Preparation process, operation method and application of flexible high-channel-number probe

Abstract

The invention discloses a preparation process, an operation method and application of a flexible high-channel-number probe, and belongs to the technical field of biomedicine. The preparation process of the flexible high-channel-number probe comprises the following steps: designing and preparing a planar electrode array; a planar electrode array and a flexible substrate are compounded, a reel core is prepared, and the flexible high-channel-number probe is manufactured through the reel core or directly rolled from the edge of a composite film, and the flexible high-channel-number probe has good mechanical matching performance with a flexible tissue, can reduce mechanical shearing caused by relative displacement between the flexible high-channel-number probe and the tissue, and can be used for preparing the flexible high-channel-number probe. And the stability of long-term neural activity recording is ensured. According to the flexible high-channel-number probe made of the reel core, after the reel core is pulled out, various different reel cores can be inserted into the hollow structure of the flexible high-channel-number probe so as to carry out optical stimulation, drug delivery and the like, and integration of various functions is achieved.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and in particular to a preparation process, an operation method and application of a flexible high-channel-number probe. Background Art

[0002] High-channel-count probes can record the activity of multiple neurons simultaneously, which is of great significance for understanding the neural mechanisms of brain function and provides a powerful tool for brain science research and treatment of neurological diseases.

[0003] Existing high-channel-count probes are usually silicon-based, metal-based, and other hard electronic devices, which have a large mechanical mismatch with soft biological tissues. Breathing, blood vessel pulsation, etc. will cause continuous relative displacement between the device and the tissue, which will then cause mechanical shearing, causing inflammatory reactions, and further affecting the stability of long-term neural activity recordings. Hard electronic devices are more difficult to apply to the gastrointestinal system, which will produce large deformations.

[0004] Although existing flexible electronic devices have low bending stiffness, their longitudinal length is limited. In brain science research on non-human primates, flexible electronic devices can usually only be implanted to the depth of the cerebral cortex and are difficult to target deep brain regions. Therefore, it is urgent to prepare flexible electronic devices with high channel counts and flexible designs to achieve stable detection of neural activity and other physiological signals in deep brain regions. Summary of the invention

[0005] The present invention provides a preparation process, an operation method and an application of a flexible high-channel number probe, which are used to solve the defects that there is a large mechanical mismatch between the existing probe and soft biological tissue, which causes mechanical shearing, causes inflammatory response, and further affects the stability of long-term neural activity recording.

[0006] In one aspect, the present invention provides a process for preparing a flexible high-channel number probe, comprising:

[0007] Design and prepare a planar electrode array that matches the characteristics of a biological body; composite the prepared planar electrode array with a prefabricated flexible substrate to form a winding area at the edge; prepare at least one reel core, and place the reel core on the winding area for winding to form a high-channel-count probe, wherein the high-channel-count probe has mechanical matching with the tissue, and when implanted in the tissue, it can reduce mechanical shearing caused by relative displacement between the tissue and the reel core.

[0008] Optionally, the planar electrode array is prepared by micro-nano processing technology, and the planar electrode array includes a base layer, a packaging layer and an electronic material layer therebetween. The base layer and the packaging layer of the planar electrode array are both thin film materials, and the thickness of the planar electrode array is 500nm to 20μm.

[0009] Optionally, the planar electrode array is directly transferred to a flexible substrate after being released from the silicon wafer, and a composite film is formed after being composited, the thickness of the flexible substrate is 1-100 μm, and the flexible substrate at least includes polydimethylsiloxane (PDMS), polystyrene-block poly(ethylene-butylene)-block polystyrene (SEBS), polyurethane (PU), Ecoflex, polystyrene-butadiene-styrene (SBS);

[0010] The method of combining the planar electrode array and the flexible substrate comprises: directly bonding the planar electrode array and the flexible substrate together after respectively processing them, wherein the processing method comprises at least plasma treatment, ultraviolet / ozone treatment, and heat treatment;

[0011] The method of compounding the planar electrode array and the flexible substrate also includes: bonding the planar electrode array and the flexible substrate with an adhesive, wherein the adhesive at least includes polyethylene glycol solution, silk fibroin solution, methacrylic acid-ethyl acrylate copolymer solution, sucrose solution, and gelatin.

