Progress in Probe-Based Sensing Techniques for In Vivo Diagnosis

Advancements in robotic surgery help to improve the endoluminal diagnosis and treatment with minimally invasive or non-invasive intervention in a precise and safe manner. Miniaturized probe-based sensors can be used to obtain information about endoluminal anatomy, and they can be integrated with medical robots to augment the convenience of robotic operations. The tremendous benefit of having this physiological information during the intervention has led to the development of a variety of in vivo sensing technologies over the past decades. In this paper, we review the probe-based sensing techniques for the in vivo physical and biochemical sensing in China in recent years, especially on in vivo force sensing, temperature sensing, optical coherence tomography/photoacoustic/ultrasound imaging, chemical sensing, and biomarker sensing

Surface Plasmon Resonance for Biosensing

The rise of photonics technologies has driven an extremely fast evolution in biosensing applications. Such rapid progress has created a gap of understanding and insight capability in the general public about advanced sensing systems that have been made progressively available by these new technologies. Thus, there is currently a clear need for moving the meaning of some keywords, such as plasmonic, into the daily vocabulary of a general audience with a reasonable degree of education. The selection of the scientific works reported in this book is carefully balanced between reviews and research papers and has the purpose of presenting a set of applications and case studies sufficiently broad enough to enlighten the reader attention toward the great potential of plasmonic biosensing and the great impact that can be expected in the near future for supporting disease screening and stratification

Roadmap on optical sensors

Optical sensors and sensing technologies are playing a more and more important role in our modern world. From micro-probes to large devices used in such diverse areas like medical diagnosis, defence, monitoring of industrial and environmental conditions, optics can be used in a variety of ways to achieve compact, low cost, stand-off sensing with extreme sensitivity and selectivity. Actually, the challenges to the design and functioning of an optical sensor for a particular application requires intimate knowledge of the optical, material, and environmental properties that can affect its performance. This roadmap on optical sensors addresses different technologies and application areas. It is constituted by twelve contributions authored by world-leading experts, providing insight into the current state-of-the-art and the challenges their respective fields face. Two articles address the area of optical fibre sensors, encompassing both conventional and specialty optical fibres. Several other articles are dedicated to laser-based sensors, micro- and nano-engineered sensors, whispering-gallery mode and plasmonic sensors. The use of optical sensors in chemical, biological and biomedical areas is discussed in some other papers. Different approaches required to satisfy applications at visible, infrared and THz spectral regions are also discussed

Analytical Development and Application of Optical Microcavities

Optical microcavities are desirable label-free sensors due to their sensitive detection capabilities. In particular, microsphere resonators achieve high sensitives by confining and recirculating light within their spherical cavity. Recirculation of light within these small, compact resonators amplifies sample-light interactions, contributing to improved sensing performance. By taking advantage of their desirable performance metrics, we have developed a variety of innovative label-free analytical platforms. For label-free biosensing, we have integrated whispering gallery mode (WGM) resonators with fluorescence imaging for the simultaneous analysis of multiple microspheres. Using this approach, we have demonstrated multiplexed detection of protein biomarkers. Current clinical tools used to diagnose ovarian cancer lack specificity and sensitivity required to achieve an accurate early diagnosis. Label-free platforms provide an opportunity to detect identified protein and non-protein disease biomarkers in order to improve diagnostic capabilities. Whispering gallery mode resonators offer a sensitive, multiplexed detection scheme to accomplish this. Specifically, our developed imaging approach allows multiple targets to be analyzed in a single assay by simultaneously monitoring WGM resonances of numerous microspheres. Microsphere resonators of particular sizes are functionalized for the detection of specific biomarkers. Putative ovarian cancer biomarkers CA-125, osteopontin, and prolactin were simultaneously quantified using WGM imaging. Additionally, the label-free platform was utilized for the detection of non-protein ovarian cancer target microRNA miR-142-3p. For biosensing applications, the small, compact size of microsphere resonators is also advantageous for integration with small volume systems. We demonstrate the incorporation of hundreds of WGM resonators in a 10 L droplet. By incorporating WGM resonators in small volume systems, such as microfluidic platforms, on-chip detection capabilities can be improved. In particular, digital microfluidic systems provide an analytical tool for precise control of discrete volume droplets, improving assay fluidics. In order to integrate WGM resonators with these small volume droplet systems, initial studies demonstrate real-time WGM detection in 10 L droplets. After determining evaporation was not an interferent, picomolar protein concentrations were measured by WGM resonators. Ultimately, these measurements can be extended to improve on-chip multiplexed immunoassay capabilities. To further explore WGM sensing applications, we developed a new analytical technique for label-free analysis of surfaces. Scanning resonator microscopy (SRM) utilizes a modified probe tip to analyze optical and topographic surface features. This novel scanning probe technique provides a label-free, non-invasive approach to investigate a variety of sample types. For material science applications, we demonstrate analysis of thin polymer films patterned by UV light using SRM. Additionally, we are interested in extending SRM measurements for the investigation of biological samples. Scanning resonator microscopy provides a label-free technique to measure protein coated surfaces, such as protein microarrays. Furthermore, for cell-based assays, label-free approaches allow for real time analysis of native biological systems. Initial investigations indicate SRM is a promising analytical tool for improving pre-clinical analysis methods for drug development and for applications in clinical diagnostics. Overall, WGM resonators are demonstrated as sensitive label-free detectors for the development of a variety of analytical tools

