A foldable brain electrode structure and its preparation method and application

Abstract

The present invention relates to the field of brain electrode technology, and in particular to a foldable brain electrode structure and a preparation method and application thereof. The foldable brain electrode structure has a first structure and a second structure, and the second structure includes a plurality of substructures; there is a preset distance between adjacent substructures so that the plurality of substructures can gather toward the center of the first structure to form an arc surface; the plurality of substructures are arranged around the edge of the first structure. The above-mentioned foldable brain electrode structure provided by the present invention has the characteristics of being applicable to arc-surface brain tissue, not easily forming stress concentration, having high conformability, being foldable, and greatly facilitating electrode implantation operations.

Description

Technical Field

[0001] The present invention relates to the technical field of brain electrodes, and in particular to a foldable brain electrode structure and a preparation method and application thereof. Background Art

[0002] EEG monitoring has always played an irreplaceable role in the diagnosis and surgical positioning of brain diseases. In recent years, with the launch of the "Brain Project" worldwide, effective and high-quality EEG signal acquisition has become increasingly important, which will directly contribute to the decoding of brain functions and promote the development of a series of high-tech technologies based on this, such as brain-computer interfaces and neural regulation.

[0003] However, the brain electrode structures in the prior art are generally planar structures, which cannot cover the cerebral cortex or even the brain tissue in irregular positions deep in the brain. In addition, since the brain electrode structure is a planar structure, when it is in an arc or covered on a tissue position with a smaller arc, it is easy to cause excessive wrinkles in the brain electrode structure, forming stress concentration, which is easy to cause damage to the brain electrode structure after long-term use. Summary of the invention

[0004] The present invention aims to solve the technical problem that the brain electrode structure in the prior art has poor coverage of brain tissue in the arc-shaped area and is easily damaged after long-term use.

[0005] In order to solve the above technical problems, the present application discloses a foldable brain electrode structure, which includes:

[0006] First structure;

[0007] A second structure, on which a recording electrode is provided; the second structure includes N substructures; N is an integer greater than or equal to 2; there is a preset distance between adjacent substructures in the N substructures, so that the N substructures can gather toward the center of the first structure to form an arc surface; the N substructures are arranged around the edge of the first structure.

[0008] Optionally, a pad array is provided on the top of the first structure or on any one of the N substructures;

[0009] The pad array is connected to the pad structure of the external connection structure accordingly.

[0010] Optionally, the recording electrode and the pad array are located on the same plane;

[0011] Each of the remaining substructures of the N substructures includes a first substrate layer, an electrode wire layer, and a first insulating layer stacked in sequence;

[0012] The electrode wire layer includes wires and the recording electrode;

[0013] One end of the wire is connected to the recording electrode, and the other end of the wire is connected to a corresponding pad in the pad array;

[0014] The insulating layer is provided with an electrode hole for exposing the recording electrode.

[0015] Optionally, the pad array is provided at the bottom of the first structure;

[0016] The recording electrode comprises a first recording electrode and a second recording electrode;

[0017] The first recording electrode is arranged on the top of the first structure;

[0018] Each of the N substructures includes a first substrate layer, a wire layer, a second substrate layer, a second recording electrode layer and a first insulating layer stacked in sequence;

[0019] The second substrate layer is provided with a first electrode hole, and the wire layer is connected to the second recording electrode of the second recording electrode layer through the first electrode hole;

[0020] A second electrode hole is provided on the first insulating layer, and the second electrode hole is used to expose the second recording electrode;

[0021] The first structure includes a third substrate layer, a fourth substrate layer, and a second insulating layer;

[0022] The third base layer is provided with a through hole array;

[0023] Each through hole in the through hole array is provided with a corresponding pad of the pad array;

[0024] The second insulating layer is provided with a third electrode hole, and the third electrode hole is used to expose the first recording electrode;

[0025] The third base layer is connected to the first base layer to form an integrated structure;

[0026] The fourth base layer is connected to the second base layer to form an integrated structure;

[0027] The first insulating layer and the second insulating layer are connected to form an integral structure.

[0028] Optionally, each of the N substructures includes a first substrate layer, a wire layer, a second substrate layer, a recording electrode layer and a first insulating layer stacked in sequence;

[0029] The second substrate layer is provided with a first electrode hole, and the wire layer is connected to the recording electrode of the recording electrode layer through the first electrode hole;

[0030] The insulating layer is provided with a second electrode hole, and the second electrode hole is used to expose the recording electrode;

[0031] The first base layer of any one of the N substructures is provided with a through hole array;

[0032] Each through hole in the through hole array is provided with a corresponding solder pad of the solder pad array.

