Measurement accuracy in silicon photonic ring resonator thermometers: identifying and mitigating intrinsic impairments.

Silicon photonic ring resonator thermometers have been shown to provide temperature measurements with a 10 mK accuracy. In this work we identify and quantify the intrinsic on-chip impairments that may limit further improvement in temperature measurement accuracy. The impairments arise from optically induced changes in the waveguide effective index, and from back-reflections and scattering at defects and interfaces inside the ring cavity and along the path between light source and detector. These impairments are characterized for 220 × 500 nm Si waveguide rings by experimental measurement in a calibrated temperature bath and by phenomenological models of ring response. At different optical power levels both positive and negative light induced resonance shifts are observed. For a ring with L = 100 µm cavity length, the self-heating induced resonance red shift can alter the temperature reading by 200 mK at 1 mW incident power, while a small blue shift is observed below 100 µW. The effect of self-heating is shown to be effectively suppressed by choosing longer ring cavities. Scattering and back-reflections often produce split and distorted resonance line shapes. Although these distortions can vary with resonance order, they are almost completely invariant with temperature for a given resonance and do not lead to measurement errors in themselves. The effect of line shape distortions can largely be mitigated by tracking only selected resonance orders with negligible shape distortion, and by measuring the resonance minimum wavelength directly, rather than attempting to fit the entire resonance line shape. The results demonstrate the temperature error due to these impairments can be limited to below the 3 mK level through appropriate design choices and measurement procedures.

Optical wavefront phase-tilt measurement using Si-photonic waveguide grating couplers.

Silicon photonic wavefront phase-tilt sensors for wavefront monitoring using surface coupling grating arrays are demonstrated. The first design employs the intrinsic angle dependence of the grating coupling efficiency to determine local wavefront tilt, with a measured sensitivity of 7 dB/°. The second design connects four gratings in an interferometric waveguide circuit to determine incident wavefront phase variation across the sensor area. In this device, one fringe spacing corresponds to 2° wavefront tilt change. These sensor elements sample a wavefront incident on the chip surface without the use of bulk optic elements, fiber arrays, or imaging arrays. Both sensor elements are less than 60 µm across and are potential unit cell sensor elements for large arrays that monitor wavefront shape across an image or pupil plane in adaptive optics systems for free-space optical communications, astronomy, and beam pointing applications.

Vertically tapered waveguide spot size converters fabricated via a linewidth controlled grey tone lithography for InP-based photonic integrated circuits.

We report a novel and simple fabrication process to realize vertically tapered spot size converters (SSC) on InP photonic integrated circuits. The vertical tapering was achieved via a linewidth controlled local optical dose variation, leading to a grey tone photoresist profile. The fabricated SSCs are compact, polarization insensitive and demonstrate a very high mode conversion efficiency of 95%. Integrated SSCs improved the overall loss by 5 dB giving a coupling loss as low as 1.3 dB/facet, for a lensed fibre with a mode field diameter of 3.0 µm. A good agreement was found between the fibre-to-fibre optical loss measurements and those predicted from simulations.

High performance InAs/InP quantum dot 34.462-GHz C-band coherent comb laser module.

We have developed an InAs/InP quantum dot (QD) C-band coherent comb laser (CCL) module with actively stabilized absolute wavelength and power, and channel spacing of 34.462 GHz with ± 100 ppm accuracy. The total output power is up to 46 mW. The integrated average relative intensity noise (RIN) values of the lasing spectrum and a filtered single channel at 1540.19 nm were -165.6 dB/Hz and -130.3 dB/Hz respectively in the frequency range from 10 MHz to 10 GHz. The optical linewidth of the 45 filtered individual channels between 1531.77 nm to 1543.77 nm ranged from 850 kHz to 2.16 MHz. We have also analyzed the noise behaviors of each individual channel.

Tropospheric Emissions: Monitoring of Pollution (TEMPO).

