Biological Lasers for Biomedical Applications

A biolaser utilizes biological materials as part of its gain medium and/or part of its cavity. It can also be a micro- or nanosized laser embedded/integrated within biological materials. The biolaser employs lasing emission rather than regular fluorescence as the sensing signal and therefore has a number of unique advantages that can be explored for broad applications in biosensing, labeling, tracking, contrast agent development, and bioimaging. This article reports on the progress in biolasers with focus on the work done in the past five years. In the end, the possible future directions of the biolaser are discussed.Biolasers and their applications in biology and biomedicine are reviewed in this progress report. The biolaser employs lasing emission rather than regular fluorescence as the sensing signal and therefore has a number of unique advantages that can be explored for broad applications in biosensing, labeling, tracking, contrast agent development, and bioimaging.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151258/1/adom201900377.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151258/2/adom201900377_am.pd

Advances in Optofluidics

Optofluidics a niche research field that integrates optics with microfluidics. It started with elegant demonstrations of the passive interaction of light and liquid media such as liquid waveguides and liquid tunable lenses. Recently, the optofluidics continues the advance in liquid-based optical devices/systems. In addition, it has expanded rapidly into many other fields that involve lightwave (or photon) and liquid media. This Special Issue invites review articles (only review articles) that update the latest progress of the optofluidics in various aspects, such as new functional devices, new integrated systems, new fabrication techniques, new applications, etc. It covers, but is not limited to, topics such as micro-optics in liquid media, optofluidic sensors, integrated micro-optical systems, displays, optofluidics-on-fibers, optofluidic manipulation, energy and environmental applciations, and so on

On-Chip Fabry-Pérot Microcavity for Refractive Index Cytometry and Deformability Characterization of Single Cells

