Lasing from a Large-Area 2D Material Enabled by a Dual-Resonance Metasurface.

Semiconducting transition metal dichalcogenides (TMDs) have gained significant attention as a gain medium for nanolasers, owing to their unique ability to be easily placed and stacked on virtually any substrate. However, the atomically thin nature of the active material in existing TMD lasers and the limited size due to mechanical exfoliation presents a challenge, as their limited output power makes it difficult to distinguish between true laser operation and other "laser-like" phenomena. Here, we present room temperature lasing from a large-area tungsten disulfide (WS2) monolayer, grown by a wafer-scale chemical vapor deposition (CVD) technique. The monolayer is placed on a dual-resonance dielectric metasurface with a rectangular lattice designed to enhance both absorption and emission, resulting in an ultralow threshold operation (threshold well below 1 W/cm2). We provide a thorough study of the laser performance, paying special attention to directionality, output power, and spatial coherence. Notably, our lasers demonstrated a coherence length of over 30 µm, which is several times greater than what has been reported for 2D material lasers so far. Our realization of a single-mode laser from a CVD-grown monolayer presents exciting opportunities for integration and the development of real-world applications.

Phase noise matching in resonant metasurfaces for intrinsic sensing stability.

Interferometry offers a precise means of interrogating resonances in dielectric and plasmonic metasurfaces, surpassing spectrometer-imposed resolution limits. However, interferometry implementations often face complexity or instability issues due to heightened sensitivity. Here, we address the necessity for noise compensation and tolerance by harnessing the inherent capabilities of photonic resonances. Our proposed solution, termed "resonant phase noise matching," employs optical referencing to align the phases of equally sensitive, orthogonal components of the same mode. This effectively mitigates drift and noise, facilitating the detection of subtle phase changes induced by a target analyte through spatially selective surface functionalization. Validation of this strategy using Fano resonances in a 2D photonic crystal slab showcases noteworthy phase stability (σ<10-4π). With demonstrated label-free detection of low-molecular-weight proteins at clinically relevant concentrations, resonant phase noise matching presents itself as a potentially valuable strategy for advancing scalable, high-performance sensing technology beyond traditional laboratory settings.

Fano Resonance-Assisted All-Dielectric Array for Enhanced Near-Field Optical Trapping of Nanoparticles.

Near-field optics can overcome the diffraction limit by creating strong optical gradients to enable the trapping of nanoparticles. However, it remains challenging to achieve efficient, stable trapping without heating and thermal effects. Dielectric structures have been used to address this issue but usually offer weak trap stiffness. In this work, we exploit the Fano resonance effect in an all-dielectric quadrupole nanostructure to realize a 20-fold enhancement of trap stiffness, compared to the off-resonance case. This enables a high effective trap stiffness of 1.19 fN/nm for 100 nm diameter polystyrene nanoparticles with 4.2 mW/µm2 illumination. Furthermore, we demonstrate the capability of the structure to simultaneously trap two particles at distinct locations within the nanostructure array.

Multiplexed Near-Field Optical Trapping Exploiting Anapole States.

Optical tweezers have had a major impact on bioscience research by enabling the study of biological particles with high accuracy. The focus so far has been on trapping individual particles, ranging from the cellular to the molecular level. However, biology is intrinsically heterogeneous; therefore, access to variations within the same population and species is necessary for the rigorous understanding of a biological system. Optical tweezers have demonstrated the ability of trapping multiple targets in parallel; however, the multiplexing capability becomes a challenge when moving toward the nanoscale. Here, we experimentally demonstrate a resonant metasurface that is capable of trapping a high number of nanoparticles in parallel, thereby opening up the field to large-scale multiplexed optical trapping. The unit cell of the metasurface supports an anapole state that generates a strong field enhancement for low-power near-field trapping; importantly, the anapole state is also more angle-tolerant than comparable resonant modes, which allows its excitation with a focused light beam, necessary for generating the required power density and optical forces. We use the anapole state to demonstrate the trapping of 100's of 100 nm polystyrene beads over a 10 min period, as well as the multiplexed trapping of lipid vesicles with a moderate intensity of <250 µW/µm2. This demonstration will enable studies relating to the heterogeneity of biological systems, such as viruses, extracellular vesicles, and other bioparticles at the nanoscale.

