Three-dimensional neural optoelectrode array with laser diode coupled optical waveguide structure

Abstract

The present invention discloses a three-dimensional neural photoelectrode array with a laser diode coupled optical waveguide structure. Most of the existing neural photoelectrodes use a chip mounter to directly couple the laser diode and the optical waveguide to achieve light stimulation. However, this optical coupling method makes the alignment of the laser diode difficult and the light loss is large. In addition, the laser diode protruding above the base of the electrode is not conducive to the three-dimensional integration of the neural photoelectrode through stacking. The present invention uses a gradient refractive index lens to focus and collimate the light beam of the laser diode, thereby improving the light coupling efficiency between it and the optical waveguide. In addition, by utilizing the in-plane electroplating bonding technology, the bonding of the laser diode without protrusions in the plane is achieved, which solves the key problem of three-dimensional stacking of neural photoelectrodes and provides a more accurate neural regulation tool for neuroscience research.

Description

Technical Field

[0001] The present invention belongs to the technical field of brain-computer interface, and specifically relates to a three-dimensional neural photoelectrode array for neural recording and light stimulation with a laser diode coupled optical waveguide structure and a preparation method thereof. Background Art

[0002] The brain-computer interface intelligent system is a bidirectional closed-loop system, which not only needs to complete the reading of brain information, but also needs to write computer instructions. Therefore, as a key device, neural microelectrodes usually need to have both recording (reading) and stimulation (writing) functions. Traditional Michigan electrodes or polymer electrodes are prone to damage neurons due to electrode polarization during electrical stimulation, and the spatial resolution of stimulation is low due to the dispersion characteristics of the current. At present, neural photostimulation based on optogenetics can effectively solve the above problems. Optogenetics introduces photosensitive proteins into specific cells to enable them to produce action potentials in response to light stimulation. Since the range of action of light and viruses can be limited to a very small area, this makes light stimulation have a higher spatial resolution than electrical stimulation. Therefore, conducting optoelectronic multifunctional integration research on neural microelectrode arrays is of great significance for achieving high temporal and spatial resolution and bidirectional closed-loop neural regulation.

[0003] In order to realize the optoelectronic multifunctional integration of neural microelectrode arrays, the commonly used method is to integrate the recording electrode with optical fiber, optical waveguide, LD (laser diode) / LED (light-emitting diode). Early studies mainly achieved light stimulation and electrical recording by attaching flexible neural microelectrodes to the surface of optical fibers. However, these methods will cause the optical fiber to be entangled, thereby restricting the free movement of behavioral animals. To avoid the use of optical fibers, the team of Professor JA Rogers of the University of Illinois in the United States transferred four laser-peeled sapphire-based micro-LEDs to flexible polymer probes, realizing the flexible injectable micro-LED light stimulation function [Kim T., McCall JG, Jung YH, et al. Injectable, cellular-scale optoelectronics with applications for wireless optogenetics. Science, 2013, 340 (6129): 211-6.]. Professor Huang Xian's team at Tianjin University integrated four blue light micro-LEDs into a flexible polymer probe, achieving simultaneous light / electrical stimulation of multiple brain regions and recording of electrophysiological signals and ion concentrations [Ling W., Yu J., Ma N., et al. Flexible Electronics and Materials for Synchronized Stimulation and Monitoring in Multi-Encephalic Regions [J]. Advanced Functional Materials, 2020: 2002644.]. Although the emergence of micro-LED neural photoelectrodes has improved the flexibility of light stimulation of neurons, the implantation of active devices also introduces noise and thermal damage near the recording channel. To this end, the K. Kampasi team at the Lawrence Livermore National Laboratory in the United States used a flexible polymer optical waveguide to introduce light emitted by the LD at the base of the electrode into the tip of the flexible probe for optical stimulation [Kampasi K., Alameda J., Sahota S., et al. Design and microfabrication strategies for thin-film, flexible optical neural implant [C]. Annual International Conference of the IEEE EMBC. IEEE, 2020: 4314-4317.]. The optical waveguide of the flexible neural microelectrode is composed of a Cytop (perfluoropolymer) cladding and an EpoCore (polymethyl methacrylate-based material) core layer, and optical stimulation can be achieved by coupling with the LD at the base.The LD-coupled optical waveguide structure can avoid thermal damage caused by the implantation of active devices, but this direct coupling causes large optical losses, and the LD protruding above the electrode base is not conducive to three-dimensional integration through stacking. The present invention uses a gradient refractive index lens to improve the optical coupling efficiency between the LD and the optical waveguide, and uses the in-plane bonding technology of the LD to solve the key problem of three-dimensional integration of neural photoelectrodes. The invention content of this patent can provide more accurate neural regulation tools for neuroscience research. Summary of the invention

[0004] The present invention aims to solve the shortcomings of low optical coupling efficiency and difficulty in achieving three-dimensional high-density integration of existing LD-coupled optical waveguide structure neural photoelectrodes. The gradient refractive index lens is used as the coupling medium between the LD and the optical waveguide to improve the optical coupling efficiency, and the LD's heterogeneous plane electroplating process is used to achieve three-dimensional high-density integration of photoelectrodes. Through three-dimensional multifunctional optoelectronic integration, the spatial detection range of the spatiotemporal resolution of neural photoelectrodes for neuron regulation is improved at the same time.