Une identification correcte et précise du phénotype et des fonctions cellulaires est fondamentale pour le diagnostic de plusieurs pathologies ainsi qu’à la compréhension de phénomènes biologiques tels que la croissance, les réponses immunitaires et l’évolution de maladies. Conséquemment, le développement de technologies de pointe offrant une mesure multiparamétrique à haut débit est capital. À cet égard, la cytométrie en flux est l’étalon de référence due à sa grande spécificité, sa grande sensibilité et ses débits élevés. Ces performances sont atteintes grâce à l’évaluation précise du taux d’émission de fluorophores, conjugués à des anticorps, ciblant certains traits cellulaires spécifiques. Néanmoins, sans ce précieux étiquetage, les propriétés physiques caractérisées par la cytométrie sont limitées à la taille et la granularité des cellules. Bien que la cytométrie en flux soit fondamentalement un détecteur optique, elle ne tire pas avantage de l’indice de réfraction, un paramètre reflétant la composition interne de la cellule. Dans la littérature, l’indice de réfraction cellulaire a été utilisé comme paramètre phénotypique discriminant pour la détection de nombreux cancers, d’infections, de la malaria ou encore de l’anémie. Également, les structures fluidiques de la cytométrie sont conçues afin d’empêcher une déformation cellulaire de se produire. Cependant, les preuves que la déformabilité est un indicateur de plusieurs pathologies et d’état de santé cellulaire sont manifestes. Pour ces raisons, l’étude de l’indice de réfraction et de la déformabilité cellulaire en tant que paramètres discriminants est une avenue prometteuse pour l’identification de phénotypes cellulaires. En conséquence, de nombreux biodétecteurs qui exploitent l’une ou l’autre de ces propriétés cellulaires ont émergé au cours des dernières années. D’une part, les dispositifs microfluidiques sont des candidats idéaux pour la caractérisation mécanique de cellules individuelles. En effet, la taille des structures microfluidiques permet un contrôle rigoureux de l’écoulement ainsi que de ses attributs. D’autre part, les dispositifs microphotoniques excellent dans la détection de faibles variations d’indice de réfraction, ce qui est critique pour un phénotypage cellulaire correcte. Par conséquent, l’intégration de composants microfluidiques et microphotoniques à l’intérieur d’un dispositif unique permet d’exploiter ces propriétés cellulaires d’intérêt. Néanmoins, les dispositifs capables d’atteindre une faible limite de détection de l’indice de réfraction tels que les détecteurs à champ évanescent souffrent de faibles profondeurs de pénétration. Ces dispositifs sont donc plus adéquats pour la détection de fluides ou de molécules. De manière opposée, les détecteurs interférométriques tels que les Fabry- Pérots sont sensibles aux éléments présents à l’intérieur de leurs cavités, lesquelles peuvent mesurer jusqu’à plusieurs dizaines de micromètres.----------Abstract Accurate identification of cellular phenotype and function is fundamental to the diagnostic of many pathologies as well as to the comprehension of biological phenomena such as growth, immune responses and diseases development. Consequently, development of state-of-theart technologies offering high-throughput and multiparametric single cell measurement is crucial. Therein, flow cytometry has become the gold standard due to its high specificity and sensitivity while reaching a high-throughput. Its marked performance is a result of its ability to precisely evaluate expression levels of antibody-fluorophore complexes targeting specific cellular features. However, without this precious fluorescence labelling, characterized physical properties are limited to the size and granularity. Despite flow cytometry fundamentally being an optical sensor, it does not take full advantage of the refractive index (RI), a valuable labelfree measurand which reflects the internal composition of a cell. Notably, the cellular RI has proven to be a discriminant phenotypic parameter for various cancer, infections, malaria and anemia. Moreover, flow cytometry is designed to prevent cellular deformation but there is growing evidence that deformability is an indicator of many pathologies, cell health and state. Therefore, cellular RI and deformability are promising avenues to discriminate and identify cellular phenotypes. Novel biosensors exploiting these cellular properties have emerged in the last few years. On one hand, microfluidic devices are ideal candidates to characterize single cells mechanical properties at large rates due to their small structures and controllable flow characteristics. On the other hand, microphotonic devices can detect very small RI variations, critical for an accurate cellular phenotyping. Hence, the integration of microfluidic and microphotonic components on a single device can harness these promising cellular physical properties. However, devices achieving very small RI limit of detection (LOD) such as evanescent field sensors suffer from very short penetration depths and thus are better suited for fluid or single molecule detection. In opposition, interference sensors such as Fabry-Pérots are sensitive to the medium inside their cavity, which can be several tens of micrometers in length, and thus are ideally suited for whole-cell measurement. Still, most of these volume sensors suffer from large LOD or require out-of-plane setups not appropriate for an integrated solution. Such a complex integration of high-throughput, sensitivity and large penetration depth on-chip is an ongoing challenge. Besides, simultaneous characterization of whole-cell RI and deformability has never been reported in the literature

Recent advances in biomedical photonic sensors: a focus on optical-fibre-based sensing

In this invited review, we provide an overview of the recent advances in biomedical pho tonic sensors within the last five years. This review is focused on works using optical-fibre technology, employing diverse optical fibres, sensing techniques, and configurations applied in several medical fields. We identified technical innovations and advancements with increased implementations of optical-fibre sensors, multiparameter sensors, and control systems in real applications. Examples of outstanding optical-fibre sensor performances for physical and biochemical parameters are covered, including diverse sensing strategies and fibre-optical probes for integration into medical instruments such as catheters, needles, or endoscopes.This work was supported by Ministerio de Ciencia e Innovación and Agencia Estatal de Investigación (PID2019-107270RB-C21/AEI/10.13039/501100011033), and TeDFeS Project (RTC-2017- 6321-1) co-funded by European FEDER funds. M.O. and J.F.A. received funding from Ministerio de Ciencia, Innovación y Universidades of Spain under Juan de la Cierva-Formación and Juan de la Cierva-Incorporación grants, respectively. P.R-V. received funding from Ministerio de Educación, Cultura y Deporte of Spain under PhD grant FPU2018/02797

Optical Response of Plasmonic Nanohole Arrays: Comparison of Square and Hexagonal Lattices

