ロボット液体ハンドリング自動化による細胞培養ハイドロゲルの作製とハイスループット薬物スクリーニングへの応用

Traditional plastic and glass culture lacks physiological relevance, undermining predictive power in drug discovery. Organoids and organs-on-chip improve biomimicry but do not scale to high-throughput screening (HTS). Even simple hydrogel coatings in HTS plates suffer from curved menisci that disrupt seeding and imaging. We present HYDRA (HYDrogels by Robotic liquid-handling Automation), an automated method to fabricate thin, planar hydrogel films directly in standard plates. Liquid-handlers dispense sub-contact volumes without wall wetting; immediate re-aspiration pins the contact line, leaving a uniform layer with controlled stiffness and thickness. Using fish gelatin hydrogel, HYDRA produces meniscus-free coatings compatible with routine 96- and 384-well workflows and plate-scale quality control. HYDRA was validated through imaging-based dose-response assays with anticancer compounds, engineered epithelial monolayers, and long-term holographic and fluorescence microscopy. It preserved pharmacological sensitivity while supporting high-content imaging on soft, biomimetic substrates, offering a practical bridge between physiological relevance and HTS scalability for early in-vitro drug testing.