An Integrated Approach to Protein Discovery and Detection From Complex Biofluids.

Ovarian cancer, a leading cause of cancer-related deaths among women, has been notoriously difficult to screen for and diagnose early, as early detection significantly improves survival. Researchers and clinicians seek routinely usable and noninvasive screening methods; however, available methods (i.e., biomarker screening) lack desirable sensitivity/specificity. The most fatal form, high-grade serous ovarian cancer, often originate in the fallopian tube; therefore, sampling from the vaginal environment provides more proximal sources for tumor detection. To address these shortcomings and leverage proximal sampling, we developed an untargeted mass spectrometry microprotein profiling method and identified cystatin A, which was validated in an animal model. To overcome the limits of detection inherent to mass spectrometry, we demonstrated that cystatin A is present at 100 pM concentrations using a label-free microtoroid resonator and translated our workflow to patient-derived clinical samples, highlighting the potential utility of early stage detection where biomarker levels would be low.

Optical Trapping and Fast Discrimination of Label-Free Bacteriophages at the Single Virion Level.

There is a recent resurgence of interest in phage therapy (the therapeutic use of bacterial viruses) as an approach to eliminating difficult-to-treat infections. However, existing approaches for therapeutic phage selection and virulence testing are time-consuming, host-dependent, and facing reproducibility issues. Here, this study presents an innovative approach wherein integrated resonant photonic crystal (PhC) cavities in silicon are used as optical nanotweezers for probing and manipulating single bacteria and single virions with low optical power. This study demonstrates that these nanocavities differentiate between a bacterium and a phage without labeling or specific surface bioreceptors. Furthermore, by tailoring the spatial extent of the resonant optical mode in the low-index medium, phage distinction across phenotypically distinct phage families is demonstrated. The work paves the road to the implementation of optical nanotweezers in phage therapy protocols.

Integrated Flexible Microscale Mechanical Sensors Based on Cascaded Free Spectral Range-Free Cavities.

Photonic mechanical sensors offer several advantages over their electronic counterparts, including immunity to electromagnetic interference, increased sensitivity, and measurement accuracy. Exploring flexible mechanical sensors on deformable substrates provides new opportunities for strain-optical coupling operations. Nevertheless, existing flexible photonics strategies often require cumbersome signal collection and analysis with bulky setups, limiting their portability and affordability. To address these challenges, we propose a waveguide-integrated flexible mechanical sensor based on cascaded photonic crystal microcavities with inherent deformation and biaxial tensile state analysis. Leveraging the advanced multiplexing capability of the sensor, for the first time, we successfully demonstrate 2D shape reconstruction and quasi-distributed strain sensing with 110 µm spatial resolution. Our microscale mechanical sensor also exhibits exceptional sensitivity with a detected force level as low as 13.6 µN in real-time measurements. This sensing platform has potential applications in various fields, including biomedical sensing, surgical catheters, aircraft and spacecraft engineering, and robotic photonic skin development.

Solid-Phase Optical Sensing Techniques for Sensitive Virus Detection.

Viral infections can pose a major threat to public health by causing serious illness, leading to pandemics, and burdening healthcare systems. The global spread of such infections causes disruptions to every aspect of life including business, education, and social life. Fast and accurate diagnosis of viral infections has significant implications for saving lives, preventing the spread of the diseases, and minimizing social and economic damages. Polymerase chain reaction (PCR)-based techniques are commonly used to detect viruses in the clinic. However, PCR has several drawbacks, as highlighted during the recent COVID-19 pandemic, such as long processing times and the requirement for sophisticated laboratory instruments. Therefore, there is an urgent need for fast and accurate techniques for virus detection. For this purpose, a variety of biosensor systems are being developed to provide rapid, sensitive, and high-throughput viral diagnostic platforms, enabling quick diagnosis and efficient control of the virus's spread. Optical devices, in particular, are of great interest due to their advantages such as high sensitivity and direct readout. The current review discusses solid-phase optical sensing techniques for virus detection, including fluorescence-based sensors, surface plasmon resonance (SPR), surface-enhanced Raman scattering (SERS), optical resonators, and interferometry-based platforms. Then, we focus on an interferometric biosensor developed by our group, the single-particle interferometric reflectance imaging sensor (SP-IRIS), which has the capability to visualize single nanoparticles, to demonstrate its application for digital virus detection.

