Three-dimensional spiral high-density neural electrode and preparation method and application thereof

Abstract

The invention relates to a three-dimensional spiral high-density neural electrode and a preparation method and application thereof. The three-dimensional spiral high-density neural electrode comprises a probe structure and a plurality of electrode sites. The probe structure is formed by curling a planar flexible electrode precursor, and at least one end of the probe structure is provided with a spiral outer surface of a three-dimensional spiral line structure. Electrode sites are distributed along a spiral path, have a size of 5-1000 [mu] m, and are used for contacting biological tissues. On the planar flexible electrode precursor, electrode sites are arranged on one or more straight lines forming an inclined angle alpha with the axial direction of the probe, and the spatial distribution is matched with the edge. Compared with the prior art, the method has the advantages that the constraint of a traditional wiring mode is broken through, the integration of high-density three-dimensional channels is realized under a micro size, and a new generation of solution is provided for a high-precision brain-computer interface, deep brain stimulation and a three-dimensional electroencephalogram.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biomedical engineering and micro-nano processing technology, and in particular to a three-dimensional spiral high-density neural electrode and a preparation method and application thereof. BACKGROUND

[0002] The rapid development of neural intervention technologies such as brain-computer interface (BCI), deep brain stimulation (DBS) and stereoelectroencephalography (SEEG) has put forward very high requirements for the performance of neural electrodes. An ideal neural electrode needs to integrate tens of thousands of channels in as small a space as possible to achieve high-throughput and high-fidelity recording and stimulation of neural activity, i.e., to develop towards "high density" and "three-dimensionality".

[0003] The current mainstream micro neural electrodes, such as Michigan electrodes or Utah arrays based on silicon micro processing technology, usually limit the electrode sites to two-dimensional planar layout. However, such a structure has an inherent and insurmountable fundamental contradiction: each additional recording or stimulation channel requires an additional independent metal wire. In a two-dimensional plane or linear cross-section, the linear growth of the number of wires inevitably leads to a tension in the wiring space, ultimately forcing the increase in the size of the device (such as the width or thickness of the probe).

[0004] For example, to integrate thousands of channels, the cross-sectional area of the probe will increase dramatically, causing unacceptable damage to the brain tissue during implantation and triggering serious immune rejection and scar reactions, greatly affecting the long-term recording performance of the electrode.

[0005] The invention disclosed in publication CN117618768A discloses a stereoscopic flexible electrode for peripheral nerve directional space stimulation recording. The electrode improves the spatial directional selectivity and fixity of peripheral nerve stimulation by combining intra-membrane and extra-membrane structures. However, this design is mainly aimed at peripheral nerve applications, and the number of electrode sites and wiring methods are still limited to traditional two-dimensional or linear layout, which cannot be directly applied to high-density recording of deep brain nerves. Each additional channel requires an additional independent wire, and the growth of the number of wires in three-dimensional space will lead to an increase in the cross-sectional area of the probe, thereby causing irreversible damage, immune rejection and scar reactions when implanted in brain tissue, affecting long-term stability.

[0006] The traditional electrode architecture cannot achieve a leap in the number of channels within a small and constant cross-sectional area while ensuring the precise positioning of electrode sites in three-dimensional brain space. This wiring limitation has become a key bottleneck in the development of the next generation of brain-computer interface technology.

[0007] Therefore, how to develop a new electrode architecture that can break the limitations of traditional wiring methods, achieve a leap in the number of channels within a small and constant cross-sectional area, and at the same time ensure the precise positioning of electrode sites in three-dimensional brain space has become a key bottleneck in promoting the development of next-generation brain-computer interface technology. Summary of the Invention

[0008] The purpose of this invention is to overcome the shortcomings of the existing technology by providing a three-dimensional spiral high-density neural electrode, its preparation method and application. Through an innovative electrode architecture, it breaks the constraints of traditional wiring methods and achieves the integration of high-density three-dimensional channels in a small size, providing a breakthrough solution for brain neural intervention.

[0009] The objective of this invention can be achieved through the following technical solutions: The first aspect of this invention provides a three-dimensional helical high-density neural electrode, comprising a probe structure and multiple electrode sites, wherein specifically: A probe structure is formed by rolling up a planar flexible electrode precursor. At least one end of the probe structure has a helical outer surface, which is a three-dimensional helical configuration. Multiple electrode sites are distributed along a spiral path on the spiral outer surface of the probe structure. The electrode sites are used to contact biological tissue, and the size of the electrode sites is 5-1000 μm. The spatial distribution of the electrode sites matches the edge of the planar flexible electrode precursor. On the planar flexible electrode precursor, the electrode sites are located on one or more straight lines that are inclined at an angle α to the axis of the probe structure.

[0010] Furthermore, the probe structure is a multi-layered spiral structure formed by curling and fixing the planar flexible electrode precursor around a central support, with 2-100 layers.

[0011] Furthermore, the central support body serves as the central support body for the planar flexible electrode precursor, and the central support body is made of at least one material selected from platinum-iridium alloy, tungsten, stainless steel, quartz, optical fiber, and polymer. The surface of the central support is coated with a biocompatible material; The central support is a hollow structure and is used for drug delivery. or, The central support is a solid structure and is used for the transmission of optical and electrical stimulation signals.

[0012] The central support provides mechanical support for the probe structure and is also used for electrical stimulation and / or drug delivery.

[0013] Further, the range of alpha is 60-88 degrees.

[0014] Further, the diameter of the probe structure is 50-1000 microns, and the length is 0.5-15 cm.

