DEVELOPMENT OF A SEMI-DISTRIBUTED INTERFEROMETER FOR SALIVA-BASED DETECTION OF IL-6 AND IL-8 IN ORAL SQUAMOUS CELL CARINOMA

Abstract

Biomarker-based diagnostics offer a promising approach for early cancer detection, while simultaneous analysis of multiple biomarkers can further improve disease diagnosis by enhancing sensitivity and specificity of the detection. Although blood-based tests are widely used for the analysis of biomarkers, they have several limitations such as invasive sampling, the requirement of trained personnel, and specialized laboratory equipment. Saliva, on the other hand, as an easily accessible and non-invasive biofluid, has gained great attention as a diagnostic fluid. Due to its close association with the oral cavity saliva has been extensively investigated as a means of diagnosing oral squamous cell carcinoma (OSCC). Among diagnostic biomolecules, concentrations of interleukin-6 (IL-6) and interleukin (IL-8) are highly correlated with OSCC development. Therefore, in this work, functionalized fiber-optic biosensor based on semi-distributed interferometer (SDI) was developed for joint detection of IL-6 and IL-8 biomarkers in saliva. The biosensor is fabricated in a simple and fast way with <1 minute fabrication time and entirely based on a common arc-fusion splicer. Surface of the biosensor is then biofunctionalized to attach antibodies specific to the biomarkers of choice. The detection system is telecom-fiber oriented and occurs real-time at room temperature using a commercially available multi-channel Fiber-Bragg grating (FBG) analyzer. As a proof-of-concept study, the detection was first validated in phosphate buffered saline (PBS) and then in artificial saliva doped with biomarkers. The data analysis strategy is based on a multi-resonance approach and takes advantage of the entire spectral features, which enhances the robustness and reliability of the detection results. Unlike single-feature approaches, multi-resonance analysis ensures greater resilience to spectral distortions, since the spectral features of the proposed sensor exhibit varying sensitivity to biomolecular interactions. This analysis showed that the sensor demonstrated a limit of detection (LoD) of 480 aM for IL-6 and 23.4 fM for IL-8 in artificial saliva with high specificity to target proteins. It successfully confirmed the ability to distinguish non-target proteins (CD44 and TNF-α).