[0005] The three-dimensional neural photoelectrode array with a laser diode coupled optical waveguide structure includes a plurality of neural photoelectrodes stacked in sequence; each neural photoelectrode includes an electrode base, a plurality of neural probes arranged in sequence and spaced apart, and a light source module installed on the side of the electrode base, the number of which is the same as the number of neural probes. Each neural probe is provided with a recording electrode point and a light stimulation point; the light stimulation point is connected to the corresponding light source module through an optical waveguide.

[0006] The light source module includes an optical coupling base, an LD laser and a gradient refractive index lens. The optical coupling port is arranged at the end of the optical waveguide. The optical coupling base includes a single crystal silicon layer, an oxide layer and an LD power supply pad. The single crystal silicon layer and the oxide layer are stacked. Two LD power supply pads are arranged on the outer side of the single crystal silicon layer at intervals. Both LD power supply pads are connected to electroplating pads. An LD positioning groove and a lens positioning groove connected together are arranged on the outer side of the single crystal silicon layer. The LD positioning groove is located between the two electroplating pads.

[0007] The LD laser and the gradient refractive index lens are installed in the LD positioning groove and the lens positioning groove respectively. The light outlet of the LD laser is connected to one end of the gradient refractive index lens. The other end of the gradient refractive index lens is coupled to the corresponding optical waveguide through an optical coupling port. The two input pads on the LD laser are respectively facing the two side walls of the LD positioning groove, and a gap is left. The input pad located on the same side of the LD laser is connected to the gold nanoparticles formed by electroplating through the electroplating pad.

[0008] Preferably, the electrode base and the plurality of neural probes are an integrated structure, together forming a photoelectrode body; the photoelectrode body comprises a silicon substrate, a lower insulating layer, a recording conductive layer, an upper insulating layer and a light stimulation layer which are stacked in sequence from bottom to top. The recording conductive layer is located between the lower insulating layer and the upper insulating layer, and comprises n groups of electrically connected recording electrode points, recording wires and recording pad structures; each group of recording electrode points, recording wires and recording pad structures comprises one or more recording electrode points; the light stimulation layer comprises n optical waveguides. n is the number of neural probes on the neural photoelectrode. The n recording electrode points are respectively located at the tips of the n neural probes; one end of the n optical waveguides is respectively located at the tips of the n neural probes to form light stimulation points of the neural probes; the other ends of the n optical waveguides extend to the electrode base respectively and are coupled to the corresponding light source modules.

[0009] Preferably, each recording pad is led out through a recording flexible flat cable.

[0010] Preferably, the electrode base is provided with a plurality of slots on both sides of the edge; an optical coupling port is provided in the middle of each slot. The number of slots is consistent with the number of light source modules; a snap-on protrusion is provided at the end of the light source module; the snap-on protrusion of the light source module is plugged into the corresponding slot of the electrode base. The end of the lens positioning groove away from the LD positioning groove passes through the snap-on protrusion and is aligned with the corresponding end of the optical waveguide.

[0011] Preferably, the snap-in protrusion on the light source module is arranged at the end of the optical coupling base.

[0012] Preferably, the LD power supply pad is led out through a stimulation flexible flat cable.

[0013] Preferably, the LD laser has a rectangular parallelepiped structure with dimensions of 600×150×90 μm. 3 The two input pads of the LD laser are located on the two opposite sides of the LD laser with the largest areas.

[0014] Preferably, the cross section of the optical waveguide is rectangular, and the cross-sectional area is not greater than 10000 μm 2 .

[0015] Preferably, the gradient refractive index lens is cylindrical, and its diameter is 100-1000 μm.

[0016] The method for preparing the three-dimensional neural photoelectrode array with a laser diode coupled optical waveguide structure comprises the following steps:

[0017] S1: The neural probes, electrode bases and optical waveguides are fabricated using processes including photolithography, reactive ion etching, deep silicon etching, plasma enhanced chemical vapor deposition, sputtering, and ion beam etching.

[0018] S2: Prepare a light source module, use the LD positioning groove and the lens positioning groove to align and fix the LD laser and the gradient refractive index lens, and realize the optical coupling between the gradient refractive index lens and the optical waveguide through the alignment between the optical coupling base and the optical coupling port.

[0019] S3: Multiple neural optodes are stacked and fixed using an alignment mold to achieve three-dimensional integration of two-dimensional neural optodes.

[0020] Preferably, the specific process of step S1 is as follows:

[0021] (1) Use SOI silicon wafer as substrate, clean the silicon wafer thoroughly and dry it for later use.

[0022] (2) Use the PECVD system to deposit a dielectric layer on the front side of the SOI silicon wafer as the lower insulating layer.

[0023] (3) A metal layer is deposited on the lower insulating layer using a magnetron sputtering system as a recording conductive layer.

[0024] (4) Use a photolithography machine to pattern the photoresist spin-coated on the metal layer into a mask structure.

