Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
  • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
  • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
  • A61N1/36103—Neuro-rehabilitation; Repair or reorganisation of neural tissue, e.g. after stroke
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/02—Details
  • A61N1/04—Electrodes
  • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
  • A61N1/0551—Spinal or peripheral nerve electrodes
• • G—PHYSICS
  • G06—COMPUTING; CALCULATING OR COUNTING
  • G06F—ELECTRIC DIGITAL DATA PROCESSING
  • G06F3/00—Input arrangements for transferring data to be processed into a form capable of being handled by the computer; Output arrangements for transferring data from processing unit to output unit, e.g. interface arrangements
  • G06F3/01—Input arrangements or combined input and output arrangements for interaction between user and computer
  • G06F3/011—Arrangements for interaction with the human body, e.g. for user immersion in virtual reality
  • G06F3/015—Input arrangements based on nervous system activity detection, e.g. brain waves [EEG] detection, electromyograms [EMG] detection, electrodermal response detection
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
  • A61B2562/04—Arrangements of multiple sensors of the same type
  • A61B2562/043—Arrangements of multiple sensors of the same type in a linear array
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
  • A61B2562/12—Manufacturing methods specially adapted for producing sensors for in-vivo measurements
  • A61B2562/125—Manufacturing methods specially adapted for producing sensors for in-vivo measurements characterised by the manufacture of electrodes

Definitions

• the present invention is directed towards electrical stimulation or sensing of neural cells. More particularly, the present invention relates to regenerative microchannel scaffolds capable of housing microelectrodes to form high-throughput peripheral nerve interfaces.
• neural prosthetics provide only a small fraction of the functionality of a natural limb.
• central neural interfaces can be divided into two major areas comprising central neural interfaces and peripheral neural interfaces.
• peripheral neural interfaces There have been a number of approaches within both of these areas, but all have met with significant difficulties and limitations.
• Central neural interfaces are plagued by the invasiveness of needing to implant electrodes directly in the brain and the fact that this will cause another injury in addition to the amputation of the limb.
• Peripheral neural interfaces are significantly less invasive as they are implanted in peripheral nerves and can be implanted at the time of amputation.
• Another large advantage peripheral neural interfaces have is that the signals obtained from peripheral nerves, closely represents the signal intended for muscle activation.
• the decoding has been taken care of by the descending pathways of the brain and spinal cord, obviating the need for artificial decoding.
• Next generation peripheral nerve prosthetics aim to interface with the original limb's remaining nervous system, which remains viable and functional for years after injury. This includes nerve tracts descending from the cortex traveling through the cerebellum and basal ganglia as well as sensory processing centers in the spine. However, even these next generation interfaces are plagued by issues stemming from damage to the nerve due to interfacing, long term stability, and stimulation and recording specificity.
• Cuff electrodes like the Flat Interface Nerve Electrode (FINE, Fig.
• the Utah Slanted Electrode Array (USEA, Fig. 2a) with needle like electrodes penetrates into the nerve and resides within individual fascicles, axon bundles.
• This design provides direct contact between electrodes and axons and leads to enhanced specificity over a large number of channels.
• the insertion causes irreparable physical damage to the nerve as shown in Fig. 2b.
• This image shows a representative histological section of a nerve at the insertion site of one of the electrodes from the USEA.
• the USEA electrodes suffer from chronic inflammation and the eventual formation of scar tissue. Due to these drawbacks, the overall efficacy has been limited to 80% of the electrodes for approximately five months.
• the Longitudinal Intrafascicular Electrode (LIFE, Fig. 3) electrode platform which is a wire like electrode that is inserted longitudinally into the nerve, has been shown to strike a balance between specificity and reliability. However, while showing some reliability, the insertion still causes damage to the remaining viable portion of the nerve. Perhaps most importantly, by design the LIFE is limited to a small number of channels when compared to the FINE or USEA and simply does not scale to the level necessary for functional and viable interfaces for amputees.
• peripheral nerve interfaces there seems to be a large tradeoff between the ability to selectively interface with individual axons versus the amount of disruption to the nerve and long-term stability as a result of trying to get in close proximity to axons.
• the Sieve Electrode (Fig. 4), the hallmark regenerative interface, is effectively a thin perforated disk that is attached to the nerve perpendicularly so the nerve is forced to regenerate through the device.
• Some of the holes in the disk have ring electrodes that contact the axons regenerating through the holes. Theoretically, each hole could have a ring electrode allowing this device to interface with an extraordinarily large number of axons.
• this design has only a few viable electrodes because the measurable extracellular potential of an axon's action potential (AP) is small, and there is a spatial dependence of the electrode to the Nodes of Ranvier where the extracellular potential of the AP is largest.
• AP axon's action potential
• the present invention comprises a peripheral nerve interface through which high- channel, bi-directional communication between an amputated nerve and a prosthetic limb can be established.
• the interface comprises a regenerative microchannel-scaffold electrode array and an integrated multiplexer/amplifier (a MicroChannel Regenerative Interface).
• Encouraging axons to grow through microchannels significantly improves the ability to record from axons by constraining the low impedance extracellular fluid and amplifying the extracellular potential of an action potential. Additionally, the present invention allows for intimate contact between small groups of axons and electrodes while enhancing recording selectivity. The present invention enables recording from regenerated axons using the electrodes housed within the microchannel scaffold. This establishes a neural prosthetic interface that can record volitional motor commands to control a robotic limb with large degrees of freedom.
• the present invention preferably comprises a regenerative neural interface to establish high-channel, bi-directional communication between protoplasmic protrusions and, for example, a prosthetic limb.
• the interface enables intimate contact between electrodes and small groups of axons while enhancing regeneration.
• the interface can comprise a thin-film PDMS/SU-8 based regenerative microchannel scaffold with microelectrodes incorporated in the microchannels. Confining regenerated axons in microchannels increases the extracellular potential resulting from an AP, thus, enhancing signal strength and recording capabilities.
• the present invention is a microchannel -based device that successfully records spontaneous single unit action potentials from regenerated axons.
• the present invention uses of polydimethylsiloxane allows for a highly flexible and stretchable scaffold, while SU-8 polymer allows for mechanical integrity of the microchannels.
• the microchannels are closed microchannels with incorporated electrodes.
• the present invention further includes methods for fabricating closed microchannels.
