WO2015119208A1 - Réseau d'électrodes et capteur biologique - Google Patents

Réseau d'électrodes et capteur biologique Download PDF

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Publication number
WO2015119208A1
WO2015119208A1 PCT/JP2015/053280 JP2015053280W WO2015119208A1 WO 2015119208 A1 WO2015119208 A1 WO 2015119208A1 JP 2015053280 W JP2015053280 W JP 2015053280W WO 2015119208 A1 WO2015119208 A1 WO 2015119208A1
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Prior art keywords
buffer layer
electrode array
biological buffer
electrode
partition wall
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PCT/JP2015/053280
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English (en)
Japanese (ja)
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一徳 栗原
隆夫 染谷
毅 関谷
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独立行政法人科学技術振興機構
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Publication of WO2015119208A1 publication Critical patent/WO2015119208A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02—Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0209—Special features of electrodes classified in A61B5/24, A61B5/25, A61B5/283, A61B5/291, A61B5/296, A61B5/053
    • A61B2562/0217—Electrolyte containing

Definitions

  • the present invention relates to an electrode array and a biosensor. This application claims priority on February 6, 2014 based on Japanese Patent Application No. 2014-021489 for which it applied to Japan, and uses the content here.
  • Organic semiconductors can be used as a means for obtaining biological information directly from cells and tissues by the softness of the material and by mounting on the surface of the human body or in the body.
  • Patent Document 2 A minimally invasive method in which an electrode is not inserted into a living body has also been developed (for example, Patent Document 2).
  • an electrode made of a metal such as platinum or gold is basically harmless to the human body, but when it directly touches a body tissue or cell, a protective reaction (inflammation) occurs between the electrode and the tissue due to an antibody reaction of living cells. Reaction) occurs. Therefore, there is a problem that long-term biological information cannot be observed.
  • a hard metal may be rubbed in a soft living body, and damage due to friction on the living body is large.
  • An object of the present invention is to provide a highly sensitive, high-definition and flexible electrode array and a biosensor that can cause extremely little damage to the living body and immune reaction of the living body and can maintain mechanical strength.
  • the present invention employs the following means.
  • a plurality of electrodes arranged on the same plane and a biological buffer layer are stacked on a base material, and an insulating partition wall is provided in the biological buffer layer so as to surround the electrodes.
  • (6) The electrode array according to any one of (1) to (5), wherein a thickness of the base material is thinner than a thickness of the biological buffer layer.
  • (7) The electrode array according to any one of (1) to (6), wherein the biological buffer layer has a Young's modulus of 1 kPa to 100 kPa.
  • the Young's modulus of the biological buffer layer, the Young's modulus of the partition wall, and the Young's modulus of the base material are in a relationship of Young's modulus of the biological buffer layer ⁇ Young's modulus of the partition wall ⁇ Young's modulus of the base material.
  • the electrode array according to any one of (1) to (7), wherein (9) A biosensor comprising the electrode array according to any one of (1) to (8), an amplifier circuit connected to each electrode of the electrode array, and a transistor connected to the amplifier circuit.
  • the present invention it is possible to provide a highly sensitive, high-definition, and flexible electrode array and biological sensor that are extremely low in damage to the living body and immune reaction of the living body and can maintain mechanical strength.
  • FIG. 5 is a diagram showing an example of a circuit configuration of signal detectors F 11 to F nm shown in FIG.
  • the configuration of the electrode array and the biological sensor to which the present invention is applied will be described with reference to the drawings.
  • the portions that become the features may be shown in an enlarged manner for the sake of convenience, and the dimensional ratios and the like of the respective components are not always the same as the actual ones.
  • the materials, dimensions, and the like exemplified in the following description are examples, and the present invention is not limited to them, and can be appropriately modified and implemented without departing from the scope of the invention.
  • the electrode array and biosensor of the present invention may include components such as layers not described below as long as the effects of the present invention are not impaired.
  • FIG. 1A is a schematic cross-sectional view of an electrode array according to an embodiment of the present invention
  • FIG. 1B is a schematic perspective view of an electrode array according to an embodiment of the present invention.
  • an electrode array 10 according to an embodiment of the present invention, a plurality of electrodes 2 arranged on the same plane of a substrate 1 and a biological buffer layer 3 are laminated, and the biological buffer layer 3 surrounds the electrodes 2. Insulating partition walls 4 are provided.
  • the biological buffer layer has conductivity and can transmit an electrical signal from the biological body to the electrode. Moreover, since it has biocompatibility, the defense reaction of a biological body can be suppressed. “Biocompatibility” means that there is no cytotoxicity and the biological rejection is small.
  • cytotoxicity test using a colony formation method is performed and there is no cytotoxicity, and a “rabbit implantation test” according to the standard is performed, It means that rejection is small.
