Composite nerve electrode and method of making same, composite nerve electrode incorporating an optical fiber and method of making same

Abstract

The application provides a composite nerve electrode and a preparation method thereof, and a composite nerve electrode combined with an optical fiber and a preparation method thereof, and relates to the technical field of medical devices, and comprises the following steps: sequentially preparing a flexible substrate layer, a metal wiring layer and an insulating layer from bottom to top on a silicon base; spin-coating photoresist on the insulating layer, and then sequentially performing photoetching and developing processes to process the photoresist sacrificial layer; depositing parylene on the photoresist sacrificial layer, and performing spin-coating photoresist, photoetching, developing and reactive ion etching to manufacture a parylene sleeve; releasing the electrode formed by the above steps from the silicon base; removing the photoresist sacrificial layer on the electrode to form a cavity, and the shape and size of the cavity are matched with the shape and size of a refined optical fiber with a removed part of the cladding assembled with the cavity.

Description

Technical Field

[0001] This application relates to the field of medical device technology, and more specifically, to a composite neural electrode and its preparation method, and a composite neural electrode combined with optical fiber and its preparation method. Background Technology

[0002] The brain is a complex electronic system, and electrodes are one of the most crucial research tools in its study. They can directly reflect the firing of neurons by detecting the electrical activity of the nervous system. However, to study the specific connections within the network, simply recording the signals in the network is insufficient. A means to stimulate neural tissue that can be easily integrated into electrodes to achieve real-time stimulation and detection is needed.

[0003] Currently, the most commonly used stimulation method is electrical stimulation. However, its many disadvantages hinder its application in detection-stimulation composite electrodes: 1. When the electrical stimulation electrode is working, it applies a bias voltage to the recording electrode around it that is far greater than the amplitude of neuronal discharge, making it very difficult to perform electrical recording while stimulating; 2. Electrical stimulation is non-selective, and all nerve cells around the stimulation electrode will be stimulated, resulting in low modulation precision; 3. Electrical stimulation is generally not safe, as it directly injects charges into the vicinity of neurons, and prolonged stimulation may lead to charge accumulation and cell damage.

[0004] Therefore, optical stimulation combined with optogenetics has gradually become a hot research area. This is because it allows for the use of different physical quantities for stimulation and recording, while simultaneously enabling measurement and recording at the same location. Second, combined with gene editing technology, optogenetic stimulation can support selective stimulation of different neuronal cell subtypes, improving the precision of nervous system regulation. Third, optogenetic stimulation uses light to activate ion channels on neuronal cell membranes, theoretically eliminating the risks associated with injected charges. Compared to electrical stimulation, it is safer and more stable.

[0005] In existing technologies, the integration of light-guiding structures with neural electrodes to create detection-stimulation composite electrodes is a key area of ​​basic research demand. Current integration methods include optical fibers, planar waveguides, and micro-light-emitting diodes (LEDs), each with different characteristics.

[0006] The existing technologies have the following drawbacks: large size, greater damage to brain tissue, more severe immune response, and unsuitability for long-term use; integrated planar waveguides have the following drawbacks: complex process, must be manufactured on a specific substrate, the overall electrode is also large in size, and more likely to cause greater brain damage; in-situ integrated microLEDs have the following drawbacks: small size after integration, but unfocused light emission, low stimulation accuracy, and high-frequency stimulation can cause the LED to heat up and damage brain tissue. Summary of the Invention

[0007] The purpose of this application is to provide a composite neural electrode and its preparation method, and a composite neural electrode combined with optical fiber and its preparation method, in order to solve the defects of related technologies such as large size, great damage to brain tissue, complex process, unfocused light emission, and low stimulation accuracy.

[0008] Additional aspects and advantages of this application will be set forth in part in the description which follows, and in part will be obvious from the description or may be learned by practice of this application.

[0009] According to a first aspect of this application, a method for preparing a composite neural electrode is provided, comprising the following steps:

[0010] A flexible substrate layer, a metal wiring layer, and an insulating layer are sequentially fabricated on a silicon substrate from bottom to top.

[0011] Photoresist is spin-coated onto the insulating layer, and then photolithography and development processes are performed sequentially to process the photoresist sacrificial layer.

