Droplet-Based Microfluidic Tool to Quantify Viscosity of Concentrating Protein Solutions

Purpose Measurement of the viscosity of concentrated protein solutions is vital for the manufacture and delivery of protein therapeutics. Conventional methods for viscosity measurements require large solution volumes, creating a severe limitation during the early stage of protein development. The goal of this work is to develop a robust technique that requires minimal sample. Methods In this work, a droplet-based microfluidic device is developed to quantify the viscosity of protein solutions while concentrating in micrometer-scale droplets. The technique requires only microliters of sample. The corresponding viscosity is characterized by multiple particle tracking microrheology (MPT). Results We show that the viscosities quantified in the microfluidic device are consistent with macroscopic results measured by a conventional rheometer for poly(ethylene) glycol (PEG) solutions. The technique was further applied to quantify viscosities of well-studied lysozyme and bovine serum albumin (BSA) solutions. Comparison to both macroscopic measurements and models (Krieger-Dougherty model) demonstrate the validity of the approach. Conclusion The droplet-based microfluidic device provides accurate quantitative values of viscosity over a range of concentrations for protein solutions with small sample volumes (similar to mu L) and high compositional resolution. This device will be extended to study the effect of different excipients and other additives on the viscosity of protein solutions.

Automated summary

This study developed a microfluidic device for quantifying the viscosity of concentrated protein solutions in micrometer-scale droplets, requiring minimal sample volume. The viscosity measurements obtained using this device were consistent with macroscopic results, demonstrating the validity of this novel approach.