  • FIG. 2A is a diagram schematically illustrating the operation of the electrode array having no partition wall
  • FIG. 2B is a diagram schematically illustrating the operation of the electrode array having the partition wall according to the embodiment of the present invention.
  • the electrode array is in contact with the living body via the biological buffer layer 3. Since the living body buffer layer 3 is soft, it can follow the shape of the living body.
  • electrical signals emitted from the nerve cells 6 are diffused to the surroundings through the biological buffer layer 3 having conductivity in the form of current. To do.
  • FIG. 2B shows the case of the electrode array 10 according to an embodiment of the present invention having the partition walls 4. Since the partition wall 4 has insulating properties, the partition wall 4 inhibits current from being diffused to the surroundings through the biological buffer layer. The electric signal emitted from the nerve cell 6 is received more strongly by the electrode 2 closest to the nerve cell 6 and is prevented from leaking to the surrounding electrode 2. Therefore, the electrode array 10 can exhibit high spatial resolution and sensitivity.
  • the material of the substrate 1 is not particularly limited. It is preferable to have a strength that serves as a base for the electrode array 10 and to maintain flexibility. Specifically, the Young's modulus is preferably 0.1 GPa to 10 GPa.
  • polyimide (PI) polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polytetrafluoroethylene (Teflon (registered trademark)), or the like can be used.
  • the thickness of the substrate 1 is preferably thinner than the thickness of the biological buffer layer 3.
  • the biological buffer layer 3 has a lower Young's modulus than the base material 1 and is soft.
  • the thickness of the substrate 1 is preferably 1 ⁇ m or more and 50 ⁇ m or less.
  • the thickness of the base material 1 is thinner than 1 ⁇ m, the base material 1 is not sufficient as a base for the electrode array 10, and the overall mechanical strength is lowered. If the thickness of the substrate 1 is greater than 50 ⁇ m, it is difficult to ensure sufficient flexibility of the electrode array 10. For example, followability to a complicated shape such as the brain is deteriorated.
  • the electrode 2 is not particularly limited. For example, gold or platinum metal, organic conductive material PEDOT / PSS, nanocarbon material, or biocompatible conductive material can be used. As the “conductive substance having biocompatibility”, a conductive gel described later can be used. Since the electrode 2 is covered with the biological buffer layer 3 having biocompatibility, it does not directly touch the living body. In order to further increase the sensitivity of the electrode array 10, it is preferable to use a highly conductive metal such as gold or platinum.
  • the biological buffer layer 3 has conductivity and biocompatibility, and a hydrophilic gel material or a material in which a conductive material is uniformly dispersed in a biocompatible polymer medium can be used.
  • a hydrophilic gel material include various high water content gels having a high water content such as hydrogel, poly 2-hydroxyethyl methacrylate (common name: polyhema), silicone hydrogel, polyrotaxane, and polyvinyl alcohol hydrogel.
  • the moisture content can be obtained by the following equation.
  • the high water content gel preferably has a water content of 20% or more, more preferably has a water content of 40% or more, and still more preferably has a water content of 50% or more.
  • body fluid saline
  • it can function as an electrode array with high biocompatibility.
  • Such a highly water-containing gel exhibits high ionic conductivity by containing a body fluid (saline). That is, even if it does not contain a conductive material, it has conductivity by itself. Therefore, even a high water content gel can function as the biological buffer layer 3.
  • the biological buffer layer 3 having higher conductivity and biocompatibility can be formed by dispersing conductive nanomaterials in these hydrophilic gels.
  • the conductive material fine metal particles, graphite, carbon black, carbon nanomaterials and the like can be used.
  • a gel-like structure in which a carbon nanomaterial doubly coated with a molecule that constitutes a hydrophilic ionic liquid and a water-soluble polymer is dispersed in a water-soluble polymer medium and the water-soluble polymer is crosslinked.
  • a conductive material conductive gel
  • the conductive gel will be described later.
  • the Young's modulus of the biological buffer layer 3 is preferably 1 kPa to 100 kPa.
  • the Young's modulus of the brain is approximately in this range, and by setting the Young's modulus of the biological buffer layer 3 to be in this range, it can be applied to soft and complex shapes such as the brain. Since the biological buffer layer 3 is soft, the contact surface can follow the complex shape of the living body, and the sensitivity of the electrode array 10 can be increased. In the laminated structure of the base material 1 and the biological buffer layer 3, the following two points are important in order to realize the followability of the contact surface to the complex shape surface of the biological body at an extremely high level.
  • the first is that the substrate 1 has a thickness and Young's modulus sufficient to achieve both flexibility and strength
  • the second is that the biological buffer layer 3 follows the contact surface with a Young's modulus comparable to that of a living body. Is to be thick. Therefore, it is preferable to satisfy the relationship of the thickness of the base material 1 ⁇ the thickness of the biological buffer layer 3 and the Young's modulus of the base material 1> the Young's modulus of the biological buffer layer 3.