• the present invention further includes for patterning electrodes on PDMS using photolithography and lift-off processes.
• the present invention further incorporates electronics that allows for multiplexing and amplification of signals from electrodes.
• the present invention further incorporates an electrical shielding wire/cage-like structure surrounding the implant.
• This cage serves a purpose similar to that of a Faraday cage, and greatly reduces noise and disruptive electromyogram signals from local muscles.
• the present invention is a polydimethylsiloxane (PDMS)/SU-8 based regenerative microchannel scaffold that provides the housing basis for integrated microelectrodes for reliable, high-throughput peripheral nerve interfacing.
• the microchannel-scaffold electrode array has been functionally evaluated through the stimulation of and single unit recordings from regenerated axons in a rat sciatic nerve model. By forcing regenerating axons to grow through microchannels with integrated microelectrodes, the intimate and isolated contact will facilitate a more selective recording and stimulation.
• a PDMS base layer is first formed, in which a microelectrode array would be fabricated if electrodes were to be incorporated into the scaffold.
• SU-8 microchannel walls are then patterned on the PDMS surface.
• a PDMS cover layer is bonded onto top of the SU-8 walls to form closed microchannels.
• Microchannel wall width and height are approximately 20 ⁇ and ⁇ , respectively; microchannel widths range from approximately 50 to 150 ⁇ ; and channel lengths range from approximately 1 to 5mm.
• the scaffold was rolled on itself forming the final implant with a total radius of approximately 1.5mm.
• DRG dorsal root ganglia
• the present invention can comprise a fabricated PDMS-based scaffold with SU-8 microchannel walls, wherein the bottom PDMS layer is approximately 50 ⁇ thick, the SU-8 microchannel walls are approximately 20 ⁇ wide and ⁇ thick, and the microchannel width is approximately 50 ⁇ .
• DRG's were cultured for one week on open scaffolds.
• the sample was stained for axons and Schwann cells, and robust growth and proliferation of axons and Schwann cells extending through the microchannels was observed.
• the axons and Schwann cells alike were aligned and oriented within the microchannels as opposed to radially spreading out where there were no microchannels.
• the present PDMS -based microchannel scaffold guides DRG neurite outgrowth along the microchannels.
• This microchannel scaffold design provides an efficient way to guide regenerating axons, and can be used as a new platform to incorporate electronics for recording and stimulation specifically from small groups of axons. By integrating a microelectrode in each microchannel to form a high-throughput electrode array, such a microchannel-scaffold electrode array significantly enhances the efficacy and reliability of peripheral nerve interfacing.
• the present PDMS/SU-8 scaffolds of varying microchannel dimensions were implanted in a rat sciatic nerve amputee animal model to validate and assess levels of regeneration axons and supporting cell type regeneration through the devices. This characterization to validate regeneration proved successful.
• the present invention can further comprise a fabricated PDMS-base scaffold with SU-8 microchannel walls.
• the bottom PDMS layer is approximately 50 ⁇ thick
• the SU-8 microchannel walls are approximately 20 ⁇ wide and ⁇ thick
• the top PDMS layer is approximately ⁇ thick
• the microchannel widths are approximately 50, 100, or 150 ⁇ .
• the present PDMS/SU-8 scaffold of approximately 150 ⁇ microchannel width can further comprise microwires integrated into the microchannels serving as microelectrodes.
• This neural interfacing device was implanted in a rat sciatic nerve animal model with the purpose of recording signals from axons that regenerated through the microchannels containing the microwires. The use of this device to record signals from regenerated axons proved to be successful.
• the present invention can further comprise a fabricated PDMS-based scaffold with SU-8 microchannel walls, wherein the microchannels have integrated microwires of approximately 60 ⁇ in diameter. These microwires can be insulated except at the very tip of the wire that resides in approximately the middle of the length of the microchannel. These microwires can extend from the device implanted in the sciatic nerve to lie just under the skin of the rat for the duration of the implantation. At the end of 12 weeks the skin is opened, the wires exposed and connected to recording equipment for the recording of sensory induced and spontaneous single unit action potentials from regenerated axons. It is believed that this embodiment of the present invention is the first microchannel-based device that has successfully recorded spontaneous single unit action potentials from regenerated axons.
• the present microchannel neural interface has proven capabilities to record spontaneous and induced action potentials from regenerated axons in vivo.
• the integrated microelectrodes provide an easy and direct connection to on-board electronics that provide the highly advantageous utilities of amplification and multiplexing.
• the present scaffolding material can be porous for increased nutrient exchange into the microchannels of the device.
• the present invention can further comprise microfluidics for nutrient and growth factor delivery into the microchannels of the device.
• the present invention can further comprise acellular nerve grafts into the microchannels to increase and stabilize axon regeneration into the microchannels of the device.
• the present invention can further comprise chemical and/or biological factors to increase and stabilize regeneration.
• chemical and/or biological factors include, among others, laminin and/or nerve growth factor (NGF). These factors additionally could be contained within degradable or non-degradable hydrogels, nanoparticles or other encapsulants.
• the present invention can further comprise chemical and/or biological factors to allow the separation of motor and sensory axons. This would allow certain microchannels to house motor axons and other microchannels to house sensory axons that could then be interfaced with in a more specific manner.
• the present invention can further comprise cells including stem cells and/or Schwann cells into the microchannels for increasing and stabilizing axon regeneration.
• the present invention can further comprise a plurality of electrodes in each channel.
• the additional electrode(s) could be used as a reference electrode, for unidirectional stimulation, and for stimulation and conduction blocking purposes in conjunction with each other.
• the present invention can further comprise an electrical shielding cage or wire-like structure around the implant to serve a purpose similar to that of a Faraday cage and reduce noise and/or disruptive electro myogram (EMG) signals from muscles.
• EMG electro myogram
• the present invention can further comprise wireless components into the On board' electronics, obviating the need for wires leading to a purcutaneous headcap. This would require the addition of a trancutaneous power source or an implantable battery for powering the recording and wireless transmitting unit.
• the present invention can be used in neural prosthetic interfacing, allowing amputees to control a prosthetic device by recording from nerves and acquire sensation from the prosthetic device by stimulating nerves.
• the device could be implanted in either peripheral nerves, the spinal cord, and/or the optic nerve.
