Portable filter-based microdevice for detection and characterization of circulating tumor cells.
Portable filter-based microdevice for detection and characterization of circulating tumor cells.
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DOI：
10.1158/1078-0432.ccr-10-1105
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发表时间：
2010-10-15
期刊：
影响因子：
--
通讯作者：
Cote RJ
中科院分区：
文献类型：
--
作者：
Lin HK;Zheng S;Williams AJ;Balic M;Groshen S;Scher HI;Fleisher M;Stadler W;Datar RH;Tai YC;Cote RJ
循环肿瘤细胞（CTC）的灵敏检测和表征可以彻底改变早期和转移性癌症患者的方法。目前的方法具有显著的局限性，包括有限的捕获效率和表征捕获的细胞的能力。在这里，我们报告了一种新的基于聚对二甲苯膜过滤器的便携式微型装置的开发，用于基于尺寸的分离，具有高回收率和直接在芯片上表征从人外周血中捕获的CTC。我们使用来自掺入肿瘤细胞系的健康供体的血液样本，在模型系统中评估了CTC捕获的灵敏度和效率。对59个模型系统样品进行了测试，以确定微型器件的回收率。此外，对来自癌症患者的10个模型系统样品和57个血液样品进行膜微滤器装置和CellSearch®平台计数以进行直接比较。使用该模型系统，当5个细胞接种在7.5ml血液中时，微型装置实现了>90%的回收率，其中回收至少一个细胞的概率为95%。使用微型装置在57名患者中的51名中鉴定出CTC，相比之下，使用CellSearch®方法的患者仅为26名。当通过两种方法检测到CTC时，除5名患者外，所有患者的微滤器装置均回收了更多的CTC。这种基于过滤器的微型设备既是捕获和分析平台，能够进行多重成像和遗传分析。这里提出的微型设备有可能使常规CTC分析在临床环境中有效管理癌症患者。
Sensitive detection and characterization of circulating tumor cell (CTC) could revolutionize the approach to patients with early stage and metastatic cancer. The current methodologies have significant limitations including limited capture efficiency and ability to characterize captured cells. Here, we report the development of a novel parylene membrane filter-based portable microdevice for size-based isolation with high recovery rate and direct on-chip characterization of captured CTC from human peripheral blood. We evaluated the sensitivity and efficiency of CTC capture in a model system using blood samples from healthy donors spiked with tumor cell lines. 59 model system samples were tested for determining the recovery rate of the microdevice. Moreover, 10 model system samples and 57 blood samples from cancer patients were subjected to both membrane microfilter device and CellSearch® platform enumeration for direct comparison. Using the model system, the microdevice achieved >90% recovery with probability of 95% recovering at least one cell when 5 are seeded in 7.5 ml of blood. CTCs were identified in 51 out of 57 patients using the microdevice, compared to only 26 patients with the CellSearch® method. When CTC were detected by both methods, greater numbers were recovered by the microfilter device in all but 5 patients. This filter-based microdevice is both a capture and analysis platform, capable of multiplexed imaging and genetic analysis. The microdevice presented here has the potential to enable routine CTC analysis in clinical setting for effective management of cancer patients.