Compressible Hollow Microlasers in Organoids for High-Throughput and Real-Time Mechanical Screening.

Mechanical stress within organoids is a pivotal indicator in disease modeling and pharmacokinetics, yet current tools lack the ability to rapidly and dynamically screen these mechanics. Here, we introduce biocompatible and compressible hollow microlasers that realize all-optical assessment of cellular stress within organoids. The laser spectroscopy yields identification of cellular deformation at the nanometer scale, corresponding to tens of pascals stress sensitivity. The compressibility enables the investigation of the isotropic component, which is the fundamental mechanics of multicellular models. By integrating with a microwell array, we demonstrate the high-throughput screening of mechanical cues in tumoroids, establishing a platform for mechano-responsive drug screening. Furthermore, we showcase the monitoring and mapping of dynamic contractile stress within human embryonic stem cell-derived cardiac organoids, revealing the internal mechanical inhomogeneity within a single organoid. This method eliminates time-consuming scanning and sample damage, providing insights into organoid mechanobiology.

The luminescent Nb2C MXene nanosheet-based whispering gallery mode-enhanced ECL strategy for miRNA-214 detection.

MiRNA-214 can regulate the expression of their downstream target genes after post-transcriptional and are involved in the biological processes of triple negative breast cancer (TNBC). In this work, the small-sized luminescent Nb2C nanosheet-based whispering gallery mode-enhanced electrochemiluminescence (ECL) strategy was successfully constructed to detect miRNA-214 in TNBC. Firstly, we have synthesized small-sized luminescent Nb2C nanosheets from Nb2AlC MXene. The Nb2C nanosheets not only exhibited more stable chemical properties and reduced the defects of the large sheet structures, but also possessed the quantum confinement effect with the discrete energy level. As a result, the prepared small-sized Nb2C nanosheets had unique luminescent and electrochemical properties. Furthermore, in order to improve the ECL performance of Nb2C nanosheets, SiO2 microspheres were self-assembled on the electrode surface by gas-liquid interface method to form whispering gallery mode structure. Because the light was continuously reflected at the interface of the microcavity in the whispering gallery mode, the ECL signal of Nb2C luminescent nanosheets was amplified largely. Finally, the whispering gallery mode-based ECL sensing platform was established. The results showed that the biosensor had a good linear correlation between the ECL intensity and the logarithm of concentration of miRNA-214 in the range of 10 fM to 100 nM with a limit of detection of 2.5 fM. The actual detection of miRNA-214 content in clinical TNBC tissue samples was realized successfully.

Nonlinear Photon Generations from Subwavelength Whispering-Gallery-Mode Resonator.

The strong light localization and long photon lifetimes in whispering gallery mode (WGM) microresonators, benefiting from a high-quality (Q) factor and a small mode volume (V), could significantly enhance light-matter interactions, enabling efficient nonlinear photon generation and paving the way for exploring novel on-chip optical functionalities. However, the leakage of energy from bending losses severely limits the improvement of the Q factor for subwavelength WGM microresonators. Here, we demonstrated an integrated self-suspended WGM microresonator that combines external rings and bridges with a microdisk on a platform of silicon on insulator, achieving about one-hundred-fold enhancement in the Q factor and an ultrasmall mode volume of 2.67(/λnSi)3 as predicted by numerical simulations. We experimentally confirmed the improved performance of the subwavelength WGM resonator with the dramatic enhancement of third-harmonic generation and second-harmonic generation on this device. Our work is anticipated to enhance light-matter interactions on small-footprint microresonators and boost the development of efficient integrated nonlinear and quantum photonics.

Rare-Earth-Metal-Free Solid-State Fluorescent Carbonized-Polymer Microspheres for Unclonable Anti-Counterfeit Whispering-Gallery Emissions from Red to Near-Infrared Wavelengths.