[0012] Optionally, the method of rolling the composite film into a high-channel-count probe includes: fixing the reel core at the edge of the winding area, rolling the composite film around the reel core into a cylindrical high-channel-count probe, and then pulling out the reel core.

[0013] Optionally, the method of rolling the composite film into a high-channel-count probe also includes: rolling up the edge of the winding area to form a self-rolling core, and gradually rolling the composite film along the self-rolling core into a cylindrical high-channel-count probe, with the flexible base surface of the composite film facing inward.

[0014] Optionally, the reel core includes a single reel core, multiple reel cores or a composite structure reel core formed by integrating reel cores of multiple different materials, the composite method includes multiple reel cores being parallelly bonded or spirally wound together, the reel core has a diameter of 30 μm-1 mm, and the reel core is made of at least one or more materials selected from metal wire, quartz tube, optical fiber, polymer wire, medical SEEG electrode, and medical intracranial pressure measurement device.

[0015] Optionally, the composite film can be composited by flexible substrates of different materials and planar electrode arrays of different materials, and the flexible high-channel-count probe can be rolled by reel cores of different materials and composite films of different composite materials.

[0016] On the other hand, the present invention provides a method for using a flexible high-channel-count probe, comprising: preparing the flexible high-channel-count probe; fixing the organism to be detected by a positioning instrument; implanting the flexible high-channel-count probe into the brain, spinal cord or other organs of the organism to be detected; and performing subsequent signal acquisition work by an acquisition device.

[0017] Optionally, the reel core needs to be pulled out after the flexible high-channel-count probe is implanted into a biological body, and the methods of implanting the flexible high-channel-count probe into a biological body at least include direct manual implantation, navigation system-assisted implantation, ultrasound-assisted implantation, and magnetic-assisted implantation.

[0018] On the other hand, the present invention also provides an application of a flexible high-channel-count probe in a biomedical scenario, wherein the flexible high-channel-count probe can be applied to biological organisms, including at least rodents, dogs, pigs, sheep, birds, and non-human primates, and the flexible high-channel-count probe is used at least for the brain, spinal cord, peripheral nerves, visceral organs, and organoids of the biological organisms.

[0019] The preparation process, operation method and application of the flexible high-channel-number probe provided by the present invention are to form a composite film by compounding a planar electrode array and a low Young's modulus and stretchable flexible substrate, and to form a cylindrical flexible high-channel-number probe by using a scroll core or directly winding the composite film from the edge of the composite film, which has good mechanical matching with flexible tissues, can reduce mechanical shearing caused by relative displacement between the tissues, and ensure the stability of long-term neural activity recording. After the scroll core is pulled out, the hollow structure of the flexible high-channel-number probe made of the scroll core can also be inserted with a variety of different scroll cores for optical stimulation, drug delivery, etc., to achieve the integration of multiple functions. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0021] Figure 1 It is a schematic diagram of a process flow of preparing a flexible high-channel number probe provided by an embodiment of the present invention;

[0022] Figure 2 is a schematic diagram of a planar electrode array of a flexible high-channel-count probe of the present invention;

[0023] Figure 3 It is a schematic diagram of the present invention using a reel core to roll a flexible high-channel-count probe;

[0024] Figure 4 It is a schematic diagram of the application of the present invention in a biological scenario. DETAILED DESCRIPTION

[0025] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be clearly and completely described below in conjunction with the drawings of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0026] As mentioned above, existing high-channel-count probes are usually hard electronic devices such as silicon-based and metal, which have large mechanical mismatches with soft biological tissues. Breathing, blood vessel pulsation, etc. will cause continuous relative displacement between the device and the tissue, which will then cause mechanical shearing, resulting in inflammatory response and further affecting the stability of long-term neural activity recordings.

