Ultrasensitive Capture, Detection, and Release of Circulating Tumor Cells Using a Nanochannel–Ion Channel Hybrid Coupled with Electrochemical Detection Technique

Abstract

With the growing demands of the early, accurate, and sensitive diagnosis for cancers, the development of new diagnostic technologies becomes increasingly important. In this study, we proposed a strategy for efficient capture and sensitive detection of circulating tumor cells (CTCs) using an array nanochannel-ion channel hybrid coupled with an electrochemical detection technique. The aptamer probe was immobilized on the ion channel surface to couple with the protein overexpressed on the CTCs membrane. Through this special molecular recognition, CTCs can be selectively captured. The trapped CTCs cover the ion channel entrance efficiently, which will dramatically block the ionic flow through channels, resulting in a varied mass-transfer property of the nanochannel-ion channel hybrid. On the basis of the changed mass-transfer properties, the captured CTCs can be sensitively detected using the electrochemical linear sweep voltammetry technique. Furthermore, due to the amplified response of array channels compared to that of a single channel, the detection sensitivity can be enhanced greatly. The results showed that acute leukemia CCRF-CEM (a type of CTC) concentration as low as 100 cells mL can be successfully captured and detected. The present method provides a simple, sensitive, and label-free technique for CTCs capture, detection, and release, which would hold great potential in the early clinical diagnosis and treatment of cancers.

Biomolecule‐Functionalized Solid‐State Ion Nanochannels/Nanopores: Features and Techniques

“…After that, the biomolecules with NH 2 such as aminated capture DNA shown in Figure a or proteins shown in Figure b can bind to the AAO/PAA nanochannels/nanopores via Schiff base reaction. [73b,97] The APTES‐GA‐Schiff base reaction is called three‐step method. Although the AAO/PAA nanochannels/nanopores are usually not asymmetry in geometry, they can be tuned by surface chemistry such as charge distribution and charge species.…”

“…b) The improved three‐step method to immobilize the bovine serum albumin (BSA) and sgc8c‐NH 2 aptamer onto the PAA membranes. Reproduced with permission . Copyright 2017, American Chemical Society.…”

“…In such case, the typical three‐step APTES‐GA‐Schiff base reaction needs to be improved. Cao et al constructed a nanochannel system to detect the circulating tumor cells (CTCs) . The aptamer probe was applied to recognize the protein overexpressed on the CTCs.…”

Bio-inspired nanochannels: fabrication, modification and bioanalytical applications

“…图 2 (A) 阳极氧化装置原理图 [26] ; (B) 两步阳极氧化工艺制备PAA膜 [28] (网络版彩图) Figure 2 (A) Schematic diagram of the apparatus for anodic oxidation [26]; (B) preparation of PAA membranes by two-step anodic oxidation [28] (color online).…”

“…[58] ; (b) 采用顺序涂覆法构建聚电解质水凝胶/多孔芳纶纳米纤维有机异质膜 [59] ; (c) 通过杂交链反应将DNA水凝胶组装 到Au包覆的锥形纳米通道尖端, 构建刺激响应的复合纳米通道 [60] (网络版彩图) [86,87] . 如图10(a)所示, 2017年, Xia课题组 [88] 图 9 (a) 通过Schiff反应修饰DNA以及DNA自组装和拆卸示意图 [81] ; (b) 将吗啡通过Schiff反应固定在PAA纳米通道上, 使用 电化学检测器实现无标记DNA检测 [82] ; (c) 适配体探针分子直接共价修饰在PAA纳米通道-离子通道杂交结构表面 [28] (网络版 彩图) Figure 9 (a) Modifying of DNA by Schiff reaction and schematic illustration of self-assembly and disassembly of DNA [81]; (b) morphino immobilized on PAA nanochannels by Schiff reaction and detected by electrochemical detector for lable-free DNA monitoring [82]; (c) aptamer probe molecules directly modified on PAA nanochannel-ionchannel hybrid [28] (color online).…”