Stable Operation of a Free-Electron Laser Driven by a Plasma Accelerator.

The breakthrough provided by plasma-based accelerators enabled unprecedented accelerating fields by boosting electron beams to gigaelectronvolt energies within a few centimeters [1-4]. This, in turn, allows the realization of ultracompact light sources based on free-electron lasers (FELs) [5], as demonstrated by two pioneering experiments that reported the observation of self-amplified spontaneous emission (SASE) driven by plasma-accelerated beams [6,7]. However, the lack of stability and reproducibility due to the intrinsic nature of the SASE process (whose amplification starts from the shot noise of the electron beam) may hinder their effective implementation for user purposes. Here, we report a proof-of-principle experiment using plasma-accelerated beams to generate stable and reproducible FEL light seeded by an external laser. FEL radiation is emitted in the infrared range, showing the typical exponential growth of its energy over six consecutive undulators. Compared to SASE, the seeded FEL pulses have energies 2 orders of magnitude larger and stability that is 3 times higher.

Free-electron lasing with compact beam-driven plasma wakefield accelerator.

The possibility to accelerate electron beams to ultra-relativistic velocities over short distances by using plasma-based technology holds the potential for a revolution in the field of particle accelerators1-4. The compact nature of plasma-based accelerators would allow the realization of table-top machines capable of driving a free-electron laser (FEL)5, a formidable tool to investigate matter at the sub-atomic level by generating coherent light pulses with sub-ångström wavelengths and sub-femtosecond durations6,7. So far, however, the high-energy electron beams required to operate FELs had to be obtained through the use of conventional large-size radio-frequency (RF) accelerators, bound to a sizeable footprint as a result of their limited accelerating fields. Here we report the experimental evidence of FEL lasing by a compact (3-cm) particle-beam-driven plasma accelerator. The accelerated beams are completely characterized in the six-dimensional phase space and have high quality, comparable with state-of-the-art accelerators8. This allowed the observation of narrow-band amplified radiation in the infrared range with typical exponential growth of its intensity over six consecutive undulators. This proof-of-principle experiment represents a fundamental milestone in the use of plasma-based accelerators, contributing to the development of next-generation compact facilities for user-oriented applications9.

Accurate spectra for high energy ions by advanced time-of-flight diamond-detector schemes in experiments with high energy and intensity lasers.

Time-Of-Flight (TOF) methods are very effective to detect particles accelerated in laser-plasma interactions, but they show significant limitations when used in experiments with high energy and intensity lasers, where both high-energy ions and remarkable levels of ElectroMagnetic Pulses (EMPs) in the radiofrequency-microwave range are generated. Here we describe a novel advanced diagnostic method for the characterization of protons accelerated by intense matter interactions with high-energy and high-intensity ultra-short laser pulses up to the femtosecond and even future attosecond range. The method employs a stacked diamond detector structure and the TOF technique, featuring high sensitivity, high resolution, high radiation hardness and high signal-to-noise ratio in environments heavily affected by remarkable EMP fields. A detailed study on the use, the optimization and the properties of a single module of the stack is here described for an experiment where a fast diamond detector is employed in an highly EMP-polluted environment. Accurate calibrated spectra of accelerated protons are presented from an experiment with the femtosecond Flame laser (beyond 100 TW power and ~ 1019 W/cm2 intensity) interacting with thin foil targets. The results can be readily applied to the case of complex stack configurations and to more general experimental conditions.

Ultrafast electron and proton bunches correlation in laser-solid matter experiments.

The interaction of an ultra-intense laser with a solid state target allows the production of multi-MeV proton and ion beams. This process is explained by the target normal sheath acceleration (TNSA) model, predicting the creation of an electric field on the target rear side, due to an unbalanced positive charge. This process is related to the emission of relativistic ultrafast electrons, occurring at an earlier time. In this work, we highlight the correlations between the ultrafast electron component and the protons by their simultaneous detection by means of an electro-optical sampling and a time-of-flight diagnostics, respectively, supported by numerical simulations showing an excellent agreement.

Time-resolved characterization of ultrafast electrons in intense laser and metallic-dielectric target interaction.

High-intensity ultrashort laser pulses interacting with thin solid targets are able to produce energetic ion beams by means of extremely large accelerating fields set by the energetic ejected electrons. The characterization of such electrons is thus important in view of a complete understanding of the acceleration process. Here, we present a complete temporal-resolved characterization of the fastest escaping hot electron component for different target materials and thicknesses, using temporal diagnostics based on electro-optical sampling with 100 fs temporal resolution. Experimental evidence of scaling laws for ultrafast electron beam parameters have been retrieved with respect to the impinging laser energy (0.4-4 J range) and to the target material, and an empirical law determining the beam parameters as a function of the target thickness is presented.