Colloidal carbon dots (CDs) have garnered much attention as metal-free photoluminescent nanomaterials, yet creation of solid-state fluorescent (SSF) materials emitting in the deep red (DR) to near-infrared (NIR) range poses a significant challenge with practical implications. To address this challenge and to engineer photonic functionalities, a micro-resonator architecture is developed using carbonized polymer microspheres (CPMs), evolved from conventional colloidal nanodots. Gram-scale production of CPMs utilizes controlled microscopic phase separation facilitated by natural peptide cross-linking during hydrothermal processing. The resulting microstructure effectively suppresses aggregation-induced quenching (AIQ), enabling strong solid-state light emission. Both experimental and theoretical analysis support a role for extended π-conjugated polycyclic aromatic hydrocarbons (PAHs) trapped within these microstructures, which exhibit a progressive red shift in light absorption/emission toward the NIR range. Moreover, the highly spherical shape of CPMs endows them with innate photonic functionalities in combination with their intrinsic CD-based attributes. Harnessing their excitation wavelength-dependent photoluminescent (PL) property, a single CPM exhibits whispering-gallery modes (WGMs) that are emission-tunable from the DR to the NIR. This type of newly developed microresonator can serve as, for example, unclonable anti-counterfeiting labels. This innovative cross-cutting approach, combining photonics and chemistry, offers robust, bottom-up, built-in photonic functionality with diverse NIR applications.

Does forced whisper have an impact on voice parameters?

OBJECTIVES: There has been the assumption that whispering may impact vocal function, leading to the widespread recommendation against its practice after phonosurgery. However, the extent to which whispering affects vocal function and vocal fold oscillation patterns remains unclear. METHODS: 10 vocally healthy subjects (5 male, 5 female) were instructed to forcefully whisper a standardized text for 10 min at a sound level of 70 dB(A), measured at a microphone distance of 30 cm to the mouth. Prior to and following the whisper loading, the dysphonia severity index was assessed. Simultaneously, recordings of high speed videolaryngoscopy (HSV), electroglottography, and audio signals during sustained phonation on the vowel /i/ (250 Hz for females and 125 Hz for males) were analyzed after segmentation of the HSV material. RESULTS: The pre-post analysis revealed only minor changes after the intervention. These changes included a rise in minimum intensity, an increase in the glottal area waveform-derived open quotient, and the glottal gap index. However, no statistically significant changes were observed in the harmonic-to-noise-ratio, the glottal- to-noise-excitation-ratio, and the electroglottographic open quotient. CONCLUSION: Overall, the study suggests that there are only small effects on vocal function in consequence of a forced whisper loading.

Observing Variation in Whispering Gallery Mode Resonance of a Trapped and Levitated Dye Doped Microdrop.

Whispering gallery mode (WGM) resonance was created in a spherical micro drop. A gradual shift in the resonance were observed. For a 600 nm droplet radius, the blue shift were 1.5, 0.7, 3.7 nm. It was estimated that such a shift corresponds to a reduction in optical radius of the droplet by 1.3, 0.6, 3.3 nm respectively. The droplet was created from a solution of glycerol, methanol and rhodamine 6G dye, and was trapped and levitated in a modified Paul trap. The WGMs were created by optically exciting the dye material from an external 532 nm cw laser beam. A shift in the WGM was observed during a gradual increase in power of the excitation laser, and a reason for such a shift was thought to be thermal evaporation of the liquid. For a larger droplet an initial 0.1 nm thermal expansion was also estimated, preceding the volume contraction. Such an expansion was negligible for a smaller droplet. The rate of change of the blue shift depends upon initial radius of the droplet. For the smaller droplet the estimated rate of change of WGM with a change in optical radius, was 0.771. For larger droplet, this rate is lower.

Bioinspired Carbonized Polymer Microspheres for Full-Color Whispering Gallery Mode Emission for White Light Emission, Unclonable Anticounterfeiting, and Chemical Sensing Applications.