[0033] Optionally, the shape of the second structure includes triangle, quadrilateral, pentagon or hexagon.

[0034] Optionally, the second structure includes M first substructures and NM second substructures; M is an integer greater than or equal to 1;

[0035] The M first substructures are arranged along the edge of the first structure and connected to the edge of the first structure;

[0036] The NM second substructures are arranged along the outer edges formed by the M first substructures, and each of the NM second substructures is connected to the corresponding first substructure.

[0037] On the other hand, the present application also discloses a method for preparing a foldable brain electrode structure, which comprises:

[0038] Providing a silicon substrate;

[0039] preparing a sacrificial layer on the silicon substrate;

[0040] preparing a support layer on the sacrificial layer;

[0041] forming a conductor layer and a recording electrode layer on the support layer in sequence;

[0042] forming an insulating layer on the recording electrode layer;

[0043] Patterning and etching the insulating layer to form an electrode hole; the electrode hole can expose the recording electrode of the recording electrode layer;

[0044] The sacrificial layer is released to obtain a foldable brain electrode structure, which includes a first structure and a second structure, and the recording electrode is arranged on the second structure; the second structure includes N substructures; N is an integer greater than or equal to 2; there is a preset distance between adjacent substructures in the N substructures, so that the N substructures can gather toward the center of the first structure to form an arc surface; the N substructures are arranged around the edge of the first structure.

[0045] Optionally, after releasing the sacrificial layer to obtain the foldable brain electrode structure, the method further includes:

[0046] Placing the foldable brain electrode structure in the inner cavity of the arc-shaped mold;

[0047] pouring silk protein solution into the inner cavity;

[0048] After drying, the folded and solidified foldable brain electrode structure is obtained.

[0049] On the other hand, the present application also discloses an application of the above-mentioned foldable brain electrode structure in collecting brain signals from deep brain nuclei.

[0050] By adopting the above technical solution, the foldable brain electrode structure provided by the present application has the following beneficial effects:

[0051] The foldable brain electrode structure has a first structure and a second structure, the second structure includes N substructures; N is an integer greater than or equal to 2; there is a preset distance between adjacent substructures in the N substructures, so that the N substructures can gather toward the center of the first structure to form an arc surface; the N substructures are arranged around the edge of the first structure, and each of the substructures is provided with a recording electrode. Since the electrode structure can be gathered into arc surfaces of different curvatures as needed, it is easy to adapt to brain tissues of different curvatures, has high application flexibility and is not easy to form stress concentration at the bend. Moreover, before placing the electrode structure on the brain tissue, it can be folded into a spherical shape, which reduces the space occupied by the brain electrode structure. When it is delivered to the designated brain tissue, it can be unfolded to form a structure of the required curvature, which has the advantages of multiple detection channels and small wound surface. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0053] Figure 1 It is a schematic diagram of the structure of the brain electrode structure in the prior art;

[0054] Figure 2 A schematic structural diagram of a first optional foldable brain electrode structure provided in this application;

[0055] Figure 3 A schematic structural diagram of a second optional foldable brain electrode structure provided in this application;

[0056] Figure 4 A schematic structural diagram of a third optional foldable brain electrode structure provided in this application;

[0057] Figure 5 A schematic structural diagram of a fourth optional foldable brain electrode structure provided in this application;

[0058] Figure 6The structure and stress distribution diagram of arc surfaces of different radii formed by the foldable brain electrode structure provided in this application;

[0059] Figure 7 A flow chart for preparing an optional foldable brain electrode structure for this application;

[0060] Figure 8 It is a structural schematic diagram of the arc mold;

[0061] Fig. 9 Schematic diagram of the location of the hypothalamic nuclei in the head.