[0015] Further, the probe structure is a multi-layer spiral structure, and there is a gap between the layers, which is filled with a high polymer material, such as ultraviolet curing resin or polyimide, to enhance mechanical stability and electrical insulation. Further, a pad array is also included, which is electrically connected to the electrode sites through metal connection lines, and is used to connect external circuits.

[0016] Further, a bendable connection neck is provided between the pad array and the main body part of the planar flexible electrode precursor; the width of the connection neck is significantly smaller than the width of the pad array and the width of the main body part of the precursor, forming a mechanical weak point, which facilitates bending of the pad array by at least 90 degrees along the connection neck to adapt to different connection spaces and directions.

[0017] Further, the tail part of the planar flexible electrode precursor is integrated with a transistor array, which is electrically connected to the microelectrode to form an active electrode structure, for realizing signal multiplexing to reduce the number of external connection interfaces; wherein the tail part region where the transistor array is located is outside the biological body cortex when implanted, avoiding direct contact with tissue fluid, thereby improving the reliability of long-term operation of the transistor array.

[0018] The second aspect of the present application provides a preparation method of the three-dimensional spiral high-density neural electrode as described above, comprising the following steps: S1, preparing a planar flexible electrode precursor, wherein a plurality of electrode sites and metal connection lines are formed on a flexible substrate through a micro-nano processing process, the electrode sites are arranged on one or more straight lines at an inclined angle to the long side direction of the substrate, and the inclined angle is a non-zero angle; S2, curling the planar flexible electrode precursor into an elongated three-dimensional probe structure, so that the probe structure has a spiral outer surface, wherein the curling process is controlled by curling parameters to make the electrode sites distributed along the spiral path; S3, fixing the formed probe structure, which can further be filled with a curing material to fill the interlayer gap, so that the electrode sites are exposed on the spiral path, and the mechanical stability and electrical insulation of the structure are ensured.

[0019] Further, in S1, the specific process of preparing the planar flexible electrode precursor includes: A silicon wafer or glass wafer substrate is used as a processing carrier, and a sacrificial layer is deposited thereon. forming a flexible substrate on the sacrificial layer, by spin-coating a polyimide precursor solution and curing by stepwise temperature increase; adopting a photolithography process to determine the pattern of electrode sites and metal connection lines on the flexible substrate, the electrode sites being preset on one or more straight lines at an oblique angle to the long side direction of the substrate, and forming a conductive structure by metal deposition and lift-off process; applying a polyimide encapsulation layer and selectively exposing the electrode sites and pad areas by reactive ion etching, and releasing the complete planar flexible electrode precursor by etching the sacrificial layer; In S1, the tail of the planar flexible electrode precursor is integrated with a transistor array, which is electrically connected to the electrode sites on the planar flexible electrode precursor, wherein the integration process includes processing the transistor units onto the flexible substrate by micro-nano processing technology, or transferring the transistor units to the flexible substrate by transfer technology, and forming metal interconnections to constitute an active electrode structure for realizing signal multiplexing to reduce the number of external connection interfaces.

[0020] Further, in S2, the specific process of rolling the planar flexible electrode precursor into an elongated three-dimensional probe structure includes: selecting a rod body of biocompatible material as a central support; fixing the starting end of the planar flexible electrode precursor to the surface of the central support; using a precision rotary table to connect the central support and rotate the central support while linearly pulling the tail end of the precursor, and adjusting the rolling parameters by controlling the rotation speed of the precision rotary table and the pulling force to make the precursor roll around the central support to form a multi-layer spiral structure, and the rolling process is controlled by parameters to make the electrode sites distributed along the spiral path.

[0021] Further, in S3, the specific process of fixing the formed probe structure includes: adopting biocompatible curing materials to fill the interlayer gaps by dispensing or capillary action; polymerizing the curing materials by ultraviolet irradiation to realize structure fixation, and the fixing process makes the electrode sites exposed to the spiral path.

[0022] Further, it also includes the step of interconnecting the pads at the tail of the electrode and the printed circuit by anisotropic conductive adhesive hot pressing or ball grid array soldering.

[0023] The third aspect of the present application provides an application of the three-dimensional spiral high-density neural electrode, which is used in high-precision brain-computer interface, deep brain stimulation or stereoelectroencephalography equipment, and realizes high-density recording of neural signals or electrical stimulation through the distribution of electrode sites along the spiral path on the three-dimensional spiral high-density neural electrode.

[0024] That is, the three-dimensional spiral high-density neural electrode based on the bevel layout preset in the application is suitable for high-channel neural signal recording and electrical stimulation, and can be widely applied to the fields of high-precision brain-computer interface (BCI), deep brain stimulation (DBS) treatment, stereoelectroencephalogram (SEEG) monitoring and neuroscience research.

[0025] Compared with the prior art, the application has the following beneficial effects: 1. High density and high spatial resolution: in the application, a planar precursor is curled into a multi-layer spiral structure, a large number of electrode channels are integrated in a small cross-sectional area, and through careful presetting of the alpha angle bevel layout, the ordered and accurate distribution of electrode sites in three-dimensional space is realized, so that the spatial resolution of signal recording is greatly improved.

[0026] 2. Implant rigidity and biocompatibility: the three-dimensional structure curled in the application and the optional central support body provide the rigidity required for implantation, so that it can be directly implanted without the need for complex auxiliary tools; the overall structure after completion still maintains flexibility, matches the modulus of brain tissue, and reduces the foreign body reaction of long-term implantation.

