Lab-on-a-Chip Optical Biosensor Platform: Micro Ring Resonator Integrated with Near-Infrared Fourier Transform Spectrometer

A micro-ring-resonator (MRR) optical biosensor based on the evanescent field sensing mechanism has been extensively studied due to its high sensitivity and compact device size. However, a suitable on-chip integrated spectrometer device has to be demonstrated for the lab-on-a-chip applications, which can read the resonance wavelength shift from MRR biosensors based on minuscule changes in refractive index. In this paper, we demonstrated the design and experimental results of the near-infrared lab-on-a-chip optical biosensor platform that monolithically integrates the MRR and the on-chip spectrometer on the silicon-on-insulator (SOI) wafer, which can eliminate the external optical spectrum analyzer for scanning the wavelength spectrum. The symmetric add-drop MRR biosensor is designed to have a free spectral range (FSR) of ~19 nm, and a bulk sensitivity of ~73 nm/RIU; then the drop-port output resonance peaks are reconstructed from the integrated spatial-heterodyne Fourier transform spectrometer (SHFTS) with the spectral resolution of ~3.1 nm and bandwidth of ~50 nm, which results in the limit of detection of 0.042 RIU. The MRR output spectrum with air- and water-claddings are measured and reconstructed from the MRR-SHFTS integrated device experimentally to validate the wavelength shifting measurement.Comment: 23 pages, 9 figures including supplementar

Phase-stabilized dual-comb spectroscopy

Optische Frequenzkämme zeichnen sich durch ihre phasenkohärenten, äquidistanten Laserlinien im Spektrum aus. Gegenwärtig werden sie unter anderem neben ihrem ursprünglichen Verwendungszweck für Frequenzmessungen verwendet. Molekulare Spektroskopie profitiert von der großen spektralen Bandbreite. Die hier vorliegende Arbeit trägt zum Fortschritt von Zwei-Kamm-Spektroskopie bei, einer frequenzkammbasierten Spielart der Fourierinterferometrie ohne bewegliche Teile. Zwei-Kamm-Spektroskopie beruht darauf, Interferenzen in der Zeit-Domäne zwischen zwei Frequenzkämmen mit gering voneinander abweichenden Wiederholraten zu messen. Die Fouriertransformierte des Interferenzmusters spiegelt dabei das Spektrum wider. Die Technik erfordert den kohärenten Betrieb zwischen beiden Frequenzkämmen über die Dauer der Messung. In dieser Arbeit wird eine neue Technik dafür vorgestellt, die auf feed-forward Kontrolle der Differenz im Versatz der Trägerwellenfrequenzen, welche oftmals das hochfrequente Rauschen der Frequenzgeneratoren tragen. Wir zeigen die Möglichkeit, im nahinfraroten Bereich durch direkte Mittelung Interferogramme mit über 2 000 Sekunden Messzeit ohne Abstriche beim Signal-zu-Rausch-Verhältnis und ohne analoge oder digitale Datenkorrektur zu erhalten. Dadurch ergibt sich eine Verbesserung von drei Größenordnungen gegenüber den vormals besten Methoden direkter Mittelung, was eine verbesserte Kontrolle systematischer Effekte bedeutet. Die Ergebnisse konnten durch doppler-verbreiterte Spektrum der v1+v3-Kombination an gasförmigem Acetylen validiert werden. Wir verwenden das entwickelte nahinfrarote Spektrometer, um Spektroskope durch abgeschwächte Totalreflexion an Gasphasen zu demonstrieren. Wir benutzen dabei die Wechselwirkung des evaneszenten Feldes an gezogenen Fasern mit wenigen Molekülen, um Gasvolumina von wenigen Zehn Pikolitern zu untersuchen. Die hohe Auflösung sowie die große spektrale Bandbreite durch Zwei-Kamm-Spektroskopie bleibt dabei erhalten. Wir erweitern die Technik von vorwärtsgerichteten Zwei-Kamm-Spektroskopie in die mittlere Infrarotregion von 3 microns, in der fundamentale Streckschwingungen von CH-, NH- und OH-Gruppen in Molekülen zu finden sind. Anhand von Spektren der v9/v11-dyad von Ethylen demonstrieren wir die gleichen Fähigkeiten des Mittelns von Interferogrammen über einen Zeitraum einer halben Stunden wie im Nahinfrarotbereich. Die Spektren haben eine Frequenzskala, die direkt an einem Wasserstoff-Maser kalibriert wurde mit einer instrumentellen Linienbreite, die drei Größenordnungen schmalbandiger ist als durch Dopplerverbreiterung gegebene Linienbreiten kleiner Moleküle bei Raumtemperatur. Diese Ergebnisse ermöglichen die präzise Bestimmung von spektralen Linien und deren Form in der mittleren Infrarotregion.Optical frequency combs are spectra of phase-coherent evenly spaced laser lines. They currently find applications beyond their initial purpose, frequency metrology. They advance techniques of molecular spectroscopy over broad spectral bandwidths. This thesis is a contribution to the progress of dual-comb spectroscopy, a comb-based technique of Fourier transform interferometry without moving parts. Dual-comb spectroscopy relies on measuring the time domain interference between two frequency combs of slightly different repetition frequencies. The Fourier transform of the interference pattern reveals the spectrum. The technique implies maintaining coherence between the two frequency combs over the time of a measurement. Here, a new technique for achieving this objective is explored: it is based on feed-forward control of the difference in carrier-envelope offset frequencies of the combs, which often carry the high-frequency noise of the synthesizers. In the near-infrared region, we show the possibility to directly average the time-domain interferograms over 2 000 seconds without any loss in signal-to-noise ratio and without any analog or digital corrections to the data. This represents an improvement of three orders of magnitude over the previous best direct averaging capabilities and this may therefore enable a better control of systematic effects. These developments are validated with Doppler-broadened spectra of the v1+v3 combination band of gaseous acetylene. We use the developed near-infrared spectrometer to demonstrate gas-phase attenuated-total-reflectance spectroscopy over broad spectral bandwidths. We use the interaction of the evanescent wave at a fiber taper with small molecules to interrogate gas volumes as little as a few tens of picoliters. The features of high resolution and broad spectral bandwidth brought by dual-comb spectroscopy are preserved. We extend the technique of feed-forward dual-comb spectroscopy to the mid-infrared 3-microns region, where the fundamental CH, NH, OH stretches in molecules are found. With spectra of the v9/v11 dyad of ethylene, we demonstrate the same capabilities of averaging interferograms during half-an-hour as in the near-infrared. The spectra have a frequency scale directly calibrated to a hydrogen maser, an instrumental line shape that is three orders of magnitude narrower than the Doppler width of small molecules at room temperature. These results open up the prospect of precise determination of line positions and line shapes in the mid-infrared range

