Rapid and ultrasensitive electromechanical detection of ions, biomolecules and SARS-CoV-2 RNA in unamplified samples

Liqian Wang^#^{1

2

3}, Xuejun Wang^#^{1

2

3}, Yungen Wu^#^{1

2

3}, Mingquan Guo^#⁴, Chenjian Gu⁵, Changhao Dai^{1

2

3}, Derong Kong^{1

2

3}, Yao Wang⁵, Cong Zhang^{1

2

3}, Di Qu⁵, Chunhai Fan⁶, Youhua Xie⁵, Zhaoqin Zhu⁷, Yunqi Liu^{3

8}, Dacheng Wei^{9

10

11}

Affiliations

¹ State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, China.
² Department of Macromolecular Science, Fudan University, Shanghai, China.
³ Laboratory of Molecular Materials and Devices, Fudan University, Shanghai, China.
⁴ Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
⁵ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
⁶ Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁷ Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. zhaoqinzhu@163.com.
⁸ Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
⁹ State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, China. weidc@fudan.edu.cn.
¹⁰ Department of Macromolecular Science, Fudan University, Shanghai, China. weidc@fudan.edu.cn.
¹¹ Laboratory of Molecular Materials and Devices, Fudan University, Shanghai, China. weidc@fudan.edu.cn.

^# Contributed equally.

PMID: 35132229
DOI: 10.1038/s41551-021-00833-7

Rapid and ultrasensitive electromechanical detection of ions, biomolecules and SARS-CoV-2 RNA in unamplified samples

Liqian Wang et al. Nat Biomed Eng. 2022 Mar.

. 2022 Mar;6(3):276-285.

doi: 10.1038/s41551-021-00833-7. Epub 2022 Feb 7.

Authors

Affiliations

¹ State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, China.
² Department of Macromolecular Science, Fudan University, Shanghai, China.
³ Laboratory of Molecular Materials and Devices, Fudan University, Shanghai, China.
⁴ Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
⁵ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
⁶ Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁷ Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. zhaoqinzhu@163.com.
⁸ Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
⁹ State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, China. weidc@fudan.edu.cn.
¹⁰ Department of Macromolecular Science, Fudan University, Shanghai, China. weidc@fudan.edu.cn.
¹¹ Laboratory of Molecular Materials and Devices, Fudan University, Shanghai, China. weidc@fudan.edu.cn.

^# Contributed equally.

PMID: 35132229
DOI: 10.1038/s41551-021-00833-7

Abstract

The detection of samples at ultralow concentrations (one to ten copies in 100 μl) in biofluids is hampered by the orders-of-magnitude higher amounts of 'background' biomolecules. Here we report a molecular system, immobilized on a liquid-gated graphene field-effect transistor and consisting of an aptamer probe bound to a flexible single-stranded DNA cantilever linked to a self-assembled stiff tetrahedral double-stranded DNA structure, for the rapid and ultrasensitive electromechanical detection (down to one to two copies in 100 μl) of unamplified nucleic acids in biofluids, and also of ions, small molecules and proteins, as we show for Hg²⁺, adenosine 5'-triphosphate and thrombin. We implemented an electromechanical biosensor for the detection of SARS-CoV-2 into an integrated and portable prototype device, and show that it detected SARS-CoV-2 RNA in less than four minutes in all nasopharyngeal samples from 33 patients with COVID-19 (with cycle threshold values of 24.9-41.3) and in none of the 54 COVID-19-negative controls, without the need for RNA extraction or nucleic acid amplification.

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Comment in

Fast and sensitive electromechanical sensing.
Inal S. Inal S. Nat Biomed Eng. 2022 Mar;6(3):223-224. doi: 10.1038/s41551-021-00841-7. Nat Biomed Eng. 2022. PMID: 35132227 No abstract available.

References

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Rapid and ultrasensitive electromechanical detection of ions, biomolecules and SARS-CoV-2 RNA in unamplified samples

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Rapid and ultrasensitive electromechanical detection of ions, biomolecules and SARS-CoV-2 RNA in unamplified samples

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