Electrochemical biosensor system using a CMOS microelectrode array provides high spatially and temporally resolved images.

The ability to view biological events in real time has contributed significantly to research in the life sciences. While video capture of real time changes in anatomical relationships is important, it is equally important to visualize real time changes in the chemical communications that drive cell behaviors. This paper describes an electrochemical imaging system capable of capturing changes in chemical gradients in live tissue slices. The system consists of a CMOS microchip with 8192 configurable Pt surface electrodes, on-chip potentiostat, on-chip control logic, and a microfluidic device designed to interface with the CMOS chip to support ex vivo tissue experimentation. All data processing and visualization methods, sensor calibrations, microfluidics fabrication, and tissue preparation and handling procedures are described. Using norepinephrine as a target analyte for proof of concept, the system is capable of differentiating concentrations of norepinephrine as low as 8 µM and up to 1024 µM with a linear response and a spatial resolution of 25.5 µm × 30.4 µm. Electrochemical imaging was tested using murine adrenal tissue as a biological model and successfully showed caffeine-stimulated release of catecholamines from live slices of adrenal tissue with temporal sensitivity. This system successfully demonstrates the use of a high-density microelectrode array for electrochemical analysis with high spatiotemporal resolution to gather chemical gradient information in parallel with optical microscopy recordings.