On-chip magnetic separation and encapsulation of cells in droplets.

ABSTRACT

Single cell study is gaining importance because of the cell-to-cell variation that exists within cell population, even after significant initial sorting. Analysis of such variation at the gene expression level could impact single cell functional genomics, cancer, stem-cell research, and drug screening. The on-chip monitoring of individual cells in an isolated environment would prevent cross-contamination, provide high recovery yield, and enable study of biological traits at a single cell level. These advantages of on-chip biological experiments is a significant improvement for a myriad of cell analyses methods, compared to conventional methods, which require bulk samples and provide only averaged information on cell structure and function. We report on a device that integrates a mobile magnetic trap array with microfluidic technology to provide the possibility of separation of immunomagnetically labeled cells and their encapsulation with reagents into picoliter droplets for single cell analysis. The simultaneous reagent delivery and compartmentalization of the cells immediately following sorting are all performed seamlessly within the same chip. These steps offer unique advantages such as the ability to capture cell traits as originated from its native environment, reduced chance of contamination, minimal use of the reagents, and tunable encapsulation characteristics independent of the input flow. Preliminary assay on cell viability demonstrates the potential for the device to be integrated with other up- or downstream on-chip modules to become a powerful single-cell analysis tool.