Subpicosecond pre-plasma dynamics of a high contrast, ultraintense laser-solid target interaction.

Using the spectral interferometry technique, we measured subpicosecond time-resolved pre-plasma scale lengths and early expansion (<12 ps) of the plasma produced by a high intensity (6 × 1018 W/cm2) pulse with high contrast (109). We measured pre-plasma scale lengths in the range of 3-20 nm, before the arrival of the peak of the femtosecond pulse. This measurement plays a crucial role in understanding the mechanism of laser coupling its energy to hot electrons and is hence important for laser-driven ion acceleration and the fast ignition approach to fusion.

Efficient second-harmonic generation of a high-energy, femtosecond laser pulse in a lithium triborate crystal.

We demonstrate the highest efficiency (∼80%) second harmonic generation of joule level, 27 fs, high-contrast pulses in a type-I lithium triborate (LBO) crystal. In comparison, potassium dihydrogen phosphate gives a maximum efficiency of 26%. LBO thus offers high-intensity (>1018-19W/cm2), ultra-high contrast femtosecond pulses, which have great potential for high energy density science and applications, particularly with nanostructured targets.

Recombination of Protons Accelerated by a High Intensity High Contrast Laser.

Short pulse, high contrast, intense laser pulses incident onto a solid target are not known to generate fast neutral atoms. Experiments carried out to study the recombination of accelerated protons show a 200 times higher neutralization than expected. Fast neutral atoms can contribute to 80% of the fast particles at 10 keV, falling rapidly for higher energy. Conventional charge transfer and electron-ion recombination in a high density plasma plume near the target is unable to explain the neutralization. We present a model based on the copropagation of electrons and ions wherein recombination far away from the target surface accounts for the experimental measurements. A novel experimental verification of the model is also presented. This study provides insights into the closely linked dynamics of ions and electrons by which neutral atom formation is enhanced.

Mapping the Damping Dynamics of Mega-Ampere Electron Pulses Inside a Solid.

We report the lifetime of intense-laser (2×10^{19} W/cm^{2}) generated relativistic electron pulses in solids by measuring the time evolution of their Cherenkov emission. Using a picosecond resolution optical Kerr gating technique, we demonstrate that the electrons remain relativistic as long as 50 picoseconds-more than 1000 times longer than the incident light pulse. Numerical simulations of the propagation of relativistic electrons and the emitted Cherenkov radiation with Monte Carlo geant4 package reproduce the striking experimental findings.

Intense femtosecond laser driven collimated fast electron transport in a dielectric medium-role of intensity contrast.

Ultra-high intensity (> 1018 W/cm2), femtosecond (~30 fs) laser induced fast electron transport in a transparent dielectric has been studied for two laser systems having three orders of magnitude different peak to pedestal intensity contrast, using ultrafast time-resolved shadowgraphy. Use of a 400 nm femtosecond pulse as a probe enables the exclusive visualization of the dynamics of highest density electrons (> 7 × 1021 cm-3) observed so far. High picosecond contrast (~109) results in greater coupling of peak laser energy to the plasma electrons, enabling long (~1 mm), collimated (divergence angle ~2°) transport of fast electrons inside the dielectric medium at relativistic speeds (~0.66c). In comparison, the laser system with a contrast of ~106 has a large pre-plasma, limiting the coupling of laser energy to the solid and yielding limited fast electron injection into the dielectric. In the lower contrast case, bulk of the electrons expand as a cloud inside the medium with an order of magnitude lower speed than that of the fast electrons obtained with the high contrast laser. The expansion speed of the plasma towards vacuum is similar for the two contrasts.

Enhanced x-ray emission from nano-particle doped bacteria.

Recently, it has been greatly appreciated that intense light matter interaction is modified due to the nano- and microstructures in the target by--surface plasmons, laser energy localization scattering etc. Extreme laser intensities produce dense plasmas and collective mechanisms generate energetic electrons, ions and hard x-rays. Recently, it is postulated that the anharmonic electron motion, driven by ultrashort, high-intensity laser pulses, provides a universal mechanism for the laser absorption. Here, we provide the first demonstration of anharmonic-resonance-aided high laser-absorption in a biological system. At intensities of ∼ 10¹6⁻¹8 W/cm², 40 fs pulses excite a plasma formed with E. coli bacteria. The density-inhomogeneities due to the micro- and nanostructures in the bacterial target increase anharmonic resonance (AHR) heating and result in a 104-fold enhancement in the hard x-ray yield compared to plain solid targets. These observations lead to novel high-energy x-ray sources that have implications to lithography, imaging and medical applications.

Terahertz acoustics in hot dense laser plasmas.

