3DMOUSEneST: a volumetric label-free imaging method evaluating embryo-uterine interaction and decidualization efficacy.

Effective interplay between the uterus and the embryo is essential for pregnancy establishment; however, convenient methods to screen embryo implantation success and maternal uterine response in experimental mouse models are currently lacking. Here, we report 3DMOUSEneST, a groundbreaking method for analyzing mouse implantation sites based on label-free higher harmonic generation microscopy, providing unprecedented insights into the embryo-uterine dynamics during early pregnancy. The 3DMOUSEneST method incorporates second-harmonic generation microscopy to image the three-dimensional structure formed by decidual fibrillar collagen, named 'decidual nest', and third-harmonic generation microscopy to evaluate early conceptus (defined as the embryo and extra-embryonic tissues) growth. We demonstrate that decidual nest volume is a measurable indicator of decidualization efficacy and correlates with the probability of early pregnancy progression based on a logistic regression analysis using Smad1/5 and Smad2/3 conditional knockout mice with known implantation defects. 3DMOUSEneST has great potential to become a principal method for studying decidual fibrillar collagen and characterizing mouse models associated with early embryonic lethality and fertility issues.

Near-Unity All-Optical Modulation of Third-Harmonic Generation with a Fano-Resonant Dielectric Metasurface.

We demonstrate all-optical modulation with a near-unity contrast of nonlinear light generation in a dielectric metasurface. We study third-harmonic generation from silicon Fano-resonant metasurfaces excited by femtosecond pulses at 1480 nm wavelength. We modulate the metasurface resonance by free carrier excitation induced by absorption of an 800 nm pump pulse, leading to up to 93% suppression of third-harmonic generation. Modulation and recovery occur on (sub)picosecond time scales. According to the Drude model, the pump-induced refractive index change blue-shifts the metasurface resonance away from the generation pulse, causing a strong modulation of third-harmonic conversion efficiency. The principle holds great promise for spatiotemporal programmability of nonlinear light generation.

Enhanced Green Light Emission from a Silicon-Based Metal-Encapsulated Nanoplasmonic Waveguide.

Integrated silicon plasmonic circuitry is becoming integral for communications and data processing. One key challenge in implementing such optical networks is the realization of optical sources on silicon platforms, due to silicon's indirect bandgap. Here, we present a silicon-based metal-encapsulated nanoplasmonic waveguide geometry that can mitigate this issue and efficiently generate light via third-harmonic generation (THG). Our waveguides are ideal for such applications, having strong power confinement and field enhancement, and an effective use of the nonlinear core area. This unique device was fabricated, and experimental results show efficient THG conversion efficiencies of η = 4.9 × 10-4, within a core footprint of only 0.24 µm2. Notably, this is the highest absolute silicon-based THG conversion efficiency presented to date. Furthermore, the nonlinear emission is not constrained by phase matching. These waveguides are envisioned to have crucial applications in signal generation within integrated nanoplasmonic circuits.

Nonlinear Chiral Metasurfaces Based on Structured van der Waals Materials.

Nonlinear chiral photonics explores the nonlinear response of chiral structures, and it offers a pathway to novel optical functionalities not accessible through linear or achiral systems. Here we present the first application of nanostructured van der Waals materials to nonlinear chiral photonics. We demonstrate the 3 orders of magnitude enhancement of the third-harmonic generation from hBN metasurfaces driven by quasi-bound states in the continuum and accompanied by strong nonlinear circular dichroism at the resonances. This novel platform for chiral metaphotonics can be employed for achieving large circular dichroism combined with high-efficiency harmonic generation in a broad frequency range.

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.

Experimental Demonstration of High-Efficiency Harmonic Generation in Photonic Moiré Superlattice Microcavities.

