WO2025054129A1 - Multi-needle therapeutic delivery system for the heart - Google Patents

Abstract

A treatment assembly for delivering treatment to a chamber of the heart can include one or more flexible splines. A medial portion of the one or more flexible splines includes a plurality of needles, and distal portions of the one or more flexible splines include an elastic material and connect to form a distal cap, and proximal portions of the one or more flexible splines connect to form a proximal cap. One or more outer sheaths cover at least a portion of the medial portion of the one or more flexible splines including the plurality of needles of the one or more flexible splines. The one or more outer sheaths include an actuation wire and one or more treatment wires fluidly connect the plurality of needles on the one or more flexible splines to at least one treatment.

Description

MULTI-NEEDLE THERAPEUTIC DELIVERY SYSTEM FOR THE HEART

CROSS-REFERENCES TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63/581,397, filed September 8, 2023, which is incorporated herein by reference in its entirety and for all purposes.

TECHNICAL FIELD

[0002] Disclosed is a multi-needle therapeutic delivery system.

BACKGROUND

[0003] Cardiovascular diseases (CVDs) continue to be a leading cause of global mortality. Contributors towards CVD include acute myocardial infarctions (MI), cardiac fibrosis, and atrial fibrillation (AFib). Existing treatments for these and other heart conditions include medications and surgical procedures, but the treatments are limited in their ability to be delivered accurately, less invasively, and at therapeutic levels. For example, although cardiac regeneration studies involving stem cells, drugs, biomaterials, growth factors, or mRNA have demonstrated promising results, their translation into clinical practice has been slow. Additionally, while single-needle catheterization offers an interventional procedure without the need for open heart surgery and enables the safe delivery of these novel treatments, its drawback lies in the limited area that can be targeted with each actuation, as the delivery relies solely on a single needle. Further, singleneedle catheterization tools often rely on individual needle manipulation which poses challenges in terms of surgery duration.

SUMMARY

[0004] Disclosed are apparatus, systems, and methods for a multi-needle therapeutic delivery system. In some embodiments, the multi-needle therapeutic delivery system is applied to the heart using a catheter-based approach.

[0005] In some aspects, the techniques described herein relate to an apparatus for delivering treatment to a heart chamber, the apparatus including: a treatment assembly that includes one or more flexible splines, wherein the one or more flexible splines include a proximal portion, a medial portion, and a distal portion, wherein the medial portion of the one or more flexible splines includes a plurality of needles, and wherein the distal portion of the one or more flexible splines include an elastic material and connect to form a distal cap, and wherein the proximal portion of the one or more flexible splines connect to form a proximal cap; one or more outer sheaths cover at least a portion of the medial portion of the one or more flexible splines including the plurality of needles of the one or more flexible splines, wherein the one or more outer sheaths include an actuation wire; and one or more treatment wires fluidly connect the plurality of needles on the one or more flexible splines to at least one treatment.

[0006] In some aspects, the techniques described herein relate to an apparatus further including: a first tubular member having a lumen, a proximal end, and a distal end, wherein the treatment assembly is configured to be compressed and slide within the lumen of the first tubular member.

[0007] In some aspects, the techniques described herein relate to an apparatus, wherein the treatment assembly includes a shape memory material.

[0008] In some aspects, the techniques described herein relate to an apparatus, wherein the first tubular member is steerable.

[0009] In some aspects, the techniques described herein relate to an apparatus, wherein the elastic material is composed of one or more of nylons, nitrile rubbers, silicones, and/or thermoplastic polyurethane (TPU).

[0010] In some aspects, the techniques described herein relate to an apparatus, wherein the one or more outer sheaths are composed of one or more of nylons, polytetrafluoroethylene (PTFE), poly(ether-b-amide) (PEBAX), polyamide, silicones, polyvinyl chloride (PVC), and/or nitinol.

[0011] In some aspects, the techniques described herein relate to an apparatus, further including: a handle controller assembly positioned on the proximal end of the first tubular member, wherein the handle controller assembly includes at least one actuator configured to actuate at least one of the plurality of needles and/or actuate at least one or the one or more outer sheaths. [0012] In some aspects, the techniques described herein relate to an apparatus, wherein the handle controller assembly further includes an actuator configured to actuate the treatment into the plurality of needles from a treatment storage component.

[0013] In some aspects, the techniques described herein relate to an apparatus, wherein the treatment storage component includes a drug tube or a syringe.

[0014] In some aspects, the techniques described herein relate to an apparatus, wherein the lumen of the first tubular member has a diameter between about 2 to 5 millimeters.

[0015] In some aspects, the techniques described herein relate to an apparatus, wherein the one or more flexible splines include 2, 4, 6, 8, or 10 splines.

[0016] In some aspects, the techniques described herein relate to an apparatus, wherein the one or more flexible splines includes nitinol, a shape memory metal, a shape memory alloy, a shape memory polymer, a shape memory composite, and/or a shape memory hybrid.

[0017] In some aspects, the techniques described herein relate to an apparatus, wherein the one or more flexible splines are shaped as a semi-ellipse or a semi-circle.

[0018] In some aspects, the techniques described herein relate to an apparatus, wherein the one or more flexible splines have a major axis between about 80-100 mm and a semi-minor axis between about 21-25 mm.

[0019] In some aspects, the techniques described herein relate to an apparatus, wherein the one or more flexible splines have a diameter between about 0.15 mm and 0.35 mm.

[0020] In some aspects, the techniques described herein relate to an apparatus, wherein needles are unidirectionally oriented towards a direction outside of the treatment assembly.

[0021] In some aspects, the techniques described herein relate to an apparatus, wherein the plurality of needles form an angle between about two degrees and ninety degrees with their respective spline when the respective outer sheath is removed. [0022] In some aspects, the techniques described herein relate to an apparatus, wherein each spline among the one or more splines includes between about 1 to 50 needles.

