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增加，导致需要能够将这些诊断扩展到其他难以接近肿瘤的患者的技术。这种诊断分析是对从肿瘤中提取的细胞或远离原发肿瘤部位的转移细胞进行的。对来自肺、乳腺或其他器官的弥散性恶性细胞进行体液评估，包括血液、尿液、积液，是对原发肿瘤组织进行检查的一种替代方法，特别是当无法在原发肿瘤部位进行活检时。例如，胸腔积液可能是患者癌症的第一个表现，因此含有一些最具诊断相关性的细胞，可作为易于获取的恶性细胞来源，用于测定指示对靶向治疗易感性的特定遗传病变。然而，这些测定的准确性受到存在大量正常细胞背景的限制。目前从体液中富集恶性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（<40%），无法进行可靠的诊断。细胞的生物物理特性已被证明是恶性表型的极特异性无标记生物标志物。在这里，我们的目标是开发一种仪器，该仪器将使用与恶性肿瘤相关的内在物理生物标志物（细胞大小和可变形性）的组合来分离目标癌细胞，具有高产率和纯度。CytoVale正在商业化一项名为“可变形细胞术”的技术，该技术每秒可检测数千个细胞的生物物理特性，并已被证明在诊断胸腔积液中的恶性肿瘤方面具有实用性。在这个项目中，CytoVale将扩展其核心技术，开发一种仪器，能够从大量体液中分离出恶性细胞，用于伴随诊断分析，比目前可用的技术具有更高的灵敏度和特异性。这将增加这些强大的检测方法的可及性，这些检测方法近年来已经证明了巨大的临床成功，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.