A General Biosensing Strategy Based on Cascade Amplification for Enhanced HIV Detection Sensitivity
Objective: Accurate and rapid detection of disease biomarkers is critical for early diagnosis, timely intervention, and effective disease management. Impact Statement: This strategy is exemplified through the development of 2 biosensors for detecting HIV-1 DNA and HIV-1 p24, biomarkers associated wi...
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American Association for the Advancement of Science (AAAS)
2025-01-01
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Series: | BME Frontiers |
Online Access: | https://spj.science.org/doi/10.34133/bmef.0139 |
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author | Yirui Zhang Jieyu Yan Wangheng Hou Qian Gao Tao Zhang Yan Gao Jingwen Li Kun Han |
author_facet | Yirui Zhang Jieyu Yan Wangheng Hou Qian Gao Tao Zhang Yan Gao Jingwen Li Kun Han |
author_sort | Yirui Zhang |
collection | DOAJ |
description | Objective: Accurate and rapid detection of disease biomarkers is critical for early diagnosis, timely intervention, and effective disease management. Impact Statement: This strategy is exemplified through the development of 2 biosensors for detecting HIV-1 DNA and HIV-1 p24, biomarkers associated with acquired immunodeficiency syndrome (AIDS). Introduction: We propose a general biosensing strategy that leverages a treble signal amplification cascade, demonstrating its versatility and applicability across diverse biomolecular targets. Methods: The method integrates multiple amplification mechanisms to achieve unparalleled sensitivity. Initially, the hybridization of 2 aided probes with the target triggers isothermal amplification facilitated by polymerase and nicking enzyme, providing a robust preliminary signal enhancement. Repeated cycles of primer extension, nicking, and signal primer dissociation then generate multiple signal primers. These primers are further amplified via rolling circle amplification (RCA), resulting in an important secondary signal boost. Finally, the amplified products activate CRISPR-Cas12a-mediated trans-cleavage, achieving a tertiary level of signal enhancement. Results: This cascade amplification approach achieves remarkable sensitivity, with detection limits of 62 aM for nucleic acids and 8.48 pg/ml for proteins, positioning it as a broadly applicable framework. Clinical samples were assayed, which indicates its capability in clinical diagnosis. Conclusion: Beyond HIV detection, the modular design of this strategy allows adaptation for various biomarkers, showcasing its potential as a universal platform for molecular diagnostics in healthcare and research. |
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language | English |
publishDate | 2025-01-01 |
publisher | American Association for the Advancement of Science (AAAS) |
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spelling | doaj-art-24d81a43e2ea4bfabd0e650d0a1933742025-07-02T08:00:13ZengAmerican Association for the Advancement of Science (AAAS)BME Frontiers2765-80312025-01-01610.34133/bmef.0139A General Biosensing Strategy Based on Cascade Amplification for Enhanced HIV Detection SensitivityYirui Zhang0Jieyu Yan1Wangheng Hou2Qian Gao3Tao Zhang4Yan Gao5Jingwen Li6Kun Han7School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou 215163, China.NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, Xiamen University, Xiamen 361102, China.Suzhou Center for Disease Control and Prevention, Suzhou 215004, China.School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.Objective: Accurate and rapid detection of disease biomarkers is critical for early diagnosis, timely intervention, and effective disease management. Impact Statement: This strategy is exemplified through the development of 2 biosensors for detecting HIV-1 DNA and HIV-1 p24, biomarkers associated with acquired immunodeficiency syndrome (AIDS). Introduction: We propose a general biosensing strategy that leverages a treble signal amplification cascade, demonstrating its versatility and applicability across diverse biomolecular targets. Methods: The method integrates multiple amplification mechanisms to achieve unparalleled sensitivity. Initially, the hybridization of 2 aided probes with the target triggers isothermal amplification facilitated by polymerase and nicking enzyme, providing a robust preliminary signal enhancement. Repeated cycles of primer extension, nicking, and signal primer dissociation then generate multiple signal primers. These primers are further amplified via rolling circle amplification (RCA), resulting in an important secondary signal boost. Finally, the amplified products activate CRISPR-Cas12a-mediated trans-cleavage, achieving a tertiary level of signal enhancement. Results: This cascade amplification approach achieves remarkable sensitivity, with detection limits of 62 aM for nucleic acids and 8.48 pg/ml for proteins, positioning it as a broadly applicable framework. Clinical samples were assayed, which indicates its capability in clinical diagnosis. Conclusion: Beyond HIV detection, the modular design of this strategy allows adaptation for various biomarkers, showcasing its potential as a universal platform for molecular diagnostics in healthcare and research.https://spj.science.org/doi/10.34133/bmef.0139 |
spellingShingle | Yirui Zhang Jieyu Yan Wangheng Hou Qian Gao Tao Zhang Yan Gao Jingwen Li Kun Han A General Biosensing Strategy Based on Cascade Amplification for Enhanced HIV Detection Sensitivity BME Frontiers |
title | A General Biosensing Strategy Based on Cascade Amplification for Enhanced HIV Detection Sensitivity |
title_full | A General Biosensing Strategy Based on Cascade Amplification for Enhanced HIV Detection Sensitivity |
title_fullStr | A General Biosensing Strategy Based on Cascade Amplification for Enhanced HIV Detection Sensitivity |
title_full_unstemmed | A General Biosensing Strategy Based on Cascade Amplification for Enhanced HIV Detection Sensitivity |
title_short | A General Biosensing Strategy Based on Cascade Amplification for Enhanced HIV Detection Sensitivity |
title_sort | general biosensing strategy based on cascade amplification for enhanced hiv detection sensitivity |
url | https://spj.science.org/doi/10.34133/bmef.0139 |
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