Recent Progress in Optical Sensors for Biomedical Diagnostics

In recent years, several types of optical sensors have been probed for their aptitude in healthcare biosensing, making their applications in biomedical diagnostics a rapidly evolving subject. Optical sensors show versatility amongst different receptor types and even permit the integration of different detection mechanisms. Such conjugated sensing platforms facilitate the exploitation of their neoteric synergistic characteristics for sensor fabrication. This paper covers nearly 250 research articles since 2016 representing the emerging interest in rapid, reproducible and ultrasensitive assays in clinical analysis. Therefore, we present an elaborate review of biomedical diagnostics with the help of optical sensors working on varied principles such as surface plasmon resonance, localised surface plasmon resonance, evanescent wave fluorescence, bioluminescence and several others. These sensors are capable of investigating toxins, proteins, pathogens, disease biomarkers and whole cells in varied sensing media ranging from water to buffer to more complex environments such as serum, blood or urine. Hence, the recent trends discussed in this review hold enormous potential for the widespread use of optical sensors in early-stage disease prediction and point-of-care testing devices.DFG, 428780268, Biomimetische Rezeptoren auf NanoMIP-Basis zur Virenerkennung und -entfernung mittels integrierter Ansätz

Photonic crystal resonances for sensing and imaging

This review provides an insight into the recent developments of photonic crystal (PhC)-based devices for sensing and imaging, with a particular emphasis on biosensors. We focus on two main classes of devices, namely sensors based on PhC cavities and those on guided mode resonances (GMRs). This distinction is able to capture the richness of possibilities that PhCs are able to offer in this space. We present recent examples highlighting applications where PhCs can offer new capabilities, open up new applications or enable improved performance, with a clear emphasis on the different types of structures and photonic functions. We provide a critical comparison between cavity-based devices and GMR devices by highlighting strengths and weaknesses. We also compare PhC technologies and their sensing mechanism to surface plasmon resonance, microring resonators and integrated interferometric sensors

Nanophotonics for bacterial detection and antimicrobial susceptibility testing

Photonic biosensors are a major topic of research that continues to make exciting advances. Technology has now improved sufficiently for photonics to enter the realm of microbiology and to allow for the detection of individual bacteria. Here, we discuss the different nanophotonic modalities used in this context and highlight the opportunities they offer for studying bacteria. We critically review examples from the recent literature, starting with an overview of photonic devices for the detection of bacteria, followed by a specific analysis of photonic antimicrobial susceptibility tests. We show that the intrinsic advantage of matching the optical probed volume to that of a single, or a few, bacterial cell, affords improved sensitivity while providing additional insight into single-cell properties. We illustrate our argument by comparing traditional culture-based methods, which we term macroscopic, to microscopic free-space optics and nanoscopic guided-wave optics techniques. Particular attention is devoted to this last class by discussing structures such as photonic crystal cavities, plasmonic nanostructures and interferometric configurations. These structures and associated measurement modalities are assessed in terms of limit of detection, response time and ease of implementation. Existing challenges and issues yet to be addressed will be examined and critically discussed

Development of nanophotonic biosensor platform towards on-chip liquid biopsy

Liquid biopsy has the potential to enable diagnosis, prognosis, and monitoring of some diseases at an early stage using body fluids from patients. This minimally invasive, label-free detection method is less likely to harm the cell’s viability through binding to the surface protein. Smart integration of liquid biopsy designs with microfluidics on a single chip will lead to a considerable reduction in the detection time (due to controlled diffusion length), and the volumes of sample, agent and reagent, and the limit of detection. Optical label-free biosensors are a powerful tool to analyze biomolecular interactions and have been widely studied in the field of biomedical and biological science and engineering. Label-free detection enables direct measurement of key characteristic properties of the chemical compound, DNA molecule, peptide, protein, virus, or cell, while eliminating experimental uncertainty induced by the effect of the label on molecular conformation, thus reducing the time and effort required for bioassay. Existing optical label-free biosensors suffer from three limitations, including low detection sensitivity, slow molecules mass transfer, and poor throughput. The goal of this dissertation is to overcome these limitations through the development of a novel and efficient modality towards liquid biopsy-based bioassay with increased detection sensitivity, speed, and throughput. To increase the detection sensitivity, we investigate the optical bound states in the continuum (BIC) of slotted high-contrast grating (sHCG) structures. We demonstrate that the sHCG support BICs and high-Q resonant modes, and the slot position can be utilized to tune and optimize the linewidth of the high-Q resonances. To overcome the mass-transfer limitation and reduce the assay time, we propose a lateral flow-through optical biosensor integrating high-contrast gratings and microfluidics on a silicon-on-insulator platform. The biosensor design allows reducing the diffusion length to a submicron scale and enhancing direct interactions between the analytes and sensing structures. Finally, we develop a high-throughput, label-free exosome vesicles (EVs) detection microarray formed on a photonic crystal (PC) biosensor surface. We design and implement a hyperspectral imaging approach to quantify the antibody and EV absorptions on the PC-based microarray consisting of a panel of seven antibodies specific to multiple membrane receptors of the target EVs. We validate that the EV microarray by adopting it to detect EVs released by macrophages for the analysis of immune responses