[0012] Parylene is deposited on the photoresist sacrificial layer, and spin-coating of photoresist, photolithography, development, and reactive ion etching are performed to fabricate a parylene sleeve.

[0013] The electrode formed by the above steps is released from the silicon substrate;

[0014] The photoresist sacrificial layer on the electrode is removed to form a cavity, the shape and size of which are adapted to the shape and size of the thinned optical fiber with the cladding removed for assembly with the cavity.

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

[0016] The released electrode is immersed in a resist remover to completely dissolve the photolithographic sacrificial layer, forming the cavity.

[0017] According to a second aspect of this application, a method for preparing a composite neural electrode incorporating optical fibers is provided, comprising the following steps:

[0018] Fabrication of thinned optical fibers;

[0019] A flexible substrate layer, a metal wiring layer, and an insulating layer are sequentially fabricated on a silicon substrate from bottom to top.

[0020] Photoresist is spin-coated onto the insulating layer, and then photolithography and development processes are performed sequentially to process the photoresist sacrificial layer.

[0021] Parylene is deposited on the photoresist sacrificial layer, and spin-coating photoresist, photolithography, development, and reactive ion etching are performed to fabricate a parylene sleeve. After etching, the residual adhesive is not removed.

[0022] The electrode formed by the above steps is released from the silicon substrate;

[0023] Remove the residual adhesive and photoresist sacrificial layer on the electrode to form a cavity, the shape and size of which are adapted to the shape and size of the thinned fiber tip.

[0024] The thinned optical fiber is inserted into the cavity to complete the assembly.

[0025] In one exemplary embodiment of this application, the step of preparing the thinned optical fiber includes:

[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 one exemplary embodiment of this application, the etching process is a hydrofluoric acid etching process; the cladding at the front end of the bare fiber is etched to a thickness of 50-60 micrometers.

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

[0029] According to a fourth aspect of this application, a composite neural electrode incorporating an optical fiber is provided, characterized in that it comprises a composite neural electrode disclosed in a third aspect of this application and a bare fiber, wherein a portion of the cladding at the front end of the bare fiber is partially removed to form a thinned optical fiber, and a light source capable of emitting optical signals is coupled to the end of the bare fiber; the composite neural electrode incorporating an optical fiber is prepared by any of the methods for preparing a composite neural electrode incorporating an optical fiber disclosed in a second aspect of this application.

[0030] In one exemplary embodiment of this application, the device further includes an adapter for connecting to an electrophysiological testing device, and an electrode mounting housing for mounting bare fibers, the electrode mounting housing being assembled below the adapter.

[0031] In one exemplary embodiment of this application, the bare fiber and the light source are connected by a wire, the end of the bare fiber away from the thinned optical fiber is connected to an optical fiber interface, the light source is configured as an optogenetic device, and the optical fiber interface and the optogenetic device are coupled together.

[0032] In one exemplary embodiment of this 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 slot and an optical fiber interface fixing hole;

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

[0034] The fiber optic slot is located on the side of the wired fixed housing facing the adapter and can communicate with the parylene sleeve. The fiber optic slot is assembled and adapted with the thinned fiber optic cable.

[0035] The fiber optic interface mounting hole is located on the side of the wired mounting housing opposite to the adapter, and can be assembled and adapted with the fiber optic interface.

[0036] In one exemplary embodiment of this application, the bare fiber is wirelessly connected to the light source, 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 surface-mount LEDs and a female connector; the female connector can conduct through the light source circuit board to the surface-mount LED circuit and control the surface-mount LED to emit light signals;

[0038] The light source connector is provided with an optical fiber jack for inserting the bare fiber. After the light source connector is assembled with the light source circuit board, the optical fiber jack is aligned with the surface-mount LED.