Multifunctional waveguide interferometer sensor: simultaneous detection of refraction and absorption with size-exclusion function

A waveguide Young interferometer is presented with simultaneous detection of complex refractive index of a liquid sample. The real part of the refractive index change (refraction) is detected by tracing phase shifts of the interferogram generated by a sensing and reference waveguide. The imaginary part of the refractive index (absorption) is determined by the attenuation of the transmitted signal at certain wavelength. Furthermore, nano-filters are fabricated atop the sensing waveguide, which enables size-exclusion filtering of species to the evanescent field. It shows capability of distinguishing small and large particles from 100 nm to 500 nm in diameter, which is further confirmed by fluorescent excitation experiments. The present sensor could find broad application in optical characterization of complex turbid media with regard to their complex refractive index

Techniques in Optical Coherence and Resonance for Sensing

Optical sensors are ubiquitous for their precision and non-contact acquisition, and have enjoyed widespread use in applications such as biosensing, environmental monitoring, and security. Despite their sensitivity, many of these sensors rely on costly laboratory instrumentation, and are not adaptable to the ever-growing volume of consumer detectors and optics that are readily available, making their application limited to benchtop analytics. This work leverages plasmonic resonances and optical coherence phenomena to make modifications upon traditional sensing formats that improve their sensitivity when deployed in off-the-shelf optical systems. In particular, we demonstrate that label-free plasmonic sensors can be combined with electrochemical impedance spectroscopic biosensors to tackle the problem of specificity in label-free sesning, demonstrate the novel use case for the plasmonic detection of thermal infrared radiation, and show that plasmonic imaging is conducive to the characterization of nanometric thin liquid films. Moreover, we show that by introducing limited dispersion to Fourier transform spectroscopy, we can efficiently use camera detector formats and imaging systems to implement a high resolution scan-less Fourier transform spectrometer. By improving the figures of merit for sensor devices, we aim to translate traditional analytical sensing instrumentation from the laboratory benchtop into the consumer marketplace, and to spearhead a host of new applications

