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Antibodies, disruptive potent therapeutic agents against pharmacological targets, face a barrier in crossing immune systems and cellular membranes. To overcome these, various strategies have been explored including shuttling via liposomes or biocamouflaged nanoparticles. Here, we demonstrate the feasibility of loading antibodies into exosome-mimetic nanovesicles derived from human red-blood-cell membranes, which can act as nanocarriers for intracellular delivery. Goat-antichicken antibodies are loaded into erythrocyte-derived nanovesicles, and their loading yields are characterized and compared with smaller dUTP-cargo molecules. Applying dual-color coincident fluorescence burst analyses, the loading yield of nanocarriers is rigorously profiled at the single-vesicle level, overcoming challenges due to size-heterogeneity and demonstrating a maximum antibody-loading yield of 38-41% at the optimal vesicle radius of 52 nm. The achieved average loading yields, amounting to 14% across the entire nanovesicle population, with more than two antibodies per loaded vesicle, are fully comparable to those obtained for the much smaller dUTP molecules loaded in the nanovesicles after additional exosome-spin-column purification. The results suggest a promising new avenue for therapeutic delivery of antibodies, potentially encompassing also intracellular targets and suitable for large-scale pharmacological applications, which relies on the exosome-mimetic properties, biocompatibility, and low-immunogenicity of bioengineered nanocarriers synthesized from human erythrocyte membranes.
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Lithium niobate, because of its nonlinear and electro-optical properties, is one of the materials of choice for photonic applications. The development of nanostructuring capabilities of thin film lithium niobate (TFLN) permits fabrication of small footprint, low-loss optical circuits. With the recent implementation of on-chip single-photon detectors, this architecture is among the most promising for realizing on-chip quantum optics experiments. In this Letter, we report on the implementation of superconducting nanowire single-photon detectors (SNSPDs) based on NbTiN on 300 nm thick TFLN ridge nano-waveguides. We demonstrate a waveguide-integrated wavelength meter based on the photon energy dependence of the superconducting detectors. The device operates at the telecom C- and L-bands and has a footprint smaller than 300 × 180 µm2 and critical currents between â¼12 and â¼14 µA, which ensures operation with minimum heat dissipation. Our results hold promise for future densely packed on-chip wavelength-multiplexed quantum communication systems.
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The possible targeting functionality and low immunogenicity of exosomes and exosome-like nanovesicles make them promising as drug-delivery carriers. To tap into this potential, accurate non-destructive methods to load them and characterize their contents are of utmost importance. However, the small size, polydispersity, and aggregation of nanovesicles in solution make quantitative characterizations of their loading particularly challenging. Here, an ad-hoc methodology is developed based on burst analysis of dual-color confocal fluorescence microscopy experiments, suited for quantitative characterizations of exosome-like nanovesicles and of their fluorescently-labeled loading. It is applied to study exosome-mimetic nanovesicles derived from animal extracellular-vesicles and human red blood cell detergent-resistant membranes, loaded with fluorescently-tagged dUTP cargo molecules. For both classes of nanovesicles, successful loading is proved and by dual-color coincident fluorescence burst analysis, size statistics and loading yields are retrieved and quantified. The procedure affords single-vesicle characterizations well-suited for the investigation of a variety of cargo molecules and biological nanovesicle combinations besides the proof-of-principle demonstrations of this study. The results highlight a powerful characterization tool essential for optimizing the loading process and for advanced engineering of biomimetic nanovesicles for therapeutic drug delivery.