[0062] The following is a supplementary description of the attached drawings:

[0063] 1-electrode array; 2-first structure; 3-second structure; 31-substructure; 311-first substructure; 312-second substructure; 4-recording electrode; 41-first recording electrode; 42-second recording electrode; 5-first substrate layer; 6-conducting wire layer; 7-second substrate layer; 71-first electrode hole; 8-second recording electrode layer; 9-first insulating layer; 91-second electrode hole; 10-third electrode hole; 11-silicon substrate; 12-sacrificial layer; 13-support layer; 14-pad array; 15-packaging layer; 16-insulating layer. DETAILED DESCRIPTION

[0064] The technical solutions in the embodiments of the present application will be described clearly and completely below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0065] The term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure or characteristic that may be included in at least one implementation of the present application. In the description of the present application, it should be understood that the orientation or positional relationship indicated by the terms "upper", "lower", "top", "bottom", etc. is based on the orientation or positional relationship shown in the accompanying drawings, which is only for the convenience of describing the present application and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation of the present application. In addition, the terms "first" and "second" are used only for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, the features defined as "first" and "second" may include one or more of the features explicitly or implicitly. Moreover, the terms "first", "second", etc. are used to distinguish similar objects, and are not necessarily used to describe a specific order or sequence. It should be understood that the data used in this way can be interchangeable where appropriate, so that the embodiments of the present application described here can be implemented in an order other than those illustrated or described here.

[0066] For the purpose of the following detailed description, it should be understood that the present invention may adopt various alternative changes and step sequences, unless expressly specified to the contrary. In addition, except in any operating examples, or otherwise indicated, all numbers representing the amount of ingredients used in the specification and claims should be understood to be modified by the term "about" in all cases. Therefore, unless otherwise indicated, the numerical parameters set forth in the following specification and the attached claims are approximate values ​​that vary according to the desired performance to be obtained by the present invention. At least it is not intended to limit the application of the doctrine of equivalents to the scope of the claims, and each numerical parameter should at least be interpreted according to the number of reported significant figures and by applying ordinary rounding techniques.

[0067] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values ​​set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0068] When a numerical range is disclosed herein, the above range is deemed to be continuous and includes the minimum and maximum values ​​of the range, as well as each value between such minimum and maximum values. Further, when a range refers to an integer, each integer between the minimum and maximum values ​​of the range is included. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be merged. In other words, unless otherwise indicated, all ranges disclosed herein should be understood to include any and all sub-ranges included therein. For example, a specified range from "1 to 10" should be deemed to include any and all sub-ranges between a minimum of 1 and a maximum of 10. Exemplary sub-ranges of ranges 1 to 10 include, but are not limited to, 1 to 6.1, 3.5 to 7.8, 5.5 to 10, etc.

[0069] See also Figure 1 , Figure 1 The schematic diagram of the structure of the brain electrode in the prior art. The entire brain electrode structure is a flat plate structure, on which an electrode array 1 can be arranged in an array. However, for a curved surface with a relatively large curvature value, when the brain electrode of the flat structure is attached to it, wrinkles are easily formed, resulting in concentrated application at that place, reducing the reliability of the brain electrode; and the connection plate at the rear end of the brain electrode in the prior art has a huge area, which is difficult to meet the surgical plan for clinical implantation and is difficult to operate clinically. Therefore, refer to Figure 2 , Figure 2 A schematic diagram of the structure of the first optional foldable brain electrode structure provided in the present application. The brain electrode structure includes a first structure 2 and a second structure 3, and a recording electrode 4 is provided on the second structure 3; the second structure 3 includes N substructures 31; N is an integer greater than or equal to 2; there is a preset distance between adjacent substructures 31 in the N substructures 31, so that the N substructures 31 can gather toward the center of the first structure 2 to form an arc surface; the N substructures 31 are arranged around the edge of the first structure 2, because the brain electrode structure can be set to fold into arc surfaces of different curvatures as needed, it is convenient to adapt to brain tissues with different arc surfaces, and because the brain electrode structure can be folded and gathered, it can be folded into a spherical shape before placing the electrode structure on the brain tissue, reducing the occupied space of the brain electrode structure, and when it is delivered to the designated brain tissue, it can be unfolded to form a structure of the required curvature, with the characteristics of multiple detection channels and small wound surface, realizing flexible electrode minimally invasive deep brain detection, breaking through the bottleneck.

[0070] Optionally, the brain electrode structure can be connected to a flexible circuit board at the rear end, and the length of the flexible circuit board is greater than 0.8 meters, so that the brain electrode structure can be released to a specified position through the nasal cavity. Optionally, the flexible circuit board and the brain electrode structure are hot-pressed by using anisotropic conductive film.

[0071] In a feasible embodiment, the second structure 3 has a shape of a triangle, a quadrilateral, a pentagon or a hexagon. The shape of the first structure 2 is not limited, and can be the same as the second structure 3, or a circle or other special shapes.