Modeling and diagnostics for plasma discharge capillaries.

In this paper, we show how plasma discharge capillaries can be numerically modeled as resistors within an RLC-series discharge circuit, allowing for a simple description of these systems, while taking into account heat and radiation losses. An analytic radial model is also provided and compared to the numerical model for plasma discharge capillaries at thermal equilibrium, with corrections due to radiation losses. Finally, diagnostic techniques based on visible spectroscopy of plasma emission lines are discussed both for atomic and molecular gases, comparing experimental results with numerical simulations and theoretical calculations.

Longitudinal Phase-Space Manipulation with Beam-Driven Plasma Wakefields.

The development of compact accelerator facilities providing high-brightness beams is one of the most challenging tasks in the field of next-generation compact and cost affordable particle accelerators, to be used in many fields for industrial, medical, and research applications. The ability to shape the beam longitudinal phase space, in particular, plays a key role in achieving high-peak brightness. Here we present a new approach that allows us to tune the longitudinal phase space of a high-brightness beam by means of plasma wakefields. The electron beam passing through the plasma drives large wakefields that are used to manipulate the time-energy correlation of particles along the beam itself. We experimentally demonstrate that such a solution is highly tunable by simply adjusting the density of the plasma and can be used to imprint or remove any correlation onto the beam. This is a fundamental requirement when dealing with largely time-energy correlated beams coming from future plasma accelerators.

Focusing of High-Brightness Electron Beams with Active-Plasma Lenses.

Plasma-based technology promises a tremendous reduction in size of accelerators used for research, medical, and industrial applications, making it possible to develop tabletop machines accessible for a broader scientific community. By overcoming current limits of conventional accelerators and pushing particles to larger and larger energies, the availability of strong and tunable focusing optics is mandatory also because plasma-accelerated beams usually have large angular divergences. In this regard, active-plasma lenses represent a compact and affordable tool to generate radially symmetric magnetic fields several orders of magnitude larger than conventional quadrupoles and solenoids. However, it has been recently proved that the focusing can be highly nonlinear and induce a dramatic emittance growth. Here, we present experimental results showing how these nonlinearities can be minimized and lensing improved. These achievements represent a major breakthrough toward the miniaturization of next-generation focusing devices.

3D-printed capillary for hydrogen filled discharge for plasma based experiments in RF-based electron linac accelerator.

Plasma-based acceleration experiments require capillaries with a radius of a few hundred microns to confine plasma up to a centimeter scale capillary length. A long and controlled plasma channel allows to sustain high fields which may be used for manipulation of the electron beams or to accelerate electrons. The production of these capillaries is relatively complicated and expensive since they are usually made with hard materials whose manufacturing requires highly specialized industries. Fine variations of the capillary shape may significantly increase the cost and time needed to produce them. In this article, we demonstrate the possibility of using 3D printed polymeric capillaries to drive a hydrogen-filled plasma discharge up to 1 Hz of repetition rate in an RF based electron linac. The plasma density distribution has been measured after several shot intervals, showing the effect of the surface ablation on the plasma density distribution. This effect is almost invisible in the earlier stages of the discharge. After more than 55000 shots (corresponding to more than 16 h of working time), the effects of the ablation on the plasma density distribution are not evident and the capillary can still be used. The use of these capillaries will significantly reduce the cost and time for prototyping, allowing us to easily manipulate their geometry, laying another building block for future cheap and compact particle accelerators.

Compact and tunable focusing device for plasma wakefield acceleration.

Plasma wakefield acceleration, either driven by ultra-short laser pulses or electron bunches, represents one of the most promising techniques able to overcome the limits of conventional RF technology and allows the development of compact accelerators. In the particle beam-driven scenario, ultra-short bunches with tiny spot sizes are required to enhance the accelerating gradient and preserve the emittance and energy spread of the accelerated bunch. To achieve such tight transverse beam sizes, a focusing system with short focal length is mandatory. Here we discuss the development of a compact and tunable system consisting of three small-bore permanent-magnet quadrupoles with 520 T/m field gradient. The device has been designed in view of the plasma acceleration experiments planned at the SPARC_LAB test-facility. Being the field gradient fixed, the focusing is adjusted by tuning the relative position of the three magnets with nanometer resolution. Details about its magnetic design, beam-dynamics simulations, and preliminary results are examined in the paper.

Ultrafast evolution of electric fields from high-intensity laser-matter interactions.

