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).
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.
|Cheung, Man C; Evans, James G; McKenna, Brian et al. (2011) Deep ultraviolet mapping of intracellular protein and nucleic acid in femtograms per pixel. Cytometry A 79:920-32|
|McKenna, Brian K; Evans, James G; Cheung, Man Ching et al. (2011) A parallel microfluidic flow cytometer for high-content screening. Nat Methods 8:401-3|
|Ueberfeld, Joern; Ehrlich, Daniel J (2009) Scaling of nucleic acid assays on microelectrophoresis array devices: high-dynamic range multi-gene readout from less than ten transcripts. Electrophoresis 30:2090-9|