Light-element-based fluorescent materials, colloidal graphene quantum dots, and carbon dots (CDs) have sparked an immense amount of scientific interest in the past decade. However, a significant challenge in practical applications has emerged concerning the development of solid-state fluorescence (SSF) materials. This study addresses this knowledge gap by exploring the unexplored photonic facets of C-based solid-state microphotonic emitters. The proposed synthesis approach focuses on carbonized polymer microspheres (CPMs) instead of conventional nanodots. These microspheres exhibit remarkable SSF spanning the entire visible spectrum from blue to red. The highly spherical shape of CPMs imparts built-in photonic properties in addition to its intrinsic CD-based attributes. Leveraging their excitation-dependent photoluminescence property, these microspheres exhibit amplified spontaneous emission, assisted by the whispering gallery mode resonance across the visible spectral region. Remarkably, unlike conventional semiconductor quantum dots or dye-doped microresonators, this single microstructure showcases adaptable resonant emission without structural/chemical modifications. This distinctive attribute enables a plethora of applications, including microcavity-assisted energy transfer for white light emission, highly sensitive chemical sensing, and secure encrypted anticounterfeiting measures. This interdisciplinary approach, integrating photonics and chemistry, provides a robust solution for light-element-based SSF with inherent photonic functionality and wide-ranging applications.

Boosted Second Harmonic Generation and Cascaded Sum Frequency Generation from a Surface Crystallized Glass Ceramic Microcavity.

The development of novel materials and structures for efficient second-order nonlinear micro/nano devices remains a significant challenge. In this study, the remarkable enhancement of second-harmonic generation (SHG) and cascaded sum frequency generation in whispering gallery mode microspheres made of surface-crystallized glass with a 6-µm Ba2TiSi2O8 crystal layer are demonstrated. Attributed to the core-shell design, the Ba2TiSi2O8 located on the surface can be efficiently coupled with whispering gallery modes, resulting in a highly efficient micron-scale cavity-enhanced second-order optical nonlinearity. Greatly enhanced SHG of the microcavity is observed, which is up to 80 times stronger than that of a non-resonant sample. Furthermore, owing to the wavelength non-selectivity of random quasi-phase matching, ultra-wideband SHG with a strong response ranging from 860 to 1600 nm and high-contrast polarization characteristics is demonstrated. The glass-ceramic-based microsphere cavity also boosts the cascading optical nonlinearity, manifested by a two-magnitude enhancement of cascaded sum frequency generation. This work delineates an efficient strategy for boosting nonlinear optical response in glass ceramics, which will open up new opportunities for applications in photonics and optical communications.

Low-Threshold Anti-Stokes Raman Microlaser on Thin-Film Lithium Niobate Chip.

Raman microlasers form on-chip versatile light sources by optical pumping, enabling numerical applications ranging from telecommunications to biological detection. Stimulated Raman scattering (SRS) lasing has been demonstrated in optical microresonators, leveraging high Q factors and small mode volume to generate downconverted photons based on the interaction of light with the Stokes vibrational mode. Unlike redshifted SRS, stimulated anti-Stokes Raman scattering (SARS) further involves the interplay between the pump photon and the SRS photon to generate an upconverted photon, depending on a highly efficient SRS signal as an essential prerequisite. Therefore, achieving SARS in microresonators is challenging due to the low lasing efficiencies of integrated Raman lasers caused by intrinsically low Raman gain. In this work, high-Q whispering gallery microresonators were fabricated by femtosecond laser photolithography assisted chemo-mechanical etching on thin-film lithium niobate (TFLN), which is a strong Raman-gain photonic platform. The high Q factor reached 4.42 × 106, which dramatically increased the circulating light intensity within a small volume. And a strong Stokes vibrational frequency of 264 cm-1 of lithium niobate was selectively excited, leading to a highly efficient SRS lasing signal with a conversion efficiency of 40.6%. And the threshold for SRS was only 0.33 mW, which is about half the best record previously reported on a TFLN platform. The combination of high Q factors, a small cavity size of 120 µm, and the excitation of a strong Raman mode allowed the formation of SARS lasing with only a 0.46 mW pump threshold.

Microsphere-Enabled Micropillar Array for Whispering Gallery Mode Virus Detection.

