Three-dimensional space-expanding spiral neural electrode, preparation method and application

Abstract

The present application relates to a kind of three-dimensional space development type helical nerve electrode, preparation method and application, comprising: spiral probe structure formed by the curl of plane flexible electrode precursor;Multiple flexible extension electrode structures are arranged on the spiral path of spiral probe structure, and form cantilever flexible structure by extending outward from plane flexible electrode precursor;Multiple electrode sites are arranged on flexible extension electrode structure;On plane flexible electrode precursor, flexible extension electrode structure is arranged along the straight line with the axial inclination angle of spiral probe structure, to form the electrode array that is distributed along spiral path and three-dimensional development outward after curling.Compared with prior art, the present application realizes the three-dimensional space distribution of electrode site in axial, circumferential and radial by the collaborative design of spiral probe structure and cantilever flexible extension electrode structure, significantly improves the spatial resolution and coverage of nerve signal acquisition and electrical stimulation, while having good tissue adaptability and biocompatibility.

Description

Technical Field

[0001] This invention relates to the fields of neural electrodes and microelectronics science and technology, and in particular to a three-dimensional spatially unfoldable spiral neural electrode, its preparation method, and its application. Background Technology

[0002] With the rapid development of neural engineering and brain-computer interface technology, implantable neural electrodes capable of long-term stable recording and modulation of neural signals in vivo have become a research hotspot. Neural electrodes are widely used in brain-computer interfaces, treatment of neurological diseases (such as deep brain stimulation for Parkinson's disease), epilepsy monitoring, and basic neuroscience research. Their performance directly affects the quality of neural signal acquisition and stimulation effects.

[0003] Traditional neural electrodes are mainly divided into two categories: rigid electrodes and flexible electrodes. Rigid electrodes are usually made of materials such as silicon and metals, which have the advantages of structural stability and high processing precision. However, because their elastic modulus is much higher than that of biological tissue, they are prone to causing significant mechanical mismatch after implantation, leading to tissue damage, inflammatory response and glial scar formation, thereby reducing signal quality and limiting long-term stability.

[0004] To address these issues, much research in recent years has shifted towards flexible neural electrodes. Flexible electrodes typically use biocompatible materials such as polyimide and parylene as a substrate, possessing excellent flexibility that can, to some extent, match the mechanical properties of brain tissue, thereby reducing implantation damage and improving long-term stability. Existing flexible electrode structures mainly include two-dimensional planar electrode arrays, thin-film electrodes, and flexible probe structures.

[0005] However, existing flexible electrodes are mainly concentrated in two-dimensional or quasi-two-dimensional structures, with electrode sites typically distributed in a single plane or linearly arranged along the probe axis. This structure has significant limitations in spatial coverage, making it difficult to achieve high-density acquisition of signals in the three-dimensional space of neural tissue, especially in complex brain regions or deep structures, where it is difficult to comprehensively acquire neural activity information.

[0006] To improve spatial coverage, some technical solutions propose fabricating electrodes as three-dimensional structures. For example, some solutions employ multi-layer stacked or folded structures to increase the spatial distribution density of electrode sites; others involve rolling or self-assembling planar flexible electrodes into tubular or helical structures, distributing electrode sites circumferentially, thereby achieving three-dimensional spatial sampling to some extent. Furthermore, some technologies utilize deployable or micromechanical structures to allow the electrodes to unfold after implantation, increasing coverage.

[0007] While the aforementioned technologies have improved the spatial distribution capability of electrodes to some extent, the following shortcomings remain. Electrode sites in existing helical or tubular structures are mostly concentrated on the surface of the structure. Although they are distributed circumferentially, they still lack the ability to expand radially outward, making it difficult to achieve true three-dimensional spatial deployment. Most existing electrode sites are fixed to the substrate surface, lacking independent flexible extension structures. In complex biological tissue environments, they cannot actively adapt to local tissue deformation, leading to insufficient or unstable contact, thus affecting signal quality. Some three-dimensional electrode structures rely on pre-set geometric shapes and lack further deformation capability after implantation, failing to dynamically adjust according to the tissue environment, potentially causing local stress concentration or tissue damage.

[0008] To further improve the three-dimensional spatial coverage of complex brain regions or deep structures, some existing technologies have designed electrodes in a three-dimensional configuration. For example, patent document CN121197664A discloses a three-dimensional helical high-density neural electrode, which forms a probe structure with a helical outer surface by rolling up a planar flexible electrode precursor, and distributing multiple electrode sites along the helical path. However, in the technical solution disclosed in CN121197664A, the electrode sites are all directly set on the outer surface of the helical structure, that is, the electrode sites are still fixed to the base surface, lacking the ability to extend independently or radially outward relative to the base. This structural feature means that in actual neural signal acquisition and stimulation, the accessible spatial range of the electrode sites is strictly limited by the geometric envelope of the helical structure surface, making it difficult to actively extend to radial tissue regions away from the structural surface. Essentially, it fails to endow the electrode sites with the ability to expand independently in three-dimensional space relative to the structural body.

[0009] Therefore, there is an urgent need for a new neural electrode structure that, while maintaining the low-damage advantage of flexible electrodes, can effectively deploy electrode sites in three-dimensional space and has good tissue adaptability and spatial sampling capabilities, thereby improving the performance of neural signal acquisition and stimulation. Summary of the Invention

[0010] To address the issues of insufficient spatial coverage, limited three-dimensional sampling capability, and insufficient tissue adaptability of existing flexible electrodes, this application proposes a three-dimensional spatially deployable spiral neural electrode, its preparation method, and its application. This electrode architecture combines a spiral probe structure with a cantilevered flexible extension electrode structure, maintaining the low-damage characteristics of flexible electrodes while achieving a three-dimensional spatial distribution of electrode sites in the axial, circumferential, and radial directions. This significantly improves the spatial resolution and coverage of neural signal acquisition and electrical stimulation.

[0011] The purpose of this invention is to overcome the defects of the prior art by providing a three-dimensional spatial unfolding spiral neural electrode, its preparation method, and its application.

[0012] The objective of this invention can be achieved through the following technical solutions: The first aspect of the present invention provides a three-dimensional spatial unfolding spiral neural electrode, comprising: a spiral probe structure formed by curling a planar flexible electrode precursor; Also includes: Multiple flexible extension electrode structures are disposed on the spiral path of the spiral probe structure, and each flexible extension electrode structure extends outward from the planar flexible electrode precursor to form a cantilevered bendable structure. Multiple electrode sites are disposed on the flexible extended electrode structure. The electrode sites are used to contact biological tissue to collect nerve signals and / or perform electrical stimulation. The size of the electrode sites is 5-1000 μm. In the planar flexible electrode precursor, the flexible extended electrode structure is arranged along a straight line at an angle α to the axis of the spiral probe structure, so as to form an electrode array distributed along the spiral path and unfolding outward in three dimensions after being rolled up.

[0013] Furthermore, the flexible extended electrode structure and the planar flexible electrode precursor used to form the helical probe structure are integrally fabricated from the same flexible substrate. After being rolled up, the flexible extended electrode structure extends outward from the outer surface of the spiral probe structure to form a cantilever structure. The cantilever structure is used to adapt to tissue resistance during or after implantation into biological tissue, thereby enhancing contact stability with biological tissue or reducing tissue damage.

[0014] Furthermore, each of the flexible extended electrode structures is provided with at least one electrode site, and multiple electrode sites on the same flexible extended electrode structure are distributed in a one-dimensional linear distribution, an array distribution, or a non-uniform distribution along the extension direction of the flexible extended electrode structure, with a spacing of 10-200 μm between adjacent electrode sites.

[0015] Furthermore, the flexible extension electrode structure has a length of 10μm-1mm, a width of 5-200μm, and a thickness of 0.5-50μm; the flexible extension electrode structure is one or more of a strip structure, a curved structure, or a forked structure, so as to form a spatial distribution with different radial extension depths after being rolled up, thereby adapting to the sampling needs of different brain tissues.

[0016] Furthermore, the multiple flexible extended electrode structures are distributed periodically or non-periodically along the helical path, and the lengths, number of electrode sites, or distribution densities of the different flexible extended electrode structures are set to be different from each other, so that the electrode array has varying electrode site densities at different axial positions and radial depths of the helical probe structure, thereby forming a multi-scale spatial distribution structure for differential sampling or stimulation of target neural tissue.

[0017] Furthermore, the tilt angle α ranges from 60° to 85°; The spiral probe structure is a multi-layered spiral structure formed by the planar flexible electrode precursor curling around a central support, with 2-100 layers. Adjacent layers are filled with a fixing layer made of UV-curable resin or polyimide. The fixing layer is used to enhance mechanical stability and electrical insulation, and the fixing layer avoids the free end of the flexible extension electrode structure to maintain the bendability of the flexible extension electrode structure.