[0027] 3. System packaging convenience: the bendable connecting neck in the application allows the pad part to be fixed flat on the skull, and the probe part is inserted vertically into the brain, greatly improving the convenience and reliability of system packaging and reducing the failure caused by lead bending fatigue.

[0028] 4. Functional integration: the central support body can have electrical stimulation and drug delivery functions; the tail part can integrate active circuits to realize in-situ signal processing and multiplexing, solving the lead bottleneck problem caused by high channel number.

[0029] 5. Preparation controllability and high reliability: the preparation process is based on mature semiconductor micro-nano processing, has high precision and good consistency; the curling process can be accurately controlled by adjusting the speed of the precision rotary table to control the diameter and pitch; interlayer filling can be further used to ensure the mechanical stability and electrical insulation reliability of the structure. BRIEF DESCRIPTION OF DRAWINGS

[0030] Figure 1 is a structural schematic diagram of a planar flexible electrode precursor in an embodiment of the application, including a partial enlarged view, which shows the layout of the electrode sites on the bevel.

[0031] Figure 2 is a three-dimensional structural schematic diagram of a three-dimensional high-density neural electrode in an embodiment of the application.

[0032] Figure 3 is a top view and a side view of a three-dimensional high-density neural electrode in an embodiment of the application, which shows the distribution of the electrode on the spiral form.

[0033] Figure 4 is a schematic diagram of the curling forming process in an embodiment of the present application.

[0034] Figure 5 is a schematic diagram of the structure of the probe head in another embodiment of the present application.

[0035] Figure 6 is a schematic diagram of the layout of the planar flexible electrode precursor with integrated transistor array at the tail in an embodiment of the present application, with a total of 2048 channels (128x16).

[0036] Explanation of the reference numerals in the drawings: 10 - planar flexible electrode precursor 11 - flexible substrate 12 - metal connection line 13 - electrode site 14 - pad array 15 - precursor long side direction 16 - bevel electrode direction 17 - connecting neck 20 - three-dimensional high-density neural electrode 21 - central support body 22 - spiral path 30 - transistor array a - tilt angle DETAILED DESCRIPTION

[0037] The present application will be described in detail below with reference to the drawings and specific embodiments. In the technical solution of the present application, if the component model, material name, connection structure, line structure, control method, algorithm and other features are not explicitly described, they are all considered as common technical features disclosed in the prior art.

[0038] The implementation of the present application will be described below by specific embodiments. Those skilled in the art can easily understand other advantages and effects of the present application from the disclosure of the present application. Although the description of the present application will be introduced in combination with the preferred embodiments, this does not mean that the features of the present application are limited to the embodiments. On the contrary, the purpose of introducing the present application in combination with the embodiments is to cover other options or modifications that can be extended based on the claims of the present application. In order to provide a deep understanding of the present application, many specific details will be included in the following description. The present application can also be implemented without using these details. In addition, in order to avoid confusion or obscure the focus of the present application, some specific details will be omitted in the description.

[0039] In the description of the present application, it should be noted that unless otherwise explicitly specified and limited, the terms "mounting", "connection", "connecting" should be understood in a broad sense, for example, it can be fixed connection, or detachable connection, or integrally connected; it can be mechanical connection, or electrical connection; it can be directly connected, or indirectly connected through an intermediate medium, or the internal communication of two elements. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0040] In addition, "upper", "lower", "left", "right", "top", "bottom", "horizontal", "vertical" used in the following description should be understood as the orientation shown in the section and the related drawings. The relative terms are only for the convenience of description, and do not mean that the device described thereby should be manufactured or operated in a particular orientation, and therefore should not be understood as a limitation on the present application.

[0041] It can be understood that although the terms "first", "second", "third" and the like are used herein to describe various components, regions, layers and / or parts, these components, regions, layers and / or parts should not be limited by these terms, and these terms are only used to distinguish different components, regions, layers and / or parts. Therefore, the first component, region, layer and / or part discussed below can be referred to as the second component, region, layer and / or part without departing from some embodiments of the present application.

[0042] The implementation process of the technical solutions of the present application will be described in detail below through a plurality of embodiments without limitation. Those skilled in the art should understand that the specific embodiments described herein are only used to explain the present application, and not to limit the protection scope of the present application.

[0043] Overall, the present application discloses a three-dimensional spiral high-density neural electrode based on bevel layout preset and a preparation method thereof. The neural electrode comprises an elongated probe body, the outer surface of which is spiral-shaped; a plurality of electrode sites are distributed along the multi-layer spiral path and exposed to contact biological tissues. The spatial distribution configuration of the electrode sites is determined by the preset layout of the planar flexible electrode precursor, specifically, a plurality of electrode sites are pre-manufactured on one or more bevels at an angle of α with the long side of the precursor. After the planar precursor is curled and shaped, the electrode sites on the bevels are accurately positioned on the three-dimensional spiral path. The present application solves the technical problem of difficult accurate control of site distribution in three-dimensional electrode space through a unique two-dimensional bevel electrode design, significantly increases the density and number of electrodes through the spiral multi-layer structure, and provides a new generation of solution for high-precision brain-computer interface, deep brain stimulation and stereotactic electroencephalogram.

[0044] One aspect of the present application relates to a three-dimensional high-density neural electrode. The electrode comprises an elongated probe body, at least partially structured to define a helical surface; and a plurality of electrode sites distributed along a helical path of the helical surface and exposed for contacting biological tissue. The spatial distribution pattern of the electrode sites is determined by a pre-set layout of a planar flexible electrode precursor, on which the electrode sites are pre-fabricated on one or more slanted lines at an angle a to the long edge of the precursor.

