JP2011030678A - Netlike bioelectrode array - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a bioelectrode array which satisfactorily fits to a complicated shape of a living body such as a brain. <P>SOLUTION: A netlike bioelectrode array includes: a netlike flexible substrate wherein a plurality of gaps are formed; a plurality of electrodes which are arranged on the netlike flexible substrate at intervals; and a plurality of wires connected to the respective electrodes and extending along the netlike flexible substrate. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

The present invention relates to a bioelectrode array, and more particularly to a bioelectrode array for performing electrical recording or electrical stimulation on a living body.

From the focus diagnosis of epilepsy, functional monitoring during neurosurgery, treatment with deep brain stimulation, and neuroprosthesis, multipoint electrodes for neurophysiological measurement have a wide range of applications in the medical, rehabilitation, and experimental science fields. In particular, there is a great demand for a bioelectrode array that is flexible, gentle to nerve tissue, and capable of recording and stimulating stably.

As a conventional bioelectrode array, a subdural multipoint electrode in which metal electrodes are arranged on a planar silicon resin sheet is widely used. However, even when trying to cover a wide range of biological tissues such as the brain and spinal cord with a flat material, the entire electrode sheet maintains a complete and stable contact with a complex shape and a tissue with a large curvature. It is difficult to do this, and the phenomenon that the electrode arranged near the edge of the sheet floats away from the living body is unavoidable. For this reason, intimate contact between the electrode and the tissue cannot be obtained completely stably in all the electrodes, which has been a hindrance to recording and stimulation by indwelling for a long time.

In addition, cortical electroencephalogram (ElectroCogogram) is attracting attention as a signal for extracting a user's intention in a brain machine interface (BMI) system. High spatial resolution compared to normal EEG, and less information, but less invasive compared to intracortical nerve signals measured by a penetrating electrode, and long-term stable recording That is why. If the detailed relationship between the ECoG signal and the intracortical signal can be known, the accuracy of intent estimation from the ECoG signal can be improved. In other words, by obtaining a solution to the inverse problem of estimating intracortical nerve signals from ECoG signals, it contributes to improving the performance of ECoG-based BMI systems. For this purpose, a nerve electrode that simultaneously measures nerve signals (spikes or local field potential) at various depths in the cortex and cortical electroencephalograms (ECoG) on the brain surface in multiple channels is useful.

Non-Patent Document 1 discloses a flexible finger-type bioelectrode array. However, each finger on which a plurality of electrodes are arranged is apt to be scattered because it is flexible, and there is a possibility that the positional relationship between adjacent fingers is shifted during mounting (as a result, the positions of the electrodes are shifted). ), May affect stable recording / stimulation. In the finger type electrode array, the tip of each finger is a free end, so if it is too fit for the uneven surface of a complex curved surface, the gap between the electrodes on the tip of the finger will increase, and the position of the electrode will be confirmed one by one Can be difficult to do. Furthermore, Non-Patent Document 1 does not focus on simultaneous measurement of an ECoG signal and an intracortical signal.

A MEMS-based flexible multichannel ECoG-electrode array, Birthe Rubehn et al 2009 J. Neural Eng. 6 036003 (10pp)

An object of the present invention is to provide an electrode array that fits well to a complex shape of a living body such as a brain.

Another object of the present invention is to provide an electrode array that enables simultaneous multichannel measurement of neural signals at various depths in the cortex and cortical electroencephalogram (ECoG) on the brain surface.

The technical means adopted by the present invention to solve this problem are as follows:
A net-like flexible substrate in which a plurality of voids are formed;
A plurality of electrodes disposed on the mesh-like flexible substrate at intervals,
A plurality of wires connected to each electrode and extending along the mesh-like flexible substrate;
A reticulated bioelectrode array comprising:
It is.
The net-like flexible substrate includes a closed outer edge and a plurality of gaps formed in a region surrounded by the outer edge.
In one aspect, the net-like flexible substrate comprises a closed outer edge and a plurality of voids formed in a region surrounded by the outer edge, and the narrow portion forming the substrate does not have any free end. Further, the net-like flexible substrate may include one or more belt-like portions extending from the closed outer edge.

  In one aspect, 30% or more of the area of the area surrounded by the outer edge of the net-like flexible substrate is occupied by the plurality of gaps.

In one embodiment, each gap has a dimension that allows insertion of a micro-piercing probe.
In one aspect, the micro-insertion type probe includes a micro-insertion type electrode and a set of a large number of micro-insertion type electrodes depending on applications such as electrical recording, electrical stimulation, drug injection, optical stimulation, and endoscope. Selected from the group consisting of: Kenzan electrode, cannula for injecting minute substances, optical fiber, and probe for microdialysis.

In one aspect, the technical means employed by the present invention are:
A net-like flexible substrate formed with a plurality of voids with dimensions allowing the insertion of a microscopic insertion electrode for intracortical signal measurement;
A plurality of electrodes for cortical electroencephalogram measurement arranged on the mesh-like flexible substrate at intervals,
A plurality of wires connected to each cortical electroencephalogram measurement electrode and extending along the mesh-like flexible substrate; and
Reticulated bioelectrode array for simultaneous measurement of intracortical signals and cortical EEG with
It is.

In one aspect, the size of each gap is a size that can accept a perfect circle with a diameter of 0.3 mm.
In one aspect, the size of each gap is a size that can accept a perfect circle with a diameter of 0.5 mm.

Since the reticulated bioelectrode array of the present invention comprises a reticulated flexible substrate in which a plurality of voids are formed,
(1) Even when targeting complicated shapes such as the brain, the electrical contact between the living body and the electrode is stable, so it can cover a wider range.
(2) Insertion type probes such as needle electrodes can be inserted through the gaps in the net.
(3) Thanks to the voids in the net, measurement / stimulation can be performed while the biological tissue is kept in a more natural state without hindering the passage of substances.

In the net-like flexible substrate, since the narrow portions forming the substrate are connected to each other, the movements of the narrow portions are constrained to each other and the positions are not easily displaced, and the multipoint electrodes maintain a fixed positional relationship with each other. Placed on a living body. Since the net-like flexible substrate covers even a complicated curved surface so as to cover the net, the positional relationship with the adjacent electrode is relatively maintained.

1 is an overall view of a mesh-like bioelectrode array according to an embodiment of the present invention. It is a photograph which shows the whole reticulated bioelectrode array which concerns on one Embodiment of this invention. The reticulated bioelectrode array shown in FIG. 2 appears in a mirror image with that of FIG. FIG. 2 is an enlarged view of an electrical contact portion with a living body in FIG. FIG. 4 is a partially enlarged view of FIG. 3. It is a figure which shows the simultaneous measurement by an ECoG electrode and a penetration type electrode. It is a schematic diagram of the simultaneous measurement experiment of the intracortical signal and the cortical electroencephalogram. The electric potential obtained by cortical electroencephalogram multi-point electric recording from the cerebrum is shown. It is a figure which shows the simultaneous measurement experiment result of the signal in a cortex and a cortical electroencephalogram. It is a figure which shows the other shape of an electrical contact part. It is a figure which shows the other shape of an electrical contact part. It is a figure which shows the other shape of an electrical contact part.

The bioelectrode array according to the present invention is a multipoint nerve electrode for performing electrical recording or electrical stimulation on a living body, and a net-like structure in which a large number of electrodes that contact the living body are arranged on the surface of a net-like flexible substrate. It is a bioelectrode array. The biological electrode array according to the present invention is a net-like flexible substrate in which a plurality of voids are formed, a plurality of electrodes arranged at intervals on the net-like flexible substrate, and connected to each electrode, And a plurality of wirings extending along the net-like flexible substrate.

The net-like flexible substrate includes a closed outer edge and a plurality of voids formed in a region surrounded by the outer edge. That is, the net-like flexible substrate is a substrate having a plurality of closed voids. A net-like flexible substrate can be obtained by forming a large gap in a sheet-like substrate except for a region where a large number of electrodes are arranged, wiring, and a portion necessary for maintaining the structure. The net-like flexible substrate is typically formed from a resin, and more specifically, parylene resin, silicon resin, and polyimide resin are exemplified. The electrode and the wiring are selected from metals having excellent conductivity such as gold. A flexible substrate including a multipoint electrode and a plurality of gaps can be manufactured by using MEMS technology. The shape of the net-like flexible substrate is square in the illustrated example, but the shape of the net-like flexible substrate can take any shape as appropriate corresponding to the shape of the living body on which the bioelectrode array is placed.

