Jérôme Extermann

Harmonic nanocrystals for biolabeling: a survey of optical properties and biocompatibility.

Nonlinear optical nanocrystals have been recently introduced as a promising alternative to fluorescent probes for multiphoton microscopy. We present for the first time a complete survey of the properties of five nanomaterials (KNbO(3), LiNbO(3), BaTiO(3), KTP, and ZnO), describing their preparation and stabilization and providing quantitative estimations of their nonlinear optical response. In the light of their prospective use as biological and clinical markers, we assess their biocompatibility on human healthy and cancerous cell lines. Finally, we demonstrate the great potential for cell imaging of these inherently nonlinear probes in terms of optical contrast, wavelength flexibility, and signal photostability.

Nanodoublers as deep imaging markers for multi-photon microscopy

We demonstrate the possibility to excite second-harmonic (SH) active Fe(IO(3))(3) nanocrystals with two distinct laser sources at 800 and 1550 nm, and we show, by a complementary experimental and numerical study, how the wavelength flexibility inherent to non-phase-matched SH nanoparticles can be efficiently exploited to increase imaging penetration depth of markers embedded in biological samples.

Nano-FROG: Frequency Resolved Optical Gating by a nanometric object

We present a technique to characterize ultrashort pulses at the focal plane of a high numerical aperture objective with unprecedented spatial resolution, by performing a FROG measurement with a single nanocrystal as nonlinear medium. This approach can be extended to develop novel phase-sensitive techniques in laser scanning microscopy, probing the microscopic environment by monitoring phase and amplitude distortions of femtosecond laser pulses.

High‐Speed Tracking of Murine Cardiac Stem Cells by Harmonic Nanodoublers

Potassium niobate nonlinear nanoparticles are used for the first time to monitor the evolution of embryonic stem cells (ESC) by second harmonic microscopy. These particles feature the complete absence of photo-bleaching and unlimited excitation wavelength flexibility. The potential of this approach is made evident for tissue-regeneration studies and applications, by capturing a high-speed movie of ESC-derived cardiomyocytes autonomously beating within a cluster. Time-resolved data are analyzed to retrieve 3D information of the contraction pattern at the cellular level.

32TW atmospheric white-light laser

Ultrahigh power laser pulses delivered by the Alise beamline (26J, 32TW pulses) have been sent vertically into the atmosphere. The highly nonlinear propagation of the beam in the air gives rise to more than 400 self-guided filaments. This extremely powerful bundle of laser filaments generates a supercontinuum propagating up to the stratosphere, beyond 20km. This constitutes the highest power “atmospheric white-light laser” to date.

Spectral phase, amplitude, and spatial modulation from ultraviolet to infrared with a reflective MEMS pulse shaper

We describe the performance of a reflective pulse-shaper based on a Micro-ElectroMechanical System (MEMS) linear mirror array. It represents a substantial upgrade of a preceding release [Opt. Lett. 35, 3102 (2010)] as it allows simultaneous piston and tilt mirror motion, allowing both phase- and binary amplitude-shaping with no wavelength restriction. Moreover, we show how the combination of in-axis and tilt movement can be used for active correction of spatial chirp.

Ultraviolet and near-infrared femtosecond temporal pulse shaping with a new high-aspect-ratio one-dimensional micromirror array

We demonstrate the capabilities of a new optical microelectromechanical systems device that we specifically developed for broadband femtosecond pulse shaping. It consists of a one-dimensional array of 100 independently addressable, high-aspect-ratio micromirrors with up to 3 μm stroke. We apply linear and quadratic phase modulations demonstrating the temporal compression of 800 and 400 nm pulses. Because of the devices surface flatness, stroke, and stroke resolution, phase shaping over an unprecedented bandwidth is attainable.

Design, simulation, fabrication, packaging, and characterization of a MEMS-based mirror array for femtosecond pulse-shaping in phase and amplitude

We present an in-detail description of the design, simulation, fabrication, and packaging of a linear micromirror array specifically designed for temporal pulse shaping of ultrashort laser pulses. The innovative features of this device include a novel comb-drive actuator allowing both piston and tilt motion for phase- and amplitude-shaping, and an X-shaped laterally reinforced spring preventing lateral snap-in while providing high flexibility for both degrees of freedom.

Identification of biological microparticles using ultrafast depletion spectroscopy

We show how an ultrafast pump-pump excitation induces strong fluorescence depletion in biological samples, such as bacteria-containing droplets, in contrast with fluorescent interferents, such as polycyclic aromatic compounds, despite similar spectroscopic properties. Application to the optical remote discrimination of biotic versus non-biotic particles is proposed. Further improvement is required to allow the discrimination of one pathogenic among other non-pathogenic micro-organisms. This improved selectivity may be reached with optimal coherent control experiments, as discussed in the paper.

Longitudinal three-dimensional visualisation of autoimmune diabetes by functional optical coherence imaging.

Aims/hypothesisIt is generally accepted that structural and functional quantitative imaging of individual islets would be beneficial to elucidate the pathogenesis of type 1 diabetes. We here introduce functional optical coherence imaging (FOCI) for fast, label-free monitoring of beta cell destruction and associated alterations of islet vascularisation.MethodsNOD mouse and human islets transplanted into the anterior chamber of the eye (ACE) were imaged with FOCI, in which the optical contrast of FOCI is based on intrinsic variations of the index of refraction resulting in a faster tomographic acquisition. In addition, the phase sensitivity allows simultaneous label-free acquisition of vascularisation.ResultsWe demonstrate that FOCI allows longitudinal quantification of progressive autoimmune insulitis, including the three-dimensional quantification of beta cell volume, inflammation and vascularisation. The substantially increased backscattering of islets is dominated by the insulin–zinc nanocrystals in the beta cell granules. This translates into a high specificity for the functional beta cell volume of islets. Applying FOCI to a spontaneous mouse model of type 1 diabetes, we quantify the modifications of the pancreatic microvasculature accompanying the progression of diabetes and reveal a strong correlation between increasing insulitis and density of the vascular network of the islet.Conclusions/interpretationFOCI provides a novel imaging technique for investigating functional and structural diabetes-induced alterations of the islets. The label-free detection of beta cell volume and infiltration together with vascularisation offers a unique extension to study ACE-transplanted human islets. These results are contributing to a deeper understanding of human islet transplant rejection and label-free in vivo monitoring of drug efficacy.