Band flipping and bandgap closing in a photonic crystal ring and its applications.

The size of the bandgap in a photonic crystal ring is typically intuitively considered to monotonically grow as the modulation amplitude of the grating increases, causing increasingly large frequency splittings between the "dielectric" and "air" bands. In contrast, here we report that as the modulation amplitude in a photonic crystal ring increases, the bandgap does not simply increase monotonically. Instead, after the initial increase, the bandgap closes and then reopens again with the two bands flipped in energy. The air and dielectric band edges are degenerate at the bandgap closing point. We demonstrate this behavior experimentally in silicon nitride photonic crystal microrings, where we show that the bandgap is closed to within the linewidth of the optical cavity mode, whose intrinsic quality factor remains unperturbed with a value ≈ 1×106. Moreover, through finite-element simulations, we show that such bandgap closing and band flipping phenomena exist in a variety of photonic crystal rings with varying unit cell geometries and cladding layers. At the bandgap closing point, the two standing wave modes with a degenerate frequency are particularly promising for single-frequency lasing applications. Along this line, we propose a compact self-injection locking scheme that integrates many core functionalities in one photonic crystal ring. Additionally, the single-frequency lasing might be applicable to distributed-feedback (DFB) lasers to increase their manufacturing yield.

Inverse design of a polarization demultiplexer for on-chip path-entangled photon-pair sources based on single quantum dots.

Epitaxial quantum dots can emit polarization-entangled photon pairs. If orthogonal polarizations are coupled to independent paths, then the photons will be path-entangled. Through inverse design with adjoint method optimization, we design a quantum dot polarization demultiplexer, a nanophotonic geometry that efficiently couples orthogonally polarized transition dipole moments of a single quantum dot to two independent waveguides. We predict 95% coupling efficiency, cross talk less than 0.1%, and Purcell radiative rate enhancement factors over 11.5 for both dipoles, with sensitivity to dipole misalignment and orientation comparable to that of conventional nanophotonic geometries. We anticipate our design will be valuable for the implementation of triggered, high-rate sources of path-entangled photon-pairs on chip.

Kerr optical parametric oscillation in a photonic crystal microring for accessing the infrared.

Continuous wave optical parametric oscillation (OPO) provides a flexible approach for accessing mid-infrared wavelengths between 2 µm and 5 µm, but operation at these wavelengths has not yet been integrated into silicon nanophotonics. Typically, a Kerr OPO uses a single transverse mode family for pump, signal, and idler modes, and relies on a delicate balance to achieve normal (but close-to-zero) dispersion near the pump and the requisite higher-order dispersion needed for phase- and frequency-matching. Within integrated photonics platforms, this approach results in two major problems. First, the dispersion is very sensitive to geometry, so that small fabrication errors can have a large impact. Second, the device is susceptible to competing nonlinear processes near the pump. In this Letter, we propose a flexible solution to infrared OPO that addresses these two problems by using a silicon nitride photonic crystal microring (PhCR). The frequency shifts created by the PhCR bandgap enable OPO that would otherwise be forbidden. We report an intrinsic optical quality factor up to (1.2 ± 0.1)×106 in the 2-µm band, and use a PhC ring to demonstrated an OPO with a threshold dropped power in the cavity of (90 ± 20) mW, with the pump wavelength at 1998 nm, and the signal and idler wavelengths at 1937 nm and 2063 nm, respectively. We further discuss how to extend the OPO spectral coverage in the mid-infrared. These results establish the PhCR OPO as a promising route for integrated laser sources in the infrared.

Fractional Optical Angular Momentum and Multi-Defect-Mediated Mode Renormalization and Orientation Control in Photonic Crystal Microring Resonators.

