Search

An electro-plasmonic optical fiber grating biosensor was designed to attract and specifically detect breast cancer biomarkers (HER2) using aptamers. The developed biosensor exhibits a high sensitivity with an enhanced limit of detection to HER2.

Plasmonic tilted fiber Bragg gratings (TFBGs) are very efficient for fast, accurate, and minimally invasive biosensing. Their transmitted amplitude spectrum is a dense comb of narrowband cladding mode resonances (full width at half maximum

An electro-plasmonic biosensor is used to attract proteins and cells on the surface of a fiber optic probe by controlled biomolecular migration. Concentrating targets on a high performance plasmon-assisted fiber grating sensor leads to a drastic enhancement of the limit of detection. This architecture relies on a biofunctionalized gold coated tilted fiber Bragg grating (TFBG) that operates as a working electrode to enable electrophoresis in the probed medium. The applied electric field triggers the attraction of proteins over a distance of almost 250 μm from the sensor surface, which is more than two orders of magnitude larger than the intrinsic penetration depth of the plasmon wave. Quantitative determination of target analytes was performed by cyclic voltammetry measurements using the gold coated fiber as an electrode, simultaneously with optical transmission measurements of the underlying fiber grating. In our work, these electro-plasmonic optrodes were used against a clinically-relevant biomarker in breast cancer diagnosis, namely HER2 (Human Epidermal Growth Factor Receptor-2). In vitro assays confirm that their limit of detection lies in the subpicomolar range for proteins, which is beyond reach of similar sensors without voltammetry. The improved detection limit is further facilitated by an improvement of the signal-to-noise ratio of the read-out process. Whole cell capture is finally demonstrated by the same micro-system.

Bare and gold-coated tilted fiber Bragg gratings (TFBGs) can nowadays be considered as a mature technology for volume and surface refractometric sensing, respectively. As for other technologies, a continuous effort is made towards the production of even more sensitive sensors, thereby enabling a high-resolution screening of the surroundings and the possible detection of rare events. To this aim, we study in this work the development of TFBG refractometers in 4-core fibers. In particular, we show that the refractometric sensitivity of the cut-off mode can reach 100 nm/RIU for a bare grating. Using another demodulation method, a tenfold sensitivity increase is obtained when tracking the extremum of the SPR (surface plasmon resonance) envelope for a gold-coated TFBG configuration. Immobilization of DNA probes was performed as a proof-of-concept to assess the high surface sensitivity of the device.

Optical fiber-based surface plasmon resonance (OF-SPR) sensors have demonstrated high versatility and performances over the last years, which propelled the technique to the heart of numerous and original biosensing concepts. In this work, we contribute to this effort and present our recent findings about the detection of breast cancer HER2 biomarkers through OF-SPR optrodes. 1 cm-long sections of 400 μm core-diameter optical fibers were covered with a sputtered gold film, yielding enhanced sensitivity to surface refractive index changes. Studying the impacts of the gold film thickness on the plasmonic spectral response, we improved the quality and reproducibility of the sensors. These achievements were correlated in two ways, using both the central wavelengths of the plasmon resonance and its influence on the bulk refractive index sensitivity. Our dataset was fed by additional biosensing experiments with a direct and indirect approach, relying on aptamers and antibodies specifically implemented in a sandwich layout. HER2 biomarkers were specifically detected at 0.6 μg/mL (5.16 nM) in label-free while the amplification with HER2-antibodies provided a nearly hundredfold signal magnification, reaching 9.3 ng/mL (77.4 pM). We believe that these results harbinger the way for their further use in biomedical samples.