• the present invention can be used in functional electrical stimulation (FES), allowing individuals suffering from various disabilities to regain function. This includes individuals suffering from many types of paralysis stemming from a spinal cord injury and could restore limb movements as well as bowel and bladder control. This can alleviate individuals suffering from the 'foot drop' syndrome
• the present invention can be used in conduction blocking, allowing for pain modulation by controlling nerves that are conducting pain signals to the brain or that have aberrant activity resulting in pain signals.
• the present invention further can be used as a tool by researchers and scientists to determine function of nerves and axons as they relate to various sensory and/or motor functions. Additionally, the present invention can be used to study how axons, their behavior, and how they interact with other tissues, change over time and after an injury.
• the present device in conjunction with tools to assess cortical activity, can also be used to study how information in the periphery as coded by axons is translated to cortical activity.
• the present invention can be used in measuring impedance, allowing doctors to monitor nerve regeneration in an individual with nerve damage. This would allow doctors to monitor bone regeneration in an individual with a bone fracture. This would allow doctors to monitor skin regeneration/growth in the subdural layers not visible to the human eye.
• the present invention is a vast improvement over conventional device that use polyimide as the substrate material.
• the general design of the conventional polyimide device includes just the bottom layer.
• a major difference between such a design and the present invention is the addition of a top PDMS layer. This fully closes the microchannels.
• a benefit is complete electrical isolation between neighboring microchannels. If this top layer is not present, then neighboring microchannels can share the same low impedance extracellular fluid and matrix surrounding the axons. This leads to increased noise and a decreased ability to differential signals from different axons. The overall result is a decreased ability to specifically and selectively interface with individual and small groups of axons.
• PDMS is a highly conformable and flexible material, and much closely matches the mechanical properties of a nerve.
• the SU-8 provides the structure needed for device integrity while maintaining the advantages of the PDMS.
• This choice of materials allows the present invention to better conform to regenerating axons and provide a scaffold for regeneration that closely matches the nerves natural environment.
• Other materials, such as polyimide, are rigid in comparison and do not provide the need flexibility and conformability to maintain a regenerating nerve over chronic periods of time.
• PDMS a highly hydrophobic material
• PDMS a highly hydrophobic material
• Those of skill in the art know that devices that utilize materials such as polyimide accumulate scar tissue over time, leading to increases in electrode impedance and a narrowing of microchannels. This results in the inability to record small amplitude action potentials, an unfavorable environment for axon growth leading to axon death, and inevitable device failure in a chronic setting.
• the present use of PDMS circumvents this issue because it prevents scar tissue accumulation on its surface.
• Another patentable distinction between the conventional polyimide device and the present invention is the use of on-board electronics. This is a huge design advantage in that it allows for a significantly less invasive testing platform in an animal model. Recordings can be more reliably taken and stimulation can be performed while the rats are awake and over a chronic period of time.
• Spontaneous signals generated from actual limb movement is recorded as opposed to just evoked signals by applying an electric current farther upstream to artificially stimulate the nerve and then recording the nerve's response.
• the onboard electronics allows for signal amplification directly after signal acquisition. This significantly increases the signal-to-noise ratio and greatly increases the ability to record specifically and selectively from axons. This platform also allows the direct integration of wireless components.
• the present invention is a regenerative neural interface to establish high-channel, bi-directional communication between an amputated nerve and a device comprising a thin-film polydimethylsiloxane (PDMS)/SU-8 based regenerative microchannel scaffold having microchannels, microelectrodes incorporated in the microchannels, and an integrated multiplexer/amplifier for large channel recordings.
• the amputated nerve can comprise groups of axons and the interface provides intimate contact between the microelectrodes and groups of axons.
• the microchannels confine axon growth to limit the volume of low impedance extracellular fluid and matrix surrounding the axon.
• the interface can further comprise a shield surrounding at least a portion of the interface, wherein when in use, the shield reduces noise and disruptive electromyogram (EMG) signals from axons.
• the scaffold can comprises a bottom layer comprising PDMS and walls comprising SU-8 polymer extending upward from the bottom layer, wherein the bottom layer and the walls form the microchannels.
• the bottom layer can have a thicknesses in the range of approximately ⁇ and 40 ⁇ .
• the walls can have a height of approximately ⁇ .
• the walls can have a width of approximately 20 ⁇ .
• the present invention is a regenerative neural interface to establish high-channel, bi-directional communication between a protoplasmic protrusion and a device comprising a bottom layer comprising PDMS, and a plurality of walls comprising SU-8 polymer extending upward from the bottom layer, the walls running approximately parallel to one another, forming microchannels, the bottom layer having a thicknesses in the range of approximately ⁇ to 40 ⁇ , the walls having a width of approximately 20 ⁇ and a height of approximately ⁇ , and the widths of at least a portion of the microchannels are in the range of approximately 50 ⁇ to 150 ⁇ .
• the interface can further comprise at least one microelectrode incorporated in at least a portion of the microchannels.
• the interface can further comprise an integrated multiplexer/amplifier.
• the interface can further comprise a shield surrounding at least a portion of the interface.
• the microchannels can have a length of approximately 3mm.
• the present invention is a rolled regenerative neural interface to establish high-channel, bi-directional communication between a protoplasmic protrusion and a device comprising a bottom layer comprising PDMS, and a plurality of walls comprising SU-8 polymer extending upward from the bottom layer, the layer and walls forming a layer of microchannels, that when rolled, form a scaffold with microchannels closed along their length.
• the bottom layer can have a thicknesses in the range of approximately ⁇ to 40 ⁇
• the walls can have a width of approximately 20 ⁇ and a height of approximately ⁇
• the widths of at least a portion of the microchannels can be in the range of approximately 50 ⁇ to 150 ⁇ .
• the rolled regenerative neural interface can have a total radius of 1.5mm.
• the present invention is a method of fabricating a regenerative neural interface.
• the method can comprise providing a PDMS bottom layer and walls forming microchannels, and patterning gold electrodes into the PDMS bottom layer with exposed portions in the microchannels forming a conformable microelectrode array (cMEA).
• the method can further comprise connecting a channel amplifier/multiplexer chip to the interface.
• the present invention is a method of fabricating a regenerative neural interface comprising providing a bottom layer comprising PDMS, providing a top layer comprising PDMS, and providing walls comprising SU-8 polymer between the bottom and top layers, forming microchannels.
