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Newly synthesized secretory proteins are released into the lumen of the endoplasmic reticulum (ER). The secretory proteins are surrounded by coat protein complex II (COPII) vesicles, and transported from the ER and reach their destinations through the Golgi apparatus. Sec12p is a guanine nucleotide exchange factor for Sar1p, which initiates COPII vesicle budding from the ER. The activation of Sar1p by Sec12p and the subsequent COPII coat assembly have been well characterized, but the events that take place upstream of Sec12p remain unclear. In this study, we isolated the novel extragenic suppressor of sec12-4, PIN4/MDT1, a cell cycle checkpoint target. A yeast two-hybrid screening was used to identify Pin4/Mdt1p as a binding partner of the casein kinase I isoform Hrr25p, which we have previously identified as a modulator of Sec12p function. Deletion of PIN4 suppressed both defects of temperature-sensitive growth and the partial protein transport observed in sec12-4 mutants. The results of this study suggest that Pin4p provides novel aspects of Sec12p modulations., (© 2020 S. Karger AG, Basel.)

Current materials used for in vitro 3D cell culture are often limited by their poor similarity to human tissue, batch-to-batch variability and complexity of composition and manufacture. Here, we present a "blank slate" culture environment based on a self-assembling peptide gel free from matrix motifs. The gel can be customised by incorporating matrix components selected to match the target tissue, with independent control of mechanical properties. Therefore the matrix components are restricted to those specifically added, or those synthesised by encapsulated cells. The flexible 3D culture platform provides full control over biochemical and physical properties, allowing the impact of biochemical composition and tissue mechanics to be separately evaluated in vitro. Here, we demonstrate that the peptide gels support the growth of a range of cells including human induced pluripotent stem cells and human cancer cell lines. Furthermore, we present proof-of-concept that the peptide gels can be used to build disease-relevant models. Controlling the peptide gelator concentration allows peptide gel stiffness to be matched to normal breast (<1 kPa) or breast tumour tissue (>1 kPa), with higher stiffness favouring the viability of breast cancer cells over normal breast cells. In parallel, the peptide gels may be modified with matrix components relevant to human breast, such as collagen I and hyaluronan. The choice and concentration of these additions affect the size, shape and organisation of breast epithelial cell structures formed in co-culture with fibroblasts. This system therefore provides a means of unravelling the individual influences of matrix, mechanical properties and cell-cell interactions in cancer and other diseases., (Copyright © 2019. Published by Elsevier B.V.)

Here we report on the broadband detection of nitrous oxide (N 2 O) and methane (CH 4 ) mixtures in dry nitrogen by using a quartz-enhanced photoacoustic (QEPAS) sensor exploiting an array of 32 distributed-feedback quantum cascade lasers, within a spectral emission range of 1190-1340 cm -1 as the excitation source. Methane detection down to a minimum detection limit of 200 ppb at 10 s lock-in integration time was achieved. The sensor demonstrated a linear response in the range of 200-1000 ppm. Three different mixtures of N 2 O and CH 4 in nitrogen at atmospheric pressure have been analyzed. The capability of the developed QEPAS sensor to selectively determine the N 2 O and CH 4 concentrations was demonstrated, in spite of significant overlap in their respective absorption spectra in the investigated spectral range., (© 2020 The Authors.)

In this paper we report methane gas photonic sensors exploiting the principle of absorption-induced redirection of light propagation in coupled resonant cavities. In particular, an example of implemented architecture consists of a Fabry-Pérot (FP) resonator coupled to a fibre ring resonator, operating in the near IR. By changing the concentration of the methane gas in the FP region, the absorption coefficient of the FP changes. In turn, the variation of the methane gas concentration allows the redirection of the light propagation in the fibre ring resonator. Then, the methane gas concentration can be evaluated by analysing the ratio between the powers of two resonant modes, counter-propagating in the fibre ring resonator. In this way, a self-referenced read-out scheme, immune to the power fluctuations of the source, has been conceived. Moreover, a sensitivity of 0.37 ± 0.04 [dB/%], defined as the ratio between resonant modes at different outputs, in a range of methane concentration included between the 0% and 5%, has been achieved. These results allow a detection limit below the lower explosive limit (LEL) to be reached with a cost-effective sensor system.

Superlattices of epitaxially connected nanocrystals (NCs) are model systems to study electronic and optical properties of NC arrays. Using elemental analysis and structural analysis by in situ X-ray fluorescence and grazing-incidence small-angle scattering, respectively, we show that epitaxial superlattices of PbSe NCs keep their structural integrity up to temperatures of 300 °C; an ideal starting point to assess the effect of gentle thermal annealing on the superlattice properties. We find that annealing such superlattices between 75 and 150 °C induces a marked red shift of the NC band-edge transition. In fact, the post -annealing band-edge reflects theoretical predictions on the impact of charge carrier delocalization in these epitaxial superlattices. In addition, we observe a pronounced enhancement of the charge carrier mobility and a reduction of the hopping activation energy after mild annealing. While the superstructure remains intact at these temperatures, structural defect studies through X-ray diffraction indicate that annealing markedly decreases the density of point defects and edge dislocations. This indicates that the connections between NCs in as-synthesized superlattices still form a major source of grain boundaries and defects, which prevent carrier delocalization over multiple NCs and hamper NC-to-NC transport. Overcoming the limitations imposed by interfacial defects is therefore an essential next step in the development of high-quality optoelectronic devices based on NC solids.

In recent years, hot injection synthesis has emerged as a promising route for the production of nanostructured transition metal dichalcogenides, in large due to its better control over the crystallinity and monodispersity compared to other solution based methods. Understanding the photophysics of excitons in the thus obtained colloidal nanosheets is of great importance to explore their potential for applications in optoelectronics. Here, we study the carrier dynamics in these few-layer colloidal WS 2 nanosheets by use of broadband transient absorption spectroscopy. The dynamics of both the bleach, linewidth broadening and energy shift across the entire visible and near-infrared spectrum, allows us to identify subpicosecond electron trapping as the main carrier loss channel. A more quantitative analysis shows that the intrinsic properties of colloidally synthesized nanosheets are on par with other synthesis methods, paving the way for this method to produce high quality nanosheets.

