Rasterionenmikroskopie

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2017

Chromatin organization revealed by nanostructure of irradiation induced ?H2AX, 53BP1 and Rad51 foci
J. Reindl, S. Girst, D.W.M. Walsh, C. Greubel, B. Schwarz, C. Siebenwirth, G.A. Drexler, A.A. Friedl and G. Dollinger; Scientific Reports 7 (2017) 40616.
Abstract: The spatial distribution of DSB repair factors ?H2AX, 53BP1 and Rad51 in ionizing radiation induced foci (IRIF) in HeLa cells using super resolution STED nanoscopy after low and high linear energy transfer (LET) irradiation was investigated. 53BP1 and ?H2AX form IRIF with same mean size of (540?±?40) nm after high LET irradiation while the size after low LET irradiation is significantly smaller. The IRIF of both repair factors show nanostructures with partial anti-correlation. These structures are related to domains formed within the chromatin territories marked by ?H2AX while 53BP1 is mainly situated in the perichromatin region. The nanostructures have a mean size of (129?±?6) nm and are found to be irrespective of the applied LET and the labelled damage marker. In contrast, Rad51 shows no nanostructure and a mean size of (143?±?13) nm independent of LET. Although Rad51 is surrounded by 53BP1 it strongly anti-correlates meaning an exclusion of 53BP1 next to DSB when decision for homologous DSB repair happened.
BibTeX:
	@article{Reindl2017,
	  author = {Reindl, Judith and Girst, Stefanie and Walsh, Dietrich W. M. and Greubel, Christoph and Schwarz, Benjamin and Siebenwirth, Christian and Drexler, Guido A. and Friedl, Anna A. and Dollinger, Günther},
	  title = {Chromatin organization revealed by nanostructure of irradiation induced ?H2AX, 53BP1 and Rad51 foci},
	  journal = {Scientific Reports},
	  year = {2017},
	  volume = {7},
	  pages = {40616},
	  url = {http://www.nature.com/articles/srep40616},
	  doi = {http://doi.org/10.1038/srep40616}
	}
	
The influence of reference radiation photon energy on high-LET RBE: comparison of human peripheral lymphocytes and human--hamster hybrid AL cells
T.E. Schmid, C. Greubel, G. Dollinger and E. Schmid; Radiation and Environmental Biophysics (2017) 1-9.
Abstract: The relative biological effectiveness (RBE) based on the induction of dicentrics in any cell type is principally an important information for the increasing application of high-LET radiation in cancer therapy. Since the standard system of human lymphocytes for measuring dicentrics are not compatible with our microbeam irradiation setup where attaching cells are essential, we used human--hamster hybrid AL cells which do attach on foils and fulfil the special experimental requirement for microbeam irradiations. In this work, the dose--response of AL cells to photons of different energy, 70 and 200 kV X-rays and 60Co γ-rays, is characterized and compared to human lymphocytes. The total number of induced dicentrics in AL cells is approximately one order of magnitude smaller. Despite the smaller α and β parameters of the measured linear--quadratic dose--response relationship, the α/β-ratio versus photon energy dependence is identical within the accuracy of measurement for AL cells and human lymphocytes. Thus, the influence of the reference radiation used for RBE determination is the same. For therapy relevant doses of 2 Gy (60Co equivalent), the difference in RBE is around 20% only. These findings indicate that the biological effectiveness in AL cells can give important information for human cells, especially for studies where attaching cells are essential.
BibTeX:
	@article{Schmid2017,
	  author = {Schmid, T. E. and Greubel, C. and Dollinger, G. and Schmid, E.},
	  title = {The influence of reference radiation photon energy on high-LET RBE: comparison of human peripheral lymphocytes and human--hamster hybrid AL cells},
	  journal = {Radiation and Environmental Biophysics},
	  year = {2017},
	  pages = {1--9},
	  url = {http://link.springer.com/article/10.1007%2Fs00411-016-0680-3},
	  doi = {http://doi.org/10.1007/s00411-016-0680-3}
	}
	

2016

Proton Minibeam Radiation Therapy Reduces Side Effects in an In Vivo Mouse Ear Model
S. Girst, C. Greubel, J. Reindl, C. Siebenwirth, O. Zlobinskaya, D. Walsh, K. Ilicic, M. Aichler, A. Walch, J. Wilkens, G. Multhoff, G. Dollinger and T. Schmid; International Journal of Radiation Oncology * Biology * Physics 95 (2016) 234-241.
Abstract: Purpose: Proton minibeam radiation therapy is a novel approach to minimize normal tissue damage in the entrance channel by spatial fractionation while keeping tumor control through a homogeneous tumor dose using beam widening with an increasing track length. In the present study, the dose distributions for homogeneous broad beam and minibeam irradiation sessions were simulated. Also, in an animal study, acute normal tissue side effects of proton minibeam irradiation were compared with homogeneous irradiation in a tumor-free mouse ear model to account for the complex effects on the immune system and vasculature in an in vivo normal tissue model.

Methods and Materials: At the ion microprobe SNAKE, 20-MeV protons were administered to the central part (7.2 x 7.2 mm2) of the ear of BALB/c mice, using either a homogeneous field with a dose of 60 Gy or 16 minibeams with a nominal 6000 Gy (4 x 4 minibeams, size 0.18 x 0.18 mm2, with a distance of 1.8 mm). The same average dose was used over the irradiated area.

Results: No ear swelling or other skin reactions were observed at any point after minibeam irradiation. In contrast, significant ear swelling (up to fourfold), erythema, and desquamation developed in homogeneously irradiated ears 3 to 4 weeks after irradiation. Hair loss and the disappearance of sebaceous glands were only detected in the homogeneously irradiated fields.

Conclusions: These results show that proton minibeam radiation therapy results in reduced adverse effects compared with conventional homogeneous broad-beam irradiation and, therefore, might have the potential to decrease the incidence of side effects resulting from clinical proton and/or heavy ion therapy.

BibTeX:
	@article{Girst2016,
	  author = {Girst, S. and Greubel, C. and Reindl, J. and Siebenwirth, C. and Zlobinskaya, O. and Walsh, D.W.M. and Ilicic, K. and Aichler, M. and Walch, A. and Wilkens, J.J. and Multhoff, G. and Dollinger, G. and Schmid, T.E.},
	  title = {Proton Minibeam Radiation Therapy Reduces Side Effects in an In Vivo Mouse Ear Model},
	  journal = {International Journal of Radiation Oncology * Biology * Physics},
	  year = {2016},
	  volume = {95},
	  pages = {234--241},
	  url = {http://www.sciencedirect.com/science/article/pii/S0360301615265856},
	  doi = {http://doi.org/10.1016/j.ijrobp.2015.10.020}
	}
	