A net-like flexible substrate is a substrate having a form similar to a net, that is, a member in which a plurality of voids (mesh) are formed between a plurality of narrow members, and a plurality of voids are formed over the entire substrate. A substrate that is formed and in which a significant percentage of the total area of the substrate is occupied by voids. In one aspect, the net-like flexible substrate is characterized in that 30% or more of the area of the region surrounded by the outer edge of the substrate is occupied by the plurality of gaps. Furthermore, it is considered that the fitting performance to the living body is improved as the void ratio increases to 40% or more and 50% or more. In one embodiment, in the net-like flexible substrate, all the electrodes are polygons (for example, FIG. 3 and FIG. 3) defined by imaginary lines (shown by alternate long and short dash lines in FIG. 10) that pass through a plurality of outermost electrodes. 10 is a square) region, and 30% or more of the area of the polygonal region is occupied by the plurality of voids. Furthermore, it is considered that the fitting performance to the living body is improved as the void ratio increases to 40% or more and 50% or more. By forming a plurality of large voids in the substrate, it is possible to obtain a good fitting performance to a living body and to keep a living tissue in a more natural state.

In the net-like flexible substrate, since a plurality of gaps occupy a large proportion, each electrode is arranged in the vicinity of any one or more gaps. When attention is paid to a certain gap, a plurality of electrodes are arranged in the vicinity of the gap, that is, a plurality of electrodes are arranged so as to surround each gap. Moreover, a large space | gap is located between electrodes because many electrodes are arrange | positioned at intervals over the whole flexible substrate provided with the several space | gap. In a net-like flexible substrate, multi-point electrodes (multiple electrodes) are arranged on the surface of a substrate made of resin, etc., and there are gaps between the multi-point electrodes, and a considerable proportion of the entire area of the substrate is occupied by the voids. It has been.

In one aspect, the net-like flexible substrate includes an outer band-shaped portion that defines an outer edge of the net-shaped flexible substrate, and an inner band-shaped portion that extends in a region surrounded by the outer band-shaped portion, and the inner band-shaped portion. Are connected to the outer belt-like portion. In one aspect, the net-like flexible board has inner strips intersecting each other. In a more specific aspect, as shown in FIGS. 1 to 3, the net-like flexible board includes a plurality of net-like flexible boards extending in the weft direction. It is a lattice-shaped flexible board | substrate provided with the inner side strip | belt-shaped part. That is, in the embodiment of FIGS. 1 to 3, the net-like flexible substrate includes a plurality of strip-shaped portions extending in the first direction and a plurality of strip-shaped portions extending in the second direction orthogonal to the first direction. It is formed in a lattice shape from the belt-like portion. In this case, the belt-like portions positioned on both outer sides in the first direction and the second direction form the outer edge of the net-like flexible substrate as the outer belt-like portion. In this aspect, the inner strips intersect at right angles (the voids are square), but the inner strips do not necessarily need to be orthogonal (the voids are parallelograms). In addition, the inner belt-shaped portions may be orthogonal to each other, and the inner belt-shaped portion may be inclined with respect to the outer belt-shaped portion.

The net-like flexible substrate may be one in which the inner band portions do not intersect each other (see FIGS. 10 and 11). Typically, the belt-shaped portion forming the flexible substrate extends linearly, but the belt-shaped portion may extend in a curved shape. Further, the net-like flexible substrate is not limited to one formed from a band-shaped portion having a constant width (in this case, the gap is a square hole), and a plurality of large substrates other than the square hole are provided over the entire substrate. For example, a hole having an arbitrary shape such as a round hole (see FIG. 9), a triangle, a polygon of five or more polygons, a star shape, a cross shape, or the like may be formed. As described above, typical shapes of the plurality of gaps formed on the net-like flexible substrate include a square (including a square and a rectangle) and a circle (including a perfect circle and an ellipse). The shape is not limited to a square or a circle, and may take any polygonal shape, star shape, or any other shape. Further, different shapes, for example, a square gap and a circular gap may be formed by mixing in one substrate.

In one embodiment, each gap has a dimension that allows insertion of a micro-piercing probe. In one aspect, one aspect of the present invention is a network-like flexible substrate in which a plurality of gaps having dimensions allowing insertion of a microscopic insertion probe are formed, and the mesh-like flexible substrate is spaced from each other. A bioelectrode array for simultaneous measurement of intracortical signals and cortical electroencephalograms, comprising a plurality of electrodes arranged and a plurality of wires connected to each electrode and extending along the mesh-like flexible substrate is there.

