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In this study, we use nanopore arrays as a platform for detecting and characterizing individual nanoparticles (NPs) in real time. Dark-field imaging of nanopores with dimensions smaller than the wavelength of light occurs under conditions where trans-illumination is blocked, while the scattered light propagates to the far-field, making it possible to identify nanopores. The intensity of scattering increases dramatically during insertion of AgNPs into empty nanopores, owing to their plasmonic properties. Thus, momentary occupation of a nanopore by a AgNP produces intensity transients that can be analyzed to reveal the following characteristics: (1) NP scattering intensity, which scales with the sixth power of the AgNP radius, shows a normal distribution arising from the heterogeneity in NP size, (2) the nanopore residence time of NPs, which was observed to be stochastic with no permselective effects, and (3) the frequency of AgNP capture events on a 21 × 21 nanopore array, which varies linearly with the concentration of the NPs, agreeing with the frequency calculated from theory. The lower limit of detection (LOD) for NPs was 130 fM, indicating that the measurement can be used in applications in which ultrasensitive detection is required. The results presented here provide valuable insights into the dynamics of NP transport into and out of nanopores and highlight the potential of nanopore arrays as powerful, massively parallel tools for nanoparticle characterization and detection.

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Near-perfect light absorbers (NPLAs), with absorbance, [Formula: see text], of at least 99%, have a wide range of applications ranging from energy and sensing devices to stealth technologies and secure communications. Previous work on NPLAs has mainly relied upon plasmonic structures or patterned metasurfaces, which require complex nanolithography, limiting their practical applications, particularly for large-area platforms. Here, we use the exceptional band nesting effect in TMDs, combined with a Salisbury screen geometry, to demonstrate NPLAs using only two or three uniform atomic layers of transition metal dichalcogenides (TMDs). The key innovation in our design, verified using theoretical calculations, is to stack monolayer TMDs in such a way as to minimize their interlayer coupling, thus preserving their strong band nesting properties. We experimentally demonstrate two feasible routes to controlling the interlayer coupling: twisted TMD bi-layers and TMD/buffer layer/TMD tri-layer heterostructures. Using these approaches, we demonstrate room-temperature values of [Formula: see text]=95% at λ=2.8 eV with theoretically predicted values as high as 99%. Moreover, the chemical variety of TMDs allows us to design NPLAs covering the entire visible range, paving the way for efficient atomically-thin optoelectronics.

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Indium-tin oxide (ITO) is used in a variety of applications due to its electrical conductivity and optical transparency. Moreover, ITO coated glass is a common working electrode for spectroelectrochemistry. Thus, the ITO substrates should exhibit well-understood spectroscopic characteristics. Here, we report anomalous potential-dependent luminescence emission from three structurally-dissimilar electrofluorogenic probe on ITO coated glass. The three probes, flavin mononucleotide, resorufin, and Nile blue, show the expected fluorescence modulation between their oxidized, emissive forms and their reduced, non-fluorescent forms at low laser irradiance and/or high concentrations. However, at high irradiance and/or low concentration, the emission intensity increases at reducing potentials, contrary to expectations. In addition, a strong interplay between probe molecule concentration and laser irradiance is observed. We attribute the anomalous behavior to a combination of (1) irradiance-dependent ITO carrier dynamics, and (2) interaction of the fluorescent probe with ITO at reducing potentials resulting in a charge transfer state with altered emission behavior. Thus, the potential- and irradiance-dependent behavior of ITO and the resulting charge transfer state may not only interfere with the observation of potential-dependent fluorescence from redox probes but can completely reverse the polarity of the potential-dependent luminescence, especially at high irradiance and low concentration.

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The low-temperature growth of materials that support high-performance devices is crucial for advanced semiconductor technologies such as integrated circuits built using monolithic three-dimensional (3D) integration and flexible electronics. However, low growth temperature prohibits sufficient atomic diffusion and directly leads to poor material quality, imposing severe challenges that limit device performance. Here, we demonstrate superior quality growth of 3D semiconductors at growth temperatures reduced by >200 °C by using two-dimensional (2D) materials as intermediate layers to optimize the potential energy barrier for adatom diffusion. We reveal the benefits of maintaining, but reducing, the potential field through the 2D layer, which coupled with the inert surface of the 2D material lowers the kinetic barriers, enabling long-distance atomic diffusion and enhanced material quality at lower growth temperatures. As model systems, GaN and ZnSe, grown using WSe2 and graphene intermediate layers, exhibit larger grains, preferred orientation, reduced strain, and improved carrier mobility, all at temperatures lower by >200 °C compared to direct growth as characterized by diffraction, X-ray photoelectron spectroscopy, Raman, and Hall measurements. The realization of high-performance materials using 2D intermediate layers can enable transformative technologies under thermal budget restrictions, and the 2D/3D heterostructures could enable promising heterostructures for future device designs.

