A Fully Metaoptical Zoom Lens with a Wide Range.

Metalenses are typically designed for a fixed focal length, restricting their functionality to static scenarios. Various methods have been introduced to achieve the zoom function in metalenses. These methods, however, have a very limited zoom range, or they require additional lenses to achieve direct imaging. Here, we demonstrate a zoom metalens based on axial movement that performs both the imaging and the zoom function. The key innovation is the use of a polynomial phase profile that mimics an aspheric lens, which allows an extended depth of focus, enabling a large zoom range. Experimental results show that this focal length variation, combined with the extended depth of focus, translates into an impressive zoom range of 11.9× while maintaining good imaging quality. We see applications for such a zoom metalens in surveillance cameras of drones or microrobots to reduce their weight and volume, thus enabling more flexible application scenarios.

Treatment strategies in patients with gynecological sarcoma: Results of the prospective intergroup real-world registry for gynecological sarcoma in Germany (REGSA-NOGGO RU1).

OBJECTIVE: Gynecological sarcomas account for 3% of all gynecological malignancies and are associated with a poor prognosis. Due to the rarity and heterogeneity of gynecological sarcomas there is still no consensus on optimal therapeutic strategies. This study's objective was to describe the treatment strategies used in patients with gynecological sarcomas in the primary course of disease. METHODS: The German prospective registry for gynecological sarcoma (REGSA) is the largest registry for gynecological sarcomas in Germany, Austria and Switzerland. Primary inclusion criteria for REGSA are histological diagnosis of sarcoma of the female genital tract, sarcoma of the breast or uterine smooth muscle tumors of uncertain malignant potential (STUMP). We evaluated data of the REGSA registry on therapeutic strategies used for primary treatment from August 2015 to February 2021. RESULTS: A total of 723 patients from 120 centers were included. Data on therapeutic strategies for primary treatment were available in 605 cases. Overall, 580 (95.9%) patients underwent primary surgery, 472 (81.4%) of whom underwent only hysterectomy. Morcellation was reported in 11.4% (n=54) of all hysterectomies. A total of 42.8% (n=202) had no further surgical interventions, whereas an additional salpingo-ophorectomy was performed in 54% (n=255) of patients. An additional lymphadenectomy was performed in 12.7% (n=60), an omentectomy in 9.5% (n=45) and intestinal resection in 6.1% (n=29) of all patients. Among 448 patients with available information, 21.4% (n=96) received chemo- or targeted therapies, more commonly as single-agent treatment than as drug combinations. Information about anti-hormonal treatment was available for 423 patients, among which 42 (9.9%) received anti-hormonal treatment, 23 (54.8%) of whom with low-grade endometrial stroma sarcomas. For radiotherapy, data of 437 patients were available, among which 29 (6.6%) patients underwent radiotherapy. CONCLUSION: Our study showed that treatment of patients with gynecologic sarcomas is heterogeneous. Further trials are needed along with more information on treatment modalities, therapy response and patient-reported outcomes to implement new treatment strategies.

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.

Detection of paracetamol binding to albumin in blood serum using 2D-IR spectroscopy.

Binding of drugs to blood serum proteins can influence both therapeutic efficacy and toxicity. The ability to measure the concentrations of protein-bound drug molecules quickly and with limited sample preparation could therefore have considerable benefits in biomedical and pharmaceutical applications. Vibrational spectroscopies provide data quickly but are hampered by complex, overlapping protein amide I band profiles and water absorption. Here, we show that two-dimensional infrared (2D-IR) spectroscopy can achieve rapid detection and quantification of paracetamol binding to serum albumin in blood serum at physiologically-relevant levels with no additional sample processing. By measuring changes to the amide I band of serum albumin caused by structural and dynamic impacts of paracetamol binding we show that drug concentrations as low as 7 µM can be detected and that the availability of albumin for paracetamol binding is less than 20% in serum samples, allowing identification of paracetamol levels consistent with a patient overdose.

Quantifying single-cell secretion in real time using resonant hyperspectral imaging.

Cell communication is primarily regulated by secreted proteins, whose inhomogeneous secretion often indicates physiological disorder. Parallel monitoring of innate protein-secretion kinetics from individual cells is thus crucial to unravel systemic malfunctions. Here, we report a label-free, high-throughput method for parallel, in vitro, and real-time analysis of specific single-cell signaling using hyperspectral photonic crystal resonant technology. Heterogeneity in physiological thrombopoietin expression from individual HepG2 liver cells in response to platelet desialylation was quantified demonstrating how mapping real-time protein secretion can provide a simple, yet powerful approach for studying complex physiological systems regulating protein production at single-cell resolution.

