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Detections of internal substances and morphologies for label-free living cells are crucial for revealing malignant diseases. With the phase serving as a coupling of refractive index (RI) (marker for substances) and thickness (morphology), existing decoupling methods mainly rely on complex integrated systems or extensive optical field information. Developing simple and rapid decoupling methods remains a challenge. This study introduces a refractive index morphology imaging microscope (RIMIM) system utilizing polarization multiplexing for label-free single living cells. By simultaneous degree of circular polarization (DOCP) imaging and noninterferometric quantitative phase imaging (QPI), the intracellular refractive index distribution (IRID) and morphology can be decoupled. The optical thickness calculated from the phase is input into the circular depolarization decay model (CDDM) of degree of circular polarization to retrieve IRID. Subsequently, the thickness can be decoupled from phase result using retrieved IRID. Experiments conducted on mouse forestomach carcinoma (MFC) cells and human kidney-2 cells (HK-2) demonstrated the RIMIM system's ability to retrieve IRID and decouple fine morphology. Additionally, the RIMIM system effectively detected membrane damage and changes in erastin-induced ferroptotic HK-2 cells, with average and root-mean-square of surface folds 65.5% and 70.0% higher than those of normal HK-2 cells. Overall, the RIMIM system provides a simple and rapid method for decoupling RI and fine morphology, showing great potential for label-free live cells' cytopathology detection.

Four biobased phosphate-containing aryl monomers with methoxy, allyl, and vinyl groups as substituents have been successfully synthesized. Copolymerizing these monomers with thiophenol or mercaptans via the photoclick thiol-ene reaction gives the polymers with refractive indices ( n D ) of 1.63-1.70 and Abbe numbers ( v D ) of 12.8-38.5. An investigation of the relationship of the v D values with the substituents on the benzene rings of the monomers indicates that methoxy and vinyl groups can collectively increase the v D values. In comparison with allyl groups, vinyl groups endow the polymers with both higher n D and v D . Moreover, these polymers also display high transmittance, high thermostability, and low haze values in the visible-light region, suggesting that these biobased functional monomers are satisfactory precursors used in the fabrication of optical devices.

The current limitations of single-molecule localization microscopy (SMLM) in deep tissue imaging, primarily due to depth-dependent aberrations caused by refractive index (RI) mismatch, present a significant challenge in achieving high-resolution images at greater depths. To extend the imaging depth, we optimized the imaging buffer of SMLM with the RI matched to that of the objective immersion medium and systematically evaluated five different RI-matched buffers, focusing on their impact on the blinking behavior of red-absorbing dyes and the quality of reconstructed super-resolution images. Particularly, we found that clear unobstructed brain imaging cocktails-based imaging buffer could match the RI of oil and was able to clear the tissue samples. With the help of the RI-matched imaging buffers, we showed high-quality dual-color 3D SMLM images with imaging depths ranging from a few micrometers to tens of micrometers in both cultured cells and sectioned tissue samples. This advancement offers a practical and accessible method for high-resolution imaging at greater depths without the need for specialized optical equipment or expertise.

A series of polymers with both high refractive index and high Abbe number have been successfully synthesized through the photoclick thiol-ene reaction between the monomers derived from biobased magnolol (or honokiol) and commercial mercaptans and thiophenols. The polymer films not only exhibit a high refractive index and a high Abbe number but also display a transmittance of up to 90% in a range of wavelengths from 550 to 2000 nm and nearly 0% in the UV region. Moreover, these polymers also display low haze values in the visible-light region as well as exhibit good thermostability. These data indicate that they have potential applications for the fabrication of optical lenses and anti-UV coatings. In particular, this series of polymers are readily used for industrialization due to its excellent optical properties but low expense, simplicity, and efficiency of synthesis.

Surface plasmon (SP) excitation in metal-coated tilted fiber Bragg gratings (TFBGs) has been a focal point for highly sensitive surface biosensing. Previous efforts focused on uniform metal layer deposition around the TFBG cross section and temperature self-compensation with the Bragg mode, requiring both careful control of the core-guided light polarization and interrogation over most of the C + L bands. To circumvent these two important practical limitations, we studied and developed an original platform based on partially coated TFBGs. The partial metal layer enables the generation of dual-comb resonances, encompassing highly sensitive (TM/EH mode families) and highly insensitive (TE/HE mode families) components in unpolarized transmission spectra. The interleaved comb of insensitive modes acts as wavelength and power references within the same spectral region as the SP-active modes. Despite reduced fabrication and measurement complexity, refractometric accuracy is not compromised through statistical averaging over seven individual resonances within a narrowband window of 10 nm. Consequently, measuring spectra over 60 nm is no longer needed to compensate for small temperature or power fluctuations. This sensing platform brings the following important practical assets: (1) a simpler fabrication process, (2) no need for polarization control, (3) limited bandwidth interrogation, and (4) maintained refractometric accuracy, which makes it a true game changer in the ever-growing plasmonic sensing domain.

Plasmonic metamaterials have opened new avenues in medical diagnostics. However, the transfer of the technology to the markets has been delayed due to multiple challenges. The need of bulky optics for signal reading from nanostructures patterned on submillimeter area limits the miniaturization of the devices. The use of objective-free optics can solve this problem, which necessitates large area patterning of the nanostructures. In this work, we utilize laser interference lithography (LIL) to pattern nanodisc-shaped metamaterial absorber nanoantennas over a large area (4 cm 2 ) within minutes. The introduction of a sacrificial layer during the fabrication process enables an inverted hole profile and a well-controlled liftoff, which ensures perfectly defined uniform nanopatterning almost with no defects. Furthermore, we use a macroscopic reflection probe for optical characterization in the near-IR, including the detection of the binding kinematics of immunologically relevant proteins. We show that the photonic quality of the plasmonic nanoantennas commensurates with electron-beam-lithography-fabricated ones over the whole area. The refractive index sensitivity of the LIL-fabricated metasurface is determined as 685 nm per refractive index unit, which demonstrates ultrasensitive detection. Moreover, the fabricated surfaces can be used multiple times for biosensing without losing their optical quality. The combination of rapid and large area nanofabrication with a simple optical reading not only simplifies the detection process but also makes the biosensors more environmentally friendly and cost-effective. Therefore, the improvements provided in this work will empower researchers and industries for accurate and real-time analysis of biological systems.

