Micro-invasive electrode arrays

Abstract

Certain aspects of the disclosure concern a device for insertion into a biological medium. The device includes a plurality of conductive electrode filaments (CEFs). Body portions of the plurality of CEFs are clustered together to form a CEF bundle. Each CEF comprises an electrically conductive filament and an electrically non-conductive coating. The electrically non-conductive coating covers an entire length of the electrically conductive filament except at a distal tip portion of the electrically conductive filament that is not covered by the electrically non-conductive coating to define an electrode. Proximal ends of the electrically conductive filaments are connected to respective conductive wires. The CEF bundle is stiffened to resist disintegration or deformation of individual CEFs such that the body portion of each CEF remains parallel to a central longitudinal axis of the CEF bundle during insertion of the CEF bundle into the biological medium.

Description

8123-112597-02MICRO-INVASIVE ELECTRODE ARRAYSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No.63 / 748,635, filed January 23, 2025, which is incorporated herein by reference in its entirety.FIELD

[0002] The present disclosure concerns micro-invasive electrode arrays and the methods of fabricating and using the same.ACKNOWLEDGMENT OF GOVERNMENT SUPPORT

[0003] This invention was made with government support under NS 107639 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND

[0004] Electrode arrays are important tools for recording electrophysiological and / or neurochemical signals in neural tissues, providing valuable insights into the functioning of neural circuits and the underlying mechanisms of behavior. Despite recent advancements in electrode array technologies, there remains significant potential for improvement, particularly in designing micro-invasive electrode arrays that facilitate the study of cellular-scale interactions between molecular and electrical neuronal signals.SUMMARY

[0005] Described herein are devices, apparatuses, and systems that can be used as micro-invasive electrode arrays, as well as methods for fabricating and using the same. As used herein, the term micro-invasive refers to electrode arrays configured to penetrate and operate within a biological medium with reduced physical disruption and insertion-related effects that would otherwise degrade recording fidelity, stimulation precision, or long-term electrical performance. In some examples, this is achieved by employing individual electrodes having dimensions comparable to cells and / or molecular-scale features in the intended biological environment, including micron-scale cross-sectional dimensions and high aspect ratios (e.g., greater than 1000). The micro-invasive electrode arrays disclosed herein can be used to record electrophysiological and / or neurochemical signals from, and / or deliver electrical stimulation to, biological tissue and / or biological fluid. By way of example, in some8123-112597-02implementations the micro-invasive electrode arrays disclosed herein can be configured for use within brain tissue. As described more fully below, the disclosed technologies overcome many deficiencies of conventional electrode array technologies.

[0006] According to certain aspects of the disclosure, a device for insertion into a biological medium includes a plurality of conductive electrode filaments (CEFs). Body portions of the plurality of CEFs are clustered together to form a CEF bundle. Each CEF comprises an electrically conductive filament and an electrically non-conductive coating. The electrically non-conductive coating covers an entire length of the electrically conductive filament except at a distal tip portion of the electrically conductive filament that is not covered by the electrically non-conductive coating to define an electrode. Proximal ends of the electrically conductive filaments are connected to respective conductive wires. The CEF bundle is stiffened to resist disintegration or deformation of individual CEFs such that the body portion of each CEF remains parallel to a central longitudinal axis of the CEF bundle during insertion of the CEF bundle into the biological medium.

[0007] In some examples, the electrically conductive filament is a carbon fiber.

[0008] Certain aspects of the disclosure concern a method for fabricating a micro-invasive electrode array for insertion into a biological medium. The method includes receiving a plurality of carbon fiber electrode threads (CFETs), each CFET comprising a carbon fiber and an electrode defined at a tip portion of the carbon fiber; and clustering body portions of the plurality of CFETs into a CFET bundle. The plurality of CFETs have different lengths such that at least some electrodes in the CFET bundle are axially offset from one another by a predefined distance.

[0009] In some examples, the method further includes creating the plurality of CFETs, comprising: receiving a plurality of carbon fibers; coating an electrically non-conductive layer over an entire length of each carbon fiber; and removing the non-conductive layer from distal tip portions of the plurality of carbon fibers to form a plurality of electrodes.

[0010] According to certain aspects of the disclosure, a method includes receiving an electrode array including a plurality of carbon fiber electrode threads (CFETs). Body portions of the plurality of CFETs are clustered into a CFET bundle. Each CFET includes a carbon fiber and an electrically non-conductive coating. The electrically non-conductive coating covers an entire length of the carbon fiber except at a distal tip portion of the carbon fiber which is not covered by the electrically non-conductive coating to define an electrode. The method further includes stiffening the CFET bundle at least temporarily and inserting the CFET bundle into a biological medium. The CFET bundle is so stiffened that when the8123-112597-02inserted CFET bundle reaches a target location of the biological medium, the body portions of the plurality of CFETs remain parallel to a central longitudinal axis of the CFET bundle.

[0011] The foregoing and other features and advantages of the disclosed technologies will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures.BRIEF DESCRIPTION OF THE DRAWINGS

[0012] FIG. 1 A schematically depicts a micro-invasive electrode array including a plurality of carbon fiber electrode threads (CFETs) clustered into a CFET bundle, according to one example.

[0013] FIG. IB is an enlarged view of a distal end portion of the CFET bundle of FIG. 1A.

[0014] FIG. 2A is a perspective view of a distal end portion of a CFET bundle, according to one example.

[0015] FIG. 2B is a cross-sectional view of the CFET bundle of FIG. 2A.

[0016] FIG. 3A depicts connecting proximal ends of a plurality of CFETs to respective conductive wires, according to one example configuration.

[0017] FIG. 3B depicts connecting proximal ends of a plurality of CFETs to respective conductive wires, according to another example configuration.

[0018] FIG. 4 is a block diagram illustrating example circuitry that can be connected to any of the CFETs disclosed herein.

[0019] FIG. 5 is a flowchart describing an example overall method for fabricating a micro-invasive electrode array.

[0020] FIG. 6A schematically depicts attaching a plurality of carbon fibers in connection with conductive wires to a fixture.

[0021] FIG. 6B schematically depicts flame etching distal end portions of the carbon fibers of FIG. 6A, according to one example.

[0022] FIG. 6C schematically depicts a plurality of CFETs formed after the flame etching of FIG. 6B.

[0023] FIG. 6D schematically depicts temporarily connecting the plurality of CFETs of FIG.6C to a circuit board for testing, according to one example.

[0024] FIG. 6E schematically depicts connecting a plurality of CFETs that were successfully tested to a circuitry, according to one example.

[0025] FIG. 6F schematically depicts clustering body portions of the CFETs of FIG. 6E into a CFET bundle, according to one example.8123-112597-02

[0026] FIG. 7 is a flowchart describing an example method for inserting a micro-invasive electrode array into a biological medium.

[0027] FIG. 8 is a block diagram of an example computing system which can be used in conjunction with the circuitry for controlling operations of the micro-invasive electrode arrays described herein.DETAILED DESCRIPTIONGeneral Considerations

[0028] For purposes of this description, certain aspects, advantages, and novel features of the embodiments of this disclosure are described herein. The disclosed methods, apparatus, and systems should not be construed as being limiting in any way. Instead, the present disclosure is directed toward all novel and nonobvious features and aspects of the various disclosed examples, alone and in various combinations and sub-combinations with one another. The methods, apparatus, and systems are not limited to any specific aspect or feature or combination thereof, nor do the disclosed examples require that any one or more specific advantages be present or problems be solved. The technologies from any example can be combined with the technologies described in any one or more of the other examples. In view of the many possible examples to which the principles of the disclosed technology may be applied, it should be recognized that the illustrated examples are only preferred examples and should not be taken as limiting the scope of the disclosed technology.

[0029] Although the operations of some of the disclosed examples are described in a particular, sequential order for convenient presentation, it should be understood that this manner of description encompasses rearrangement, unless a particular ordering is required by specific language set forth herein. For example, operations described sequentially may in some cases be rearranged or performed concurrently. Moreover, for the sake of simplicity, the attached figures may not show the various ways in which the disclosed methods can be used in conjunction with other methods. Additionally, the description sometimes uses terms like “provide” or “achieve” to describe the disclosed methods. These terms are high-level abstractions of the actual operations that are performed. The actual operations that correspond to these terms may vary depending on the particular implementation and are readily discernible by one of ordinary skill in the art. Any theories of operation are to facilitate explanation, but the disclosed systems, methods, and apparatus are not limited to such theories of operation.8123-112597-02

[0030] As used in this application and in the claims, the singular forms “a," “an," and “the” include the plural forms unless the context clearly dictates otherwise. As used herein, “and / or” means “and” or “or,” as well as “and” and “or.” Additionally, the term “includes” means “comprises.” Further, the terms “coupled” and “connected” generally mean electrically, electromagnetically, and / or physically (e.g., mechanically or chemically) coupled or linked and does not exclude the presence of intermediate elements between the coupled or associated items absent specific contrary language.

[0031] As used herein, the term “proximal” refers to a position, direction, or portion of a device that is closer to the user or operator of the electrode array and further away from the electrode array insertion site. As used herein, the term “distal” refers to a position, direction, or portion of a device that is further away from the user or operator of the electrode array and closer to the electrode array insertion site. The terms “longitudinal” and “axial” refer to an axis extending in the proximal and distal directions, unless otherwise expressly defined.

[0032] Directions and other relative references (e.g., inner, outer, upper, lower, top, bottom, etc.) may be used to facilitate discussion of the drawings and principles herein, but are not intended to be limiting. For example, certain terms may be used such as “inside,” “outside,” “interior,” “exterior,” and the like. Such terms are used, where applicable, to provide some clarity of description when dealing with relative relationships, particularly with respect to the illustrated examples. Such terms are not, however, intended to imply absolute relationships, positions, and / or orientations. For example, with respect to an object, an “upper” part can become a “lower” part simply by turning the object over. Nevertheless, it is still the same part and the object remains the same.