Biogratings: Diffractive Transducers for Biosensing in Photonic Platforms

Tesis por compendio[ES] El desarrollo científico y tecnológico de las últimas décadas ha dado lugar a sistemas sensores capaces de obtener, procesar y transmitir información sobre multitud de aspectos físicos y químicos, y utilizarla para mejorar aspectos clave de multitud de áreas de nuestra sociedad. Los sensores químicos son dispositivos compactos y miniaturizados capaces de ofrecer soluciones alternativas a las técnicas de análisis instrumental convencionales. En especial, los biosensores han adquirido gran relevancia por los avances que han supuesto para sectores estratégicos como el diagnóstico clínico, la industria alimentaria y el medio ambiente. Los biosensores ópticos se basan en interacciones entre la luz y la materia para transducir eventos de bioreconocimiento y presentan prestaciones importantes como la estabilidad, inmunidad a estímulos externos y versatilidad en el desarrollo de aproximaciones sin marcaje (label-free). Este último aspecto suele aprovechar fenómenos nanoscópicos y su desarrollo se encuentra muy ligado al progreso de la nanociencia y nanotecnología. Un aspecto clave en el biosensado sin marcaje consiste en descubrir y desarrollar nuevas estrategias de transducción. En este sentido, aunque se encuentren aun en una etapa temprana de desarrollo, los biosensores difractivos presentan un gran potencial en términos de simplicidad, miniaturización, y capacidad para minimizar señales no deseadas fruto de interacciones no específicas, entre otros aspectos.[CA] El desenvolupament científic i tecnològic de les últimes dècades ha donat lloc a sistemes sensors capaços d'obtindre, processar i transmetre informació sobre multitud d'aspectes físics i químics, i utilizar-la per a millorar aspectes clau de multitud d'arees de la nostra societat. Els sensors químics són dispositius compactes i miniaturitzats capaços d'oferir solucions alternatives a les tècniques d'analisi instrumental convencionals. Especialment, els biosensors han adquirit gran rellevància pels avanços que han suposat per als sectors estratègics com el diagnòstic clínic, la industria alimentària i el medi ambient. Els biosensors òptics es basen en interaccions entre la llum i la matèria per a transduir esdeveniments de bioreconèixement i presenten prestacions importants com estabilitat, immunitat a estímuls externs i versatilitat en el desenvolupament d'aproximacions sense marcatge (label-free). Aquest últim aspecte sol aprofitat fenòmens nanoscòpics i el seu desenvolupament es troba molt lligat al progrés de la nanociència i nanotecnologia. Un aspecte clau en el biosensat sense marcatge consisteix a descobrir i desenvolupar noves estratègies de transducció. En aquest sentit, encara que es troben fins i tot en una etapa primerenca de desenvolupament, els biosensors difractius presenten un gran potencial en termes de simplicitat, miniaturització, i capacitat per a minimitzar senyals no desitjats fruit d'interaccions no específiques, entre altres aspectes.[EN] The scientific and technological progress in recent decades has given rise to sensor systems capable of obtaining, processing, and transmitting information on a multitude of physical and chemical aspects and using it to improve key aspects of many areas of our society. Chemical sensors are compact, miniaturized devices capable of offering alternative solutions to conventional instrumental analysis techniques. In particular, biosensors have become highly relevant due to the progress they have brought to strategic sectors such as clinical diagnostics, the food industry, and the environment. Optical biosensors rely on interactions between light and matter to transduce biosensing events and provide important features such as stability, immunity to external stimuli, and versatility in the development of label-free approaches. This last aspect usually exploits nanoscopic phenomena and its development in closely linked to the progress in nanoscience and nanotechnology. A key aspect of label-free biosensing is the discovery and development of new transduction strategies. In this regard, although they are at an early stage of development, diffractive biosensors offer great potential in terms of simplicity, miniaturization, and the ability to minimize unwanted signals from non-specific interactions, among other aspects.This work was financially supported by the Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación (MCIN/AEI/10.13039/501100011033) co-funded by the European Union “ERDF A way of making Europe” (PID2019-110713RB-I00, TED2021-132584B-C21, PID2019-110877GB-I00), Ministerio de Economía y Competitividad (TEC2016-80385-P), Generalitat Valenciana (PROMETEO/2019/048 PROMETEO/2020/094, PROMETEO/2021/015, IDIFEDER/2021/046). A.J.D. ackowledges the FPI-UPV 2017 grant program. The authors acknowledge Instituto de Microelectrónica de Barcelona CNM-CSIC for the support in the fabrication of the measured chip samples on the Multiproject CNM-VLC silicon nitride technology platform.Juste Dolz, AM. (2023). Biogratings: Diffractive Transducers for Biosensing in Photonic Platforms [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/194251Compendi