• the present invention is a neural interface comprising a base layer comprising a polymeric organosilicon compound, and at least two channel walls comprising phenol formaldehyde resin, the walls and base layer forming a channel, wherein the channel accommodates regenerating a protoplasmic protrusion.
• the channel can comprise an electrical conductor for communication with a protoplasmic protrusion.
• the polymeric organosilicon compound can comprise polydimethylsiloxane (PDMS).
• the phenol formaldehyde resin can comprise an epoxy-based negative photoresist.
• the phenol formaldehyde resin can comprise SU-8 polymer.
• the PDMS provides a flexible and stretchable scaffold, and the SU-8 polymer provides mechanical integrity to the microchannels.
• the present interface can be used in a variety of environments and ways, including to control machines other than prosthetic limbs.
• Fig. 1 is a schematic of a FINE peripheral nerve interface.
• Fig. 2(a) is an micrograph of USEA
• Fig. 2(b) is an example of physical damage to nerve caused by USEA insertion (scale bar is 50 ⁇ ).
• Fig. 3 is a schematic of a LIFE peripheral nerve interface.
• Fig. 4 is a micrograph of a Regenerative Sieve peripheral nerve interface.
• Fig. 5 is an illustration of isolated axons regenerating through microchannels.
• Fig. 6 is an exploded view of the overall microchannel assembly of the present invention according to a preferred embodiment.
• Fig. 7 is a top view of a portion of the microchannel assembly of Fig. 6.
• Fig. 8 depicts an exemplary embodiment of the present scaffold after rolling.
• Figs. 9(a)-(c) illustrate an embodiment of the present invention functionally evaluated in vivo through the stimulation of and single unit recordings from regenerated axons in a rat sciatic nerve amputee model.
• Fig. 10 illustrates the fabrication process (not to scale) for the bottom PDMS layer and SU-8 microchannel walls of the regenerative microchannel scaffold, according to a preferred embodiment of the present invention.
• Fig. 11 is a micrograph of the bottom PDMS layer and SU-8 microchannels walls of the present invention according to exemplary embodiments.
• Fig. 12 illustrates the fabrication process of adding the top PDMS layer to complete the regenerative microchannel scaffold.
• Figs. 13(a)-(c) are images of the regenerative microchannel scaffold in a unrolled and rolled configuration showing how the top PDMS layer contacts the bottom PDMS layer once rolled.
• Fig. 14 illustrates the fabrication process of patterning titanium and gold electrodes and traces using an NR4-8000P photoresist in a photolithography and lift-off based process.
• Figs. 15(a)- (c) illustrates the actual electrode, trace, and bonding pad design for the present invention along with how two different electrode referencing paradigms are incorporated into the device.
• the electrode region is highlighted in orange, the bond pad region is highlighted in red, and the traces connect the two regions.
• Fig. 16 is a micrograph of titanium/gold electrodes, traces, and bonding pads patterned on a base PDMS layer using the NR4-8000P photolithography and lift-off process.
• Fig. 17 illustrates the fabrication process of insulating the titanium/gold traces using an NR4-8000P photoresist in a sacrificial-post based process.
• Fig. 18 depicts a side view of the present invention after the complete fabrication process and bonding of electronic components including the chip for amplification and multiplexing.
• Fig. 19 is a micrograph view from the top of the microchannels with incorporated titanium/gold electrodes and traces prior to being rolled.
• Fig. 20 is a micrograph of the present invention with after the microchannels have been rolled with incorporated titanium/gold electrodes and traces, and incorporated electronics for multiplexing and amplification.
• Fig. 21 illustrates the present invention ready for implantation, after it has been encased in an outer tubing to aid with nerve suturing to the front of the microchannels, after being encased in an electrical shield comprising a cage or wiring to reduce noise and disruptive EMG signals, and after attaching signal extraction wires to the chip.
• Figs. 22(a)-(c) are fluorescent micrographs of an in vitro dorsal root ganglia (DRG) culture on the PDMS/SU-8 microchannels.
• axons are shown as red
• Schwann cells are shown as green.
• Sub-images a-c show the axons and supporting Schwann cells proliferated extremely well, were aligned and oriented within the microchannels, and even seemed to grow towards the microchannels.
• Fig. 23 is an illustration of the rat sciatic nerve amputee animal model used for testing in the present invention.
• the animal model comprises first transecting the sciatic nerve.
• the device is sutured to the proximal and distal nerve stumps so that regenerating axons grow through the device in response to cues from the distal end.
• the distal nerve is again transected approximately 2mm distal to the end of the device and a portion of the nerve excised. This leaves what we term a 2mm 'distal nerve stump' on the distal end of the device.
• a portion of the nerve is excised in order to prevent regenerating axons from reinnervating their original targets.
• Signal extraction wires are then tunneled subcutaneously along the back of the rat to a percutaneous headcap where they can be connected to wires leading to an electrophysiology computer.
• Fig. 24 is a characteristic fluorescent micrograph of the present invention comprising a cross-section of a regenerative microchannel scaffold with 150 ⁇ wide microchannels after being implanted for eight weeks in a rat sciatic nerve amputee animal model.
• cell nuclei are shown in blue
• axons are shown in red
• the support Schwann cells are shown in green. It is clear from the image that axons and Schwann cells populated the microchannels well.
• Fig. 25 is a characteristic fluorescent micrograph of the present invention comprising a cross-section of a regenerative microchannel scaffold with ⁇ wide microchannels after being implanted for eight weeks in a rat sciatic nerve amputee animal model.
• cell nuclei are shown in blue
• axons are shown in red
• the support Schwann cells are shown in green. It is clear from the image that axons and Schwann cells populated the microchannels as well as in the 150 ⁇ wide microchannels. This provides concrete proof that using this type of scaffold will greatly benefit a microchannel based neural interface.
• Fig. 26 is a characteristic fluorescent micrograph of the present invention comprising a cross-section of a regenerative microchannel scaffold with 50 ⁇ wide microchannels after being implanted for eight weeks in a rat sciatic nerve amputee animal model.
• cell nuclei are shown in blue
• axons are shown in red
• the support Schwann cells are shown in green. It is clear from the image that axons and Schwann cells did not populate the microchannels well providing concrete proof that microchannels of this are not usable in a microchannel based neural interface.
