Three-dimensional nerve probe array with variable rigidity

Abstract

The invention discloses a three-dimensional nerve probe array with variable rigidity. The array is formed by alternately stacking a plurality of rigidity-variable two-dimensional nerve probe array modules and a plurality of separation gaskets along the thickness direction, and an adhesive is applied to the peripheral side surface of a stacked body to form an edge sealing adhesive layer, so that the stacked body is locked into an integral three-dimensional structure. Each two-dimensional nerve probe array module comprises a modulus variable polymer layer and a two-dimensional nerve electrode structure, the modulus variable polymer layer has high modulus under the in-vitro low-temperature dry condition and is converted into low modulus in the body temperature and body fluid infiltration environment, so that the three-dimensional nerve probe array is integrally high in rigidity before implantation and is integrally soft after implantation. The spacer is made of a low modulus elastomeric polymer for setting interlayer spacing and providing flexible cushioning. The three-dimensional nerve probe array can be integrally implanted, repeated puncture and trauma are reduced, mechanical matching with brain tissue is improved after implantation, and three-dimensional high-flux long-term stable nerve recording is achieved.

Description

Technical Field

[0001] This invention relates to the field of implantable neural electrode technology, and more specifically to a three-dimensional neural probe array with variable stiffness. Background Technology

[0002] Brain-computer interface (BCI) technology, which involves implanting neural electrodes to interact with brain tissue, holds significant promise for applications in basic neuroscience research, disease mechanism analysis, and the reconstruction of motor and sensory functions. Among the key components of a BCI system is a neural probe array capable of multi-channel, high spatial resolution recording in the cerebral cortex and even deep brain regions.

[0003] Existing implantable neural probes mainly fall into two categories: rigid probes and flexible probes. Probes based on rigid inorganic materials such as silicon have high bending stiffness and structural stability, making them less prone to bending or displacement during implantation, and facilitating the simultaneous implantation of multiple probes in a three-dimensional array. However, their Young's modulus is much higher than that of brain tissue. After implantation, with respiratory movements, heartbeats, and the slow deformation of brain tissue, the probe generates continuous micro-friction and shear stress at the interface with surrounding tissues, which can easily induce chronic inflammatory responses and glial scarring, leading to attenuation of the recorded signal quality.

[0004] Flexible neural probes are mostly made of polymeric materials such as polyimide, Parylene C, and SU-8. Their low bending stiffness allows them to better conform to the micro-deformations of brain tissue, reducing local stress concentration and improving long-term biocompatibility and recording stability. However, flexible neural probes lack sufficient stiffness during implantation, typically requiring auxiliary means such as soluble rigid supports and delivery needles to increase initial stiffness, increasing surgical steps and operational complexity. To achieve a three-dimensional electrode distribution, current technologies rely on repeated implantation of single or a few probes, resulting in long overall implantation times, significant accumulated tissue trauma, and the interlayer spacing and recording depth of each electrode layer being highly dependent on the surgeon's operation, making precise control and reproducibility difficult.

[0005] In recent years, variable-stiffness neural probes that can maintain high stiffness in vitro and reduce stiffness after implantation under the influence of body temperature and fluids have attracted attention. However, existing solutions are mostly limited to single probes or two-dimensional layouts. In summary, current technology lacks a neural probe array structure that can accurately implant a three-dimensional probe array in a single, "rigid array" configuration during the implantation phase, improving implantation efficiency and reducing tissue damage caused by repeated punctures; and that can soften as a whole after implantation and integration into the physiological environment, allowing the three-dimensional probe array to mechanically match brain tissue during long-term service, thus balancing the needs of efficient array implantation and long-term stable recording. Summary of the Invention

[0006] The purpose of this invention is to provide a variable stiffness three-dimensional neural probe array. During the implantation stage, the array has a high stiffness structure similar to a rigid probe array, which facilitates the one-time and precise overall implantation of the probe array. In the physiological environment, the array as a whole transforms into a flexible state, thereby reducing long-term mechanical mismatch with brain tissue and achieving high-throughput, three-dimensionally controllable distribution of long-term stable neural recording.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A variable stiffness three-dimensional neural probe array includes at least two variable stiffness two-dimensional neural probe array modules, several spacers, an alignment structure, and an adhesive layer. The variable stiffness two-dimensional neural probe array modules and spacers are stacked alternately along the array thickness direction. After alignment based on the alignment structure and edge sealing and curing of the adhesive layer, an overall three-dimensional neural probe array structure is formed.