The development of a dual-gas quartz-enhanced photoacoustic (QEPAS) sensor capable of simultaneous detection of water vapor and alternatively methane or nitrous oxide is reported. A diode laser and a quantum cascade laser (QCL) excited independently and simultaneously both the fundamental and the first overtone flexural mode of the quartz tuning fork (QTF), respectively. The diode laser targeted a water absorption line located at 7181.16 cm -1 (1.392 μm), while the QCL emission wavelength is centered at 7.71 μm and was tuned to target two strong absorption lines of methane and nitrous oxide, located at 1297.47 and 1297.05 cm -1 , respectively. Two sets of microresonator tubes were positioned, respectively, at the antinode points of the fundamental and the first overtone flexural modes of the QTF to enhance the QEPAS signal-to-noise ratio. Detection limits of 18 ppb for methane, 5 ppb for nitrous oxide and 20 ppm for water vapor have been achieved at a lock-in integration time of 100 ms.

A plasma-enhanced atomic layer deposition (PE-ALD) process to deposit metallic gold is reported, using the previously reported Me 3 Au(PMe 3 ) precursor with H 2 plasma as the reactant. The process has a deposition window from 50 to 120 °C with a growth rate of 0.030 ± 0.002 nm per cycle on gold seed layers, and it shows saturating behavior for both the precursor and reactant exposure. X-ray photoelectron spectroscopy measurements show that the gold films deposited at 120 °C are of higher purity than the previously reported ones (<1 at. % carbon and oxygen impurities and <0.1 at. % phosphorous). A low resistivity value was obtained (5.9 ± 0.3 μΩ cm), and X-ray diffraction measurements confirm that films deposited at 50 and 120 °C are polycrystalline. The process forms gold nanoparticles on oxide surfaces, which coalesce into wormlike nanostructures during deposition. Nanostructures grown at 120 °C are evaluated as substrates for free-space surface-enhanced Raman spectroscopy (SERS) and exhibit an excellent enhancement factor that is without optimization, only one order of magnitude weaker than state-of-the-art gold nanodome substrates. The reported gold PE-ALD process therefore offers a deposition method to create SERS substrates that are template-free and does not require lithography. Using this process, it is possible to deposit nanostructured gold layers at low temperatures on complex three-dimensional (3D) substrates, opening up opportunities for the application of gold ALD in flexible electronics, heterogeneous catalysis, or the preparation of 3D SERS substrates.

The role and importance of mechanical properties of cells and tissues in cellular function, development and disease has widely been acknowledged, however standard techniques currently used to assess them exhibit intrinsic limitations. Recently, Brillouin microscopy, a type of optical elastography, has emerged as a non-destructive, label- and contact-free method that can probe the viscoelastic properties of biological samples with diffraction-limited resolution in 3D. This led to increased attention amongst the biological and medical research communities, but it also sparked debates about the interpretation and relevance of the measured physical quantities. Here, we review this emerging technology by describing the underlying biophysical principles and discussing the interpretation of Brillouin spectra arising from heterogeneous biological matter. We further elaborate on the technique's limitations, as well as its potential for gaining insights in biology, in order to guide interested researchers from various fields.

Surface-Enhanced Raman Spectroscopy (SERS) allows for the highly specific detection of molecules by enhancing the inherently weak Raman signals near the surface of plasmonic nanostructures. A variety of plasmonic nanostructures have been developed for SERS signal excitation and collection in a conventional free-space microscope, among which the gold nanodomes offer one of the highest SERS enhancements. Nanophotonic waveguides have recently emerged as an alternative to the conventional Raman microscope as they can be used to efficiently excite and collect Raman signals. Integration of plasmonic structures on nanophotonic waveguides enables reproducible waveguide-based excitation and collection of SERS spectra, such as in nanoplasmonic slot waveguides. In this paper, we compare the SERS performance of gold nanodomes, in which the signal is excited and collected in free space, and waveguide-based nanoplasmonic slot waveguide. We evaluate the SERS signal enhancement and the SERS background of the different SERS platforms using a monolayer of nitrothiophenol. We show that the nanoplasmonic slot waveguide approaches the gold nanodomes in terms of the signal-to-background ratio. We additionally demonstrate the first-time detection of a peptide monolayer on a waveguide-based SERS platform, paving the way towards the SERS monitoring of biologically relevant molecules on an integrated lab-on-a-chip platform.

Photonic integrated circuits (PICs) enable the miniaturization of optical quantum circuits because several optic and electronic functionalities can be added on the same chip. Integrated single photon emitters (SPEs) are central building blocks for such quantum photonic circuits. SPEs embedded in 2D transition metal dichalcogenides have some unique properties that make them particularly appealing for large-scale integration. Here we report on the integration of a WSe 2 monolayer onto a Silicon Nitride (SiN) chip. We demonstrate the coupling of SPEs with the guided mode of a SiN waveguide and study how the on-chip single photon extraction can be maximized by interfacing the 2D-SPE with an integrated dielectric cavity. Our approach allows the use of optimized PIC platforms without the need for additional processing in the SPE host material. In combination with improved wafer-scale CVD growth of 2D materials, this approach provides a promising route towards scalable quantum photonic chips.

