A novel imaging-based multi-sample viscometry application for advancing monoclonal antibody development.

Abstract

The increasing demand for monoclonal antibodies (mAbs) as therapeutic agents highlights the ever-growing necessity of optimizing sample-selection procedures; the rate-limiting step of therapy development. One such mAb property test is viscosity, which affects syringeability, concentration dose, and patient experience. Current viscometry methods, such as cone and plate rheometry, although accurate, are limited by low throughput, high sample volume requirements, and lack of automation, driving up the cost and time of mAb development. This paper introduces an innovative imaging-based viscometry application that significantly mitigates these issues. By integrating a wide-field camera with a fluorescence microscope and Python-based single particle tracking (SPT) software, this approach allows for rapid, low-volume (down to 2μl) viscosity measurements of mAb solutions. Using 200 nm yellow-green fluorescent polystyrene beads as tracers, the system ensures accurate macroviscosity assessments of protein solutions and the capability for high-throughput analysis. The platform's precision and sensitivity were validated using bovine serum albumin and viscosity standard solutions, followed by a single-blinded study using Immunoglobulin G1 and G2 (IgG1/IgG2) solutions of varying concentrations (⩽150 mg ml^-1) and viscosities (2-31 cP). When compared to the unblinded values, the SPT blinded sample analysis resulted in a linear fit ofR²= 0.97 and an average error of 2.1 cP. Our findings suggest that this novel platform can substantially streamline and enhance the mAb development process, offering a feasible solution to one of the industry's pressing challenges.