Cellular internalization of large therapeutic agents such as proteins or nucleic acids is a challenging task because of the presence of the plasma membrane. One strategy to facilitate intracellular drug uptake is to induce transient pores in the cell membrane through physical delivery strategies. Physical approaches are attractive as they offer more generic applicability compared with viral or biochemical counterparts. Pulsed laser light can induce the endothermic carbon-steam reaction in carbon-nanoparticle suspensions to produce explosive photoacoustic effects in the surrounding medium. In this study, for the first time, these photoacoustic forces were used to transiently permeabilize the cell membrane to deliver macromolecules into cells. Intracellular delivery using this method was demonstrated in multiple cell types for uptake of small molecules, proteins and DNA. At optimized conditions, uptake was seen in up to 50% of cells with nearly 100% viability and in 90% of cells with ≥90% viability, which compared favorably with other physical methods of drug delivery. Cellular bioeffects were shown to be a consequence of laser-carbon interaction and correlated with properties of the carbon and laser, such as carbon concentration and size, laser pulse duration, wavelength, intensity and exposure time. Similar results were observed using two different lasers, a femtosecond Ti: Sapphire laser and a nanosecond Nd: YAG laser. Uptake was also shown in murine skeletal muscles in vivo with up to 40% efficiency compared to non-irradiated controls. This synergistic use of nanotechnology with advanced laser technology could provide an alternative to viral and chemical-based drug and gene delivery.

No description available.

We have investigated processes of ionization, energy absorption and subsequent explosion of atomic and molecular clusters under intense laser illumination using numerical as well as analytical methods. In particular, we focused on the response of composite clusters, those consisting of different atomic elements, to intense light pulses. Another major theme is the effect of the molecular structure of clusters on their Coulomb explosion. The action of intense laser pulses on clusters leads to fundamental, irreversible changes: they turn almost instantaneously into nanoplasmas and subsequently disintegrate into separate ions and electrons. Due to this radical transformation, remarkable new features arise. Transient cluster nanoplasmas are capable of absorbing enormous amounts of laser energy. In some cases more than 90 % of incident laser energy is absorbed by a gas of clusters with a density much smaller than that of a solid. After the efficient absorption, the energy is transformed into production of energetic ions, electrons, photons, and even neutrons. Composite clusters show especially interesting behavior when they interact with intense laser pulses. Nanoplasmas formed in composite clusters may absorb even more laser energy, than those formed in homogeneous clusters, as we demonstrate in this work. One of the most important results of this thesis is the identification of a novel type of plasma resonance. This resonance is enabled by an unusual ellipsoidal shape of the nanoplasma created during the ionization process in a helium droplet doped with just a few xenon atoms. In contrast to the conventional plasma resonance, which requires significant ion motion, here, the resonant energy absorption occurs at a remarkably fast rate, within a few laser cycles. Therefore, this resonance is not only the most efficient (like the conventional resonance), but also, perhaps, the fastest way to transfer laser energy to clusters. Recently, dedicated experimental studies of this effect were performed at the Max Planck Institute in Heidelberg. Their preliminary results confirm our prediction of a strong, avalanche-like ionization of the helium droplet with a small xenon cluster inside. A conventional plasma resonance, which relies on the cluster explosion, also exhibits interesting new properties when it occurs in a composite xenon-helium cluster with a core-shell geometry. We have revealed an intriguing double plasma resonance in this system. This was the first theoretical study of the influence of the helium embedding on the laser- driven nanoplasma dynamics. Our results demonstrate the important role of the interaction between xenon and helium parts of the cluster. Understanding this interaction is necessary in order to correctly interpret the experimental results. We have elucidated several important properties of Coulomb explosion in atomic and molecular clusters. Specifically, it was found that the kinetic energy distribution of ions after the Coulomb explosion of an atomic cluster is quite similar to the initial potential energy distribution of ions and is only weakly influenced by ion overtake effects, as was believed before. For the case of molecular hydrogen clusters, we have shown that the alignment of molecules inside the cluster affects its Coulomb explosion. Investigation of the dynamical processes in composite and molecular clusters induced by intense laser pulses is a step towards understanding them in more complex nano-objects, such as biomolecules or viruses. This is of great interest in the context of x-ray diffractive imaging of biomolecules with atomic resolution, which is one of the main goals of new x-ray free electron laser facilities.