  • the thickness of the biological buffer layer 3 is preferably 0.002 mm or more and 5 mm or less. If the thickness of the biological buffer layer 3 is less than 0.002 mm, there is a problem that the rigidity of the electrodes of the electrode array cannot be sufficiently absorbed and the rigidity of the surface of the biological buffer layer 3 is increased. On the other hand, if it is thicker than 5 mm, the spatial resolution cannot be increased. It cannot be inserted into a narrow gap.
  • the partition wall 4 has an insulating property and is disposed so as to surround the electrode 2 in the biological buffer layer 3. By disposing the electrode 2 so as to surround the electrode 2, it is possible to suppress an electrical signal emitted from the living body from leaking to the surrounding electrodes (crosstalk) via the biological buffer layer 3 having conductivity. . That is, the highly sensitive electrode array 10 can be formed.
  • the partition wall 4 is harder than the biological buffer layer 3. Therefore, the biological buffer layer 3 can be supported like the skeleton of the partition walls 4, and the mechanical strength of the electrode array 10 can be increased.
  • the partition walls 4 can help the substrate 1 and the biological buffer layer 3 to adhere to each other, and can increase the mechanical strength of the electrode array 10. In general, it is difficult to obtain strong adhesion between the biological buffer layer 3 and the electrode 2. Therefore, the biological buffer layer 3 may come off from the electrode 2. However, by providing the partition wall 4, the contact surface of the biological buffer layer 3 is increased, and the adhesion can be increased.
  • the material of the partition wall 4 is preferably harder than the biological buffer layer 3 and has a softness that does not damage the living body. That is, it is preferable to satisfy the relationship of Young's modulus of the biological buffer layer ⁇ Young's modulus of the partition wall ⁇ Young's modulus of the base material. Specifically, the Young's modulus of the partition wall is preferably 0.5 MPa to 2000 MPa, more preferably 1 MPa to 1000 MPa. Since the partition 4 has hardness, the biological buffer layer 3 can be supported like the skeleton of the partition 4, and the mechanical strength of the electrode array 10 can be increased.
  • the partition walls 4 for example, silicon elastomer, polyvinyl alcohol (PVA), fluorine elastomer, epoxy resin, or the like can be used. Since conductivity lower than that of the biological buffer material 3 is required, it is preferable that the moisture content is low. In order to perform patterning in accordance with the electrode array, a photocurable material is preferable.
  • the arrangement of the partition walls 4 only needs to surround the electrode 2, and the arrangement thereof is not particularly limited, such as a tetragonal lattice arrangement, a honeycomb lattice arrangement, a random arrangement, and a rectangular lattice arrangement. From the viewpoint of ease of production, a square lattice arrangement is preferable. From the viewpoint of mechanical strength, a honeycomb lattice arrangement is preferable. In any case, it is necessary to surround the periphery of the electrode 2.
  • the shape of the partition wall 4 does not need to stand vertically with respect to the base material 1 and may have a taper.
  • the height of the partition wall 4 is preferably substantially the same as the thickness of the biological buffer layer 3.
  • the purpose of the partition wall 4 is to prevent electrical signals from the living body from leaking out through the biological buffer layer 3. Therefore, the height of the partition wall 4 and the thickness of the biological buffer layer 3 do not have to be completely the same. Even when the height of the partition wall 4 is slightly lower than the thickness of the biological buffer layer 3, current leakage can be sufficiently prevented and crosstalk can be suppressed. Further, even when the height of the partition wall 4 is slightly higher than the thickness of the biological buffer layer 3, the biological buffer layer 3 can sufficiently follow the living body by pressing the electrode array against the living body. Therefore, the electrical signal from the living body can be sufficiently transmitted to the electrode. In addition, since the biological buffer layer 3 is partitioned by the partition walls 4, the occurrence of crosstalk can be suppressed.
  • “slightly” means a range within 30% of the thickness of the biological buffer layer 3.
  • the height of the partition wall 4 is preferably substantially the same as the thickness of the biological buffer layer 3, but among them, the height of the partition wall 4 is preferably lower than the thickness of the biological buffer layer 3.
  • the height of the partition wall 4 is preferably 50% or more, more preferably 80% or more, and further preferably 90% or more with respect to the thickness of the biological buffer layer 3.
  • “the height of the partition wall 4 is lower than the thickness of the biological buffer layer 3” means that the entire partition wall 4 is covered with the biological buffer layer 3. That is, the entire partition wall 4 is preferably covered with the biological buffer layer 3.
  • the influence on the living body can be suppressed and the selectivity of the material constituting the partition wall 4 can be increased. Moreover, if the height of the partition wall 4 with respect to the thickness of the biological buffer layer 3 is high, the electrical shielding effect can be enhanced.
