Dual-Signal Imaging Mode Based on Fluorescence and Electrochemiluminescence for Ultrasensitive Visualization of SARS-CoV-2 Spike Protein

Accurate and reliable detection of SARS-CoV-2 is critical for the effective prevention and rapid containment of COVID-19. Current approaches suffer from complex procedures or a single signal readout, resulting in an increased risk of false negatives and low sensitivity. Here, we developed a fluorescence (FL) and electrochemiluminescence (ECL) dual-mode imaging platform based on a self-powered DNAzyme walker to achieve accurate surveillance of SARS-CoV-2 spike protein at the single-molecule level. The specific activation of the DNAzyme walker by the target protein provides the power for the system’s continuous running, enabling the simultaneous recording of the reduction in fluorescence spots and the appearance of ECL spots generated by the Ru-doped metal–organic framework (MOF) emitter. Therefore, the constructed imaging platform can achieve dual-mode detection of spike protein via reverse dual-signal feedback, which could effectively eliminate false-positive or false-negative signals and improve the detection accuracy and sensitivity with a low detection limit. In particular, the dual-mode accuracy of spike protein diagnosis in samples has been significantly improved compared to single-signal output means. In addition, this dual-mode imaging platform may become a prospective diagnostic device for other infectious viruses.