REAL TIME ELECTRONIC CELL SENSING SYSTEM AND APPLICATIONS FOR CYTOTOXICITY PROFILING AND COMPOUND ASSAYS
First Claim
1. A method of investigating a mechanism of action of a compound, comprising:
- providing a device for monitoring cell-substrate impedance, wherein the device comprises two or more wells, each comprising an individually addressable electrode array, further wherein each electrode array comprises two electrode structures, each of which comprises multiple electrode elements, further wherein the electrode structures of each electrode array have substantially the same surface area;
attaching the device to an impedance analyzer;
adding cells to two or more wells;
adding a test compound to at least one of the wells comprising cells to form at least one test compound well;
providing at least one control well comprising cells that does not receive test compound;
monitoring impedance of the at least one test compound well and the at least one control well to obtain a series of impedance measurements including before adding the test compound and three or more time points after adding the test compound;
plotting impedance measurements from the at least three time points versus time to obtain at least one test compound impedance curve and at least one control impedance curve; and
comparing the impedance curves from the at least one test compound well and the at least one control well to determine a time frame at which the test compound has a significant effect on cell growth or behavior, wherein determining the time frame provides information on changes in cell status in response to the test compound, wherein the cell status is selected from the group consisting of cell attachment or adhesion status, cell growth or proliferation status, the number of viable or dead cells, cytoskeletal organization or structure, and the number of cells going through apoptosis or necrosis.
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Accused Products
Abstract
The invention provides methods of investigating a mechanism of action of a compound, which includes providing a device for monitoring cell-substrate impedance; attaching the device to an impedance analyzer; adding cells to two or more wells; adding a test compound to at least one of the wells and providing at least one control well; monitoring impedance of the wells to obtain a series of impedance measurements; plotting impedance measurements to obtain impedance curves and comparing the impedance curves to determine a time frame at which the test compound has a significant effect on cell growth or behavior. Determining the time frame provides information on changes in cell status in response to the test compound, including cell attachment or adhesion status, cell growth or proliferation status, the number of viable or dead cells, cytoskeletal organization or structure, and the number of cells going through apoptosis or necrosis.
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Citations
19 Claims
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1. A method of investigating a mechanism of action of a compound, comprising:
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providing a device for monitoring cell-substrate impedance, wherein the device comprises two or more wells, each comprising an individually addressable electrode array, further wherein each electrode array comprises two electrode structures, each of which comprises multiple electrode elements, further wherein the electrode structures of each electrode array have substantially the same surface area; attaching the device to an impedance analyzer; adding cells to two or more wells; adding a test compound to at least one of the wells comprising cells to form at least one test compound well; providing at least one control well comprising cells that does not receive test compound; monitoring impedance of the at least one test compound well and the at least one control well to obtain a series of impedance measurements including before adding the test compound and three or more time points after adding the test compound; plotting impedance measurements from the at least three time points versus time to obtain at least one test compound impedance curve and at least one control impedance curve; and comparing the impedance curves from the at least one test compound well and the at least one control well to determine a time frame at which the test compound has a significant effect on cell growth or behavior, wherein determining the time frame provides information on changes in cell status in response to the test compound, wherein the cell status is selected from the group consisting of cell attachment or adhesion status, cell growth or proliferation status, the number of viable or dead cells, cytoskeletal organization or structure, and the number of cells going through apoptosis or necrosis. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 15)
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12. A method of investigating a mechanism of action of a compound, comprising:
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providing a device for monitoring cell-substrate impedance, wherein the device comprises two or more wells, each comprising an individually addressable electrode array, further wherein each electrode array comprises two electrode structures, each of which comprises multiple electrode elements, further wherein the electrode structures of each electrode array have substantially the same surface area; attaching the device to an impedance analyzer; adding cells to two or more wells; adding a test compound to at least one of the wells comprising cells to form at least one test compound well; providing at least one control well comprising cells that does not receive test compound; monitoring impedance of the at least one test compound well and the at least one control well to obtain a series of impedance measurements including before adding the test compound and three or more time points after adding the test compound; deriving a cell index, a normalized cell index, or a delta cell index from the impedance measurements from the at least one test compound well and the at least one control well; plotting the cell indices, the normalized cell indices, or the delta cell indices to provide at least one test compound concentration CI curve and at least one control CI curve; and comparing the CI curves from the at least one test compound well and the at least one control well to determine a time frame at which the test compound has a significant effect on cell growth or behavior, wherein determining the time frame provides information on changes in cell status in response to the test compound, wherein the cell status is selected from the group consisting of cell attachment or adhesion status, cell growth or proliferation status, the number of viable or dead cells, cytoskeletal organization or structure, and the number of cells going through apoptosis or necrosis. - View Dependent Claims (13, 14, 16, 17, 18, 19)
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Specification