Thin-Film Neural Interfaces With Stent-Assisted Deployment

The present disclosure relates to thin-film lead assemblies and neural interfaces with stent-assisted deployment, and methods of microfabricating thin-film lead assemblies and neural interfaces. Particularly, aspects of the present disclosure are directed to a medical device having a thin-film neural interface, a stent, and a cable. The thin-film neural interface includes a first supporting structure, electrodes formed on the first supporting structure, and an encapsulation material encasing a portion of the first supporting structure. The cable includes a second supporting structure, conducive traces formed on the second supporting structure and electrically connected with the electrodes, and the encapsulation material encasing at least a portion of the second supporting structure. The stent is at least partially embedded in the encapsulation material encasing the portion of the first supporting structure, and the thin-film neural interface is helically wrapped around at least a portion of the stent.

FIELD

The present disclosure relates to thin-film neural interfaces, and in particular to thin-film neural interfaces with stent-assisted deployment, methods of fabricating thin-film neural interfaces incorporating a stent, and methods for delivering thin-film neural interfaces with stent-assisted deployment.

BACKGROUND

Normal neural activity is an intricate balance of electrical and chemical signals, which can be disrupted by a variety of causes (genetic, chemical or physical trauma) that affect the nervous system, causing cognitive, motor and sensory impairments. The ability to monitor brain electrical and chemical activity in real time and with noninvasive or minimally invasive techniques is important for both the understanding of nervous system functioning in health and disease and the development of effective treatment options for those disorders. Moreover, the ability to restore the diseased nervous system to an intact and normal-functioning state or substitute lost function with brain-actuated assistive devices is dependent on techniques to translate that monitoring information into effective treatment modalities, e.g., to stimulate brain tissue and modulate brain activity. One example of neuroprosthesis/brain-machine interface (BMI) and neuromodulation technology, deep brain stimulation (DBS), has proven to be effective for treatment of essential tremor disorder, Parkinson's disease, dystonia, epilepsy and psychiatric disorders such as depression, obsessive compulsive disorder and Tourette syndrome. Another example of neuroprosthesis/BMI and neuromodulation technology, brain-computer interfacing (BCI), translates specific features of signals recorded from the brain into outputs that allow the user to act on the world without the participation of peripheral nerves and muscles and has proven effective for motor rehabilitation following stroke, Parkinson's disease, and psychiatric disorders.

Neuroprosthesis/BMI and neuromodulation devices and systems tend to have a similar form factor, derived from their predecessors, e.g. the pacemaker or defibrillator. Such neuroprosthesis/BMI and neuromodulation devices and systems typically comprise an implantable, semi-implantable or external processing unit (e.g., a neurostimulator with a pulse generator, a processor with signal recorder, or the like) having electronics connected to a lead assembly that can deliver electrical pulses to or record signals from electrodes interfaced with nerves or nerve bundles via a neural interface. The lead assembly is typically formed of a conductive material and takes the form of an insulated wire connected to the neural interface via a connector on one end (e.g., a distal end) and optionally the electronics of the processing unit via another connector on another end (e.g., a proximal end). In some instances (e.g., deep implants), the lead assembly comprises additional conductors and connectors such as extension wires or a cable connected via connectors between the electrodes and the electronics of the processing unit. Neural interfaces may function as a stimulation or brain signal monitoring (and translation) device. The primary function of a BMI or, equivalently, BCI, is the monitoring of brain signals (and translation). In other words, a BMI is a neuroprosthetic system able to directly convey commands to the external world circumventing the conventional neuromuscular pathways. On the other hand, the primary function of a neurostimulation device is the recording of signals from nerves and the generation and providing of stimulation signals to nerves (sometimes in response to the recording). The brain recording and/or stimulating neuroprosthetics are often employed either for treatment of neurologic conditions and their symptoms (e.g., deep brain stimulation) or for the replacement of impaired sensory modalities (e.g., retinal implants) and may involve neuromodulation through the stimulation of nerves or brain tissue.

BRIEF SUMMARY

In various embodiments, a medical device is provided that comprises: a thin-film neural interface comprising: a first portion of a supporting structure comprised of dielectric material; a wiring layer formed on the first portion of the supporting structure; one or more electrodes formed on the first portion of the supporting structure and electrically connected to the wiring layer; and one or more encapsulation layers encasing a portion of the first portion of the supporting structure; a stent at least partially embedded in the one or more encapsulation layers, where the thin-film neural interface is helically wrapped around at least a portion of the stent; and a cable comprising: a second portion of the supporting structure comprised of the dielectric material; one or more conductive traces formed on the second portion of the supporting structure and electrically connected with the wiring layer; and the one or more encapsulation layers encasing at least a portion of the second portion of the supporting structure.

In some embodiments, the cable further comprises a polymer tube and the second portion of the supporting structure is helically wrapped around the polymer tube.

In some embodiments, the polymer tube comprises a lumen.

In some embodiments, the one or more encapsulation layers comprise a first encapsulation layer and a second encapsulation layer, the first encapsulation layer encases the portion of the first portion of the supporting structure leaving at least top surfaces of the one or more electrodes exposed, and the first encapsulation layer and the second encapsulation layer completely encase the second portion of the supporting structure.

In some embodiments, the stent is at least partially embedded in the first encapsulation layer.

In some embodiments, the dielectric material is liquid crystal polymer.

In some embodiments, the one or more encapsulation layers are comprised of polyurethane.

In some embodiments, the thin-film neural interface is helically wrapped around at least the portion of the stent such that an edge to edge distance of less than 0.5 mm is present between each turn of helixes.

In some embodiments, the second portion of the supporting structure is helically wrapped around the polymer tube such that an edge to edge distance of at least 0.5 mm is present between each turn of helixes.

In some embodiments, the cable further comprises a proximal end and a distal end, and the thin-film neural interface is disposed at the distal end of the cable.

In some embodiments, the medical device further comprises: a connector disposed at the proximal end of the cable and electrically connected to the one or more conductive traces; and a neurostimulator or computing device electrically connected with the one or more electrodes via the connector, the one or more conductive traces, and the wiring layer.

In various embodiments, a method of manufacturing a thin-film lead assembly is provided that comprises: forming a first layer of polymer on a polymer tube and a first heat shrink tube disposed on a mandrel; obtaining a thin-film structure comprising a neural interface portion and a cable portion; helically wrapping the cable portion around the polymer tube and the neural interface portion around the first heat shrink tube; forming a second layer of polymer on the cable portion; placing a second heat shrink tube over the second layer of polymer and the neural interface portion; heating the cable portion and the neural interface portion to: (i) reflow the first layer of polymer and the second layer of polymer around at least a portion of the cable portion, (ii) reflow the first layer of polymer around a portion of the neural interface portion, and (iii) recover the second heat shrink tube defining an outer diameter of the cable portion; unwrapping the neural interface portion from the first heat shrink tube; helically wrapping the neural interface portion around at least a portion of a stent; placing a third heat shrink tube over the neural interface portion; and heating the neural interface portion to: (i) reflow the first layer of polymer around at least a portion of the stent, (ii) recover the third heat shrink tube compressing the neural interface portion and the stent, and (iii) obtain the thin-film lead assembly.

In some embodiments, the method further comprises obtaining an initial structure comprising: (i) the polymer tube disposed around a first portion of the mandrel, and (ii) the first heat shrink tube disposed around a second portion of the mandrel.

In some embodiments, the neural interface portion comprises: a first portion of a supporting structure, a wiring layer formed on the first portion of the supporting structure, and one or more electrodes formed on the first portion of the supporting structure and electrically connected to the wiring layer, and where the cable portion comprises a second portion of the supporting structure, and one or more conductive traces formed on the second portion of the supporting structure and electrically connected with the wiring layer.

In some embodiments, the first portion of the supporting structure is comprised of liquid crystal polymer, the second portion of the supporting structure is comprised of liquid crystal polymer, the first layer of polymer is comprised of polyurethane, and the second layer of polymer is comprised of polyurethane.

In some embodiments, the method further comprises removing the third heat shrink tube and inserting the thin-film lead assembly into a delivery device that maintains the neural interface portion and the stent in a compressed configuration.