Plasmon-exciton coupling for signal amplification and biosensing : fundamentals and application

Surface plasmon resonance (SPR) is the collective oscillation of frequency-matched free-space photons and surface electrons at a metal/dielectric interface. Their inherent sensitivity to refractive index changes and ability to couple with exciton species and enhance light-matter interaction make them ideal candidates for low-concentration analyte detection compared to conventional biosensors. The use of metal nanostructures and nanomaterials to excite SPR represents the current state-of-the-art. However, the challenges associated with repeatable synthesis of uniform nanomaterials, complex nanostructure fabrication, low SPR generation efficiency and limited understanding of the mechanism of plasmon-exciton coupling for signal amplification have motivated the search for alternative architectures and procedures. The uniform and repeatable gold nanoslit (NS) and nanoledge (NL) array architectures offers a promising route towards addressing the above issues, and hence this research attempts to take advantage of these platforms to achieve efficient SPR generation and exciton coupling for biosensing applications. The overarching scope of this dissertation extends to the design, fabrication, and optimization of metal NS and NL structures for SPR generation and sensing applications. Emphasis is placed on investigating the mechanism of optical signal enhancement arising from plasmon-exciton coupling (PEC) with particular focus on (a) exploring the role of geometry and size of the nanostructures (b) examining the influence of SPR spectral mode overlap with exciton’s absorption and/or emission energies on the overall optical signal in a NS or NL system, and (c) investigating the analytical sensitivity and signal transduction of the PEC system to biomolecular interactions. The nanoimprinting technique based on soft lithography for NS fabrication, which is used in this work for NS array fabrication, required addressing a critical issue, namely PDMS diffusion into nanoscale patterns for high aspect ratio realization. This was mitigated by curing temperature variation and incubation time to achieve 50 nm-130 nm width NS arrays with an intense, broad spectral response that red-shifts and diminishes with increasing NS width. The 50 nm width structure exhibited ~57× optical enhancement when coupled with acridine orange, a fluorescence dye, whose absorption and emission spectra closely overlaps with plasmonic spectra. A sensitive assay for detecting DNA hybridization was generated using the interaction of the selected SARS-CoV-2 ssDNA and dsDNA with AO to trigger the metachromatic behaviour of the dye to produce a strong optical signal amplification on the formation of AO-ssDNA complex and a quenched signal upon hybridization to the complementary target DNA along with a blue shift in the fluorescence of AO-dsDNA. The SARS-CoV-2 DNA hybridization assay, based on the PEC exhibited 0.21 nM sensitivity to complementary strand target, distinguished 1-, 2-, and 3-base mismatched DNA targets, reusability of ~6 x with 96% signal recovery, stable for up to 10 days at room temperature. Regarding the NL sensing platform, the principle of the sensing mechanism is based on plasmon-mediated extraordinary optical transmission (EOT) whose wavelength red-shifts with increase in refractive index (RI) at near-metal surface. The NL plasmonic-based biosensor fabricated using a patented E-beam writing method exhibited ~ 384.08 nm/RIU sensitivity, limit of detection to cardiac troponin I (TnI) at 0.079 ng/mL, 0.084 ng/mL and 0.097 ng/mL in PBS buffer, human serum, and human blood, respectively. The direct measurement of TnI in whole human blood without any purification or sample preparation step highlights the significance of the sensing platform for point-of-care detection. Thus, this work innovates (a) a tunable SPR to meet the requirement for plasmon-exciton spectral overlap for optical signal amplification, (b) the mechanism of optical enhancements due to PEC in NS arrays, and (c) a new application of PEC in NS and EOT in NL for the sensitive detection of SARS-CoV-2 DNA hybridization and cardiovascular biomarker TnI in human blood, respectively. The enhanced light-matter interactions have a broader impact beyond healthcare to light harvesting for solar cells, heat generation for cancer therapy, and photocatalysis for nanoscale reactions like water splitting