[0008] In the above technical solution, the variable stiffness two-dimensional neural probe array module further includes a variable modulus polymer layer and a two-dimensional neural electrode structure disposed on the variable modulus polymer layer. The variable modulus polymer layer and the two-dimensional neural electrode structure are integrally connected, so that the two-dimensional neural probe array module has high overall bending stiffness in vitro and significantly reduced overall bending stiffness in vivo, thereby realizing the variation of the module stiffness.

[0009] Furthermore, the two-dimensional neural electrode structure can consist of multiple neural electrodes, their wires, and pads disposed on the same flexible substrate. The neural electrodes, their wires, and pads are fixed to the flexible substrate by an encapsulation material. The flexible substrate and encapsulation material can be made of polymer materials such as polyimide, SU-8, or Parylene C. The neural electrodes and their wires are made of gold or platinum, and the adhesion between the gold or platinum and the flexible substrate is enhanced by chromium or titanium. The two-dimensional neural electrode structure is fabricated using conventional micro / nano fabrication processes (such as sputtering / evaporation, electroplating, photolithography, etching, etc.).

[0010] Furthermore, the variable modulus polymer layer is a temperature-fluid responsive smart material. It exists in a high modulus state in a dry environment below body temperature and transforms into a low modulus state in a body temperature and fluid-infiltrated environment. This variable modulus polymer layer is adhered to the flexible substrate of the two-dimensional neural electrode structure. In a dry environment at room temperature, it exists in a glassy or high modulus state, and transforms into a low modulus state after absorbing water at 37°C, thereby significantly altering the overall bending stiffness of the module. Preferably, the thickness of the variable modulus polymer layer is 0.05-0.1 mm, and the material is thiol / olefin-acrylate, polylactic acid, or polynorbornene. Its elastic modulus is 1-5 GPa in a dry state at 25°C, and decreases to 10-50 MPa after absorbing water at 37°C. This ensures that the probe array has sufficient axial and bending stiffness to penetrate the brain tissue during implantation, significantly reducing the mechanical mismatch between the probe and brain tissue after implantation.

[0011] Furthermore, the spacer is disposed between two adjacent layers of variable-stiffness two-dimensional neural probe array modules to form a preset interlayer spacing and provide soft cushioning. The spacer is preferably made of a flexible material with a Young's modulus of less than 10 MPa, such as polydimethylsiloxane (PDMS), Ecoflex, or other elastic polymers with good biocompatibility and long-term stability. Its thickness is preferably 0.2-1 mm to reduce rigid mechanical coupling between layers while ensuring interlayer recording resolution.

[0012] Furthermore, the alignment structure is located at the edge region of the variable stiffness two-dimensional neural probe array module and the separator, for achieving planar alignment of multiple variable stiffness two-dimensional neural probe array modules during the stacking process. The alignment structure may include positioning holes and / or mechanical limiting frames formed on the two-dimensional probe array module and the separator. In actual assembly, mechanical pins, alignment jigs, or a vision alignment system can be used to achieve precise inter-layer stacking of multi-layer array modules using the aforementioned alignment structure.

[0013] Furthermore, the adhesive layer is disposed on the outer peripheral side of the stacked structure formed by the variable stiffness two-dimensional neural probe array module and the spacer, and is used to form a sealing adhesive layer along the outer edge of the three-dimensional array, thereby locking the alternately stacked layers into an overall three-dimensional structure. The adhesive layer preferably uses UV-curable adhesive, PDMS, epoxy adhesive, biomedical adhesive, or other biocompatible adhesives, and is applied to the outer peripheral side of the stacked structure by dot coating. After curing, it ensures both the overall structural strength and the stability of the relative positions between layers, while avoiding the formation of an excessively thick or hard adhesive layer at the interlayer interfaces, thus preserving the overall flexibility of the three-dimensional array in a soft state.

[0014] The variable stiffness three-dimensional neural probe array of the present invention can be formed by alternately stacking 2-20 layers of variable stiffness two-dimensional neural probe array modules and separator pads. By adjusting the number of layers, the thickness of the separator pads, and the arrangement of each layer of neural probes in the two-dimensional plane, three-dimensional sampling distribution with different recording depths and spatial resolutions can be achieved according to the volume and anatomical structure of the target brain region.