The microscopic probe includes a microscopic electrode, a sword mountain electrode consisting of a set of microscopic electrodes, a cannula for injection of a micro substance (glass tube, metal cannula, etc.), an optical fiber (for light source, endoscope) And a microdialysis probe. The dimension of each space | gap of the net-like flexible substrate concerning this invention has the dimension which accept | permits the insertion of the micro penetration type probe which can be used. For example, when the bioelectrode array is used for simultaneous measurement of intracortical signals and cortical electroencephalograms, the voids of the mesh-like flexible substrate need to have dimensions that allow insertion of microscopic insertion electrodes for intracortical signal measurement.

The micro-penetrating probe used with the bioelectrode array is typically a metal micro-penetrating electrode or a sword mountain electrode consisting of a set of many metal micro-penetrating electrodes. The metal micro-penetrating electrode includes a metal wire (tungsten, stainless steel, etc.) having a diameter of about 25-50 μm at the base, a tungsten electrode of about 250 μm, an iridium electrode, those coated with parylene or epoxy, There are various types such as thick metal wires of 500 μm or more and glass tubes bundled as one electrode. Considering the minimum size required for a general micro-penetrating electrode to penetrate the gap, the dimension of each gap is a dimension that can accept a perfect circle having a diameter of at least 0.3 mm. For example, when the gap is a square, the dimension of each gap is 0.3 mm × 0.3 mm or more. When the gap is a circle, the dimension of each gap is the diameter of each gap (in the case of an ellipse). (Minor axis) is 0.3 mm or more. Furthermore, when using a sword mountain electrode, in order for all the electrodes to be inserted into the corresponding gaps, considering that the displacement is accumulated, the dimension of each gap should be a circle with a diameter of at least 0.5 mm. It is an acceptable dimension. For example, when the gap is square, the size of each gap is 0.5 mm × 0.5 mm or more, and when the gap is circular, the diameter of each gap (short diameter in the case of an ellipse) is: It is 0.5 mm or more.

In one embodiment, the shapes and dimensions of the air gaps are the same, and are arranged at regular intervals (for example, in the weft direction). If the spacing between the gaps is constant, it is advantageous to insert each of the sword-mount type electrodes made up of a plurality of tiny insertion electrodes.

In one aspect, each electrode is arrange | positioned at each cross | intersection part (part where strip | belt-shaped parts cross | intersect) of a net-like flexible substrate. By arranging each electrode at each intersection, it becomes easy to perform wiring processing of each electrode. Moreover, disposing each electrode at each intersection means that a plurality of electrodes are disposed in the vicinity of each gap as a result. In one aspect, the electrodes are spaced equidistant from one another. It is considered that data can be easily analyzed by acquiring data from electrodes at equal intervals. Also, in the study of simultaneous measurement of intracortical signals and cortical EEG and estimating the former from the latter, it is considered that data measured at equal intervals is easier to handle.

The feature of this embodiment is that the electrodes are arranged at each crossing portion of the net-like flexible substrate, the wiring is applied to the belt-like portion of the substrate that connects the crossing portions, and the other portions are open as hollow holes. It is in. The wiring is embedded in the substrate. Utilizing a technology that enables fine processing of parylene resin and gold by MEMS technology, the parylene of the substrate is removed except for gold electrodes (contact points with living bodies) arranged in a grid and parts necessary for maintaining wiring and structure. We have developed a mesh-like multi-point nerve electrode that can be covered with a wide range of flexible tissue such as the brain and spinal cord by hollowing out the resin. Hereinafter, the bioelectrode array according to the embodiment will be described in detail with reference to the drawings as appropriate. Numerical values indicating the dimensions of each element and the number of electrodes are merely examples, and the numerical values do not limit the configuration of the present invention except as described in the claims.

An overall view of the bioelectrode array according to this example is shown in FIG. 1, and a photograph of the bioelectrode array is shown in FIG. In FIG. 1, the left lattice portion is an electrical contact portion 1 with a living body, the central linear portion is a wiring portion 2, and the contact portion 3 with a connector is drawn on the right side. The electrical contact portion 1 is an electrical stimulation portion or a measurement portion made of a net-like flexible substrate having a multipoint electrode. In this embodiment, the overall shape of the electrical contact portion 1 is a square, but any shape can be adopted so as to match the shape of the living body on which the electrical contact portion 1 is placed.

