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 (~ μL) 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. Graphical abstract: [Figure not available: see fulltext.]