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: 9024477
• 负责人: John A. Viator
• 金额: $ 27.54万
• 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/9024477
• 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; Health; Human; Immunohistochemistry; In Vitro; Incidence; Lasers; Lead; Lesion; Leukocytes; Light; Lung; 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; melanoma; nanoparticle; prognostic; 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）是从实体肿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可能是转移的指标。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疾病状态的信息，从而实现适当的治疗管理。此外，ctc的分离可能使科学家能够研究有关癌症生物学的基本问题。研究人员开发了一种光声流量计，用于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）。与传统的依靠激光反射和诱导荧光信号的流式细胞术不同，该装置在黑色素瘤细胞中产生光波。这些光声波是特定于色素细胞的，如黑色素瘤，产生强大的激光诱导声信号，与荧光等光信号相比，衰减很小。光声流法可以检测血液样本中的单个cmc。在光声流量计中，不是连续流动，而是将血细胞悬浮液分离成微升的液滴，由相似体积的空气分离。这种两相流的安排允许在小体积中隔离任何cmc，从而实现捕获和隔离以进行进一步研究。研究人员将对一组IV期黑色素瘤患者进行分子分析，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。这一新信息可能用于开发阻断转移性疾病的方法。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，以确定cmc与转移的关系，从而实现积极的临床管理。