IMR: Development of The Multiscope: An Array Microscope for High Throughput Microliter Rheology

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Technical Abstract: The mechanical properties of biomaterials are important in many areas of biomedical engineering and biology. For mechanical response, important examples include the rheological properties of polymeric solutions, biofluids and engineered tissue scaffolds. Although it is increasingly clear that the mechanical properties of tissue scaffolds affect gene expression and cell differentiation, rheological measurements are so tedious that they are the primary bottleneck in testing a library of small molecules or monomers. The recent development of high throughput screening (HTS) technologies and the development of small molecule, monomer and protein libraries are revolutionizing polymer science and pharmaceutical research. Similarly, revolutions in combinatorial materials science have changed the way in which new materials with tuned properties are discovered.Unfortunately, there is a striking lack of technologies available for mechanical measurements within a HTS or combinatorial setting. We will develop a rheology high throughput screening technology that will use microbead techniques, both as passive diffusive tracers and as magnetic bead probes driven by applied magnetic fields. We target the rheological characterization of microliter specimens at a rate of 100 per hour in a traditional multiwell plate geometry. This combination will permit the study of the time course of rheology in polymerizing samples, in engineered tissue scaffolds and biofluids.Public Abstract: The mechanical properties of materials are of great interest in developing new technologies. Two examples include new polymers for flexible electronics that may enable "smart" clothing, and opportunities for replaceable tissues where the stiffness of the gel determines whether new cells will grow and thrive. The way that science discovers new materials has undergone a radical change in the past decade. Instead of mixing up one chemical batch at a time, we have developed "libraries" of chemicals, large collections of molecules that can be pulled from the shelf to create new mixtures. These collections can contain hundreds of thousands of different molecules. This means that we need new ways to rapidly try each new combination to see if it will work. The technology that will be developed under this grant uses small beads that are pulled through the material to measure if the material is thick like honey, or flows like water.Further, it will determine if the material is "springy" and can vibrate in a manner similar to jello. The project expects that the new system will speed up materials discovery by about 100, and allow us to make full use of the broad range of molecular combinations available to researchers.