We present a hitherto unobserved facet of hydrodynamics, namely the generation of an ultrahigh frequency acoustic disturbance in the terahertz frequency range, whose origins are purely hydrodynamic in nature. The disturbance is caused by differential flow velocities down a density gradient in a plasma created by a 30 fs, 800 nm high-intensity laser (∼5×10(16) W/cm(2)). The picosecond scale observations enable us to capture these high frequency oscillations (1.9±0.6 THz) which are generated as a consequence of the rapid heating of the medium by the laser. Adoption of two complementary techniques, namely pump-probe reflectometry and pump-probe Doppler spectrometry provides unambiguous identification of this terahertz acoustic disturbance. Hydrodynamic simulations well reproduce the observations, offering insight into this process.

Direct observation of turbulent magnetic fields in hot, dense laser produced plasmas.

Turbulence in fluids is a ubiquitous, fascinating, and complex natural phenomenon that is not yet fully understood. Unraveling turbulence in high density, high temperature plasmas is an even bigger challenge because of the importance of electromagnetic forces and the typically violent environments. Fascinating and novel behavior of hot dense matter has so far been only indirectly inferred because of the enormous difficulties of making observations on such matter. Here, we present direct evidence of turbulence in giant magnetic fields created in an overdense, hot plasma by relativistic intensity (10(18) W/cm(2)) femtosecond laser pulses. We have obtained magneto-optic polarigrams at femtosecond time intervals, simultaneously with micrometer spatial resolution. The spatial profiles of the magnetic field show randomness and their k spectra exhibit a power law along with certain well defined peaks at scales shorter than skin depth. Detailed two-dimensional particle-in-cell simulations delineate the underlying interaction between forward currents of relativistic energy "hot" electrons created by the laser pulse and "cold" return currents of thermal electrons induced in the target. Our results are not only fundamentally interesting but should also arouse interest on the role of magnetic turbulence induced resistivity in the context of fast ignition of laser fusion, and the possibility of experimentally simulating such structures with respect to the sun and other stellar environments.

Ultrafast optics of solid density plasma using multicolor probes.

We present time-resolved reflectivity and transmissivity of hot, overdense plasma by employing a multicolor probe beam, consisting of harmonics at wavelengths of 800 nm, 400 nm and 266 nm. The hot-dense plasma, formed by exciting a fused silica target with a 30 fs, 2 × 10(17) W cm(-2) intensity pulse, shows a sub-picosecond transition in reflectivity (transmissivity), and a wavelength-dependent fall (rise) in the reflected (transmitted) signal. A simple model of probe absorption in the plasma via inverse bremsstrahlung is used to determine electron-ion collision frequency at different plasma densities.

PolySialic Acid Nanoparticles Actuate Complement-Factor-H-Mediated Inhibition of the Alternative Complement Pathway: A Safer Potential Therapy for Age-Related Macular Degeneration.

The alternative pathway of the complement system is implicated in the etiology of age-related macular degeneration (AMD). Complement depletion with pegcetacoplan and avacincaptad pegol are FDA-approved treatments for geographic atrophy in AMD that, while effective, have clinically observed risks of choroidal neovascular (CNV) conversion, optic neuritis, and retinal vasculitis, leaving room for other equally efficacious but safer therapeutics, including Poly Sialic acid (PSA) nanoparticle (PolySia-NP)-actuated complement factor H (CFH) alternative pathway inhibition. Our previous paper demonstrated that PolySia-NP inhibits pro-inflammatory polarization and cytokine release. Here, we extend these findings by investigating the therapeutic potential of PolySia-NP to attenuate the alternative complement pathway. First, we show that PolySia-NP binds CFH and enhances affinity to C3b. Next, we demonstrate that PolySia-NP treatment of human serum suppresses alternative pathway hemolytic activity and C3b deposition. Further, we show that treating human macrophages with PolySia-NP is non-toxic and reduces markers of complement activity. Finally, we describe PolySia-NP-treatment-induced decreases in neovascularization and inflammatory response in a laser-induced CNV mouse model of neovascular AMD. In conclusion, PolySia-NP suppresses alternative pathway complement activity in human serum, human macrophage, and mouse CNV without increasing neovascularization.

Comprehensive Ocular and Systemic Safety Evaluation of Polysialic Acid-Decorated Immune Modulating Therapeutic Nanoparticles (PolySia-NPs) to Support Entry into First-in-Human Clinical Trials.