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

[0040] The method for fabricating a composite neural electrode provided in the exemplary embodiments of this application involves spin-coating photoresist onto an insulating layer, followed by photolithography and development processes to fabricate a photoresist sacrificial layer. Next, parylene is deposited on the sacrificial layer, and spin-coating photoresist, photolithography, development, and reactive ion etching are performed to create a parylene sleeve. A partially clad bare fiber is then thinned and inserted into the parylene sleeve. Because the thinned fiber provides good focusing, and because the partial cladding of the bare fiber is removed, the size of the composite neural electrode is reduced, thereby reducing brain damage. Specifically, in fabricating the parylene sleeve, a sacrificial layer is used as the cavity filler. After depositing parylene on the sacrificial layer, a parylene sleeve is fabricated through spin-coating photoresist, photolithography, development, and reactive ion etching. The sacrificial layer is then removed to obtain a cavity capable of accommodating the thinned fiber. When fabricating the thinned optical fiber, part of the cladding of the bare fiber is removed. It's important to note that the cladding cannot be completely removed; this is to effectively reduce the diameter of the bare fiber while maintaining the light-guiding capability of the thinned fiber after partial cladding removal. Because the cavity size is matched to the size of the thinned optical fiber, when the thinned fiber is inserted into the cavity, the parylene sleeve not only prevents direct contact and short-circuiting between the thinned fiber and the fluid in the biological body, but also provides good stability for the thinned fiber. Therefore, it is easy to see that the fabrication process of the above-mentioned composite neural electrode is simple and easy to operate. Furthermore, the thinned optical fiber used has good focusing effect, and by reducing the size of the bare fiber, the size of the composite neural electrode is effectively reduced, thereby reducing brain injury.

[0041] It should be understood that the above general description and the following detailed description are exemplary and explanatory only, and do not limit this application. Attached Figure Description

[0042] The accompanying drawings, which are incorporated in and form part of this specification, illustrate embodiments consistent with this application and, together with the description, serve to explain the principles of this application. It is obvious that the drawings described below are merely some embodiments of this application, and those skilled in the art can obtain other drawings based on these drawings without any inventive effort.

[0043] Figure 1 Bottom view of the composite neural electrode provided by the present invention;

[0044] Figure 2 Enlarged bottom view of the tip portion of the composite neural electrode provided by the present invention;

[0045] Figure 3 A layered structure diagram of the composite neural electrode metal wiring provided by the present invention;

[0046] Figure 4 A top view of the composite neural electrode provided by the present invention;

[0047] Figure 5 A partial schematic diagram of the needle tip portion of the composite neural electrode provided by the present invention;

[0048] Figure 6 A schematic diagram of the circuit adapter board for the composite nerve electrode provided by the present invention.

[0049] Figure 7 A top view of the circuit adapter board for the composite neural electrode provided by the present invention;

[0050] Figure 8 A side view of the circuit adapter board for the composite neural electrode provided by the present invention;

[0051] Figure 9 A schematic diagram of the method for connecting the composite neural electrode to the circuit adapter board provided for the invention;

[0052] Figure 10 A schematic diagram of the top of the wired fixing shell of the composite neural electrode combined with optical fiber provided by the present invention.

[0053] Figure 11 A schematic diagram of the bottom of the wired fixing shell of the composite neural electrode combined with optical fiber provided by the present invention;

[0054] Figure 12 A schematic diagram of the assembly of the composite neural electrode with optical fiber provided by the present invention, including the wired fixing shell, bare fiber, and optical fiber interface;

[0055] Figure 13 A schematic diagram of the top of the wireless fixing shell in the composite neural electrode combined with optical fiber provided by the present invention;

[0056] Figure 14 A schematic diagram of the bottom of the wireless fixing shell in the composite neural electrode combined with optical fiber provided by the present invention;

[0057] Figure 15 A schematic diagram of the light source and fiber optic connector in the composite neural electrode combined with optical fiber provided by the present invention.

[0058] Figure 16 A schematic diagram illustrating the assembly of the light source, fiber optic connector, and wireless mounting housing in the composite neural electrode incorporating optical fibers provided by this invention.

[0059] Figure 17 This is a schematic diagram of the assembly of the composite neural electrode with optical fiber, wireless fixing shell, and bare fiber provided by the present invention.

[0060] Figure 18A diagram of a closed-loop feedback control system architecture in a wired configuration provided by the present invention;

[0061] Figure 19 This invention provides a closed-loop feedback control system architecture diagram for wireless applications.

