Temperature-insensitive label-free SARS-CoV-2 spike protein detection based on complementary refractive index and temperature dependence of multi-mode interference and grating resonance

We demonstrated temperature-insensitive, label-free detection of SARS-CoV-2 spike protein (SSP) by harnessing the complementary refractive index and temperature dependence of multi-mode interference (MMI) created by a no-core fiber (NCF) and phase-matched resonance generated by a long-period fiber grating (LPFG). To combine MMI and grating resonance, primarily sensitive to the surrounding medium refractive index (SMRI) and ambient temperature, respectively, a fiber-optic transducer was fabricated by splicing an NCF segment with an LPFG inscribed on double-clad fiber. The transducer was functionalized with human ACE2 receptors to selectively capture SSP. The functionalized sensor head exhibited high SSP selectivity, with overall average wavelength displacements of -253.33 and -160.00 pm in PBS and saliva, respectively, for SSP with concentrations ranging from 1 to 104 ng/mL. These spectral shifts are associated with localized SMRI modulations on the sensor surface induced by specific binding between SSP and ACE2. We also examined the cross-reactivity of the sensor head for MERS-CoV spike protein to confirm its SSP specificity. Moreover, we proved the capability of temperatureindependent SSP detection and ambient temperature measurement by scrutinizing the temperature effect on the sensor performance. Our functionalized fiber transducer showed great promise as a temperature-insensitive and portable platform for rapid SSP detection.