Biologics Discovery

Accelerating Discovery: Development of a High-throughput Mammalian Expression Platform as Part of a Fully Integrated Biologics Workflow

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  Melissa Crisp, PhD

  Senior Research Scientist, Automation
  Eili Lilly and Company

The success of antibody discovery relies heavily on the ability to interrogate large, diverse antibody pools. However, the number of clones that can be screened for function is often limited by the capacity to express a large numbers of proteins at concentrations adequate for downstream cell-based assays. Bottlenecks in expression typically diminish success rates and often require project teams to re-initiate antibody discovery campaigns resulting in delays in timelines.
At the Lilly Biotechnology Center in San Diego, we have established a workflow utilizing both integrated automation systems, as well as stand-alone equipment, to overcome the limitations of throughput in the discovery of protein therapeutics. This “Islands of Automation” approach was strategically designed to allow for maximal flexibility in the incorporation of future antibody discovery technologies, as well as for cost efficiencies. Furthermore, this approach allows for intermittent quality control checks as well as parsing of plates either directly to project teams or to the next workstation.
At the centerpiece is a high-throughput mammalian expression platform, capable of performing ~4000 small-scale transient transfections/day. This system, built in collaboration with Wako Automation, evolved from a semi-automated process and this conversion required careful consideration of equipment selection, consumables cost, custom engineering as well as process redundancy to ensure minimal downtime. We have also streamlined this workflow to accommodate multiple plate types via a simple barcoding system and dynamic allocation of plates to cytomat shakers, effectively increasing efficiency, reducing FTE time and lowering reagent costs.
The expression platform requires communication with both upstream and downstream automation systems for seamless data tracking, accomplished through linkages with Beckman Coulter’s DART (Data Acquisition and Reporting Tool) and our in-house LIMS. In addition, evaluation of the overall workflow across the integrated automation systems identified key bottlenecks that were addressed through purchases and enablement of key stand-alone instruments.