[0027] In view of this, the present invention provides a preparation process of a flexible high-channel number probe, which can improve the mechanical matching with biological tissues and reduce the mechanical shearing caused by relative displacement with tissues. The present invention solves this problem in the following ways:

[0028] Please refer to the instruction manual Figure 1 As shown in the figure, the present invention provides a preparation process of a flexible high-channel number probe, comprising the following steps:

[0029] S100, design and prepare a planar electrode array that matches the characteristics of the organism;

[0030] S200, compounding the prepared planar electrode array and the prefabricated flexible substrate, and forming a winding area at the edge;

[0031] S300, prepare at least one reel core, and place the reel core on the winding area for winding to form a high-channel-count probe. The high-channel-count probe has good mechanical matching with the tissue, and when implanted into the tissue, it can reduce mechanical shearing caused by relative displacement between the tissue and the reel core.

[0032] The present invention uses the above method to bond a planar electrode array made by micro-nano processing technology and a low Young's modulus and stretchable flexible substrate to obtain a composite film, and uses the composite film to roll a flexible high-channel number probe. After the probe is implanted in a biological body, the relative displacement between the device and the tissue caused by the biological body's breathing, blood vessel pulsation, etc. can be reduced, and then the mechanical shear caused by the relative displacement can be reduced, and the mechanical matching of the probe and the biological tissue can be improved, so as to achieve synchronous, long-term and stable detection of neural activities from the cortex to deep multiple brain regions. The Young's modulus of the planar electrode array is usually greater than 500MPa, and the Young's modulus of the flexible substrate is less than 10MPa. The Young's modulus of the composite film is related to the Young's modulus of the planar electrode array and the flexible substrate film material and the thickness ratio of the two films, as shown in the following formula:

[0033]

[0034] Among them, E 1 is the Young's modulus of the planar electrode array, E 2 is the Young's modulus of the flexible substrate. 1 is the thickness of the planar electrode array, h 2 is the thickness of the flexible substrate, and E 1 Greater than E 2 Therefore, the Young's modulus of the composite film is lower than that of the planar electrode array film of the same thickness used alone for winding.

[0035] in,

[0036] so,

[0037] Where E 1 Greater than E 2 ,h 1 ,h 2 are all positive numbers,

[0039] So E 复合薄膜 -E 1 Less than zero, E 复合薄膜 Less than E 1 ;

[0040] Similarly, is greater than zero, so E 复合薄膜 Greater than E 2 Therefore, under the same thickness, the Young's modulus of the high-channel-count probe made of the composite film is lower than that of the high-channel-count probe made of the planar electrode array alone, which can better fit the biological tissue to be detected and reduce the mechanical shear caused by the relative displacement with the tissue.

[0041] In order to further explain the implementation process of the above embodiment, the present invention provides another preferred embodiment. In another preferred embodiment of the present invention, in step S100, the planar electrode array includes a recording site area, a densely arranged conductive trace area and an interconnection area, such as Figure 2 and Figure 3 As shown, the recording sites can be set to 128, 256, 1024 or more sites, with different numbers, multiple distribution densities, multiple axial and lateral spatial distributions (including spacing, positions, etc.). The interconnection area includes multiple designs to be suitable for multiple connection methods with the back-end circuit, including flip-chip soldering, silver glue connection, wire bonding, direct contact, etc.

[0042] The planar electrode array described in the present invention comprises a base layer, a packaging layer and an electronic material layer, wherein the electronic material layer is made of gold, platinum, copper, aluminum, silver, titanium, chromium, nickel, tantalum, palladium, molybdenum, iridium, titanium nitride, iridium oxide, carbon nanotubes, graphene, and a combination of these and / or other similar elements. The thickness of the metal layer is less than 100 nm, and the effect on the Young's modulus of the flexible probe as a whole is small and can be ignored. The base layer and packaging layer materials of the planar electrode array are made of thin film materials, such as polyimide (PI), SU-8, polyethylene terephthalate (PET), polyparaxylene-C or Teflon. The planar electrode array is made of micro-nano processing technology, such as thin film deposition technology, photolithography technology, plasma etching technology, which can achieve high density, high throughput and large area. The thickness of the planar electrode array is 500 nm to 20 μm.

