549c High-Throughput and High-Content Screening of Antibody Responses from Single Cells

J. Christopher Love1, Adebola Ogunniyi1, Eliseo Papa2, Eduardo Guillen3, Jae H. Choi3, and Craig M. Story4. (1) Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Bldg. 66-456, Cambridge, MA 02139, (2) Health Sciences & Technology, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, (3) Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02139, (4) Biology, Gordon College, 255 Grapevine Rd., Wenham, MA 01984

The development of new vaccines is limited in part by the challenges of profiling the diversity in antibody responses generated to infectious diseases or candidate vaccines to diseases. This talk will describe a soft lithographic technology that uses an array of subnanoliter containers to isolate large numbers of individual antibody-secreting cells and print protein microarrays of the corresponding antibodies from each cell. The microarrays can be interrogated to characterize the specificity, isotype, and affinity of each clone. It is also possible to identify antibodies reacting to particular epitopes such as phosphorylated tyrosines. The cells of interest identified in the screens can be retrieved for expansion or genetic sequencing.