The nanophysiometer: BioMEMS for high bandwidth detection of cellular activity in subnanoliter volumes

To monitor the dynamics of single cells with a high bandwidth, we have developed a BioMEMS device wherein a single cell can be trapped and monitored in a subnanoliter volume that provides control over the extracellular environment. The PDMS multilayer chips, based on a technology pioneered by Stephen Quake, et al., have fluidic and control layers separated by a thin membrane. Intersections of fluidic and control layers serve as valves that can be actuated by pressurizing control lines. A series array of valves can be used as a peristaltic pump. The polymer structure is sealed to an interdigitated thin-film microelectrode array on a glass slide for electrochemical detection of various analytes and simultaneous fluorescence imaging. On-chip pumps and valves allow the transport of fluid to the sampling volume and its isolation and flushing. The BioMEMS device can be used as a biosensor by incorporating living cells into the sampling volume. We present initial results from measurements of oxygen uptake and/or acidification rates of single cardiac myocytes in subnanoliter volumes with simultaneous recording of the transmembrane potential using fluorescent dyes. The technology can be easily extended for high-content drug screening devices or for measuring cellular response and dynamics with millisecond resolution.