Thursday, May 2, 2013
Spalding Laboratory 106 (Hartley Memorial Seminar Room)
Chemical Engineering Seminar
Engineering single-cell bioanalytic processes to evaluate complex cellular systems
J. Christopher Love, Latham Family Career Development Professor, Chemical Engineering, Massachusetts Institute of Technology
The majority of analytical technologies used to assess the identities and functional capacities of cells yield average measures of their phenotypes. These measures obscure unique individuals that contribute significantly to the collective behavior or that may be of particular interest in discovery-based research. This talk will introduce an integrated approach for single-cell analysis based on the defined modular unit operations that allow biological measurements across multiple scales and time. The bioanalytic operations rely on the use of microfabricated arrays of subnanoliter containers (10^5-10^6) to isolate individual or small numbers of cells within a population. Two specific applications of these technologies for massively parallel single-cell analyses will be presented. First, an integrated analysis of individual cells within a clonal population of Pichia pastoris -- a yeast used for production of heterologous proteins in biomanufacturing -- reveals new insights to the dynamics of secretion by individual clones and how non-genetic variations alter the uniformity of the population. The implications of these factors on the challenges of strain engineering for biomanufacturing will be discussed. Second, the talk will outline how similar approaches to assessing lineages and functions can start to improve the resolution of clinical monitoring in human diseases, particularly for chronic human diseases such as HIV/AIDS. The approaches described provide a new basis for advanced clinical monitoring of cellular responses to candidate vaccines and highly quantitative diagnostics.