journal article·2026-03

Accelerated CRISPR/Cas12a‐Based Point‐of‐Care Diagnostics Through Critical Coupling Distance Control

Tong Su, Dan Zhu, Xiaojian Li, Zhibei Qu, Fang Li, Dongming Zhao, Guoqing Shao, Zhixin Feng, Shao Su, Jie Chao, Xiaolei Zuo, Chunhai Fan, Lianhui Wang

Advanced Materials· Volume 38· Issue 16
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Abstract

ABSTRACT Prompt pathogen detection in resource‐limited settings remains constrained by energy‐intensive instrumentation and a shortage of trained personnel. The CRISPR/Cas12a‐based diagnostic technology, despite its robustness as a promising tool, is constrained by suboptimal detection speed and sensitivity. Here we designed triblock DNA‐mediated spherical nucleic acids (tSNA) that acts as a spatially confined reporter with critical coupling distances between substrates, enabling Cas12a protein to rapidly identify concentrated and stretched single‐stranded substrates with size‐matching intervals. Precise control of distances on tSNA of varying sizes revealed a direct correlation between trans‐cleavage efficiency and coupling distance, indicating that only when the distance exceeds the protein size can it offer an appropriate reaction space. It demonstrates a rapid “scooting” reaction model on tSNA, resulting in a trans‐cleavage rate of 10 nm A30‐tSNA 12 times faster and a sensitivity that is two orders of magnitude higher than that in bulk solution. Furthermore, tSNA can serve as a novel recognition and colorimetric element in lateral‐flow strips, thereby reducing the detection time for pathogen nucleic acids to just 3 min. This “size‐matching” model of tSNA offers a new perspective on the regulation of Cas12a enzymatic activity, establishing a versatile platform to advance diagnostic development through ultrafast, CRISPR‐powered POC systems.
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Research context

OpenAlex topics: CRISPR and Genetic Engineering · Advanced biosensing and bioanalysis techniques · Biosensors and Analytical Detection

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Flexible Electronics (LoFE) & Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology Institute of Advanced Materials (IAM) Nanjing University of Posts and Telecommunications Nanjing China

Institute of Molecular Medicine Shanghai Key Laboratory for Nucleic Acids Chemistry and Nanomedicine Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai China

State Key Laboratory of Transducer Technology Shanghai Institute of Microsystem and Information Technology Chinese Academy of Sciences Shanghai China

Department of Medicinal Chemistry School of Pharmacy Fudan University Shanghai China

State Key Laboratory for Animal Disease Control and Prevention National High Containment Facilities For Animal Diseases Control and Prevention Harbin Veterinary Research Institute Chinese Academy of Agricultural Sciences Harbin China

Institute of Veterinary Medicine Jiangsu Academy of Agricultural Sciences Key Laboratory of Veterinary Biological Engineering and Technology Ministry of Agriculture Nanjing China

Macao Translational Medicine Center National Center for Translational Medicine (Shanghai) Maocao Branch Macau University of Science and Technology Macau SAR China

School of Chemistry and Chemical Engineering Frontiers Science Center For Transformative Molecules and National Center For Translational Medicine Shanghai Jiao Tong University Shanghai China

Funding

National Natural Science Foundation of China

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