Abstract: A method of assessing cytolysis of cancer cells, the method including: providing a cell substrate impedance monitoring cartridge having a plurality of chambers, each chamber having an electrode array configured for measuring cell-substrate impedance, wherein different chambers are preloaded with different target cells embodied as cancer cells of different lineage, origin or stage; adding effector cells to the plurality chambers for interaction with the target cells, wherein the effector cells are immune cells; monitoring cell-substrate impedance of the plurality of chambers before and after adding the effector cells and optionally deriving an impedance-based parameter from the impedances; and determining effectiveness of effector cell killing of the different target cells by comparing the impedances or impedance-based parameters over time.

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: 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: 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: 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, 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: 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: 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.

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: 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 a method of measuring cytolytic activity including providing a device capable of monitoring cell-substrate impedance operably connected to an impedance analyzer, adding target cells to at least one well of the device, adding effector cells to the at least one well, monitoring impedance of the at least one well and optionally determining a cell index from the impedance, wherein monitoring impedance includes measuring impedance during at least one time point before and at least one time point after adding effector cells, and determining viability of said target cells after adding effector cells by comparing the impedance or optionally the cell index at the at least one time point after adding effector cells to the impedance or optionally the cell index at the at least one time point before adding effector cells.

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 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 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.

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 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 a method of measuring cytolytic activity including providing a device capable of monitoring cell-substrate impedance operably connected to an impedance analyzer, adding target cells to at least one well of the device, adding effector cells to the at least one well, monitoring impedance of the at least one well and optionally determining a cell index from the impedance, wherein monitoring impedance includes measuring impedance during at least one time point before and at least one time point after adding effector cells, and determining viability of said target cells after adding effector cells by comparing the impedance or optionally the cell index at the at least one time point after adding effector cells to the impedance or optionally the cell index at the at least one time point before adding effector cells

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, 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.