Composite neural electrode and preparation method thereof, composite neural electrode combined with optical fiber and preparation method of composite neural electrode

Abstract

The invention provides a composite neural electrode and a preparation method thereof, and a composite neural electrode combined with an optical fiber and a preparation method thereof, and relates to the technical field of medical instruments, and the preparation method comprises the following steps: sequentially preparing a flexible substrate layer, a metal wiring layer and an insulating layer on a silicon substrate from bottom to top; photoresist is spin-coated on the insulating layer, then photoetching and developing processes are sequentially carried out, and a photoresist sacrificial layer is processed; depositing poly-p-xylylene on the photoresist sacrificial layer, and performing spin coating of photoresist, photoetching, developing and reactive ion etching to manufacture a poly-p-xylylene sleeve; releasing the electrode formed in the above step from the silicon substrate; the photoresist sacrificial layer on the electrode is removed, a cavity is formed, and the shape and the size of the cavity are matched with the shape and the size of a refined optical fiber which is used for being assembled with the cavity and is subjected to partial cladding removal.

Description

Technical Field

[0001] This application relates to the technical field of medical devices. Specifically, it relates to a composite nerve electrode and its preparation method, as well as a composite nerve electrode combined with an optical fiber and its preparation method. Background Art

[0002] The brain is a complex electronic system. In its research, electrodes are one of the most core research tools, which can directly reflect the discharge of neurons by detecting the electrical activities of the nervous system. However, in order to study the specific connection relationships in the network, simply recording the signals in the network is insufficient. At this time, a means of stimulating nerve tissue is required, and it is convenient to be integrated into the electrode to achieve real-time stimulation and detection.

[0003] Currently, the commonly used stimulation method is electrical stimulation. However, its many disadvantages have hindered its application in detection-stimulation composite electrodes: 1. When the electrical stimulation electrode works, it will apply a bias voltage far exceeding the amplitude of neuron discharge to the recording electrodes around it, which makes it very difficult to perform electrical recording while performing electrical stimulation; 2. Electrical stimulation is non-selective, and all nerve cells around the stimulation electrode will be stimulated, resulting in low regulation accuracy; 3. The safety of electrical stimulation is average. Since it directly injects charges near neurons, long-term stimulation may cause charge accumulation and damage cells.

[0004] Therefore, optical stimulation combined with optogenetic technology has gradually become a hot research direction. This is because it enables the use of different physical quantities for stimulation and recording, and makes it possible to measure and record at the same time and at the same position; second, combined with gene editing technology, optogenetic stimulation can support selective stimulation of different subtypes of nerve cells, improving the accuracy of nervous system regulation; third, optogenetic stimulation uses light to activate ion channels on the neuron cell membrane, and in principle, there is no risk caused by injecting charges. It is safer and more stable than electrical stimulation.

[0005] In the prior art, the integrated detection-stimulation composite electrode integrating a light guiding structure and a nerve electrode is a key requirement for basic research. Currently, the integration methods include optical fibers, planar waveguides, micro light-emitting diodes (LEDs), etc., and different structures have different characteristics.

[0006] In the prior art, the defects of integrated optical fibers are: large size, large damage to brain tissue, easy to cause more serious immune reactions, and not conducive to long-term use; the defects of integrated planar waveguides are: complex process, must be manufactured on a specific substrate, the overall electrode is also large in size, and is easy to cause greater brain damage; the defects of in-situ integrated micro-LEDs are: small size after integration, but the light emission is not focused, the stimulation accuracy is low, and high-frequency stimulation will cause the LED to heat up and damage brain tissue. Summary of the Invention

[0007] The objective of the present application is to provide a composite nerve electrode, a preparation method thereof, a composite nerve electrode combined with an optical fiber, and a preparation method thereof, aiming to solve the defects in the related art, such as large size, great damage to brain tissue, complex process, unfocused light emission, and low stimulation accuracy.

[0008] Additional aspects and advantages of the present application will be partly elaborated in the following description, and partly will become apparent from the description, or can be learned through the practice of the present application.

[0009] According to the first aspect of the present application, a preparation method of a composite nerve electrode is provided, including the following steps:

[0010] Prepare a flexible substrate layer, a metal wiring layer, and an insulating layer on a silicon substrate from bottom to top;

[0011] Spin coat photoresist on the insulating layer, and then perform photolithography and development processes in sequence to process a photoresist sacrificial layer;

[0012] Deposit parylene on the photoresist sacrificial layer, and perform spin coating of photoresist, photolithography, development, and reactive ion etching to fabricate a parylene sleeve;

[0013] Release the electrode formed by the above steps from the silicon substrate;

[0014] Remove the photoresist sacrificial layer on the electrode to form a cavity, and the shape and size of the cavity are adapted to the shape and size of the refined optical fiber of the removed partial cladding used for assembling with the cavity.