In this paper, we propose a novel, miniaturized non-dispersive infrared (NDIR) CO 2 sensor implemented on a silicon chip. The sensor has a simple structure, consisting of a hollow metallic cylindrical cavity along with access waveguides. A detailed analysis of the proposed sensor is presented. Simulation with 3D ray tracing shows that an integrating cylinder with 4 mm diameter gives an equivalent optical path length of 3 . 5 cm. The sensor is fabricated using Deep Reactive Ion Etching (DRIE) and wafer bonding. The fabricated sensor was evaluated by performing a CO 2 concentration measurement, showing a limit of detection of ∼100 ppm. The response time of the sensor is only ∼2.8 s, due to its small footprint. The use of DRIE-based waveguide structures enables mass fabrication, as well as the potential co-integration of flip-chip integrated midIR light-emitting diodes (LEDs) and photodetectors, resulting in a compact, low-power, and low-cost NDIR CO 2 sensor.

A theoretical model describing the acoustic coupling between two resonator tubes in spectrophones exploiting custom-made quartz tuning forks (QTFs) is proposed. The model is based on an open-end correction to predict the optimal tube length. A calculation of the sound field distribution from one tube exit allowed for the estimation of the optimal radius as a function of the QTF prong spacing and the sound wavelength. The theoretical predictions have been confirmed using experimental studies employing a custom QTF with a fundamental flexural mode resonance frequency of 15.8 kHz and a quality factor of 15,000 at atmospheric pressure. The spacing between the two prongs was 1.5 mm. Spectrophones mounting this QTF were implemented for the quartz-enhanced photoacoustic detection of water vapor in air in the mid-infrared spectral range.

Single-photon sources and detectors are indispensable building blocks for integrated quantum photonics, a research field that is seeing ever increasing interest for numerous applications. In this work, we implemented essential components for a quantum key distribution transceiver on a single photonic chip. Plasmonic antennas on top of silicon nitride waveguides provide Purcell enhancement with a concurrent increase of the count rate, speeding up the microsecond radiative lifetime of IR-emitting colloidal PbS/CdS quantum dots (QDs). The use of low-fluorescence silicon nitride, with a waveguide loss smaller than 1 dB/cm, made it possible to implement high extinction ratio optical filters and low insertion loss spectrometers. Waveguide-coupled superconducting nanowire single-photon detectors allow for low time-jitter single-photon detection. To showcase the performance of the components, we demonstrate on-chip lifetime spectroscopy of PbS/CdS QDs. The method developed in this paper is predicted to scale down to single QDs, and newly developed emitters can be readily integrated on the chip-based platform.

CH 3 NH 3 PbI 3 planar-structure perovskite solar cells were fabricated with the configuration FTO/ZnO/CH 3 NH 3 PbI 3 /Au. ZnO nanoparticles were synthesized by the precipitation method. Three different deposition methods including spin-coating, spraying and successive ionic layer adsorption and reaction (SILAR) were applied to fabricate the ZnO films as electron transport layers. Certain analyses, such as XRD, SEM, FESEM, UV-visible and I - V measurements, were carried out to evaluate the performance of the cells. The best cell performance was achieved for the perovskite solar cell with a ZnO film coated by the spin method. The average efficiency was 7% without using any hole transport materials and 10.25% using spiro-OMeTAD as a hole transport material. The average efficiencies of the cells coated by the spraying and SILAR methods using spiro-OMeTAD, were found to be 8.64% and 7.7% respectively. This study demonstrates the versatility of the spray and SILAR coating methods and their potential for fabricating low-cost, large scale, flexible and mass produced perovskite solar cells., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: A novel medical device has been developed to address an unmet need of standardizing and facilitating heart rate recording during neonatal resuscitation. In a time-critical emergency resuscitation, where failure can mean death of an infant, it is vital that clinicians are provided with information in a timely, precise, and clear manner to capacitate appropriate decision making. This new technology provides a hands-free, wireless heart rate monitoring solution that easily fits the clinical pathway and procedure for neonatal resuscitation., Objective: This study aimed to understand the requirements of the interface design for a new device by using a human factors approach. This approach combined a traditional user-centered design approach with an applied cognitive task analysis to understand the tasks involved, the cognitive requirements, and the potential for error during a neonatal resuscitation scenario., Methods: Fourteen clinical staff were involved in producing the final design requirements. Two pediatric doctors supported the development of a visual representation of the activities associated with neonatal resuscitation. This design was used to develop a scenario-based workshop. Two workshops were carried out in parallel and involved three pediatric doctors, three neonatal nurses, two advance neonatal practitioners, and four midwives. Both groups came together at the end to reflect on the findings from the separate sessions., Results: The outputs of this study have provided a comprehensive description of information requirements during neonatal resuscitation and enabled product developers to understand the preferred requirements of the user interface design for the device. The study raised three key areas for the designers to consider, which had not previously been highlighted: (1) interface layout and information priority, as heart rate should be central and occupy two-thirds of the screen; (2) size and portability, to enable positioning of the product local to the baby's head and allow visibility from all angles; and (3) auditory feedback, to support visual information on heart rate rhythm and reliability of the trace with an early alert for intervention while avoiding parental distress., Conclusions: This study demonstrates the application of human factors and the applied cognitive task analysis method, which identified previously unidentified user requirements. This methodology provides a useful approach to aid development of the clinical interface for medical devices., (©Laura Pickup, Alexandra Lang, Lara Shipley, Caroline Henry, James Carpenter, Damon McCartney, Matthew Butler, Barrie Hayes-Gill, Don Sharkey. Originally published in JMIR Human Factors (http://humanfactors.jmir.org), 08.06.2019.)