We have investigated processes of ionization, energy absorption and subsequent explosion of atomic and molecular clusters under intense laser illumination using numerical as well as analytical methods. In particular, we focused on the response of composite clusters, those consisting of different atomic elements, to intense light pulses. Another major theme is the effect of the molecular structure of clusters on their Coulomb explosion. The action of intense laser pulses on clusters leads to fundamental, irreversible changes: they turn almost instantaneously into nanoplasmas and subsequently disintegrate into separate ions and electrons. Due to this radical transformation, remarkable new features arise. Transient cluster nanoplasmas are capable of absorbing enormous amounts of laser energy. In some cases more than 90 % of incident laser energy is absorbed by a gas of clusters with a density much smaller than that of a solid. After the efficient absorption, the energy is transformed into production of energetic ions, electrons, photons, and even neutrons. Composite clusters show especially interesting behavior when they interact with intense laser pulses. Nanoplasmas formed in composite clusters may absorb even more laser energy, than those formed in homogeneous clusters, as we demonstrate in this work. One of the most important results of this thesis is the identification of a novel type of plasma resonance. This resonance is enabled by an unusual ellipsoidal shape of the nanoplasma created during the ionization process in a helium droplet doped with just a few xenon atoms. In contrast to the conventional plasma resonance, which requires significant ion motion, here, the resonant energy absorption occurs at a remarkably fast rate, within a few laser cycles. Therefore, this resonance is not only the most efficient (like the conventional resonance), but also, perhaps, the fastest way to transfer laser energy to clusters. Recently, dedicated experimental studies of this effect were performed at the Max Planck Institute in Heidelberg. Their preliminary results confirm our prediction of a strong, avalanche-like ionization of the helium droplet with a small xenon cluster inside. A conventional plasma resonance, which relies on the cluster explosion, also exhibits interesting new properties when it occurs in a composite xenon-helium cluster with a core-shell geometry. We have revealed an intriguing double plasma resonance in this system. This was the first theoretical study of the influence of the helium embedding on the laser- driven nanoplasma dynamics. Our results demonstrate the important role of the interaction between xenon and helium parts of the cluster. Understanding this interaction is necessary in order to correctly interpret the experimental results. We have elucidated several important properties of Coulomb explosion in atomic and molecular clusters. Specifically, it was found that the kinetic energy distribution of ions after the Coulomb explosion of an atomic cluster is quite similar to the initial potential energy distribution of ions and is only weakly influenced by ion overtake effects, as was believed before. For the case of molecular hydrogen clusters, we have shown that the alignment of molecules inside the cluster affects its Coulomb explosion. Investigation of the dynamical processes in composite and molecular clusters induced by intense laser pulses is a step towards understanding them in more complex nano-objects, such as biomolecules or viruses. This is of great interest in the context of x-ray diffractive imaging of biomolecules with atomic resolution, which is one of the main goals of new x-ray free electron laser facilities.:1. Introduction 1 2. Interaction of clusters with intense laser pulses 5 2.1. Cluster formation and structure . . . . . . . . . . . . . . . . . . 