NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 12 Medical Drive, Singapore 117598, Singapore.
Biosens Bioelectron. 2010 Dec 15;26(4):1701-5. doi: 10.1016/j.bios.2010.07.054. Epub 2010 Jul 22.
The isolation of circulating tumor cells (CTCs) using microfluidics is attractive as the flow conditions can be accurately manipulated to achieve an efficient separation. CTCs are rare events within the peripheral blood of metastatic cancer patients which makes them hard to detect. The presence of CTCs is likely to indicate the severity of the disease and increasing evidences show its use for prognostic and treatment monitoring purposes. We demonstrated an effective separation using a microfluidic device to utilize the unique differences in size and deformability of cancer cells to blood cells. Using physical structures placed in the path of blood specimens in a microchannel, CTCs which are generally larger and stiffer are retained while most blood constituents are removed. The placements of the structures are optimized by computational analysis to enhance the isolation efficiency. With blood specimens from metastatic lung cancer patients, we confirmed the successful detection of CTCs. The operations for processing blood are straightforward and permit multiplexing of the microdevices to concurrently work with different samples. The microfluidic device is optically transparent which makes it simple to be integrated to existing laboratory microscopes and immunofluorescence staining can be done in situ to distinguish cancer cells from hematopoietic cells. This also minimizes the use of expensive staining reagents, given the small size of the microdevice. Identification of CTCs will aid in the detection of malignancy and disease stage as well as understanding the phenotypic and genotypic expressions of cancer cells.
使用微流控技术分离循环肿瘤细胞（CTC）具有吸引力，因为可以精确控制流动条件以实现有效的分离。在转移性癌症患者的外周血中，CTC 是罕见事件，这使得它们难以检测到。CTC 的存在可能表明疾病的严重程度，越来越多的证据表明其可用于预后和治疗监测目的。我们展示了一种有效的分离方法，使用微流控设备利用癌细胞与血细胞在大小和变形性方面的独特差异。通过在微通道中的血液样本路径中放置物理结构，通常较大且较硬的 CTC 被保留，而大多数血液成分被去除。通过计算分析优化结构的放置位置，以提高分离效率。使用来自转移性肺癌患者的血液样本，我们成功地检测到了 CTC。处理血液的操作简单，并且允许对微器件进行多路复用，以同时与不同的样本一起工作。微流控设备是光学透明的，因此很容易集成到现有的实验室显微镜中，并且可以原位进行免疫荧光染色，以区分癌细胞和造血细胞。由于微器件的体积较小，这也最大限度地减少了昂贵的染色试剂的使用。CTC 的鉴定将有助于检测恶性肿瘤和疾病阶段，并了解癌细胞的表型和基因型表达。