FIG. 3 is an enlarged view of the electrical contact portion 1 of FIG. The electrical contact portion 1 is a lattice-shaped flexible substrate having a substantially square shape (about 6 mm square) as a whole. The lattice-shaped flexible substrate is formed by forming square-shaped voids (0.75 mm square) 4 having the same shape and the same dimensions in 5 rows and 5 columns at equal intervals in the weft direction on a rectangular substrate. The grid-like flexible substrate includes four belt-like portions 5A, 5B, 5C, and 5D that extend in four directions so as to define the outer edge 10 of the electrical contact portion 1 (grid-like flexible substrate), and four belt-like shapes. In the region surrounded by the portions 5A, 5B, 5C, and 5D, it is composed of four belt-like portions 6 extending in the longitudinal direction and four belt-like portions 7 extending in the weft direction. The width of the strips 6 and 7 is 0.25 mm, which is smaller than the size of the gap (0.75 mm square). The strips 5A, 5C, and 7 are parallel, and the strips 5B, 5D, and 6 are parallel. The strips 5A, 5C, and 7 and the strips 5B, 5D, and 6 extend at right angles.

The end portions in the length direction of the band-shaped portion 5A are respectively integrated with the end portions of the band-shaped portions 5B and 5D, and the end portions in the length direction of the band-shaped portion 5B are respectively integrated with the band-shaped portions 5A and 5C. The lengthwise ends are integral with the strips 5B and 5D, respectively, and the lengthwise ends of the strip 5D are integral with the strips 5A and 5C, respectively. That is, the outer edge 10 of the electrical contact portion 1 is closed. The lengthwise ends of each strip 6 are integral with the sides of the strips 5A, 5C, respectively, and the lengthwise ends of each strip 7 are integral with the sides of the strips 5B, 5D, respectively. That is, both end portions in the length direction of each of the strip portions 5A, 5B, 5C, 5D, 6, and 7 are respectively integrated with the other strip portions and do not have any free ends. The electrical contact portion 1 made of a lattice-shaped flexible substrate can be flexibly deformed along the shape of the living body, but the displacements of the belt-like portions 5A, 5B, 5C, 5D, 6, and 7 are restricted to each other. . Therefore, even when the lattice-shaped flexible substrate is deformed by fitting to the shape of the living body, the multipoint electrodes are arranged in a fixed positional relationship with each other.

Thirty-six electrodes 8 are arranged at the intersections (36 locations) of the strips 5A, 5B, 5C, 5D, 6, and 7. Specifically, the intersection between the strip 5A and the strip 5B, the intersection between the strip 5B and the strip 5C, the intersection between the strip 5C and the strip 5D, and between the strip 5D and the strip 5A. Intersection, intersection between strip 5A and strip 6, intersection between strip 5C and strip 6, intersection between strip 5B and strip 7, intersection between strip 5D and strip 7 The electrode 8 is disposed at the intersection of the strip 6 and the strip 7. As shown in FIG. 4, four electrodes 8 are arranged in the vicinity of each of the four corners of each rectangular gap 4.

Each electrode 8 has a square shape of 50 μm square, and the electrode interval on the lattice-shaped flexible substrate is 1 mm. The electrodes 8 are arranged at regular intervals (1 mm intervals) in the weft direction at 6 rows and 6 columns to constitute a multipoint electrode. Thus, the substrate of the electrical contact portion 1 has a net-like shape by providing a 0.75 mm square gap between the electrodes having a 1 mm interval. A wiring 9 extends from each electrode 8. Each wiring is used for performing electrical stimulation (including current stimulation and voltage stimulation) by each electrode 8 and taking out an electrical signal from each electrode 8. The wiring 9 is embedded in a substrate made of parylene resin and is electrically insulated.

As described above, in the electrical contact portion 1 (lattice-shaped flexible substrate), the 6-row 6-column 36-channel electrodes 8 are arranged in an array. In the evaluation experiment, two of these channels are used as reference electrodes, and two channels are used as ground electrodes, so that there are 32 channels per probe. For example, by using two bioelectrode arrays, one for each hemisphere, a total of 64 channels of cortical electroencephalograms and more intracortical signals can be measured.

Each electrode 8 is connected to a wiring 9 extending through the strips 5A, 5B, 5C, 5D, 6, and 7. The widths of the outer strips 5A, 5B, 5C, and 5D are 0.905 mm, 0.625 mm, 0.585 mm, and 0.945 mm, respectively, and are designed to be wider than the widths of the inner strips 6 and 7. It has become. Furthermore, the width of the strips 5A and 5D is designed to be larger than the width of the strips 5B and 5C. A plurality of wires extend in parallel in the outer belt-like portions 5A, 5B, 5C, and 5D, while a single wire 9 extends in the inner belt-like portions 6 and 7. As is apparent from FIGS. 3 and 4, the inner belt-like portions 6 and 7 have a portion where no wiring exists.

