Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA.
Clin Cancer Res. 2010 Oct 15;16(20):5011-8. doi: 10.1158/1078-0432.CCR-10-1105. Epub 2010 Sep 28.
Sensitive detection and characterization of circulating tumor cells (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. Fifty-nine model system samples were tested to determine 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 five are seeded in 7.5 mL of blood. CTCs were identified in 51 of 57 patients using the microdevice, compared with only 26 patients with the CellSearch method. When CTCs were detected by both methods, greater numbers were recovered by the microfilter device in all but five 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 the clinical setting for the effective management of cancer patients.
循环肿瘤细胞(CTC)的敏感检测和特征分析可能会彻底改变早期和转移性癌症患者的治疗方法。目前的方法存在显著的局限性,包括有限的捕获效率和对捕获细胞进行特征分析的能力。在这里,我们报告了一种新型的基于聚对二甲苯膜的便携式微器件的开发,该微器件可用于基于大小的分离,具有高回收率和直接在芯片上对人外周血中捕获的 CTC 进行特征分析。
我们使用来自健康供体血液中掺入肿瘤细胞系的血液样本在模型系统中评估了 CTC 捕获的灵敏度和效率。测试了 59 个模型系统样本以确定微器件的回收率。此外,对 10 个模型系统样本和 57 个癌症患者的血液样本进行了膜微滤器装置和 CellSearch 平台计数,以进行直接比较。
在模型系统中,该微器件在 7.5 毫升血液中接种五个细胞时,回收率超过 90%,95%的概率至少回收一个细胞。使用微器件在 57 名患者中的 51 名中鉴定出了 CTC,而 CellSearch 方法仅在 26 名患者中鉴定出了 CTC。当两种方法都检测到 CTC 时,除了五名患者外,微滤器装置在所有患者中都回收了更多的 CTC。
这种基于滤器的微器件既是一种捕获和分析平台,也能够进行多重成像和基因分析。本文介绍的微器件有可能在临床环境中实现常规 CTC 分析,从而有效管理癌症患者。