[0072] In a possible embodiment, see Figure 3 , Figure 3 This is a schematic diagram of the structure of the second optional foldable EEG electrode structure provided by the present application. The substructures 31 in the second structure 3 are arranged around the edge of the first structure 2. Of course, depending on the size of the curved surface to be covered, in order to make the EEG electrode structure cover as many curved surfaces as possible; see Figure 4 , Figure 4 A schematic diagram of the structure of the third optional foldable brain electrode structure provided by the present application. The second structure 3 includes M first substructures 311 and NM second substructures 312, where M is an integer greater than or equal to 1, the M first substructures 311 are arranged along the edge of the first structure 2 and connected to the edge of the first structure 2, the NM second substructures 312 are arranged along the outer edge formed by the M first substructures 311, and each of the NM second substructures 312 is connected to the corresponding first substructure 311. Of course, in order to further increase the coverage area of ​​the electrode structure while reducing stress concentration at the bending point, the second structure 3 can be further divided into multi-layer substructures 31, that is, the second structure 3 can include M first substructures 311, L second substructures 312 and NML third substructures 31, wherein N is an integer greater than or equal to 3, L is an integer greater than or equal to 1, the first substructure 311 is a substructure 31 directly connected to the edge of the first structure 2, the second substructure 312 is a substructure 31 connected to the outer edge of the first substructure 311, and the third substructure 31 is a substructure 31 connected to the outer edge of the second substructure 312.

[0073] It should be noted that the outer edges of the first substructure 311 , the second substructure 312 and the third substructure 31 are edges away from the center of the first structure 2 .

[0074] Generally, the brain electrode structure includes a connected recording electrode 4 and a pad array 14, wherein the recording electrode 4 is used to collect electroencephalographic signals, and the pad array 14 is used to connect to an external signal acquisition device. In a feasible embodiment, the recording electrode 4 and the pad array 14 are located on the same plane; each substructure 31 of the remaining substructures 31 of the N substructures 31 includes a first base layer 5, an electrode wire layer 6 and a first insulating layer 16 stacked in sequence, and the electrode wire layer 6 includes a wire and the recording electrode 4, one end of the wire is connected to the recording electrode 4, and the other end of the wire is connected to the corresponding pad in the pad array 14, and the first insulating layer 16 is provided with an electrode hole for exposing the recording electrode 4. Optionally, the pad array 14 can be arranged on the top of the first structure 2, or on the top of any substructure 31 of the N substructures 31.

[0075] In another feasible embodiment, the recording electrode 4 and the pad array 14 can be located on opposite sides of the entire brain electrode structure, so that the side with the recording electrode 4 can be better attached to the brain tissue. Figure 5 , Figure 5 A schematic diagram of the structure of the fourth optional foldable brain electrode structure provided by the present application. The pad array 14 can be arranged at the bottom of the first structure 2, the recording electrode 4 includes a first recording electrode 41 and a second recording electrode 42, the first recording electrode 41 is arranged on the top of the first structure 2, each substructure 31 of the N substructures 31 includes a first base layer 5, a wire layer 6, a second base layer 7, a second recording electrode layer 8 and a first insulating layer 16 stacked in sequence, the second base layer 7 is provided with a first electrode hole 71, the wire layer 6 is connected to the second recording electrode 42 of the second recording electrode layer 8 through the first electrode hole 71, the first insulating layer 16 is provided with a second electrode hole 91, and the The second electrode hole 91 is used to expose the second recording electrode 42. The first structure 2 includes a third base layer, a fourth base layer and a second insulating layer. The third base layer is provided with a through hole array. Each through hole in the through hole array is provided with a corresponding pad of the pad array 14. The second insulating layer is provided with a third electrode hole 10. The third electrode hole 10 is used to expose the first recording electrode 41. The third base layer is connected to the first base layer 5 to form an integrated structure. The fourth base layer is connected to the second base layer 7 to form an integrated structure. The first insulating layer 16 is connected to the second insulating layer to form an integrated structure.

[0076] Optionally, when the pad array 14 is located at the bottom of the overall structure, a fourth base layer can be provided between the wire layer 6 and the first recording electrode 41, so as to isolate the pad array from the first recording electrode 41, and avoid direct conduction between other pads on the pad array 14 and the first recording electrode 41, thereby short-circuiting the second recording electrode 42; and because the pad array is provided at the bottom, the corresponding top can also be provided with a recording electrode 4, so as to further effectively utilize the surface of the brain electrode and increase the number of channels for signal acquisition.

[0077] It should be noted that a fourth electrode hole is provided on the fourth base layer, so that the wire layer 6 can be connected to the first recording electrode 41 through the fourth electrode hole.

