A Simple, Robust Method for Cellular Electrical Interfacing Using Molecular Patterning

We present a simple and robust strategy for improving the signal levels of microelectrode array (MEA) recordings from cultures of electrically excitable cells through the engineering of the dielectric surface surrounding the electrodes. A patterned two-component self-assembled monolayer (SAM)-cell membrane interface introduced onto this dielectric surface improves the seal impedance between the cell and MEA, increasing the amplitude of the recorded signals to more closely approach intracellular potentials. Application of this technique to cardiomyocytes derived from human induced pluripotent stem cells (iPSC) results in an almost 3-fold improvement in intracellular-like recording yield compared to traditional Matrigel coatings and a 3-fold increase in signal amplitude compared to a single-component SAM. This technique is simple to translate to most commercial and custom MEAs, including high-density complementary metal-oxide-semiconductor (CMOS) MEAs, and can be easily combined with nanowires, micromushrooms, and optimized electroporation sequences for further signal-level enhancements.