5 2.1.1. Cluster formation . . . . . . . . . . . . . . . . . . . . . . 5 2.1.2. Cluster structure . . . . . . . . . . . . . . . . . . . . . . 6 2.1.3. Composite clusters . . . . . . . . . . . . . . . . . . . . . 7 2.2. Matter in intense light fields . . . . . . . . . . . . . . . . . . . . 9 2.2.1. Laser sources . . . . . . . . . . . . . . . . . . . . . . . . 9 2.2.2. Atoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 2.3. Clusters under intense laser pulses . . . . . . . . . . . . . . . . . 11 2.3.1. Three stages of intense laser-cluster interaction . . . . . 12 2.3.2. Pathways of cluster ionization and energy absorption . . 13 2.3.3. Composite clusters in intense laser fields . . . . . . . . . 14 2.4. Scenarios of cluster explosion . . . . . . . . . . . . . . . . . . . 15 2.4.1. Coulomb explosion vs. quasi-neutral expansion . . . . . 15 2.4.2. Anisotropic explosion . . . . . . . . . . . . . . . . . . . . 17 2.5. Comparison between experiment and theory . . . . . . . . . . . 18 3. Theoretical methods for intense laser-cluster interaction 21 3.1. The Hamiltonian . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.2. Survey of simulation methods . . . . . . . . . . . . . . . . . . . 22 3.2.1. Quantum methods . . . . . . . . . . . . . . . . . . . . . 22 3.2.2. Classical methods . . . . . . . . . . . . . . . . . . . . . . 23 3.3. Our method: classical microscopic molecular dynamics . . . . . 24 3.3.1. Initial configuration . . . . . . . . . . . . . . . . . . . . . 24 3.3.2. Integrating the equations of motion . . . . . . . . . . . . 26 3.3.3. Observables . . . . . . . . . . . . . . . . . . . . . . . . . 28 3.4. The role of quantum effects . . . . . . . . . . . . . . . . . . . . 31 4. Cluster nanoplasma: a statistical approach 33 4.1. Vlasov-Poisson formalism . . . . . . . . . . . . . . . . . . . . . . 33 4.2. Nanoplasma electrons at quasi-equilibrium . . . . . . . . . . . . 34 4.2.1. Self-consistent potential and electron density . . . . . . . 34 4.2.2. Energy distribution of nanoplasma electrons . . . . . . . 36 4.3. Harmonic oscillator model . . . . . . . . . . . . . . . . . . . . . 41 4.3.1. Derivation from kinetic equations . . . . . . . . . . . . . 42 4.3.2. Comparison with the molecular dynamics results . . . . 44 4.4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 5. Ionization and energy absorption in helium droplets doped with xenon clusters 47 5.1. Local ignition and anisotropic nanoplasma growth . . . . . . . . 48 5.1.1. Cluster size dependence . . . . . . . . . . . . . . . . . . 50 5.1.2. Nanoplasma resonance during its anisotropic growth . . 51 5.1.3. Range of laser frequencies and intensities . . . . . . . . . 55 5.1.4. Plasma resonance for circular polarization . . . . . . . . 56 5.1.5. Summary and future work . . . . . . . . . . . . . . . . . 57 5.2. Electron migration and its influence on the cluster expansion . . 59 5.2.1. Charging dynamics . . . . . . . . . . . . . . . . . . . . . 59 5.2.2. Explosion dynamics . . . . . . . . . . . . . . . . . . . . . 61 5.3. Interplay between nanoplasma expansion and its electronic response 63 5.3.1. Single pulse: time-dependence . . . . . . . . . . . . . . . 64 5.3.2. Two pulses: a pump-probe study . . . . . . . . . . . . . 67 5.4. Conclusions and outlook . . . . . . . . . . . . . . . . . . . . . . 71 6. Coulomb explosions of atomic and molecular clusters 75 6.1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 6.2. Analytical treatment of the Coulomb explosion . . . . . . . . . . 