Missing mass effect in biosensor's QCM applications.
Nowadays, liquid applications of quartz crystal microbalance (QCM) opened a way for in situ studies of proteins, vesicles and cells adsorbed from the solution onto the QCM surface. The sensitivity of QCM to the viscoelasticity of the adsorbed biomaterial can be a reason of the experimentally observed deviation from a linear dependence of QCM resonant frequency on mass deposition (the so-called Sauerbrey relation) and can limit its application for biosensoring. Presented here rigorous theoretical analysis explains the deviation from ideal mass response of soft overlayers in the contact with liquid. The fundamental result of the theory is the analog of Sauerbrey relation for layered viscous/viscoelastic medium which can be exploited for the correct physical interpretation of QCM experimental data in biofluids, in particular for measurements of the 'true' surface mass of adsorbed biomolecular films. We predict a new physical effect 'missing mass' of the sample in liquid phase measurements and compare the results given by our theory with QCM measurements on supported membranes.