ZnO nanostructure-modified QCM for dynamic monitoring of cell adhesion and proliferation

Noninvasive examination of live cell function in real-time is essential in advancing the understanding of the dynamic progression of cell's biological processes. We present a dynamic and noninvasive method of monitoring the adhesion and proliferation of bovine aortic endothelial cells (BAEC) using a ZnO nanostructure-modified quartz crystal microbalance (ZnOnano-QCM) biosensor. The ZnOnano-QCM biosensor consists of a conventional QCM with ZnO nanostructures directly grown on its sensing electrode deployed in-situ of a standard cell culture environment. Cell adhesion to the ZnO surfaces with various morphologies is studied and the optimal morphology is chosen for the BAEC adhesion. The ZnOnano-QCM biosensor displays enhanced sensitivity compared to the standard QCM sensor with ~10 times higher frequency shift and motional inductance, and ~4 times higher measured motional resistance at full confluency. The dynamic motional resistance and inductance relating to the cells' viscoelastic properties during growth are extracted from the measured time-evolving acoustic spectra. The Butterworth-Van-Dyck (BVD) model is adapted for the ZnOnano-QCM biosensor system and is used to correlate the measured time-evolving acoustic spectra with the motional characteristics of cell attachment and proliferation.