Fluorescent nanodiamonds (fNDs) containing nitrogen vacancy (NV) centers are promising candidates for quantum sensing in biological environments. This work describes the fabrication and implementation of electrospun poly lactic-co-glycolic acid (PLGA) nanofibers embedded with fNDs for optical quantum sensing in an environment, which recapitulates the nanoscale architecture and topography of the cell niche. A protocol that produces uniformly dispersed fNDs within electrospun nanofibers is demonstrated and the resulting fibers are characterized using fluorescent microscopy and scanning electron microscopy (SEM). Optically detected magnetic resonance (ODMR) and longitudinal spin relaxometry results for fNDs and embedded fNDs are compared. A new approach for fast detection of time varying magnetic fields external to the fND embedded nanofibers is demonstrated. ODMR spectra are successfully acquired from a culture of live differentiated neural stem cells functioning as a connected neural network grown on fND embedded nanofibers. This work advances the current state of the art in quantum sensing by providing a versatile sensing platform that can be tailored to produce physiological-like cell niches to replicate biologically relevant growth environments and fast measurement protocols for the detection of co-ordinated endogenous signals from clinically relevant populations of electrically active neuronal circuits., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We propose a new method for performing photonic circuit simulations based on the scatter matrix formalism. We leverage the popular deep-learning framework PyTorch to reimagine photonic circuits as sparsely connected complex-valued neural networks. This allows for highly parallel simulation of large photonic circuits on graphical processing units in time and frequency domain while all parameters of each individual component can easily be optimized with well-established machine learning algorithms such as backpropagation.

Mach-Zehnder interferometers are integrated photonic sensors that have yielded excellent detection limits down to 10 -7  RIU. They are of particular interest due to their large design freedom, allowing for example application in promising point-of-care compatible read-out schemes. The attainable detection limit of such sensors can interact with the sensor design in different ways, depending on the dominant origin of noise which can either be influencing a single sensor arm, both sensor arms or can be unrelated to the sensor itself. In this work, the interaction of these three noise regimes with the sensor design is examined. The regimes are combined into a framework that predicts the limit of detection as a function of sensor design. A set of experimental results confirms the validity of this obtained theoretical framework. This analysis provides a blueprint for optimization of MZI photonic sensors under any combination of read-out method and measurement circumstances.

Cells sense and respond to external physical forces and substrate rigidity by regulating their cell shape, internal cytoskeletal tension, and stiffness. Here we show that the combination of micropillar traction force and noncontact Brillouin microscopy provides access to cell-generated forces and intracellular mechanical properties at optical resolution. Actin-rich cytoplasmic domains of 3T3 fibroblasts showed significantly higher Brillouin shifts, indicating a potential increase in stiffness when adhering on fibronectin-coated glass compared to soft PDMS micropillars. Our findings demonstrate the complementarity of micropillar traction force and Brillouin microscopy to better understand the relation between cell force generation and the intracellular mechanical properties., Competing Interests: The authors declare that there are no conflicts of interest related to this article.

Polymer-based single-microring biosensors usually have a small free spectral range (FSR) that hampers the tracing of the spectrum shifting in the measurement. A cascade of two microring resonators based on the Vernier effect, is applied in this article in order to make up for this defect. A small FSR difference between the reference microring and the sensing microring is designed, in order to superpose the periodic envelope signal onto the constituent peaks, which makes it possible to continuously track the spectrum of the sensor. The optical polymer material, Ormocore, which has a large transparent window, is used in the fabrication. The biosensor is fabricated by using an UV-based soft imprint technique, which is considered to be cost-effective and suitable for mass production. By optimizing the volume ratio of Ormocore and the maT thinner, the device can be fabricated almost without a residual layer. The device works at a wavelength of 840 nm, where water absorption loss is much lower than at the infrared wavelengths. A two-step fitting method, including single-peak fitting and whole-envelope fitting, is applied in order to trace the spectral shift accurately. Finally, the two-cascaded-microrings biosensor is characterized, and the obtained FSR is 4.6 nm, which is 16 times larger than the FSR of the single microring biosensor demonstrated in our previous work. Moreover, the sensitivity can also be amplified by 16-fold, thanks to the Vernier effect.

We report on the label-free real-time optical monitoring of DNA hybridization upon exposure to a flow of complementary DNA at different concentrations. The biosensor is composed of a silicon nitride integrated unbalanced Mach-Zehnder interferometer (MZI), with an integrated arrayed waveguide grating as a spectral filter. This MZI has been shown to have both sufficient multiplexing capability and limit of detection on the order of 10  -  6 RIU. Probe DNA, consisting of a 36-mer fragment is covalently immobilized on the silicon nitride integrated biosensor. The wavelength shift is monitored upon complementary DNA targets being flown over the sensor. Concentrations of 1 pM can be easily detected. Also, an alternative route to modify the sensor surface with carboxylic groups using the photochemical reaction of fatty acids is proposed and preliminary XPS results are presented. Moreover, preliminary results for DNA obtained from a rolling circle amplification (RCA-DNA) process and spiked in a realistic amplification buffer are presented., ((2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).)

An ideal illumination for light sheet fluorescence microscopy entails both a localized and a propagation invariant optical field. Bessel beams and Airy beams satisfy these conditions, but their non-diffracting feature comes at the cost of the presence of high-energy side lobes that notably degrade the imaging contrast and induce photobleaching. Here, we demonstrate the use of a light droplet illumination whose side lobes are suppressed by interfering Bessel beams of specific k-vectors. Our droplet illumination readily achieves more than 50% extinction of the light distributed across the Bessel side lobes, providing a more efficient energy localization without loss in transverse resolution. In a standard light sheet fluorescence microscope, we demonstrate a two-fold contrast enhancement imaging micron-scale fluorescent beads. Results pave the way to new opportunities for rapid and deep in vivo observations of large-scale biological systems.

Supercontinuum generation in Kerr media has become a staple of nonlinear optics. It has been celebrated for advancing the understanding of soliton propagation as well as its many applications in a broad range of fields. Coherent spectral broadening of laser light is now commonly performed in laboratories and used in commercial "white light" sources. The prospect of miniaturizing the technology is currently driving experiments in different integrated platforms such as semiconductor on insulator waveguides. Central to the spectral broadening is the concept of higher-order soliton fission. While widely accepted in silica fibers, the dynamics of soliton decay in semiconductor waveguides is yet poorly understood. In particular, the role of nonlinear loss and free carriers, absent in silica, remains an open question. Here, through experiments and simulations, we show that nonlinear loss is the dominant perturbation in wire waveguides, while free-carrier dispersion is dominant in photonic crystal waveguides.

