Multiplexed and high-bandwidth DNA computing circuits with superresolution DNA origami displays

DNA computing circuits leverage molecular interactions to construct a highly parallel and biologically compatible information processing paradigm. However, their development has been constrained by a critical gap between intrinsic computational parallelism and the limited readout bandwidth. Multibit outputs from complex circuits often require multiple separate tests, limiting the integration and debugging efficiency. Here, we overcome this bottleneck by decoupling computation from readout via a DNA origami display-based interface by integrating strand displacement and unstable binding reactions. We convert multibit molecular outputs from DNA circuits into spatially resolved geometric bits, enabling direct visualization via superresolution microscopy for high-throughput readout. We experimentally demonstrated the direct readout of an 8-bit decoder circuit and simultaneous display of 16 parallel-running logic gates. This high-bandwidth platform unlocks capabilities in circuit debugging and multiplexed execution, paving the way for large-scale DNA computing and high-throughput biosensing.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-11-13
DOI
https://doi.org/10.1073/pnas.2517114122
Primary Topic
Advanced biosensing and bioanalysis techniques
Type
article
Field-Weighted Citation Impact
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article

Multiplexed and high-bandwidth DNA computing circuits with superresolution DNA origami displays

Chunhai Fan, Hui Lv, Li Jiang, Sisi Jia et al.
Proceedings of the National Academy of Sciences
Advanced biosensing and bioanalysis techniques
article

Multiplexed and high-bandwidth DNA computing circuits with superresolution DNA origami displays

Chunhai Fan, Hui Lv, Li Jiang, Sisi Jia, Yuqing Tang, Kai Xia, Zheze Dai, Qian Li, Fei Wang, Ke Ke, Zhikun Zhao, Zhongchao Jin, Jun Liu
article en

Abstract

DNA computing circuits leverage molecular interactions to construct a highly parallel and biologically compatible information processing paradigm. However, their development has been constrained by a critical gap between intrinsic computational parallelism and the limited readout bandwidth. Multibit outputs from complex circuits often require multiple separate tests, limiting the integration and debugging efficiency. Here, we overcome this bottleneck by decoupling computation from readout via a DNA origami display-based interface by integrating strand displacement and unstable binding reactions. We convert multibit molecular outputs from DNA circuits into spatially resolved geometric bits, enabling direct visualization via superresolution microscopy for high-throughput readout. We experimentally demonstrated the direct readout of an 8-bit decoder circuit and simultaneous display of 16 parallel-running logic gates. This high-bandwidth platform unlocks capabilities in circuit debugging and multiplexed execution, paving the way for large-scale DNA computing and high-throughput biosensing.

Proceedings of the National Academy of SciencesVol. 122(46)
Shanghai University (CN), Jiaxing University (CN), Shanghai Institute of Materia Medica (CN), Shanghai Zhangjiang Laboratory (CN), Lenovo (China) (CN), Chemical Synthesis Lab (SG)
Openalex Percentile: Top 70%
Advanced biosensing and bioanalysis techniques
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