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Device life time is a significant consideration in the cost of ownership of quantum cascade lasers (QCLs). The life time of QCLs beyond an initial burn-in period has been studied previously; however, little attention has been given to predicting premature device failure where the device fails within several hundred hours of operation. Here, we demonstrate how standard electrical and optical device measurements obtained during an accelerated burn-in process can be used in a simple support vector machine to predict premature failure with high confidence. For every QCL that fails, at least one of the measurements is classified as belonging to a device that will fail prematurely-as much as 200 h before the actual failure of the device. Furthermore, for devices that are operational at the end of the burn-in process, the algorithm correctly classifies all the measurements. This work will influence future device analysis and could lead to insights on the physical mechanisms of premature failure in QCLs.

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Myxococcus xanthus is a common soil bacterium with a complex life cycle, which is known for production of secondary metabolites. However, little is known about the effects of nutrient availability on M. xanthus metabolite production. In this study, we utilize confocal Raman microscopy (CRM) to examine the spatiotemporal distribution of chemical signatures secreted by M. xanthus and their response to varied nutrient availability. Ten distinct spectral features are observed by CRM from M. xanthus grown on nutrient-rich medium. However, when M. xanthus is constrained to grow under nutrient-limited conditions, by starving it of casitone, it develops fruiting bodies, and the accompanying Raman microspectra are dramatically altered. The reduced metabolic state engendered by the absence of casitone in the medium is associated with reduced, or completely eliminated, features at 1140 cm-1, 1560 cm-1, and 1648 cm-1. In their place, a feature at 1537 cm-1 is observed, this feature being tentatively assigned to a transitional phase important for cellular adaptation to varying environmental conditions. In addition, correlating principal component analysis heat maps with optical images illustrates how fruiting bodies in the center co-exist with motile cells at the colony edge. While the metabolites responsible for these Raman features are not completely identified, three M. xanthus peaks at 1004, 1151, and 1510 cm-1 are consistent with the production of lycopene. Thus, a combination of CRM imaging and PCA enables the spatial mapping of spectral signatures of secreted factors from M. xanthus and their correlation with metabolic conditions.

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We demonstrate coupling to and control over the broadening and dispersion of a mid-infrared leaky mode, known as the Berreman mode, in samples with different dielectric environments. We fabricate subwavelength films of AlN, a mid-infrared epsilon-near-zero material that supports the Berreman mode, on materials with a weakly negative permittivity, strongly negative permittivity, and positive permittivity. Additionally, we incorporate ultra-thin AlN layers into a GaN/AlN heterostructure, engineering the dielectric environment above and below the AlN. In each of the samples, coupling to the Berreman mode is observed in angle-dependent reflection measurements at wavelengths near the longitudinal optical phonon energy. The measured dispersion of the Berreman mode agrees well with numerical modes. Differences in the dispersion and broadening for the different materials is quantified, including a 13 cm-1 red-shift in the energy of the Berreman mode for the heterostructure sample.

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Printing techniques using nanomaterials have emerged as a versatile tool for fast prototyping and potentially large-scale manufacturing of functional devices. Surfactants play a significant role in many printing processes due to their ability to reduce interfacial tension between ink solvents and nanoparticles and thus improve ink colloidal stability. Here, a colloidal graphene quantum dot (GQD)-based nanosurfactant is reported to stabilize various types of 2D materials in aqueous inks. In particular, a graphene ink with superior colloidal stability is demonstrated by GQD nanosurfactants via the π-π stacking interaction, leading to the printing of multiple high-resolution patterns on various substrates using a single printing pass. It is found that nanosurfactants can significantly improve the mechanical stability of the printed graphene films compared with those of conventional molecular surfactant, as evidenced by 100 taping, 100 scratching, and 1000 bending cycles. Additionally, the printed composite film exhibits improved photoconductance using UV light with 400 nm wavelength, arising from excitation across the nanosurfactant bandgap. Taking advantage of the 3D conformal aerosol jet printing technique, a series of UV sensors of heterogeneous structures are directly printed on 2D flat and 3D spherical substrates, demonstrating the potential of manufacturing geometrically versatile devices based on nanosurfactant inks.