TEMPO was selected in 2012 by NASA as the first Earth Venture Instrument, for launch between 2018 and 2021. It will measure atmospheric pollution for greater North America from space using ultraviolet and visible spectroscopy. TEMPO observes from Mexico City, Cuba, and the Bahamas to the Canadian oil sands, and from the Atlantic to the Pacific, hourly and at high spatial resolution (~2.1 km N/S×4.4 km E/W at 36.5°N, 100°W). TEMPO provides a tropospheric measurement suite that includes the key elements of tropospheric air pollution chemistry, as well as contributing to carbon cycle knowledge. Measurements are made hourly from geostationary (GEO) orbit, to capture the high variability present in the diurnal cycle of emissions and chemistry that are unobservable from current low-Earth orbit (LEO) satellites that measure once per day. The small product spatial footprint resolves pollution sources at sub-urban scale. Together, this temporal and spatial resolution improves emission inventories, monitors population exposure, and enables effective emission-control strategies. TEMPO takes advantage of a commercial GEO host spacecraft to provide a modest cost mission that measures the spectra required to retrieve ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), formaldehyde (H2CO), glyoxal (C2H2O2), bromine monoxide (BrO), IO (iodine monoxide),water vapor, aerosols, cloud parameters, ultraviolet radiation, and foliage properties. TEMPO thus measures the major elements, directly or by proxy, in the tropospheric O3 chemistry cycle. Multi-spectral observations provide sensitivity to O3 in the lowermost troposphere, substantially reducing uncertainty in air quality predictions. TEMPO quantifies and tracks the evolution of aerosol loading. It provides these near-real-time air quality products that will be made publicly available. TEMPO will launch at a prime time to be the North American component of the global geostationary constellation of pollution monitoring together with the European Sentinel-4 (S4) and Korean Geostationary Environment Monitoring Spectrometer (GEMS) instruments.

Transgenic mouse model of IgM+ lymphoproliferative disease mimicking Waldenström macroglobulinemia.

Waldenström macroglobulinemia (WM) is a low-grade incurable immunoglobulin M+ (IgM+) lymphoplasmacytic lymphoma for which a genetically engineered mouse model of de novo tumor development is lacking. On the basis of evidence that the pro-inflammatory cytokine, interleukin 6 (IL6), and the survival-enhancing oncoprotein, B cell leukemia 2 (BCL2), have critical roles in the natural history of WM, we hypothesized that the enforced expression of IL6 and BCL2 in mice unable to perform immunoglobulin class switch recombination may result in a lymphoproliferative disease that mimics WM. To evaluate this possibility, we generated compound transgenic BALB/c mice that harbored the human BCL2 and IL6 transgenes, EµSV-BCL2-22 and H2-Ld-hIL6, on the genetic background of activation-induced cytidine deaminase (AID) deficiency. We designated these mice BCL2+IL6+AID- and found that they developed-with full genetic penetrance (100% incidence) and suitably short latency (93 days median survival)-a severe IgM+ lymphoproliferative disorder that recapitulated important features of human WM. However, the BCL2+IL6+AID- model also exhibited shortcomings, such as low serum IgM levels and histopathological changes not seen in patients with WM, collectively indicating that further refinements of the model are required to achieve better correlations with disease characteristics of WM.

FOXM1 is a therapeutic target for high-risk multiple myeloma.

The transcription factor forkhead box M1 (FOXM1) is a validated oncoprotein in solid cancers, but its role in malignant plasma cell tumors such as multiple myeloma (MM) is unknown. We analyzed publicly available MM data sets and found that overexpression of FOXM1 prognosticates inferior outcome in a subset (~15%) of newly diagnosed cases, particularly patients with high-risk disease based on global gene expression changes. Follow-up studies using human myeloma cell lines (HMCLs) as the principal experimental model system demonstrated that enforced expression of FOXM1 increased growth, survival and clonogenicity of myeloma cells, whereas knockdown of FOXM1 abolished these features. In agreement with that, constitutive upregulation of FOXM1 promoted HMCL xenografts in laboratory mice, whereas inducible knockdown of FOXM1 led to growth inhibition. Expression of cyclin-dependent kinase 6 (CDK6) and NIMA-related kinase 2 (NEK2) was coregulated with FOXM1 in both HMCLs and myeloma patient samples, suggesting interaction of these three genes in a genetic network that may lend itself to targeting with small-drug inhibitors for new approaches to myeloma therapy and prevention. These results establish FOXM1 as high-risk myeloma gene and provide support for the design and testing of FOXM1-targeted therapies specifically for the FOXM1(High) subset of myeloma.

