside or outside the device from, for example, body movement or impact, or simply handling of the device during implantation; the apparatus is configured so that of the therapeutic substance that is used to charge or fill the reservoir, no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5, 0.25, or .1%, or any value or range of values therebetween in 0.1% increments of the therapeutic substance diffuses and/or elutes through the tubes and/or the silicone bodies; the apparatus is configured so that of the therapeutic substance that leaves the reservoir and enters the body, at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100%, or any value or range of values therebetween in 0.1% increments of such is a result of diffusion, including diffusion through the distinct barrier, within any one or more of the timeframes detailed herein (or in total); the therapeutic substance is water-based, and the apparatus is configured so that the therapeutic substance diffuses out while the water remains in the delivery system and salts, etc., and diffuses into the reservoir to address the concentration gradient; the apparatus is configured so that net water movement into the apparatus (osmosis) is avoided; the apparatus includes a therapeutic solution that is isotonic to match the osmolarity of perilymph to avoid osmosis is utilized; there is no membrane across the opening, where the therapeutic substance or otherwise the active ingredient, actually comes out of the water, and then passes into the membrane, and then passes back into the water of the cochlea; the therapeutic substance does not leave the water that is located in the reservoir at the time of charging with the therapeutic substance; the diffusion is a diffusion of the therapeutic substance, as opposed to the principle of operation of the membrane. In an embodiment, there is no semi-permeable membrane that is used in / bounding the reservoir; the apparatus includes a 100 micrometer thick membrane, which membrane does not impact the release rate, or reduces the rate by at most 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1% or any value or range of values therebetween in 0.1% increments from the rate that would be present in the absence of the membrane; the apparatus is completely free of hydrogel. In an embodiment, at least 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% of all therapeutic substance delivered to the human by the apparatus (by mass and/or by volume) is delivered to the human without the use of hydrogel; the apparatus includes sound pressure wave mitigation and/or prevention; the apparatus is configured to avoid sound energy that travels through the skin and impinges upon the tubes and/or sound energy that creates movements or otherwise waves of fluid motion of the perilymph within the cochlea creates pressure waves within the reservoir of the therapeutic substance delivery apparatus; the apparatus is configured so that a total water amount of the therapeutic substance delivery system at the time of implantation is within 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, or 0.5%, or any value or range of values therebetween in 0.05% increments of the value of water amount at the point when 80, 85, 90, or 95% of the therapeutic substance has diffused out of the system into the body; the apparatus is configured so that within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, 500, 550, 600, 700, 800, 900, 1000, 1250, 1500, 1750, 2000, 2250, 2500, 3000, 3500, 4000, 4500, or 5000 hours after first entering the cochlea / the outlet coming into contact with the perilymph or pertinent body fluid, at least and/or no more than 50, 55, 60, 65, 70, 75, 80, 85, 90, 91, 92, 93, 94, or 95%, or any value or range of values in 1% increments of the therapeutic substance that was in the reservoir at the time that the outlet (whether with a barrier or not, and if more outlets, from when the first and/or last outlet) came into contact with the body fluid remains in the reservoir owing to diffusion through the distinct barrier into the cochlea or pertinent body cavity or body space; the barrier reduces the flow rate by at most 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1% or any value or range of values therebetween in 0.1% increments relative to that which would exist int eh absence of the barrier; the barrier is an invisible barrier; the apparatus is configured so that the fluid is retained therein by capillary forces / actions; the apparatus is configured so that the effective cross-sectional area of the barrier is at most 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1% or any value or range of values therebetween in 0.1% increments of the cross-sectional area of the second lumen; the therapeutic substance delivery system is a valveless system and/or a flow restrictor less system (save for the substantial barrier(s) to the extent they are considered flow restrictors); the apparatus includes a lead assembly, and no portion of the lead assembly is saturated and/or no portion of the implantable portion is saturated with a therapeutic substance, with the possible exception of a barrier if present or at least a portion of the barrier in at least some exemplary embodiments; an embodiment, the silicone of the lead assembly and/or any of the tubes, or otherwise the material of the tubes, is not porous and/or is not aerated; the apparatus includes a conduit device that includes a first conduit section having a first cross-sectional area normal to a direction of extension of the first conduit section (or normal to the direction of molecule movement during delivery to the recipient) that is larger than a second cross-sectional area of a second conduit section normal to a direction of extension of the second conduit section (or normal to the direction of molecule movement during delivery to the recipient); the cross-sectional area of the second conduit section is such that a release rate of the therapeutic substance from the apparatus at and/or after Y days of release into the recipient (the “at” is the Y day mark (e.g., 7 days - it must meet the requirements at the 7 day mark), the “after” is the Y day and later (e.g., 7, 8, 9, 10, 11, 12 days, and so on - it must meet the requirement on a day at or after the Y day, whether that is the 7^th day or the 10^th day is covered)) is less than X% of that which would exist if the first cross-sectional area was the same as the second cross-sectional area, all other things being equal, where Y is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60,

70, 80, 90, or 100, or any value or range of values therebetween in 1 increment, and X is 70,