Integrated photonic microcavities have demonstrated powerful enhancement of nonlinear effects, but they face a challenge in achieving critical coupling for sufficient use of incident pump power. In this work, we first experimentally demonstrate that highly efficient third-harmonic generation (THG) and detectable second-harmonic generation (SHG) can be produced from high-Q photonic moiré superlattice microcavities, where a critical coupling condition can be achieved via selecting a magic angle. Furthermore, at the magic angle of 13.17°, critical coupling is satisfied, resulting in a normalized THG conversion efficiency of 136%/W2 at a relatively low peak pump power of 6.8 MW/cm2, which is 3 orders of magnitude higher than the best results reported previously. Our work shows the power of photonic moiré superlattices in enhancing nonlinear optical performances through flexible and feasible engineering resonant modes, which can be applied in integrated frequency conversion and generation of quantum light sources.

Rapid on-site histology of lung and pleural biopsies using higher harmonic generation microscopy and artificial intelligence analysis.

Lung cancer is both one of the most prevalent and lethal cancers. To improve health outcomes while reducing the healthcare burden, it becomes crucial to move towards early detection and cost-effective workflows. Currently there is no method for on-site rapid histological feedback on biopsies taken in diagnostic endoscopic or surgical procedures. Higher harmonic generation (HHG) microscopy is a laser-based technique that provides images of unprocessed tissue. Here, we report the feasibility of a HHG portable microscope in the clinical workflow in terms of acquisition time, image quality and diagnostic accuracy in suspected pulmonary and pleural malignancy. 109 biopsies of 47 patients were imaged and a biopsy overview image was provided within a median of 6 minutes after excision. The assessment by pathologists and an artificial intelligence (AI) algorithm showed that image quality was sufficient for a malignancy or non-malignancy diagnosis in 97% of the biopsies, and 87% of the HHG images were correctly scored by the pathologists. HHG is therefore an excellent candidate to provide rapid pathology outcome on biopsy samples enabling immediate diagnosis and (local) treatment.

Application of the Knife-Edge Technique on Transition Metal Dichalcogenide Monolayers for Resolution Assessment of Nonlinear Microscopy Modalities.

We report application of the knife-edge technique at the sharp edges of WS2 and MoS2 monolayer flakes for lateral and axial resolution assessment in all three modalities of nonlinear laser scanning microscopy: two-photon excited fluorescence (TPEF), second- and third-harmonic generation (SHG, THG) imaging. This technique provides a high signal-to-noise ratio, no photobleaching effect and shows good agreement with standard resolution measurement techniques. Furthermore, we assessed both the lateral resolution in TPEF imaging modality and the axial resolution in SHG and THG imaging modality directly via the full-width at half maximum parameter of the corresponding Gaussian distribution. We comprehensively analyzed the factors influencing the resolution, such as the numerical aperture, the excitation wavelength and the refractive index of the embedding medium for the different imaging modalities. Glycerin was identified as the optimal embedding medium for achieving resolutions closest to the theoretical limit. The proposed use of WS2 and MoS2 monolayer flakes emerged as promising tools for characterization of nonlinear imaging systems.

Spatially Resolved Nonlinear Plasmonics.

Nonlinear optical plasmonics investigates the emission of plasmonic nanoantennas with the aid of nonlinear spectroscopy. Here we introduce nonlinear spatially resolved spectroscopy (NSRS) which is capable of imaging the k-space as well as spatially resolving the THG signal of gold nanoantennas and investigating the emission of individual antennas by wide-field illumination of entire arrays. Hand in hand with theoretical simulations, we demonstrate our ability of imaging various oscillation modes inside the nanostructures and therefore spatial emission hotspots. Upon increasing intensity of the femtosecond excitation, an individual destruction threshold can be observed. We find certain antennas becoming exceptionally bright. By investigating those samples taking structural SEM images of the nanoantenna arrays afterward, our spatially resolved nonlinear image can be correlated with this data proving that antennas had deformed into a peanut-like shape. Thus, our NSRS setup enables the investigation of a nonlinear self-enhancement process of nanoantennas under critical laser excitation.