[0033] In any of the examples described herein, unless specified otherwise, a value’s range (e.g., from a first end point to a second end point, or between a first end point and a second endpoint) is inclusive of the specified end points.

[0034] In any of the examples described herein, unless specified otherwise, the terms “approximately” and “about” mean that the listed value and any value that is within 20% of the listed value. For example, “about 10 mm” means any value between about 8 mm and about 12 mm, inclusive.Overview of Electrode Arrays for Deep Brain Structures

[0035] Electrode arrays for deep brain structures have revolutionized our understanding of brain activity, particularly in the context of neural circuits and neurochemical dynamics. Electrode arrays can be used for simultaneous recording of electrical signals from neurons and application of deep brain stimulation (DBS) to modulate neural activity. However, the8123-112597-02development of electrode arrays for use in complex and deeply embedded brain regions presents several technical challenges, particularly in non-human primates and humans.

[0036] First, precise targeting of deep brain structures such as the striatum or thalamus, located 15-35 mm below the cortical surface in non-human primates and up to 90 mm in humans, can be a significant challenge. Electrode arrays must be robust enough to traverse the brain's intricate architecture without causing significant tissue damage. Their physical design must prevent buckling or breakage during insertion, particularly for the longer lengths required to reach deep targets. Electrode arrays optimized for smaller animals, such as rodents, are often inadequate for these larger brains due to differences in scale, both in depth and in the volume of target structures.

[0037] Volumetric density of electrode array presents another challenge. Volumetric density can be defined as the number of recording and / or stimulation electrodes per cubic centimeter of brain tissue. Optimizing this metric can be important for achieving high-resolution, multisite recordings and / or stimulation across spatially heterogeneous brain regions.Conventionally, each electrode is inserted through a guide tube, which requires a single dural penetration to traverse the stiff dura mater. These guide tubes, typically exceeding 400 microns in diameter, limit the number of electrodes that can be safely inserted without causing significant trauma or increasing the risk of complications such as stroke or hemorrhage. Empirical observations suggest that exceeding 30 dural penetrations per square centimeter in a single procedure can lead to severe side effects, including stroke, seizures, hemorrhage, and heightened infection risk. As a result, this constraint imposes a practical maximum volumetric density of approximately 30 electrodes per cubic centimeter in conventional designs.

[0038] Another technical challenge for electrode arrays is the ability to record both electrical and neurochemical signals simultaneously from the same region. Understanding how neurotransmitters, such as dopamine, interact with neural circuits during behavior can help unraveling the complexities of brain function. Dopamine plays an important role in learning, motivation, and neuroplasticity, but current technologies are often unable to capture the realtime interaction between dopamine release and neuronal spiking in awake, behaving subjects. This gap in technology is particularly significant in non-human primates and / or humans, where the ability to monitor both types of signals in close proximity is important for studying naturalistic behaviors. This challenge is compounded when there is a need for both recording signals from a deep brain structure and stimulating the same region.8123-112597-02

[0039] Spatial heterogeneity in neural signals and their dynamic interactions with behavior present significant challenges for neural recording systems. Neurochemical and electrophysiological activities vary widely across different brain regions, even within localized areas of the same structure. For example, dopamine release in the striatum occurs across spatial scales ranging from micrometer-scale domains to broader millimeter-scale waves, requiring electrode arrays capable of capturing diverse dynamics with high spatial resolution. This challenge is compounded when trying to link cellular-level neuronal activity with complex behaviors like decision-making or learning, which demand not only precise spatial and temporal resolution but also simultaneous recordings from multiple interconnected brain regions. For instance, activity in one region, such as the prefrontal cortex, can influence and be influenced by deep structures like the basal ganglia. Current techniques, such as wide-field imaging with fluorescent reporters, offer insights into spatial neurochemical distributions but often lack the resolution needed to track both electrical and chemical signals in a highly localized and coordinated manner across brain regions.Developing comprehensive neural recording systems that capture these multi-regional interactions can be important for understanding how neural networks drive behavior.

[0040] Additionally, chronic recording in non-human primates and / or humans poses specific obstacles, especially when aiming for long-term studies of neural dynamics over days, weeks, or months. While advances in micro-invasive sensors, such as carbon fiber-based electrodes, have allowed for stable, long-term recordings in rodent models, translating these technologies to non-human primates and / or humans remains a major hurdle. The larger brain volumes and deeper structures in primates require more durable, flexible, and biocompatible materials that can maintain their functionality over extended periods without causing inflammation or signal degradation. Ensuring that these sensors can withstand the mechanical stress of prolonged brain implantation is important to achieving consistent and reliable data collection. Similar challenges exist for chronic DBS in non-human primates and / or humans, where electrode array must remain functional and biocompatible over extended periods to avoid tissue damage and maintain therapeutic efficacy.

[0041] The scalability of current neural recording platforms also remains limited. State-of-the-art electrode arrays support dense multi-channel recording, enabling high-resolution data collection across multiple sites. However, these systems are often optimized primarily for electrical recordings and do not yet fully address the need for integrated neurochemical measurements, particularly in species like non-human primates or humans, where the ability to combine electrical and chemical sensing is important for understanding complex brain8123-112597-02functions. While ongoing efforts aim to develop multi-modal electrode arrays capable of recording both electrical activity and neurochemical signals, current designs remain suboptimal for non-human primate and human applications. Challenges include ensuring precise sensor placement, achieving sufficient signal sensitivity for both modalities, and maintaining biocompatibility over extended periods. Additionally, the development of a multi-channel DBS system that integrates recording and stimulation capabilities across multiple regions simultaneously has yet to be realized.

[0042] A recent advancement in electrode array design involves the development of flexible “electrode-thread” arrays composed of ultrathin (about 10 microns diameter) carbon fiber electrode threads (CFETs) bundled into a single insertion point. During implantation, the innate flexibility of the CFETs allows them to splay laterally in deep brain tissue, enabling measurements from multiple horizontally distributed targets with a single-entry penetration. This design can increase volumetric density by allowing simultaneous recordings across a wider spatial area compared to conventional electrode arrays. However, a limitation of this approach is that the splaying process results in random electrode positioning, making it difficult to precisely control the placement of individual electrodes within the target regions.

[0043] The technologies described herein address many of the challenges described above. Specifically, the disclosed electrode arrays, based on flexible CFETs, enable simultaneous recording of electrophysiological and neurochemical signals, including in regions such as the striatum, thalamus, and basal ganglia. Importantly, the disclosed technologies can ensure electrodes achieve predetermined spatial configurations after insertion into a biological medium (e.g., brain tissue), allowing precise targeting of specific biological regions. This controlled placement minimizes random electrode positioning, ensuring consistent electrode alignment with targeted neural regions, which can improve spatial resolution, enhance data reliability, and reduce variability across experiments. Designed for long-term use, these electrode arrays support stable, chronic recordings and can integrate DBS capabilities. With configurations of 16-32 channels in a single insertion, these electrode arrays can achieve volumetric densities of up to 960 electrodes per cubic centimeter. Their adaptability for use in multiple brain regions and species, including non-human primates and humans, makes them powerful tools for studying neural circuits and advancing clinical applications.

[0044] Although the following embodiments describe brain tissue as an example target medium for electrode array insertion, the disclosed electrode arrays are not limited to use within brain tissue. Rather, the electrode arrays described herein can be inserted into and operated within a variety of biological media, including other neural tissues (e.g., spinal cord,8123-112597-02dorsal root ganglion, peripheral nerves, etc.), gastrointestinal tract, organs (e.g., cochlea, etc.), muscle tissue, and biological fluids, depending on the intended application. Accordingly, references to brain tissue throughout this disclosure are provided for illustrative purposes and should not be construed as limiting the scope of the disclosed technologies.Exemplary Overall Structure of Electrode Arrays

[0045] FIGS. 1A-1B schematically depict (not drawn to scale) a micro-invasive electrode array 100 that can be inserted into a biological medium (e.g., brain tissue), according to one example.

[0046] The electrode array 100 includes a plurality of carbon fiber electrode threads 102 (CFETs). Body portions 104 of the plurality of CFETs 102 are clustered together to form a CFET bundle 120. The CFET bundle 120 extends in axial direction and has a central longitudinal axis 122.

[0047] In some examples, the plurality of CFETs 102 can be clustered together by applying a bonding agent 128. The bonding agent 128 can facilitate the aggregation of the CFETs 102 into a cohesive bundle, ensuring its structural integrity during handling and insertion.

[0048] In some examples, the bonding agent 128 is configured to provide sufficient adhesive strength to stiffen the CFET bundle 120, resisting disintegration of the CFET bundle 120 and / or deformation of individual CFETs 102 and maintaining the parallel alignment of the body portions 104 of the CFETs 102 along the central longitudinal axis 122.

[0049] The bonding agent 128 can be formulated to be biocompatible, reducing the likelihood of adverse biological reactions when implanted in the biological medium.

[0050] In some examples, the bonding agent 128 can be maltose, a biodegradable material that gradually dissolves upon exposure to physiological fluids after insertion. Other biocompatible materials with similar adhesive properties (e.g., polyethylene glycol, etc.) may also be employed.

[0051] In some examples, the bonding agent 128 can be composed of non-dis solvable materials. For instance, the bonding agent 128 can include polydimethylsiloxane (PDMS) and / or polyethylene glycol diacrylate (PEGDA).