Whispering gallery modes (WGMs) in circularly symmetric optical microresonators exhibit integer quantized angular momentum numbers due to the boundary condition imposed by the geometry. Here, we show that incorporating a photonic crystal pattern in an integrated microring can result in WGMs with fractional optical angular momentum. By choosing the photonic crystal periodicity to open a photonic band gap with a band-edge momentum lying between that of two WGMs of the unperturbed ring, we observe hybridized WGMs with half-integer quantized angular momentum numbers (m∈Z+1/2). Moreover, we show that these modes with fractional angular momenta exhibit high optical quality factors with good cavity-waveguide coupling and an order of magnitude reduced group velocity. Additionally, by introducing multiple artificial defects, multiple modes can be localized to small volumes within the ring, while the relative orientation of the delocalized band-edge states can be well controlled. Our Letter unveils the renormalization of WGMs by the photonic crystal, demonstrating novel fractional angular momentum states and nontrivial multimode orientation control arising from continuous rotational symmetry breaking. The findings are expected to be useful for sensing and metrology, nonlinear optics, and cavity quantum electrodynamics.

Purcell-Enhanced Single Photon Source Based on a Deterministically Placed WSe2 Monolayer Quantum Dot in a Circular Bragg Grating Cavity.

We demonstrate a deterministic Purcell-enhanced single photon source realized by integrating an atomically thin WSe2 layer with a circular Bragg grating cavity. The cavity significantly enhances the photoluminescence from the atomically thin layer and supports single photon generation with g(2)(0) < 0.25. We observe a consistent increase of the spontaneous emission rate for WSe2 emitters located in the center of the Bragg grating cavity. These WSe2 emitters are self-aligned and deterministically coupled to such a broadband cavity, configuring a new generation of deterministic single photon sources, characterized by their simple and low-cost production and intrinsic scalability.

Sensitive LC-MS/MS method for quantification of rivaroxaban in plasma: Application to pharmacokinetic studies.

Rivaroxaban is an anticoagulant (orally active direct Xa inhibitor) considered to reduce the risk of stroke and systemic embolism and treat deep vein thrombosis, pulmonary embolism, and other cardiovascular complications. Bioanalytical methods for rivaroxaban quantification in plasma are necessary for application in pharmacokinetic studies, as well as in drug therapeutic monitoring. In this work, we developed and validated a sensitive bioanalytical method using LC-MS/MS for rivaroxaban quantification in human plasma using an one-step liquid-liquid extraction. The linear concentration range was 1-600 ng/mL. The bioanalytical method was also applied to pharmacokinetic studies in healthy volunteers under fasting and fed conditions. The results demonstrated that the method is rapid, sensitive, and adequate for application in pharmacokinetic studies.

Hyperspectral study of the coupling between trions in WSe2 monolayers to a circular Bragg grating cavity.

Circular Bragg gratings compose a very appealing photonic platform and nanophotonic interface for the controlled light-matter coupling of emitters in nanomaterials. Here, we discuss the integration of exfoliated monolayers of WSe2 with GaInP Bragg gratings. We apply hyperspectral imaging to our coupled system, and explore the spatio-spectral characteristics of our coupled monolayer-cavity system. Our work represents a valuable step towards the integration of atomically thin quantum emitters in semiconductor nanophotonic cavities.

Indistinguishable Photons from Deterministically Integrated Single Quantum Dots in Heterogeneous GaAs/Si3N4 Quantum Photonic Circuits.

Silicon photonics enables scaling of quantum photonic systems by allowing the creation of extensive, low-loss, reconfigurable networks linking various functional on-chip elements. Inclusion of single quantum emitters onto photonic circuits, acting as on-demand sources of indistinguishable photons or single-photon nonlinearities, may enable large-scale chip-based quantum photonic circuits and networks. Toward this, we use low-temperature in situ electron-beam lithography to deterministically produce hybrid GaAs/Si3N4 photonic devices containing single InAs quantum dots precisely located inside nanophotonic structures, which act as efficient, Si3N4 waveguide-coupled on-chip, on-demand single-photon sources. The precise positioning afforded by our scalable fabrication method furthermore allows observation of postselected indistinguishable photons. This indicates a promising path toward significant scaling of chip-based quantum photonics, enabled by large fluxes of indistinguishable single-photons produced on-demand, directly on-chip.