Rapid detection of pathogens and analytes at the point of care offers an opportunity for prompt patient management and public health control. This paper reports an open microfluidic platform coupled with active whispering gallery mode (WGM) microsphere resonators for the rapid detection of influenza viruses. The WGM microsphere resonators, precoated with influenza A polyclonal antibodies, are mechanically trapped in the open micropillar array, where the evaporation-driven flow continuously transports a small volume (∼µL) of sample to the resonators without auxiliaries. Selective chemical modification of the pillar array changes surface wettability and flow pattern, which enhances the detection sensitivity of the WGM resonator-based virus sensor. The optofluidic sensing platform is able to specifically detect influenza A viruses within 15 min using a few microliters of sample and displays a linear response to different virus concentrations.

Continuous adiabatic frequency conversion for FMCW-LiDAR.

Continuous tuning of the frequency of laser light serves as the fundamental basis for a myriad of applications spanning basic scientific research to industrial settings. These applications encompass endeavors such as the detection of gravitational waves, the development of precise optical clocks, environmental monitoring for health and ecological purposes, as well as distance measurement techniques. However, achieving a broad tuning range exceeding 100 GHz along with sub-microsecond tuning times, inherent linearity in tuning, and coherence lengths beyond 10 m presents significant challenges. Here, we demonstrate that electro-optically driven adiabatic frequency converters utilizing high-Q microresonators fabricated from lithium niobate possess the capability to convert arbitrary voltage signals into frequency chirps with temporal resolutions below 1 µs. The temporal evolution of the frequency correlates accurately with the applied voltage signal. We have achieved to generate 200-ns-long frequency chirps with deviations of less than 1 % from perfect linearity without requiring supplementary measures. The coefficient of determination is R 2 > 0.999 . Moreover, the coherence length of the emitted light exceeds 20 m. To validate these findings, we employ the linear frequency sweeps for Frequency-Modulated Continuous Wave (FMCW) LiDAR covering distances ranging from 0.5 to 10 m. Leveraging the demonstrated nanosecond-level tuning capabilities, coupled with the potential to tune the eigenfrequency of lithium-niobate-based resonators by several hundred GHz, our results show that electro-optically driven adiabatic frequency converters can be used in applications that require ultrafast and flexible continuous frequency tuning characterized by inherent linearity and substantial coherence length.

Temperature Sensitivity Control of an Inkjet-Printed Optical Resonator on Pillar.

We report a whispering gallery mode resonator on a pillar using inkjet printing combined with traditional microfabrication techniques. This approach enables several different polymers on the same chip for sensing applications. However, polymers inherently exhibit sensitivity to multiple stimuli. To mitigate temperature sensitivity, careful selection of design parameters is crucial. By precisely tuning the undercut-to-radius ratio of the resonator, a linear dependence in temperature sensitivity ranging from -41.5 pm/°C to 23.4 pm/°C, with a zero-crossing point at 47.6% is achieved. Consequently, it is feasible to fabricate sensing devices based on undercut microdroplets with minimal temperature sensitivity. The lowest measured temperature sensitivity obtained was 5.9 pm/°C, for a resonator with an undercut-to-radius ratio of 53%.

Low Part-Per-Trillion, Humidity Resistant Detection of Nitric Oxide Using Microtoroid Optical Resonators.

