RESUMEN
The interaction of bacteria on nanopatterned surfaces has caught attention since the discovery of the bactericidal property of cicada wing surfaces. While many studies focused on the inspiration of such surfaces, nanolithography-based techniques are seldom used due to the difficulties in fabricating highly dense (number of pillars per unit area), geometrical nanostructured surfaces. Here we present a systematic modelling approach for optimising the electron beam lithography parameters in order to fabricate biomimicked nanopillars of varying patterned geometries. Monte Carlo simulation was applied to optimize the beam energy and pattern design prior to the experimental study. We optimized the processing parameters such as exposure factor, write field size, pitch, the different types and thicknesses of the PMMA resist used, and the shape of the feature (circle or a dot) for the fabrication of nanopillars to achieve the best lift-off with repeatable result. Our simulation and experimental results showed that a circle design with a voltage of 30 kV and 602 nm thickness of PMMA 495 A4 as base layers and 65 nm of PMMA 950 A2 as top layer achieves the best results. The antibacterial activity was also validated on the representative fabricated titanium nanopillar surface. The surface with a base diameter of 94.4 nm, spike diameter of 12.6 nm, height of 115.6 nm, density of 43/µm2, aspect ratio of 2.16 and centre to centre distance of 165.8 nm was the optimum surface for antibacterial activity. Such a systematic design approach for fabrication of insect wing-mimicked closely packed nanopillars have not been investigated before which provides an excellent platform for biomedical Ti implants.
Asunto(s)
Biomimética/métodos , Hemípteros , Nanotecnología/métodos , Titanio , Alas de Animales , Animales , Antibacterianos/química , Simulación por Computador , Método de Montecarlo , Nanoestructuras/química , Polimetil Metacrilato , Propiedades de SuperficieRESUMEN
Reconfigurable photonic circuits have applications ranging from next-generation computer architectures to quantum networks, coherent radar and optical metamaterials. Here, we demonstrate an on-chip high quality microcavity with resonances that can be electrically tuned across a full free spectral range (FSR). FSR tuning allows resonance with any source or emitter, or between any number of networked microcavities. We achieve it by integrating nanoelectronic actuation with strong optomechanical interactions that create a highly geometry-dependent effective refractive index. This allows low voltages and sub-nanowatt power consumption. We demonstrate a basic reconfigurable photonic network, bringing the microcavity into resonance with an arbitrary mode of a microtoroidal optical cavity across a telecommunications fibre link. Our results have applications beyond photonic circuits, including widely tuneable integrated lasers, reconfigurable optical filters for telecommunications and astronomy, and on-chip sensor networks.
RESUMEN
The interactions of block copolymers with surfaces can be controlled by coating those surfaces with appropriate statistical copolymers. Usually, a statistical copolymer comprised of monomer units identical to those of the block copolymer is used; that is, typically a poly(styrene)-stat-poly(methyl methacrylate) (PS-stat-PMMA) is used to direct the alignment of poly(styrene)-block-poly(methyl methacrylate) (PS-block-PMMA), and poly(styrene)-stat-poly(2-vinylpyridine) (PS-stat-P2VP) has been used for poly(styrene)-block-poly(2-vinylpyridine) (PS-block-P2VP). Reports of controlling the orientation of block copolymers with statistical copolymers with a dissimilar composition are limited. Here, we demonstrate that this method can be further extended to show that PS-stat-PMMA can be used to control the wetting properties of poly(styrene)-block-poly(D,L-lactide) (PS-block-PDLA). Surfaces were modified with a series of cross-linked PS-stat-PMMA-stat-glycidyl methacrylate terpolymers, and the surface chemistries and energies were assessed using angle-dependent X-ray photoelectron spectroscopy and the two-liquid harmonic method, respectively. From these experiments, an expected neutral compositional window was identified for symmetrical PS-block-PDLA. Moreover, high-resolution SEM, AD-XPS, and grazing-incidence SAXS measurements were used to evaluate the morphology of PS-block-PDLA as a function of the surface composition of the underlying cross-linked copolymer films, and the neutral composition was found to range from 32 to 38 mol % of PS, in the bulk polymer. Ultimately, we demonstrated the determination of nonpreferential surface compositions that allow the self-assembly of lamellae with sizes in the sub-10 nm regime that are oriented perpendicular to the substrate. These findings have important implications for the use of PS-block-PDLA block copolymers in directed self-assembly, most specifically in advanced lithographic processes.
Asunto(s)
Poliésteres/química , Poliestirenos/química , Estructura Molecular , Poliestirenos/síntesis químicaRESUMEN
The introduction of immune checkpoint inhibitors has demonstrated significant improvements in survival for subsets of cancer patients. However, they carry significant and sometimes life-threatening toxicities. Prompt prediction and monitoring of immune toxicities have the potential to maximise the benefits of immune checkpoint therapy. Herein, we develop a digital nanopillar SERS platform that achieves real-time single cytokine counting and enables dynamic tracking of immune toxicities in cancer patients receiving immune checkpoint inhibitor treatment - broader applications are anticipated in other disease indications. By analysing four prospective cytokine biomarkers that initiate inflammatory responses, the digital nanopillar SERS assay achieves both highly specific and highly sensitive cytokine detection down to attomolar level. Significantly, we report the capability of the assay to longitudinally monitor 10 melanoma patients during immune inhibitor blockade treatment. Here, we show that elevated cytokine concentrations predict for higher risk of developing severe immune toxicities in our pilot cohort of patients.
