Gel Microdrop Technology For Rapid Isolation of Rare and High Producer Cells

Nature Medicine, May 1997, vol.3 #5, pp.583-585

James C. Weaver, Patricia McGrath, and Sharlene Adams

Increasing use of monoclonal antibodies and recombinant proteins has created a demand for methods that accelerate and simplify generation of stable cell lines. Mammalian cell-line development involves isolation or engineering of protein-secreting cells and screening for specificity and high productivity. Heterogeneous populations of fused or transfected cells are repeatedly assayed to confirm and quantify secretion of a desired protein, such as immunoglobulin. Traditional methods require distribution of individual cells into microtiter wells and analysis of supernatants for the secreted product by ELISA assays. The effort required to plate cells, to obtain detectable levels of secretion, assay supernatants and to recover positive clones is labor-intensive and slow; the entire process can take weeks to months. Producer cells are frequently overgrown by nonsecreting fast growers, making recovery nearly impossible. Clonal instability often wreaks havoc with product development timelines when isolated cells do not withstand the rigors of large-scale manufacturing.

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