Highly sensitive detection of cancer cells is of great importance for evaluating cancer development and improving survival rates. Here, we developed a split aptamer mediated proximity-induced hybridization chain reaction (HCR) strategy to meet this purpose. In this strategy, two split aptamer initiator probes, Sp-a and Sp-b, and two HCR hairpin probes, H1 and H2 were designed. The split aptamer initiator probes contained two components, split aptamer domains being responsible for target recognition, and the split initiator parts serving as the HCR promoter. In the presence of target cells, Sp-a and Sp-b would self-assemble on the cell surfaces, allowing the formation of an intact nicked initiator to activate the HCR reaction. Benefit from low background split aptamers and HCR amplification, this strategy presented high sensitivity in quantitative detection with a detection limit of 18 cells in 150 μL of binding buffer. Moreover, the approach exhibited excellent specificity to target cells in 10% fetal bovine serum and mixed cell samples, which was favorable for clinical diagnosis in complex biological environment. In addition, by changing the split aptamers attached to the split initiator, the proposed strategy can be expanded to detect various kinds of target cells. It may provide a novel and useful applicable platform for the sensitive detection of cancer cells in biomedicine and tumor-related studies.

癌细胞的高灵敏度检测对于评估癌症的发展和提高生存率非常重要。在这里，我们开发了拆分适体介导的邻近诱导杂交链反应（HCR）策略，以实现此目的。在此策略中，设计了两个拆分的适体引发剂探针Sp-a和Sp-b，以及两个HCR发夹探针H1和H2。分裂的适体引发剂探针包含两个成分，分裂的适体结构域负责靶标识别，分裂的引发剂部分用作HCR启动子。在存在靶细胞的情况下，Sp-a和Sp-b会在细胞表面自组装，从而形成完整的带切口的引发剂来激活HCR反应。受益于低背景拆分的适体和HCR扩增，该策略在定量检测中表现出高灵敏度，在150μL结合缓冲液中的检测限为18个细胞。此外，该方法对10％胎牛血清和混合细胞样品中的靶细胞表现出优异的特异性，这有利于复杂生物环境中的临床诊断。另外，通过改变附着于分裂起始物的分裂适体，可以扩展所提出的策略以检测各种靶细胞。它可以为生物医学和肿瘤相关研究中癌细胞的灵敏检测提供一个新颖而有用的适用平台。有利于复杂生物环境下的临床诊断。另外，通过改变附着于分裂起始物的分裂适体，可以扩展所提出的策略以检测各种靶细胞。它可以为生物医学和肿瘤相关研究中癌细胞的灵敏检测提供一个新颖而有用的适用平台。有利于复杂生物环境下的临床诊断。另外，通过改变附着于分裂起始物的分裂适体，可以扩展所提出的策略以检测各种靶细胞。它可以为生物医学和肿瘤相关研究中癌细胞的灵敏检测提供一个新颖而有用的适用平台。