65, 60, 55, 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21,

20, 19.5, 19, 18.5, 18, 17.5, 17, 16.5, 16, 15.5, 15, 14.5, 14, 13.5, 13, 12.5, 12, 11.5, 11, 10.5,

10, 9.75, 9.5, 9.25, 9.0, 8.75, 8.5, 8.25, 8.0, 7.75, 7.5, 7.25, 7.0, 6.75, 6.5, 6.25, 6.0, 5.75, 5.5, 5.25, 5.0, 4.9, 4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, 3.0, 2.9, 2.8, 2.7, 2.6., 2.5, 2.4, 2.3, 2.2, 2.1, 2.0, 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1, 1.0, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or 0.1, or any value or range of values therebetween in 0.01 increments; the apparatus is configured so that if the length of the first and second conduit sections is constant (they can be different consistent with the teachings above), and the cross- sectional area of the first conduit section is constant, and the type of therapeutic substance in the reservoir is the same, and there is no pressure gradient or pressure change relative to that which is the case for the comparison, and there is no temperature change, etc., the abovenoted release rates will be obtained for the different second cross-sectional area relative to that which would be the case if the second cross-sectional area is the same as the first cross- sectional area; the apparatus is configured so that the first conduit section has a first cross-sectional area normal to a direction of extension (molecule movement) that is at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, or 100, or any value or range of values therebetween in 1 increment times larger than a second cross-sectional area of a second conduit section, and the first conduit section has a first length that is larger than a second length of the second conduit section, the length of the second conduit section is such that a release rate of the therapeutic substance from the apparatus after Y days of release into a human is less than 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19.5, 19,

18.5, 18, 17.5, 17, 16.5, 16, 15.5, 15, 14.5, 14, 13.5, 13, 12.5, 12, 11.5, 11, 10.5, 10, 9.75, 9.5, 9.25, 9.0, 8.75, 8.5, 8.25, 8.0, 7.75, 7.5, 7.25, 7.0, 6.75, 6.5, 6.25, 6.0, 5.75, 5.5, 5.25, 5.0, 4.9, 4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, or 3.0, or any value or range of values therebetween in 0.01 increments of that which would be the case if the first length was 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30, or any value or range of values therebetween in 1 increment times the second length, all other things being equal; the cistern has an internal volume of at least an order of magnitude larger than that of the delivery tube; the delivery tube device has a first section having a first cross-sectional area normal to a direction of extension of the first section that is larger than a second cross-sectional area of a second section of the delivery tube device, the second cross-sectional area being normal to a direction of extension of the second section. In an embodiment, the first cross-sectional area is such that a release rate of the therapeutic substance from the apparatus after Y days of release into a human is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4,

2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.5, 4, 4.5, or 5 times, or any value or range of values therebetween in 0.01 increments that which would be the case if the first cross-sectional area was the same as the second cross-sectional area and/or no more than 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.5, 4, 4.5, 5, 5.5, or 6 times, or any value or range of values therebetween in 0.01 increments that which would be the case if the first cross- sectional area was the same as the second cross-sectional area, all other things being equal; the first cross-sectional area is such that a release rate of the therapeutic substance from the apparatus after Y days of release into a human is within 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30% or any value or range of values therebetween in 0.1% increments that which would be the case if the first cross- sectional area was the same as the second cross-sectional area, all other things being equal; the delivery tube device has a first section having a first length that is larger than a second length of a second section of the delivery tube device, and the first section has a first cross-sectional area normal to a direction of extension of the first section that is at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90 or 100 or any value or range of values therebetween in 1 increment times larger than a second cross-sectional area of the second section of the delivery tube device normal to a direction of extension of the second section. The length of the first section is at least four times larger than the length of the second section, and the length of the first section is such that a release rate of the therapeutic substance from the apparatus after seven days of release into a human is within 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1% or any value or range of values therebetween in 0.1% increments of that which would exist if the length of the first section was at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 or any value or range of values therebetween in 1 increment times larger than the length of the second section, all other things being equal; the delivery tube device has a first section having a first length that is larger than a second length of a second section of the delivery tube device; the first section has a first cross-sectional area normal to a direction of extension of the first section that is larger than a second cross-sectional area of the second section of the delivery tube device normal to a direction of extension of the second section; the second cross-sectional area is such that a release rate of the therapeutic substance at and/or after 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours of release into a human of the therapeutic substance from the apparatus is less than X% of that which would exist if the first cross-sectional area was the same as the second cross- sectional area; the second cross-sectional area is such that a release rate of the therapeutic substance at and/or after 12 hours of release into the human of the therapeutic substance from the apparatus is within X% of that which would exist if the second cross-sectional area was at least one of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 times smaller or 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 times larger; the outlet(s) can be located radially along the second tube; the outlets are sized and dimensioned to take into account that the concentration gradient changes along the length of the second tube; or the outlets provide a release rate that is within 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 8, 8, 7, 6, 5, 4, 3, 2, or 1%, or any value or range of values there between in 0.1 % increments between 2, 3,

4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 outlets or at least 50 or 60 or 70 or 80 or 90% of the outlets or all of the outlets that are axially spaced out from one another / provide for delivery at a given location that is the same for a comparable number of other locations.