Single Molecule Localization Microscopy (SMLM) offers enhanced spatial resolution in optical microscopy, providing detailed insights into the spatial organization of proteins in cells at the nanoscale. Over the past decade, SMLM has progressively incorporated the capability to retrieve the orientations of single molecules using their polarized dipolar emission pattern. This Review explores recent advancements in Single Molecule Orientation and Localization Microscopy (SMOLM), which yields super-resolved images of molecular 3D orientations, wobble, and 3D positions. This advancement opens possibilities to explore the nanoscale organization and conformation of biological molecules as well as to monitor and design local 3D optical fields in nanophotonics. The Review covers the principles of SMOLM, discusses recent advances and applications in biology and photonics, and finally highlights exciting future directions and challenges in the field.

Quantum confinement in monolayer semiconductors results in optical properties intricately linked to electrons, which can be manipulated by external electric fields. These optoelectronic features offer untapped potential for studying biological electrical activity. In addition to their relatively high quantum yields, picosecond level emission lifetimes make these materials particularly promising for monitoring biological voltages with high spatiotemporal resolution. To this end, we investigate exciton to trion conversion in angstrom thick semiconductors to experimentally demonstrate label-free, dual-polarity, all-optical detection of electrical activity, via changes in photoluminescence, in cardiomyocyte cultures with ultrahigh temporal resolution. We devise a physical model to elucidate that this conversion process is inherently governed by the quantum statistics of the background electrons induced by biological activity. We show that monolayer MoS enables completely bias-free tetherless operation due to its substantial trion density originating from intrinsic sulfur vacancies introduced during chemical vapor deposition. Our work opens up an unexplored avenue of opportunities for label-free all-optical voltage sensing using angstrom thick semiconductor materials whose applications have been elusive in the biological domain. This line of thinking at the intersection of biology and quantum science can potentially lead to the discovery of non-ubiquitous quantum materials for detection of biological electrical activity.

Optical super-resolution microscopy is a key technology for structural biology that offers high imaging contrast and live-cell compatibility. Minimal (fluorescence) photon flux microscopy, or MINFLUX, is an emerging super-resolution technique that localizes single fluorophores with high spatiotemporal precision by targeted scanning of a patterned excitation beam featuring a minimum. MINFLUX offers super-resolution imaging with nanometre resolution. When tracking single fluorophores, MINFLUX can achieve nanometre spatial and submillisecond temporal resolution over long tracks, greatly outperforming camera-based techniques. In this Review, we present the basic working principle of MINFLUX and explain how it can reach high photon efficiencies. We then outline the advantages and limitations of MINFLUX, describe recent extensions and variations of MINFLUX and, finally, provide an outlook for future developments.

Quasi-bound states in the continuum (qBICs) achieved through symmetry breaking in photonic metasurfaces are a powerful approach for engineering resonances with high quality factors and tunability. However, miniaturization of these devices is limited as the in-plane unit-cell size typically scales linearly with the resonant wavelength. By contrast, polariton resonators can be deeply subwavelength, offering a promising solution for achieving compact devices. Here we demonstrate that low-loss mid-infrared surface phonon polaritons enable metasurfaces supporting qBICs with unit-cell volumes up to 10 times smaller than the free-space volume . Using 100-nm-thick free-standing silicon carbide membranes, we achieve highly confined qBIC states with exceptional robustness against incident-angle variations, a feature unique among qBIC systems. This absence of angular dispersion enables mid-infrared vibrational sensing of thin, weakly absorbing molecular layers using a reflective objective, a method that typically degrades resonance quality in standard qBIC metasurfaces. We introduce surface-phonon-polariton-based qBICs as a platform for ultraconfined nanophotonic systems, advancing the miniaturization of mid-infrared sensors and devices for thermal radiation engineering.

