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

项目摘要 目前，没有标准指南遵循核心针吸活检(CNB)采集和 准备工作。每年采购数百万个CNBS作为首选的微创手术 基于这些小样本的生物标志物诊断乳腺癌和评估治疗策略 生物群落。然而，病理学中的下游步骤最初不是为cnbs-a设计的。 一系列不规范的人工操作程序。它们是：充分性测试、固定和 脱水、石蜡包埋、薄片、图像形态分析染色、 免疫组织化学(IHC)分析，随后进行显微解剖以丰富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，以做出 诊断，使用西雅图华盛顿大学的CoreView毫米流设备。自动化 电脑控制的流体泵帮助去除针头上的CNB，输送，清洁和污渍 为CNBS设计的可重复系统中的组织表面。与密歇根大学合作 加州大学戴维斯分校将使用紫外光表面激发显微镜的新方法， 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……里面 此外，MUSE将扩大到包括相同CNB的多路复用分子。高临床率 对个性化医学的影响是通过这种多重荧光免疫染色提供的 活检以确定与虚拟H&E共同注册的ER/PR和HER2表达水平。 在护理点进行多路复用缪斯成像的整个过程允许标本保持不固定 在这个过程中，未来将其中一个CNBS分选到基因组和其他组学分析中 这就要求生物标记物的产量和质量都很高。另外1到2个CNBS可以继续注入福尔马林 固定石蜡包埋常规组织病理学工作流程用于未来的快速验证 评估体系。在这项可行性研究中，第一台分子和形态CNB仪器 将基于CoreView-MUSE专利技术设计和制造。测试将比较 将CNB表面图像与常规薄片H&E和IHC进行了比较，并对其质量和性能进行了分析 从这两种方法中提取RNA的数量。全自动化的试点测试将决定 从针到多模式充分性确定的最终处理速度应该在 在看护点的5到15分钟。一旦开发并验证了对乳腺癌的治疗， CoreView-MUSE系统将扩展到肺癌、胰腺癌和其他依赖CNB的癌症 准确地从病变中采集癌症样本，并提供表型分类以保证精确度 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.