[0023] In some aspects, the techniques described herein relate to an apparatus, wherein the plurality of needles are composed of stainless steel, titanium and/or nitinol.

[0024] In some aspects, the techniques described herein relate to an apparatus, wherein the plurality of needles are attached to the one or more flexible splines using an adhesive polymer.

[0025] In some aspects, the techniques described herein relate to an apparatus, wherein the plurality of needles have a flat distal end.

[0026] In some aspects, the techniques described herein relate to an apparatus, wherein the plurality of needles have an inner diameter between about 0.05 and 2.7 mm and an outer diameter between about 0.16 mm and 3.4 mm.

[0027] In some aspects, the techniques described herein relate to an apparatus, wherein the plurality of needles have a length of between about 0.5 mm to 6 mm.

[0028] In some aspects, the techniques described herein relate to an apparatus, wherein the plurality of needles are attached to the one or more flexible splines using a fluid-sealed joint with spring action.

[0029] In some aspects, the techniques described herein relate to an apparatus, wherein the at least one treatment includes one or more of a pharmaceutical agent, a drug, stem cells, biomaterials, growth factors, mRNA, and/or gene therapies.

[0030] In some aspects, the techniques described herein relate to a method that includes advancing a distal end of a tubular member to a chamber of the heart; sliding the treatment assembly through a lumen of the tubular member and such that the proximal cap of the treatment assembly aligns or passes the distal end of the tubular member; expanding the treatment assembly in the chamber of the heart such that the flexible splines contact one or more surfaces of the chamber of the heart; actuating the outer sheath to expose plurality of needles located on the flexible splines; and applying the treatment to one or more surfaces of the chamber of the heart via the plurality of needles. [0031] The details of one or more variations of the subject matter described herein are set forth in the accompanying drawings and the description below. Other features and advantages of the subject matter described herein will be apparent from the description and drawings, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The accompanying drawings, which are incorporated in and constitute a part of this specification, show certain aspects of the subject matter disclosed herein and, together with the description, help explain some of the principles associated with the disclosed implementations. In the drawings,

[0033] FIG. 1A provides a first view of a treatment assembly in accordance with some aspects of the present disclosure.

[0034] FIG. IB provides a second view of the treatment assembly in accordance with some aspects of the present disclosure.

[0035] FIG. 1C provides a third view of the treatment assembly in accordance with some aspects of the present disclosure.

[0036] FIG. 2 illustrates an example of a proximal cap of a treatment assembly in accordance with some aspects of the present disclosure.

[0037] FIG. 3 illustrates an example of a distal cap of a treatment assembly in accordance with some aspects of the present disclosure.

[0038] FIG. 4 illustrates an example of a distal cap of a treatment assembly in accordance with some aspects of the present disclosure.

[0039] FIG. 5 illustrates an example of a proximal cap of a treatment assembly in accordance with some aspects of the present disclosure.

[0040] FIGS. 6A-6B illustrate an example of a needle assembly of a treatment assembly in accordance with some aspects of the present disclosure. [0041] FIGS. 7A-7D illustrate an example of a needle assembly of a treatment assembly in accordance with some aspects of the present disclosure.

[0042] FIG. 8 provides a flow-chart for treating a patient using a treatment assembly in accordance with some aspects of the present disclosure.

[0043] FIG. 9 provides an illustration of a process for treating a patient using the treatment assembly described herein in accordance with some aspects of the present disclosure.

[0044] FIG. 10A-10C provide an illustration of an experimental setup for a treatment assembly in accordance with some aspects of the present disclosure.

[0045] FIG. 11 illustrates experimental results for a treatment assembly in accordance with some aspects of the present disclosure.

[0046] FIGS. 12A-12C illustrate experimental results for a treatment assembly in accordance with some aspects of the present disclosure.

DETAILED DESCRIPTION

[0047] A multi-needle therapeutic delivery system can be used in the heart to provide treatment for cardiovascular disease (CVD) including acute myocardial infarctions (MI), cardiac fibrosis, and atrial fibrillation (AFib), and the like. As discussed herein, the multi-needle therapeutic device can include a treatment assembly that includes one or more flexible splines including a plurality of needles. The multi-needle therapeutic device can be advanced to a target area such as a chamber of the heart such that a treatment can be applied. Treatments can include, but are not limited to, stem cells, drugs, biomaterials, growth factors, or mRNA. The multi-needle therapeutic delivery system can provide improved accuracy for targeting therapeutic treatments that can be delivered less invasively to a patient.

[0048] FIGS. 1A-1C provides various views of an apparatus for delivering treatment to a heart chamber. FIG. 1A provides a first isometric view of a treatment assembly 100. FIG. IB provides a second view of the treatment assembly 100. FIG. 1C provides a third view of a section of the treatment assembly 100. [0049] Treatment assembly 100 includes a plurality of flexible splines 115. Each of the flexible splines 115 can include a proximal portion 115a, a medial portion 115b, and a distal portion 115c. One or more needles 111 can be located among the medial portion 115b of the flexible spline 115. The distal portions 115c of the flexible splines can connect to engage with a distal cap 113. The proximal portions 115a of the flexible splines can connect to engage with a proximal cap 103.

[0050] Each of the flexible splines 115 can include an outer sheath 107 that is configured to cover at least a portion of the medial portion 115b of the flexible spline. The outer sheath 107 can be positioned to cover the plurality of needles 111 and can include an actuation wire 109. A treatment wire 105 can be fluidly connected to the plurality of needles 111 and be configured to deliver a treatment to a target area, such as a heart chamber. The treatment assembly 100 can be advanced through a catheter device 101 that is positioned about the target area.