[0045] According to some embodiments of the present application, a neural electrode device with high-density recording / stimulating sites is provided. The device can be used for recording and / or stimulating neural electrical activities. The size of the device can be adjusted according to practical needs (e.g., diameter 50-1000 μm, length 0.5-15 cm) so that the device can be applied to various organisms and brain regions, including cerebral cortex and deep brain regions. The arrangement of electrode sites (including number, position and spacing) can be designed according to practical needs to achieve high spatiotemporal resolution recording of neural network activities in specific brain regions.

[0046] Figure 1 is a structural schematic diagram of an exemplary planar flexible electrode precursor according to some embodiments of the present application. Figure 1 is a local enlarged view of the electrode sites on the slanted edge.

[0047] The planar flexible electrode precursor 10 can be used to prepare a three-dimensional high-density neural electrode. Before designing the planar flexible electrode precursor 10, a mathematical modeling and design optimization system for the electrode needs to be established. A parameterized geometric model based on Archimedes spiral (r = a + bθ) is constructed, and a curvature compensation parameter is introduced according to experimental results to accurately describe the site spatial coordinates; key parameters such as the diameter of the rotation axis, the edge a angle, the site size, the PI layer thickness and the stress gradient are optimized; and COMSOL finite element software is used for mechanical simulation to optimize the coiled structure.

[0048] Then, the planar flexible electrode precursor 10 is prepared by micro-nano processing technology. As shown in Figure 1 The planar flexible electrode precursor 10 comprises a flexible substrate 11, a metal connection line 12, electrode sites 13 and a pad array 14. The electrode sites 13 are pre-set on the slanted edge electrode direction 16 at an angle a to the long edge direction 15 of the precursor, and this unique design is the key to achieving the accurate distribution of electrodes in the final three-dimensional structure.

[0049] In some embodiments, the a angle can range from 1° to 89°, preferably 60° to 88°. This angle range has been verified by a large number of experiments to achieve the optimal electrode spatial distribution density and uniformity after three-dimensional coiling.

[0050] The size of the electrode sites 13 can range from 5-1000 μm, preferably 10-50 μm, to accommodate the need of recording single neuron or neuron cluster activities. The distance between adjacent electrode sites can be adjusted according to the spatial resolution requirement, typically ranging from 20-200 μm. The electrode material can include titanium, gold, platinum, iridium or their oxides, as well as biocompatible conductive materials such as titanium nitride.

[0051] The metal connecting lines 12 connect the electrode sites 13 with the pad array 14, with a line width of 1-20 μm and a distance between adjacent lines of 2-20 μm.

[0052] The pad array 14 is used to connect external circuits and can be arranged at the tail of the precursor body. In some embodiments, a bendable connecting neck 17 can be provided between the pad array 14 and the precursor body, facilitating a 90 degree bending of the pads to accommodate different implantation angles and connection requirements.

[0053] Figure 2 Figure 3 shows a schematic diagram of a three-dimensional high-density neural electrode according to some embodiments of the present application. Figure 2 Figure 3 is a perspective view, including a top view and a side view, showing the distribution of the electrode in a spiral form.

[0054] The three-dimensional high-density neural electrode 20 is obtained by rolling the planar flexible electrode precursor 10 into a shape. As shown in Figure 2 the electrode presents an elongated spiral structure with the electrode sites 13 precisely exposed on the spiral path 22. A central support 21 is located at the center of the electrode, providing mechanical support and can serve as a functional component.

[0055] As shown in Figure 3, viewed from the top Figure 3A , the electrode sites 13 are evenly distributed in the circumferential direction; viewed from the side Figure 3B , the electrode sites 13 present an ordered arrangement in the axial direction. This three-dimensional distribution allows the electrode to collect neural signals from multiple spatial dimensions, greatly improving the efficiency and density of signal collection.

[0056] The surface of the central support 21 is coated with biocompatible materials, including metals, ceramics or polymer materials. In some embodiments, the central support 21 can be a hollow structure for delivering drugs or reagents. The diameter of the central support 21 can range from 50-500 μm, preferably 100-300 μm. In some embodiments, the central support 21 is a solid structure, and the central support is used for transmission of optical or electrical stimulation signals.

[0057] Figure 4A schematic diagram of a coiling process according to some embodiments of the present application is shown. The coiling process is accomplished by a precision device, which includes a section of a fixed planar flexible electrode precursor 10, and a pulling force applied to the other end to rotate it around a central support 21 until a predetermined helical structure is formed.

[0058] In some embodiments, the coiling process is performed by a pulling system, which can be a precision rotary table. By controlling the rotation speed and pulling force of the precision rotary table, the diameter and pitch of the final structure can be precisely controlled. The coiling speed is usually in the range of 1-100 rpm, and the pulling force is in the range of 0.01-1 N.

[0059] The formed structure is fixed by biocompatible adhesive or UV-cured resin. There can be gaps between the layers filled with high-molecular materials to enhance the mechanical stability and electrical insulation of the structure.

[0060] Figure 5 A schematic diagram of a structure with a helical tapering probe tip according to another embodiment of the present application is shown. The helical layers and the spacing between the layers depend on the size of the angle a. After the coiling process, the probe tip naturally forms a tapering structure.

[0061] Figure 6 A schematic diagram of a planar flexible electrode precursor layout with integrated transistor array at the tail according to some embodiments of the present application is shown. This embodiment shows a specific implementation of 2048 channels (128 signal lines x 16 gate control lines, 144 interfaces).