[0078] In a feasible embodiment, each of the N substructures 31 includes a first substrate layer 5, a wire layer 6, a second substrate layer 7, a recording electrode layer and a first insulating layer 16 stacked in sequence, a first electrode hole 71 is provided on the second substrate layer 7, and the wire layer 6 is connected to the recording electrode 4 of the recording electrode layer through the first electrode hole 71, and a second electrode hole 91 is provided on the insulating layer 16, and the second electrode hole 91 is used to expose the recording electrode 4, and the first substrate layer 5 of any substructure 31 of the N substructures 31 is provided with a through hole array, and each through hole in the through hole array is provided with a corresponding pad of the pad array 14. In other words, the pad array 14 is located on any substructure 31, and of course, the recording electrode 4 is provided on the first structure 2.

[0079] It should be noted that, although the recording electrodes 4 are not distinguished in the above description, it should be known that the number of recording electrodes 4 is the same as the number of pads in the pad array 14 and they are connected one-to-one, and a recording electrode 4 may be provided on each substructure 31.

[0080] The foldable brain electrode structure can then be shaped using silk protein solution to form a ball, and after being implanted in the body and reaching the designated signal collection point, the protein can be dissolved in the body fluid environment to restore flexibility. This makes the brain electrode structure highly flexible, foldable, and conformally adherent, with good operability, and can achieve high-precision minimally invasive detection of electrical signals in deep brain nuclei.

[0081] By attaching the above-mentioned foldable brain electrode structure to curved surfaces of different curvatures, the flexible electrode device can be tightly attached to the curved surface using only the surface tension of water; the device can be folded into a ball under the action of external force, and the conductive performance of the device is not affected during this process. Figure 6 , Figure 6 The structure and stress distribution diagram of arc surfaces of different radii formed by the foldable brain electrode structure provided in this application. Figure 6Figure a1 in the figure is a schematic diagram of the structure of the brain electrode structure with a curved surface radius of 2.5 mm. Figure 6 Figure a2 in is the stress distribution diagram of Figure a1; Figure 6 Figure b1 in the figure is a schematic diagram of the structure of the brain electrode structure with a curved surface radius of 5 mm. Figure 6 Figure b2 in is the stress distribution diagram of Figure b1; Figure 6 Figure c1 in the figure is a schematic diagram of the structure of the brain electrode structure with a curved surface radius of 20 mm. Figure 6 Figure c2 is the stress distribution diagram of Figure c1; from this, it can be seen that the foldable brain electrode structure provided by the present application has less stress concentration, and as the radius of curvature increases, that is, the unfolding of the brain electrode structure, the area of ​​high stress concentration of the structure gradually decreases.

[0082] Optionally, the foldable brain electrode structure disclosed in this application can be applied to the detection of a wide range of EEG signals in neuroscience research and signal collection related to cutting-edge technology and artificial intelligence due to its foldability. It is designed for deep brain nuclei of the hypothalamus, and its special contour design can conform to the curved surface; the slender signal transmission circuit board is matched with mature craniopharyngioma surgery; the flexible skull base electrode combined with silk protein solution can be temporarily shaped before implantation, and after being implanted in the body and reaching the designated signal collection point, the protein is dissolved in the body fluid environment to restore flexibility; it can achieve high-precision minimally invasive detection of electrical signals in deep brain nuclei.

[0083] See also Figure 7 , Figure 7 The present application also discloses a method for preparing a foldable brain electrode structure, which comprises:

[0084] 1) Provide a silicon substrate 11, such as Figure 7 As shown in Figure (a).

[0085] 2) Prepare a sacrificial layer 12 on the silicon substrate 11, such as Figure 7 As shown in Figure (b).

[0086] Optionally, the material of the sacrificial layer 12 includes aluminum, and the thickness ranges from 8000 to 10000 angstroms; optionally, the thickness of the sacrificial layer 12 is 1 micron.

[0087] 3) A support layer 13 is prepared on the sacrificial layer 12 .

[0088] Optionally, step 3) may be specifically described as: a flexible material layer may be formed on the sacrificial layer 12 by a spin coating process, and the flexible material layer may be patterned to form the support layer 13 .

[0089] Optionally, the flexible material layer comprises polyimide.

[0090] Optionally, after the above-mentioned flexible material layer is spin-coated, it is also required to be cured at a preset temperature.

[0091] Optionally, the curing temperature is 200 degrees Celsius.

[0092] 4) The conductor layer 6 and the recording electrode layer are formed on the support layer 13 in sequence.