[0025] (5) Use an ion beam etching system to pattern the metal layer into recording electrode points, recording wires, and recording pad structures.

[0026] (6) A dielectric layer is deposited on the recording conductive layer as an upper insulating layer using a PECVD system.

[0027] (7) Use a photolithography machine to pattern the photoresist spin-coated on the upper insulating layer into a mask structure.

[0028] (8) Use a reactive ion etching system to open windows in the upper insulating layer to expose the recording electrode points and recording pad structure.

[0029] (9) Use a photolithography machine to pattern the photoresist spun on the upper insulating layer into a mask structure.

[0030] (10) Use a reactive ion etching system to remove the exposed upper insulating layer and lower insulating layer.

[0031] (11) Use a deep silicon etching system to remove the exposed top layer of silicon to form the front contour of the neural photoelectrode.

[0032] (12) Using a photolithography machine, the photosensitive polymer spin-coated on the upper insulating layer is patterned into an optical waveguide structure.

[0033] (13) Use a spin coater to spin coat a layer of photoresist on the front side of the SOI silicon wafer as a protective layer. Then, use a photolithography machine to pattern the photoresist spin-coated on the back side of the SOI into a mask structure.

[0034] (14) Use a reactive ion etching system to remove the exposed back oxide layer.

[0035] (15) Use a deep silicon etching system to remove the exposed underlying silicon.

[0036] (16) Use a reactive ion etching system to remove the exposed back buried oxide layer. Then, place the SOI in acetone to remove the resist.

[0037] Preferably, the specific process of step S2 is as follows:

[0038] (1) Using silicon oxide wafer as substrate, sputtering, photolithography patterning, ion beam etching and deep silicon etching are performed successively to realize micro-fabrication preparation of optical coupling base.

[0039] (2) Use a placement machine to place the LD laser into the LD positioning groove along the surface where the pad is located, so that its light outlet faces the gradient refractive index lens.

[0040] (3) Use an electroplating pen to electroplate gold nanoparticles between the input pad of the LD laser and the electroplating pad on the optical coupling base, so that the input pad of the LD laser is connected to the corresponding electroplating pad.

[0041] (4) Place the gradient refractive index lens into the positioning groove on the optical coupling base, align it with the LD laser, and then fix it.

[0042] (5) Use a hot press to attach the ACF conductive adhesive to the LD power supply pad.

[0043] (6) Use a hot press to bond the recording flexible cable to the LD power supply pad to achieve anisotropic conduction.

[0044] Preferably, the specific process of step S3 is as follows:

[0045] (1) Insert the optical coupling base into the optical coupling port of the electrode base and fix it with epoxy resin glue to achieve optical coupling between the gradient refractive index lens and the optical waveguide.

[0046] (2) Multiple neural photoelectrodes are placed in an alignment mold for stacking and alignment. Subsequently, adjacent neural photoelectrodes are fixed using instant adhesive.

[0047] (3) The stacked and fixed neural photoelectrode array is removed from the mold.

[0048] The present invention has the following beneficial effects:

[0049] 1. The present invention installs the input pads toward the left and right sides into the corresponding positioning grooves, and adopts the electroplating bonding process of the non-planar pads to achieve the conduction between the input pads of the LD laser and the electroplating pads on the optical coupling base which are perpendicular to each other, so that the LD laser is bonded and integrated inside the optical coupling base, overcoming the problem that the LD laser protrudes at the electrode base, making it difficult to stack the optical electrodes, so that the three-dimensional integration of the neural optical electrodes based on the LD coupling optical waveguide structure has higher stacking density and flexibility.

[0050] 2. The present invention uses a gradient refractive index lens as a coupling medium between the LD and the optical waveguide, which can greatly improve the optical coupling efficiency and reduce the optical coupling loss between the LD and the optical waveguide.

[0051] 3. The present invention separates the optical coupling base from the electrode base, and by increasing the distance between the LD and the recording channel, the interference of the electromagnetic radiation generated when the LD is working on the recording electrode point can be greatly reduced. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Figure 1 A schematic diagram of the overall structure of the three-dimensional neural photoelectrode array provided by the present invention;

[0053] Figure 2 is a cross-sectional schematic diagram of the neural probe and the electrode base in the present invention;

[0054] Figure 3 is a three-dimensional schematic diagram of the optical coupling base in the present invention;

[0055] Figure 4 It is a schematic diagram of the in-plane electroplating bonding of the input pad and the electroplating pad in the present invention.

[0056] Figure 5 This is a process flow chart of step S1 in the present invention.

[0057] Figure 6 It is a process flow chart of step S2 in the present invention. DETAILED DESCRIPTION

[0058] The present invention will be further described below in conjunction with the accompanying drawings.