Probing the Optical Response and Local Dielectric Function of an Unconventional Si@MoS2 Core-Shell Architecture.

Heterostructures of optical cavities and quantum emitters have been highlighted for enhanced light-matter interactions. A silicon nanosphere, core, and MoS2, shell, structure is one such heterostructure referred to as the core@shell architecture. However, the complexity of the synthesis and inherent difficulties to locally probe this architecture have resulted in a lack of information about its localized features limiting its advances. Here, we utilize valence electron energy loss spectroscopy (VEELS) to extract spatially resolved dielectric functions of Si@MoS2 with nanoscale spatial resolution corroborated with simulations. A hybrid electronic critical point is identified ∼3.8 eV for Si@MoS2. The dielectric functions at the Si/MoS2 interface is further probed with a cross-sectioned core-shell to assess the contribution of each component. Various optical parameters can be defined via the dielectric function. Hence, the methodology and evolution of the dielectric function herein reported provide a platform for exploring other complex photonic nanostructures.

Fabry-Perot Resonance in 2D Dielectric Grating for Figure of Merit Enhancement in Refractive Index Sensing.

We have recently reported in our previous work that one-dimensional dielectric grating can provide an open structure for Fabry-Perot mode excitation. The grating gaps allow the sample refractive index to fill up the grating spaces enabling the sample to perturb the Fabry-Perot mode resonant condition. Thus, the grating structure can be utilized as a refractive index sensor and provides convenient sample access from the open end of the grating with an enhanced figure of merit compared to the other thin-film technologies. Here, we demonstrate that 2D grating structures, such as rectangular pillars and circular pillars, can further enhance refractive index sensing performance. The refractive index theory for rectangular pillars and circular pillars are proposed and validated with rigorous coupled wave theory. An effective refractive index theory is proposed to simplify the 2D grating computation and accurately predict the Fabry-Perot mode positions. The 2D gratings have more grating space leading to a higher resonant condition perturbation and sensitivity. They also provide narrower Fabry-Perot mode reflectance dips leading to a 4.5 times figure of merit enhancement than the Fabry-Perot modes excited in the 1D grating. The performance comparison for thin-film technologies for refractive index sensing is also presented and discussed.

Organic Semiconductor Micro/Nanocrystals for Laser Applications.

Organic semiconductor micro/nanocrystals (OSMCs) have attracted great attention due to their numerous advantages such us free grain boundaries, minimal defects and traps, molecular diversity, low cost, flexibility and solution processability. Due to all these characteristics, they are strong candidates for the next generation of electronic and optoelectronic devices. In this review, we present a comprehensive overview of these OSMCs, discussing molecular packing, the methods to control crystallization and their applications to the area of organic solid-state lasers. Special emphasis is given to OSMC lasers which self-assemble into geometrically defined optical resonators owing to their attractive prospects for tuning/control of light emission properties through geometrical resonator design. The most recent developments together with novel strategies for light emission tuning and effective light extraction are presented.

Vapor Sensing with Polymer Coated Straight Optical Fiber Microtapers Based on Index Sensitive Interference Spectroscopy of Surface Stress Birefringence.

Optical microfiber tapers provide an advantageous platform for sensing in aqueous and gas environments. We study experimentally the photonic transmission in optical fiber tapers coated with polymethyl methacrylate (PMMA), a polymeric material widely used in optical applications. We demonstrate a durable and simple humidity sensing approach incorporating tapered microfibers attached to silicon (Si) substrate coated with active polymer layer. A model is described for the load stress effect on the birefringence giving rise to interferences in the transmission spectra, strongly dependent on the coating layer thickness, and disappearing following its slow uniform removal. The sensing approach is based on characterization of the interference patterns observed in the transmission spectra of the taper in the NIR range. The device demonstrated persistent detection capability in humid environment and a linear response followed by saturation to calibration analytes. In each analyte of interest, we define principal components and observe unique calibration plot regimes in the principal component space, demonstrating vapor sensing using polymer coated microtapers.