[0093] Optionally, the preparation process may be different depending on the structural design. Figure 2 or Figure 3 The structure of the substrate 13 can be specifically represented as follows: patterning a through hole array on the support layer 13; sputtering to form a pad array 14 at the through hole array; and then sequentially forming a wire layer 6 and a recording electrode layer. The wire layer 6 is a wire connecting the recording electrode 4 and the bottom pad array 14.

[0094] Optionally, the wire layer 6 and the recording electrode layer may be formed by a magnetron sputtering process.

[0095] Optionally, if prepared as Figure 4 The structure shown in FIG. 1 is a structure in which the support layer 13 is determined as the support layer 13. Then, step 4) can be represented as: patterning a through hole array on the layer, and sputtering to form a pad array 14 (such as Figure 7 ), and sputtering forms a conductor layer 6 (as shown in FIG. Figure 7 A flexible material layer is formed on the conductor layer 6 by a spin coating process, and the flexible material layer is patterned to obtain a packaging layer 15, and a second electrode hole 91 is formed on the packaging layer 15 (as shown in FIG. Figure 7 As shown in FIG. (f) in FIG. 1 , a recording electrode layer is sputtered on the packaging layer 15; the wire layer 6 is connected to the recording electrode layer through the second electrode hole 91 (as shown in FIG. Figure 7 as shown in Figure (g) in the figure).

[0096] Optionally, the material of the pad array 14 includes Cr / Au / Cr or Cr / Ni / Au / Cr, wherein the thickness of the sputtered Au layer ranges from 350 to 5000 angstroms, the thickness of the sputtered Ni layer ranges from 1000 to 1500 angstroms, and the thickness of the sputtered Cr layer ranges from 300 to 500 angstroms.

[0097] Optionally, the thickness of the support layer 13 is 2-3 micrometers.

[0098] Optionally, the thickness of the encapsulation layer 15 is in the range of 1 to 2 micrometers, and the curing temperature is in the range of 240 to 260 degrees Celsius.

[0099] Optionally, the materials of the wire layer 6 and the recording electrode layer include Cr / Au, and for the wire layer 6, the thickness of the Cr / Au material ranges from 300 / 3500 angstroms to 500 / 5000 angstroms, and for the recording electrode layer, the thickness of the Cr / Au material ranges from 300 / 3000 angstroms to 500 / 5000 angstroms.

[0100] 5) forming an insulating layer 16 on the recording electrode layer, such as Figure 7 As shown in Figure (h).

[0101] Optionally, the material of the insulating layer 16 is the same as that of the base layer, both of which are flexible materials.

[0102] Optionally, the thickness of the insulating layer 16 is in the range of 5 to 8 micrometers, and the temperature for curing the flexible material layer is in the range of 280 to 320 degrees Celsius.

[0103] 6) Patterning and etching the insulating layer 16 to form electrode holes; the electrode holes can expose the recording electrode 4 of the recording electrode layer, such as Figure 7 As shown in Figure (i) in .

[0104] 7) Release the sacrificial layer 12 to obtain a foldable brain electrode structure (such as Figure 7 As shown in Figure (g) in the figure, the foldable brain electrode structure includes a first structure 2 and a second structure 3, and the recording electrode 4 is arranged on the second structure 3; the second structure 3 includes N substructures 31; N is an integer greater than or equal to 2; there is a preset distance between adjacent substructures 31 in the N substructures 31, so that the N substructures 31 can gather toward the center of the first structure 2 to form an arc surface; the N substructures 31 are arranged around the edge of the first structure 2, which can be seen in Figure 5 .

[0105] It should be noted that during the preparation process, a metal connection layer (such as Figure 7 As shown in Figure (d) in the figure, a metal connection layer is also sputtered in the first electrode hole 71 connecting the wire layer 6 with the upper recording electrode 4. The metal connection layer can be Cr / Au, and the thickness of the Cr / Au material ranges from 300 / 3500 angstroms to 500 / 5000 angstroms.

[0106] In a feasible embodiment, after releasing the sacrificial layer 12 to obtain the foldable brain electrode structure, the method further includes:

[0107] 8) Placing the foldable brain electrode structure in the inner cavity of the arc-shaped mold.

[0108] Optional, see Figure 8 , Figure 8Schematic diagram of the structure of the arc-shaped mold. The mold with spherical hollow grooves can be made using polydimethylsiloxane (PDMS).

[0109] The foldable brain electrode structure is assembled with the flexible circuit board at the rear end, and the assembled device is placed in the mold so that the brain electrode structure is completely attached to the inner wall of the spherical cavity.

