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

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.

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 I _DS-V _DS 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.