[0059] like Figure 1As shown, a three-dimensional neural photoelectrode array with a laser diode coupled optical waveguide structure includes a plurality of neural photoelectrodes stacked in sequence; each neural photoelectrode includes an electrode base 2, and a plurality of neural probes 1 arranged in sequence and spaced apart, and a light source module 3 installed on the electrode base 2 and the number of which is the same as the number of neural probes 1. Each light source module 3 provides a light signal to a corresponding light stimulation point at the tip of a neural probe 1. Thus, a three-dimensional neural photoelectrode array with a spatial structure is formed. A plurality of slots are provided on both sides of the electrode base 2; and an optical coupling port 6 is provided in the middle of each slot. The number of slots is consistent with the number of light source modules 3; a snap-on protrusion is provided at the end of the light source module 3; and the snap-on protrusion of the light source module 3 is plugged into the corresponding slot of the electrode base 2. The light source module 3 with a separate design is docked with the electrode base 2.

[0060] like Figure 2 As shown, the electrode base 2 and multiple neural probes 1 are an integrated structure, which together constitute the main body of the photoelectrode; the main body of the photoelectrode includes a silicon substrate 12, a lower insulating layer 13, a recording conductive layer 14, an upper insulating layer 15 and a light stimulation layer 16 which are stacked in sequence from bottom to top. The recording conductive layer 14 is located between the lower insulating layer 13 and the upper insulating layer 15, and includes n groups of electrically connected recording electrode points 4, recording wires and recording pad structures; each recording pad is led out through a recording soft flat cable 7; thereby transmitting the neural signal at the neural probe 1 to the recording soft flat cable 7 of the electrode base 2. The light stimulation layer 16 includes n optical waveguides 5. n is the number of neural probes 1 on a neural photoelectrode.

[0061] The n recording electrode points 4 are respectively located at the tips of the n neural probes 1; one end of the n optical waveguides 5 is respectively located at the tips of the n neural probes 1, forming a light stimulation point of the neural probes 1; the other ends of the n optical waveguides 5 are respectively extended to the optical coupling ports 6 at the middle positions of the n slots of the electrode base 2; the optical waveguides 5 are used to achieve efficient transmission of lasers on the neural probes 1 and the electrode base 2. The optical waveguides 5 are arranged in a straight line on the neural probes 1; the optical waveguides 5 are arranged in a curved manner on the electrode base 2, so that the optical signal can be input from both sides of the electrode base 2 and output from the tips of each neural probe 1.

[0062] The light source module 3 includes an optical coupling base 8, an LD laser 9, a gradient refractive index lens 10 and a stimulation flexible flat cable 11. The optical coupling port 6 is arranged at the end of the optical waveguide 5. The clamping protrusion on the light source module 3 is arranged at the end of the optical coupling base 8.

[0063] like Figure 3As shown, the optical coupling base 8 includes a single crystal silicon layer 17, an oxide layer 18 and an LD power supply pad 21. The single crystal silicon layer 17 and the oxide layer 18 are stacked. Two LD power supply pads 21 are spaced apart on the outer surface of the single crystal silicon layer 17. Electroplating pads 23 are connected to the edges of the two LD power supply pads 21. The LD power supply pad 21 and the electroplating pad 23 are formed by one-time patterning. An LD positioning groove 20 and a lens positioning groove 19 connected together are provided on the side of the single crystal silicon layer 17 away from the oxide layer 18. The LD positioning groove 20 is located between the two electroplating pads 23. The end of the lens positioning groove 19 away from the LD positioning groove 20 passes through the snap-in protrusion and is aligned with the corresponding end of the optical waveguide 5. The oxide layer 18 provides an insulating medium for the LD power supply pad 21.

[0064] The LD laser 9 and the gradient refractive index lens 10 are installed in the LD positioning groove 20 and the lens positioning groove 19 respectively. The light outlet of the LD laser 9 is butted with one end of the gradient refractive index lens 10. The other end of the gradient refractive index lens 10 is coupled with the corresponding optical waveguide 5 through the optical coupling port 6. The two input pads 22 located on the opposite sides of the LD laser 9 are respectively arranged opposite to the two side walls of the LD positioning groove 20 with a gap. The two input pads 22 on the LD laser 9 are used to power the LD laser 9. Therefore, the input pads 22 and the electroplating pads 23 are respectively located on two mutually perpendicular planes with a gap in the middle; the input pads 22 and the electroplating pads 23 located on the same side of the LD laser 9 are connected through the gold nanoparticles 24 formed by electroplating, thereby realizing the non-plane conduction between the input pads 22 and the electroplating pads 23, overcoming the problem that the two input pads of the LD laser 9 in the prior art can only be horizontally arranged on the side of the electrode base, resulting in obvious protrusions on the electrode base and multiple photoelectrodes cannot be stacked.

[0065] The LD power supply pad 21 is led out through the stimulation flexible flat cable 11, thereby realizing the control of the LD laser 9. The neural photoelectrode uses the stimulation flexible flat cable 11 to power the LD laser 9 so that it emits laser light. The laser light emitted from the LD laser 9 is focused by the gradient refractive index lens 10 and then injected into the entrance of the optical waveguide 5 located at the optical coupling port 6. The laser light is transmitted through the optical waveguide 5 located on the electrode base 2 and the neural probe 1 and reaches the tip of the neural probe 1, thereby realizing optical stimulation of neurons. Subsequently, the recording electrode point 4 located near the exit of the optical waveguide 5 transmits the light-induced neural electrical signal to the recording flexible flat cable 7 located at the electrode base 2 via the recording wire and the recording pad.

