Development of a Plasmonic On-Chip System to Characterize Changes from External Perturbations in Cardiomyocytes

Today’s heart-on-a-chip devices are hoped to be the state-of-the-art cell and tissue characterizing tool, in clinically applicable regenerative medicine and cardiac tissue engineering. Due to the coupled electromechanical activity of cardiomyocytes (CM), a comprehensive heart-on-a-chip device as a cell characterizing tool must encompass the capability to quantify cellular contractility, conductivity, excitability, and rhythmicity. This dissertation focuses on developing a successful and statistically relevant surface plasmon resonance (SPR) biosensor for simultaneous recording of neonatal rat cardiomyocytes’ electrophysiological profile and mechanical motion under normal and perturbed conditions. The surface plasmon resonance technique can quantify (1) molecular binding onto a metal film, (2) bulk refractive index changes of the medium near (nm) the metal film, and (3) dielectric property changes of the metal film. We used thin gold metal films (also called chips) as our plasmonic sensor and obtained a periodic signal from spontaneously contracting CMs on the chip. Furthermore, we took advantage of a microfluidic module for controlled drug delivery to CMs on-chip, inhibiting and promoting their signaling pathways under dynamic flow. We identified that ionic channel activity of each contraction period of a live CM syncytium on a gold metal sensor would account for the non-specific ion adsorption onto the metal surface in a periodic manner. Moreover, the contraction of cardiomyocytes following their ion channel activity displaces the medium, changing its bulk refractive index near the metal surface. Hence, the real-time electromechanical activity of CMs using SPR sensors may be extracted as a time series we call the Plasmonic Cardio-Eukaryography Signal (P-CeG). The P-CeG signal render opportunities, where state-of-the-art heart-on-a-chip device complexities may subside to a simpler, faster and cheaper platform for label-free, non-invasive, and high throughput cellular characterization