Asunto(s)
Inmunoterapia/métodos , Melanoma/terapia , Monitorización Inmunológica/métodos , Espectrometría Raman/métodos , Quimiocina CX3CL1/inmunología , Quimiocina CX3CL1/metabolismo , Estudios de Cohortes , Citocinas/inmunología , Citocinas/metabolismo , Factor Estimulante de Colonias de Granulocitos/inmunología , Factor Estimulante de Colonias de Granulocitos/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Ipilimumab/efectos adversos , Ipilimumab/inmunología , Ipilimumab/uso terapéutico , Melanoma/inmunología , Melanoma/metabolismo , Microscopía Confocal/métodos , Proyectos Piloto , Reproducibilidad de los ResultadosRESUMEN
Genetic tags allow rapid localization of tagged proteins in cells and tissues. APEX, an ascorbate peroxidase, has proven to be one of the most versatile and robust genetic tags for ultrastructural localization by electron microscopy (EM). Here, we describe a simple method, APEX-Gold, which converts the diffuse oxidized diaminobenzidine reaction product of APEX into a silver/gold particle akin to that used for immunogold labelling. The method increases the signal-to-noise ratio for EM detection, providing unambiguous detection of the tagged protein, and creates a readily quantifiable particulate signal. We demonstrate the wide applicability of this method for detection of membrane proteins, cytoplasmic proteins, and cytoskeletal proteins. The method can be combined with different EM techniques including fast freezing and freeze substitution, focussed ion beam scanning EM, and electron tomography. Quantitation of expressed APEX-fusion proteins is achievable using membrane vesicles generated by a cell-free expression system. These membrane vesicles possess a defined quantum of signal, which can act as an internal standard for determination of the absolute density of expressed APEX-fusion proteins. Detection of fusion proteins expressed at low levels in cells from CRISPR-edited mice demonstrates the high sensitivity of the APEX-Gold method.
Asunto(s)
Tomografía con Microscopio Electrónico/métodos , Técnicas Genéticas , Imagenología Tridimensional/métodos , Animales , Ascorbato Peroxidasas , Congelación , Oro , Ratones , ProteínasRESUMEN
Spatial control of the orientation of block copolymers (BCPs) in thin films offers enormous opportunities for practical nanolithography applications. In this study, we demonstrate the use of a substrate comprised of poly(4-acetoxystyrene) to spatially control interfacial interactions and block copolymer orientation over different length scales. Upon UV irradiation poly(4-acetoxystyrene) undergoes a photo-Fries rearrangement yielding phenolic groups available for further functionalization. The wetting behaviour of PS-b-PMMA deposited on the poly(4-acetoxystyrene) films could be precisely controlled through controlling the UV irradiation dose. After exposure, and a mild post-exposure treatment, the substrate switches from asymmetric, to neutral and then to symmetric wetting. Upon exposure through photomasks, a range of high fidelity micro-patterns consisting of perpendicularly oriented lamellar microdomains were generated. Furthermore, the resolution of chemically patterned poly(4-acetoxystyrene) substrate could be further narrowed to submicrometer scale using electron beam lithography. When the BCP was annealed on an e-beam modified poly(4-acetoxystyrene) surface, the interface between domains of parallel and perpendicular orientation of the BCPs was well defined, especially when compared with the substrates patterned using the photomask.
RESUMEN
Single-crystal cubic silicon carbide has attracted great attention for MEMS and electronic devices. However, current leakage at the SiC/Si junction at high temperatures and visible-light absorption of the Si substrate are main obstacles hindering the use of the platform in a broad range of applications. To solve these bottlenecks, we present a new platform of single crystal SiC on an electrically insulating and transparent substrate using an anodic bonding process. The SiC thin film was prepared on a 150 mm Si with a surface roughness of 7 nm using LPCVD. The SiC/Si wafer was bonded to a glass substrate and then the Si layer was completely removed through wafer polishing and wet etching. The bonded SiC/glass samples show a sharp bonding interface of less than 15 nm characterized using deep profile X-ray photoelectron spectroscopy, a strong bonding strength of approximately 20 MPa measured from the pulling test, and relatively high optical transparency in the visible range. The transferred SiC film also exhibited good conductivity and a relatively high temperature coefficient of resistance varying from -12â¯000 to -20â¯000 ppm/K, which is desirable for thermal sensors. The biocompatibility of SiC/glass was also confirmed through mouse 3T3 fibroblasts cell-culturing experiments. Taking advantage of the superior electrical properties and biocompatibility of SiC, the developed SiC-on-glass platform offers unprecedented potentials for high-temperature electronics as well as bioapplications.
Asunto(s)
Temperatura , Animales , Línea Celular , Electrodos , Vidrio , Ratones , Espectroscopía de FotoelectronesRESUMEN
In this paper we image the highly confined long range plasmons of a nanoscale metal stripe waveguide using quantum emitters. Plasmons were excited using a highly focused 633 nm laser beam and a specially designed grating structure to provide stronger incoupling to the desired mode. A homogeneous thin layer of quantum dots was used to image the near field intensity of the propagating plasmons on the waveguide. We observed that the photoluminescence is quenched when the QD to metal surface distance is less than 10 nm. The optimised spacer layer thickness for the stripe waveguides was found to be around 20 nm. Authors believe that the findings of this paper prove beneficial for the development of plasmonic devices utilising stripe waveguides.