[0062] Explanation of reference numerals in the attached figures:

[0063] 1. Flexible substrate layer; 2. Metal wiring layer; 3. Electrical detection points; 4. Lead-out pads; 5. Insulating layer; 6. Parylene sleeve; 7. Cavity; 8. Titanium layer; 9. Platinum layer; 10. Gold layer; 11. Omnetics interface socket; 12. Omnetics interface; 13. Circuit adapter board; 14. Positioning holes on PCB; 15. Ribbon cable pads; 16. Anisotropic conductive film; 17. Wired mounting shell; 18. Through slot; 19. Fiber optic interface fixing hole; 20. Positioning post; 21. Fiber optic slot; 22. Fiber optic interface; 23. Bare fiber; 24. Thinned fiber optic cable; 25. Wireless fixing shell; 26. Light source fixing slot; 27. Light source circuit board; 28. Female connector; 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

[0064] Exemplary embodiments will now be described more fully with reference to the accompanying drawings. However, these exemplary embodiments can be implemented in many 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 therefore their detailed descriptions will be omitted. Furthermore, the drawings are merely illustrative of this 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 an icon to another, these terms are used only for convenience, such as according to the orientation of the examples in the accompanying drawings. It is understood that if the device of the icon is flipped so that it is upside down, the component described as "upper" will become the component described as "lower." When a structure is "upper" of another structure, it may mean that the structure is integrally formed on the other structure, or that the structure is "directly" mounted on the other structure, or that the structure is "indirectly" mounted on the other structure through another structure.

[0066] The terms “a,” “one,” “the,” and “at least one” are used to indicate the existence of one or more elements / components / etc.; the terms “including” and “having” are used to indicate an open-ended inclusion and to mean that there may be other elements / components / etc. in addition to the listed elements / components / etc.; the terms “first” and “second” are used only as markers and are not a limitation on the number of objects.

[0067] Example 1

[0068] Reference Figures 1 to 5 The present application provides a composite neural electrode, comprising a flexible substrate layer 1, a metal wiring layer 2, an electrical detection site 3, a lead-out pad 4, an insulating layer 5, a parylene sleeve 6, and a cavity 7.

[0069] The flexible substrate layer 1, serving as the first layer of the entire electrode, is made of polyimide, exhibiting good biocompatibility. With a thickness of 4 micrometers, it acts as an insulator at the bottom and maintains good adhesion to the metal wiring layer 2. Electrical detection sites 3 and lead-out pads 4 are etched into the flexible substrate layer 1 at the tip and tail of the composite neural electrode, respectively, exposing the metal wiring layer 2 at these locations to receive neurophysiological signals.

[0070] The metal wiring layer 2 is the second layer of the entire composite neural electrode, with a total thickness of 100-130 nanometers. It serves to connect the electrical detection sites 3 and lead-out pads 4 of each channel in the composite neural electrode. The metal used in the metal wiring layer 2 has a three-layer structure: from bottom to top, it consists of a titanium layer 8, a platinum layer 9, and a gold layer 10, with thicknesses of approximately 10 nanometers, 50 nanometers, and 50 nanometers, respectively. The titanium layer 8 serves as an adhesion layer for the platinum layer 9. At locations where the metal is exposed, such as the electrical detection sites 3 and lead-out pads 4, the titanium layer 8 is selectively removed to allow the platinum layer 9 to become the metal actually in contact with the nerve tissue. This is because the platinum layer 9 has a lower electrochemical impedance, resulting in a higher signal-to-noise ratio when acquiring electrophysiological signals. The top gold layer 10 reduces the resistance of the metal wiring layer 2 itself, and its good ductility allows the metal wiring layer 2 to maintain electrical conductivity even under bending.

[0071] The insulating layer 5, the third layer of the entire electrode, is made of parylene and is approximately 2 micrometers thick. The insulating layer 5 completely covers the metal wiring layer 2, thus preventing it from coming into contact with biological fluids and causing a short circuit. Parylene has good biocompatibility and is safe and reliable.