Label-Free Optical Resonator-Based Biosensors.

The demand for biosensor technology has grown drastically over the last few decades, mainly in disease diagnosis, drug development, and environmental health and safety. Optical resonator-based biosensors have been widely exploited to achieve highly sensitive, rapid, and label-free detection of biological analytes. The advancements in microfluidic and micro/nanofabrication technologies allow them to be miniaturized and simultaneously detect various analytes in a small sample volume. By virtue of these advantages and advancements, the optical resonator-based biosensor is considered a promising platform not only for general medical diagnostics but also for point-of-care applications. This review aims to provide an overview of recent progresses in label-free optical resonator-based biosensors published mostly over the last 5 years. We categorized them into Fabry-Perot interferometer-based and whispering gallery mode-based biosensors. The principles behind each biosensor are concisely introduced, and recent progresses in configurations, materials, test setup, and light confinement methods are described. Finally, the current challenges and future research topics of the optical resonator-based biosensor are discussed.

Fiber Optic Refractive Index Sensors Based on a Ball Resonator and Optical Backscatter Interrogation.

In this work, we introduced fabrication and interrogation of simple and highly sensitive fiber-optic refractive index (RI) sensors based on ball resonators built on the tip of single-mode fibers. The probes have been fabricated through a CO2 fiber splicer, with a fast (~600 s) and repeatable method. The ball resonator acted as a weak interferometer with a return loss below -50 dB and was interrogated with an optical backscatter reflectometer measuring the reflection spectrum. The ball resonators behaved as weak interferometers with a shallow fringe and a spectrum that appeared close to a random signal, and RI sensitivity could be measured either through wavelength shift or amplitude change. In this work, we reported four samples having sensitivity ranges 48.9-403.3 nm/RIU and 256.0-566.2 dB/RIU (RIU = refractive index unit). Ball resonators appeared as a sensitive and robust platform for RI sensing in liquid and can be further functionalized for biosensing.

Spectral Phase Shift Interferometry for Refractive Index Monitoring in Micro-Capillaries.

In this work, we demonstrate spectral phase-shift interferometry operating in the near-infrared wavelength range for refractive index (RI) monitoring of fluidic samples in micro-capillaries. A detailed theoretical model was developed to calculate the phase-sensitive spectral reflectivity when low-cost rectangular glass micro-capillaries, filled with samples with different refractive indices, are placed at the end of the measurment arm of a Michelson interferometer. From the phase-sensitive spectral reflectivity, we recovered the cosine-shaped interferometric signal as a function of the wavelength, as well as its dependence on the sample RI. Using the readout radiation provided by a 40-nm wideband light source with a flat emission spectrum centered at 1.55 µm and a 2 × 1 fiberoptic coupler on the common input-output optical path, experimental results were found to be in good agreement with the expected theoretical behavior. The shift of the micro-capillary optical resonances, induced by RI variations in the filling fluids (comparing saline solution with respect to distilled water, and isopropanol with respect to ethanol) were clearly detected by monitoring the positions of steep phase jumps in the cosine-shaped interferometric signal recorded as a function of the wavelength. By adding a few optical components to the instrumental configuration previously demonstrated for the spectral amplitude detection of resonances, we achieved phase-sensitive detection of the wavelength positions of the resonances as a function of the filling fluid RI. The main advantage consists of recovering RI variations by detecting the wavelength shift of "sharp peaks", with any amplitude above a threshold in the interferometric signal derivative, instead of "wide minima" in the reflected power spectra, which are more easily affected by uncertainties due to amplitude fluctuations.

Laser-Inscribed Diamond Waveguide Resonantly Coupled to Diamond Microsphere.