  • the partition wall 4 is preferably made of a biocompatible material. If the height of the partition wall 4 and the thickness of the living body buffer layer 3 are substantially the same, the partition wall 4 may directly touch the living body. Therefore, in order to suppress damage to the living body, the partition wall 4 is also preferably made of a material having biocompatibility.
  • a material having the biocompatibility of the partition wall 4 for example, a silicon elastomer, a fluorine elastomer, or the like can be used among the materials of the partition wall 4 described above. This is a material having a relatively high Young's modulus relative to the material shown in the biological buffer layer 3 described above.
  • a ground wiring 5 is provided in the partition wall 4 or in the lower part of the partition wall 4.
  • the partition 4 alone cannot sufficiently insulate, and crosstalk occurs.
  • the ground wiring 5 By providing the ground wiring 5 in the partition 4 or at the bottom of the partition 4, the electric signal leaking through the partition 4 can be cut, and crosstalk can be further suppressed. That is, the sensitivity of the electrode array 10 can be further increased.
  • the ground wiring 5 only needs to have conductivity, and metal, ITO, or the like can be used.
  • the carbon nanomaterial double-coated with the molecule constituting the hydrophilic ionic liquid and the water-soluble polymer is the water-soluble polymer.
  • a conductive gel dispersed in a medium and crosslinked with this water-soluble polymer can be used.
  • the ionic liquid is also referred to as a normal temperature molten salt or simply a molten salt, and is a salt that exhibits a molten state in a wide temperature range including normal temperature.
  • a hydrophilic ionic liquid among various conventionally known ionic liquids, a hydrophilic ionic liquid can be used.
  • N, N-diethyl-N-methyl-N- (2-methoxyethyl) ammonium tetrafluoroborate (DEMEBF 4 ) can be mentioned.
  • the carbon nanomaterial is a component composed of carbon atoms and structured in a nanometer size (for example, one CNT), and the carbon atoms of the component are generally van der Waals forces. It means what is stuck.
  • it refers to carbon nanotubes, carbon nanofibers (carbon fibers having a diameter of 10 nm or less), carbon nanohorns, fullerenes, and the like.
  • a fine carbon nanomaterial of 10 nm or less exhibits good dispersibility in water.
  • a carbon nanotube has a structure in which a graphene sheet in which carbon atoms are arranged in a hexagonal network is a single-layer or a multi-layer and is rounded in a cylindrical shape (single-wall nanotube (SWNT), double-wall nanotube (DWNT), multi-wall nanotube
  • SWNT single-wall nanotube
  • DWNT double-wall nanotube
  • the carbon nanotube that can be used as the carbon nanomaterial is not particularly limited. Any of SWNT, DWNT, and MWNT may be used.
  • Carbon nanotubes can generally be produced by laser ablation, arc discharge, thermal CVD, plasma CVD, gas phase, combustion, or the like. Regardless of the carbon nanotube produced by the carbon nanotube used here, a plurality of types of carbon nanotubes may be used.
  • Carbon nanotubes tend to aggregate due to van der Waals forces between carbon nanotubes. Therefore, usually, a plurality of carbon nanotubes exist in the form of bundles or aggregates. However, in the presence of an ionic liquid, the bundle or aggregate can be subdivided by applying a shearing force (reducing entanglement of carbon nanotubes). By sufficiently subdividing, the van der Waals force that binds the carbon nanotubes is weakened and separated into individual carbon nanotubes, and the ionic liquid can be adsorbed to the individual carbon nanotubes. it can. As a result, it is possible to obtain a composition comprising carbon nanotubes and an ionic liquid, including single carbon nanotubes covered with ionic liquid molecules.
  • the means for applying a shearing force used in the subdividing step is not particularly limited, and a wet pulverizing apparatus capable of applying a shearing force such as a ball mill, a roller mill, or a vibration mill can be used.
  • the entanglement of the carbon nanotubes can be reduced by mixing the carbon nanotubes with the ionic liquid and performing the above-described subdividing step.
  • the molecules of the ionic liquid are bonded to the surface of the carbon nanotubes with reduced entanglement by the “cation- ⁇ ” interaction, the carbon nanotubes are further bonded through the ionic bonds to form a gel composition.
  • a gel composition can be considered.
  • rinsing the gel composition with, for example, physiological saline or ethanol a single ionic liquid molecule layer can be formed on the surface of the carbon nanotube.
  • water and a water-soluble polymer it is possible to produce a composition in which carbon nanotubes covered with molecules constituting an ionic liquid are dispersed in a water-soluble polymer medium.
  • the water-soluble polymer is not particularly limited as long as it is a polymer that can be dissolved or dispersed in water. It is more preferable if it can be crosslinked in water.
