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Accelerating personalized medicine: miniaturized patient-derived organoid drug screening for predicting cancer
Yasmine Abouleila1, Lidwien P Smabers2, Timo Voskuilen1
1HUB Organoids B.V. (HUB), Utrecht, The Netherlands, now is part of the Life Science Business of Merck KGaA, Darmstadt, Germany.
Abstract:
Patient-derived-organoids (PDOs) are valuable tools for predicting individual responses to cancer treatments. However, current screening methods require large numbers of PDOs, resulting in long turnaround times and limiting clinical use. This study aimed to streamline the process by automating PDO seeding with the Yamaha Cell Handler™ (YCH). We optimized the YCH to pick and place up to ten PDOs per well, significantly reducing sample requirements compared to conventional methods. Assay optimization included evaluating seeding densities, devices, readouts, and measurement techniques. We validated the miniaturized assay by comparing it to standard screens and correlating organoid responses with patient outcomes. Our proof-of-concept demonstrated that mCRC PDOs respond to chemotherapy and targeted treatments in a way that closely matches results from traditional assays. This miniaturized automated platform enables efficient, high-quality drug screening with fewer cells, offering promising potential for faster, personalized cancer treatment predictions in clinical settings.
Insights
This study introduces an automated method using the Yamaha Cell Handler™ to miniaturize patient-derived organoid (PDO) drug screening. This innovation reduces cell requirements and speeds up personalized cancer treatment predictions.
Area of Science:
- Oncology
- Biotechnology
- Drug Discovery
Background:
- Patient-derived organoids (PDOs) are crucial for predicting individual cancer treatment responses.
- Current PDO screening methods are limited by high cell requirements, long turnaround times, and restricted clinical applicability.
Purpose of the Study:
- To streamline and miniaturize PDO drug screening by automating the seeding process using the Yamaha Cell Handler™ (YCH).
- To optimize and validate a high-throughput, low-cell-input assay for predicting patient responses to cancer therapies.
Main Methods:
- Automated seeding of up to ten PDOs per well using the YCH, optimizing sample requirements.
- Miniaturized assay development involving evaluation of seeding densities, devices, readouts, and measurement techniques.
- Validation by comparing miniaturized assay results with standard screens and correlating organoid drug responses with patient outcomes.
Main Results:
- The YCH was optimized for efficient PDO seeding, significantly reducing sample needs.
- Miniaturized assay development and validation confirmed its reliability and efficiency.
- Miniature patient-derived organoid screening closely mirrored results from traditional assays, demonstrating responsiveness to chemotherapy and targeted treatments.
Conclusions:
- The automated, miniaturized PDO platform enables efficient, high-quality drug screening with reduced cell input.
- This approach offers significant potential for accelerating personalized cancer treatment predictions in clinical settings.
