Collaborative Proposal: Instrumental Development of Microfluidics-Based Fluorescence Activated Cell Sorting Device for Research and Education

Harvard University, Cambridge MA

Investigators

Abstract

This award is for the development of a microfluidic-based fluorescent-activated cell sorting device (M-FACS). The M-FACS will combine the single droplet control of microfluidics with the cell screening and sorting of a FACS. If successful, the M-FACS will allow one to encapsulate individual cells, add additional compounds to each cell, incubate these and then sort the results, all at 1000-10,000 cells per second, allowing good statistics to be obtained on a distribution of a population of cells. M-FACS will enable the study of chemicals excreted by cells or presented on their surface. It will likewise enable using individual cells in an assay that screens a large library. This would significantly increase the utility of FACS. One way to encapsulate individual cells within drops is through the use of microfluidic techniques. Individual cells can be suspended in drops in an inert carrier fluid. Moreover, it is also feasible to completely control these drops: they can be combined with other drops, they can be divided into smaller drops, they can be interrogated with optical probes, and they can be sorted with electric fields. This new technology will be supported with essential theoretical work to fully understand the new possibilities that will be available. The M-FACS overcomes one significant limitation of FACS: with FACS, the cells must be sorted as soon as they are encapsulated. The M-FACS will qualitatively change the applicability of FACS. It will allow using cells as part of an assay, testing them against a library of compounds, and sorting the cells based on the results. It will allow cell growth to be a criterion of the sorting. This will allow myriad new problems to be investigated. A desk-top Fluorescence-Activated Cell Sorting machine with greatly extended capabilities will be of great benefit to the broader scientific community. The machine will be developed by students and post docs, both experimental and theoretical. They will receive training in a field that merges engineering with biology to create novel devices that enable new science. The work will also be disseminated at a workshop that will describe the completed device.