[0066] The LD laser 9 has a rectangular parallelepiped structure with dimensions of 600×150×90 μm. 3 The two input pads 22 are respectively located on two side surfaces of 600 μm×150 μm; the laser beam emitted by the LD laser 9 is perpendicular to the end surface of the LD laser 9 .

[0067] The cross section of the optical waveguide 5 is rectangular, and the cross-sectional area is not greater than 10000 μm 2 .

[0068] The gradient refractive index lens 10 is cylindrical, and has a diameter of 100 μm to 1000 μm.

[0069] The LD laser 9 is completely located inside the LD positioning groove 20 , or partially extends out of the LD positioning groove 20 ; the gradient refractive index lens 10 is completely located inside the lens positioning groove 19 , or partially extends out of the lens positioning groove 19 .

[0070] The recording flexible flat cable 7 and the stimulation flexible flat cable 11 are both connected to the metal pads thereunder via anisotropic conductive adhesive (ACF).

[0071] Example 1

[0072] The method for preparing the three-dimensional neural photoelectrode array with a laser diode coupled optical waveguide structure comprises the following steps:

[0073] S1: The neural probe, electrode base and optical waveguide are fabricated using processes including photolithography, reactive ion etching, deep silicon etching, plasma enhanced chemical vapor deposition (PECVD), sputtering, and ion beam etching.

[0074] S2: Prepare a light source module 3; use the LD positioning groove and the lens positioning groove to align and fix the LD laser and the gradient refractive index lens, and achieve optical coupling between the gradient refractive index lens and the optical waveguide through alignment between the optical coupling base and the optical coupling port 6.

[0075] S3: Multiple neural optoelectronic electrodes with integrated LD-coupled optical waveguide structures are stacked and fixed using an alignment mold to achieve three-dimensional high-density integration of two-dimensional neural optoelectronic electrodes.

[0076] As a preferred embodiment, the specific process of step S1 is as follows Figure 4 As shown:

[0077] (1) Using SOI silicon wafer (top silicon layer 10-50 microns, buried oxide layer 0.5-2 microns, bottom silicon layer 200-500 microns) as the substrate, the silicon wafer was ultrasonically cleaned in acetone, ethanol and deionized water for 5 minutes each. Then, it was dried with nitrogen and baked in an oven at 180°C for 3 hours.

[0078] (2) Use the PECVD system to deposit a 1 μm thick silicon oxide layer on the front side of the SOI silicon wafer as the lower insulating layer.

[0079] (3) A chromium / gold (30 / 300 nm) metal layer was deposited on the lower insulating layer using a magnetron sputtering system as a recording conductive layer.

[0080] (4) A 5 μm thick positive photoresist is spin-coated on the front of the SOI silicon wafer and pre-baked. The photoresist is then patterned into a mask structure for ion beam etching using a photolithography machine.

[0081] (5) Use an ion beam etching system to pattern the metal layer into recording electrode points, recording wires, and recording pad structures. Then, place the SOI silicon wafer in acetone to remove the glue and clean it in ethanol and deionized water. Finally, dry it on a hot plate and set it aside.

[0082] (6) A 1 μm thick silicon oxide dielectric layer is deposited on the recording conductive layer using a PECVD system as an upper insulating layer.

[0083] (7) Spin-coat a 5 μm thick positive photoresist on the front of the SOI silicon wafer and pre-bake it. Then, use a photolithography machine to pattern the photoresist into a mask structure for reactive ion etching.

[0084] (8) Use a reactive ion etching system to open windows in the upper insulating layer to expose the recording electrode points and recording pad structure.

[0085] (9) Spin-coat a 5 μm thick positive photoresist on the front of the SOI silicon wafer and pre-bake it. Then, use a photolithography machine to pattern the photoresist into a mask structure for reactive ion etching.

[0086] (10) Use a reactive ion etching system to remove the exposed upper insulating layer and lower insulating layer.

[0087] (11) Use a deep silicon etching system to remove the exposed top layer of silicon to form the front contour of the neural photoelectrode. Subsequently, the SOI silicon wafer is placed in acetone to remove the glue and cleaned in ethanol and deionized water. Finally, it is dried on a hot plate and set aside.

[0088] (12) Spin-coat a negative SU-8 photoresist with a thickness of 1-100 μm on the front of the SOI silicon wafer and pre-bake it. Then, use a photolithography machine to pattern the SU-8 photoresist into an optical waveguide structure.

[0089] (13) A 5 μm thick positive photoresist is spin-coated on the front of the SOI silicon wafer using a spin coater and baked as a protective layer. Subsequently, a 5 μm thick positive photoresist is spin-coated on the back of the SOI silicon wafer and pre-baked. Next, a photolithography machine is used to pattern the photoresist into a mask structure for back-side reactive ion etching.

[0090] (14) Use a reactive ion etching system to remove the exposed back silicon oxide.

[0091] (15) Use a deep silicon etching system to remove the exposed underlying silicon.

[0092] (16) The exposed back buried oxide layer is removed using a reactive ion etching system. Subsequently, the SOI silicon wafer is placed in acetone for degumming and then cleaned in ethanol and deionized water. Finally, the released neural photoelectrode is placed on a hot plate for drying and then used for later use.