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This feature issue presents recent progress in long-wavelength photonics, focusing on wavelengths that span the mid-infrared (3-50 µm), the long-wavelength infrared (30-60 µm), and the terahertz (60-300 µm) portions of the electromagnetic spectrum. The papers in this feature issue report recent progress in the generation, manipulation, detection, and use of light across this long-wave region of the "photonics spectrum," including novel sources and cutting edge advances in detectors, long-wavelength non-linear processes, optical metamaterials and metasurfaces, and molecular spectroscopy. The range of topics covered in this feature issue provide an excellent insight into the expanding interest in long-wavelength photonics, which could open new possibilities for basic research and applications in industries that span health, environmental, and security.

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BACKGROUND: Liquid biopsy offers the ability to non-invasively analyze the genome of a tumor through circulating tumor DNA (ctDNA) to identify targetable and prognostic genomic alterations. Few studies have rigorously analyzed ctDNA results and determined the fidelity with which they recapitulate the genomics of a sequenced tissue sample obtained from the same tumor. The clinical utility study (CUS) for the FoundationACT™ ctDNA assay (Foundation Medicine, Cambridge, MA, USA; NCT02620527) is a multi-center prospective clinical study for multiple solid tumor types to compare genomic profiling of paired tissue and blood samples from the same patient. In this subset of the study, paired specimens from 96 patients with colorectal cancer (CRC) were analyzed with comprehensive genomic profiling (CGP) of the tumor tissue sample (FoundationOne®) and blood sample (FoundationACT™). METHODS: Both samples underwent CGP using the hybrid capture-based Illumina Hi-Seq technology. Maximum somatic allele frequency (MSAF) was used to estimate the fraction of ctDNA in the sample. The set of genes and targeted regions common to both tumor and liquid were compared for each subject. RESULTS: Among these patients, 61% were male; 74% had clinical stage IV disease, 19% had clinical stage III disease, and 7% had clinical stage II disease. Time between the tissue biopsy and liquid biopsy (range, 0-709 days) had a significant impact on the positive percent agreement (PPA) between the two assays. Eighty percent of cases had evidence of ctDNA in the blood (MSAF >0). For all cases with MSAF >0, 171 base substitutions and insertions/deletions (indels) were identified in the tumor, and 79% (PPA) of these identical alterations were also identified in matched ctDNA samples; PPA increased to 87% for cases <270 days between the tissue and liquid biopsy, 95% for <90 days, and 100% PPA for <30 days. All known and likely short variants in KRAS, NRAS, and BRAF were analyzed independently as testing of these genes is recommended by the National Comprehensive Cancer Network (NCCN) for patients with CRC and have therapeutic implications. For NCCN genes, PPA was 80% for all time points for short variants; PPA increased to 90% for cases <270 days between the tissue and liquid biopsy. There was high concordance for KRAS G12X between tissue and liquid: overall percent agreement (97%), PPA (93%), negative percent agreement (NPA) (100%), positive predictive value (PPV) (100%), and negative predictive value (NPV) (96%) for the <270 day cohort. CONCLUSIONS: In cases where tumor tissue profiling is not possible, these results provide compelling evidence that genomic profiling of ctDNA in late stage CRC shows a high concordance with tumor tissue sequencing results and can be used to identify most clinically relevant alterations capable of guiding therapy for these patients.

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Sub-diffraction hyperbolic metamaterial resonators are promising structures for engineering light-matter interactions in semiconductor-based emitters and materials. The optical properties of these resonators are determined by a number of device characteristics including the metamaterial permittivity and resonator geometry. In this letter, we develop an optical model based on the modified long wavelength approximation to calculate the radiative and non-radiative photon loss of the resonators. We fabricate and characterize 11 different resonator arrays to demonstrate the effectiveness of model. Using the model, we demonstrate how the radiative properties of the resonators can be engineered via the design of the semiconductor metamaterial and the aspect ratio of the resonator. Over the explored design space, we demonstrate an eightfold increase in the radiative rate compared to the non-radiative rate. Our work reduces the complexity of designing sub-diffraction hyperbolic metamaterial resonators, allowing broader incorporation of these optical structures into novel devices and materials.

