An optical-frequency synthesizer using integrated photonics.

Optical-frequency synthesizers, which generate frequency-stable light from a single microwave-frequency reference, are revolutionizing ultrafast science and metrology, but their size, power requirement and cost need to be reduced if they are to be more widely used. Integrated-photonics microchips can be used in high-coherence applications, such as data transmission 1 , highly optimized physical sensors 2 and harnessing quantum states 3 , to lower cost and increase efficiency and portability. Here we describe a method for synthesizing the absolute frequency of a lightwave signal, using integrated photonics to create a phase-coherent microwave-to-optical link. We use a heterogeneously integrated III-V/silicon tunable laser, which is guided by nonlinear frequency combs fabricated on separate silicon chips and pumped by off-chip lasers. The laser frequency output of our optical-frequency synthesizer can be programmed by a microwave clock across 4 terahertz near 1,550 nanometres (the telecommunications C-band) with 1 hertz resolution. Our measurements verify that the output of the synthesizer is exceptionally stable across this region (synthesis error of 7.7 × 10-15 or below). Any application of an optical-frequency source could benefit from the high-precision optical synthesis presented here. Leveraging high-volume semiconductor processing built around advanced materials could allow such low-cost, low-power and compact integrated-photonics devices to be widely used.

Sub-picoliter Traceability of Microdroplet Gravimetry and Microscopy.

Gravimetry typically lacks the resolution to measure single microdroplets, whereas microscopy is often inaccurate beyond the resolution limit. To address these issues, we advance and integrate these complementary methods, introducing simultaneous measurements of the same microdroplets, comprehensive calibrations that are independently traceable to the International System of Units (SI), and Monte-Carlo evaluations of volumetric uncertainty. We achieve sub-picoliter agreement of measurements of microdroplets in flight with volumes of approximately 70 pL, with ensemble gravimetry and optical microscopy both yielding 95% coverage intervals of ±0.6 pL, or relative uncertainties of ±0.9%, and root-mean-square deviations of mean values between the two methods of 0.2 pL or 0.3%. These uncertainties match previous gravimetry results and improve upon previous microscopy results by an order of magnitude. Gravimetry precision depends on the continuity of droplet formation, whereas microscopy accuracy requires that optical diffraction from an edge reference matches that from a microdroplet. Applying our microscopy method, we jet and image water microdroplets suspending fluorescent nanoplastics, count nanoplastic particles after deposition and evaporation, and transfer volumetric traceability to the number concentrations of single microdroplets. We expect that our methods will impact diverse fields involving dimensional metrology and volumetric analysis of microdroplets, including inkjet microfabrication, disease transmission, and industrial sprays.

Unmasking the Resolution-Throughput Tradespace of Focused-Ion-Beam Machining.

Focused-ion-beam machining is a powerful process to fabricate complex nanostructures, often through a sacrificial mask that enables milling beyond the resolution limit of the ion beam. However, current understanding of this super-resolution effect is empirical in the spatial domain and nonexistent in the temporal domain. This article reports the primary study of this fundamental tradespace of resolution and throughput. Chromia functions well as a masking material due to its smooth, uniform, and amorphous structure. An efficient method of in-line metrology enables characterization of ion-beam focus by scanning electron microscopy. Fabrication and characterization of complex test structures through chromia and into silica probe the response of the bilayer to a focused beam of gallium cations, demonstrating super-resolution factors of up to 6 ± 2 and improvements to volume throughput of at least factors of 42 ± 2, with uncertainties denoting 95% coverage intervals. Tractable theory models the essential aspects of the super-resolution effect for various nanostructures. Application of the new tradespace increases the volume throughput of machining Fresnel lenses by a factor of 75, enabling the introduction of projection standards for optical microscopy. These results enable paradigm shifts of sacrificial masking from empirical to engineering design and from prototyping to manufacturing.

So, You Want to Have a Nanofab? Shared-Use Nanofabrication and Characterization Facilities: Cost-of-Ownership, Toolset, Utilization, and Lessons Learned.