[0093] like Figure 5 As shown, the specific process of step S2 is as follows:

[0094] (1) Using an oxidized silicon wafer (single crystal silicon thickness 300-500 microns, oxide layer thickness 0.5-2 microns) as a substrate, a layer of chromium / gold (30 / 300nm) is sputtered on the silicon wafer to form a metal layer. Subsequently, the metal layer is patterned into LD power supply pads and electroplating pads using photolithography patterning and ion beam etching. Next, LD positioning grooves and lens positioning groove structures are formed using photolithography patterning and deep silicon etching.

[0095] (2) Use a placement machine to place the LD laser into the LD positioning slot so that its light outlet faces the gradient refractive index lens.

[0096] (3) Use an electroplating pen to electroplate gold nanoparticles between the input pads on both sides of the LD laser and the two electroplating pads on the optical coupling base, so that the input pads on both sides of the LD laser are connected to the two electroplating pads respectively.

[0097] (4) Place the gradient refractive index lens into the lens positioning groove on the optical coupling base so that it is aligned with the light outlet of the LD laser. Then, use ultraviolet light curing glue to fix the gradient refractive index lens to the lens positioning groove.

[0098] (5) Use a hot press to attach the ACF conductive adhesive to the LD power pad. The specific steps are: use tape to fix the optical coupling base on the glass slide; attach the ACF conductive adhesive above the LD power pad; place the glass slide directly under the pressure head of the hot press, aligning the pressure head with the ACF conductive adhesive; adjust the pressure of the hot press to 0.14MPa, the temperature to 140℃, the hot press time to 3 seconds, and start pre-pressing. After the pre-pressing is completed, tear off the isolation film on the surface of the ACF.

[0099] (6) Use a hot press to bond the recording flexible cable to the LD power supply pad to achieve anisotropic conduction. The specific steps are: align the pad of the recording flexible cable with the LD power supply pad and attach them together through ACF; place the slide glass directly under the pressure head of the hot press so that the pressure head is aligned with the ACF; adjust the pressure of the hot press to 0.18MPa, the temperature to 240℃, and the hot pressing time to 18 seconds to perform the pressing.

[0100] The specific process of step S3 is as follows:

[0101] (1) Insert the optical coupling base into the optical coupling port of the electrode base and fix it with epoxy resin glue to achieve optical coupling between the gradient refractive index lens and the optical waveguide.

[0102] (2) Multiple neural photoelectrodes are placed in an alignment mold for stacking and alignment, and then adjacent neural photoelectrodes are fixed using instant adhesive.

[0103] (3) The stacked and fixed neural photoelectrode array is removed from the mold.

[0104] Example 2

[0105] A method for preparing a three-dimensional neural photoelectrode array having a laser diode coupled optical waveguide structure, the difference between this embodiment and embodiment 1 is that: the process of step S1 is different;

[0106] The specific process of step S1 in this embodiment is as follows Figure 4 As shown:

[0107] (1) Using SOI silicon wafer (top silicon layer 10-50 microns, buried oxide layer 0.5-2 microns, bottom silicon layer 200-500 microns) as the substrate, the silicon wafer was ultrasonically cleaned in acetone, ethanol and deionized water for 5 minutes each. Then, it was dried with nitrogen and baked in an oven at 180°C for 3 hours.

[0108] (2) Use the PECVD system to deposit a 0.2 μm thick layer of silicon nitride on the front side of the SOI silicon wafer as the lower insulating layer.

[0109] (3) A titanium / gold (30 / 300 nm) metal layer was deposited on the lower insulating layer using a magnetron sputtering system as a recording conductive layer.

[0110] (4) A 5 μm thick positive photoresist is spin-coated on the front of the SOI silicon wafer and pre-baked. The photoresist is then patterned into a mask structure for ion beam etching using a photolithography machine.

[0111] (5) Use an ion beam etching system to pattern the metal layer into recording electrode points, recording wires, and recording pad structures. Then, place the SOI silicon wafer in acetone to remove the glue and clean it in ethanol and deionized water. Finally, dry it on a hot plate and set it aside.

[0112] (6) A 0.8 μm thick silicon oxide dielectric layer is deposited on the metal layer using a PECVD system as an upper insulating layer.

[0113] (7) Spin-coat a 5 μm thick positive photoresist on the front of the SOI silicon wafer and pre-bake it. Then, use a photolithography machine to pattern the photoresist into a mask structure for reactive ion etching.

[0114] (8) Use a reactive ion etching system to open windows in the upper insulating layer to expose the recording electrode points and recording pad structure.

[0115] (9) Spin-coat a 5 μm thick positive photoresist on the front of the SOI silicon wafer and pre-bake it. Then, use a photolithography machine to pattern the photoresist into a mask structure for reactive ion etching.

[0116] (10) Use a reactive ion etching system to remove the exposed upper insulating layer and lower insulating layer.

