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1.
Nat Commun ; 10(1): 2328, 2019 05 24.
Article in English | MEDLINE | ID: mdl-31127090

ABSTRACT

Alkali metal vapors enable access to single electron systems, suitable for demonstrating fundamental light-matter interactions and promising for quantum logic operations, storage and sensing. However, progress is hampered by the need for robust and repeatable control over the atomic vapor density and over the associated optical depth. Until now, a moderate improvement of the optical depth was attainable through bulk heating or laser desorption - both time-consuming techniques. Here, we use plasmonic nanoparticles to convert light into localized thermal energy and to achieve optical depths in warm vapors, corresponding to a ~16 times increase in vapor pressure in less than 20 ms, with possible reload times much shorter than an hour. Our results enable robust and compact light-matter devices, such as efficient quantum memories and photon-photon logic gates, in which strong optical nonlinearities are crucial.

2.
Drug Deliv Transl Res ; 9(5): 956-967, 2019 10.
Article in English | MEDLINE | ID: mdl-31016477

ABSTRACT

Optical poration, or drilling, of the human nail has the potential to drastically improve transungual drug delivery. However, this approach is accompanied by thermal damage to the nail tissue surrounding the laser radiation-created pore. In this paper, fluorescence microscopy has been employed to quantitatively evaluate thermal damage to the nail induced by laser ablation with 80 MHz, nanojoule, femtosecond pulses delivered via a hollow-core fibre. An empirical relation has been established between the intensity of the resulting fluorescence signal and temperature to which the nail was exposed. Using this relationship, detailed temperature maps have been created of the areas surrounding the pores, enabling the mechanism of poration to be better understood. It was deduced that plasma-mediated ablation is primarily responsible for nail tissue ablation at the centre of the pore, while cumulative photothermal processes dominate at the pore edges. It is concluded, furthermore, that temperature mapping represents a useful new tool with which to optimise the process of nail poration. The method is potentially generic and may be applicable to other biological materials.


Subject(s)
Laser Therapy/methods , Nails/radiation effects , Adult , Humans , Lasers , Porosity , Spectrum Analysis, Raman , Temperature
3.
J Control Release ; 268: 72-77, 2017 Dec 28.
Article in English | MEDLINE | ID: mdl-29051061

ABSTRACT

Drug treatment of diseases of the human nail remains a difficult challenge; topical therapy, in particular, is limited by very poor transport of active agents across the nail itself. The objective of this research was to examine the potential of controlled, and fibre-optic delivered, femtosecond laser light pulses to provide new pathways and opportunities for drug access to targets within and beneath the nail plate. Optical, confocal fluorescence and scanning electron microscopies demonstrated partial and complete laser poration of human nail samples, with the energy per pore and the exposure duration being the key modulating parameters that determined the extent of ablation achieved. Parallel measurements of the penetration of a model drug across laser-treated nails showed that complete poration resulted in essentially complete circumvention of the diffusion barrier, an array of 100 pores in 0.2cm2 area of nail permitting a 103-fold increase in initial drug uptake. Partial ablation of the nail created pores that extended to a range of depths; the nail material adjacent to the ablated area was rendered porous in appearance presumably due to local thermal perturbation of the nail structure. These openings offer, as a result, potential sites in which topical drug formulations might be sequestered post-poration and from which slow, sustained delivery of the active agent into and through the nail may be envisaged.


Subject(s)
Drug Delivery Systems , Lasers , Nails/metabolism , Administration, Topical , Adult , Caffeine/administration & dosage , Humans , Microscopy, Electron, Scanning , Nails/ultrastructure , Porosity
4.
J Biophotonics ; 9(1-2): 144-54, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26449289

ABSTRACT

Laser poration of the skin locally removes its outermost, barrier layer, and thereby provides a route for the diffusion of topically applied drugs. Ideally, no thermal damage would surround the pores created in the skin, as tissue coagulation would be expected to limit drug diffusion. Here, a femtosecond pulsed fiber laser is used to porate mammalian skin ex vivo. This first application of a hollow core negative curvature fiber (HC-NCF) to convey a femtosecond pulsed, visible laser beam results in reproducible skin poration. The effect of applying ink to the skin surface, prior to ultra-short pulsed ablation, has been examined and Raman spectroscopy reveals that the least, collateral thermal damage occurs in inked skin. Pre-application of ink reduces the laser power threshold for poration, an effect attributed to the initiation of plasma formation by thermionic electron emission from the dye in the ink. Poration under these conditions significantly increases the percutaneous permeation of caffeine in vitro. Dye-enhanced, plasma-mediated ablation of the skin is therefore a potentially advantageous approach to enhance topical/transdermal drug absorption. The combination of a fiber laser and a HC-NCF, capable of emitting and delivering femtosecond pulsed, visible light, may permit a compact poration device to be developed.