In some embodiments, the thin-film neural interface is helically wrapped around at least the portion of the stent such that an edge to edge distance of less than 0.5 mm is present between each turn of helixes.

In some embodiments, the cable portion is helically wrapped around the polymer tube such that an edge to edge distance of at least 0.5 mm is present between each turn of helixes.

In some embodiments, the unwrapping the neural interface portion comprises cutting through the reflowed first layer of polymer along a cut line defined by the first portion of a supporting structure, separating helixes of the neural interface portion along the cut line, and unwrapping the neural interface portion from the first heat shrink tube.

In various embodiments, a method of delivering a neural interface to a target biological structure is provided that comprises: obtaining a thin-film lead assembly comprising: a thin-film structure comprising a neural interface portion and a cable portion, where the neural interface portion comprises: a first portion of a supporting structure, one or more electrodes formed on the first portion of the supporting structure, and one or more encapsulation layers encasing a portion of the first portion of the supporting structure, and where the cable portion comprises: a second portion of the supporting structure, the one or more encapsulation layers encasing at least a portion of the second portion of the supporting structure, and a polymer tube with a lumen and the second portion of the supporting structure is helically wrapped around the polymer tube; a stent at least partially embedded in the one or more encapsulation layers, where the thin-film neural interface is helically wrapped around at least a portion of the stent; and a delivery device disposed over the thin-film lead assembly that maintains the neural interface portion and the stent in a compressed configuration; inserting a guide wire into the lumen of the thin-film lead assembly; delivering, using the guide wire, the thin-film lead assembly to the target biological structure; removing the delivery device and guide wire from the thin-film lead assembly; and deploying, using the stent, the neural interface, where the deploying comprises expanding the stent from the compressed configuration to an expanded configuration that places the one or more electrodes into contact with the target biological structure.

In some embodiments, the second portion of the supporting structure is helically wrapped around the polymer tube such that an edge to edge distance of at least 0.5 mm is present between each turn of helixes, and where the thin-film neural interface is helically wrapped around at least the portion of the stent such that an edge to edge distance of less than 0.5 mm is present between each turn of helixes.

DETAILED DESCRIPTION

The following disclosure describes thin-film lead assemblies and neural interfaces with stent-assisted deployment, methods of microfabricating thin-film lead assemblies and neural interfaces incorporating a stent formed on the neural interface, and stent-assisted deployment methods for delivering thin-film lead neural interfaces. As used herein, the phrases “microfabrication” and “microfabricating” refers to the process of fabricating miniature structures on micrometer scales and smaller. The major concepts and principles of microfabrication are microlithography, doping, thin-films, etching, bonding, and polishing. As used herein, the phrase “thin-films” refers to a layer of material ranging from fractions of a nanometer (monolayer) to several micrometers in thickness (e.g., between a few nanometers to about 100 μm, or the thickness of a few atoms). Thin-films may be deposited by applying a very thin film of material (e.g., between a few nanometers to about 100 μm, or the thickness of a few atoms) onto a substrate surface to be coated, or onto a previously deposited layer of thin film. In various embodiments, the thin-film lead assemblies and neural interfaces provided herein comprise a base polymer body (e.g., a supporting structure), at least one conductive trace formed on the base polymer body, a stent embedded in the base polymer body with electrodes wrapped around the stent, where the one or more electrodes are in electrical connection with the at least one conductive trace formed on the base polymer body.

Limitations associated with conventional thin-film lead assemblies and neural interfaces is that individual electrodes are manually attached to a substrate, and thus are mechanically unstable and can lead to open circuits with the neural tissue during catheter delivery or stent deployment. For example, neural interfaces that include electrodes can be manually attached to a substrate using a curable adhesive, welding, or a conductive epoxy, which are fragile and not reliable for long-term use. Materials like conductive epoxy are not biocompatible and are not suitable for long-term use. Even if the electrodes are securely attached to a substrate for long-term use in endovascular procedures, processes that involve adhesive bonding and welding are labor intensive and require manual attachment of each electrode to the substrate. Additionally, there is a desire to use smaller electrodes with higher electrode density for improved electrical stimuli. However, there are many challenges to creating such a neural interface. For example, adhesion of electrodes can degrade over time under exposure to bodily fluid, exposing an open circuit to the tissue. This ultimately results in mechanical and/or performance failure.

To address these limitations and problems, the thin-film lead assemblies and neural interfaces of various embodiments disclosed herein comprises a stent that is incorporated (e.g., embedded) in one or more layers of the supporting structure of the neural interface, where the electrode assembly (e.g., one or more electrodes in electrical connection with one or more conductive traces of the plurality of conductive traces) wraps around the stent for stent-assisted deployment of the thin-film neural interface. For example, a thin-film lead assembly may comprise a thin-film neural interface comprising: a first portion of a supporting structure comprised of dielectric material; a wiring layer formed on the first portion of the supporting structure; one or more electrodes formed on the first portion of the supporting structure and electrically connected to the wiring layer; and one or more encapsulation layers encasing a portion of the first portion of the supporting structure. The thin-film lead assembly may further comprise a stent at least partially embedded in the one or more encapsulation layers, where the thin-film neural interface is helically wrapped around at least a portion of the stent. The thin-film lead assembly may further comprise a cable comprising: a second portion of the supporting structure comprised of the dielectric material; one or more conductive traces formed on the second portion of the supporting structure and electrically connected with the wiring layer; and the one or more encapsulation layers encasing at least a portion of the second portion of the supporting structure.

In some embodiments, a method of manufacturing a thin-film lead assembly is provided that comprises: forming a first layer of polymer on a polymer tube and a first heat shrink tube disposed on a mandrel; obtaining a thin-film structure comprising a neural interface portion and a cable portion; helically wrapping the cable portion around the polymer tube and the neural interface portion around the first heat shrink tube; forming a second layer of polymer on the cable portion; placing a second heat shrink tube over the second layer of polymer and the neural interface portion; heating the cable portion and the neural interface portion to: (i) reflow the first layer of polymer and the second layer of polymer around at least a portion of the cable portion, (ii) reflow the first layer of polymer around a portion of the neural interface portion, and (iii) recover the second heat shrink tube defining an outer diameter of the cable portion; unwrapping the neural interface portion from the first heat shrink tube; helically wrapping the neural interface portion around at least a portion of a stent; placing a third heat shrink tube over the neural interface portion; and heating the neural interface portion to: (i) reflow the first layer of polymer around at least a portion of the stent, (ii) recover the third heat shrink tube compressing the neural interface portion and the stent, and (iii) obtain the thin-film lead assembly.

In some embodiments, a method of delivering a neural interface is provided that comprises: a obtaining a thin-film lead assembly comprising: a thin-film structure comprising a neural interface portion and a cable portion, where the neural interface portion comprises: a first portion of a supporting structure, one or more electrodes formed on the first portion of the supporting structure, and one or more encapsulation layers encasing a portion of the first portion of the supporting structure, and where the cable portion comprises: a second portion of the supporting structure, the one or more encapsulation layers encasing at least a portion of the second portion of the supporting structure, and a polymer tube with a lumen and the second portion of the supporting structure is helically wrapped around the polymer tube; a stent at least partially embedded in the one or more encapsulation layers, where the thin-film neural interface is helically wrapped around at least a portion of the stent; and a delivery device disposed over the thin-film lead assembly that maintains the neural interface portion and the stent in a compressed configuration; inserting a guide wire into the lumen of the thin-film lead assembly; delivering, using the guide wire, the thin-film lead assembly to the target biological structure; removing the delivery device and guide wire from the thin-film lead assembly; and deploying, using the stent, the neural interface, where the deploying comprises expanding the stent from the compressed configuration to an expanded configuration that places the one or more electrodes into contact with the target biological structure.

Advantageously, these approaches provide a thin-film neural interface, which has improved adhesion between the stent and the electrodes, a smaller footprint, and greater design flexibility. This solution is scalable to interface multiple electrodes with tissue using thin film substrates, and thus enabling several therapeutic opportunities for neurostimulation. Furthermore even for applications where multiple electrodes are not required, various embodiments can be miniaturized to make the implant minimally invasive, additionally may make invasive anatomies to become accessible (or navigable) due to the miniaturization. It should be understood that although deep brain neurostimulation are provided as examples of some embodiments, this solution is applicable to all interfaces, leads, and devices that need electrodes/sensors interfaced with tissue.