The remarkable frequency stability of resonant systems in the optical domain (optical cavities and atomic transitions) can be harnessed at frequency scales accessible by electronics using optical frequency division. This capability is revolutionizing technologies spanning time keeping to high-performance electrical signal sources. A version of the technique called two-point optical frequency division (2P-OFD) is proving advantageous for application to high-performance signal sources. In 2P-OFD, an optical cavity anchors two spectral endpoints defined by lines of a frequency comb. The comb need not be self-referenced, which greatly simplifies the system architecture and reduces power requirements. Here, a 2P-OFD microwave signal source is demonstrated with record-low phase noise using a microcomb. Key to this advance is a spectral endpoint defined by a frequency-agile single-mode dispersive wave that is emitted by the microcomb soliton. Moreover, the system frequency reference is a compact all-solid-state optical cavity with a record factor. A hybridly packaged version of the system offers excellent longer term stability. The results advance integrable microcomb-based signal sources into the performance realm of much larger microwave sources.

The softness of liquid crystals, their anisotropic material properties, their strong response to external fields and their ability to align on patterned surfaces makes them unsurpassable for a number of photonic applications, such as flat-panel displays, light modulators, tunable filters, entangled photon light sources, lasers and many others. However, the microscale integration of liquid crystals into microphotonic devices that not only perform like silicon photonic chips but also use less energy, operate exclusively on light, are biocompatible and can self-assemble has not been explored. Here we demonstrate a soft-matter photonic chip that integrates tunable liquid-crystal microlasers and laser microprinted polymer waveguides. We demonstrate the control of the liquid crystal's microlaser emission by nanosecond optical pulses and introduce the concept of resonant stimulated-emission depletion to switch the light by light. This opens a way to design an entirely new class of photonic integrated devices that can be made both biodegradable and biocompatible with a rich variety of applications in medicine, wearable photonics and logic circuits. We anticipate that soft-matter photonic circuits will not only outperform solid-state photonics in terms of a huge reduction in the number of production steps, the use of non-toxic chemicals and a better energy efficiency, but also could open an avenue to the paradigm of soft-matter photonics.

Microfluidics allows for the precise control of small sample volumes through spatial confinement and exact routing of fluids. Usually, this is achieved by physical barriers. However, the rigidity of these barriers limits flexibility in certain applications. We introduce an optofluidic approach that leverages structured light and photothermal conversion to create dynamic, reconfigurable fluidic boundaries that can be easily integrated in existing setups. This system enables the controlled manipulation of fluids and particles by generating adjustable three-dimensional thermal landscapes. We demonstrate that our reconfigurable approach replicates the functions of traditional barriers and allows real-time adjustments for tasks such as individual particle steering and size-based sorting in heterogeneous mixtures. These results highlight the potential for adaptive and multifunctional microfluidic systems in applications such as chemical synthesis, lab-on-chip devices and microbiology.

Vortex phenomena are ubiquitous in nature. In optics, despite the availability of numerous techniques for vortex generation and detection, topological protection of vortex transport with desired orbital angular momentum (OAM) remains a challenge. Here, by use of topological disclination, we demonstrate a scheme to confine and guide vortices featuring arbitrary high-order charges. Such a scheme relies on twofold topological protection: a non-trivial winding in momentum space due to chiral symmetry, and a non-trivial winding in real space due to the complex coupling of OAM modes across the disclination structure. We unveil a vorticity-coordinated rotational symmetry, which sets up a universal relation between the vortex topological charge and the rotational symmetry order of the system. As an example, we construct photonic disclination lattices with a single core but different symmetries and achieve robust transport of an optical vortex with preserved OAM solely corresponding to one selected zero-energy vortex mode at the mid-gap. Furthermore, we show that such topological structures can be used for vortex filtering to extract a chosen OAM mode from mixed excitations. Our results illustrate the fundamental interplay of vorticity, disclination and higher-order topology, which may open a new pathway for the development of OAM-based photonic devices such as vortex guides, fibres and lasers.