Metasurface-enhanced mid-infrared spectroscopy in the liquid phase.

Vibrational spectroscopy is an important tool in chemical and biological analysis. A key issue when applying vibrational spectroscopy to dilute liquid samples is the inherently low sensitivity caused by short interaction lengths and small extinction coefficients, combined with low target molecule concentrations. Here, we introduce a novel type of surface-enhanced infrared absorption spectroscopy based on the resonance of a dielectric metasurface. We demonstrate that the method is suitable for probing vibrational bands of dilute analytes with a range of spectral linewidths. We observe that the absorption signal is enhanced by 1-2 orders of magnitude and show that this enhancement leads to a lower limit of detection compared to attenuated total reflection (ATR). Overall, the technique provides an important addition to the spectroscopist's toolkit especially for probing dilute samples.

Crowding-induced morphological changes in synthetic lipid vesicles determined using smFRET.

Lipid vesicles are valuable mesoscale molecular confinement vessels for studying membrane mechanics and lipid-protein interactions, and they have found utility among bio-inspired technologies, including drug delivery vehicles. While vesicle morphology can be modified by changing the lipid composition and introducing fusion or pore-forming proteins and detergents, the influence of extramembrane crowding on vesicle morphology has remained under-explored owing to a lack of experimental tools capable of capturing morphological changes on the nanoscale. Here, we use biocompatible polymers to simulate molecular crowding in vitro, and through combinations of FRET spectroscopy, lifetime analysis, dynamic light scattering, and single-vesicle imaging, we characterize how crowding regulates vesicle morphology. We show that both freely diffusing and surface-tethered vesicles fluorescently tagged with the DiI and DiD FRET pair undergo compaction in response to modest concentrations of sorbitol, polyethylene glycol, and Ficoll. A striking observation is that sorbitol results in irreversible compaction, whereas the influence of high molecular weight PEG-based crowders was found to be reversible. Regulation of molecular crowding allows for precise control of the vesicle architecture in vitro, with vast implications for drug delivery and vesicle trafficking systems. Furthermore, our observations of vesicle compaction may also serve to act as a mechanosensitive readout of extramembrane crowding.

Tween-20 Induces the Structural Remodeling of Single Lipid Vesicles.

The solubilization of lipid membranes by Tween-20 is crucial for a number of biotechnological applications, but the mechanistic details remain elusive. Evidence from ensemble assays supports a solubilization model that encompasses surfactant association with the membrane and the release of mixed micelles to solution, but whether this process also involves intermediate transitions between regimes is unanswered. In search of mechanistic origins, increasing focus is placed on identifying Tween-20 interactions with controllable membrane mimetics. Here, we employed ultrasensitive biosensing approaches, including single-vesicle spectroscopy based on fluorescence and energy transfer from membrane-encapsulated molecules, to interrogate interactions between Tween-20 and submicrometer-sized vesicles below the optical diffraction limit. We discovered that Tween-20, even at concentrations below the critical micellar concentration, triggers stepwise and phase-dependent structural remodeling events, including permeabilization and swelling, in both freely diffusing and surface-tethered vesicles, highlighting the substantial impact the surfactant has on vesicle conformation and stability prior to lysis.

Beyond Q: The Importance of the Resonance Amplitude for Photonic Sensors.

Resonant photonic sensors are enjoying much attention based on the worldwide drive toward personalized healthcare diagnostics and the need to better monitor the environment. Recent developments exploiting novel concepts such as metasurfaces, bound states in the continuum, and topological sensing have added to the interest in this topic. The drive toward increasingly higher quality (Q)-factors, combined with the requirement for low costs, makes it critical to understand the impact of realistic limitations such as losses on photonic sensors. Traditionally, it is assumed that the reduction in the Q-factor sufficiently accounts for the presence of loss. Here, we highlight that this assumption is overly simplistic, and we show that losses have a stronger impact on the resonance amplitude than on the Q-factor. We note that the effect of the resonance amplitude has been largely ignored in the literature, and there is no physical model clearly describing the relationship between the limit of detection (LOD), Q-factor, and resonance amplitude. We have, therefore, developed a novel, ab initio analytical model, where we derive the complete figure of merit for resonant photonic sensors and determine their LOD. In addition to highlighting the importance of the optical losses and the resonance amplitude, we show that, counter-intuitively, optimization of the LOD is not achieved by maximization of the Q-factor but by counterbalancing the Q-factor and amplitude. We validate the model experimentally, put it into context, and show that it is essential for applying novel sensing concepts in realistic scenarios.

