High-speed reliable detection of cancer cells in blood

描述(由申请人提供)：检测外周血中循环肿瘤细胞(CTCs)的医学价值现已确立，一种特殊的方法已获得FDA的批准，用于治疗转移患者。虽然它的价值是明确的，但在应用上也受到限制。例如，报道的结果对很大比例的转移性患者没有提供信息，并且没有对早期阶段的验证。癌症生物工程研究伙伴关系(CBRP)建议开发一种CTC检测技术，以克服这些限制。我们将开发一种新的仪器，光纤阵列扫描技术(FAST)细胞仪，它可以有效地扫描检测CTCs所需的大量细胞，并开发一种针对细胞保留进行优化的细胞准备方案。我们将利用这些进展来调查是否有比目前方法所显示的更多的转移性患者患有CTC。我们还将研究CTC检测在早期癌症患者中的医学效果。此外，我们将调查诊断时分期的应用，以及纵向治疗监测和长期患者管理的应用。这项工作将临床肿瘤学与生物物理分析方法和光学机械工程相结合。CBRP将开发一种罕见的细胞检测系统，该系统可以在2分钟内分析大约5000万个细胞，灵敏度为10%的假阴性，假阳性率低于1/107。CBRP的主要研究人员通过一种多学科方法开发了初步的概念验证，该方法在领先的机构帕洛阿尔托研究中心(PARC)和斯克里普斯研究所(TSRI)以及参与机构斯克里普斯诊所和斯克里普斯癌症中心的光学设计、统计软件分析、实验医学、肿瘤学和病理学之间建立了联系。牵头研究人员是首席研究员理查德·布鲁斯博士(PARC)，他还将领导光学和系统工程工作；彼得·库恩博士(TSRI)，他将领导实验过程；以及豪尔赫·涅瓦医学博士(TSRI和斯克里普斯癌症中心)，他将领导CBRP的肿瘤学和病理学。牵头调查人员是各自领域的专家，为CBRP的多学科研究方案提供所需的专业知识。

DESCRIPTION (provided by applicant): The medical value of detecting circulating tumor cells (CTCs) in peripheral blood is now established, and a specific approach has FDA approval for managing metastatic patients. While the value is clear, it is also limited in application. For example, the reported results are uninformative for a large percentage of metastatic patients, and no validation exists for earlier stages. The cancer bioengineering research partnership (CBRP) proposes to develop a technology for CTC detection that overcomes these limitations. We will develop a new instrument, the Fiber Array Scan Technology (FAST) cytometer that efficiently scans the large numbers of cells required to detect CTCs and a cell preparation protocol that is optimized for cell retention. We will use these developments to investigate whether more metastatic patients have CTCs than current approaches indicate. We will also investigate the medical efficacy of CTC detection in early stage cancer patients. In addition we will investigate applications for staging at diagnosis, as well as for longitudinal therapy monitoring and long-term patient management. The effort integrates clinical oncology with biophysical analysis methods and opto-mechanical engineering. The CBRP will develop a rare cell detection system that can analyze approximately 50 million cells in 2 minutes with a sensitivity of 10% false negatives and a false positive ratio of less than 1 in 107. The Lead Investigators of the CBRP have developed the initial proof of concept through a multidisciplinary approach bridging optical design, statistical software analysis, experimental medicine, oncology, and pathology at the leading institutions, the Palo Alto Research Center (PARC) and The Scripps Research Institute (TSRI), as well as at the participating institutions, Scripps Clinic and the Scripps Cancer Center. The lead investigators are Richard Bruce, Ph.D. (PARC), who is the principal investigator and will in addition lead the optical and system engineering efforts; Peter Kuhn, Ph.D. (TSRI), who will lead the experimental processing; and Jorge Nieva, MD (TSRI and Scripps Cancer Center), who will lead the oncology and pathology of the CBRP. The lead investigators are experts in their respective fields and provide the required expertise for the multi-disciplinary research program of the CBRP.