Brillouin microscopy is an emerging optical elastography technique that can be used to assess mechanical properties of biological samples in a three-dimensional, all-optical and hence non-contact fashion. However, the low cross-section of spontaneous Brillouin scattering produces weak signals that often necessitate prolonged exposure times or illumination dosages that are potentially harmful for biological samples. Here we present a new approach for highly multiplexed and therefore rapid spectral acquisition of the Brillouin-scattered light. Specifically, by exploiting a custom-built Fourier-transform imaging spectrometer and the symmetric properties of the Brillouin spectrum, we experimentally demonstrate full-field 2D spectral Brillouin imaging of phantoms as well as biological samples, at a throughput of up to 40,000 spectra per second, with a precision of ~70 MHz and an effective 2D image acquisition speed of 0.1 Hz over a ~300 × 300 µm field of view. This represents an approximately three-orders-of-magnitude improvement in speed and throughput compared with standard confocal methods, while retaining high spatial resolution and the capability to acquire three-dimensional images of photosensitive samples in biology and medicine.

The absorption of light via interband optical transitions plays a key role in nature and applied technology, enabling efficient photosynthesis and photovoltaic cells, fast photodetectors or sensitive (quantum) light-matter interfaces. In many such photonic systems, enhancing the light absorption strength would be beneficial for yielding higher device efficiency and enhanced speed or sensitivity. So far, however, cavity-free light absorbers feature poorly engineerable absorption rates, consistent with the notion that the coupling strength between the initial and final states is an intrinsic material parameter. By contrast, greatly enhanced absorption rates had been theoretically predicted for superradiant systems, which feature giant oscillator strength through spatially extended coherent oscillations of the electron polarization. Unlike for emission processes, however, experimental realizations of superradiance in absorption-'superabsorption'-remain sparse and require complicated excited-state engineering approaches. Here we report superabsorption by the time reversal of single-photon superradiance in large CsPbBr perovskite quantum dots. Optical spectroscopy reveals a bandgap absorption that strongly increases with the quantum dot volume, consistent with a giant exciton wavefunction. Configuration-interaction calculations, quantitatively agreeing with the experiment, attribute the observed single-photon superabsorption to strong electron-hole pair-state correlations. The approach brings new opportunities for the development of more efficient optoelectronic devices and quantum light-matter interfaces.

Metasurfaces provide an ideal platform for optical sensing because they produce strong light-field confinement and enhancement over extended regions that allow us to identify deep-subwavelength layers of organic and inorganic molecules. However, the requirement of using external light sources involves bulky equipment that hinders point-of-care applications. Here we introduce a plasmonic sensor with an embedded source of light provided by quantum tunnel junctions. An optically resonant, doubly periodic nanowire metasurface serves as a top contact for the junction and provides extremely uniform emission over large areas, amplified by plasmonic nanoantenna modes that simultaneously enhance the spectral and refractive index sensitivity. As a proof of concept, we demonstrate spatially resolved refractometric sensing of nanometre-thick polymer and biomolecule coatings. Our results open exciting prospects based on a disruptive platform for integrated electro-optical biosensors.

Recently, machine learning has had remarkable impact in scientific to everyday-life applications. However, complex tasks often require the consumption of unfeasible amounts of energy and computational power. Quantum computation may lower such requirements, although it is unclear whether enhancements are reachable with current technologies. Here we demonstrate a kernel method on a photonic integrated processor to perform a binary classification task. We show that our protocol outperforms state-of-the-art kernel methods such as gaussian and neural tangent kernels by exploiting quantum interference, and provides further improvements in accuracy by offering single-photon coherence. Our scheme does not require entangling gates and can modify the system dimension through additional modes and injected photons. This result gives access to more efficient algorithms and to formulating tasks where quantum effects improve standard methods.

Multispectral imaging is an established method to extend the number of colours usable in fluorescence imaging beyond the typical limit of three or four. However, standard approaches are poorly suited to live-cell imaging owing to the need to separate light into many spectral channels, and unmixing algorithms struggle with low signal-to-noise ratio data. Here we introduce an approach for multispectral imaging in live cells that comprises an iterative spectral unmixing algorithm and eight-channel camera-based image-acquisition hardware. This enables the accurate unmixing of low signal-to-noise ratio datasets captured at video rates, while maintaining diffraction-limited spatial resolution. We use this approach on a commercial spinning-disk confocal microscope and a home-built oblique-plane light-sheet microscope to image one to seven spectrally distinct fluorophore species simultaneously, using both fluorescent protein fusions and small-molecule dyes. We further develop protein-binding proteins (minibinders), labelled with organic fluorophores, and use these in combination with our multispectral imaging approach to study the endosomal trafficking of cell-surface receptors at endogenous levels.