• Fig. 27 is a micrograph of the present invention, placed on a dime, used for a terminal experiment in a rat sciatic nerve animal model.
• the present invention was integrated with microwires serving as microelectrodes in regenerative microchannel scaffolds with 150 ⁇ wide microchannels.
• Fig. 28 shows spontaneous action potential recording data as obtained through the present invention integrated with microwires while the animal was at rest.
• the left column of images shows raw data collected using the microwires from two representative channels (1 and 7) showing spontaneous action potentials clearly visible over the background noise with a SNR of approximately 2: 1.
• the middle column shows the shape of individual single unit spontaneous action potentials isolated from the two representative channels.
• the right column shows the inter- spike-interval of these spontaneous action potentials showing that top action potential form channel 1 was highly periodic along with the action potential from channel 7. This is in contrast to the other two action potentials form channel 1 which had highly sporadic firing rates.
• Fig. 29 shows the firing rate of action potentials in channel 7 at rest (top image) and in response to tactile stimulation (bottom image) of the 4th knuckle on the rat's paw. It can be clearly seen that the firing rat increased from approximately 3Hz to approximately 9Hz in response to the sensory stimulation.
• Ranges may be expressed herein as from “about” or “approximately” one particular value and/or to “about” or “approximately” another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value.
• Figs. 6 and 7 illustrate a neural interface 10 comprising a base layer 14 comprising a polymeric organosilicon compound and at least two channel walls 16 comprising phenol formaldehyde resin, the walls 16 and base layer 14 forming a channel 20, wherein the channel 20 accommodates regenerating a protoplasmic protrusion 22.
• a channel is a passage or tunnel forming a conduit through which an axon can regenerate or grow.
• the channel is open at both ends to allow the entry and exit of regenerating nerve axons, and need not be closed along its length (have a top), but in an exemplary embodiment, the channel is closed to surround the regenerating nerve axons within the channel.
• the channel can include an number of cross-sectional shapes, including having a round (e.g. oval or circular) cross-section, or an angular (e.g. square or rectangular) cross- section.
• the channel 20 can comprise an electrical conductor 18 for communication with the protoplasmic protrusion, the electrical conductor preferably being an electrode.
• the polymeric organosilicon compound can comprise polydimethylsiloxane (PDMS), and the phenol formaldehyde resin can comprise an epoxy-based negative photoresist, preferably SU-8 polymer.
• the neural interface 10 comprises microchannels 20 composed of top 12 and bottom 14 PDMS layers, and SU-8 polymer walls 16 with incorporated gold electrodes 18.
• the PDMS top and bottom layer 12, 14 thicknesses Ti and T 2 , respectively, can be approximately ⁇ and 40 ⁇ , respectively.
• the microchannels walls 16 can have a width W 2 and height He of approximately 20 ⁇ and ⁇ , respectively.
• the widths W3 of the microchannels 20 can range from approximately 50 ⁇ to 150 ⁇ , and with the optimal being ⁇ as determined from in vivo regeneration studies.
• the microchannel 20 lengths Li + L 2 can range from approximately .95mm to 5mm.
• the layer of microchannels formed as the interface 10 can be rolled to form an overall scaffold 30, with a total radius HR of approximately 1.5mm, as shown in Fig. 8.
• the implantation setup shown in Figs. 9(a)-(c) involves mounting the proximal stump of a transected sciatic nerve to one end of the scaffold 30 and allowing the nerve 22 to disassemble and regenerate through the microchannels 20 as shown in Fig. 6.
• the regenerating axons in the nerve are expected to integrate with the microelectrodes 18 inside the microchannels 20.
• the microelectrodes 18 can be wired to the integrated ⁇ -board' electronics by a short PDMS cable.
• the ⁇ -board' electronics will help to reduce recording noise and power for stimulation, as well as allow for multiplexing that will reduce the number of wires needed.
• the VOs of the electronics can be wired to a percutaneous head stage through subcutaneous wires.
• the one or more electrodes can, for example, detect extracellular electrical signals in the microchannel when an axon in the microchannel transmits an action potential or generate extracellular electrical signals in the microchannel that stimulate an action potential in the axon.
• Extracellular electrical signals produced when an axon in the microchannel transmits an action potential may be detected by one or more electrodes exposed to the interior of the microchannel (i.e. a recording array).
• the one or more electrodes therefore allow information relating to action potentials in the axon to be gathered and analyzed.
• Action potentials from motor and sensory axons may be recorded and analyzed in this way.
• Information gathered from a motor axon may be amplified, recorded and processed and may be used for a range of purposes, for example, to drive a prosthetic limb, to supply information to a muscle stimulator downstream of the site of injury or to study nerve traffic in the regenerated nerve fiber.
• One or more electrodes coupled to the microchannel may be useful in transmitting artificial action potentials to an axon in the microchannel by means of capacitive coupling and/or the passage of Faradaic currents between the electrode surface and the axon (i.e. a stimulation array).
• Artificial action potentials may be produced, for example, in response to input from sensors, such as temperature or pressure sensors, and transmitted via the electrode to a sensory axon in the microchannel, to provide sensory input to the nervous system.
• the interior of the microchannels provides an environment that promotes and supports growth of one or more of axons, glial cells and blood vessels within the microchannel.
• the microchannels can contain a gel or other drug delivery vehicle for the sustained display or controlled release of chemical and/or biological factors. This provides a structure that encourages axon growth and glial invasion.
• a gel comprises a matrix of fibers contained in an interstitial electrically conductive medium. Suitable gels can be formed from fibrous materials such as MatrigelTM (BD Biosciences), collagen, agarose, haluronic acid, and spider silk using standard techniques.
• the microchannels can comprise one or more biological factors that promote growth of one or more axons, glial cells and blood vessels. The biological factors can be incorporated in a gel within the microchannel or attached to the inner walls of the microchannel.
• Biological factors include promoters of axon growth and Schwann cell invasion, such as laminin, fibronectin, collagen type 4, and heparan sulphate proteoglycans, or molecules comprising the axon growth promoting domains of those molecules.
• the microchannels can contain a neurotrophic factor such as nerve growth factor, brain derived neurotrophic factor and/or neurotrophin 3.
• Schwann cell growth factors such as neuregulins can be employed.
