Volume 20, Issue 18 2307421
Research Article

A Spatially Controlled Proximity Split Tweezer Switch for Enhanced DNA Circuit Construction and Multifunctional Transduction

Dan Bai

Dan Bai

Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), College of Laboratory Medicine, Chongqing Medical Laboratory Microfluidics and SPRi Engineering Research Center, Chongqing Medical University, No. 1 Yi Xue Yuan Road, Chongqing, 400016 P. R. China

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Jianhong Zhang

Jianhong Zhang

Clinical Laboratories, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 P. R. China

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Yaoyi Zhang

Yaoyi Zhang

Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), College of Laboratory Medicine, Chongqing Medical Laboratory Microfluidics and SPRi Engineering Research Center, Chongqing Medical University, No. 1 Yi Xue Yuan Road, Chongqing, 400016 P. R. China

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Hongyan Yu

Hongyan Yu

Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), College of Laboratory Medicine, Chongqing Medical Laboratory Microfluidics and SPRi Engineering Research Center, Chongqing Medical University, No. 1 Yi Xue Yuan Road, Chongqing, 400016 P. R. China

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Li Zhang

Li Zhang

Department of Forensic, Chongqing Medical University, Chongqing, 400016 P. R. China

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Xiaole Han

Xiaole Han

Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), College of Laboratory Medicine, Chongqing Medical Laboratory Microfluidics and SPRi Engineering Research Center, Chongqing Medical University, No. 1 Yi Xue Yuan Road, Chongqing, 400016 P. R. China

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Ke Lv

Ke Lv

Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 40016 P. R. China

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Li Wang

Li Wang

The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 P.R. China

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Wang Luo

Wang Luo

Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), College of Laboratory Medicine, Chongqing Medical Laboratory Microfluidics and SPRi Engineering Research Center, Chongqing Medical University, No. 1 Yi Xue Yuan Road, Chongqing, 400016 P. R. China

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You Wu

You Wu

Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), College of Laboratory Medicine, Chongqing Medical Laboratory Microfluidics and SPRi Engineering Research Center, Chongqing Medical University, No. 1 Yi Xue Yuan Road, Chongqing, 400016 P. R. China

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Xi Zhou

Xi Zhou

Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), College of Laboratory Medicine, Chongqing Medical Laboratory Microfluidics and SPRi Engineering Research Center, Chongqing Medical University, No. 1 Yi Xue Yuan Road, Chongqing, 400016 P. R. China

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Weitao Wang

Weitao Wang

Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), College of Laboratory Medicine, Chongqing Medical Laboratory Microfluidics and SPRi Engineering Research Center, Chongqing Medical University, No. 1 Yi Xue Yuan Road, Chongqing, 400016 P. R. China

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Tong Feng

Tong Feng

Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), College of Laboratory Medicine, Chongqing Medical Laboratory Microfluidics and SPRi Engineering Research Center, Chongqing Medical University, No. 1 Yi Xue Yuan Road, Chongqing, 400016 P. R. China

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Guoming Xie

Corresponding Author

Guoming Xie

Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), College of Laboratory Medicine, Chongqing Medical Laboratory Microfluidics and SPRi Engineering Research Center, Chongqing Medical University, No. 1 Yi Xue Yuan Road, Chongqing, 400016 P. R. China

E-mail: [email protected]

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First published: 10 December 2023
Citations: 2

Abstract

DNA strand displacement reactions are vital for constructing intricate nucleic acid circuits, owing to their programmability and predictability. However, the scarcity of effective methods for eliminating circuit leakages has hampered the construction of circuits with increased complexity. Herein, a versatile strategy is developed that relies on a spatially controlled proximity split tweezer (PST) switch to transduce the biomolecular signals into the independent oligonucleotides. Leveraging the double-stranded rigidity of the tweezer works synergistically with the hindering effect of the hairpin lock, effectively minimizing circuit leakage compared with sequence-level methods. In addition, the freely designed output strand is independent of the target binding sequence, allowing the PST switch conformation to be modulated by nucleic acids, small molecules, and proteins, exhibiting remarkable adaptability to a wide range of targets. Using this platform, established logical operations between different types of targets for multifunctional transduction are successfully established. Most importantly, the platform can be directly coupled with DNA catalytic circuits to further enhance transduction performance. The uniqueness of this platform lies in its design straightforwardness, flexibility, scalable intricacy, and system compatibility. These attributes pave a broad path toward nucleic acid-based development of sophisticated transduction networks, making them widely applied in basic science research and biomedical applications.

Conflict of Interest

The authors declare no conflict of interest.

Data Availability Statement

Research data are not shared.

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