[0052] Each CFET 102 includes a carbon fiber 110 and an electrically non-conductive coating 108 (also referred to as electrically non-conductive layer). The electrically non-conductive coating 108 can coat or cover an entire length of the carbon fiber 110 except at a distal tip portion 106 of the carbon fiber which is not covered by the electrically non-conductive coating 108 to define an electrode which can directly contact the surrounding tissue. Thus, the distal tip portion 106 of each carbon fiber can also be referred to as an8123-112597-02“electrode” hereinafter. In some examples, the electrode 106 is exposed to the surrounding biological medium. In other examples, one or more additional coatings or surface treatments can be applied to the electrode 106 to modify electrochemical properties of the electrode, such as charge injection capacity and / or analyte sensitivity, while still permitting electrical and / or electrochemical interaction with the surrounding biological medium.

[0053] In some examples, the electrically non-conductive coating 108 can be a polymer coating, such as parylene. In one specific example, the polymer can be parylene C. In other examples, instead of a polymer coating, the electrically non-conductive coating 108 can comprise one or more layers of a different electrically non-conductive material or combination of electrically non-conductive materials, such as silicon oxide, aluminum oxide, silicon nitride, or combinations thereof. The electrically non-conductive coating electrically insulates each CFET 102 along its length, thereby inhibiting undesired charge injection, electrical interference, and / or signal coupling from external sources or from other CFETs in the CFET bundle. In this manner, the electrically non-conductive coating helps ensure that signals conducted along each CFET 102 remain electrically isolated and are primarily attributable to interactions occurring at corresponding electrode regions.

[0054] In some examples, the electrically non-conductive coating 108 can be composed of other insulation materials such as polyimide, ethylene tetrafluoroethylene (ETFE), polytetrafluoroethylene (PTFE), etc.

[0055] The CFET bundle 120 has a proximal end 124 and a distal end 126. The distal end 126 is a terminal end defined by at least one of the electrodes 106 in the CFET bundle 120. The distance between the proximal end 124 and the distal end 126 defines an axial length (LI) of the CFET bundle 120.

[0056] In some examples, as illustrated in FIG. 1A, proximal ends of the plurality of CFETs 102 can be aggregated together to define the proximal end 124 of the CFET bundle 120. In such cases, the proximal end 124 represents the terminal ends of the individual CFETs 102 (or terminal ends of the carbon fibers 110). The axial length of each individual CFET 102 (or each individual carbon fiber 110) is less than or equal to the axial length (LI) of the CFET bundle 120.

[0057] In other examples, the proximal end 124 of the CFET bundle 120 can be spaced apart from (e.g., positioned distal to) the proximal ends of individual CFETs 102. In this configuration, segments or proximal end portions of some individual CFETs 102 can extend out of the proximal end 124 and diverge outwardly from one another. Thus, at least some8123-112597-02CFETs 102 (or individual carbon fibers 110) can have axial lengths that are longer than the axial length (LI) of the CFET bundle 120.

[0058] In some examples, proximal ends of the carbon fibers 110 are connected to respective conductive wires 130, e.g., using silver epoxy or the like. The conductive wires 130 can also be coated with the electrically non -conductive coating 108 for insulation to prevent electrical interference between adjacent conductive wires. In some examples, the conductive wires 130 can be copper wires. In other examples, the conductive wires 130 can be composed of other flexible metals and / or metal alloys, such as silver, gold, etc. In still other examples, the conductive wires 130 can comprise conductive polymers such as polypyrrole and / or polyaniline.

[0059] Each conductive wire 130 can be connected to a corresponding pad 132 on a printed circuit board (PCB) 140. In some examples, the PCB 140 can be flexible (e.g., the substrate of the PCB can be composed of polyimide or the like). Wire traces 134 on the PCB 140 can connect the pads 132 to one or more circuitries configured to control operations of the electrodes 106. For example, one circuit in electrical communication with one or more conductive wires can be configured to measure electrophysiological and / or neurochemical signals of the biological medium surrounding one or more electrodes (which can also be referred to as “sensing electrodes”) in the CFET bundle 120. As another example, one circuit in electrical communication with one or more conductive wires can be configured to deliver electrical pulses to one or more electrodes (which can also be referred to as “stimulating electrodes” or “pacing electrodes”) in the CFET bundle 120. Exemplary circuitries and configurations of the electrodes are described further below.

[0060] In some examples, the conductive wires 130 are elongated such that individual CFETs of the CFET bundle 120 can be directly connected to the one or more circuitries described above without an intervening PCB. In some examples, the conductive wires 130 can be connected to a PCB that is positioned above an implantation site and is distinct from the PCB 140, where the PCB above the implantation site can be configured to wirelessly transmit signals between the conductive wires 130 and remotely located one or more circuitries. In some examples, rather than being coupled to the PCB 140 via conductive wires, individual CFETs can be directly connected to pads 132 of the PCB 140 using a conductive bonding material, such as a silver epoxy or other electrically conductive adhesive. In some examples, any portion of the CFET bundle 120 that is not implanted in biological medium can be covered by an insulating material to electrically isolate the conductive wires 130 and reduce signal interference.8123-112597-02

[0061] Although carbon fiber electrode threads (CFETs) are described herein as an illustrative example, it should be understood that the disclosed electrode arrays are not limited to carbon fiber-based filaments. In various examples, the electrode threads can instead be formed from other electrically conductive filaments, such as metal filaments, metal-alloy filaments, conductive polymer filaments, carbon-based filaments other than carbon fiber (e.g., carbon nanotube fibers, graphene-based filaments, glassy carbon filaments, etc.), or combinations thereof. In such examples, the electrode threads may be more generally referred to as conductive electrode filaments (CEFs), and can be coated, bundled, stiffened, and electrically coupled in the same or similar manner as described herein with respect to CFETs. All such variations are considered within the scope of the disclosed technologies.Exemplary Arrangements of Electrodes

[0062] The electrodes 106 in the CFET bundle 120 can have a predefined spatial arrangement to facilitate optimal contact with biological medium upon insertion.

[0063] In some examples, an electrode in the CFET bundle 120 that is positioned closer to the central longitudinal axis 122 can extend to a more distal location than another electrode in the CFET bundle 120 that is positioned more peripherally. This arrangement can ensure that each electrode 106 is positioned for direct and consistent contact with the biological medium. Specifically, a centrally located CFET 102 being longer than its peripheral counterparts can prevent scenarios where the electrode of the central CFET could be obscured or shielded by neighboring CFETs. For instance, if the central CFET were shorter and surrounded by longer CFETs, the electrode in the central CFET might fail to make adequate contact with biological medium, resulting in reduced recording or stimulation efficiency.

[0064] In some examples, one or more electrodes 106 of the CFETs are positioned at or near a curved distal end surface of the CFET bundle 120. This curved end surface may, for example, take a conical or tapered shape, or other geometries suited for facilitating interaction with a biological medium. In some cases, the curvature of the end surface can facilitate smoother insertion of the CFET bundle 120 into the biological medium and reduce tissue trauma. In one specific example, the distal end surface of the CFET bundle 120 is tapered to form a pointed tip to facilitate smooth insertion into a target biological medium.

[0065] In some examples, each electrode 106 in the CFET bundle 120 is configured to maintain direct contact with the surrounding biological medium after insertion. For example, the electrodes 106 of the CFETs can be arranged in a helical pattern around the CFET bundle 120. This helical configuration may improve electrode-tissue contact across a larger surface8123-112597-02area of the CFET bundle 120. Additionally, this helical arrangement may improve spatial distribution of the electrodes 106 (e.g., more uniform electrode coverage) across a relatively large biological region, which may improve the quality of data collection from that region. Furthermore, the helical arrangement allows for recording and / or stimulation at varying depths along the length of the CFET bundle 120 as well as laterally around its circumference, enabling comprehensive neural interfacing.

[0066] To further illustrate, FIGS. 2A-2B depicts another electrode array 200 including a plurality of CFETs 202 forming a CFET bundle 220. Similar to the example depicted in FIGS. 1A-1B, each CFET 202 includes a carbon fiber 210 coated with an electrically non-conductive coating 208 (e.g., polymer coating) along its entire length except at the distal end portion which is not covered by the electrically non-conductive coating 208 as an electrode 206. In some examples, one or more of the electrodes 206 are exposed to the surrounding biological medium. In other examples, one or more additional coatings or surface treatments can be applied to the electrodes 206 to modify electrochemical properties of the electrodes while still permitting electrical and / or electrochemical interaction with the surrounding biological medium. As shown, the electrodes 206 are arranged in a helical pattern around and along the CFET bundle 220. This helical pattern is formed by the sequential positioning of the electrodes 206 along a spiral trajectory that wraps around the central longitudinal axis and follows the outer circumference of the CFET bundle 220.Exemplary Dimensions of Electrode Arrays

[0067] The electrode arrays disclosed herein are configured to be sufficiently rigid and long to penetrate and reach deep brain structures. Despite their rigidity, these electrode arrays are configured to be micro-invasive such that the target biological medium is minimally perturbed and has a reduced likelihood of scar formation. Any of the electrode arrays disclosed herein (e.g., 100, 200) can be fabricated in specific dimensions that are critical to reduce trauma or injury when inserting them into the biological medium. Some representative dimension parameters of the electrode arrays are described below with reference to FIGS. 1A-1B, using the electrode array 100 as an example.

[0068] In some examples, each CFET 102 in the CFET bundle 120 can have an aspect ratio between 1000 and 20000. In some examples, the aspect ratio of the CFETs 102 can range between 2000 and 10000. Such high aspect ratio ensures that the CFETs 102 are sufficiently long and slender, facilitating penetration into deep brain tissue or other biological medium while minimizing insertion forces and reducing potential damage to surrounding structures.8123-112597-02

[0069] In some examples, each carbon fiber 110 (including the electrode 106) can have an outer diameter between 2 and 10 microns, or between 4 and 8 microns. In one specific example, the carbon fiber 110 has an outer diameter of 7 microns. In another specific example, the carbon fiber has an outer diameter of 5 microns.