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

[0073] Reference Figure 6 , Figure 7 and Figure 8 As shown in the embodiments of this application, the composite neural electrode further includes a converter for converting the ribbon cable on the composite neural electrode into an electrical interface common to detection devices. The converter includes an interface jack, an interface, a circuit adapter board 13, a positioning hole 14, and ribbon cable pads 15. In this application, the interface jack is set to an Omnetics interface jack 11, and the interface is set to an Omnetics interface 12. This is, of course, merely an illustrative example and not a limitation.

[0074] Specifically, one end of the adapter is an Omnetics interface 12, which is soldered onto the circuit adapter board 13. The Omnetics interface 12 is a universal interface for various neurophysiological signal detection devices, therefore the adapter is compatible with multiple neurophysiological signal detection devices, and a single interface supports up to 32 electrical channels. The Omnetics interface jack 11 on the adapter can achieve a very secure connection with the Omnetics pin interface on the detection device. Of course, this is not a limitation.

[0075] The ribbon cable pad 15 is about 3 mm long and about 100 micrometers wide, with a total of 32 pads. It is the same size as the lead-out pad 4 at the tail of the electrode. Therefore, it can be understood that both the lead-out pad 4 and the electrical detection point 3 should have 32 pads.

[0076] Reference Figure 9 As shown, an anisotropic conductive film 16 is disposed between the ribbon cable pad 15 and the lead-out 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, it can achieve a one-to-one correspondence between each channel on the electrode and the circuit on the adapter board. After the anisotropic conductive film 16 is fixed on the ribbon cable pad 15 of the adapter board, the lead-out pad 4 of the electrode and the ribbon cable pad 15 of the circuit adapter board 13 are aligned under a microscope, and finally, a hot press is used to achieve electrical conduction in the vertical direction between the two.

[0077] Example 2

[0078] Reference Figure 12As shown, this application discloses a composite neural electrode incorporating optical fiber, including the composite neural electrode described in Example 1, and also including bare fiber 23. Bare fiber 23 is a quartz bare fiber with a diameter of 125 micrometers, but this is not a limitation. Partial cladding is removed from the front end of bare fiber 23 to form a thinned optical fiber 24. In this application, the cladding of bare fiber 23 is removed to a diameter of 50 micrometers, but this is not a limitation. It is worth noting that the cladding cannot be completely removed; the purpose is to preserve the normal light-guiding capability of the optical fiber. Removing part of the cladding effectively reduces its size, thereby significantly reducing implantation damage.

[0079] In this embodiment, the bare fiber 23 can transmit optical signals. By coupling the bare fiber 23 to a light source capable of emitting optical signals, and simultaneously implanting a thinner optical fiber 24 into a specific brain region of the patient, optical signals can be transmitted to that specific brain region to perform optogenetic stimulation on the neural tissue within that region. In this application, the bare fiber 23 and the light source can be connected via wired or wireless means.

[0080] Reference Figures 10-17 As shown in the embodiment of this 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] Furthermore, when the bare fiber 23 is wired to the light source, the electrode fixing housing is configured as a wired fixing housing 17. When the bare fiber 23 is wirelessly connected to the light source, the electrode fixing housing is configured 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 furthest from the thinned fiber 24 is connected to the optical interface 22. The wired fixing housing 17 is manufactured as a single unit using a 3D printer and has a through slot 18, an optical fiber interface fixing hole 19, a positioning post 20, and an optical fiber slot 21. The through slot 18 passes through the wired fixing housing 17, the optical fiber interface fixing hole 19 is located on the side of the wired fixing housing 17 away from the circuit adapter plate 13, and the optical fiber slot 21 is located on the side of the wired fixing housing 17 facing the circuit adapter plate 13. After the wired fixing housing 17 and the circuit adapter plate 13 are assembled, the optical fiber slot 21 can communicate with the parylene sleeve 6. The positioning post 20 is an integral structure with the wired fixing housing 17 and is located on the side facing the circuit adapter plate 13.

[0083] The fiber optic interface fixing hole 19 on the wired mounting housing 17 serves to fix the fiber optic interface 22. The diameter of the fiber optic interface fixing hole 19 is slightly larger than the outer diameter of the fiber optic interface 22 by 0.5 mm. This allows the fiber optic interface 22 to be adjusted back and forth after being inserted into the fiber optic interface fixing hole 19. After proper adjustment, it is completely fixed here using medical silicone. In order to allow the bare fiber 23 to be properly inserted into the parylene sleeve 6, the through groove 18 acts as a guide for the bare fiber 23, allowing the bare fiber 23 to pass through smoothly.