Nanohole arrays in metal films allow extraordinary optical transmission (EOT); the phenomenon is highly advantageous for biosensing applications. In this article, we theoretically investigate the performance of refractive index sensors, utilizing square and hexagonal arrays of nanoholes, that can monitor the spectral position of EOT signals. We present near- and far-field characteristics of the aperture arrays and investigate the influence of geometrical device parameters in detail. We numerically compare the refractive index sensitivities of the two lattice geometries and show that the hexagonal array supports larger figure-of-merit values due to its sharper EOT response. Furthermore, the presence of a thin dielectric film that covers the gold surface and mimics a biomolecular layer causes larger spectral shifts within the EOT resonance for the hexagonal array. We also investigate the dependence of the transmission responses on hole radius and demonstrate that hexagonal lattice is highly promising for applications demanding strong light transmission.Brno University of Technology (Project CZ.1.07/2.3.00/30.0039

Organic lasers: recent developments on materials, device geometries, and fabrication techniques

MCG acknowledges financial support through the ERC Starting Grant ABLASE (640012) and the European Union Marie Curie Career Integration Grant (PCIG12-GA-2012-334407). AJCK acknowledges financial support by the German Federal Ministry for Education and Research through a NanoMatFutur research group (BMBF grant no. 13N13522).Organic dyes have been used as gain medium for lasers since the 1960s, long before the advent of today’s organic electronic devices. Organic gain materials are highly attractive for lasing due to their chemical tunability and large stimulated emission cross section. While the traditional dye laser has been largely replaced by solid-state lasers, a number of new and miniaturized organic lasers have emerged that hold great potential for lab-on-chip applications, biointegration, low-cost sensing and related areas, which benefit from the unique properties of organic gain materials. On the fundamental level, these include high exciton binding energy, low refractive index (compared to inorganic semiconductors), and ease of spectral and chemical tuning. On a technological level, mechanical flexibility and compatibility with simple processing techniques such as printing, roll-to-roll, self-assembly, and soft-lithography are most relevant. Here, the authors provide a comprehensive review of the developments in the field over the past decade, discussing recent advances in organic gain materials, which are today often based on solid-state organic semiconductors, as well as optical feedback structures, and device fabrication. Recent efforts toward continuous wave operation and electrical pumping of solid-state organic lasers are reviewed, and new device concepts and emerging applications are summarized.PostprintPeer reviewe

An Optofluidic Surface Enhanced Raman Spectroscopy Microsystem for Sensitive Detection of Chemical and Biological molecules

As the human population grows, there is an increasing demand for early detection of a variety of analytes in different fields. This demand mainly includes early and sensitive detection of pathogens, disease biomarkers, pesticides, food contaminants, and explosives. To address this, lab-on-a-chip (LOC) technology has emerged as a tool to improve portability, automation and sensitivity of sensors by taking advantage of integrated laboratory functions on a miniaturized chip. It is agreed that LOC has the potential to make various sensing modules practical for real- world applications. In this work, we have developed a highly sensitive, portable, and automated optofluidic surface enhanced Raman spectroscopy (SERS) microsystem for chemical and biological detection. SERS is a powerful molecular identification technique that combines laser spectroscopy with optical properties of metal nanoparticles. Optofluidic SERS is defined as the synergistic use of microfluidic functions to improve the performance of SERS. By leveraging microfluidic functions, the optofluidic SERS microsystem mixes and concentrates the sample and nanoparticles resulting in an improved performance as compared to conventional open microfluidic SERS systems. The device requires low sample volume and has multiplexed detection capabilities. Moreover, it is suitable for on-site detection of analytes in the field because of its improved automation and portability due to the integrated fiber optics. The final device consists of two regions of packed silica beads inside microchannels for biomolecular interaction as well as sample concentration for SERS measurements. Additionally, an on-chip micromixer and fiber optics are integrated into the device. Optical fibers aligned to the detection zone make the biosensor alignment-free, which greatly improves automation. Practical applications for the detection of real-world analytes (e.g., pesticides, fungicides, food contaminants, and DNA sequences) are demonstrated utilizing our optofluidic SERS microsystem. Detection of biological samples could be extended to proteins and proteolytic enzymes through displacement assays. Consequently, the integration of microfluidic functions, including a microporous reaction zone, a nanoparticle concentration zone, and a micromixer, combined with the use of integrated fiber optics and portable spectrometers, make our microsystem suitable for on-site detection of analytes at trace levels