The interaction of high-power ultra-short lasers with materials offers fascinating wealth of transient phenomena which are in the core of novel scientific research. Deciphering its evolution is a complicated task that strongly depends on the details of the early phase of the interaction, which acts as complex initial conditions. The entire process, moreover, is difficult to probe since it develops close to target on the sub-picosecond timescale and ends after some picoseconds. Here we present experimental results related to the fields and charges generated by the interaction of an ultra-short high-intensity laser with metallic targets. The temporal evolution of the interaction is probed with a novel femtosecond resolution diagnostics that enables the differentiation of the contribution by the high-energy forerunner electrons and the radiated electromagnetic pulses generated by the currents of the remaining charges on the target surface. Our results provide a snapshot of huge pulses, up to 0.6 teravolt per meter, emitted with multi-megaelectronvolt electron bunches with sub-picosecond duration and are able to explore the processes involved in laser-matter interactions at the femtosecond timescale.

Femtosecond dynamics of energetic electrons in high intensity laser-matter interactions.

Highly energetic electrons are generated at the early phases of the interaction of short-pulse high-intensity lasers with solid targets. These escaping particles are identified as the essential core of picosecond-scale phenomena such as laser-based acceleration, surface manipulation, generation of intense magnetic fields and electromagnetic pulses. Increasing the number of the escaping electrons facilitate the late time processes in all cases. Up to now only indirect evidences of these important forerunners have been recorded, thus no detailed study of the governing mechanisms was possible. Here we report, for the first time, direct time-dependent measurements of energetic electrons ejected from solid targets by the interaction with a short-pulse high-intensity laser. We measured electron bunches up to 7 nanocoulombs charge, picosecond duration and 12 megaelectronvolts energy. Our 'snapshots' capture their evolution with an unprecedented temporal resolution, demonstrat- ing a significant boost in charge and energy of escaping electrons when increasing the geometrical target curvature. These results pave the way toward significant improvement in laser acceleration of ions using shaped targets allowing the future development of small scale laser-ion accelerators.

Sub-picosecond snapshots of fast electrons from high intensity laser-matter interactions.

The interaction of a high-intensity short-pulse laser with thin solid targets produces electron jets that escape the target and positively charge it, leading to the formation of the electrostatic potential that in turn governs the ion acceleration. The typical timescale of such phenomena is on the sub-picosecond level. Here we show, for the first time, temporally-resolved measurements of the first released electrons that escaped from the target, so-called fast electrons. Their total charge, energy and temporal profile are provided by means of a diagnostics based on Electro-Optical Sampling with temporal resolution below 100 fs.

Two-Color Radiation Generated in a Seeded Free-Electron Laser with Two Electron Beams.

We present the experimental evidence of the generation of coherent and statistically stable two-color free-electron laser radiation obtained by seeding an electron beam double peaked in energy with a laser pulse single spiked in frequency. The radiation presents two neat spectral lines, with time delay, frequency separation, and relative intensity that can be accurately controlled. The analysis of the emitted radiation shows a temporal coherence and a shot-to-shot regularity in frequency significantly enhanced with respect to the self-amplified spontaneous emission.

Dosimetry of very high energy electrons (VHEE) for radiotherapy applications: using radiochromic film measurements and Monte Carlo simulations.

Very high energy electrons (VHEE) in the range from 100-250 MeV have the potential of becoming an alternative modality in radiotherapy because of their improved dosimetry properties compared with MV photons from contemporary medical linear accelerators. Due to the need for accurate dosimetry of small field size VHEE beams we have performed dose measurements using EBT2 Gafchromic® film. Calibration of the film has been carried out for beams of two different energy ranges: 20 MeV and 165 MeV from conventional radio frequency linear accelerators. In addition, EBT2 film has been used for dose measurements with 135 MeV electron beams produced by a laser-plasma wakefield accelerator. The dose response measurements and percentage depth dose profiles have been compared with calculations carried out using the general-purpose FLUKA Monte Carlo (MC) radiation transport code. The impact of induced radioactivity on film response for VHEEs has been evaluated using the MC simulations. A neutron yield of the order of 10(-5) neutrons cm(-2) per incident electron has been estimated and induced activity due to radionuclide production is found to have a negligible effect on total dose deposition and film response. Neutron and proton contribution to the equivalent doses are negligible for VHEE. The study demonstrates that EBT2 Gafchromic film is a reliable dosimeter that can be used for dosimetry of VHEE. The results indicate an energy-independent response of the dosimeter for 20 MeV and 165 MeV electron beams and has been found to be suitable for dosimetry of VHEE.

Compton scattering for spectroscopic detection of ultra-fast, high flux, broad energy range X-rays.