Resonant photonic refractive index sensors have made major advances based on their high sensitivity and contact-less readout capability, which is advantageous in many areas of science and technology. A major issue for the technological implementation of such sensors is their response to external influences, such as vibrations and temperature variations; the more sensitive a sensor, the more susceptible it also becomes to external influences. Here, we introduce a novel bowtie-shaped sensor that is highly responsive to refractive index variations while compensating for temperature changes and mechanical (linear and angular) vibrations. We exemplify its capability by demonstrating the detection of salinity to a precision of 0.1%, corresponding to 2.3 × 10 -4 refractive index units in the presence of temperature fluctuations and mechanical vibrations. As a second exemplar, we detected bacteria growth in a pilot industrial environment. Our results demonstrate that it is possible to translate high sensitivity resonant photonic refractive index sensors into real-world environments.

The emergence of complex biological modalities in the biopharmaceutical industry entails a significant expansion of the current analytical toolbox to address the need to deploy meaningful and reliable assays at an unprecedented pace. Size exclusion chromatography (SEC) is an industry standard technique for protein separation and analysis. Some constraints of traditional SEC stem from its restricted ability to resolve complex mixtures and notoriously long run times while also requiring multiple offline separation conditions on different pore size columns to cover a wider molecular size distribution. Two-dimensional liquid chromatography (2D-LC) is becoming an important tool not only to increase peak capacity but also to tune selectivity in a single online method. Herein, an online 2D-LC framework in which both dimensions utilize SEC columns with different pore sizes is introduced with a goal to increase throughput for biomolecule separation and characterization. In addition to improving the separation of closely related species, this online 2D SEC-SEC approach also facilitated the rapid analysis of protein-based mixtures of a wide molecular size range in a single online experimental run bypassing time-consuming deployment of different offline SEC methods. By coupling the second dimension with multiangle light scattering (MALS) and differential refractive index (dRI) detectors, absolute molecular weights of the separated species were obtained without the use of calibration curves. As illustrated in this report for protein mixtures and vaccine processes, this workflow can be used in scenarios where rapid development and deployment of SEC assays are warranted, enabling bioprocess monitoring, purity assessment, and characterization.

Carbon quantum dots (CQDs) are one of the most promising types of fluorescent nanomaterials due to their exceptional water solubility, excellent optical properties, biocompatibility, chemical inertness, excellent refractive index, and photostability. Nitrogen-containing CQDs, which include amino acid based CQDs, are especially attractive due to their high quantum yield, thermal stability, and potential biomedical applications. Recent studies have attempted to improve the preparation of amino acid based CQDs. However, the highest quantum yield obtained for these dots was only 44%. Furthermore, the refractive indices of amino acid derived CQDs were not determined. Here, we systematically explored the performance of CQDs prepared from all 20 coded amino acids using modified hydrothermal techniques allowing more passivation layers on the surface of the dots to optimize their performance. Intriguingly, we obtained the highest refractive indices ever reported for any CQDs. The values differed among the amino acids, with the highest refractive indices found for positively charged amino acids including arginine-CQDs (∼2.1), histidine-CQDs (∼2.0), and lysine-CQDs (∼1.8). Furthermore, the arginine-CQDs reported here showed a nearly 2-fold increase in the quantum yield (∼86%) and a longer decay time (∼8.0 ns) compared to previous reports. In addition, we also demonstrated that all amino acid based CQD materials displayed excitation-dependent emission profiles (from UV to visible) and were photostable, water-soluble, noncytotoxic, and excellent for high contrast live cell imaging or bioimaging. These results indicate that amino acid based CQD materials are high-refractive-index materials applicable for optoelectronic devices, bioimaging, biosensing, and studying cellular organelles in vivo. This extraordinary RI may be highly useful for exploring cellular elements with different densities.

Modifying material properties in simple macromolecules such as polyethylene (PE) is achieved by different connection modes of ethylene monomers resulting in a plurality of possible topologies-from highly linear to dendritic species. However, the challenge still lies within the experimental identification of the topology and conformation of the isolated macromolecules because of their low solubility, which demands methods with specific solvents and high operating temperatures. Additionally, a separation technique has to be coupled to different detection methods to meet the specific demands of the respective characterization goal. In this work, we report a quadruple-detector high temperature size exclusion chromatography (HT-SEC) system which contains online multiangle laser light scattering, dynamic light scattering, differential viscometry, and differential refractometry detectors. Quadruple-detector HT-SEC was successfully applied to explore the full range of physical parameters of various PE samples with different branching topologies ranging from highly linear macromolecules, polymers with moderate level of branching, to highly branched PEs with hyperbranched structure. This method is a useful tool not only to investigate molecular weight, mass distribution, and size but also to enable access to important factors which describe the conformation in dilute solution and branching density. [ABSTRACT FROM AUTHOR]

The analysis of small particles, including extracellular vesicles and viruses, is contingent on their ability to scatter sufficient light to be detected. These detection methods include flow cytometry, nanoparticle tracking analysis, and single particle reflective image sensing. To standardize measurements and enable orthogonal comparisons between platforms, a quantifiable limit of detection is required. The main parameters that dictate the amount of light scattered by particles include size, morphology, and refractive index. To date, there has been a lack of accessible techniques for measuring the refractive index of nanoparticles at a single-particle level. Here, we demonstrate two methods of deriving a small particle refractive index using orthogonal measurements with commercially available platforms. These methods can be applied at either a single-particle or population level, enabling the integration of diameter and scattering cross section values to derive the refractive index using Mie theory.

We report an online analytical platform based on the coupling of asymmetrical flow field-flow fractionation (AF4) and native mass spectrometry (nMS) in parallel with UV-absorbance, multi-angle light scattering (MALS), and differential-refractive-index (UV-MALS-dRI) detectors to elucidate labile higher-order structures (HOS) of protein biotherapeutics. The technical aspects of coupling AF4 with nMS and the UV-MALS-dRI multi-detection system are discussed. The "slot-outlet" technique was used to reduce sample dilution and split the AF4 effluent between the MS and UV-MALS-dRI detectors. The stability, HOS, and dissociation pathways of the tetrameric biotherapeutic enzyme (anticancer agent) l-asparaginase (ASNase) were studied. ASNase is a 140 kDa homo-tetramer, but the presence of intact octamers and degradation products with lower molecular weights was indicated by AF4-MALS/nMS. Exposing ASNase to 10 mM NaOH disturbed the equilibrium between the different non-covalent species and led to HOS dissociation. Correlation of the information obtained by AF4-MALS (liquid phase) and AF4-nMS (gas phase) revealed the formation of monomeric, tetrameric, and pentameric species. High-resolution MS revealed deamidation of the main intact tetramer upon exposure of ASNase to high pH (NaOH and ammonium bicarbonate). The particular information retrieved from ASNase with the developed platform in a single run demonstrates that the newly developed platform can be highly useful for aggregation and stability studies of protein biopharmaceuticals.