Subject(s)
Ablation Techniques , Drug Delivery Systems/methods , Lasers , Skin/metabolism , Animals , Caffeine/metabolism , Drug Delivery Systems/instrumentation , Optical Fibers , Porosity , Swine , Time Factors
5.
J Control Release ; 212: 103-12, 2015 Aug 28.
Article in English | MEDLINE | ID: mdl-26087467

ABSTRACT

The effect of incorporating the lipidic medium-chain triglyceride (MCT) into polymeric film-forming systems (FFS) for topical drug delivery has been evaluated. First, the in vitro release of betamethasone-17-valerate (BMV), a representative dermatological drug, was determined from FFS comprising either hydrophobic polyacrylate co-polymers, or hydrophilic hydroxypropyl cellulose, with and without MCT. Release was enhanced from both polymers in the presence of MCT. Atomic force microscopy imaging and nanoindentation of FFS with MCT revealed two-phase structured films with softer inclusions (0.5 to 4µm in diameter) surrounded by a more rigid structure. Chemical mapping with Raman micro-spectroscopy showed that MCT was primarily confined to the inclusions within the polymer, which predominated in the surrounding film. BMV was distributed throughout the film but was more concentrated outside the inclusions. Furthermore, while BMV dissolved better into the hydrophobic films, it was more soluble in the MCT inclusions in hydrophilic films, suggesting its increased availability for diffusion from these softer regions of the polymer and explaining the release enhancement observed. Second, ex vivo skin penetration studies clearly revealed that uptake of BMV was higher from hydrophobic FFS than that from the more hydrophilic polymer due, at least in part, to the superior anti-nucleation efficiency of the former. Drug was quickly taken up into the SC from which it then diffused continuously over a sustained period into the lower, viable skin layers. In the presence of MCT, the overall uptake of BMV was increased and provides the basis for further optimisation of FFS as simple, convenient and sustained formulations for topical therapy.


Subject(s)
Betamethasone Valerate/chemistry , Drug Delivery Systems , Polymers/chemistry , Triglycerides/chemistry , Administration, Cutaneous , Animals , Betamethasone Valerate/administration & dosage , Betamethasone Valerate/pharmacokinetics , Drug Liberation , Ear , Polymers/administration & dosage , Skin/metabolism , Skin Absorption , Swine , Triglycerides/administration & dosage
6.
J Invest Dermatol ; 133(6): 1565-71, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23223139

ABSTRACT

Atomic force microscopy (AFM) can image biological samples and characterize their mechanical properties. However, the low aspect ratio of standard AFM probes typically limits these measurements to surface properties. Here, the intracellular mechanical behavior of human corneocytes is determined using "nanoneedle" AFM probes. The method evaluates the forces experienced by a nanoneedle as it is pushed into and then retracted from the cell. Indentation loops yield the stiffness profile and information on the elastic and nonelastic mechanical properties at a specific depth below the surface of the corneocytes. A clear difference between the softer ∼50-nm-thick external layer and the more rigid internal structure of corneocytes is apparent, which is consistent with the current understanding of the structure of these cells. There are also significant variations in the mechanical properties of corneocytes from different volunteers. The small diameter of the nanoneedle allows this "mechanical tomography" to be performed with high spatial resolution, potentially offering an opportunity to detect biomechanical changes in corneocytes because of, e.g., environmental factors, aging, or dermatological pathologies.


Subject(s)
Epidermis/physiology , Epidermis/ultrastructure , Microscopy, Atomic Force/methods , Nanotechnology/methods , Skin Aging/physiology , Adult , Elasticity , Elasticity Imaging Techniques/methods , Epidermal Cells , Humans , Middle Aged , Stress, Mechanical , Surface Properties , Weight-Bearing/physiology , Young Adult
7.
Biophys J ; 98(3): 478-87, 2010 Feb 03.
Article in English | MEDLINE | ID: mdl-20141762

