Unique laser coding technology to fight falsified medicines.

Based on WHO statistics, counterfeit medicines represent 10% of the global drug trade. According to Directive 2011/62/EU as regards the prevention of falsified medicines from entering into the legal supply chain, a unique identification should be put on each box of drugs to be able to track and trace them. The objective of this study is to develop a technology to mark an individual traceability code directly on the surface of the tablet. By using this technique, anyone with a camera-enabled phone and a suitable application installed should be able to authenticate these drugs. By marking the medicine's surface, patients could be protected from fake drugs. The aim of the present work was to study how different types of lasers affect the film coating of the tablet during the laser marking intervention. To sum up, the present findings may contribute to efficient and reliable laser marking solutions in the unique identification procedure. Based on our measurement results, it can be stated that the excimer UV laser is clearly the most suitable marking instrument for anti-counterfeiting coding on solid coated tablet form as this caused the least amount of chemical degradation of the polymer film.

Comparison of cerebrocortical microvascular effects of different hypoxic-ischemic insults in piglets: a laser-speckle imaging study.

The newborn pig is a widely accepted large animal model of hypoxic/ischemic (H/I) encephalopathy (HIE) of the term neonate appropriate for translational research. The methodology of the induction of H/I stress shows extensive variability of the literature, and little is known how these affect study outcome. The purpose of the present study was to determine the cerebrocortical microvascular effects of different H/I insults used in current HIE piglet models. For the semiquantitative study of cerebrocortical blood flow, we developed a methodological innovation: an operating microscope was converted into a custom-designed laser-speckle imager. Anesthetized, air-ventilated newborn pigs (n=7) were fitted with a closed cranial window. Speckle image series (2 ms, 1 Hz) were collected during baseline conditions, during transient bilateral carotid artery occlusion (BCAO), hypoxic (FiO(2)=0.1) hypoxia, hypoxia + BCAO, and asphyxia induced by suspending ventilation. Laser-speckle contrast analysis was performed off-line over parenchymal and arteriolar regions of interests, and pial arteriolar diameters were also determined for detailed analysis of cortical perfusion changes. Under normoxic conditions, transient BCAO did not affect parenchymal perfusion or pial arteriolar diameters. Hypoxia induced marked cortical hyperemia in 5 out of 7 piglets, with simultaneous increases in pial arteriolar diameters and arteriolar flow velocity, however, BCAO could not even affect these hypoxia-induced perfusion changes. In contrast to hypoxia or hypoxia + BCAO, asphyxia inevitably led also to severe cerebrocortical ischemia. In summary, acute reversible BCAO does not reduce cerebrocortical blood flow in the piglet, and thus it likely does not exacerbate the effect of hypoxic ventilation. Asphyxia elicits not only severe hypoxia, but also severe brain ischemia. These microcirculatory effects must be taken into consideration when assessing results obtained in the various HIE piglet models.

Immobilization of urease by laser techniques: synthesis and application to urea biosensors.

Urease thin films have been immobilized using matrix-assisted pulsed laser evaporation for biosensor applications in clinical diagnostics. The targets exposed to laser radiation were made of frozen composites that had been manufactured by dissolving urease in distilled water. An UV KrF* (lambda = 248 nm, tauFWHM congruent with 30 ns, nu = 10 Hz) excimer source was used for the multipulse laser irradiation of the targets that were cooled down to solidification using Peltier elements. The incident laser fluence was set at 0.4 J/cm2. The surface morphology and chemical bonding states of the laser immobilized urease thin films were investigated by atomic force microscopy and Fourier transform infrared spectroscopy. The enzymatic activity and kinetics of the immobilized urease were assayed by the Worthington method, which monitors urea hydrolysis by coupling ammonia production to a glutamate dehydrogenase reaction. Decreased absorbance was found at 340 nm and correlated with the enzymatic activity of urease.

Sub-wavelength ripples in fused silica after irradiation of the solid/liquid interface with ultrashort laser pulses.

Laser-induced backside wet etching (LIBWE) is performed using ultrashort 248 nm laser pulses with a pulse duration of 600 fs to obtain sub-wavelength laser-induced periodic surface structures (LIPSS) on the back surface of fused silica which is in contact with a 0.5 mol l(-1) solution of pyrene in toluene. The LIPSS are strictly one-dimensional patterns, oriented parallel to the polarization of the laser radiation, and have a constant period of about 140 nm at all applied laser fluences (0.33-0.84 J cm(-2)) and pulse numbers (50-1000 pulses). The LIPSS amplitude varies due to the inhomogeneous fluence in the laser spot. The LIPSS are examined with scanning electron microscopy (SEM) and atomic force microscopy (AFM). Their power spectral density (PSD) distribution is analysed at a measured area of 10 µm × 10 µm. The good agreement of the measured and calculated LIPSS periods strongly supports a mechanism based on the interference of surface-scattered and incident waves.

