(79e) High-Throughput Microrheology in a Microfluidic Device

Rheological characterization of hydrogels enables the design and engineering of these scaffolds for therapeutic applications, such as wound healing and tissue regeneration. Due to growing complexity of hydrogels in efforts to recapitulate the extracellular matrix, materials have become synthetically laborious and expensive.  Therefore, during the characterization of this material an ideal method would maximize the number of samples measured while minimizing the amount of material used and measurement acquisition time. To meet this end, we have developed a technique that combines sample preparation within a microfluidic device with multiple particle tracking (MPT) microrheological measurements, named µ²rheology. In µ²rheology, 50 – 100 droplets are created within a microfluidic device varying the composition of each droplet using linear pumping programs. MPT measurements are taken of stationary droplets sealed within the device. MPT is a passive microrheological technique that measures the Brownian motion of fluorescently labeled probe particle embedded within a material. The particle trajectories are directly related to rheological properties, such as creep compliance and viscosity, using the Generalized Stokes-Einstein Relation. MPT is chosen as the measurements technique due to the inherently small samples size required for accurate measurements (4-40 µL), short acquisition time and ability to determine sample homogeneity. In this work we validate µ²rheology by measuring droplets from a serial dilution of glycerine. Viscosity measurements from µ²rheology agree with both tabulated data and individually prepared MPT measurements. The utility of the technique is illustrated with measurements of the high molecular weight heparin (HMWH) overlap concentration and creation of a gelation state diagram of a HMWH-PEG hydrogelator, which identifies the composition where a gel will form. Both measurements illustrate the fine gradient in composition achieved by microfluidic sample preparation and precise rheological measurements using MPT. Overall, our methods can be used to thoroughly screen the material rheological properties, yielding a high information density, but requiring only small volumetric amounts.