76 6.2.1. Steplike density profile . . . . . . . . . . . . . . . . . . . 76 6.2.2. Kinetic approach . . . . . . . . . . . . . . . . . . . . . . 79 6.2.3. Gradually decreasing initial density . . . . . . . . . . . . 83 6.3. Coulomb explosions of atomic and molecular hydrogen clusters: a molecular dynamics study . . . . . . . . . . . . . . . . . . . . 84 6.3.1. Kinetic energy distributions of ions (KEDI) . . . . . . . 85 6.3.2. Information loss during the explosion . . . . . . . . . . . 87 6.3.3. Ion overtake processes . . . . . . . . . . . . . . . . . . . 90 6.3.4. Non-radial motion of ions . . . . . . . . . . . . . . . . . 91 6.3.5. Three-body effects in Coulomb explosion . . . . . . . . . 93 6.4. Conclusions and outlook . . . . . . . . . . . . . . . . . . . . . . 96 7. Conclusions and outlook 97 7.1. Physical conclusions . . . . . . . . . . . . . . . . . . . . . . . . 97 7.2. Methodological conclusions . . . . . . . . . . . . . . . . . . . . . 99 7.3. Research perspectives . . . . . . . . . . . . . . . . . . . . . . . . 100 A. Suppression of the cluster barrier 101 B. Structure determination for Xen@Hem clusters 103 C. Calculation of the time-dependent phase shift 107 D. Potential of a uniformly charged spheroid 109 E. On the possibility of molecular alignment inside hydrogen clusters 111 Bibliography

Ein Ziel der Arbeit war die Entwicklung eines Verfahrens zur 3D-Positionierung auf Basis elektrooptischer Pseudostreckenmessung. Ein zweites Ziel war die Entwicklung eines Reflexgoniometers zur zweiachsigen Winkelmessung. Im Rahmen der Arbeit wurden die Grundlagen zur instrumentellen Umsetzung beider Verfahren erarbeitet, die Genauigkeitspotentiale ermittelt und mögliche Anwendungen für die einzelnen Schlüsseltechnologien und deren Kombination abgeleitet. In einer Prototyp-Entwicklung wurden Vorschläge für die wesentlichen Funktionselemente des räumlichen Weg- bzw. Winkelmesssystems gemacht. Hierzu gehören das kardanisch aufgehängte Etalon, die temperaturstabilisierte Laseroptik und die temperaturkalibrierte CCD der Winkelmesseinheit (Reflexgoniometer), die Systeme zur Erzeugung und Detektion ultrakurzer Laserpulse, eine elastische Optik, Möglichkeiten zur Formung des transversalen Strahlprofils, das TCSPC-System und die zur Auswertung und Kalibrierung notwendigen Algorithmen, wie z.B. die Autokollimation eines Lasers. ("Veröffentlicht von der Deutschen Geodätischen Kommission Reihe C (Dissertationen) unter der Nummer C 614 (München 2008; ISBN 3 7696 5053 0; 2; 144 S.") / One goal of the thesis was the development of a method for three-dimensional positioning based on electro-optical measurement of pseudo ranges. Another goal was the development of a reflex goniometer for biaxial angle measurement. Within the scope of this thesis the basics for the instrumental realisation of both methods were developed, the accuracy potentials were determined and possible applications for the separate key technologies and their combination were deduced. In a prototype development proposals were made for the main functional elements of the spatial distance and angle measurement systems. These include the gimbal mounted etalon, the temperature stabilised laser optics and the temperature calibrated CCD of the angle measurement device (reflex goniometer), the systems for creation and detection of ultrashort laser pulses, an elastic optical device, possibilities of transversal beam shaping, the TCSPC system and the algorithms which are necessary for analysis and calibration, e.g. the autocollimation of a laser.