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Exosomas , Vesículas Extracelulares , Animales , Biomimética , Sistemas de Liberación de Medicamentos/métodos , Exosomas/metabolismo , Vesículas Extracelulares/metabolismo , FluorescenciaRESUMEN
Monolayer semiconducting transition metal dichalcogenides are a strongly emergent platform for exploring quantum phenomena in condensed matter, building novel optoelectronic devices with enhanced functionalities. Because of their atomic thickness, their excitonic optical response is highly sensitive to their dielectric environment. In this work, we explore the optical properties of monolayer thick MoSe2 straddling domain wall boundaries in periodically poled LiNbO3. Spatially resolved photoluminescence experiments reveal spatial sorting of charge and photogenerated neutral and charged excitons across the boundary. Our results reveal evidence for extremely large in-plane electric fields of ≃4000 kV/cm at the domain wall whose effect is manifested in exciton dissociation and routing of free charges and trions toward oppositely poled domains and a nonintuitive spatial intensity dependence. By modeling our result using drift-diffusion and continuity equations, we obtain excellent qualitative agreement with our observations and have explained the observed spatial luminescence modulation using realistic material parameters.
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We demonstrate enhanced optical parametric gains occurring at the edge of periodically poled LiNbO3 (PPLN) regions. Experiments performed in MgO-doped PPLN samples, pumped at 532 nm with parametric signal outputs around 800 nm and 1550 nm, exhibit good agreement with numerical simulations of the nonlinear wave dynamics in the system, based on the assumption of an average refractive index increase Δn = 5.3×10-5 in the PPLN region. Excitation in proximity to the PPLN edge with a pump power of 8.1 mW results in a 3.6-fold output power increase with respect to parametric generation inside the PPLN area.
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Nonlinear optical processes are an essential tool in modern optics, with a broad spectrum of applications, including signal processing, frequency conversion, spectroscopy and quantum optics. Ordinary parametric devices nevertheless still suffer from relatively low gains and wide spectral emission. Here we demonstrate a unique configuration for phase-matching multiple nonlinear processes in a monolithic 2D nonlinear photonic crystal, resulting in the coherent parametric emission of four signal and idler modes, featuring an exponential gain enhancement equal to the Golden Ratio. The results indicate a new route towards compact high-brightness and coherent sources for multi-photon generation, manipulation and entanglement, overcoming limitations of conventional parametric devices.
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Photoinduced enhanced Raman spectroscopy from a lithium niobate on insulator (LNOI)-silver nanoparticle template is demonstrated both by irradiating the template with 254 nm ultraviolet (UV) light before adding an analyte and before placing the substrate in the Raman system (substrate irradiation) and by irradiating the sample in the Raman system after adding the molecule (sample irradiation). The photoinduced enhancement enables up to an â¼sevenfold increase of the surface-enhanced Raman scattering signal strength of an analyte following substrate irradiation, whereas an â¼threefold enhancement above the surface-enhanced signal is obtained for sample irradiation. The photoinduced enhancement relaxes over the course of â¼10 h for a substrate irradiation duration of 150 min before returning to initial signal levels. The increase in Raman scattering intensity following UV irradiation is attributed to photoinduced charge transfer from the LNOI template to the analyte. New Raman bands are observed following UV irradiation, the appearance of which is suggestive of a photocatalytic reaction and highlight the potential of LNOI as a photoactive surface-enhanced Raman spectroscopy substrate.
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Polarization switching in ferroelectric materials underpins a multitude of applications ranging from nonvolatile memories to data storage to ferroelectric lithography. While traditionally considered to be a functionality of the material only, basic theoretical considerations suggest that switching is expected to be intrinsically linked to changes in the electrochemical state of the surface. Hence, the properties and dynamics of the screening charges can affect or control the switching dynamics. Despite being recognized for over 50 years, analysis of these phenomena remained largely speculative. Here, we explore polarization switching on the prototypical LiNbO3 surface using the combination of contact mode Kelvin probe force microscopy and chemical imaging by time-of-flight mass-spectrometry and demonstrate pronounced chemical differences between the domains. These studies provide a consistent explanation to the anomalous polarization and surface charge behavior observed in LiNbO3 and point to new opportunities in chemical control of polarization dynamics in thin films and crystals via control of surface chemistry, complementing traditional routes via bulk doping, and substrate-induced strain and tilt systems.
