Photoacoustic detection, capture, and analysis of circulating melanoma cells

描述(申请人提供)：循环肿瘤细胞(CTCs)是那些从实体肿瘤中分离出来，扩散到全身并有可能产生其他肿瘤的细胞。因此，CTC可能是转移的指标。它们的检测可能为临床医生提供迄今为止无法获得的关于晚期癌症患者疾病状态的信息，从而使适当的治疗管理成为可能。此外，CTCs的分离可能使科学家能够研究癌症生物学的基本问题。研究人员开发了一种光声流量计来检测和分离黑色素瘤患者血液样本中存在的循环黑色素瘤细胞(CMC)。与依赖激光反射和诱导荧光信号的传统流式细胞术不同，该设备在有色黑色素瘤细胞中产生光声波。这些光声波专用于黑色素瘤等有色细胞，产生强大的激光诱导的声信号，与荧光等光学信号相比衰减很小。光声流量计可以检测血液样本中的单个CMC。在光声流量计中，血细胞悬浮液不是连续流动，而是被相似体积的空气分离成微升液滴。这种两相流的布置允许在小体积中隔离任何CMC，从而能够捕获和隔离以供进一步研究。使用一组IV期黑色素瘤患者，研究人员将进行分子分析，以研究增殖指数、上皮-间充质转化和其他问题，这将为转移过程提供新的见解。这一新信息可能被用来开发阻断转移疾病的方法。最后，研究人员将建立一个统计模型，对80名早期黑色素瘤患者进行测试，确定CMC与转移的相关性，从而实现积极的临床管理。

DESCRIPTION (provided by applicant): Circulating tumor cells (CTCs) are those cells that have separated from solid tumors, spreading throughout the body with potential to create other tumors. Thus, CTCs may be indicators of metastasis. Their detection may provide clinicians with heretofore unavailable information about disease state in advanced cancer patients, enabling proper management of therapy. Additionally, isolation of CTCs may allow scientists to investigate fundamental questions about cancer biology. The investigators developed a photoacoustic flowmeter to detect and isolate circulating melanoma cells (CMCs) present in blood samples of melanoma patients. Unlike conventional flow cytometry that relies on laser reflectance and induced fluorescent signals, this device generates photoacous- tic waves in pigmented melanoma cells. These photoacoustic waves are specific to pigmented cells, such as melanoma, creating robust laser induced acoustic signals that attenuate very little in comparison to optical signals like fluorescence. Photoacoustic flowmetry allows detection of single CMCs in blood samples. In the photoacoustic flowmeter, rather than continuous flow, the blood cell suspension is separated into microliter droplets separated by similar volumes of air. This arrangement of two phase flow allows isolation of any CMCs in small volumes, enabling capture and isolation for further study. Using a group of Stage IV melanoma patients, the investigators will perform molecular assays to investigate proliferation index, epithelial-mesenchymal transition, and other issues that will pro- vide new insight into the process of metastasis. This new information may be used to develop means to interrupt metastatic disease. Finally, the investigators will create a statistical model, tested on 80 early stage melanoma patients, that wil determine the association of CMCs with the transition to metastasis, enabling proactive clinical management.