Droplet-based microfluidic platform for viscosity measurement over extended concentration range

Rheology of concentrated protein solutions is crucial for the understanding of macromolecular crowding dynamics as well as the formulation of protein therapeutics. The cost and scarcity of most protein samples prevents wide-scale rheological studies as conventional viscosity measurement methods require large sample volume. There is a growing need for a precise and robust viscosity measurement tool that minimizes consumption and simplifies the handling of highly concentrated protein solutions. This objective is achieved by combining microfluidics and microrheology: we developed a specific microsystem to study the viscosity of aqueous solutions at high concentrations. The PDMS chip allows in situ production, storing and monitoring of water-in-oil nanoliter droplets. We perform precise viscosity measurements inside individual droplets by particle-tracking microrheology of fluorescent probes. Pervaporation of water through a PDMS membrane induces aqueous droplet shrinking, concentrating the sample up to 150 times, thus allowing viscosity measurements along an extended concentration range in just one experiment. The methodology is precisely validated by studying the viscosity of sucrose solutions. Two model proteins are also studied with sample consumption reduced to as little as 1 mu L of diluted solution, showcasing the viability of our approach for the study of biopharmaceuticals.

Automated summary

The rheology of concentrated protein solutions is crucial for understanding macromolecular crowding dynamics and protein therapeutics formulation. However, conventional viscosity measurement methods are limited by cost and scarcity of protein samples. To address this issue, we developed a microsystem combining microfluidics and microrheology that allows for precise and robust viscosity measurements of high-concentration aqueous solutions. Our methodology, validated by studying sucrose solutions, enables viscosity measurements along an extended concentration range in just one experiment. This approach showcases its viability for the study of biopharmaceuticals with minimal sample consumption.