Three-dimensional writing inside silicon using a 2-µm picosecond fiber laser

International audienc

Lot-to-lot consistency of a tetravalent dengue vaccine in healthy adults in Australia: a randomised study

Background: The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vac-cine (CYD-TDV) has undergone extensive clinical trials. Here safety and consistency of immunogenicityof phase III manufacturing lots of CYD-TDV were evaluated and compared with a phase II lot and placeboin a dengue-naïve population.Methods: Healthy 18–60 year-olds were randomly assigned in a 3:3:3:3:1 ratio to receive three sub-cutaneous doses of either CYD-TDV from any one of three phase III lots or a phase II lot, or placebo,respectively in a 0, 6, 12 month dosing schedule. Neutralising antibody geometric mean titres (PRNT50GMTs) for each of the four dengue serotypes were compared in sera collected 28 days after the thirdvaccination—equivalence among lots was demonstrated if the lower and upper limits of the two-sided95% CIs of the GMT ratio were ≥0.5 and ≤2.0, respectively.Results: 712 participants received vaccine or placebo and 614 (86%) completed the study; 17 (2.4%) par-ticipants withdrew after adverse events. Equivalence of phase III lots was demonstrated for 11 of 12pairwise comparisons. One of three comparisons for serotype 2 was not statistically equivalent. GMTsfor serotype 2 in phase III lots were close to each other (65.9, 44.1 and 58.1, respectively).Conclusions: Phase III lots can be produced in a consistent manner with predictable immune responseand acceptable safety profile similar to previously characterised phase II lots. The phase III lots maybe considered as not clinically different as statistical equivalence was shown for serotypes 1, 3 and 4across the phase III lots. For serotype 2, although equivalence was not shown between two lots, the GMTsobserved in the phase III lots were consistently higher than those for the phase II lot. As such, in our view,biological equivalence for all serotypes was demonstrated.Joseph Torresi, Leon G. Heron, Ming Qiao, Joanne Marjason, Laurent Chambonneau, Alain Bouckenooghe, Mark Boaz, Diane van der Vliet, Derek Wallace, Yanee Hutagalung, Michael D. Nissen, Peter C. Richmon

PLoS One

OBJECTIVE: To evaluate the association of rainy season with overall dengue disease incidence and with the efficacy of the Sanofi Pasteur recombinant, live, attenuated, tetravalent vaccine (CYD-TDV) in two randomized, controlled multicenter phase III clinical trials in Asia and Latin America. METHODS: Rainy seasons were defined for each study site using climatological information from the World Meteorological Organization. The dengue attack rate in the placebo group for each study month was calculated as the number of symptomatic, virologically-confirmed dengue events in a given month divided by the number of participants at risk in the same month. Time-dependent Cox proportional hazard models were used to test whether rainy season was associated with dengue disease and whether it modified vaccine efficacy in each of the two trials and in both of the trials combined. FINDINGS: Rainy season, country, and age were all significantly associated with dengue disease in both studies. Vaccine efficacy did not change during the rainy season in any of the analyses. CONCLUSIONS: Although dengue transmission and exposure are expected to increase during the rainy season, our results indicate that CYD-TDV vaccine efficacy remains constant throughout the year in endemic regions

Quantitative-phase microscopy of nanosecond laser-induced micro-modifications inside silicon

International audienceLaser-induced permanent modification inside silicon has been recently demonstrated by using tightly focused nanosecond sources at a 1550 nm wavelength. We have developed a quantitative-phase microscope operating in the near-infrared domain to characterize the laser-induced modifications deep into silicon. By varying the number of applied laser pulses and the energy, we observe porous and densified regions in the focal region. The observed changes are associated with refractive index variations jΔnj exceeding 10 −3 , enough to envision the laser writing of optical functionalities inside silicon