An inflammation-resolving polysialic acid-decorated PLGA nanoparticle (PolySia-NP) has been developed to treat geographic atrophy/age-related macular degeneration and other conditions caused by macrophage and complement over-activation. While PolySia-NPs have demonstrated pre-clinical efficacy, this study evaluated its systemic and intraocular safety. PolySia-NPs were evaluated in vitro for mutagenic activity using Salmonella strains and E. coli, with and without metabolic activation; cytotoxicity was evaluated based on its interference with normal mitosis. PolySia-NPs were administered intravenously in CD-1 mice and Sprague Dawley rats and assessed for survival and toxicity. Intravitreal (IVT) administration in Dutch Belted rabbits and non-human primates was assessed for ocular or systemic toxicity. In vitro results indicate that PolySia-NPs did not induce mutagenicity or cytotoxicity. Intravenous administration did not show clastogenic activity, effects on survival, or toxicity. A single intravitreal (IVT) injection and two elevated repeat IVT doses of PolySia-NPs separated by 7 days in rabbits showed no signs of systemic or ocular toxicity. A single IVT inoculation of PolySia-NPs in non-human primates demonstrated no adverse clinical or ophthalmological effects. The demonstration of systemic and ocular safety of PolySia-NPs supports its advancement into human clinical trials as a promising therapeutic approach for systemic and retinal degenerative diseases caused by chronic immune activation.

PolySialic acid-nanoparticles inhibit macrophage mediated inflammation through Siglec agonism: a potential treatment for age related macular degeneration.

Age-related macular degeneration (AMD) is a chronic, progressive retinal disease characterized by an inflammatory response mediated by activated macrophages and microglia infiltrating the inner layer of the retina. In this study, we demonstrate that inhibition of macrophages through Siglec binding in the AMD eye can generate therapeutically useful effects. We show that Siglecs-7, -9 and -11 are upregulated in AMD associated M0 and M1 macrophages, and that these can be selectively targeted using polysialic acid (PolySia)-nanoparticles (NPs) to control dampen AMD-associated inflammation. In vitro studies showed that PolySia-NPs bind to macrophages through human Siglecs-7, -9, -11 as well as murine ortholog Siglec-E. Following treatment with PolySia-NPs, we observed that the PolySia-NPs bound and agonized the macrophage Siglecs resulting in a significant decrease in the secretion of IL-6, IL-1ß, TNF-α and VEGF, and an increased secretion of IL-10. In vivo intravitreal (IVT) injection of PolySia-NPs was found to be well-tolerated and safe making it effective in preventing thinning of the retinal outer nuclear layer (ONL), inhibiting macrophage infiltration, and restoring electrophysiological retinal function in a model of bright light-induced retinal degeneration. In a clinically validated, laser-induced choroidal neovascularization (CNV) model of exudative AMD, PolySia-NPs reduced the size of neovascular lesions with associated reduction in macrophages. The PolySia-NPs described herein are therefore a promising therapeutic strategy for repolarizing pro-inflammatory macrophages to a more anti-inflammatory, non-angiogenic phenotype, which play a key role in the pathophysiology of non-exudative AMD.

A bright point source of ultrashort hard x-ray pulses using biological cells.

We demonstrate that the interaction of intense femtosecond light on a plain solid substrate can be substantially altered by a few micron layer coating of bacterial cells, live or dead. Using E. Coli cells, we show that at an intensity of 10(16)W cm(-2), the bremsstraahlung hard x-ray emission (up to 300 keV), is increased by more than two orders of magnitude as compared to a plain glass slab. Particle-in-cell simulations carried out by modeling the bacterial cells as ellipsoidal particles show that the hot electron generation is indeed enhanced by the presence of microstructures. This new methodology should pave way for using microbiological systems of varied shapes to control intense laser produced plasmas for EUV/x-ray generation.

Macroscopic transport of mega-ampere electron currents in aligned carbon-nanotube arrays.

We demonstrate that aligned carbon-nanotube arrays are efficient transporters of laser-generated mega-ampere electron currents over distances as large as a millimeter. A direct polarimetric measurement of the temporal and the spatial evolution of the megagauss magnetic fields (as high as 120 MG) at the target rear at an intensity of (10(18)-10(19)) W/cm2 was corroborated by the rear-side hot electron spectra. Simulations show that such high magnetic flux densities can only be generated by a very well collimated fast electron bunch.

Luminous, relativistic, directional electron bunches from an intense laser driven grating plasma.

Bright, energetic, and directional electron bunches are generated through efficient energy transfer of relativistic intense (~ 1019 W/cm2), 30 femtosecond, 800 nm high contrast laser pulses to grating targets (500 lines/mm and 1000 lines/mm), under surface plasmon resonance (SPR) conditions. Bi-directional relativistic electron bunches (at 40° and 150°) are observed exiting from the 500 lines/mm grating target at the SPR conditions. The surface plasmon excited grating target enhances the electron flux and temperature by factor of 6.0 and 3.6, respectively, compared to that of the plane substrate. Particle-in-Cell simulations indicate that fast electrons are emitted in different directions at different stages of the laser interaction, which are related to the resultant surface magnetic field evolution. This study suggests that the SPR mechanism can be used to generate multiple, bright, ultrafast relativistic electron bunches for a variety of applications.

