This invention focuses on the marriage of solid-state electronics and
neuronal function to create a new high-throughput electrophysiological
assay to determine a compound's acute and chronic effect on cellular
function. Electronics, surface chemistry, biotechnology, and fundamental
neuroscience are integrated to provide an assay where the reporter
element is an array of electrically active cells. This innovative
technology can be applied to neurotoxicity, and to screening compounds
from combinatorial chemistry, gene function analysis, and basic
neuroscience applications. The system of the invention analyzes how the
action potential is interrupted by drugs or toxins. Differences in the
action potentials are due to individual toxins acting on different
biochemical pathways, which in turn affects different ion channels,
thereby changing the peak shape of the action potential differently for
each toxin. Algorithms to analyze the action potential peak shape
differences are used to indicate the pathway(s) affected by the presence
of a new drug or compound; from that, aspects of its function in that
cell are deduced. This observation can be exploited to determine the
functional category of biochemical action of an unknown compound. An
important aspect of the invention is surface chemistry that permits
establishment of a high impedance seal between cell and a metal
microelectrode. This seal recreates the interface that enables functional
patch-clamp electrophysiology with glass micropipettes, and allows
extracellular electrophysiology on a microelectrode array. Thus, the
invention teaches the feasibility of using living cells as diagnostics
for high throughput real-time assays of cell function.