Simultaneous detection of SARS-CoV-2 S1 protein by using flexible electrochemical and Raman enhancing biochip.

Flexible laser-scribed graphene (LSG) substrates with gold nanoislands have been developed as biochips for in situ electrochemical (EC) and surface-enhanced Raman scattering (SERS) biodetection (biomolecules and viral proteins). A flexible biochip was fabricated using CO2 laser engraving polyimide (PI) films to form a 3D porous graphene-like nanostructure. Gold nanoislands were deposited on the LSG substrates to enhance the intensity of the Raman signals. Moreover, the addition of auxiliary and reference electrodes induced a dual-function EC-SERS biochip with significantly enhanced detection sensitivity. The biochip could selectively and easily capture SARS-CoV-2 S1 protein through the SARS-CoV-2 S1 antibody immobilized on EC-SERS substrates using 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The grafted antibody specifically bound to SARS-CoV-2, resulting in a significant increase in the SERS signal of the target analyte. The limit of detection (LOD) of the SARS-CoV-2 S1 protein was 5 and 100 ng/mL by using EC and SERS detection, respectively. Although the LOD of the SARS-CoV-2 S1 protein detected using SERS is only 100 ng/mL, it can provide fingerprint information for identification. To improve the LOD, EC detection was integrated with SERS detection. The three-electrode detection chip enables the simultaneous detection of SERS and EC signals, which provides complementary information for target identification. The dual-functional detection technology demonstrated in this study has great potential for biomedical applications, such as the rapid and sensitive detection of SARS-CoV-2.