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We describe the behavior of optical trajectories in multipass rotationally asymmetric cavities (RACs) using a phase-space motivated approach. Emphasis is placed on generating long optical paths. A trajectory with an optical path length of 18 m is generated within a 68 cm3 volume. This path length to volume ratio (26.6 cm-2) is large compared to current state of the art multipass cells such as the cylindrical multipass cell (6.6 cm-2) and astigmatic Herriott cell (9 cm-2). Additionally, the effect of small changes to the input conditions on the path length is studied and compared to the astigmatic Herriott cell. This work simplifies the process of designing RACs with long optical path lengths and could lead to broader implementation of these multipass cells.

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The interaction of hafnium oxide (HfO2) nanoparticles (NPs) with X-ray and mid-infrared radiation was investigated to assess the potential as a multifunctional diagnostic probe for X-ray computed tomography (CT) and/or mid-infrared biosensing. HfO2 NPs of controlled size were prepared by a sol-gel process and surface functionalized with polyvinylpyrrolidone, resulting in relatively spherical and monodispersed NPs with a tunable mean diameter in the range of ∼7-31 nm. The X-ray attenuation of HfO2 NPs was measured over 0.5-50 mM concentration and compared with Au NPs and iodine, which are the most prominent X-ray contrast agents currently used in research and clinical diagnostic imaging, respectively. At clinical CT tube potentials >80 kVp, HfO2 NPs exhibited superior or similar X-ray contrast compared to Au NPs, while both exhibited significantly greater X-ray contrast compared to iodine, due to the favorable location of the k-shell absorption edge for hafnium and gold. Moreover, energy-dependent differences in X-ray attenuation enabled simultaneous quantitative molecular imaging of each agent using photon-counting spectral (multi-energy) CT. HfO2 NPs also exhibited a strong mid-infrared absorption in the Reststrahlen band from ∼250-800 cm(-1) and negative permittivity below 695 cm(-1), which can enable development of mid-infrared biosensors and contrast agents, leveraging surface enhanced mid-infrared and/or phonon polariton absorption.

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BACKGROUND: The present phase II, open-label, multicenter study explored the feasibility, safety, and tolerability of eribulin, a novel non-taxane microtubule inhibitor, plus capecitabine as adjuvant therapy. PATIENTS AND METHODS: Postmenopausal women with early-stage, human epidermal growth factor receptor 2 (HER2)-negative, estrogen-receptor (ER)-positive breast cancer received four 21-day cycles of treatment with eribulin mesylate (1.4 mg/m(2) intravenously on days 1 and 8 of each cycle) combined with capecitabine (900 mg/m(2) orally twice daily on days 1-14 of each cycle [standard schedule] or 1500 mg orally twice daily using a 7-days on/7-days off schedule [weekly schedule]). Feasibility was determined by the relative dose intensity (RDI) of the combination using prespecified criteria for 80% of patients achieving an RDI of ≥ 85%, with a lower 95% confidence boundary > 70%. RESULTS: The mean RDI was 90.6%, and the feasibility rate was 81.3% among women (n = 67, mean age, 61.3 years) receiving the standard schedule and 95.6% and 100% among women (n = 10, mean age 62.3 years) receiving the weekly schedule. Dose reductions, missed doses, and withdrawals due to adverse events (most commonly hand-foot syndrome) ascribed to capecitabine led to a higher RDI (93.5% vs. 87.8%) and feasibility rate (82.8% vs. 71.9%) for eribulin than for capecitabine using the standard dosing schedule. The most common adverse events were alopecia and fatigue. CONCLUSION: Eribulin plus capecitabine with standard or weekly dosing schedules is feasible in patients with early-stage, HER2-negative, ER-positive breast cancer. Full-dose eribulin (1.4 mg/m(2) on days 1 and 8) with capecitabine (1500 mg orally twice daily, 7 days on/7 days off) is recommended as a regimen for further evaluation.

