(519f) Microrheology of Monoclonal and Bispecific Antibodies

A key challenge encountered in the current development of therapeutic protein solutions is the need to measure their viscosity to identify stable, syringeable formulations in a large composition space. Commercially available techniques such as capillary viscometry and rotational rheometers are frequently used, but require relatively large sample volumes. This sample size requirement restricts the number of rheological measurements in the early development stage when only small amounts of protein are typically available.

This talk will focus on characterizing the viscosity of protein therapeutics over a wide range of compositions with a minimal amount of material. Microrheology techniques are powerful methods to study scarce biomaterials [1]. We use multiple particle tracking (MPT) to provide a high throughput sample processing platform for protein therapeutics. This work examines the microviscosity of three IgG monoclonal antibodies and two bispecific monoclonal antibodies assembled from IgG half-antibodies over a large range of concentrations (1â??180 mg/mL). The protein solutions exhibit Newtonian fluid behavior over a frequency range of 0.05 to 30 s^-1, and do not show evidence of further microstructure development due to protein-protein association. An analysis of covariance demonstrates the high accuracy of small volume microrheology measurements. Based on the relative error between measured and tabulated viscosities, the uncertainty of viscosities derived from particle tracking is less than 2% of the true value.

[1] K.M. Schultz & E.M. Furst. Soft Matter 8, 6198-6205, 2012.