Self-Assembled DNA Machine and Selective Complexation Recognition Enable Rapid Homogeneous Portable Quantification of Lung Cancer CTCs
Yue Wang,
Congcong Shen,
Chengyong Wu,
Zixuan Zhan,
Runlian Qu,
Yi Xie,
Piaopiao Chen
Affiliations
Yue Wang
Department of Laboratory Medicine, Med+X Center for Manufacturing, Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, National Clinical Research Center for Geriatrics, West China Hospital,
Sichuan University, Chengdu, Sichuan 610041, China.
Congcong Shen
Department of Laboratory Medicine, Med+X Center for Manufacturing, Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, National Clinical Research Center for Geriatrics, West China Hospital,
Sichuan University, Chengdu, Sichuan 610041, China.
Chengyong Wu
Department of Laboratory Medicine, Med+X Center for Manufacturing, Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, National Clinical Research Center for Geriatrics, West China Hospital,
Sichuan University, Chengdu, Sichuan 610041, China.
Zixuan Zhan
Department of Laboratory Medicine, Med+X Center for Manufacturing, Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, National Clinical Research Center for Geriatrics, West China Hospital,
Sichuan University, Chengdu, Sichuan 610041, China.
Runlian Qu
Department of Laboratory Medicine, Med+X Center for Manufacturing, Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, National Clinical Research Center for Geriatrics, West China Hospital,
Sichuan University, Chengdu, Sichuan 610041, China.
Yi Xie
Department of Laboratory Medicine, Med+X Center for Manufacturing, Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, National Clinical Research Center for Geriatrics, West China Hospital,
Sichuan University, Chengdu, Sichuan 610041, China.
Piaopiao Chen
Department of Laboratory Medicine, Med+X Center for Manufacturing, Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, National Clinical Research Center for Geriatrics, West China Hospital,
Sichuan University, Chengdu, Sichuan 610041, China.
In this study, we systematically investigated the interactions between Cu2+ and various biomolecules, including double-stranded DNA, Y-shaped DNA nanospheres, the double strand of the hybridization chain reaction (HCR), the network structure of cross-linked HCR (cHCR), and small molecules (PPi and His), using Cu2+ as an illustrative example. Our research demonstrated that the coordination between Cu2+ and these biomolecules not only is suitable for modulating luminescent material signals through complexation reactions with Cu2+ but also enhances signal intensities in materials based on chemical reactions by increasing spatial site resistance and local concentration. Building upon these findings, we harnessed the potential for signal amplification in self-assembled DNA nanospheres and the selective complexation modulation of calcein in conjunction with the aptamer targeting mucin 1 as a recognition probe. We applied this approach to the analysis of circulating tumor cells, with the lung cancer cell line A549 serving as a representative model. Our assay, utilizing both a fluorometer and a handheld detector, achieved impressive detection limits of ag/ml and single-cell levels for mucin 1 and A549 cells, and this approach was successfully validated using 46 clinical samples, yielding 100% specificity and 86.5% sensitivity. Consequently, our strategy has paved the way for more portable and precise disease diagnosis.
