When the quartz crystal microbalance (QCM) is operated in contact with solution and used to detect inertia increases caused by macromolecules binding to its surface, resonance frequency shifts are reported in the literature to be greater than, less than, and the same as an identical macromolecular mass would cause as a dry layer. A previous report of wet and dry M13 DNA giving the same, linear frequency versus mass response is examined. The M13 data are shown to follow the reciprocal of the square root of mass, not the reported linear relationship. New experiments on RNA duplexes oscillated in solution are reported. A lossy polymer layer is placed between the QCM and RNA. When changes in density, viscosity, and included water are eliminated, the response remains linear for a constant adlayer thickness. The expectation that response per unit mass should decrease with distance from the QCM surface is demonstrated. Total decoupling of mass lying beyond the acoustic overlayer is also demonstrated. The present results are placed in context with recently published results from a study of progressively thicker protein layers bound to the QCM.

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