[0018] Furthermore, it also includes a pad array, which is electrically connected to each of the electrode sites via metal connection lines; A flexible connecting neck is provided between the pad array and the planar flexible electrode precursor. The connecting neck is used to achieve bending at any angle to alleviate mechanical stress concentration and adapt to different external connection spaces and directions.

[0019] Furthermore, the planar flexible electrode precursor and the flexible extension electrode structure are integrally made of the same biocompatible flexible material, and there is no mechanical connection interface between the flexible extension electrode structure and the planar flexible electrode precursor. The biocompatible flexible material is at least one of polyimide or Parylene.

[0020] A second aspect of the present invention provides a method for preparing a three-dimensional spatially unfolded spiral neural electrode as described above, comprising the following steps: S1. Preparation of planar flexible electrode precursor: Multiple flexible extended electrode structures are formed on a flexible substrate using micro-nano fabrication technology. The flexible extended electrode structures are integrally prepared with the flexible substrate, and electrode sites and metal connection lines are formed on the flexible extended electrode structures. The flexible extended electrode structure is arranged on the planar flexible electrode precursor along a straight line at an angle α to the preset curling axis, so as to be distributed along a spiral path after subsequent curling and forming. S2. The planar flexible electrode precursor is rolled into a spiral probe structure, so that the flexible extended electrode structure is distributed along the spiral path and extends outward from the outer surface of the spiral probe structure to form a three-dimensional spatial unfolding structure. S3. Fix the curled structure by filling the interlayer with UV-curable resin or polyimide and curing it, with the filling area avoiding the free end of the flexible extended electrode structure, so that the flexible extended electrode structure maintains its outward unfolded state and bendable characteristics, and exposes the electrode sites in three-dimensional space.

[0021] The third aspect of the present invention is an application of the three-dimensional spatial unfolding spiral neural electrode as described above, wherein the three-dimensional spatial unfolding spiral neural electrode is used to implant into target neural tissue to achieve high-density neural signal acquisition and / or electrical stimulation in three-dimensional space through the electrode sites on the flexible extended electrode structure in brain-computer interface, deep brain stimulation or stereotactic electroencephalography equipment, and to cover neural regions at different depths and orientations under a single implantation path.

[0022] Compared with the prior art, the present invention has the following beneficial effects: This invention forms a helical probe structure by curling a planar flexible electrode precursor, and sets up a cantilevered flexible extension electrode structure extending outward from the planar flexible electrode precursor along the helical path. This allows the electrode sites to be distributed not only axially and circumferentially along the helical path, but also radially outward through the flexible extension electrode structure, thereby forming a discretely distributed electrode array in three-dimensional space. This structural design effectively solves the problems of insufficient spatial coverage and limited three-dimensional sampling capability of existing flexible electrodes, significantly improving the spatial resolution and coverage of neural signal acquisition and electrical stimulation.

[0023] The flexible extension electrode structure and the spiral probe structure are integrally formed from the same flexible substrate, forming a cantilevered and bendable structure. During or after implantation into biological tissue, it can adapt to the tissue resistance and bend accordingly, thereby enhancing the contact stability with biological tissue, reducing local stress concentration, minimizing tissue damage, and improving long-term stability and biocompatibility after implantation.

[0024] By arranging flexible extension electrode structures along a straight line at an angle α to the axis of the spiral probe structure on the planar flexible electrode precursor, the spatial distribution of electrode sites along the spiral path can be precisely controlled after being rolled up. Combined with the design of flexible extension electrode structures of different lengths, shapes and distribution densities, a multi-scale spatial distribution structure is formed, which can adapt to the differentiated sampling or stimulation needs of different brain tissues. Attached Figure Description

[0025] Figure 1 This is a schematic diagram of the planar unfolded structure of the three-dimensional spatial unfolding spiral nerve electrode in an embodiment of the present invention; Figure 2 These are schematic diagrams illustrating various forms of the flexible extended electrode structure in embodiments of the present invention; Figure 3This is a schematic diagram of a planar flexible electrode precursor being rolled into a spiral probe structure in an embodiment of the present invention; Figure 4 This is a side view of the three-dimensional spatial unfolding spiral nerve electrode in an embodiment of the present invention; Figure 5 This is a schematic diagram of the structure in an embodiment of the present invention, showing that the connecting neck adopts a horizontally extended staggered layout.

[0026] Among them, 10-planar flexible electrode precursor, 11-flexible substrate, 12-connection neck, 13-pad array, 14-metal connection line, 15-flexible extension electrode structure, 16-electrode site on extension structure, 17-central support, and α-tilt angle. Detailed Implementation

[0027] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments. Any preparation methods, materials, structures, or composition ratios not explicitly described in this technical solution are considered common technical features disclosed in the prior art or existing commercial products.

[0028] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of the embodiments of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used in this specification is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

[0030] Example 1: like Figure 1 and Figure 4 As shown, this embodiment provides a three-dimensional spatial unfolding spiral neural electrode, the core of which is to realize the three-dimensional spatial distribution of electrode sites in the axial, circumferential and radial directions by transforming the spatial configuration of the planar flexible electrode precursor 10.

[0031] The neural electrode includes a helical probe structure formed by curling a planar flexible electrode precursor 10. Specifically, the planar flexible electrode precursor 10 has a thin film shape with a specific geometric contour in its planar state, and its main region is a flexible substrate 11 on which conductive lines and electrode structures are formed using micro- and nano-fabrication processes. When the planar flexible electrode precursor 10 is curled around a central support 17, the original planar structure is transformed into a three-dimensional helical shape extending along the axial direction, forming a helical probe structure. The outer surface of this helical probe structure forms a continuous helical path, providing a basic framework for the spatial arrangement of electrode sites. It should be understood that although... Figure 3 The diagram shows a method of curling around the central support 17, but in other embodiments, a self-supporting curling method without a central support can also be used, as long as a stable spiral probe structure can be formed.

[0032] Along the helical path of the helical probe structure, multiple flexible extension electrode structures 15 are provided, each extending outward from the planar flexible electrode precursor 10 to form a cantilevered, bendable structure. It should be noted that the flexible extension electrode structures 15 are not attached to the helical probe structure after being rolled up, but are integrally formed onto the edge region of the flexible substrate 11 while the planar flexible electrode precursor 10 is still in a planar state. Figure 1 As shown, on the planar flexible electrode precursor 10, the flexible extension electrode structure 15 is arranged along a straight line at an angle α to the axis of the spiral probe structure.

[0033] When the planar flexible electrode precursor 10 is rolled up, the flexible extension electrode structures 15, originally arranged along an inclined straight line, undergo spatial remapping as the flexible substrate 11 bends, naturally distributing along a helical path. Since the flexible extension electrode structures 15 extend outward from the edge of the flexible substrate 11, after rolling, these structures unfold outward from the outer surface of the helical probe structure, forming a radially extending cantilevered flexible structure. This planar inclined arrangement determines the mapping relationship of the three-dimensional helical unfolding morphology, allowing the electrode sites to not only be distributed axially and circumferentially along the helical path but also to extend radially outward through the cantilevered structure, thus forming a discretely distributed electrode array in three-dimensional space. The specific value of the tilt angle α determines the pitch distribution and radial unfolding density of the flexible extension electrode structures 15 after rolling.

[0034] Multiple electrode sites 16 are disposed on the flexible extended electrode structure 15. These electrode sites 16 are used to contact biological tissue to acquire neural signals and / or perform electrical stimulation. The electrode sites 16 are functional regions that directly form an electrochemical interface with neurons or neural tissue, and their size ranges from 5 to 1000 μm. When the electrode site size is small, for example, in the range of 5 to 50 μm, a single electrode site can contact fewer neurons, thereby achieving higher single-cell recording resolution, suitable for scenarios requiring precise differentiation of individual neuronal firing activity; however, excessively small sizes can lead to a significant increase in interfacial impedance, reducing signal quality. When the electrode site size is large, for example, in the range of 200 to 1000 μm, the contact area between the electrode site and the tissue increases, and the interfacial impedance decreases, which is beneficial for low-noise field potential recording or safe charge injection electrical stimulation, but the spatial resolution will decrease accordingly. Therefore, the size range of 5 to 1000 μm allows the neural electrodes of this embodiment to flexibly select appropriate electrode site sizes according to the target brain region, signal type, and application requirements, achieving an optimal balance between signal resolution and tissue contact area. The electrode sites 16 can be located on the end face of the flexible extended electrode structure 15, or they can be distributed along the extension path of the flexible extended electrode structure 15. The specific layout will be described in detail in subsequent embodiments in conjunction with flexible extended electrode structures of different shapes.