Inscribing diffraction gratings in bulk silicon with nanosecond laser pulses

International audienceDiffraction gratings are transversally inscribed in the bulk of monolithic crystalline silicon with infrared nanosecond laser pulses. Nanoscale material analyses of the modifications composing the gratings show that they rely on laser-induced stress associated with a positive refractive index change as confirmed with phase-shift interferometry. Characterizations of the optical properties of the gratings, including the diffraction angles and the efficiency of the different orders, are carried out. The refractive index change obtained from these measurements is in good agreement with the phase-shift measurements. Finally, we show that the grating diffraction efficiency depends strongly on the laser writing speed. Ultrafast laser pulses (i.e., in the femtosecond regime) offer the possibility to tailor the properties of glasses for writing wave-guides [1], storing data eternally [2], and inducing second-harmonic generation [3], for instance. By inscribing permanent diffraction gratings in the bulk of fused silica, Sudrie et al. have demonstrated that the control of the refractive index is essential for the functionalization of the material [4]. Transposing this technique to crystalline silicon (c-Si) would be of broad interest for applications in silicon photonics, terahertz physics, and Raman silicon lasers [5]. Moreover, the laser inscription of dif-fraction gratings in this semiconductor material would open the path to the writing of Bragg gratings, as it has existed in glasses for decades [6]. However, the main issue associated with the interaction between infrared (IR) femtosecond laser pulses and the bulk c-Si through a plane surface sample is the delo-calization of the energy mainly due to plasma defocusing [7]. To date, three strategies have been adopted for overcoming these limitations and functionalizing c-Si. The first one relies on femtosecond irradiation through a spherical interface for completely suppressing the refraction at the surface [8]. The second strategy consists of a femtosecond irradiation at a high repetition rate (250 kHz) provoking cumulative effects [9]. Finally, the much less costly third approach employs pulses with a duration on the order of or higher than 1 ps for drastically reducing the nonlinear and plasma effects protecting the bulk of c-Si [10-12]. The underlying mechanisms are the production of a dense plasma induced by two-photon absorption followed by high-temperature hydrodynamic phenomena. Indeed, analyses of the laser-induced modifications have revealed that these pulses are able to produce a wide variety of material structures from voids to densified phases [13-16]. Therefore, this emerging long pulse duration regime could be suitable for functionalizing c-Si in the volume. Recently, Tokel et al. have suggested the possibility to inscribe gratings based on a negative refractive index change inside silicon for evaluating the efficiency of holograms written by back-reflected nanosecond laser pulses [11]. However, no characterizations of such components were provided. In this Letter, we demonstrate the inscription of diffraction gratings in the bulk of c-Si with nanosecond pulses at 0.01 mm/s writing speed and analyze their optical properties. Material characterizations of the laser-written lines composing the gratings show that the modifications consist of stress, as confirmed by quantitative phase-shift interferometry which, moreover, gives access to a refractive index change of 3.6 × 10 −3. The injection of IR continuous-wave (CW) light in the gratings enables us to evaluate their optical properties in terms of angles and diffraction efficiency of the different orders. Moreover, the measurements of the grating geometry, as well as the diffraction efficiency, allow us to retrieve a theoretical value for the refractive index change which is consistent with the one found by phase-shift measurements. Finally, gratings inscribed at 0.5 mm/s exhibit a mediocre diffraction efficiency, which is explained by the morphology of the written lines and confirms that the adjustment of the writing speed is paramount for optimizing the function given to the material. The experimental setup employed for writing diffraction gratings inside c-Si is schematically depicted in Fig. 1. It relies on 5 ns duration (full width at half-maximum) Gaussian laser pulses (in red) at a 1.55 μm wavelength and a 1 kHz repetition rate emitted by an Er-doped fiber laser (MWTech, PFL-1550). The beam is focused inside a 1 mm thick (100)-oriented mono-lithic c-Si sample by means of an objective lens of numerical aperture NA 0.7. At the focus positioned at the center of the sample, the beam is Gaussian with a waist w 0 1.4 μm Letter Vol. 43, No. 24 / 15 December 2018 / Optics Letters 6069 0146-9592/18/246069-04 Journa

Writing waveguides inside monolithic crystalline silicon with nanosecond laser pulses

International audienceDirect three-dimensional (3D) laser writing of waveguides is highly advanced in a wide range of bandgap materials, but has no equivalent in silicon so far. We show that nanosecond laser single-pass irradiation is capable of producing channel micro-modifications deep into crystalline silicon. With an appropriate shot overlap, a relative change of the refractive index exceeding 10-3 is obtained without apparent nonuniformity at the micrometer scale. Despite the remaining challenge of propagation losses, we show that the created structures form, to the best of our knowledge, the first laser-written waveguides in the bulk of monolithic silicon samples. This paves the way toward the capability of producing 3D architectures for the rapidly growing field of silicon photonics. (C) 2016 Optical Society of Americ

Positive- and negative-tone structuring of crystalline silicon by laser-assisted chemical etching

International audienceWe demonstrate a structuring method for crystalline silicon using nanosecond laser internal irradiation followed by chemical etching. We show a dramatic dependence of the etch rate on the laser-writing speed. Enhanced isotropic etch rates of silicon by laser-induced internal damage were recently demonstrated with strong acids, but our results add the possibility to obtain reduced etch rates leading to different topographies. Material analyses indicate the possibility to efficiently produce high-aspect ratio channels, thanks to laser-induced porosities, as well as silicon micro-bumps due to highly stressed regions. This holds promises for fabricating microfluidic, photovoltaic, and micro-electromechanical systems

Competing Nonlinear Delocalization of Light for Laser Inscription Inside Silicon with a 2- µ m Picosecond Laser

International audienceThe metrology of laser-induced damage usually finds a single transition from 0% to 100% damage probability when progressively increasing the laser energy in experiments. We observe that picosecond pulses at 2-µm wavelength focused inside silicon provide a response that strongly deviates from this. Supported by nonlinear propagation simulations and energy flow analyses, we reveal an increased light delocalization for near critical power conditions. This leads to a nonmonotonic evolution of the peak delivered fluence as a function of the incoming pulse of the energy, a situation more complex than the clamping of the intensity until now observed in ultrafast regimes. Compared to femtosecond lasers, our measurements show that picosecond sources lead to reduced thresholds for three-dimensional (3D) writing inside silicon that is highly desirable. However, strong interplays between nonlinear effects persist and should not be ignored for the performance of future technological developments. We illustrate this aspect by carefully retrieving from the study the conditions for a demonstration of 3D data inscription inside a silicon wafer

Transverse ultrafast laser inscription in bulk silicon

In-volume ultrafast laser direct writing of silicon is generally limited by strong nonlinear propagation effects preventing the initiation of modifications. By employing a triple-optimization procedure in the spectral, temporal and spatial domains, we demonstrate that modifications can be repeatably produced inside silicon. Our approach relies on irradiation at $\approx 2$-$\mu$m wavelength with temporally-distorted femtosecond pulses. These pulses are focused in a way that spherical aberrations of different origins counterbalance, as predicted by point spread function analyses and in good agreement with nonlinear propagation simulations. We also establish the laws governing modification growth on a pulse-to-pulse basis, which allows us to demonstrate transverse inscription inside silicon with various line morphologies depending on the irradiation conditions. We finally show that the production of single-pulse repeatable modifications is a necessary condition for reliable transverse inscription inside silicon.Comment: 13 pages, 12 figure