Structural parameters effect on the electrical and electroluminescence properties of silicon nanocrystals/SiO2 superlattices.

The effect of the oxide barrier thickness (tSiO2) reduction and the Si excess ([Si]exc) increase on the electrical and electroluminescence (EL) properties of Si-rich oxynitride (SRON)/SiO2 superlattices (SLs) is investigated. The active layers of the metal-oxide-semiconductor devices were fabricated by alternated deposition of SRON and SiO2 layers on top of a Si substrate. The precipitation of the Si excess and thus formation of Si nanocrystals (NCs) within the SRON layers was achieved after an annealing treatment at 1150 °C. A structural characterization revealed a high crystalline quality of the SLs for all devices, and the evaluated NC crystalline size is in agreement with a good deposition and annealing control. We found a dramatic conductivity enhancement when the Si content is increased or the SiO2 barrier thickness is decreased, due to a larger interaction of the carrier wavefunctions from adjacent layers. EL recombination dynamics were studied, revealing radiative recombination decay times of the order of tens of microseconds. Lower lifetimes were found at higher [Si]exc, attributed to exciton confinement delocalization, whereas intermediate barrier thicknesses present the slowest decay. The electrical-to-light conversion efficiency increases monotonously at thicker barriers and smaller Si contents. We ascribe these effects mainly to free carriers, which enhance carrier transport through the SLs while strongly quenching light emission. Finally, the combination of the different results led us to conclude that tSiO2 âˆ¼ 2 nm and [Si]exc from 12 to 15 at% are the ideal structure parameters for a balanced electro-optical response of Si NC-based SLs.

(18)F-FDG-PET/CT imaging in an IL-6- and MYC-driven mouse model of human multiple myeloma affords objective evaluation of plasma cell tumor progression and therapeutic response to the proteasome inhibitor ixazomib.

(18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are useful imaging modalities for evaluating tumor progression and treatment responses in genetically engineered mouse models of solid human cancers, but the potential of integrated FDG-PET/CT for assessing tumor development and new interventions in transgenic mouse models of human blood cancers such as multiple myeloma (MM) has not been demonstrated. Here we use BALB/c mice that contain the newly developed iMyc(ΔEµ) gene insertion and the widely expressed H2-L(d)-IL6 transgene to demonstrate that FDG-PET/CT affords an excellent research tool for assessing interleukin-6- and MYC-driven plasma cell tumor (PCT) development in a serial, reproducible and stage- and lesion-specific manner. We also show that FDG-PET/CT permits determination of objective drug responses in PCT-bearing mice treated with the investigational proteasome inhibitor ixazomib (MLN2238), the biologically active form of ixazomib citrate (MLN9708), that is currently in phase 3 clinical trials in MM. Overall survival of 5 of 6 ixazomib-treated mice doubled compared with mice left untreated. One outlier mouse presented with primary refractory disease. Our findings demonstrate the utility of FDG-PET/CT for preclinical MM research and suggest that this method will play an important role in the design and testing of new approaches to treat myeloma.

Photonic wire biosensor microarray chip and instrumentation with application to serotyping of Escherichia coli isolates.

