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Spatiotemporal analysis of cell event membrane-localized biomarkers is crucial for elucidating disease mechanisms and advancing precision medicine. However, due to the limited computing capacity of monovalent logic elements and constraints on signal amplification strategies, current multi-target discrimination is inefficient, hindering progress. Here, we introduce an innovative platform that achieves integrated enhancement of DNA logic gating and spatially confined signals at the membrane interface.In the design, we developed next-generation integrated DNA logic gate elements (iLGE) by encoding traditional monovalent DNA logic units into a multivalent tandem architecture, enabling parallel Boolean operations on multiple biomarkers, tripling computational efficiency and reducing spatial dependence.In addition, by embedding DNA enzyme-mediated signal switches and substrates into multivalent amphiphilic DNA scaffolds, it is possible to design DNA walking devices (DWDs) that can stably anchor to the cell membrane and achieve a dual spatially constrained signal amplification strategy.The platform exhibits high sensitivity and precision in detecting local nucleic acids, proteins, and specific cells at the engineered cell membrane interface, enabling accurate capture and analysis of events including cell damage, cell carcinogenesis, and interactions between NK cells and tumor cells. It provides a novel integrated diagnostic and analytical platform for exploring membrane-localized events and their associated disease mechanisms.

Innovation Points

1. The core innovation of this study lies in overcoming the computational bottleneck of traditional monovalent DNA logic elements. By designing a multivalent tandem architecture, integrated logic gate elements were created, enabling parallel Boolean operations on multiple membrane biomarkers. This approach increased computational efficiency threefold and reduced spatial dependence, laying a technical foundation for the synchronous analysis of complex cell interface signals.2. Another key innovation of the platform is the construction of a membrane-anchored DNA walker device. By combining a DNAzyme signal switch with an amphiphilic scaffold, the process of signal generation and amplification is strictly confined to the vicinity of the membrane interface. This spatial confinement strategy greatly enhances the signal-to-noise ratio and specificity of local detection.

Original link

Integrated DNA logic gate-driven cell membrane confined amplification system for imaging cellular events

Pub Date : 2025-11-20

DOI: 10.1016/j.nantod.2025.102934

Zhenzhen Guo,  Yue Qiu,  Yang Wang,  Jiali Zhang,  Xiaotong Jiang,  Danyu Wang,  Hua Yi,  Mengyu Huang,  Peiru Chen ,  Fangmei Zhang,  Yan Liang,  Fengming Chen,  Hua Gao,  Qiuxia Yang,  Kaixiang Zhang