Abstract: Epigenetic changes in cellular DNA are increasingly linked to pathology and disease where understanding nuance in epigenetic dysregulation is driving therapeutic development. Spatial epigenomic context is imperative to understanding the spatiotemporal dynamics of gene expression and can identify previously unknown crosstalk between cell populations. Despite this shift, development of spatial tools for epigenomics lags behind the widely available tools for spatial RNA-sequencing. Here we present Portal96, a major improvement in throughput and resolution to the Deterministic Barcoding in Tissue for spatial-omics sequencing (DBiT-seq) platform to map chromatin accessibility and histone modifications at the cellular level in tissue. Invented by the research group of Dr. Rong Fan, Professor of Biomedical Engineering at Yale University, DBiT-seq's unique microfluidics and Next-Generation Sequencing-based approach enables high-fidelity spatial barcoding of nearly any analyte on a wide variety of tissues. This unbiased approach has enabled the first characterization of the epigenome with spatial context at the cellular level (published in Science and Nature). The AtlasXomics Portal96 platform enables spatial epigenomic profiling of 3.8mm x 3.8mm of tissue with 20um resolution, 4x more data from the same tissue section than the original academic device. The new 96-channel microfluidics chip design greatly improves precision in cell typing, covers more anatomical features, and identifies additional regulatory elements. 96-channel spatial epigenome mapping of wide range of tissues including brain, cancer and kidney reveal a true complexity of anatomical structures and tumor heterogeneity, as well as cis-regulatory elements controlling cellular function. Spatial epigenomics allows researchers to profile all cell types in a given tissue at once, rather than profiling dissociated cells or clonal populations. The current Portal96 platform allows researchers to collect genome wide data on the epigenome, which can be parsed to pinpoint the epigenetic mechanisms and specific genes underpinning many different biological questions within the same tissue. The flexibility of the DBiT-seq platform lends itself to the development of future multi-omics applications, which will be developed by AtlasXomics. Future development will allow for simultaneously profiling of chromatin accessibility (spatial ATAC-seq) and the transcriptome directly in tissue.