Biomechanical enrichment of malignant cells enabling companion diagnostics

描述(由申请人提供)：在癌症治疗中使用伴随诊断来指导药物选择的兴起导致了对能够将这些诊断扩展到更多难以接触到肿瘤的患者的技术的需求。这种诊断分析是对从肿瘤中提取的细胞或在远离原发肿瘤部位发现的转移细胞上进行的。评估体液(包括血液、尿液、积液)是否有来自肺、乳房或其他器官的播散性恶性细胞，是检查原发肿瘤组织的替代方法，尤其是当无法在原发肿瘤部位进行活组织检查时。例如，胸腔积液可能是患者癌症的第一个表现，因此包含一些与诊断最相关的细胞，可以作为一种容易获得的恶性细胞来源来分析特定的遗传损伤，表明对靶向治疗的敏感性。然而，这些分析的准确性受到正常细胞大背景的存在的限制。目前从体液中提纯恶性肿瘤细胞用于这些检测的方法可能需要事先了解恶性肿瘤的类型，而这通常是无法获得的，或者导致纯度不足(&lt；40%)才能确定诊断。细胞的生物物理特性已被证明是恶性表型的极其特异的无标记生物标记物。在这里，我们的目标是开发一种仪器，它将使用与恶性肿瘤相关的内在物理生物标记物-细胞大小和变形能力-的组合来高产率和高纯度地分离靶癌细胞。CytoVale正在商业化一项名为“可变形细胞术”的技术，该技术每秒分析数千个细胞的生物物理性质，并已证明在诊断胸腔积液中的恶性肿瘤方面是有用的。在其核心技术的基础上，CytoVale将在该项目中开发一种仪器，该仪器将能够从大量体液中分离出用于伴随诊断分析的恶性细胞，具有比现有技术更高的灵敏度和特异性。这将增加这些强大的分析方法的可及性，这些方法近年来在临床上取得了巨大的成功，从而改善了患者的预后。

DESCRIPTION (provided by applicant): The rise in using companion diagnostics to guide selection of pharmacological agents in cancer treatment has led to a need for technologies which can extend these diagnostics to additional patients with difficult to access tumors. Such diagnostic assays are performed on cells extracted from tumors or metastatic cells found distant from the primary tumor site. Evaluation of bodily fluids, including blood, urine, effusions, for disseminated malignant cells originating from the lung, breast or other organs is an alternative to examination of primary tumor tissue, especially when biopsy is not possible at the primary tumor site. For example, pleural effusions, which can be the first presentation of a patient's cancer and thus contain some of the most diagnostically relevant cells, could be used as an easily accessible source of malignant cells to assay specific genetic lesions indicative of susceptibility to targeted therapies. However, the accuracy of these assays is limited by the presence of a large background of normal cells. Current approaches for enriching malignant cells from bodily fluids for these assays can require prior knowledge about the type of malignancy, which is often unavailable, or result in insufficient purity (<40%) for confident diagnoses. Biophysical properties of cells have been shown to be extremely specific label-free biomarkers of malignant phenotypes. Here, we aim to develop an instrument which will isolate target cancer cells using a combination of intrinsic physical biomarkers associated with malignancy - cell size and deformability - with high yield and purity. CytoVale is commercializing a technology, 'deformability cytometry', which assays the biophysical properties of thousands of cells per second and has demonstrated utility in diagnosing malignancy in pleural effusions. Expanding upon its core technology, CytoVale will, in this project, develop an instrument which will be able to isolate malignant cells for companion diagnostic assays, from large volumes of bodily fluids, with higher sensitivity and specificity than currently available techniques. This wil increase the accessibility of these powerful assays which have demonstrated immense clinical success in recent years, thereby improving patient outcomes.