Wearable, mobile, and point-of-care (POC) sensors comprise a rapidly expanding field of devices aimed at improving human health by relaying real-time biometric data such as heart rate and glucose levels. The current scope of what these devices can offer healthcare is limited by their inability to measure biomarkers associated with inflammation, well-being, and disease. Photonic biosensors that integrate sensing elements directly with spectrometers, lasers, and detectors are an attractive approach to enabling POC sensors, with distinct advantages in terms of size, weight, power consumption, and cost. Here, we have demonstrated for the first time the integration of photonic microring resonator biosensors with an on-chip microring filter bank spectrometer for the controlled detection of inflammatory biomarker C-reactive protein (CRP) in serum. We demonstrate that sensor and spectrometer performance is tolerant of temperature variation, as temperature dependence moves in parallel. Finally, we assess the impact of manufacturing variability on the 300 mm wafer scale on the performance of the spectrometer. Taken together, these results suggest that integration of on-chip ring filter bank spectrometers with ring resonator-based biosensors constitutes an attractive approach toward cost-effective integrated sensor development.

The fascination with the optical properties of naturally occurring systems has been driven in part by nature's ability to produce a diverse palette of vibrant colors from a relatively small number of common structural motifs. Within this context, some cephalopod species have evolved skin cells called iridophores and leucophores whose constituent ultrastructures reflect light in different ways but are composed of the same high refractive index material─a protein called reflectin. Although such natural optical systems have attracted much research interest, measuring the refractive indices of biomaterial-based structures across multiple different environments and establishing theoretical frameworks for accurately describing the obtained refractive index values has proven challenging. Herein, we employ a synergistic combination of experimental and computational methodologies to systematically map the three-dimensional refractive index distributions of model self-assembled reflectin-based structures both in vivo and in vitro . When considered together, our findings may improve understanding of squid skin cell functionality, augment existing methods for characterizing protein-based optical materials, and expand the utility of emerging holotomographic microscopy techniques.

Rapid and reliable characterization of heterogeneous nanoparticle suspensions is a key technology across the nanosciences. Although approaches exist for homogeneous samples, they are often unsuitable for polydisperse suspensions, as particles of different sizes and compositions can lead to indistinguishable signals at the detector. Here, we introduce holographic nanoparticle tracking analysis, holoNTA, as a straightforward methodology that decouples size and material refractive index contributions. HoloNTA is applicable to any heterogeneous nanoparticle sample and has the sensitivity to measure the intrinsic heterogeneity of the sample. Specifically, we combined high dynamic range k-space imaging with holographic 3D single-particle tracking. This strategy enables long-term tracking by extending the imaging volume and delivers precise and accurate estimates of both scattering amplitude and diffusion coefficient of individual nanoparticles, from which particle refractive index and hydrodynamic size are determined. We specifically demonstrate, by simulations and experiments, that irrespective of localization uncertainty and size, the sizing sensitivity is improved as our extended detection volume yields considerably longer particle trajectories than previously reported by comparable technologies. As validation, we measured both homogeneous and heterogeneous suspensions of nanoparticles in the 40-250 nm size range and further monitored protein corona formation, where we identified subtle differences between the nanoparticle-protein complexes derived from avidin, bovine serum albumin, and streptavidin. We foresee that our approach will find many applications of both fundamental and applied nature where routine quantification and sizing of nanoparticles are required.

Most label-free techniques rely on measuring refractive index or mass change on the sensor surface. Thus, it is challenging for them to measure small molecules or enzymatic processes that only induce a minor mass change on the analyte molecules. Here, we have developed a technique by combining Surface Plasmon Resonance sensing with an Oscillating Biomolecule Layer approach (SPR-OBL) to enhance the sensitivity of traditional SPR. In addition to the inherent mass sensitivity, SPR-OBL is also sensitive to the charge and conformational change of the analyte; hence it overcomes the mass limit and is able to detect small molecules. We show that the multimetric SPR-OBL measurement allows for sensing any changes regarding mass, charge, and conformation, which expands the detection capability of SPR.

This paper first reports a liquid-core hydrogel optical fiber fluorescence probe. It is composed of a liquid core, a high-refractive-index hydrogel fiber core, and a low-refractive-index hydrogel fiber cladding, which is completely different from many existing optical fiber fluorescence probes. The sensing solution with sensitive materials is sealed as a liquid core, and it can sufficiently react with small-molecule targets penetrating through the hydrogel fiber cladding and core, thus inducing variations in the fluorescence signals. These fluorescence signals can be localized and transmitted within the probe and finally collected and quantified for target detection. This proposed probe can be simply and rapidly fabricated and reused, and it was proven to have high sensitivity, accuracy, and selectivity in practical applications. Therefore, this liquid-core hydrogel optical fiber fluorescence probe will enable a novel sensing platform for small-molecule analyte detection that faces on-site detection challenges.

The need for self-referencing is extremely important in the field of biosensing. In this manuscript, we report on the study, design, and validation of a dual-region self-referencing fiber-optic surface plasmon resonance biosensor. One region is intended to measure and monitor the binding events of the biological sample under test, while the other one is designed to be used as a reference channel to compensate for external factors, such as bulk refractive index modifications and temperature oscillations, that can negatively affect the biomolecular interaction measurement. Two different configurations for the biosensor probe are presented and investigated here, both theoretically and experimentally. First, the theoretical performance of the proposed biosensor probes, in terms of surface plasmon resonance wavelength shift, was simulated using a numerical model. Afterward, they were experimentally validated in sucrose-water solutions and showed a response to refractive index and temperature changes with sensitivities up to 2000 nm/RIU and 1.559 nm/°C, respectively. Finally, an aptamer-based bioassay and a high-resolution melting assay were successfully implemented on the two proposed configurations, demonstrating the feasibility of analyzing the binding events and measuring other external signal modifications simultaneously using the same biosensor probe.