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Single-molecule detection by surface-enhanced Raman scattering (SERS) is a powerful spectroscopic technique that is of interest for the sensor development field. An important aspect of optimizing the materials used in SERS-based sensors is the ability to have a high density of "hot spots" that enhance the SERS sensitivity to the single-molecule level. Photodeposition of gold (Au) nanoparticles through electric-field-directed self-assembly on a periodically proton-exchanged lithium niobate (PPELN) substrate provides conditions to form well-ordered microscale features consisting of closely packed Au nanoparticles. The resulting Au nanoparticle microstructure arrays (microarrays) are plasmon-active and support nonresonant single-molecule SERS at ultralow concentrations (<10-9-10-13 M) with excitation power densities <1 × 10-3 W cm-2 using wide-field imaging. The microarrays offer excellent SERS reproducibility, with an intensity variation of <7.5% across the substrate. As most biomarkers and molecules do not support resonance enhancement, this work demonstrates that PPELN is a suitable template for high-sensitivity, nonresonant sensing applications.
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We investigate polarization-insensitive waveguide designs afforded by the interplay of material and waveguide birefringence in LiNbO3-on-insulator photonic wires. Fundamental mode birefringence-free operation in the 0.8-1.8 µm spectral range is predicted for a suitable choice of waveguide widths in the 375-600 nm range. Optimized buried waveguide designs yield broadband (1350-1625 nm) index matching between TE00 and TM00 modes. Furthermore, simultaneous phase- and group-velocity matching at infrared wavelengths appears feasible for pulse durations as short as 100 fs.
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The properties of ferroelectric domain walls can significantly differ from those of their parent material. Elucidating their internal structure is essential for the design of advanced devices exploiting nanoscale ferroicity and such localized functional properties. Here, we probe the internal structure of 180° ferroelectric domain walls in lead zirconate titanate (PZT) thin films and lithium tantalate bulk crystals by means of second-harmonic generation microscopy. In both systems, we detect a pronounced second-harmonic signal at the walls. Local polarimetry analysis of this signal combined with numerical modelling reveals the existence of a planar polarization within the walls, with Néel and Bloch-like configurations in PZT and lithium tantalate, respectively. Moreover, we find domain wall chirality reversal at line defects crossing lithium tantalate crystals. Our results demonstrate a clear deviation from the ideal Ising configuration that is traditionally expected in uniaxial ferroelectrics, corroborating recent theoretical predictions of a more complex, often chiral structure.
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The editors introduce the focus issue on "Advanced Solid-State Lasers (ASSL) 2015", which is based on the topics presented at a congress of the same name held in Berlin, Germany, from October 4 to October 9, 2015. This focus issue, jointly prepared by Optics Express and Optical Materials Express, includes 23 contributed papers (17 for Optics Express and 6 for Optical Materials Express) selected from the voluntary submissions from attendees who presented at the congress and have extended their work into complete research articles. We hope this focus issue offers a good snapshot of a variety of topical discussions held at the congress and will contribute to the further expansion of the associated research areas.
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Photodeposition of silver nanoparticles onto chemically patterned lithium niobate having alternating lithium niobate and proton exchanged regions has been previously investigated. Here, the spatially defined photodeposition of gold nanoparticles onto periodically proton exchanged lithium niobate is demonstrated. It is shown that the location where the gold nanoparticles form can be tailored by altering the concentration of HAuCl4. This enables the possibility to sequentially deposit gold and silver in different locations to create bimetallic arrays. The cytocompatibility of photodeposited gold, silver, and bimetallic ferroelectric templates to osteoblast-like cells is also investigated. Gold samples provide significantly greater cell biocompatibility than silver samples. These results highlight a potential route for using photodeposited gold on lithium niobate as a template for applications in cellular biosensing.
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The editors introduce the focus issue on "Advanced Solid-State Lasers (ASSL) 2014," which is based on the topics presented at a congress of the same name held in Shanghai, China, from October 27 to November 1, 2014. This focus issue, jointly prepared by Optics Express and Optical Materials Express, includes 28 contributed papers (21 for Optics Express and 7 for Optical Materials Express) selected from the voluntary submissions by attendees who presented at the congress and have extended their work into complete research articles. We hope this focus issue offers a useful snapshot of the variety of topical discussions held at the congress and will contribute to the further expansion of the associated research areas.