II. Neuroprosthesis/BMI Devices and Systems with a Thin-Film Neural Interface

FIG.1shows a neurostimulation/BMI system100in accordance with some aspects of the present disclosure. In various embodiments, the neurostimulation/BMI system100includes a computing device105and a thin-film lead assembly110. In various embodiments, the computing device105can be implantable, semi-implantable, or an external system. The computing device105may include a housing115, a feedthrough assembly120, a power source125, an antenna130, and an electronics module135. For applications where the computing device105is implanted, the housing115may be comprised of materials that are biocompatible such as bioceramics or bioglasses for radio frequency transparency, or metals such as titanium. In some embodiments, the size and shape of the housing115may be selected such that the computing device105can be implanted within a patient. In the example shown inFIG.1, the feedthrough assembly120is attached to a hole in a surface of the housing115such that the housing115is hermetically sealed. The feedthrough assembly120may include one or more feedthroughs (i.e., electrically conductive elements, pins, wires, tabs, pads, etc.) mounted within and extending through the surface of the housing115or a cap from an interior to an exterior of the housing115. The power source125may be within the housing115and connected (e.g., electrically connected) to the electronics module135to power and operate the components of the electronics module135. The antenna130may be connected (e.g., electrically connected) to the electronics module135for wireless communication with external devices via, for example, radiofrequency (RF) telemetry.

In some embodiments, the electronics module135may be connected (e.g., electrically connected) to interior ends of the feedthrough assembly120such that the electronics module135is able to apply a signal or electrical current to conductive traces of the thin-film lead assembly110connected to exterior ends of the feedthrough assembly120. The electronics module135may include discrete and/or integrated electronic circuit components that implement analog and/or digital circuits capable of producing the functions attributed to the neuromodulation or BMI devices or systems such as applying neural stimulation to a patient or sensing and recording electrical activity from a patient. In various embodiments, the electronics module135may include software and/or electronic circuit components such as a pulse generator140that generates a signal to deliver a voltage, current, optical, or ultrasonic stimulation to a nerve or artery/nerve plexus via electrodes, a controller145that determines or senses electrical activity and physiological responses via the electrodes and sensors, controls stimulation parameters of the pulse generator140(e.g., control stimulation parameters based on feedback from the physiological responses), causes delivery of the stimulation via the pulse generator140and electrodes, and/or records the determined or sensed electrical activity in a storage device, and a memory150with program instructions operable on by the pulse generator140and the controller145to perform one or more processes for: (i) applying or delivering neural stimulation, or (ii) translating neuronal information into commands capable of controlling external software or hardware such as a computer or robotic arm.

In various embodiments, the thin-film lead assembly110is a monolithic structure that includes a cable155or lead body and a thin-film neural interface160. In some embodiments, the thin-film neural interface160(e.g., an electrode assembly) comprises a thin-film structure having one or more electrodes162(i.e., recording electrodes, neurostimulation electrodes, sensors, or combinations thereof) wrapped around a stent165. In some embodiments, the thin-film neural interface160is formed at a distal end of the cable155. The thin-film neural interface160may be formed from the same supporting structure170as the cable155. The supporting structure170includes a base dielectric material such as a polymer having suitable dielectric, flexibility and biocompatibility characteristics that provides support for microelectronic structures including conductive traces175, electrodes162, wiring layers180, optional contacts, etc. The wiring layer180may be used to directly or indirectly electrically connect the electrodes162with the one or more conductive traces175. The conductive traces175may be used to directly or indirectly electrically connect the electrodes162with the electronics module135. The term “directly”, as used herein, may be defined as being without something in between. The term “indirectly”, as used herein, may be defined as having something in between.

In some embodiments, the thin-film lead assembly110further includes a connector185. In certain embodiments, the connector185is bonding material that bonds conductor material of the cable155to the electronics module135of the device105(e.g., the neurostimulator) via the feedthrough assembly120. The bonding material may be a conductive epoxy or a metallic solder or weld such as platinum. In other embodiments, the connector185is conductive wire, conductive traces, or bond pads (e.g., a wire, trace, or bond pads formed of a conductive material such as copper, silver, or gold) formed on a substrate and bonds a conductor of the cable155to the electronics module135of the device105. In alternative embodiments, the device105and the cable155are designed to connect with one another via a mechanical connector185such as a pin and sleeve connector, snap and lock connector, flexible printed circuit.

FIGS.2A and2Bshow a thin-film lead assembly200(e.g., the thin-film lead assembly110described with respect toFIG.1) in accordance with aspects of the present disclosure. In various embodiments, the thin-film lead assembly200comprises a cable205and a thin-film neural interface210electrically connected to the cable205. The cable205has a proximal end215and a distal end220. As used herein, the term “proximal end” refers to a first end of the cable, while the term “distal end” refers to a second end opposing the first end. For example, the proximal end may be an end of the cable, which is closest to the user, and the distal end may be an end of the cable, which is furthest from the user. In some embodiments, the thin-film neural interface210is disposed at the distal end220of the cable205.

The cable205may comprise a supporting structure225and one or more conductive traces230formed on a portion of the supporting structure225. As used herein, the term “formed on” refers to a structure or feature that is formed on a surface of another structure or feature, a structure or feature that is formed within another structure or feature, or a structure or feature that is formed both on and within another structure or feature. In some embodiments, the supporting structure225extends from the proximal end215to the distal end220. The supporting structure225is made of one or more layers of dielectric material (i.e., an insulator). The dielectric material may be selected from the group of electrically nonconductive materials consisting of organic or inorganic polymers, ceramics, glass, glass-ceramics, polyimide-epoxy, epoxy-fiberglass, and the like. For example, the dielectric material may be a polymer of imide monomers (i.e., a polyimide), a liquid crystal polymer (LCP) such as Kevlar®, parylene, polyether ether ketone (PEEK), or combinations thereof. In certain instances, the supporting structure225comprises one or more layers of LCP.

In various embodiments, the supporting structure225has a thickness (t) from the proximal end215to the distal end220. In some embodiments, the thickness (t) is from 10 μm to 950 μm, for example about 150 μm or about 500 μm. As used herein, the terms “substantially,” “approximately,” and “about” are defined as being largely but not necessarily wholly what is specified (and include wholly what is specified) as understood by one of ordinary skill in the art. In any disclosed embodiment, the term “substantially,” “approximately,” or “about” may be substituted with “within [a percentage] of” what is specified, where the percentage includes 0.1, 1, 5, and 10 percent. In some embodiments, the supporting structure225has a length (1) of 5 cm to 150 cm or 50 cm to 100 cm, e.g., about 75 cm. In some embodiments, the supporting structure225has a width (w) from a first side to a second side. In some embodiments, the width (w) is from 0.5 mm to 5 mm, for example about 0.6 mm or about 4 mm.

In various embodiments, the one or more conductive traces230are a plurality of traces, for example, two or more conductive traces or from two to forty-eight conductive traces (e.g., one conductive trace for each electrode/sensor). The plurality of conductive traces230are comprised of one or more layers of conductive material. The conductive material selected for the one or more conductive traces230should have good electrical conductivity and may include pure metals, metal alloys, combinations of metals and dielectrics, and the like. For example, the conductive material may be copper (Cu), gold (Au), silver (Ag), gold/chromium (Au/Cr), etc. In some embodiments, it is also desirable that the conductive material selected for the one or more conductive traces230have thermal expansion characteristics or a coefficient of thermal expansion (CTE) that is approximately equal to that of CTE of the supporting structure225. Matching the CTE of components that contact one another is desirable because it eliminates the development of thermal stresses, which may occur during fabrication and the operation of the cable, and thus eliminates a known cause of mechanical failure in the components.