[0084] Reference Figure 7 and Figure 11 As shown, when the wired mounting housing 17 is installed with the adapter, the positioning post 20 is inserted into the positioning hole 14. The positioning post serves to position and connect the circuit adapter board 13. The diameter of the positioning post 20 is slightly smaller than the diameter of the positioning hole 14 on the circuit adapter board 13 by about 0.5 mm. This structure allows the adapter board to be easily removed after it is locked in place, as the friction is not very high. After assembly, this part is completely fixed with medical silicone.

[0085] Reference Figure 5 and Figure 12 As shown, since the fiber optic 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 bare fiber 23 to bend as a whole, which may result in breakage or damage. Therefore, the bare fiber 23 is bent at the fiber optic slot 21 so that it is in the same plane as the parylene sleeve 6. The good toughness of the quartz fiber allows it to bend at this point without breaking.

[0086] During assembly, the thinned optical fiber 24 is first passed through the parylene sleeve 6, and then the wired fixing housing 17 is connected from the rear, simultaneously connecting the positioning post 20 and the optical fiber interface fixing hole 19. After connection, all components are completely fixed with medical silicone. Utilizing the rigidity of the thinned optical fiber 24, the composite electrode can be directly implanted without auxiliary devices.

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

[0088] The through slot 18, positioning post 20, and fiber optic slot 21 have the same functions as the wired fixing housing 17, and will not be described in detail here. In addition, the source fixing slot 26 is used to connect the components to the light source circuit board 27 and the fiber optic connector 30. Similarly, each side of the slot 26 is 0.5 mm away from the fiber optic connector 30 to facilitate assembly and adjustment. After adjustment, it is completely fixed with medical silicone.

[0089] Reference Figure 15 As shown in this embodiment, when the bare fiber 23 is wirelessly connected to the light source, the light source used is an LED light source. The light source circuit board 27 is provided with a female connector 28 and a surface-mount LED 29, and the fiber optic connector 30 is provided with a fiber optic jack 31.

[0090] The surface-mount LEDs 29 on the light source circuit board 27 serve as the light source for stimulation. Different colors of LEDs can be selected to meet different photodynamic regulation sequences, such as blue and red. In addition, the light source circuit board 27 also has a current-limiting resistor (not shown for simplicity) and a female connector 28 soldered on it to protect the LEDs. The female connector 28 is used to connect to the control circuit to control the blinking of the surface-mount LEDs 29, thereby controlling the surface-mount LEDs 29 to emit light signals.

[0091] Reference Figure 15 and Figure 16 As shown, the fiber optic connector 30 is made using high-precision 3D printing in one piece. It has a light jack 31 for connecting with the fiber optic cable. Its inner diameter is slightly larger than 125 micrometers. The light source circuit board 27 is nested inside the fiber optic connector 30. The light jack 31 is aligned with the light-emitting center of the patch LED 29 to improve the coupling efficiency between the fiber optic cable and the LED. The fiber optic connector 30 is nested in the light source fixing slot 26.

[0092] Reference Figure 17 As shown, during assembly, after inserting the thinned optical fiber 24 into the parylene sleeve 6, the wireless fixing housing 25 is assembled from the rear at an angle, simultaneously connecting the positioning post 20 and the optical jack 31. After adjusting the position to be normal, it is completely fixed with medical silicone.

[0093] Reference Figure 18 As shown in this embodiment, when the bare fiber 23 is wired to the light source, its feedback control 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 connects to the circuit adapter board 13 via its Omnetics interface 12 to transmit the acquired signals wiredly to the computer 34. The computer 34 has signal processing and analysis algorithms, and performs closed-loop feedback control through the wired stimulation architecture 33 when a specific signal is detected in real time, according to experimental requirements. The laser light source and the fiber optic interface on the electrode in the wired stimulation architecture 33 are wiredly connected via fiber optic patch cords.

