Plasmonic biosensing with tilted fiber Bragg gratings interrogated using a 512-pixel spectrometer.

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 < 1 nm) that is usually demodulated using highly resolved (wavelength resolution < 10 pm) devices. This work demonstrates the possibility of using a coarsely resolved spectrometer (166 pm) to read out the amplitude spectrum of a gold-coated TFBG. A refined analysis of the spectral content has allowed us to develop signal processing that provides a refractometric sensitivity of 2656 nm/RIU. This is a fivefold improvement compared to previously reported read-out techniques. Biosensing has then been successfully implemented with gold-coated TFBGs implemented in reflection mode for the detection of insulin, with specific antibodies grafted on the gold surface. Our experimental work is a first step toward the industrialization of the FBG technology, as it opens the door to fast parallel biosensing, profiting from the multiple sensing channels (up to 64) of the interrogator and its high processing speed (repetition rate up to 3 kHz).

Plasmonic sensors based on tilted Bragg gratings in multicore optical fibers.

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.

Multimodal plasmonic optical fiber grating aptasensor.

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.

Optical Fiber Gratings Immunoassays.

Optical fibers are of growing interest for biosensing, especially for point-of-care and biomedical assays. Their intrinsic properties bestow them sought-after assets for the detection of low concentrations of analytes. Tilted fiber Bragg gratings (TFBGs) photo-inscribed in the core of telecommunication-grade optical fibers are known to be highly-sensitive refractometers. In this work, we present different strategies to use them for label-free immunoassays. Bare, gold-sputtered, gold-electroless-plated (ELP) and hybrid configurations are biofunctionalized with antibodies, aiming at the detection of cancer biomarkers. We discuss the relative performances of the tested configurations and show that each leads to singular key features, which therefore drives their selection as a function of the target application. The most sensitive configuration presents a limit of detection of 10-12 g/mL in laboratory settings and was successfully used ex vivo in freshly resected lung tissues.

Insulin biotrapping using plasmofluidic optical fiber chips: A benchmark.

Plasmonic optical fiber-based biosensors are currently in their early stages of development as practical and integrated devices, gradually making their way towards the market. While the majority of these biosensors operate using white light and multimode optical fibers (OFs), our approach centers on single-mode OFs coupled with tilted fiber Bragg gratings (TFBGs) in the near-infrared wavelength range. Our objective is to enhance surface sensitivity and broaden sensing capabilities of OF-based sensors to develop in situ sensing with remote interrogation. In this study, we comprehensively assess their performance in comparison to the gold-standard plasmonic reference, a commercial device based on the Kretschmann-Raether prism configuration. We present their refractive index sensitivity and their capability for insulin sensing using a dedicated microfluidics approach. By optimizing a consistent surface biotrapping methodology, we elucidate the dynamic facets of both technologies and highlight their remarkable sensitivity to variations in bulk and surface properties. The one-to-one comparison between both technologies demonstrates the reliability of optical fiber-based measurements, showcasing similar experimental trends obtained with both the prismatic configuration and gold-coated TFBGs, with an even enhanced limit of detection for the latter. This study lays the foundation for the detection of punctual molecular interactions and opens the way towards the detection of spatially and temporally localized events on the surface of optical probes.

Electro-plasmonic-assisted biosensing of proteins and cells at the surface of optical fiber.

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.

HER2 breast cancer biomarker detection using a sandwich optical fiber assay.

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.

HER2 biosensing through SPR-envelope tracking in plasmonic optical fiber gratings.

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.

Rapid Detection of Circulating Breast Cancer Cells Using a Multiresonant Optical Fiber Aptasensor with Plasmonic Amplification.

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.

Non-enzymatic D-glucose plasmonic optical fiber grating biosensor.

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 ±â€¯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.