A whispering gallery mode based biosensor platform for single enzyme analysis

Enzymes catalyze most of the biochemical reactions in our cells. The functionality of enzymes depends on their dynamics starting from small bond vibrations in the fs timescale to large domain motions in the microsecond-millisecond timescale. Understanding the precise and rapid positioning of atoms within a catalytic site by an enzyme’s molecular movements is crucial for understanding biomolecular processes and for realizing synthetic biomolecular machines in the longer term. Hence, sensors capable of studying enzymes over a wide range of amplitudes and timescale and ideally one enzyme at a time are required. Many capable single-molecule techniques have been established in the past three decades, each with its pros and cons. This thesis presents the development of one such single-molecule sensor. The sensor is based on plasmonically enhanced whispering gallery mode resonators and is capable of studying enzyme kinetics and large-scale dynamics over the timescale of ns-seconds. Unlike fluorescence techniques which require labeling of the enzymes with dyes, the technique presented in this work detects single enzymes immobilized on the surface of plasmonic gold nanoparticles. A fast, low-noise, lock-in method is utilized to extract sensor signals in the microsecond timescale. Using a model enzyme, the ability of the sensor to detect conformational fluctuations of single enzymes is shown. Further, the thermodynamics of the enzyme is studied and the relevant thermodynamic parameters are extracted from the single-molecule data. Additionally, we extract the heat capacity changes associated with the enzyme using the single-molecule data. The sensor system presented in this thesis in the future could enable a fast, real-time, rapid throughput, lab-on-chip sensor system for studying single enzymes for both research and clinical use.Engineering and Physical Sciences Research Council (EPSRC)Engineering and Physical Sciences Research Council (EPSRC

Trends in photonic lab-on-chip interferometric biosensors for point-of-care diagnostics

Portable point-of care (POC) devices for in vitro diagnostics will be a milestone for the achievement of universal healthcare and environmental protection. The main goal is to reach a rapid, user-friendly and highly sensitive portable tool which can provide immediate results in any place at any time while having a competitive cost. Integrated optical (IO) waveguide based-biosensors are the most suitable candidates to achieve this ambitious objective. They are able to operate in real samples (such as blood, urine, wastewater…) affording relevant sensitivities even under a label-free scheme. In addition, arrays of IO sensors for multiplexed analysis can be integrated in lab-on-chip (LOC) platforms, providing a truly cost-effective fabrication and miniaturization. Among the different IO biosensors, interferometric ones have demonstrated the highest sensitivity for label-free detection ever reported. Although the first interferometric biosensors were developed in the early nineties, they focused mainly on preliminary proof-of-concept studies; only recently the resilient potential of interferometric biosensors as highly advanced POC devices has firmly emerged. This review provides an overview of the state-of-the art in photonic interferometric biosensors, their main biofunctionalisation routes and their integration in LOC platforms, while maintaining a special focus on the real analytical applications achieved so far

