Flexible Micro Spring Array Device for High-Throughput Enrichment of Viable Circulating Tumor Cells
Flexible Micro Spring Array Device for High-Throughput Enrichment of Viable Circulating Tumor Cells
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DOI：
10.1373/clinchem.2013.206805
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发表时间：
2014-02-01
影响因子：
9.3
通讯作者：
Zheng, Si-Yang
中科院分区：
文献类型：
--
作者：
Harouaka, Ramdane A.;Zhou, Ming-Da;Zheng, Si-Yang
背景技术背景：引起远处器官转移的循环肿瘤细胞（CTC）的传播占癌症相关死亡的大多数。CTC已被确立为具有已知预后价值的癌症生物标志物。用于离体分析的活CTC的富集可以进一步改善癌症诊断并指导治疗选择。我们设计了一种新的灵活的微弹簧阵列（FMSA）设备，用于独立于抗原expression.METHODS的活CTC富集：与以前的微过滤设备不同，在微尺度上的灵活结构最大限度地减少细胞损伤，以保持活力，同时最大限度地提高吞吐量，使快速富集直接从全血中，无需样品预处理。装置性能方面的捕获效率，富集对白细胞，活力和增殖能力进行了表征。CTC和CTC微团簇从乳腺癌、肺癌和结直肠癌患者的临床样本中富集。结果：FMSA装置在0.5 cm 2装置上在< 10 min内从7.5 mL全血样本中富集肿瘤细胞，捕获效率为90%，富集率高于104，存活率高于80%。FMSA在21个临床样本中的16个（约76%）中检测到至少1个CTC，相比之下，用商业CellSearch（R）系统检测到的18个中的4个（约22%）。有超过100个测试新鲜全血samples.Conclusions堵塞的发生率：FMSA设备提供了一个多功能的平台，能够从临床相关体积的全血中进行可行的富集和CTC分析。(C)2013年美国临床化学协会
BACKGROUND: The dissemination of circulating tumor cells (CTCs) that cause metastases in distant organs accounts for the majority of cancer-related deaths. CTCs have been established as a cancer biomarker of known prognostic value. The enrichment of viable CTCs for ex vivo analysis could further improve cancer diagnosis and guide treatment selection. We designed a new flexible micro spring array (FMSA) device for the enrichment of viable CTCs independent of antigen expression.METHODS: Unlike previous microfiltration devices, flexible structures at the micro scale minimize cell damage to preserve viability, while maximizing throughput to allow rapid enrichment directly from whole blood with no need for sample preprocessing. Device performance with respect to capture efficiency, enrichment against leukocytes, viability, and proliferability was characterized. CTCs and CTC microclusters were enriched from clinical samples obtained from breast, lung, and colorectal cancer patients.RESULTS: The FMSA device enriched tumor cells with 90% capture efficiency, higher than 104 enrichment, and better than 80% viability from 7.5-mL whole blood samples in < 10 min on a 0.5-cm(2) device. The FMSA detected at least 1 CTC in 16 out of 21 clinical samples (approximately 76%) compared to 4 out of 18 (approximately 22%) detected with the commercial CellSearch((R)) system. There was no incidence of clogging in over 100 tested fresh whole blood samples.CONCLUSIONS: The FMSA device provides a versatile platform capable of viable enrichment and analysis of CTCs from clinically relevant volumes of whole blood. (C) 2013 American Association for Clinical Chemistry