Proton Minibeam Radiotherapy
Stefanie Girst; Dissertation, Universität der Bundeswehr München, 2016.
Abstract: The risk of developing adverse side effects in the normal tissue after radiotherapy is often limiting for the dose that can be applied to the tumor. Proton minibeam radiotherapy, a spatially fractionated radiotherapy method using sub-millimeter proton beams, similar to grid therapy or microbeam radiation radiotherapy (MRT) using X-rays, has recently been invented at the ion microprobe SNAKE in Munich. The aim of this new concept is to minimize normal tissue injuries in the entrance channel and especially in the skin by irradiating only a small percentage of the cells in the total irradiation field, while maintaining tumor control via a homogeneous dose in the tumor, just like in conventional broad beam radiotherapy. This can be achieved by optimizing minibeam sizes and distances according to the prevailing tumor size and depth such that after widening of the minibeams due to proton interactions in the tissue, the overlapping minibeams produce a homogeneous dose distribution throughout the tumor. The aim of this work was to elucidate the prospects of minibeam radiation therapy compared to conventional homogeneous broad beam radiotherapy in theory and in experimental studies at the ion microprobe SNAKE. Treatment plans for model tumors of different sizes and depths were created using the planning software LAP-CERR, to elaborate suitable minibeam sizes and distances for the individual tumors. Radiotherapy-relevant inter-beam distances required to obtain a homogeneous dose in the target volume were found to be in the millimeter range. First experiments using proton minibeams of only 10 µm and 50 µm size (termed microchannels in the corresponding publication Zlobinskaya et al. 2013) and therapy-conform larger dimensions of 100 µm and 180 µm were performed in the artificial human in-vitro skin model EpiDermFT (MatTek). The corresponding inter-beam distances were 500 ?m, 1mm and 1.8mm, respectively, leading to irradiation of only a few percent of the cells in the skin tissue, but with significantly increased doses (up to 5000 Gy) compared to the average dose of 2 Gy, which was applied homogeneously in further skin samples for comparison. Gaussian-shaped minibeams of even larger sizes (?=260 µm and 520 µm, inter-beam distance 1.8mm) were analyzed in further experiments to evaluate the effect of increasing beam sizes as in deeper-lying tissues. Acute side effects were quantified via the MTT tissue viability test and the release of inflammatory proteins into the culture medium and showed improved results for minibeam compared to homogeneous irradiation. Genetic damage, an indicator for secondary tumor induction, was analyzed via the micronucleus test in the epidermal keratinocytes and was less than half for minibeams up to 180 µm size compared to homogeneous fields. Increasing minibeam sizes, i.e. increasing fractions of irradiated skin receiving a dose higher than the average dose of 2 Gy) increased the number of micronuclei per divided cell, but never exceeded the genetic damage induced by a homogeneous dose distribution. A more authentic and representative in-vivo skin model, accounting for higher complexity with blood vessels, further cell types, follicles glands and especially a working immune system, was used in the next step to further examine the side effects of minibeam radiotherapy compared to homogeneous irradiation. The central part of the ear of adult BALB/c mice was irradiated with 20 MeV protons, using an average dose of 60 Gy in a field of 7.2 x 7.2mm². The 4 x 4 minibeams of nominal 6000 Gy had a size of 180x180 µm2 and inter-beam distances of 1.8 mm, as in previous in-vitro skin experiments. Minibeam irradiation induced no ear swelling or other visible skin reaction at any time, while significant ear swelling (up to 4-fold), skin reddening (erythema) and desquamation developed in homogeneously irradiated ears 3-4 weeks after irradiation. Loss of hair and sebaceous glands only occurred in the homogeneous irradiation fields and did not recover during the monitoring phase of 90 days. Taken together all theoretical considerations and experimental findings, proton minibeam radiation therapy appears suitable for the implementation in clinical tumor therapy using protons and/or heavy ions, as it reduces side effects in the normal tissue compared to conventional broad beam irradiation. However, the upper limit of the minibeam size for tissue sparing and the technical feasibility are still to be elucidated as current technologies might have to be improved and adapted for the generation of sub-millimeter proton beams of energies up to 250 MeV at therapy plants.
BibTeX:
	@phdthesis{Girst2016diss,
	  author = {Stefanie Girst},
	  title = {Proton Minibeam Radiotherapy},
	  school = {Universität der Bundeswehr München},
	  year = {2016},
	  url = {http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:706-4569}
	}
	
Hydrogen analysis depth calibration by CORTEO Monte-Carlo simulation
M. Moser, P. Reichart, A. Bergmaier, C. Greubel, F. Schiettekatte and G. Dollinger; Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 371 (2016) 161-166.
Abstract: Abstract Hydrogen imaging with sub-?m lateral resolution and sub-ppm sensitivity has become possible with coincident proton-proton (pp) scattering analysis (Reichart et al., 2004). Depth information is evaluated from the energy sum signal with respect to energy loss of both protons on their path through the sample. In first order, there is no angular dependence due to elastic scattering. In second order, a path length effect due to different energy loss on the paths of the protons causes an angular dependence of the energy sum. Therefore, the energy sum signal has to be de-convoluted depending on the matrix composition, i.e. mainly the atomic number Z, in order to get a depth calibrated hydrogen profile. Although the path effect can be calculated analytically in first order, multiple scattering effects lead to significant deviations in the depth profile. Hence, in our new approach, we use the CORTEO Monte-Carlo code (Schiettekatte, 2008) in order to calculate the depth of a coincidence event depending on the scattering angle. The code takes individual detector geometry into account. In this paper we show, that the code correctly reproduces measured pp-scattering energy spectra with roughness effects considered. With more than 100 ?m thick Mylar-sandwich targets (Si, Fe, Ge) we demonstrate the deconvolution of the energy spectra on our current multistrip detector at the microprobe SNAKE at the Munich tandem accelerator lab. As a result, hydrogen profiles can be evaluated with an accuracy in depth of about 1% of the sample thickness.
BibTeX:
	@article{Moser2016,
	  author = {Moser, M. and Reichart, P. and Bergmaier, A. and Greubel, C. and Schiettekatte, F. and Dollinger, G.},
	  title = {Hydrogen analysis depth calibration by CORTEO Monte-Carlo simulation},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms},
	  year = {2016},
	  volume = {371},
	  pages = {161-166},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X15009428},
	  doi = {http://doi.org/10.1016/j.nimb.2015.09.069}
	}
	