[0035] Through the above structural design, this embodiment achieves the synergistic operation of the helical probe structure and the cantilevered flexible extension electrode structure. After implantation into biological tissue, the helical probe structure provides axial and circumferential basic support and electrode distribution, while the outwardly extending flexible extension electrode structure 15 penetrates into the radially surrounding tissue, enabling the electrode sites 16 to form a high-density discrete distribution network in three-dimensional space, significantly improving the spatial coverage and resolution of neural signal acquisition and electrical stimulation.

[0036] Example 2: Based on the three-dimensional spatial unfolding spiral neural electrode described in Example 1, the flexible extended electrode structure 15 and the planar flexible electrode precursor 10 used to form the spiral probe structure are integrally formed from the same flexible substrate 11. Figure 1The magnified view clearly shows that the flexible extended electrode structure 15 is not attached to the edge of the flexible substrate 11 through subsequent bonding, welding, or mechanical clamping. Instead, it is directly defined from the same continuous flexible material layer during the fabrication of the flexible substrate 11 using the same photolithography or etching process. In other words, there are no physical joints or abrupt material transitions between the flexible extended electrode structure 15 and the flexible substrate 11; they belong to the same whole at the molecular chain level or material continuum level. This integrated molding design allows the flexible extended electrode structure 15 to extend outward from the outer surface of the spiral probe structure after being rolled up, forming a cantilever structure. The cantilever structure refers to the flexible extended electrode structure 15 being connected to the main body of the spiral probe structure only at its root, while the remaining parts, including the extension section and the area where the electrode sites 16 at the ends are located, are in a free-floating state, capable of independent bending deformation under external force.

[0037] To ensure the mechanical properties and biocompatibility of this integrated structure at the material level, in this embodiment, the planar flexible electrode precursor 10 and the flexible extension electrode structure 15 are integrally made of the same biocompatible flexible material. There is no mechanical connection interface between the flexible extension electrode structure 15 and the planar flexible electrode precursor 10. This biocompatible flexible material is at least one of polyimide or Parylene. Parylene is a polymer formed by chemical vapor deposition, possessing excellent conformability, low permeability, and superior biocompatibility. It can be deposited at room temperature to form a flexible film with a low defect rate, making it particularly suitable as an encapsulation material or substrate material for long-term implantable devices. In actual fabrication, depending on the tissue mechanical properties of the target implantation site, a composite scheme can be selected, using polyimide alone, Parylene alone, or polyimide as the structural layer and Parylene as the outer encapsulation layer. Regardless of the specific material combination used, the core principle is that there is no mechanical connection interface between the flexible extension electrode structure 15 and the flexible substrate 11, thereby helping to reduce the failure risks such as interface delamination and fatigue fracture commonly found in traditional spliced ​​structures.

[0038] The technological advantages of this integrated, interface-free design are particularly evident after the spiral probe structure is rolled into shape. When the planar flexible electrode precursor 10 is rolled into a multi-layered spiral structure, the root region of the flexible extension electrode structure 15 will be subjected to continuous bending stress and interlayer constraint force. If there is an adhesive interface or material discontinuity at the root, during long-term implantation, stress concentration is easily generated at the interface due to repeated bending caused by the tiny pulsations of brain tissue, respiratory movements, or changes in body position. This can lead to the initiation and propagation of microcracks, ultimately causing the flexible extension electrode structure 15 to peel off or break from the spiral probe structure. However, in the integrated structure of this embodiment, since the root region and the flexible substrate 11 are made of the same continuous material, the stress can be evenly distributed and dissipated throughout the root region, without abrupt stress concentration points. Therefore, the root of the cantilever structure has excellent fatigue resistance.

[0039] Furthermore, the cantilever structure of this embodiment possesses an important dynamic adaptability. This cantilever structure is designed to adapt to tissue resistance during or after implantation into biological tissue, thereby enhancing contact stability or reducing tissue damage. Specifically, when the helical probe structure is implanted into the target neural tissue, the helical body provides axial penetration force based on its initial structural stiffness, while the outwardly extending flexible electrode structure 15 experiences radial and tangential resistance from the surrounding tissue upon contact. Since the flexible electrode structure 15 is only micrometers thick, its bending stiffness is extremely low. Therefore, under the influence of tissue resistance, these cantilever structures do not forcefully pierce or cut the tissue like a rigid needle tip, but rather undergo gentle bending deformation in accordance with the natural texture of the tissue. This adaptive bending allows the electrode site 16 to adhere to the surface of the neuronal cluster with moderate contact force, ensuring stable coupling at the electrochemical interface without compressing neurons or microvessels due to excessive contact pressure, thus significantly reducing tissue damage.

[0040] Example 3: Based on the three-dimensional spatial unfolding spiral neural electrode described in Embodiments 1 and 2, this embodiment further describes in detail the layout of the electrode sites 16 on the flexible extension electrode structure 15 and the size and geometry of the flexible extension electrode structure 15 itself.

[0041] Regarding the distribution of electrode sites 16 on the flexible extension electrode structure 15, each flexible extension electrode structure 15 has at least one electrode site 16, and multiple electrode sites 16 on the same flexible extension electrode structure 15 are distributed in a one-dimensional linear, array, or non-uniform manner along the extension direction of the flexible extension electrode structure 15, with a spacing of 10-200 μm between adjacent electrode sites 16. The one-dimensional linear distribution refers to multiple electrode sites 16 arranged in a straight line along the length of the flexible extension electrode structure 15, and the spacing between each electrode site can be equidistant or unequal as needed. For example, the spacing between electrode sites can be denser in the region near the root of the flexible extension electrode structure 15, while the spacing can be appropriately wider in the region near the end. This non-uniform linear distribution helps to simultaneously achieve local high-density sampling and a large spatial coverage on a single extension electrode.

[0042] The spacing between adjacent electrode sites 16 is set to 10-200 μm. The lower limit of 10 μm is limited by the precision of micro-nano fabrication technology and the physical requirement to prevent signal crosstalk between adjacent electrode sites, while the upper limit of 200 μm ensures that a sufficient number of electrode sites can be arranged within the limited length of the flexible extended electrode structure 15 to achieve effective spatial sampling density. It should be understood that although this embodiment lists several typical distribution methods, in practical applications, the distribution of electrode sites on the same flexible extended electrode structure 15 is not limited to these. A gradual distribution with increasing spacing along the extension direction can also be adopted, or a customized non-uniform arrangement can be made according to the spatial location of the neuronal cell body layer of the target brain region, as long as it can meet the needs of specific neural signal acquisition or electrical stimulation.

[0043] Regarding the dimensions and geometry of the flexible extension electrode structure 15, the length of the flexible extension electrode structure 15 is 10μm-1mm, the width is 5-200μm, and the thickness is 0.5-50μm. The flexible extension electrode structure 15 can be one or more of a strip structure, a curved structure, or a forked structure, so as to form a spatial distribution with different radial extension depths after being rolled up, thereby adapting to the sampling needs of different brain tissues.

[0044] In terms of structural form, the flexible extended electrode can be adopted. Figure 2 (a) or Figure 2 The different configurations shown in (b) can be strip-shaped, curved, or bifurcated to adapt to different spatial distribution requirements.

[0045] Furthermore, the number of electrode sites is not limited and can be adjusted and configured according to actual application requirements. For example, such as Figure 2As shown in (c), multiple electrode sites can be set on a flexible extension electrode. In a preferred embodiment, four electrode sites are set on a flexible extension electrode to achieve high-density signal acquisition or stimulation function in a local area.

[0046] In specific implementations, the flexible extended electrode structure 15 can optionally be a strip structure. A strip structure refers to a flexible extended electrode extending outwards in a straight line from the edge of the flexible substrate 11 with a roughly constant width, forming a long, thin rectangular strip. In this configuration, the electrode sites 16 are typically distributed linearly in one dimension along the extension direction of the strip structure. For example, on a strip structure with a length of 200 μm and a width of 20 μm, three circular electrode sites with a diameter of 15 μm can be sequentially arranged along its centerline, with a spacing of 50 μm between adjacent electrode sites. The advantage of the strip structure lies in its simple geometry, large tolerance in the fabrication process, and ability to provide a uniform extension depth in the radial direction after being rolled up, making it suitable for uniformly sampling neurons within a specific depth range in brain tissue.

[0047] In specific implementations, the flexible extension electrode structure 15 can optionally be a curved structure. A curved structure means that as the flexible extension electrode extends outward from the flexible substrate 11, its extension path is not a straight line, but has a certain curvature, such as an arc, S-shape, or wave shape. This curved design is not merely geometric decoration, but has a clear functional purpose. On the one hand, the curved path increases the effective length of the flexible extension electrode. Under the same radial projection distance, the curved structure can provide a longer electrode placement space than the strip structure, thereby accommodating more electrode sites or achieving a wider electrode site spacing.