Performance limitations of resonant refractive index sensors with low-cost components.

Resonant biosensors are attractive for diagnostics because they can detect clinically relevant biomarkers with high sensitivity and in a label-free fashion. Most of the current solutions determine their detection limits in a highly stabilised laboratory environment, which does, however, not apply to real point-of-care applications. Here, we consider the more realistic scenario of low-cost components and an unstabilised environment and consider the related design implications. We find that sensors with lower quality-factor resonances are more fault tolerant, that a filtered LED lightsource is advantageous compared to a diode laser, and that a CMOS camera is preferable to a CCD camera for detection. We exemplify these findings with a guided mode resonance sensor and experimentally determine a limit of detection of 5.8 ± 1.7×10-5 refractive index units (RIU), which is backed up by a model identifying the various noise sources. Our findings will inform the design of high performance, low cost biosensors capable of operating in a real-world environment.

Ultra-thin transmissive crystalline silicon high-contrast grating metasurfaces.

Dielectric metasurfaces made from crystalline silicon, titanium dioxide, gallium nitride and silicon nitride have developed rapidly for applications in the visible wavelength regime. High performance metasurfaces typically require the realisation of subwavelength, high aspect ratio nanostructures, the fabrication of which can be challenging. Here, we propose and demonstrate the operation of high performance metasurfaces in ultra-thin (100 nm) crystalline silicon at the wavelength of 532 nm. Using optical beam analysis, we discuss fabrication complexity and show that our approach is more fabrication-tolerant than the nanofin approach, which has so far produced the highest performance metasurfaces, but may be difficult to manufacture, especially when using nanoimprint lithography.

Influence of patient and tumor characteristics on therapy persistence with letrozole in postmenopausal women with advanced breast cancer: results of the prospective observational EvAluate-TM study.

BACKGROUND: Treatment of postmenopausal, hormone receptor-positive metastatic breast cancer (MBC) patients varies despite clear therapy guidelines, favoring endocrine treatment (ET). Aim of this study was to analyze persistence of palliative aromatase inhibitor (AI) monotherapy in MBC patients. METHODS: EvAluate-TM is a prospective, multicenter, noninterventional study to evaluate treatment with letrozole in postmenopausal women with hormone receptor-positive breast cancer. To assess therapy persistence, defined as the time from therapy start to the end of the therapy (TTEOT), two pre-specified study visits took place after 6 and 12 months. Competing risk survival analyses were performed to identify patient and tumor characteristics that predict TTEOT. RESULTS: Out of 200 patients, 66 patients terminated treatment prematurely, 26 (13%) of them due to causes other than disease progression. Persistence rate for reasons other than progression at 12 months was 77.7%. Persistence was lower in patients who reported any adverse event (AE) in the first 30 days of ET (89.5% with no AE and 56% with AE). Furthermore, patients had a lower persistence if they reported compliance problems in the past before letrozole treatment. CONCLUSIONS: Despite suffering from a life-threatening disease, AEs of an AI will result in a relevant number of treatment terminations that are not related to progression. Some subgroups of patients have very low persistence rates. Especially with regard to novel endocrine combination therapies, these data imply that some groups of patients will need special attention to guide them through the therapy process. TRIAL REGISTRATION: Clinical Trials Number: CFEM345DDE19.

Ultrahigh Numerical Aperture Metalens at Visible Wavelengths.

Subwavelength imaging requires the use of high numerical aperture (NA) lenses together with immersion liquids in order to achieve the highest possible resolution. Following exciting recent developments in metasurfaces that have achieved efficient focusing and novel beam-shaping, the race is on to demonstrate ultrahigh-NA metalenses. The highest NA that has been demonstrated so far is NA = 1.1, achieved with a TiO2 metalens and back-immersion. Here, we introduce and demonstrate a metalens with a high NA and high transmission in the visible range, based on crystalline silicon (c-Si). The higher refractive index of silicon compared to TiO2 allows us to push the NA further. The design uses the geometric phase approach also known as the Pancharatnam-Berry (P-B) phase, and we determine the arrangement of nanobricks using a hybrid optimization algorithm (HOA). We demonstrate a metalens with NA = 0.98 in air, a bandwidth (full width at half-maximum, fwhm) of 274 nm, and a focusing efficiency of 67% at 532 nm wavelength, which is close to the transmission performance of a TiO2 metalens. Moreover, and uniquely so, our metalens can be front-immersed into immersion oil and achieve an ultrahigh NA of 1.48 experimentally and 1.73 theoretically, thereby demonstrating the highest NA of any metalens in the visible regime reported to the best of our knowledge. The fabricating process is fully compatible with microelectronic technology and therefore scalable. We envision the front-immersion design to be beneficial for achieving ultrahigh-NA metalenses as well as immersion metalens doublets, thereby pushing metasurfaces into practical applications such as high resolution, low-cost confocal microscopy and achromatic lenses.

