CELL CLINICS FOR BLOELECTRONIC INTERFACE WITH SINGLE CELLS

We describe integrated microstructures and instrumentation for capture and characterization of large numbers of individual cells. Each of these “cell clinics” consists of a cell-sized cavity and a lid that can be opened and closed by hinges constructed from polypyrrole microactuators linking rigid plates to the substrate. These clinics are fabricated on integrated circuit substrates to bring sensors, actuation, computation, and control together at the scale of a single cell. Sensing modalities are tailored for specific applications; we have designed and begun to fabricate and test prototypes of cell clinics for impedance measurements, extracellular recording and stimulation of electrically active cells, and optical measurements. The first generation of cell clinics is constructed on a silicon substrate with electrodes incorporated into the bottom of the vials. Dissociated adult Xenopus laevis brainstem neurons have been cultured to test these single cell biosensors. Custom integrated complementary metal oxide semiconductor (CMOS) electronics including amplifiers, filters, and optical detection circuitry will be incorporated as the substrate for the next generation of cell clinics. Large arrays of cell clinics can be produced at high volume and low cost using simple low-temperature post-processing steps on commercially fabricated integrated circuits. The potential applications are numerous, spanning a spectrum from detailed physiological studies of specific mechanisms to whole cell studies of ecology or developmental biology to collecting concentrated cell secretions to statistical studies of assayed cell properties. 1