[0048] In specific implementation, the flexible extension electrode structure 15 can optionally be a bifurcated structure. A bifurcated structure refers to the flexible extension electrode branching during the extension process, with a main trunk branching into two or more sub-branches, resulting in an overall tree-like or antler-like shape. This form allows for the creation of multiple spatially separated electrode site areas on a single flexible extension electrode structure, thereby multiplying the radial and circumferential spatial coverage density. For example... Figure 2 In the specific example shown in (d), the bifurcated structure has two sub-branches, each with two electrode sites, for a total of four electrode sites arranged in an array. The spacing between adjacent electrode sites can be set as needed within the range of 10-200 μm, for example, 80 μm. After being rolled up, the different sub-branches unfold in slightly different radial directions, allowing the four electrode sites to form a small three-dimensional sampling cluster in space. This enables simultaneous recording of the firing activity of neurons from different directions within a local area, which has significant advantages for applications requiring the analysis of local neural microcircuits.

[0049] Example 4: Based on the three-dimensional spatial unfolding spiral neural electrode described in Examples 1 to 3, this embodiment further describes in detail the spatial distribution pattern of multiple flexible extended electrode structures 15 on the spiral path and the resulting multi-scale sampling capability.

[0050] In this embodiment, multiple flexible extended electrode structures 15 are distributed periodically or non-periodically along the helical path. The lengths, number of electrode sites 16, or distribution densities of the different flexible extended electrode structures 15 are set to be different from each other. This results in varying electrode site densities at different axial positions and radial depths of the helical probe structure, forming a multi-scale spatial distribution structure for differentiated sampling or stimulation of target neural tissue. The multi-scale spatial distribution structure referred to here means that the distribution density of electrode sites 16 in three-dimensional space is not uniform and constant, but rather intentionally designed as an alternating pattern of sparse and dense distributions and varying lengths, based on the functional requirements of different axial positions and radial depths on the helical probe structure.

[0051] Specifically, this embodiment provides a typical example of a non-periodic multi-scale configuration. In this example, the flexible extended electrode structure 15 near the top of the helical probe structure is relatively short, for example, about 50 μm in length. On these shorter extended electrodes, the distribution density of electrode sites 16 is relatively high; for example, 2 to 3 electrode sites are set within a length of 50 μm. The spacing between adjacent electrode sites can be a smaller value within the range of 10-200 μm, such as 20-30 μm. This short and dense configuration allows the top region of the helical probe structure to concentrate the acquisition of signals from local neuronal clusters within a small spatial volume, achieving high single-cell recording resolution. Simultaneously, the flexible extended electrode structure 15 near the bottom of the helical probe structure is longer, for example, about 500 μm in length. On these longer extended electrodes, the distribution density of electrode sites 16 is relatively low; for example, 1 to 2 electrode sites are set within a length of 500 μm. The spacing between adjacent electrode sites can be a larger value within the range of 10-200 μm, such as 150-200 μm. This long and sparse configuration allows the bottom region of the helical probe structure to cover a large radial tissue area with fewer electrode channels, making it suitable for acquiring field potential signals or performing large-scale electrical stimulation.

[0052] Example 5: Based on the three-dimensional spatial unfolding spiral neural electrode described in Examples 1 to 4, this example further details the numerical range of the tilt angle α and the interlayer fixation method of the spiral probe structure.

[0053] Combination Figure 3As shown, in this embodiment, the helical probe structure is a multi-layered helical structure formed by the planar flexible electrode precursor 10 being rolled around a central support 17, with 2-100 layers. Specifically, after the planar flexible electrode precursor 10 is released from the silicon substrate, one end is fixed to the surface of the central support 17. Then, a precision rotating device drives the central support 17 to rotate, causing the planar flexible electrode precursor 10 to be wound layer by layer onto the central support 17. The central support 17 can be a thin metal wire, such as a platinum-iridium alloy wire, or a fiber made of a biocompatible polymer; its diameter determines the inner diameter of the helical probe structure. During the winding process, the helical pitch, interlayer gap, and final outer diameter can be precisely controlled by controlling the rotation speed of the rotating device and the tension applied to the planar flexible electrode precursor 10. The range of 2-100 layers covers various needs from extremely fine microprobes to larger deep electrodes. When the number of layers is small, such as 2-10 layers, the outer diameter of the spiral probe structure is small, making it suitable for implantation in narrow nucleus regions deep in the brain. When the number of layers is large, such as 50-100 layers, the spiral probe structure has a larger outer diameter and higher structural strength, and can arrange more flexible extension electrode structures 15 over a longer axial distance, making it suitable for scenarios requiring large-area coverage, such as cortical EEG monitoring or field potential recording of large brain regions.

[0054] The tilt angle α ranges from 60° to 85°. The tilt angle α referred to here is the angle between the arrangement direction of the flexible extension electrode structure 15 and the axis of the spiral probe structure when the planar flexible electrode precursor 10 is in a planar state. This angle is not arbitrarily chosen, but determined after in-depth analysis of curling geometry and repeated experimental verification. When the planar flexible electrode precursor 10 is curled into a spiral structure, the flexible extension electrode structure 15, originally arranged along a tilted straight line, undergoes a spatial coordinate mapping transformation.

[0055] In a preferred embodiment, the tilt angle α is set to 75°. When α is 75°, after the planar flexible electrode precursor 10 is rolled up, each flexible extension electrode structure 15 is evenly distributed along the spiral path, and an appropriate spacing is maintained between adjacent extension electrodes in the axial direction. This avoids excessive spatial overlap of electrode sites 16 due to insufficient spacing, which would waste limited channel resources, and also prevents sampling blind spots due to excessive spacing. At the same time, in the radial direction, each flexible extension electrode structure 15 can fully unfold outward, with its free end away from the outer surface of the spiral probe structure, forming a distinct cantilevered flexible structure, thereby maximizing the advantage of radial spatial coverage.

[0056] To more clearly illustrate the critical significance of the tilt angle α, two comparative examples are set up below for comparative analysis.

[0057] Comparative Example 1: If the tilt angle α is greater than 85°, for example, 88° or close to 90°. In this case, the angle between the arrangement direction of the flexible extension electrode structure 15 on the planar flexible electrode precursor 10 and the axial direction is too large, meaning that within the same planar length, the flexible extension electrode structures 15 arranged along the tilted straight line are more densely packed. After being rolled into shape, the axial spacing of these densely packed flexible extension electrode structures 15 on the helical path becomes very narrow, causing adjacent extension electrodes to easily overlap or cross in space when radially unfolded. This overlap not only causes the sampling areas of the electrode sites 16 to highly overlap, wasting valuable electrode channel resources, but may also cause adjacent flexible extension electrode structures 15 to hook or entangle with each other during implantation, increasing implantation resistance and even causing structural damage. In addition, when the excessively overlapping extension electrodes undergo adaptive bending due to tissue resistance, they may mechanically interfere with each other, affecting their independent bending ability, thereby weakening the tissue compliance that the cantilever structure should have.

[0058] Comparative Example 2: If the tilt angle α is less than 60°, for example, 45° or smaller, then after the planar flexible electrode precursor 10 is rolled up, the axial spacing of the flexible extension electrode structure 15 along the spiral path is relatively large, resulting in a relatively sparse distribution of the electrode sites 16 in space. In other words, the electrode density along the spiral direction between the extension electrodes is reduced, which may not be able to fully cover the target neural tissue, thereby reducing the three-dimensional spatial sampling efficiency. In this case, it is necessary to appropriately increase the tilt angle α to improve the axial density of the extended electrodes after rolling up, thereby improving the spatial coverage of surrounding neurons.

[0059] As can be seen from the above comparative examples, the tilt angle range of 60°-85° is not an arbitrary interval, but rather a key parameter window that ensures the flexible extended electrode structure 15, after being rolled up, avoids excessive overlap while achieving sufficient radial expansion. Within this window, the specific value of the tilt angle can be fine-tuned according to the target application scenario. For example, when more flexible extended electrode structures 15 need to be arranged within a shorter axial distance to achieve high-density sampling, a tilt angle closer to the lower limit, such as around 80°, can be selected, at which point the distribution density of the extended electrodes is higher. When each flexible extended electrode structure 15 needs to achieve a higher radial expansion depth to cover more surrounding tissue, a tilt angle closer to the upper limit, such as around 65°, can be selected, at which point the radial extension of the extended electrodes is larger. In this embodiment, 75° is preferred as the balance point, achieving a good compromise between distribution density and radial expansion depth.

