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

技术摘要：生物材料的力学性能在生物医学工程和生物学的许多领域都具有重要意义。对于机械响应，重要的例子包括聚合物溶液、生物流体和工程组织支架的流变性。尽管人们越来越清楚组织支架的机械性能影响基因表达和细胞分化，但流变学测量是如此繁琐，以至于它们是测试小分子或单体文库的主要瓶颈。最近高通量筛选(HTS)技术的发展以及小分子、单体和蛋白质文库的发展正在给聚合物科学和制药研究带来革命性的变化。同样，组合材料科学的革命已经改变了发现具有可调性能的新材料的方式。不幸的是，在高温超导或组合环境中，可用于机械测量的技术严重不足。我们将开发一种流变学高通量筛选技术，该技术将使用微珠技术，既作为被动扩散示踪剂，也作为外加磁场驱动的磁珠探头。我们的目标是在传统的多孔板几何结构中，以每小时100的速度对微升样品进行流变学表征。这一结合将使在聚合样品、工程组织支架和生物流体中的流变学的时间进程的研究成为可能。两个例子包括用于柔性电子产品的新型聚合物，这可能使服装变得智能，以及用于可替代组织的机会，其中凝胶的硬度决定了新细胞是否会生长和茁壮成长。在过去的十年里，科学发现新材料的方式发生了根本性的变化。我们没有一次混淆一批化学物质，而是开发了化学物质的“图书馆”，即可以从货架上取出的大量分子集合，以创造新的混合物。这些收集可能包含数十万种不同的分子。这意味着我们需要新的方法来快速尝试每一种新的组合，看看它是否有效。根据这项拨款将开发的技术使用穿过材料的小珠子来测量材料是否像蜂蜜一样稠密，或者像水一样流动。此外，它还将确定材料是否具有弹性，是否可以以类似果冻的方式振动。该项目预计，新系统将使材料发现速度加快约100%，并使我们能够充分利用研究人员可用的广泛分子组合。

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.