Photonic Biosensors: Detection, Analysis and Medical Diagnostics.

The necessity of personalised diagnoses and ad hoc treatments for individual patients is driving the outbreak of personalised nanomedicine in research and in clinical studies in the healthcare field [...].

Transition Metal Dichalcogenide Dimer Nanoantennas for Tailored Light-Matter Interactions.

Transition metal dichalcogenides have emerged as promising materials for nanophotonic resonators because of their large refractive index, low absorption within a large portion of the visible spectrum, and compatibility with a wide range of substrates. Herein, we use these properties to fabricate WS2 double-pillar nanoantennas in a variety of geometries enabled by the anisotropy in the crystal structure. Using dark-field spectroscopy, we reveal multiple Mie resonances, to which we couple WSe2 monolayer photoluminescence and achieve Purcell enhancement and an increased fluorescence by factors up to 240 for dimer gaps of 150 nm. We introduce postfabrication atomic force microscope repositioning and rotation of dimer nanoantennas, achieving gaps as small as 10 ± 5 nm, which enables a host of potential applications, including strong Purcell enhancement of single-photon emitters and optical trapping, which we study in simulations. Our findings highlight the advantages of using transition metal dichalcogenides for nanophotonics by exploring applications enabled by their properties.

Perturbation approach to improve the angular tolerance of high-Q resonances in metasurfaces.

The interest in high quality factor (high-Q) resonances in metasurfaces has been rekindled with the rise of the bound states in the continuum (BIC) paradigm, which describes resonances with apparently limitlessly high quality-factors (Q-factors). The application of BICs in realistic systems requires the consideration of the angular tolerance of resonances, however, which is an issue that has not yet been addressed. Here, we develop an ab-initio model, based on temporal coupled mode theory, to describe the angular tolerance of distributed resonances in metasurfaces that support both BICs and guided mode resonances (GMRs). We then discuss the idea of a metasurface with a perturbed unit cell, similar to a supercell, as an alternative approach for achieving high-Q resonances and we use the model to compare the two. We find that, while sharing the high-Q advantage of BIC resonances, perturbed structures feature higher angular tolerance due to band planarization. This observation suggests that such structures offer a route toward high-Q resonances that are more suitable for applications.

Novel Micro-Nano Optoelectronic Biosensor for Label-Free Real-Time Biofilm Monitoring.

According to the World Health Organization forecasts, AntiMicrobial Resistance (AMR) is expected to become one of the leading causes of death worldwide in the following decades. The rising danger of AMR is caused by the overuse of antibiotics, which are becoming ineffective against many pathogens, particularly in the presence of bacterial biofilms. In this context, non-destructive label-free techniques for the real-time study of the biofilm generation and maturation, together with the analysis of the efficiency of antibiotics, are in high demand. Here, we propose the design of a novel optoelectronic device based on a dual array of interdigitated micro- and nanoelectrodes in parallel, aiming at monitoring the bacterial biofilm evolution by using optical and electrical measurements. The optical response given by the nanostructure, based on the Guided Mode Resonance effect with a Q-factor of about 400 and normalized resonance amplitude of about 0.8, allows high spatial resolution for the analysis of the interaction between planktonic bacteria distributed in small colonies and their role in the biofilm generation, calculating a resonance wavelength shift variation of 0.9 nm in the presence of bacteria on the surface, while the electrical response with both micro- and nanoelectrodes is necessary for the study of the metabolic state of the bacteria to reveal the efficacy of antibiotics for the destruction of the biofilm, measuring a current change of 330 nA when a 15 µm thick biofilm is destroyed with respect to the absence of biofilm.

Dielectric nanohole array metasurface for high-resolution near-field sensing and imaging.