[0060] Regarding the interlayer fixation of the helical probe structure, in this embodiment, a fixing layer formed of UV-curable resin or polyimide is filled between adjacent layers. This fixing layer enhances mechanical stability and electrical insulation, and avoids the free end of the flexible extended electrode structure 15 to maintain its bendability. Specifically, after the planar flexible electrode precursor 10 is rolled into a helical probe structure, although adjacent layers of the helix maintain contact through rolling tension, this contact is unstable. During implantation or after long-term implantation, interlayer slippage or loosening may occur due to tissue movement, thus affecting the spatial stability of the electrode site 16. To address this issue, in this embodiment, after rolling, a low-viscosity UV-curable resin, such as medical-grade UV-curable resin like Norland Optical Adhesive 81, or polyimide, is introduced into the gaps between the helical layers.

[0061] The filling area must avoid the free end of the flexible extended electrode structure 15. The free end refers to the suspended portion of the flexible extended electrode structure 15 extending outward from the edge of the flexible substrate 11, including the area where the extension section and the electrode site 16 at the end are located. When filling with the fixing material, by controlling the coating amount, viscosity, and flow time before curing of the filling material, the fixing material is ensured to fill only the main gap area between the spiral layers, without diffusing to the free end area of ​​the flexible extended electrode structure 15.

[0062] Example 6: This embodiment provides a method for fabricating a three-dimensional spatially unfoldable spiral neural electrode as described in any of the foregoing embodiments. This method organically combines planar micro-nano fabrication technology with three-dimensional curling molding technology, achieving integrated fabrication of a spiral probe structure and a cantilevered flexible extended electrode structure. The process offers strong controllability and can precisely regulate the distribution morphology of electrode sites in three-dimensional space. The following describes the method in conjunction with… Figure 1 and Figure 3 The preparation method is described in detail in steps S1 to S3.

[0063] Step S1: Fabrication of planar flexible electrode precursor 10: Multiple flexible extended electrode structures 15 are formed on a flexible substrate 11 using micro-nano fabrication technology. The flexible extended electrode structures 15 are integrally formed with the flexible substrate 11, and electrode sites 16 and metal connection lines 14 are formed on the flexible extended electrode structures 15. The flexible extended electrode structures 15 are arranged on the planar flexible electrode precursor 10 along a straight line at an angle α to the preset curling axis, so that they can be distributed along a spiral path after subsequent curling.

[0064] Specifically, step S1 begins with a clean silicon wafer, which serves as a temporary carrier substrate, providing a rigid support platform for subsequent thin film deposition and photolithography processes. First, a layer of polyimide precursor solution is coated onto the silicon wafer surface using a spin-coating process. The spin-coating parameters can be adjusted according to the target thickness; for example, spreading at a low speed first, then spinning out a uniform film at a high speed. After spin-coating, the silicon wafer is placed in an oven or hot plate for stepped temperature curing, causing the polyimide precursor to undergo an imidization reaction, forming a dense and stable flexible substrate 11. The thickness of the flexible substrate 11 can be selected as needed, ranging from several micrometers to tens of micrometers, for example, 5-20 μm. This thickness range ensures sufficient mechanical strength during subsequent rolling while maintaining necessary flexibility after implantation.

[0065] After the flexible substrate 11 is cured, the geometric contour of the flexible extension electrode structure 15 is defined by photolithography. During the layout design stage, the flexible extension electrode structure 15 is not randomly arranged, but rather positioned along a straight line at an angle α to the preset curling axis. The preset curling axis refers to the direction of the central axis around which the planar flexible electrode precursor 10 will be curled in subsequent step S2, which is the axis of the final spiral probe structure. The specific value of the angle α is determined during layout design, with a preferred range of 60°-85°, for example, 75°. The pattern on the layout is transferred to the photoresist layer on the flexible substrate 11 using photolithography. Then, the polyimide layer is patterned using oxygen plasma etching or reactive ion etching processes, forming outwardly extending branch structures at the edge regions of the flexible substrate 11. These branch structures are the flexible extension electrode structures 15. Since the flexible extension electrode structure 15 and the flexible substrate 11 are etched from the same polyimide film, there are no material interfaces or mechanical bonding surfaces between them.

[0066] After forming the geometric contour of the flexible extended electrode structure 15, the next step is to fabricate the metal interconnects 14 and electrode sites 16. First, photoresist is spin-coated onto the surfaces of the flexible substrate 11 and the flexible extended electrode structure 15, and the patterns of the metal interconnects and electrode sites are defined using photolithography. Then, a metal adhesion layer and a conductive layer are deposited sequentially using physical vapor deposition methods such as electron beam evaporation or magnetron sputtering. The adhesion layer is typically made of titanium or chromium, with a thickness of approximately 10-20 nm. Its function is to enhance the adhesion between the conductive layer and the polyimide substrate, preventing metal peeling during subsequent curling or implantation. The conductive layer is typically made of gold or platinum, with a thickness of approximately 100-300 nm. Gold has excellent conductivity and biocompatibility, while platinum has higher electrochemical stability, making it suitable for scenarios requiring charge-injection electrostimulation. After deposition, the photoresist and the metal above it are removed using a lift-off process, leaving the patterned metal interconnects 14 and electrode sites 16. Metal connection lines 14 originate from each electrode site 16, converge inward along the extension direction of the flexible extended electrode structure 15, and finally connect to the pad array area at the tail of the planar flexible electrode precursor 10. The electrode sites 16 are located at the end of the flexible extended electrode structure 15 or on the extension path, and their size is designed in the range of 5-1000 μm according to specific application requirements.

[0067] After the metal structure is fabricated, a layer of polyimide, approximately 2-10 μm thick, is typically spin-coated as a top encapsulation insulating layer. This encapsulation layer covers the metal interconnects 14, and windows are created only in the electrode sites 16 and the pad array area using photolithography and etching processes. This exposes the electrode sites 16 for contact with biological tissue, and simultaneously exposes the pad areas for subsequent connection to external circuitry. The purpose of the encapsulation layer is to prevent short circuits or corrosion of the metal circuits after implantation due to contact with tissue fluid, ensuring the long-term reliability of the electrodes.

[0068] After completing all the above planar process steps, the sacrificial layer between the silicon wafer and the flexible substrate 11 is removed by wet etching, and the entire planar flexible electrode precursor 10 is released from the silicon wafer to obtain an independent, freely bendable flexible thin film structure.

[0069] Step S2: The planar flexible electrode precursor 10 is rolled into a spiral probe structure, so that the flexible extension electrode structure 15 is distributed along the spiral path and extends outward from the outer surface of the spiral probe structure to form a three-dimensional spatial unfolding structure.

[0070] Specifically, combined Figure 3As shown, the curling process in step S2 requires the aid of a precision rotating device and a central support 17. The central support 17 can be a thin metal wire, such as a platinum-iridium alloy wire or stainless steel wire with a diameter of 100-300 μm, or a fiber made of a biocompatible polymer. One end of the planar flexible electrode precursor 10 obtained in step S1 is fixed to the surface of the central support 17. The fixing method can be point bonding using a small amount of UV-curable adhesive, or temporary fixing by mechanical clamping. Then, the precision rotating device is activated, causing the central support 17 to rotate uniformly around its own axis. During the rotation, a constant and moderate tension is applied to the planar flexible electrode precursor 10, causing it to tightly wrap layer by layer around the central support 17. The rotation speed, tension, and the angle between the planar flexible electrode precursor 10 and the central support 17 together determine the pitch, interlayer gap, and outer diameter of the final helical probe structure. For example, the rotation speed can be controlled within the range of 10-200 rpm, and the tension can be controlled within the range of 0.1-10 mN. By adjusting these parameters, a spiral structure with 2-100 layers can be obtained, with an outer diameter ranging from hundreds of micrometers to several millimeters.

[0071] During the curling process, since the flexible extension electrode structures 15 on the planar flexible electrode precursor 10 are arranged along a straight line at an angle α to the axial direction, when the flexible substrate 11 is curled into a spiral shape, these flexible extension electrode structures 15 undergo a spatial mapping transformation from planar coordinates to cylindrical spiral coordinates. The flexible extension electrode structures 15, which were originally arranged along the inclined straight line, are naturally distributed along the spiral path after curling. And since they extend outward from the edge of the flexible substrate 11, after curling, these structures will unfold outward from the outer surface of the spiral probe structure, forming a radially extending cantilever structure.

[0072] Step S3: Fix the rolled structure, including filling the interlayer with UV-curable resin or polyimide and curing it. The filling area avoids the free end of the flexible extended electrode structure 15, so that the flexible extended electrode structure 15 maintains its outward unfolded state and bendable characteristics, and exposes the electrode site 16 in three-dimensional space.