Depletion of Histone Demethylase Jarid1A Resulting in Histone Hyperacetylation and Radiation Sensitivity Does Not Affect DNA Double-Strand Break Repair
C. Penterling, G.A. Drexler, C. Böhland, R. Stamp, C. Wilke, H. Braselmann, R.B. Caldwell, J. Reindl, S. Girst, C. Greubel, C. Siebenwirth, W.Y. Mansour, K. Borgmann, G. Dollinger, K. Unger and A.A. Friedl; PLoS ONE 11 (6) (2016) e0156599.
Abstract: Histone demethylases have recently gained interest as potential targets in cancer treatment and several histone demethylases have been implicated in the DNA damage response. We investigated the effects of siRNA-mediated depletion of histone demethylase Jarid1A (KDM5A, RBP2), which demethylates transcription activating tri- and dimethylated lysine 4 at histone H3 (H3K4me3/me2), on growth characteristics and cellular response to radiation in several cancer cell lines. In unirradiated cells Jarid1A depletion lead to histone hyperacetylation while not affecting cell growth. In irradiated cells, depletion of Jarid1A significantly increased cellular radiosensitivity. Unexpectedly, the hyperacetylation phenotype did not lead to disturbed accumulation of DNA damage response and repair factors 53BP1, BRCA1, or Rad51 at damage sites, nor did it influence resolution of radiation-induced foci or rejoining of reporter constructs. We conclude that the radiation sensitivity observed following depletion of Jarid1A is not caused by a deficiency in repair of DNA double-strand breaks.
BibTeX:
	@article{Penterling2016,
	  author = {Penterling, Corina and Drexler, Guido A. and Böhland, Claudia and Stamp, Ramona and Wilke, Christina and Braselmann, Herbert and Caldwell, Randolph B. and Reindl, Judith and Girst, Stefanie and Greubel, Christoph and Siebenwirth, Christian and Mansour, Wael Y. and Borgmann, Kerstin and Dollinger, Günther and Unger, Kristian and Friedl, Anna A.},
	  title = {Depletion of Histone Demethylase Jarid1A Resulting in Histone Hyperacetylation and Radiation Sensitivity Does Not Affect DNA Double-Strand Break Repair},
	  journal = {PLoS ONE},
	  year = {2016},
	  volume = {11},
	  number = {6},
	  pages = {e0156599},
	  url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156599},
	  doi = {http://doi.org/10.1371/journal.pone.0156599}
	}
	
Superresolution light microscopy shows nanostructure of carbon ion radiation-induced DNA double-strand break repair foci
R.L. Perez, G. Best, N.H. Nicolay, C. Greubel, S. Rossberger, J. Reindl, G. Dollinger, K.-J. Weber, C. Cremer and P.E. Huber; Faseb 30 (2016) 2767-2776.
Abstract: Carbon ion radiation is a promising new form of radiotherapy for cancer, but the central question about the biologic effects of charged particle radiation is yet incompletely understood. Key to this question is the understanding of the interaction of ions with DNA in the cell’s nucleus. Induction and repair of DNA lesions including double-strand breaks (DSBs) are decisive for the cell. Several DSB repair markers have been used to investigate these processes microscopically, but the limited resolution of conventional microscopy is insufficient to provide structural insights. We have applied superresolution microscopy to overcome these limitations and analyze the fine structure of DSB repair foci. We found that the conventionally detected foci of the widely used DSB marker ?H2AX (Ø700–1000 nm) were composed of elongated subfoci with a size of  100 nm consisting of even smaller subfoci elements (Ø40–60 nm). The structural organization of the subfoci suggests that they could represent the local chromatin structure of elementary DSB repair units at the DSB damage sites. Subfoci clusters may indicate induction of densely spaced DSBs, which are thought to be associated with the high biologic effectiveness of carbon ions. Superresolution microscopy might emerge as a powerful tool to improve our knowledge of interactions of ionizing radiation with cells.
BibTeX:
	@article{Perez2016,
	  author = {Ramon Lopez Perez and Gerrit Best and Nils H. Nicolay and Christoph Greubel and Sabrina Rossberger and Judith Reindl and Günther Dollinger and Klaus-Josef Weber and Christoph Cremer and Peter E. Huber},
	  title = {Superresolution light microscopy shows nanostructure of carbon ion radiation-induced DNA double-strand break repair foci},
	  journal = {Faseb},
	  year = {2016},
	  volume = {30},
	  pages = {2767-2776},
	  url = {http://www.fasebj.org/content/30/8/2767},
	  doi = {http://doi.org/10.1096/fj.201500106R}
	}
	
Deuterium microscopy using 17 MeV deuteron-deuteron scattering
P. Reichart, M. Moser, C. Greubel, K. Peeper and G. Dollinger; Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 371 (2016) 178-184.
Abstract: Abstract Using 17 MeV deuterons as a micrometer focused primary beam, we performed deuterium microscopy by using the deuteron-deuteron (dd) scattering reaction. We describe our new box like detector setup consisting of four double sided silicon strip detectors (DSSSD) with 16 strips on each side, each covering up to 0.5 sr solid angle for coincidence detection. This method becomes a valuable tool for studies of hydrogen incorporation or dynamic processes using deuterium tagging. The background from natural hydrocarbon or water contamination is reduced by the factor 150 ppm of natural abundance of deuterium in hydrogen. Deuterium energies of up to 25 MeV, available at the microprobe SNAKE, are ideal for the analysis of thin freestanding samples so that the scattered particles are transmitted to the detector. The differential cross section for the elastic scattering reaction is about the same as for pp-scattering ( 100 mb/sr). The main background due to nuclear reactions is outside the energy window of interest. Deuteron-proton (dp) scattering events give an additional signal for hydrogen atoms, so the H/D-ratio can be monitored in parallel.
BibTeX:
	@article{Reichart2016,
	  author = {Reichart, Patrick and Moser, Marcus and Greubel, Christoph and Peeper, Katrin and Dollinger, Günther},
	  title = {Deuterium microscopy using 17 MeV deuteron-deuteron scattering},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms},
	  year = {2016},
	  volume = {371},
	  pages = {178-184},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X15009489},
	  doi = {http://doi.org/10.1016/j.nimb.2015.09.075}
	}
	

2015

Ionoacoustic characterization of the proton Bragg peak with submillimeter accuracy
W. Assmann, S. Kellnberger, S. Reinhardt, S. Lehrack, A. Edlich, P.G. Thirolf, M. Moser, G. Dollinger, M. Omar, V. Ntziachristos and K. Parodi; Medical Physics 42 (2) (2015) 567-574.
Abstract: Purpose: Range verification in ion beam therapy relies to date on nuclear imaging techniques which require complex and costly detector systems. A different approach is the detection of thermoacoustic signals that are generated due to localized energy loss of ion beams in tissue (ionoacoustics). Aim of this work was to study experimentally the achievable position resolution of ionoacoustics under idealized conditions using high frequency ultrasonic transducers and a specifically selected probing beam.

Methods: A water phantom was irradiated by a pulsed 20 MeV proton beam with varying pulse intensity and length. The acoustic signal of single proton pulses was measured by different PZT-based ultrasound detectors (3.5 and 10 MHz central frequencies). The proton dose distribution in water was calculated by Geant4 and used as input for simulation of the generated acoustic wave by the matlab toolbox k-WAVE.

Results: In measurements from this study, a clear signal of the Bragg peak was observed for an energy deposition as low as 10e12 eV. The signal amplitude showed a linear increase with particle number per pulse and thus, dose. Bragg peak position measurements were reproducible within ±30 ?m and agreed with Geant4 simulations to better than 100 ?m. The ionoacoustic signal pattern allowed for a detailed analysis of the Bragg peak and could be well reproduced by k-WAVE simulations.