[0062] One end of the transistor array 30 (drain) is electrically connected to the electrode site 13, and the other end (source) is connected to the pad array 14. There are 16 gate lines for 128 channels sharing one gate. The above design constitutes an active electrode structure for implementing signal multiplexing. This design can significantly reduce the number of external connection interfaces and improve system integration. The size of each transistor unit can be in the range of 20x20 μm 2 to 100x100 μm 2 .

[0063] In some embodiments, the device can also integrate functional units including temperature sensors, pH sensors, or neurochemical detection electrodes, etc. to realize multi-modal signal acquisition.

[0064] The three-dimensional high-density neural electrode prepared by the present application can be widely used in high-precision brain-computer interfaces, deep brain stimulation (DBS), and stereoelectroencephalography (SEEG) devices, etc.

[0065] The above examples are merely preferred embodiments of the present application, and do not limit the patent scope of the present application. Any equivalent structure or process transformation, or direct or indirect application in other related technical fields, based on the content of the present application specification and drawings, are also included in the patent protection scope of the present application.

[0066] Example 1 A basic structure of three-dimensional high-density neural electrode and preparation thereof The present example elaborates a specific preparation process and core structural features of a three-dimensional high-density neural electrode. The device has a three-dimensional spiral electrode structure, which can be formed by rolling a planar flexible precursor with a specific design.

[0067] First step: micro-nano processing preparation of planar flexible electrode precursor Referring to Figure 1 , the planar flexible electrode precursor 10 is prepared by the following steps: A 4-inch silicon Handle wafer with 300 nm thermal oxide on the surface is selected as the processing substrate. First, a 300 nm thick aluminum layer is deposited on the wafer as a sacrificial layer by electron beam evaporation. Then, a polyimide precursor solution (model HD-2610) is coated using a spin coating process, and after stepwise temperature curing (100°C / 5 minutes + 200°C / 10 minutes + 300°C / 60 minutes), a flexible substrate 11 with a thickness of 5 μm is formed.

[0068] s1813 photoresist is used to define electrode and wire patterns on the polyimide substrate using photolithography. Then, a 10 nm thick titanium (Ti) adhesion layer and a 300 nm thick gold (Au) conductive layer are deposited in sequence by magnetron sputtering technology. The photoresist and the metal thereon are removed by lift-off process to form precise metal connection lines 12 and electrode sites 13 distributed at the ends of the lines. The key innovation of the present application is that the electrode sites 13 (circular, diameter 20 μm) are not randomly or conventionally arranged, but are pre-designed and accurately manufactured on a diagonal line 16 at an angle of α = 88° to the long edge direction 15 of the flexible substrate (see Figure 1 partial enlarged view). This specific angle is optimized to ensure that after the planar structure is rolled, the electrode sites can form the desired spiral distribution in three-dimensional space.

[0069] After the patterning of the metal layer, a 5 μm thick layer of polyimide is spin-coated and cured again as the upper encapsulation layer, covering all the metal connection lines 12 to provide electrical protection and insulation. By a reactive ion etching (RIE) process with oxygen and carbon tetrafluoride (CF4) as etching gases, the polyimide above the electrode sites 13 area and the tail pad array 14 area is selectively removed, exposing these functional interfaces. Finally, the processed wafer is immersed in an aluminum etchant (e.g., Type A from Transene Company Inc.) to dissolve the aluminum sacrificial layer, thus releasing the complete, flexible planar electrode precursor 10 from the rigid silicon Handle wafer, and after a thorough rinse with deionized water, the precursor is dried for use.

[0070] Second step: coiling of the three-dimensional helical structure Referring to Fig. 3, Figure 4 and Figure 5 the above prepared planar flexible electrode precursor 10 is coiled into a three-dimensional structure: A platinum-iridium (Pt-Ir) alloy wire with a diameter of 200 μm is provided as the central support 21. The material is chosen based on its excellent biocompatibility, high mechanical strength, good electrical conductivity, and MRI compatibility. One end of the central support 21 is fixed to the rotation chuck of a precision coiling device.

[0071] The starting end of the planar flexible electrode precursor 10 (corresponding to the tip of the future probe) is carefully temporarily and initially fixed to the surface of the central support 21 with a small amount of biocompatible instant adhesive (e.g., cyanoacrylate). The precision rotation stage is activated and set to rotate at a constant speed of 30 revolutions per minute. At the same time, a pulling clamp controlled by a high-precision linear displacement stage holds the tail end of the precursor 10 (one end of the pad array 14) and applies a constant and small axial pulling force (about 0.08 N).

[0072] Under the precise rotation and traction, the planar flexible electrode precursor 10 is uniformly and smoothly coiled around the central support 21. Through real-time monitoring and feedback control, it is ensured that there is no wrinkle or misalignment during the coiling process. This process continues until the precursor 10 is completely coiled, finally forming a three-dimensional neural electrode 20 with an outer diameter of 300 μm, a length of about 2.0 cm, and a multi-layer (e.g., 5-8 layers) helical structure. Since the electrode sites 13 on the precursor 10 are pre-set on the 88° diagonal line, they are naturally and accurately positioned and exposed on the helical path 22 of the final three-dimensional structure (as shown in Figure 2 and Fig. 3), forming a pencil-like structure and achieving accurate mapping from two-dimensional design to three-dimensional spatial distribution.

[0073] Third step: structure fixation and functional integration After the coiling, the temporary fixed helical structure needs to be permanently solidified: A high-precision micro-droplet dispensing system is used to precisely drop a low-viscosity, biocompatible ultraviolet (UV) curing adhesive (e.g., Norland Optical Adhesive 81) onto the surface of the helical structure. Using capillary action, the UV adhesive quickly penetrates and fills all the tiny gaps between the layers. Subsequently, a UV light source with a wavelength of 365 nm is used to irradiate the structure from multiple angles, with an intensity of 100 mW / cm 2 for 120 seconds, allowing the UV adhesive to fully cure.