[0073] Specifically, after the curling and shaping in step S2, although the adjacent layers of the spiral probe structure maintain contact through curling tension and interlayer friction, this contact state may change during long-term implantation due to tissue movement, body fluid infiltration, or material stress relaxation, leading to interlayer slippage or structural loosening, which in turn affects the spatial stability of the electrode site 16. To solve this problem, step S3 performs interlayer fixation on the curled structure.

[0074] First, prepare a low-viscosity UV-curable resin—such as medical-grade UV-curable adhesive like Norland Optical Adhesive 81—or a diluted polyimide precursor solution as a filler material. The low viscosity allows the filler material to spontaneously penetrate into the tiny gaps between the helical layers through capillary action, without the need for external pressure, thus avoiding mechanical disturbance to the helical structure. After the filler material is introduced into the interlayer gaps, it is cured by UV irradiation or thermal curing. For example, when using a UV-curable resin, a 365nm UV light source is used at approximately 100mW / cm². 2 When exposed to high-intensity irradiation for tens of seconds to several minutes, the resin can be completely cured, forming a solid, fixed layer. When using diluted polyimide, thermal curing is achieved through a stepped heating process.

[0075] The filling area must avoid the free end of the flexible extended electrode structure 15. The free end refers to the suspended portion of the flexible extended electrode structure 15 extending outward from the edge of the flexible substrate 11, including the area where the extension section and the electrode site 16 at the end are located. In practice, this selective filling can be achieved in several ways. For example, a temporary water-soluble protective layer, such as a polyvinyl alcohol film, can be pre-coated on the free end region of the flexible extended electrode structure 15 before introducing the filling material. After the filling material cures, the protective layer can be dissolved and removed with water, thereby releasing the free end.

[0076] Example 7: This embodiment provides an application method for a three-dimensional spatially unfoldable spiral neural electrode as described in any of the foregoing embodiments. The core of this application method lies in implanting the three-dimensional spatially unfoldable spiral neural electrode into the target neural tissue, so as to achieve high-density neural signal acquisition and / or electrical stimulation in three-dimensional space through the electrode sites 16 on the flexible extended electrode structure 15 in brain-computer interface, deep brain stimulation or stereotactic electroencephalography equipment, and to cover neural regions at different depths and orientations under a single implantation path.

[0077] Specifically, the application process of this embodiment begins with implanting a helical probe structure into the target neural tissue via stereotactic surgery. Taking deep brain nuclei as an example, such as the subthalamic nucleus, the medial part of the globus pallidus, or the hippocampus, the surgeon first plans the implantation path based on preoperative imaging data, and then advances the helical probe structure along the predetermined path to the target tissue. During the advancement process, the main body of the helical probe structure, namely the multi-layered helical structure formed by the coiling of the planar flexible electrode precursor 10, provides axial and circumferential basic support and electrode distribution. The so-called axial distribution means that as the helical probe structure penetrates deeper along the implantation path, the flexible extension electrode structures 15 located on different helical layers are naturally distributed at different axial depth positions, thereby forming a series of sampling points in the longitudinal direction of the implantation path. The so-called circumferential distribution means that because the outer surface of the helical probe structure has a continuous helical path, the flexible extension electrode structures 15 located on this helical path will cover different circumferential angles on any axial cross section, thereby achieving circumferential signal acquisition on the same depth plane.

[0078] Meanwhile, the outwardly extending flexible electrode structures 15 penetrate radially into the surrounding tissue. Because the flexible electrode structures 15 are cantilevered, flexible structures extending outward from the outer surface of the helical probe structure, they do not adhere tightly to the surface of the helical body after implantation, but rather extend radially outward into the peripheral nerve tissue far from the helical body. With a single implantation path, the electrode sites 16 are not only distributed along the central axis occupied by the helical probe structure, but also extend radially through the flexible electrode structures 15 of varying lengths, reaching neuronal clusters at different distances from the center of the implantation path. For example, electrode sites 16 on shorter flexible electrode structures 15 (e.g., 50-100 μm) can collect neuronal signals immediately adjacent to the implantation path, while electrode sites 16 on longer flexible electrode structures 15 (e.g., 500 μm-1 mm) can penetrate deeper into the surrounding tissue farther from the center of the implantation path, collecting neuronal activity from the outermost periphery.

[0079] Through the coordinated distribution of the axial, circumferential, and radial dimensions described above, the neural electrode of this embodiment can achieve high-density three-dimensional spatial coverage of the target neural tissue with a single implantation path. This coverage method is fundamentally different from traditional linearly arranged electrodes or surface electrodes. The electrode sites of traditional linear electrodes are only distributed along the implantation axis. Although they can cover different depths, they can only collect signals in a single direction on the same depth plane and cannot acquire circumferential and radial spatial information. Although traditional helical electrodes increase the circumferential distribution, the electrode sites are still tightly attached to the helical surface and lack the ability to extend radially outward. In contrast, the neural electrode of this embodiment, through the design of the cantilevered flexible extension electrode structure 15, further increases the radial extension dimension on the basis of the axial and circumferential distribution provided by the helical probe structure, thereby forming a discretely distributed three-dimensional electrode array in three-dimensional space.

[0080] In brain-computer interface (BCI) applications, this three-dimensional spatial coverage capability has significant clinical value. BCI systems require the simultaneous acquisition of high-density neural signals from multiple brain regions to decode complex motor intentions or cognitive states. In this embodiment, after the neural electrodes are implanted into the motor cortex or parietal cortex, the helical probe structure extends along the longitudinal direction of the cortical columns. Electrode sites 16 at different axial positions can respectively acquire neuronal activity from different layers of the cortex, such as layers II / III and layer V. Simultaneously, because the flexible extended electrode structure 15 unfolds circumferentially and radially, multiple electrode sites 16 on the same depth plane can simultaneously record the firing activity of neurons from different functional columns or directions. This multi-dimensional signal acquisition capability enables the BCI system to obtain richer and more comprehensive neural information, thereby improving the accuracy of motion trajectory decoding or the degree of freedom in cursor control.

[0081] In deep brain stimulation applications, the neural electrodes of this embodiment also exhibit unique advantages. Taking the stimulation of the subthalamic nucleus in Parkinson's disease as an example, the subthalamic nucleus is a small but functionally well-defined nucleus. Its dorsolateral region is mainly responsible for sensory and motor functions, while the ventromedial region is related to cognitive and limbic system functions. When the helical probe structure is implanted into the subthalamic nucleus, the flexible extension electrode structure 15 located proximal to the helix can cover the dorsolateral region of the nucleus, while the extension electrode located distally can cover the ventromedial region. Because the flexible extension electrode structures 15 of different lengths extend to different depths in the radial direction, doctors can selectively activate or harvest neuronal clusters in specific subregions according to the patient's symptoms. For example, for patients with predominantly motor symptoms, the electrode site 16 covering the dorsolateral region can be preferentially used for stimulation.

[0082] In stereoscopic electroencephalography (EEG) monitoring applications, the neural electrodes of this embodiment can significantly improve the accuracy of epileptic focus localization. Localization of epileptic foci typically requires the implantation of multiple deep electrodes in the suspected lesion area to record abnormal discharge activity during ictal and interictal periods. Because the neural electrodes of this embodiment can cover a wide area in the axial, circumferential, and radial dimensions with a single implantation path, a single electrode can acquire richer spatial information than traditional electrodes. For example, when the helical probe structure is implanted into the medial temporal lobe, the electrode sites 16 on the flexible extended electrode structure 15 can simultaneously monitor the electrical activity of different subregions of the hippocampus, different nuclei of the amygdala, and the surrounding cortex. This wide-area, high-density coverage allows physicians to more accurately delineate the origin and propagation pathway of epileptic discharges, thus providing a more reliable basis for planning the surgical resection area.

[0083] From a microscopic mechanism perspective, the application advantages of this embodiment stem from the dynamic adaptive behavior of the flexible extension electrode structure 15 after implantation. As described in Embodiment 2, the flexible extension electrode structure 15 undergoes adaptive bending due to tissue resistance during or after implantation into biological tissue. This adaptive bending brings two important clinical benefits at the application level. First, the adaptive bending allows the electrode site 16 to adhere to the surface of the neuronal cluster with moderate contact force, ensuring stable coupling of the electrochemical interface without compressing neurons or microvessels due to excessive contact pressure, thereby maintaining stable signal quality during long-term implantation. Second, when the brain tissue undergoes slight displacement due to respiration, heartbeat, or changes in body position, the flexible extension electrode structure 15 can utilize its extremely low bending stiffness and high flexibility to synchronously passively comply with the slight tissue displacement, thereby achieving adaptive following with the brain tissue and maintaining effective contact between the electrode site 16 and the target neuron at all times, avoiding the signal attenuation or loss problems caused by tissue retraction of traditional rigid electrodes. This dynamic adaptive mechanism is the key to the continuous provision of high-quality neural signals by the neural electrode of this embodiment under long-term implantation conditions.