Nanofabrication/characterization facilities enable research and development activities across a host of science and engineering disciplines. The collection of tools and supporting infrastructure necessary to construct, image, and measure micro- and nanoscale materials, devices, and systems is complex and expensive to establish, and it is costly to maintain and optimize. As a result, these facilities are typically operated in a shared-use mode. We discuss the key factors that must be considered to successfully create and sustain such facilities. These include the need for long-term vision and institutional commitment, and the hands-on involvement of managers in facility operations. We consider startup, operating, and recapitalization costs, together with algorithms for cost recovery and tool-time allocation. The acquisition of detailed and comprehensive project and tool-utilization data is essential for understanding and optimizing facility operations. Only such a data-driven decision-making approach can maximize facility impact on institutional goals. We illustrate these concepts using the National Institute of Standards and Technology (NIST) NanoFab as our test case, but the methodologies and resources presented here should be useful to all those faced with this challenging task.

Interlocking Kerr-microresonator frequency combs for microwave to optical synthesis.

We report accurate phase stabilization of an interlocking pair of Kerr-microresonator frequency combs. The two combs, one based on silicon nitride and one on silica, feature nearly harmonic repetition frequencies and can be generated with one laser. The silicon-nitride comb supports an ultrafast-laser regime with three-optical-cycle, 1-picosecond-period soliton pulses and a total dispersive-wave-enhanced bandwidth of 170 THz, while providing a stable phase-link between optical and microwave frequencies. We demonstrate nanofabrication control of the silicon-nitride comb's carrier-envelope offset frequency and spectral profile. The phase-locked combs coherently reproduce their clock with a fractional precision of <6×10-13/τ, a behavior we verified through 2 h of measurement to reach <3×10-16. Our work establishes Kerr combs as a viable technology for applications like optical-atomic timekeeping and optical synchronization.

Nondegenerate Parametric Resonance in Large Ensembles of Coupled Micromechanical Cantilevers with Varying Natural Frequencies.

We investigate the collective dynamics and nondegenerate parametric resonance (NPR) of coplanar, interdigitated arrays of microcantilevers distinguished by their cantilevers having linearly expanding lengths and thus varying natural frequencies. Within a certain excitation frequency range, the resonators begin oscillating via NPR across the entire array consisting of 200 single-crystal silicon cantilevers. Tunable coupling generated from fringing electrostatic fields provides a mechanism to vary the scope of the NPR. Our experimental results are supported by a reduced-order model that reproduces the leading features of our data including the NPR band. The potential for tailoring the coupled response of suspended mechanical structures using NPR presents new possibilities in mass, force, and energy sensing applications, energy harvesting devices, and optomechanical systems.

Flow sensor based on the snap-through detection of a curved micromechanical beam.

We report on a flow velocity measurement technique based on snap-through detection of an electrostatically actuated, bistable micromechanical beam. We show that induced elecro-thermal Joule heating and the convective air cooling change the beam curvature and consequently the critical snap-through voltage (VST ). Using single crystal silicon beams, we demonstrate the snap-through voltage to flow velocity sensitivity of dV ST/du ≈ 0.13 V s m -1 with a power consumption of ≈ 360 µ W. Our experimental results were in accord with the reduced order, coupled, thermo-electro-mechanical model prediction. We anticipate that electrostatically induced snap-through in curved, micromechanical beams will open new directions for the design and implementation of downscaled flow sensors for autonomous applications and environmental sensors.

Actuation of higher harmonics in large arrays of micromechanical cantilevers for expanded resonant peak separation.

A large array of elastically coupled micro cantilevers of variable length is studied experimentally and numerically. Full-scale finite element modal analysis is implemented to determine the spectral behavior of the array and to extract a global coupling matrix. A compact reduced order model is used for numerical investigation of the array's dynamic response. Our model results show that at a given excitation frequency within a propagation band, only a finite number of beams respond. Spectral characteristics of individual cantilevers, inertially excited by an external piezoelectric actuator, were measured in vacuum using laser interferometry. The theoretical and experimental results collectively show that the resonant peaks corresponding to individual beams are clearly separated when operating in vacuum at the 3rd harmonic. Distinct resonant peak separation, coupled with the spatially-confined modal response, make higher harmonic operation of tailored, variable-length cantilever arrays well suited for a variety of resonant based sensing applications.