The one or more conductive traces230may be deposited onto a surface of the supporting structure225by using thin film deposition techniques well known to those skilled in the art such as by sputter deposition, chemical vapor deposition, metal organic chemical vapor deposition, electroplating, electroless plating, and the like. In some embodiments, the thickness of the one or more conductive traces230is dependent on the particular impedance desired for conductor, in order to ensure excellent signal integrity (e.g., electrical signal integrity for stimulation or recording). For example, if a conductor having a relatively high impedance is desired, a small thickness of conductive material should be deposited onto the supporting structure225. If, however, a signal plane having a relatively low impedance is desired, a greater thickness of electrically conductive material should be deposited onto the supporting structure225. In certain embodiments, each of the one or more conductive traces230has a thickness (d). In some embodiments, the thickness (d) is from 0.5 μm to 100 μm or from 25 μm to 50 μm, for example about 25 μm or about 40 μm. In some embodiments, each of the one or more conductive traces225has a length (m) of about 5 cm to 200 cm or 50 cm to 150 cm, e.g., about 80 cm. In certain embodiments, each of the one or more conductive traces230extends from the proximal end215to the distal end220. In some embodiments, each of the one or more conductive traces230has a width (y) from 2.0 μm to 500 μm, for example about 30 μm or about 50 μm.

The cable205may further comprise a base tube235. The base tube235may comprise a medical grade polymer material. In certain instances, the medical grade polymer is a soft polymer such as silicone. The supporting structure225and conductive traces230may be helically wrapped around the base tube235. As used herein, the phrases “helical” or “helically wrapped” refer to a device fabricated with plural helixes or helices, which are a type of smooth space curve, i.e. a curve in three-dimensional space. The helixes may be wrapped in a clockwise direction or anti-clockwise direction. The helixes have the property that a tangent line at any point makes a constant angle with a fixed line called the axis. In some instances, the supporting structure225and conductive traces230are wrapped loosely around the base tube235. The “wrapped loosely” configuration means that the turns are loosely packed with an edge to edge distance of at least 0.5 mm between each turn of the helixes.

The cable205may further comprise one or more encapsulation layers240. The one or more encapsulation layers240may completely encase at least a portion of the supporting structure225and the one or more conductive traces230. The one or more encapsulation layers240may be comprised of a medical grade polymer material. In some embodiments, the medical grade polymer is thermosetting plastic or thermoplastic. For example, the medical grade polymer may be a soft polymer such as silicone, a polymer dispersion such as latex, a chemical vapor deposited poly(p-xylylene) polymer such as parylene, or a polyurethane such as Bionate® Thermoplastic Polycarbonate-urethane (PCU) or CarboSil® Thermoplastic Silicone-Poly carbonate-urethane (TSPCU).

The thin-film neural interface210comprises a supporting structure225′, one or more encapsulation layers240′, and a stent245embedded at least partially within the one or more encapsulation layers240′. As used herein, “embedded at least partially” means at least 30% of an object (in this instance the stent) is embedded within the other object (in this instance the one or more encapsulation layers). The supporting structure225′ provides support for microelectronic structures including one or more electrodes250, a wiring layer255, and optional contact(s). In various embodiments, the supporting structure225of the cable205and the supporting structure225′ of the thin-film neural interface210are the same structure (i.e., the supporting structure is continuous through the thin-film lead assembly), which creates a monolithic thin-film lead assembly200. The wiring layer255electrically connects each of the one or more electrodes250to the one or more conductive traces230. In some instances, the wiring layer255may be formed continuously with the one or more conductive traces230. For example, each of the one or more conductive traces230may extend from the supporting structure225through the supporting structure225′ (as the wiring layer255) and terminate at one or more of the electrodes250.

In some embodiments, the one or more encapsulation layers240of the cable205and the one or more encapsulation layers240′ of the thin-film neural interface210are the same structure (i.e., the encapsulation layer is continuous through the thin-film lead assembly), which creates a monolithic thin-film lead assembly200. However, the one or more encapsulation layers240′ of the thin-film neural interface210are not disposed over at least a top surface of the one or more electrodes250such that the one or more electrodes250can directly interface with a biological structure. Consequently, the one or more encapsulation layers240′ of the thin-film neural interface210may have less layers of material (e.g., polymer) as compared to the one or more encapsulation layers240of the cable205.

In some embodiments, the stent245comprises a mesh framework that is collapsible and expandable, as shown inFIGS.2A and2B. The stent245can include any mechanical framework or scaffolding that positions the one or more electrodes250within a body lumen, such as a vessel, and facilitates interfacing the one or more electrodes250with a biological structure such as tissue or fluid. For example, the stent245may be collapsed during insertion of the thin-film lead assembly200in a subject (e.g., a human patient), and the stent245may expand to take the shape of a surrounding body lumen when deployed in the subject. In certain instances, the stent245may be adapted to expand when deployed out of an end of a delivery device such as a sheath disposed around the thin-film lead assembly200(see, e.g.,FIGS.7A and7B). Additionally, the stent245may be adapted to contract when retracted into the end of the delivery device. Thus, the stent245may be adapted to be deployed, retrieved, and re-deployed. The redeployment may take place at a different region within the subject to that of the earlier deployment.

The stent245is made of an inert material, which can remain functional in the body for long periods of time (e.g., several months to years). For example, the stent245may be laser cut or woven from the inert material in any suitable shape, e.g., a column or tube. In some embodiments, the stent245is a mesh tube made of medical-grade metal such as stainless steel or cobalt alloy metal, which fits into a biological structure and expands radially against the walls of the biological structure. In other embodiments, the stent245is a self-expanding (e.g., temperature sensitive) mesh tube made of medical-grade “smart metals.” For example, the stent245may be made of stainless steel, platinum, or shape memory alloys containing nickel and titanium (e.g., nitinol). Shape memory alloys refer to alloys that retain their original shape when exposed to certain conditions (e.g., temperature or pressure). These stents are designed to contract or expand under certain conditions (e.g., contract in cold temperature and expand or return to their original shape under warm temperatures).

The supporting structure225′ and microelectronic structures may be helically wrapped around the stent245. The helixes may be wrapped in a clockwise direction or anti-clockwise direction. In some instances, the supporting structure225′ and microelectronic structures are wrapped tightly around the stent245. The “wrapped tightly” configuration means that the turns are tightly packed with an edge to edge distance of less than 0.5 mm between each turn of the helixes. The one or more electrodes250are wrapped around the stent245for stimulating and/or sensing activity of biological structures such as tissue and/or fluid proximal to the thin-film neural interface210. The one or more electrodes250may be arranged in any suitable configuration on the supporting structure225′ such that the one or more electrodes250take on any suitable arrangement wrapped around the stent245. For example, the one or more electrodes250can be arranged as follows: sinusoidal arrangement of electrodes; spiral arrangement of electrodes to enable 360° contact of the electrodes to the wall of a vessel once deployed; and a dense arrangement of electrodes for increased coverage. In some embodiments, the stent245is laser cut or woven in a manner such that there is additional material or markers where the thin-film neural interface210can wrap around the stent245to assist with electrical connection stability of the one or more electrodes250and uniformity of electrode locations.

While the thin-film lead assembly has been described at some length and with some particularity with respect to a specific design and/or performance need, it is not intended that the thin-film lead assembly be limited to any such particular design and/or performance need. Instead, it should be understood the thin-film lead assembly described herein is an exemplary embodiment, and that the thin-film lead assembly is to be construed with the broadest sense to include variations of the specific design and/or performance need described herein, as well as other variations that are well known to those of skill in the art. In particular, the shape and location of components and layers in the thin-film lead assembly may be adjusted or modified to meet specific design and/or performance needs. Furthermore, it is to be understood that other structures have been omitted from the description of the thin-film lead assembly for clarity. The omitted structures may include sensor structures, insulating layers, interconnect components, passive devices, etc.