[0094] Reference Figure 19As shown in this embodiment, 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 electrophysiological signal front-end amplification chip developed by Intan, a microprocessor module, and a wireless communication module. The multi-channel electrode signals acquired by the Omnetics interface 12 serve as the input to the Intan chip. The chip amplifies and converts the signals from analog to digital, and the wireless communication module controlled by the microprocessor module transmits them to the computer 34 in real time. Similarly, the computer 34 has signal processing and analysis algorithms. Based on experimental requirements, closed-loop feedback control is performed through the wireless stimulation architecture 36 when a specific signal is detected in real time. The wireless stimulation architecture 36 receives instructions from the computer 34 through the wireless communication module controlled by the microprocessor module and uses the output voltage pulses from the LED driver circuit controlled by the microprocessor to drive the flashing of the surface-mount LEDs 29 on the connected light source circuit board 27.

[0095] Example 3

[0096] In this application embodiment, a method for preparing a composite neural electrode is disclosed, which is used to prepare the composite neural electrode in Example 1, and includes the following steps:

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

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

[0099] Parylene is deposited on the photoresist sacrificial layer, and spin-coating photoresist, photolithography, development, and reactive ion etching are performed to fabricate the 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, the shape and size of which are adapted to the shape and size of the thinned optical fiber 24 with its cladding removed for assembly with the cavity 7.

[0102] Specifically, in this 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 using a magnetron sputtering method as sacrificial layers for release;

[0103] A 4-micrometer-thick layer of polyimide was prepared by spin coating;

[0104] Photoresist is spin-coated onto the polyimide layer, and then photolithography and development processes are performed sequentially to process photoresist with the same shape as the designed flexible substrate layer 1. The pattern is then transferred to the polyimide layer by reactive ion etching.

[0105] Use acetone to remove the photoresist residue from the etching process, spin-coate the photoresist again, and then perform photolithography and development processes in sequence to process photoresist with the same shape as the designed metal wiring 2.

[0106] Using magnetron sputtering deposition, a 10 nm titanium layer 8, a 50 nm platinum layer 9, and a 50 nm gold layer 10 were deposited sequentially. After deposition, acetone was used to dissolve and remove the photoresist to obtain conductive patterns on the polyimide layer.

[0107] Chemical vapor deposition of parylene is performed, followed by spin coating of photoresist, photolithography, development, and reactive ion etching to create an insulating layer 5 made of parylene. After etching, residual photoresist is removed.

[0108] Photoresist is spin-coated again, and then photolithography and development processes are performed sequentially to process the photoresist sacrificial layer, the shape of which is the same as that of cavity 7.

[0109] Parylene is deposited by chemical vapor deposition, followed by spin coating of photoresist, photolithography, development, and reactive ion etching to fabricate the parylene sleeve 6. The residual photoresist is not removed after etching.

[0110] The electrodes are removed from the silicon wafer by electrolytic aluminum.

[0111] The released electrode is immersed in a photoresist remover solution to completely dissolve the residual photoresist and the photoresist sacrificial layer, forming cavity 7.

[0112] Example 4

[0113] This application discloses a method for fabricating a composite neural electrode incorporating optical fibers, used to prepare the composite neural electrode incorporating optical fibers in Example 2. It includes the method for fabricating the composite neural electrode in Example 3, and further includes preparing a thinned optical fiber 24 and inserting the thinned optical fiber 24 into the cavity 7 to complete the assembly.

[0114] In the embodiments of the application, the steps for fabricating the thinned optical fiber 24 include using an etching process to remove a portion of the cladding at the front end of the bare fiber 23 to form the thinned optical fiber 24. Further, in this application, the etching process used is a hydrofluoric acid etching process, and the cladding at the front end of the bare fiber 23 is etched to a diameter of 50-60 micrometers.

[0115] Other embodiments of this application will readily conceive of by those skilled in the art upon consideration of the specification and practice of the embodiments thereof. This application is intended to cover any variations, uses, or adaptations of this application that follow the general principles of this application and include common knowledge or customary techniques in the art not claimed in this application. The specification and embodiments are to be considered exemplary only, and the true scope and spirit of this application are indicated by the appended claims.