Conclusions: The authors have studied the ionoacoustic signal of the Bragg peak in experiments using a 20 MeV proton beam with its correspondingly localized energy deposition, demonstrating submillimeter position resolution and providing a deep insight in the correlation between the acoustic signal and Bragg peak shape. These results, together with earlier experiments and new simulations (including the results in this study) at higher energies, suggest ionoacoustics as a technique for range verification in particle therapy at locations, where the tumor can be localized by ultrasound imaging. This acoustic range verification approach could offer the possibility of combining anatomical ultrasound and Bragg peak imaging, but further studies are required for translation of these findings to clinical application.

BibTeX:
	@article{Assmann2015,
	  author = {Assmann, W. and Kellnberger, S. and Reinhardt, S. and Lehrack, S. and Edlich, A. and Thirolf, P. G. and Moser, M. and Dollinger, G. and Omar, M. and Ntziachristos, V. and Parodi, K.},
	  title = {Ionoacoustic characterization of the proton Bragg peak with submillimeter accuracy},
	  journal = {Medical Physics},
	  year = {2015},
	  volume = {42},
	  number = {2},
	  pages = {567--574},
	  url = {http://scitation.aip.org/content/aapm/journal/medphys/42/2/10.1118/1.4905047},
	  doi = {http://doi.org/10.1118/1.4905047}
	}
	
Live cell imaging at the Munich ion microbeam SNAKE - a status report
G.A. Drexler, C. Siebenwirth, S.E. Drexler, S. Girst, C. Greubel, G. Dollinger and A.A. Friedl; Radiation Oncology 10 (2015) 42.
Abstract: Ion microbeams are important tools in radiobiological research. Still, the worldwide number of ion microbeam facilities where biological experiments can be performed is limited. Even fewer facilities combine ion microirradiation with live-cell imaging to allow microscopic observation of cellular response reactions starting very fast after irradiation and continuing for many hours. At SNAKE, the ion microbeam facility at the Munich 14 MV tandem accelerator, a large variety of biological experiments are performed on a regular basis. Here, recent developments and ongoing research projects at the ion microbeam SNAKE are presented with specific emphasis on live-cell imaging experiments. An overview of the technical details of the setup is given, including examples of suitable biological samples. By ion beam focusing to submicrometer beam spot size and single ion detection it is possible to target subcellular structures with defined numbers of ions. Focusing of high numbers of ions to single spots allows studying the influence of high local damage density on recruitment of damage response proteins.
BibTeX:
	@article{Drexler2015,
	  author = {Drexler, Guido A. and Siebenwirth, Christian and Drexler, Sophie E. and Girst, Stefanie and Greubel, Christoph and Dollinger, Günther and Friedl, Anna A.},
	  title = {Live cell imaging at the Munich ion microbeam SNAKE - a status report},
	  journal = {Radiation Oncology},
	  year = {2015},
	  volume = {10},
	  pages = {42},
	  url = {http://ro-journal.biomedcentral.com/articles/10.1186/s13014-015-0350-7},
	  doi = {http://doi.org/10.1186/s13014-015-0350-7}
	}
	
Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation
S. Girst, C. Marx, E. Bräuer-Krisch, A. Bravin, S. Bartzsch, U. Oelfke, C. Greubel, J. Reindl, C. Siebenwirth, O. Zlobinskaya, G. Multhoff, G. Dollinger, T. Schmid and J. Wilkens; Physica Medica 31 (0) (2015) 615-620.
Abstract: The risk of developing normal tissue injuries often limits the radiation dose that can be applied to the tumour in radiation therapy. Microbeam Radiation Therapy (MRT), a spatially fractionated photon radiotherapy is currently tested at the European Synchrotron Radiation Facility (ESRF) to improve normal tissue protection. MRT utilizes an array of microscopically thin and nearly parallel X-ray beams that are generated by a synchrotron. At the ion microprobe SNAKE in Munich focused proton microbeams (“proton microchannels”) are studied to improve normal tissue protection. Here, we comparatively investigate microbeam/microchannel irradiations with sub-millimetre X-ray versus proton beams to minimize the risk of normal tissue damage in a human skin model, in vitro. Skin tissues were irradiated with a mean dose of 2 Gy over the irradiated area either with parallel synchrotron-generated X-ray beams at the ESRF or with 20 MeV protons at SNAKE using four different irradiation modes: homogeneous field, parallel lines and microchannel applications using two different channel sizes. Normal tissue viability as determined in an MTT test was significantly higher after proton or X-ray microchannel irradiation compared to a homogeneous field irradiation. In line with these findings genetic damage, as determined by the measurement of micronuclei in keratinocytes, was significantly reduced after proton or X-ray microchannel compared to a homogeneous field irradiation. Our data show that skin irradiation using either X-ray or proton microchannels maintain a higher cell viability and DNA integrity compared to a homogeneous irradiation, and thus might improve normal tissue protection after radiation therapy.
BibTeX:
	@article{Girst2015,
	  author = {Girst, S. and Marx, C. and Bräuer-Krisch, E. and Bravin, A. and Bartzsch, S. and Oelfke, U. and Greubel, C. and Reindl, J. and Siebenwirth, C. and Zlobinskaya, O. and Multhoff, G. and Dollinger, G. and Schmid, T.E. and Wilkens, J.J.},
	  title = {Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation},
	  journal = {Physica Medica},
	  year = {2015},
	  volume = {31},
	  number = {0},
	  pages = {615--620},
	  url = {http://www.sciencedirect.com/science/article/pii/S1120179715000952},
	  doi = {http://doi.org/10.1016/j.ejmp.2015.04.004}
	}
	
The influence of the channel size on the reduction of side effects in microchannel proton therapy
S. Girst, C. Greubel, J. Reindl, C. Siebenwirth, O. Zlobinskaya, G. Dollinger and T.E. Schmid; Radiation and Environmental Biophysics 54 (3) (2015) 335-342.
Abstract: The potential of proton microchannel radiotherapy to reduce radiation effects in the healthy tissue but to keep tumor control the same as in conventional proton therapy is further elucidated. The microchannels spread on their way to the tumor tissue resulting in different fractions of the healthy tissue covered with doses larger than the tumor dose, while the tumor gets homogeneously irradiated. The aim of this study was to evaluate the effect of increasing channel width on potential side effects in the normal tissue. A rectangular 180 × 180 µm2 and two Gaussian-type dose distributions of ? = 260 µm and ? = 520 µm with an interchannel distance of 1.8 mm have been applied by 20-MeV protons to a 3D human skin model in order to simulate the widened channels and to compare the irradiation effects at different endpoints to those of a homogeneous proton irradiation. The number of protons applied was kept constant at all irradiation modes resulting in the same average dose of 2 Gy. All kinds of proton microchannel irradiation lead to higher cell viability and produce significantly less genetic damage than homogeneous proton irradiation, but the reduction is lower for the wider channel sizes. Our findings point toward the application of microchannel irradiation for clinical proton or heavy ion therapy to further reduce damage of normal tissues while maintaining tumor control via a homogeneous dose distribution inside the tumor.
BibTeX:
	@article{Girst2015a,
	  author = {Girst, Stefanie and Greubel, Christoph and Reindl, Judith and Siebenwirth, Christian and Zlobinskaya, Olga and Dollinger, Günther and Schmid, Thomas E.},
	  title = {The influence of the channel size on the reduction of side effects in microchannel proton therapy},
	  booktitle = {Radiation and Environmental Biophysics},
	  journal = {Radiation and Environmental Biophysics},
	  year = {2015},
	  volume = {54},
	  number = {3},
	  pages = {335--342},
	  url = {http://link.springer.com/article/10.1007%2Fs00411-015-0600-y},
	  doi = {http://doi.org/10.1007/s00411-015-0600-y}
	}
	