[0117] (11) Use a deep silicon etching system to remove the exposed top layer of silicon to form the front electrode outline. Then, place the SOI silicon wafer in acetone to remove the glue and clean it in ethanol and deionized water. Finally, dry it on a hot plate and set it aside.

[0118] (12) Spin-coat a negative EpoCore photoresist with a thickness of 1-100 microns on the front of the SOI silicon wafer and perform pre-baking. Subsequently, use a photolithography machine to pattern the EpoCore photoresist into an optical waveguide structure.

[0119] (13) A 5 μm thick positive photoresist is spin-coated on the front of the SOI silicon wafer using a spin coater and baked as a protective layer. Subsequently, a 5 μm thick positive photoresist is spin-coated on the back of the SOI silicon wafer and pre-baked. Next, a photolithography machine is used to pattern the photoresist into a mask structure for back-side reactive ion etching.

[0120] (14) Use a reactive ion etching system to remove the exposed back silicon oxide.

[0121] (15) Use a deep silicon etching system to remove the exposed underlying silicon.

[0122] (16) The exposed back buried oxide layer is removed using a reactive ion etching system. Subsequently, the SOI silicon wafer is placed in acetone for degumming and then cleaned in ethanol and deionized water. Finally, the released neural photoelectrode is placed on a hot plate for drying and then used for later use.

[0123] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art may make various modifications or variations within the scope of the claims, which do not affect the essence of the present invention.

Claims

1. A three-dimensional neural photoelectrode array with a laser diode coupled optical waveguide structure, comprising a plurality of neural photoelectrodes stacked in sequence; characterized in that: Each neural photoelectrode comprises an electrode base (2), a plurality of neural probes (1) arranged in sequence and spaced apart from each other, and light source modules (3) installed on the side of the electrode base (2) and the number of which is the same as the number of the neural probes (1); each neural probe (1) is provided with a recording electrode point (4) and a light stimulation point; the light stimulation point is connected to the corresponding light source module (3) via an optical waveguide (5); The light source module (3) comprises an optical coupling base (8), an LD laser (9) and a gradient refractive index lens (10); the optical coupling port (6) is arranged at the end of the optical waveguide (5); the optical coupling base (8) comprises a single crystal silicon layer (17), an oxide layer (18) and an LD power supply pad (21); the single crystal silicon layer (17) and the oxide layer (18) are stacked; two LD power supply pads (21) are arranged at intervals on the upper side of the single crystal silicon layer (17); the two LD power supply pads (21) are both connected to an electroplating pad (23); an LD positioning groove (20) and a lens positioning groove (19) connected together are arranged on the upper side of the single crystal silicon layer (17); the LD positioning groove (20) is located between the two electroplating pads (23) and is arranged perpendicular to the two electroplating pads (23); The LD laser (9) and the gradient refractive index lens (10) are respectively installed in the LD positioning groove (20) and the lens positioning groove (19); the light outlet of the LD laser (9) is butted against one end of the gradient refractive index lens (10); the other end of the gradient refractive index lens (10) is coupled to the corresponding optical waveguide (5) through the optical coupling port (6); the two input pads (22) on the LD laser (9) are located in the LD positioning groove (20) and are respectively parallel to the two side walls of the LD positioning groove (20), and a gap is left between the two side walls of the LD positioning groove (20); the input pads (22) and the electroplating pads (23) are respectively located on two mutually perpendicular planes with a gap in between; The input pad (22) and the electroplating pad (23) located on the same side of the LD laser (9) are connected via gold nanoparticles (24) formed by electroplating, thereby achieving non-planar conduction between the input pad (22) and the electroplating pad (23).

2. The three-dimensional neural photoelectrode array with a laser diode coupled optical waveguide structure according to claim 1, characterized in that: The electrode base (2) and the plurality of neural probes (1) are an integrated structure, and together constitute a photoelectrode body; the photoelectrode body comprises a silicon substrate (12), a lower insulating layer (13), a recording conductive layer (14), an upper insulating layer (15), and a light stimulation layer (16) which are stacked in sequence from bottom to top; the recording conductive layer (14) is located between the lower insulating layer (13) and the upper insulating layer (15), and comprises n groups of electrically connected recording electrode points (4), recording wires, and recording pad structures; the light stimulation layer (16) comprises n optical waveguides (5); n is the number of neural probes (1) on the neural photoelectrode; the n recording electrode points (4) are respectively located at the tips of the n neural probes (1); one end of the n optical waveguides (5) is respectively located at the tips of the n neural probes (1), forming a light stimulation point of the neural probe (1); the other ends of the n optical waveguides (5) respectively extend to the electrode base (2) and are coupled to the corresponding light source modules (3).

3. The three-dimensional neural photoelectrode array with a laser diode coupled optical waveguide structure according to claim 1, characterized in that: The electrode base (2) is provided with a plurality of slots at both side edges; an optical coupling port (6) is provided at the middle position of each slot; the number of the slots is consistent with the number of the light source modules (3); a clamping protrusion is provided at the end of the light source module (3); the clamping protrusion of the light source module (3) is plugged into the corresponding slot of the electrode base (2); the end of the lens positioning groove (19) away from the LD positioning groove (20) passes through the clamping protrusion and is aligned with the end of the corresponding optical waveguide (5).