Random lasing in uniform perovskite thin films.

Following the very promising results obtained by the solar cell community, metal halide perovskite materials are increasingly attracting the attention of other optoelectronics researchers, especially for light emission applications. Lasing with both engineered and self-assembled resonator structures, such as microcrystal networks, has now been successfully observed, with the low cost and the simple solution-based process being a particular attraction. The ultimate in simplicity, however, would be to observe lasing from a continuous thin film, which has not been reported yet. Here, we show random lasing action from such a simple perovskite layer. Our lasers work at room temperature; they are deposited on unpatterned glass substrates and they exhibit a minimum threshold value of 10 µJ/cm2. By carefully controlling the solution processing conditions, we can determine whether random lasing occurs or not, using identical precursors. A rather special feature is that some of the films exhibit single and dual mode lasing action, which is rarely observed in random lasers. Our work fully exploits the simplicity of the solution-based process and thereby adds an important capability into the emerging field of perovskite-based light emitters.

Paths to light trapping in thin film GaAs solar cells.

It is now well established that light trapping is an essential element of thin film solar cell design. Numerous light trapping geometries have already been applied to thin film cells, especially to silicon-based devices. Less attention has been paid to light trapping in GaAs thin film cells, mainly because light trapping is considered less attractive due to the material's direct bandgap and the fact that GaAs suffers from strong surface recombination, which particularly affects etched nanostructures. Here, we study light trapping structures that are implemented in a high-bandgap material on the back of the GaAs active layer, thereby not perturbing the integrity of the GaAs active layer. We study photonic crystal and quasi-random nanostructures both by simulation and by experiment and find that the photonic crystal structures are superior because they exhibit fewer but stronger resonances that are better matched to the narrow wavelength range where GaAs benefits from light trapping. In fact, we show that a 1500 nm thick cell with photonic crystals achieves the same short circuit current as an unpatterned 4000 nm thick cell. These findings are significant because they afford a sizeable reduction in active layer thickness, and therefore a reduction in expensive epitaxial growth time and cost, yet without compromising performance.

Optical trapping with planar silicon metalenses.

Contactless manipulation of micron-scale objects in a microfluidic environment is a key ingredient for a range of applications in the biosciences, including sorting, guiding, and analysis of cells and bacteria. Optical forces are powerful for this purpose but, typically, require bulky focusing elements to achieve the appropriate optical field gradients. To this end, realizing the focusing optics in a planar format would be very attractive and conducive to the integration of such microscale devices, either individually or as arrays. Here we report on, to the best of our knowledge, the first experimental demonstration of optical trapping using planar silicon metalenses illuminated with a collimated laser beam. The structures consist of high-contrast gratings with a locally varying period and duty cycle. They are designed to mimic parabolic reflectors with a numerical aperture of 0.56 at a vacuum wavelength of 1064 nm. We achieve both two- and three-dimensional trapping in water, with the latter realized by omitting the central Fresnel zones. This Letter highlights the versatility of such lithographically defined metastructures for exerting optical forces without the need for traditional optical elements.

Dual-Mode Electro-Optical Techniques for Biosensing Applications: A Review.

The monitoring of biomolecular interactions is a key requirement for the study of complex biological processes and the diagnosis of disease. Technologies that are capable of providing label-free, real-time insight into these interactions are of great value for the scientific and clinical communities. Greater understanding of biomolecular interactions alongside increased detection accuracy can be achieved using technology that can provide parallel information about multiple parameters of a single biomolecular process. For example, electro-optical techniques combine optical and electrochemical information to provide more accurate and detailed measurements that provide unique insights into molecular structure and function. Here, we present a comparison of the main methods for electro-optical biosensing, namely, electrochemical surface plasmon resonance (EC-SPR), electrochemical optical waveguide lightmode spectroscopy (EC-OWLS), and the recently reported silicon-based electrophotonic approach. The comparison considers different application spaces, such as the detection of low concentrations of biomolecules, integration, the tailoring of light-matter interaction for the understanding of biomolecular processes, and 2D imaging of biointeractions on a surface.

Cross-phase modulation-induced spectral broadening in silicon waveguides.