Microlens arrays (MLAs) are acquiring a key role in the micro-optical system, which have been widely applied in the fields of imaging processing, light extraction, biochemical sensing, and display technology. Compared with solid MLAs, liquid MLAs have received extensive attention due to their natural smooth interface and adjustability. However, manufacturing tunable liquid MLAs with ideal structures is still a key challenge for current technologies. In this paper, a novel and simple optofluidic method is demonstrated, enabling the tunable focusing and high-quality imaging of liquid MLAs. Tunable droplets are fabricated and self-assembled into arrays as the MLAs, which can be easily adjusted to focus, form images, and display different focal lengths. Tuning of MLAs' focusing properties (range from 550 to 5370 μm) is demonstrated by changing the refractive index (RI) of the droplets with a fixed size of 200 μm, which can be changed by adjusting the flow rates of the two branch streams. Also, the corresponding numerical apertures of the MLAs range from 0.026 to 0.26. Furthermore, the MLAs' functionality for microparticle imaging applications is also illustrated. Combining the MLAs with a 4× objective, microparticle imaging is magnified two times, and the resolution has also been improved on the original basis. Besides, both the size and RI of the MLAs in an optofluidic chip can be further adjusted to detect samples at different positions. These MLAs have the merits of high optical performance, a simple fabrication procedure, easy integration, and good tunability. Thus, it shows promising opportunities for many applications, such as adaptive imaging and sensing.

Time-resolved measurements of changes in the size and shape of nanobiological objects and layers are crucial to understand their properties and optimize their performance. Optical sensing is particularly attractive with high throughput and sensitivity, and label-free operation. However, most state-of-the-art solutions require intricate modeling or multiparameter measurements to disentangle conformational or thickness changes of biomolecular layers from complex interfacial refractive index variations. Here, we present a dual-band nanoplasmonic ruler comprising mixed arrays of plasmonic nanoparticles with spectrally separated resonance peaks. As electrodynamic simulations and model experiments show, the ruler enables real-time simultaneous measurements of thickness and refractive index variations in uniform and heterogeneous layers with sub-nanometer resolution. Additionally, nanostructure shape changes can be tracked, as demonstrated by quantifying the degree of lipid vesicle deformation at the critical coverage prior to rupture and supported lipid bilayer formation. In a broader context, the presented nanofabrication approach constitutes a generic route for multimodal nanoplasmonic optical sensing.

The refractive index (RI) is a fundamental physical property of materials. Although measurement of the RI of biological nanoparticles (BNPs) in aqueous media is of great importance to basic research and biomedical applications, it is hampered by their tiny size, large intrinsic heterogeneity, and weak scattering. Here, we report the development of a label-free technique that can determine the RI of individual viruses and small extracellular vesicles (sEVs) with high precision and an analysis rate up to 10 000 particles per minute. This was achieved via the combination of high-sensitivity light-scattering detection by nanoflow cytometry (nFCM) and the Mie theory calculation. With the measured RIs for T7 virions, T7 capsids, and sEVs, the concentrations of nucleic acid in viral particles and protein in the lumen of sEVs were estimated. Furthermore, building upon a simplified core-shell model, the RIs of sEVs ranging from 40 to 200 nm were obtained. By using these RIs, a statistically robust size distribution of sEVs was acquired in minutes with accuracy and resolution matched closely with those of cryo-TEM measurements. Our approach could become an important tool in the RI determination of single BNPs.

A photoreceptor on the retina acts as an optical waveguide to transfer an individual photonic signal to the cell inside, which is determined by the refractive index of internal materials. Under the photoactivation of photoreceptors making conformational and chemical variation in a visual cell, the optical signal modulation is demonstrated using an artificial photoreceptor-based waveguide with a controlling beam refraction. Two types of nanodiscs are made of human photoreceptor proteins, short-wavelength-sensitive opsin and rhodopsin, with spectral sensitivity. The refractive index and nonlinear features of those two photosensitive nanodiscs are investigated as fundamental properties. The photonanodiscs are photoactivated in such a way that allow refractive index tuning over 0.18 according to the biological function of the respective proteins with color-dependent response.

Metasurfaces are 2D artificial materials consisting of arrays of metamolecules, which are exquisitely designed to manipulate light in terms of amplitude, phase, and polarization state with spatial resolutions at the subwavelength scale. Traditional micro/nano-optical sensors (MNOSs) pursue high sensitivity through strongly localized optical fields based on diffractive and refractive optics, microcavities, and interferometers. Although detections of ultra-low concentrations of analytes have already been demonstrated, the label-free sensing and recognition of complex and unknown samples remain challenging, requiring multiple readouts from sensors, e.g ., refractive index, absorption/emission spectrum, chirality, etc . Additionally, the reliability of detecting large, inhomogeneous biosamples may be compromised by the limited near-field sensing area from the localization of light. Here, we review recent advances in metasurface-based MNOSs and compare them with counterparts using micro-optics from aspects of physics, working principles, and applications. By virtue of underlying the physics and design flexibilities of metasurfaces, MNOSs have now been endowed with superb performances and advanced functionalities, leading toward highly integrated smart sensing platforms.

Nanophotonic waveguides that implement long optical pathlengths on chips are promising to enable chip-scale gas sensors. Nevertheless, current absorption-based waveguide sensors suffer from weak interactions with analytes, limiting their adoptions in most demanding applications such as exhaled breath analysis and trace-gas monitoring. Here, we propose an all-dielectric metamaterial-assisted comb (ADMAC) waveguide to greatly boost the sensing capability. By leveraging large longitudinal electric field discontinuity at periodic high-index-contrast interfaces in the subwavelength grating metamaterial and its unique features in refractive index engineering, the ADMAC waveguide features strong field delocalization into the air, pushing the external optical field confinement factor up to 113% with low propagation loss. Our sensor operates in the important but underdeveloped long-wave infrared spectral region, where absorption fingerprints of plentiful chemical bonds are located. Acetone absorption spectroscopy is demonstrated using our sensor around 7.33 μm, showing a detection limit of 2.5 ppm with a waveguide length of only 10 mm.

