# US 6,297,025 B1 · Measurement of complete electrical waveforms of tissue or cells > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 6,297,025 B1 - Document ID: US6297025B1 - Status: Granted - Kind: B1 - Application number: 08/662,629 - Filed: 1996-06-13 - Granted: 2001-10-02 - Earliest claimed: 1994-06-13 - Assignees: Matsushita Electric Industrial Co., Ltd. - Inventors: Hirokazu Sugihara; Akihito Kamei; Yasushi Kobayashi; Makoto Taketani; Tadayasu Mitsumata - Web page: https://patentgrep.com/patent/US6297025B1 ## CPC - G01N 33/4836: {using multielectrode arrays} - C12M 21/08: {for producing artificial tissue or for ex-vivo cultivation of tissue (prostheses A61F2/00, grafts A61L27/00)} - C12M 41/00: {Means for regulation, monitoring, measurement or control, e.g. flow regulation (controlling or regulating chemical, physical or physicochemical processes B01J19/0006; heating or cooling apparatus for laboratory use B01L7/00; electro optical investigation of individual particles, flow cytometers G01N15/14; automatic analysis G01N35/00; controlling or regulating in general G06N)} - C12M 41/46: {of cellular or enzymatic activity or functionality, e.g. cell viability} - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS} ## Abstract A method of observing a physical and chemical property of a tissue or cell by using an apparatus which comprises at least a cell culturing means, an environment conditioning means, an observing means and a comparing means, comprising the steps of (A) culturing the tissue or cell by the cell culturing means, (B) maintaining a first physical and chemical environment around the tissue or cell by the cell culturing means, (C) observing a first physical and chemical property of the tissue or cell in the first physical and chemical environment by the observing means, (D) changing the first physical and chemical environment to a second physical and chemical environment by the environment conditioning means, (E) observing a second physical and chemical property of the tissue or cell in the second physical and chemical environment by the observing means, and (F) comparing the first physical and chemical property of the tissue or cell with the second physical and chemical property of the tissue or cell by the comparing means. ## Claims ### Claim 1 A method for observing electrical waveforms in a tissue slice by providing an apparatus which comprises at least cell culturing components, environment conditioning components for changing a culture medium or the physical or chemical property of the tissue slice, a plurality of electrodes on a substrate, said electrodes being of a sufficient number to allow detection and stimulation of electrical waveforms in said tissue slice, and a comparator, the method comprising the steps of: (A) culturing the tissue slice by the cell culturing components; (B) maintaining a first physical and chemical environment around the tissue slice by the cell culturing components; (C) observing a first complete electrical waveform of the tissue slice in the first physical and chemical environment by the plurality of electrodes; (D) changing the first physical and chemical environment to a second physical and chemical environment by the environment conditioning components; (E) observing a second complete electrical waveform of the tissue slice in the second physical and chemical environment by the plurality of electrodes; and (F) comparing the first electrical waveform of the tissue slice with the second electrical waveform of the tissue slice by the comparator. ### Claim 2 (depends on 1) The method of claim 1 wherein the step of changing the first physical and chemical environment to a second physical and chemical environment comprises substituting a second culture medium for use in the cell culturing components for a first culture medium used in the cell culturing components. ### Claim 3 A method for observing electrical waveforms in a tissue slice by using an apparatus which comprises at least cell culturing components, environment conditioning components for changing a culture medium or the physical or chemical property of the tissue slice, a plurality of electrodes on a substrate, said electrodes being of a sufficient number to allow detection and stimulation of electrical waveforms in said tissue slice, and a comparator, the method comprising the steps of: (A) culturing the tissue slice by the cell culturing components; (B) maintaining a first physical and chemical environment around the tissue slice by the cell culturing components; (C) observing a first electrical waveform of the tissue slice in the first physical and chemical environment by the plurality of electrodes; (D) electrically stimulating said tissue slice by the plurality of electrodes; (E) observing a second electrical waveform of the tissue slice in the second physical and chemical environment by the plurality of electrodes; and (F) comparing the first electrical waveform of the tissue slice with the second electrical waveform of the tissue slice by the comparator. ### Claim 4 (depends on 3) The method of claim 3 further including a step of changing the first physical and chemical environment to a second physical and chemical environment by substituting a second culture medium for a first culture medium used in the cell culturing components. ### Claim 5 (depends on 1) The method of claim 1 further comprising the step of stimulating said tissue slice after said step (B). ### Claim 6 (depends on 1) The method of claim 1 further comprising the step of stimulating said tissue slice after said step (D). ### Claim 7 (depends on 1) The method of claim 1 wherein the tissue slice is a neural or muscle tissue. ### Claim 8 (depends on 1) The method of claim 1 wherein the tissue slice is postnatal. ### Claim 9 (depends on 1) The method of claim 1 wherein the detection and stimulation of electrical waveforms is performed by the electrodes on the substrate. ### Claim 10 (depends on 1) The method of claim 1 further comprising repeating steps (E) and (F) until a chronic effect is observed in said second electrical waveform. ### Claim 11 (depends on 1) The method of claim 1 wherein step (E) is conducted at least three days after step (D). ### Claim 12 (depends on 1) The method of claim 1 wherein said electrodes each having an electrode area of 4×102 μm2 to 4×104 μm2. ### Claim 13 (depends on 3) The method of claim 3 wherein each of said electrodes is coated with a covering for increasing the adhesion of the tissue slice to said plurality of electrodes. ### Claim 14 (depends on 13) The method of claim 13 wherein said covering comprises collagen. ### Claim 15 (depends on 14) The method of claim 14 wherein said collagen has a thickness of about 50 μm or less.