Optical fiber sensors are of growing interest in biomedical applications, especially for early diagnosis and in situ assays. Their intrinsic properties bring numerous assets for the detection of low concentrations of analytes, such as easy light injection and the possibility to obtain remote and real-time interrogation of very low amounts of analytes. Among the different optical fiber configurations, tilted fiber Bragg gratings (TFBGs) manufactured in the core of telecommunication-grade optical fibers are known to be highly-sensitive and temperature-compensated refractometers, as they couple light to the surrounding medium. In our work, we have used different strategies to turn them into labelfree (plasmonic) immunosensors. Bare and gold-sputtered configurations were biofunctionalized with antibodies and aptamers, aiming at the detection of cancer biomarkers. In this paper, we review the biofunctionalization processes that can be used in these different cases and discuss the obtained performances. For the most sensitive configuration, we report an experimental limit of detection of 10−12 g/mL in laboratory settings.
Tilted fiber Bragg gratings (TFBGs) coupled to the surface plasmon resonance (SPR) phenomenon represent a powerful sensing solution especially for biodetection purposes. Indeed, the excitation of plasmonic waves at the metal-coated surface of the sensor brings a significant improvement in terms of surface sensitivity. Until now, most of experimental results involving SPR have been obtained by using TFBGs inscribed in standard single-mode optical fibers (SMF), which requires the use of a polarizer to select the right state of polarization for plasmonic excitation. Investigations for the development of even more sensitive or robust sensing tools remain a topic of current interest. In this study, the bulk and surface refractometric sensitivities of plasmonic TFBGs photo-inscribed in multimode fiber (MMF) are compared to the one of standard SMF. Gold-coated TFBG in SMF exhibits a sensitivity value of ~102 nm/RIU. Plasmonic MMF TFBGs are more sensitive with a value of ~124 nm/RIU (enhancement of ~22 %) and open the way to multiplexing thanks to the narrowness of their spectral response. Surface refractometry was also assessed through HER2 bioassays (Human Epidermal Growth Factor Receptor-2), a breast cancer biomarker. For that purpose, aptasensors based on antiHER2 aptamers were developed and tested by using these two fiber types. Similar surface sensitivities were obtained for both fiber types.
Biosensors are expected to provide fast, sensitive, and robust detection at low cost. Despite all these constraints which weigh on the development of emerging technologies and conception of new prototypes, the major challenge is still to carry out measurements in complex matrices and hard-to-reach environments. Optical fibers are perfectly suited to fulfill these requirements. In this paper, we investigate the use of tilted fiber Bragg gratings (TFBGs) photo-inscribed in the core of telecommunication-grade optical fibers as biosensors. Thanks to their high refractive index sensitivity, they are able to track molecular interactions happening on their surface. We present different strategies to use them for label-free immunoassays. Bare, gold-sputtered, gold electroless-plated (ELP), and hybrid configurations were functionalized with antibodies, aiming at the detection of cancer biomarkers. We discuss the relative performances of these four configurations and show that each leads to singular key features, driving their own selection as a function of the target application. The optrodes were tested in laboratory settings but also in gelled phantoms and in human resected lung tissues to study the surface plasmon excitation inside complex media, and to discriminate the nature of the tissue through biomarkers detection.
The detection of circulating tumor cells (CTCs) represents an important goal in oncological diagnosis and treatment, as CTCs are responsible for metastasis in several forms of cancer and are present at very low concentration. Their detection should occur at around 1-10 cells/mL of blood for diagnosis purpose. In this work, we propose an all-fiber plasmonic aptasensor featuring multiple narrowband resonances in the near-infrared wavelength range to detect metastatic breast cancer cells. To this aim, specific aptamers against mammaglobin-A proteins were selected and immobilized as bioreceptors on the optical fiber surface. In vitro assays confirm that label-free and real-time detection of cancer cells (LOD of 49 cells/mL) occurs within 5 minutes, while the additional use of functionalized gold nanoparticles allows a two-fold amplification of the biosensor response. Differential measurements on selected optical resonances were used to process the sensor response and results were confirmed by microscopy analysis. The detection of only 10 cancer cells/mL was performed with relevant specificity against non-target cells with comparable sizes and shapes.
Biosensing using optical fibers allows the detection of low concentrated analyte, bringing point-of-care and remote analyses. Tilted fiber Bragg gratings (TFBGs) are permanent structures photo-inscribed inside the core of telecommunication-grade optical fibers and are known to be highly sensitive refractometers. In this paper, we present a hybrid gold deposition method to monitor thin depositions in real time though the inherent properties of the spectra. This yield Surface Plasmon Resonance (SPR) enhancements that is of interest for the detection of low concentrations of analytes. We show how to functionalize our sensors against proteic biomarkers. This strategy is one of a series to manufacture TFBGs platforms adapted for biosensing.