Whispering-gallery microresonators have the potential to become the building blocks for optical circuits. However, encoding information in an optical signal requires on-demand tuning of optical resonances. Tuning is achieved by modifying the cavity length or the refractive index of the microresonator. Due to their solid, nondeformable structure, conventional microresonators based on bulk materials are inherently difficult to tune. In this work, we fabricate irreversibly tunable optical microresonators by using semiconductor nanocrystals. These nanocrystals are first assembled into colloidal spherical superparticles featuring whispering-gallery modes. Exposing the superparticles to shorter ligands changes the nanocrystal surface chemistry, decreasing the cavity length of the microresonator by 20% and increasing the refractive index by 8.2%. Illuminating the superparticles with ultraviolet light initiates nanocrystal photo-oxidation, providing an orthogonal channel to decrease the refractive index of the microresonator in a continuous fashion. Through these approaches, we demonstrate optical microresonators tunable by several times their free spectral range.

Predicting the properties of materials prior to their synthesis is of great significance in materials science. Optical materials exhibit a large number of interesting properties that make them useful in a wide range of applications, including optical glasses, optical fibers, and laser optics. In all of these applications, refraction and its chromatic dispersion can directly reflect the characteristics of the transmitted light and determine the practical utility of the material. We demonstrate the feasibility of reconstructing chromatic-dispersion relations of well-known optical materials by aggregating data over a large number of independent sources, which are contained within a material database of experimentally determined refractive indices and wavelength values. We also employ this database to develop a machine-learning platform that can predict refractive indices of compounds without needing to know the structure or other properties of a material of interest. We present a web-based application that enables users to build their customized machine-learning models; this will help the scientific community to conduct further research into the discovery of optical materials.

Entangled photon pairs are predicted to linearize and increase the efficiency of two-photon absorption, allowing continuous wave laser diodes to drive ultrafast time-resolved spectroscopy and nonlinear processes. Despite a range of theoretical studies and experimental measurements, inconsistencies in the value of the entanglement-enhanced interaction cross section persist. A spectrometer that can temporally and spectrally characterize the entangled photon state before, during, and after any potential two-photon excitation event is constructed. For the molecule rhodamine 6G, which has a virtual state pathway, any entangled two-photon interaction is found to be equal to or weaker than classical, single-photon scattering events. This result can account for the discrepancies among the wide variety of entangled two-photon absorption cross sections reported from different measurement techniques. The reported instrumentation can unambiguously separate classical and entangled effects and therefore is important for the growing field of nonlinear and multiphoton entangled spectroscopy.

To manipulate the light-matter interaction effectively, we often rely on high refractive index inorganic nanoparticles. Such materials are contained essentially in everything that looks colorful or white: from paints to coatings but also in processed food, toothpaste, and cosmetic products. As these nanoparticles can accumulate in the human body and environment, there is a strong need to replace them with more biocompatible counterparts. In this work, we introduce various types of cellulose-based microparticles (CMPs) of four sizes with optimized dimensions for efficient light scattering that can replace traditional inorganic particles. We demonstrate that the produced materials can be exploited as highly efficient scattering enhancers, with designed optical performance. Finally, exploiting these cellulose colloids, we fabricated scattering materials and high transmittance/haze films with record performances with respect to the state-of-the-art values. The renewable and biocompatible nature of our systems, combined with their excellent optical properties, allows for the use of our cellulose-based particles in paints, LEDs, and solar cell devices and especially in applications where the biocompatibility of the component is essential, such as in food and pharmaceutical coatings.

Silicon (Si) is promising as a field enhancement material because of its high abundance, low toxicity, and high refractive index. The field enhancement effect intensifies light-matter interactions, which improves photocatalysis, solar cell performance, and sensor sensitivity. To manufacture field enhancement materials on a production scale, the fabrication technique must be simple, cost-effective, fast, and highly reproducible and must produce a high enhancement factor (EF). Herein, we report on an economical and efficient fabrication method for a field enhancement substrate consisting of a two-dimensional Si wire array (2D-SiWA). This substrate was demonstrated as a fluorescence sensor with high sensitivity (EF > 200) and composed of a large area (6.0 mm 2 ). In addition, single wire spectroscopy was used to identify very high reproducibility of the sensor sensitivity in regular regions (97%) and a mixture of regular and irregular regions (87%) of the 2D-SiWA. The large-area Si fluorescence sensor fabrication was cost-effective and rapid and was 50× less expensive, 20×faster, and 60,000×larger than the typical electron beam lithography method.

Salinity is an indispensable parameter for various applications such as biomedical diagnostics, environmental chemical analysis, marine monitoring, etc. Miniaturized salinity sensors have significant potential in portable applications in various scenarios and designs with highly desirable features of convenience, reliability, economy, and high sensitivity and also the capability of real-time measurements. Herein, we demonstrate a highly refractive index-sensitive sensor based on a microscale III-nitride chip that consists of a light emitter and a photodetector. This highly monolithically integrated chip shows an excellent sensitivity of salinity of 2606 nA/(mol/L) (or 446 nA/%) and a response time of 0.243 s. In addition, wireless communication technologies can be easily integrated with the sensing device, which enables automatic remote control for data collection and postprocessing. Remarkably, a polymer-based antifouling coating on the surface of the sensing chip has been established to significantly improve its long-term stability in mimicked marine water. The demonstrated ultrasensitive, ultracompact, cost-effective, fast response, wireless-compatible, and easy-to-use features endow the current device with a huge potential for in situ salinity sensing under varying environmental conditions.

In situ refractive index sensors integrated with nanoaperture-based optical tweezers possess stable and sensitive responsivity to single nanoparticles. In most existing works, detection events are only identified using the total light intensity with directivity information ignored, leading to a low signal-to-noise ratio. Here, we propose to detect an optically trapped 20 nm silica particle by monitoring directivity of a plasmonic antenna. The main and secondary radiation lobes of the antenna reverse upon trapping because the particle-induced perturbation negates the relative phase between two antenna elements, leading to a significant change of the antenna front-to-back ratio. As a result, we obtain a signal-to-noise ratio of 20, with an order-of-magnitude improvement as compared to the intensity-only detection scheme.