[0051] A catheter device 101 can be composed of a first tubular member having a lumen, a proximal end, and a distal end. The treatment assembly 100 can be configured to be compressed and slide within the lumen of the first tubular member until it is deployed in a target area, such as a chamber of the heart. The catheter device 101 can be steerable, in that a medical provider can advance and move the catheter device as needed. The catheter device 101 can have any suitable dimension for holding the treatment assembly. For example, in some embodiments, the lumen of the first tubular member can have a diameter between about 2 to 5 millimeters.

[0052] The catheter device 101 can include a handle controller assembly that is positioned on an opposite end of the treatment assembly. The handle controller assembly can include at least one actuator that is configured to control the operation of the needles and/or outer sheaths of the treatment assembly. In some embodiments, the handle control assembly can also position and steer the catheter device 101, move the treatment assembly 100 in the lumen of the catheter device 101, or move the treatment assembly 100 with respect to the catheter device 101.

[0053] In some embodiments, the catheter device 101 can be guided into position by a guiding catheter having an inner and outer diameter of about 4mm, and about 5mm, respectively. For example, in some embodiments a 10.5Fr device catheter and a 12Fr guiding catheter can be used. [0054] The treatment assembly 100 can include a plurality of flexible splines 115. In the illustrated example, the treatment assembly 100 includes four flexible splines 115. In some embodiments, the treatment assembly can include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 splines. In some embodiments, the splines can be flexible in that their shape can be altered. For example, the splines can have a first, compressed shape when the treatment assembly is in the lumen of the catheter and have a second, expanded shape when the treatment assembly is deployed in a target area such as a chamber of the heart. Flexible splines 115 can be composed of one or more of nitinol, a shape memory metal, a shape memory alloy, a shape memory polymer, a shape memory composite, and/or a shape memory hybrid. As used herein, “flexible” may refer to the shapememory properties of the splines. Flexible splines 115 can have shape-memory properties in that they can be deformed or modified and then return to a pre-deformed configuration. In some embodiments, the flexible splines can be biased towards their respective shapes in an expanded configuration such as those illustrated in FIGS. 1A-1C. Accordingly, the flexible splines can be biased to revert to their expanded configuration when the treatment assembly 100 is advanced through the catheter device 101 and deployed and the compressive pressure applied by the catheter device 101 to the treatment assembly is removed. Flexible splines 115 can be shaped to revert to a substantially semi-elliptical shape. The flexible splines can have any suitable length and curvature for engaging with a target area. For example, when the target area is a chamber of the heart, the flexible spline can be configured to have a major axis between about 80 and 100 mm and a semi-major axis between about 21-25 mm. In some embodiments, the flexible splines can have a diameter between about 0.15 mm and 0.35 mm.

[0055] As illustrated in FIGS. 1 A-1C, a plurality of flexible splines can interface with a proximal cap at a first end and a distal cap at a second end. A basket-like structure results from the plurality of flexible splines being connected at a proximal cap and at a distal cap while having a semielliptical shape. In some embodiments, the basket-like structure can be sized to fit a target area for delivery of a treatment. For example, the basket-like structure can be sized to fit a chamber of the heart. Indeed, for a treatment assembly configured for treating the left or right ventricle, the basket assembly may be approximately 55 to 65 mm in diameter. For a treatment assembly configured for treating the left or right atrium, the basket assembly may be approximately 45 to 55 mm in diameter. [0056] As shown, the flexible splines can include a proximal portion 115a positioned adjacent to the proximal cap 103, a medial portion 115b, and a distal portion 115c positioned adjacent to the distal cap 113. The medial portion 115b of the flexible splines can include one or more needles 111. Needles 111 can be configured for delivering a treatment to a target area. One or more needles 111 can be spaced along a medial portion 115b of the flexible spline. Spacing can be uniform or varied between adjacent needles. Additionally, needle placement and spacing can be uniform or varied across the flexible splines. A flexible spline can include any number of needles 111. For example, a flexible spline can include 1 needle, 2 needles, 3 needles,.. . 50 needles, and the like.

[0057] As illustrated in FIGS. 1 A-1C, the needles 111 can be unidirectionally oriented towards a direction outside of the treatment assembly. For example, the needles 111 can be positioned and oriented away from a center of the basket.

[0058] In some embodiments, the needles 111 can be composed of stainless steel, nitinol, and/or titanium. In some embodiments, the needles 111 can have a diameter between about 0.18 and 0.26 mm. In some embodiments, the needles 111 can have an inner diameter between about 0.05 and 2.7 mm and an outer diameter between about 0.16 mm and 3.4 mm. In some embodiments, the needles 111 can have a length between about 2 and 4 mm. In some embodiments, the needles can have a flat distal end that is configured to elude a treatment. A second end of the needle can be configured to be fluidly connected with a treatment wire. For example, the treatment wire can be in fluid connection with one or more treatment storage compartments. Treatment wires can also be referred to as a drug or therapeutic delivery channel or tube.

[0059] As will be discussed further below, various methods for integrating a needle with the flexible spline can be used. In some embodiments, a needle may form an angle between about thirty and forty degrees with their respective spline, when an outer sheath is removed. In some embodiments, the needle 111 connects to a needle assembly backing 117.

[0060] Various configurations for needle assemblies are discussed below.

[0061] An outer sheath 107 can have a substantially cylindrical shape and surround a flexible spline 115 along a longitudinal portion of the flexible spline. For example, an outer sheath 107 can be configured to cover at least a medial portion 115b of the flexible spline and cover the needles 111 positioned on the flexible spline 115. An outer sheath 107 can be composed of one or more of nylons, polytetrafluoroethylene (PTFE), poly(ether-b-amide) (PEBAX), polyamide, silicones, polyvinyl chloride (PVC), and/or nitinol.