FIGS.3A(top view) and3B (cross-sectional view) show a thin-film neural interface300with stent-assisted deployment (e.g., the neural interface described with respect toFIGS.2A and2B) in accordance with aspects of the present disclosure. The thin-film neural interface300comprises a supporting structure305having a proximal end310and a distal end315. The supporting structure305comprises a front side320, a back side325, and opposing edges330,335. In some embodiments, the supporting structure305is made of one or more layers of dielectric material (i.e., an insulator). The dielectric material may be selected from the group of electrically nonconductive materials consisting of organic or inorganic polymers, ceramics, glass, glass-ceramics, polyimide-epoxy, epoxy-fiberglass, and the like. In certain embodiments, the dielectric material is a polymer of imide monomers (i.e., a polyimide), a liquid crystal polymer (LCP) such as Kevlar®, parylene, polyether ether ketone (PEEK), or combinations thereof. In certain instances, the supporting structure305comprises one or more layers of LCP. The supporting structure305has a width (w) from the proximal end310to the distal end315. In some embodiments, the width (w) is from 0.01 mm to 3 mm, for example about 0.08 mm or about 0.5 mm. In some embodiments, the supporting structure305has a length (1) of 1 mm to 20 cm or 1 mm to 50 mm, e.g., about 10 mm. In some embodiments, the supporting structure225has a thickness (t) from the front side320to the back side325. In some embodiments, the thickness (t) is from 10 μm to 950 μm, for example about 150 μm or about 500 μm0.

The thin-film neural interface300further comprises one or more electrodes345in electrical connection with a wiring layer350directly or via optional contacts355. The one or more electrodes345are formed on the supporting structure305. In some embodiments, the top surface of the one or more electrodes345is coplanar with the top surface of the supporting structure305. In other embodiments, the top surface of the one or more electrodes345is raised above the top surface of the supporting structure305. The one or more electrodes345may be comprised of conductive material such as copper (Cu), gold (Au), silver (Ag), gold/chromium (Au/Cr), platinum (Pt), platinum/iridium (Pt/Ir), titanium (Ti), gold/titanium (Au/Ti), or any alloy thereof, for example. The one or more electrodes345may have a thickness (z) of from 0.1 μm to 50 μm, from 0.3 μm to 30 μm, from 0.5 μm to 20 μm, or from 1 μm to 15 μm. In certain embodiments, the contact(s)355are formed on the supporting structure305and provide electrical contact between the one or more electrodes345and the wiring layer350. The contact(s)355may be comprised of conductive material such as copper (Cu), gold (Au), silver (Ag), gold/chromium (Au/Cr), platinum (Pt), platinum/iridium (Pt/Ir), titanium (Ti), gold/titanium (Au/Ti), or any alloy thereof, for example.

The wiring layer350may be formed on the supporting structure305. In various embodiments, the wiring layer350is formed continuously with the one or more conductive traces357of the cable, and is comprised of various metals or alloys thereof, for example, copper (Cu), gold (Au), silver (Ag), gold/chromium (Au/Cr), platinum (Pt), platinum/iridium (Pt/Ir), titanium (Ti), gold/titanium (Au/Ti), or any alloy thereof. The wiring layer350may have a thickness (x) of from 0.5 μm to 100 μm, from 0.5 μm to 15 μm, from 0.5 μm to 10 μm, or from 0.5 μm to 5 μm. In some embodiments, a top surface of the wiring layer350is coplanar with a top surface of the supporting structure305. In other embodiments, the wiring layer350is embedded within the supporting structure305. In yet other embodiments, the wiring layer350is formed on the top surface of the supporting structure305and the top surface of the wiring layer350is raised above the top surface of the supporting structure305.

The thin-film neural interface300further comprises one or more encapsulation layers360formed on at least a portion of the supporting structure305. The one or more encapsulation layers360are formed on the back side325and wrap around over the opposing edges330,335. In some instances, the one or more encapsulation layers360may further wrap around over the opposing edges330,335to the front side320. However, the one or more encapsulation layers360do not cover the top surface of the one or more electrodes345. The one or more encapsulation layers360may be comprised of a medical grade polymer material. In some embodiments, the medical grade polymer is thermosetting plastic or thermoplastic. For example, the medical grade polymer may be a soft polymer such as silicone, a polymer dispersion such as latex, a chemical vapor deposited poly(p-xylylene) polymer such as parylene, or a polyurethane such as Bionate® Thermoplastic Polycarbonate-urethane (PCU) or CarboSil® Thermoplastic Silicone-Poly carbonate-urethane (TSPCU)

The thin-film neural interface300further comprises a stent365embedded within the one or more encapsulation layers360. Specifically, some or all of the stent365is at least partially embedded within the one or more encapsulation layers360. The stent365may be embedded within the one or more encapsulation layers360via reflow of the one or more encapsulation layers360, as described in detail herein. Advantageously, the stent365being embedded within the one or more encapsulation layers360attaches the one or more electrodes345to the stent365such that the one or more electrodes345move with the stent365as it expands and collapses. This avoids having to manually attach the one or more electrodes345to the stent365using a curable adhesive, welding, or a conductive epoxy, which are fragile and not reliable for long-term use.

V. Methods for Fabricating Lead Assemblies and Neural Interfaces

FIGS.4A-4Eshow structures and respective processing steps for fabricating a thin-film structure400(e.g., a portion of the thin-film lead assembly as described with respect toFIGS.1,2A,2B,3A, and3B) in accordance with various embodiments. It should be understood by those of skill in the art that thin-film structure400can be manufactured in a number of ways using a number of different tools. In general, however, the methodologies and tools used to form the structures of the various embodiments can be adopted from integrated circuit (IC) technology. For example, the structures of the various embodiments, e.g., supporting structure, conductive traces, electrodes, sensors, wiring layers, bond/contact pads, etc., may be built with or without a substrate and realized in films of materials patterned by photolithographic processes. In particular, the fabrication of various structures described herein may typically use three basic building blocks: (i) deposition of films of material on a substrate and/or previous film(s), (ii) applying a patterned mask on top of the film(s) by photolithographic imaging, and (iii) etching the film(s) selectively to the mask.

As used herein, the term “depositing” may include any known or later developed techniques appropriate for the material to be deposited including but not limited to, for example: chemical vapor deposition (CVD), low-pressure CVD (LPCVD), plasma-enhanced CVD (PECVD), semi-atmosphere CVD (SACVD) and high density plasma CVD (HDPCVD), rapid thermal CVD (RTCVD), ultra-high vacuum CVD (UHVCVD), limited reaction processing CVD (LRPCVD), metalorganic CVD (MOCVD), sputtering deposition, ion beam deposition, electron beam deposition, laser assisted deposition, thermal oxidation, thermal nitridation, spin-on methods, physical vapor deposition (PVD), atomic layer deposition (ALD), chemical oxidation, molecular beam epitaxy (MBE), plating (e.g., electroplating), or evaporation.

FIG.4Ashows a supporting structure comprising a first polymer layer405overlying an optional substrate410(e.g., a backer). In various embodiments, the supporting structure may be provided, obtained, or fabricated as a single wafer or panel. The substrate410may be comprised of any type of metallic or non-metallic material. For example, the substrate410may be comprised of but not limited to silicon, germanium, silicon germanium, silicon carbide, and those materials consisting essentially of one or more Group III-V compound semiconductors having a composition defined by the formula AlX1GaX2InX3AsY1PY2NY3SbY4, where X1, X2, X3, Y1, Y2, Y3, and Y4 represent relative proportions, each greater than or equal to zero and X1+X2+X3+Y1+Y2+Y3+Y4=1 (1 being the total relative mole quantity). Substrate410may additionally or alternatively be comprised of Group II-VI compound semiconductors having a composition ZnA1CdA2SeB1TeB2, where A1, A2, B1, and B2 are relative proportions each greater than or equal to zero and A1+A2+B1+B2=1 (1 being a total mole quantity). The processes to provide, obtain, or fabricate substrate410, as illustrated and described, are well known in the art and thus, no further description is provided herein.

