High-angle deflection of metagrating-integrated laser emission for high-contrast microscopy.

Flat metaoptics components are looking to replace classical optics elements and could lead to extremely compact biophotonics devices if integrated with on-chip light sources and detectors. However, using metasurfaces to shape light into wide angular range wavefronts with high efficiency, as is typically required in high-contrast microscopy applications, remains a challenge. Here we demonstrate curved GaAs metagratings integrated on vertical-cavity surface-emitting lasers (VCSELs) that enable on-chip illumination in total internal reflection and dark field microscopy. Based on an unconventional design that circumvents the aspect ratio dependent etching problems in monolithic integration, we demonstrate off-axis emission centred at 60° in air and 63° in glass with > 90% and > 70% relative deflection efficiency, respectively. The resulting laser beam is collimated out-of-plane but maintains Gaussian divergence in-plane, resulting in a long and narrow illumination area. We show that metagrating-integrated VCSELs of different kinds can be combined to enable rapid switching between dark-field and total internal reflection illumination. Our approach provides a versatile illumination solution for high-contrast imaging that is compatible with conventional microscopy setups and can be integrated with biophotonics devices, such as portable microscopy, NIR-II range bioimaging, and lab-on-a-chip devices.

A 310 nm Optically Pumped AlGaN Vertical-Cavity Surface-Emitting Laser.

Ultraviolet light is essential for disinfection, fluorescence excitation, curing, and medical treatment. An ultraviolet light source with the small footprint and excellent optical characteristics of vertical-cavity surface-emitting lasers (VCSELs) may enable new applications in all these areas. Until now, there have only been a few demonstrations of ultraviolet-emitting VCSELs, mainly optically pumped, and all with low Al-content AlGaN cavities and emission near the bandgap of GaN (360 nm). Here, we demonstrate an optically pumped VCSEL emitting in the UVB spectrum (280-320 nm) at room temperature, having an Al0.60Ga0.40N cavity between two dielectric distributed Bragg reflectors. The double dielectric distributed Bragg reflector design was realized by substrate removal using electrochemical etching. Our method is further extendable to even shorter wavelengths, which would establish a technology that enables VCSEL emission from UVA (320-400 nm) to UVC (<280 nm).

High-power single transverse and polarization mode VCSEL for silicon photonics integration.

We demonstrate a 6.5 mW single transverse and polarization mode GaAs-based oxide-confined VCSEL at 850 nm. High power is enabled by a relatively large oxide aperture and an epitaxial design for low resistance, low optical loss, and high slope efficiency VCSELs. With the oxide aperture supporting multiple polarization unrestrained transverse modes, single transverse and polarization mode operation is achieved by a transverse and polarization mode filter etched into the surface of the VCSEL. While the VCSEL is specifically designed for light source integration on a silicon photonic integrated circuit, its performance in terms of power, spectral purity, polarization, and beam properties are of great interest for a large range of applications.

Oncogenic mutations at the EGFR ectodomain structurally converge to remove a steric hindrance on a kinase-coupled cryptic epitope.

Epidermal growth factor receptor (EGFR) signaling is initiated by a large ligand-favored conformational change of the extracellular domain (ECD) from a closed, self-inhibited tethered monomer, to an open untethered state, which exposes a loop required for strong dimerization and activation. In glioblastomas (GBMs), structurally heterogeneous missense and deletion mutations concentrate at the ECD for unclear reasons. We explore the conformational impact of GBM missense mutations, combining elastic network models (ENMs) with multiple molecular dynamics (MD) trajectories. Our simulations reveal that the main missense class, located at the I-II interface away from the self-inhibitory tether, can unexpectedly favor spontaneous untethering to a compact intermediate state, here validated by small-angle X-ray scattering (SAXS). Significantly, such intermediate is characterized by the rotation of a large ECD fragment (N-TR1), deleted in the most common GBM mutation, EGFRvIII, and that makes accessible a cryptic epitope characteristic of cancer cells. This observation suggested potential structural equivalence of missense and deletion ECD changes in GBMs. Corroborating this hypothesis, our FACS, in vitro, and in vivo data demonstrate that entirely different ECD variants all converge to remove N-TR1 steric hindrance from the 806-epitope, which we show is allosterically coupled to an intermediate kinase and hallmarks increased oncogenicity. Finally, the detected extraintracellular coupling allows for synergistic cotargeting of the intermediate with mAb806 and inhibitors, which is proved herein.

eBDIMS server: protein transition pathways with ensemble analysis in 2D-motion spaces.

