Multi-modal biochip for simultaneous, real-time measurement of adhesion and electrical activity of neurons in culture

Recent evidence suggests that integrin-mediated adhesion of neurons has immediate functional implications for learning and memory. In addition, adhesion of neurons to artificial substrates often determines the effectiveness and life of implants in the brain and peripheral nervous system. In this study, we present a novel biochip capable of simultaneous, quantitative, real-time monitoring of integrin-mediated adhesion and electrophysiology of primary neurons in vitro. The proposed technology combines acoustic micro-resonators capable of tracking changes in mechanics of the adhering neuronal layer, and microelectrode arrays for recording extracellular unit activity. Our results showed in four different experimental paradigms that the acoustic sensor response to adhering cells is correlated to integrin-mediated adhesion and that the micro-sensor is capable of monitoring the dynamics of neuronal adhesion over a period of 9 days. Finally, using our unique dual measurement platform, we performed simultaneous, real-time measurement of integrin-mediated adhesion and single cell electrophysiology in a neuronal culture. The sensitivities of the micro-resonators were 4-5 orders of magnitude greater than the sensitivity of the macro-scale resonators in response to adhering neurons. This multi-functional sensor platform offers insight into the interplay between integrin-mediated adhesion and neural function on a temporal resolution beyond any currently available experimental method and can therefore potentially lead to novel discoveries on the interactions between neuronal adhesion and function.