Sensitive electrochemiluminescence detection of cancer cells based on a CdSe/ZnS quantum dot nanocluster by multibranched hybridization chain reaction on gold nanoparticles

In this work, we prepared a novel amplified electrochemiluminescence (ECL) signal probe based on a CdSe/ZnS quantum dot (QD) nanocluster by multibranched DNA hybridization chain reaction (HCR) on gold nanoparticles (GNPs), and developed a sensitive ECL biosensor for the detection of cancer cells. Firstly, a new gold nanorod-hematite nanostructure was used as a magnetic nano-amplified platform to assemble abundant capture DNA (aptamer) on the electrode. Next, the probe DNA was hybridized with the aptamers and multibranched HCR was initiated on the GNPs. Thus the numerous QD nanoclusters showed highly intense ECL signal. Finally, the electrodes were incubated in target cancer cells for 50 min. Upon specific recognition of target cells to aptamers, the signal probes were released from the electrode. Thus a small amount of target cells can trigger the release of a large number of QDs, leading to a remarkable amplification of ECL signal, which was used for sensitive detection of cancer cells. The change of ECL signal was linear to the cell concentrations in the range of 500-10 000 cells mL(-1), and the detection limit was 230 cells mL(-1) at 3s. A series of five duplicate measurements of 2000 cells mL(-1) were used for estimating the precision, and the relative standard was 6.1%. Importantly, the proposed strategy combines the excellent ECL of QDs with cooperative amplification of HCR and the nano-enhanced effect of GNPs, which enables sensitive and selective detection of cancer cells. So far, the QD nanocluster has been used as an ECL signal probe for assays of cancer cells for the first time, and has great potential for early clinical applications in the diagnosis of cancer.

在这项工作中，我们通过在金纳米粒子（GNPs）上进行多分支DNA杂交链式反应（HCR），基于CdSe/ZnS量子点（QD）纳米簇制备了一种新型的放大电化学发光（ECL）信号探针，并开发了一种用于检测癌细胞的灵敏ECL生物传感器。首先，一种新型的金纳米棒 - 赤铁矿纳米结构被用作磁性纳米放大平台，以便在电极上组装大量的捕获DNA（适体）。接下来，探针DNA与适体杂交，并且在GNPs上引发多分支HCR。因此，众多的QD纳米簇显示出高强度的ECL信号。最后，将电极在目标癌细胞中孵育50分钟。在目标细胞与适体特异性识别后，信号探针从电极上释放。因此，少量的目标细胞能够触发大量量子点的释放，导致ECL信号显著放大，这可用于癌细胞的灵敏检测。在500 - 10000个细胞/毫升的范围内，ECL信号的变化与细胞浓度呈线性关系，在3倍标准偏差下检测限为230个细胞/毫升。对2000个细胞/毫升进行了一系列五次重复测量以评估精密度，相对标准偏差为6.1%。重要的是，所提出的策略将量子点优异的ECL性能与HCR的协同放大以及GNPs的纳米增强效应相结合，能够对癌细胞进行灵敏且选择性的检测。到目前为止，QD纳米簇首次被用作检测癌细胞的ECL信号探针，在癌症诊断的早期临床应用中具有巨大潜力。