More specifically, each of the strip portions 5A, 5D has a width dimension that allows 18 wires to extend in parallel. Each of the strip portions 5B and 5C has a width dimension that allows eight wires to extend in parallel. By concentrating the wiring 9 on the outer belt-like portions 5A, 5B, 5C, and 5D, the width of the inner belt-like portions 6 and 7 is made as small as possible to form a larger gap 4. The outer belt-like portions 5A, 5B, 5C, and 5D are narrow belt-like portions that are wider than the inner belt-like portions 6 and 7, but have a width dimension that does not hinder good fitting to a living body.

The electrical contact portion 1 (grid-like flexible substrate) and the connector connection portion 3 are physically and electrically connected by the wiring portion 2. Although the wiring part 2 extends from the part shifted to the belt-like part 5D of the belt-like part 5A, the extension part of the wiring part 2 is not limited. For example, the wiring part 2 extends from the central part in the longitudinal direction of the belt-like part 5A. May be extended. In the wiring portion, 36 wires extend in parallel. In the embodiment, the wiring part 2 has a width of about 2 mm and a length of about 15 mm. The connector connecting portion 3 is designed so that it can be connected to a 36 channel connector of Omnitec. The multi-channel connector is further electrically connected to the first stage multi-point amplifier (multi-point head amplifier).

The bioelectrode array has a structure in which a gold wiring layer with a thickness of about 200 nm is sandwiched between two layers of parylene C (poly (monochloro-para-xylylene)) film (thickness: about 10 μm). The length is about 20 μm. In the connection portion 3 between the portion where the electrode 8 of the electrical contact portion 1 is arranged and the connector, a window is opened in the upper parylene layer, and the gold wiring layer is exposed. In the electrode 8 of the electrical contact portion 1, the gold is subjected to platinum black treatment to increase the effective surface area and reduce the electrode impedance.

The bioelectrode array according to the example was prepared by the following steps.
Step 1: Design the electrode array using CAD software.
Step 2: A photomask is created using an electron beam drawing apparatus which is a shared use apparatus of VDEC (University of Tokyo Large Scale Integrated System Design Education Center).
Step 3: Parylene C is coated on a silicon wafer (thickness 10 μm).
Step 4: Further, gold is deposited by a resistance heating vacuum deposition apparatus (thickness: about 200 nm).
Step 5: Gold patterning is performed (including a series of steps of resist application, photomask exposure, development, gold etching, and resist removal).
Step 6: Coat Parylene C for the upper layer (thickness: about 10 μm).
Step 7: Aluminum for masking is deposited by a resistance heating type vacuum deposition apparatus.
Step 8: Pattern the aluminum mask.
Step 9: Parylene is etched by an oxygen plasma etching apparatus (this opens a window in the electrode portion, and the parylene is scraped down to the silicon wafer outside the outer shape of the electrode and in the through hole portion of the mesh portion. ).
Step 10: Peel off the electrode from the silicon wafer.
Step 11: The connector made by Omnitechs and the connector connecting portion are bonded with a conductive adhesive. Furthermore, the entire connector connecting portion is covered with an epoxy adhesive.
Step 12: Measure electrode impedance of all electrodes.
Step 13: Perform platinum black treatment (plating process).
Step 14: Measure the electrode impedance of all electrodes again.
The electrode impedance (1 kHz) was about 50 k to 100 kΩ in Step 12, but was about 5 k to 20 kΩ in Step 14 due to the platinum black treatment.

In this way, a net-like flexible substrate that is formed in a lattice form from a plurality of strips extending in the weft direction and has a plurality of gaps at equal intervals in the weft direction is prepared. By using a bio-electrode array in which electrodes are arranged at equal intervals in the weft direction at each intersection, the following operational effects can be obtained.

The net-like (lattice-like) flexible substrate fits much more flexibly than a sheet-like conventional electrode even in a biological tissue such as a brain having a three-dimensionally complicated shape or a large curvature. At the same time, electrical contact with a living body can be achieved and maintained stably. The net-like (lattice-like) flexible substrate fits well to the curved brain surface, and can be applied to a wider range of biological tissues.