Transport of a high brightness proton beam through the Munich tandem accelerator
M. Moser, C. Greubel, W. Carli, K. Peeper, P. Reichart, B. Urban, T. Vallentin and G. Dollinger; Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 348 (0) (2015) 34-42.
Abstract: Basic requirement for ion microprobes with sub-?m beam focus is a high brightness beam to fill the small phase space usually accepted by the ion microprobe with enough ion current for the desired application. We performed beam transport simulations to optimize beam brightness transported through the Munich tandem accelerator. This was done under the constraint of a maximum ion current of 10 ?A that is allowed to be injected due to radiation safety regulations and beam power constrains. The main influence of the stripper foil in conjunction with intrinsic astigmatism in the beam transport on beam brightness is discussed. The calculations show possibilities for brightness enhancement by using astigmatism corrections and asymmetric filling of the phase space volume in the x- and y-direction.
BibTeX:
	@article{Moser2015,
	  author = {Moser, M. and Greubel, C. and Carli, W. and Peeper, K. and Reichart, P. and Urban, B. and Vallentin, T. and Dollinger, G.},
	  title = {Transport of a high brightness proton beam through the Munich tandem accelerator},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms},
	  year = {2015},
	  volume = {348},
	  number = {0},
	  pages = {34--42},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X14009495},
	  doi = {http://doi.org/10.1016/j.nimb.2014.11.068}
	}
	
Nanoscopic exclusion between Rad51 and 53BP1 after ion irradiation in human HeLa cells
J. Reindl, G.A. Drexler, S. Girst, C. Greubel, C. Siebenwirth, S.E. Drexler, G. Dollinger and A.A. Friedl; Physical Biology 12 (6) (2015) 066005.
Abstract: Many proteins involved in detection, signalling and repair of DNA double-strand breaks (DSB) accumulate in large number in the vicinity of DSB sites, forming so called foci. Emerging evidence suggests that these foci are sub-divided in structural or functional domains. We use stimulated emission depletion (STED) microscopy to investigate localization of mediator protein 53BP1 and recombination factor Rad51 after irradiation of cells with low linear energy transfer (LET) protons or high LET carbon ions. With a resolution better than 100 nm, STED microscopy and image analysis using a newly developed analyzing algorithm, the reduced product of the differences from the mean, allowed us to demonstrate that with both irradiation types Rad51 occupies spherical regions of about 200 nm diameter. These foci locate within larger 53BP1 accumulations in regions of local 53BP1 depletion, similar to what has been described for the localization of Brca1, CtIP and RPA. Furthermore, localization relative to 53BP1 and size of Rad51 foci was not different after irradiation with low and high LET radiation. As expected, 53BP1 foci induced by low LET irradiation mostly contained one Rad51 focal structure, while after high LET irradiation, most foci contained >1 Rad51 accumulation.
BibTeX:
	@article{Reindl2015,
	  author = {Judith Reindl and Guido A Drexler and Stefanie Girst and Christoph Greubel and Christian Siebenwirth and Sophie E Drexler and Günther Dollinger and Anna A Friedl},
	  title = {Nanoscopic exclusion between Rad51 and 53BP1 after ion irradiation in human HeLa cells},
	  journal = {Physical Biology},
	  year = {2015},
	  volume = {12},
	  number = {6},
	  pages = {066005},
	  url = {http://stacks.iop.org/1478-3975/12/i=6/a=066005},
	  doi = {http://doi.org/10.1088/1478-3975/12/6/066005}
	}
	
Investigation of EBT2 and EBT3 films for proton dosimetry in the 4–20 MeV energy range
S. Reinhardt, M. Würl, C. Greubel, N. Humble, J. Wilkens, M. Hillbrand, A. Mairani, W. Assmann and K. Parodi; Radiation and Environmental Biophysics 54 (1) (2015) 71-79.
Abstract: Radiochromic films such as Gafchromic EBT2 or EBT3 films are widely used for dose determination in radiation therapy because they offer a superior spatial resolution compared to any other digital dosimetric 2D detector array. The possibility to detect steep dose gradients is not only attractive for intensity-modulated radiation therapy with photons but also for intensity-modulated proton therapy. Their characteristic dose rate-independent response makes radiochromic films also attractive for dose determination in cell irradiation experiments using laser-driven ion accelerators, which are currently being investigated as future medical ion accelerators. However, when using these films in ion beams, the energy-dependent dose response in the vicinity of the Bragg peak has to be considered. In this work, the response of these films for low-energy protons is investigated. To allow for reproducible and background-free irradiation conditions, the films were exposed to mono-energetic protons from an electrostatic accelerator, in the 4–20 MeV energy range. For comparison, irradiation with clinical photons was also performed. It turned out that in general, EBT2 and EBT3 films show a comparable performance. For example, dose–response curves for photons and protons with energies as low as 11 MeV show almost no differences. However, corrections are required for proton energies below 11 MeV. Care has to be taken when correction factors are related to an average LET from depth–dose measurements, because only the dose-averaged LET yields similar results as obtained in mono-energetic measurements.
BibTeX:
	@article{Reinhardt2015,
	  author = {Reinhardt, S. and Würl, M. and Greubel, C. and Humble, N. and Wilkens, J.J. and Hillbrand, M. and Mairani, A. and Assmann, W. and Parodi, K.},
	  title = {Investigation of EBT2 and EBT3 films for proton dosimetry in the 4–20 MeV energy range},
	  journal = {Radiation and Environmental Biophysics},
	  year = {2015},
	  volume = {54},
	  number = {1},
	  pages = {71--79},
	  url = {http://link.springer.com/article/10.1007%2Fs00411-014-0581-2},
	  doi = {http://doi.org/10.1007/s00411-014-0581-2}
	}
	
