Single-cell droplet microfluidics for metagenomics and cancer multiomics

Author(s): Demaree, Benjamin Robert | Advisor(s): Abate, Adam | Abstract: Cellular heterogeneity is inherent to many biological systems, across both normal and disease states. For example, diverse ensembles of microbes in the natural environment fulfill distinct roles related to nutrient metabolism and gas fixation. In human cancers, genetic and phenotypic heterogeneity is observed among cells originating from a common oncogenic clone. Understanding biological heterogeneity, whether for metabolic engineering applications or the design of cancer therapeutics, begins at the fundamental unit of the organism: a single cell. Droplet microfluidics enables analyses of single cells at a biologically-relevant scale through rapid compartmentalization and manipulation of millions of parallel reactions. In this thesis, I describe the development and application of single-cell genomics platforms leveraging droplet microfluidics to interrogate many individual genomes. These technologies enable single-cell metagenomics and multiomic analysis of single cancer cells, providing new insights into the extent of cellular heterogeneity and its implications across biology.