Small biomolecule immunosensing with plasmonic optical fiber grating sensor.

This study reports on the development of a surface plasmon resonance (SPR) optical fiber biosensor based on tilted fiber Bragg grating technology for direct detection of small biomarkers of interest for lung cancer diagnosis. Since SPR principle relies on the refractive index modifications to sensitively detect mass changes at the gold coated surface, we have proposed here a comparative study in relation to the target size. Two cytokeratin 7 (CK7) samples with a molecular weight ranging from 78 kDa to 2.6 kDa, respectively CK7 full protein and CK7 peptide, have been used for label-free monitoring. This work has first consisted in the elaboration and the characterization of a robust and reproducible bioreceptor, based on antibody/antigen cross-linking. Immobilized antibodies were then utilized as binding agents to investigate the sensitivity of the biosensor towards the two CK7 antigens. Results have highlighted a very good sensitivity of the biosensor response for both samples diluted in phosphate buffer with a higher limit of detection for the larger CK7 full protein. The most groundbreaking nature of this study relies on the detection of small biomolecule CK7 peptides in buffer and in the presence of complex media such as serum, achieving a limit of detection of 0.4 nM.

Fiber-Optic SPR Immunosensors Tailored To Target Epithelial Cells through Membrane Receptors.

We report, for the first time, the use of a surface plasmon resonance (SPR) fiber-optic immunosensor for selective cellular detection through membrane protein targeting. The sensor architecture lies on gold-coated tilted fiber Bragg gratings (Au-coated TFBGs) photoimprinted in the fiber core via a laser technique. TFBGs operate in the near-infrared wavelength range at ∼1550 nm, yielding optical and SPR sensing characteristics that are advantageous for the analyses of cellular bindings and technical compatibility with relatively low-cost telecommunication-grade measurement devices. In this work, we take consider their numerous assets to figure out their ability to selectively detect intact epithelial cells as analytes in cell suspensions in the range of 2-5 × 10(6) cells mL(-1). For this, the probe was first thermally annealed to ensure a strong adhesion of the metallic coating to the fiber surface. Its surface was then functionalized with specific monoclonal antibodies via alkanethiol self-assembled monolayers (SAMs) against extracellular domain of epidermal growth factor receptors (EGFRs) and characterized by peak force tapping atomic force microscopy. A differential diagnosis has been demonstrated between two model systems. The developed immunosensors were able to monitor, in real time, the specific attachment of single intact cells in concentrations from 3 × 10(6) cells mL(-1). Such results confirm that the developed probe fits the lab-on-fiber technology and has the potential to be used as a disposable device for in situ and real-time clinical diagnosis.

Near-infrared grating-assisted SPR optical fiber sensors: design rules for ultimate refractometric sensitivity.

Plasmonic optical fiber sensors are continuously developed for (bio)chemical sensing purposes. Recently, surface plasmon resonance (SPR) generation was achieved in gold-coated tilted fiber Bragg gratings (TFBGs). These sensors probe the surrounding medium with near-infrared narrowband resonances, which enhances both the penetration depth of the evanescent field in the external medium and the wavelength resolution of the interrogation. They constitute a unique configuration to probe all the fiber cladding modes individually. We use them to analyze the modal distribution of gold-coated telecommunication-grade optical fibers immersed in aqueous solutions. Theoretical investigations with a finite-difference complex mode solver are confirmed by experimental data obtained on TFBGs. We show that the refractometric sensitivity varies with the mode order and that the global SPR envelope shift in response to surrounding refractive index (SRI) changes higher than 1e-2 RIU (refractive index unit) can be ~25% bigger than the local SPR mode shift arising from SRI changes limited to 1e-4 RIU. We bring clear evidence that the optimum gold thickness for SPR generation lies in the range between 50 and 70 nm while a cladding diameter decrease from 125 µm to 80 µm enhances the refractometric sensitivity by ~20%. Finally, we demonstrate that the ultimate refractometric sensitivity of cladding modes is ~550 nm/RIU when they are probed by gold-coated TFBGs.

Surface plasmon resonance in eccentric femtosecond-laser-induced fiber Bragg gratings.

