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 10 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 temperature-independent 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.