A biosensor system based on the response of living cells was demonstra
ted that can detect specific components of a complex mixture fractiona
ted by a microcolumn separation technique. This system uses ligand-rec
eptor binding and signal-transduction pathways to biochemically amplif
y the presence of an analyte after electrophoretic separation. The tra
nsduced signal was measured by means of two approaches: (i) fluorescen
ce determination of intracellular calcium concentrations in one or mor
e rat PC-12 cells and (ii) measurement of transmembrane current in a X
enopus laevis oocyte microinjected with messenger RNA that encodes a s
pecific receptor. This analysis system has the potential to identify b
iologically active ligands present in a complex mixture with exception
al sensitivity and selectivity.