Two Photon Absorption Properties of CBHB and DEABHB Single Crystals for Optical Limiting Applications.

Novel materials of (E)-N'-(4-chlorobenzylidene)-4-hydroxybenzohydrazide (CBHB) and (E)-N'-(4-(diethylamino) benzylidene)-4-hydroxybenzohydrazide (DEABHB) were synthesized by condensation reaction process and solvent evaporation method was employed to grow CBHB and DEABHB single crystals at room temperature. Lattice parameters of CBHB and DEABHB compounds were recorded using single crystal X-ray diffraction method. The presence of functional groups of the synthesized CBHB and DEABHB compounds were confirmed by Fourier transform infrared and Fourier transform Raman spectral analyses. Various intermolecular interactions were studied using Hirshfeld surface analysis. Thermal stability of the hydrazone Schiff base compounds CBHB and DEABHB were studied by thermogravimetric and differential thermal analyses. Third order nonlinear optical properties of CBHB and DEABHB were measured using open aperature Z scan technique. Two photon absorption coefficient and optical limiting properties of the crystals were reported from the Z scan studies.

Optical Bound States in the Continuum Enabled by Magnetic Resonances Coupled to a Mirror.

Dielectric metasurfaces made of high refractive index and low optical loss materials have emerged as promising platforms to achieve high-quality factor modes enabling strong light-matter interaction. Bound states in the continuum have shown potential to demonstrate narrow spectral resonances but often require asymmetric geometry and typically feature strong polarization dependence, complicating fabrication and limiting practical applications. We introduce a novel approach for designing high-quality bound states in the continuum using magnetic dipole resonances coupled to a mirror. The resulting metasurface has simple geometric parameters requiring no broken symmetry. To demonstrate the unique features of our photonic platform we show a record-breaking third harmonic generation efficiency from the metasurface benefiting from the strongly enhanced electric field at high-quality resonances. Our approach mitigates the shortcomings of previous platforms with simple geometry enabling facile and large-area fabrication of metasurfaces paving the way for applications in optical sensing, detection, quantum photonics, and nonlinear devices.

Chiral Third-Harmonic Metasurface for Multiplexed Holograms.

Chiral nonlinear metasurfaces could natively synergize nonlinear wavefront manipulation and circular dichroism, offering enhanced capacity for multifunctional and multiplexed nonlinear metasurfaces. However, it is still quite challenging to simultaneously enable strong chiral response, precise wavefront control, high nonlinear conversion efficiency, and independent functions on spins and chirality. Here, we propose and experimentally demonstrate multiplexed third-harmonic (TH) holograms with four channels based on a chiral Au-ZnO hybrid metasurface. Specifically, the left- and right-handed circularly polarized (LCP and RCP) components of the TH holographic images can be designed independently under the excitation of an LCP (or RCP) fundamental beam. In addition, the TH conversion efficiency is measured to be as large as 10-5, which is 8.6 times stronger than that of a bare ZnO film with the same thickness. Thus, our work provides a promising platform for realizing efficient and multifunctional nonlinear nanodevices.

Observation of Ultrafast Self-Action Effects in Quasi-BIC Resonant Metasurfaces.

High-index dielectric metasurfaces can support sharp optical resonances enabled by the physics of bound states in the continuum (BICs) often manifested in experiments as quasi-BIC resonances. They provide a way to enhance light-matter interaction at the subwavelength scale bringing novel opportunities for nonlinear nanophotonics. Strong narrow-band field enhancement in quasi-BIC metasurfaces leads to an extreme sensitivity to a change of the refractive index that may limit nonlinear functionalities for the pump intensities beyond the perturbative regime. Here we study ultrafast self-action effects observed in quasi-BIC silicon metasurfaces and demonstrate how they alter the power dependence of the third-harmonic generation efficiency. We study experimentally a transition from the subcubic to supercubic regimes for the generated third-harmonic power driven by a blue-shift of the quasi-BIC in the multiphoton absorption regime. Our results suggest a way to implement ultrafast nonlinear dynamics in high-index resonant dielectric metasurfaces for nonlinear meta-optics beyond the perturbative regime.