[0043] In another preferred embodiment of the present invention, in step S200, the flexible substrate described in the present invention is made of a thin film material, for example: polydimethylsiloxane (PDMS), polystyrene-block poly(ethylene-butylene)-block polystyrene (SEBS), polyurethane (PU), Ecoflex, polystyrene-butadiene-styrene (SBS), and the method for compounding the flexible substrate and the planar electrode array includes releasing the prepared planar electrode array from the silicon wafer and directly transferring it to the flexible substrate, and the planar electrode array can be directly bonded to the flexible substrate after treatment, and the treatment method includes plasma treatment, ultraviolet / ozone treatment, and heat treatment. After the treatment, the surfaces of the two materials are activated to increase the surface energy, and polar chemical functional groups (such as hydroxyl groups and carboxyl groups) are introduced to form a weak chemical bond connection or physical intercalation between the planar electrode array and the flexible substrate to achieve bonding.

[0044] An adhesive can also be added between the two to bond them together. The adhesive includes polyethylene glycol solution, silk fibroin solution, methacrylic acid-ethyl acrylate copolymer solution, sucrose solution, and gelatin. The method of adding the adhesive includes placing the adhesive solution at the end surface of the planar electrode array and the flexible substrate, and the adhesive enters the gap between the planar electrode array and the flexible substrate due to the capillary force of the liquid, or spin-coating the adhesive on the surface of the flexible substrate, and then transferring the planar electrode array to the flexible substrate. After the probe is implanted in the biological tissue, the adhesive will dissolve in the tissue fluid and will not produce additional effects, and will not increase the stiffness of the probe, so the effect of the adhesive on flexibility can be ignored. The method of compounding the flexible substrate and the planar electrode array also includes directly processing the flexible substrate to the surface of the planar electrode array through a micro-nano processing process, and the thickness of the flexible substrate is 1-100 μm.

[0045] In another preferred embodiment of the present invention, in S300, the flexible high-channel-count probe described in the present invention is wound in two ways: the first is to fix the winding reel core to the edge of the winding area of ​​the composite film, and the composite film can be rolled around the reel core into a cylindrical high-channel-count probe, and then the reel core is taken out; the second is to roll up the composite film from the edge of the winding area to form a self-reel core, and then gradually wind it to form a cylindrical high-channel-count probe.

[0046] High-channel-count probes include probes formed by various composite films wound around various reel cores. The recording site distribution of the planar electrode array is the sites distributed along the axial and lateral directions of the reel on the probe surface after winding. The recording sites include various distributions, sizes, densities and numbers. The interconnection area of ​​the planar electrode array is the interconnection part of the probe after winding, which is used for connection with the back-end circuit. The connection methods include flip-chip soldering, silver glue connection, wire bonding, direct contact, etc.

[0047] Based on the above content, when the high-channel number probe described in the present invention is wound through a reel core, the reel core is placed on the winding edge of the composite film, thereby winding into a cylindrical high-channel number probe, and the reel core may include a variety of diameters, lengths, materials and uses, such as: metal wires, quartz tubes, optical fibers, polymer wires, medical SEEG electrodes, medical intracranial pressure measurement devices, a single reel core, multiple reel cores or a composite structure reel core formed by integrating reel cores of multiple different materials; the composite structure reel core can be replaced with a single reel core after winding; the single reel core can also be replaced with reel cores of different diameters, lengths, materials and uses after winding. The integration method of the reel core can be adopted, such as: multiple metal wires are parallelly bonded together, multiple metal wires are spirally wound together, wherein the metal wires include at least tungsten wire, nickel-titanium wire, nickel-chromium wire, stainless steel wire, and the diameter of the reel core is 30μm-1mm. After the scroll core is pulled out, the hollow structure of the flexible high-channel-count probe rolled up by the scroll core can be inserted into a variety of different scroll cores for optical stimulation, drug delivery, etc., to achieve the integration of multiple functions.