Plant myosin XI acts as a motive force for cytoplasmic streaming through interacting with actin filaments within the cell. Arabidopsis thaliana (At) has 13 genes belonging to the myosin XI family. Previous reverse genetic approaches suggest that At myosin XIs are partially redundant, but are functionally diverse for their specific tasks within the plant. However, the tissue-specific expression and enzymatic properties of myosin XIs have to date been poorly understood, primarily because of the difficulty in cloning and expressing large myosin XI genes and proteins. In this study, we cloned full-length cDNAs and promoter regions for all 13 At myosin XIs and identified tissue-specific expression (using promoter-reporter assays) and motile and enzymatic activities (using in vitro assays). In general, myosins belonging to the same class have similar velocities and ATPase activities. However, the velocities and ATPase activities of the 13 At myosin XIs are significantly different and are classified broadly into three groups based on velocity (high group, medium group and low group). Interestingly, the velocity groups appear roughly correlated with the tissue-specific expression patterns. Generally, ubiquitously expressed At myosin XIs belong to the medium-velocity group, pollen-specific At myosin XIs belong to the high-velocity group and only one At myosin XI (XI-I) is classified as belonging to the low-velocity group. In this study, we demonstrated the diversity of the 13 myosin XIs in Arabidopsis at the molecular and tissue levels. Our results indicate that myosin XIs in higher plants have distinct motile and enzymatic activities adapted for their specific roles.

Tuberculosis (TB) is the leading global cause of death from a single infectious agent. Registered incidence rates are low, especially in low-resource countries with weak health systems, due to the disadvantages of current diagnostic techniques. A major effort is directed to develop a point-of-care (POC) platform to reduce TB deaths with a prompt and reliable low-cost technique. In the frame of the European POCKET Project, a novel POC platform for the direct and noninvasive detection of TB in human urine was developed. The photonic sensor chip is integrated in a disposable cartridge and is based on a highly sensitive Mach-Zehnder Interferometer (MZI) transducer combined with an on-chip spectral filter. The required elements for the readout are integrated in an instrument prototype, which allows real-time monitoring and data processing. In this work, the novel POC platform has been employed for the direct detection of lipoarabinomannan (LAM), a lipopolysaccharide found in the mycobacterium cell wall. After the optimization of several parameters, a limit of detection of 475 pg/mL (27.14 pM) was achieved using a direct immunoassay in undiluted human urine in less than 15 min. A final validation of the technique was performed using 20 clinical samples from TB patients and healthy donors, allowing the detection of TB in people regardless of HIV coinfection. The results show excellent correlation to those obtained with standard techniques. These promising results demonstrate the high sensitivity, specificity and applicability of our novel POC platform, which could be used during routine check-ups in developing countries.

Fibre Bragg grating (FBG) strain sensors are not only a very well-established research field, but they are also acquiring a bigger market share due to their sensitivity and low costs. In this paper we review FBG strain sensors with high focus on the underlying physical principles, the interrogation, and the read-out techniques. Particular emphasis is given to recent advances in highly-performing, single head FBG, a category FBG strain sensors belong to. Different sensing schemes are described, including FBG strain sensors based on mode splitting. Their operation principle and performance are reported and compared with the conventional architectures. In conclusion, some advanced applications and key sectors the global fibre-optic strain sensors market are envisaged, as well as the main market players acting in this field.

Silicon nitride (SiN) is emerging as a competitive platform for CMOS-compatible integrated photonics. However, active devices such as modulators are scarce and still lack in performance. Ideally, such a modulator should have a high bandwidth, good modulation efficiency, low loss, and cover a wide wavelength range. Here, we demonstrate the first electro-optic modulators based on ferroelectric lead zirconate titanate (PZT) films on SiN, in both the O-band and C-band. Bias-free operation, bandwidths beyond 33 GHz and data rates of 40 Gbps are shown, as well as low propagation losses (α ≈ 1 dB cm -1 ). A half-wave voltage-length product of 3.2 V cm is measured. Simulations indicate that further improvement is possible. This approach offers a much-anticipated route towards high-performance phase modulators on SiN.

In this Letter, owing to an error during the production process, the author affiliations were listed incorrectly. Affiliation number 5 (Colleges of Nanoscale Science and Engineering, State University of New York (SUNY)) was repeated, and affiliation numbers 6-8 were incorrect. In addition, the phrase "two oxide thickness variants" should have been "two gate oxide thickness variants". These errors have all been corrected online.

The need for miniaturized, fully integrated semiconductor lasers has stimulated significant research efforts into realizing unconventional configurations that can meet the performance requirements of a large spectrum of applications, ranging from communication systems to sensing. We demonstrate a hybrid, silicon  photonics-compatible photonic crystal (PhC) laser architecture that can be used to implement cost-effective, high-capacity light sources, with high side-mode suppression ratio and milliwatt output output powers. The emitted wavelength is set and controlled by a silicon PhC cavity-based reflective filter with the gain provided by a III-V-based reflective semiconductor optical amplifier (RSOA). The high power density in the laser cavity results in a significant enhancement of the nonlinear absorption in silicon in the high Q -factor PhC resonator. The heat generated in this manner creates a tuning effect in the wavelength-selective element, which can be used to offset external temperature fluctuations without the use of active cooling. Our approach is fully compatible with existing fabrication and integration technologies, providing a practical route to integrated lasing in wavelength-sensitive schemes., Competing Interests: The authors declare that they have no conflict of interest.