Highly Efficient Multiphoton Absorption of Zinc-AIEgen Metal-Organic Frameworks.

A series of luminescent frameworks was synthesized from the selective combination of aggregation induced emission (AIE)-linker tetra-(4-carboxylphenyl)ethylene (H4 TCPE) and Zn2+ . Complex 1 was formed by the close packing of Zn-TCPE hinge, and isostructural complexes 2-5 were constructed by the linkage of Zn-TCPE layer and pillar ligands. These complexes exhibit highly efficient multiphoton excited photoluminescence (MEPL) and concomitant third-harmonic generation (THG). The multiphoton absorption (MPA) parameters of 1 are superior to other multiphoton emission materials including the perovskite nanocrystals. The incorporation of pillar linkers slows down the charge transfer between layers of Zn-TCPE, and the aromatic core of pillar linkers has a great influence on the MPA performance of the corresponding frameworks.

Nonlinear Imaging with All-Dielectric Metasurfaces.

Nonlinear metasurfaces incorporate many of the functionalities of their linear counterparts such as wavefront shaping, but simultaneously they perform nonlinear optical transformations. This dual functionality leads to a rather unintuitive physical behavior which is still widely unexplored for many photonic applications. The nonlinear processes render some basic principles governing the functionality of linear metasurfaces. Exemplarily, the superposition principle and the geometric optics approximation become not directly applicable to nonlinear metasurfaces. On the other hand, nonlinear metasurfaces facilitate new phenomena that are not possible in the linear regime. Here, we study the imaging of objects through a dielectric nonlinear metalens. We illuminate objects by infrared light and record their generated images at the visible third-harmonic wavelengths. We revisit the classical lens theory and suggest a generalized Gaussian lens equation for nonlinear imaging, verified both experimentally and analytically. We also demonstrate experimentally higher-order spatial correlations facilitated by the nonlinear metalens, resulting in additional image features.

Enhanced Nonlinear Light Generation in Oligomers of Silicon Nanoparticles under Vector Beam Illumination.

All-dielectric nanoparticle oligomers have recently emerged as promising candidates for nonlinear optical applications. Their highly resonant collective modes, however, are difficult to access by linearly polarized beams due to symmetry restraints. In this paper, we propose a new way to increase the efficiency of nonlinear processes in all-dielectric oligomers by tightly focused azimuthally polarized cylindrical vector beam illumination. We demonstrate two orders enhancement of the third-harmonic generation signal, governed by a collective optical mode represented by out-of-plane magnetic dipoles. Crucially, the collective mode is characterized by strong electromagnetic field localization in the bulk of the nonlinear material. For comparison, we measure third-harmonic generation in the same oligomer pumped with linearly and radially polarized fundamental beams, which both show significantly lower harmonic output. We also provide numerical analysis to describe and characterize the observed effect. Our findings open a new route to enhance and modulate the third-harmonic generation efficiency of Mie-resonant isolated nanostructures by tailoring the polarization of the pump beam.

Label-Free Multiphoton Microscopy: Much More Than Fancy Images.

Multiphoton microscopy has recently passed the milestone of its first 30 years of activity in biomedical research. The growing interest around this approach has led to a variety of applications from basic research to clinical practice. Moreover, this technique offers the advantage of label-free multiphoton imaging to analyze samples without staining processes and the need for a dedicated system. Here, we review the state of the art of label-free techniques; then, we focus on two-photon autofluorescence as well as second and third harmonic generation, describing physical and technical characteristics. We summarize some successful applications to a plethora of biomedical research fields and samples, underlying the versatility of this technique. A paragraph is dedicated to an overview of sample preparation, which is a crucial step in every microscopy experiment. Afterwards, we provide a detailed review analysis of the main quantitative methods to extract important information and parameters from acquired images using second harmonic generation. Lastly, we discuss advantages, limitations, and future perspectives in label-free multiphoton microscopy.

