Fluorescent single particle tracking enables high sensitivity viscometry measurements of micro-volume samples.

Abstract

Measuring the viscosities of high-value materials at the microscale with minimal waste is essential for increasing turnaround times during drug development in the pharmaceutical industry. Currently, viscometers on the market fail to meet these needs as they can only process a limited number of samples at a time and still require large (>100 μL) loading volumes for accurate readings. Previously, researchers have parameterized fluorescence correlation spectroscopy (FCS) at low volumes to predict antibody behaviors at higher concentrations using the generalized Stokes-Einstein equation. However, these methods lack the ability to produce measurements at a fast turnaround rate. Here, we use a wide field camera-based fluorescence microscope modality and particle tracking system in parallel with a Python PT software to measure the viscosities of multiple solutions using a 10-μL working volume. We applied the generalized Stokes-Einstein equation to the coefficient output of the PT Python software to obtain our final viscosity values. We obtained values of viscosity with an overall error of +-4cP, and the sample preparation method resulted in consistent readings for up to 5 hours after initial preparation. Viscosity readouts obtained using this method will allow for multi-sample imaging on a single chip using minuscule (10 μL) volumes, revolutionizing the efficiency of sample selection during drug development.