Damage threshold of LiF crystal irradiated by femtosecond hard XFEL pulse sequence.

Here we demonstrate the results of investigating the damage threshold of a LiF crystal after irradiating it with a sequence of coherent femtosecond pulses using the European X-ray Free Electron Laser (EuXFEL). The laser fluxes on the crystal surface varied in the range ∼ 0.015-13 kJ/cm2 per pulse when irradiated with a sequence of 1-100 pulses (tpulse ∼ 20 fs, Eph = 9 keV). Analysis of the surface of the irradiated crystal using different reading systems allowed the damage areas and the topology of the craters formed to be accurately determined. It was found that the ablation threshold decreases with increasing number of X-ray pulses, while the depth of the formed craters increases non-linearly and reaches several hundred nanometers. The obtained results have been compared with data already available in the literature for nano- and picosecond pulses from lasers in the soft X-ray/VUV and optical ranges. A failure model of lithium fluoride is developed and verified with simulation of material damage under single-pulse irradiation. The obtained damage threshold is in reasonably good agreement with the experimentally measured one.

Auger electrons and DNA double-strand breaks studied by using iodine-containing chemicals.

Irradiation of high Z elements such as iodine, gold, gadolinium with monochromatic X-rays causes photoelectric effects that include the release of Auger electrons. Decay of radioactive iodine such as I-123 and I-125 also results in multiple events and some involve the generation of Auger electrons. These electrons have low energy and travel only a short distance but have a strong effect on DNA damage including the generation of double-strand breaks. In this chapter, we focus on iodine and discuss various studies that used iodine-containing chemicals to generate Auger electrons and cause DNA double-strand breaks. First, DNA synthesis precursors containing iodine were used to place iodine on DNA. DNA binding dyes such as iodine Hoechst were investigated for Auger electron generation and DNA breaks. More recently, iodine containing nanoparticles were developed. We describe our study using tumor spheroids loaded with iodine nanoparticles and synchrotron-generated monochromatic X-rays. This study led to the demonstration that an optimum effect on DNA double-strand break formation is observed with a 33.2keV X-ray which is just above the K-edge energy of iodine.

Iodine containing porous organosilica nanoparticles trigger tumor spheroids destruction upon monochromatic X-ray irradiation: DNA breaks and K-edge energy X-ray.

X-ray irradiation of high Z elements causes photoelectric effects that include the release of Auger electrons that can induce localized DNA breaks. We have previously established a tumor spheroid-based assay that used gadolinium containing mesoporous silica nanoparticles and synchrotron-generated monochromatic X-rays. In this work, we focused on iodine and synthesized iodine-containing porous organosilica (IPO) nanoparticles. IPO were loaded onto tumor spheroids and the spheroids were irradiated with 33.2 keV monochromatic X-ray. After incubation in CO2 incubator, destruction of tumor spheroids was observed which was accompanied by apoptosis induction, as determined by the TUNEL assay. By employing the γH2AX assay, we detected double strand DNA cleavages immediately after the irradiation. These results suggest that IPO first generate double strand DNA breaks upon X-ray irradiation followed by apoptosis induction of cancer cells. Use of three different monochromatic X-rays having energy levels of 33.0, 33.2 and 33.4 keV as well as X-rays with 0.1 keV energy intervals showed that the optimum effect of all three events (spheroid destruction, apoptosis induction and generation of double strand DNA breaks) occurred with a 33.2 keV monochromatic X-ray. These results uncover the preferential effect of K-edge energy X-ray for tumor spheroid destruction mediated by iodine containing nanoparticles.

Destruction of tumor mass by gadolinium-loaded nanoparticles irradiated with monochromatic X-rays: Implications for the Auger therapy.

Synchrotron generated monochromatic X-rays can be precisely tuned to the K-shell energy of high Z materials resulting in the release of the Auger electrons. In this work, we have employed this mechanism to destruct tumor spheroids. We first loaded gadolinium onto the surface of mesoporous silica nanoparticles (MSNs) producing gadolinium-loaded MSN (Gd-MSN). When Gd-MSN was added to the tumor spheroids, we observed efficient uptake and uniform distribution of Gd-MSN. Gd-MSN also can be taken up into cancer cells and localize to a site just outside of the cell nucleus. Exposure of the Gd-MSN containing tumor spheroids to monochromatic X-ray beams resulted in almost complete destruction. Importantly, this effect was observed at an energy level of 50.25 keV, but not with 50.0 keV. These results suggest that it is possible to use precisely tuned monochromatic X-rays to destruct tumor mass loaded with high Z materials, while sparing other cells. Our experiments point to the importance of nanoparticles to facilitate loading of gadolinium to tumor spheroids and to localize at a site close to the nucleus. Because the nanoparticles can target to tumor, our study opens up the possibility of developing a new type of radiation therapy for cancer.

