Assuring Clonality on the Beacon Digital Cell Line Development Platform.,Biotechnology Journal

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Assuring Clonality on the Beacon Digital Cell Line Development Platform.
Biotechnology Journal ( IF 4.7 ) Pub Date : 2019-11-27 , DOI: 10.1002/biot.201900247
Kim Le ₁ , Christopher Tan ₁ , Huong Le ₁ , Jasmine Tat ₁ , Ewelina Zasadzinska ₁ , Jonathan Diep ₁ , Ryan Zastrow ₁ , Chun Chen ₁ , Jennitte Stevens ₁

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During biomanufacturing cell lines development, the generation and screening for single-cell derived subclones using methods that enable assurance of clonal derivation can be resource- and time-intensive. High-throughput miniaturization, automation, and analytic strategies are often employed to reduce such bottlenecks. The Beacon platform from Berkeley Lights offers a strategy to eliminate these limitations through culturing, manipulating, and characterizing cells on custom nanofluidic chips via software-controlled operations. However, explicit demonstration of this technology to provide high assurance of a single cell progenitor has not been reported. Here, a methodology that utilizes the Beacon instrument to ensure high levels of clonality is described. It is demonstrated that the Beacon platform can efficiently generate production cell lines with a superior clonality data package, detailed tracking, and minimal resources. A stringent in-process quality control strategy is established to enable rapid verification of clonal origin, and the workflow is validated using representative Chinese hamster ovary-derived cell lines stably expressing either green or red fluorescence protein. Under these conditions, a >99% assurance of clonal origin is achieved, which is comparable to existing imaging-coupled fluorescence-activated cell sorting seeding methods.

更新日期：2019-11-28

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