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All-semiconductor, highly anisotropic metamaterials provide a straightforward path to negative refraction in the mid-infrared. However, their usefulness in applications is restricted by strong frequency dispersion and limited spectral bandwidth. In this work, we show that by stacking multiple metamaterials of varying thickness and doping into one compound metamaterial, bandwidth is increased by 27% over a single-stack metamaterial, and dispersion is reduced.

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Most nurses will not go to another county and provide healthcare education, but will care for patients from other countries and faiths who practice traditions that impact how they manage their illness. This author shares his experience in Mauritania, which provides an excellent example for understanding issues in cross-cultural diabetic education. Universal principles for cross-cultural health education are offered.

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We characterize a strongly anisotropic waveguide consisting of alternating 80 nm layers of n(+)-InGaAs and i-AlInAs on InP substrate. A strong increase in the transverse magnetic (TM) reflection at lambda = 8.4 microm corresponds to a characteristic low-order mode cutoff for the left-handed waveguide. The subsequent decrease of TM reflection at lambda = 11.5 microm represents the onset of right-handed no-cutoff light guiding. Good qualitative agreement is found when the experimental results are compared to finite element and transfer-matrix frequency domain simulations.

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An optical metamaterial is a composite in which subwavelength features, rather than the constituent materials, control the macroscopic electromagnetic properties of the material. Recently, properly designed metamaterials have garnered much interest because of their unusual interaction with electromagnetic waves. Whereas nature seems to have limits on the type of materials that exist, newly invented metamaterials are not bound by such constraints. These newly accessible electromagnetic properties make these materials an excellent platform for demonstrating unusual optical phenomena and unique applications such as subwavelength imaging and planar lens design. 'Negative-index materials', as first proposed, required the permittivity, epsilon, and permeability, mu, to be simultaneously less than zero, but such materials face limitations. Here, we demonstrate a comparatively low-loss, three-dimensional, all-semiconductor metamaterial that exhibits negative refraction for all incidence angles in the long-wave infrared region and requires only an anisotropic dielectric function with a single resonance. Using reflection and transmission measurements and a comprehensive model of the material, we demonstrate that our material exhibits negative refraction. This is furthermore confirmed through a straightforward beam optics experiment. This work will influence future metamaterial designs and their incorporation into optical semiconductor devices.

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We demonstrate an In(0.635)Al(0.356)As/In(0.678)Ga(0.322)As strain compensated quantum cascade laser that employs heterogeneous injector regions for low voltage defect operation. The active core consists of interdigitated undoped and doped injectors followed by nominally identical wavelength optical transitions. The undoped injector regions are designed with reduced voltage defect while the doped injectors are of a more conventional design. The measured average voltage defect is less than 79 meV. At 80 K, a 2.3 mm long, back facet high reflectance coated laser has an emission wavelength of 4.7 mum and outputs 2.3 W pulsed power with a peak wall-plug efficiency of 19%.

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The analog, rebeccamycin tartrate salt (NSC 655649, Cancer Therapy Evaluation Program, National Cancer Institute) has broad preclinical anti-neoplastic activity. Preliminary data from phase I study demonstrated antitumor activity in colorectal carcinoma. This phase II trial evaluates its efficacy in patients with minimally treated metastatic colorectal cancer. Eligibility included Karnofsky performance status > or = 70%, age > or = 18 years and bidimensionally measurable disease. Thirteen patients were treated with NSC 655649 at 500 mg/m2 by central venous catheter once every 3 weeks by bolus injection. Thirty-four cycles (median [range] 2 [1-6]) of therapy were administered. Twelve patients are eligible for response assessment. No major objective responses were seen using the RECIST criteria; however stable disease was observed in three patients with mean duration of 15 weeks. The median time to progression was 8 weeks. There was no toxic death. Four patients received only one cycle of treatment, and three had disease progression. Toxicities were tolerable and hematologic toxicity was the most common. The median (range) granulocyte and platelet nadir counts were 2043/microl (116-16,374/microl) and 276 x 10(3)/ microl (5-769), respectively. Non-hematologic toxicities were moderate, including generalized weakness/fatigue, nausea/vomiting, diarrhea and anorexia. One patient required dose reduction; three patients required dose delays. NSC 655649 at this dose and schedule is inactive against advanced previously minimally treated metastatic colorectal cancer and further study of this drug as a single agent in this disease using an every three-week schedule is not warranted.

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