The thickness characterization of transparent protective coatings on functional, transparent materials is often problematic. In this paper, a toolbox to determine the thicknesses of a transparent coating on functional window films is presented. The toolbox consists of a combination of secondary ion mass spectrometry and profilometry and can be transferred to other transparent polymeric materials. A coating was deposited on designed model samples, which were characterized with cross-sectional views in transmission and in scanning/transmission electron microscopy and ellipsometry. The toolbox was then used to assess the thicknesses of the protective coatings on the pilot-scale window films. This coating was synthesized using straightforward sol-gel alkoxide chemistry. The kinetics of the condensation are studied in order to obtain a precursor that allows fast drying and complete condensation after simple heat treatment. The shelf life of this precursor solution was investigated in order to verify its accordance to industrial requirements. Deposition was performed successfully at low temperatures below 100 &deg;C, which makes deposition on polymeric foils possible. By using roll-to-roll coating, the findings of this paper are easily transferrable to industrial scale. The coating was tested for scratch resistance and adhesion. Values for the emissivity (&epsilon;) of the films were recorded to justify the use of the films obtained as infrared reflective window films. In this work, it is shown that the toolbox measures similar thicknesses to those measured by electron microscopy and can be used to set a required thickness for protective coatings.

Polymers are promising materials for fabricating photonic integrated waveguide devices. Versatile functional devices can be manufactured using a simple process, with low cost and potential mass-manufacturing. This paper reviews the recent progress of polymer photonic integrated devices fabricated using the UV imprinting technique. The passive polymer waveguide devices for wavelength filtering, power splitting, and light collecting, and the active polymer waveguide devices based on the thermal-optic tuning effect, are introduced. Then, the electro-optic (EO) modulators, by virtue of the high EO coefficient of polymers, are described. Finally, the photonic biosensors, which are based on low-cost and biocompatible polymer platforms, are presented.

This paper discusses the physical nature and the numerical modeling of a novel approach of periodic structures for applications as photonic sensors. The sensing is based on the high sensitivity to the cover index change of the notch wavelength. This sensitivity is due to the effect of abnormal blocking of the guided wave propagating along the silicon wire with periodic strips overhead it through the silica buffer. The structure sensing is numerically modeled by 2D and 3D finite difference time domain (FDTD) method, taking into account the waveguide dispersion. The modeling of the long structures (more than 1000 strips) is accomplished by the 2D method of lines (MoL) with a maximal implementation of the analytical feature of the method. It is proved that the effect of abnormal blocking could be used for the construction of novel types of optical sensors.

Expansion of the wavelength range for an ultrafast laser is an important ingredient for extending its range of applications. Conventionally, optical parametric amplification (OPA) has been employed to expand the laser wavelength to the infrared (IR) region. However, the achievable pulse energy and peak power have been limited to the mJ and the GW level, respectively. A major difficulty in the further energy scaling of OPA results from a lack of suitable large nonlinear crystals. Here, we circumvent this difficulty by employing a dual-chirped optical parametric amplification (DC-OPA) scheme. We successfully generate a multi-TW IR femtosecond laser pulse with an energy of 100 mJ order, which is higher than that reported in previous works. We also obtain excellent energy scaling ability, ultrashort pulses, flexiable wavelength tunability, and high-energy stability, which prove that DC-OPA is a superior method for the energy scaling of IR pulses to the 10 J/PW level.

A grating-assisted trimodal interferometer biosensor is proposed and numerically analyzed. A long period grating coupler, for adjusting the power between the fundamental mode and the second higher order mode, is investigated, and is shown to act as a conventional directional coupler for adjusting the power between the two arms. The trimodal interferometer can achieve maximal fringe visibility when the powers of the two modes are adjusted to the same value by the grating coupler, which means that a better limit of detection can be expected. In addition, the second higher order mode typically has a larger evanescent tail than the first higher order mode in bimodal interferometers, resulting in a higher sensitivity of the trimodal interferometer. The influence of fabrication tolerances on the performance of the designed interferometer is also investigated. The power difference between the two modes shows inertia to the fill factor of the grating, but high sensitivity to the modulation depth. Finally, a 2050 2&pi;/RIU (refractive index unit) sensitivity and 43 dB extinction ratio of the output power are achieved.

Microwave index engineering has been investigated in order to properly design slow-wave coplanar waveguides suitable for a wide range of applications in microwave, photonics, plasmonics and metamaterials. The introduction and optimization of novel capacitive and inductive elements is proposed as a design approach to increase the microwave index while keeping the impedance close to 50 Ω to ensure the compatibility with external electronic devices. The contribution of inductive and capacitive elements and their influence on the performance of the slow-wave coplanar waveguide has been systematically analyzed. As a result, a microwave index as high as 11.6 has been experimentally demonstrated in a frequency range up to 40 GHz which is, to the best of our knowledge, the largest microwave index obtained so far in coplanar waveguides.

Electronic and photonic technologies have transformed our lives-from computing and mobile devices, to information technology and the internet. Our future demands in these fields require innovation in each technology separately, but also depend on our ability to harness their complementary physics through integrated solutions 1,2 . This goal is hindered by the fact that most silicon nanotechnologies-which enable our processors, computer memory, communications chips and image sensors-rely on bulk silicon substrates, a cost-effective solution with an abundant supply chain, but with substantial limitations for the integration of photonic functions. Here we introduce photonics into bulk silicon complementary metal-oxide-semiconductor (CMOS) chips using a layer of polycrystalline silicon deposited on silicon oxide (glass) islands fabricated alongside transistors. We use this single deposited layer to realize optical waveguides and resonators, high-speed optical modulators and sensitive avalanche photodetectors. We integrated this photonic platform with a 65-nanometre-transistor bulk CMOS process technology inside a 300-millimetre-diameter-wafer microelectronics foundry. We then implemented integrated high-speed optical transceivers in this platform that operate at ten gigabits per second, composed of millions of transistors, and arrayed on a single optical bus for wavelength division multiplexing, to address the demand for high-bandwidth optical interconnects in data centres and high-performance computing 3,4 . By decoupling the formation of photonic devices from that of transistors, this integration approach can achieve many of the goals of multi-chip solutions 5 , but with the performance, complexity and scalability of 'systems on a chip' 1,6-8 . As transistors smaller than ten nanometres across become commercially available 9 , and as new nanotechnologies emerge 10,11 , this approach could provide a way to integrate photonics with state-of-the-art nanoelectronics.

