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Small scale rheology for screening scarce materials

Eric Furst (University of Delaware)

Rheological measurements that characterize the flow properties of a substance can be difficult to perform for many emerging materials, especially when a material is demanding to synthesize or prohibitively expensive. Fortunately, microrheology methods can be used when a material's availability is limited, since it requires small sample volumes, ranging on the order of 1nL-10μL. In addition, microrheology has several complementary features that make it indispensable for characterizing scarce materials, specifically those developed for therapeutic applications. These factors include measurement acquisition times on the order of seconds, a large dynamic frequency response, and exquisite sensitivity to incipient properties.

Microrheology uses the motion dispersed micrometer-diameter probe particles to measure the surrounding material's rheology. The technique can be divided into two approaches that are distinguished by the driving force of the probe motion. In the first, active microrheology, the embedded probe particles move in response to an external force, typically generated by optical tweezers or magnetic fields. In the second, passive microrheology, the Brownian or thermal motion of the embedded probe particles is measured and the rheological properties are calculated by the Generalized Stokes-Einstein Relation (GSER). The introduction of passive microrheology has stimulated many of the advances in biomaterial microrheology over the past two decades.

In this talk, I will describe recent work on high-throughput viscometry and rheology using a combination of microrheology and microfluidics. A series of microrheology samples is generated as droplets in an immiscible spacer fluid using a microfluidic T-junction. The compositions of the sample droplets are continuously varied over a wide range. Viscosity measurements are made in each droplet using multiple particle tracking microrheology. I will review the key design and operating parameters, including the droplet size, flow rates, rapid fabrication methods and passive microrheology techniques. The combination of microrheology with microfluidics maximizes the number of viscosity measurements while simultaneously minimizing the sample preparation time and amount of material, and should be particularly suited to the characterization of protein solution viscosities of therapeutic agents. I will conclude with an outlook of future work, including the microrheology of monoclonal antibody (mAb) solutions.

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