There is a current need for new analytical techniques to more fully characterize the biophysical properties of solutions of protein therapeutics. Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) is a nanomechanical, acoustic technique that allows in-situ analysis of protein viscosity, protein surface interactions and fibrillation of proteins at surfaces.

QCM-D functions by simultaneously tracking the changes in resonance frequency of an oscillating quart crystal (Df) and, by periodically short circuiting the driving voltage to the crystal, recording the decay of the damped oscillations or the energy dissipation (DD) of the system. QCM-D reveals both mass changes on the sensor surface, as measured by changes in frequency of the quartz crystal and provides novel insights regarding structural (viscoelastic) properties of the adsorbed material related to the dissipation parameter before, during and after the interaction or reaction.

Specifically, QCM-D has been used to measure the viscosity of high concentration protein solutions of Bovine Serum Albumin (BSA) as a model protein. QCM-D was able to accurately measure the viscosity of small volumes (~20 mL) of BSA at a wide range of concentrations that correlated well with established literature values. Along with viscosity measurements, QCM-D also simultaneously measures the amount of protein adsorbed onto the surface.

Additionally, QCM-D has been used to measure the spontaneous, surface induced, protein fibrillation of glucagon as a model system for both fibrillation induced protein folding diseases and for protein fibrillation prevalent in the long term storage of protein therapeutics.

In summary, QCM-D is an ideal analytical technique to study protein viscosity and spontaneous, surface induced protein fibrillation towards more thorough characterization of protein therapeutics.