Sub-micrometer 20 MeV protons or 45 MeV lithium spot irradiation enhances yields of dicentric chromosomes due to clustering of DNA double-strand breaks
T. Schmid, W. Friedland, C. Greubel, S. Girst, J. Reindl, C. Siebenwirth, K. Ilicic, E. Schmid, G. Multhoff, E. Schmitt, P. Kundrát and G. Dollinger; Mutation Research/Genetic Toxicology and Environmental Mutagenesis 793 (2015) 30-40.
Abstract: Abstract In conventional experiments on biological effects of radiation types of diverse quality, micrometer-scale double-strand break (DSB) clustering is inherently interlinked with clustering of energy deposition events on nanometer scale relevant for DSB induction. Due to this limitation, the role of the micrometer and nanometer scales in diverse biological endpoints cannot be fully separated. To address this issue, hybrid human-hamster AL cells have been irradiated with 45 MeV (60 keV/?m) lithium ions or 20 MeV (2.6 keV/?m) protons quasi-homogeneously distributed or focused to 0.5 × 1 ?m2 spots on regular matrix patterns (point distances up to 10.6 × 10.6 ?m), with pre-defined particle numbers per spot to provide the same mean dose of 1.7 Gy. The yields of dicentrics and their distribution among cells have been scored. In parallel, track-structure based simulations of DSB induction and chromosome aberration formation with PARTRAC have been performed. The results show that the sub-micrometer beam focusing does not enhance DSB yields, but significantly affects the DSB distribution within the nucleus and increases the chance to form DSB pairs in close proximity, which may lead to increased yields of chromosome aberrations. Indeed, the experiments show that focusing 20 lithium ions or 451 protons per spot on a 10.6 ?m grid induces two or three times more dicentrics, respectively, than a quasi-homogenous irradiation. The simulations reproduce the data in part, but in part suggest more complex behavior such as saturation or overkill not seen in the experiments. The direct experimental demonstration that sub-micrometer clustering of DSB plays a critical role in the induction of dicentrics improves the knowledge on the mechanisms by which these lethal lesions arise, and indicates how the assumptions of the biophysical model could be improved. It also provides a better understanding of the increased biological effectiveness of high-LET radiation.
BibTeX:
	@article{Schmid2015,
	  author = {Schmid, T.E. and Friedland, W. and Greubel, C. and Girst, S. and Reindl, J. and Siebenwirth, C. and Ilicic, K. and Schmid, E. and Multhoff, G. and Schmitt, E. and Kundrát, P. and Dollinger, G.},
	  title = {Sub-micrometer 20 MeV protons or 45 MeV lithium spot irradiation enhances yields of dicentric chromosomes due to clustering of DNA double-strand breaks},
	  booktitle = {Insights into formation and consequences of chromosome aberrations: Report on the 11th International Symposium on Chromosomal Aberrations (ISCA 11), Rhodes , Greece, September 12-14, 2014},
	  journal = {Mutation Research/Genetic Toxicology and Environmental Mutagenesis},
	  year = {2015},
	  volume = {793},
	  pages = {30--40},
	  url = {http://www.sciencedirect.com/science/article/pii/S1383571815002053},
	  doi = {http://doi.org/10.1016/j.mrgentox.2015.07.015}
	}
	
Determination of the accuracy for targeted irradiations of cellular substructures at SNAKE
C. Siebenwirth, C. Greubel, S. Drexler, S. Girst, J. Reindl, D. Walsh, G. Dollinger, A. Friedl, T. Schmid and G. Drexler; Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 348 (0) (2015) 137-142.
Abstract: In the last 10 years the ion microbeam SNAKE, installed at the Munich 14 MV tandem accelerator, has been successfully used for radiobiological experiments by utilizing pattern irradiation without targeting single cells. Now for targeted irradiation of cellular substructures a precise irradiation device was added to the live cell irradiation setup at SNAKE. It combines a sub-micrometer single ion irradiation facility with a high resolution optical fluorescence microscope. Most systematic errors can be reduced or avoided by using the same light path in the microscope for beam spot verification as well as for and target recognition. In addition online observation of the induced cellular responses is possible. The optical microscope and the beam delivering system are controlled by an in-house developed software which integrates the open-source image analysis software, CellProfiler, for semi-automatic target recognition.
BibTeX:
	@article{Siebenwirth2015,
	  author = {Siebenwirth, C. and Greubel, C. and Drexler, S.E. and Girst, S. and Reindl, J. and Walsh, D.W.M. and Dollinger, G. and Friedl, A.A. and Schmid, T.E. and Drexler, G.A.},
	  title = {Determination of the accuracy for targeted irradiations of cellular substructures at SNAKE},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms},
	  year = {2015},
	  volume = {348},
	  number = {0},
	  pages = {137--142},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X15000865},
	  doi = {http://doi.org/10.1016/j.nimb.2015.01.064}
	}
	
Quantification of water in hydrous ringwoodite
S.-M. Thomas, S.D. Jacobsen, C.R. Bina, P. Reichart, M. Moser, E.H. Hauri, M. Koch-Müller, J.R. Smyth and G. Dollinger; Frontiers in Earth Science 2 (2015) 38/1-10.
Abstract: Ringwoodite, ?-(Mg,Fe)2SiO4, in the lower 150 km of Earth's mantle transition zone (410–660 km depth) can incorporate up to 1.5–2 wt% H2O as hydroxyl defects. We present a mineral-specific IR calibration for the absolute water content in hydrous ringwoodite by combining results from Raman spectroscopy, secondary ion mass spectrometry (SIMS) and proton-proton (pp)-scattering on a suite of synthetic Mg- and Fe-bearing hydrous ringwoodites. H2O concentrations in the crystals studied here range from 0.46 to 1.7 wt% H2O (absolute methods), with the maximum H2O in the same sample giving 2.5 wt% by SIMS calibration. Anchoring our spectroscopic results to absolute H-atom concentrations from pp-scattering measurements, we report frequency-dependent integrated IR-absorption coefficients for water in ringwoodite ranging from 78,180 to 158,880 Lmol?1cm?2, depending upon frequency of the OH absorption. We further report a linear wavenumber IR calibration for H2O quantification in hydrous ringwoodite across the Mg2SiO4-Fe2SiO4 solid solution, which will lead to more accurate estimations of the water content in both laboratory-grown and naturally occurring ringwoodites. Re-evaluation of the IR spectrum for a natural hydrous ringwoodite inclusion in diamond from the study of Pearson et al. (2014) indicates the crystal contains 1.43 ± 0.27 wt% H2O, thus confirming near-maximum amounts of H2O for this sample from the transition zone.
BibTeX:
	@article{Thomas2015,
	  author = {Thomas, Sylvia-Monique and Jacobsen, Steven D. and Bina, Craig R. and Reichart, Patrick and Moser, Marcus and Hauri, Erik H. and Koch-Müller, Monika and Smyth, Joseph R. and Dollinger, Günther},
	  title = {Quantification of water in hydrous ringwoodite},
	  journal = {Frontiers in Earth Science},
	  year = {2015},
	  volume = {2},
	  pages = {38/1-10},
	  url = {http://www.frontiersin.org/earth_and_planetary_materials/10.3389/feart.2014.00038/abstract},
	  doi = {http://doi.org/10.3389/feart.2014.00038}
	}
	