Introducing Intermolecular Cation-π Interactions for Water-Stable Low Dimensional Hybrid Lead Halide Perovskites.

Optoelectronically active hybrid lead halide perovskites dissociate in water. To prevent this dissociation, here, we introduce long-range intermolecular cation-π interactions between A-site cations of hybrid perovskites. An aromatic diamine like 4,4'-trimethylenedipyridine, if protonated, can show a long-range cation-π stacking, and therefore, serves as our A-site cation. Consequently, 4,4'-trimethylenedipyridinium lead bromide [(4,4'-TMDP)Pb2 Br6 ], a one-dimensional hybrid perovskite, remains completely stable after continuous water treatment for six months. Mechanistic insights about the cation-π interactions are obtained by single-crystal X-ray diffraction and nuclear magnetic resonance spectroscopy. The concept of long-range cation-π interaction is further extended to another A-site cation 4,4'-ethylenedipyridinium ion (4,4'-EDP), forming water-stable (4,4'-EDP)Pb2 Br6 perovskite. These water-stable perovskites are then used to fabricate white light-emitting diode and for light up-conversion through tunable third-harmonic generation. Note that the achieved water stability is the intrinsic stability of perovskite composition, unlike the prior approach of encapsulating the unstable perovskite material (or device) by water-resistant materials. The introduced cation-π interactions can be a breakthrough strategy in designing many more compositions of water-stable low-dimensional hybrid perovskites.

Non-invasive Imaging Techniques: From Histology to In Vivo Imaging : Chapter of Imaging in Oncology.

In this chapter, we will introduce and review molecular-sensitive imaging techniques, which close the gap between ex vivo and in vivo analysis. In detail, we will introduce spontaneous Raman spectral imaging, coherent anti-Stokes Raman scattering (CARS), stimulated Raman scattering (SRS), second-harmonic generation (SHG) and third-harmonic generation (THG), two-photon excited fluorescence (TPEF), and fluorescence lifetime imaging (FLIM). After reviewing these imaging techniques, we shortly introduce chemometric methods and machine learning techniques, which are needed to use these imaging techniques in diagnostic applications.

Evidence of Cascaded Third-Harmonic Generation in Noncentrosymmetric Gold Nanoantennas.

The optimization of nonlinear optical processes on the nanoscale is a crucial step for the integration of complex functionalities into compact photonic devices and metasurfaces. In such systems, photon upconversion can be achieved with higher efficiencies via third-order processes, such as third-harmonic generation (THG), thanks to the resonantly enhanced volume currents. Conversely, second-order processes, such as second-harmonic generation (SHG), are often inhibited by the symmetry of metal lattices and of common nanoantenna geometries. SHG and THG processes in plasmonic nanostructures are generally treated independently because they typically represent small perturbations in the light-matter interaction mechanisms. In this work, we demonstrate that this paradigm does not hold for plasmon-enhanced nonlinear optics by providing evidence of a sum-frequency generation (SFG) process seeded by SHG, which sizably contributes to the overall THG yield. We address this mechanism by unveiling a characteristic fingerprint in the polarization state of the THG emission from gold noncentrosymmetric nanoantennas, which directly reflects the asymmetric distribution of second-harmonic fields within the structure and does not depend on the model one employs to describe photon upconversion. We suggest that such cascaded processes may also appear for structures that exhibit only moderate SHG yields. The presence of this peculiar mechanism in THG from plasmonic nanoantennas at telecommunication wavelengths allows us to gain further insight into the physics of plasmon-enhanced nonlinear optical processes. This could be crucial in the realization of nanoscale elements for photon conversion and manipulation operating at room temperature.