Simultaneous Protein Adsorption and Viscosity Measurement using Micropillar-Enhanced Acoustic Wave (μPAW) Device for Pharmaceutical Applications

Abstract

At the early stages of drug development, the amount of drug materials is rather limited. In this case, viscosity measurement is often postponed to the later stages, where grams of proteins can be produced. Therefore, it is necessary to develop a viscometer capable of measuring the viscosity with high accuracy while requiring low sample volume. This study presents a novel viscosity measurement technique based on measuring the resonance frequency and motional resistance of a micropillar-enhanced acoustic wave (μPAW) device. The μPAW was developed by fabricating micropillars on the quartz crystal microbalance substrate in order to achieve ultra-high sensitivity, thanks to a unique coupling between the micropillar and the resonator. The experimental measurements demonstrated a nonlinear relationship between the density and viscosity of the fluid and the response of μPAW. A calibration correlation was developed using the response of μPAW in aqueous glycerol and sucrose solutions. The measurements were then extended using high-concentration BSA solutions as the model of protein solution. The main advantage of the μPAW device in this work over other viscometers is the ability to simultaneously measure solution viscosity and protein adsorption on the surface. This is a huge step forward in the development of sensing systems for the pharmaceutical industry, where real-time sensing of target biological proteins and measuring the viscosity of a solution is required.