A novel microfabricated device to measure hormone/neurotransmitter release with millisecond temporal resolution

We are developing a novel readout for secretion of hormones and neurotransmitter on micro/nanofabricated chips. Traditional biochemical assays of signaling molecules secreted from cells are slow, cumbersome and have, at best, a temporal resolution of several seconds. On the other hand, electrochemical measurement of hormone or transmitter secretion can obtain millisecond temporal resolution if the diffusion distance between the release site on the cell and the working electrode is within 1 micron. Carbon fiber microelectrodes can have millisecond time resolution, but can only measure release from a small fraction of the cell surface. We have fabricated arrays of Au electrodes in wells micromachined on the surface of silicon microchips. Each well/microelectrode roughly conforms to the shape of a single cell in order to capture release from a large fraction of the surface area of each cell with minimal diffusional delays. This paper will present details of the microfabrication process flow as well as initial results demonstrating millisecond-resolution measurement of catecholamine secretion from adrenal chromaffin cells. Our goal for this project is to develop enabling technology for massively parallel Systems on a Chip such as cell-based biosensors to detect neurotoxins and high-throughput assays of drugs that affect neurotransmitter release.