[0062] The outer sheath 107 can be actuated via one or more actuation wires 109. An actuation wire 109a, 109b can be composed of an elastic material. For example, the elastic material can include one or more of nylons, nitinol, nitrile rubbers, silicones, and/or thermoplastic polyurethane (TPU). In some embodiments the elastic material can be composed of nitinol strings that thread together to form a unit.

[0063] In some embodiments, a first actuation wire 109a has a first end that engages with a proximal cap and a second end that engages with the outer sheath. A second actuation wire 109b has a first end that engages with a distal cap and a second end that engages with the outer sheath. Actuation wires 109, 109a, 109b can be connected to the outer sheath using Loctite plastic bonder and the like. As will be discussed further below, one or more actuation wires can be configured to translate the outer sheath 107 with respect to the flexible spline 115, such that one or more needles 111 can be exposed.

[0064] As discussed above, a proximal cap 103 can include one or more recesses configured to engage with and/or attach to the treatment wires, flexible splines, and actuation wires. The proximal cap 103 can be composed of bio-compatible polymers, metals, and the like. The proximal cap can have a diameter smaller than the interior diameter of the lumen of the delivery catheter, such that the basket fits within the catheter. In some embodiments, the plurality of treatment wires that are in the treatment assembly 100 can connect to form a single treatment wire that is fluidly coupled to a treatment storage compartment. For example, a treatment storage component can include a syringe that pushes medications through a single treatment wire that spans the length of the catheter device 101 and then provides the treatment fluid to the plurality of treatment wires 105 that engage with the plurality of needles.

[0065] Similarly, the distal cap 113 also includes one or more recesses configured to engage with and/or attach to the treatment wires, flexible splines, and actuation wires. The distal cap 113 can be composed of bio-compatible polymers, metals, and the like. In some embodiments, the actuation wires engaging between the outer sheath and the distal cap can be composed of a material having elastic properties. In some embodiments, the treatment wires, flexible splines and actuation wires can be secured to the distal cap using an adhesive.

[0066] For example, in some embodiments, the actuation wire includes a first actuation wire that connects between the proximal cap and the outer sheath and a second actuation wire that connects between the distal cap and the outer sheath. In some embodiments the material for the actuation wire between the distal cap and outer sheath can be composed of an elastic material. For example, the material for the actuation wire between the distal cap and the outer sheath can be more elastic than between the proximal cap and the outer sheath. Examples of materials used for the elastic actuation wire can include, but are not limited to, nitrile butyl rubber (NBR/NR) configured to have a greater than 500% elongation at break and a tensile strength above about 30 MPa.

[0067] In some embodiments, proximal cap 103 and distal cap 113 can be sized to be between about 2.5 mm and 3mm in diameter.

[0068] FIG. 2 provides an illustration of a proximal cap. Proximal cap 203 (analogous to proximal cap 103 in FIGS. 1A-1C) includes a plurality of recesses 204 configured to engage with and/or attach to treatment wires 205, flexible splines 215, and/or actuation wires.

[0069] As shown in FIG. 2 the proximal cap 203 can be located in proximity of the distal end of the catheter 201. The proximal cap 203 can include a plurality of recesses 204 sized to fit and receive the respective treatment wires 205, flexible splines 215, and/or actuation wires.

[0070] FIG. 3 illustrates a distal cap 303. As illustrated by some embodiments, a first side 306 of the distal cap 303 can be configured to face the basket assembly. The first side 306 can include a plurality of recesses 304 configured to engage with a treatment wire and/or flexible spline. In some embodiments, the recesses 304 can be configured to traverse a portion of the distal cap 303 but not the entire depth of the distal cap 303. The recesses 304 can be connected to a channel 310 positioned on a second side 312 of the proximal cap. In the illustrated embodiment, treatment wires that engage with the recesses 304 on the first side 306 can be terminated at the distal cap 303. Channel 310 can be an access hole configured to introduce and Loctite glue and the like to close the distal cap 303. As illustrated in FIG. 3, the distal cap 303 can also include a groove 308 configured to attach and engage with a needle deployment string. As shown, in some embodiments, the groove 308 can be substantially a half-cylindrical shape and configured to form a cut-out on a surface of the distal cap 303. Alternative shapes and configurations for recesses 304, channels 310, and grooves 308 are envisioned.

[0071] FIG. 4 provides an illustrations of a distal caps. Distal cap 413 (analogous to cap 113 in FIGS. 1A-1C) includes a plurality of recesses 404 configured to engage with and/or attach to treatment wires 405, flexible splines 415, and/or actuation wires 409.

[0072] FIG. 5 provides an illustration of a proximal cap. Proximal cap 513 includes a plurality of recesses 504 for engaging with and/or attach to treatment wires, flexible splines, and/or actuation wires. As illustrated in FIG. 5, the recesses 504 can span a portion of the depth of the proximal cap 513 and have an interior surface. The proximal cap 513 can include any number of recesses 504 and may vary based on the number of splines in the treatment assembly.

[0073] A basket assembly composed of flexible splines, treatment wires, and actuation wires can span the distance between the proximal cap and the distal cap.

[0074] FIGS. 6A-6B illustrate an example of a needle assembly in accordance with needle 111 of FIGS. 1A-1C. As discussed above, a plurality of needles can be spaced along a medial portion of a flexible splines. The needles can be configured to elude a drug or other treatment to a target area. In some embodiments, the needles can be covered by an outer sheath prior to when they are deployed. In some embodiments, the needles 111 can be deployed simultaneously. In some embodiments the needles 111 can be deployed individually.

