Médéric Loyez

Cancer biomarker sensing using packaged plasmonic optical fiber gratings: Towards in vivo diagnosis

This work presents the development of an innovative plasmonic optical fiber (OF) immunosensor for the detection of cytokeratin 17 (CK17), a biomarker of interest for lung cancer diagnosis. The development of this sensing platform is such that it can be assessed in non-liquid environments, demonstrating that a surface plasmon resonance (SPR) can be excited in this case. For this purpose, detections have been first carried out on CK17 encapsulated in gel matrix in the aim of mimicking tissue samples. Gold-coated OF immunosensors were embedded in a specifically designed packaging providing enough stiffness to penetrate into soft matters. Resulting reflected spectra have revealed, for the first time, the presence of a stable SPR signal recorded in soft matters. Experiments conducted to detect CK17 trapped in a porous polyacrylamide gel matrix have highlighted the specific and selective biosensor response towards the target protein. Finally, the packaged OF immunosensor has been validated by a preliminary test on human lung biopsy, which has confirmed the ex-vivo CK17 detection. Consequently, this work represents an important milestone towards the detection of biomarkers in tissues, which is still a clinical challenge for minimally-invasive in vivo medical diagnosis.

Plasmonic Optical Fiber-Grating Immunosensing: A Review

Plasmonic immunosensors are usually made of a noble metal (in the form of a film or nanoparticles) on which bioreceptors are grafted to sense analytes based on the antibody/antigen or other affinity mechanism. Optical fiber configurations are a miniaturized counterpart to the bulky Kretschmann prism and allow easy light injection and remote operation. To excite a surface plasmon (SP), the core-guided light is locally outcoupled. Unclad optical fibers were the first configurations reported to this end. Among the different architectures able to bring light in contact with the surrounding medium, a great quantity of research is today being conducted on metal-coated fiber gratings photo-imprinted in the fiber core, as they provide modal features that enable SP generation at any wavelength, especially in the telecommunication window. They are perfectly suited for use with cost-effective high-resolution interrogators, allowing both a high sensitivity and a low limit of detection to be reached in immunosensing. This paper will review recent progress made in this field with different kinds of gratings: uniform, tilted and eccentric short-period gratings as well as long-period fiber gratings. Practical cases will be reported, showing that such sensors can be used in very small volumes of analytes and even possibly applied to in vivo diagnosis.

Evaluation of gold layer configuration for plasmonic fiber grating biosensors

Gold-coated fiber Bragg gratings (FBGs) are nowadays a mature technology for lab-on-fiber sensing based on surface plasmon resonance (SPR) excitation. Tilted FBGs bring valuable assets such as easy light injection, remote operation in very small volumes of analytes and immunity to temperature fluctuations. Different gold configurations have been reported to date, without considering their relative performances in terms of biochemical sensing. In this work, we experimentally study the impact of the gold coating on the cladding mode distribution in the tilted FBG amplitude spectrum and subsequently on its sensitivity to cytokeratins used as biomarkers for cancer diagnosis. Some relevant configurations of gold coatings are produced and tested, relying on both the sputtering and electroless plating (ELP) processes. The obtained results confirm that the coating thickness and its roughness drive the biosensing performances. The experimental limit of detection for cytokeratins 17 sensing reaches 14 fM for the most sensitive configurations.

Requirements for surface plasmon resonance excitation in air with slightly tilted fiber Bragg gratings

Surface plasmon resonance (SPR) excitation has been widely studied in the well-known Kretschmann prism configuration, leading to a large variety of refractometric optical sensors. In recent research, this bulky optical device has found a counterpart thanks to the use of metal-coated optical fibers, mainly allowing to considerably reduce the size of the sensors. Some approaches make use of multimode, etched or unclad fibers while the grating- based alternatives are mostly focused on uniform, long period or tilted fiber Bragg gratings (TFBGs). However, plasmonic optical fiber sensing has been pretty much restricted to aqueous solutions due to the remarkable applications of these devices in (bio)chemical sensing. This work gives the roadmap through SPR excitation in air by using a 10° TFBG refractometer. With regard to aforementioned developments, the photo-inscription process is carried out with an excimer laser emitting at 193 nm, which creates the grating planes in a position close to the core-cladding interface. By doing so, it is possible to obtain a cladding mode resonance comb covering the range of the spectrum that corresponds to refractive index values around the one of the air, without the need of using highly tilted FBGs. Indeed, the coupling of cladding modes to the outer medium can be observed in the optical transmitted spectrum of a bare TFBG. In addition, the thickness of the gold thin-film deposited at the grating location is reduced to one third of the one used for SPR excitation in liquids. In this way, all the cladding modes are reflected by the metal when the TFBG is immersed in solution but when it is left in the air a SPR signature appears in the spectrum. The methods described in the present paper are intended to support further developments on plasmonic optical fiber solutions applied to refractive index sensing in gaseous atmospheres.

Coating influence on the refractometric sensitivity of plasmonic optical fiber grating spectral combs

Gold-coated tilted fiber Bragg gratings (TFBGs) can now be considered as a mature technology for lab-on-fiber sensing based on surface plasmon resonance (SPR) excitation. This sensing architecture brings considerable assets such as easy light injection, temperature fluctuations immunity and remote operation in very small volumes of analytes. Different metal configurations have been used so far, without considerations about their relative performances in terms of surrounding refractive index (SRI) sensing. In this work, we study the impact of the coating on the cladding mode distribution in the TFBG transmitted amplitude spectrum and subsequently on its SRI sensitivity. Different configurations of gold coating are produced and tested, relying on both the sputtering and electroless deposition processes. Interesting spectral features are reported, confirming that the coating thickness and its relative disparity are important design parameters that drive the overall sensing performances.

Cytokeratins Biosensing Using Tilted Fiber Gratings

Optical fiber gratings have widely proven their applicability in biosensing, especially when they are coupled with antibodies for specific antigen recognition. While this is customarily done with fibers coated by a thin metal film to benefit from plasmonic enhancement, in this paper, we propose to study their intrinsic properties, developing a label-free sensor for the detection of biomarkers in real-time without metal coatings for surface plasmon resonances. We focus on the inner properties of our modal sensor by immobilizing receptors directly on the silica surface, and reporting the sensitivity of bare tilted fiber Bragg gratings (TFBGs) used at near infrared wavelengths. We test different strategies to build our sensing surface against cytokeratins and show that the most reliable functionalization method is the electrostatic adsorption of antibodies on the fiber, allowing a limit of detection reaching 14 pM by following the guided cladding modes near the cut-off area. These results present the biodetection performance that TFBGs bring through their modal properties for different functionalizations and data processing strategies.