The nitric oxide radical plays pivotal roles in physiological as well as atmospheric contexts. Although the detection of dissolved nitric oxide in vivo has been widely explored, highly sensitive (i.e., low part-per-trillion level), selective, and humidity-resistant detection of gaseous nitric oxide in air remains challenging. In the field, humidity can have dramatic effects on the accuracy and selectivity of gas sensors, confounding data, and leading to overestimation of gas concentration. Highly selective and humidity-resistant gaseous NO sensors based on laser-induced graphene were recently reported, displaying a limit of detection (LOD) of 8.3 ppb. Although highly sensitive (LOD = 590 ppq) single-wall carbon nanotube NO sensors have been reported, these sensors lack selectivity and humidity resistance. In this report, we disclose a highly sensitive (LOD = 2.34 ppt), selective, and humidity-resistant nitric oxide sensor based on a whispering-gallery mode microtoroid optical resonator. Excellent analyte selectivity was enabled via novel ferrocene-containing polymeric coatings synthesized via reversible addition-fragmentation chain-transfer polymerization. Utilizing a frequency locked optical whispering evanescent resonator system, the microtoroid's real-time resonance frequency shift response to nitric oxide was tracked with subfemtometer resolution. The lowest concentration experimentally detected was 6.4 ppt, which is the lowest reported to date. Additionally, the performance of the sensor remained consistent across different humidity environments. Lastly, the impact of the chemical composition and molecular weight of the novel ferrocene-containing polymeric coatings on sensing performance was evaluated. We anticipate that our results will have impact on a wide variety of fields where NO sensing is important such as medical diagnostics through exhaled breath, determination of planetary habitability, climate change, air quality monitoring, and treating cardiovascular and neurological disorders.

Quantifying local stiffness and forces in soft biological tissues using droplet optical microcavities.

Mechanical properties of biological tissues fundamentally underlie various biological processes and noncontact, local, and microscopic methods can provide fundamental insights. Here, we present an approach for quantifying the local mechanical properties of biological materials at the microscale, based on measuring the spectral shifts of the optical resonances in droplet microcavities. Specifically, the developed method allows for measurements of deformations in dye-doped oil droplets embedded in soft materials or biological tissues with an error of only 1 nm, which in turn enables measurements of anisotropic stress inside tissues as small as a few pN/µm2. Furthermore, by applying an external strain, Young's modulus can be measured in the range from 1 Pa to 35 kPa, which covers most human soft tissues. Using multiple droplet microcavities, our approach could enable mapping of stiffness and forces in inhomogeneous soft tissues and could also be applied to in vivo and single-cell experiments. The developed method can potentially lead to insights into the mechanics of biological tissues.

Determination of Enantiomeric Excess by Optofluidic Microlaser near Exceptional Point.

Enantiomeric excess (ee) is an essential indicator of chiral drug purification in the pharmaceutical industry. However, to date the ee determination of unknown concentration enantiomers generally involves two separate techniques for chirality and concentration measurement. Here, a whispering-gallery mode (WGM) based optofluidic microlaser near exceptional point to achieve the ee determination under unknown concentration with a single technique is proposed. Exceptional point induces the unidirectional WGM lasing, providing the optofluidic microlaser with the novel capability to measure chirality by polarization, in addition to wavelength-based concentration detection. The dual-parameters detection of optofluidic microlaser empowers it to achieve ee determination of various unknown enantiomers without additional concentration measurements, a feat that is challenging to accomplish with other methods. Featuring the sensitivity enhancement and miniature structure of the WGM sensors, the obtained chiroptical response of the present approach is ≈30-fold higher than that of the conventional optical rotation-based polarimeter, and the reagent consumption is reduced by three orders of magnitude.

Hollow-microsphere-integrated optofluidic immunochip for myocardial infarction biomarker microanalysis.

This work developed an optofluidic immunochip that uses whispering gallery mode with fiber laser enhancement, for the rapid detection of a key biomarker cardiac troponin I for acute myocardial infarction (AMI). The immunochip adopted an innovative design, using perforated hollow glass microspheres (HGMS) as carriers, with antibodies immobilized on the inner surface of the HGMS, thereby achieving ultra-low sample consumption. The performance of the immunochip was improved by fiber laser, including spectral width compression to 0.019 nm, optical signal-to-noise ratio amplification to 63.17 dB, and an enhancement in the limit of detection to 5 pg/mL. Moreover, this immunochip can provide results within 15 min, making it highly suitable for early AMI risk management. Compared to the standard electrochemiluminescence detection method, although some differences exist in the results of the immunochip due to the principle of detection and differences in antibody affinity, its positive reference value can be calculated as 0.0754 ng/mL, with a successful recognition rate of 88% for positive patients. The immunosensor is integrated on a polydimethylsiloxane substrate, with a compact size suitable for use in point-of-care devices and AMI self-screening, as well as rapid disease screening and microanalysis of various biomarkers, offering new possibilities for applications in these fields.

