<br/><br/>The manufacture of therapeutic biologics relies on understanding and harnessing mammalian cells to secrete desired proteins. Generating a highly productive cell line however typically involves long timelines and resource intensive, due to the need to screen large numbers of candidates in protein production studies. As a result, miniaturization and automation strategies are often employed to allow for reductions in resources and higher throughput. However, current automation approaches rely on the use of standard cell culture vessels and bulky liquid handling equipment. The Beacon platform from Berkeley Lights offers to eliminate these bottlenecks through growing cells on custom nanofluidic chips. Berkeley Lights’ OptoElectro Positioning (OEP) technology projects light patterns to activate photoconductors that gently repel cells to manipulate single cells on nanofluidic culturing chips. Integrate fluorescence imaging capabilities allow for analytics of cells in real time. Together, using this fully integrated technology platform, common cell culture tasks can be programmed through software, allowing maintenance and analysis of thousands of cell lines in parallel on a single chip.<br/><br/>We describe the ability to perform key cell line development work on the Beacon platform. We demonstrate that Chinese hamster ovary (CHO) cell lines can be isolated, cultured, screened, and exported at high efficiency. We then compare this process head to head with a FACS-enabled microtiter plate-based workflow across four active biologics programs. Resulting subclones from both Beacon and FACS processes were evaluated in small scale production experiments and bench-scale controlled bioreactors comparing growth, productivity, and product quality. We demonstrate the ability to generate a diverse and comparable set of candidate clonal cell lines with reduced resources. Additionally, we performed validation experiments to demonstrate that the Beacon process provides high assurances of clonal derivation and zero cross-contamination events. Together, the Beacon enables high quality production cell lines with improved data packages, detailed tracking, high assurance of clonality, reduced resources, and decreased cycle times.

Implementation of the Beacon nanofluidic platform into a manufacturing cell line development process

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.