In Vitro-In Vivo Correlation for Desvenlafaxine Succinate Monohydrate Extended Release Tablets.

The objective of this study was to develop a dissolution test in order to establish an in vitro-in vivo correlation (IVIVC) model for desvenlafaxine succinate monohydrate (DVSM) extended release (ER) tablets. The in vitro release characteristics of the drug were determined using USP apparatus 1 at 75 rpm, with volume of HCl pH 1.2, acetate buffer solution (ABS) pH 4.5, or phosphate buffer solution (PBS) pH 6.8. In vivo plasma concentrations and pharmacokinetic parameters in healthy volunteers were obtained from a bioequivalence study. The similarity factors f1 and f2 were used to compare the dissolution data. The IVIVC model was developed using fraction dissolved and fraction absorbed of the reference product. For predictability, the results showed that the percentage prediction error (%PE) value of Cmax was 7.63%. The observed low prediction error for Cmax demonstrated that the IVIVC model was valid for this parameter.

A randomized, single-dose, two-sequence, two-period, crossover study to assess the bioequivalence between two formulations of clonazepam tablet in healthy subjects.

Clonazepam is a benzodiazepine commonly prescribed to treat panic disorder, epilepsy, anxiety, depression and certain types of seizures. This study aimed to evaluate the bioequivalence between two formulations of clonazepam tablets in order to meet regulatory requirements for marketing in Colombia and other countries in Latin America. An open-label, randomized, single-dose, two-period, two-sequence, two-treatment crossover study was conducted in 36 healthy subjects of both genders. Subjects received a single dose of clonazepam 2 mg test tablet (Sanofi-Aventis de Colombia S.A.) and reference product (Rivotril®, Produtos Roche Químicos e Farmacêuticos S.A.) under fasting conditions according to a randomly assigned order with a 21-day washout period. Serial blood samples were collected up to 96 h post-dose. Plasma concentrations of clonazepam were obtained by a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated using non-compartmental methods. A total of 36 healthy subjects were enrolled and 31 of them completed the study. Twenty-nine adverse events were reported (11 events with test product versus 18 events with reference product). There were no serious adverse events during the study. Geometric mean ratios (90% confidence intervals) for Cmax and AUC0-96h were 103.28% (98.10-108.64) and 102.50% (99.87-105.19), respectively. The test formulation of clonazepam 2 mg tablet manufactured by Sanofi-Aventis de Colombia S.A. was considered bioequivalent to reference product Rivotril® (Produtos Roche Químicos e Farmacêuticos S.A.) according to regulatory requirements. Both formulations were safe and well-tolerated during the study.

Nanoscale Mapping and Spectroscopy of Nonradiative Hyperbolic Modes in Hexagonal Boron Nitride Nanostructures.

The inherent crystal anisotropy of hexagonal boron nitride (hBN) provides the ability to support hyperbolic phonon polaritons, that is, polaritons that can propagate with very large wave vectors within the material volume, thereby enabling optical confinement to exceedingly small dimensions. Indeed, previous research has shown that nanometer-scale truncated nanocone hBN cavities, with deep subdiffractional dimensions, support three-dimensionally confined optical modes in the mid-infrared. Because of optical selection rules, only a few of the many theoretically predicted modes have been observed experimentally via far-field reflection and scattering-type scanning near-field optical microscopy (s-SNOM). The photothermal induced resonance (PTIR) technique probes optical and vibrational resonances overcoming weak far-field emission by leveraging an atomic force microscope (AFM) probe to transduce local sample expansion caused by light absorption. Here we show that PTIR enables the direct observation of previously unobserved, dark hyperbolic modes of hBN nanostructures. Leveraging these optical modes and their wide range of angular and radial momenta could provide a new degree of control over the electromagnetic near-field concentration, polarization in nanophotonic applications.

Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study.

Benznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease.

Assessing fabrication tolerances for a multilevel 2D binary grating for 3D multifocus microscopy.

