Automated Cell Line Development With Greater Than 99% Monoclonality On the Beacon® Platform

For all cell lines used in production for commercial therapeutics, FDA guidelines require assurance of monoclonality. This standard means that typical cell line development (CLD) campaigns often require multiple rounds of cloning easily spanning several weeks to months. However, Berkeley Lights, Inc. (BLI) has developed the ability to save time and money spent on CLD processes via automation. The uniquely powerful Beacon® optofluidic platform performs single-cell cloning, growth and titer measurements, and recovery of top clones with unrivaled (>99%) monoclonality assurance in just 5 days (1).

The Beacon Platform

The Beacon optofluidic platform merges novel microfluidic design with semiconductor technology to conduct single-cell experiments — thousands at once — in parallel. Central to the platform’s function, an OptoSelect™ chip overlays a microfluidic system on a light-activated phototransistor array. A system designed this way enables rapid, precise cloning through the movement and positioning of cells using controlled patterns of light. Importantly, each cell can be visually tracked throughout the entire process.

Thousands of individual cells can be cloned, cultured, and assayed providing a complete visual record of every clone.

Each OptoSelect chip contains thousands of flow-isolated single nanoliter chambers, known as NanoPen™ chambers, which physically isolate clones from flow while still enabling on-chip culture with diffusion-based media exchange. Multiple OptoSelect chips are run in parallel within the Beacon platform, allowing several thousand clones to be isolated, cultured, assayed, and recovered for downstream scale-up.

The Case Study

In contrast to typical CLD processes, workflows executed on the Beacon optofluidic platform verify single-cell status for each and every clone — loading and isolating cells within patented NanoPen chambers helps maintain monoclonality during expansion and antibody productivity assays.

An extensive verification study was undertaken to provide statistical confirmation that clones recovered from the Beacon optofluidic platform have a high probability of maintaining >99% monoclonality.

*Le, K. et al. (2020). Assuring clonality on the Beacon digital cell line development platform. J Biotechnol. 15(1).