[0048] Based on the above content, the high channel count probe of the present invention is wound with one side of the flexible substrate facing the reel core when it is wound using the reel core. After the winding is completed, the microwires of the reel core are pulled out one by one when the reel core is pulled out.

[0049] The flexible high-channel-count probe has the characteristics of high-channel number and high-density site arrangement; the flexible probe can contain thousands or even tens of thousands of sites; the site distribution density can be flexibly designed, and the sites can be arranged at a high density; the spatial distribution of the sites can be flexibly designed, and the sites can be distributed axially and laterally along the scroll, including the spacing and position, which can be flexibly designed, and the planar electrode array is prepared by standard micro-nano processing technology and composited with a flexible substrate to form a composite film. The polymer material used in the planar electrode array has good mechanical properties, and the high-density, high-throughput and large-area micro-nano processing technology thereon is mature and reliable; the flexible substrate has a low Young's modulus and high stretchability, so the probe after the composite film is wound is not easy to break and has strong operability, so that the flexible high-channel-count probe has good mechanical matching with the tissue.

[0050] The reel core used for winding operation can be selected from metal wire, polymer wire, optical fiber, medical SEEG electrode, medical intracranial pressure measurement device, etc., so as to realize the synchronous operation and multi-functional integration of electrical measurement, electrical stimulation and other measurements. In the same experiment, since the reel core is removable, it is possible to replace multiple functional reel cores to achieve different functions, so that the flexible high-channel probe has multi-functional detection functions, and when the flexible high-channel probe is implanted, it can avoid causing large-area wounds to the organism and achieve minimally invasive implantation.

[0051] Based on the same general inventive concept, the present invention also protects a method for using a flexible high-channel-count probe, which comprises the following steps:

[0052] S1. preparing the above-mentioned flexible high-channel number probe;

[0053] S2, fixing the organism to be detected by a positioning device;

[0054] S3, implanting the flexible high-channel number probe into the organism to be detected;

[0055] S4. Perform subsequent signal acquisition work through acquisition equipment.

[0056] For example, in an embodiment of the present invention, the above steps may include:

[0057] In S1, the interconnection area of ​​the probe is connected to the back-end circuit to realize signal collection. The interconnection method includes flip-chip soldering, silver glue connection, wire bonding, direct contact, etc. The back-end circuit includes a printed circuit board, a flexible flat cable, and a flexible circuit board.

[0058] In S2, the organism to be detected is fixed by a positioning instrument, and the high-channel-count probe is fixed on the clamping arm. The high-channel probe may include a reel core or may not include a reel core.

[0059] In S3, the high-channel-count probe is implanted into a living body by direct manual implantation or navigation system-assisted implantation, ultrasound-assisted implantation, or magnetic-assisted implantation.

[0060] Determine the implantation path to achieve the implantation of the probe without a scroll core and retain it in the organism. The implantation method includes opening a bone window and removing the dura mater. For the flexible probe whose scroll core has been pulled out before implantation, a soluble polymer can be injected into the hollow structure of the flexible probe to temporarily enhance the implantation rigidity of the probe, and then the probe without a scroll core can be implanted into the brain tissue; or the probe with a scroll core can be implanted into the brain tissue and then the scroll core can be pulled out to obtain a probe without a scroll core and retained in the organism. The extraction method includes using a single clamping arm method to completely implant the probe and then extract the scroll core; using a double clamping arm method to slowly extract the scroll core while the probe is implanted, and completely extract the scroll core after the probe is completely implanted. For the flexible probe formed by the self-scrolling core, the implantation rigidity of the probe can be temporarily enhanced by coating the probe surface with a soluble polymer, and then the self-scrolling core probe can be directly implanted into the brain tissue, or the self-scrolling core probe can be implanted into the brain tissue by magnetic assistance.

[0061] In S4, subsequent signal acquisition is performed through the acquisition device.