Surface Nanoscale Axial Photonics (SNAP) for Optofluidics

Sensing with optical whispering gallery modes (WGMs) is a rapidly developing detection method in modern microfluidics research. This method explores the perturbations of spectra of WGMs propagating along the wall of an optical microresonator to characterize the liquid medium inside it. Out of the many available types of WGM microresonators, the surface nanoscale axial photonics (SNAP) platform enables fabrication of resonant ultralow loss photonics structures at the surface of an optical fiber with unprecedented precision currently approaching 0.1 angstroms. In this work, first we explore a new technique for the creation of SNAPs, by using a regular hydrogen-oxygen torch, which requires less equipment than current techniques. The transmission spectra shows that light can be fully localized by pulling a fiber, with very low loss resonant modes. We then present the first demonstration of a platform with potential for microfluidic sensing based on SNAP microresonators fabricated in silica capillary fiber with ultra-thin walls by local annealing with a focused CO2 laser and internal etching with hydrofluoric acid. This demonstration paves the groundwork for advanced microfluidic sensing with SNAP microresonators. Finally, we show that light circulating in a silica microcapillary can be fully localized by evanescent coupling to a water droplet forming a high Q-factor microresonator. The discovered phenomenon suggests a novel method for microfluidics sensing and a new type of tunable resonant microfluidic-based photonic devices

Active slow light in silicon photonic crystals : tunable delay and Raman gain

In the past decade, great research effort was inspired by the need to realise active optical functionalities in silicon, in order to develop the full potential of silicon as a photonic platform. In this thesis we explore the possibility of achieving tunable delay and optical gain in silicon, taking advantage of the unique dispersion capabilities of photonic crystals. To achieve tunable optical delay, we adopt a wavelength conversion and group velocity dispersion approach in a miniaturised engineered slow light photonic crystal waveguide. Our scheme is equivalent to a two-step indirect photonic transition, involving an alteration of both the frequency and momentum of an optical pulse, where the former is modified by the adiabatic tuning possibilities enabled by slow light. We apply this concept in a demonstration of continuous tunability of the delay of pulses, and exploit the ultrafast nature of the tuning process to demonstrate manipulation of a single pulse in a train of two pulses. In order to address the propagation loss intrinsic to slow light structures, with a prospect for improving the performance of the tunable delay device, we also investigate the nonlinear effect of stimulated Raman scattering as a means of introducing optical gain in silicon. We study the influence of slowdown factors and pump-induced losses on the evolution of a signal beam along the waveguide, as well as the role of linear propagation loss and mode profile changes typical of realistic photonic crystal structures. We then describe the work conducted for the experimental demonstration of such effect and its enhancement due to slow light. Finally, as the Raman nonlinearity may become useful also in photonic crystal nanocavities, which confine light in very small volumes, we discuss the design and realisation of structures which satisfy the basic requirements on the resonant modes needed for improving Raman scattering

Stimulated Brillouin Scattering in Integrated Circuits: Platforms and Applications

Coherent interactions between light and sound have been of significant interest since the invention of the laser. Stimulated Brillouin scattering (SBS) is a type of coherent interaction where light is scattered from optically generated acoustic waves. SBS is a powerful tool for optical and microwave signal processing, with applications ranging from telecommunications and Radar, to spatial sensing and microscopy. Over the last decade there has been increasing interest in the investigation of Brillouin scattering at device scales smaller than the wavelength of light. New interactions with the waveguide boundaries in these systems are capable of altering the strength of SBS, from complete suppression to orders of magnitude increases. The landmark demonstration of Brillouin scattering in planar waveguides, just six years ago, represents a new frontier for this field. This work explores the effective generation and harnessing of stimulated Brillouin scattering within modern photonic circuits. After establishing the foundations of linear and nonlinear optical circuits, we investigate the Brillouin processes available in multimode waveguides. We experimentally demonstrate giant Brillouin amplification using spiral waveguides consisting of soft-glass materials. We then integrate this soft-glass onto the standard platform for photonic circuits, silicon on insulator, without any reduction in performance. We apply these advanced devices to the field of microwave photonics and create high suppression microwave filters with functionality far beyond traditional electronic circuits. This thesis is a significant step towards Brillouin enabled integrated photonic processors