Plasmonic tilted fiber Bragg gratings (TFBGs) are well-suited for accurate, rapid and minimally-invasive biosensing. They present a very dense transmitted amplitude spectrum of narrowband cladding mode resonances (full width at half maximum < 1 nm). This response is commonly demodulated using highly-resolved interrogators (wavelength resolution < 10 pm). This work investigates the possibility of reading-out the amplitude spectrum of a gold-coated TFBG by using a coarsely resolved spectrometer (166 pm). A refractometric sensitivity of 2656 nm/RIU has been observed thanks to a refined analysis of the spectral content which has led to the development a more efficient signal processing. This value represents a fivefold enhancement compared to previously reported read-out methods. Biosensing has been successfully achieved with gold-coated TFBGs used in reflection mode for the detection of insulin, with specific antibodies grafted on the gold surface. Our experimental study is an advance towards an industrialization of the FBG technology, as it opens the way to rapid parallel biodetection, benefiting from the multiple sensing channels (up to 64) of the interrogator as well as its high processing speed (repetition rate up to 3 kHz).
Plasmonic optical fiber Bragg gratings offer a large range of opportunities in many biosensing applications by providing well-suited solutions for continuous and accurate monitoring. One of the most preferred configurations relies on surface plasmon resonance (SPR) implemented on tilted fiber Bragg grating (TFBG) by covering it with a very thin metal sheath (mostly gold), responsible for a drastic sensitivity improvement. When bioreceptors are immobilized onto the sensitive area, a plasmonic TFBG-based sensor leads to a highly sensitive and specific biosensor. Nevertheless, all possibilities using such a versatile platform were not totally investigated yet. Indeed, in addition to generate a plasmonic effect, the gold layer can also serve as a working electrode in an electrochemical set-up. By applying an electric field, it is possible to attract and detect molecules in solution. In this work, we developed the technique in the frame of the detection of the HER2 (Human Epidermal Growth Factor Receptor-2) protein, a relevant biomarker in breast cancer diagnosis. For that purpose, we biofunctionalized the probe using anti-HER2 aptamers with a high affinity to HER2 before performing a specific electrophoresis on gold-coated gratings. Results show a significant improvement in the sensitivity in comparison with the common non-electrochemical approach. The strength of this new sensing method is based on the ability to tweeze and detect targeted biomarkers with the same sensor. This method opens the way to more robust and reliable biosensing measurements with enhanced sensitivity.
Heart failure (HF) is a serious and debilitating cardiovascular disease responsible for high mortality and morbidity rates worldwide, as well as expensive healthcare costs. In HF, there is an increase in circulating concentrations of cardiac biomarkers such as N-terminal B-type natriuretic peptide (NT-proBNP), which can be used for its diagnosis and prognosis. Biosensors have emerged as an appealing alternative to conventional methods of detection, being capable of providing a quick response and allowing detection at point of care. Tilted fiber Bragg gratings (TFBGs) present a high sensitivity to refractive index (RI) variations occurring in the surrounding medium and hence were employed in this work to develop a biosensor for NT-proBNP detection. Two immunosensors were exploited based on a bare TFBG and a gold coated TFBG (Au-TFBG), and, in both cases, distinct spectral demodulation methods were studied to evaluate the sensing performance. The NT-proBNP detection was carried out using the immunosensors properly biofunctionalized, in the 0.01-1000 ng/mL concentration range. The best performance results were obtained by computing the lower envelope of the spectra and following its variations for both bare and Au-coated TFBGs, with the latter exhibiting a lower limit of detection of 0.19 ng/mL. Moreover, a control test was done for each immunosensor to test the specificity. The findings reached in the present work highlight the great diversity of spectral demodulation methods and their impact on the sensing performance, having to be considered upon comparison between TFBG-based biosensors.
Gold-coated tilted fiber Bragg gratings (TFBGs) have been extensively studied over the past years, particularly for biosensing purposes. Surface Plasmon Resonance (SPR) is generated through the deposition of a gold layer of appropriate thickness onto the grating region. The combination of SPR and TFBG permits to create a comb-like spectrum of narrow-band cladding mode resonances, which is usually demodulated by tracking the change of optical features of a selected peak. Here, for the first time to the best of our knowledge, a twenty-fold more sensitive demodulation technique based on the intersection of the upper and lower envelopes of gold-coated TFBG spectra is presented. This method has been successfully applied in biosensing for the detection of HER2 (Human Epidermal Growth Factor Receptor-2) proteins, a crucial breast cancer biomarker. Some practical improvements have also been proposed and assessed: first, a uniform FBG has been superimposed on the TFBG to reduce the read-out wavelength span to 10 nm instead of 70 nm, while keeping the temperature-compensated measurements; second, a microfluidic system has been designed and integrated to inject the samples towards the sensor at controlled flow rates. All these novelties make this sensing platform even more attractive and promising for use in practical applications.
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.
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.
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.
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.
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