Regeneration of rabbit cornea following excimer laser photorefractive keratectomy: a study on gap junctions, epithelial junctions and epidermal growth factor receptor expression in correlation with cell proliferation.

Corneal wound repair was investigated in rabbits following excimer laser ablation of a 6 mm diameter and 90 microm deep disc. In the healing process particular attention was focused on the epithelium where gap junction expression and the rearrangement of desmosomes and hemidesmosomes were correlated with cell proliferation and epidermal growth factor receptor expression. Immunofluorescence-based confocal laser scanning microscopy, semithin resin section morphology and electron microscopy were utilized. In resting cornea two isotypes of gap junctions, confined to different regions in the same basal epithelial cells, were detected. Particulate connexin43 (alpha1) immunostaining was concentrated on the apical while the connexin26 type (beta2) in the baso-lateral cell membranes. This is the first report of connexin26 in the cornea. Connexin43 was found also in corneal keratocytes and endothelial cell. Since the two connexins do not form functioning heteromeric channels and have selective permeabilities they may serve alternative pathways for direct cell-cell communication in the basal cell layer. During regeneration both connexins were expressed throughout the corneal epithelium including the migrating cells. They also showed transient up-regulation 24 hr after wounding in the form of overlapping relocation to the upper cell layers. At this time, basal epithelial cells at the limbal region, adjacent to the wound and those migrating over the wounded area all expressed membrane bound epidermal growth factor receptor and they were highly proliferating. In conclusion, like in other stratified epithelia connexin26 is also expressed in the cornea. Transient up-regulation and relocation of connexins within the regenerating epithelium may reflect the involvement of direct cell-cell communication in corneal wound healing. Mitotic activity in the migrating corneal epithelial cells is also a novel finding which is probably the sign of the excessive demand for new epithelial cells in larger wounds not met alone by the proliferating limbal stock.

Atomic force microscopic study of the human cornea following excimer laser keratectomy.

The aim of this study was to examine the corneal surface structures with a new investigative method, the atomic force microscope following 193 nm excimer laser photoablation. Fresh human corneas were irradiated in vitro with an increasing number of impulses emitted by a 193 nm ArF laboratory excimer laser in order to produce either smooth flat surfaces or stair-like formations within the cornea. The corneas were investigated in a Topometrix(R) atomic force microscope in their native state. For comparison, three corneas were fixed with glutaraldehyde and processed for scanning electron microscopy. Atomic force microscopy and scanning electron microscopy revealed the same surface characteristics of photoablated corneas, though the preparation for scanning electron microscopy induced considerable shrinkage of the tissues. The layers of the cornea could be distinguished from each other and deeper ablations of the stroma produced a rougher surface. On the lateral walls of ablated stairs small droplets of ejected material could be seen with scanning electron microscope. Atomic force microscope produces three-dimensional images of the scanned native corneal surfaces and it could be a valuable tool to investigate the corneal smoothness. Our investigations have provided similar results as those obtained with scanning electron microscopy showing that the laser-ablated corneal surface remains relatively smooth. We suggest that the formation of condense droplets of ejected materials is based on hydrodynamic motions induced by boiling water solutions.

Plume emission, shock wave and surface wave formation during excimer laser ablation of the cornea.

Excimer lasers are now used for corneal surgery; however, the physical processes occurring during photoablation of the cornea are incompletely understood. High speed laser-based photographic arrangement was constructed. The temporal resolution was better than 1 ns. The setup could work as a Schlieren arrangement, which is sensitive to the refractive index change caused by the shock wave propagating in the air above the eye. With minor changes the setup was converted into a shadowgraph, which could detect the ablation plume and the waves propagating on the surface of the eye. Due to the impact of the excimer laser pulse onto the surface of the cornea, a shock wave was generated in the air. The shadowgraph clearly showed the ejection of the ablated cornea. The ejection velocity of the plume was found to be over 600 m/s. It was shown for the first time that the recoil forces of the plume are generating a wave on the surface of the eye. The laser-based high speed photographic arrangement is a powerful arrangement in the study of physical effects occurring during photoablation of the cornea.