In the biomedical detection context, plasmonic tilted fiber Bragg gratings (TFBGs) have been demonstrated to be a very accurate and sensitive sensing tool, especially well-adapted for biochemical detection. In this work, we have developed an aptasensor following a triple strategy to improve the overall sensing performances and robustness. Single polarization fiber (SPF) is used as biosensor substrate while the demodulation is based on tracking a peculiar feature of the lower envelope of the cladding mode resonances spectrum. This method is highly sensitive and yields wavelength shifts several tens of times higher than the ones reported so far based on the tracking of individual modes of the spectrum. An amplification of the response is further performed through a sandwich assay by the use of specific antibodies. These improvements have been achieved on a biosensor developed for the detection of the HER2 (Human Epidermal Growth Factor Receptor-2) protein, a relevant breast cancer biomarker. These advanced developments can be very interesting for point-of-care biomedical measurements in a convenient practical way.

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.

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.

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.

The detection of circulating tumor cells (CTCs), which are responsible for metastasis in several forms of cancer, represents an important goal in oncological diagnosis and treatment. These cells remain extremely challenging to detect, despite numerous previous studies, due to their low concentration (1-10 cells/mL of blood). In this work, an all-fiber plasmonic aptasensor featuring multiple narrowband resonances in the near-infrared wavelength range was developed to detect metastatic breast cancer cells. To this aim, specific aptamers against mammaglobin-A were selected and immobilized as receptors on the sensor surface. In vitro assays confirm that the label-free and real-time detection of cancer cells [limit of detection (LOD) of 49 cells/mL] occurs within 5 min, while the additional use of functionalized gold nanoparticles allows a 2-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. The detection of only 10 cancer cells/mL was achieved with relevant specificity against control cells and with quick response time.

We report bioassays with gold-coated tilted fiber Bragg gratings functionalized with aptamers for both proteins and cells sensing. Our work is focused towards the measurement of relevant cancer biomarkers. © 2020 The Author(s)

Saccharide sensors represent a broad research area in the scope of sensing devices and their involvement in the medical diagnosis field is particularly relevant for cancer detection at early stage. In that context, we present a non-enzymatic optical fiber-based sensor that makes use of plasmon-assisted tilted fiber Bragg gratings (TFBGs) functionalized for D-glucose biosensing through polydopamine (PDA)-immobilized concanavalin A (Con A). Our probe allows a live and accurate monitoring of the PDA layer deposition leading improved surface biochemistry. The SPR shift observed was assessed to 3.83 ± 0.05 nm within 20 min for a 2 mg/mL dopamine solution. Tests performed in different D-Glucose solutions have revealed a limit of detection close to 10−7 M with the highest sensitivity in the 10−6 to 10−4 M range. This configuration has the capability to overcome the limitations of current enzyme-based solutions.