Revealing the second harmonic generation in a femtosecond laser-driven cluster-based plasma by analyzing shapes of Ar XVII spectral lines.

We present experiments dealing with a femtosecond laser-driven cluster-based plasma, where by analyzing the nonlinear phenomenon of satellites of spectral lines of Ar XVII, we revealed the nonlinear phenomenon of the generation of the second harmonic of the laser frequency. For performing this analysis we developed new results in the theory of satellites of spectral lines. From such lineshape analysis we found, in particular, that the efficiency of converting the short (40 fs) intense (3x10¹8 W/cm²) incident laser light into the second harmonic was 2%. This result is in the excellent agreement with the 2-Dimensional Particle-In-Cell (2D PIC) simulation that we also performed. There is also an order of magnitude agreement between the thresholds for the SHG found from the line shape analysis and from the 2D PIC simulations.

3D visualization of XFEL beam focusing properties using LiF crystal X-ray detector.

Here, we report, that by means of direct irradiation of lithium fluoride a (LiF) crystal, in situ 3D visualization of the SACLA XFEL focused beam profile along the propagation direction is realized, including propagation inside photoluminescence solid matter. High sensitivity and large dynamic range of the LiF crystal detector allowed measurements of the intensity distribution of the beam at distances far from the best focus as well as near the best focus and evaluation of XFEL source size and beam quality factor M(2). Our measurements also support the theoretical prediction that for X-ray photons with energies ~10 keV the radius of the generated photoelectron cloud within the LiF crystal reaches about 600 nm before thermalization. The proposed method has a spatial resolution ~0.4-2.0 µm for photons with energies 6-14 keV and potentially could be used in a single shot mode for optimization of different focusing systems developed at XFEL and synchrotron facilities.

A laser-plasma-produced soft X-ray laser at 89 eV generates DNA double-strand breaks in human cancer cells.

While it has been expected that X-ray laser will be widely applied to biomedical studies, this has not been achieved to date and its biological effects such as DNA damage have not been evaluated. As a first step for its biological application, we developed a culture cell irradiation system, particularly designed for a plasma-driven soft X-ray laser pulse, to investigate whether the soft X-ray laser is able to induce DNA double strand breaks (DSBs) in living cells or not. The human adenocarcimona cell line A549 was irradiated with the soft X-ray laser at a photon energy of 89 eV and the repair focus formation of the DSBs was assessed by immunofluorescence staining with antiphosphorylated DNA-PKcs (p-DNA-PKcs), ATM (p-ATM) and γ-H2AX antibody. The p-DNA-PKcs, ATM, and γ-H2AX foci were clearly identified after soft X-ray laser irradiation. Furthermore, the increase in the X-ray laser shot number, even from a single shot, results in the increase in p-DNA-PKcs foci. These results are the first evidence that the 89 eV soft X-ray laser is able to induce DSB in living cells. Our study demonstrated that this irradiation system is a useful tool for investigating the radiobiological effect of soft X-ray laser.

Observation and theory of X-ray mirages.

The advent of X-ray lasers allowed the realization of compact coherent soft X-ray sources, thus opening the way to a wide range of applications. Here we report the observation of unexpected concentric rings in the far-field beam profile at the output of a two-stage plasma-based X-ray laser, which can be considered as the first manifestation of a mirage phenomenon in X-rays. We have developed a method of solving the Maxwell-Bloch equations for this problem, and find that the experimentally observed phenomenon is due to the emergence of X-ray mirages in the plasma amplifier, appearing as phase-matched coherent virtual point sources. The obtained results bring a new insight into the physical nature of amplification of X-ray radiation in laser-induced plasma amplifiers and open additional opportunities for X-ray plasma diagnostics and extreme ultraviolet lithography.

