Gelsomina De Stasio

The probing depth of total electron yield in the sub-keV range: TEY-XAS and X-PEEM

X-ray absorption spectra can be collected in multiple ways, each exhibiting a different probing depth. The total electron yield signal contains contributions from primary, Auger and secondary electrons. We present data on the total electron yield probing depth at core level energies ranging from 77 to 929 eV. By coating materials with chromium overlayers, we find that the maximum probing depth increases with core level energy from 15 to 141 A. We demonstrate that the Auger electron contribution to total electron yield intensity is negligible, therefore X-ray absorption spectra acquired in X-ray PhotoElectron Emission spectroMicroscopy (X-PEEM) are equivalent to spectra acquired by total electron yield. We find that the signal intensity decreases exponentially with coating thickness, and that total electron yield probing depth and Auger electron range (calculated in the continuously slowing down approximation) are similar at low energies, but diverge for kinetic energies above 400 eV.

Compensation of charging in X-PEEM: a successful test on mineral inclusions in 4.4 Ga old zircon.

We present a new differential-thickness coating technique to analyze insulating samples with X-ray PhotoElectron Emission spectroMicroscopy (X-PEEM). X-PEEM is non-destructive, analyzes the chemical composition and crystal structure of minerals and can spatially resolve chemical species with a resolution presently reaching 35 nm. We tested the differential coating by analyzing a 4.4 billion-year-old zircon (ZrSiO(4)) containing silicate inclusions. We observed quartz (SiO(2)) inclusions smaller than 1microm in size that can only be analyzed non-destructively with synchrotron spectromicroscopies. With the removal of charging we greatly extend the range of samples that can be analyzed by X-PEEM.

MEPHISTO spectromicroscope reaches 20 nm lateral resolution

The recently described tests of the synchrotron imaging photoelectron spectromicroscope MEPHISTO (Microscope a Emission de PHotoelectrons par Illumination Synchrotronique de Type Onduleur) were complemented by further resolution improvements and tests, which brought the lateral resolution down to 20 nm. Images and line plot profiles demonstrate such performance.

Are gadolinium contrast agents suitable for gadolinium neutron capture therapy

Abstract Objective: Gadolinium neutron capture therapy (GdNCT) is a potential treatment for malignant tumors based on two steps: (1) injection of a tumor-specific 157Gd compound; (2) tumor irradiation with thermal neutrons. The GdNC reaction can induce cell death provided that Gd is proximate to DNA. Here, we studied the nuclear uptake of Gd by glioblastoma (GBM) tumor cells after treatment with two Gd compounds commonly used for magnetic resonance imaging, to evaluate their potential as GdNCT agents. Methods: Using synchrotron X-ray spectromicroscopy, we analyzed the Gd distribution at the subcellular level in: (1) human cultured GBM cells exposed to Gd-DTPA or Gd-DOTA for 0–72hours; (2) intracerebrally implanted C6 glioma tumors in rats injected with one or two doses of Gd-DOTA, and (3) tumor samples from GBM patients injected with Gd-DTPA. Results: In cell cultures, Gd-DTPA and Gd-DOTA were found in 84% and 56% of the cell nuclei, respectively. In rat tumors, Gd penetrated the nuclei of 47% and 85% of the tumor cells, after single and double injection of Gd-DOTA, respectively. In contrast, in human GBM tumors 6.1% of the cell nuclei contained Gd-DTPA. Discussion: Efficacy of Gd-DTPA and Gd-DOTA as GdNCT agents is predicted to be low, due to the insufficient number of tumor cell nuclei incorporating Gd. Although multiple administration schedules in vivo might induce Gd penetration into more tumor cell nuclei, a search for new Gd compounds with higher nuclear affinity is warranted before planning GdNCT in animal models or clinical trials.

Charging phenomena in PEEM imaging and spectroscopy.

Spectromicroscopy with the imaging technique of X-ray photoelectron emission microscopy (X-PEEM) is a microchemical analytical tool installed in many synchrotron radiation laboratories, and which is finding application in diverse fields of research. The method of sample analysis, X-ray absorption spectroscopy, does not encounter the same problems as X-ray photoemission spectroscopy when sample charging occurs, hence even good insulators may often be analyzed without any apparent artifacts in images or spectra. We show, however, that charging effects cannot be neglected. We model the effect of surface charge formation on the secondary electron yield from uniform samples to demonstrate that surface charge primarily reduces the yield of electrons which may contribute to the detected signal. We illustrate that on non-uniform insulating samples, localized centers of charge may substantially affect microscope imaging and resolution as the electrostatic field close to the surface is distorted. Finally, in certain circumstances non-uniform surface charge may lead to unexpected lineshapes in X-ray absorption spectra causing, in some extreme cases, negative spectra. These negative spectra are explained, and several strategies are reviewed to minimize the impact of sample charging when analyzing poorly conducting samples of any nature.