Dielectric metasurfaces support resonances that are widely explored both for far-field wavefront shaping and for near-field sensing and imaging. Their design explores the interplay between localised and extended resonances, with a typical trade-off between Q-factor and light localisation; high Q-factors are desirable for refractive index sensing while localisation is desirable for imaging resolution. Here, we show that a dielectric metasurface consisting of a nanohole array in amorphous silicon provides a favourable trade-off between these requirements. We have designed and realised the metasurface to support two optical modes both with sharp Fano resonances that exhibit relatively high Q-factors and strong spatial confinement, thereby concurrently optimizing the device for both imaging and biochemical sensing. For the sensing application, we demonstrate a limit of detection (LOD) as low as 1 pg/ml for Immunoglobulin G (IgG); for resonant imaging, we demonstrate a spatial resolution below 1 µm and clearly resolve individual E. coli bacteria. The combined low LOD and high spatial resolution opens new opportunities for extending cellular studies into the realm of microbiology, e.g. for studying antimicrobial susceptibility.

An update on our ability to monitor castration-resistant prostate cancer dynamics with cell-free DNA.

Introduction: Prostate cancer is one of the most frequent tumors worldwide. Due to the lack of reliable markers, patients are usually diagnosed at a late stage when it becomes castration-resistant prostate cancer (CRPC) with a worse outcome. Thus, it is essential to ameliorate the clinical management of these patients. Nowadays, the use of liquid biopsy represents a minimally invasive way to provide a complete molecular landscape of prostate cancer. Thus, this review aims to outline the clinical value of cell-free DNA in real-time monitoring of metastatic CRPC (mCRPC).Areas covered: This comprehensive review explores in detail the characteristics as well as clinical applications of plasma DNA analysis in mCRPC.Expert opinion: The assessment of circulating tumor DNA fraction is a valid and robust biomarker in mCRPC able to predict clinical outcome and monitor disease evolution during treatment. Recently, several methods (i.e. next generation sequencing and digital droplet PCR) are used to investigate genomics in cell-free DNA and novel nanotechnology-based approaches are currently under evaluation in order to improve clinical management of mCRPC patients.

Extended Kalman Filtering Projection Method to Reduce the 3σ Noise Value of Optical Biosensors.

Optical biosensors have experienced a rapid growth over the past decade because of their high sensitivity and the fact that they are label-free. Many optical biosensors rely on tracking the change in a resonance signal or an interference pattern caused by the change in refractive index that occurs upon binding to a target biomarker. The most commonly used method for tracking such a signal is based on fitting the data with an appropriate mathematical function, such as a harmonic function or a Fano, Gaussian, or Lorentz function. However, these functions have limited fitting efficiency because of the deformation of data from noise. Here, we introduce an extended Kalman filter projection (EKFP) method to address the problem of resonance tracking and demonstrate that it improves the tolerance to noise, reduces the 3σ noise value, and lowers the limit of detection (LOD). We utilize the method to process the data of experiments for detecting the binding of C-reactive protein in a urine matrix with a chirped guided mode resonance sensor and are able to improve the LOD from 10 to 1 pg/mL. Our method reduces the 3σ noise value of this measurement compared to a simple Fano fit from 1.303 to 0.015 pixels. These results demonstrate the significant advantage of the EKFP method to resolving noisy data of optical biosensors.

Common-path interferometric label-free protein sensing with resonant dielectric nanostructures.

Research toward photonic biosensors for point-of-care applications and personalized medicine is driven by the need for high-sensitivity, low-cost, and reliable technology. Among the most sensitive modalities, interferometry offers particularly high performance, but typically lacks the required operational simplicity and robustness. Here, we introduce a common-path interferometric sensor based on guided-mode resonances to combine high performance with inherent stability. The sensor exploits the simultaneous excitation of two orthogonally polarized modes, and detects the relative phase change caused by biomolecular binding on the sensor surface. The wide dynamic range of the sensor, which is essential for fabrication and angle tolerance, as well as versatility, is controlled by integrating multiple, tuned structures in the field of view. This approach circumvents the trade-off between sensitivity and dynamic range, typical of other phase-sensitive modalities, without increasing complexity. Our sensor enables the challenging label-free detection of procalcitonin, a small protein (13 kDa) and biomarker for infection, at the clinically relevant concentration of 1 pg mL-1, with a signal-to-noise ratio of 35. This result indicates the utility for an exemplary application in antibiotic guidance, and opens possibilities for detecting further clinically or environmentally relevant small molecules with an intrinsically simple and robust sensing modality.

