Acoustic resonators with integrated microfluidic channels for ultra-high Q-factor: a new paradigm for in-liquid gravimetric detection

Biosensing is a critical area of research that involves detecting and measuring biological molecules. Among the various types of biosensors, acoustic biosensors are attractive for their simplicity, robustness, and low cost, particularly in point-of-care (POC) applications. However, the quality factor (Q-factor) of acoustic biosensors is often low, limiting their sensitivity and accuracy in terms of in-liquid gravimetric detection for biosensing applications. In this dissertation, we present a novel approach that eliminates nearly all dissipation and damping from sample liquids, rendering a significant improvement in Q-factor for in-liquid gravimetric detection. We constructed rigid microfluidic channels to confine liquids and the associated acoustic energy, thereby eliminating acoustic radiation damping. We also used the channels' side walls to create pressure waves, confining the liquids within and suppressing acoustic damping due to the viscous layer. The quartz crystal microbalance (QCM) was selected as the model system for implementing the new paradigm due to its widespread usage in various applications, simplicity, cost-effectiveness, and relevance of its principles to other types of acoustic biosensors. We hypothesized that the ratio of the wavelength of the pressure wave to the width of the channels is a crucial determining factor for optimal performance. We then tested the hypothesis by building the microfluidic QCM (the µ-QCM) to improve the Q-factor of conventional QCM. The combination of experiments, simulations, and theoretical studies demonstrated a 10-fold improvement in the Q-factor. The new system offers many other advantages, including direct data interpretation, minimized sample volume requirement, and easier temperature control for in-liquid gravimetric detection. Additionally, the same principles can be applied to other acoustic biosensors, benefiting the entire field.