MEPHISTO: Performance tests of a novel synchrotron imaging photoelectron spectromicroscope

We discuss the scheme and test performances of this recently commissioned system in its final configuration. The tests show that the improvements in the electron optics system with respect to other instruments in the same class made it possible to reach lateral resolutions in the 50 nm range. They also demonstrate rather good spectromicroscopy and spectroscopy performances, reliability and flexibility of operation.

Motexafin-Gadolinium Taken Up In vitro by at Least 90% of Glioblastoma Cell Nuclei

Purpose: We present preclinical data showing the in vitro intranuclear uptake of motexafin gadolinium by glioblastoma multiforme cells, which could serve as a prelude to the future development of radiosensitizing techniques, such as gadolinium synchrotron stereotactic radiotherapy (GdSSR), a new putative treatment for glioblastoma multiforme. Experimental Design: In this approach, administration of a tumor-seeking Gd-containing compound would be followed by stereotactic external beam radiotherapy with 51-keV photons from a synchrotron source. At least two criteria must be satisfied before this therapy can be established: Gd must accumulate in cancer cells and spare the normal tissue; Gd must be present in almost all the cancer cell nuclei. We address the in vitro intranuclear uptake of motexafin gadolinium in this article. We analyzed the Gd distribution with subcellular resolution in four human glioblastoma cell lines, using three independent methods: two novel synchrotron spectromicroscopic techniques and one confocal microscopy. We present in vitro evidence that the majority of the cell nuclei take up motexafin gadolinium, a drug that is known to selectively reach glioblastoma multiforme. Results: With all three methods, we found Gd in at least 90% of the cell nuclei. The results are highly reproducible across different cell lines. The present data provide evidence for further studies, with the goal of developing GdSSR, a process that will require further in vivo animal and future clinical studies.

Abscisic acid-induced microheterogeneity in phospholipid vesicle: a fluorescence study.

Changes in the thermal behavior of DMPC (dimyristoyl-r-phosphatidylcholine) and an equimolar mixture of DMPC and DMPE (dimyristoyl-L-phosphatidylethanolamine) induced by the plant hormone abscisic acid (ABA) have been investigated using fluorescent probes. The fluorescence decay of the hydrophobic probe 1,6-diphenyl-1,3,5-hexatriene (DPH) in these vesicles has been measured using frequency-domain fluorometry, and has been analyzed using both models of discrete exponential components and continuous lifetime distributions. In the DMPC vesicles, using the distributional approach, higher center and width values were observed in the presence of abscisic acid (ABA), indicating a decrease in the dielectric constant of the lipid phase that we attribute to a decrease in the water concentration within the bilayer. Moreover, the presence of ABA in the liposomes increased the phospholipid phase transition temperature. The addition of ABA to the DMPC/DMPE mixture strongly increased the microheterogeneity of the system as reported by the FWHM (full-width at half-maximum) of the distributional approach.

The multidisciplinarity of spectromicroscopy: from geomicrobiology to archaeology

Abstract Synchrotron X-ray PhotoElectron Emission Microscopy (X-PEEM) is a useful tool to investigate the microchemical composition of a variety of different samples, including cells in culture, tissue sections, magnetic material, bacteria, rocks, materials science, tribology and archaeology specimens. The MEPHISTO X-PEEM, installed at the Wisconsin Synchrotron Radiation Center, reached a peak resolution of 20 nm, has been extensively used for the last 4 years to explore all of the above systems. The experiments reported here are some of the most unusual ones for this technique: ZnS precipitating bacteria, Mn and Fe oxide rocks and archaeological coins. The microchemistry of each one of these samples delivered new results.

Soft-x-ray transmission photoelectron spectromicroscopy with the MEPHISTO system

We complemented with data taken in transmission mode the recently described tests of the novel spectromicroscope MEPHISTO (Microscope a Emission de Photoelectrons par Illumination Synchrotronique de type Onduleur). Transmitted x rays were converted by a photocathode into photoelectrons, which were subsequently electron-optically processed by the spectromicroscope producing submicron-resolution images. Test images demonstrated excellent contrast.