[0075] FIGS. 6A-6B provide an illustration of a design for deploying and retracting the needles simultaneously. As illustrated a needle 601 can be connected to a flexible spline and the treatment wire 605 using a connector and/or pulley-assembly 603. The pulley assembly 603 can include a first element 604 that modulates the orientation of the needle 601. The pulley assembly 603 can include a second element 606 that is engaged with the actuation wire 607. The first element 604 can include a first ring that is fixed on the needle 601. The second element 606 can include of a second ring that is fixed on the actuation wire 607. The first element 604 and the second element 606 can be connected such that there is one degree of freedom and when the wire 607 is pulled the second element 606 will move the first element 604 such that the needle 601 is raised. Subsequently, a treatment can flow through the treatment wire 611 , through the needle 601, and be delivered to a target area such as the heart wall. A drug channel 609 can fluidly connect the base of the needle 601 to the treatment wire 611. In this manner, the plurality of needles can be actuated at the same time by the actuation wire. Thus, treatment can be delivered to multiple sites such as along the heart wall, simultaneously.

[0076] FIGS. 7A-7D illustrate a mechanism for the needle assembly in accordance with needle 111 of FIGS. 1A-1C. Illustrated in FIGS. 7A-7D is a needle assembly that uses two telescoping tubes with multiple needles that are controlled by a slider. As shown, the needles can be deployed and retracted out of and into the outer sheath. The illustrated needle assembly includes two telescoping tubes with angled holes or notches. The angled holes or notches are configured to allow a needle to pass through at an angle. Movement of the tubes can be moderated by an actuation wire connected to a slider in a handle assembly. In some embodiments, the needles can be attached to the treatment wire at an angle between about 2 degrees and 90 degrees. In some embodiments, the needles can be attached to the treatment wire at an angle between about 20 degrees and 40 degrees. An outer sheath can translate with respect to an inner sheath that is attached to the needle. As the outer sheath moves, the needle tip is exposed. In some embodiments, the outer sheath can be positioned over the needles to isolate the needle tips from the environment. Accordingly, the outer sheath can be engaged with an actuation wire. Pulling actuation wire may cause the outer sheath the reversibly translate with respect to the needle and inner sheath. The outer sheath can include a plurality of notches aligned with the respective needles.

[0077] FIG. 7A provides an schematic diagram for a needle assembly. As shown a needle 701 can be embedded within an inner sheath 703. The needle 701 can have a length of about 2 - 4.5 mm and can reach a height of about 0.5 to 2 mm from the inner sheath 703. The needle 701 can form a 2 degree to 90 degree angle with the drug wire 705.

[0078] FIG. 7B provides an illustration of the needle assembly. As shown, in a deployed configuration, the needle 701 can form an angle with the flexible spline. The needle 701 engages with an inner sheath 703 and can be attached with an adhesive. The needle protrudes through a notch 707 in the outer sheath 709. The adhesive can include a biocompatible adhesive or other type of mechanism. Examples of adhesives include Loctite Plastic Bonder and other types of medical-grade materials may be used as well. In some embodiments, the notch can have an opening between about 0.15 - 0.275 mm. The notch can be any suitable shape to accommodate a needle. For example, the notch can be sized to accommodate a needle between 30 - 34 Gauge. An actuation wire engages with the other sheath only. The outer sheath can be attached to the actuation wire using loctite plastic bonder or a similar adhesive.

[0079] FIG. 7C illustrates the needle assembly in a first deployed configuration, where the needle 701 is deployed or in a position to engage with a target area. The needle 701 is attached to an inner sheath 703 using an adhesive and a portion of the needle 701 traverses the inner sheath 703 and engages with a channel fluidly connected to the treatment wire.

[0080] As shown in FIG. 7D, the inner sheath 703 can be moved with respect to the outer sheath 709. For example, the inner sheath 703 can be translated with respect to the outer sheath 709 (see arrow A), such that the needles are retracted from the position illustrated in FIG. 7C to the position shown in FIG. 7D.

[0081] In some embodiments, the needle assembly can be attached to the treatment wire using a fluid-sealed joint with spring action. The fluid-sealed joint can be biased such that the needle is radially released as the notch in the outer sheath aligns with a tip of the needle. In some embodiments, a thin layer of glue is applied to the outside of the drug delivery tube or treatment wire to attach the needle to the drug delivery tube or treatment wire at the specified angle.

[0082] In some embodiments, saline can be flushed between the inner sheath and the drug tube to prevent the backflow of blood.

[0083] Inter-needle spacing, or how far apart needles should be positioned on the flexible spline can be dependent on the treatment type. For example, inter-needle spacing for delivering a gene therapeutic may be different from inter-needle spacing for a mRNA treatment and the like. In some embodiments, the appropriate inter-needle spacing can be determined using a model that seeds cardiomyocytes on a gel, with similar stiffness as the target heart region, and then injecting the gene into the seeded cardiomyocytes. The detected depth of the gene inside the cell can guide inter-needle spacing and design. [0084] In some embodiments, the needles are preferably smooth and reliably deploy at an angle of 2 degrees to 90 degrees and retract to a position where they lie flat within the inner catheter sheath. The needles may be sized to penetrate the heart tissue without protruding through it, ideally reaching a depth of 40-60% of the heart wall’s thickness. This ensures accurate delivery while minimizing the risk of complications. Flow testing may be used to ensure consistent and reliable drug administration. Needles can have a gauge between about 14G to 35G, which may depend on the application or type of treatment being applied.

