Trouble Shooting Drug Screening Method
Boosting Efficiency in Large-Scale Drug Discovery
Client: Large Pharmaceutical Company
Industry: Biotechnology/Pharmaceuticals
Project Overview: The client was engaged in a large-scale drug screening campaign aimed at identifying novel inhibitors of G protein-coupled receptors (GPCRs). Utilizing a cell-based high-throughput assay (HTS) and robotic handling methods in a 384-well plate format, the client encountered a significant issue: a substantial number of test wells exhibited little to no signal, undermining the screening results and delaying drug discovery efforts.
Challenges:
- Inconsistent cell adhesion to the wells of the 384-well plates, leading to poor signal responses.
- The robotic system failed to detect or correct the problem early in the screening process.
- A high level of variability in test well data, increasing the rate of false negatives and complicating data analysis.
GOTBio’s Role: GOTBio was hired to troubleshoot the problem and provide actionable solutions to improve the efficiency and reliability of the screening process. The team visited the client’s screening facility, observed the entire process from start to finish, and conducted a thorough assessment of the workflow and equipment involved.
Solution: After a comprehensive evaluation, GOTBio identified the root cause of the problem: inconsistent cell adhesion to the well plates was causing weak or no signal in the test wells. GOTBio developed and implemented a series of solutions to address this issue:
- De Novo Testing Program: GOTBio designed a de novo testing protocol, optimizing the extracellular matrix (ECM) coating on the 384-well plates to improve adhesion. The ECM coating was tailored to the specific cell line used in the assay, facilitating stronger and more consistent cell attachment to the plastic wells.
- Checkpoint Controls: New checkpoint controls were introduced along the assay pipeline to ensure consistent cell loading and adhesion before the addition of drug compounds. These controls included automated validation of cell adherence before proceeding to the next stage of the screening process, significantly reducing variability between wells.
- Improved Process Monitoring: GOTBio worked with the client’s team to refine robotic handling procedures, including adjusting pipetting techniques to ensure uniform distribution of cells across all wells.
Outcomes:
- Improved Signal Consistency: The number of wells showing a reliable signal significantly increased, leading to higher-quality data.
- Reduced False Negatives: With more consistent cell adhesion, the overall integrity of the screening data improved, reducing the number of false negatives.
- Enhanced Screening Efficiency: The optimized workflow reduced rework and delays, enabling the client to accelerate their drug discovery timelines.
- Client Satisfaction: GOTBio’s quick and effective intervention saved the client both time and resources, restoring confidence in their screening platform.
Conclusion: GOTBio’s strategic troubleshooting and process improvements allowed the client to resume their GPCR inhibitor screening with enhanced precision and efficiency. This project showcases GOTBio’s ability to quickly diagnose complex issues in biotech workflows and deliver tailored solutions that drive better outcomes for large-scale drug discovery programs.