[0015] In an exemplary embodiment of the present application, the step of removing the photoresist sacrificial layer on the electrode to form a cavity includes:

[0016] Immerse the released electrode in a stripping solution to completely dissolve the photoresist sacrificial layer and form the cavity.

[0017] According to the second aspect of the present application, a preparation method of a composite nerve electrode combined with an optical fiber is provided, including the following steps:

[0018] Prepare a refined optical fiber;

[0019] Prepare a flexible substrate layer, a metal wiring layer, and an insulating layer on a silicon substrate from bottom to top;

[0020] Spin coat photoresist on the insulating layer, and then perform photolithography and development processes in sequence to process a photoresist sacrificial layer;

[0021] Deposit parylene on the photoresist sacrificial layer, and perform spin coating of photoresist, photolithography, development, and reactive ion etching to fabricate a parylene sleeve. After etching is completed, do not remove the residual glue;

[0022] releasing the electrode formed by the above steps from the silicon substrate;

[0023] Removing the residual glue and the sacrificial photoresist layer on the electrode to form a cavity, the shape and size of the cavity being adapted to the shape and size of the front end of the thinned optical fiber;

[0024] Inserting the thinned optical fiber into the cavity completes the assembly.

[0025] In an exemplary embodiment of the present application, the step of preparing a thinned optical fiber comprises:

[0026] The thinned optical fiber is formed by removing part of the cladding at the front end of the bare fiber using an etching process.

[0027] In an exemplary embodiment of the present application, the etching process is a hydrofluoric acid etching process; the cladding at the front end of the bare fiber is corroded to a thickness of 50-60 microns.

[0028] According to a third aspect of the present application, a composite neural electrode is provided, characterized in that it is prepared by any one of the preparation methods of the composite neural electrode in the first aspect.

[0029] According to the fourth aspect of the present application, a composite neural electrode combined with optical fiber is provided, characterized in that it comprises a composite neural electrode disclosed in the third aspect of the present application and a bare fiber, wherein part of the cladding at the front end of the bare fiber is removed to form a thinned optical fiber, and the end of the bare fiber is coupled to a light source capable of emitting an optical signal; the composite neural electrode combined with optical fiber is prepared by any one of the preparation methods of the composite neural electrode combined with optical fiber disclosed in the second aspect of the present application.

[0030] In an exemplary embodiment of the present application, it also includes an adapter for connecting with an electrophysiological detection device, and an electrode fixing shell for installing a bare fiber, and the electrode fixing shell is assembled below the adapter.

[0031] In an exemplary embodiment of the present application, a wired connection is arranged between the bare fiber and the light source, an end of the bare fiber away from the thinning optical fiber is connected to a fiber optic interface, the light source is arranged as an optogenetic device, and the fiber optic interface and the optogenetic device are coupled and connected.

[0032] In an exemplary embodiment of the present application, the electrode fixing housing is configured as a wired fixing housing, and the wired fixing housing is provided with a through groove, an optical fiber card slot and an optical fiber interface fixing hole;

[0033] The through slot passes through the wired fixing housing, and the bare fiber can pass through the through slot;

[0034] The optical fiber card slot is provided on a side of the wired fixed housing facing the adapter, and can be communicated with the polyparaxylene sleeve, and the optical fiber card slot is adapted to the thinned optical fiber assembly;

[0035] The optical fiber interface fixing hole is arranged on a side of the wired fixing housing away from the adapter, and can be assembled and adapted with the optical fiber interface.

[0036] In an exemplary embodiment of the present application, the bare fiber and the light source are arranged to be wirelessly connected, and the light source includes a light source circuit board and a light source connector that can be assembled with the light source circuit board;

[0037] The light source circuit board is equipped with a SMD LED and a female connector; the female connector can be connected to the SMD LED circuit through the light source circuit board and control the SMD LED to emit a light signal;

[0038] The light source connector is provided with an optical fiber jack into which the bare fiber can be inserted. After the light source connector is assembled with the light source circuit board, the optical fiber jack is aligned with the SMD LED.

