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采用微椭圆滤器高度灵敏地捕获循环肿瘤细胞。

Highly-sensitive capture of circulating tumor cells using micro-ellipse filters.

机构信息

Institute of Semiconductors, Chinese Academy of Sciences, Beijing, 100083, China.

Division of Nanobionic Research, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, Jiangsu, 215123, China.

出版信息

Sci Rep. 2017 Apr 4;7(1):610. doi: 10.1038/s41598-017-00232-6.

Abstract

Circulating tumor cells (CTCs) detection, enumeration and characterization with microfluidic chips has critical significance in cancer prognosis offering a non-invasive "liquid biopsy". Based on physical differences of size and deformability, we explore micro-ellipse filters consisting of microfuidic slits in series gradually narrowed. Slender tunnels sensitively capture tumor cells with slim chance to escape. Tumor cells could reside at capture sites organized by arrays of micro-ellipse microposts enduring less stress. Circular elliptical microstructures produce smooth flow minimally reducing any damage. "Air Suction" could extremely shorten capture. Capture efficiency comes out to be a robust yield of 90% and percentage obeys Gaussian distribution at various stages. With rare number accurately enumerated, micro-Ellipse filters have been tested high efficiently capturing tumor cells in both whole and lysed blood. To clinically validate the device, the microfluidic chip was utilized to identify and capture CTCs from metastatic breast, colon and non-small-cell lung (NSCLC) cancer patients. CTCs were detected positive in all samples with 4 patients having more than 20 CTCs. Those sensitive results are consistent with theoretical expectation. Efficient micro-ellipse filters enable clinical enumeration of metastasis, on-chip anti-cancer drug responses and biological molecular analysis.

摘要

基于大小和变形能力的物理差异,我们探索了由串联逐渐变窄的微流道狭缝组成的微椭圆滤器。细长的隧道能够灵敏地捕获肿瘤细胞,肿瘤细胞几乎没有机会逃脱。肿瘤细胞可以驻留在由微椭圆微柱阵列组织的捕获位置,从而承受较小的压力。圆形椭圆形微结构产生平滑的流动,最小化任何损伤。“空气抽吸”可以极大地缩短捕获时间。捕获效率高达 90%,并且在各个阶段的百分比都服从高斯分布。通过对罕见数量的准确计数,微椭圆滤器已被证明能够高效地从整个和裂解的血液中捕获肿瘤细胞。为了临床验证该设备,利用微流控芯片从转移性乳腺癌、结肠癌和非小细胞肺癌(NSCLC)患者中识别和捕获 CTCs。所有样本的 CTC 检测均呈阳性,其中 4 例患者的 CTC 超过 20 个。这些敏感的结果与理论预期一致。高效的微椭圆滤器能够实现转移的临床计数、芯片上的抗癌药物反应和生物分子分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b86/5428045/4f4cf7aa6510/41598_2017_232_Fig1_HTML.jpg

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