The structural coloration and decoloration are problems of scientific interest for a long time. Hence, the fundamental investigations on structures and the optical properties of insect wings have been performed. As a part of such studies, we elucidate the optical properties of green lacewing wings via observation and simulation. First, we elucidate the surface pattern of green lacewing wings using a two-dimensional fast Fourier transform. A cross-shaped pattern of a Fourier spectrum is obtained, and the concise wing model with the surface protrusions arranged in a square grid on a base substrate is constructed in reference to the obtained Fourier spectrum. Next, we perform a finite-difference time-domain (FDTD) simulation to elucidate a light path through wings with and without surface protrusions. The FDTD simulation results indicate that the surface protrusions of a wing increase and decrease the intensity of the transmitted and reflected light, respectively, which is an antireflection behavior. This phenomenon was also observed in the case of 45° incident light. The intensity of transmitted light coupled to wings is induced by surface protrusions with a stepwise refractive index between air and a substrate, which induces antireflection. In particular, transmitted light is increased by the surface protrusions of wings in the range of 500-800 nm wavelength. The intensities of transmitted and reflected light are affected by the direction of incident electric field (polarization) in the case of wings with protrusions arranged in the same direction (parallel). Hence, the surface protrusions are arranged in a square grid to reduce the influence of the polarization direction.

Highly sensitive detection of refractive index (RI) is essential for the analysis of the bio-microenvironment and basic cellular reactions. To achieve this, optic-fiber RI sensors based on localized surface plasmon resonance (LSPR) have been widely used for their flexibility and high sensitivity. However, the current optic-fiber RI sensors are mainly fabricated using glass, which makes them face the challenges in biocompatibility and biosafety. In this work, a RI sensor with high sensitivity is fabricated using metal-nanostructure-decorated spider silk. The spider silk, which is directly dragged from Araneus ventricosus , is natural protein-based biopolymer with low attenuation, good biocompatibility and biodegradability, large RI, great flexibility, and easy functionalization. Hence, the spider silk can be an ideal alternative to glass for sensing in biological environments with a wide RI range. Different kinds of metal nanostructures, such as gold nanorods (GNRs), gold nanobipyramids (GNBP), and Ag@GNRs, are decorated on the surface of the spider silk utilizing the surface viscidity of the silk. By directing a beam of white light into the spider silk, the LSPR of the metal nanostructures was excited and a highly sensitive RI sensing (the highest sensitivity of 1746 nm per refractive index was achieved on the GNBP-decorated spider silk) was obtained. This work may pave a new way to precise and sensitive biosensing and bioanalysis.

An optical control of many working optoelectronic systems (real-time sensors, optical modulators, light amplifiers, or phase retarders) giving efficient optical gain or remote signal modulation is currently included as scientifically and industrially interesting. In here, an oxazolone derivative as the multifunctional organic system is given in this contribution. The molecule possesses a stilbene group and an oxazolone heteroatomic ring, which implies effective refractive index manipulation and multimode lasing action, respectively. The light modulation is repeatable and stable, also in the hundreds of Hz regime. On the other hand, the amplified optical signal can be easily generated by an external optical pumping source. Thus, signal control is fully available, as is read-in and read-out of the information in real time. Furthermore, this third-order, nonlinear, optical phenomenon using a third harmonic generation technique was also observed. We discovered that only by changing the energy and time regime of the supplied optical signal is the optical or nonlinear optical response observed. Two heteroenergetic molecular states ( trans ( E ) and cis ( Z )) can efficiently operate in modern multifunctional optoelectronic systems, which can provide and generate an optical signal. Such functionalities are commonly used in all-optical photonic switchers and logic gates and can be utilized in optical-core networks and computers.

Imaging platforms that enable long-term, high-resolution imaging of biofilms are required to study cellular level dynamics within bacterial biofilms. By combining high spatial and temporal resolution and low phototoxicity, lattice light sheet microscopy (LLSM) has made critical contributions to the study of cellular dynamics. However, the power of LLSM has not yet been leveraged for biofilm research because the open-on-top imaging geometry using water-immersion objective lenses is not compatible with living bacterial specimens; bacterial growth on the microscope's objective lenses makes long-term time-lapse imaging impossible and raises considerable safety concerns for microscope users. To make LLSM compatible with pathogenic bacterial specimens, we developed hermetically sealed, but optically accessible, microfluidic flow channels that can sustain bacterial biofilm growth for multiple days under precisely controllable physical and chemical conditions. To generate a liquid- and gas-tight seal, we glued a thin polymer film across a 3D-printed channel, where the top wall had been omitted. We achieved negligible optical aberrations by using polymer films that precisely match the refractive index of water. Bacteria do not adhere to the polymer film itself, so that the polymer window provides unobstructed optical access to the channel interior. Inside the flow channels, biofilms can be grown on arbitrary, even nontransparent, surfaces. By integrating this flow channel with LLSM, we were able to record the growth of S. oneidensis MR-1 biofilms over several days at cellular resolution without any observable phototoxicity or photodamage.

Both the nonclose-packed structure and the large refractive index contrast of guanine nanocrystals and cytosols in iridophores play a vital role in the dynamic camouflage of chameleons, including the bright skin color and color tuning sensitivity to external stimulus. Here, the nonclose-packed photonic crystals consisting of ZnS nanospheres and polymers, which have similar refractive indices with guanine nanocrystals and cytosols, respectively, are constructed by a two-step filling strategy. ZnS@SiO 2 nanospheres are self-assembled to build intermediate close-packed photonic crystals followed by filling polymers in their interstices. The nonclose-packed photonic crystal is successfully achieved when the silica portion is etched by HF solution and refilled by polymers. Excitingly, the stimulus response of the designed photonic crystal is as sensitive as the skin of chameleons due to the similar contrast of refractive indices and nonclose-packed structure. The reflection peak of the structure can blue-shift more than 200 nm as the temperature increases from 30 to 55 °C or under 20% compressional strain. This work not only builds the nonclose-packed photonic crystals by introducing a two-step filling strategy but also proves that high refractive contrast in photonic crystals is an effective strategy to achieve ultrasensitivity, which is highly desirable for various applications.