[0039] The exemplary embodiments of the present application may have some or all of the following beneficial effects:

[0040] A method for preparing a composite nerve electrode provided by an exemplary embodiment of the present application includes spin - coating a photoresist on an insulating layer, and then successively performing photolithography and development processes to process the photoresist sacrificial layer; then depositing parylene on the sacrificial layer, and performing spin - coating photoresist, photolithography, development, and reactive ion etching to fabricate a parylene sleeve; a bare fiber with a partially removed cladding is made into a refined optical fiber and can be inserted into the parylene sleeve. Since the refined optical fiber can have a good focusing effect and because a part of the cladding of the bare fiber is removed, the size of the composite nerve electrode is reduced, thereby reducing brain damage. Specifically, when fabricating the parylene sleeve, the sacrificial layer is used as a filler for the cavity. After depositing parylene on the sacrificial layer, then through the processes of spin - coating photoresist, photolithography, development, and reactive ion, a parylene sleeve can be fabricated. Then, by removing the sacrificial layer, a cavity that can accommodate the refined optical fiber can be obtained. When fabricating the refined optical fiber, a part of the cladding of the bare fiber is removed. It should be noted that the cladding of the bare fiber cannot be completely removed. The purpose is to effectively reduce the diameter of the bare fiber and ensure the light - guiding ability of the refined optical fiber after removing a part of the cladding. Since the size of the cavity is adapted to the size of the refined optical fiber, when the refined optical fiber is inserted into the cavity, the parylene sleeve can not only prevent the refined optical fiber from being short - circuited due to direct contact with the liquid in the organism, but also provide good stability for the refined optical fiber. Therefore, it is not difficult to see that the manufacturing process of the above - mentioned composite nerve electrode is simple and easy to operate. At the same time, the refined optical fiber used has a good focusing effect, and by reducing the size of the bare fiber, the size of the composite nerve electrode is effectively reduced, thereby reducing brain damage.

[0041] It should be understood that the above general description and the following detailed description are only exemplary and explanatory, and cannot limit the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] The accompanying drawings herein are incorporated into the specification and constitute a part of this specification, showing embodiments consistent with the present application, and are used together with the specification to explain the principles of the present application. Obviously, the drawings in the following description are only some embodiments of the present application. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0043] Figure 1 The bottom view of the composite nerve electrode provided by the present invention;

[0044] Figure 2 The enlarged bottom view of the tip part of the composite nerve electrode provided by the present invention;

[0045] Figure 3 The hierarchical structure diagram of the metal wiring of the composite nerve electrode provided by the present invention;

[0046] Figure 4 Top view of the composite nerve electrode provided by the present invention;

[0047] Figure 5 Partial schematic diagram of the tip part of the composite nerve electrode provided by the present invention;

[0048] Figure 6 Overall schematic diagram of the circuit adapter board of the composite nerve electrode provided by the present invention;

[0049] Figure 7 Top view of the circuit adapter board of the composite nerve electrode provided by the present invention;

[0050] Figure 8 Side view of the circuit adapter board of the composite nerve electrode provided by the present invention;

[0051] Figure 9 Schematic diagram of the connection method between the composite nerve electrode provided by the invention and the circuit adapter board;

[0052] Figure 10 Overall schematic diagram of the top of the wired fixed housing in the composite nerve electrode combined with an optical fiber provided by the present invention;

[0053] Figure 11 Overall schematic diagram of the bottom of the wired fixed housing in the composite nerve electrode combined with an optical fiber provided by the present invention;

[0054] Figure 12 Assembly schematic diagram of the composite nerve electrode combined with an optical fiber provided by the present invention with the wired fixed housing, bare fiber, and fiber optic interface;

[0055] Figure 13 Overall schematic diagram of the top of the wireless fixed housing in the composite nerve electrode combined with an optical fiber provided by the present invention;

[0056] Figure 14 Overall schematic diagram of the bottom of the wireless fixed housing in the composite nerve electrode combined with an optical fiber provided by the present invention;

[0057] Figure 15 Overall schematic diagram of the light source and fiber optic connector in the composite nerve electrode combined with an optical fiber provided by the present invention;

[0058] Figure 16 Assembly schematic diagram between the light source, fiber optic connector, and wireless fixed housing in the composite nerve electrode combined with an optical fiber provided by the present invention;

[0059] Figure 17 Assembly schematic diagram of the composite nerve electrode combined with an optical fiber provided by the present invention with the wireless fixed housing and bare fiber;

[0060] Figure 18The architecture diagram of the closed-loop feedback regulation system in the case of wired connection provided by the present invention;

[0061] Figure 19 The architecture diagram of the closed-loop feedback regulation system in the case of wireless connection provided by the present invention.

[0062] Description of the reference numerals in the drawings:

[0063] 1. Flexible substrate layer; 2. Metal wiring layer; 3. Electrical detection site; 4. Lead-out pad; 5. Insulating layer; 6. Parylene sleeve; 7. Cavity; 8. Titanium layer; 9. Platinum layer; 10. Gold layer; 11. Omnetics interface jack; 12. Omnetics interface; 13. Circuit adapter board; 14. Positioning holes on the PCB; 15. FFC pad; 16. Anisotropic conductive film; 17. Wired fixed housing; 18. Through groove; 19. Fiber optic interface fixing hole; 20. Positioning post; 21. Fiber optic card slot; 22. Fiber optic interface; 23. Bare fiber; 24. Refined fiber optic; 25. Wireless fixed housing; 26. Light source fixing slot; 27. Light source circuit board; 28. Female header interface; 29. SMD LED; 30. Fiber optic connector; 31. Fiber optic jack; 32. Wired detection architecture; 33. Wired stimulation architecture; 34. Computer; 35. Wireless detection architecture; 36. Wireless stimulation architecture. Detailed implementation manners