We perform a comprehensive theoretical assessment of fabrication tolerances for a 2D eight-level binary phase grating that is the central element of a multi-focal plane 3D microscopy apparatus. The fabrication process encompasses a sequence of aligned lithography and etching steps with stringent requirements on layer-to-layer overlay, etch depth and etched sidewall slope, which we show are nonetheless achievable with state-of-the-art optical lithography and etching tools. We also perform broadband spectroscopic diffraction pattern measurements on a fabricated grating, and show how such measurements can be valuable in determining small fabrication errors in diffractive optical elements.

The Nanolithography Toolbox.

This article introduces in archival form the Nanolithography Toolbox, a platform-independent software package for scripted lithography pattern layout generation. The Center for Nanoscale Science and Technology (CNST) at the National Institute of Standards and Technology (NIST) developed the Nanolithography Toolbox to help users of the CNST NanoFab design devices with complex curves and aggressive critical dimensions. Using parameterized shapes as building blocks, the Nanolithography Toolbox allows users to rapidly design and layout nanoscale devices of arbitrary complexity through scripting and programming. The Toolbox offers many parameterized shapes, including structure libraries for micro- and nanoelectromechanical systems (MEMS and NEMS) and nanophotonic devices. Furthermore, the Toolbox allows users to precisely define the number of vertices for each shape or create vectorized shapes using Bezier curves. Parameterized control allows users to design smooth curves with complex shapes. The Toolbox is applicable to a broad range of design tasks in the fabrication of microscale and nanoscale devices.

Rapid and sensitive ultra-high-pressure liquid chromatography method for quantification of antichagasic benznidazole in plasma: application in a preclinical pharmacokinetic study.

Benznidazole (BNZ) and nifurtimox are the only drugs available for treating Chagas disease. In this work, we validated a bioanalytical method for the quantification of BNZ in plasma aimed at improving sensitivity and time of analysis compared with the assays already published. Furthermore, we demonstrated the application of the method in a preclinical pharmacokinetic study after administration of a single oral dose of BNZ in Wistar rats. A Waters® Acquity UHPLC system equipped with a UV-vis detector was employed. The method was established using an Acquity® UHPLC HSS SB C18 protected by an Acquity® UHPLC HSS SB C18 VanGuard guard column and detection at 324 nm. The mobile phase consisted of ultrapure water-acetonitrile (65:35), and elution was isocratic. The mobile phase flow rate was 0.55 mL/min, the volume of injection was 1 µL, and the run time was just 2 min. The samples were kept at 25°C until injection and the column at 45°C for the chromatographic separation. The sample preparation was performed by a rapid protein precipitation with acetonitrile. The linear concentration range was 0.15-20 µg/mL. The pharmacokinetic parameters of BNZ in rats were determined and the method was considered sensitive, fast and suitable for application in pharmacokinetic studies.

Traceable localization enables accurate integration of quantum emitters and photonic structures with high yield.

In a popular integration process for quantum information technologies, localization microscopy of quantum emitters guides lithographic placement of photonic structures. However, a complex coupling of microscopy and lithography errors degrades registration accuracy, severely limiting device performance and process yield. We introduce a methodology to solve this widespread but poorly understood problem. A new foundation of traceable localization enables rapid characterization of lithographic standards and comprehensive calibration of cryogenic microscopes, revealing and correcting latent systematic effects. Of particular concern, we discover that scale factor deviation and complex optical distortion couple to dominate registration errors. These novel results parameterize a process model for integrating quantum dots and bullseye resonators, predicting higher yield by orders of magnitude, depending on the Purcell factor threshold as a quantum performance metric. Our foundational methodology is a key enabler of the lab-to-fab transition of quantum information technologies and has broader implications to cryogenic and correlative microscopy.

Tramadol/Diclofenac Fixed-Dose Combination for Acute Pain Management: Bioavailability Assessment of a Generic Product.