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In this work, the influence of substrate surface charge on in vitro osteoblast cell proliferation on ferroelectric lithium niobate (LN) crystal surfaces is investigated. LN has a spontaneous polarization along the z-axis and is thus characterized by positive and negative bound polarization charge at the +z and -z surfaces. Biocompatibility of LN was demonstrated via culturing and fluorescence imaging of MC3T3 osteoblast cells for up to 11 days. The cells showed enhanced proliferation rates and improved osteoblast function through mineral formation on the positively and negatively charged LN surfaces compared to electrostatically neutral x-cut LN and a glass cover slip control. These results highlight the potential of LN as a template for investigating the role of charge on cellular processes.
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Materiales Biocompatibles/farmacología , Proliferación Celular/efectos de los fármacos , Niobio/farmacología , Osteoblastos/efectos de los fármacos , Óxidos/farmacología , Células 3T3 , Animales , Ratones , Osteoblastos/citologíaRESUMEN
We develop a general model, based on a (2+1)D unidirectional pulse propagation equation, for describing broadband noncollinear parametric interactions in 2D quadratic lattices. We apply it to the analysis of twin-beam optical parametric generation in hexagonally poled LiTaO3, gaining further insights into experimental observations.
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The editors introduce the focus issue on "Advanced Solid-State Lasers (ASSL) 2013," which is based on the topics presented at a congress of the same name held in Paris, France, from October 27 to November 1, 2013. This focus issue, jointly prepared by Optics Express and Optical Materials Express, includes 21 contributed papers (18 for Optics Express and 3 for Optical Materials Express) selected from the voluntary submissions from attendees who presented at the congress and have extended their work into complete research articles. We hope this focus issue offers a good snapshot of a variety of topical discussions held at the congress and will contribute to the further expansion of the associated research areas.
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We investigate spatial localization in a quadratic nonlinear medium in the presence of randomness. By means of numerical simulations and theoretical analyses we show that, in the down conversion regime, the transverse random modulation of the nonlinear susceptibility generates localizations of the fundamental wave that grow exponentially in propagation. The localization length is optically controlled by the pump intensity that determines the amplification rate. The results also apply to cubic nonlinearities.
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Photodeposition of metallic nanostructures onto ferroelectric surfaces is typically based on patterning local surface reactivity via electric field poling. Here, we demonstrate metal deposition onto substrates which have been chemically patterned via proton exchange (i.e., without polarization reversal). The chemical patterning provides the ability to tailor the electrostatic fields near the surface of lithium niobate crystals, and these engineered fields are used to fabricate metallic nanostructures. The effect of the proton exchange process on the piezoelectric and electrostatic properties of the surface is characterized using voltage-modulated atomic force microscopy techniques, which, combined with modeling of the electric fields at the surface of the crystal, reveal that the deposition occurs preferentially along the boundary between ferroelectric and proton-exchanged regions. The metallic nanostructures have been further functionalized with a target probe molecule, 4-aminothiophenol, from which surface-enhanced Raman scattering (SERS) signal is detected, demonstrating the suitability of chemically patterned ferroelectrics as SERS-active templates.
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Cristalización/métodos , Nanopartículas del Metal/química , Nanopartículas del Metal/efectos de la radiación , Resonancia por Plasmón de Superficie/métodos , Campos Electromagnéticos , Luz , Sustancias Macromoleculares/química , Ensayo de Materiales , Nanopartículas del Metal/ultraestructura , Conformación Molecular , Oxidación-Reducción , Propiedades de SuperficieRESUMEN
We theoretically and experimentally investigate multistep parametric processes in broadband optical parametric generators (OPGs) based on periodically poled 1 mol. % MgO-doped stoichiometric LiTaO3. We demonstrate that parametric collateral processes may deplete or enhance spectral portions of the OPG output, depending on pump pulse duration.