[0064] Now, the exemplary embodiments will be described more fully with reference to the accompanying drawings. However, the exemplary embodiments can be implemented in various forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this application will be thorough and complete, and will fully convey the concept of the exemplary embodiments to those skilled in the art. The same reference numerals in the drawings denote the same or similar structures, and thus their detailed descriptions will be omitted. In addition, the drawings are only schematic illustrations of the present application and are not necessarily drawn to scale.

[0065] Although relative terms such as "upper" and "lower" are used in this specification to describe the relative relationship of one component of the icon to another component, these terms are used in this specification only for convenience, for example, according to the directions in the examples of the drawings. It can be understood that if the device of the icon is turned upside down, the component described as "upper" will become the component described as "lower". When a structure is "on" another structure, it may mean that a structure is integrally formed on another structure, or that a structure is "directly" disposed on another structure, or that a structure is "indirectly" disposed on another structure through another structure.

[0066] The terms "a", "an", "the" and "at least one" are used to denote the presence of one or more elements / components / etc.; the terms "comprising" and "having" are used to mean an open inclusion and refer to the possibility of the existence of additional elements / components / etc. in addition to the listed elements / components / etc.; the terms "first", "second" are used only as labels and do not limit the quantity of their objects.

[0067] Example 1

[0068] Referring Figures 1 to 5 As described above, in an embodiment of the present application, a composite nerve electrode is provided, which includes a flexible substrate layer 1, a metal wiring layer 2, an electrical detection site 3, an extraction pad 4, an insulating layer 5, a parylene sleeve 6 and a cavity 7.

[0069] The flexible substrate layer 1 is the first layer of the entire electrode and is made of polyimide. It has good biocompatibility, a thickness of 4 microns, serves as the bottom insulation, and has good adhesion to the metal wiring layer 2 thereon. At the tip and the tail of the composite nerve electrode, the shapes of the electrical detection site 3 and the extraction pad 4 are etched respectively, and the metal wiring layer 2 at these positions is exposed to receive the neuroelectrophysiological signals.

[0070] The metal wiring layer 2 is the second layer of the entire composite nerve electrode, with an overall thickness of 100 - 130 nanometers, and serves to connect the electrical detection sites 3 and the extraction pads 4 of each channel in the composite nerve electrode in a one-to-one correspondence. The metal used in the metal wiring layer 2 has a three-layer structure, which is a titanium layer 8, a platinum layer 9, and a gold layer 10 from bottom to top, with thicknesses of about 10 nanometers, about 50 nanometers, and about 50 nanometers respectively. The titanium layer 8 serves as an adhesion layer for the platinum layer 9. At the positions where the metal is exposed, such as the electrical detection site 3 and the extraction pad 4, the titanium layer 8 is selectively removed to enable the platinum layer 9 to be the metal actually in contact with the nerve tissue, because the interface of the platinum layer 9 has a lower electrochemical impedance and can have a higher signal-to-noise ratio when collecting electrophysiological signals. The topmost gold layer 10 serves to reduce the resistance of the metal wiring layer 2 itself, and at the same time, its good ductility enables the metal wiring layer 2 to still be electrically conductive under certain bending conditions.

[0071] The insulating layer 5 is the third layer of the entire electrode and is made of parylene, with a thickness of about 2 microns. The insulating layer 5 completely covers the metal wiring layer 2 to prevent the metal wiring layer 2 from being short-circuited due to contact with the liquid in the organism. Parylene has good biological safety and reliable performance.

[0072] The parylene sleeve 6 is the fourth layer of the entire electrode, with a thickness of 5-6 microns. The cavity 7 formed inside it allows the refined optical fiber 24 to be inserted and assembled. The parylene sleeve 6 itself is a transparent material, ensuring that optical signals can smoothly enter the interior of nerve tissue.

[0073] Referring Figure 6 , Figure 7 and Figure 8 As shown, in the embodiment of the present application, the composite nerve electrode further includes a converter. The adapter is used to transfer the cable on the composite nerve electrode to a general electrical interface on the detection device. The adapter includes an interface jack, an interface, a circuit transfer board 13, a positioning hole 14, and a cable pad 15. In the present application, the interface jack is set as an Omnetics interface jack 11, and the interface is set as an Omnetics interface 12. Of course, this is only for illustrative purposes and not restrictive.