Displacement Sensing Based on Resonant Frequency Monitoring of Electrostatically Actuated Curved Micro Beams.

The ability to control nonlinear interactions of suspended mechanical structures offers a unique opportunity to engineer rich dynamical behavior that extends the dynamic range and ultimate device sensitivity. We demonstrate a displacement sensing technique based on resonant frequency monitoring of curved, doubly clamped, bistable micromechanical beams interacting with a movable electrode. In this configuration, the electrode displacement influences the nonlinear electrostatic interactions, effective stiffness and frequency of the curved beam. Increased sensitivity is made possible by dynamically operating the beam near the snap-through bistability onset. Various in-plane device architectures were fabricated from single crystal silicon and measured under ambient conditions using laser Doppler vibrometry. In agreement with the reduced order Galerkin-based model predictions, our experimental results show a significant resonant frequency reduction near critical snap-through, followed by a frequency increase within the post-buckling configuration. Interactions with a stationary electrode yield a voltage sensitivity up to ≈ 560 Hz/V and results with a movable electrode allow motion sensitivity up to ≈ 1.5 Hz/nm. Our theoretical and experimental results collectively reveal the potential of displacement sensing using nonlinear interactions of geometrically curved beams near instabilities, with possible applications ranging from highly sensitive resonant inertial detectors to complex optomechanical platforms providing an interface between the classical and quantum domains.

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.

Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium.

The ideal agent for prevention and treatment of uterine abnormal contractility has not been found. The polyphenol resveratrol possesses a wide spectrum of pharmacologic properties, but its influence on the contractility of human myometrium is not defined. The present study evaluated the effect of resveratrol on the oxytocin-induced contractions of human term pregnant myometrium in vitro and the contribution of different K(+) channels to resveratrol action. Resveratrol induced a concentration-dependent relaxation of myometrium contractions (pD2 value and maximal responses were 4.52 and 82.25%, respectively). Glibenclamide, a selective blocker of ATP-sensitive (KATP), iberiotoxin, a selective blockers of big-calcium sensitive (BK(Ca)) and 4-aminopiridine, a non-selective blocker of voltage-sensitive (Kv) channels induced a significant shift to the right of the concentration-response curves of resveratrol. Inhibition achieved by 0.1 mM resveratrol was insensitive to all K(+) channel blockers. A K(+) channel opener, pinacidil, inhibited oxytocin-induced contractions of pregnant myometrium with comparable potency and efficacy to resveratrol (pD2 values and maximal relaxation were 4.52 and 83.67%, respectively). Based on K(+) channel opener/blocker affinities, it appears that the inhibitory response of resveratrol involves different myometrial K(+) channels. When applied in high concentrations, resveratrol has an additional K(+)-channel-independent mechanism(s) of action. Furthermore, immunohistochemistry staining and western blot analyses detected the presence and distribution of KATP, BK(Ca) and Kv channel proteins in pregnant myometrium.

Dynamics of impurity attraction and repulsion of an intrinsic localized mode in a driven 1-D cantilever array.

Both low frequency and high frequency impurity modes have been produced in a SiN micromechanical cantilever array by illumination with either an infrared or visible laser. When such laser-induced impurities are placed near a driven intrinsic localized mode (ILM), it is either repelled or attracted. By measuring the linear response spectrum for these two cases, it was found that vibrational hopping of the ILM takes place when the natural frequency of the ILM and an intrinsic even symmetry linear local mode are symmetrically located about the driven ILM frequency so that parametric excitation of these two linear modes is enhanced, amplifying the lateral motion of the ILM. Numerical simulations are consistent with these signature findings. It is also demonstrated that the correct sign of the observed interaction can be found with a harmonic lattice-impurity model but the magnitude of the effect is enhanced in a nonlinear lattice.