• growth factors such as fibroblast growth factor 1 and platelet derived growth factor can be employed.
• growth factors such as vascular endothelial growth factor (VEGF) cam be employed.
• VEGF vascular endothelial growth factor
• IL 4 interleukin 4
• the microchannels accommodate growing axons in an extracellular fluid which is naturally produced by the surrounding tissue.
• This fluid provides an ionic conductive medium that contacts the one or more electrodes and allows the detection of action potentials propagating in the axon by the one or more electrodes.
• the microchannels can also accommodate glial cells, such as Schwann cells, and blood vessels.
• a 40 ⁇ PDMS (Sylgard 184, Dow Corning) base layer was first spun on glass, in which an MEA would be fabricated if electrodes were to be incorporated into the scaffold.
• the PDMS base layer was treated with oxygen plasma to increase the adhesion between PDMS and SU-8.
• a ⁇ layer of SU-8 (SU-8 2100, MicroChem Corp) was then spun on top of the PDMS.
• the SU-8 was cured, exposed, and developed forming the patterned microchannel walls on the PDMS base layer.
• the width and length of the microchannel walls were approximately 20 ⁇ and 10mm respectively.
• the width of the microchannels ranged from approximately 50-150 ⁇ .
• An example of the resulting base PDMS layer with SU-8 microchannel walls forming open microchannels with a 75 ⁇ width is depicted in Fig. 11. In this image, the SU-8 microchannel walls are reflecting on the clear base PDMS layer.
• polyacrylic acid PAA
• a preferred fabrication process of adding the top PDMS layer polyacrylic acid (PAA) is first spun on another glass slide and dried. This is done twice. A ⁇ layer of PDMS is immediately spun on the PAA layers and partially cured. The bottom PDMS layer with the SU-8 microchannel walls is treated with oxygen plasma to increase the adhesion between the two layers. The two glass slides are place together with weight on top and baked until the top PDMS layer is fully cured. Finally, the glass slide sandwich is soaked in water until the PAA dissolves and allows an easy removal of the top glass slide. The simplified process is depicted in Fig. 12. An example of the resulting closed microchannels each with 150 ⁇ widths is shown in Fig.
• Fig. 13(b) depicts a microchannel scaffold with a ⁇ width after it has been rolled to form the implantable tubular construct.
• Fig. 13(c) shows a close up of the microchannels and clearly shows where the top PDMS layer of one of the microchannel layers meets the bottom PDMS layer of another microchannel layer.
• the present invention has been successfully fabricated as an regenerative microchannel scaffold using PDMS as the base and cover layers, and SU-8 as the microchannel walls.
• the devices capability of being rolled to form a three-dimensional scaffold has also been verified.
• FIG. 14 A preferred fabrication process for incorporating the titanium and gold electrodes, traces, and bond pads into the bottom PDMS layer is illustrated in Fig. 14.
• a photoresist that is preferably NR4-8000P is spun on. This is cured by baking in an oven before exposing and developing the NR4-8000P according to the electrode, trace, and bond pad design.
• This design is illustrated in Fig. 15 and also depicts how two different referencing paradigms are incorporated into the device. These referencing paradigms are bi-polar and tri-polar and allow a user to choose in real-time which to use in order to best reduce noise and improve action potential recordings.
• Fig. 15 the electrode region is highlighted in orange, the bond pad region is highlighted in red, and the traces connect the two regions.
• titanium is first deposited using preferably an E-Beam Evaporator to serve as an adhesion layer between the gold and PDMS base. Gold is then deposited preferably using the method on top of the titanium. Finally, the remaining NR4-8000P is stripped away leaving behind the titanium/gold electrodes, traces, and bond pads. An example of this is shown in Fig. 16 where three micrograph images of the electrodes, traces, and bond pads have been stitched together to give a complete high-resolution image.
• FIG. 17 A preferred fabrication for insulating the titanium/gold traces is illustrated in Fig. 17 and starts with a base PDMS layer with electrodes, traces and bond pads already patterned on it.
• First the sample is treated with oxygen plasma to increase the adhesion with the NR4-8000P which is then spun on immediately.
• the NR4-8000P is then cured, exposed, and developed so that all that remains are posts covering the electrodes and bond pads on the sample.
• the sample is again treated with oxygen plasma to increase the bonding of the base layer with the PDMS insulation layer.
• the PDMS insulation layer approximately ⁇ thick, is immediately spun on and cured.
• the sample is then plasma etched using preferably oxygen and carbon-tetrafluoride to remove the possible thin layer of PDMS covering the NR4-8000P sacrificial posts. Finally, the sacrificial posts are stripped away using preferably Resist Remover 41 leaving behind titanium/gold PDMS insulated traces with openings in the insulation corresponding to the electrodes and bond pads.
• SU-8 microchannel walls and top PDMS layer can be added to the sample.
• a micrograph of the resulting structure is shown in Fig. 18. This image has been taken as viewed through the top PDMS layer where one can clearly see the SU-8 microchannel walls, microchannels, and titanium/gold electrodes and traces.
• a preferred fabrication for incorporating the electronics of the present invention involves placing conductive epoxy on the bonding pads of the electronics, whether that is a PCB, chip or some other electrical component. This is laid with the bonding pads facing up. The PDMS sample is then flipped so its bonding pads are facing down. The bonding pads are lined up under a microscope and placed gently together so the conductive epoxy is connecting the bonding pads on the PDMS substrate to the bonding pads on the electronic components. Finally the sample is cured at length to ensure the conductive epoxy has firmly bonded to both sets of bond pads.
• FIG. 19 A schematic of a device after this step is shown in Fig. 19 where the image is a cross- section of the device showing the electronic components, conductive epoxy, titanium/gold, and microchannels prior to being rolled.
• FIG. 20 A micrograph of the device after these fabrication steps is shown in Fig. 20. In this image, the microchannels have been rolled and the chip for signal amplification and multiplexing has been bonded to the bonding pads on the PDMS substrate using conductive epoxy which is not visible.
• a preferred process for preparing the device for implantation first involves placing the rolled microchannels inside an outer tube that is longer than the microchannels by preferably at least 1mm on both ends.
• This tube serves allows the nerve to be sutured into the tube so that it is directly facing the opening of the microchannels.
• a grounded electrical shield preferably comprising a cage or wire is placed around the implant to reduce noise and local EMG signals in the same way a Faraday cage helps reduce noise.
