A microliter capillary rheometer for characterization of protein solutions.

Rheometry is an important characterization tool for therapeutic protein solutions because it determines syringeability and relates indirectly to solution stability and thermodynamic interactions. Despite the maturity of rheometry, there remains a need for a rheometer that meets the following three needs of the biopharamaceutical industry: small volume; large dynamic range of shear rates; and no air-sample interface. Here, we report the development of a miniaturized capillary rheometer that meets these needs and is potentially scalable to a multiwell format. These measurements consume only a few microliters of sample and have an uncertainty of a few percent. We demonstrate its performance on monoclonal antibody solutions at different concentrations and temperatures. The instrument has a dynamic range of approximately three decades (in shear rate) and can measure Newtonian, shear thinning, and yielding behaviors, which are representative of the different solution behaviors typically encountered. We compare our microliter capillary rheometer with existing instruments to describe the range of parameter space covered by our device.