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.