[0074] The interlayer filling material formed after curing (not separately labeled in the figure) plays a triple key role: Mechanical anchoring: firmly bonds each layer of flexible precursor together, forming a highly mechanically integrated overall structure, significantly enhancing the longitudinal stiffness of the probe (beneficial for implantation) and resistance to transverse shear forces.

[0075] Electrical insulation: effectively prevents short circuits or signal crosstalk between adjacent layer metal connection lines 12, ensuring electrical independence of each electrode channel.

[0076] Biocompatible encapsulation: provides an inert, stable barrier between the internal metal lines and biological tissue.

[0077] At this point, the central support body 21 is permanently encapsulated in the center of the electrode, becoming an inseparable functional component of the neural electrode. It not only serves as a mandrel during preparation, but also continues to provide core mechanical support in the final product, and can be used as a separate macroelectrode for future electrical stimulation applications.

[0078] Example 2 An active electrode with integrated multiplexing function This embodiment details the implementation of a highly integrated three-dimensional high-density neural electrode. Based on all the features of Example 1, the electrode further integrates active signal processing functions, achieving signal multiplexing through the introduction of a transistor array, fundamentally solving the fundamental contradiction between high-channel number electrodes and limited external connection interfaces.

[0079] This embodiment details the implementation of a highly integrated active three-dimensional high-density neural electrode. Based on all the features of Example 1, the electrode achieves on-chip signal switching and reading by introducing a transistor array and using an innovative multiplexing wiring architecture, fundamentally solving the core contradiction between ultra-high channel number recording and limited external leads.

[0080] First step: preparation of a planar flexible electrode precursor integrating a transistor array First, a 6-inch standard silicon Handle wafer was used as the processing substrate, and a 100-nm-thick nickel (Ni) layer was deposited on the surface thereof by an electron beam evaporation process, as a sacrificial layer for a subsequent release step.

[0081] Subsequently, the following micro-nano processing steps were performed: Preparation of a flexible substrate and a lower encapsulation layer: a polyimide (PI-2610) precursor solution was spin-coated on the wafer covered with the nickel sacrificial layer, and after soft baking (120°C, 2 minutes) and hard baking (350°C, 1 hour) at different temperatures, a 3-μm-thick patterned flexible substrate 11 was formed. The polyimide layer simultaneously served as the bottom insulating encapsulation of the subsequent transistor array.

[0082] Integration of a transistor array 30: on the flexible substrate 11, an NMOS transistor unit (25 μm × 25 μm in size) prepared in advance on a standard silicon CMOS process line was accurately transferred to a predetermined position on the polyimide substrate by using a laser-induced forward transfer (LIFT) technique. Subsequently, a thin layer of polyimide (PI-2610) was spin-coated and cured, for fixing, passivating, and insulating the transistor array.

[0083] Fabrication of metal interconnections: a hard mask (such as an aluminum layer) and a reactive ion etching (RIE) process were used to open contact holes in the polyimide layer covering the transistor array, to expose the source, drain, and gate metal pads of the transistor. Subsequently, a titanium / gold (Ti / Au, 10 / 100 nm) metal layer was deposited by photolithography and electron beam evaporation, and was patterned by a lift-off process, to form the first layer of metal interconnections connecting the transistor electrodes to subsequent circuit lines.

[0084] Fabrication of multilayer wiring and electrode sites: to achieve high-density wiring and avoid signal line crossings, a multilayer wiring technique was used. First, a 2-μm-thick polyimide layer was spin-coated as an interlayer dielectric, and was etched by RIE to form vias to the first layer of metal. Subsequently, the photolithography, metal deposition (Ti / Au), and lift-off processes were repeated to form the second layer of metal connection lines 12, electrode sites 13 distributed at the ends of the connection lines, and a pad array 14. The core of the present application is that the electrode sites 13 are precisely preset on a diagonal line at an angle of α = 60° to the long side direction 15 of the precursor. Each electrode site 13 (20 μm × 20 μm in size) is connected to the source electrode of a dedicated NMOS transistor through a metal connection line 12.

[0085] Fabrication of a low-impedance iridium oxide functional layer: After completing the prototype of gold electrode site 13, photolithography was performed again. Photoresist was used to precisely define the electrode site regions where impedance reduction was required, while other areas (including wires and pads) were completely covered and protected. A porous, oxygen-rich iridium oxide (IrOx) film with a thickness of approximately 500 nm was sputtered from the iridium target using an RF magnetron sputtering system. Subsequently, the photoresist and redundant IrOx film on it were removed using a lift-off process. This step reduced the electrode-electrolyte interface impedance by more than an order of magnitude, significantly improving the signal-to-noise ratio and stimulation efficiency of signal acquisition.

[0086] Innovative cabling design: such as Figure 6 As shown, this embodiment integrates a total of 2048 recording channels. The transistor array 30 employs a highly efficient row-column multiplexing architecture: the gates of 128 adjacent channel transistors are interconnected, sharing a single gate control line, thus forming 16 gate lines; simultaneously, the drains of the 16 channel transistors are interconnected via output buses, forming 128 output buses (16 × 128 = 2048). This design allows the bioelectrical signals from 2048 channels to be read out using only 144 physical leads through 16 gate control lines and 128 output buses, reducing the number of external connection interfaces by more than an order of magnitude compared to direct lead-out schemes.

