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The single cell as a microplate well

Nature Biotechnology volume 18, pages 1039–1040 (2000)Cite this article

Given our incomplete understanding of protein structure/function relationships, directed evolution is currently the most rapid route to engineer desired protein properties, such as stability, affinity, activity, specificity. In particular, new applications of antibodies and enzymes have blossomed with the broad availability of inventive screening and mutagenesis strategies. In this issue, Olsen et al.1 describe a bacterial display/cell surface capture approach to enzyme evolution that they applied to engineering of an unusual protease specificity.

The primary advantages of flow cytometry3 lie in numbers—in screening of large libraries, and in quantitative assays. Superlative prefixes struggle to keep pace with the throughput of screening technology, as yesterday's HTS is eclipsed by today's UHTS. Following this trend, how many U's must be appended to describe commercially available flow cytometers that quantify cellular multicolor fluorescence and sort 50,000 cells/s (the equivalent of about one million 1,536-well microplates per workshift)? In order to take advantage of this blazing speed, the challenge is to develop assays that confine the gene, enzyme, and reaction product to a cell-sized particle.

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Figure 1: Necessary display and assay linkages for directed evolution of enzymes.

© Bob Crimi

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  1. the J.R. Mares Professor of Chemical Engineering and Bioengineering at the Massachusetts Institute of Technology, Cambridge, 02139, MA

    K. Dane Wittrup

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  1. K. Dane Wittrup
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Wittrup, K. The single cell as a microplate well. Nat Biotechnol 18, 1039–1040 (2000). https://doi.org/10.1038/80223

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