AtlasXomics will develop a transformative single-cell resolution multi-omics platform to helpresearchers and drug developers understand the cell-cell interactions that drive tissue functionand disease. With this SBIR application, AtlasXomics will improve upon its existing DeterministicBarcoding in Tissue for spatial omics sequencing (DBiT-seq) which combines microfluidics andnext generation sequencing (NGS) to enable researchers to spatially map the cell tissuearchitecture across the transcriptome (~20,000 genes), epigenome (genome-wide chromatinaccessibility and histone modifications) and proteome (hundreds of proteins simultaneously). Theplatform received significant market interest after its recent publication in Cell in 2020 and itsfeature in Nature's 2020 methods of the year.The spatial omics market has seen rapid growth where in 2020 alone, the spatial transcriptomicsfield has attracted over $100M in venture capital to address a potential market that is estimatedto be as large as $10 billion dollars. However, there is still no spatial omics platform that canachieve both single-cell resolution and comprehensive coverage of the multiple omics to trulydecipher the cell-to-cell interactions that drive disease. By providing single-cell, multi-omic spatialdata to as many researchers as possible, AtlasXomics can help enable a new era of discoveryinto tissue function and disease.DBiT-seq uniquely utilizes microfluidics to annotate target analytes (mRNA, proteins and/or otherbiomolecules) in situ (in tissue) with DNA barcodes in a grid of rows and columns, similar to achessboard, that are then quantified through Next-Generation Sequencing (NGS). The keyadvantage of this method is that reagents are diffused into tissue, disturbing their biology andspatial configuration as little as possible while creating a high-fidelity molecular image. Our long-term goal is to industrialize this versatile tool from academic proof-of-concept to a robust,affordable, and scalable discovery platform.In Specific Aim 1, we will develop a new prototype device that achieves single cell resolution byrefining our existing microfluidic design. In Specific Aim 2, we will use this device to create detailedsingle cell multi-omics maps (epigenome, transcriptome and proteome) of the mouse embryo. Wewill then validate our results by comparing them to standard methods, such as single-cellsequencing, immunofluorescence, and single-molecule fluorescence in situ hybridization(smFISH). In Phase II, we plan to scale the platform by improving useability through automation,and by improving performance through expanding the applications of the platform.
Public Health Relevance Statement: Like people, cells live in and are influenced by their communities. However, no tool allows
researchers to make single-cell resolution multi-omic maps of cells in tissue. AtlasXomics will
improve the spatial resolution of its existing multi-omic technology to to fill this gap and enable
researchers to investigate how cells interact with each other through the multiple, crucial lenses
of transcriptomics, proteomics, and epigenomics.
Project Terms: | <µfluidic>
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