Individual, living cells are complex, analog signal processors. That is, they use biochemical processes to transform some number of inputs, such as ligands for receptors, to produce some output (move, regulate certain genes, activate pathways for extracellular secretions). Both the unique, accumulated history of stimuli experienced by the cell and stochastic molecular events strongly influence these outcomes. Each cell is, therefore, distinct, and collections of cells are not uniform populations, but rather complex ensembles comprising many individuals. Modern biology has made remarkable progress in understanding the mechanisms by which cells operate (and cooperate in multicellular organisms), but many of these insights result from studying the average states and functions of cells. There is an increasing realization, however, that characterizing the heterogeneities of cells is important for describing the time-dependent responses of complete biological systems—for example, the coordinated cellular immune responses to infectious agents.
New technologies capable of measuring multiple characteristics of single cells in a quantitative manner over time, and in large numbers (10,000 to 1,000,000), would accelerate the understanding of the macroscopic responses of multicellular biological systems as well as the collective properties of clonal populations (bacterial colonies, mammalian cell lines). Broadly, our research combines ideas from materials science and interfacial chemistry to enable new micro- and nanotechnologies for studying the biology of complex collections of cells in a quantitative manner. We focus on developing methods to determine multiple qualities that define the identity, function, and genetic content of individual cells. Using these tools, we aim to construct detailed profiles that describe the state and evolution of a multicellular population. Such profiles will make it possible 1) to understand the precise cellular signatures that characterize an immune response to one disease state or another, 2) to examine the biological variations that can arise in clonal populations of cells used for bioprocess manufacturing, and 3) to identify extremely rare cells within large libraries of variants (e.g, ones producing unique engineered enzymes or antibodies).
Three current areas of research in the lab are: