Dynamic monitoring of activation of G-protein coupled receptor (GPCR) and receptor tyrosine kinase (RTK) in living cells using real-time microelectronic cell sensing technology

A method of identifying a compound capable of interacting with a G-Protein Coupled Receptor (GPCR) comprising:

• a) providing a device capable of measuring cell-substrate impedance, wherein said device comprises at least two wells, each comprising a conductive electrode array on a non-conductive substrate further wherein said device is operably connected to an impedance analyzer and a computer;
• b) adding test cells to at least one of said at least two wells for attachment to said conductive electrode array to form at least one test well, and adding control cells to at least another well for attachment to said conductive electrode array to form at least one control well, wherein said test cells express a GPCR and said control cells do not express said GPCR or express said GPCR at a lesser level than said test cells;
• c) determining first cell indices from first impedances, wherein said first impedances are cell-substrate impedances measured from said at least one test well and from said at least one control well immediately preceding step d);
• d) adding a compound to said at least one test well and to said at least one control well;
• e) determining second cell indices from second impedances wherein said second impedances are cell-substrate impedances measured from said at least one test well and from said at least one control well after step d);
• f) determining the change in cell index of said at least one test well by comparing said second cell index of said at least one test well to said first cell index of said at least one test well, and determining the change in cell index of said at least one control well by comparing said second cell index of said at least one control well to said first cell index of the said at least one control well;
• g) comparing said changes in cell index between said at least one test well and said at least one control well;
• and
• h) identifying said compound interacts with said GPCR if said comparison demonstrates at least a 1% difference between said change in cell index for said at least one test well and said change in cell index for said at least one control well.