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

Light matter interaction in hybrid plasmonic/photonic nanogaps

The aim of this thesis is to study the processes of light matter interaction at the nanoscale in hybrid nano gaps that are made from both metals and dielectrics. This approach enables the possibility to use both the optical properties of a dielectric, such as low losses and high-quality factor, with the small mode volume typical of a metal. High quality factor and small modal volume together make a high Purcell factor, which is the enhancement of the spontaneous emission rate due to the surrounding cavity environment. Both the size and the time scales involved in this study range in the nanometre and nano second, respectively.The architecture used for the study of the hybrid nano gaps consists of a substrate containing a Distributed Bragg Reflector (DBR) and a 10 nm thick emitting layer. On top of this layer lies a small concentration of gold nano spheres. Two different emitting dipole orientations have been studied, vertical and horizontal. The vertical orientation is parallel to the nano gap dipole moment while in the case of the horizontal orientation, it is perpendicular to it. These two emitting dipole orientations have been used to perform two different experiments exploiting different properties of the DBR. DBRs have been used for two purposes, reflectors and 1-d photonic crystals. These two applications are used to investigate different properties of the hybrid nano gaps. Indeed, DBRs have a highly reflective spectral region called photonic stopband, outside of it there are some highly localised reflectivity minima called Bragg modes.The first hybrid nano gap application explored is the directional nano antenna. In this approach the DBR is used as a reflector and the nano cavity is used to control the direction of the emission. Because of the Fermi golden rule, the dipole moment of the emitter and the nano gap must be parallel to achieve the largest coupling possible. The dipole orientation parallel to the cavity dipole moment is called vertical and it has been probed using the emitter Lumogen Red. This dye exhibits a high quantum yield, low photo bleaching and a good vertical orientability when spun on a surface in form of a film. In this configuration, the light is emitted by the layer at very large angle compared to the surface, roughly 60 degrees. The system can measure up to 64 degrees since the objective numerical aperture is 0.9/1. In this nanogap the nanoparticle acts like a directional antenna and 65% of the emitted light gets redirected at angles not accessible by emitters on their own. Spectrally dispersed k-space imaging has been used to perform such a measurement. This study has demonstrated how the light emission cone is a function of the nano particle size. The narrowest emission cone observed was found to occur for a 500 nm diameter particle size. This configuration showed an enhancement emission factor ranging from 30 up to 60.The second nano gap configuration used the DBR as photonic crystal to achieve localised Tamm plasmon generation. These results are described in chapter 6. The minimum in the reflectivity spectrum of the DBR is called the 1st Bragg mode. In this mode the impinging radiation can penetrate inside the stack and not propagate outside. Tamm states are surface states that can be excited at the interface between a DBR stack and a metal film. Super Tamm are more localised Tamm states that can be excited only by replacing the metallic film with a finite structure such as a micro disk. In this thesis, a new form of localised super Tamm states has been excited. This novelty state has been named Isolated super Tamm modes. The disk has been replaced with a gold nano sphere. Isolated super Tamm modes have been proved to have an intermediate spectral position between the 1st Bragg mode and the super Tamm

Bio-molecular applications of recent developments in optical tweezers

In the past three decades, the ability to optically manipulate biomolecules has spurred a new era of medical and biophysical research. Optical tweezers (OT) have enabled experimenters to trap, sort, and probe cells, as well as discern the structural dynamics of proteins and nucleic acids at single molecule level. The steady improvement in OT\u2019s resolving power has progressively pushed the envelope of their applications; there are, however, some inherent limitations that are prompting researchers to look for alternatives to the conventional techniques. To begin with, OT are restricted by their one-dimensional approach, which makes it difficult to conjure an exhaustive three-dimensional picture of biological systems. The high-intensity trapping laser can damage biological samples, a fact that restricts the feasibility of in vivo applications. Finally, direct manipulation of biological matter at nanometer scale remains a significant challenge for conventional OT. A significant amount of literature has been dedicated in the last 10 years to address the aforementioned shortcomings. Innovations in laser technology and advances in various other spheres of applied physics have been capitalized upon to evolve the next generation OT systems. In this review, we elucidate a few of these developments, with particular focus on their biological applications. The manipulation of nanoscopic objects has been achieved by means of plasmonic optical tweezers (POT), which utilize localized surface plasmons to generate optical traps with enhanced trapping potential, and photonic crystal optical tweezers (PhC OT), which attain the same goal by employing different photonic crystal geometries. Femtosecond optical tweezers (fs OT), constructed by replacing the continuous wave (cw) laser source with a femtosecond laser, promise to greatly reduce the damage to living samples. Finally, one way to transcend the one-dimensional nature of the data gained by OT is to couple them to the other large family of single molecule tools, i.e., fluorescence-based imaging techniques. We discuss the distinct advantages of the aforementioned techniques as well as the alternative experimental perspective they provide in comparison to conventional OT