In this Phase I SBIR study, AtlasXomics will develop a next-generation spatial deposition process to expand tissue type compatibility, minimize end-user processing, and allow adaptation into larger automation workflows. Epigenetics is critical in regulating gene expression in healthy and diseased tissue cells. Incorporating genome-wide epigenetics illuminates research into cancer, neurodegenerative diseases, and systems biology. Systematic epigenomic tissue analysis will allow researchers to bring to bear the power of spatial multi-modal omics to a broad range of disease research. An epigenomics tool accessible to bench scientists remains an unmet need. AtlasXomics launched the first genome-wide spatial epigenomics tool, spatial-ATAC-seq, built on our Deterministic Barcoding in Tissue for spatial omics sequencing (DBiT-seq) platform. An automatable version of our DBiT-seq device will provide this missing puzzle piece but requires greater flexibility, throughput, and ease of use. Early adopters applied our assays to human melanoma, brain cancer, and neurodegenerative diseases. Based on positive early adopter feedback, we have set key objectives for a next-generation product with 1) improved ease of use, 2) greater flexibility for application to a wider array of tissue types, 3) larger field of view (FOV) approaching single-cell resolution, and 4) at a lower cost for large-scale epigenomics studies. To meet this critical need, AtlasXomics will develop a process substantially reducing the end user’s process steps and pain points, delivering a widely accessible spatial platform. We have developed a prototype FlowGel process using the current commercial consumable (25um resolution, 2.5x2.5mm FOV) to map chromatin accessibility in fresh-frozen mouse brains. Once finalized, the process and consumables will be transferable to all other AtlasXomics applications currently in development. The positive results from this proof-of-principal study set the groundwork for AtlasXomics to deliver a more robust, user-friendly, low-cost spatial epigenomic product. Aim 1: Prove the FlowGel at a larger FOV dramatically minimizes researchers’ bench time, reducing human error and improving quality. Aim 2: Make the FlowGel chip and hardware and demonstrate their superior performance with various tissue types over our current commercial technology. Transition to Phase II. We will supply three customers with FlowGel kits and training to carry out FlowGel-enabled spatial assays and map out product requirements for small labs and more extensive automated operations.