Multiplexed Microphotonic Ring Resonator Platform for Simultaneous Detection of SARS-CoV-2 Spike Protein and Respiratory Syncytial Virus-F Protein

The persistent burden imposed by SARS-CoV-2, respiratory syncytial virus (RSV), and other respiratory viruses highlights the demand for real-time, label-free diagnostics capable of multipathogen detection. Despite numerous proposals, existing biosensors have yet to achieve the trifecta of sub-nanomolar sensitivity, simultaneous targeting, and a truly compact footprint. Here, we show a multiplexed photonic biosensor based on cascaded microring resonators (MRRs) that can detect two different viral glycoproteins, such as the SARS-CoV-2 spike protein and the RSV-F protein, at sub-nanomolar concentrations. Three strip-waveguide rings (radii =99, 100, 101 μm; TE mode at 1310 nm) were designed via finite-element modeling and fabricated on a Si3N4-on-insulator platform using e-beam lithography and inductively coupled plasma reactive ion etching (ICP-RIE). Preliminary results demonstrate a quality factor of the order of 105 and a mean bulk sensitivity value of 150 nm/RIU, evaluated in gradually concentrated ethanol solutions flowing on the sensor surface. A common bus waveguide enables wavelength-division multiplexing (WDM). Selective, oriented immobilization of anti-spike and anti-F antibodies is achieved through a protein A interfacial layer, while the central ring is intentionally left bare as an on-chip reference. By sweeping the wavelength of a continuous wave (CW) laser across each resonance, real-time resonance shifts are monitored and quantified via Lorentzian peak fitting. By functionalizing distinct rings with viral proteins-specific antibodies, our chip achieves detection limits of approximately 0.16 nM for the SARS-CoV-2 spike protein and 0.14 nM for the RSV-F protein, matching or surpassing the performance of conventional single-target optical biosensors. Our design allows the analysis of multiple viral antigens in parallel, reducing sample volume and overall test duration. Moreover, an on-chip reference ring ensures robust signal stability by compensating for nonspecific effects, thereby enhancing accuracy and reproducibility. These findings underscore the promise of integrated photonics to reshape point-of-care diagnostics, especially in decentralized or resource-limited settings. We anticipate that this platform’s versatility can be extended to detect additional pathogens or biomolecules, providing a scalable and cost-effective tool for rapid clinical decision-making and epidemiological surveillance.