Microfluidic rheometer for characterization of protein unfolding and aggregation in microflows.

Effective and accurate methods for characterizing rheological changes of proteins by alteration of their level, composition, or conformation are of significant clinical and biotechnological utility. Current implementations to measure rheological properties of a fluid, however, require mechanically moving components or off-chip measurement setups, thereby preventing incorporation of them into microenvironments. Thus, it is challenging for the development of a simple and effective means for rheological measurement in microenvironments. We demonstrate a new class of rheometer that balances between a sample and reference fluid with a common pressure drop, thereby enabling simple and accurate measurement of fluid viscosity, and eliminating the use of standard pressure gauges and complicate theoretical calculations. We also demonstrate the robustness of the rheometer for practical applications by measuring minute changes in a rheological property of bovine serum albumin (BSA) by chemical and thermal denaturation. Blood-plasma viscosity is determined by various macromolecules such as fibrinogen, immunoglobulin, lipoproteins, and albumin that serve many important functions in blood flow including supply of insoluble fibrin clot, identification of foreign objects, and transport of molecules with low water solubility. This important rheological parameter can be influenced by diseases and metal ions with alteration of protein level, composition, and conformation. The elevated viscosity significantly increases the risk of inflammatory disease, coronary heart disease, and stroke, and can result in rheologically impaired microcirculation, accompanied by redblood-cell aggregation, platelet thrombogenesis, and vascular dysfunction. Therefore, effective and accurate methods for characterizing rheological changes of fluids containing molecules by alteration of their level, composition, or conformation are of significant clinical and biotechnological utility, and