Characterisation of particle-surface interactions via anharmonic acoustic transduction

Most transduction methods for measuring particle-surface interactions are unable to differentiate the strength of interaction and thus rely largely on extensive washing to reduce ubiquitous non-specific background. Label-based methods, in particular, are limited in wide applicability due to their inherent operational complexity. On the other hand, label-free force-spectroscopic methods that can differentiate particle-surface interaction strength are skill-demanding and time-consuming. Here, we present a label-free anharmonic (nonlinear) acoustic transduction method employing the quartz crystal resonator that reads out ligand-receptor binding based on the interaction strength. We show that while stronger specific interactions are transduced more strongly, and in linear proportionality to the ligand concentration on microparticles, non-specific interactions are significantly attenuated. This allows ligand quantification with high specificity and sensitivity in realtime under flow without separate washing steps. Constructing an analytical model of a quartz resonator, we can relate the number and type (specific vs. non-specific) of ligand-receptor interactions with the change in characteristic nonlinearity coefficient of the resonator. The entirely-electronic and microfluidic-integrable transduction method could potentially allow a simple, fast and reliable approach for characterising particle-surface interactions with economy of scale.