[0070] The thickness of the electrically non-conductive coating around the carbon fiber 110 is configured to provide sufficient insulation of the carbon fiber. In some examples, the carbon fiber with electrically non-conductive coating (e.g., the body portion 104 of each CFET) can have an outer diameter that is between 0.1 and 10 microns larger than the outer diameter of the uncoated carbon fiber 110. In some examples, the outer diameter of the carbon fiber coated with the electrically non-conductive layer can be between 0.5 and 5 microns, or between 1 and 2 microns, larger than the outer diameter of the uncoated carbon fiber. In some examples, the body portion 104 of CFET 102 can have an outer diameter between 5 and 12 microns. In one specific example, when the uncoated carbon fiber 110 has an outer diameter of about 7 microns, the outer diameter of each CFET 102 (including the carbon fiber 110 and the surrounding electrically non-conductive coating 108) can be about 10 microns.

[0071] In some examples, each CFET 102 in the CFET bundle 120 can have an axial length that is between 1 mm and 100 mm, or between 5 mm and 50 mm. This variable length allows the electrodes 106 to reach both superficial brain locations (e.g., cortex) and deep brain structures (e.g., striatum). In some examples, the longest CFET 102 can define the axial length (LI) of the CFET bundle 120.

[0072] In some examples, the conductive wires 130 electrically coupled to the CFETs 102 have dimensions selected to provide electrical isolation, flexibility, and mechanical robustness for routing signals to corresponding circuitries. In some examples, each conductive wire 130 can have an outer diameter between about 25 microns and about 40 microns and includes an insulating coating, such as polyimide or parylene, having a thickness between about 1.5 microns and about 2 microns. The axial length of the conductive wires 130 can vary based on application requirements and can range, for example, from about 5 mm to about 200 mm or longer. In some examples, a bundle of conductive wires 130 can be further enclosed within an additional insulating sheath, such as polyolefin tubing, having a shrunken outer diameter of about 150-200 microns.

[0073] In some examples, an axial length (L2) of the electrodes 106 can vary based on the configuration of the electrode. For instance, when an electrode 106 is configured to measure electrophysiological signals of the surrounding biological medium, L2 can be in a range8123-112597-02between 5 and 300 microns, or between 5 and 100 microns. On the other hand, when an electrode 106 is configured to measure neurochemical signals (e.g., signals indicating changes in dopamine concentration), L2 can be in a relatively longer range, e.g., between 100 and 300 microns or between 100 and 500 microns, to achieve a desired sensitivity of measurement. As another example, when an electrode 106 is configured to deliver stimulation pulses, L2 can be in a range between 1 micron and 6 millimeters, or between 5 microns and 5 millimeters.

[0074] In some examples, instead of, and / or in lieu of, varying the length of the electrodes 106 to achieve desired electrode performance, surface treatments can be applied to the electrodes 106 to enhance its functionality. For instance, coating the electrodes 106 with PEDOT (poly(3,4-ethylenedioxythiophene)) or other conductive polymers can increase its surface roughness, thereby increasing the effective surface area without altering the axial length (L2). This allows for L2 to remain relatively small (e.g., between 1 and 5 microns for measuring electrophysiological signals, etc.), while still providing a sufficiently large surface area to improve signal sensitivity and reduce impedance. Other non-coating methods, such as laser etching, can also be used to increase the effective surface area of the electrodes 106. In some examples, regardless of their axial length (L2), the electrodes 106 in the CFET bundle 120 can have different surface areas. An electrode with a smaller surface area can be configured to measure electrophysiological signal of the surrounding biological medium, whereas another electrode with a larger surface area can be configured to measure neurochemical signal of the surrounding biological medium.

[0075] The electrodes 106 in the CFET bundle 120 are configured to be spaced apart from one another to avoid contacting each other that would cause shorting between the electrodes. On the other hand, in some circumstances, at least one pair of electrodes 106 can be arranged in close proximity so that the pair of electrodes can be employed to simultaneously measure, respectively, electrophysiological signals and neurochemical signals within a focal vicinity of the biological medium. Simultaneous measurement within such a focal vicinity allows direct observation of the interactions between molecular and electrical neuronal signals, which can be important for understanding synaptic plasticity and adaptive behaviors within the biological medium.

[0076] In some examples, at least one pair of immediately adjacent electrodes 106 in the CFET bundle 120 can be axially offset from one another by a predefined distance (L3), also referred to as “pitch” hereinafter. This pitch helps distribute the electrode tips spatially within the biological medium, enhancing coverage for recording and stimulation across8123-112597-02different depths while reducing interference between adjacent electrodes. In some examples, the pitch can also define the spatial extent of the focal vicinity in which simultaneous measurements of neurochemical and electrophysiological signals occur. In some examples, the pitch between two immediately adjacent electrodes can range between 10 microns and 2 millimeters, or between 10 and 500 microns. In some examples, the pitch between two immediately adjacent electrodes can be smaller than 10 microns (e.g., between 1 and 10 microns) so long as the two immediately adjacent electrodes 106 do not axially overlap with one another. In some examples, two electrodes in the CFET bundle 120 can be located at the same axial level (i.e., the axial distances from the two electrodes to the proximal end 124 are identical) so long as the two electrodes are radially and / or circumferentially spaced apart from one another to prevent shorting between the two electrodes (e.g., one or more CFETs can be positioned between the two electrodes located at the same axial level).

[0077] The number of CFETs 102 forming the CFET bundle 120 can vary, thereby resulting in different number of electrodes 106 in the CFET bundle 120. In some examples, the CFET bundle 120 can include between 2 and 1000 CFETs 102 (or electrodes 106). In one example, the CFET bundle 120 can include between 16 and 32 CFETs 102 (or electrodes 106). This latter range can provide sufficient channel density for high-resolution data acquisition while keeping the overall bundle size manageable for safe insertion into the biological medium. For instance, the overall diameter of the CFET bundle 120 can be approximately d x / n, where d is the diameter of the individual CFET 102, and n is the number of CFETs in the CFET bundle 120. Thus, if each CFET 102 has an outer diameter of 10 microns, a bundle of 32 CFETs will have an overall diameter about 56.6 microns, which is significantly smaller than the diameter of conventional guide tubes used for dural penetrations. Depending on application requirements, the CFET bundle 120 can include as few as 2 CFETs or more than 32 CFETs, offering flexibility to accommodate various experimental or clinical needs. In some examples, for a given target overall diameter (D) of the CFET bundle 120 selected based on application constraints, the maximum number (n) of CFETs 102 that can be accommodated within the CFET bundle 120 can be approximated as n ~ (D / d)2.

[0078] In some examples, for CFET bundles comprising between 2 and 32 CFETs formed from carbon fibers with electrically non-conductive coatings as described herein, an overall outer diameter of the CFET bundle 120 can range between about 10 microns and about 60 microns. It should be understood that this example range may vary if the carbon fibers are8123-112597-02replaced with other conductive filaments and / or if different coating materials or thicknesses are used.Exemplary Configurations of Conductive Wires

[0079] As described above, carbon fibers of an electrode array can be connected to respective conductive wires which are further connected to one or more control circuits. FIGS. 3A-3B show two different configurations of conductive wires.

[0080] In the examples depicted in FIGS. 3A-3B, body portions of a plurality of CFETs 302 are grouped together to form a CFET bundle 320. Similarly, each CFET 302 includes a carbon fiber coated with an electrically non-conductive coating along its entire length except at its distal end portion which is not covered by the electrically non-conductive coating as an electrode (which may be exposed to the surrounding biological medium, or may include one or more additional surface coatings to modify electrochemical properties of the electrode, as described above). Different from the example of FIG. 1 A where the proximal end 124 of the CFET bundle 120 represents the terminal ends of the individual CFETs 102, proximal end portions of the CFETs 302 extend out of a proximal end 324 of the CFET bundle 320 and diverge outwardly from one another in the examples of FIGS. 3A-3B.

[0081] As shown, proximal ends 312 of the carbon fibers in the CFETs 302 can be connected to distal end portions 336 of the respective conductive wires 330 (similar to the conductive wire 130), e.g., using a conductive bonding agent such as silver epoxy or the like. A proximal end portion 338 of each conductive wire 330 can be connected to a corresponding pad 332 (similar to the pad 132), which can be further connected (e.g., via a flexible PCB) to a circuit configured to control operations of the electrode located at the distal end portion of the carbon fiber.

[0082] In the example depicted in FIG. 3A, the proximal end portions 338 of the conductive wires 330 are substantially parallel to each other (and extend in axial direction). The distal end portions 336 of the conductive wires 330 are oriented in radial directions extending toward to the proximal end 324 of the CFET bundle 320. Thus, at least some of the conductive wires 330 bend between the proximal end portions 338 and the distal end portions 336. The proximal end portions of the CFETs 302 extend from the proximal end 324 of the CFET bundle 320 and fan out progressively as they approach the distal end portions 336 of the conductive wires 330.