[0084] Example 8: Based on the three-dimensional spatial unfolding spiral neural electrode described in Examples 1 to 7, this example further details the rear-end connection structure of the electrode. The rear-end connection structure is the key hub for the transition of the implanted neural electrode from an in vivo functional unit to an external signal processing system, and its design quality directly determines the electrical connection reliability and mechanical stability of the entire device under long-term implantation conditions.

[0085] Combination Figure 1As shown, the three-dimensional spatial unfolding spiral neural electrode of this embodiment also includes a pad array 13, which is electrically connected to each electrode site 16 via metal connection lines 14. Specifically, in the tail region of the planar flexible electrode precursor 10, the metal connection lines 14 originate from the electrode sites 16 on each flexible extended electrode structure 15, converge inward along the surface of the flexible substrate 11, and finally extend to the pad array 13 at the tail. The pad array 13 is an interface region composed of multiple independent metal pads arranged in a certain manner. Each pad corresponds to an independent channel of an electrode site 16, and a one-to-one electrical connection is achieved through the metal connection lines 14. The arrangement of the pad array 13 can be a single-row linear arrangement or a multi-row staggered arrangement, the specific layout of which depends on the total number of electrode channels and the space requirements for docking with external connectors. The material of the pads is usually the same as that of the metal connection lines 14, such as a titanium / gold or chromium / gold composite layer, to ensure good conductivity and welding reliability. The size and spacing of the pad array 13 are determined according to the subsequent connection method with the external circuit board. For example, when anisotropic conductive film thermoforming is used, the pad spacing can be set to 100-200μm; when micro-nano pin connectors are used, the pad spacing can be increased to 300-500μm accordingly.

[0086] A flexible connecting neck 12 is provided between the pad array 13 and the planar flexible electrode precursor 10. The connecting neck 12 is designed to bend at any angle to alleviate mechanical stress concentration and adapt to different external connection spaces and orientations. The connecting neck 12 refers to a transition structure located between the main body region of the planar flexible electrode precursor 10 and the tail pad array 13. Figure 1 As can be seen, the connecting neck 12 is a long, thin strip in a planar state, with one end connected to the main body area of ​​the flexible substrate 11 and the other end extending to the pad array 13. The width of the connecting neck 12 is usually narrower than that of the main body area of ​​the flexible substrate 11. For example, the width of the main body area may be several millimeters, while the width of the connecting neck 12 can be narrowed to several hundred micrometers to about one millimeter. This narrowing design makes the connecting neck 12 significantly less stiff in bending than the main body area, thus achieving good bendability.

[0087] In a preferred embodiment, the metal connecting lines 14 integrated within the connecting neck 12 adopt a serpentine routing layout, and the flexible substrate material in the connecting neck 12 region is replaced with a polydimethylsiloxane (PDMS) elastomer material with excellent ductility and high elasticity. Since commonly used polyimide (PI) materials, while compliant, lack elastic ductility, they cannot effectively release stress through their own tensile deformation when faced with large-angle complex bending or torsion. Therefore, this embodiment utilizes PDMS, which has high biocompatibility, low Young's modulus, and extremely high elongation at break, as a substrate to support and coordinate the dynamic deformation of the metal lines.

[0088] The term "serpentine routing" refers to a design where the metal connection line 14 does not follow a straight line from the main body of the flexible substrate 11 to the pad array 13 within the connection neck 12. Instead, it is arranged in a meandering, serpentine path, similar to multiple consecutive S-shaped bends connected in series. This serpentine routing design ensures that when the metal line bends in the connection neck 12, the tensile or compressive strain generated by the bend is not concentrated at a single point but distributed across various bends in the serpentine routing. Each bend only bears a small portion of the total strain. From a mechanical perspective, when the connection neck 12 is bent at a certain angle, if the metal line is arranged in a straight line, the local strain at the bend point may reach several percent or even tens of percent, far exceeding the elastic limit of the metal material, easily leading to fatigue fracture after repeated bending. However, with serpentine routing, the same bending angle is decomposed into the superposition of small deformations in multiple bends. The local strain of each bend can be controlled within the elastic range of the metal material, thereby significantly improving the fatigue life of the metal line. The specific geometric parameters of the serpentine trace—such as the radius of curvature of the bends, the bend angle, and the spacing between adjacent bends—can be optimized based on the expected bend angle range of the neck 12 and the material properties of the metal circuit. For example, when gold is used as the conductive layer, the radius of curvature of the serpentine trace can be set to 50-200 μm, and the arc can be set to 30°-60° to ensure that the local strain of the metal circuit remains within a safe range when the neck 12 bends at ±90° or even larger angles.

[0089] In another alternative embodiment, the spatial layout of the connecting neck 12 was optimized to further reduce mechanical damage to the rear electrical connection structure caused by the three-dimensional roll forming process. Combined with... Figure 1 and Figure 5 As shown, in the aforementioned embodiment, the connecting neck 12 extends axially upward directly from the tail of the main body region of the flexible substrate 11. Under this initial layout, when the planar flexible electrode precursor 10 is rolled up around the central axis of the central support 17 in step S2, the connecting neck 12 is easily passively rolled into the spiral structure along with the main body region, or subjected to strong circumferential shear force and bending stress superimposed at the rolling junction.

[0090] This embodiment improves the planar layout structure: after the metal connecting lines 14 converge at the tail, they first move laterally (e.g., along a direction perpendicular to the preset curling axis)... Figure 5As shown in the diagram, the neck 12 extends a predetermined distance to the right, forming a transverse stress isolation zone. Subsequently, the neck 12 extends from the end of this transverse stress isolation zone to the outer pad array 13 in a direction parallel to the predetermined curling axis. This transversely extended staggered arrangement allows the neck 12 to be completely detached from the main curling core area of ​​the planar flexible electrode precursor 10 in space. During the curling process in step S2, when the main body area of ​​the flexible substrate 11 is tightly wrapped around the central support 17 to form the spiral probe body, the neck 12 remains independently suspended and does not participate in any three-dimensional curling deformation. This fundamentally avoids the mechanical and physical damage caused by curling stress, interlayer friction, and capillary filler adhesive to the neck 12 and pad array 13.

[0091] By introducing lateral extensional misalignment, the mechanical stress concentration at the probe tail is significantly reduced in the final three-dimensional spatial unfolding spiral neural electrode structure. This also provides a more free and independent assembly space for the subsequent docking and hot pressing of the pad array 13 with the external space, significantly improving the process robustness of clinical implantation and system integration.

[0092] Example 9: This embodiment uses the application of the three-dimensional spatially unfolding spiral neural electrode described in any of the preceding embodiments in deep brain stimulation therapy for Parkinson's disease as an example to further illustrate the specific value of multi-scale spatial distribution structure and three-dimensional spatial coverage capability in clinical practice. Parkinson's disease is a common neurodegenerative disease, the core pathological mechanism of which is the progressive loss of dopaminergic neurons in the substantia nigra of the midbrain, leading to abnormal basal ganglia circuit function. Deep brain stimulation, by implanting electrodes into specific nuclei and applying high-frequency electrical pulses, can effectively improve patients' motor symptoms and is currently an important treatment for mid-to-late stage Parkinson's disease. The subthalamic nucleus is one of the most commonly used stimulation targets. However, although this nucleus is small in size, it has clear functional divisions. Its dorsolateral region mainly receives projections from the primary motor cortex and supplementary motor area, and is responsible for the integration and processing of sensory and motor information; while the ventromedial region has extensive fiber connections with the prefrontal cortex and limbic system, participating in the regulation of cognitive and emotional functions. When traditional linearly arranged electrodes are implanted into the STN, the electrode contacts are only distributed along the implantation axis, making it difficult to accurately cover both the dorsolateral motor area and the ventromedial cognitive association area simultaneously under the same implantation path. Clinically, this often presents a dilemma: when the stimulation intensity is increased to fully improve motor symptoms, the current may diffuse into the ventromedial cognitive association area, causing side effects such as cognitive decline and mood fluctuations; on the other hand, reducing the stimulation intensity to avoid side effects may result in insufficient improvement of motor symptoms.

