Abstract

AbstractControlling the distance of molecular recognition and signal transduction at the nano–bio interface plays a vital role in sensing molecular interactions, which significantly impacts how a biomarker sensor performs in terms of sensitivity, specificity, detection threshold, and response time. However, conventional biosensing interfaces without the design of distance constraint show limited molecular interactions, hindering target accessibility and mass transport. Nuclei acid‐enabled engineering of biosensing interfaces facilitates highly regulated orientation and programmable density control of biomolecules, providing an effective strategy to improve the performance of biosensing platforms for early diagnosis of diseases and regulation of cellular activities. This review summarizes the recent advances in nucleic acid‐based engineering of biosensing interfaces from a unique perspective of distance constraint effects. The roles of structural nucleic acids in delicately programmed assemblies, functional nucleic acids in molecular recognition, and sensor reactions at well‐controlled distances are highlighted. Then applications of advanced biosensing platforms with the effect of distance constraint are introduced. Finally, the current challenges and future directions for developing such biosensors that can compete effectively to meet the requirements of point‐of‐care testing are also discussed.

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