An all-diamond photonic circuit was implemented by integrating a diamond microsphere with a femtosecond-laser-written bulk diamond waveguide. The near surface waveguide was fabricated by exploiting the Type II fabrication method to achieve stress-induced waveguiding. Transverse electrically and transverse magnetically polarized light from a tunable laser operating in the near-infrared region was injected into the diamond waveguide, which when coupled to the diamond microsphere showed whispering-gallery modes with a spacing of 0.33 nm and high-quality factors of 105. By carefully engineering these high-quality factor resonances, and further exploiting the properties of existing nitrogen-vacancy centers in diamond microspheres and diamond waveguides in such configurations, it should be possible to realize filtering, sensing and nonlinear optical applications in integrated diamond photonics.

Fused Microknot Optical Resonators in Folded Photonic Tapers for in-Liquid Durable Sensing.

Optical microknot fibers (OMFs) serve as localized devices, where photonic resonances (PRs) enable self-interfering elements sensitive to their environment. However, typical fragility and drifting of the knot severely limit the performance and durability of microknots as sensors in aqueous settings. Herein we present the fabrication, electrical fusing, preparation, and persistent detection of volatile liquids in multiple wetting⁻dewetting cycles of volatile compounds and quantify the persistent phase shifts with a simple model relating to the ambient liquid, enabling durable in-liquid sensing employing OMF PRs.

Mode-Splitting for Refractive Index Sensing in Fluorescent Whispering Gallery Mode Microspheres with Broken Symmetry.

Whispering gallery mode (WGM) resonators have become increasingly diverse in terms of both architecture and applications, especially as refractometric sensors, allowing for unprecedented levels of sensitivity. However, like every refractometric sensor, a single WGM resonator cannot distinguish temperature variations from changes in the refractive index of the surrounding environment. Here, we investigate how breaking the symmetry of an otherwise perfect fluorescent microsphere, by covering half of the resonator with a high-refractive-index (RI) glue, might enable discrimination of changes in temperature from variations in the surrounding refractive index. This novel approach takes advantage of the difference of optical pathway experienced by WGMs circulating in different equatorial planes of a single microsphere resonator, which induces mode-splitting. We investigated the influence of the surrounding RI of the microsphere on mode-splitting through an evaluation of the sphere's WGM spectrum and quality factor (Q-factor). Our results reveal that the magnitude of the mode-splitting increases as the refractive index contrast between the high-refractive-index (RI) glue and the surrounding environment increases, and that when they are equal no mode-splitting can be seen. Investigating the refractive index sensitivity of the individual sub modes resulting from the mode-splitting unveils a new methodology for RI sensing, and enables discrimination between surrounding refractive index changes and temperature changes, although it comes at the cost of an overall reduced refractive index sensitivity.

Optical Microbottle Resonators for Sensing.

Whispering gallery mode (WGM) optical microresonators have been shown to be the basis for sensors able to detect minute changes in their environment. This has made them a well-established platform for highly sensitive physical, chemical, and biological sensors. Microbottle resonators (MBR) are a type of WGM optical microresonator. They share characteristics with other, more established, resonator geometries such as cylinders and spheres, while presenting their unique spectral signature and other distinguishing features. In this review, we discuss recent advances in the theory and fabrication of different kinds of MBRs, including hollow ones, and their application to optofluidic sensing.

Review of Microbottle Resonators for Sensing Applications.

Microbottle resonators (MBR) are bottle-like structures fabricated by varying the radius of an optical fiber. MBRs can support whispering gallery modes (WGM) by the total internal reflection of the light coupled into the MBRs. MBRs have a significant advantage in sensing and other advanced optical applications due to their light confinement abilities in a relatively small mode volume and having high Q factors. This review starts with an introduction to MBRs' optical properties, coupling methods, and sensing mechanisms. The sensing principle and sensing parameters of MBRs are discussed here as well. Then, practical MBRs fabrication methods and sensing applications are presented.

Progress and Perspective toward Continuous-Wave Organic Solid-State Lasers.

