Implantable biomedical microsystems

Implantable antennas have many important healthcare applications. One key aspect for a successful communication process from the implantable device to the on or off-body receiver is the accurate evaluation of the in-body path losses. These losses include, mainly, the attenuation and the reflection losses. Usually, normal incidence is considered for the calculation of the reflection losses between the tissue layers. However, this is not very accurate as the incident wave may be oblique at the boundary between the tissue layers. Therefore, in this paper the influence of oblique incidence on the reflection losses in a multilayer human body model is investigated. The reflection losses at the bone/muscle, muscle/fat and fat/skin layers are calculated at 403 MHz considering the cases of parallel and perpendicular polarization oblique incidence. The results are analyzed and compared with those of normal incidence. They show that larger losses are obtained at some angles for the case of oblique incidence compared to those for the case of normal incidence (about 241.16% larger reflection loss is obtained at an incident angle of 85° for the case of oblique incidence/perpendicular polarization at the fat/skin interface in comparison with that for normal incidence). Hence, it is very important to take the oblique incidence into consideration to provide more accurate in-body path loss calculations.

We present a high-energy local power supply based on a flexible and solid-state supercapacitor for miniature wireless implantable medical devices. Wireless radio-frequency (RF) powering recharges the supercapacitor through an antenna with an RF rectifier. A power management circuit for the super-capacitive system includes a boost converter to increase the breakdown voltage required for powering device circuits, and a parallel conventional capacitor as an intermediate power source to deliver current spikes during high current transients (e.g., wireless data transmission). The supercapacitor has an extremely high area capacitance of ~1.3 mF/mm2, and is in the novel form of a 100 μm-thick thin film with the merit of mechanical flexibility and a tailorable size down to 1 mm2 to meet various clinical dimension requirements. We experimentally demonstrate that after fully recharging the capacitor with an external RF powering source, the supercapacitor-based local power supply runs a full system for electromyogram (EMG) recording that consumes ~670 μW with wireless-data-transmission functionality for a period of ~1 s in the absence of additional RF powering. Since the quality of wireless powering for implantable devices is sensitive to the position of those devices within the RF electromagnetic field, this high-energy local power supply plays a crucial role in providing continuous and reliable power for medical device operations.

We present a contact lens-like platform that is wirelessly powered by an external coil embedded in eyeglasses via magnetic resonance coupling at 13.56 MHz. The platform is composed of a transparent parylene film as a host substrate, an embedded spiral inductor as a power receiving coil, and metal interconnects for additional electronics. A multilayer thin-film parylene packaging process is used to meet the form factor of a contact lens. A 36 μm-thick metal plating technique is employed on a parylene film to enhance the quality factor (Q) of the receiving coil (Q=27.3 at 13.56 MHz). The power transfer method and techniques to compensate for coil misalignment are demonstrated on a pig eye, achieving a power transfer efficiency of 17.5 % at a 20-mm powering distance. The effect of tissue on the coil and the power transfer efficiency is examined. The high power transfer efficiency along with the wearable prototype demonstrated herein make promising progress toward smart contact lens in ocular diagnostics.

This paper presents a novel framework on a remotely
powered implantable glucose monitoring system. The RF signal
interaction with the biological tissue under investigation has been
characterized. The implantable unit is remotely powered by an
external unit through inductive coupling. The novelty of this
work resides in the design of two efficient class E Power
Amplifiers (PAs) with power efficiency of 76% and 73% for the
external power unit and the implantable unit respectively. The
implantable wireless transmitter utilizes low power
communication protocol, Bluetooth low energy, to transmit the
measured glucose data to patient’s mobile phone or PDA.