The first polymer layer405may be comprised of one or more layers of dielectric material (i.e., an insulator). The dielectric material may be selected from the group of electrically nonconductive materials consisting of organic or inorganic polymers, ceramics, glass, glass-ceramics, polyimide-epoxy, epoxy-fiberglass, and the like. In certain embodiments, the dielectric material is a polyimide, polyurethane, a LCP, parylene, a PEEK, or combinations thereof. The forming of the first polymer layer405may include depositing and curing a dielectric material directly on the substrate410without an adhesion promoter. For example, a solution comprised of an imidizable polyamic acid compound dissolved in a vaporizable organic solvent without an adhesion promoter may be deposited (e.g., spin coated) onto the substrate410. The solution may then be heated at a temperature, preferably less than 250° C., to imidize the polyamic acid compound to form the desired polyimide and vaporize the solvent. The first polymer layer405may then be thinned to a desired thickness by planarization, grinding, wet etch, dry etch, oxidation followed by oxide etch, or any combination thereof. This process can be repeated to achieve a desired thickness for the first polymer layer405. In some embodiments, the first polymer layer405may have a thickness from 10 μm to 300 μm.

FIGS.4A,4B and4Cshow forming a cable portion411and neural interface portion412of the thin-film structure400. Specifically,FIGS.4A and4Bshow conductive traces415formed in a pattern on the cable portion411of the first polymer layer405. In some embodiments, forming the conductive traces415may include depositing a seed layer (e.g., a copper (Cu) seed layer, a gold (Au) seed layer, a silver (Ag) seed layer, a gold/chromium (Au/Cr) seed layer, platinum (Pt) seed layer, platinum/iridium (Pt/Ir) seed layer, etc.) over the first polymer layer405. The seed layer may be configured to enable forming of a conductive trace on the first polymer layer405(e.g., through Cu electroplating, Au electroplating, Sn electroplating, Ag electroplating, Au/Cr electroplating, platinum (Pt) electroplating, platinum/iridium (Pt/Ir) electroplating, etc.). Optionally, and prior to forming of the seed layer, an adhesion layer may be deposited over the first polymer layer405to enable adequate application of the seed layer. Deposition of either or both of the adhesion layer and seed layer may include sputter deposition

Following deposition of the seed layer, a resist pattern may be formed above the first polymer layer405. The resist pattern may include openings that align over at least a portion of the first polymer layer405for forming of a plurality of conductive traces415(e.g., a conductive layer with a cross-sectional thickness of 0.5 μm to 100 μm or from 25 μm to 50 μm) on the first polymer layer405. For example, the resist may be patterned with openings to form: (i) a first conductive trace415over a first region of the first polymer layer405, (ii) a second conductive trace415over a second region of the first polymer layer405, and (iii) a third conductive trace415over a third region of the first polymer layer405. It should be understood by those of skill in the art that different patterns and shapes are also contemplated by the present disclosure to maximize the length of the thin-film structure400.

In various embodiments, the conductive traces415may be deposited through electroplating (e.g., through Cu electroplating, Au electroplating, Sn electroplating, Ag electroplating, Au/Cr electroplating, etc.) and may be positioned over at least a portion of the first polymer layer405(e.g., the first region, the second region, and the third region). The electroplating may be performed at a current density of about 4.0 mA/cm2 to about 4.5 mA/cm2. In some embodiments, the exposed area or portion of the first polymer layer405may encompass about 8 cm2to about 10 cm2. The current may be about 14 mA to about 18 mA and the duration may be from about 110 minutes to about 135 minutes to form the conductive traces415having a thickness of about 8 μm to about 10 μm. In other embodiments, the exposed area or portion of the first polymer layer405may encompass about 10 cm2to about 18 cm2. The current may be about 18 mA to about 28 mA and the duration may be from about 35 minutes to about 50 minutes to form the wiring layer having a thickness of about 2 μm to about 5 μm.

Following the deposition of the conductive traces415, the intermediate structure may be subjected to a strip resist to remove the resist pattern and expose portions of the seed layer (portions without wire formation), and optionally the adhesion layer. The exposed portions of the seed layer, and optionally the adhesion layer, may then be subjected to an etch (e.g., wet etch, dry etch, etc.) to remove those portions, thereby isolating the conductive traces415over at least a portion of the first polymer layer405.

FIG.4Cshows an optional second polymer layer420formed over the conductive traces415and the first polymer layer405. The second polymer layer420may be comprised of dielectric material (i.e., an insulator). The dielectric material may be selected from the group of electrically nonconductive materials consisting of organic or inorganic polymers, ceramics, glass, glass-ceramics, polyimide-epoxy, epoxy-fiberglass, and the like. In certain embodiments, the dielectric material is a polyimide, a LCP, silicone, parylene, a PEEK, or combinations thereof. The second polymer layer420may be comprised of the same material or a different material from that of the first polymer layer405. The forming of the second polymer layer420may include depositing and curing of a polymer material directly on the conductive traces415and the first polymer layer405. The second polymer layer420may then be thinned to a desired thickness by planarization, grinding, wet etch, dry etch, oxidation followed by oxide etch, or any combination thereof. This process can be repeated to achieve a desired thickness for the second polymer layer420. In some embodiments, the second polymer layer420may have a thickness from 10 μm to 300 μm.

In various embodiments, a third polymer layer422may be formed over the second polymer layer420. In some embodiments, the third polymer layer422is only formed over a portion of the second polymer layer420. The third polymer layer422may be comprised of dielectric material (i.e., an insulator). The dielectric material may be selected from the group of electrically nonconductive materials consisting of organic or inorganic polymers, ceramics, glass, glass-ceramics, polyimide-epoxy, epoxy-fiberglass, and the like. In some embodiments, the dielectric material is a polyimide, a LCP, silicone, parylene, a PEEK, or combinations thereof. The third polymer layer may be comprised of the same material or a different material from that of the first polymer layer405and the second polymer layer420. In some embodiments, the first polymer layer405comprises LCP, the second polymer layer420comprises LCP, and the third polymer layer422comprises LCP.

In various embodiments, the thin-film structure400may further comprise one or more additional supporting structures that may support one or more additional electronic structures of the neural interface portion412such as an electrode, sensor, conductor, and/or connector.FIGS.4B-4Fshow forming the neural interface portion412of the thin-film structure400on the supporting structure formed inFIG.4Athat is electrically connected to the conductive traces415formed inFIGS.4A and4B. As shown inFIGS.4B and4C, forming the neural interface portion412comprises forming a wiring layer425in a pattern on the first polymer layer405and/or the second polymer layer420. The wiring layer425may be formed at the same time as forming the conductive traces415, or may be formed subsequent to forming the conductive traces415. For example, the wiring layer425and the conductive traces415may be deposited as a continuous layer of conductive material, or may be deposited as two separate metallization layers of conductive material that are in electrical contact with one another. The wiring layer425may be formed in the same manner as described in detail with respect to the conductive traces415.

In some embodiments, forming the neural interface portion412further comprises forming the second polymer layer420and/or the third polymer layer422over the wiring layer425and the first polymer layer405. As described herein, the second polymer layer420may be comprised of dielectric material (i.e., an insulator) selected from the group of electrically nonconductive materials consisting of organic or inorganic polymers, ceramics, glass, glass-ceramics, polyimide-epoxy, epoxy-fiberglass, and the like. In certain embodiments, the dielectric material is a polyimide, a LCP, parylene, silicone, a PEEK, or combinations thereof. The second polymer layer420may be comprised of the same material or a different material from that of the first polymer layer405.

As shown inFIG.4D, forming the neural interface portion412further comprises forming contact vias430in the second polymer layer420or the third polymer layer422to the wiring layer425. The contact vias430can e.g. be formed using conventional lithographic, etching, and cleaning processes, known to those of skill in the art.FIG.4Eshows electrodes (optionally one or more sensors)435and contacts440formed on and within the contact vias430to the portion of the top surface the wiring layer425. In various embodiments, the electrodes435(optionally one or more sensors) and contacts440may be formed using conventional processes. For example, a conductive material may be blanket deposited on the second polymer layer420, including within the contact vias430and in contact with the portion of the top surface the wiring layer425. The conductive material may be copper (Cu), gold (Au), silver (Ag), gold/chromium (Au/Cr), platinum (Pt), platinum/iridium (Pt/Ir), titanium (Ti), gold/titanium (Au/Ti), or any alloy thereof, for example. Once the conductive material is deposited, the conductive material may be patterned using conventional lithography and etching processes to form at least one electrode435or a pattern of electrodes435as shown inFIG.4E, for example. In some embodiments, at least one electrode435is formed on the second polymer layer420such that the at least one electrode435is in electrical contact with at least a portion of a top surface of the wiring layer425. In some embodiments, the pattern of electrodes435may include each electrode435spaced apart from one another via a portion or region445of the second polymer layer420. It should be understood by those of skill in the art that different patterns are also contemplated by the present disclosure.

