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Microfluidics Platform for Spatial Multi-Omics Analysis of Tissue at Single Cell Resolution

用于单细胞分辨率组织空间多组学分析的微流控平台

基本信息

批准号：
10483029
负责人：
Joseph Charles Gennaro
金额：
$ 22.2万
依托单位：
ATLASXOMICS INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-01 至 2022-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10483029
关键词：
Address Adoption Affect Architecture Automation Automobile Driving Bar Codes Biology Cancer Biology Capital Cell Communication Cell physiology Cells Chromatin Clinical Pathology Communities DNA Data Developmental Biology Device Designs Devices Diffuse Dimensions Disease Elements Embryo Environment Feedback Fishes Fluorescent in Situ Hybridization Genes Goals Heterogeneity Immunofluorescence Immunologic In Situ Incidence Industrialization Maps Messenger RNA Methods Microfluidic Microchips Microfluidics Mus Nature Neurosciences Performance Persons Pharmaceutical Preparations Phase Population Population Characteristics Proteins Proteome Proteomics Publications Reagent Research Research Personnel Resolution Services Small Business Innovation Research Grant Surveys System Technology Tissues base commercial application commercialization design detector early detection biomarkers epigenome epigenomics genome-wide histone modification improved interest lens molecular imaging multiple omics next generation sequencing protein profiling prototype rapid growth response single cell analysis single cell sequencing single molecule single-cell RNA sequencing technological innovation tissue processing tool transcriptome transcriptomics

项目摘要

Project Summary – Abstract AtlasXomics will develop a transformative single-cell resolution multi-omics platform to help researchers and drug developers understand the cell-cell interactions that drive tissue function and disease. With this SBIR application, AtlasXomics will improve upon its existing Deterministic Barcoding in Tissue for spatial omics sequencing (DBiT-seq) which combines microfluidics and next generation sequencing (NGS) to enable researchers to spatially map the cell tissue architecture across the transcriptome (~20,000 genes), epigenome (genome-wide chromatin accessibility and histone modifications) and proteome (hundreds of proteins simultaneously). The platform received significant market interest after its recent publication in Cell in 2020 and its feature in Nature’s 2020 methods of the year. The spatial omics market has seen rapid growth where in 2020 alone, the spatial transcriptomics field has attracted over $100M in venture capital to address a potential market that is estimated to be as large as $10 billion dollars. However, there is still no spatial omics platform that can achieve both single-cell resolution and comprehensive coverage of the multiple omics to truly decipher the cell-to-cell interactions that drive disease. By providing single-cell, multi-omic spatial data to as many researchers as possible, AtlasXomics can help enable a new era of discovery into tissue function and disease. DBiT-seq uniquely utilizes microfluidics to annotate target analytes (mRNA, proteins and/or other biomolecules) in situ (in tissue) with DNA barcodes in a grid of rows and columns, similar to a chessboard, that are then quantified through Next-Generation Sequencing (NGS). The key advantage of this method is that reagents are diffused into tissue, disturbing their biology and spatial 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 by refining our existing microfluidic design. In Specific Aim 2, we will use this device to create detailed single cell multi-omics maps (epigenome, transcriptome and proteome) of the mouse embryo. We will then validate our results by comparing them to standard methods, such as single-cell sequencing, 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.

项目摘要-摘要 AtlasXology将开发一种变革性的单细胞分辨率多组学平台，以帮助研究人员和药物开发人员了解驱动组织功能的细胞-细胞相互作用和疾病。有了这一SBIR应用程序，AtlasXology将在其现有确定性的基础上进行改进用于空间组学测序的组织条码(DBiT-seq)结合了微流体和下一代测序(NGS)使研究人员能够在空间上绘制细胞组织图跨转录组(约20,000个基因)、表观基因组(全基因组染色质)的体系结构可及性和组蛋白修饰)和蛋白质组(同时有数百种蛋白质)。这个 Platform在2020年发表在Cell上后，受到了市场的极大兴趣，它的在《自然》评选的2020年度最佳方法中有所体现。空间组学市场增长迅速，仅在2020年，空间转录组学菲尔德已经吸引了超过1亿美元的风险投资，以满足估计的潜在市场高达100亿美元。然而，仍然没有空间组学平台可以同时实现单细胞分辨率和多重组学的全面覆盖，以真正破译导致疾病的细胞间的相互作用。通过提供单细胞、多组体的空间将数据提供给尽可能多的研究人员，AtlasXology可以帮助实现一个新的发现时代组织功能和疾病。 DBiT-seq独一无二地利用微流控技术来注释目标分析物(mRNA、蛋白质和/或其他生物分子)在由行和列组成的网格中原位(在组织中)具有DNA条形码，类似于棋盘，然后通过下一代测序(NGS)进行量化。钥匙这种方法的优点是，试剂扩散到组织中，干扰它们的生物学和在创建高保真分子图像的同时尽可能少的空间配置。我们的长- 学期目标是将这一多功能工具从学术概念验证转化为强大的经济实惠且可扩展的发现平台。在具体目标1中，我们将开发一种新的原型设备，通过以下方式实现单细胞分辨率完善我们现有的微流控设计。在特定的目标2中，我们将使用此设备来创建详细的小鼠胚胎的单细胞多组学图谱(表观基因组、转录组和蛋白质组)。我们然后将我们的结果与单细胞等标准方法进行比较，以验证我们的结果测序、免疫荧光和单分子荧光原位杂交 (SmFISH)。在第二阶段，我们计划通过自动化提高可用性来扩展平台，并通过扩展平台的应用来提高性能。