Estudio y diseño de dispositivos ópticos biosensores depositados con películas delgadas basados en detección de longitud de onda de resonancias

A lo largo de esta tesis se presenta el estudio y diseño de varias plataformas de guía-ondas ópticas, con el fin de ver su viabilidad a la hora de usarlas como biosensores sobre fibra óptica u otros sustratos fotónicos. En este trabajo se depositan estructuras ópticas como una fibra monomodo desnuda, un estrechamiento en fibra óptica o una fusión de fibras mono – multi – monomodo (SMS) con películas delgadas de materiales usando técnicas nanotecnológicas como el ensamblado capa a capa (LbL-assembly) o el sputtering. Además, se dedica un capítulo al estudio de microresonadores toroidales depositados por rotación (spin-coating). El objetivo es generar o mejorar las prestaciones en resolución y sensibilidad de los fenómenos resonantes que se pueden obtener en estas estructuras ópticas, para luego detectar reacciones biológicas que den lugar a un futuro diagnóstico precoz de enfermedades.Along this thesis, the study and design of several optical waveguide platforms is presented, in order to check their viability when used as biosensors based on either optical fiber or other photonic substrates. In this work, some fiber-optic-based structures such as cladding removed multimode structures, tapered single-mode fibers and single-mode – multimode – single-mode fibers are deposited with thin-films of materials, using nanotechnology-based methods such as layer-by-layer assembly (LbL-assembly) or sputtering. Moreover, a brief chapter is focused on the study of toroidal microring resonators deposited by spin-coating. The final objective is to generate or enhance the parameters of the resonant phenomena obtained in these structures, in terms of resolution and sensitivity. Then, a biological detection is addressed and characterized, to see if they are able to perform a future early diagnosis for illnesses.La realización de este trabajo ha sido posible gracias a las aportaciones económicas recibidas por parte de la Universidad Pública de Navarra (UPNA), así como del patrocinio de la UPNA y del Ministerio de Economía y Competitividad, a través de los proyectos CICYT fondos FEDER TEC2010-17805, TEC2013-43679-R e IPT-2011-1212-920000 (PMEL).Programa Oficial de Doctorado en Ingeniería y Arquitectura (RD 1393/2007)Ingeniaritzako eta Arkitekturako Doktoretza Programa Ofiziala (ED 1393/2007

Microbead-Based Biosensing in Microfluidic Devices

Microbeads are frequently used as a solid support to capture target analytes of interest, such as proteins and nucleic acids, from a biological sample. The integration of microbeads into microfluidic systems for biological testing is an area of growing interest. Such lab-on-chip systems are designed to integrate several functions of a conventional laboratory onto a single chip. As a platform to capture targets, beads offer several advantages over planar surfaces such as large surface areas to support biological interactions (increasing sensitivity), the availability of libraries of beads of various types from many vendors, and array-based formats capable of detecting multiple targets simultaneously (multiplexing). This dissertation describes the development and characterization of microbead-based biosensing devices. A customized hot embossing technique was used to stamp an array of microwells in a thin plastic substrate where appropriately functionalized agarose microbeads were selectively placed within a conduit. Functionalized quantum dot nanoparticles were pumped through the conduit and used as a fluorescent label to monitor binding to the bead. Three-dimensional finite element simulations were carried out to model the mass transfer and binding kinetics on the beads’ surfaces and within the porous beads. The theoretical predictions were critically compared and favorably agreed with experimental observations. A novel method of bead pulsation was shown to improve binding kinetics in porous beads. In addition, the dissertation discusses other types of bead arrays and demonstrates alternative bead-based target capture and detection strategies. This work enhances our understanding of bead-based microfluidic systems and provides a design and optimization tool for developers of point-of-care, lab-on-chip devices for medical diagnosis, food and water quality inspection, and environmental monitoring

Enabling Technology in Optical Fiber Communications: From Device, System to Networking

This book explores the enabling technology in optical fiber communications. It focuses on the state-of-the-art advances from fundamental theories, devices, and subsystems to networking applications as well as future perspectives of optical fiber communications. The topics cover include integrated photonics, fiber optics, fiber and free-space optical communications, and optical networking