SUMMARY: Understanding how proteins transition between different conformers, and how conformers relate to each other in terms of structure and function, is not trivial. Here, we present an online tool for transition pathway generation between two protein conformations using Elastic Network Driven Brownian Dynamics Importance Sampling, a coarse-grained simulation algorithm, which spontaneously predicts transition intermediates trapped experimentally. In addition to path-generation, the server provides an interactive 2D-motion landscape graphical representation of the transitions or any additional conformers to explore their structural relationships. AVAILABILITY AND IMPLEMENTATION: eBDIMS is available online: http://ebdims.biophysics.se/ or as standalone software: https://github.com/laura-orellana/eBDIMS, https://github.com/cabergh/eBDIMS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Thermal lensing effects on lateral leakage in GaN-based vertical-cavity surface-emitting laser cavities.

Lateral leakage of light has been identified as a detrimental loss source in many suggested and experimentally realized GaN-based VCSELs. In the present work we include thermal effects to realistically account for the substantial Joule heating in these devices. In contrast to what could be expected from the previous results, the induced thermal lensing does not make antiguided cavities more positively guided, so that they approach the unguided regime with extremely high lateral leakage. Rather, thermal lensing strongly suppresses lateral leakage for both antiguided and guided cavities. This is explained in terms of lowered launch of power from the central part of the cavity and/or lower total internal reflection in the peripheral part; the former effect is active in all cavities whereas the latter only contributes to the very strongly reduced leakage in weakly antiguided cavities. Thermal lensing suppresses lateral leakage both for the fundamental and the first higher order mode, but a strong modal discrimination is still achieved for the antiguided cavities. Thus, strongly antiguided cavities could be used to achieve single-mode devices, but at the cost of slightly higher threshold gain and stronger temperature dependent performance characteristics.

Silicon-integrated short-wavelength hybrid-cavity VCSEL.

We demonstrate a short-wavelength hybrid-cavity vertical-cavity surface-emitting laser (VCSEL) heterogeneously integrated on silicon. A GaAs-based "half-VCSEL" has been attached to a dielectric distributed Bragg reflector (DBR) on a silicon wafer using ultra-thin divinylsiloxane-bis-benzocyclobutene (DVS-BCB) adhesive bonding, thereby creating a cavity with the standing-wave optical field extending over the silicon- and GaAs-based parts of the cavity. A 9 µm oxide aperture diameter VCSEL with a threshold current of 1.2 mA produces 1.6 mW optical output power at 6.0 mA bias current with a wavelength of ~845 nm.

Dynamic Behavior of Vitronectin at the Cell-Material Interface.

Considering that vitronectin (VN) can promote both cell adhesion and matrix degradation, it is likely to play a dual role at the cell-biomaterial interface. In this paper we therefore describe details of the dynamic interplay between matrix adhesion and pericellular proteolysis in endothelial cells adhered to glass model substratum. Initially we show that coating concentration determines protein organization at the surface. When the protein coating density approached saturation (63 ng cm-2), VN spontaneously organized itself in multimeric aggregates at the surface (30-50 nm in diameter). At subsaturation protein density (17 ng cm-2) VN molecules were present predominantly as single entities, indicating that a minimum coating density was required for VN multimerization. By fluorescent visualization of surface-associated VN in different ways, we provide the first evidence of significant proteolytic remodelling of VN by endothelial cells (HUVECs) at the sites of αv integrin clusters. The degree of proteolysis was estimated using a novel approach relying on dequenching of FITC-labeled VN upon proteolytic activity, showing that about one-third of the surface-associated VN was proteolytically altered by adhering HUVECs. In addition, we demonstrate that HUVECs can internalize surface-associated VN and deposit it in a linear pattern along longitudinal actin filaments. Deposited VN was partly colocalized with urokinase receptors. Taken altogether, we elucidate the complex and dynamic behavior of VN during initial cell-biomaterials interactions, the equilibrium if which could have a significant impact on the biocompatibility of any blood contacting implants.

Analysis of structurally sensitive loss in GaN-based VCSEL cavities and its effect on modal discrimination.

