High-Throughput BioMEMS

描述（由申请人提供）：我们将开发用于高通量、高含量、基于细胞的筛选的方法和平行流仪器，用于小稀有细胞组分的表型分析和操作，以及用于来自1-100个流动细胞的多重表达分析。我们将为蛋白质错误折叠疾病，特别是神经退行性疾病，如帕金森氏症（模式生物：酵母）的机制和小分子研究的组合缩放提供手段。以及用于（罕见）原代造血干细胞（小鼠）的高含量细胞计数研究。 公共卫生相关性：该计划将为基于细胞的高通量、高内容筛选（HCS）开发新的仪器和方法。该计划解决了严重限制HCS的瓶颈：（i）扩大到药物发现，（ii）处理高度异质的原代细胞类型的小样本;（iii）寻找稀有细胞（例如寻找用于癌症诊断的多能细胞）和（iv）基于图像的分选/富集。

DESCRIPTION (provided by applicant): We will develop methods and parallel flow instrumentation for high-throughput, high- content, cell-based screening, for phenotyping and manipulation of small rare-cell fractions, and for multiplexed expression analysis from 1-100 cells in flow. We will provide means for combinatorial scaling of mechanistic and small-molecule studies of protein misfolding disease, particularly neurodegenerative diseases such as Parkinson's (model organism: yeast). And for high-content cytometry studies with (rare) primary hematopoietic stem cells (mouse). PUBLIC HEALTH RELEVANCE: This program would develop new instrumentation and methods for cell-based high- throughput, high-content screening (HCS). The program addresses bottlenecks that severely limit HCS for (i) scale-up to drug discovery, (ii) for handling of small samples of highly heterogeneous primary cell types; (iii) for finding rare cells (e.g. finding pluripotent cells for cancer diagnostics) and, (iv) image-based sorting/enrichment.