  • the following examples can be given.
  • Synthetic polymer (1) ionic polyacrylic acid (anionic) Polystyrene sulfonic acid (anionic) Polyethyleneimine (cationic) MPC polymer (Zwitterion) (2) Nonionic Polyvinylpyrrolidone (PVP) Polyvinyl alcohol (polyvinyl acetate saponified product) Polyacrylamide (PAM) Polyethylene oxide (PEO) 2.
  • Natural polymers (mostly polysaccharides) Starch Gelatin Hyaluronic acid Alginic acid Dextran protein (eg water-soluble collagen) 3.
  • Semi-synthetic polymer eg cellulose solubilized) Carboxymethylcellulose (CMC) Hydroxypropyl cellulose (HPC) Cellulose derivatives such as methylcellulose (MC) Water-soluble chitosan (can also be classified as “2. Natural polymers”)
  • water-soluble polymer examples include polyrotaxane.
  • Polyrotaxane is cyclic at both ends (both ends of a linear molecule) of a pseudopolyrotaxane in which the opening of a cyclic molecule (rotator) is skewered by a linear molecule (axis).
  • a blocking group is arranged so that the molecule is not released.
  • polyrotaxane using ⁇ -cyclodextrin as a cyclic molecule and polyethylene glycol as a linear molecule can be used.
  • the water-soluble polymer medium is preferably a compound having a group that reacts with a crosslinking agent. With such a reactive group, a strong film can be formed by crosslinking.
  • the water-soluble polymer is preferably photocrosslinkable.
  • the molecular layer of the ionic liquid enclosing the carbon nanomaterial may be a monomolecular layer.
  • the surface of the carbon nanomaterial and the molecule of the ionic liquid are bonded by a “cation- ⁇ ” interaction.
  • the molecules of the ionic liquid encapsulating the carbon nanomaterial are selected.
  • This layer can be a monomolecular layer.
  • the molecular layer can be a monomolecular layer.
  • a thin polyrotaxane layer of about 5 nm can be formed on the monomolecular layer of DEMEBF 4 .
  • the dispersion concentration of the carbon nanotubes can be made high, and a highly conductive material can be obtained.
  • a conductive member such as an electronic contact made of such a conductive material, electrons move between carbon nanotubes through a thin DEMEBF 4 molecular layer and a polyrotaxane layer, and a current flows.
  • the surface of the carbon nanomaterial and the molecule of the ionic liquid are strongly bonded by the “cation- ⁇ ” interaction. Therefore, the molecules of the ionic liquid bonded to the surface of the carbon nanomaterial do not come out of the water-soluble polymer medium. Molecules of the ionic liquid that are not bonded to the surface of the carbon nanomaterial can be removed, for example, by rinsing with physiological saline or ethanol.
  • the carbon nanomaterial contained therein is doubly covered with the ionic liquid molecules and the water-soluble polymer. There is virtually no touch.
  • This conductive material has high flexibility. Therefore, it is excellent in followability to the surface of an organ or the like in a living body, and an extremely good interface can be formed between the organ and the like.
  • the conductive material may have a high conductivity.
  • This conductive material is a first step in which a hydrophilic ionic liquid, a carbon nanomaterial, and water are mixed to obtain a first dispersion system in which the carbon nanomaterial covered with molecules constituting the ionic liquid is dispersed. And a first dispersion system, a water-soluble polymer and water are mixed to obtain a second dispersion system in which the carbon nanomaterial covered with the molecules constituting the ionic liquid and the water-soluble polymer are dispersed. It can manufacture by a manufacturing method provided with 2 processes.
  • the carbon nanomaterial may be subdivided by applying a shearing force.
  • a shearing force By applying a shearing force, the bundle or aggregation of the carbon nanomaterial can be covered with a hydrophilic ionic liquid in a state in which the carbon nanomaterial is further dissolved.
  • the method may further include a step of preparing a composition in which the carbon nanomaterial is dispersed in a water-soluble polymer medium and the water-soluble polymer is crosslinked. Thereby, a moldability and workability improve.
  • a rinsing step may be further provided to remove molecules constituting the ionic liquid that is not bound to the carbon nanomaterial. Thereby, a moldability and workability improve.
  • This rinsing step can be performed with, for example, physiological saline, ethanol, or a liquid that does not break the gel. This rinsing process may be performed at any stage.
  • the conductive material can contain other substances as long as the effects of the present invention are not impaired.
  • the manufacturing method of the said conductive material can include another process in the range which does not impair the effect of this invention.
  • the electrode array 10 includes a first step for producing a plurality of electrodes 2 on a substrate 1 using a mask, a second step for producing a partition 4 so as to surround the electrode 2 using photolithography, and a partition And a third step of laminating the biological buffer layer 3 in the bank surrounded by 4.