[0087] Fabrication of the upper encapsulation layer and exposure of the pads: Finally, a 3μm thick layer of polyimide is spin-coated as the upper encapsulation layer to provide insulation protection for the entire structure. The electrode site 13 region and all 144 pads of the tail pad array 14 are selectively exposed by reactive ion etching (RIE).

[0088] Release precursor: The processed wafer is immersed in a 30% ferric chloride (FeCl3) solution and the nickel sacrificial layer is etched and dissolved at room temperature to release the complete planar flexible electrode precursor 10 that integrates the transistor array 30. After being thoroughly cleaned with deionized water, it is ready for use.

[0089] Step 2: Curling and System Integration Prepare the central support: Take a section of high-purity tungsten wire with a diameter of 100 μm as the central support 21. Tungsten material has extremely high rigidity, excellent biocompatibility and good conductivity, which can provide robust mechanical support and can also be used as a macroelectrode for DC electrical stimulation or impedance monitoring.

[0090] Precise coiling process: One end of the central support 21 is fixed on a precision rotary table. The starting end (head) of the planar flexible electrode precursor 10 is temporarily adhered to the surface of the central support 21 using micro ultraviolet curing glue. Start the precision rotary table to rotate the central support 21 at a constant speed of 30 revolutions per minute, while the tail of the precursor is pulled by a computer-controlled linear platform and a constant axial tension of about 0.1 N is applied. This process ensures that the precursor is uniformly and tightly coiled around the central support, and by precisely controlling the rotation speed and tension, a three-dimensional neural electrode 20 with a multi-layer spiral structure with an outer diameter of 250 μm and a length of about 5 cm is finally formed.

[0091] Permanent fixation and insulation: A low-viscosity, biocompatible ultraviolet curing resin (such as GM-30010) is introduced into the interlayer gap of the spiral structure using a vacuum-assisted capillary filling technique. Subsequently, the entire structure is irradiated from multiple angles using an ultraviolet light source, causing the resin to fully cure within a few minutes, forming a solid interlayer filling material that permanently shapes the multi-layer spiral structure and ensures electrical insulation between layers.

[0092] Step 3: Function verification and application advantages The final three-dimensional high-density neural electrode 20 integrates 2048 electrode sites 13. Due to the integration of the innovative row-column multiplexing architecture (16 gate lines x 128 output buses) inside, only 144 physical leads are needed to access all channels, greatly reducing the complexity and interconnection risk of system packaging.

[0093] In application, the electrode is implanted into the target brain area (such as the cerebral cortex or deep nuclear group). The electrode sites 13 designed based on the α angle form an orderly distribution in three-dimensional space, allowing efficient acquisition of neural signals. The external control circuit switches the signals of the selected row (128 channels) to the 128 output buses by sequentially applying activation voltages to the 16 gate lines, thereby achieving high-speed round-robin acquisition of all 2048 channel signals in a time-division multiplexing manner.

[0094] Example 3 Active three-dimensional high-density neural electrode with drug delivery function This embodiment details the implementation of a multifunctional highly integrated three-dimensional high-density neural electrode of the present application. Based on Example 2, the electrode further integrates a local drug delivery function, enabling simultaneous operation of electrophysiological recording, electrical stimulation intervention, and chemical drug intervention on neural activity, providing an unprecedented powerful tool for studying neural circuit function and treating nervous system diseases.

[0095] Step 1: Preparation of planar flexible electrode precursor integrating transistor array and microfluidic structure This step is basically the same as Example 2, using the same micro-nano processing technology to prepare a planar flexible electrode precursor 10 integrated with a 1024-channel transistor array. Key features include: Fabricating metal connection lines 12 and electrode sites 13 on the flexible polyimide substrate 11 Electrode sites 13 are arranged at an angle of a = 75° on the precursor The integrated transistor array 30 realizes a 32x32 multiplexing architecture Fabricating a pad array 14 for external connection Second step: preparing a hollow central support and curling Preparation of the hollow central support: Take a piece of fused quartz capillary with an outer diameter of 120 μm and an inner diameter of 80 μm as the central support 21. The quartz material has excellent biocompatibility, high insulation and good mechanical properties. The hollow lumen itself constitutes an independent macroscopic fluid channel.

[0096] Curling and alignment: Fix the hollow central support 21. Fix the starting end of the planar flexible electrode precursor 10, ensuring that the internal microfluidic outlet is spatially accurately aligned with the lumen inlet of the central support 21. Start the curling device to rotate and pull the precursor at a speed of 20 revolutions per minute, so that it is tightly wound around the central support 21.

[0097] Fixing: Since there is no gap between the layers of the spiral structure in this case, fixing the tail of the multi-layer spiral structure with UV curing resin can achieve fixation.

[0098] Interface connection: Using a ball mounting machine and a chip mounting machine, the external FPC ribbon and the pad array 14 are electrically connected, and the other end of the external FPC ribbon is connected to a control circuit board including a collection chip.

[0099] The electrodes prepared in this example have the ability of high-density recording, electrical stimulation, drug delivery and signal preprocessing, and this multi-mode operation enables researchers to monitor the changes in neural network activity in real time while applying chemical intervention, providing a powerful experimental tool for understanding neural circuit function.

[0100] The above only describes several most representative specific embodiments of the present application, but the protection scope of the present application is not limited thereto. Any changes, substitutions or equivalent improvements within the technical principles and technical solutions disclosed by the present application can be easily thought of by those skilled in the art, such as using different flexible materials (such as poly-p-xylylene), different metal materials (such as titanium nitride), or different curling and fixing methods (such as biocompatible hot melt adhesive), which should be included in the protection scope of the present application.

