Abstract:
Methods of identifying whether a biologically active agent affects an oncogene addicted pathway within a cancer cell, by introducing a biologically active agent suspected of affecting an oncogene addicted pathway to a first well and a negative control to a second well, and introducing a stimulating agent that stimulates the oncogene addicted pathway to both wells; monitoring cell-substrate impedance of the two wells and optionally determining cell indices from impedance values; generating an impedance based curve for each of the two wells from the impedance values or from the cell indices; comparing the impedance-based curves to determine a degree of similarity; and if significantly different concluding the biologically active agent affects the oncogene addicted pathway within the cancer cells.
Abstract:
A method of performing an assay of a response of two or more cell types to a test compound, including: providing a device for monitoring cell-substrate impedance, adding at least two different cell types to the device; adding at least one test compound to form at least two test compound wells; providing at least two control wells; monitoring impedance of the at least two test compound wells and of the at least two control wells at three or more time points after adding the at least one test compound; and analyzing measured impedance from the at least two test compound wells and from the at least two control wells at the three or more time points to obtain information on the response of the different cell types to the at least one test compound.
Abstract:
Use of cell-substrate impedance based methods for screening for agonists of G-Protein Coupled Receptors (GPCRs) or inhibitors of a Receptor Tyrosine Kinases (RTKs), identifying compounds that affect GPCR or RTK pathways, validating molecular targets involved in a GPCR or RTK signaling pathways, monitoring dose-dependent functional activation of GPCR or RTK; determining desensitization of a GPCR and identifying a compound capable of affecting RTK activity in cancer cell proliferation.
Abstract:
A method of performing an assay of a response of two or more cell types to a test compound, including: providing a device for monitoring cell-substrate impedance, adding at least two different cell types to the device; adding at least one test compound to form at least two test compound wells; providing at least two control wells; monitoring impedance of the at least two test compound wells and of the at least two control wells at three or more time points after adding the at least one test compound; and analyzing measured impedance from the at least two test compound wells and from the at least two control wells at the three or more time points to obtain information on the response of the different cell types to the at least one test compound.
Abstract:
Methods for identifying compounds that modulate cellular responses stimulated by IgE, which include providing an impedance-based system that monitors cell-substrate impedance of cells on a substrate; introducing cells to the substrate of the system; adding at least one test compound and IgE to the cells, wherein the at least one test compound is suspected of modulating cell responses stimulated by the IgE; adding an antigen to the cells; monitoring the cell-substrate impedance of cells on the substrate; and analyzing the cell-substrate impedance to evaluate whether the at least one test compound alters a cellular response to stimulation with the IgE.
Abstract:
Methods for identifying compounds that modulate cellular responses stimulated by IgE, which include providing an impedance-based system that monitors cell-substrate impedance of cells on a substrate; introducing cells to the substrate of the system; adding at least one test compound and IgE to the cells, wherein the at least one test compound is suspected of modulating cell responses stimulated by the IgE; adding an antigen to the cells; monitoring the cell-substrate impedance of cells on the substrate; and analyzing the cell-substrate impedance to evaluate whether the at least one test compound alters a cellular response to stimulation with the IgE.
Abstract:
Devices, systems and methods for monitoring excitable cells, such as cardiomyocytes, on microelectrode arrays that couple the electro-stimulation of excitable cells to induce or regulate cardiomyocyte beating and the simultaneous measurement of impedance and extracellular recording to assess changes in cardiomyocyte beating, viability, morphology or electrophysical properties in response to a plurality of treatments.
Abstract:
A system for monitoring cell-substrate impedance of excitable cells and monitoring the beating cycle of cardiomyocytes, the system including: a device for monitoring cell-substrate impedance at 20 millisecond time resolution, the device having one or more wells on a nonconductive substrate, wherein at least one well of the one or more wells comprises an electrode array fabricated on the substrate for measurement of cell-substrate impedance at 20 millisecond time resolution; an impedance analyzer that measures cell-substrate impedance from the at least one well at 20 millisecond time resolution; electronic circuitry that electrically connects the electrode array from the at least one well to the impedance analyzer; and a software program that analyzes the measured cell-substrate impedance.
Abstract:
A method of identifying a therapeutic compound for treating cancer in a human subject, the method including: providing a device that measures cell-substrate impedance; culturing cancer cells in the at least two wells, wherein the cancer cells are obtained from a human subject and have a receptor tyrosine kinase (RTK) pathway; adding to a first well a proposed therapeutic compound that affects an RTK pathway and an RTK stimulating factor for the RTK pathway to form a test well, and adding to another well the RTK stimulating factor to form a control well; continuously monitoring cell-substrate impedance of the at least two wells; and determining a difference in impedance or optionally in cell index between the test well and control well; and if significantly different, concluding the proposed therapeutic compound is therapeutically active in the RTK pathway within the cancer cells of the human subject.
Abstract:
A method of determining a beating parameter of cells that undergo excitation contraction coupling, the method including providing a cell analysis device having a substrate and a sensor that measures cell adhesion or attachment to the substrate in millisecond time resolution; adding excitable cells capable of undergoing excitation contraction coupling to the substrate; monitoring cell adhesion or attachment of the excitable cells to the substrate in millisecond time resolution; and calculating one or more beating parameters from the monitored adhesion.