[0015] This invention also provides a method for assembling a variable stiffness three-dimensional neural probe array, comprising the following steps: S1: Provides multiple variable stiffness two-dimensional neural probe array modules, each module comprising a variable modulus polymer layer and a two-dimensional neural electrode structure disposed thereon. The two-dimensional neural probe array module is provided with alignment holes or limiting structures.

[0016] S2: Provides multiple spacers made of flexible material with preset thickness and opening shape. The spacers have alignment holes or limiting structures that match the variable stiffness two-dimensional neural probe array module. The spacers are preferably made of elastic polymers with certain surface adhesion, such as PDMS and Ecoflex.

[0017] S3: Variable stiffness two-dimensional neural probe array modules and spacer pads are alternately stacked in a preset order to form a multi-layered stacked structure. During stacking, the planar position of each module is adjusted by inserting alignment pins through alignment holes, using mechanical limiting frames, or identifying geometric alignment marks under a microscope. Because the spacer pad material itself has a certain degree of adhesion, the stacked modules can be initially fixed without the application of adhesives, facilitating relative positional stability during alignment.

[0018] S4: Apply an adhesive to the outer peripheral surface of the multi-layer stacked structure and cure it to reliably fix the variable stiffness two-dimensional neural probe array modules and the spacers into an integrated three-dimensional array structure. The adhesive can be a biocompatible adhesive such as UV-curable adhesive, PDMS, epoxy adhesive, or biomedical adhesive.

[0019] Through the above steps, a three-dimensional neural probe array with overall structural stability, controllable interlayer spacing, and overall flexibility in a soft state is obtained. In practical use, the three-dimensional neural probe array can be placed in a low-temperature and dry environment before implantation to keep the variable modulus polymer layer in a high modulus state, so as to provide sufficient overall stiffness during the implantation stage. After implantation and equilibration with body temperature and body fluid environment, the elastic modulus of the variable modulus polymer layer decreases, and the overall bending stiffness of the three-dimensional neural probe array decreases, thereby improving the mechanical compatibility with brain tissue and reducing long-term mechanical stimulation.

[0020] In the above method, the variable stiffness two-dimensional neural probe array module can be obtained through the following fabrication approach: First, a two-dimensional neural electrode structure is fabricated on a rigid substrate using processes such as photolithography, sputtering / evaporation, and etching; then, a rigid template made of materials such as SU-8 that matches the shape of the two-dimensional electrode is used as the master mold, and a flexible mold with a negative probe cavity is obtained by PDMS molding; then, the two-dimensional neural electrode structure is placed into the flexible mold cavity with the electrode opening facing downwards, and a polymer precursor with adjustable modulus is poured or dripped into the mold to complete cross-linking, curing, and demolding, thus obtaining the variable stiffness two-dimensional neural probe array module.

[0021] Compared with the prior art, the present invention has the following beneficial effects: This invention expands the variable stiffness neural probes, originally designed for two-dimensional layouts, into a three-dimensional neural probe array that can be implanted as a whole by alternately stacking multiple variable stiffness two-dimensional neural probe array modules with low-modulus spacers along the thickness direction and applying adhesive only to the outer periphery of the stacked structure to form a sealing structure. Before implantation, when the variable modulus polymer layers in each module are in a high-modulus state, the three-dimensional array exhibits an overall high-stiffness probe array, allowing the three-dimensional probe array to be delivered to the target brain region simultaneously in a single surgical procedure, improving implantation efficiency and reducing tissue damage caused by repeated punctures. After implantation and in the body temperature and fluid environment, the variable modulus polymer layers soften, causing a decrease in the overall bending stiffness of the three-dimensional array. Combined with the flexible buffering effect of the spacers, this effectively alleviates the long-term mechanical mismatch between the probes and brain tissue, reducing the risk of chronic inflammatory reactions, glial scar formation, and neuronal apoptosis, and facilitating the acquisition of long-term stable neural recording signals.

[0022] This invention achieves regular stacking and precise control of interlayer spacing of multi-layer variable stiffness two-dimensional probe array modules through low-modulus separator pads. This avoids the problems of uncontrollable interlayer distance and complex implantation trajectory in traditional multiple single-layer implantation methods, and allows for flexible design of three-dimensional sampling distribution and recording depth according to the needs of different brain regions.