  • the electrode 2 can be formed by sputtering or vapor deposition.
  • the barrier rib 4 is formed so as to surround the electrode 2 using photolithography.
  • a spacer is set on the substrate 1 and the material of the partition walls 4 is filled in the space surrounded by the spacer.
  • the filled partition 4 material is irradiated with UV through a mask. Thereafter, by washing away unnecessary portions, only the portions irradiated with UV can be left as the partition walls 4.
  • the first step and the second step may be reversed. That is, the partition wall may be formed first, and then the electrode 2 may be formed through a mask.
  • the biological buffer layer 3 is stacked in a bank surrounded by the partition walls 4. At this time, the biological buffer layer 3 may also be laminated on the partition wall 4.
  • the biological buffer layer 3 can use the conductive gel described above.
  • FIG. 3 is a schematic view schematically showing a cross section of a biosensor according to an embodiment of the present invention.
  • the biological sensor of the present invention includes an electrode array 10, an amplifier circuit 101 connected to each electrode 2 of the electrode array 10, and a transistor T connected to the amplifier circuit.
  • Such a transistor T is connected by a plurality of bit lines and word lines, and information from each electrode can be output to the outside.
  • FIG. 4 is a diagram illustrating an example of a circuit configuration of the biosensor according to the embodiment of the present invention.
  • a biosensor 100 receives a signal generated from a living body at a plurality of electrodes 2 11 to 2 nm .
  • the received signal is amplified by the amplifier circuit 101, and is passed through a plurality of signal transfer transistors T 11 to T nm , a plurality of bit lines BL 1 to BL m, and a plurality of word lines WL 1 to WL n. Output to the outside.
  • the plurality of electrodes 2 11 to 2 nm correspond to each electrode 2 of the electrode array 10.
  • the capacitor 102 may be included as necessary.
  • each output unit of the signal detectors F 11 to F n1 belonging to the first column includes transistors T 11 to T n1 for signal transfer.
  • the signal detectors F 12 to F n2 belonging to the second column are connected to the bit line BL 1 via the signal transfer transistors T 12 to T n2 and connected to the bit line BL 2 via the signal transfer transistors T 12 to T n2. Yes.
  • the output units of the signal detectors F 1m to F nm belonging to the m-th column are connected to the bit line BL m via the signal transfer transistors T 1m to T nm .
  • the gates of the signal transfer transistors T 11 to T 1m provided in the signal detectors F 11 to F 1m belonging to the first row are word lines.
  • Each gate of signal transfer transistors T 21 to T 2m connected to WL 1 and provided in signal detectors F 21 to F 2m belonging to the second row is connected to word line WL 2 .
  • the gates of the signal transfer transistors T n1 to T nm provided in the signal detectors F n1 to F nm belonging to the n-th row are connected to the word line WL n .
  • a plurality of signal detectors F 11 to F nm are arranged in a matrix, and a signal transfer transistor T 11 is formed by the word lines WL 1 to WL n and the bit lines BL 1 to BL m. by selecting ⁇ T nm, it becomes possible to read from each of the signal detectors F 11 ⁇ F nm signals selectively.
  • FIG. 5 is a diagram showing an example of the circuit configuration of the signal detectors F 11 to F nm shown in FIG. All of the signal detectors F 11 to F nm in FIG. 4 have the same configuration. As shown in FIG. 5, each of the signal detectors F 11 to F nm includes an electrode 2 and an amplifier circuit 101. Further, a capacitor 102 may be provided. An electrical signal from a living body is applied to the electrode 2.
  • the capacitor 102 is for cutting a direct current component included in a biological signal from the subject.
  • the capacitor 102 is connected between the electrode 2 and the input part of the amplifier circuit 101. That is, the input portion of the amplifier circuit 101 is capacitively coupled to the electrode 2 via the capacitor 102.
  • the capacitor 102 has a capacitance value of about 670 nF, for example, and has a SAM / AlO x structure composed of a self-assembled monolayer (Self-Assembled Monolayer; Sam) and aluminum oxide (AlO x ).
  • the amplifier circuit 101 includes transistors 1011 to 1014 and a resistance element 1015.
  • the transistors 1011 to 1014 are flexible p-type organic transistors.
  • the organic transistor constituting the amplifier circuit 101 has a gate width of, for example, 600 ⁇ m and a gate length of 20 ⁇ m. In this example, a drain current of about ⁇ 100 ⁇ A was confirmed.
  • the present invention is not limited to this example, and an n-type organic transistor may be used instead of the p-type organic transistor. Considering the difference in operational stability and carrier mobility, the p-type organic transistor can stably obtain a larger drain current than the n-type organic transistor, which is compared with the n-type organic transistor. It is advantageous.