[0085] FIG. 8 provides a flow-chart for treating a patient using a treatment assembly. As illustrated in FIG. 8, a process 800 for treating a patient using a treatment assembly can include advancing the distal end of the tubular member to a chamber of the heart 801, sliding the treatment assembly through the lumen of the tubular member such that the proximal cap of the treatment assembly aligns or passes the distal end of the tubular member 803, expanding the treatment assembly in the chamber of the heart such that the flexible splines contact one or more surfaces of the chamber of the heart 805, actuating the outer sheath to expose plurality of needles located on the flexible splines 807, and applying the treatment to one or more surfaces of the chamber of the heart via the plurality of needles 809.

[0086] After a treatment is finished being delivered, the treatment assembly can be retracted into the catheter. Concurrently, the actuation wire can be pulled in the opposite direction so that the needle is returned to a substantially horizontal position. In some embodiments, the actuation wire can be relaxed for retracting the needles to their horizontal position.

[0087] FIG. 9 provides an illustration of a process for treating a patient using the treatment assembly described herein. As shown in FIG. 9, in a first step 901 a treatment assembly can be held by a catheter 911. The catheter 911 can be advanced to a target area such as a chamber of the heart. As shown in step 903, the treatment assembly 913 can be deployed from the catheter 911. As shown in step 905, the basket-like structure can be expanded such that the flexible splines are moved way from each other. As shown in step 907, the needles 915 can be deployed after the treatment assembly 913 is expanded.

[0088] The catheter such as catheter 911 can be guided into the intended position inside the heart so that a clinician can control the needle deployment mechanism. In some embodiments, a clinician can have access to a dial that is directly connected to the outer sheaths via actuation wires, allowing for a simple and effective method to extend and retract the device and the needles separately.

[0089] The multi-needle therapeutic device described herein can be used to deliver treatments such as pharmaceutical therapeutics, gene therapy, stem cells, drugs, biomaterials, growth factors, mRNA and the like.

[0090] The multi-needle therapeutic device can take treatments stored in a treatment storage component and provide them to a target area via needles. For example, the treatment storage component can include a drug tube or a syringe. In some embodiments, the treatment storage component is configured to remain outside of a patient and further configured to be fluidly connected via one or more treatment wires that run the length of the catheter and treatment assembly. In some embodiments, the treatment storage component is a drug tube that is configured to be embedded within a catheter or within the basket-frame of the treatment assembly.

[0091] The treatment storage component can include a drug tube with a diameter between about 0.35-0.8 mm and outer diameter of 0.45-1 mm and the like.

[0092] In some implementations, the multi-needle therapeutic delivery system can provide improved administration of pharmaceutical medications, such as those for treating cardiovascular disease. A particular challenge associated with the administration of pharmaceutical medications for treating cardiovascular disease lies in their administration. Typically taken orally or injected into the bloodstream, these drugs circulate throughout the body before reaching the heart. Accordingly, to reach therapeutic amounts of treatment, it is often necessary to administer high doses, which in turn can be toxic to other organs such as the liver. Accordingly, the multi-needle therapeutic delivery system described herein can advantageously allow for the targeted delivery of pharmaceutical medications to the precise locations they are needed and at doses that are nontoxic.

[0093] Additionally, while advancements in regenerative therapeutics, including stem cells, biomaterials, growth factors, and mRNA, offer potential solutions to cardiovascular disease, the translation of research findings into clinical practice has encountered significant delays. While myocardial delivery using percutaneous catheter systems has emerged as a promising approach to locally deliver therapeutic agents directly into the myocardium because these methods minimize invasiveness, reduces cost, and allows for multiple administrations of therapy, conventional systems are restricted to delivering to a specific site at a time. Further, this approach faces another challenge in the form of a restricted area that can be targeted with each injection. Since each administration relies on a single needle, surgeons must carefully steer and maneuver it to reach the desired locations within the heart chamber. As a result, performing multiple injections becomes a time-consuming process, significantly prolonging the overall duration of the surgery. Therefore, while the single-needle catheterization tool holds promise for interventional procedures without the need for open-heart surgery and enables the safe delivery of novel treatments, its reliance on individual needle manipulation poses challenges in terms of surgical consistency and time management. By contrast, advantageously the disclosed treatment assembly is able to provide muti-site delivery of a treatment.

[0094] Additionally, while prior treatments for cardiac disease have used oral medication. The use of oral medication only helps prevent heart-related symptoms, such as a stroke, but does not treat the disease itself. Patient compliance with daily medication eventually arises as an issue as well. The described approach may reduce procedure time, create minimal tissue scarring, and deliver therapeutics to a larger surface area of the heart wall simultaneously.

[0095] Prior treatments for cardiac disease have also used ablation as a treatment, which involves inducing scarring in the heart to disrupt irregular signals. However, some ablation techniques involve open heart surgery and are slow, complex, and invasive procedures. Additionally, even catheter based techniques for ablation include the risk of heart scarring, recurrence of atrial fibrillation, and/or radiation exposure.

[0096] Additionally, the disclosed multi-needle therapeutic delivery system utilizes a catheterbased approach similar to cardiac ablation, cardiac mapping, and single-needle intramyocardial delivery. Accordingly, the technical adjustments needed for physicians to utilize the disclosed multi-needle therapeutic delivery system will be minimal and easily adaptable.

[0097] Additionally, while the disclosed systems can deliver therapeutics to the entire heart chamber with only a single injection, prior devices would need many injections to achieve the same coverage. Additionally, each procedure using a single-needle delivery requires cardiac mapping to locate where in the chamber the disease is located. Since the disclosed system treats the entire heart chamber, cardiac mapping is unnecessary which reduces the procedure time by at least 50% and simplifies the procedure for physicians, all while delivering better treatment options.

[0098] In some embodiments, the disclosed systems can be used to provide cell delivery, cell therapy, gene therapy, drug delivery, cardiac mapping, and regenerative medicine for one or more chambers of the heart.