[0023] This invention employs alignment structures such as alignment holes and limiting frames located on the edge regions of the two-dimensional neural probe module and the separating pad, combined with an adhesive layer applied only to the outer periphery of the stacked structure for curing, to achieve high-precision assembly and integrated packaging of the multi-layer probe array module, improve the geometric consistency and assembly yield of the three-dimensional array, and facilitate mass production and standardized manufacturing. Attached Figure Description

[0024] Figure 1 These are schematic diagrams of the variable stiffness three-dimensional neural probe arrays in embodiments 1 and 3 of the present invention. Figure 2 This is a schematic cross-sectional view of the variable stiffness two-dimensional neural probe array module in embodiments 1, 2, and 3 of the present invention; Figure 3 This is a schematic diagram of the device structure of the variable stiffness two-dimensional neural probe array module in embodiments 1, 2, and 3 of the present invention; Figure 4 for Figure 3 Enlarged view of the area circled in the middle; Figure 5 This is a schematic diagram of the stacked structure of a variable stiffness two-dimensional neural probe array module and a separator pad in embodiments 1 and 3 of the present invention. Detailed Implementation

[0025] To make the objectives, technical solutions, and beneficial effects of this invention clearer, the invention will be further described in detail below with reference to specific embodiments and accompanying drawings. It should be understood that the specific embodiments of this invention are for illustrative purposes only and are not intended to limit the invention. Without departing from the spirit and scope of the claims, those skilled in the art can make various modifications or substitutions to the following embodiments, and all such modifications or substitutions should fall within the protection scope of this invention.

[0026] Example 1: Variable stiffness three-dimensional neural probe array.

[0027] This embodiment addresses the problems of existing flexible neural probe arrays, which are mostly two-dimensional structures and difficult to achieve three-dimensional neural recording through a single implantation, while rigid neural probe arrays can be implanted in three dimensions but suffer from poor long-term stability. It provides a three-dimensional neural probe array with variable stiffness. See also... Figure 1 The variable stiffness three-dimensional neural probe array in this embodiment includes: three layers of variable stiffness two-dimensional neural probe array modules 10, a spacer 20 sandwiched between two adjacent layers of variable stiffness two-dimensional neural probe array modules 10, two through holes 30 integrated in the edge region of the modules 10 and the spacer 20 for precise alignment of the multi-layer module planar positions, and an adhesive layer 40 disposed on the outer periphery of the stacked structure to fix each layer as a whole. Through the synergistic cooperation of the above structures, the three-dimensional neural probe array exhibits high stiffness during the implantation stage to achieve single-time implantation of the array, and transforms into a flexible structure as a whole in the physiological environment, thereby achieving the unity of three-dimensional neural recording and long-term stable service.

[0028] like Figure 2As shown, each layer of the variable stiffness two-dimensional neural probe array module 10 comprises, from bottom to top: a variable modulus polymer layer 110, a polymer substrate layer 120, a metal conductive layer 130, and a polymer encapsulation layer 140. In this embodiment, the variable modulus polymer layer 110 is a polymer based on a thiol-olefin / acrylate crosslinking network, with a thickness of 0.05 mm. In a dry state at 25°C, it is in a high-modulus glass state with an elastic modulus of approximately 2500 MPa, providing sufficient axial and bending stiffness to resist puncture loads from brain tissue. At 37°C and when saturated with water, it transforms into a low-modulus rubber state, with the elastic modulus decreasing to approximately 20 MPa, thus achieving the variable stiffness behavior of the two-dimensional neural probe array module. The polymer substrate layer 120 and the polymer encapsulation layer 140 are made of polyimide with a thickness of 5 μm. The metal conductive layer 130 includes a 10 nm thick chromium adhesion layer and a 100 nm thick gold conductive layer. In other embodiments, the polymer substrate layer 120 and the polymer encapsulation layer 140 may also be made of biocompatible flexible polymer materials such as SU-8 and Parylene C, which does not constitute a limitation of the present invention.

[0029] like Figure 3 and Figure 4 As shown, the variable stiffness two-dimensional neural probe array module 10 includes, along its length, a pad segment 101, a connecting wire segment 102, and multiple probes 103 capable of penetrating brain tissue. In this embodiment, a two-dimensional neural probe array module containing three probes 103 is used as an example. Each probe 103 is equipped with 16 electrodes 131, has a probe length of 2 mm, and the center-to-center distance between adjacent probes is 0.6 mm to accommodate the thickness of the cerebral cortex and the distribution of recording channels. Those skilled in the art can adjust the number of probes, probe length, and number of channels according to different target brain regions and recording resolution requirements.