In the net-like flexible substrate, since a physically large gap 4 is vacant between the electrodes 8, another probe such as a microneedle electrode or a substance injection cannula can be freely passed through the gap 4, that is, a net hole. And can be used as a new tool for biological measurement. For example, by inserting insertion electrodes (metal wire array, silicon probe array, flexible insertion electrode array using parylene, etc.) from the gap 4, simultaneous measurement as shown in FIG. 5 can be realized. In FIG. 5, ● on the microscopic insertion electrode 13 represents each electrode of a multipoint electrode in the depth direction, and ▲ schematically represents a cell body of a nerve cell (neuron).

The presence of the gap 4 does not prevent various substances and cerebrospinal fluid from coming and going through the holes of the net even when the net-like flexible substrate is in contact with the living body. Measurement can be performed non-invasively in a state closer to nature than a sheet electrode.

In the electrical contact portion 1, the electrodes 8 are arranged at the intersections of the grid-like strips, so that the positional relationship with the adjacent electrodes 8 is relatively maintained. For example, the brain in a certain range is systematically mapped. Suitable for doing. Furthermore, it is possible to insert an insertion-type probe or the like from the gap 4 having an appropriate coordinate based on the mapping result.

Experimental example

An animal experiment was conducted by arranging the reticulated bioelectrode array according to the example in the rat brain. We succeeded in the simultaneous measurement by the combination of cortical electroencephalogram measurement and the insertion type electrode (8 channel silicon probe array, tungsten wire electrode) inserted from the gap 4. In order to cover and record a wide area including the visual area of the cerebrum, it is necessary for all the electrodes 8 to stably adhere to the brain along the curve, which is realized by a net-like form (see FIG. 6). It was confirmed from FIG. 7 that the contact between the electrical contact portion 1 and the brain surface was achieved with all the electrodes 8 (32 channels). It can be seen that the cerebral electrical activity actually recorded by the bioelectrode array according to this example was obtained at all 32 measurement points.

The net-like bioelectrode array according to the embodiment can be used as an electrode for simultaneous measurement of an intracortical signal and a cortical electroencephalogram. Integrated use with the insertion electrode can be realized by the network structure.

FIG. 6 is a schematic diagram of an experiment of simultaneous recording. From the rat visual cortex, ECoG recording (ECoG) with a reticular bioelectrode array (electrical contact portion 1) and spike activity recording with a fine insertion electrode 13 (unit ) At the same time. The data in Fig. 8 shows the spatial distribution of ECoG waveforms recorded with a reticulated bioelectrode array in relation to the visual stimulus CONTRA on the contralateral eye and IPSI on the ipsilateral eye, and the actual positional relationship on the brain surface. It is arranged and represented according to The visual stimulus was presented for 500 ms using black and white stripes. It can be seen that IPSI has a more limited response than CONTRA.

The middle row shows the frequency of the spike firing frequency recorded from the micro-penetrating electrode inserted in the same experiment, the location of the upper smile mark, that is, the site where the same response is obtained with IPSI and CONTRA by ECoG. The stimulus start is plotted with time zero. It was found that IPSI produces a strong visual response as well as CONTRA.

The lower row displays the same data as the middle row in a form called “rastergram”. One horizontal line corresponds to one trial, and data for 40 trials are arranged. In each trial, a small dot represents a single spike activity.

Although the bioelectrode array provided with the net-like flexible substrate has been described based on the grid-like flexible substrate, the net-like flexible substrate is not limited to the grid-like substrate. Other shapes of the electrical contact portion 1, that is, a net-like flexible substrate are shown in FIGS. 9 to 11, the same reference numerals are assigned to the same elements as those of the electrical contact portion 1 shown in FIGS. 1 to 3. The description relating to FIGS. 1 to 3 can be used for the description of the elements given the same reference numerals. 9 to 11, the wiring is omitted. 9 to 11 are for presenting the basic shape of a net-like flexible substrate. The number of electrodes, the number of strips, the number of voids, the extending direction of the strips, and the dimensional ratio of each element are as follows. It is not limited to the illustrated one, and can be changed as appropriate.

The net-like flexible substrate shown in FIG. 9 has a rectangular shape as a whole, and large circular holes 4 are formed at equal intervals in the weft direction in the region surrounded by the four outer edges 10. A significant proportion of the area is occupied by voids. Electrodes 8 are arranged so as to sandwich each gap 4.