All Photonic Bandgap Bragg Fiber Refractometers

Un réfractomètre est un senseur optique permettant de mesurer l’indice de réfraction d’une substance. Depuis que Ernst Abbe a inventé le premier réfractomètre de laboratoire dans les années soixante du dix-neuvième siècle, d’importants efforts ont été faits pour développer de nouveaux types de spectromètres avec une meilleure résolution et une empreinte plus petite. De nos jours, la réfractométrie est une technique fiable largement utilisée dans de nombreux domaines scientifiques et industriels, soit en ce qui a trait aux senseurs biologiques et chimiques, aux tests médicaux, à la gradation des bijoux, à l’industrie pharmaceutique, etc. Récemment, les réfractomètres à base de fibre ont attiré beaucoup l’attention grâce à leurs avantages uniques : leurs faibles pertes, leur légèreté, leur immunité à l’interférence électromagnétique, leur résistance aux environnements hostiles, leur passivité électrique et la possibilité de multiplexage. Aujourd’hui encore, la recherche et le développement de nouveaux réfractomètres à base de fibre ayant de plus hautes résolutions, de plus petites empreintes et un faible coût constituent encore le principal sujet de recherche en réfractométrie. Dans cette thèse, nous proposerons et fabriquerons expérimentalement un réfractomètre à base de fibre servant à la détection de faibles changements d’indice de réfraction dans des échantillons liquides. La composante principale de ce réfractomètre est une fibre de Bragg creuse, possédant un coeur creux entouré par une alternance de couches de polyméthacrylate de méthyl (PMMA) et de polystyrène (PS) servant de réflecteur de Bragg. Le mécanisme de base de cette fibre est la détection de résonance; les variations d’indice de réfraction de l’échantillon liquide induisent un changement de guidage résonant de la fibre, changeant ainsi l’intensité et la fréquence de résonance de la transmission. Les simulations théoriques et la caractérisation expérimentale sont faites pour confirmer les propriétés de ce mécanisme. De plus, nous étudierons en détail les performances de ce réfractomètre à base de fibre de Bragg en s’attardant à la sensibilité, à la plage dynamique, aux pertes d’insertion/couplage, au temps de réponse et à la dépendance de la sensibilité en fonction de la longueur de la fibre. Nous démontrerons expérimentalement que la sensibilité atteint 1400 nm par unité d’indice de réfraction (RIU), ce qui est comparable à la sensibilité propre aux autres réfractomètres à base de fibre microstructurée, et même aux réfractomètres basés sur la résonance de plasmon de surface. Nous noterons aussi que le temps de réponse du réfractomètre développé dans notre laboratoire est beaucoup plus petit que celui des----------Abstract A refractometer is an optical sensor that can be used to measure the refractive index of a substance. Ever since Ernst Abbe invented the first laboratory refractometer in the late sixties of the nineteenth century, tremendous efforts have been undertaken to develop various types of refractometers with better resolution and smaller footprint. Nowadays, refractometry becomes a reliable technique that is widely used in a variety of scientific and industrial fields such as bio/chemical sensing, food industry, medical/clinical examination, jewelry gradation, pharmaceutical and cosmetic industry, to name a few. In recent years, fiber-based refractometers have drawn considerable attention due to their unique advantages such as low signal loss (attenuation), light weight, immunity to electromagnetic interference, resistance to harsh environments, electrical passivity, and possibility of multiplexing. To date, the R&D (research and development) of novel fiber-based refractometers with advantages of high sensitivity, small footprint and low cost still constitutes the main research topic in refractometric studies. In this thesis, we firstly propose and experimentally demonstrate a fiber-based refractometer for sensing small changes in the refractive index of liquid analytes. The key component of the refractometer is a hollow-core polymer Bragg fiber, which features a large hollow core surrounded by an alternating polymethyl methacrylate (PMMA)/polystyrene (PS) multilayer as a Bragg reflector. This Bragg fiber refractometer operates on a resonant sensing mechanism, namely, variations in the refractive index of a liquid analyte filling the fiber core modify the resonant guidance of the fiber, thus leading to both intensity changes and spectral shifts in the fiber transmission. Both theoretical simulations and experimental characterizations are carried out to verify this resonant sensing mechanism of the proposed Bragg fiber refractometer. Moreover, we present a comprehensive study of the factors that affect the performance of Bragg fiber refractometers. These factors include sensitivity, dynamic range, insertion/coupling loss, response time and dependence of the refractometer sensitivity on the fiber length. We experimentally demonstrate that sensitivity of the Bragg fiber refractometers is very high, and is ~1400 nm/refractive index unit (RIU) which is comparable to that of the microstructured-fiber-based refractometers and surface-plasmon-resonance-based refractometers. We also note that such a sensitivity is equivalent to a refractometer resolution of ~7×10-5 RIU, assuming that 0.1 nm spectral shift can be accurately measured (0.1 nm is the typical resolutio