[0030] In this embodiment, the structure and operation of a variable stiffness three-dimensional neural probe array are illustrated using a stack of three variable stiffness two-dimensional neural probe array modules as an example. Those skilled in the art can adjust the number of variable stiffness two-dimensional neural probe array modules to 2-20 layers as needed to adapt to different brain region sizes and three-dimensional sampling requirements; all of these are optional embodiments of the present invention.

[0031] A spacer 20 is disposed between two adjacent layers of variable-stiffness two-dimensional neural probe array modules 10 to form a preset interlayer spacing and provide flexible buffering. In this embodiment, the spacer 20 is made of elastic polymer PDMS with a thickness of 0.6 mm to achieve an interlayer spacing of approximately 0.6 mm between adjacent probe modules. Those skilled in the art can design the thickness of the spacer to be within the range of 0.2-1 mm according to the thickness of the target brain region and the recording depth distribution requirements. The low modulus characteristics of the spacer 20 provide a flexible buffer channel after the variable-modulus polymer layer 110 softens, allowing each probe layer to deform in tandem with the macroscopic displacement and local micro-movement of the brain tissue while maintaining the preset interlayer spacing, thus avoiding stress concentration caused by rigid coupling between layers.

[0032] like Figure 3 and Figure 5 As shown, to ensure precise alignment of the variable stiffness two-dimensional neural probe array modules 10 in the planar direction, in this embodiment, through holes 30 are provided as alignment structures in the edge regions of the variable stiffness two-dimensional neural probe array modules 10 and the separator shims 20. During assembly, the variable stiffness two-dimensional neural probe array modules 10 and the separator shims 20 engage with the alignment pins on the fixture through the through holes 30 to achieve repetitive positioning in the plane, avoiding relative misalignment of the multi-layer flexible modules during stacking and curing. If necessary, geometric limiting structures can also be provided at the edge of the modules to further improve assembly accuracy.

[0033] The adhesive layer 40 is used to fix the stacked variable-stiffness two-dimensional neural probe array module 10 and the spacer 20 into an integral structure after alignment is completed. In this embodiment, the adhesive is UV-curable silicone (model Loctite SI5055), which is applied to the outer peripheral side of the stacked structure to form an adhesive layer 40 along the outer edge of the three-dimensional array, achieving overall locking of each layer. The adhesiveness of the spacer 20 material itself can provide initial interface fixation during assembly, and the adhesive layer 40 provides long-term structural stability after curing. By confining the adhesive mainly to the outer peripheral side of the array, rather than filling a large area of ​​the interlayer interface, this embodiment avoids introducing a high-modulus hard shell between layers while ensuring the overall structural strength, maximizing the overall flexibility of the three-dimensional array in a soft state and its mechanical matching with brain tissue.

[0034] Through the above structure, the variable stiffness three-dimensional neural probe array described in this embodiment exhibits high stiffness in a dry state at room temperature, and can be inserted into brain tissue as a whole, improving the efficiency of neural probe implantation. After implantation, in the body temperature and cerebrospinal fluid environment, the variable modulus polymer layer 110 softens, and the overall bending stiffness of the three-dimensional array decreases. Combined with the elastic buffering effect of the separator 20, it better adapts to the long-term micro-deformation and physiological pulsation of brain tissue, reduces the mechanical stimulation of the electrode-tissue interface, and is conducive to obtaining high-throughput, three-dimensionally controllable and long-term stable neural recording signals.

[0035] Example 2: Method for fabricating a variable stiffness two-dimensional neural probe array module.

[0036] This embodiment provides a method for fabricating a variable stiffness two-dimensional neural probe array module 10 for use in the variable stiffness three-dimensional neural probe array described in Embodiment 1. This method involves forming a two-dimensional neural electrode structure on a silicon wafer through micro-nano fabrication, and then using a mold to infuse and solidify a variable stiffness polymer precursor solution, thereby achieving the integral molding of the variable modulus polymer layer 110 and the two-dimensional flexible thin-film probe array. The method includes the following steps: S1: A 100-300 nm thick aluminum layer is deposited as a sacrificial layer on a 4-inch polished silicon wafer by vapor deposition or magnetron sputtering. A 3-5 μm thick polyimide layer is spin-coated onto the aluminum sacrificial layer and cured to obtain the polymer substrate layer 120.