A new grating X-ray spectrometer for 2-4 keV enabling a separate observation of In-Lß and Sn-Lα emissions of indium tin oxide.

A new multilayer-coated varied line-spaced grating, JS4000, was fabricated and tested for extending the upper limit of a grating X-ray spectrometer for electron microscopy. This grating was designed for 2-3.8 keV at a grazing incidence angle of 1.35°. It was revealed that this new multilayer structure enables us to take soft-X-ray emission spectra continuously from 1.5 to 4.3 keV at the same optical setting. The full-width at half maximum of Te-L(α1,2) (3.8 keV) emission peak was 27 eV. This spectrometer was applied to indium tin oxide particles and clearly resolved Sn-L(α) (3444 eV) and In-L(ß1) (3487 eV) peaks, which could not be resolved by a widely used energy-dispersive X-ray spectrometer.

Demonstration of partially transparent thick metallic sodium in the vacuum ultraviolet spectral range.

We describe the direct measurement of actual transmittance of sodium samples with thickness of a 2 mm and 3 mm in a spectral range >115 nm, resulting in >50% transmittance of 3 mm thick solid and liquid sodium samples including transmission of a pair of the windows at the wavelength of 120 nm, giving an extinction coefficient of ~10(-6) to ~10(-7) which represents the sodium with a few cm thickness to be partially transparent for this wavelength. To confirm the measurement, we perform simple imaging experiments by the ultra-violet light passing through a 8 mm-thick sodium sample to illuminate a mesh as an object, resulting in obtaining a clear image.

Laminar and blazed type holographic gratings for a versatile soft x-ray spectrograph attached to an electron microscope and their evaluation in the 50-200 eV range.

Laminar and blazed type holographic varied-line-spacing spherical gratings for use in a versatile soft x-ray flat-field spectrograph attached to an electron microscope are designed, fabricated, and evaluated. The absolute diffraction efficiencies of laminar (or blazed) master and replica gratings at 86.00° incidence evaluated by synchrotron radiation show over 5% (or 8%) in the 50-200 eV range with the maxima of 22% (or 26%-27%). Also the resolving power evaluated by a laser produced plasma source is in excess of 700 at the energy near the K emission spectrum of lithium (~55 eV) for all gratings. Moreover, the K emission spectrum of metallic Li with high spectral resolution is successfully observed with the spectrograph attached to a transmission electron microscope.

Experimental verification of femtosecond laser ablation schemes by time-resolved soft x-ray reflective imaging.

Pump and probe reflective imaging using a soft x-ray laser probe was applied to the observation of the early stage of femtosecond laser ablation process on platinum. In strongly excited area, drastic and fast reflectivity drop was observed. In moderately excited area, the decay of the reflectivity is slower than that in the strongly excited area, and the reflectivity reaches its minimum at t = 160 ps. In weakly excited area, laser-induced reflectivity change was not observed. In addition, the point where the reflectivity dip was observed at t = 10 ps and t = 40 ps, coincides with the position of the edge of reflectivity drop at t = 160 ps. These results give the critical information about the femtosecond laser ablation.

γ-H2AX and phosphorylated ATM focus formation in cancer cells after laser plasma X irradiation.

The usefulness of laser plasma X-ray pulses for medical and radiation biological studies was investigated, and the effects of laser plasma X rays were compared with those of conventional sources such as a linear accelerator. A cell irradiation system was developed that used copper-Kα (8 keV) lines from an ultrashort high-intensity laser to produce plasma. The absorbed dose of the 8 keV laser plasma X-ray pulse was estimated accurately with Gafchromic® EBT film. When the cells were irradiated with approximately 2 Gy of laser plasma X rays, the circular regions on γ-H2AX-positive cells could be clearly identified. Moreover, the numbers of γ-H2AX and phosphorylated ataxia telangiectasia mutated (ATM) foci induced by 8 keV laser plasma X rays were comparable to those induced by 4 MV X rays. These results indicate that the laser plasma X ray source may be useful for radiation biology studies.

Single-shot picosecond interferometry with one-nanometer resolution for dynamical surface morphology using a soft X-ray laser.