A microbeam slit system for high beam currents
T. Vallentin, M. Moser, S. Eschbaumer, C. Greubel, T. Haase, P. Reichart, T. Rösch and G. Dollinger; Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 348 (0) (2015) 43-47.
Abstract: A new microbeam slit system for high beam currents of 10 ?A was built up to improve the brightness transport of a proton beam with a kinetic energy of up to 25 MeV into the microprobe SNAKE. The new slit system features a position accuracy of less than 1 ?m under normal operating conditions and less than 2 ?m if the beam is switched on and off. The thermal management with a powerful watercooling and potential-free thermocouple feedback controlled heating cables is optimized for constant slit aperture at thermal power input of up to 250 W. The transparent zone is optimized to 0.7 ?m due to the use of tungsten formed to a cylindrical surface with a radius r = 100 mm and mechanically lapped surface to minimize small angle scattering effects and to minimize the number of ions passing the slits with low energy loss. Electrical isolation of the slit tip enables slit current monitoring, e.g. for tandem accelerator feedback control. With the ability to transport up to 10 ?A of protons with the new microslit system, the brightness B_exp transported into the microprobe was increased by a factor of 2 compared to low current injection using the old slit system.
BibTeX:
	@article{Vallentin2015,
	  author = {Vallentin, T. and Moser, M. and Eschbaumer, S. and Greubel, C. and Haase, T. and Reichart, P. and Rösch, T. and Dollinger, G.},
	  title = {A microbeam slit system for high beam currents},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms},
	  year = {2015},
	  volume = {348},
	  number = {0},
	  pages = {43--47},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X14010313},
	  doi = {http://doi.org/10.1016/j.nimb.2014.12.015}
	}
	

2014

Three-dimensional microscopy of deuterium in tungsten
K. Peeper, M. Moser, P. Reichart, E. Markina, S. Elgeti (Lindig), M. Balden, T. Schwarz-Selinger, M. Mayer and G. Dollinger; Physica Scripta T159 (2014) 014070.
Abstract: The hydrogen isotope retention in tungsten is an important issue for fusion devices. In this paper we study the possibility of using a ? m-focused deuterium beam in order to quantify deuterium distributions in microscopic dimensions. Due to the lack of cross-section data for deuteron-deuteron-scattering (dd-scattering) a validated reference sample is needed. For this purpose we used a15 ? m thick aluminum foil covered by a-C:D-layers that have been deposited in a CD 4 plasma discharge from both sides. At the SNAKE facility of the Munich tandem accelerator we already established a three-dimensional microscopy of hydrogen using protons within an energy range between 17 and 25 MeV. Now, we have tested the possibility for deuteron microscopy. As a first application we analyzed a25 ? m foil implanted with 2.0 × 10 20 atom cm ?2 deuterons.
BibTeX:
	@article{Peeper2014,
	  author = {Peeper, K. and Moser, M. and Reichart, P. and Markina, E. and Elgeti (Lindig), S. and Balden, M. and Schwarz-Selinger, Th. and Mayer, M. and Dollinger, G.},
	  title = {Three-dimensional microscopy of deuterium in tungsten},
	  journal = {Physica Scripta},
	  year = {2014},
	  volume = {T159},
	  pages = {014070},
	  url = {http://stacks.iop.org/1402-4896/2014/i=T159/a=014070},
	  doi = {http://doi.org/10.1088/0031-8949/2014/T159/014070}
	}
	
A Microbeam Slit System for High Beam Currents
Thomas Vallentin; Masters-Thesis, Universität der Bundeswehr München, 2014.
Abstract: A new microbeam slit system for high beam currents of 10 µA was built up to improve the brightness transport of a proton beam with a kinetic energy of up to 25 MeV into the microprobe SNAKE. The new slit system features a position accuracy of less than 1 µm under normal operating conditions and less than 2 µm if the beam is switched on and off [1]. The thermal management with a powerful watercooling and potential-free thermocouple feedback controlled heating cables is optimized for constant slit aperture. The transparent zone is reduced to 0.7 µm due to the use of mechanically lapped tungsten as slit tip material to reduce small angle scattering effects and to reduce the number of ions passing the slits with low energy loss. The slits feature electrical isolation of the slit tip to make slit current monitoring possible, e.g. for tandem feedback control. With the high possible thermal power input of 250 W we could measure for the first time the high-energy beam brightness B_exp of injected beams with high emittances of eps_in = 2pi mmmrad. The brightness B_exp transported into the microprobe was improved to B_exp = 2 µA/(mm2 mrad2 MeV) and therefore brightness loss through the tandem accelerator was around 25 %. The higher transported brightness B_exp gives the opportunity to achieve the high resolution of the single ion, cell irradiation setup [8, 7] ( 320 nm) also at higher current of I_exp = 100 pA for materials analysis [5].
BibTeX:
	@mastersthesis{Vallentin2014ma,
	  author = {Vallentin, Thomas},
	  title = {A Microbeam Slit System for High Beam Currents},
	  school = {Universität der Bundeswehr München},
	  year = {2014}
	}
	
The Effects of Ultra-High Dose Rate Proton Irradiation on Growth Delay in the Treatment of Human Tumor Xenografts in Nude Mice
O. Zlobinskaya, C. Siebenwirth, C. Greubel, V. Hable, R. Hertenberger, N. Humble, S. Reinhardt, D. Michalski, B. Röper, G. Multhoff, G. Dollinger, J. Wilkens and T. Schmid; Radiation Research 181 (2) (2014) 177-183.
Abstract: The new technology of laser-driven ion acceleration (LDA) has shown the potential for driving highly brilliant particle beams. Laser-driven ion acceleration differs from conventional proton sources by its ultra-high dose rate, whose radiobiological impact should be investigated thoroughly before adopting current clinical dose concepts. The growth of human FaDu tumors transplanted onto the hind leg of nude mice was measured sonographically. Tumors were irradiated with 20 Gy of 23 MeV protons at pulsed mode with single pulses of 1 ns duration or continuous mode (?100 ms) in comparison to controls and to a dose-response curve for 6 MV photons. Tumor growth delay and the relative biological effectiveness (RBE) were calculated for all irradiation modes. The mean target dose reconstructed from Gafchromic films was 17.4 ± 0.8 Gy for the pulsed and 19.7 ± 1.1 Gy for the continuous irradiation mode. The mean tumor growth delay was 34 ± 6 days for pulsed, 35 ± 6 days for continuous protons, and 31 ± 7 days for photons 20 ± 1.2 Gy, resulting in RBEs of 1.22 ± 0.19 for pulsed and 1.10 ± 0.18 for continuous protons, respectively. In summary, protons were found to be significantly more effective in reducing the tumor volume than photons (P The new technology of laser-driven ion acceleration (LDA) has shown the potential for driving highly brilliant particle beams. Laser-driven ion acceleration differs from conventional proton sources by its ultra-high dose rate, whose radiobiological impact should be investigated thoroughly before adopting current clinical dose concepts. The growth of human FaDu tumors transplanted onto the hind leg of nude mice was measured sonographically. Tumors were irradiated with 20 Gy of 23 MeV protons at pulsed mode with single pulses of 1 ns duration or continuous mode (?100 ms) in comparison to controls and to a dose-response curve for 6 MV photons. Tumor growth delay and the relative biological effectiveness (RBE) were calculated for all irradiation modes. The mean target dose reconstructed from Gafchromic films was 17.4 ± 0.8 Gy for the pulsed and 19.7 ± 1.1 Gy for the continuous irradiation mode. The mean tumor growth delay was 34 ± 6 days for pulsed, 35 ± 6 days for continuous protons, and 31 ± 7 days for photons 20 ± 1.2 Gy, resulting in RBEs of 1.22 ± 0.19 for pulsed and 1.10 ± 0.18 for continuous protons, respectively. In summary, protons were found to be significantly more effective in reducing the tumor volume than photons (P
BibTeX:
	@article{Zlobinskaya2014,
	  author = {Zlobinskaya, O. and Siebenwirth, C. and Greubel, C. and Hable, V. and Hertenberger, R. and Humble, N. and Reinhardt, S. and Michalski, D. and Röper, B. and Multhoff, G. and Dollinger, G. and Wilkens, J.J. and Schmid, T.E.},
	  title = {The Effects of Ultra-High Dose Rate Proton Irradiation on Growth Delay in the Treatment of Human Tumor Xenografts in Nude Mice},
	  booktitle = {Radiation Research},
	  journal = {Radiation Research},
	  year = {2014},
	  volume = {181},
	  number = {2},
	  pages = {177--183},
	  url = {http://www.rrjournal.org/doi/abs/10.1667/RR13464.1},
	  doi = {http://doi.org/10.1667/RR13464.1}
	}
	