[0074] Specifically, one end of the adapter is an Omnetics interface 12, which is welded to the circuit transfer board 13. The Omnetics interface 12 is a general interface for various current nerve electrophysiological signal detection devices. Therefore, the adapter can be compatible with various nerve electrophysiological signal detection devices, and a single interface supports up to 32 electrical channels at most. The Omnetics interface jack 11 on it can achieve a very reliable connection with the Omnetics pin interface on the detection device. Of course, this is not restrictive.

[0075] The cable pad 15 is about 3 mm long and about 100 microns wide, with a total of 32, which is the same size as the lead pad 4 at the tail of the electrode. Therefore, it can be understood that both the lead pad 4 and the electrical detection site 3 should be 32.

[0076] Referring Figure 9 As shown, an anisotropic conductive film 16 is provided between the cable pad 15 and the lead pad 4. The anisotropic conductive film 16 can achieve electrical interconnection in the vertical direction under the action of heat and pressure, while remaining insulated in the horizontal direction. Therefore, one-to-one connection between each channel on the electrode and the circuit on the transfer board can be achieved. After the anisotropic conductive film 16 is fixed on the cable pad 15 of the transfer board, the lead pad 4 of the electrode and the cable pad 15 of the circuit transfer board 13 are aligned under a microscope, and finally a hot press is used to make them conduct electricity in the vertical direction.

[0077] Embodiment 2

[0078] Referring Figure 12As shown, in the embodiment of the present application, a composite neural electrode combined with an optical fiber is disclosed, including the composite neural electrode described in Example 1, and also including a bare fiber 23. The bare fiber 23 is set to be a quartz bare fiber with a diameter of 125 microns, which is of course not restrictive. A portion of the cladding is removed from the front end of the bare fiber 23 to form a thinned optical fiber 24. In the present application, the bare fiber 23 is clad to a diameter of 50 microns, which is of course not restrictive. It is worth noting that the cladding cannot be completely removed. The purpose is to retain the normal light-guiding ability of the optical fiber. Removing part of the cladding effectively reduces its size, thereby greatly reducing implant damage.

[0079] In the embodiment of the present application, the bare fiber 23 can transmit optical signals, and the bare fiber 23 is coupled to a light source that can emit optical signals, and the thinned optical fiber 24 is implanted in a specific brain area of ​​the patient's brain, so that the optical signal can be transmitted to the specific brain area and the neural tissue in the specific brain area can be optically stimulated. In the present application, the bare fiber 23 and the light source can be wired, wirelessly connected, or set to be wirelessly connected.

[0080] Reference Figures 10 - 17 As shown, in the embodiment of the present application, it also includes an electrode fixing shell for fixing the bare fiber 23, and the electrode fixing shell is assembled and fixed with the adapter plate.

[0081] Further, when the bare fiber 23 and the light source are connected by wire, the electrode fixing housing is set as a wired fixing housing 17. When the bare fiber 23 and the light source are connected by wireless, the electrode fixing housing is set as a wireless fixing housing 25.

[0082] Reference Figure 10 , Figure 11 and Figure 12 As shown, when the bare fiber 23 is wired to the light source, the end of the bare fiber 23 away from the thinning fiber 24 is connected to the optical interface 22. The wired fixed housing 17 is manufactured in an integrated manner using a 3D printer, and is provided with a through groove 18, a fiber interface fixing hole 19, a positioning column 20, and a fiber card slot 21. The through groove 18 runs through the wired fixed housing 17, the fiber interface fixing hole 19 is provided on the side of the wired fixed housing 17 away from the circuit adapter board 13, and the fiber card slot 21 is provided on the side of the wired fixed housing 17 facing the circuit adapter board 13. The fiber card slot 21 can be connected to the polyparaxylene sleeve 6 after the wired fixed housing 17 and the circuit adapter board 13 are assembled. The positioning column 20 is an integral structure with the wired fixed housing 17 and is provided on the side facing the circuit adapter board 13.

[0083] The optical fiber interface fixing holes 19 on the wired fixing housing 17 serve to fix the optical fiber interface 22. The aperture of the optical fiber interface fixing holes 19 is slightly larger than the outer diameter of the optical fiber interface 22 by 0.5 mm. This allows the optical fiber interface 22 to adjust the front-back distance after being inserted into the optical fiber interface fixing holes 19. After adjustment to the appropriate position, medical-grade silicone is used here to fix it completely. To enable the bare fiber 23 to be inserted into the parylene sleeve 6 normally, the through groove 18 provides clearance for the bare fiber 23, allowing the bare fiber 23 to pass through smoothly.

