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Research Article

Highly sensitive, scalable, and rapid SARS-CoV-2 biosensor based on In2O3 nanoribbon transistors and phosphatase

Mingrui Chen1,§, Dingzhou Cui2,§, Zhiyuan Zhao1, Di Kang6, Zhen Li3, Shahad Albawardi4, Shahla Alsageer4, Faisal Alamri4, Abrar Alhazmi4, Moh. R. Amer4,5(), Chongwu Zhou1,2()
Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089, USA
Ming Hsieh Department of Electrical Engineering, University of Southern California, Los Angeles, California 90089, USA
Department of Physics and Astronomy, University of Southern California, Los Angeles, California 90089, USA
Center of Excellence for Green Nanotechnologies, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia
Department of Electrical Engineering, 420 Westwood Plaza, 5412 Boelter Hall, University of California, Los Angeles, Los Angeles, California 90095, USA
eDNA Biotech, Pasadena, California 91107, USA

§ Mingrui Chen and Dingzhou Cui contributed equally to this work.

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Graphical Abstract

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A scalable SARS-CoV-2 electronic biosensor using stable phosphatase as enzyme reporter wasdeveloped, which exhibited excellent detection limits. Detection of both spike protein and spikeprotein IgG antibody was achieved in transport and physiological mediums.

Abstract

Developing convenient and accurate SARS-CoV-2 antigen test and serology test is crucial in curbing the global COVID-19 pandemic. In this work, we report an improved indium oxide (In2O3) nanoribbon field-effect transistor (FET) biosensor platform detecting both SARS-CoV-2 antigen and antibody. Our FET biosensors, which were fabricated using a scalable and cost-efficient lithography-free process utilizing shadow masks, consist of an In2O3 channel and a newly developed stable enzyme reporter. During the biosensing process, the phosphatase enzymatic reaction generated pH change of the solution, which was then detected and converted to electrical signal by our In2O3 FETs. The biosensors applied phosphatase as enzyme reporter, which has a much better stability than the widely used urease in FET based biosensors. As proof-of-principle studies, we demonstrate the detection of SARS-CoV-2 spike protein in both phosphate-buffered saline (PBS) buffer and universal transport medium (UTM) (limit of detection [LoD]: 100 fg/mL). Following the SARS-CoV-2 antigen tests, we developed and characterized additional sensors aimed at SARS-CoV-2 IgG antibodies, which is important to trace past infection and vaccination. Our spike protein IgG antibody tests exhibit excellent detection limits in both PBS and human whole blood ((LoD): 1 pg/mL). Our biosensors display similar detection performance in different mediums, demonstrating that our biosensor approach is not limited by Debye screening from salts and can selectively detect biomarkers in physiological fluids. The newly selected enzyme for our platform performs much better performance and longer shelf life which will lead our biosensor platform to be capable for real clinical diagnosis usage.

Keywords

biosensorindium oxide transistorphosphataseSARS-CoV-2 spike proteinSARS-CoV-2 spike IgG antibody

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Nano Research
Volume 15 Issue 6,
June 2022
Pages 5510-5516
DOI: 10.1007/s12274-022-4190-0
Cite this article:
Chen M, Cui D, Zhao Z, et al. Highly sensitive, scalable, and rapid SARS-CoV-2 biosensor based on In2O3 nanoribbon transistors and phosphatase. Nano Research, 2022, 15(6): 5510-5516. https://doi.org/10.1007/s12274-022-4190-0
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