A critical component of optical communications is the availability of a suitable waveguide technology for the transport of electromagnetic waves with low loss over a broad spectral range. In the past four decades, despite extensive research, the attenuation and spectral bandwidth of silica-based optical fibres have remained relatively unchanged, with state-of-the-art fibres offering values of 0.14 dB km and 26 THz below 0.2 dB km, respectively. Here we report a microstructured optical waveguide with unprecedented transmission bandwidth and attenuation, with a measured loss of 0.091 dB km at 1,550 nm that remains below 0.2 dB km over a window of 66 THz. Instead of a traditional solid glass core, this innovative optical fibre features a core of air surrounded by a meticulously engineered glass microstructure to guide light. This approach not only reduces attenuation and other signal degradation phenomena, but it also increases transmission speeds by 45%. Furthermore, the approach theoretically supports further loss reductions and operation at wavelengths where broader bandwidth amplifiers exist, potentially heralding a new era in long-distance communications as well as remote delivery of laser beams.

Highly compact lasers with a low threshold and stable single-mode operation are in great demand for integrated optoelectronics. However, considerable side leakages and radiation losses in small cavities substantially degrade the quality () factor, posing a substantial obstacle in pursuing high-performance miniature lasers. Here we propose and experimentally demonstrate a flat-band laser supplemented by multiple bound states in the continuum. By simultaneously confining light in all three dimensions, a high factor of ~1,440 in an ultracompact terahertz quantum cascade laser cavity with a lateral size of ~3 is reported. The field confinement makes it possible to realize an electrically pumped single-mode terahertz laser with a low threshold current density, despite the small device footprint. This surface-emitting laser emits a well-defined beam with good directionality. The demonstrated multibound-state-assisted flat-band design is also applicable to other wavelength regimes, offering a route to energy-efficient, monolithically integrated and ultracompact laser sources that suit a wide range of applications.

Transparent conducting oxides are highly doped semiconductors that exhibit favourable optical features compared with metals, including reduced material losses, tuneable electronic and optical properties, and enhanced damage thresholds. Recently, the photonic community has renewed its attention towards these materials, recognizing their remarkable nonlinear optical properties in the near-infrared spectrum. The exceptionally large and ultrafast change in the refractive index, which can be optically induced in these compounds, extends beyond the boundaries of conventional perturbative analysis and makes this class of materials the closest approximation to a time-varying system. Here we report the spatio-spectral fission of an ultrafast pulse trespassing a thin film of aluminium zinc oxide with a non-stationary refractive index. By applying phase conservation to this time-varying layer, our model can account for both space and time refraction and explain, in quantitative terms, the spatial separation of both spectrum and energy. Our findings represent an example of extreme nonlinear phenomena on subwavelength propagation distances, which provides new insights into transparent conducting oxides' transient optical properties. This can be critical for the ongoing research on photonic time crystals, on-chip generation of non-classical states of light, integrated optical neural networks, ultrafast beam steering and frequency-division multiplexing.

Fast detector arrays enable an effective implementation of image scanning microscopy, which overcomes the trade-off between spatial resolution and signal-to-noise ratio of confocal microscopy. However, current image scanning microscopy approaches do not provide optical sectioning and fail with thick samples unless the detector size is limited, thereby introducing a new trade-off between optical sectioning and signal-to-noise ratio. Here we propose a method that overcomes such a limitation. From single-plane acquisition, we reconstruct an image with digital and optical super-resolution, high signal-to-noise ratio and enhanced optical sectioning. On the basis of the observation that imaging with a detector array inherently embeds axial information, we designed a straightforward reconstruction algorithm that inverts the physical model of image scanning microscopy image formation. We present a comprehensive theoretical framework and validate our method with images of biological samples captured using a custom setup equipped with a single-photon avalanche diode array detector. We demonstrate the feasibility of our approach by exciting fluorescence emission in both linear and nonlinear regimes. Moreover, we generalize the algorithm for fluorescence lifetime imaging, fully exploiting the single-photon timing ability of the single-photon avalanche diode array detector. Our method outperforms conventional reconstruction techniques and can be extended to any laser scanning microscopy technique.