[0037] S2: Spin-coat photoresist AZ5214 onto the polymer substrate 120 obtained in step S1, and after 1 minute of pre-baking, apply 260 mJ / cm⁻¹. 2 The i-line of the dose is exposed and developed to obtain a patterned photoresist. Then, a 10 nm thick chromium layer and a 100 nm thick gold layer are sequentially deposited by evaporation or magnetron sputtering to obtain a metal conductive layer 130. The photoresist is then stripped in acetone to obtain the metal patterns of electrodes, wires and pads.

[0038] S3: A 3-5 μm thick layer of polyimide is spin-coated onto the conductive metal layer 130 and cured to obtain a polymer encapsulation layer 140. Photoresist AZ5214 is spin-coated onto the polymer encapsulation layer 140, and the outline and electrode opening pattern of the two-dimensional neural probe array module are formed by photolithography and development. Subsequently, aluminum with a thickness of 100-300 nm is deposited by evaporation or magnetron sputtering, and the photoresist is stripped in acetone to obtain patterned aluminum, which serves as a hard mask for subsequent plasma etching processes.

[0039] S4: The polyimide not masked by aluminum is removed using inductively coupled plasma etching (ICP-E) or reactive ion etching (RIE). The etched silicon wafer is then immersed in 10% dilute hydrochloric acid to remove the aluminum mask and sacrificial layer, releasing the two-dimensional flexible thin-film probe array. After rinsing in deionized water, the prepared two-dimensional neural electrode structure is obtained.

[0040] S5: To achieve the variable stiffness function, this embodiment selects a modulus-variable polymer based on a thiol-olefin / acrylate crosslinking network. Tricyclo[5.2.1.02,6]decanediethanol diacrylate, tris[2-(3-mercaptopropionyloxy)ethyl]isocyanurate, and 1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione are mixed in a ratio of 31 mol%:34.5 mol%:34.5 mol%. Then, 0.1% of 2,2-dimethoxy-2-phenylacetylphenyl ketone is added. The mixture is stirred using a magnetic stirrer for 20 minutes, followed by 10 minutes of ultrasonic degassing to obtain the modulus-variable polymer precursor solution.

[0041] S6: SU-8 2050 photoresist is spin-coated onto a 4-inch silicon wafer and cured to form a 50μm thick SU-8 layer. A raised structure corresponding to the shape of the two-dimensional neural electrode structure is then fabricated using photolithography to obtain the SU-8 male mold. Using the SU-8 male mold as the female mold, PDMS prepolymer (5% curing agent by mass) is poured in, cured, and peeled off to obtain a PDMS female mold with a negative probe cavity. This PDMS female mold is used to define the contour and thickness of the variable modulus polymer layer 110, achieving precise spatial distribution of the variable modulus polymer layer 110 on the back side of the probe.

[0042] S7: Place the two-dimensional neural electrode structure obtained in step S4 into the corresponding cavity of the PDMS negative mold obtained in step S6 with the electrode opening facing down. Then, drop or inject the variable modulus polymer precursor liquid obtained in step S5 into the cavity of the PDMS negative mold. The precursor liquid forms a covering layer on the back of the two-dimensional neural electrode structure by scraping.

[0043] S8: Place the PDMS negative mold filled with the two-dimensional neural electrode structure and the polymer precursor liquid with variable modulus obtained in step S7 under a UV lamp to solidify the precursor liquid. After solidification, cool it and demold the entire structure from the PDMS negative mold to obtain the variable stiffness two-dimensional neural probe array module 10.

[0044] Example 3: Assembly method of variable stiffness three-dimensional neural probe array.

[0045] This embodiment provides an assembly method for the variable stiffness three-dimensional neural probe array described in Embodiment 1. The method uses the variable stiffness two-dimensional neural probe array module 10 described in Embodiment 2 as the basic unit. Through alternating stacking with flexible spacers, planar alignment, and peripheral edge sealing with adhesive, a three-dimensional array structure with controllable interlayer spacing and overall flexibility is achieved. Specifically, the method includes the following steps: S1: Alignment pins matching the alignment holes are set on the assembly fixture. The variable stiffness two-dimensional neural probe array module 10 and the separator shims 20 are stacked alternately in a preset order. The alignment holes and alignment pins are used to achieve repeated positioning of each layer of modules in the plane. After the stacking is completed and the designed number of layers is reached, a stacked structure composed of multiple flexible modules and separator shims is obtained.