[0083] In the example depicted in FIG. 3B, each conductive wire 330 (including both the proximal end portion 338 and the distal end portion 336) is orientated in the radial direction extending toward the proximal end 324 of the CFET bundle 320 (i.e., no bending between the8123-112597-02proximal end portion 338 and distal end portion 336). In this configuration, each conductive wire 330, along with the proximal end portion of the CFET 302 to which it is connected, aligns in a nearly straight path from the proximal end 324 of the CFET bundle to the pad 332 to which the conductive wire 330 are connected. This radial orientation of the conductive wires 330 may offer mechanical advantages. Unlike the parallel arrangement of the proximal end portions 338 depicted in FIG. 3A, where tensile forces from the CFETs 302 can create lateral stress on the bent conductive wires 330, the radial orientation of the conductive wires 330 shown in FIG. 3B ensures that any pulling force from the CFETs 302 remains aligned with the longitudinal axis of the conductive wires 330. This alignment can lower the risk of lateral deformation or bending of the conductive wires 330, thus reducing the likelihood of wire breakage during handling or operation.

[0084] The conductive wires can also have different configurations when no CFET extends out of the proximal end of the CFET bundle. For instance, in the example depicted in FIG.1A, conductive wires 130 extend between the proximal end 124 of the CFET bundle 120 and the corresponding pads 132. Proximal portions of the conductive wires 130 are substantially parallel to each other (and extend in axial direction). Distal portions of the conductive wires fan out from the proximal end 124 (like the proximal end portions of the CFETs 302 of FIG.3A). As another example, the proximal end 324 of the CFET bundle 320 in FIG. 3B may represent terminal ends of the CFETs 302, and each conductive wire 330 can extend in the radial direction and connect between the proximal end 324 and the corresponding pad 332.Exemplary Circuits

[0085] FIG. 4 is a block diagram depicting an instrument or interface platform 400 which includes one or more circuits (also referred to as “head stages” hereinafter) that can be connected to any of the electrode arrays disclosed herein. In some examples, one or more head stages connected to an electrode array can be deemed as parts of the electrode array.

[0086] As described herein, a head stage refers to an electronic module that interfaces with the electrodes (e.g., 106, 206) of an electrode array. In some examples, a head stage can provide signal amplification, filtering, and data acquisition (e.g., including sampling and analog-to-digital conversion) for the recorded signals. In some examples, a head stage may also include one or more circuits for delivering electrical stimulation pulses to specific electrodes. In some examples, multiple head stages can be independently configured to handle electrophysiological signal measurements, neurochemical signal measurements, and / or electrical stimulation, depending on the configuration of the electrode array. The interface platform 400 may also include, or in communication with, a computing system that8123-112597-02coordinates the activities of the head stages, processes incoming signals, and transmits the data to an external device for further analysis and storage. An example computing system 800 is shown in FIG. 8 and described further below.

[0087] In a non-limiting example, FIG. 4 shows that the interface platform 400 includes a first head stage 410, a second head stage 420, and a third head stage 430. The first head stage 410 can include one or more circuits configured to measure electrophysiological signals of the biological medium from a connected electrode of the electrode array. The second head stage 420 can include one or more circuits configured to measure neurochemical signals of the biological medium from another connected electrode of the electrode array. The third head stage 430 can include one or more circuits configured to generate electrical pulses to yet another connected electrode of the electrode array.

[0088] As shown in FIG. 4, the first head stage 410 can be a voltage-follower head stage including an amplifier 412 with a sufficiently high input impedance. Local field potentials and / or neuronal spike activities picked up by an electrode of the electrode array can be fed to an input end 414 of the amplifier 412 for amplification and signal conditioning.

[0089] The second head stage 420 can include a current-to-voltage converter 422 that allows recording electrochemical current during simultaneous application of a control signal to induce reduction and oxidation (redox) reaction of targeted electroactive chemicals (e.g., dopamine), as used in fast-scan cyclic voltammetry (FSCV). For instance, electrochemical current detected by an electrode of the electrode array can be provided to one input end 424 of the current-to-voltage converter 422, while a control signal can be applied to another input end 426 of the current-to-voltage converter 422. The control signal can be programmed (e.g., by the computing system 800 of FIG. 8) and generated by a signal generator. For instance, for detecting dopamine or other catecholamines, the control signal can be generated as a triangular voltage waveform ramping from -0.4 V to 1.3 at a scan rate of 400 V / s, and such waveform can be applied at a rate of 10 Hz and held at -0.4V between scans. The reduction and oxidation (redox) process can lead to current changes indicative of dopamine oxidation at approximately 0.6 V (where dopamine is converted to dopamine-o-quinone) and dopamine reduction near -0.2 V (where dopamine-o-quinone is converted back to dopamine). These current changes are proportional to the concentration of dopamine in the vicinity of the electrode. By using background-subtracted voltammograms and applying techniques like principal component analysis, the measured current signals can be distinguished from other interfering molecular signals, allowing for accurate estimation of change in dopamine concentration.8123-112597-02

[0090] The third head stage 430 can be configured to generate electrical pulses for neural stimulation. For instance, the third head stage 430 can include a pulse generator 432 that delivers controlled electrical stimuli through an electrode of the electrode array. These pulses can be programmed to modulate neural activity in the surrounding biological medium, enabling precise intervention in neural circuits. In some examples, the pulse generator 432 can be programmed to control various parameters such as pulse shape, pulse width, and pulse frequency to tailor the stimulation to specific experimental or therapeutic needs. For example, rectangular or biphasic pulse shapes can be used, with pulse widths ranging from microseconds to milliseconds, and frequencies from a few Hertz to several hundred Hertz. These parameters can be adjusted dynamically by the computing system 800 to achieve the desired neural response and optimize the effectiveness of stimulation.

[0091] Although three separate head stages are shown in FIG. 4, it should be understood that the interface platform 400 can include one, two, or more than three head stages. In some examples, any two or all three of the head stages depicted in FIG. 4 can be combined into one integrated head stage. In some examples, one or more of the head stages of FIG. 4 can have multiple duplicates, each of which can have the same or different parameter settings.Exemplary Electrode Configurations

[0092] As described above, one or more electrodes in an electrode array can be configured as sensing electrodes for measuring neurochemical and / or electrophysiological signals of the surrounding biological medium, or as pacing electrode for delivering electrical pulses to the surrounding biological medium (e.g., for DBS).

[0093] Configuration of the electrodes in an electrode array can be implemented by selectively connecting the CFETs of the electrode array to various head stages (e.g., 410, 420, 430, etc.). Any of the electrode arrays described herein (e.g., 100, 200) can be multi-modal.

[0094] For instance, the electrode array 100 of FIG. 1 A can be configured for dual modalities by assigning different functionalities to the electrodes 106 within the CFET bundle 120. In one example, one subset of electrodes can be connected to a head stage (e.g., 410) configured to measure electrophysiological signals in their surrounding region, while another subset of electrodes can be connected to a separate head stage (e.g., 420) configured for measuring neurochemical signals in their respective areas.

[0095] As another example, one subset of electrodes in the electrode array 100 can be configured as sensing electrodes (e.g., to measure electrophysiological and / or neurochemical signals in their surrounding regions), whereas another subset of electrodes can be configured8123-112597-02as pacing electrodes (e.g., connected to the head stage 430) to deliver electrical pulses to their surrounding areas.

[0096] As another example, one or more electrodes of the electrode array 100 can be configured as both sensing electrodes and pacing electrodes by employing switching head stages (e.g., via external commands and / or programmed software) that alternates between sensing and pacing modes.

[0097] More sophisticated combination of modalities can be implemented. For example, in a tri -modal configuration, a first subset of electrodes in the electrode array 100 can be dedicated to measuring electrophysiological signals, a second subset of electrodes in the electrode array 100 can be dedicated to measuring neurochemical signals, and a third subset of electrodes in the electrode array 100 can be configured to deliver electrical stimulation to the surrounding biological medium.Example Overall Method for Fabricating Electrode Arrays

[0098] FIG. 5 is a flowchart describing an example overall method 500 for fabricating an electrode array.

[0099] At step 510, a plurality of CFETs (such as 102 or 202) can be created.

[0100] At step 520, body portions of the plurality of CFETs can be clustered into a CFET bundle (e.g., 120 or 220).

[0101] The step 510 can include several sub-steps.

[0102] At step 512, a plurality of carbon fibers can be received. The plurality of carbon fibers can have predetermined dimensions (e.g., in terms of outer diameter and / or axial length).

[0103] At step 514, each carbon fiber can be coated with an electrically non-conductive layer (e.g., polymer coating or the like) over its entire length.

[0104] At step 516, the electrically non-conductive layer can be removed from distal tip portions of the plurality of carbon fibers to form a plurality of electrodes.

[0105] The plurality of CFETs can be configured to have different lengths such that at least some electrodes in the CFET bundle are axially offset from one another by a predefined distance.Exemplary Fabrication Process

[0106] Additional details for creating the CFETs and other aspects of fabricating the electrode arrays are described further below in reference to FIGS. 6A-6F. It should be understood that the specific fabrication setups, parameters, materials, and operations described below are non-limiting, and alternative configurations or methods may be utilized8123-112597-02to achieve similar outcomes. Variations in material properties, dimensions, and fabrication techniques can be adapted to meet specific application requirements or to enhance the performance of the electrode arrays in various experimental and / or clinical settings.

[0107] FIG. 6A (not drawn to scale) shows a fixture 600 to which a plurality of carbon fibers 610 can be attached. The plurality of carbon fibers 610 can be pre-cut to predetermined lengths. In some examples, the plurality of carbon fibers 610 can have about the same axial length.

[0108] In some examples, the fixture 600 can be made of aluminum. The fixture 600 can have two opposing arms 612, 614, which can be connected by a side bar 618. Thus, the two arms 612, 614 and the side bar 618 can define a void space or slot 615 of the fixture 600. One arm 612 can be substantially straight, whereas the other arm 614 can have a wedged shape forming a predetermined angle relative to the straight arm 612.