[0110] 9) Pour the silk protein solution into the inner cavity.

[0111] Optionally, the silk protein solution can be prepared by the following method: the silkworm cocoons are boiled in a 0.02 mol / L Na2CO3 aqueous solution for 30 minutes, and then rinsed with distilled water 3 times (30 minutes each time) to remove Na2CO3 and sericin. After drying in air for about 12 hours, the degummed cocoons are dissolved in a 9.3 mol / L LiBr solution at 60°C for about 4 hours. The solution is dialyzed for 2 days using a Slide-A-Lyzer dialysis cassette (molecular weight cutoff, MWCO=3500, Pierce, USA). Subsequently, centrifuged twice at 18000 rpm, each time for 20 minutes. By measuring the volume and final dry weight of the solution, it is determined that the final concentration of silk is about 6-7wt%.

[0112] Optionally, the concentration of the silk protein solution may also be in the range of 7 to 15 wt %. The concentration of the shaping solution only affects the length of time it takes for the flexible electrode to recover its flexibility after the dissolved protein is in the body fluid environment.

[0113] 10) After drying, take it out to obtain a foldable brain electrode structure after folding and solidification.

[0114] It should be noted that by pouring the above-mentioned silk protein solution into the mold and drying it in a clean room environment for 24 hours; after demolding, the front end brain electrode structure can be shaped into a small ball with a radius of about 4 mm (depending on the mold radius, the optional range is 3 to 5 mm).

[0115] The flexible skull base electrode made according to the above manufacturing process is attached to curved surfaces of different curvatures. The flexible electrode device can be tightly fitted to the curved surface simply by using the surface tension of water; the device can be folded into a ball under the action of external force, and the conductive performance of the device is not affected in this process.

[0116] On the other hand, the present application also discloses an application of the above-mentioned foldable brain electrode structure to collect brain signals from deep brain nuclei. The deep brain nuclei can be the hypothalamic nuclei, which are the center for regulating basic physiological activities of the human body and participate in regulating the autonomic nervous system, such as controlling water and salt metabolism, regulating body temperature, eating, sleep, reproduction, visceral activities and emotions, etc., affecting the activities of the nervous system and other multiple physiological systems. It can be considered as a bridge for communication between multiple physiological systems and an indispensable key link in the study of closed-loop brain neural pathways. However, the academic community has not yet reported on the detection of electrical signals in this area. See Fig. 9 , Fig. 9 This is a schematic diagram of the location of the hypothalamic nucleus in the head. If the existing deep brain stimulation / collection method is used, it will inevitably cause damage to brain tissue. The flexible electrode is implanted through the nasal cavity and placed at the hypothalamic nucleus at the base of the skull.

[0117] Optionally, the above-mentioned brain electrode structure can be used to collect brain signals from the hypothalamic nuclei after tumor removal. The cavity left after tumor removal (see Fig. 9 ), so that the physiological electrical signals of the hypothalamic nuclei can be directly collected.

[0118] from Fig. 9 It can be seen that although the shape and size of the cavity formed by the tumor are different, they are all dome-shaped as a whole. Therefore, the foldable brain electrode structure designed as above can adapt to the cavity arch surface with different curvature radii, ensuring that the brain electrode structure can be closely attached to the cavity surface. And the outer contour of the plane similar to the unfolding of the sphere provided by the present application can also be folded and spliced ​​to restore it to a small spherical surface (see above). Figure 8 ), thereby facilitating the shape fixation of the device and facilitating surgical implantation operations.

[0119] The above are only optional embodiments of the present application and are not intended to limit the present application. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present application should be included in the protection scope of the present application.

Claims

1. A foldable brain electrode structure, characterized in that: include: First structure (2); a second structure (3), wherein a recording electrode (4) is provided on the second structure (3); the second structure (3) comprises N substructures (31); N is an integer greater than or equal to 2; there is a preset distance between adjacent substructures (31) in the N substructures (31), so that the N substructures (31) can gather toward the center of the first structure (2) to form an arc surface; and the N substructures (31) are arranged around the edge of the first structure (2); A pad array (14) is provided on the top of the first structure (2) or on any one of the N substructures (31); The pad array (14) is connected correspondingly to the pad structure of the external connection structure; Each of the N substructures is provided with a recording electrode (4); The foldable brain electrode structure can form a spherical structure after being placed in a silk protein solution and folded and solidified.

