Rapid Needle Biopsy Assessment at Point of Care to advance personalized cancer therapy

项目摘要 目前，对于空芯针活检（CNB）采集没有标准指南， 准备.每年采购数百万CNB作为首选微创手术， 诊断乳腺癌和评估基于这些小的生物标志物的治疗策略 生物标本然而，病理学的下游步骤最初并不是为CNB设计的- a 一系列不标准的手工程序。它们是：充分性测试、固定和 脱水、石蜡包埋、薄切片、染色用于基于图像的形态学分析， 免疫组织化学（IHC）分析，随后显微切割以富集RNA提取。 我们的项目旨在快速评估CNB的充分性，癌细胞的存在，以使一个 诊断，使用来自华盛顿大学，西雅图的CoreView毫流装置。自动化 计算机控制的射流泵有助于从针头中取出CNB，运输，清洁和染色 用于CNB的可重复系统中的组织表面。在与大学的合作中， 加州戴维斯，新的方法显微镜与紫外线表面激发将被使用， 快速生成的图像似乎与用于充分性测试的标准H&E图像相匹配。在 此外，MUSE将扩展到包括相同CNB的多重分子。较高的临床 对个体化医疗的影响是由这种多重荧光免疫染色提供的。 活组织检查以确定与虚拟H&E共配准的ER/PR和HER 2表达水平。的 在护理点的多路复用MUSE成像的整个过程允许标本保持不固定 在这个过程中，将其中一个CNB分类到基因组学和其他组学分析中， 这需要高产量和高质量的生物标志物。其他1或2个CNB可以继续进入福尔马林 固定石蜡包埋常规组织病理学工作流程，为今后的快速验证提供参考 评价体系在这项可行性研究中，第一个分子和形态CNB仪器 将基于CoreView-MUSE专利技术进行设计和制造。试验将比较 CNB表面图像与常规薄切片H&E和IHC相比， 这两种方法的RNA量。全自动化的试点测试将决定 从针到多模态充分性确定的最终处理速度应在 5到15分钟。一旦开发并验证了乳腺癌， CoreView-MUSE系统将扩展到依赖CNB的肺癌，胰腺癌和其他癌症 从病变中准确地采集癌症样本，并提供表型分类， 治疗

Project Summary Currently there are no standard guidelines followed for core needle biopsy (CNB) acquisition and preparation. Millions of CNBs are procured annually as the preferred minimally invasive procedure for diagnosing breast cancer and assessing therapeutic strategies based on biomarkers from these small biospecimens. However, the downstream steps in pathology were originally not designed for CNBs – a series of manual procedures that are not standardized. These are: adequacy testing, fixation & dehydration, paraffin embedding, thin-sectioning, staining for image-based morphological analysis, immuno-histochemical (IHC) analysis, and subsequent microdissection to enrich for RNA extraction. Our project is designed to rapidly evaluate the CNB for adequacy, the presence of cancer cells to make a diagnosis, using CoreView millifluidic device from the University of Washington, Seattle. Automated computer-controlled fluidic pumps help to remove the CNB from the needle, transport, clean and stain the tissue surface in a repeatable system designed for CNBs. In partnership with the University of California at Davis, the new method of microscopy with ultraviolet surface excitation will be used which rapidly produces images appear to match the standard H&E images used for adequacy testing. In addition, MUSE will be expanded to include multiplexed molecular of the same CNB. High clinical impact for personalized medicine is provided by this multiplexed fluorescence immunostaining of the biopsy to determine ER/PR and HER2 expression levels that are co-registered with the virtual H&E. The entire process of multiplexed MUSE imaging at the point of care allows the specimen to remain unfixed during this process, which triages one of the CNBs into genomic and other ‘omics analyses in the future that require high yield and quality of biomarkers. The other 1 or 2 CNBs can continue into formalin fixed paraffin embedded conventional histopathology work flow for the future validation of this rapid assessment system. In this feasibility study, the first molecular and morphological CNB instrumentation will be designed and fabricated based on CoreView-MUSE patented technologies. Testing will compare the CNB surface images compared to conventional thin section H&E and IHC as well as the quality and quantity of RNA from these two approaches. Pilot testing of full automation will determine the ultimate speed of processing from needle to multimodal adequacy determination that should range from 5 to 15 minutes at the point of care. Once developed and validated for breast cancer, the CoreView-MUSE system will be expanded to lung, pancreas, and other cancers that rely on CNB accurately sampling cancer from the lesion and providing phenotype classifications for precision therapies.