Particle tracking microrheology of protein solutions

Abstract

Video-based particle tracking microrheology that requires ∼2 μl per sample is used to measure the viscosity of protein solutions of monoclonal antibodies. Direct imaging provides an immediate assessment of probe stability and the validity of the microrheology measurement. Precise measurements are made by choosing a displacement lag time that is a balance between minimizing tracking error while maximizing the number of sampled particle displacements. The excess kurtosis α2 of the probe displacement probability distribution and its test statistic Zα2 are used to set the optimal lag time. The viscosity is calculated by fitting a Gaussian distribution to the sampled displacements. Microrheology viscosities for two monoclonal antibody solutions are in good agreement with bulk rheology. Using a similar comparison of the microrheology of sucrose solutions with a correlation relating viscosity and concentration, an analysis of covariance (p = 0.941) 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.