[0109] The proximal end of each carbon fiber 610 can be attached to a conductive wire 630 (e.g., using a conductive bonding agent such as silver epoxy or the like) to form a carbon fiber and conductive wire assembly. In some examples, the conductive wires 630 can be copper wires. Proximal ends of the conductive wires 630 can be temporarily affixed to discrete locations on the straight arm 612, e.g., by using a tape 616A or other attachment means. Distal ends of the carbon fibers 610 can be temporarily affixed to discrete locations on the opposing arm 614, e.g., by using another tape 616B or other attachment means. As shown, the tape 616A can extend along the arm 612 and be substantially straight, whereas the tape 616B can extend along the arm 614 and form an oblique angle relative to the tape 616A.

[0110] Placement of the carbon fiber and conductive wire assemblies on the fixture 600 is arranged so that they separate from one another and extend between the two opposing arms 612, 614. The placement is also elevated above the void space or slot 615 due to the thickness of the arms 612, 614. In some examples, the plurality of carbon fiber and conductive wire assemblies are arranged to be parallel to each other.

[0111] In some examples, the fixture 600 loaded with the carbon fibers 610 and conductive wires 630 connected with silver epoxy can be placed in an oven to cure the silver epoxy at about 80-90 degrees Celsius for 2-3 hours.

[0112] In some examples, the fixture 600 can be placed in a vacuum deposition chamber for coating the carbon fiber and conductive wire assemblies with a polymer, such as parylene-C, using a vapor deposition process. For instance, the parylene can be vaporized in the vacuum deposition chamber, where it condenses onto the surface of each carbon fiber 610 and its connected conductive wire 630, forming a thin, conformal coating that provides electrical8123-112597-02insulation. In some examples, the vapor deposition process can be continued until the parylene coating has a predetermined thickness (e.g., between about 1-3 microns). The elevated and separate arrangement of the carbon fiber and conductive wire assemblies on the fixture 600 facilitates uniform exposure to the vapor, reducing the risk of shadowing or incomplete coverage during the deposition process.

[0113] In some examples, a liquid adhesion promoter (e.g., a mixture of 3-(Trimethoxysilyl)propyl methacrylate, isopropyl alcohol, and distilled water at a volumetric ratio of 1 : 1000: 1000) can be used to enhance the adhesion of parylene onto the carbon fibers 610 and conductive wires 630. This adhesion promoter can be applied before the parylene deposition process to ensure strong bonding between the parylene and the carbon fiber and conductive wire assemblies.

[0114] After parylene coating the carbon fiber and conductive wire assemblies, the parylene at the distal tip portions of the carbon fibers 610 can be removed so as to form exposed electrodes. This can be achieved via various etching techniques, such as reactive ion etching (RIE), plasma etching, laser etching, flame etching, etc.

[0115] For instance, flame etching can be used to heat the distal tip portions of the carbon fibers 610 to remove the parylene coating thereof. The heating can also cut the distal tip portions of the carbon fibers 610 into predetermined lengths. FIG. 6B (not drawn to scale) schematically illustrates a flame etching process. The fixture 600 is shown flipped such that the side previously facing upward in FIG. 6A is facing downward in FIG. 6B. A flame torch 638 can be placed adjacent to, and move in a controlled manner along, the inner edge of the arm 614. The controlled movement and positioning of the flame torch 638 allow selective removal of the polymer coating of a desired length (e.g., between 10 and 300 microns) at the distal end portions, and cutting the carbon fibers 610 at their distal tip portions in the meantime.

[0116] FIG. 6C (not drawn to scale) shows a plurality of CFETs 602 created after the flame etching process depicted in FIG. 6B. Each CFET 602 has a body portion 604 comprising the carbon fiber covered by the polymer coating and an electrode 606 (not covered by the polymer coating) at the distal end portion. Due to the wedged shape of the arm 614, the resulting CFETs 602 have varying axial lengths, corresponding to etching positions along the angled arm 614 during the flame etching process. The electrodes 606, no longer affixed to the arm 614, are now free-standing.

[0117] To prevent the CFETs 602 from sticking to each other due to electrostatic and other physical interactions (which can be challenging due to their significant aspect ratios), an8123-112597-02aluminum foil or similar material can be used as a static grounding underneath the fixture 600 during the fabrication process. In some examples, barriers (e.g., paper points or the like) can be placed between CFETs 602 to isolate individual units and prevent direct contact.Additionally, cleanroom wipes can be used during handling to minimize the adhesion of particles to the CFETs 602.

[0118] In some examples, the flame etching process depicted in FIG. 6B can be assisted by a frozen medium 636, such as dry ice or the like. The flipped fixture 600 allows portions of the polymer-coated carbon fibers to be immersed into the frozen medium 636 retained in a container 601. Specifically, the distal tip portions of the carbon fibers 610 can be heated while at least portions of the carbon fibers located proximal to the distal tip portions can be frozen in ice. Thus, such flame etching process can also be referred to as cryogenic flame etching. The use of the frozen medium 636 can stabilize the carbon fiber assemblies or CFETs (e.g., securing them in ice), preventing movement caused by air drafts or mechanical forces that could otherwise result in uneven etching or damage. This controlled environment can also reduce the risk of collapse associated with longer carbon fibers (as in conventional water-based flame etching process), enabling precise and reliable flame etching of the distal tip portions. After the flame etching, the frozen medium 636 is allowed to thaw.

[0119] In some examples, the created CFETs 602 can be tested in vitro to ensure proper functionality. As shown in FIG. 6D (not drawn to scale), the electrodes 606 can be submerged in a saline solution 644 contained in a beaker 642, which allows for the evaluation of background current and noise levels. The testing can be performed by temporarily connecting the CFETs 602 to a test PCB 640’. For example, the test PCB 640’ can have a plurality of pads 632’ to which the conductive wires 630 can be connected to (e.g., via soldering). Wire traces 634’ on the test PCB 640’ can connect the pads 632’ to a test circuit 648 through a connector 646. The test circuit 648 can be configured for FSCV and / or impedance testing.

[0120] This in vitro testing process can help detecting any structural defects in the carbon fibers 610 (e.g., detecting perforations in the parylene insulated parts of the carbon fibers, etc.), and ensure that both the background current and noise level fall within a desired range. For instance, for dopamine detection, an electrode 606 can be deemed satisfactory if the current noise is below a predefined threshold (e.g., less than 0.05 nA), and the background current falls within a predefined range (e.g., 800-1000 nA). If no structural defects are detected (indicated by low noise and absence of artifacts) but the cunent exceeds the acceptable range, the electrode 606 can be trimmed and retested. For electrophysiological8123-112597-02recordings, impedance measurements (e.g., via electrochemical impedance spectroscopy) can also be used to assess the electrode 606. In some examples, the electrode length can be limited to 100 microns or less to optimize single-cell recordings of electrophysiological signals. In some examples, surface modifications, such as PEDOT coatings, can be applied to increase surface roughness and adjust the electrode’ s surface area as needed.

[0121] CFETs 602 that successfully passed the in vitro test can be detached from the test PCB 640’ and reconnected to another PCB 640, as depicted in FIG. 6E (not drawn to scale). Similarly, the PCB 640 has a plurality of pads 632 to which the conductive wires 630 can be connected to (e.g., via soldering). Wire traces 634 on the PCB 640 can connect the pads 632 to one or more circuits (e.g., the head stages 410, 420, and / or 430 of FIG. 4) configured to control operations of the electrodes 606 (e.g., for measuring electrophysiological and / or neurochemical signals, and / or for delivering electrical stimulations).

[0122] These successfully tested CFETs 602 can be assembled to form an electrode array, as illustrated in FIG. 6F (not drawn to scale). Specifically, these CFETs 602 can be clustered into a CFET bundle 620. In some examples, these CFETs 602 (which can have different axial lengths) can be clustered so that a centrally located CFET is longer than its peripheral counterparts, as described above. In some examples, the electrodes 606 can be arranged in a helical pattern around and along the CFET bundle 620, similar to the example depicted in FIG. 2A.

[0123] In some examples, the clustering can be performed by coating the body portions 604 of the CFETs with a bonding agent 628, such as maltose or the like. An example dip-coating method involves heating maltose until molten and then carefully lowering and lifting the CFET bundle 620 through the molten solution at a controlled rate to achieve a uniform coating.

[0124] In the example depicted in FIG. 6F, a proximal end 624 of the CFET bundle 620 represents the terminal ends of the individual CFETs 602, and conductive wires 630 extending between the pads 632 and the proximal end 624 are arranged in a similar configuration as the example shown in FIG. 1 A. In other examples, proximal end portions of the CFETs 602 can extend out of the proximal end 624 of the CFET bundle 620 and diverge outwardly from one another (similar to the example depicted in FIG. 3A), and / or the conductive wires 630 can be oriented in radial directions extending toward the proximal end8123-112597-02Example Implantation Method

[0125] FIG. 7 is a flowchart describing an example overall method 700 of implanting an electrode array into a target biological medium, such as a brain tissue.

[0126] At step 710, an electrode array is received. The electrode array includes a plurality of CFETs. Body portions of the plurality of CFETs are clustered into a CFET bundle. Each CFET includes a carbon fiber and an electrically non-conductive coating. The electrically non-conductive coating covers an entire length of the carbon fiber except at a distal tip portion of the carbon fiber which is not covered by the electrically non-conductive coating to define an electrode.

[0127] At step 720, the CFET bundle is stiffened at least temporarily.

[0128] At step 730, the stiffened CFET bundle is inserted into a biological medium.

[0129] The CFET bundle is so stiffened that when the inserted CFET bundle reaches a target location of the biological medium, the body portions of the plurality of CFETs remain parallel to a central longitudinal axis of the CFET bundle. In other words, insertion of the CFET bundle into the biological medium does not cause separation or splaying of the individual CFETs.