FIG.4Fshows the thin-film structure400including the first polymer layer405, the conductive traces415, the wiring layer425, the second polymer layer420, the electrodes435, and the contacts440detached from the substrate410. In some embodiments, detaching the thin-film structure400from the substrate410may include removal of the substrate (e.g., selective etching), and cleaning (e.g., a step-wise rinsing process) at least top surfaces of the electrodes435and the second polymer layer420with acetone, isopropyl alcohol, non-ionic surfactant, a liquid detergent system, and/or deionized water to remove residual material such as remaining adhesive material.

FIGS.5A-5Jshow cross-sectional views of the structures and respective processing steps for fabricating a thin-film lead assembly500and structures thereof described inFIGS.1,2A,2B,3A,3B, and4A-4F.FIG.5Ashows a beginning structure505for a thin-film lead assembly. The beginning structure505comprises a polymer tube510disposed around a first portion515of a mandrel520. The polymer tube510is comprised of a medical grade polymer material, for example, a soft polymer such as silicone. The polymer tube510covers a region of the mandrel520upon which the cable of the thin-film lead assembly is to be formed. The beginning structure505further comprises a first heat shrink tube525disposed around a second portion530of the mandrel520. In some instances, the first heat shrink tube525is comprised of one or more polymer resins, for example, a fluoropolymer such as the FluoroPEELZ® peelable heat shrink tubes, fluorinated ethylene propylene (FEP), etc. The first heat shrink tube525covers a region of the mandrel520upon which the neural interface of the thin-film lead assembly is to be formed.

FIG.5Bshows forming a first layer of polymer535(e.g., a layer of the encapsulation layers) on the polymer tube510and the first heat shrink tube525to obtain a first intermediate structure537. The first layer of polymer535may be comprised of a medical grade polymer material. In some embodiments, the medical grade polymer is a thermosetting plastic or thermoplastic. For example, the medical grade polymer may be a soft polymer such as silicone, a polymer dispersion such as latex, a chemical vapor deposited poly(p-xylylene) polymer such as parylene, or a polyurethane such as Bionate® PCU or CarboSil® TSPCU. In certain instances, the first layer of polymer535is polyurethane.

FIG.5Cshows a thin-film structure540(e.g., the thin-film structure400may be obtained as discussed with respect toFIGS.4A-4F) being wrapped around the first intermediate structure537. The thin-film structure540comprises a cable portion542and a neural interface portion543. The cable portion542comprises a supporting structure545and conductive traces550. The cable portion is helically wrapped around the first layer of polymer535formed on the polymer tube510. The helixes may be wrapped in a clockwise direction or anti-clockwise direction. In some instances, the cable portion542is wrapped loosely around the first layer of polymer535formed on the polymer tube510. The “wrapped loosely” configuration means that the turns are loosely packed with an edge to edge distance of at least 0.5 mm between each turn of the helixes. The neural interface portion543comprises the supporting structure545, wiring layer555, one or more electrodes560, and optional contacts (not shown). The neural interface portion543is helically wrapped around the first layer of polymer535formed on the heat shrink tube525. The helixes may be wrapped in a clockwise direction or anti-clockwise direction. In some instances, the neural interface portion543is wrapped tightly around the first layer of polymer535formed on the heat shrink tube525. The “wrapped tightly” configuration means that the turns are tightly packed with an edge to edge distance of less than 0.5 mm between each turn of the helixes.

FIG.5Dshows forming a second layer of polymer565(e.g., a layer of the encapsulation layers) on the cable portion542of the thin-film structure540. The second layer of polymer565may be comprised of a medical grade polymer material. In some embodiments, the medical grade polymer is a thermosetting plastic or thermoplastic. For example, the medical grade polymer may be a soft polymer such as silicone, a polymer dispersion such as latex, a chemical vapor deposited poly(p-xylylene) polymer such as parylene, or a polyurethane such as Bionate® PCU or CarboSil® TSPCU. As shown, the second layer of polymer565is not formed on the neural interface portion543of the of the thin-film structure540such that the second layer of polymer565does not cover a top surface of the one or more electrodes560.FIG.5Dfurther shows a second heat shrink tube570placed over the second layer of polymer565and the neural interface portion543of the of the thin-film structure540to obtain a second intermediate structure572. In some instances, the second heat shrink tube570is comprised of one or more polymer resins, for example, a fluoropolymer such as the FluoroPEELZ® peelable heat shrink tubes, FEP, etc.

FIG.5Eshows the second intermediate structure572being heated to: (i) heat shrink the first heat shrink tube525to define an inner diameter (i) of the neural interface portion543of the thin-film structure540, (ii) heat shrink the second heat shrink tube570to define a first outer diameter (o) of the cable portion542of the thin-film structure540and a second outer diameter (o′) of the neural interface portion543of the thin-film structure540(where the first outer diameter is greater than the second outer diameter because of the second layer of polymer565formed over the cable portion542), and (iii) at the same time melt and reflow (thermal reflow) the first layer of polymer535and the second layer of polymer565to encase completely or partially each of the cable portion542and the neural interface portion543in the polymer. The heating process may include baking the second intermediate structure572in an oven, use of a heat gun, application of hot air, like methods, or any combination thereof. In some instances, the second intermediate structure572is heated at 180° C. to 210° C., for example about 200° C., for 15 to 40 minutes, for example 25 minutes. In certain instances, the first heat shrink tube525and the second heat shrink tube570shrink or recover at a given temperature (e.g., about 200° C.) and the first layer of polymer535and the second layer of polymer565reflow at or about the same given temperature (e.g., about 200° C.).

Consequently, as the second intermediate structure572is heated to the given temperature, the first heat shrink tube525maintains its size (nowhere to shrink because it is wrapped onto the mandrel520) and defines a smooth inner surface with a precisely controlled inner diameter (i) of the neural interface portion543. Substantially simultaneously, the second heat shrink tube570shrinks (because at a same time/temperature the first layer of polymer535and the second layer of polymer565are liquefying allowing for the second heat shrink tube570to shrink) to define a smooth outer surface with a precisely controlled first outer diameter (o) of the cable portion542and a precisely controlled second outer diameter (o′) of the neural interface portion543. Substantially simultaneously, the first layer of polymer535and the second layer of polymer565liquefy and flow around the helically wrapped cable portion542of the thin-film structure540(the thin-film structure540does not liquefy because it comprises a polymer (e.g., LCP) with a higher reflow temperature than the given temperature) and completely encase the cable portion542within the polymer. Substantially simultaneously, the first layer of polymer535liquefies and flows around the helically wrapped neural interface portion543of the thin-film structure540(the thin-film structure540does not liquefy because it comprises a polymer (e.g., LCP) with a higher reflow temperature than the given temperature) and partially encases the neural interface portion543within the polymer (only partially because the second layer of polymer565is not formed over the neural interface portion543, thus leaving exposed the top surface of the electrodes). Thereafter, the second intermediate structure572is cooled (e.g., at ambient temperature), the first heat shrink tube525and the second heat shrink tube570are peeled away, and the mandrel520is withdrawn to obtain the third intermediate structure575, as shown inFIG.5F.

FIG.5Fshows the neural interface portion543of the third intermediate structure575being unwrapped from the first heat shrink tube525. The unwrapping process includes cutting through a portion of the neural interface portion543to unwrap the polymer layers. In some instances, a laser is used to cut through the reflowed first layer of polymer535along a line defined by the supporting structure545. In certain instances, the reflowed first layer of polymer535is cut in such a manner that the reflowed first layer of polymer535remains partially encasing the neural interface portion543within the polymer (e.g., remains encasing at least the bottom and sides of the supporting structure545). The unwrapping process includes separating the neural interface portion543helixes along the cut line and unwrapping the neural interface portion543from the first heat shrink tube525.

