We demonstrate real-time experimental evidence for mass underestimation, to analyse high molecular weight biomolecules while using Quartz Crystal Microbalance (QCM) platform. For this, we present an experimental evidence with an assay consisting of an aptamer-antibody sandwich model with norovirus-like particles (NoVLPs). We combine this with the proximity ligation assay to generate bulky rolling circle products on a gold spot centralized quartz resonator surface. Real-time monitoring of the assay build-up reflects that bulky NoVLPs and amplified oligonucleotides generate fluctuating signals during measurement using a microfluidic QCM sensor. Such an understanding of mass underestimation for heavier molecules becomes indispensable to get deeper insights into molecular interactions in biotechnology studied using QCM devices.