[0130] The CFET bundle can be stiffened in different ways. In some examples, the CFET bundle can be stiffened by applying a bonding agent to the CFET bundle to bind adjacent CFETs together and increase structural integrity during handling and insertion. In some examples, the bonding agent is dissolvable or bioabsorbable and is configured to have a dissolving rate such that at least a predefined amount of the bonding agent remains present until the CFET bundle reaches a target location within the biological medium. Example dissolvable bonding agents include polyethylene glycol (PEG), maltose, silk fibroin, or other bioabsorbable materials. In other examples, the bonding agent can be non-dissolvable or substantially permanent after implantation, such that the CFET bundle remains stiffened during and after insertion. In each of the foregoing examples, the bonding agent can comprise a non-conductive material or chemical selected to maintain the relative positioning of the CFETs. The properties of the bonding agent, including stiffness, adhesion strength, and, where applicable, dissolving behavior, can be selected or adjusted based on material composition, molecular weight, concentration, particle size, or other material parameters.

[0131] In lieu of, or in addition to, using the bonding agent, the CFET bundle can be mechanically stiffened. For example, FIG. 6F shows that a needle 650 can be temporally attached to the CFET bundle 620. The needle 650 can be made of materials that provide both stiffness and biocompatibility, such as silicon, tungsten, stainless steel, or the like.8123-112597-02

[0132] In some examples, the needle can be attached to the outside of the CFET bundle via any of the dissolvable bonding agents described above. After the needle-reinforced CFET bundle is inserted into the biological medium and the electrode array reaches the target location, and after the bonding agent used for needle attachment is dissolved, the needle can be retracted and removed from the biological medium, thus leaving the electrode array securely positioned at the target site while maintaining its preconfigured spatial arrangement, enabling precise and stable neural recording or stimulation.Example Applications

[0133] The electrode arrays disclosed herein can be employed in a wide range of research, diagnostic, and / or therapeutic applications involving interaction with a biological medium.

[0134] In some examples, the electrode arrays can be used in neuromodulation applications involving recording and / or stimulation of neural tissue. For instance, the electrode arrays can be used in closed-loop stimulation systems in which electrophysiological and / or neurochemical signals are sensed and used to adjust stimulation parameters in real time. Such configurations can be applied, by way of example, to DBS therapies for neurological or psychiatric conditions, including Parkinson’s disease and mood disorders, where real-time feedback can improve therapeutic efficacy and personalization.

[0135] In some examples, the disclosed electrode arrays can be used for high-channel-count neurochemical sensing, including measurement of neurotransmitters such as dopamine or other analytes, optionally in combination with simultaneous electrophysiological recording. This capability supports applications in studying spatially heterogeneous neurochemical dynamics, evaluating disease mechanisms, monitoring treatment response, serving as a quantitative endpoint in clinical or translational research studies, and / or providing feedback signals for adaptive stimulation. In some implementations, the electrode arrays disclosed herein can be configured to sense different neurochemical species by selecting appropriate electrode surface treatments or sensing modalities.

[0136] In some examples, the electrode arrays disclosed herein can be used in research involving animal models, including rodents or non-human primates, to obtain high spatial resolution electrophysiological and / or neurochemical data over acute or chronic time scales. In such implementations, the electrode arrays can facilitate chamber-less implantation approaches, reduce invasiveness, and allow greater flexibility in target selection while supporting long-term recordings.

[0137] In some examples, the electrode arrays disclosed herein can be configured for interaction with peripheral neural structures and / or other non-brain biological media. For8123-112597-02instance, the electrode arrays can be used for stimulation and / or recording of peripheral nerves (e.g., the vagus nerve), dorsal root ganglia, or other ganglionic structures, for applications such as neuromodulation, pain management, and / or sensory interfacing. In some examples, the electrode arrays can be used in neural prosthetic systems to record neural activity associated with motor intent and / or to deliver stimulation to restore sensory feedback. In some examples, the electrode arrays can be configured for stimulation and / or sensing in auditory or vestibular structures, including cochlear implant applications.

[0138] In some examples, the electrode arrays disclosed herein can be adapted for use in non-neural biological tissues or biological fluids. For instance, the electrode arrays can be used for stimulation or sensing in muscle tissue, organs, and / or fluid-filled biological environments. In some implementations, the electrode arrays can be configured for electrochemical sensing applications, including transdermal sensing, intravascular sensing, and / or monitoring of biochemical markers in biological fluids, optionally using needle-assisted insertion techniques.

[0139] It should be understood that the above example applications are non-exclusive. Other applications, modifications, and use cases will be apparent to those skilled in the art in view of this disclosure and are considered within the scope of the disclosed technologies.Example Computing Systems

[0140] FIG. 8 depicts an example of a suitable computing system 800 which can be integrated with or in communication with the interface platform 400 of FIG. 4. The computing system 800 is not intended to suggest any limitation as to scope of use or functionality of the present disclosure, as the innovations can be implemented in diverse computing systems.

[0141] With reference to FIG. 8, the computing system 800 includes one or more processing units 810, 815 and memory 820, 825. In FIG. 8, this basic configuration 830 is included within a dashed line. The processing units 810, 815 execute computer-executable instructions, such as for implementing some of the features described in the examples herein. A processing unit can be a general-purpose central processing unit (CPU), processor in an application-specific integrated circuit (ASIC), or any other type of processor. In a multiprocessing system, multiple processing units execute computer-executable instmctions to increase processing power. For example, FIG. 8 shows a central processing unit 810 as well as a graphics processing unit or co-processing unit 815. The tangible memory 820, 825 can be volatile memory (e.g., registers, cache, RAM), non-volatile memory (e.g., ROM, EEPROM, flash memory, etc.), or some combination of the two, accessible by the processing8123-112597-02unit(s) 810, 815. The memory 820, 825 stores software 880 controlling operations of the head stages (e.g., for measuring signals from and / or delivering electrical pulses to neural probes), in the form of computer-executable instructions suitable for execution by the processing unit(s) 810, 815.

[0142] A computing system 800 can have additional features. For example, the computing system 800 includes storage 840, one or more input devices 850, one or more output devices 860, and one or more communication connections 870, including input devices, output devices, and communication connections for interacting with a user. An interconnection mechanism (not shown) such as a bus, controller, or network interconnects the components of the computing system 800. Typically, operating system software (not shown) provides an operating environment for other software executing in the computing system 800, and coordinates activities of the components of the computing system 800.

[0143] The tangible storage 840 can be removable or non-removable, and includes magnetic disks, magnetic tapes or cassettes, CD-ROMs, DVDs, or any other medium which can be used to store information in a non-transitory way and which can be accessed within the computing system 800. The storage 840 stores instructions for the software implementing one or more innovations described herein.

[0144] The input device(s) 850 can be an input device such as a keyboard, mouse, pen, or trackball, a voice input device, a scanning device, touch device (e.g., touchpad, display, or the like) or another device that provides input to the computing system 800. The output device(s) 860 can be a display, printer, speaker, CD-writer, or another device that provides output from the computing system 800.

[0145] The communication connection(s) 870 enable communication over a communication medium to another computing entity. The communication medium conveys information such as computer-executable instructions, audio or video input or output, or other data in a modulated data signal. A modulated data signal is a signal that has one or more of its characteristics set or changed in such a manner as to encode information in the signal. By way of example, and not limitation, communication media can use an electrical, optical, RF, or other carrier.

[0146] The innovations can be described in the context of computer-executable instructions, such as those included in program modules, being executed in a computing system on a target real or virtual processor (e.g., which is ultimately executed on one or more hardware processors). Generally, program modules or components include routines, programs, libraries, objects, classes, components, data structures, etc. that perform particular tasks or8123-112597-02implement particular abstract data types. The functionality of the program modules can be combined or split between program modules as desired in various examples. Computerexecutable instructions for program modules can be executed within a local or distributed computing system.

[0147] For the sake of presentation, the detailed description uses terms like “determine” and “use" to describe computer operations in a computing system. These terms are high-level descriptions for operations performed by a computer and should not be confused with acts performed by a human being. The actual computer operations corresponding to these terms vary depending on implementation.Example Clauses

[0148] In view of the above-described implementations of the disclosed subject matter, this application discloses the additional clauses enumerated below.

[0149] Clause 1. A device for insertion into a biological medium, the device comprising: a plurality of conductive electrode filaments (CEFs), wherein body portions of the plurality of CEFs are clustered together to form a CEF bundle, wherein each CEF comprises an electrically conductive filament and an electrically non-conductive coating, the electrically non-conductive coating covering an entire length of the electrically conductive filament except at a distal tip portion of the electrically conductive filament that is not covered by the electrically non-conductive coating to define an electrode, wherein proximal ends of the electrically conductive filaments are connected to respective conductive wires, wherein the CEF bundle is stiffened to resist disintegration or deformation of individual CEFs such that the body portion of each CEF remains parallel to a central longitudinal axis of the CEF bundle during insertion of the CEF bundle into the biological medium.

[0150] Clause 2. The device of clause 1, wherein a first electrode in the CEF bundle is closer to the central longitudinal axis than a second electrode in the CEF bundle, wherein the first electrode extends to a more distal location than the second electrode.

[0151] Clause 3. The device of any one of clauses 1-2, wherein the electrically conductive filament is a carbon fiber.

[0152] Clause 4. The device of any one of clauses 1-2, wherein the electrodes of the plurality of the CEFs are arranged in a helical pattern around the CEF bundle.

[0153] Clause 5. The device of any one of clauses 1-4, wherein the conductive wires are orientated in radial directions extending toward a proximal end of the CEF bundle.

[0154] Clause 6. The device of any one of clauses 1-5, wherein each CEF has an aspect ratio between 2000 and 10000.8123-112597-02

[0155] Clause 7. The device of any one of clauses 1-6, wherein each CEF has an outer diameter between 5 and 12 microns.