EXPERIMENTAL DATA AND RESULTS

Experiment #1 : Needle Force

[0099] In accordance with the treatment assembly described herein, experiments were performed to verify needle puncture properties and/or flow of treatment.

[0100] FIG. 10A provides an illustration of a schematic setup in which two syringes 1001 are fluidly connected with a spline having needles 1003. A first syringe includes saline. A second syringe contains a drug with a color dye. The illustrated setup is a model with lOx size components when compared to a clinical embodiment. A surface 1005 composed of Oomoo-25 having a modulus of 100 psi which lies between the modulus of a healthy and diseased heart at a 10X scale that is 75-145 psi was used to simulate the mechanical properties of the myocardium. The insertion of the needles into Oomoo 25, which is a tin-cured silicone rubber that has a relatively high stiffness that mimics the myocardium tissue, and to measure the flow of liquids through the needles for uniform distribution was studied.

[0101] Additionally, the needle and inner sheath connection were tested by forcefully pulling the needles out of the inner sheath to check the adhesive connection strength. The test was performed 10 times for each of the three needles attached, and they all passed without any detachment. This device was then tested to verify its ability to successfully puncture into the tissue. The needles were deployed from the inner sheath into the artificial myocardium. Once inserted, the artificial myocardium was manually palpitated to check if the needles moved out of the artificial tissue. This test was repeated 10 times and the needle was able to puncture into the test specimen and stay stable each time. [0102] Moreover, the needle’s insertion and retraction capability was tested. The needle was deployed out of the inner sheath, inserted into the Oomoo 25, and then retracted back into the sheath 10 times. The device passed the test each time. Finally, the device’s ability to deliver the drug was tested. The device was set up in a deployed state, i.e. the needles were out of the inner sheath. A 30 mL syringe filled with test liquid was connected to the user-end of the device. The liquid was ejected from the syringe and visually monitored. No leaks were detected in the device throughout the consistent and continuous flow of test liquid from the needles.

[0103] FIGS. 10B and 10C display an example of a general test setup of the device. As shown, all three needles experienced a consistent level of flow output. Needle stability, puncturing ability, insertion/retraction, and drug flow was shown.

[0104] Experiment #2 - Verification of Needle Spacing

[0105] FIG. 11 illustrates dye diffusion testing used to compare needle gauges (e.g., 30G, 32G) and determine needle spacing. Dye was injected into agarose gel having various viscosities modeling heart health. For example, agarose at 1% can model a spongy heart. Agarose at 2% can model a healthy heart. Agarose at 3% can model a stiff heart. Images of the agarose gel were taken at various time points 1100. Images were processed to view the diffusion area by applying a spectrum filter 1 101. The resultant diffusion area and radii were used to determine needle spacing on each flexible spline.

[0106] Experiment #3 - Diffusion Gradient

[0107] FIGS. 12A illustrates the results from multi-needle and single-needle tests performed on porcine heart tissue from the right atrium and right ventricle. In some embodiments, the experimental data can be used to determine how many needles are positioned on an flexible splines so as to provide treatment to the entire heart chamber. A flexible spline with 8 needles was tested on a piece of dead ventricle and atrial tissue from a porcine animal to measure diffusion of the dye into the myocardium, as illustrated in FIG. 12A.

[0108] Prior to the multi-needle experiment, single-needle tests were performed to help determine the spacing between each needle using dye diffusion into the myocardium using a 30G needle as illustrated in FIG. 12B and using a 32G needle as illustrated in FIG. 12C. Results from the experiment are shown in FIGS. 12B and 12C. FIG. 12B illustrates the diffusion area for a 30 Gauge needle over time for a 1% agarose gel, a 2% agarose gel, and a 3% agarose gel. FIG. 12C illustrates the diffusion area for a 32 Gauge needle over time for a 1% agarose gel, a 2% agarose gel, and a 3% agarose gel. Based on the diffusion area, the inter-needle distance can be determined. For example, for a 32 Gauge needle, it was determined that an inter-needle distance of 4.2 mm is favored to provide the suitable diffusion profile. The experiments illustrated in FIGS. 12A-12C can be used to determine the number of needles required on each arm, the fluid flow, and the diffusion gradient of the dye delivered. The data illustrated in FIG. 12A for the multi-needle test data, indicates a dye diffusion limit is at around 20-30 minutes and diffused to a surface area of about 4mm². As the upper limit of the right atrial heart tissue’s surface area is 180mm², it is indicated that approximately 60 needles can be used to cover the entire heart chamber. Accordingly, at a spacing of 4.2mm between each needle (as determined from the single-needle testing data in FIGS. 12B and 12C), and a treatment assembly including six flexible splines may need approximately ten needles on each spline.

[0109] The right ventricle may utilize a different number of flexible splines and/or needles due to the different topographical structure of the tissue of the right ventricle with respect to the right atrium.