Compton side-scattering has been used to simultaneously downshift the energy of keV to MeV energy range photons while attenuating their flux to enable single-shot, spectrally resolved, measurements of high flux X-ray sources to be undertaken. To demonstrate the technique a 1 mm thick pixelated cadmium telluride detector has been used to measure spectra of Compton side-scattered radiation from a Cobalt-60 laboratory source and a high flux, high peak brilliance X-ray source of betatron radiation from a laser-plasma wakefield accelerator.

Observation of time-domain modulation of free-electron-laser pulses by multipeaked electron-energy spectrum.

We present the experimental demonstration of a new scheme for the generation of ultrashort pulse trains based on free-electron-laser (FEL) emission from a multipeaked electron energy distribution. Two electron beamlets with energy difference larger than the FEL parameter ρ have been generated by illuminating the cathode with two ps-spaced laser pulses, followed by a rotation of the longitudinal phase space by velocity bunching in the linac. The resulting self-amplified spontaneous emission FEL radiation, measured through frequency-resolved optical gating diagnostics, reveals a double-peaked spectrum and a temporally modulated pulse structure.

Spatially resolved analysis of Kα x-ray emission from plasmas induced by a femtosecond weakly relativistic laser pulse at various polarizations.

Spatially resolved K-shell spectroscopy is used here to investigate the interaction of an ultrashort laser pulse (λ=800 nm, τ=40 fs) with a Ti foil under intense irradiation (Iλ(2)=2×10(18)Wµm(2)cm(-2)) and the following fast electron generation and transport into the target. The effect of laser pulse polarization (p, s, and circular) on the Kα yield and line shape is probed. The radial structure of intensity and width of the lines, obtained by a discretized Abel deconvolution algorithm, suggests an annular distribution of both the hot electron propagation into the target and the target temperature. An accurate modeling of Kα line shapes was performed, revealing temperature gradients, going from a few eV up to 15-20 eV, depending on the pulse polarization. Results are discussed in terms of mechanisms of hot electron generation and of their transport through the preplasma in front of the target.

TIMP3 regulates migration, invasion and in vivo tumorigenicity of thyroid tumor cells.

Papillary thyroid carcinoma (PTC) arises from the thyroid follicular epithelium and represents the most frequent thyroid malignancy. PTC is associated with gene rearrangements generating RET/PTC and TRK oncogenes, and to the BRAFV600E activating point mutation. A role of tumor-suppressor genes in the pathogenesis of PTC has not been assessed yet. The tissue inhibitor of metalloproteinase-3 (TIMP3) gene, encoding a metalloproteinases inhibitor and capable of inhibiting growth, angiogenesis, invasion and metastasis of several cancers, was found to be silenced by promoter methylation in a consistent fraction of PTCs, in association with tumor aggressiveness and BRAFV600E mutation, thus suggesting an oncosuppressor role. To explore this possibility, in this study we performed gene expression and functional studies. Analysis of gene expression data produced in our laboratory as well as meta-analysis of publicly available data sets confirmed the downregulation of TIMP3 gene expression in PTC with respect to normal thyroid. The functional consequences of TIMP3 downregulation were investigated in the PTC-derived NIM1 cell line, in which the expression of TIMP3 is silenced. Restoration of TIMP3 expression by exposure to soluble TIMP3 protein or by complementary DNA transfection had no effect on the growth rate of NIM1 cells. Instead, it affected the adhesive, migratory and invasive capabilities of NIM1 cells by modulating several proteins involved in these processes. A striking effect was observed in vivo, as TIMP3 reduced the tumorigenicity of NIM1 cells by repressing angiogenesis and macrophage infiltration. Our data indicate that the loss of TIMP3 expression exerts a functional role in the pathogenesis of PTC.

IGFBP7: an oncosuppressor gene in thyroid carcinogenesis.

Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted protein involved in several cellular processes, including proliferation, senescence and apoptosis. Loss of IGFBP7 expression is a critical step in the development of human tumors, including melanoma and colon cancer. By microarray gene expression studies, we have detected downregulation of IGFBP7 gene expression in follicular and papillary thyroid tumors in comparison with normal thyroid tissue. Evaluation of publicly available PTC microarray gene expression data sets confirmed, in a consistent fraction of tumors, the downregulation of IGFBP7 transcript levels. The functional consequence of IGFBP7 downregulation was addressed in the PTC-derived NIM1 cell line in which IGFBP7 expression is repressed by promoter hypermethylation. Exposure to soluble IGFBP7 protein or restoration of IGFBP7 expression by complementary DNA transfection reduced growth rate, migration, anchorage-independent growth and tumorigenicity of NIM1 cells. We show that the effects of IGFBP7 are related to apoptosis. Our data suggest that loss of IGFBP7 expression has a functional role in thyroid carcinogenesis, and it may represent a possible basis for therapeutic strategies.