[0046] S2: Adhesive is continuously or intermittently applied along the array edge on the outer peripheral side of the aligned multilayer stacked structure to form an adhesive layer 40 surrounding the outer edge of the array, locking each layer module 10 and the spacer 20 into a whole. The adhesive can be a biocompatible material such as UV-curable silicone, low-modulus epoxy, or biomedical adhesive. After the adhesive has cured, a stable overall structure with controllable interlayer spacing is obtained. Figure 1 The three-dimensional neural probe array with variable stiffness is shown.

Claims

1. A three-dimensional neural probe array with variable stiffness, characterized in that, include: The system comprises at least two variable stiffness two-dimensional neural probe array modules, several spacers, an alignment structure, and an adhesive layer; the variable stiffness two-dimensional neural probe array modules and spacers are stacked alternately along the array thickness direction; the alignment structure is used for planar alignment of the two-dimensional neural probe array modules; the adhesive layer is disposed on the outer peripheral side of the stacked structure formed by the variable stiffness two-dimensional neural probe array modules and spacers, thereby forming an overall three-dimensional neural probe array structure. The variable stiffness two-dimensional neural probe array module includes a variable modulus polymer layer and a two-dimensional neural electrode structure disposed on the variable modulus polymer layer; the variable modulus polymer layer is a temperature-fluid responsive smart material, which is in a high modulus state in a dry environment below body temperature, and transforms into a low modulus state in a body temperature and body fluid immersion environment. The alignment structure is located at the edge region of the variable stiffness two-dimensional neural probe array module and the separating pad.

2. The variable stiffness three-dimensional neural probe array according to claim 1, characterized in that, The variable stiffness two-dimensional neural probe array module includes at least two neural probes disposed on the same substrate, with a spacing of 0.2-1 mm between adjacent neural probes.

3. The variable stiffness three-dimensional neural probe array according to claim 1, characterized in that, The separator is a flexible material selected from biocompatible polymers with a Young's modulus of less than 10 MPa.

4. The variable stiffness three-dimensional neural probe array according to claim 1, characterized in that, The thickness of the variable modulus polymer layer is 0.05-0.1 mm.

5. The variable stiffness three-dimensional neural probe array according to claim 1, characterized in that, The thickness of the separator is 0.2-1 mm.

6. The variable stiffness three-dimensional neural probe array according to claim 1, characterized in that, The alignment structure includes at least two sets of through-holes disposed on the variable stiffness two-dimensional neural probe array module and the separator pad, wherein the through-holes penetrate the variable stiffness two-dimensional neural probe array module and the separator pad along the thickness direction.

7. The variable stiffness three-dimensional neural probe array according to claim 1, characterized in that, The adhesive layer is a biomedical adhesive or other biocompatible adhesive.

8. The variable stiffness three-dimensional neural probe array according to claim 1, characterized in that, The variable stiffness three-dimensional neural array is formed by alternating stacking of 2-20 layers of variable stiffness two-dimensional neural probe array modules and separating pads.

9. The variable stiffness three-dimensional neural probe array according to any one of claims 1-8, characterized in that, Its assembly method includes the following steps: S1: The two-dimensional neural probe array module and the separator pad are stacked alternately in a preset order to form a multi-layer stacked structure; S2: Alignment between layers is achieved by positioning holes provided on the variable stiffness two-dimensional neural probe array module and the separator pad, wherein the adhesiveness of the separator pad material itself is used to initially fix the multi-layer stacked structure. S3: Apply adhesive to the outer peripheral side of the multi-layer stacked structure and cure it to fix the variable stiffness two-dimensional neural probe array module and the separator into an integral structure, which is the variable stiffness three-dimensional neural probe array.

10. The variable stiffness three-dimensional neural probe array according to any one of claims 1-8, characterized in that, The method of use is as follows: Before implantation, the three-dimensional neural probe array is placed in a dry environment below body temperature so that the variable modulus polymer layer is in a high modulus state. After implantation is completed and the array is in a physiological environment, the overall stiffness of the three-dimensional neural probe array is reduced by utilizing the decrease in the elastic modulus of the variable modulus polymer layer to adapt to the mechanical properties of brain tissue.

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