Whispering-Gallery Mode Micro-Ring Resonator Integrated with a Single-Core Fiber Tip for Refractive Index Sensing.

A micro-ring resonator structure was fabricated via the two-photon polymerization technique directly on a single-mode fiber tip and tested for refractive index sensing application. The micro-ring structure was used to excite whispering-gallery modes, and observations of the changes in the resonance spectrum introduced by changes in the refractive index of the environment served as the sensing principle. The proposed structure has the advantages of a very simple design, allowing for measurements in reflection mode, relatively easy and fast fabrication and integration with a single tip of a standard single-mode fiber, which allowed for quick and convenient measurements in the optical setup. The performance of the structure was characterized, and the resonant spectrum giving high potential for refractive index sensing was measured. Future perspectives of the research are addressed.

Soft Biomimetic Fiber-Optic Tactile Sensors Capable of Discriminating Temperature and Pressure.

Tactile sensors with high softness and multisensory functions are highly desirable for applications in humanoid robotics, smart prosthetics, and human-machine interfaces. Here, we report a soft biomimetic fiber-optic tactile (SBFT) sensor that offers skin-like tactile sensing abilities to perceive and discriminate temperature and pressure. The SBFT sensor is fabricated by encapsulating a macrobent fiber Bragg grating (FBG) in an elastomeric droplet-shaped structure that results in two optical resonances associated with the FBG and excited whispering gallery modes (WGMs) propagating along the bent region. Benefiting from the different thermo-optic and stress-optic effects of FBG and WGM resonances, the pressure and temperature can be fully decoupled with a high precision of 0.2 °C and 0.8 mN, respectively. To achieve a compact system for signal demodulation, a single-cavity dual-comb fiber laser is developed to interrogate the SBFT sensor based on dual-comb spectroscopy, which enables fast spectral sampling with a single photodiode. We show that the SBFT sensor is capable of perceiving pressure, temperature, and hardness in touching soft tissues and human skins, demonstrating great promise for soft tissue palpation and human-like robotic perception.

Confirmation of Dissipative Sensing Enhancement in a Microresonator Using Multimode Input.

Optical microresonators have proven to be especially useful for sensing applications. In most cases, the sensing mechanism is dispersive, where the resonance frequency of a mode shifts in response to a change in the ambient index of refraction. It is also possible to conduct dissipative sensing, in which absorption by an analyte causes measurable changes in the mode linewidth and in the throughput dip depth. If the mode is overcoupled, the dip depth response can be more sensitive than the linewidth response, but overcoupling is not always easy to achieve. We have recently shown theoretically that using multimode input to the microresonator can enhance the dip-depth sensitivity by a factor of several thousand relative to that of single-mode input and by a factor of nearly 100 compared to the linewidth sensitivity. Here, we experimentally confirm these enhancements using an absorbing dye dissolved in methanol inside a hollow bottle resonator. We review the theory, describe the setup and procedure, detail the fabrication and characterization of an asymmetrically tapered fiber to produce multimode input, and present sensing enhancement results that agree with all the predictions of the theory.

Automatic Alignment Method for Controlled Free-Space Excitation of Whispering-Gallery Resonances.

Whispering-gallery mode microresonators have gained wide popularity as experimental platforms for different applications, ranging from biosensing to nonlinear optics. Typically, the resonant modes of dielectric microresonators are stimulated via evanescent wave coupling, facilitated using tapered optical fibers or coupling prisms. However, this method poses serious shortcomings due to fabrication and access-related limitations, which could be elegantly overcome by implementing a free-space coupling approach; although additional alignment procedures are needed in this case. To address this issue, we have developed a new algorithm to excite the microresonator automatically. Here, we show the working mechanism and the preliminary results of our experimental method applied to a home-made silica microsphere, using a visible laser beam with a spatial light modulator and a software control.