  • the amplifier circuit 101 is not limited to an organic transistor, and can be configured using any amplifier element depending on the application.
  • the drain of the transistor 1011 constituting the amplifier circuit 101 is connected to the power supply node VDD (high potential node), and the gate thereof is connected to the input portion of the amplifier circuit 101.
  • the drain of the transistor 1012 is connected to the source of the transistor 1011, and the source of the transistor 1012 is connected to the ground node.
  • the drain of the transistor 1013 is connected to the power supply node VDD, and the gate of the transistor 1013 is connected to the input portion of the amplifier circuit 101.
  • the drain and gate of the transistor 1014 are connected to the source of the transistor 1013 together with the gate of the transistor 1012, and the source of the transistor 1014 is connected to the low potential node VSS.
  • a resistance element 1015 is connected between the input part and the output part of the amplifier circuit 101.
  • the resistance element 1015 is for returning the output signal of the amplifier circuit 101 to the input unit.
  • the resistance element 1015 has a resistance value of about 20 M ⁇ , for example, and is made of, for example, a carbon paste having flexibility and conductivity.
  • the resistance element 1015 can be formed using any material without being limited to this example.
  • the resistance element 1015 need not be formed integrally with the amplifier circuit 101, and may be provided as an external resistor.
  • Example 12 ⁇ m polyimide was prepared as a substrate. First, a rectangular (square) electrode matrix was formed in a grid pattern on the substrate. The material was gold and formed by vapor deposition through a mask. That is, 64 electrodes were produced. Next, a spacer having a thickness of 1 mm was installed, and a region surrounded by the spacer was filled with silicon elastomer. In order to form a grid-like partition wall structure, a UV curable silicone elastomer was used here.
  • the UV curable silicone elastomer has siloxane as the main chain and has a functional group (for example, methacryloyl group) at the terminal for radical polymerization by UV light irradiation.
  • a photoinitiator for example, an aromatic ketone such as acetophenone or 2,2-dimethoxy-2-phenylacetophenone
  • the silicon elastomer was cured by UV exposure through a mask in which 1 mm lines were formed in a grid pattern at intervals of 7 mm in accordance with the previously formed electrode matrix.
  • the UV exposure at this time was carried out using a light box (W532 ⁇ D450 ⁇ H100 mm) manufactured by SUNHAYATO, using Black light FL15BL (trade name) manufactured by NEC having a UV wavelength of 300 nm to 400 nm as a light source.
  • FIG. 6 is a photograph in which a partition made of silicon elastomer was produced on a substrate and gold was deposited as an electrode in a cell surrounded by the partition.
  • a biological buffer layer is produced.
  • a conductive medium uniformly dispersed in a biocompatible polymer medium can be used.
  • Composition in which carbon nanotubes covered with molecules constituting N, N-diethyl-N-methyl-N- (2-methoxyethyl) ammonium tetrafluoroborate (DEMEBF 4 ) are dispersed in polyrotaxane as a biological buffer layer was used.
  • FIG. 7 is a diagram schematically showing a production procedure of a composition that is crosslinked to become a biological buffer layer in the example of the present invention.
  • This composition was prepared by using 30 mg of a commercially available carbon nanotube (MWNT, length 10 ⁇ m, diameter 5 nm) and N, N-diethyl-N-methyl-N- (2-methoxyethyl) ammonium, which is a hydrophilic ionic liquid.
  • Tetrafluoroborate (DEMEBF 4 ) 60 mg was mixed and stirred. Stirring was performed in deionized water at 25 ° C. for 1 week at a rotation speed of 700 rpm or higher using a magnetic stirrer.
  • the resulting suspension was treated with a high pressure jet mill homogenizer (60 MPa; Nano-jet pal, JN10, Jokoh) to give a black material.
  • This gel-like substance is filled into a bank surrounded by a partition made of a silicon elastomer that has already been prepared.
  • the polyrotaxane was crosslinked to disperse the carbon nanotubes covered with the molecules constituting the DEMEBF 4 in the polyrotaxane medium, thereby producing a biological buffer layer in which the polyrotaxane was crosslinked.
  • the thickness of the biological buffer layer and the height of the partition made of silicon elastomer were set to 1 mm.
  • FIG. 8A is a graph showing an output result measured by an electrode opposed to a portion where the input voltage is applied when an input voltage of 100 mV is applied to a certain point of the electrode array of the example.
  • FIG. 8B is a graph showing an output result measured by an electrode facing a portion where the input voltage is applied when an input voltage of 100 mV is applied to a certain point of the electrode array of the example.
  • the vertical axis represents output voltage
  • the XY axis represents position coordinates.
  • XY of the graph is 7 mm ⁇ 7 mm, which is one cell size surrounded by the partition wall in the embodiment.
  • This output result is an output result measured by one electrode facing the point where the input voltage is applied.