ABSTRACT

Understanding the structural organization and distribution of proteins in biological cells is of fundamental importance in biomedical research. The use of conventional fluorescent microscopy for this purpose is limited due to its relatively low spatial resolution compared to the size of a single protein molecule. Atomic force microscopy (AFM), on the other hand, allows one to achieve single-protein resolution by scanning the cell surface using a specialized ligand-coated AFM tip. However, because this method relies on short-range interactions, it is limited to the detection of binding sites that are directly accessible to the AFM tip. We developed a method based on magnetic (long-range) interactions and applied it to investigate the structural organization and distribution of endothelin receptors on the surface of smooth muscle cells. Endothelin receptors were labeled with 50-nm superparamagnetic microbeads and then imaged with magnetic AFM. Considering its high spatial resolution and ability to "see" magnetically labeled proteins at a distance of up to 150 nm, this approach may become an important tool for investigating the dynamics of individual proteins both on the cell membrane and in the submembrane space.


Subject(s)
Electromagnetic Fields , Microscopy, Atomic Force/methods , Microspheres , Animals , Aorta/cytology , Aorta/metabolism , Biotinylation , Cells, Cultured , Endothelin-1/metabolism , Fluorescein-5-isothiocyanate , Imaging, Three-Dimensional/methods , Male , Microscopy, Confocal , Muscle Cells/cytology , Muscle Cells/metabolism , Muscle, Smooth/cytology , Muscle, Smooth/metabolism , Rats , Rats, Wistar
8.
Nanotechnology ; 21(4): 045302, 2010 Jan 29.
Article in English | MEDLINE | ID: mdl-20009170

ABSTRACT

The use of spot-exposure electron-beam-induced deposition (EBID) to immobilize targeted nanoparticles on a substrate is demonstrated, and investigated using experiment and simulation. Nanoparticles are secured in place through the build-up of carbonaceous material that forms in the region between a particle and substrate when an energetic electron beam is focused onto the particle and projected through to the substrate. Material build-up directly affects the strength of adhesion to the surface, and can be controlled through electron dosage and beam energy. By selectively immobilizing specific particles within surface agglomerations and removing the excess, we illustrate the potential for spot-exposure EBID as a new technique for nanofabrication.

9.
Nanotechnology ; 20(28): 285308, 2009 Jul 15.
Article in English | MEDLINE | ID: mdl-19546500

ABSTRACT

Proximity effects causing thickening and bending of closely spaced, free-standing pillars grown by electron-beam-induced deposition are investigated. It is shown that growth of a new pillar induces deposition of a layer of additional material on the side of already grown pillars facing the new pillar. We present experimental results which suggest that the bending of pillars is caused by shrinkage of the newly formed layer on exposure to the primary electron beam.


Subject(s)
Nanostructures/chemistry , Nanostructures/ultrastructure , Nanotechnology/methods , Microscopy, Electron, Scanning
10.
Nanotechnology ; 19(44): 445302, 2008 Nov 05.
Article in English | MEDLINE | ID: mdl-21832725

ABSTRACT

The mechanism of electron-beam-induced immobilization of nanoparticles on a substrate has been studied both experimentally and theoretically. Experiments have been performed for the case of 200-350 nm Co-Ni nanoparticles secured to a substrate using a 30 keV electron beam. Atomic force microscopy studies reveal that the fixing occurs due to the formation of a deposit beneath the nanoparticles, causing strong bonding to the substrate, even for a thin layer. Measurements of the lateral forces required to displace the immobilized nanoparticles have shown that a deposit layer of 0.5 nm results in a tenfold increase in the bonding strength. A comparison of measured profiles with the results of computer simulations clearly reveals that the major role in the formation of the deposit is played by low-energy electrons generated by energetic primary electrons in both the nanoparticles and substrate. It is also shown that the efficiency of bonding decreases with decreasing energy of primary electrons. Different strategies for electron-beam-induced immobilization of nanoparticles and optimization of the processes are discussed.

11.
J Phys Chem B ; 109(18): 8565-9, 2005 May 12.
Article in English | MEDLINE | ID: mdl-16852011

ABSTRACT

Optical absorption and photoluminescence (PL) properties of colloidal TiO(2) nanotubes, produced by the alkali hydrothermal method, were studied at room temperature in the range 300-700 nm. Nanotubes having an internal diameter in the range 2.5-5 nm have very similar optical properties, in contrast to the expected behavior for quasi-1-D systems. This is explained by the complete thermal smearing of all 1-D effects, due to the large effective mass of charge carriers in TiO(2), resulting in an apparent 2-D behavior of TiO(2) nanotubes.

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