The Microscale Life Sciences Center (MLSC) is a National Institutes of Health (NIH) National Human Genome Research Institute (NHGRI) Center of Excellence in Genomic Science (CEGS). The MLSC is one of the first of three CEGS ever funded by the NIH NHGRI in the nation. In September 2006, the MLSC was awarded a second five-year $18 million federal grant from the National Human Genome Research Institute of the National Institutes of Health. The MLSC comprises the combined research expertise of leading researchers in their respective fields from Arizona State University, University of Washington, the Fred Hutchinson Cancer Research Center, and Brandeis University.

Increasingly, it is becoming apparent that understanding, predicting, and diagnosing disease states is confounded by the inherent heterogeneity of in situ cell populations. The Microscale Life Sciences Center (MLSC) is focused on solving this problem, by developing microscale technology for genomic-level and multi-parameter single cell analysis, and applying that technology to fundamental problems of biology and health.

The MLSC is developing microscale instrument modules to measure multiple parameters in living cells in real time to correlate cellular events with genomic information (e.g. gene expression and genomic rearrangements). These modules comprise a low-cost, flexible, reconfigurable, benchtop toolbox with state-of-the-art detection and analysis features to enable scientists to pursue and solve scientific questions that require analysis of heterogeneous cell populations. The microsystem modules are used for real-time quantitative assessment of expression of different genes and the resulting phenotypes as a function of environmental (and cell-to-cell) interactions. The MLSC progress to date includes the development of microsystems with multiple sensors, environmental control, and cell manipulation capability. To ensure broad applicability, experiments have been performed with yeast, macrophages, T-cells, and bacteria. Current capabilities in live cells include measurement of substrate-dependent O2 consumption rates and measurement of expression from multiple genes using fluorescent reporters, while in fixed cells we are developing the ability to carry out qPCR and qRT-PCR on multiple genes simultaneously and to generate single cell proteomics profiles.

As we expand technology capabilities, we are focusing this technology on a set of interconnected problems involving in situ cellular heterogeneity that link genomics to phenotype to health. These interrelated challenges all have the common theme of pathways to cell damage and cell death and include pro-inflammatory cell death (pyroptosis), programmed cell death (apoptosis), and avoidance of cell death (neoplastic progression). The disease states represented by this suite of problems include cancer, heart disease, and stroke.