CAREER: Label-Free Cell Sorting Based on Single-Cell Metabolism

Santa Clara University, Santa Clara CA

Investigators

Abstract

The project will develop technology to selectively isolate cancer cells. This will allow characterization at the single cell level to enable effective, targeted cancer therapies. Laboratory modules that incorporate relevant technologies will be designed to provide inspirational, discovery-based experiences that have been shown to be critical for both directing and retaining students in science and engineering fields. This work will be performed at a primarily undergraduate institution, where exposure of undergraduates to authentic research experiences will engage a diverse cross-section of students. Experimental kits and teaching material will be developed and offered through established programs and networks to hundreds of students per year at local socioeconomically disadvantaged middle school and high schools. Wide dissemination of these modules via source material, website, and videos will encourage the development of a capable biotechnology workforce. High glucose metabolism is one hallmark of cancer. Cancer cells are programmed to convert glucose to lactate. High levels of lactate in tumors are associated with metastasis, recurrence, and poor outcomes. Cells that exhibit high lactate secretion rates are therefore specific targets for therapy. The study of these important and rare cells requires efficient tools for their isolation. A novel label-free microfluidic platform will be used for the fast and inexpensive isolation of single cells based on cellular metabolism. Single-cell whole transcriptome analysis will connect gene expression to cell phenotype in a quantitative fashion. It will reveal the cell-to-cell heterogeneity in gene expression and clarify the determinants of highly malignant cancer cells. As glycolysis is a clear indicator of cell vitality, the platform will also be used to quickly and easily separate live and dead cells for applications in pharmacology and toxicology. Ultimately, the technology developed in this proposal can be applied to isolate cells or subpopulations based on cellular metabolism for a broad range of applications in cell biology, bioenergy, biotechnology and medicine. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.