Highly localized refractive index modulations are photo-written in the core of pure silica fiber using point-by-point focused UV femtosecond pulses. These specific gratings exhibit a comb-like transmitted amplitude spectrum, with polarization-dependent narrowband cladding mode resonances. In this work, eccentric gratings are surrounded by a gold sheath, allowing the excitation of surface plasmon polaritons (SPP) for radially-polarized light modes. The spectral response is studied as a function of the surrounding refractive index and a maximum sensitivity of 50 nm/RIU (refractive index unit) is reported for a well-defined cladding-mode resonance among the spectral comb. This novel kind of plasmonic fiber grating sensor offers rapidity of production, design flexibility, and high temperature stability.

Anomalous effective strain-optic constants of nonparaxial optical fiber modes.

We demonstrate that the experimental strain-optic coefficients for strong guided modes are not consistent with the accepted photoelastic theory. It is shown that for modes with significant nonparaxial components, such as modes guided by strong refractive index differences or in waveguides with dimensions that are much larger than the wavelengths used, the photoelastic theory should be modified to include the effect of the longitudinal components of the electromagnetic fields of the modes. Moreover, we highlight that the strain-optics coefficients depend on the state of polarization of the mode and provide a formula to calculate the necessary corrections.

Highly sensitive detection of molecular interactions with plasmonic optical fiber grating sensors.

Surface Plasmon resonance (SPR) optical fiber biosensors constitute a miniaturized counterpart to the bulky prism configuration and offer remote operation in very small volumes of analyte. They are a cost-effective and relatively straightforward technique to yield in situ (or even possibly in vivo) molecular detection. The biosensor configuration reported in this work uses nanometric-scale gold-coated tilted fiber Bragg gratings (TFBGs) interrogated by light polarized radially to the optical fiber outer surface, so as to maximize the optical coupling with the SPR. These gratings were recently associated to aptamers to assess their label-free biorecognition capability in buffer and serum solutions. In this work, using the well-acknowledged biotin-streptavidin pair as a benchmark, we go forward in the demonstration of their unique sensitivity. In addition to the monitoring of the self-assembled monolayer (SAM) in real time, we report an unprecedented limit of detection (LOD) as low as 2 pM. Finally, an immunosensing experiment is realized with human transferrin (dissociation constant Kd~10(-8) M(-1)). It allows to assess both the reversibility and the robustness of the SPR-TFBG biosensors and to confirm their high sensitivity.

Polarized spectral combs probe optical fiber surface plasmons.

The high-order cladding modes of conventional single mode fiber come in semi-degenerate pairs corresponding to mostly radially or mostly azimuthally polarized light. Using tilted fiber Bragg gratings to excite these mode families separately, we show how plasmonic coupling to a thin gold coating on the surface of the fiber modifies the effective indices of the modes differently according to polarization and to mode order. In particular, we show the existence of a single "apolarized" grating resonance, with equal effective index for all input polarization states. This special resonance provides direct evidence of the excitation of a surface plasmon on the metal surface but also an absolute wavelength reference that allows for the precise localization of the most sensitive resonances in refractometric and biochemical sensing applications. Two plasmon interrogation methods are proposed, based on wavelength and amplitude measurements. Finally, we use a biotin-streptavidin biomolecular recognition experiment to demonstrate that differential spectral transmission measurements of a fine comb of cladding mode resonances in the vicinity of the apolarized resonance provide the most accurate method to extract information from plasmon-assisted Tilted fiber Bragg gratings, down to pM concentrations and at least 10(-5) refractive index changes.

Interrogation technique for TFBG-SPR refractometers based on differential orthogonal light states.

The generation of near-IR surface plasmon resonance in gold-coated tilted fiber Bragg gratings is strongly dependent on both the polarization state of the transmission light and the property of confining materials (including the coating materials and surrounding media). These dependencies can be advantageously used to demodulate the amplitude spectrum and retrieve the surrounding refractive index. In this paper, we present an automated demodulation technique that measures the surrounding refractive index by comparing the differential amplitude of resonance peaks near the plasmon attenuation for two orthogonal amplitude spectra recorded in the same operating conditions. A mean sensitivity of more than 500 nm per refractive index unit is reported. This new refractive index measurement method is shown to be accurate to 5×10(-5) over a full range of 0.01 in water solutions.