When the quartz crystal microbalance (QCM) is operated in contact with
solution and used to detect inertia increases caused by macromolecule
s binding to its surface, resonance frequency shifts are reported in t
he literature to be greater than, less than, and the same as an identi
cal macromolecular mass would cause as a dry layer. A previous report
of wet and dry M13 DNA giving the same, linear frequency versus mass r
esponse is examined. The M13 data are shown to follow the reciprocal o
f the square root of mass, not the reported linear relationship. New e
xperiments on RNA duplexes oscillated in solution are reported. A loss
y polymer layer is placed between the QCM and RNA. When changes in den
sity, viscosity, and included water are eliminated, the response remai
ns linear for a constant adlayer thickness. The expectation that respo
nse per unit mass should decrease with distance from the QCM surface i
s demonstrated, Total decoupling of mass lying beyond the acoustic ove
rlayer 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.