[0084] Refer to Figure 7 and Figure 11 As shown, when the wired fixing housing 17 is installed with the adapter, the positioning posts 20 are inserted into the positioning holes 14. The positioning posts serve to position and connect the circuit adapter board 13. The diameter of the positioning posts 20 is slightly smaller than the diameter of the positioning holes 14 on the circuit adapter board 13 by about 0.5 mm. Such a structure allows the adapter board to be easily removed after being clamped, and after assembly, medical-grade silicone is used here to fix it completely.

[0085] Refer to Figure 5 and Figure 12 As shown, since the optical fiber interface 22 and the parylene sleeve 6 are not in the same plane, if the bare fiber 23 is directly inserted into the parylene sleeve 6, it will cause the entire bare fiber 23 to bend, thus potentially risking breakage or damage. Therefore, the bare fiber 23 is bent at the optical fiber slot 21 to be in the same plane as the parylene sleeve 6. The good toughness of the quartz optical fiber allows it to bend here without breaking.

[0086] During assembly, first pass the refined optical fiber 24 through the parylene sleeve 6, then connect the wired fixing housing 17 from the rear oblique direction, and at the same time complete the connection of the positioning posts 20 and the optical fiber interface fixing holes 19. After the connection is completed, medical-grade silicone is used to fix all components completely. Utilizing the rigidity of the refined optical fiber 24, the composite electrode can be directly implanted without auxiliary devices.

[0087] Refer to Figure 13 and Figure 14 As shown, when the connection between the bare fiber 23 and the light source is wireless, the wireless fixing housing 25 is provided with a through groove 18, a light source fixing groove 26, positioning posts 20, and an optical fiber slot 21; the light source fixing groove is connected to the through groove 18.

[0088] Among them, the functions of the through groove 18, the positioning posts 20, and the optical fiber slot 21 are the same as those of the wired fixing housing 17, and will not be elaborated here. In addition, the light source fixing groove 26 is a component for connecting with the light source circuit board 27 and the optical fiber connector 30. Similarly, each side is 0.5 mm away from the optical fiber connector 30 to facilitate assembly and adjustment. After adjustment is completed, medical-grade silicone is used to fix it completely.

[0089] Referring to Figure 15 As shown, in the embodiment of the present application, when the bare fiber 23 is wirelessly connected to the light source, the light source used is an LED light source. A female header interface 28 and surface-mounted LEDs 29 are provided on the light source circuit board 27, and a fiber optic jack 31 is provided on the fiber optic connector 30.

[0090] The surface-mounted LEDs 29 on the light source circuit board 27 are light sources for light stimulation, and LEDs of different colors can be selected to meet different optogenetic regulation preludes, such as blue, red, etc. In addition, a current-limiting resistor for protecting the LEDs (not shown for simplicity of illustration) and a female header interface 28 are also soldered on the light source circuit board 27. The female header interface 28 is used to connect to the control circuit to achieve blinking control of the surface-mounted LEDs 29, thereby controlling the surface-mounted LEDs 29 to emit optical signals.

[0091] Referring to Figure 15 and Figure 16 As shown, the fiber optic connector 30 is integrally fabricated using high-precision 3D printing. It is provided with a fiber optic jack 31 for connecting to the optical fiber, and its inner diameter is slightly larger than 125 microns. The light source circuit board 27 is nested inside the fiber optic connector 30, and the fiber optic jack 31 is aligned with the emission center of the surface-mounted LEDs 29 to improve the coupling efficiency between the optical fiber and the LED. The fiber optic connector 30 is nested in the light source fixing groove 26.

[0092] Referring to Figure 17 As shown, during assembly, after inserting a part of the diameter-refined optical fiber 24 into the parylene sleeve 6, the wireless fixing housing 25 is assembled from the obliquely rearward direction, and at the same time, the positioning post 20 and the fiber optic jack 31 are connected. After adjusting the position to be normal, it is completely fixed using medical-grade silicone.

[0093] Referring to Figure 18 As shown, in the embodiment of the present application, when the bare fiber 23 is wired to the light source, its feedback regulation architecture includes a wired detection architecture 32, a wired stimulation architecture 33, and a computer 34. The wired acquisition architecture 32 uses various electrophysiological acquisition devices commonly used in biological experiments and is connected to the circuit adapter board 13 through the Omnetics interface 12 thereon, and transmits the acquired signals to the computer 34 in a wired manner. The computer 34 has signal processing and analysis algorithms, and performs closed-loop feedback regulation through the wired stimulation architecture 33 when detecting specific signals in real time according to experimental requirements. The laser light source in the wired stimulation architecture 33 is wired to the fiber optic interface on the electrode through a fiber optic jumper.