Claims

1. A three-dimensional spiral high-density neural electrode, characterized in that, include: A probe structure is formed by rolling up a planar flexible electrode precursor. At least one end of the probe structure has a helical outer surface, which is a three-dimensional helical configuration. Multiple electrode sites are distributed along a spiral path on the spiral outer surface of the probe structure. The electrode sites are used to contact biological tissue, and the size of the electrode sites is 5-1000 μm. The spatial distribution of the electrode sites matches the edge of the planar flexible electrode precursor. On the planar flexible electrode precursor, the electrode sites are located on one or more straight lines that are inclined at an angle α to the axis of the probe structure.

2. The three-dimensional spiral high-density neural electrode according to claim 1, characterized in that, The probe structure is a multi-layered spiral structure formed by curling and fixing the planar flexible electrode precursor around a central support, with 2-100 layers.

3. The three-dimensional spiral high-density neural electrode according to claim 2, characterized in that, The central support body serves as the central support body for the planar flexible electrode precursor, and the central support body is made of at least one material selected from platinum-iridium alloy, tungsten, stainless steel, quartz, and polymer. The surface of the central support is coated with a biocompatible material; The central support is a hollow structure and is used for drug delivery. or, The central support is a solid structure and is used for the transmission of optical and electrical stimulation signals.

4. The three-dimensional spiral high-density neural electrode according to claim 1, characterized in that, The range of α is 60°-88°.

5. A three-dimensional spiral high-density neural electrode according to claim 1, characterized in that, The probe structure is a multi-layered spiral structure with gaps between the layers. These gaps are filled with a polymer material, which is either a UV-curable resin or polyimide. The polymer material is used to enhance mechanical stability and electrical insulation. The three-dimensional spiral high-density neural electrode includes a pad array, which is electrically connected to the electrode site via a metal connection line for connecting to an external circuit. A flexible connection neck is provided between the pad array and the planar flexible electrode precursor. The pad array can be bent at least 90 degrees along the connection neck to adapt to different connection spaces and directions.

6. A method for preparing a three-dimensional spiral high-density neural electrode as described in any one of claims 1 to 5, characterized in that, Includes the following steps: S1. Fabricating a planar flexible electrode precursor, wherein multiple electrode sites and metal connection lines are formed on a flexible substrate using micro-nano fabrication technology, wherein the electrode sites are located on one or more straight lines at an angle to the long side of the substrate, and the angle is non-zero. S2. The planar flexible electrode precursor is rolled into a slender three-dimensional probe structure, so that the probe structure has a spiral outer surface, wherein the rolling process controls the rolling parameters to distribute the electrode sites along the spiral path. S3. Fix the formed probe structure so that the electrode sites are exposed on the helical path, and ensure the mechanical stability and electrical insulation of the structure.

7. The method for preparing a three-dimensional spiral high-density neural electrode according to claim 1, characterized in that, In S1, the specific process for preparing the planar flexible electrode precursor includes: A silicon wafer or glass substrate is used as the processing carrier, and a sacrificial layer is deposited on it; A flexible substrate is formed on the sacrificial layer, and then cured by spin-coating a polyimide precursor liquid and stepwise temperature increase. The electrode sites and metal interconnect patterns are determined on a flexible substrate using photolithography, and a conductive structure is formed by metal deposition and lift-off processes. The electrode sites are pre-set on one or more straight lines that are inclined at an angle to the long side of the substrate. A polyimide encapsulation layer is applied and electrode sites and pad areas are selectively exposed by reactive ion etching. The complete planar flexible electrode precursor is then released by etching the sacrificial layer. S1 also includes an integrated transistor array at the tail of the planar flexible electrode precursor. The transistor array is electrically connected to the electrode sites on the planar flexible electrode precursor. The integration process includes processing the transistor units onto the flexible substrate using micro-nano fabrication technology, or transferring the transistor units onto the flexible substrate using transfer technology, and forming a metal interconnect to constitute an active electrode structure for signal multiplexing to reduce the number of external connection interfaces.

8. The method for preparing a three-dimensional spiral high-density neural electrode according to claim 1, characterized in that, In S2, the specific process of rolling the planar flexible electrode precursor into a slender three-dimensional probe structure includes: A rod made of biocompatible material was selected as the central support. The starting end of the planar flexible electrode precursor is fixed to the surface of the central support. The system uses a precision rotary table connected to a central support, which rotates the central support while linearly pulling the tail end of the precursor. By controlling the rotation speed and traction force of the precision rotary table, the coiling parameters are adjusted to cause the precursor to coil around the central support, forming a multi-layered spiral structure. The coiling process is controlled by parameters to ensure that the electrode sites are distributed along the spiral path.

9. The method for preparing a three-dimensional spiral high-density neural electrode according to claim 1, characterized in that, In S3, the specific process of fixing the formed probe structure includes: Biocompatible curing materials are used to fill the interlayer gaps through dispensing or capillary action; The curing material is polymerized by ultraviolet light irradiation, thereby fixing the structure. The fixing process exposes the electrode sites to the helical path.

10. An application of the three-dimensional spiral high-density neural electrode as described in any one of claims 1 to 5, characterized in that, The three-dimensional spiral high-density neural electrode is used in high-precision brain-computer interfaces, deep brain stimulation or stereotactic electroencephalography (EEG) devices. The distribution of the electrode sites along the spiral path on the three-dimensional spiral high-density neural electrode enables high-density recording or electrical stimulation of neural signals.

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