A complete photonic wire molecular biosensor microarray chip architecture and supporting instrumentation is described. Chip layouts with 16 and 128 independent sensors have been fabricated and tested, where each sensor can provide an independent molecular binding curve. Each sensor is 50 µm in diameter, and consists of a millimeter long silicon photonic wire waveguide folded into a spiral ring resonator. An array of 128 sensors occupies a 2 × 2 mm2 area on a 6 × 9 mm2 chip. Microfluidic sample delivery channels are fabricated monolithically on the chip. The size and layout of the sensor array is fully compatible with commercial spotting tools designed to independently functionalize fluorescence based biochips. The sensor chips are interrogated using an instrument that delivers sample fluid to the chip and is capable of acquiring up to 128 optical sensor outputs simultaneously and in real time. Coupling light from the sensor chip is accomplished through arrays of sub-wavelength surface grating couplers, and the signals are collected by a fixed two-dimensional detector array. The chip and instrument are designed so that connection of the fluid delivery system and optical alignment are automated, and can be completed in a few seconds with no active user input. This microarray system is used to demonstrate a multiplexed assay for serotyping E. coli bacteria using serospecific polyclonal antibody probe molecules.

The feed-forward loop between YB-1 and MYC is essential for multiple myeloma cell survival.

Y-box binding protein 1 (YB-1) functions as a translational regulator and has been suggested to elevate MYC mRNA translation via an internal ribosome entry segment (IRES) point mutation in multiple myeloma (MM). We show that YB-1-mediated translation of MYC mRNA occurs independently of the reported IRES mutation, as 87 MM patients (n=88) and all tested human MM cell lines (HMCLs) were negative for the mutation. We show for the first time that positive MYC staining predicts YB-1 co-expression in malignant plasma cells and YB-1/MYC co-expression increases from 30% in medullary to 70% in extramedullary MM. YB-1 knockdown in HMCLs reduced both MYC protein levels and MYC mRNA in the polysomal fraction, providing a mechanism by which YB-1 controls MYC translation. MYC transcription of YB-1 is demonstrated in HMCLs as MYC knockdown resulted in reduced YB-1 protein and mRNA levels. Furthermore, MYC activation in non-malignant mouse embryonic fibroblasts (MEFs) increased YB-1 mRNA, clearly indicating that MYC drives YB-1 transcription. Importantly, perturbation of the MYC/YB-1 oncogenic circuit leads to apoptosis in HMCLs. Here, we demonstrate that these two proteins co-regulate each other via combined transcriptional/translational activity establishing their pivotal role in MM cell survival. We therefore suggest that targeting the YB-1/mRNA interaction provides a new strategy for MM drug development.

Highly tolerant tunable waveguide polarization rotator scheme.

Integrated polarization rotators are known to exhibit stringent fabrication tolerances, which severely handicap their practical application. Here we present a general polarization rotator scheme that enables both the compensation of fabrication errors and wavelength tunability. The scheme is described analytically, and a condition for perfect polarization conversion is established. Simulations of a silicon-on-insulator polarization rotator show polarization extinction ratios in excess of 40 dB even in the presence of large fabrication errors that in a conventional rotator configuration degrade the extinction ratio to below 5 dB. Additionally, wavelength tuning over ±30 nm is shown.

Colorless directional coupler with dispersion engineered sub-wavelength structure.

Directional couplers are extensively used devices in integrated optics, but suffer from limited operational wavelength range. Here we use, for the first time, the dispersive properties of sub-wavelength gratings to achieve a fivefold enhancement in the operation bandwidth of a silicon-on-insulator directional coupler. This approach does not compromise the size or the phase response of the device. The sub-wavelength grating based directional coupler we propose covers a 100 nm bandwidth with an imbalance of ≤ 0.6 dB between its outputs, as supported by full 3D FDTD simulations.

All-optical wavelength conversion for 10 Gb/s DPSK signals in a silicon ring resonator.

We demonstrate all-optical wavelength conversion at 10 Gb/s for differential phase-shift keyed (DPSK) data signals in the C-band, based on four-wave mixing (FWM) in a silicon ring resonator. Error-free operation with a system penalty of ~4.1 dB at 10⁻9 BER is achieved.