FIG.5Gshows the unwrapped neural interface portion543being rewrapped around a stent580. The neural interface portion543is helically wrapped around the stent580. The helixes may be wrapped in a clockwise direction or anti-clockwise direction. In some instances, the neural interface portion543is wrapped tightly around the stent580. The “wrapped tightly” configuration means that the turns are tightly packed with an edge to edge distance of less than 0.5 mm between each turn of the helixes.FIG.5Hshows a third heat shrink tube585placed over the neural interface portion543and the stent580to obtain a fourth intermediate structure590. In some instances, the thirst heat shrink tube585is comprised of one or more polymer resins, for example, a fluoropolymer such as the FluoroPEELZ® peelable heat shrink tubes, FEP, etc. The third heat shrink tube585covers the neural interface of the neural interface portion543and the stent580; whereas the cable portion542remains uncovered.

FIG.5Ishows the neural interface portion543of the fourth intermediate structure590being heated to: (i) heat shrink the third heat shrink tube585to compress the stent580to a compressed configuration, and (ii) at the same time melt and reflow (thermal reflow) the first layer of polymer535to encase completely or partially the stent580in the polymer. The heating process may include baking the neural interface portion543of the fourth intermediate structure590in an oven, use of a heat gun, application of hot air, like methods, or any combination thereof. In some instances, the neural interface portion543of the fourth intermediate structure590is heated at 180° C. to 210° C., for example about 200° C., for 15 to 40 minutes, for example 25 minutes. In certain instances, the fourth heat shrink tube585shrinks or recovers at a given temperature (e.g., about 200° C.) and the first layer of polymer535reflows at or about the same given temperature (e.g., about 200° C.). Consequently, as the neural interface portion543of the fourth intermediate structure590is heated to the given temperature, the third heat shrink tube585shrinks (because the stent580can compress under force) to define a compressed configuration with a precisely controlled outer diameter (o″). Substantially simultaneously, the first layer of polymer535liquefies and flows around and through the mesh structure of the stent580and completely or partially encases the stent580within the polymer. Thereafter, the fourth intermediate structure590is cooled (e.g., at ambient temperature) to obtain the thin-film lead assembly500, as shown inFIG.5J. Optionally, the third heat shrink tube may be removed and the thin-film lead assembly may be inserted into a delivery device that maintains the neural interface portion and the stent in a compressed configuration.

While the manufacturing processes of a thin-film lead assembly and structures thereof have been described at some length and with some particularity with respect to a specific steps, it is not intended that the processes be limited to any such particular set of steps. Instead, it should be understood the manufacturing processes described herein are exemplary embodiments, and that the manufacturing processes are to be construed with the broadest sense to include variations of the steps to meet specific design and/or performance need described herein, as well as other variations that are well known to those of skill in the art. For example, the various intermediate and final structures described may be adjusted or modified with treatments to increase wettability of the thin-film lead assembly or to seal the ends of the lumens to meet specific design and/or performance needs. Furthermore, it is to be understood that other steps have been omitted from the description of the manufacturing processes for simplicity and clarity. The omitted steps may include obtaining or fabricating the polymer tubes, waiting predetermined amounts of time for curing or thermosetting, etc.

VI. Methods for Delivering a Thin-Film Lead Assembly

FIG.6depicts a simplified flowchart depicting processing performed for accessing a site of a target biological structure in a patient and delivering a medical device or system for neurostimulation or interfacing to the site of the target biological structure according to various embodiments. As noted herein, the flowchart ofFIG.6illustrates the architecture, functionality, and operation of possible implementations of systems, devices, and methods described with respect toFIGS.1,2A,2B,3A,3B,4A-4F, and5A-5J. In this regard, each block in the flowchart or block diagrams comprises one or more processes or procedures. It should also be noted that, in some alternative implementations, the processes or procedures noted in each block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and/or flowchart illustration, and combination of blocks in the block diagrams and/or flowchart illustration, can be implemented manually by a user such as a surgeon or by special purpose hardware-based systems that perform the specified functions or acts, or combinations of special purpose hardware and computer instructions stored on a non-transitory storage medium.

FIG.6shows a method of delivering a thin-film lead assembly to a target biological structure. At step605, a thin-film lead assembly is placed within a delivery device (e.g., a delivery sheath) in a compressed configuration to deliver the thin-film lead assembly to a target biological structure. Alternatively, a medical device is obtain comprising the thin-film lead assembly predisposed within a delivery device (e.g., a delivery sheath) in a compressed configuration to deliver the thin-film lead assembly to a target biological structure. As shown inFIG.7A, the delivery device705is configured to compress a portion of or the entire length the thin-film neural interface710and the stent715, which allows efficient delivery of the thin-film lead assembly700regardless of the orientation of the stent715. In addition, use of the delivery device705can prevent engagement/interfacing of the thin-film lead assembly700with tissue or bodily fluid until the delivery device705is removed or the stent715is deployed from the delivery device705. The delivery device705may comprise a removable material (e.g., peelable or absorbable material) that surrounds or covers at least the thin-film neural interface710and the stent715. In some instances, the delivery device705is made from one or more of an implantable grade resorbable or non-resorbable polymer and/or metal material. In certain instances, the delivery device705comprises one or more of polypropylene, polyester, nylon, polyether ether ketone (PEEK), polyurethane, polycarbonate, titanium, and stainless steel.

With reference back toFIG.6, at optional step610, one or more incisions are made in a subject (e.g., a patient) to access a target biological structure. At step615, the thin-film lead assembly is inserted and/or guided into a cavity of a body (optionally through the one or more incisions) to a target site of the biological system. As shown inFIG.7A, the cable portion720of the thin-film lead assembly700comprises a lumen725that extends from a proximal end730of the thin-film lead assembly700through the stent715to a distal end735of the thin-film lead assembly700. The lumen725may have a diameter wide enough to receive a guide wire740for guiding the thin-film lead assembly700to a target site of the biological system. At step620, once the thin-film lead assembly reaches the target site of the biological system, the delivery device is retracted from at least the thin-film neural interface, and the stent is used to deploy the thin-film neural interface. A shown inFIG.7B, once the thin-film lead assembly700is at a target location, the delivery device705is removed from the distal end735of the thin-film lead assembly700and the guide wire740is removed from the lumen725. Thereafter, the thin-film neural interface710is deployed using the stent715. The deploying comprises expanding the stent715from the compressed configuration (FIG.7A) to an expanded configuration (FIG.7B) that places the electrodes745into contact with the target biological structure (e.g., a blood vessel wall).

In some instances, the stent715is deployed and expands automatically once the delivery device is retracted from the stent715(e.g., once the compression force provided by the delivery device is removed, the stent automatically expands (for example, memory shape expansion)). In other instances, the stent715is deployed and expands semi-automatically or manually once the delivery device is retracted from the stent715(e.g., once the compression force provided by the delivery device is removed, the stent is expanded using one or more mechanism such as balloon assisted deployment). In some instances, the stent715is deployed in a blood vessel and the stent715is a cylindrical mesh tube such that blood flow is uninterrupted through the blood vessel. Advantageously, the helical wrapping of the thin-film neural interface710around the stent715allows for the thin-film neural interface710to loosen and expand as the stent715expands. Moreover, the “wrapped tightly” configuration means that the thin-film neural interface710can support a dense arrangement electrodes745for interfacing consistently with the target biological structure.

With reference back toFIG.6, at step625, the thin-film lead assembly is connected to a computing device (e.g., a pulse generator or an interfacing processor). As described with respect toFIG.1, the computing device can be implantable, semi-implantable, or an external system. At step630, the neural interface is used to provide neurostimulation and/or sense electrical activity at the target biological structure.

While the invention has been described in detail, modifications within the spirit and scope of the invention will be readily apparent to the skilled artisan. It should be understood that aspects of the invention and portions of various embodiments and various features recited above and/or in the appended claims may be combined or interchanged either in whole or in part. In the foregoing descriptions of the various embodiments, those embodiments which refer to another embodiment may be appropriately combined with other embodiments as will be appreciated by the skilled artisan. Furthermore, the skilled artisan will appreciate that the foregoing description is by way of example only, and is not intended to limit the invention.