• signal extraction wires are connected to the electronics.
• Regenerative microchannel scaffolds lacking the PDMS cover layer were used for the in vitro experiments.
• the open regenerative microchannel scaffolds were placed at the bottom of tissue culture wells.
• Dorsal root ganglia (DRG's) were explanted from the spinal cords of PI rat pups. The nerve roots were removed and the DRG's were placed on the open scaffolds at the entrance to the microchannels.
• the DRG's were incubated with only a thin layer of DMEM/F12 media with approximately 10% FBS and 50 ng/mL nerve growth factor (NGF) (Roche).
• NGF nerve growth factor
• the wells were fully covered with the same media.
• the media, including NGF were replaced every two days for a total of seven days. After seven days the DRG's were fixed with approximately 4% paraformaldehyde in PBS for approximately 20 minutes and washed three times with IX PBS.
• axons and Schwann cells were stained overnight at approximately 4°C with the primary neurofilament 160 kDa (NF160, 1:500, mouse IgGl, Sigma) and primary S-100 respectively.
• the secondary antibodies goat anti- mouse IgGl Alexa 488/594 and goat anti-rabbit IgG Alexa 488/594 were used respectively.
• Cell nuclei were labeled with DAPI (10 ⁇ , Invitrogen). The fluorescently labeled cells and nuclei were visualized using a Zeiss upright microscope and the images were captures with an Olympus digital camera.
• FIG. 11 A micrograph of the scaffolds lacking the PDMS cover layer fabricated for in vitro DRG culturing is shown in Fig. 11. To reiterate, this open scaffold has microchannel widths of 75 ⁇ . The cultured DRGs adhered well to these open scaffolds.
• a fluorescent micrograph shows an example DRG (the large bright circle) cultured on a scaffold with 50 ⁇ microchannel widths.
• the SU-8 microchannel walls auto- fluoresce while the microchannels themselves appear as dark horizontal lines and are positioned to the left of the DRG.
• the main image shows two overlaid images of axons (shown in red) and non-neuronal Schwann cells (shown in green), while the subsets show the separate fluorescent images. When the axons and Schwann cells overlap in the main image, they appear as orange. As seen from the main image, both the neurites and Schwann cells grew and proliferated in a robust manner.
• Fig. 22(a) and Fig. 22(b) show that axon extension and Schwann cell migration were aligned and oriented along the direction of the microchannels.
• Fig. 22(c) shows that the axons and Schwann cells actually extended processes and migrated towards the microchannels in some cases. It should also be noted that there does appear to be more neurite extension and Schwann cells growth on the SU-8 channel walls as opposed to on the PDMS. However, this will not negatively affect the scaffold in vivo because in a preferred embodiment, there is a top PDMS layer and once inside the channel, it does not matter which wall the axons and cells grow on.
• the substrate and structural materials of the present microchannel scaffold are biocompatible and can support the growth of multiple cells types, DRG axons and non-neuronal cells. Furthermore, the capability of the microchannel design to guide and direct DRG axon outgrowth and non-neuronal cell migration along and through the microchannels has been verified. These results show that the present microchannel design provides an extremely robust method to guide regenerating axons and can be used as a fundamentally sound platform to incorporate electronics for chronic recording and stimulation of axons.
• Regenerative microchannel scaffolds shown in Fig. 13(b) were used for the in vivo experiments. These scaffold had widths of approximately 50, 100 or 150 ⁇ . This experiment was to validate and assess levels of regeneration axons and supporting cell type regeneration through the regenerative microchannel scaffolds. Additionally, this experiment was to identify the microchannel dimension that hold the fewest number of regenerating axons while ensuring that a majority of microchannels actually contain axons when the varying parameter is the microchannel width.
• the three variations of widths tested were approximately 50, 100, or 150 ⁇ .
• the scaffolds were implanted in a rat sciatic nerve amputee model for approximately eight weeks.
• the specific animal model comprises first transecting the sciatic nerve.
• the device was sutured to the proximal and distal nerve stumps so that regenerating axons grow through the device in response to cues from the distal end.
• the distal nerve was again transected approximately 2mm distal to the end of the device and a portion of the nerve excised. This leaves what we term a 2mm 'distal nerve stump' on the distal end of the device.
• a portion of the nerve was excised in order to prevent regenerating axons from reinnervating their original targets.
• the implantation model is illustrated in Fig. 23.
• the regenerative microchannel scaffolds were explanted, they were fixed for approximately two hours in approximately 4% paraformaldehyde. To prepare the scaffolds for cryosectioning, they were transferred to an approximately 30% sucrose in PBS solution and incubated at approximately 4°C for one-two days until saturation. Finally, the samples were embedded in O.C.T. gel and frozen for cryosectioning with a Leica CM30505 cryostat. Cross- sections of the scaffold were taken in the middle of the scaffold corresponding to the region that holds electrodes. This region was analyzed for axons numbers per microchannel. The present invention needed to be sectioned at very thick intervals (approximately ⁇ ) in order to maintain sample integrity.
• the sections taken were immunohistologically stained for markers of axons (NF-160), Schwann cells, (S-100), and cell nuclei (DAPI).
• the basic staining process involved first incubating the sections for approximately one hour at room temperature in a blocking solution of goat serum in PBS, then incubating overnight at approximately 4°C in a mixture of primary antibody and blocking solution.
• the sections were washed and incubated for approximately one hour at room temperature in a solution of secondary antibody (goat anti-rabbit IgG Alexa 488/594, and goat anti-mouse IgGl Alexa 488/594) mixed in 0.5% triton in PBS.
• the sections were be washed, dried, and cover slipped for evaluation under a Zeiss LSM 510 NLO confocal microscope.
• Fluorescent micrographs of representative sections of the regenerative microchannel scaffolds with microchannels widths of approximately 150, 100, or 50 ⁇ are shown in Fig. 24, Fig. 25, and Fig. 26, respectively.
• axons are shown in red
• Schwann cells are shown in green
• cell nuclei are shown in blue.
• the scaffold itself is black, however in some cases the SU-8 auto-fluoresces and appears a faint orange or blue depending on the figure. It can be clearly seen in both Fig. 24 and Fig. 25 that the 150 and ⁇ microchannels support the robust growth and integration of tissue including importantly axons and Schwann cells.