In vivo imaging of self-illuminating bio-and chemiluminescent reporters is used to observe the physiology of small animals. However, strong light scattering by biological tissues results in poor spatial resolution of the optical imaging, which also degrades the quantitative accuracy. To overcome this challenging problem, focused ultrasound is used to modulate the light from the reporter at the ultrasound frequency. This produces an ultrasound switchable light 'beacon' that reduces the influence of light scattering in order to improve spatial resolution. The experimental results demonstrate that apart from light modulation at the ultrasound frequency (AC signal at 3.5 MHz), ultrasound also increases the DC intensity of the reporters. This is shown to be due to a temperature rise caused by insonification that was minimized to be within acceptable mammalian tissue safety thresholds by adjusting the duty cycle of the ultrasound. Line scans of bio-and chemiluminescent objects embedded within a scattering medium were obtained using ultrasound modulated (AC) and ultrasound enhanced (DC) signals. Lateral resolution is improved by a factor of 12 and 7 respectively, as compared to conventional CCD imaging. Two chemiluminescent sources separated by ~10 mm at ~20 mm deep inside a 50 mm thick chicken breast have been successfully resolved with an average signal-to-noise ratio of approximately 8-10 dB., Competing Interests: The authors declare that there are no conflicts of interest related to this article.

Bioluminescence imaging has shown great potential for studying and monitoring disease progression in small animal pre-clinical imaging. However, absolute bioluminescence source recovery through tomographic multi-wavelength measurements is often hindered through the lack of quantitative accuracy and suffers from both poor localisation and quantitative recovery. In this work a method to incorporate a permissible region strategy through not only a priori location (permissible region) but also based on a model of light propagation and hence light sensitivity is developed and tested using both simulations and experimental data. Reconstructions on two different numerical models (a simple slab, and the digital version of a heterogeneous mouse) show an improvement of localisation and recovery of intensity (around 25% for the slab model and around 10% for the digital mouse model). This strategy is also used with experimental data from a phantom gel, which demonstrated an improved recovered tomographic image., Competing Interests: The authors do not have any conflict of interest to declare.

We describe a rapid one-step method to biotinylate virtually any biological or non-biological surface. Contacting a solution of biotin-spacer-lipid constructs with a surface will form a coating within seconds on non-biological surfaces or within minutes on most biological membranes including membrane viruses. The resultant biotinylated surface can then be used to interact with avidinylated conjugates, beads, vesicles, surfaces or cells.

We present a numerical study of a passive integrated photonics reservoir computing platform based on multimodal Y-junctions. We propose a novel design of this junction where the level of adiabaticity is carefully tailored to capture the radiation loss in higher-order modes, while at the same time providing additional mode mixing that increases the richness of the reservoir dynamics. With this design, we report an overall average combination efficiency of 61% compared to the standard 50% for the single-mode case. We demonstrate that with this design, much more power is able to reach the distant nodes of the reservoir, leading to increased scaling prospects. We use the example of a header recognition task to confirm that such a reservoir can be used for bit-level processing tasks. The design itself is CMOS-compatible and can be fabricated through the known standard fabrication procedures.

Although the functionality of the lens water channels aquaporin 1 (AQP1; epithelium) and AQP0 (fiber cells) is well established, less is known about the role of AQP5 in the lens. Since in other tissues AQP5 functions as a regulated water channel with a water permeability (P H2O ) some 20 times higher than AQP0, AQP5 could function to modulate P H2O in lens fiber cells. To test this possibility, a fluorescence dye dilution assay was used to calculate the relative P H2O of epithelial cells and fiber membrane vesicles isolated from either the mouse or rat lens, in the absence and presence of HgCl 2 , an inhibitor of AQP1 and AQP5. Immunolabeling of lens sections and fiber membrane vesicles from mouse and rat lenses revealed differences in the subcellular distributions of AQP5 in the outer cortex between species, with AQP5 being predominantly membranous in the mouse but predominantly cytoplasmic in the rat. In contrast, AQP0 labeling was always membranous in both species. This species-specific heterogeneity in AQP5 membrane localization was mirrored in measurements of P H2O , with only fiber membrane vesicles isolated from the mouse lens, exhibiting a significant Hg 2+ -sensitive contribution to P H2O . When rat lenses were first organ cultured, immunolabeling revealed an insertion of AQP5 into cortical fiber cells, and a significant increase in Hg 2+ -sensitive P H2O was detected in membrane vesicles. Our results show that AQP5 forms functional water channels in the rodent lens, and they suggest that dynamic membrane insertion of AQP5 may regulate water fluxes in the lens by modulating P H2O in the outer cortex.

Colloidal quantum dots (QDs) raise more and more interest as solution-processable and tunable optical gain materials. However, especially for infrared active QDs, optical gain remains inefficient. Since stimulated emission involves multifold degenerate band-edge states, population inversion can be attained only at high pump power and must compete with efficient multi-exciton recombination. Here, we show that mercury telluride (HgTe) QDs exhibit size-tunable stimulated emission throughout the near-infrared telecom window at thresholds unmatched by any QD studied before. We attribute this unique behaviour to surface-localized states in the bandgap that turn HgTe QDs into 4-level systems. The resulting long-lived population inversion induces amplified spontaneous emission under continuous-wave optical pumping at power levels compatible with solar irradiation and direct current electrical pumping. These results introduce an alternative approach for low-threshold QD-based gain media based on intentional trap states that paves the way for solution-processed infrared QD lasers and amplifiers.