Le laser à impulsions ultra-courtes constitue un procédé innovant et très avantageux pour la découpe de céramiques piézoélectriques PZT. Grâce à un fort confinement spatiotemporel de l’énergie au cours de l’interaction, ce système minimise les dégâts collatéraux et préserve l’intégrité physique du matériau sur des échelles micrométriques. Néanmoins, une propagation de faisceau mal maîtrisée, associée à des mécanismes d’interaction complexes fonction de la cible irradiée, peuvent impliquer de fortes disparités sur la qualité d’usinage. Dans le cadre d’une application industrielle donnée, ces travaux nous ont donc permis d’approfondir les principales étapes d’optimisation d’un tel procédé selon des critères de reproductibilité, de qualité et de rapidité. Pour cela, nous avons tout d’abord souligné l’influence des propriétés gaussiennes des faisceaux et de leur perturbation afin de définir la distribution énergétique au niveau des plans de focalisation. Aussi, la quantification de l’interaction via les critères de seuil et de taux d’ablation, d’incubation et de saturation a contribué à comprendre la réaction du matériau de manière macroscopique. Les problèmes méthodologiques inhérents à leurs calculs ont été mis en évidence et ont permis par la suite d’anticiper les formes d’usinage ainsi que les temps de procédé. Dans un second temps, l’optimisation des paramètres laser s’est appuyée sur des caractérisations aussi bien qualitatives pour l’aspect visuel que quantitatives avec l’estimation de la stoechiométrie et des contraintes résiduelles au niveau des flancs d’usinage. Nous avons en outre tiré profit de la piézoélectricité afin de développer une méthode d’observation in situ de la réponse à l’onde de choc laser contribuant à la compréhension des fissurations apparentes. Nous proposons au terme de ce travail un jeu de paramètres optimal pour la découpe de PZT assurant une bonne répétabilité du procédé tout en minimisant les défauts d’usinage comme la fissuration, les dépôts de surface et les irrégularités de bords. Des essais sur la mise en forme spatio-temporelle de faisceau sont enfin abordés principalement en tant que perspective d’accélération du procédé et encouragent son utilisation pour une future industrialisation / Lasers delivering ultrashort pulses are innovative and very attractive tools for cutting piezoelectric PZT ceramics. Thanks to an efficient spatiotemporal confinement of the energy during the interaction, these systems reduce collateral damage and preserve the physical integrity of the material on a micrometric scale. Nevertheless, uncontrolled beam propagation associated with complex interaction mechanisms depending on the irradiated target can involve large disparities on machining quality. In the context of an industrial application, this study describes the main steps of optimization of such a process according to criteria of reproducibility, quality and speed. To this purpose, we first pointed out the influence of Gaussian beam properties and their disturbance to define the energy distribution at focal planes. Thus, the quantification of the interaction with the ablation threshold, the ablation rate, incubation and saturation helped to understand the reaction of the material macroscopically. Methodological issues coming from their calculations have been highlighted while machining shapes and processing times were anticipated. Secondly, the optimization of laser parameters was based on both qualitative and quantitative characterizations. Electronic microscopy was rather used for visual appreciations whereas stoichiometry and residual stress estimations were employed to quantify the quality of side walls. We also took benefit from piezoelectricity to develop an in situ observation method which succeeded in detecting the electrical response to the laser shock wave and mainly contributed to the understanding of visible cracks. We finally propose an optimum set of parameters for cutting PZT ensuring good repeatability of the process while minimizing machining defects such as cracking, surface recast and jagged sides. Tests with spatiotemporal beam shaping were finally presented primarily as perspectives of processing time decrease so as to promote its use for future industrialization

Ein Ziel der Arbeit war die Entwicklung eines Verfahrens zur 3D-Positionierung auf Basis elektrooptischer Pseudostreckenmessung. Ein zweites Ziel war die Entwicklung eines Reflexgoniometers zur zweiachsigen Winkelmessung. Im Rahmen der Arbeit wurden die Grundlagen zur instrumentellen Umsetzung beider Verfahren erarbeitet, die Genauigkeitspotentiale ermittelt und mögliche Anwendungen für die einzelnen Schlüsseltechnologien und deren Kombination abgeleitet. In einer Prototyp-Entwicklung wurden Vorschläge für die wesentlichen Funktionselemente des räumlichen Weg- bzw. Winkelmesssystems gemacht. Hierzu gehören das kardanisch aufgehängte Etalon, die temperaturstabilisierte Laseroptik und die temperaturkalibrierte CCD der Winkelmesseinheit (Reflexgoniometer), die Systeme zur Erzeugung und Detektion ultrakurzer Laserpulse, eine elastische Optik, Möglichkeiten zur Formung des transversalen Strahlprofils, das TCSPC-System und die zur Auswertung und Kalibrierung notwendigen Algorithmen, wie z.B. die Autokollimation eines Lasers. ("Veröffentlicht von der Deutschen Geodätischen Kommission Reihe C (Dissertationen) unter der Nummer C 614 (München 2008; ISBN 3 7696 5053 0; 2; 144 S.") / One goal of the thesis was the development of a method for three-dimensional positioning based on electro-optical measurement of pseudo ranges. Another goal was the development of a reflex goniometer for biaxial angle measurement. Within the scope of this thesis the basics for the instrumental realisation of both methods were developed, the accuracy potentials were determined and possible applications for the separate key technologies and their combination were deduced. In a prototype development proposals were made for the main functional elements of the spatial distance and angle measurement systems. These include the gimbal mounted etalon, the temperature stabilised laser optics and the temperature calibrated CCD of the angle measurement device (reflex goniometer), the systems for creation and detection of ultrashort laser pulses, an elastic optical device, possibilities of transversal beam shaping, the TCSPC system and the algorithms which are necessary for analysis and calibration, e.g. the autocollimation of a laser.