[0110] In the descriptions above and in the claims, phrases such as “at least one of’ or “one or more of’ may occur followed by a conjunctive list of elements or features. The term “and/or” may also occur in a list of two or more elements or features. Unless otherwise implicitly or explicitly contradicted by the context in which it is used, such a phrase is intended to mean any of the listed elements or features individually or any of the recited elements or features in combination with any of the other recited elements or features. For example, the phrases “at least one of A and B;” “one or more of A and B;” and “A and/or B” are each intended to mean “A alone, B alone, or A and B together.” A similar interpretation is also intended for lists including three or more items. For example, the phrases “at least one of A, B, and C;” “one or more of A, B, and C;” and “A, B, and/or C” are each intended to mean “A alone, B alone, C alone, A and B together, A and C together, B and C together, or A and B and C together.” Use of the term “based on,” above and in the claims is intended to mean, “based at least in part on,” such that an unrecited feature or element is also permissible. [0111] The subject matter described herein can be embodied in systems, apparatus, methods, and/or articles depending on the desired configuration. The implementations set forth in the foregoing description do not represent all implementations consistent with the subject matter described herein. Instead, they are merely some examples consistent with aspects related to the described subject matter. Although a few variations have been described in detail above, other modifications or additions are possible. In particular, further features and/or variations can be provided in addition to those set forth herein. For example, the implementations described above can be directed to various combinations and subcombinations of the disclosed features and/or combinations and subcombinations of several further features disclosed above. In addition, the logic flows depicted in the accompanying figures and/or described herein do not necessarily require the particular order shown, or sequential order, to achieve desirable results. For example, the logic flows may include different and/or additional operations than shown without departing from the scope of the present disclosure. One or more operations of the logic flows may be repeated and/or omitted without departing from the scope of the present disclosure. Other implementations may be within the scope of the following claims.

Claims

CLAIMS We claim:

1. An apparatus for delivering treatment to a heart chamber, the apparatus comprising: a treatment assembly comprising: one or more flexible splines, wherein the one or more flexible splines comprise a proximal portion, a medial portion, and a distal portion, wherein the medial portion of the one or more flexible splines comprises a plurality of needles, and wherein the distal portion of the one or more flexible splines comprise an elastic material and connect to form a distal cap, and wherein the proximal portion of the one or more flexible splines connect to form a proximal cap; one or more outer sheaths cover at least a portion of the medial portion of the one or more flexible splines including the plurality of needles of the one or more flexible splines, wherein the one or more outer sheaths comprise an actuation wire; and one or more treatment wires fluidly connect the plurality of needles on the one or more flexible splines to at least one treatment.

2. The apparatus of claim 1 further comprising: a first tubular member having a lumen, a proximal end, and a distal end, wherein the treatment assembly is configured to be compressed and slide within the lumen of the first tubular member.

3. The apparatus of claim 1, wherein the treatment assembly comprises a shape memory material.

4. The apparatus of claim 2, wherein the first tubular member is steerable.

5. The apparatus of claim 1, wherein the elastic material is composed of one or more of nylons, nitrile rubbers, silicones, nitinol, and/or thermoplastic polyurethane (TPU).

6. The apparatus of claim 1, wherein the one or more outer sheaths are composed of one or more of nylons, polytetrafluoroethylene (PTFE), poly(ether-b-amide) (PEBAX), polyamide, silicones, polyvinyl chloride (PVC), and/or nitinol.

7. The apparatus of claim 2, further comprising: a handle controller assembly positioned on the proximal end of the first tubular member, wherein the handle controller assembly comprises at least one actuator configured to actuate at least one of the plurality of needles and/or actuate at least one or the one or more outer sheaths.

8. The apparatus of claim 7, wherein the handle controller assembly further comprises an actuator configured to actuate the treatment into the plurality of needles from a treatment storage component.

9. The apparatus of claim 8, wherein the treatment storage component comprises a drug tube or a syringe.

10. The apparatus of claim 2, wherein the lumen of the first tubular member has a diameter between about 2 to 5 millimeters.

11. The apparatus of claim 1, wherein the one or more flexible splines comprise 2, 4, 6, 8, or 10 splines.

12. The apparatus of claim 1, wherein the one or more flexible splines comprises nitinol, a shape memory metal, a shape memory alloy, a shape memory polymer, a shape memory composite, and/or a shape memory hybrid.

13. The apparatus of claim 1, wherein the one or more flexible splines are shaped as a semiellipse or a semi-circle.

14. The apparatus of claim 13, wherein the one or more flexible splines have a major axis between about 80-100 mm and a semi-minor axis between about 21-25 mm.

15. The apparatus of claim 1, wherein the one or more flexible splines have a diameter between about 0.15 mm and 0.35 mm.

16. The apparatus of claim 1, wherein needles are unidirectionally oriented towards a direction outside of the treatment assembly.

17. The apparatus of claim 1, wherein the plurality of needles form an angle between about two degrees and ninety degrees with their respective spline when the respective outer sheath is removed.

18. The apparatus of claim 1, wherein each spline among the one or more splines includes between about 1 to 50 needles.

19. The apparatus of claim 1, wherein the plurality of needles are composed of stainless steel, titanium and/or ni tinol.

20. The apparatus of claim 1, wherein the plurality of needles are attached to the one or more flexible splines using an adhesive polymer.

21. The apparatus of claim 1, wherein the plurality of needles have a flat distal end.

22. The apparatus of claim 1, wherein the plurality of needles have an inner diameter between about 0.05 and 2.7 mm and an outer diameter between about 0.16 mm and 3.4 mm.

23. The apparatus of claim 1, wherein the plurality of needles have a length of between about 0.5 mm to 6 mm.

24. The apparatus of claim 1, wherein the plurality of needles are attached to the one or more flexible splines using a fluid-sealed joint with spring action.

25. The apparatus of claim 1, wherein the at least one treatment comprises one or more of a pharmaceutical agent, a drug, stem cells, biomaterials, growth factors, mRNA, and/or gene therapies.

26. A method of treating a patient using the apparatus of claim 1, the method comprising: advancing a distal end of a tubular member to a chamber of the heart;

27. sliding the treatment assembly through a lumen of the tubular member and such that the proximal cap of the treatment assembly aligns or passes the distal end of the tubular member; expanding the treatment assembly in the chamber of the heart such that the flexible splines contact one or more surfaces of the chamber of the heart; actuating the outer sheath to expose plurality of needles located on the flexible splines; and applying the treatment to one or more surfaces of the chamber of the heart via the plurality of needles.