Surface-enhanced Raman scattering provides a promising technology for sensitive and selective detection of protease activity by monitoring peptide cleavage. Not only are peptides and plasmonic hotspots similarly sized, Raman fingerprints also hold large potential for spectral multiplexing. Here, we use a gold-nanodome platform for real-time detection of trypsin activity on a CALNNYGGGGVRGNF substrate peptide. First, we investigate the spectral changes upon cleavage through the SERS signal of liquid-chromatography separated products. Next, we show that similar patterns are detected upon digesting surface-bound peptides. We demonstrate that the relative intensity of the fingerprints from aromatic amino acids before and after the cleavage site provides a robust figure of merit for the turnover rate. The presented method offers a generic approach for measuring protease activity, which is illustrated by developing an analogous substrate for endoproteinase Glu-C.

This paper is an overview of current gyroscopes and their roles based on their applications. The considered gyroscopes include mechanical gyroscopes and optical gyroscopes at macro- and micro-scale. Particularly, gyroscope technologies commercially available, such as Mechanical Gyroscopes, silicon MEMS Gyroscopes, Ring Laser Gyroscopes (RLGs) and Fiber-Optic Gyroscopes (FOGs), are discussed. The main features of these gyroscopes and their technologies are linked to their performance., Competing Interests: The authors declare no conflict of interest.

Structural colors enable the creation of a spectrum of nonfading colors without pigments, potentially replacing toxic metal oxides and conjugated organic pigments. However, significant challenges remain to achieve the contrast needed for a complete gamut of colors and a scalable process for industrial application. We demonstrate a feasible solution for producing structural colors inspired by bird feathers. We have designed core-shell nanoparticles using high-refractive index (RI) (~1.74) melanin cores and low-RI (~1.45) silica shells. The design of these nanoparticles was guided by finite-difference time-domain simulations. These nanoparticles were self-assembled using a one-pot reverse emulsion process, which resulted in bright and noniridescent supraballs. With the combination of only two ingredients, synthetic melanin and silica, we can generate a full spectrum of colors. These supraballs could be directly added to paints, plastics, and coatings and also used as ultraviolet-resistant inks or cosmetics.

The availability of silicon photonic integrated circuits (ICs) in the 2-4 μm wavelength range enables miniature optical sensors for trace gas and bio-molecule detection. In this paper, we review our recent work on III-V-on-silicon waveguide circuits for spectroscopic sensing in this wavelength range. We first present results on the heterogeneous integration of 2.3 μm wavelength III-V laser sources and photodetectors on silicon photonic ICs for fully integrated optical sensors. Then a compact 2 μm wavelength widely tunable external cavity laser using a silicon photonic IC for the wavelength selective feedback is shown. High-performance silicon arrayed waveguide grating spectrometers are also presented. Further we show an on-chip photothermal transducer using a suspended silicon-on-insulator microring resonator used for mid-infrared photothermal spectroscopy., Competing Interests: The authors declare no conflict of interest.

Because several studies have shown that exogenous miR-199a has antiviral effects against various viruses, including herpesviruses, we examined how miR-199a exerts its antiviral effects using epithelial tumour cell lines infected with herpes simplex virus-1 (HSV-1). We found that both miR-199a-5p and -3p impair the secondary envelopment of HSV-1 by suppressing their common target, ARHGAP21, a Golgi-localized GTPase-activating protein for Cdc42. We further found that the trans-cisternae of the Golgi apparatus are a potential membrane compartment for secondary envelopment. Exogenous expression of either pre-miR-199a or sh-ARHGAP21 exhibited shared phenotypes i.e. alteration of Golgi function in uninfected cells, inhibition of HSV-1 secondary envelopment, and reduction of trans-Golgi proteins upon HSV-1 infection. A constitutively active form of Cdc42 also inhibited HSV-1 secondary envelopment. Endogenous levels of miR-199a in epithelial tumour cell lines were negatively correlated with the efficiency of HSV-1 secondary envelopment within these cells. These results suggest that miR-199a is a crucial regulator of Cdc42 activity on Golgi membranes, which is important for the maintenance of Golgi function and for the secondary envelopment of HSV-1 upon its infection.

We have designed multifunctional silver alginate hydrogel microcontainers referred to as loaded microcapsules with different sizes by assembling them via a template assisted approach using natural, highly porous calcium carbonate cores. Sodium alginate was immobilized into the pores of calcium carbonate particles of different sizes followed by cross-linking via addition of silver ions, which had a dual purpose: on one hand, the were used as a cross-linking agent, albeit in the monovalent form, while on the other hand they have led to formation of silver nanoparticles. Monovalent silver ions, an unusual cross-linking agent, improve the sensitivity to ultrasound, lead to homogeneous distribution of silver nanoparticles. Silver nanoparticles appeared on the shell of the alginate microcapsules in the twin-structure as determined by transmission electron microscopy. Remote release of a payload from alginate containers by ultrasound was found to strongly depend on the particle size. The possibility to use such particles as a platform for label-free molecule detection based on the surface enhanced Raman scattering was demonstrated. Cytotoxicity and cell uptake studies conducted in this work have revealed that microcontainers exhibit nonessential level of toxicity with an efficient uptake of cells. The above-described functionalities constitute building blocks of a theranostic system, where detection and remote release can be achieved with the same carrier.

In this paper we present a detailed theoretical investigation of the electric field induced mixing effect, in which the up and down frequency-conversion processes are obtained by inducing an effective second order susceptibility via the periodic spatial distribution of reversed biased p-i-n junctions. The possibility of realizing a frequency generation process within an integrated microring resonator is demonstrated here, by simulations, in the silicon on insulator platform. Furthermore, general physical features have been investigated by means of a comparative analysis of the frequency generation performance as a function of the input pump power, the linear and nonlinear losses, and the coupling factors. A conversion efficiency of 627.5 %/W has been obtained for the second harmonic generation process. Therefore, an improvement of 4 to 50 times with respect to the straight waveguides is achieved, depending on the cavity ring radius. Finally, for the up/down conversion, from telecom idler to mid-IR and from Mid-IR to telecom signal, respectively, an efficiency of 85.9%/W and 454.4 %/W has been obtained in the silicon microring resonator, respectively.