4. The three-dimensional neural photoelectrode array with a laser diode coupled optical waveguide structure according to claim 1, characterized in that: The clamping protrusion on the light source module (3) is arranged at the end of the optical coupling base (8).

5. The three-dimensional neural photoelectrode array with a laser diode coupled optical waveguide structure according to claim 1, characterized in that: The LD laser (9) has a rectangular parallelepiped structure with dimensions of 600×150×90 µm. 3 The two input pads (22) of the LD laser (9) are located on two opposite sides of the LD laser (9) with the largest areas.

6. The three-dimensional neural photoelectrode array with a laser diode coupled optical waveguide structure according to claim 1, characterized in that: The cross section of the optical waveguide (5) is rectangular, and the cross-sectional area is not greater than 10000 μm 2 The gradient refractive index lens (10) is cylindrical and has a diameter of 100 to 1000 µm.

7. The method for preparing a three-dimensional neural photoelectrode array having a laser diode coupled optical waveguide structure according to claim 1, characterized in that: The following steps are involved: S1: Fabrication of neural probes, electrode bases, and optical waveguides using processes including photolithography, reactive ion etching, deep silicon etching, plasma enhanced chemical vapor deposition, sputtering, and ion beam etching; S2: Prepare a light source module, use the LD positioning groove and the lens positioning groove to align and fix the LD laser and the gradient refractive index lens, and achieve optical coupling between the gradient refractive index lens and the optical waveguide through alignment between the optical coupling base and the optical coupling port; S3: Multiple neural optodes are stacked and fixed using an alignment mold to achieve three-dimensional integration of two-dimensional neural optodes.

8. The method for preparing a three-dimensional neural photoelectrode array having a laser diode coupled optical waveguide structure according to claim 7, characterized in that: The specific process of step S1 is as follows: (1) Using SOI silicon wafer as substrate, the silicon wafer is thoroughly cleaned and dried for later use; (2) using a PECVD system to deposit a dielectric layer on the front side of the SOI silicon wafer as a lower insulating layer; (3) depositing a metal layer as a recording conductive layer on the lower insulating layer using a magnetron sputtering system; (4) using a photolithography machine to pattern the photoresist spin-coated on the metal layer into a mask structure; (5) using an ion beam etching system to pattern the metal layer into recording electrode points, recording wires, and recording pad structures; (6) depositing a dielectric layer as an upper insulating layer on the recording conductive layer using a PECVD system; (7) using a photolithography machine to pattern the photoresist spun on the upper insulating layer into a mask structure; (8) using a reactive ion etching system to open windows in the upper insulating layer to expose the recording electrode points and the recording pad structure; (9) using a photolithography machine to pattern the photoresist spin-coated on the upper insulating layer into a mask structure; (10) using a reactive ion etching system to remove the exposed upper insulating layer and lower insulating layer; (11) using a deep silicon etching system to remove the exposed top layer of silicon to form the front contour of the neural photoelectrode; (12) using a photolithography machine to pattern the photosensitive polymer spin-coated on the upper insulating layer into an optical waveguide structure; (13) Spin coating a layer of photoresist as a protective layer on the front side of the SOI silicon wafer using a spin coating machine; Then, a photolithography machine is used to pattern the photoresist spun on the back of the SOI into a mask structure; (14) using a reactive ion etching system to remove the exposed back oxide layer; (15) using a deep silicon etching system to remove the exposed underlying silicon; (16) Use a reactive ion etching system to remove the exposed back buried oxide layer; then, place the SOI in acetone to remove the resist.

9. The method for preparing a three-dimensional neural photoelectrode array having a laser diode coupled optical waveguide structure according to claim 7, characterized in that: The specific process of step S2 is as follows: (1) Using silicon oxide wafer as substrate, sputtering, photolithography patterning, ion beam etching and deep silicon etching are performed successively to realize micro-fabrication preparation of optical coupling base; (2) Use a chip mounter to place the LD laser into the LD positioning groove along the surface where the pad is located, so that its light outlet faces the gradient refractive index lens; (3) using an electroplating pen to electroplate gold nanoparticles between the input pad of the LD laser and the electroplating pad on the optical coupling base, so that the input pad of the LD laser is conductively connected to the corresponding electroplating pad; (4) Place the gradient refractive index lens into the positioning groove on the optical coupling base, align it with the LD laser, and then fix it; (5) Use a hot press to attach the ACF conductive adhesive to the LD power supply pad; (6) Use a hot press to bond the recording flexible cable to the LD power supply pad to achieve anisotropic conduction.

10. The method for preparing a three-dimensional neural photoelectrode array having a laser diode coupled optical waveguide structure according to claim 7, characterized in that: The specific process of step S3 is as follows: (1) inserting the optical coupling base into the optical coupling port of the electrode base and fixing it with epoxy resin glue to achieve optical coupling between the gradient refractive index lens and the optical waveguide; (2) placing multiple neural optodes into an alignment mold for stacking and alignment; Subsequently, the adjacent neural optodes were fixed using instant glue; (3) The stacked and fixed neural photoelectrode array is removed from the mold.

Images