A continuous-wave (CW) organic solid-state laser is highly desirable for spectroscopy, sensing, and communications, but is a significant challenge in optoelectronics. The accumulation of long-lived triplet excitons and relevant excited-state absorptions, as well as singlet-triplet annihilation, are the main obstacles to CW lasing. Here, progress in singlet- and triplet-state utilizations in organic gain media is reviewed to reveal the issues in working with triplets. Then, exciton behaviors that inhibit light oscillations during long excitation pulses are discussed. Further, recent advances in increasing organic lasing pulse widths from microseconds toward the indication of CW operation are summarized with respect to molecular designs, advanced resonator architectures, triplet scavenging, and potential triplet contribution strategies. Finally, future directions and perspectives are proposed for achieving stable CW organic lasers with significant triplet contribution.

From Whispering Gallery Mode Resonators to Biochemical Sensors.

Optical biosensors are frontrunners for the rapid and real-time detection of analytes, particularly for low concentrations. Among them, whispering gallery mode (WGM) resonators have recently attracted a growing focus due to their robust optomechanical features and high sensitivity, measuring down to single binding events in small volumes. In this review, we provide a broad overview of WGM sensors along with critical advice and additional "tips and tricks" to make them more accessible to both biochemical and optical communities. Their structures, fabrication methods, materials, and surface functionalization chemistries are discussed. We propose this reflection under a pedagogical approach to describe and explain these biochemical sensors with a particular focus on the most recent achievements in the field. In addition to highlighting the advantages of WGM sensors, we also discuss and suggest strategies to overcome their current limitations, leaving room for further development as practical tools in various applications. We aim to provide new insights and combine different knowledge and perspectives to advance the development of the next generation of WGM biosensors. With their unique advantages and compatibility with different sensing modalities, these biosensors have the potential to become major game changers for biomedical and environmental monitoring, among many other relevant target applications.

Resonant-Cavity-Enhanced Electrochromic Materials and Devices.

With rapid advances in optoelectronics, electrochromic materials and devices have received tremendous attentions from both industry and academia for their strong potentials in wearable and portable electronics, displays/billboards, adaptive camouflage, tunable optics, and intelligent devices, etc. However, conventional electrochromic materials and devices typically present some serious limitations such as undesirable dull colors, and long switching time, hindering their deeper development. Optical resonators have been proven to be the most powerful platform for providing strong optical confinement and controllable lightmatter interactions. They generate locally enhanced electromagnetic near-fields that can convert small refractive index changes in electrochromic materials into high-contrast color variations, enabling multicolor or even panchromatic tuning of electrochromic materials. Here, resonant-cavity-enhanced electrochromic materials and devices, an advanced and emerging trend in electrochromics, are reviewed. In this review, w e will focus on the progress in multicolor electrochromic materials and devices based on different types of optical resonators and their advanced and emerging applications, including multichromatic displays, adaptive visible camouflage, visualized energy storage, and applications of multispectral tunability. Among these topics, principles of optical resonators, related materials/devices and multicolor electrochromic properties are comprehensively discussed and summarized. Finally, the challenges and prospects for resonant-cavity-enhanced electrochromic materials and devices are presented.

Planar Optofluidic Integration of Ring Resonator and Microfluidic Channels.

We report an optofluidic hybrid silicon-polymer planar ring resonator with integrated microfluidic channels for efficient liquid delivery. The device features a planar architecture of intersecting liquid-core waveguides and microfluidic channels. A low-loss integration of microfluidic channels is accomplished by exploiting the interference pattern created by the self-imaging effect in the multimode interference-based coupler waveguides. Numerical simulations have been performed in order to minimize the propagation losses along the ring loop caused by the integration of microfluidic channels. The device has been fabricated and optically characterized by measuring the quality factor, obtaining a value of 4 × 103. This result is comparable with the quality factor of an optofluidic ring with the same optical layout but without integrated microfluidic channels, thus, confirming the suitability of the proposed approach for microfluidics integration in planar optofluidic design.