Monitoring of individual bacteria using electro-photonic traps.

Antimicrobial resistance (AMR) describes the ability of bacteria to become immune to antimicrobial treatments. Current testing for AMR is based on culturing methods that are very slow because they assess the average response of billions of bacteria. In principle, if tests were available that could assess the response of individual bacteria, they could be much faster. Here, we propose an electro-photonic approach for the analysis and the monitoring of susceptibility at the single-bacterium level. Our method employs optical tweezers based on photonic crystal cavities for the trapping of individual bacteria. While the bacteria are trapped, antibiotics can be added to the medium and the corresponding changes in the optical properties and motility of the bacteria be monitored via changes of the resonance wavelength and transmission. Furthermore, the proposed assay is able to monitor the impedance of the medium surrounding the bacterium, which allows us to record changes in metabolic rate in response to the antibiotic challenge. For example, our simulations predict a variation in measurable electrical current of up to 40% between dead and live bacteria. The proposed platform is the first, to our knowledge, that allows the parallel study of both the optical and the electrical response of individual bacteria to antibiotic challenge. Our platform opens up new lines of enquiry for monitoring the response of bacteria and it could lead the way towards the dissemination of a new generation of antibiogram study, which is relevant for the development of a point-of-care AMR diagnostics.

Design of an ultra-compact graphene-based integrated microphotonic tunable delay line.

The design of a continuously tunable optical delay line based on a compact graphene-based silicon Bragg grating is reported. High performance, in terms of electro-optical switching time (tswitch < 8 ns), delay range (Δτ = 200 ps), and figure of merit FOM = Δτ/A = 1.54x105 ps/mm2, has been achieved with an ultra-compact device footprint (A ~1.3 x 10-3 mm2), so improving the state-of-the-art of integrated optical delay lines. A continuous and complete tunability of the delay time can be achieved with a very low delay loss ( = 0.03 dB/ps) and a weak power consumption ( = 0.05 mW/ps). A flat bandwidth B = 1.19 GHz has been calculated by exploiting the slow-light effect in the device. This performance makes the proposed optical delay line suitable for several applications in Microwave Photonics (MWP), such as beamsteering/beamforming, for which large delay range, flat and wide bandwidth and small volume are required.

Design of a New Ultracompact Resonant Plasmonic Multi-Analyte Label-Free Biosensing Platform.

In this paper, we report on the design of a bio-multisensing platform for the selective label-free detection of protein biomarkers, carried out through a 3D numerical algorithm. The platform includes a number of biosensors, each of them is based on a plasmonic nanocavity, consisting of a periodic metal structure to be deposited on a silicon oxide substrate. Light is strongly confined in a region with extremely small size (=1.57 µm²), to enhance the light-matter interaction. A surface sensitivity Ss = 1.8 nm/nm has been calculated together with a detection limit of 128 pg/mm². Such performance, together with the extremely small footprint, allow the integration of several devices on a single chip to realize extremely compact lab-on-chip microsystems. In addition, each sensing element of the platform has a good chemical stability that is guaranteed by the selection of gold for its fabrication.

Photonic and Plasmonic Nanotweezing of Nano- and Microscale Particles.

The ability to manipulate and sense biological molecules is important in many life science domains, such as single-molecule biophysics, the development of new drugs and cancer detection. Although the manipulation of biological matter at the nanoscale continues to be a challenge, several types of nanotweezers based on different technologies have recently been demonstrated to address this challenge. In particular, photonic and plasmonic nanotweezers are attracting a strong research effort especially because they are efficient and stable, they offer fast response time, and avoid any direct physical contact with the target object to be trapped, thus preventing its disruption or damage. In this paper, we critically review photonic and plasmonic resonant technologies for biomolecule trapping, manipulation, and sensing at the nanoscale, with a special emphasis on hybrid photonic/plasmonic nanodevices allowing a very strong light-matter interaction. The state-of-the-art of competing technologies, e.g., electronic, magnetic, acoustic and carbon nanotube-based nanotweezers, and a description of their applications are also included.