[0094] Referring to Figure 19As shown, in the embodiment of the present application, when the bare fiber 23 is wirelessly connected to the light source, its feedback control architecture includes a wireless detection architecture 35, a wireless stimulation architecture 36, and a computer 34. The wireless acquisition architecture 35 includes a dedicated front-end amplification chip for electrophysiological signals developed by Intan, a microprocessor module, and a wireless communication module. Among them, the multi-channel electrode signals collected by the Omnetics interface 12 are used as the input of the Intan chip. After the chip amplifies and performs analog-to-digital conversion on the signals, the wireless communication module controlled by the microprocessor module transmits the signals to the computer 34 in real time. Similarly, there are signal processing and analysis algorithms on the computer 34. According to the experimental requirements, when specific signals are detected in real time, closed-loop feedback control is performed through the wireless stimulation architecture 36. The wireless stimulation architecture 36 receives the instructions sent by the computer 34 through the wireless communication module controlled by the microprocessor module, and uses the LED drive circuit controlled by the microprocessor to output voltage pulses to drive the flashing of the surface-mounted LED 29 on the light source circuit board 27 connected thereto.

[0095] Embodiment 3

[0096] In the embodiment of the present application, a method for preparing a composite nerve electrode is disclosed, which is used to prepare the composite nerve electrode in Embodiment 1, and includes the following steps:

[0097] A flexible substrate layer 1, a metal wiring layer 2, and an insulating layer 5 are sequentially prepared from bottom to top on the silicon substrate;

[0098] Photoresist is spin-coated on the insulating layer 5, and then lithography and development processes are sequentially performed to process the photoresist sacrificial layer;

[0099] Parylene is deposited on the photoresist sacrificial layer, and photoresist is spin-coated, lithography, development, and reactive ion etching are performed to fabricate a parylene sleeve 6;

[0100] The electrode formed by the above steps is released from the silicon substrate;

[0101] The photoresist sacrificial layer on the electrode is removed to form a cavity 7, and the shape and size of the cavity 7 are adapted to the shape and size of the refined optical fiber 24 of the removed partial cladding used for assembling with the cavity 7.

[0102] Specifically, in the present application, the silicon substrate is set as a silicon wafer, and 10 nanometers of titanium and 500 nanometers of aluminum are sequentially deposited on the silicon wafer by magnetron sputtering as the sacrificial layer for release;

[0103] A 4-micron-thick polyimide is prepared by spin coating;

[0104] On the polyimide layer, photoresist is spin-coated, and then lithography and development processes are sequentially performed to process the photoresist with the same shape as the designed flexible substrate layer 1, and the pattern is transferred to the polyimide layer through reactive ion etching;

[0105] Use acetone to remove the residual photoresist after etching, spin-coat the photoresist again, and then perform photolithography and development processes in sequence to process a photoresist with the same shape as the designed metal wiring 2;

[0106] Using the magnetron sputtering deposition method, deposit a 10-nanometer titanium layer 8, a 50-nanometer platinum layer 9, and a 50-nanometer gold layer 10 in sequence. After the deposition is completed, use acetone to dissolve and strip the photoresist to obtain a conductive pattern on the polyimide layer;

[0107] Chemically vapor-deposit parylene, and perform spin-coating of photoresist, photolithography, development, and reactive ion etching to fabricate an insulating layer 5 made of parylene. After the etching is completed, remove the residual photoresist;

[0108] Spin-coat the photoresist again, and then perform photolithography and development processes in sequence to process a photoresist sacrificial layer with the same shape as the cavity 7;

[0109] Chemically vapor-deposit parylene, and perform spin-coating of photoresist, photolithography, development, and reactive ion etching to fabricate a parylene sleeve 6. After the etching is completed, do not remove the residual glue.

[0110] Use the method of electrolytic aluminum to release the electrode from the silicon wafer.

[0111] Immerse the released electrode in the stripping solution to completely dissolve the residual photoresist and the photoresist sacrificial layer, forming a cavity 7.

[0112] Example 4

[0113] In the embodiment of the present application, a preparation method of a composite nerve electrode combined with an optical fiber is disclosed, which is used to prepare the composite nerve electrode combined with an optical fiber in Example 2. It includes the preparation method of the composite nerve electrode in Example 3, and also includes preparing a refined optical fiber 24 and inserting the refined optical fiber 24 into the cavity 7 to complete the assembly.

[0114] In the embodiment of the application, the steps for preparing the refined optical fiber 24 include using an etching process to remove a part of the cladding at the front end of the bare optical fiber 23 to form the refined optical fiber 24. Further, in the present application, the etching process adopted is a hydrofluoric acid etching process, and the cladding at the front end of the bare optical fiber 23 is etched to a diameter of 50-60 microns.

[0115] Those skilled in the art will readily conceive of other embodiments of the present application after considering the specification and practicing the embodiments of the present application. The present application is intended to cover any variations, uses, or adaptations of the present application, which follow the general principles of the present application and include known common general knowledge or conventional technical means in the technical field not claimed in the present application. The specification and the embodiments are only regarded as exemplary, and the true scope and spirit of the present application are pointed out by the appended claims.

