Semi-Automated Cell Line Generation

Traditional single-cell colony isolation remains a significant bottleneck in drug discovery due to intensive manual labor and susceptibility to pipetting errors, which limit throughput and scalability. EnquBio, a San Diego-based CRO, has developed an optimized, semi-automated workflow that integrates high-content imaging (HCI) with precision liquid handling.

The workflow utilizes the Revvity Operetta CLS to identify and map single-cell colonies within 384-well microplates, generating a digital coordinate map for downstream processing. The CERTUS FLEX liquid dispenser then utilizes this map to precisely dispense dissociation reagents. Finally, the Opentrons Flex™ platform reformats these colonies into 96-well plates for expansion.

This high-throughput screening (HTS) compatible workflow was validated by generating human GLP-1 receptor (GLP-1R) clones. We successfully isolated and characterized four functional colonies within three weeks, identifying clones with distinct high and low surface receptor expression profiles. Pharmacological validation was performed using the full agonist GLP-1 and the non-peptide partial agonist Orforglipron (LY3502970). This semi-automated approach accelerates the identification of high-quality screening materials while ensuring robust data traceability consistent with GxP standards.