• microchannel widths A majority of microchannels in both microchannel widths have axon regeneration within them to the benefit of neural interfacing. This is in contrast to the 50 ⁇ microchannel width which clearly does not support regenerating axons and Schwann cells as seen in Fig. 26.
• the purpose of this experiment was to record spontaneous and sensory induced single unit action potentials from axons regenerated through the microchannels of the present invention.
• the present invention integrated with eight microwires, shown in Fig. 27, approximately 60 ⁇ in diameter serving as microelectrodes was implanted in a rat sciatic nerve animal model for 12 weeks.
• the microwires were insulated except at the very tip of the wire which resided in approximately the middle of the length of the microchannel.
• the microwires extended from the device implanted in the sciatic nerve to lie just under the skin of the rat for the duration of the implantation. Given the diameter of the microwires, the 150 ⁇ wide microchannels were used as the net area was closest to the ⁇ width shown to be optimal in the previous in vivo study.
• the rat was anesthetized using anesthetic cocktail (Acepromazine, 0.5 mg/ml, ketamine HCl, 65 mg/ml and Xylazine, 7.5 mg/ml).
• the skin of the rat was then opened exposing the ends of the microwires leading away from the device.
• the wires were connected to a Cerebus 128 channel data acquisition system (Cyberkinetics Inc.) for signal acquisition and amplified using a sampling rate of 30 kHz for neural spike data. Once the wires were connected, resting signals were recorded for the purpose of proving that the present invention capably records spontaneous single unit action potentials from regenerated axons.
• sensory evoked action potentials were evoked using tactile stimulation of the rat foot pad to further prove the ability of the present invention to record single unit action potentials in response to a normal environmental stimulus.
• the raw signals were filtered at 300 and 8000 Hz.
• Thresholding and K- means semi-automatic offline sorting were used to identify individual action potential waveforms.
• Fig. 28 An example of spontaneous action potential recordings is shown in Fig. 28.
• the left column of images shows raw data collected using the microwires from two representative channels (1 and 7) showing spontaneous action potentials clearly visible over the background noise with a SNR of approximately 2: 1.
• the middle column shows the shape of individual single unit spontaneous action potentials isolated from the two representative channels.
• the right column shows the inter- spike-interval of these spontaneous action potentials showing that top action potential form channel 1 was highly periodic along with the action potential from channel 7. This is in contrast to the other two action potentials form channel 1 which had highly sporadic firing rates.
• Fig. 29 representatively shows how the firing rate of axons in channel 7 increased by approximately three fold in response to tactile stimulation of the 4th toe on the rat paw.
• the present invention further comprises methods for fabricating closed microchannels.
• a preferred fabrication protocol comprises SU-8 microchannel walls fabrication after electrode insulation, as follows:
• a preferred fabrication protocol comprises the addition of top PDMS layer to the microchannels, as follows:
• PAA Polyacrylic Acid, water soluble polymer
• Another preferred fabrication protocol comprises the addition of top PDMS layer to the microchannels, as follows:
• PAA Polyacrylic Acid, water soluble polymer
• the present invention further comprises methods for patterning electrodes on PDMS using photolithography and lift-off processes.
• a preferred fabrication protocol comprises electrode patterning using 30 ⁇ NR4-8000 photolithography and lift-off, as follows:
• This undercut can be quite important and will really only be present in the low feature density areas.
• High feature density areas will have straighter side walls instead of an undercut. If the sample is exposure for the calculated time, the high density areas will take longer to develop and result in delamination of the photoresist from the PDMS substrate.
• Another preferred fabrication protocol comprises insulation of electrode traces except at electrode active sites using NR4-8000p sacrificial posts, as follows:
• This undercut can be quite important and will really only be present in the low feature density areas.
• High feature density areas will have straighter side walls instead of an undercut. If the sample is exposure for the calculated time, the high density areas will take longer to develop and result in delamination of the photoresist from the PDMS substrate.
• the present policy further comprises integration of electronics for multiplexing and amplification.
• a preferred integration protocol comprises:
• PCB printed circuit board
• the present invention further comprises another exemplary integration of electronics for multiplexing and amplification protocol comprising:
• a prototype regenerative microchannel scaffold using PDMS as the base and cover layers and SU-8 as the microchannel walls has been successfully fabricated. Additionally, a first step in developing an integration method for on-board electronics to aid in signal extraction has been made and further validated the present invention's capability of being rolled to form a three- dimensional scaffold.
• the substrate and structural materials of the scaffold have been shown to be non-toxic by supporting the growth of multiple cells types, DRG neurites and non-neuronal cells. Furthermore, the capability of the microchannel design to guide and direct DRG neurite outgrowth and non-neuronal cell migration along and through the microchannels has been verified. These results show that the microchannel design provides a method to guide regenerating axons, and can be used as a novel platform to incorporate electronics for chronic recording and stimulation from small specific groups of axons.
• the neural interface has an integrated microelectrode in each microchannel to form a high-throughput electrode array.
• a microchannel-scaffold electrode array has potential to significantly enhance the efficacy and reliability of peripheral nerve interfacing. This is based upon the rational that confining an axon to a microchannel limits the volume of the low impedance extracellular fluid and matrix surrounding the axon.
• the present invention itself will house upwards of 100 microchannels and each of these channels can hold an incorporated electrode in future generations of the device.
• the channels of the device in future generations can be used for different purposes where many can be used towards the control of a neural prosthetic and many can be used towards providing sensory feedback.
• each microchannel could be stimulated and the individual asked if they feel anything. This would allow the sensory mapping of the microchannels. This type of analysis is already conducted in deep brain stimulation surgeries where surgeons ask patients what they are feeling during the surgery.
• the microchannels could record patient induced motor axon AP's allowing the motor mapping of the microchannels.
• This technology would close the prosthetic control loop allowing amputees to "feel" with their prosthetic limb.
• the On board' electronics can provide a simple direct connection between the present invention and any prosthetic device a user would desire.
• the invention can also be used as a research tool significantly advancing knowledge of nerves because this device will provide an ability to "map" nerves based on active sets of axons during movements and sensations.
• the success of this invention paves the way for a high degree of control, proprioception, tactile feedback, and other sensation in future neural prostheses, positively affecting amputees and individuals with disabilities.

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