Automated Cell Culture Solutions to Accelerate Rare Disease Treatment Development

We propose to purchase a CellXpress.ai system that integrates a liquid handling robot, a microscope, a centrifuge, an incubator, and an AI-enabled operating system to automate most steps in cell culture. This system can run multiple cell culture workflows in parallel for 2D and 3D culture of multiple cell types and streamlines key tasks such as monitoring, feeding, and passaging cell cultures. Real-time machine learning-assisted decision-making interprets images from the inbuilt microscope. These capabilities substantially enhance experimental throughput, minimize hands-on time, and maximize operational capacity. They also improve experimental rigor via systematic process reproducibility, controlling the environment, and recording all experimental steps and images in a database. Furthermore, the system improves the experience of trainees, by reducing out of hours work that can conflict with caring responsibilities and lessens environmental impact by reducing travel requirements. In short, it allows scientists to focus on science. This cutting-edge technology, which currently does not exist in the UK, would be undertaken as a collaboration with Molecular Devices, who built the system and have offered a £432,243.45 discount. Our joint teams would work together to apply the system to experimental challenges, yielding expanded capabilities and shareable protocols. Our primary requirement for the CellXpress.ai is to create a high-throughput testing platform for genome-targeted therapies, such as antisense oligonucleotides (ASOs) and CRISPR-based editing, as part of the new MRC Centre of Research Excellence (CoRE) in Therapeutic Genomics. Our MRC CoRE aims to accelerate the development of genome-targeted therapies for rare monogenic disorders. Over 4,500 such disorders have been identified, with the vast majority lacking effective therapies; genome-targeted therapies have achieved dramatic clinical success in a few disorders, but development costs hinder wider application. Systematically testing thousands of genome-targeted therapies would allow us to predict future safe and effective therapies for many disorders, minimizing development costs. Cell culture is the major limiting factor on throughout, hence the need for the CellXpress.ai; the improved reproducibility and imaging data would further enhance the utility of these data. Building on the UK’s genomic infrastructure, including Genomics England, the Nucleic Acid Therapeutic Accelerator, and the Rare Therapies Launch Pad, it would position the UK at the forefront of rare disease therapy development. The wider application of the CellXpress.ai is to create scalable, reproducible human-derived disease models that closely mimic human biology to understand disease aetiology, identify biomarkers and develop therapies. Here the potential applications are vast and there is substantial benefit for knowledge sharing across research groups and tissues. As such, we plan to embed the CellXpress.ai at the heart of an existing induced pluripotent stem cell (iPSC) Small Research Facility (SRF) for use by the Oxford community and collaborating commercial partners. The capabilities of the CellXpress.ai will foster innovation for multiple initiatives, including genomic screens for regulatory noncoding sequences, assessing regenerative potential of cardiac tissue, and understanding inflammatory bowel disorders. The automated system aligns with the UK's commitment to ethical research practices by reducing reliance on animal testing, promoting reproducibility, and fostering an inclusive and supportive research environment.