2. The foldable brain electrode structure according to claim 1, characterized in that: The recording electrode (4) and the pad array (14) are located on the same plane; Each substructure (31) in the remaining substructures (31) of the N substructures (31) comprises a first base layer (5), a wire layer (6) and a first insulating layer (9) stacked in sequence; The wire layer (6) comprises wires and the recording electrodes (4); One end of the wire is connected to the recording electrode (4), and the other end of the wire is connected to a corresponding pad in the pad array (14); The first insulating layer (9) is provided with an electrode hole for exposing the recording electrode (4).

3. The foldable brain electrode structure according to claim 1, characterized in that: The pad array (14) is provided at the bottom of the first structure (2); The recording electrode (4) comprises a first recording electrode (41) and a second recording electrode (42); The first recording electrode (41) is provided on the top of the first structure (2); Each of the N substructures (31) comprises a first substrate layer (5), a wire layer (6), a second substrate layer (7), a second recording electrode layer (8) and a first insulating layer (9) stacked in sequence; The second substrate layer (7) is provided with a first electrode hole (71), and the wire layer (6) is connected to the second recording electrode (42) of the second recording electrode layer (8) through the first electrode hole (71); A second electrode hole (91) is provided on the first insulating layer (9), and the second electrode hole (91) is used to expose the second recording electrode (42); The first structure (2) comprises a third base layer, a fourth base layer and a second insulating layer; The third base layer is provided with a through hole array; Each through hole in the through hole array is provided with a corresponding solder pad of the solder pad array (14); A third electrode hole (10) is provided on the second insulating layer, and the third electrode hole (10) is used to expose the first recording electrode (41); The third base layer is connected to the first base layer (5) to form an integrated structure; The fourth base layer and the second base layer (7) are connected to form an integral structure; The first insulating layer (9) and the second insulating layer are connected to form an integral structure.

4. The foldable brain electrode structure according to claim 1, characterized in that: Each of the N substructures (31) comprises a first substrate layer (5), a wire layer (6), a second substrate layer (7), a recording electrode layer and a first insulating layer (9) stacked in sequence; The second substrate layer (7) is provided with a first electrode hole (71), and the wire layer (6) is connected to the recording electrode (4) of the recording electrode layer through the first electrode hole (71); A second electrode hole (91) is provided on the first insulating layer (9), and the second electrode hole (91) is used to expose the recording electrode (4); The first base layer (5) of any one of the N substructures (31) is provided with a through-hole array; Each through hole in the through hole array is provided with a corresponding solder pad of the solder pad array (14).

5. The foldable brain electrode structure according to claim 1, characterized in that: The shape of the second structure (3) includes a triangle, a quadrilateral, a pentagon or a hexagon.

6. The foldable brain electrode structure according to claim 1, characterized in that: The second structure (3) includes M first substructures (311) and NM second substructures (312); M is an integer greater than or equal to 1; The M first substructures (311) are arranged along the edge of the first structure (2) and connected to the edge of the first structure (2); The NM second substructures (312) are arranged along the outer edges formed by the M first substructures (311), and each second substructure (312) among the NM second substructures (312) is connected to the corresponding first substructure (311).

7. A method for preparing the foldable brain electrode structure according to any one of claims 1 to 6, characterized in that: include: Providing a silicon substrate (11); Preparing a sacrificial layer (12) on the silicon substrate (11); Preparing a support layer (13) on the sacrificial layer (12); A conductor layer (6) and a recording electrode layer are sequentially formed on the support layer (13); forming an insulating layer (16) on the recording electrode layer; Patterning and etching the insulating layer (16) to form an electrode hole; the electrode hole can expose the recording electrode (4) of the recording electrode layer; The sacrificial layer (12) is released to obtain a foldable brain electrode structure, the foldable brain electrode structure comprising a first structure (2) and a second structure (3), the second structure (3) being provided with the recording electrode (4); the second structure (3) comprising N substructures (31); N being an integer greater than or equal to 2; a preset distance between adjacent substructures (31) in the N substructures (31), so that the N substructures (31) can gather toward the center of the first structure (2) to form an arc surface; and the N substructures (31) are arranged around the edge of the first structure (2).

8. The preparation method according to claim 7, characterized in that: After releasing the sacrificial layer (12) to obtain a foldable brain electrode structure, the method further comprises: Placing the foldable brain electrode structure in the inner cavity of the arc-shaped mold; pouring silk protein solution into the inner cavity; After drying, the folded and solidified foldable brain electrode structure is obtained.

Images