Photoacoustic detection, capture, and analysis of circulating melanoma cells

循环黑色素瘤细胞的光声检测、捕获和分析

• 批准号: 8624122
• 负责人: John A. Viator
• 金额: $ 29.54万
• 依托单位: DUQUESNE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-20 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8624122
• 关键词: Acoustics; Advanced Malignant Neoplasm; Air; Attenuated; Basic Science; Biological; Biological Assay; Biology; Blood; Blood Cells; Blood Tests; Blood specimen; Breast; Cancer Biology; Cancer Patient; Cancerous; Cell Count; Cells; Centrifugation; Clinical; Clinical Management; Country; Data; Detection; Devices; Disease; Epithelial; Flow Cytometry; Flowmeters; Flowmetry; Fluorescence; Fluorescent in Situ Hybridization; Gold; Human; Immunohistochemistry; In Vitro; Incidence; Lasers; Lead; Lesion; Leukocytes; Light; Lymph; Malignant Neoplasms; Melanoma Cell; Mesenchymal; Mesenchyme; Metastatic to; Molecular; Monitor; Nature; Neoplasm Circulating Cells; Neoplasm Metastasis; Optics; Patients; Phase; Pigmentation physiologic function; Pigments; Predictive Value; Process; Property; Prostate; Relapse; Research Personnel; Risk; S-Phase Fraction; Scientist; Signal Transduction; Solid Neoplasm; Stage Grouping; Staging; Statistical Models; Stem cells; Suspension substance; Suspensions; System; Technology; Testing; Time; Ultrasonics; United States; Whole Blood; cancer type; cell type; clinical care; comparative; human subject; insight; interest; lifetime risk; lung melanoma; melanoma; nanoparticle; prognostic; public health relevance; response; transcription factor; tumor

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.

描述（由申请人提供）：循环肿瘤细胞（CTC）是从实体瘤中分离出来的细胞，扩散到全身，有可能产生其他肿瘤。因此，CTC可以是转移的指标。它们的检测可以为临床医生提供迄今为止无法获得的关于晚期癌症患者的疾病状态的信息，从而能够适当地管理治疗。此外，CTC的分离可以让科学家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的循环黑色素瘤细胞（CMC）。与依赖于激光反射和诱导荧光信号的传统流式细胞术不同，该设备在色素性黑色素瘤细胞中产生光声波。这些光声波对色素细胞（例如黑色素瘤）是特异性的，产生鲁棒的激光诱导的声信号，其与荧光等光学信号相比衰减非常小。 光声流量计允许检测血液样品中的单个CMC。 在光声流量计中，血细胞悬浮液被分离成由类似体积的空气分离的微升液滴，而不是连续流动。两相流的这种布置允许以小体积分离任何CMC，使得能够捕获和分离用于进一步研究。 使用一组IV期黑色素瘤患者，研究者将进行分子测定，以研究增殖指数、上皮-间质转化和其他问题，这些问题将为转移过程提供新的见解。这一新的信息可用于开发中断转移性疾病的方法。最后，研究人员将创建一个统计模型，在80名早期黑色素瘤患者中进行测试，以确定CMC与转移的相关性，从而实现积极的临床管理。