Doppler spectrometry for ultrafast temporal mapping of density dynamics in laser-induced plasmas.

We present high resolution measurements of the ultrafast temporal dynamics of the critical surface in moderately overdense, hot plasma by using two-color, pump-probe Doppler spectrometry. Our measurements clearly capture the initial inward motion of the plasma inside the critical surface of the pump laser which is followed by outward expansion. The measured instantaneous velocity and acceleration profiles are very well reproduced by a hybrid simulation that uses a 1D electromagnetic particle-in-cell simulation for the initial evolution and a hydrodynamics simulation for the later times. The combination of high temporal resolution and dynamic range in our measurements clearly provides quantitative unraveling of the dynamics in this important region, enabling this as a powerful technique to obtain ultrafast snapshots of plasma density and temperature profiles for providing benchmarks for simulations.

Measuring the lifetime of intense-laser generated relativistic electrons in solids via gating their Cherenkov emission.

Optical Kerr gating technique has been employed to investigate the life history of relativistic electrons in solids by temporally gating their Cherenkov emission. Mega-ampere currents of relativistic electrons are created during ultra-intense (2 × 1019 W/cm2) laser-solid interactions. In order to measure the lifetime of these relativistic electrons in solids, we temporally gate their Cherenkov emission using an optical Kerr gate (OKG). The OKG is induced in a nonlinear medium, namely, carbon-di-sulphide (CS2), with a measured gate-width (FWHM) of 2 ps. The gate femtosecond laser pulse is synchronized with the intense interaction pulse generating relativistic electrons. The arrival time of the gate laser pulse on the CS2 cell is varied with the help of a delay stage. We find that Cherenkov emission from relativistic electrons created with a ultra-short laser pulse (25 fs) lives as long as 120 ps, a few thousand times that of the incident light pulse.

Towards Remote Lightning Manipulation by Meters-long Plasma Channels Generated by Ultra-Short-Pulse High-Intensity Lasers.

Remote manipulation (triggering and guiding) of lightning in atmospheric conditions of thunderstorms has been the subject of intense scientific research for decades. High power, ultrashort-pulse lasers are considered attractive in generating plasma channels in air that could serve as conductors/diverters for lightning. However, two fundamental obstacles, namely the limited length and lifetime of such plasma channels prevented their realization to this date. In this paper, we report decisive experimental results of our multi-element broken wire concept that extends the generated plasma channels to the required tens of meters range. We obtain 13-meter-long plasma wire, limited only by our current experimental setup, with plasma conditions that could be sufficient for the leader initiation. This advance, coupled with our demonstrated method of laser heating for long time sustenance of the plasma channel, is a major, significant step towards controlling lightning.

A gated Thomson parabola spectrometer for improved ion and neutral atom measurements in intense laser produced plasmas.

Ions of high energy and high charge are accelerated from compact intense laser produced plasmas and are routinely analysed either by time of flight or Thomson parabola spectrometry. At the highest intensities where ion energies can be substantially large, both these techniques have limitations. Strong electromagnetic pulse noise jeopardises the arrival time measurement, and a bright central spot in the Thomson parabola spectrometer affects the signal to noise ratio of ion traces that approach close to the central spot. We present a gated Thomson parabola spectrometer that addresses these issues and provides an elegant method to improvise ion spectrometry. In addition, we demonstrate that this method provides the ability to detect and measure high energy neutral atoms that are invariably present in most intense laser plasma acceleration experiments.

Highly efficient broadband terahertz generation from ultrashort laser filamentation in liquids.

Generation and application of energetic, broadband terahertz pulses (bandwidth ~0.1-50 THz) is an active and contemporary area of research. The main thrust is toward the development of efficient sources with minimum complexities-a true table-top setup. In this work, we demonstrate the generation of terahertz radiation via ultrashort pulse induced filamentation in liquids-a counterintuitive observation due to their large absorption coefficient in the terahertz regime. The generated terahertz energy is more than an order of magnitude higher than that obtained from the two-color filamentation of air (the most standard table-top technique). Such high terahertz energies would generate electric fields of the order of MV cm-1, which opens the doors for various nonlinear terahertz spectroscopic applications. The counterintuitive phenomenon has been explained via the solution of nonlinear pulse propagation equation in the liquid medium.