Abstract

Due to the complexity and variability of the cellular metabolic process and the physiological environment inside and outside the cell, higher requirements are needed on the application of DNA molecular logic gate in cell analysis. In addition, heterogeneity of tumor cells tends to lead to false positives in the clinical diagnosis of a single target, even those with the same cancer type. To address these issues above, we have developed a novel DNA molecular logic gate responsive nanomachine for bispecific recognition and computation of cell membranes. Only when two membrane proteins, MUC1 and EpCAM as model proteins, exist simultaneously, the DNA molecular logic gate can be activated to perform “AND” logic operation and generate amplified “ON” fluorescence signal from the cell membrane. Therefore, our proposed dual-specific “recognition-biocomputing” DNA molecular logic gate has achieved highly accurate imaging analysis of dual-target membrane proteins in situ. Furthermore, the logic gate responsive DNA nanomachine can also be used to analyze target cells in complex cell samples with excellent specificity, which will meet the needs of biomedicine and their application in clinical diagnosis and provide new tools for the biomedical application of DNA molecular logic gates in complex cell systems.