We analytically and experimentally investigate cross-phase modulation (XPM) in silicon waveguides. In contrast to the well known result in pure Kerr media, the spectral broadening ratio of XPM to self-phase modulation is not two in the presence of either two-photon absorption (TPA) or free carriers. The physical origin of this change is different for each effect. In the case of TPA, this nonlinear absorption attenuates and slightly modifies the pulse shape due to differential absorption in the pulse peak and wings. When free carriers are present two different mechanisms modify the dynamics. First, free-carrier absorption performs a similar role to TPA, but is additionally asymmetric due to the delayed free-carrier response. Second, free-carrier dispersion induces an asymmetric blue phase shift which competes directly with the symmetric Kerr-induced XPM red shift. We confirm this analysis with pump-probe experiments in a silicon photonic crystal waveguide.

Ultrafast laser plasma doping of Er3+ ions in silica-on-silicon for optical waveguiding applications.

An ultrafast laser plasma doping (ULPD) technique is used for high concentration doping of erbium ions into silica-on-silicon substrate. The method uses a femtosecond laser to ablate material from TeO2-ZnO-Na2O-Er2O3 (Er-TZN) target glass. The laser-generated plasma modifies the silica network, producing a high-index-contrast optical layer suited to the production of on-chip integrated optical circuits. Cross-sectional analysis using scanning electron microscope with energy dispersive x-ray spectroscopy revealed homogeneous intermixing of the host silica with Er-TZN, which is unique to ULPD. The highly doped layer exhibits spectroscopic characteristics of erbium with photoluminescence lifetimes from 10.79 to 14.07 ms.

Single mode thermal emission.

We report on the properties of a thermal emitter which radiates into a single mode waveguide. We show that the maximal power of thermal radiation into a propagating single mode is limited only by the temperature of the thermal emitter and does not depend on other parameters of the waveguide. Furthermore, we show that the power of the thermal emitter cannot be increased by resonant coupling. For a given temperature, the enhancement of the total emitted power is only possible if the number of excited modes is increased. Either a narrowband or a broadband thermal excitation of the mode is possible, depending on the properties of the emitter. We finally discuss an example system, namely a thermal source for silicon photonics.

Non-degenerate two-photon absorption in silicon waveguides: analytical and experimental study.

We theoretically and experimentally investigate the nonlinear evolution of two optical pulses in a silicon waveguide. We provide an analytic solution for the weak probe wave undergoing non-degenerate two-photon absorption (TPA) from the strong pump. At larger pump intensities, we employ a numerical solution to study the interplay between TPA and photo-generated free carriers. We develop a simple and powerful approach to extract and separate out the distinct loss contributions of TPA and free-carrier absorption from readily available experimental data. Our analysis accounts accurately for experimental results in silicon photonic crystal waveguides.

How to assess light trapping structures versus a Lambertian Scatterer for solar cells?

We propose a new figure of merit to assess the performance of light trapping nanostructures for solar cells, which we call the light trapping efficiency (LTE). The LTE has a target value of unity to represent the performance of an ideal Lambertian scatterer, although this is not an absolute limit but rather a benchmark value. Since the LTE aims to assess the nanostructure itself, it is, in principle, independent of the material, fabrication method or technology used. We use the LTE to compare numerous proposals in the literature and to identify the most promising light trapping strategies. We find that different types of photonic structures allow approaching the Lambertian limit, which shows that the light trapping problem can be approached from multiple directions. The LTE of theoretical structures significantly exceeds that of experimental structures, which highlights the need for theoretical descriptions to be more comprehensive and to take all relevant electro-optic effects into account.

Contra-directional coupling into slotted photonic crystals for spectrometric applications.

We propose and demonstrate the concept of a contra-directional coupler between a W1 and a slotted photonic crystal waveguide. The bandwidth and operating wavelength of such a coupler can be controlled via its geometrical parameters, and power transfer is not periodic unlike in the more familiar codirectional case. Light of specific wavelengths can be extracted from the W1 mode into air slot modes using this design, with W1/slot coupling efficiencies of up to 99±1%, and waveguide extracted coupling efficiencies of up to 51±12% demonstrated experimentally. Combining several of these couplers in series, we demonstrate the spectral filtering functionality on-chip. The device therefore combines the well-known sensing function of the slotted waveguide geometry with the spectrometer function, thus uniting two essential biosensor functions in a monolithic device.

Phase-sensitive amplification in silicon photonic crystal waveguides.

We experimentally demonstrate phase-sensitive amplification in a silicon photonic crystal waveguide based on pump-degenerate four-wave mixing. An 11 dB phase-extinction ratio is obtained in a record compact 196 µm nanophotonic device due to broadband slow light, in spite of the presence of two-photon absorption and free carriers. Numerical calculations show good agreement with the experimental results.