[0156] Clause 8. The device of any one of clauses 1-7, wherein the CEF bundle includes between 2 and 1000 CEFs.

[0157] Clause 9. The device of any one of clauses 1-8, where at least one pair of immediately adjacent electrodes in the CEF bundle are axially offset from one another by a predefined distance between 10 and 500 microns.

[0158] Clause 10. The device of any one of clauses 1 -9, further comprising one or more circuits in electrical communication with the conductive wires, wherein the one or more circuits are configured to measure electrophysiological or neurochemical signals of the biological medium surrounding one or more electrodes in the CEF bundle, or deliver electrical pulses to at least one electrode in the CEF bundle.

[0159] Clause 11. A method for fabricating an electrode array for insertion into a biological medium, the method comprising: receiving a plurality of carbon fiber electrode threads (CFETs), each CFET comprising a carbon fiber and an electrode defined at a tip portion of the carbon fiber; and clustering body portions of the plurality of CFETs into a CFET bundle, wherein the plurality of CFETs have different lengths such that at least some electrodes in the CFET bundle are axially offset from one another by a predefined distance.

[0160] Clause 12. The method of claim 11, further comprising creating the plurality of CFETs, comprising: receiving a plurality of carbon fibers; coating an electrically non-conductive layer over an entire length of each carbon fiber; and removing the non-conductive layer from distal tip portions of the plurality of carbon fibers to form a plurality of electrodes.

[0161] Clause 13. The method of clause 12, wherein creating the plurality of CFETs further comprises: attaching proximal ends of the plurality of carbon fibers to respective conductive wires; affixing the conductive wires to discrete locations on a first arm of a fixture; and affixing the distal tip portions of the plurality of carbon fibers to discrete locations on a second arm of the fixture situated on an opposite side of the first arm such that the plurality of carbon fibers are separated from one another and extend between the first arm and the second arm.

[0162] Clause 14. The method of any one of clauses 12-13, wherein removing the electrically non-conductive layer comprises heating the distal tip portions of the plurality of carbon fibers coated with the electrically non-conductive layer, wherein the heating is configured to cut the distal tip portions of the plurality of carbon fibers into predetermined lengths.8123-112597-02

[0163] Clause 15. The method of clause 14, wherein removing the electrically non-conductive layer further comprises heating the distal tip portions of the plurality of carbon fibers while freezing at least portions of the plurality of carbon fibers located proximal to the distal tip portions in ice.

[0164] Clause 16. The method of any one of clauses 12-15, further comprising connecting proximal ends of the plurality of carbon fibers to one or more circuits, wherein the one or more circuits are configured to measure electrophysiological or neurochemical signals of the biological medium surrounding one or more electrodes in the CFET bundle, or deliver electrical pulses to at least one electrode in the CFET bundle, or both.

[0165] Clause 17. The method of any one of clauses 11-16, wherein the clustering comprises coating the body portions of the plurality of the CFETs with a bonding agent.

[0166] Clause 18. A method comprising: receiving an electrode array comprising a plurality of carbon fiber electrode threads (CFETs), wherein body portions of the plurality of CFETs are clustered into a CFET bundle, wherein each CFET comprises a carbon fiber and an electrically non-conductive coating, the electrically non-conductive coating covering an entire length of the carbon fiber except at a distal tip portion of the carbon fiber which is not covered by the electrically non-conductive coating to define an electrode; stiffening the CFET bundle at least temporarily; and inserting the CFET bundle into a biological medium, wherein the CFET bundle is so stiffened that when the inserted CFET bundle reaches a target location of the biological medium, the body portions of the plurality of CFETs remain parallel to a central longitudinal axis of the CFET bundle.

[0167] Clause 19. The method of clause 18, wherein stiffening the CFET bundle comprises applying a dissolvable bonding agent to the CFET bundle, wherein the bonding agent is configured to have a dissolving rate which allows that at least a predefined amount of the bonding agent remains undissolved until the CFET bundle reaches the target location of the biological medium.

[0168] Clause 20. The method of any one of clauses 18-19, wherein stiffening the CFET bundle comprises attaching a needle to the CFET bundle.

[0169] The technologies from any clause can be combined with the technologies described in any one or more of the other clauses. In view of the many possible examples to which the principles of the disclosed technology can be applied, it should be recognized that the illustrated embodiments are examples of the disclosed technology and should not be taken as a limitation on the scope of the disclosed technology. Rather, the scope of the claimed subject matter is defined by the following claims and their equivalents.

Claims

8123-112597-02We claim:

1. A device for insertion into a biological medium, the device comprising:a plurality of conductive electrode filaments (CEFs),wherein body portions of the plurality of CEFs are clustered together to form a CEF bundle,wherein each CEF comprises an electrically conductive filament and an electrically non-conductive coating, the electrically non-conductive coating covering an entire length of the electrically conductive filament except at a distal tip portion of the electrically conductive filament that is not covered by the electrically non-conductive coating to define an electrode, wherein proximal ends of the electrically conductive filaments are connected to respective conductive wires,wherein the CEF bundle is stiffened to resist disintegration or deformation of individual CEFs such that the body portion of each CEF remains parallel to a central longitudinal axis of the CEF bundle during insertion of the CEF bundle into the biological medium.

2. The device of claim 1, wherein a first electrode in the CEF bundle is closer to the central longitudinal axis than a second electrode in the CEF bundle, wherein the first electrode extends to a more distal location than the second electrode.

3. The device of claim 1, wherein the electrically conductive filament is a carbon fiber.

4. The device of claim 1, wherein the electrodes of the plurality of the CEFs are arranged in a helical pattern around the CEF bundle.

5. The device of claim 1, wherein the conductive wires are orientated in radial directions extending toward a proximal end of the CEF bundle.

6. The device of claim 1, wherein each CEF has an aspect ratio between 2000 and 10000.

7. The device of claim 1, wherein each CEF has an outer diameter between 5 and 12 microns.8123-112597-028. The device of claim 1, wherein the CEF bundle includes between 2 and 1000 CEFs.

9. The device of claim 1, where at least one pair of immediately adjacent electrodes in the CEF bundle are axially offset from one another by a predefined distance between 10 and 500 microns.

10. The device of claim 1 , further comprising one or more circuits in electrical communication with the conductive wires, wherein the one or more circuits are configured to measure electrophysiological or neurochemical signals of the biological medium surrounding one or more electrodes in the CEF bundle, or deliver electrical pulses to at least one electrode in the CEF bundle.

11. A method for fabricating an electrode array for insertion into a biological medium, the method comprising:receiving a plurality of carbon fiber electrode threads (CFETs), each CFET comprising a carbon fiber and an electrode defined at a tip portion of the carbon fiber; and clustering body portions of the plurality of CFETs into a CFET bundle,wherein the plurality of CFETs have different lengths such that at least some electrodes in the CFET bundle are axially offset from one another by a predefined distance.

12. The method of claim 11, further comprising creating the plurality of CFETs, comprising:receiving a plurality of carbon fibers;coating an electrically non-conductive layer over an entire length of each carbon fiber; andremoving the non-conductive layer from distal tip portions of the plurality of carbon fibers to form a plurality of electrodes.

13. The method of claim 12, wherein creating the plurality of CFETs further comprises:attaching proximal ends of the plurality of carbon fibers to respective conductive wires;affixing the conductive wires to discrete locations on a first arm of a fixture; and8123-112597-02affixing the distal tip portions of the plurality of carbon fibers to discrete locations on a second arm of the fixture situated on an opposite side of the first arm such that the plurality of carbon fibers are separated from one another and extend between the first arm and the second ami.

14. The method of claim 12, wherein removing the electrically non-conductive layer comprises heating the distal tip portions of the plurality of carbon fibers coated with the electrically non-conductive layer, wherein the heating is configured to cut the distal tip portions of the plurality of carbon fibers into predetermined lengths.

15. The method of claim 14, wherein removing the electrically non-conductive layer further comprises heating the distal tip portions of the plurality of carbon fibers while freezing at least portions of the plurality of carbon fibers located proximal to the distal tip portions in ice.

16. The method of claim 12, further comprising connecting proximal ends of the plurality of carbon fibers to one or more circuits, wherein the one or more circuits are configured to measure electrophysiological or neurochemical signals of the biological medium surrounding one or more electrodes in the CFET bundle, or deliver electrical pulses to at least one electrode in the CFET bundle, or both.

17. The method of claim 11, wherein the clustering comprises coating the body portions of the plurality of the CFETs with a bonding agent.

18. A method comprising:receiving an electrode array comprising a plurality of carbon fiber electrode threads (CFETs), wherein body portions of the plurality of CFETs are clustered into a CFET bundle, wherein each CFET comprises a carbon fiber and an electrically non-conductive coating, the electrically non-conductive coating covering an entire length of the carbon fiber except at a distal tip portion of the carbon fiber which is not covered by the electrically non-conductive coating to define an electrode;stiffening the CFET bundle at least temporarily; andinserting the CFET bundle into a biological medium,8123-112597-02wherein the CFET bundle is so stiffened that when the inserted CFET bundle reaches a target location of the biological medium, the body portions of the plurality of CFETs remain parallel to a central longitudinal axis of the CFET bundle.

19. The method of claim 18, wherein stiffening the CFET bundle comprises applying a dissolvable bonding agent to the CFET bundle, wherein the bonding agent is configured to have a dissolving rate which allows that at least a predefined amount of the bonding agent remains undissolved until the CFET bundle reaches the target location of the biological medium.

20. The method of claim 18, wherein stiffening the CFET bundle comprises attaching a needle to the CFET bundle.

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