— This paper reports on the design, implementation, and test of a stimulation back-end, for an implantable retinal prosthesis. In addition to traditional rectangular pulse shapes, the circuit features biphasic stimulation pulses with both rising and falling exponential shapes, whose time constants are digitally programmable. A class-B second generation current conveyor is used as a wide-swing, high-output-resistance stimulation current driver, delivering stimulation current pulses of up to ±96 µA to the target tissue. Duration of the generated current pulses is programmable within the range of 100 µs to 3 ms. Current-mode digital-to-analog converters (DACs) are used to program the amplitudes of the stimulation pulses. Fabricated using the IBM 130 nm process, the circuit consumes 1.5´1.5 mm 2 of silicon area. According to the measurements, the DACs exhibit DNL and INL of 0.23 LSB and 0.364 LSB, respectively. Experimental results indicate that the stimuli generator meets expected requirements when connected to electrode-tissue impedance of as high as 25 kΩ. Maximum power consumption of the proposed design is 3.4 mW when delivering biphasic rectangular pulses to the target load. A charge pump block is in charge of the upconversion of the standard 1.2-V supply voltage to ±3.3V.

In this paper, we present the design, fabrication and characterization of implantable coils, operating at 13.56 MHz ISM band for biomedical applications. Rogers RO 4003C substrate was used for the prototype of the implantable coil while Rogers RO 3850 flexible substrate was used for the external transmitter coil. The Inkjet masking technique was used for the patterning the planar coil on the flexible sub-strate. Wireless power transfer efficiency measurements were conducted in free space and water environments, varying the operating distance between the prototype coils from 5 mm to 20 mm, featuring transfer efficiencies upto 55% and 35% ,respectively.

Prototype fully biocompatible organic lightemitting diodes are investigated, with a view to creating a suitable and high-performance light source as a medical implant device. A selection of organic LED materials that have potential suitability for the biological environment are examined. First, the biocompatibility of selected OLED materials was evaluated by the study of cell adhesion and cytotoxicity of HeLa cells cultured on the candidate materials. Thus it was possible to design a device structure composed entirely of biocompatible materials. Second, the characterization of the electroluminescence properties of the prototype OLED is shown and its limitation evaluated. Third, the aqueous stability of the fully biocompatible light source is examined. There is strong evidence that fully biocompatible and stable light-emitting implant devices can be easily constructed. This is the first time a fully biocompatible organic light-emitting diode, albeit embryonic, is reported, with the hope that it may lead to further research to optimize the device performance. Some suggestions on suitable device properties towards in vivo transition are provided.

Implantable medical devices usually require a battery to operate and this can represent a severe restriction. In most cases, the implantable medical devices must be surgically replaced because of the dead batteries; therefore, the longevity of the whole implantable medical device is determined by the battery lifespan. For this reason, researchers have been studying energy harvesting techniques from the human body in order to obtain batteryless implantable medical devices. The human body is a rich source of energy and this energy can be harvested from body heat, breathing, arm motion, leg motion or the motion of other body parts produced during walking or any other activity. In particular, the main human-body energy sources are kinetic energy and thermal energy. This paper reviews the state-of-art in kinetic and thermoelectric energy harvesters for powering implantable medical devices. Kinetic energy harvesters are based on electromagnetic, electrostatic and piezoelectric conversion. The different energy harvesters are analyzed highlighting their sizes, energy or power they produce and their relative applications. As they must be implanted, energy harvesting devices must be limited in size, typically about 1 cm3. The available energy depends on human-body positions; therefore, some positions are more advantageous than others. For example, favorable positions for piezoelectric harvesters are hip, knee and ankle where forces are significant. The energy harvesters here reported produce a power between 6 nW and 7.2 mW; these values are comparable with the supply requirements of the most common implantable medical devices; this demonstrates that energy harvesting techniques is a valid solution to design batteryless implantable medical devices.

Optogenetics is a revolutionary neuromodulation technique to excite or inhibit the activity of the targeted neurons that express light-sensitive opsin proteins. Opto-neurostimulators as neural interface devices are significantly important for optogenetic applications in neuroscience and future clinical research. To date, a wide variety of optical stimulators have been developed and could be classified into two broad categories: single-channel and multi-channel stimulators. Although multi-channel opto-neurostimulators allow spatially controlled optical stimulation of cells, they require complicated fabrication procedures and might require specialized coupling strategies at the distal end of the optical source. As an alternative, single-channel opto-neurostimulators are gradually being prevalent in many applications for their simplicity, ease of use, and low cost. We have reviewed a variety of single-channel optogenetic neural stimulators that were developed in recent years, based on different light sources, material selection, and tethered or wireless systems. This paper accumulates and summarizes these single-channel opto-neurostimulators to provide a comprehensive outlook for the trend of this field.