Using highly coherent radiation at a wavelength of 13.9 nm from a Ag-plasma soft X-ray laser, we constructed a pump-and-probe interferometer based on a double Lloyd's mirror system. The spatial resolutions are evaluated with a test pattern, showing 1.8-mum lateral resolution, and 1-nm depth sensitivity. This instrument enables a single-shot observation of the surface morphology with a 7-ps time-resolution. We succeeded in observing a nanometer scale surface dilation of Pt films at the early stage of the ablation process initiated by a 70 fs near infrared pump pulse.

Note: Application of laser produced plasma K alpha x-ray probe in radiation biology.

A dedicated radiation biology x-ray generation and exposure system has been developed. 8.0 keV in energy x-ray pulses generated with a femtosecond-laser pulse was used to irradiate sample cells through a custom-made culture dish with a silicon nitride membrane. The x-ray irradiation resulted in DNA double-strand breaks in the nucleus of a culture cell that were similar to those obtained with a conventional x-ray source, thus demonstrating the feasibility of radiobiological studies utilizing a single burst of x-rays focused on single cell specimens.

Demonstration of a highly coherent 13.9 nm x-ray laser from a silver tape target.

A highly coherent 13.9 nm x-ray laser (XRL) is generated under an oscillator-amplifier configuration using a new tape target system and a driver laser system with a 0.1 Hz repetition rate. The output energy is comparable to the XRL generated with a silver-deposited slab target, and the pointing stability using the new tape target system is better than conventional slab targets.

Propagation-based phase-contrast enhancement of nanostructure images using a debris-free femtosecond-laser-driven cluster-based plasma soft x-ray source and an LiF crystal detector.

We demonstrate in-line phase-contrast imaging of nanothickness foils by using a relatively large, polychromatic, debris-free femtosecond-laser-driven cluster-based plasma soft x-ray source, and a high-resolution, large dynamic range LiF crystal detector. The spatial coherence length of radiation in our setup reached a value of 5 microm on the sample plane, which is enough to observe phase-contrast enhancement in the images registered by the detector placed only a few hundred micrometers behind the object. We have developed a tabletop soft x-ray emission source, which emits radiation within a 4pi sr solid angle, and which allows one to obtain contact and propagation-based phase-contrast imaging of nanostructures with 700 nm spatial resolutions. This advance could be of utility for metrology applications.

Development and performance test of a soft x-ray polarimeter and ellipsometer for complete polarization analysis.

A new apparatus for polarimetric and ellipsometric measurements based on the rotating-analyzer method in the soft x-ray region has been designed, constructed, and installed in the soft x-ray beamline (BL-11) at the SR Center of Ritsumeikan University, Shiga, Japan. It can realize the optical configurations for the complete polarization analysis by using six independently movable drive shafts. A demonstration of the capabilities of the apparatus has been performed using Mo/Si multilayer polarizers deposited by an ion beam sputtering method. It is for the first time shown that the degree of linear polarization of monochromatized light from the BL-11 is approximately 87% at 92 eV since the beamline has been constructed.

Observation of a plasma waveguide in a preformed plasma pumped by double-pulse laser irradiation for the efficient soft x-ray amplification.

A molybdenum slab target was irradiated by double pulses of a line-focused chirped-pulse-amplification Nd:glass laser. A probe beam was injected in the plasma in the longitudinal direction, and we found that the probe beam was guided in the plasma with the plasma length of up to 4.3 mm at the time of 0.8-1.5 ns after the peak of the second pulse. Comparison with hydrodynamics code implied that the electron-density dip or flat region was formed, which was favorable for the efficient soft x-ray lasing under the coupling of the seed x-ray and the x-ray amplifier.

Characterization of a high-brilliance soft x-ray laser at 13.9 nm by use of an oscillator-amplifier configuration.

We have improved a highly coherent x-ray laser at 13.9 nm using an oscillator-amplifier configuration. To improve a high-brilliance x-ray laser, we adopted traveling wave pumping for the amplifier target and rotated the amplifier target 3-4 mrad in the counterclockwise direction. Thereby, a seed x-ray laser can be amplified by medium plasma of the amplifier target with a high gain coefficient. The amplified x-ray laser has the output energy of approximately 1.3 microJ, corresponding to a large photon flux of 6.5 x 10(10) photons/pulse and a high peak brilliance of 5 x 10(26) photons/(s x mm(2) x mrad(2) x 0.01% bandwidth).