Nature Biotechnology 24, 703 - 707 (2006)
Published online: 14 May 2006; | doi:10.1038/nbt1210
A microengraving method for rapid selection of single cells producing antigen-specific antibodiesJ Christopher Love1, 2, 3, Jehnna L Ronan1, 2, Gijsbert M Grotenbreg1, 2, Annemarthe G van der Veen1, 2
& Hidde L Ploegh1, 21
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA. 2
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. 3
CBR Institute for Biomedical Research, 200 Longwood Ave., Boston, Massachusetts 02115, USA.
Correspondence should be addressed to J Christopher Love love@cbrinstitute.org or Hidde L Ploegh ploegh@wi.mit.edu Monoclonal antibodies that recognize specific antigens of interest are used as therapeutic agents and as tools for biomedical research1. Discovering a single monoclonal antibody requires retrieval of an individual hybridoma from polyclonal mixtures of cells producing antibodies with a variety of specificities. The time required to isolate hybridomas by a limiting serial-dilution, however, has restricted the diversity and breadth of available antibodies. Here we present a soft lithographic method based on intaglio printing to generate microarrays comprising the secreted products of single cells. These engraved arrays enable a rapid (<12 h) and high-throughput (>100,000 individual cells) system for identification, recovery and clonal expansion of cells producing antigen-specific antibodies. This method can be adapted, in principle, to detect any secreted product in a multiplexed manner.
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