The multimodal analgesia strategy for acute pain involves using 2 or more analgesic medications with distinct mechanisms of action. This study assessed the bioavailability and tolerability of 2 tramadol hydrochloride (50 mg)/diclofenac sodium (50 mg) fixed-dose combination formulations under fed conditions to attend the Brazilian regulatory requirements for generic product registration. An open-label, randomized, single-dose, 2-period, 2-way crossover trial was conducted, including healthy subjects of both sexes. Subjects received a single dose of either the test or reference formulation of tramadol/diclofenac fixed-dose combination tablets with a 7-day washout period. Blood samples were collected up to 36 hours after dosing for tramadol and 12 hours for diclofenac and quantified using a validated liquid chromatography-tandem mass spectrometry method. Of 56 subjects enrolled, 53 completed the study. The 90% confidence intervals for maximum plasma concentration and area under the concentration-time curve from time 0 to the last quantifiable concentration were within acceptable bioequivalence limits of 80%-125%. Considering the results presented in this study, the test formulation is bioequivalent to the reference formulation and could be interchangeable in medical practice.

A chip-scale, telecommunications-band frequency conversion interface for quantum emitters.

We describe a chip-scale, telecommunications-band frequency conversion interface designed for low-noise operation at wavelengths desirable for common single photon emitters. Four-wave-mixing Bragg scattering in silicon nitride waveguides is used to demonstrate frequency upconversion and downconversion between the 980 nm and 1550 nm wavelength regions, with signal-to-background levels > 10 and conversion efficiency of ≈ -60 dB at low continuous wave input pump powers (< 50 mW). Finite element simulations and the split-step Fourier method indicate that increased input powers of ≈ 10 W (produced by amplified nanosecond pulses, for example) will result in a conversion efficiency > 25 % in existing geometries. Finally, we present waveguide designs that can be used to connect shorter wavelength (637 nm to 852 nm) quantum emitters with 1550 nm.

Electromagnetically induced transparency and wideband wavelength conversion in silicon nitride microdisk optomechanical resonators.

We demonstrate optomechanically mediated electromagnetically induced transparency and wavelength conversion in silicon nitride (Si3N4) microdisk resonators. Fabricated devices support whispering gallery optical modes with a quality factor (Q) of 10(6), and radial breathing mechanical modes with a Q=10(4) and a resonance frequency of 625 MHz, so that the system is in the resolved sideband regime. Placing a strong optical control field on the red (blue) detuned sideband of the optical mode produces coherent interference with a resonant probe beam, inducing a transparency (absorption) window for the probe. This is observed for multiple optical modes of the device, all of which couple to the same mechanical mode, and which can be widely separated in wavelength due to the large band gap of Si3N4. These properties are exploited to demonstrate frequency up-conversion and down-conversion of optical signals between the 1300 and 980 nm bands with a frequency span of 69.4 THz.

Multi-mode microcavity frequency engineering through a shifted grating in a photonic crystal ring.

Frequency engineering of whispering-gallery resonances is essential in microcavity nonlinear optics. The key is to control the frequencies of the cavity modes involved in the underlying nonlinear optical process to satisfy its energy conservation criterion. Compared to the conventional method that tailors dispersion by cross-sectional geometry, thereby impacting all cavity mode frequencies, grating-assisted microring cavities, often termed as photonic crystal microrings, provide more enabling capabilities through mode-selective frequency control. For example, a simple single period grating added to a microring has been used for single frequency engineering in Kerr optical parametric oscillation (OPO) and frequency combs. Recently, this approach has been extended to multi-frequency engineering by using multi-period grating functions, but at the cost of increasingly complex grating profiles that require challenging fabrication. Here, we demonstrate a simple approach, which we term as shifted grating multiple mode splitting (SGMMS), where spatial displacement of a single period grating imprinted on the inner boundary of the microring creates a rotational asymmetry that frequency splits multiple adjacent cavity modes. This approach is easy to implement and presents no additional fabrication challenges compared to an unshifted grating, and yet is very powerful in providing multi-frequency engineering functionality for nonlinear optics. We showcase an example where SGMMS enables OPO across a wide range of pump wavelengths in a normal-dispersion device that otherwise would not support OPO.