Trends in Nanophotonics-Enabled Optofluidic Biosensors

Optofluidic sensors integrate photonics with micro/nanofluidics to realize compact devices for the label-free detection of molecules and the real-time monitoring of dynamic surface binding events with high specificity, ultrahigh sensitivity, low detection limit, and multiplexing capability. Nanophotonic structures composed of metallic and/or dielectric building blocks excel at focusing light into ultrasmall volumes, creating enhanced electromagnetic near-fields ideal for amplifying the molecular signal readout. Furthermore, fluidic control on small length scales enables precise tailoring of the spatial overlap between the electromagnetic hotspots and the analytes, boosting light-matter interaction, and can be utilized to integrate advanced functionalities for the pre-treatment of samples in real-world-use cases, such as purification, separation, or dilution. In this review, the authors highlight current trends in nanophotonics-enabled optofluidic biosensors for applications in the life sciences while providing a detailed perspective on how these approaches can synergistically amplify the optical signal readout and achieve real-time dynamic monitoring, which is crucial in biomedical assays and clinical diagnostics

Parametric Optimization of Visible Wavelength Gold Lattice Geometries for Improved Plasmon-Enhanced Fluorescence Spectroscopy

The exploitation of spectro-plasmonics will allow for innovations in optical instrumentation development and the realization of more efficient optical biodetection components. Biosensors have been shown to improve the overall quality of life through real-time detection of various antibody-antigen reactions, biomarkers, infectious diseases, pathogens, toxins, viruses, etc. has led to increased interest in the research and development of these devices. Further advancements in modern biosensor development will be realized through novel electrochemical, electromechanical, bioelectrical, and/or optical transduction methods aimed at reducing the size, cost, and limit of detection (LOD) of these sensor systems. One such method of optical transduction involves the exploitation of the plasmonic resonance of noble metal nanostructures. This thesis presents the optimization of the electric (E) field enhancement granted from localized surface plasmon resonance (LSPR) via parametric variation of periodic gold lattice geometries using finite difference time domain (FDTD) software. Comprehensive analyses of cylindrical, square, star, and triangular lattice feature geometries were performed to determine the largest surface E-field enhancement resulting from LSPR for reducing the LOD of plasmon-enhanced fluorescence (PEF). The design of an optical transducer engineered to yield peak E-field enhancement and, therefore, peak excitation enhancement of fluorescent labels would enable for improved emission enhancement of these labels. The methodology presented in this thesis details the optimization of plasmonic lattice geometries for improving current visible wavelength fluorescence spectroscopy

Undamaged measurement of the sub-micron diaphragm and gap by tri-beam interference

A simple, high-accuracy and non-destructive method for the measurement of diaphragm thickness and microgap width based on modulated tri-beam interference is demonstrated. With this method, a theoretical estimation error less than 0.5% for a diaphragm thickness of ~1 μm is achievable. Several fiber-tip air bubbles with different diaphragm thicknesses (6.25, 5.0, 2.5 and 1.25 μm) were fabricated to verify our proposed measurement method. Furthermore, an improved technique was introduced by immersing the measured object into a liquid environment to simplify a four-beam interference into tri-beam one. By applying this improved technique, the diaphragm thickness of a fabricated in-fiber rectangular air bubble is measured to be about 1.47 μm, and the averaged microgap width of a standard silica capillary is measured to be about 10.07 μm, giving a corresponding measurement error only 1.27% compared with actual scanning electron microscope (SEM) results