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: The present invention includes devices and methods for transfecting a cell or cell population and dynamic monitoring of cellular events. A variety of microelectronic devices are provide that incorporate functions such as electroporation, modulation of a transmembrane potential and dynamic monitoring of cellular functions and mechanisms.

Abstract: Methods for identifying a compound capable of interacting with a Receptor Tyrosine Kinase (RTK) including providing a device capable of measuring cell-substrate impedance, adding test cells expressing a RTK to the device, measuring first impedances, adding a compound to at least one compound well and adding a vehicle control to at least one control well, measuring second impedances of the compound well and the control well, determining the change in the impedance for the compound well and the one control well, comparing the change in impedance between the compound well and the control well, and identifying the compound interacts with the RTK if the comparison demonstrates a significant difference between the change in impedance.

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: An insert device and co-culture device assembly incorporating the insert device, which includes an insert chamber with two fluid impermeable side walls that extend from a microporous bottom to an open top to form an inner cavity. The first side wall is shaped to form a convex arc that follows between about half of a circumference of the well and less than an entire circumference of the well. The second side wall joins ends of the first side wall and protrudes inward towards a center of the convex arc. A flange extends outward from or beneath the top and is notched to form a gap adjacent to the second side wall, which forms an access port allowing access to the lower chamber with a micropipette tip when the insert device is inserted into a well of a single or multi-well plate.

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.

Abstract: Use of impedance devices in methods of generating a time dependent cellular profiles (TCRP) for the modulation of oncogene addicted cells and comparing the impedance-based TCRP to controls or knowns to identify signature time dependent cellular profiles.

Abstract: Methods for identifying a compound capable of interacting with a Receptor Tyrosine Kinase (RTK) including providing a device capable of measuring cell-substrate impedance, adding test cells expressing a RTK to the device, measuring first impedances, adding a compound to at least one compound well and adding a vehicle control at least one control well, measuring second impedances of the compound well and the control well, determining the change in the impedance for the compound well and the one control well, comparing the change in impedance between the compound well and the control well, and identifying the compound interacts with the RTK if the comparison demonstrates a significant difference between the change in impedance.

Abstract: The present application includes systems and methods for identifying a compound capable of interacting with a G-Protein Coupled Receptor (GPCR) or Receptor Tyrosine Kinase (RTK) including providing a device capable of measuring cell-substrate impedance operably connected to an impedance analyzer, adding test cells expressing a GPCR or a RTK to wells of the device, measuring first impedances of the wells and optionally determining first cell indices from the first impedances, adding a compound to at least one well containing test cells to form at least one compound well and adding a vehicle control to at least another well containing test cells to form at least one control well, measuring second impedances of the compound well and the control well and optionally determining second cell indices from the second impedances, determining the change in the impedance or cell index for the compound well and the one control well, comparing the change in impedance or cell index between the compound well and the control

Abstract: The present invention includes devices and methods for transfecting a cell or cell population and dynamic monitoring of cellular events. A variety of microelectronic devices are provide that incorporate functions such as electroporation, modulation of a transmembrane potential and dynamic monitoring of cellular functions and mechanisms.

Abstract: Novel compounds having a fused bicyclic heteroaromatic ring system substituted with a heteroaryl five-membered ring are disclosed. The compounds inhibit growth of a variety of types of cancer cells, and are thus useful for treating cancer. Efficacy of these compounds is demonstrated with a system for monitoring cell growth/migration, which shows they are potent inhibitors of growth and/or migration of cancer cells. In addition, compounds of the invention were shown to stop growth of tumors in vivo, and to reduce the size of tumors in vivo. Compositions comprising these compounds, and methods to use these compounds and compositions for treatment of cancers, are disclosed.

Abstract: The present invention includes devices and methods for transfecting a cell or cell population and dynamic monitoring of cellular events. A variety of microelectronic devices are provide that incorporate functions such as electroporation, modulation of a transmembrane potential and dynamic monitoring of cellular functions and mechanisms.

Abstract: The present invention includes devices, systems, and methods for assaying cells using cell-substrate impedance monitoring. In one aspect, the invention provides cell-substrate impedance monitoring devices that comprise electrode arrays on a nonconducting substrate, in which each of the arrays has an approximately uniform electrode resistance across the entire array. In another aspect, the invention provides cellular assays that use impedance monitoring to detect changes in cell behavior or state. In some preferred aspects, the assays are designed to investigate the affects of compounds on cells, such as cytotoxicity assays.

Abstract: A method of determining one or more beating parameters for use in cardiomyocyte beating analysis including: providing a cell analysis device including wells, each well including a sensor capable of monitoring beating of cardiomyoctes in millisecond time resolution; adding cardiomyocytes to the wells; monitoring the beating of the cardiomyocytes in millisecond time resolution to obtain a plurality of beating measurements; and calculating one or more beating parameters from the plurality of beating measurements.

Abstract: The present invention provides methods of multi-dimensional profiling of biologically active agents and determining their effects on biological systems. The methods of the present invention include real-time impedance monitoring of cellular responses to biologically active agents and categorization of cellular kinetic profiles into mechanism specific cellular response profile groups. The grouping of similar cellular response profiles allows the correlation between agent and mechanism, thus allowing for the identification of potential therapeutic applications of agents or further study of cellular responses or mechanisms.

Abstract: The present invention includes devices, systems, and methods for assaying cells using cell-substrate impedance monitoring. In one aspect, the invention provides cell-substrate impedance monitoring devices that comprise electrode arrays on a nonconducting substrate, in which each of the arrays has an approximately uniform electrode resistance across the entire array. In another aspect, the invention provides cell-substrate monitoring systems comprising one or more cell-substrate monitoring devices comprising multiple wells each having an electrode array, an impedance analyzer, a device station that connects arrays of individual wells to the impedance analyzer, and software for controlling the device station and impedance analyzer. In another aspect, the invention provides cellular assays that use impedance monitoring to detect changes in cell behavior or state. In some preferred aspects, the assays are designed to investigate the affects of compounds on cells, such as cytotoxicity assays.

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.

Abstract: Devices and methods for performing extracellular recording of cells, such as excitable cells, cardiomyocytes, and cardiomyocyte precursor cells is provided. An exemplary device includes a nonconductive substrate forming or provided as a base of one or more wells; a recording electrode positioned on the substrate within the well, wherein the recording electrode is accessible to cells when a cell sample is added to the device; and a reference electrode positioned within the well in a cell-free zone, the cell-free zone characterized as free from contact with cells when the cell sample is added to the device, thereby preventing contact between cells and the reference electrode.

Abstract: The present invention includes devices, systems, and methods for assaying cells using cell-substrate impedance monitoring. In one aspect, the invention provides cell-substrate impedance monitoring devices that comprise electrode arrays on a nonconducting substrate, in which each of the arrays has an approximately uniform electrode resistance across the entire array. In another aspect, the invention provides cell-substrate monitoring systems comprising one or more cell-substrate monitoring devices comprising multiple wells each having an electrode array, an impedance analyzer, a device station that connects arrays of individual wells to the impedance analyzer, and software for controlling the device station and impedance analyzer. In another aspect, the invention provides cellular assays that use impedance monitoring to detect changes in cell behavior or state. The methods can be used to test the effects of compounds on cells, such as in cytotoxicity assays.

Abstract: The present invention includes devices and methods for dynamically monitoring cell adhesion and cell spreading. Cells are added to a microelectronic cell sensor array operably connected to an impedance analyzer. The device also includes a coating including biological molecule or organic compound capable of interacting with the cell. Cell adhesion and cell mobility is determined by detecting changes in impedance and comparing impedance or cell index values between samples.