The dynamic scattering of light impacts sensing and communication technologies throughout the electromagnetic spectrum. Here we introduce a new way to control the propagation of light through time-varying complex media. Our strategy is based on the observation that in many dynamic scattering systems, some parts of the medium will change configuration more slowly than others. We experimentally demonstrate a suite of new techniques to identify and guide light through the more temporally stable channels within dynamic scattering media-threading optical fields around multiple highly dynamic pockets hidden at unknown locations inside. We first show how the temporal fluctuations in scattered light can be suppressed by optimizing the wavefront of the incident field. Next, we demonstrate how to accelerate this procedure by two orders of magnitude using a physically realized form of adjoint gradient descent optimization. Finally, we show how the time-averaged transmission matrix reveals a basis of temporal fluctuation eigenchannels that can be used to increase the stability of beam shaping through time-varying complex media such as bending multimode fibres. Our work has potential future applications to a variety of technologies reliant on general wave phenomena subject to dynamic conditions, from optics to microwaves and acoustics.

Multicolour fluorescence imaging is crucial to simultaneously visualize multiple targets in cells, enabling the study of complicated cellular processes. Common multicolour methods rely on using fluorophores with sufficiently different spectral or lifetime characteristics. Here we present a new multicolour imaging strategy on a standard fluorescence microscope, where up to four fluorophores with high spectral overlap can be resolved using a single-colour optical configuration. We find that under electrochemical modulation, the fluorophores are regulated between the bright and dim states, with each displaying a distinct fluorescence response pattern. These unique fluorescence potential profiles enable the effective separation of different fluorophores through linear unmixing. We also demonstrate that electrochemical fluorescence switching is readily applicable to four-colour STED imaging. With no modification to the optical setups and easy adaptation to different microscopes, we anticipate that colour unmixing based on electrochemical fluorescence switching will provide an easily accessible multicolour imaging pathway for discoveries in diverse fields.

Quantum walks on photonic platforms represent a physics-rich framework for quantum measurements, simulations and universal computing. Dynamic reconfigurability of photonic circuitry is key to controlling the walk and retrieving its full operation potential. Universal quantum processing schemes based on time-bin encoding in gated fibre loops have been proposed but not demonstrated yet, mainly due to gate inefficiencies. Here we present a scalable quantum processor based on the discrete-time quantum walk of time-bin-entangled photon pairs on synthetic temporal photonic lattices implemented on a coupled fibre-loop system. We utilize this scheme to path-optimize quantum state operations, including the generation of two- and four-level time-bin entanglement and the respective two-photon interference. The design of the programmable temporal photonic lattice enabled us to control the dynamic of the walk, leading to an increase in the coincidence counts and quantum interference measurements without recurring to post-selection. Our results show how temporal synthetic dimensions can pave the way towards efficient quantum information processing, including quantum phase estimation, Boson sampling and the realization of topological phases of matter for high-dimensional quantum systems in a cost-effective, scalable and robust fibre-based setup.

Achieving atomic resolution in electron microscopy has historically been hindered by spherical aberration, a fundamental limitation of conventional electron lenses. Its correction typically requires complex assemblies of electromagnetic multipoles. Here we demonstrate that third-order spherical aberration in a cylindrically symmetric electron lens with an associated aberration coefficient of  ≈ 2.5 m can be compensated to near-zero via interaction with a shaped light field. By analysing distortions in the high-magnification point-projection electron images of optical standing waves, we quantify the spherical aberration before and after light-induced correction. The spatial distribution of the correction optical field is precisely characterized in situ using ultrafast four-dimensional scanning transmission electron microscopy utilizing the transverse deflection of electrons induced by the optical ponderomotive force. Such a combined characterization and correction approach introduces a new paradigm for optical control in electron beams and opens a pathway towards compact and tunable light-based correctors for high-resolution electron microscopy.