Lateral loss causes optical energy to leave the laser cavity in the transverse, lateral, direction, and is sometimes neglected to simplify the numerical simulations. However, in contrast to outcoupling and absorption losses, we show that the lateral loss can change drastically with only nanometer-sized changes of the cavity structure, from being virtually zero to becoming the major source of cavity loss, since the cavity becomes antiguiding. This can be explained as the opening of a channel of efficient resonant lateral leakage of optical power at a certain oblique propagation angle. A number of different realizations of current apertures and top mirror designs in GaN-based VCSEL cavities, which have been suggested for realization of microcavity lasers emitting in the blue wavelength range, are simulated. Many of these are shown to lead to unintentional antiguiding, which can more than double the threshold gain for lasing. Notably, for strong enough antiguiding the resonant lateral leakage decreases so that the threshold gain values might again be tolerable. This regime has been suggested for robust single-mode operation since earlier predictions, building on analogies with slab waveguides, hinted at a very strong suppression of higher order modes. However, our simulations indicate that for the VCSEL cavities the derived formulas grossly overestimate the modal discrimination.

Fibrinogen nanofibers for guiding endothelial cell behavior.

This paper describes the biological consequences of presenting electrospun fibrinogen (FBG) to endothelial cells as a spatially organized nanofibrous matrix. Aligned and randomly oriented FBG nanofibers with an average diameter of less than 200 nm were obtained by electrospinning of native FBG solution. Electrophoretic profiling confirmed that the electrospun FBG resembled the native protein structure, and fluorescent tracing of FITC-labeled FBG showed that electrospun fibers withstood immersion in physiological solutions reasonably well for several days. With respect to cellular interactions, the nanofibrous FBG matrix provided better conditions for initial recognition by human umbilical vein endothelial cells compared to pre-adsorbed FBG on a flat surface. Furthermore, the spatial organization of electrospun FBG fibers presented opportunities for guiding the cellular behavior in a way that is not possible when the protein is presented in another form (e.g. adsorbed or soluble). For example, on aligned FBG fibers, cells rapidly oriented themselves along the fibers, and time-lapse recordings revealed pronounced cellular movements restricted to the fiber direction. In great contrast, on randomly deposited fibers, cells acquired a stellate-like morphology and became locally immobilized by the fibers. We also show that the FBG fiber orientation significantly influenced both the cytoskeleton organization in confluent cell layers and the orientation of the extracellular fibronectin matrix secreted by the cells. In conclusion, this study demonstrates that electrospun FBG nanofibers can be a promising tool for guiding endothelial cell behavior for tissue engineering applications.

Assessment of VCSEL thermal rollover mechanisms from measurements and empirical modeling.

We use an empirical model together with experimental measurements for studying mechanisms contributing to thermal rollover in vertical-cavity surface-emitting lasers (VCSELs). The model is based on extraction of the temperature dependence of threshold current, internal quantum efficiency, internal optical loss, series resistance and thermal impedance from measurements of output power, voltage and lasing wavelength as a function of bias current over an ambient temperature range of 15-100 °C. We apply the model to an oxide-confined, 850-nm VCSEL, fabricated with a 9-µm inner-aperture diameter and optimized for high-speed operation, and show for this specific device that power dissipation due to linear power dissipation (sum total of optical absorption, carrier thermalization, carrier leakage and spontaneous carrier recombination) exceeds power dissipation across the series resistance (quadratic power dissipation) at any ambient temperature and bias current. We further show that the dominant contributors to self-heating for this particular VCSEL are quadratic power dissipation, internal optical loss, and carrier leakage. A rapid reduction of the internal quantum efficiency at high bias currents (resulting in high temperatures) is identified as being the major cause of thermal rollover. Our method is applicable to any VCSEL and is useful for identifying the mechanisms limiting the thermal performance of the device and to formulate design strategies to ameliorate them.

30 Gbps 4-PAM transmission over 200 m of MMF using an 850 nm VCSEL.

We present high speed real time, error free 4-PAM transmission for short range optical links based on a VCSEL operating at 850 nm, a multimode fibre and a simple intensity detector. Transmission speeds of 25 Gbps and 30 Gbps are demonstrated, and the maximum fibre reaches were 300 m and 200 m, respectively. The 4-PAM is also compared with OOK transmission at 25 Gbps, and we find that at this bit rate 4-PAM increases the error free transmission distance in the multimode fibre by 100 m, compared to OOK.

Diffraction loss in long-wavelength buried tunnel junction VCSELs analyzed with a hybrid coupled-cavity transfer-matrix model.

