摘要： Fiber-optic biosensors can offer great advantages over other optical technology platforms thanks to the typical features of optical fibers. Moreover, the opportunity of depositing nm-thick overlays on optical fibers with a high degree of accuracy, repeatability and reproducibility has enabled spreading the application domains of this technology. Recently, the concept of guided mode resonance has been exploited in thin film coated fiber-optic sensors, under the name of lossy mode resonance (LMR). LMR occurs when the real part of the thin film permittivity is positive and greater in magnitude than both its own imaginary part and the permittivity of the material surrounding the thin film. Therefore, metallic oxides and polymers can be used to generate LMRs, instead of the noble metals typically used in SPR devices. Instead of using multi-mode fibers, D-shaped single-mode fibers have been used to excite LMR, which enables tracking the spectral displacement of the 1st LMR, the most sensitive LMR, at wavelengths in the NIR, where the sensitivity is enhanced if compared to the visible region. By coating the D-shaped region of the fiber with a nanometric layer of tin oxide (SnO2) and integrating it into an ad-hoc microfluidic system, an ultra-low detection limit (LOD) biosensing device has been developed. The sensing principle is quite simple: when the target analyte interacts with the fiber-functionalized surface, this induces a change in the optical properties of the overlay (i.e. effective refractive index and thickness); in turn, this causes a change in the spectral position of the LMR that can be accurately and precisely measured through a conventional wavelength interrogation system. The deposition of the tin oxide layer (roughly 160-180 nm), which is performed with a DC sputter machine (ND-SCS200, Nadetech S.L.), has been characterized by FESEM images (UltraPlus Carl Zeiss Inc.). The round inset of the same figure details the functionalization of the sensitive region, which is carried out with the deposition of a nm-thick polymeric layer of poly(methyl-methacrylate) (Eudragit L100) that provides free functionalities necessary for the IgG antibody immobilization. The assay has been completed by spiking increasing concentrations of anti-IgG antigen (from 1 pg mL-1 up to 10 μg mL-1) in a real sample of CRP-free human serum. The real-time tracking of the LMR shift has enabled following all the biochemical steps during the assay implementation and then the calibration curve (n=4) of the proposed biosensor has been obtained, together with the sigmoidal fit with the Hill function, which is a well-accepted mathematical model used to quantify the degree of interaction between ligand binding sites. A LOD of 150 fg mL-1 has been attained. This result has confirmed a big leap in performance thanks to the capability to detect analyte concentrations down to few fM in real samples, enhancing the LOD by three orders of magnitude when compared with other fiber-based configurations and matching a LOD comparable with the most outstanding optical technology platforms.