We report a free-floating, wirelessly-powered, single channel opto neurostimulator consisting of a reflector-coupled microscale light emitting diode (µLED) and a mm-sized receiver (Rx) coil for untethered optogenetics neuromodulation. An optimized two-coil inductive link delivers over 4 mW instantaneous power at a low operating frequency to continuously drive the µLED while minimizing device invasiveness and tissue exposure to electromagnetic radiation. The reflector-coupled µLED enables significantly enhanced light intensity compared to a bare µLED. The temperature increase of the activated stimulators is <1 ºC, well below the safety limit of biomedical implants. In vivo experiment and histological analysis verify the efficacy of wireless optical stimulation in the rat cortex, using c-Fos as a report of light-evoked neuronal activity.

Electronic telemetry devices have enabled many novel and important data collection and experimental opportunities for difficult to observe species. Externally attached devices have limited retention and may affect thermoregulation, energetics, social and reproductive behavior, visibility, predation risk and entanglement. Internally placed, surgically implanted devices can mitigate some of these effects and may open additional experimental opportunities. How‑ ever, improper implementation can significantly affect animals and data. From a review of recent studies using fully implanted tags and studying their effects, we present 15 specific best practice recommendations for the use of such tags in pinnipeds. Recommendations address issues including device size, coating and sterilization, implantation surgery and effect assessment, within the framework of the Three R's: Reduction, Refinement, Replacement. While devel‑ oped for pinnipeds, these recommendations could apply to other aquatic mammals and vertebrates and to partially implanted or even external tags.

We report a monolithic wafer-level fabrication method for a hemispherical reflector coupled light-emitting-diode (LED) array using isotropic etching of silicon. These neural stimulators collect the backside as well as the front side emission of the µ-LEDs and thus provide higher intensity, which is imperative for opsin expressions in optogenetics experiments. Aluminum was used as the reflective layer and the planarization of polymer on the reflector cavity was done using polydimethylsiloxane (PDMS). The lateral and vertical profiles of silicon etching were measured and the light intensity increase due to the reflector was investigated. It was found that the intensity increases by a minimum of 49% and maximum of 65% when coupling a reflector with the µ-LEDs.

Beyond their biocompatibility, implanted electrodes for neuromuscular stimulation require careful consideration of conductivity, stability, and charge delivery capacity (CDC) to avoid irreversible faradaic reactions. To study these requirements, metal electrodes of platinum (Pt), gold (Au), and titanium (Ti) on flexible liquid crystal polymer are fabricated using electron-beam evaporation, and investigated by electrochemical impedance spectroscopy, cyclic voltammetry and atomic force microscopy. A theoretical model is used to explain the physical functionalities. Frequency dependent electrochemical interfacial impedance is observed. The impedance as well as long-term electrochemical stability is influenced by the surface roughness, reactivity and capacitance of the electrodes. Pt electrode offers lower impedance in the neuromuscular stimulation frequencies and higher CDC than that of Ti and Au, but is not as stable as Au electrode.

The stability of the laser bonded titanium coated glass/polyimide microjoints were studied in vivo by implanting on a rat brain surface for 10 days. In the current state, the strength of the joints were measured by a specially designed instrument called “pressure test” equipment where the samples were subjected to a variable pressure load (using high pressure nitrogen) controlled by a pressure regulator. The strength of the joints seems to degrade by about 28% as a result of soaking in rat brain. The bond degradation in rat brain implants is similar compared with those soaked in artificial cerebrospinal fluid (CSF) solution. Polyimide uptakes water through existing pores in it and also water gets in the joint region through the edges of the samples. Water might have caused oxidation of the chemical bonds which are thought to have formed by the laser fabrication process. A separate set of samples were created using same parameters for testing the hermeticity of the laser bonds. The samples were also exposed to rat brain CSF and were tested for hermiticity at the end of 10 days exposure time. It was observed that the implanted samples retained their hermeticity although the bond strength degraded by about 28%. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009