Intra-cavity diffraction in VCSELs is a loss mechanism that potentially can cause a significant decrease in efficiency and a rise in the threshold current, particularly in cavities with small lateral features with a high index contrast. One such VCSEL type is the 2.3 microm GaSb-based buried tunnel junction (BTJ) VCSEL studied in this work, where the BTJ induced topology of the top layers gives rise to excess loss through diffraction. Diffraction loss is difficult to measure, and also the numerical estimation must be done with care because of the non-axial propagation of the diffracted fields. We present a simulation method with spatially varying dimensionality, such that the field is three-dimensional (3D) in the entire cavity, whereas the material structure of the cavity is modelled in 3D near the BTJ and the layers with a varying topology, but elsewhere is assumed to be 1D like in a regular DBR structure. We find that the diffraction loss displays a non-monotonic behaviour as a function of the BTJ diameter, but as expected it rapidly increases below a certain diameter of the BTJ and may even become the dominant cause of loss in some device designs. We also show that the diffraction loss can be much reduced if the layers above the BTJ can be deposited such that the surface profile becomes smoother with increasing distance from the BTJ.

Surface modifications of silicon nitride for cellular biosensor applications.

Thin films of silicon nitride (Si3N4) can be used in several kinds of micro-sized biosensors as a material to monitor fine environmental changes related to the process of bone formation in vitro. We found however that Si3N4 does not provide optimal conditions for osseointegration as osteoblast-like MG-63 cells tend to detach from the surface when cultured over confluence. Therefore Si3N4 was modified with self-assembled monolayers bearing functional end groups of primary amine (NH2) and carboxyl (COOH) respectively. Both these modifications enhanced the interaction with confluent cell layers and thus improve osseointegration over Si3N4. Furthermore it was observed that the NH2 functionality increased the adsorption of fibronectin (FN), promoted cell proliferation, but delayed the differentiation. We also studied the fate of pre-adsorbed and secreted FN from cells to learn more about the impact of above functionalities for the development of provisional extracellular matrix on materials interface. Taken together our data supports that Si3N4 has low tissue integration but good cellular biocompatibility and thus is appropriate in cellular biosensor applications such as the ion-sensitive field effect transistor (ISFET). COOH and NH2 chemistries generally improve the interfacial tissue interaction with the sensor and they are therefore suitable substrates for monitoring cellular growth or matrix deposition using electrical impedance spectroscopy.

Uncooled 2.5 Gb/s operation of 1.3 mum GaInNAs DQW lasers over a wide temperature range.

Ridge waveguide 1.3 mum GaInNAs lasers were fabricated from high quality double quantum well material grown by molecular beam epitaxy. Short cavity (250 mum) lasers have low threshold currents and small temperature dependencies of threshold current and slope efficiency, with a characteristic temperature of the threshold current as high as 200 K. The temperature stability allows for uncooled 2.5 Gb/s operation up to temperatures as high as 110 degrees C with a constant modulation voltage and only the bias current adjusted for constant average output power. Under these conditions, an extinction ratio larger than 6 dB and a spectral rms-width smaller than 2 nm are obtained.

Efficient and individually controllable mechanisms for mode and polarization selection in VCSELs, based on a common, localized, sub-wavelength surface grating.

We have theoretically investigated the combined fundamental-mode and polarization selection in 850-nm oxide-confined vertical-cavity surface-emitting lasers (VCSELs) using a locally etched sub-wavelength surface grating. The physical mechanisms behind the selection are, first, the strongly polarization sensitive effective refractive index of the volume occupied by the grating structure, and second, the dramatic change of the reflectivity of a multi-layer Bragg mirror that can occur by simply changing the refractive index of the outermost layer. For a VCSEL cavity this layer is the surface layer and its refractive index is changed by the introduction of the sub-wavelength grating; in this case the grating leads to a higher reflectivity for the desired polarization. By localizing the surface grating area to a carefully chosen region near the optical axis it is therefore possible to ensure that the fundamental mode experiences a high reflectivity, or low cavity loss, while other modes experience more of the low-reflectance region of the peripheral part of the Bragg mirror and thus suffer higher loss. Cold-cavity calculations on a VCSEL with oxide aperture and grating region diameters of 4.5 microm and 2.5 microm, respectively, indicate that a loss difference of ~20 cm(-1) between the fundamental mode and the first higher order mode can be obtained simultaneously with an orthogonal polarization mode discrimination of >15 cm-1. Based on previous experience, these values should enable robust single-mode operation with only the desired polarization orientation. What is also important, for the lasing mode the introduction of a sub-wavelength grating has no detrimental effect, so its characteristics, such as threshold current, slope efficiency, and far-field profile are unaffected. Moreover, since the effective index is a result of an averaging over several sub-wavelength grating periods, it is fairly insensitive to the detailed shape of the grating grooves, which should relax the fabrication tolerances.