A novel flexible approach for high-throughput single-cell phenotyping and genotyping

PROJECT SUMMARY Single cell genomics has become an essential tool to explore cellular heterogeneity, understand what makes cells different from each other or in their response to disease and search for cells with valuable therapeutic properties. Despite tremendous advances in the technologies enabling single cell analysis, combining sequencing based genomic analysis and more traditional imaging-based cellular assays remains a challenge. Many projects require to combine several technologies to collect both phenotyping and genotyping information, making experimental design and execution as well as result interpretation challenging. To overcome these limitations and allow the direct measurement and correlation of a cell’s phenotype, physiological conditions and molecular signatures, Flexomics is developing the next generation of cell analysis platform combining imaging and sequencing-based readouts. Our proprietary platform uses a high-density picowell array specifically designed for single cell isolation and fluorescent imaging of the captured cells combined with a unique high- throughput nucleic-acid barcoding system that can be deciphered both by fluorescence microscopy and by sequencing. This approach allows us to implement gold-standard image-based functional assays to measure and correlate live cell responses and sequencing data for 100,000s individual cells in parallel. Building on our promising feasibility result, we propose to demonstrate the flexibility, deployability and commercial potential of our platform by: (1) demonstrating the ability of our platform to select for cells with specific phenotypes to be enriched for sequencing analysis, (2) building the required data processing, visualization tools and user interface combining imaging and sequencing data necessary for the deployment of our platform, (3) generating proof of concept data at a customer site on complex heterogeneous clinical sample. At the end of this Phase II grant, we will be ideally positioned to expand our beta testing program to additional customers and engage with strategic partners and investors to drive the adoption of our platform.