[0093] When the three-dimensional spatially unfolding spiral neural electrode of this embodiment is implanted into the STN nucleus, the spiral probe structure extends along the predetermined implantation path, and the flexible extension electrode structure 15 on it unfolds in three-dimensional space within the STN nucleus. Specifically, in conjunction with the multi-scale spatial distribution structure described in detail in Embodiment 4 above, in this application scenario, the flexible extension electrode structure 15 located at the proximal end of the spiral probe structure is designed to be relatively short, for example, 50-150 μm, and the electrode sites 16 are arranged in a relatively dense configuration. After implantation, these short extension electrodes mainly cover the dorsolateral region of the STN nucleus, and their electrode sites 16 are located near the neuronal clusters in the sensorimotor functional area. Due to the limited radial extension depth of the short extension electrodes, their spatial receptive fields are relatively concentrated, enabling the acquisition of local field potentials and neuronal firing activities in the dorsolateral region with high spatial resolution. At the same time, during electrical stimulation, the stimulation current is also confined within a small tissue volume, making it difficult to diffuse towards the ventromedial direction. Meanwhile, the flexible extension electrode structure 15 located at the distal end of the spiral probe structure is designed to be relatively long, for example, 300-800 μm, and the electrode sites 16 are arranged in a relatively sparse configuration. These extended electrodes, once implanted, can penetrate deep into the ventromedial region of the STN nucleus, reaching neuronal clusters in the cognitive association area. Due to the greater radial extension depth of the extended electrodes, their electrode sites 16 can cover surrounding tissues farther from the center of the implantation path, thereby enabling effective monitoring and intervention in the ventromedial region.

[0094] Through the aforementioned multi-scale configuration of short and dense proximal electrodes and long and sparse distal electrodes, the neural electrodes in this embodiment form a three-dimensional sampling and stimulation network with spatially variable resolution characteristics within the STN nucleus. From a microscopic mechanism perspective, the reason this configuration can improve motor symptoms while avoiding cognitive side effects is fundamentally due to the fact that the length difference of the flexible extended electrode structure 15 and the density difference of the electrode sites 16 jointly determine the spatial receptive field and stimulation diffusion range of each electrode channel. For the short extended electrodes located proximal to the spiral and covering the dorsolateral sensorimotor area, physicians can selectively apply higher-intensity electrical stimulation pulses through these electrode sites 16. Because the stimulation current diffusion range of the short extended electrodes is limited, the current density is mainly concentrated around the sensorimotor neurons in the dorsolateral region, effectively modulating abnormal motor circuit activity, thereby significantly improving symptoms such as tremor, rigidity, and bradykinesia in patients. For the long extended electrodes located distal to the spiral and covering the ventromedial cognitive association area, physicians can monitor the neural activity state of the ventromedial region in real time through these electrode sites 16. Once abnormal high-frequency oscillations or changes in discharge patterns are detected, stimulation parameters can be adjusted promptly to avoid overstimulation of that area. More importantly, since the flexible extended electrode structures 15 of different lengths and positions are spatially independent of each other, doctors can precisely select which electrode sites to activate and which to inhibit based on the patient's individualized symptom spectrum and electrophysiological response. They can even dynamically switch the stimulation configuration within different time windows to achieve truly adaptive closed-loop stimulation.

[0095] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. In the above embodiments, a three-dimensional spatially unfoldable neural electrode combining a helical probe structure and a cantilevered flexible extension electrode structure was used as an example for illustration. However, those skilled in the art should understand that parameters such as the specific shape, size, distribution pattern, tilt angle α, number of helical layers, and interlayer fixing method of the flexible extension electrode structure can be appropriately adjusted within the technical scope disclosed in this invention according to actual application requirements. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in this invention should be included within the scope of protection of this invention. Therefore, the scope of protection of this invention should be determined by the scope of the claims.

Claims

1. A three-dimensional spatially unfolding spiral neural electrode, comprising: The spiral probe structure is formed by curling up a planar flexible electrode precursor (10); Its characteristic is that it further includes: Multiple flexible extension electrode structures (15) are disposed on the spiral path of the spiral probe structure, and each of the flexible extension electrode structures (15) extends outward from the planar flexible electrode precursor (10) to form a cantilevered bendable structure; Electrode sites (16) are disposed on the flexible extended electrode structure (15). The electrode sites (16) are used to contact biological tissue to collect nerve signals and / or perform electrical stimulation. The size of the electrode sites (16) is 5-1000 μm. In the planar flexible electrode precursor (10), the flexible extended electrode structure (15) is arranged along a straight line at an angle α to the axis of the spiral probe structure, so as to form an electrode array distributed along the spiral path and unfolded outward in three dimensions after being rolled up.

2. The three-dimensional spatial unfolding spiral neural electrode according to claim 1, characterized in that, The flexible extended electrode structure (15) and the planar flexible electrode precursor (10) used to form the helical probe structure are integrally fabricated from the same flexible substrate (11). The flexible extended electrode structure (15) extends outward from the outer surface of the spiral probe structure after being rolled into a cantilever structure. The cantilever structure is used to adapt to the tissue resistance during or after implantation into biological tissue, so as to enhance the contact stability with biological tissue or reduce tissue damage.

3. The three-dimensional spatial unfolding spiral neural electrode according to claim 1, characterized in that, At least one electrode site (16) is provided on each of the flexible extension electrode structures (15), and the multiple electrode sites (16) on the same flexible extension electrode structure (15) are distributed in a one-dimensional linear distribution, an array distribution or a non-uniform distribution along the extension direction of the flexible extension electrode structure (15), and the spacing between adjacent electrode sites (16) is 10-200 μm.

4. The three-dimensional spatial unfolding spiral neural electrode according to claim 1, characterized in that, The flexible extension electrode structure (15) has a length of 10μm-1mm, a width of 5-200μm, and a thickness of 0.5-50μm. The flexible extension electrode structure (15) is one or more of a strip structure, a curved structure, or a forked structure, so as to form a spatial distribution with different radial extension depths after being rolled up, thereby adapting to the sampling needs of different brain tissues.

5. A three-dimensional spatial unfolding spiral neural electrode according to claim 1, characterized in that, Multiple flexible extended electrode structures (15) are periodically or non-periodically distributed on the spiral path, and the lengths, number or distribution densities of the different flexible extended electrode structures (15) are set to be different from each other, so that the electrode array has varying electrode site densities at different axial positions and radial depths of the spiral probe structure, in order to form a multi-scale spatial distribution structure.

6. The three-dimensional spatial unfolding spiral neural electrode according to claim 1, characterized in that, The range of the tilt angle α is 60°-85°; The spiral probe structure is a multi-layered spiral structure formed by the planar flexible electrode precursor (10) curling around the central support (17), with 2-100 layers, and a fixing layer formed by UV-curable resin or polyimide is filled between adjacent layers.

7. The three-dimensional spatial unfolding spiral neural electrode according to claim 1, characterized in that, It also includes a pad array (13), which is electrically connected to each of the electrode sites (16) via metal connection lines (14); A flexible connecting neck (12) is provided between the pad array (13) and the planar flexible electrode precursor (10). The connecting neck (12) is used to achieve bending at any angle to alleviate mechanical stress concentration and to adapt to different external connection spaces and directions.

8. A three-dimensional spatial unfolding spiral neural electrode according to claim 1, characterized in that, The planar flexible electrode precursor (10) and the flexible extended electrode structure (15) are integrally made of the same biocompatible flexible material, which is at least one of polyimide or Parylene.

9. A method for preparing a three-dimensional spatially unfolding spiral neural electrode as described in any one of claims 1 to 8, characterized in that, Includes the following steps: S1. Preparation of planar flexible electrode precursor (10): Multiple flexible extended electrode structures (15) are formed on a flexible substrate (11) by micro-nano fabrication process. The flexible extended electrode structures (15) are integrated with the flexible substrate (11), and electrode sites (16) and metal connection lines (14) are formed on the flexible extended electrode structures (15). The flexible extended electrode structure (15) is arranged on the planar flexible electrode precursor (10) along a straight line at an angle α to the preset curling axis, so as to be distributed along a spiral path after subsequent curling and forming. S2. The planar flexible electrode precursor (10) is rolled into a spiral probe structure, so that the flexible extended electrode structure (15) is distributed along the spiral path and extends outward from the outer surface of the spiral probe structure to form a three-dimensional spatial unfolding structure. S3. Fix the rolled structure, including filling the interlayer with UV-curable resin or polyimide and curing it, the filling area avoiding the free end of the flexible extended electrode structure (15), so that the flexible extended electrode structure (15) maintains an outward unfolded state and bendable characteristics, and the electrode site (16) is exposed in three-dimensional space.

10. An application of a three-dimensional spatial unfolding spiral neural electrode as described in any one of claims 1 to 8, characterized in that, Used in brain-computer interfaces, deep brain stimulation or stereotactic electroencephalography devices to achieve high-density neural signal acquisition and / or electrical stimulation in three-dimensional space through the electrode sites (16) on the flexible extended electrode structure (15).

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