SBIR TOPIC 403 PHASE I: DEVELOPMENT OF SPATIAL MICRO-PURIFICATION TECHNOLOGY

肿瘤微环境（TME）由多种细胞类型组成，包括肿瘤细胞、癌症亚克隆、化生、不典型增生、结缔组织增生、反应性成纤维细胞以及巨噬细胞和淋巴细胞亚类的复杂免疫反应。测量TME中每个细胞成分的分子状态对于了解肿瘤的发生和发展以及确定癌症与正常宿主细胞之间的相互作用非常重要。然而，目前大多数肿瘤分子分析都是在异质大样本或粗解剖细胞群上进行的，通常是将多种不同的细胞类型混合在一起，只产生有限的空间背景。因此，TME的基本位置信息是不可用的。该提案描述了一种新的DNA测序和组织切片的基因组分析技术，称为空间微纯化，它可以发展成一种商业设备，允许对肿瘤微环境（TME）进行局部的、细胞类型的特定询问。这种用于肿瘤空间分子分析的新技术的开发和部署将提供对细胞基因型和形态之间关系的更深入理解，为癌症患者开发新的诊断、预后或治疗干预提供有价值的信息。

The tumor microenvironment (TME) comprises a mixture of cell types, including tumor cells, cancer subclones, metaplasia, dysplasia, desmoplasia, reactive fibroblasts, and a complex immune response of macrophages and lymphocyte subclasses. Measuring the molecular status of each cellular component within the TME is important to understanding tumor initiation and progression as well as in determining the interplay between cancer and normal host cells. However, today most molecular analyses of tumors are performed on heterogeneous bulk samples or on crudely macrodissected cell populations, typically mixing together multiple different cells types and generating only limited spatial context. Thus, essential positional information on the TME is not available. The proposal describes a new DNA sequencing and genomic analysis technology for histological slides called spatial micropurification, which can be developed into a commercial device that will permit localized, cell-type specific interrogation of the tumor micro-environment (TME). Development and deployment of this novel technology for spatial molecular profiling of tumors will provide a deeper understanding of the relationship between cell genotype and morphology, providing valuable information toward development of new diagnostic, prognostic, or therapeutic interventions for patients with cancer.