10 has four belt-like portions 5A, 5B, 5C, and 5D that extend in four directions so as to define the outer edge 10 of the electrical contact portion 1, and four belt-like portions 5A and 5B. It is comprised from the two strip | belt-shaped parts 11 extended in the weft direction in the area | region enclosed by 5C, 5D. A plurality of electrodes 8 are arranged in the belt-like portions 5A, 5C, and 11 at intervals.

The net-like flexible substrate shown in FIG. 11 includes four belt-like portions 5A, 5B, 5C, and 5D that extend in four directions so as to define the outer edge 10 of the electrical contact portion 1, and the four belt-like portions 5A and 5B. 5C and 3D, and three strips 12 extending obliquely in a region surrounded by 5C and 5D. A plurality of electrodes 8 are arranged in the belt-like portions 5A, B, 5C, 5D, and 12 at intervals.

The reticulated bioelectrode array according to the present invention has been described based on a reticulated flexible substrate that extends in a generally two-dimensional plane. However, the reticulated flexible substrate according to the present invention is not limited to a planar substrate. It will be understood by those skilled in the art that the substrate may be a three-dimensional substrate. For example, the net-like flexible substrate may partially include a curved surface portion. By using a net-like flexible substrate having a curved surface portion in advance and further bending the substrate, the substrate can be satisfactorily fitted to a tissue having a higher curvature, for example, a smaller tissue such as a peripheral nerve or retina. In addition, by reworking a net-like substrate that does not have a curved surface portion in advance, such as making a curved surface of a cylinder by curving opposite sides of a rectangular flexible substrate and fixing them at a position aligned in front, Can also make a three-dimensional surface shape. Further, the net-like flexible substrate is not limited to one formed from one plane portion, and the net-like flexible substrate may be formed from a combination of a plurality of planes (plane and plane, plane and curved surface). For example, a T-shaped net-like flexible substrate is formed by providing a second net-like flexible substrate extending in a rising manner with respect to the first net-like flexible substrate, and the first net-like flexible substrate is attached to the brain. By fitting the second reticulated flexible substrate to the brain surface in the brain groove, the recording can be taken from both sides.

The reticulated bioelectrode array according to the present invention can be used as a nerve electrode used for medical treatment (diagnosis / treatment), medical rehabilitation support by brain machine interface, basic research of life science, and the like.

DESCRIPTION OF SYMBOLS 1 Electrical contact part 2 Wiring part 3 Connection part 4 Space | gap 5A, 5B, 5C, 5D Outer strip | belt-shaped part 6 Inner strip | belt-shaped part (longitudinal direction)
7 Inner band (weft direction)
8 Electrode 10 Outer edge of electrical contact part 11 Band-shaped part 12 Band-shaped part 13 Micro insertion type electrode

Claims (8)

A net-like flexible substrate in which a plurality of voids are formed;
A plurality of electrodes disposed on the mesh-like flexible substrate at intervals,
A plurality of wires connected to each electrode and extending along the mesh-like flexible substrate;
A reticulated bioelectrode array comprising:   The reticulated bioelectrode array according to claim 1, wherein the reticulated flexible substrate includes a closed outer edge and a plurality of voids formed in a region surrounded by the outer edge.   The reticulated bioelectrode array according to claim 2, wherein 30% or more of the area of the region surrounded by the outer edge of the reticulated flexible substrate is occupied by the plurality of gaps.   The mesh-like bioelectrode array according to any one of claims 1 to 3, wherein each gap has a dimension that allows insertion of a microscopic probe.   5. The micro penetration probe is selected from a micro penetration electrode, a sword electrode comprising a set of a plurality of micro penetration electrodes, a cannula for injection of a micro substance, an optical fiber, and a probe for micro dialysis. The reticulated bioelectrode array as described. A net-like flexible substrate formed with a plurality of voids with dimensions allowing the insertion of a microscopic insertion electrode for intracortical signal measurement;
A plurality of electrodes for cortical electroencephalogram measurement arranged on the mesh-like flexible substrate at intervals,
A plurality of wires connected to each cortical electroencephalogram measurement electrode and extending along the mesh-like flexible substrate; and
A reticulated bioelectrode array for simultaneous measurement of intracortical signals and cortical EEG.   The mesh-like bioelectrode array according to any one of claims 1 to 6, wherein each void has a dimension capable of receiving a perfect circle having a diameter of 0.3 mm.   The mesh-like bioelectrode array according to any one of claims 1 to 7, wherein each gap has a dimension capable of accepting a perfect circle having a diameter of 0.5 mm.