Capture, release and culture of circulating tumor cells from pancreatic cancer patients using an enhanced mixing chip.
Capture, release and culture of circulating tumor cells from pancreatic cancer patients using an enhanced mixing chip.
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DOI：
10.1039/c3lc51017d
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发表时间：
2014-01-07
期刊：
影响因子：
6.1
通讯作者：
Fan ZH
中科院分区：
文献类型：
--
作者：
Sheng W;Ogunwobi OO;Chen T;Zhang J;George TJ;Liu C;Fan ZH
来自外周血的循环肿瘤细胞（CTCs）为癌症诊断和疾病监测提供了重要信息。对这种“液体活检”的分析有望引领癌症患者个性化治疗和实时监测的新时代。但是血液中ctc的极度罕见使得它们的分离和表征在技术上具有挑战性。本文报道了一种用于高效、高纯度肿瘤细胞捕获的几何增强混合（GEM）芯片的研制。我们还成功地展示了捕获的肿瘤细胞的释放和培养，以及从癌症患者中分离ctc。该高性能微芯片基于几何优化的微混合器结构，增强了横向流动和流动折叠，最大限度地提高了ctc与抗体包被表面之间的相互作用。在优化的通道几何形状和流速下，在缓冲液中捕获尖刺肿瘤细胞时，捕获效率达到>90%，纯度为>84%。通过在1ml裂解血和全血中分离广泛的尖刺肿瘤细胞（50-50,000），进一步验证了该系统。结合胰蛋白酶化和高流速洗涤，捕获的肿瘤细胞被有效释放。释放的细胞是有活力的，能够增殖，与未经过捕获和释放过程的完整细胞相比没有差异。此外，我们将该设备用于检测转移性胰腺癌患者血液中的ctc；18个样本中有17个发现了ctc（>94%）。我们还测试了该设备在监测胰腺癌患者对抗癌药物治疗的反应方面的潜在效用，以及CTC数与肿瘤临床计算机断层扫描（CT扫描）的相关性。该技术在CTC的精确计数、CTC的生物学研究和肿瘤转移、癌症诊断和治疗监测等方面具有广阔的应用前景。
Circulating tumor cells (CTCs) from peripheral blood hold important information for cancer diagnosis and disease monitoring. Analysis of this “liquid biopsy” holds the promise to usher in a new era of personalized therapeutic treatments and real-time monitoring for cancer patients. But the extreme rarity of CTCs in blood makes their isolation and characterization technologically challenging. This paper reports the development of a geometrically enhanced mixing (GEM) chip for high-efficiency and high-purity tumor cell capture. We also successfully demonstrated the release and culture of the captured tumor cells, as well as the isolation of CTCs from cancer patients. The high-performance microchip is based on geometrically optimized micromixer structures, which enhance the transverse flow and flow folding, maximizing the interaction between CTCs and antibody-coated surfaces. With the optimized channel geometry and flow rate, the capture efficiency reached >90% with a purity of >84% when capturing spiked tumor cells in buffer. The system was further validated by isolating a wide range of spiked tumor cells (50–50,000) in 1 mL of lysed blood and whole blood. With the combination of trypsinization and high flow rate washing, captured tumor cells were efficiently released. The released cells were viable and able to proliferate, and showed no difference compared with intact cells that were not subjected to the capture and release process. Furthermore, we applied the device for detecting CTCs from metastatic pancreatic cancer patients’ blood; and CTCs were found from 17 out of 18 samples (>94%). We also tested the potential utility of the device in monitoring the response to anti-cancer drug treatment in pancreatic cancer patients, and the CTC numbers correlated with the clinical computed tomograms (CT scans) of tumors. The presented technology shows great promise for accurate CTC enumeration, biological studies of CTCs and cancer metastasis, as well as for cancer diagnosis and treatment monitoring.
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影响因子：
10.3
作者：
Moldenhauer, Gerhard;Salnikov, Alexei V.;Faulstich, Heinz
通讯作者：
Faulstich, Heinz
影响因子：
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作者：
Schiro, Perry G.;Zhao, Mengxia;Kuo, Jason S.;Koehler, Karen M.;Sabath, Daniel E.;Chiu, Daniel T.
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影响因子：
11.2
作者：
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158.5
作者：
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通讯作者：
Hayes, DF
影响因子：
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作者：
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通讯作者：
Ingber, Donald E.