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. 2022 Mar 28;15(6):5510–5516. doi: 10.1007/s12274-022-4190-0

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

Mingrui Chen 1,#, Dingzhou Cui 2,#, Zhiyuan Zhao 1, Di Kang 6, Zhen Li 3, Shahad Albawardi 4, Shahla Alsageer 4, Faisal Alamri 4, Abrar Alhazmi 4, Moh R Amer 4,5,✉, Chongwu Zhou 1,2,✉
PMCID: PMC8959552  PMID: 35371413

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.

graphic file with name 12274_2022_4190_Fig1_HTML.jpg

Electronic Supplementary Material

Supplementary material (materials and methods for device fabrication, functionalization of In2O3 devices, photographs of the liquid gate measurement setup, mobilities of the nine devices labeled in Fig. 1(b), family curves of IDS-VDS with the liquid gate setup and current change after bubbling the substrate solution (current vs. time curve for S1 antigen detection)) is available in the online version of this article at 10.1007/s12274-022-4190-0.

Keywords: biosensor, indium oxide transistor, phosphatase, SARS-CoV-2 spike protein, SARS-CoV-2 spike IgG antibody

Electronic Supplementary Material

12274_2022_4190_MOESM1_ESM.pdf (2MB, pdf)

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

Acknowledgements

We would like to acknowledge the financial support of this research by King Abdul-Aziz City for Science and Technology (KACST) through The Center of Excellence for Nanotechnologies (CEGN).

Footnotes

Mingrui Chen and Dingzhou Cui contributed equally to this work.

Contributor Information

Moh. R. Amer, Email: mamer@seas.ucla.edu

Chongwu Zhou, Email: chongwuz@usc.edu.

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Supplementary Materials

12274_2022_4190_MOESM1_ESM.pdf (2MB, pdf)

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

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