Automated Targeting of Cells to Electrochemical Electrodes Using a Surface Chemistry Approach for the Measurement of Quantal Exocytosis

Here, we describe a method to fabricate a multichannel high-throughput microchip device for the measurement of quantal transmitter release from individual cells. Instead of bringing carbon-fiber electrodes to cells, the device uses a surface chemistry approach to bring cells to an array of electrochemical microelectrodes. The microelectrodes are small and cytophilic in order to promote adhesion of a single cell, whereas all other areas of the chip are covered with a thin cytophobic film to block cell attachement and facilitate the movement of cells to electrodes. This cytophobic film also insulates unused areas of the conductive film; thus, the alignment of cell docking sites to working electrodes is automatic. Amperometric spikes resulting from single-granule fusion events were recorded on the device and had amplitudes and kinetics similar to those measured using carbon-fiber microelectrodes. Use of this device will increase the pace of basic neuroscience research and may also find applications in drug discovery or validation.