Profiling Cellular Populations At the Single Cell Level With Drop-Based Microfluidics

Populations of cells have substantial heterogeneity that is important for their function and understanding. This variability is reflected in cell to cell variations of genetic and epigenetic features that are quickly averaged when characterized without single-cell resolution. We developed a method for single-cell profiling that combines drop-based microfluidics with genomics and DNA barcoding. The method is based on encapsulating individual cells in micron-size droplets, lysing the cells inside the droplets, and labeling the cellular content with molecular barcodes unique to each droplet. When sequenced, each barcode is used to group DNA fragments that originate in the same cell, yielding multiple density maps for individual cells. The platform is compatible with both DNA and RNA, uses ligation or hybridization to attach the barcodes and can be scaled up to a large number of cells ultimately limited only by the capacity and cost of Next-Gen sequencing.