Claims

1. A method for preparing a composite neural electrode, characterized in that: The following steps are involved: A flexible substrate layer, a metal wiring layer and an insulating layer are sequentially prepared from bottom to top on a silicon substrate; Spin-coating a photoresist on the insulating layer, and then sequentially performing photolithography and development processes to process the photoresist sacrificial layer; Depositing polyparaxylene on the photoresist sacrificial layer, and performing spin coating of photoresist, photolithography, development, and reactive ion etching to produce a polyparaxylene sleeve; releasing the electrode formed by the above steps from the silicon substrate; The photoresist sacrificial layer on the electrode is removed to form a cavity, the shape and size of the cavity being adapted to the shape and size of the thinned optical fiber with a portion of the cladding removed and used for assembly with the cavity.

2. The method for preparing the composite neural electrode according to claim 1, characterized in that: The step of removing the sacrificial photoresist layer on the electrode to form a cavity comprises: The released electrode is immersed in a degumming solution to completely dissolve the photolithography sacrificial layer to form the cavity.

3. A method for preparing a composite neural electrode combined with an optical fiber, characterized in that: The following steps are involved: preparing thinned optical fibers; A flexible substrate layer, a metal wiring layer and an insulating layer are sequentially prepared from bottom to top on a silicon substrate; Spin-coating a photoresist on the insulating layer, and then sequentially performing photolithography and development processes to process the photoresist sacrificial layer; Depositing polyparaxylene on the photoresist sacrificial layer, and performing spin coating of photoresist, photolithography, development, and reactive ion etching to produce a polyparaxylene sleeve, without removing residual glue after etching; releasing the electrode formed by the above steps from the silicon substrate; Removing the residual glue and the sacrificial photoresist layer on the electrode to form a cavity, the shape and size of the cavity being adapted to the shape and size of the front end of the thinned optical fiber; Inserting the thinned optical fiber into the cavity completes the assembly.

4. The method for preparing a composite neural electrode combined with an optical fiber according to claim 3, characterized in that: The step of preparing the thinned optical fiber comprises: The thinned optical fiber is formed by removing part of the cladding at the front end of the bare fiber using an etching process.

5. The method for preparing a composite neural electrode combined with an optical fiber according to claim 4, characterized in that: The etching process is a hydrofluoric acid etching process; the cladding at the front end of the bare fiber is corroded to a thickness of 50-60 microns.

6. A composite neural electrode, characterized in that: The composite neural electrode is prepared by the preparation method of claim 1 or 2.

7. A composite neural electrode combined with an optical fiber, characterized in that: It comprises a composite neural electrode and a bare fiber as described in claim 6, wherein part of the cladding at the front end of the bare fiber is removed to form a thinned optical fiber, and the end of the bare fiber is coupled to a light source capable of emitting an optical signal; the composite neural electrode combined with an optical fiber is prepared by the preparation method of a composite neural electrode combined with an optical fiber according to any one of claims 3-5.

8. The composite neural electrode combined with optical fiber according to claim 7, characterized in that: It also includes an adapter for connecting with an electrophysiological detection device, and an electrode fixing shell for installing a bare fiber, wherein the electrode fixing shell is assembled below the adapter.

9. The composite neural electrode combined with optical fiber according to claim 8, characterized in that: The bare fiber and the light source are wiredly connected, one end of the bare fiber away from the thinning fiber is connected with a fiber interface, the light source is an optogenetic device, and the fiber interface and the optogenetic device are coupled and connected.

10. The composite neural electrode combined with optical fiber according to claim 9, characterized in that: The electrode fixing housing is configured as a wired fixing housing, and the wired fixing housing is provided with a through groove, an optical fiber card slot and an optical fiber interface fixing hole; The through slot passes through the wired fixing housing, and the bare fiber can pass through the through slot; The optical fiber card slot is provided on a side of the wired fixed housing facing the adapter, and can be communicated with the polyparaxylene sleeve, and the optical fiber card slot is adapted to the thinned optical fiber assembly; The optical fiber interface fixing hole is arranged on a side of the wired fixing housing away from the adapter, and can be assembled and adapted with the optical fiber interface.

11. The composite neural electrode combined with optical fiber according to claim 8, characterized in that: The bare fiber and the light source are arranged to be wirelessly connected, and the light source comprises a light source circuit board and a light source connector that can be assembled with the light source circuit board; The light source circuit board is equipped with a SMD LED and a female connector; the female connector can be connected to the SMD LED circuit through the light source circuit board and control the SMD LED to emit a light signal; The light source connector is provided with an optical fiber jack into which the bare fiber can be inserted. After the light source connector is assembled with the light source circuit board, the optical fiber jack is aligned with the SMD LED.

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