Two-dimensional transition metal dichalcogenides are promising candidates for ultrathin light modulators due to their highly tunable excitonic resonances at visible and near-infrared wavelengths. At cryogenic temperatures, large excitonic reflectivity in monolayer molybdenum diselenide (MoSe 2 ) has been shown, but the permittivity and index modulation have not been studied. Here, we demonstrate large gate-tunability of complex refractive index in monolayer MoSe 2 by Fermi level modulation and study the doping dependence of the A and B excitonic resonances for temperatures between 4 and 150 K. By tuning the charge density, we observe both temperature- and carrier-dependent epsilon-near-zero response in the permittivity and transition from metallic to dielectric near the A exciton energy. We attribute the dynamic control of the refractive index to the interplay between radiative and non-radiative decay channels that are tuned upon gating. Our results suggest the potential of monolayer MoSe 2 as an active material for emerging photonics applications.

Herein, a novel liquid crystal microarray (LCM) film with optical regulation ability is first constructed by combining liquid crystals (LC) and the highly ordered microporous structure of inverse opal photonic crystals (IOPhCs). The LCM films are fabricated by infiltrating LC molecules into the LC polymer with the structure of IOPhCs, and their properties are very different from those without the LC. Interestingly, the optical property of LCM films can be controlled by changing the orientation of LC molecules, which varies with the interfacial force. In combination with polarization images, spectral reflection peak, circular dichroism spectra, potential difference, and fluorescence images of LCM films, the mechanism of this change is investigated. It is found that the exposed basic group of single-stranded DNA is the key to the change of the optical property of LC microarrays. Meanwhile, the optical signals of LC microarrays based on the PhCs provide a novel LC signal mode for an LC sensing system (microspectral signal mode), and it can be recorded by a fiber-optic spectrometer, which is a great improvement on LC sensing signals. Therefore, the LC microarray sensing signal can be used for accurate analysis of targets by the change of the reflection peak intensity of PhCs. When the LC molecules are induced by different aptamers, the LC microarray sensing interface can be further used for the determination of different targets, such as cocaine and Hg 2+ . The research on LCM films is of significant value for the development of LC sensing technology and also shows great application prospects in biochemical sensing fields.

A method to enable surface plasmon resonance (SPR) sensors to discriminate between bulk and surface-localized refractive index changes is demonstrated with modified gold-coated tilted fiber Bragg grating SPR sensors (TFBG-SPR). Without this capability, all high-resolution SPR sensors should be using reference channels and strict temperature control to prevent the contamination of the desired detection of surface-localized chemical or binding events by drift of the refractive index of the medium, in which the experiment is carried out. The very fine comb of high-quality-factor resonances of a TFBG-SPR device coupled to the large differential sensitivity of some of the resonances to various perturbations is used to measure unambiguously the refractive index changes within a surface layer thinner than 25 nm from those of the bulk surrounding. The enabling modification of the conventional TFBG-SPR is a reduction of the gold coating from its optimum value near 50-30 nm: at this lower thickness, a surface plasmon wave can still be excited by a limited number of cladding mode resonances, but at the same time, the metal is thin enough to allow modes away from the SPR to tunnel across the metal and probe the bulk RI value. Measurements and simulations of the deposition of a self-assembled monolayer of 1-dodecanethiol in ethanol show that the bulk refractive index changes as small as 0.0004 can be distinguished from the formation of a 1 nm thick coating on the surface of the fiber.

Terahertz (THz) spectroscopy is a powerful tool for unambiguously extracting complex-valued material properties (e.g., refractive index, conductivity, etc.) from a wide range of samples, with applications ranging from materials science to biology. However, extracting complex refractive indices from THz time-domain spectroscopy data can prove challenging, especially for multilayer samples. These challenges arise from the large number of transmission-reflection paths the THz pulse can take through the sample layers, leading to unwieldy strings of Fresnel coefficients. This issue has often been addressed using various approximations. However, these approximations are only applicable to specific classes of samples and can give erroneous results when misapplied. An alternative to this approach is to programmatically model all possible paths through the sample. The many paths through the sample layers can be modeled as a tree that branches at every point where the paths diverge, i.e., whenever the pulse can either be transmitted or reflected. This tree can then be used to generate expressions relating the unknown refractive index to the observed time domain data. Here, we provide a freely available open-source package implementing this method as both a MATLAB library and a corresponding graphical user interface, which can also be run without a MATLAB license ( https://github.com/YaleTHz/nelly ). We have tested this method for a range of samples and compared the results to commonly used approximations to demonstrate its accuracy and wide applicability. Our method consistently gives better agreement than common approximations.

Phycobiliproteins are a class of light-harvesting fluorescent proteins existing in cyanobacteria and microalgae, which harvest light and convert it into electricity. Owing to recent demands on environmental-friendly and renewable apparatuses, phycobiliproteins have attracted substantial interest in bioenergy and sustainable devices. However, converting energy from biological materials remains challenging to date. Herein, we report a novel scheme to enhance biological light-harvesting through light-matter interactions at the biointerface of whispering-gallery modes (WGMs), where phycobiliproteins were employed as the active gain material. By exploiting microdroplets as a carrier for light-harvesting biomaterials, strong local electric field enhancement and photon confinement at the cavity interface resulted in significantly enhanced bio-photoelectricity. A threshold-like behavior was discovered in photocurrent enhancement and the WGM modulated fluorescence. Systematic studies of biologically produced photoelectricity and optical mode resonance were carried out to illustrate the impact of the cavity quality factor, structural geometry, and refractive indices. Finally, a biomimetic system was investigated by exploiting cascade energy transfer in phycobiliprotein assembly composed of three light-harvesting proteins. The key findings not only highlight the critical role of optical cavity in light-harvesting but also offer deep insights into light energy coupling in biomaterials.

A multifunction, high-sensitivity, and temperature-compensated optical fiber DNA hybridization sensor combining surface plasmon resonance (SPR) and Mach-Zehnder interference (MZI) has been designed and implemented. We demonstrate, for the first time to our knowledge, the dual-parameter measurement of temperature and refractive index (RI) by simultaneously using SPR and MZI in a simple single-mode fiber (SMF)-no-core fiber (NCF)-SMF structure. The experimental results show RI sensitivities of 930 and 1899 nm/RIU and temperature sensitivities of 0.4 and -1.4 nm/°C for the MZI and SPR, respectively. We demonstrate a sensitivity matrix used to simultaneously detect both parameters, solving the problem of temperature interference of RI variation-based biosensors. In addition, the sensor can also distinguish biological binding events by detecting the localized RI changes at the fiber's surface. We realize label-free sensing of DNA hybridization detection by immobilizing probe DNA (pDNA) onto the fiber as the probe to capture complementary DNA (cDNA). The experimental results show that the sensor can qualitatively detect cDNA after temperature compensation, and the limit of detection (LOD) of the sensor reaches 80 nM. The proposed sensor has advantages of high sensitivity, real time, low cost, temperature compensation, and low detection limit and is suitable for in situ monitoring, high-precision sensing of DNA molecules, and other related fields, such as gene diagnosis, kinship judgment, environmental monitoring, and so on.