Introduction Antibiotic detection has become a major issue in many fields such as water analysis, food control, health, etc. Besides the immediate dangers, the spread of antibiotics everywhere provokes the phenomenon of bacterial resistance which, on the long run, will cause health issues. Indeed, the excessive use of antibiotics allows the bacteria to mutate and thus develop resistance, requiring the development of new compounds. This work aims to develop and characterize a sensing material to detect multiple antibiotics in liquid phase using various methods. The idea is to conceive low power sensors or even disposable sensors. Therefore, sensors should be low cost and compatible for mass production. The most interesting sensitive materials seem to be molecularly imprinted polymers (also called MIP) using conductive polymers [1],[2]. Synthesis of the MIP Polypyrrole (PPy) is chosen as conductive polymer to be molecularly imprinted. Pyrrole (Py) is used as the cross-linker and pyrrole-3-carboxylic acid as the functional monomer, to obtain chemical interactions between polymer and the target molecule (also called “template”). The synthesis is performed in-situ (also called bulk polymerization) in aqueous media by mixing the target molecule, the functional monomer and the cross-linker with the oxidizer, ammonium persulfate (APS), while pH value is set to around 2.2, well below the template’s pKa to allow better interactions between monomers and the template. While oxidative polymerization takes place, temperature is kept at 30 °C, for 2 hours. The polymer is deposited everywhere in the reactor, and also on the substrates used to get the sensor. The next step, so-called extraction, consists in removing the template from the polymer. It is performed by using a solution of methanol and HCl (9:1) wherein substrates are immersed for 2 hours [3]. Then, substrates are stored in PBS (phosphate buffered saline) solution before being tested. Non-Imprinted Polymers (NIP) are also synthetized following the same steps, except that the template is not present during the synthesis. Measurement methods Polymerization has been performed on various substrates allowing to use multiple sensing methods to explore as much path as possible. Up to now, sensors had been performed and tested on chemoresistive plastic IDE sensors to perform impedimetric measurements, on quartz crystal microbalance substrates to perform mass variation measurements and on glass slide to perform UV/VIS/NIR absorbance measurements (the ultimate goal is to use the sensing material on optical fibers), as shown on Fig.1. Results and Conclusions Sensors are tested in PBS 0.5x solution (half the usual concentration). After the extraction step carried out on the various substrates, detection is performed by adding the target antibiotic into the PBS solution. Fig. 2 shows impedance measurements and this parameter grows nearly linearly as soon as we add a dozen ppb of the antibiotic. Fig.3 shows that for the same measurement method, the NIP nearly doesn’t react when we add the template, which means that the imprinting is functional and significantly increases the performance of the sensor. Fig. 4 and Fig. 5 show the evolution of the NIR spectrum of the sensing layers after contact with the antibiotic, for the MIP ad NIP, respectively. This method exhibits some limitation with a saturation above 50 ppb. Fig.6 shows the mass evolution on a quartz microbalance of the sensitive layer in contact with the target antibiotic and an interferent with the same concentrations to show the sensor specificity. The response shown to the interferent is quite weak in comparison with the one corresponding to the target molecule. In conclusion, the sensors were found to be able to detect concentrations of approximately 15 ppb and are close to the detection limits of conventional methods (10 ppb). In addition, they have proven their specificity to the target molecule by showing no reaction when exposed to the usual interferents. We showed that the MIP is suitable for both impedimetric sensors as well as for optical sensors (optical fibers or dipsticks for instance). References [1] S. A.Piletsky, N. W.Turner, P. Laitenberger, Molecularly imprinted polymers in clinical diagnostics – future potential and existing problems, Medical Engineering & Physics , 28 (2006), 971-977. doi:10.1016/j.medengphy.2006.05.004 [2] M. Díaz-Bao, R. Barreiro, J. M. Miranda, A. Cepeda et P. Regal, Fast HPLC-MS/MS Method for Determining Penicillin Antibiotics in Infant Formulas Using Molecularly Imprinted Solid-Phase Extraction, Journal of Analytical Methods in Chemistry, 2015 (2015). doi: 10.1155/2015/959675 [3] J. L. Urraca, A. J. Hall, M. C. Moreno‐Bondi, B. Sellergren, A Stoichiometric Molecularly Imprinted Polymer for the Class‐Selective Recognition of Antibiotics in Aqueous Media, Angewandte Chemie, 118 (2006), 5282-5285. doi: 10.1002/ange.200601636 Figure 1

Tilted fiber Bragg gratings (TFBGs) are now a well-established technology in the scientific literature, bringing numerous advantages, especially for biodetection. Significant sensitivity improvements are achieved by exciting plasmon waves on their metal-coated surface. Nowadays, a large part of advances in this topic relies on new strategies aimed at providing sensitivity enhancements. In this work, TFBGs are produced in both single-mode and multimode telecommunication-grade optical fibers, and their relative performances are evaluated for refractometry and biosensing purposes. TFBGs are biofunctionalized with aptamers oriented against HER2 (Human Epidermal Growth Factor Receptor-2), a relevant protein biomarker for breast cancer diagnosis. In vitro assays confirm that the sensing performances of TFBGs in multimode fiber are higher or identical to those of their counterparts in single-mode fiber, respectively, when bulk refractometry or surface biosensing is considered. These observations are confirmed by numerical simulations. TFBGs in multimode fiber bring valuable practical assets, featuring a reduced spectral bandwidth for improved multiplexing possibilities enabling the detection of several biomarkers.