In der vorliegenden Arbeit werden die nichtlinearen optischen Eigenschaften der Materialien Lithiumniobat und Di-Zinn-Hexathiohypodiphosphat aufgrund der Suszeptibilität 3. Ordnung und kleiner Polaronen untersucht. Zudem wird gezeigt, dass die Interferenz verschiedenfarbiger Laserpulse die Aufzeichnung von statischen und dynamischen holographischen Gittern ermöglicht. Ein Teil dieser Arbeit ist in den im Anhang angegebenen 6 Publikationen bereits veröffentlicht. Lithiumniobat wird mit einer Erweiterung des Z-Scan Experiments untersucht, welches die Pulslängenabhängige Messung der nichtlinearen Absorption und der nichtlinearen Brechungsindexänderung ermöglicht. Dabei konnte festgestellt werden, dass bei sehr kurzen Pulslängen von 70 fs ein Effekt der Polaronen auf die nichtlineare Absorption vernachlässigbar ist und die Zwei-Photonen-Absorption die nichtlineare Absorption dominiert. Mit größerer Pulslänge gibt es allerdings Abweichungen zwischen der Theorie der Zwei-Photonen-Absorption und den Messergebnissen. Mit der Entwicklung eines Polaronen-Anregungs-Modells, welches eine polaronische Absorption aufgrund wiederholtem optisch induziertem Hopping annimmt, konnte dieser Effekt konsistent erklärt werden. Die Messungen der nichtlinearen Brechungsindexänderung lassen darauf schließen, dass sowohl freie Ladungsträger als auch kleine Polaronen neben der Suszeptibilität 3. Ordnung einen Einfluss auf die Brechungsindexänderung haben, da eine nichtlineare Abhängigkeit von der Intensität auch bei Pulslängen von 70 fs festgestellt werden konnte. Analog dazu konnte in Di-Zinn-Hexathiohypodiphosphat ein großer Zwei-Photonen-Absorptionskoeffizient festgestellt werden, welcher für Photonenenergien nahe der Bandkante Werte zeigt, die größer sind als theoretischen Überlegungen zeigen. Eine transiente Absorption nach optischer Anregung, gemessen durch ein Anreg-Abtast-Experiment, sowie Literatur legen nahe, dass in Di-Zinn-Hexathiohypodiphosphat gebundene Lochpolaronen durch optische Anregung entstehen können. Durch den hohen Zwei-Photonen-Absorptionskoeffizienten konnte das Aufzeichnen eines kontrastreichen, dynamischen Amplitudengitters mittels Femtosekundenpulsen gezeigt und nachgewiesen werden. Die Kürze der Femtosekundenpulse ermöglicht aber nicht nur das Aufzeichnen eines Zwei-Photonen-Absorptionsgitters aufgrund der hohen Intensitäten, sondern erlaubt zudem die Beobachtung von Interferenz zwischen verschiedenfarbigen Pulsen. In der Zeitspanne der Pulslänge beträgt die Bewegung der Interferenzstreifen, welche in der Größenordnung der Lichtgeschwindigkeit liegt, nur ein Bruchteil der Streifendistanz, sodass das Interferenzmuster eingefroren und beobachtbar erscheint. Somit lassen sich statische Hologramme in holographischen Filmen, wie auch dynamische Hologramme aufzeichnen. Über ein dynamisches holographisches Gitter mittels Zwei-Photonen-Absorption konnte so eine Frequenzkonversion durch Dopplerverschiebung in Lithiumniobat gezeigt werden.