[0062] Based on the same general inventive concept, the present invention also protects the application of a flexible high-channel-count probe in biomedical scenarios. Specifically, the flexible high-channel-count probe described in the present invention can be applied to organisms including rodents, dogs, pigs, sheep, birds, non-human primates, as well as to the brain, spinal cord, peripheral nerves, visceral organs, and organoids of organisms, and can perform intraoperative recording and long-term recording. The flexible high-channel-count probe can also be used for electrical signal recording and stimulation, neurochemical recording, biochemistry and pressure sensing.

[0063] The flexible high-channel probe provided by the present invention has good mechanical matching with flexible tissues and can meet the application requirements of various organisms; when winding, a reel core with different diameters, lengths, materials or uses can be used for winding operations to achieve a combination of multiple functions such as electrical measurement and stimulation, neurochemical recording, biochemistry and pressure sensing. In the study of the central nervous system, this probe can be used to synchronously detect neural activity from the cerebral cortex to multiple deep brain regions and from the dorsal to ventral side of the spinal cord; it can detect electrical and chemical signals of the highly active gastrointestinal system; it can be wrapped around the surface of peripheral nerves to stably detect neural signals.

[0064] Flexible high-channel-count probes can be minimally invasively implanted into a living body. Furthermore, for the probes wound with a scroll core, after the scroll core is pulled out, the hollow structure thereof can be inserted into a variety of different scroll cores for optical stimulation, drug delivery, etc., to achieve the integration of multiple functions.

[0065] For example, the flexible high-channel-count probe without a scroll core described in the present invention is prepared by a micro-nano processing technology to obtain a planar electrode array, the planar electrode array has 256 recording sites, the polyimide planar electrode array is released from the silicon wafer, and the polyimide planar electrode array is transferred to the PDMS substrate to form a composite film, and the planar electrode array has a recording site area, a conductive wiring area, and an interconnection area. The edge of the composite film is rolled up to form a self-rolling core, and then gradually wound to form a cylindrical high-channel-count probe.

[0066] Another example: the flexible high-channel count probe comprising a scroll core described in the present invention is prepared by a micro-nano processing technology to obtain a planar electrode array, the planar electrode array has 256 recording sites, the SEBS solution is spin-coated onto the polyimide planar electrode array on the silicon wafer to form a composite film, the composite film is released from the silicon wafer, the composite film is transferred to a winding substrate, 5 50μm tungsten wires are twisted together, the composite film is wound around it into a roll, and then the 50μm tungsten wires are pulled out one by one and replaced with 100μm tungsten wires.

[0067] In summary, the preparation process, operation method and application in biological scenarios of the flexible high-channel number probe described in the present invention have the following advantages:

[0068] (1) High number of channels and high-density site arrangement: The flexible probe can contain thousands or even tens of thousands of sites; the site distribution density can be flexibly designed, and the sites can be arranged at a high density; the spatial distribution of the sites can be flexibly designed, and the sites can be distributed along the axial and lateral directions of the scroll, including the spacing and position, which can be flexibly designed.

[0069] (2) High mechanical matching with biological tissues: The planar electrode array is prepared by standard micro-nano processing technology and composited with a flexible substrate to form a composite film. The polymer material used in the planar electrode array has good mechanical properties, and the high-density, high-throughput and large-area micro-nano processing technology on it is mature and reliable; the flexible substrate has a low Young's modulus and high stretchability, so the probe after the composite film is wound is not easy to break, has strong operability and high mechanical matching.

[0070] (3) Multifunctionality: The reel core used for winding operation can be selected from metal wire, polymer wire, optical fiber, medical SEEG electrode, medical intracranial pressure measurement device, etc., so as to realize the synchronous operation and multifunctional integration of electrical measurement, electrical stimulation and other measurements. In the same experiment, since the reel core is removable, multiple functional reel cores can be replaced to achieve different functions.

[0071] (4) Less traumatic: The flexible probe can be implanted with minimal invasion, thus avoiding the formation of large-area wounds in the organism.

