Department of Bioengineering, University of Texas at Arlington, Texas 76019, USA.
Cancer. 2012 Feb 15;118(4):1145-54. doi: 10.1002/cncr.26349. Epub 2011 Jul 15.
The detection of a small number of circulating tumor cells (CTCs) is important, especially in the early stages of cancer. Small numbers of CTCs are hard to detect, because very few approaches are sensitive enough to differentiate these from the pool of other cells. Improving the affinity of a selective, surface-functionalized molecule is important given the scarcity of CTCs in vivo. There are several proteins and aptamers that provide such high affinity; however, using surface nanotexturing increases this affinity even further.
The authors report an approach to improve the affinity of tumor cell capture by using novel aptamers against cell membrane overexpressed epidermal growth factor receptors (EGFRs) on a nanotextured polydimethylsiloxane (PDMS) substrate. Surface-immobilized aptamers were used to specifically capture tumor cells from physiologic samples.
The nanotexturing of PDMS increased surface roughness at the nanoscale. This increased the effective surface area and resulted in a significantly higher degree of surface functionalization. The phenomenon resulted in increased density of immobilized EGFR-specific RNA aptamer molecules and provided significantly higher efficiency to capture cancer cells from a mixture. The data indicated that CTCs could be captured and enriched, leading to higher yield yet higher background.
A comparison between glass slides, plain PDMS, and nanotextured PDMS functionalized with aptamers demonstrated that a 2-fold approach of using aptamers on nanotextured PDMS can be important for cancer cytology devices, and especially for the idea of a "lab-on-chip," toward higher yield in capture efficiency.
检测少量的循环肿瘤细胞(CTCs)很重要,尤其是在癌症的早期阶段。由于很少有方法能够足够灵敏地将这些细胞与其他细胞区分开来,因此很难检测到少量的 CTCs。鉴于 CTCs 在体内的稀缺性,提高选择性、表面功能化分子的亲和力很重要。有几种蛋白质和适体可以提供如此高的亲和力;然而,使用表面纳米织构化可以进一步提高这种亲和力。
作者报告了一种使用针对细胞膜过表达表皮生长因子受体(EGFRs)的新型适体来提高肿瘤细胞捕获亲和力的方法,该适体固定在纳米结构化聚二甲基硅氧烷(PDMS)基底上。表面固定的适体用于从生理样本中特异性捕获肿瘤细胞。
PDMS 的纳米织构化增加了纳米尺度上的表面粗糙度。这增加了有效表面积,并导致表面功能化程度显著提高。这种现象导致固定的 EGFR 特异性 RNA 适体分子的密度增加,并显著提高了从混合物中捕获癌细胞的效率。数据表明,可以捕获和富集 CTCs,从而提高产量,但背景也会更高。
将玻璃载玻片、普通 PDMS 与用适体功能化的纳米结构化 PDMS 进行比较表明,在纳米结构化 PDMS 上使用适体的 2 倍方法对于癌症细胞学设备很重要,特别是对于“片上实验室”的想法,以提高捕获效率的产量。