Rapid Prototyping of Nanofluidic Slits in a Silicone Bilayer.

This article reports a process for rapidly prototyping nanofluidic devices, particularly those comprising slits with microscale widths and nanoscale depths, in silicone. This process consists of designing a nanofluidic device, fabricating a photomask, fabricating a device mold in epoxy photoresist, molding a device in silicone, cutting and punching a molded silicone device, bonding a silicone device to a glass substrate, and filling the device with aqueous solution. By using a bilayer of hard and soft silicone, we have formed and filled nanofluidic slits with depths of less than 400 nm and aspect ratios of width to depth exceeding 250 without collapse of the slits. An important attribute of this article is that the description of this rapid prototyping process is very comprehensive, presenting context and details which are highly relevant to the rational implementation and reliable repetition of the process. Moreover, this process makes use of equipment commonly found in nanofabrication facilities and research laboratories, facilitating the broad adaptation and application of the process. Therefore, while this article specifically informs users of the Center for Nanoscale Science and Technology (CNST) at the National Institute of Standards and Technology (NIST), we anticipate that this information will be generally useful for the nanofabrication and nanofluidics research communities at large, and particularly useful for neophyte nanofabricators and nanofluidicists.

Graphene metallization of high-stress silicon nitride resonators for electrical integration.

High stress stoichiometric silicon nitride resonators, whose quality factors exceed one million, have shown promise for applications in sensing, signal processing, and optomechanics. Yet, electrical integration of the insulating silicon nitride resonators has been challenging, as depositing even a thin layer of metal degrades the quality factor significantly. In this work, we show that graphene used as a conductive coating for Si3N4 membranes reduces the quality factor by less than 30% on average, which is minimal when compared to the effect of conventional metallization layers such as chromium or aluminum. The electrical integration of Si3N4-Graphene (SiNG) heterostructure resonators is demonstrated with electrical readout and electrostatic tuning of the frequency by up to 0.3% per volt. These studies demonstrate the feasibility of hybrid graphene/nitride mechanical resonators in which the electrical properties of graphene are combined with the superior mechanical performance of silicon nitride.

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.

Photothermal self-oscillation and laser cooling of graphene optomechanical systems.

By virtue of their low mass and stiffness, atomically thin mechanical resonators are attractive candidates for use in optomechanics. Here, we demonstrate photothermal back-action in a graphene mechanical resonator comprising one end of a Fabry-Perot cavity. As a demonstration of the utility of this effect, we show that a continuous wave laser can be used to cool a graphene vibrational mode or to power a graphene-based tunable frequency oscillator. Owing to graphene's high thermal conductivity and optical absorption, photothermal optomechanics is efficient in graphene and could ultimately enable laser cooling to the quantum ground state or applications such as photonic signal processing.

High, size-dependent quality factor in an array of graphene mechanical resonators.

Graphene's unparalleled strength, stiffness, and low mass per unit area make it an ideal material for nanomechanical resonators, but its relatively low quality factor is an important drawback that has been difficult to overcome. Here, we use a simple procedure to fabricate circular mechanical resonators of various diameters from graphene grown by chemical vapor deposition. In addition to highly reproducible resonance frequencies and mode shapes, we observe a striking improvement of the membrane quality factor with increasing size. At room temperature, we observe quality factors as high as 2400 ± 300 for a resonator 22.5 µm in diameter, about an order of magnitude greater than previously observed quality factors for monolayer graphene. Measurements of quality factor as a function of modal frequency reveal little dependence of Q on frequency. These measurements shed light on the mechanisms behind dissipation in monolayer graphene resonators and demonstrate that the quality factor of graphene resonators relative to their thickness is among the highest of any mechanical resonator demonstrated to date.

Oxidative stress and inflammation parameters-novel biomarkers for idiopathic pulmonary fibrosis.