[0072] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A process for preparing a flexible high-channel number probe, characterized in that: include: Design and prepare planar electrode arrays that match biological characteristics; Compounding the prepared planar electrode array with a prefabricated flexible substrate and forming a winding region at the edge; At least one reel core is prepared, and the reel core is placed on the winding area for winding to form a high-channel-count probe. The high-channel-count probe has mechanical matching with the tissue and can reduce mechanical shearing caused by relative displacement between the tissue and the reel core when implanted into the tissue.

2. The preparation process according to claim 1, characterized in that: The planar electrode array is prepared by micro-nano processing technology, and includes a base layer, a packaging layer and an electronic material layer therebetween. The base layer and the packaging layer of the planar electrode array are both thin film materials, and the thickness of the planar electrode array is 500nm to 20μm.

3. The preparation process according to claim 1, characterized in that: The planar electrode array is directly transferred to a flexible substrate after being released from the silicon wafer, and a composite film is formed after being composited. The thickness of the flexible substrate is 1-100 μm, and the flexible substrate at least includes polydimethylsiloxane (PDMS), polystyrene-block poly(ethylene-butylene)-block polystyrene (SEBS), polyurethane (PU), Ecoflex, and polystyrene-butadiene-styrene (SBS); The method of combining the planar electrode array and the flexible substrate comprises: directly bonding the planar electrode array and the flexible substrate together after respectively processing them, wherein the processing method comprises at least plasma treatment, ultraviolet / ozone treatment, and heat treatment; The method of compounding the planar electrode array and the flexible substrate also includes: bonding the planar electrode array and the flexible substrate with an adhesive, wherein the adhesive at least includes polyethylene glycol solution, silk fibroin solution, methacrylic acid-ethyl acrylate copolymer solution, sucrose solution, and gelatin.

4. The preparation process according to claim 1, characterized in that: The method of rolling the composite film into a high-channel-count probe includes: fixing the reel core at the edge of the winding area, rolling the composite film around the reel core into a cylindrical high-channel-count probe, and then pulling out the reel core.

5. The preparation process according to claim 1, characterized in that: The method of rolling the composite film into a high-channel-count probe also includes: rolling up the edge of the winding area to form a self-rolling core, and gradually rolling the composite film along the self-rolling core into a cylindrical high-channel-count probe, with the flexible base surface of the composite film facing inward.

6. The preparation process according to claim 1, characterized in that: The reel core includes a single reel core, multiple reel cores or a composite structure reel core formed by integrating reel cores of multiple different materials. The composite method includes parallel bonding or spiral winding of multiple reel cores together. The reel core has a diameter of 30 μm-1 mm. The reel core is made of at least one or more materials selected from metal wire, quartz tube, optical fiber, polymer wire, medical SEEG electrode and medical intracranial pressure measurement device.

7. The preparation process according to claim 3, characterized in that: The composite film can be composited by flexible substrates of different materials and planar electrode arrays of different materials, and the flexible high-channel-count probe can be rolled by reel cores of different materials and composite films of different composite materials.

8. A method for using a flexible high-channel-number probe, characterized in that: The following steps are involved: Prepare the flexible high-channel-number probe as described in any one of claims 1 to 7; The organism to be detected is fixed by a positioning device; The flexible high-channel-count probe is implanted into the brain, spinal cord or other organs of the organism to be detected by using a clamping arm; Subsequent signal collection work is carried out through the acquisition equipment.

9. The method of use according to claim 7, characterized in that: After the flexible high-channel-count probe is implanted in a biological body, the reel core needs to be pulled out. The methods of implanting the flexible high-channel-count probe in a biological body at least include direct manual implantation, navigation system-assisted implantation, ultrasound-assisted implantation, and magnetic-assisted implantation.

10. Application of a flexible high-channel number probe in biomedical scenarios, characterized in that: The flexible high-channel-count probe can be applied to organisms, including at least rodents, dogs, pigs, sheep, birds, and non-human primates. The flexible high-channel-count probe is used at least for the brain, spinal cord, peripheral nerves, visceral organs, and organoids of the organisms.

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