The functional anal. of single ion channel proteins presents a serious bottleneck in the process of finding new pharmacol. active compds. Currently available single channel recording methods are not suited for automation and miniaturization. However, new techniques such as combinatorial chem. and combinatorial genetics, which produce large amts. of potential drugs and mutant proteins, demand efficient and reliable screening as well as low sample consumption. Here we present a novel, silicon chip-based assay to probe the function of channel proteins. Membrane vesicles were electrophoretically positioned and fused across micrometer sized holes in the chip surface. Seal resistances up to 1000 GW obtained after a few seconds positioning time, allowed the detailed anal. of single ion channel currents. Std. sample vols. in the microliter range strongly reduce sample consumption, making the application of this technique in parallelized, highly sensitive biosensing devices for large-scale functional screening feasible. [on SciFinder (R)]