Claims

1. A method for preparing a composite neural electrode, characterized in that, Includes the following steps: A flexible substrate layer, a metal wiring layer, and an insulating layer are sequentially fabricated on a silicon substrate from bottom to top. Photoresist is spin-coated onto the insulating layer, and then photolithography and development processes are performed sequentially to process the photoresist sacrificial layer. Parylene is deposited on the photoresist sacrificial layer, and spin-coating of photoresist, photolithography, development, and reactive ion etching are performed to fabricate a parylene sleeve. The electrode formed by the above steps is released from the silicon substrate; The photoresist sacrificial layer on the electrode is removed to form a cavity, the shape and size of which are adapted to the shape and size of the thinned optical fiber with the cladding removed 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 photoresist sacrificial layer on the electrode to form a cavity includes: The released electrode is immersed in a resist remover to completely dissolve the photolithographic sacrificial layer, forming the cavity.

3. A method for preparing a composite neural electrode incorporating optical fibers, characterized in that, Includes the following steps: Fabrication of thinned optical fibers; A flexible substrate layer, a metal wiring layer, and an insulating layer are sequentially fabricated on a silicon substrate from bottom to top. Photoresist is spin-coated onto the insulating layer, and then photolithography and development processes are performed sequentially to process the photoresist sacrificial layer. Parylene is deposited on the photoresist sacrificial layer, and spin-coating photoresist, photolithography, development, and reactive ion etching are performed to fabricate a parylene sleeve. After etching, the residual adhesive is not removed. The electrode formed by the above steps is released from the silicon substrate; Remove the residual adhesive and photoresist sacrificial layer on the electrode to form a cavity, the shape and size of which are adapted to the shape and size of the thinned fiber tip. The thinned optical fiber is inserted into the cavity to complete the assembly.

4. The method for preparing the composite neural electrode combined with optical fiber according to claim 3, characterized in that, The steps for preparing the thinned optical fiber include: 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 the composite neural electrode combined with 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 etched to a thickness of 50-60 micrometers.

6. A composite neural electrode, characterized in that, It is prepared by the method for preparing a composite neural electrode as described in claim 1 or 2.

7. A composite neural electrode incorporating optical fibers, characterized in that, The invention includes a composite neural electrode as described in claim 6 and a bare fiber, wherein a portion of the cladding at the front end of the bare fiber is removed to form a thinned optical fiber, and a light source capable of emitting optical signals is coupled to the end of the bare fiber; the composite neural electrode combined with the optical fiber is prepared by any one of the preparation methods of the composite neural electrode combined with the optical fiber according to claims 3-5.

8. A composite neural electrode incorporating optical fibers according to claim 7, characterized in that, It also includes an adapter for connecting to electrophysiological testing equipment, and an electrode mounting housing for mounting bare fibers, the electrode mounting housing being assembled below the adapter.

9. A composite neural electrode incorporating optical fibers according to claim 8, characterized in that, The bare fiber is connected to the light source via a wired connection. The end of the bare fiber away from the thinned optical fiber is connected to an optical fiber interface. The light source is configured as an optogenetic device. The optical fiber interface and the optogenetic device are coupled together.

10. A composite neural electrode incorporating optical fibers 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, a fiber optic slot and a fiber optic interface fixing hole; The through groove extends through the wired fixing housing, and the bare fiber can pass through the through groove; The fiber optic slot is located on the side of the wired fixed housing facing the adapter and can communicate with the parylene sleeve. The fiber optic slot is assembled and adapted with the thinned fiber optic cable. The fiber optic interface mounting hole is located on the side of the wired mounting housing opposite to the adapter, and can be assembled and adapted with the fiber optic interface.

11. A composite neural electrode incorporating optical fibers according to claim 8, characterized in that, The bare fiber is wirelessly connected to the light source, 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. The light source circuit board is equipped with surface-mount LEDs and a female connector; the female connector can conduct through the light source circuit board to the surface-mount LED circuit and control the surface-mount LED to emit light signals; The light source connector is provided with an optical fiber jack for inserting the bare fiber. After the light source connector is assembled with the light source circuit board, the optical fiber jack is aligned with the surface-mount LED.

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