OBJECTIVE: The pathophysiological mechanisms of idiopathic pulmonary fibrosis (IPF) are not well elucidated. It is assumed that oxidative stress and inflammation are the key underlying culprits for its onset and progression. To gain deeper insight into these processes, we have evaluated several oxidative stress parameters, inflammation markers [i.e., high sensitivity C-reactive protein (hsCRP), serum amyloid A1 (SAA1)], soluble programmed cell death-ligand 1 (sPD-L1), and 25-hydroxyvitamin D [25(OH)D] in IPF patients. PATIENTS AND METHODS: Biochemistry analyses were done in 30 consecutive IPF patients and 30 age and gender-matched healthy control group (CG). RESULTS: IPF patients had significantly higher advanced oxidation protein products (p<0.001), pro-oxidant-antioxidant balance (p=0.010), total oxidative status (p<0.001), and ischemia modified albumin (p<0.001) compared to CG. Lower total antioxidant status and total sulfhydryl groups (tSGH) and significantly higher sPD-L1, hsCRP (p<0.001 for all), SAA1 proteins (p=0.014) and [25(OH)D] severe deficiency [11.0 (9.6-15.1) nmol/L] in IPF patients compared to CG were observed. Paraoxonase 1 activity and hsCRP level were lower, while tSHG and sPD-L1 were higher in IPF patients with more severe disease (i.e., II+III stage compared to I stage, p<0.05 for all). CONCLUSIONS: IPF patients are in a state of profound oxidative stress compared to healthy people. The inflammatory component of the disease was confirmed by higher hsCRP and SAA1, but lower [25(OH)D] in IPF than in healthy people. Also, higher levels of sPD-L1 in patients with IPF compared to healthy individuals suggest that sPD-L1 may have a significant role in immune response in IPF.

A randomized, double-blind, placebo-controlled study evaluating the efficacy of propolis and N-acetylcysteine in exacerbations of chronic obstructive pulmonary disease.

OBJECTIVE: Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) accelerate the progressive impairment of lung function and general health. Together with maintenance therapy for chronic obstructive pulmonary disease (COPD), N-acetylcysteine (NAC) and natural propolis have demonstrated pharmacological properties that address crucial pathophysiological processes underlying COPD and may prevent AECOPDs. This study aims at responding to dose-dependent efficacy and safety concerns regarding a propolis-NAC combination for the reduction of COPD exacerbation rates. PATIENTS AND METHODS: This was a single-center, randomized, double-blind, phase IV trial with three treatment arms: Placebo and two active substance groups, one (AS-600) received 600 mg of NAC + 80 mg of propolis while the other (AS-1,200) received 1,200 mg of NAC + 160 mg of propolis. Following an AECOPD, frequent-exacerbation phenotype patients (n=46) were assigned a once-daily three-month therapy with the study drug and one year follow-up. The primary endpoint was the COPD exacerbation incidence rate during the follow-up period as a measure of dose-dependent efficacy of NAC-propolis combination compared to placebo. RESULTS: There was a statistically significant difference in the AECOPD incidence rate: 52.6% in patients that received placebo, 15.4% that received AS-600 and only 7.1% that received AS-1,200 (Fisher's exact test, p = 0.013). Compared to placebo, AECOPD frequency was significantly lower only in AS-1,200 (p=0.009). Compared to placebo, the relative risk for exacerbation was 0.29 in AS-600 and 0.13 in AS-1,200. No adverse events related to the treatment were reported. CONCLUSIONS: Oral combination of natural propolis with NAC confirmed formulation efficiency with a favorable safety profile. Our results need to be confirmed by larger clinical trials.

Experimental observation of the bifurcation dynamics of an intrinsic localized mode in a driven 1D nonlinear lattice.

Linear response spectra of a driven intrinsic localized mode in a micromechanical array are measured as it approaches two fundamentally different kinds of bifurcation points. A linear phase mode associated with this autoresonant state softens in frequency and its amplitude grows as the upper frequency bifurcation point is approached, similar to the soft-mode kinetic transition for a single driven Duffing resonator. A lower frequency bifurcation point occurs when the four-wave-mixing partner of this same phase mode intercepts the top of the extended wave branch, initiating a second kinetic transition process.