Cosolvent-free (solventless) hydrolytic polycondensation of fluoroalkyltrimethoxysilanes of linear fluoroalkyl groups of the form R = C n F 2 n +1 C 2 H 4 ( n = 1, 4, and 8) and methyltrimethoxysilane followed by thermal curing yielded dense polymeric silsesquioxane (SQ) resins with low refractive indices and deep-ultraviolet transparency with an ultraviolet absorption edge at ∼210 nm. The refractive index at 589 nm was adjustable at ∼1.35-1.39, and the lowest value was ∼1.354 for the stiff resin and ∼1.347 for the soft resin of poly(R- co -Me-SQ) prepared at n = 8. The refractive indices of these resins were consistent with the linear combinations of molar refractivities of constituent functional groups, and there were no free-volume anomalies.

Waveguide enhanced Raman spectroscopy (WERS) utilizes simple, robust, high-index contrast dielectric waveguides to generate a strong evanescent field, through which laser light interacts with analytes residing on the surface of the waveguide. It offers a powerful tool for the direct identification and reproducible quantification of biochemical species and an alternative to surface enhanced Raman spectroscopy (SERS) without reliance on fragile noble metal nanostructures. The advent of low-cost laser diodes, compact spectrometers, and recent progress in material engineering, nanofabrication techniques, and software modeling tools have made realizing portable and cheap WERS Raman systems with high sensitivity a realistic possibility. This review highlights the latest progress in WERS technology and summarizes recent demonstrations and applications. Following an introduction to the fundamentals of WERS, the theoretical framework that underpins the WERS principles is presented. The main WERS design considerations are then discussed, and a review of the available approaches for the modification of waveguide surfaces for the attachment of different biorecognition elements is provided. The review concludes by discussing and contrasting the performance of recent WERS implementations, thereby providing a future roadmap of WERS technology where the key opportunities and challenges are highlighted.

Accessing cell growth on adhesive substrates is critical for identifying biophysical properties of cells and their therapeutic response to drug therapies. However, optical techniques have low sensitivity, and their reliability varies with cell type, whereas microfluidic technologies rely on cell suspension. In this paper, we introduced a plasmonic functional assay platform that can precisely measure cell weight and the dynamic change in real-time for adherent cells. Possessing this ability, our platform can determine growth rates of individual cells within only 10 min to map the growth profile of populations in short time intervals. The platform could successfully determine heterogeneity within the growth profile of populations and assess subpopulations exhibiting distinct growth profiles. As a proof of principle, we investigated the growth profile of MCF-7 cells and the effect of two intracellular metabolisms critical for their proliferation. We first investigated the negative effect of serum starvation on cell growth. We then studied ornithine decarboxylase (ODC) activity, a key enzyme which is involved in proliferation, and degraded under low osmolarity that inhibits cell growth. We successfully determined the significant distinction between growth profiles of MCF-7 cells and their ODC-overproducing variants that possess strong resistance to the negative effects of low osmolarity. We also demonstrated that an exogenous parameter, putrescine, could rescue cells from ODC inhibition under hypoosmotic conditions. In addition to the ability of accessing intracellular activities through ex vivo measurements, our platform could also determine therapeutic behaviors of cancer cells in response to drug treatments. Here, we investigated difluoromethylornithine (DFMO), which has antitumor effects on MCF-7 cells by inhibiting ODC activity. We successfully demonstrated the susceptibility of MCF-7 cells to such drug treatment, while its DFMO-resistant subpopulation could survive in the presence of this antigrowth agent. By rapidly determining cell growth kinetics in small samples, our plasmonic platform may be of broad use to basic research and clinical applications.

Photonic crystals (PhCs) display photonic stop bands (PSBs) and at the edges of these PSBs transport light with reduced velocity, enabling the PhCs to confine and manipulate incident light with enhanced light-matter interaction. Intense research has been devoted to leveraging the optical properties of PhCs for the development of optical sensors for bioassays, diagnosis, and environmental monitoring. These applications have furthermore benefited from the inherently large surface area of PhCs, giving rise to high analyte adsorption and the wide range of options for structural variations of the PhCs leading to enhanced light-matter interaction. Here, we focus on bottom-up assembled PhCs and review the significant advances that have been made in their use as label-free sensors. We describe their potential for point-of-care devices and in the review include their structural design, constituent materials, fabrication strategy, and sensing working principles. We thereby classify them according to five sensing principles: sensing of refractive index variations, sensing by lattice spacing variations, enhanced fluorescence spectroscopy, surface-enhanced Raman spectroscopy, and configuration transitions.

For biomedical photoacoustic applications, an ongoing challenge in simultaneous volumetric imaging and spectroscopic analysis arises from ultrasonic detectors lacking high sensitivity to pressure transients over a broad spectral bandwidth. Photoacoustic impulses can be measured on the basis of the ultrafast temporal dynamics and highly sensitive response of surface plasmon polaritons to the refractive index changes. Taking advantage of the ultra-sensitive phase shift of surface plasmons caused by ultrasonic perturbations instead of the reflectivity change [as is the case for traditional surface plasmon resonance (SPR) sensors], a novel SPR sensor based on phase-shifted interrogation was developed for the broadband measurement of photoacoustically induced pressure transients with improved detection sensitivity. Specifically, by encoding the acoustically modulated phase change into time-varying interference intensity, our sensor achieved an almost five-fold sensitivity enhancement (∼98 Pa noise-equivalent pressure) compared with the reflectivity-mode SPR sensing technologies (∼470 Pa) while retaining a broadband acoustic response of ∼174 MHz. Incorporating our sensor into an optical-resolution photoacoustic microscope, we performed label-free imaging of a zebrafish eye in vivo , enabling simultaneous volumetric visualization and spectrally resolved discrimination of anatomical features. This novel sensing technology has potential for advancing biomedical ultrasonic and/or photoacoustic investigations.