  • the electrode array of the example shows an output result of 45 mV for an input voltage of 100 mV (see FIG. 8A), whereas the electrode array of the comparative example outputs an output result of 23 mV for an input voltage of 100 mV. It can only be seen (see FIG. 8B). Also, it can be seen from the graph that the electrode array of the example shows a detection result with a higher peak, and the sensitivity of the electrode array is higher.
  • FIG. 9A is a graph simulating an output result measured by an electrode facing a portion where the input voltage is applied when an input voltage of 100 mV is applied to a certain point of the electrode array of the example.
  • FIG. 9B is a graph simulating the output result measured by the electrode facing the portion where the input voltage was applied when an input voltage of 100 mV was applied to a certain point of the electrode array of the comparative example.
  • the vertical axis represents output voltage
  • the XY axis represents position coordinates.
  • electrostatic field analysis was performed using a finite difference method.
  • the size of the finite difference grid is a cube having a side of 1 mm, and a grid of 58 ⁇ 58 in the direction parallel to the substrate and one grid in the thickness direction perpendicular to the substrate.
  • the electrode array of the example shows an output result of 100 mV for an input voltage of 100 mV (see FIG. 9A), whereas the electrode array of the comparative example outputs an output result of 30 mV for an input voltage of 100 mV. It can only be seen (see FIG. 9B). It is clear from the graph that the electrode array of the example shows a detection result with a higher peak, and the sensitivity of the electrode array is higher.

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Abstract

Réseau d'électrodes (10) situé sur un substrat (1), comportant, dans l'ordre indiqué, une pluralité d'électrodes (2) disposées sur le même plan, et couche tampon biologique (3). Une séparation isolante (4), disposée de manière à encercler les électrodes (2), est située dans la couche tampon biologique (3).
PCT/JP2015/053280 2014-02-06 2015-02-05 Réseau d'électrodes et capteur biologique WO2015119208A1 (fr)

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JP2018174995A (ja) * 2017-04-03 2018-11-15 株式会社テクサー 生体信号計測装置用電極及びそれを備える生体信号計測装置
JP2018186957A (ja) * 2017-04-28 2018-11-29 日東電工株式会社 生体センサ用積層体および生体センサ

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JPH02143908U (fr) * 1989-05-10 1990-12-06
JPH03706U (fr) * 1989-05-26 1991-01-08
JPH04244171A (ja) * 1991-01-29 1992-09-01 Nitto Denko Corp 生体電極用パッド
JPH07185016A (ja) * 1993-09-01 1995-07-25 Makoto Haga イオントフォレシス用生体適用デバイス
JP2001190694A (ja) * 2000-01-07 2001-07-17 Nitto Denko Corp 生体用の電極構造体
JP2008237929A (ja) * 2000-12-28 2008-10-09 Z-Tech (Canada) Inc 疾患を検出及び診断するための改善された電気インピーダンス法及び装置
JP2011513038A (ja) * 2008-03-12 2011-04-28 ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア 生理学的な活動を記録し変調するためのフレキシブルかつ拡張可能なセンサアレイ
JP2011518578A (ja) * 2007-11-08 2011-06-30 コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ 再位置決め可能な電極、並びに心臓療法のための電極の位置を特定するためのシステム及び方法

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JPH0180147U (fr) * 1987-11-20 1989-05-30
JPH02143908U (fr) * 1989-05-10 1990-12-06
JPH03706U (fr) * 1989-05-26 1991-01-08
JPH04244171A (ja) * 1991-01-29 1992-09-01 Nitto Denko Corp 生体電極用パッド
JPH07185016A (ja) * 1993-09-01 1995-07-25 Makoto Haga イオントフォレシス用生体適用デバイス
JP2001190694A (ja) * 2000-01-07 2001-07-17 Nitto Denko Corp 生体用の電極構造体
JP2008237929A (ja) * 2000-12-28 2008-10-09 Z-Tech (Canada) Inc 疾患を検出及び診断するための改善された電気インピーダンス法及び装置
JP2011518578A (ja) * 2007-11-08 2011-06-30 コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ 再位置決め可能な電極、並びに心臓療法のための電極の位置を特定するためのシステム及び方法
JP2011513038A (ja) * 2008-03-12 2011-04-28 ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア 生理学的な活動を記録し変調するためのフレキシブルかつ拡張可能なセンサアレイ

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018174995A (ja) * 2017-04-03 2018-11-15 株式会社テクサー 生体信号計測装置用電極及びそれを備える生体信号計測装置
JP2018186957A (ja) * 2017-04-28 2018-11-29 日東電工株式会社 生体センサ用積層体および生体センサ
JP7037285B2 (ja) 2017-04-28 2022-03-16 日東電工株式会社 生体センサ用積層体および生体センサ

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