2013

Subdiffusion Supports Joining Of Correct Ends During Repair Of DNA Double-Strand Breaks
S. Girst, V. Hable, G.A. Drexler, C. Greubel, C. Siebenwirth, M. Haum, A.A. Friedl and G. Dollinger; Scientific Reports 3 (2013) 2511.
Abstract: The mobility of damaged chromatin regions in the nucleus may affect the probability of mis-repair. In this work, live-cell observation and distance tracking of GFP-tagged DNA damage response protein MDC1 was used to study the random-walk behaviour of chromatin domains containing radiation-induced DNA double-strand breaks (DSB). Our measurements indicate a subdiffusion-type random walk process with similar time dependence for isolated and clustered DSBs that were induced by 20 MeV proton or 43 MeV carbon ion micro-irradiation. As compared to normal diffusion, subdiffusion enhances the probability that both ends of a DSB meet, thus promoting high efficiency DNA repair. It also limits their probability of long-range movements and thus lowers the probability of mis-rejoining and chromosome aberrations.
BibTeX:
	@article{Girst2013,
	  author = {Girst, S. and Hable, V. and Drexler, G. A. and Greubel, C. and Siebenwirth, C. and Haum, M. and Friedl, A. A. and Dollinger, G.},
	  title = {Subdiffusion Supports Joining Of Correct Ends During Repair Of DNA Double-Strand Breaks},
	  journal = {Scientific Reports},
	  year = {2013},
	  volume = {3},
	  pages = {2511},
	  url = {http://www.nature.com/articles/srep02511},
	  doi = {http://doi.org/10.1038/srep02511}
	}
	
Einfluss der zeitlichen und räumlichen Fokussierung auf die strahlenbiologische Wirksamkeit von Protonen.
Christoph Greubel; Dissertation, Universität der Bundeswehr München, 2013.
Abstract: In dieser Arbeit wurde der Einfluss von auf Nanosekunden gepulster (zeitlich fokussierter) Dosisdeposition, im zweiten Teil von auf Submikrometer (räumlich) fokussierter Dosisdeposition auf die relative biologische Wirksamkeit, RBE, studiert. Die Effekte gepulster Bestrahlung auf Nanosekunden Zeitskala sind vor allem für eine mögliche Anwendung der Laserbeschleunigung von Ionen in der Tumortherapie, welche die Dosisdeposition auf einer Nanosekunden Zeitskala erwarten lässt, von Bedeutung. Zur Untersuchung wurde die Wachstumsverzögerung von zwei menschlichen Plattenepitelkarzinomen aus dem Mund- und Rachenraum, FaDu und XF354, im Mausmodell nach Bestrahlung mit einer Fraktion von nominell 20 Gy gemessen. In Ermangelung geeigneter lasergetriebener Ionenstrahlen wurde hierzu mittels konventioneller Technik am Rasterionenmikroskop SNAKE am Müchener Tandembeschleuniger ein auf 1,3 ns (volle Halbwertsbreite) gepulster 23 MeV Protonenstrahl mit einer Fluenz pro Einzelpuls von bis zu 109 cm-2 präpariert, sowie ein kontinuierlicher Protonenstrahl zur Dosisdeposition auf Millisekunden Zeitskala für direkte Vergleichsmessungen. Die Bestrahlung der maximal 4 mm tiefen und 7 mm im Durchmesser messenden Tumore erfolgt voxelweise, wobei die komplette Fluenz eines Voxels mit einem Nanosekunden Puls appliziert wird. An jedem Punkt im Tumor deponiert mindestens ein Puls eine Dosis zwischen 1,0 Gy und 2,7 Gy. Der RBE für die Wachstumsverzögerung von FaDu Tumoren bezüglich 6 MV Röntgenstrahlung wurde nach kontinuierlicher Dosisdeposition zu 1,10 ± 0,14, nach gepulster Dosisdeposition zu 1,22 ± 0,17 gemessen. Auch für die XF354 Tumore konnte kein signifikanter Unterschied in der Wachstumsverzögerung gemessen werden. Die Messungen zeigen keine Anzeichen für eine geänderte Wirksamkeit von Nanosekunden gepulster Dosisdeposition. Im zweiten Teil der Arbeit wurden die Auswirkungen von räumlich fokussierter Dosisdeposition am Endpunkt der Induktion von dizentrischen Chromosomen und Mikrokernen untersucht. Durch die Submikrometer Fokussierung von niedrig-LET 20 MeV Protonen kann eine räumliche Dosisverteilung generiert werden, welche qualitativ jener von Schwerionen mit hohem LET ähnelt, so dass die Wirkung von dichtionisierender hoch-LET Strahlung modelliert werden kann. Hierzu wurden AL-Zellen mit einer Dosis von jeweils 1,7 Gy in drei verschiedenen Modi bestrahlt: Die Bestrahlung mit Submikrometer fokussierten 20 MeV Protonen folgt einer 5,4 µm x 5,4 µm Matrix, wobei 117 Protonen pro Matrixpunkt appliziert werden. Die Bestrahlung mit 55 MeV Kohlenstoffionen erfolgt im selben Muster mit je einem Ion pro Matrixpunkt. Zufällig verteilte 20 MeV Protonen werden mit einer Fluenz von 4,01 µm-2 appliziert. Der RBE für die Induktion von Mikrokernen steigt durch die Fokussierung der Protonen von 1,28 ± 0,07 nach zufällig verteilter Protonenbestrahlung auf 1,48 ± 0,07 nach fokussierter Protonenapplikation, der RBE für die Induktion von dizentrischen Chromosomen steigt von 1,41 ± 0,14 auf 1,92 ± 0,15. Der von Kohlenstoffionen induzierte RBE ist mit 2,20 ± 0,09 für Mikrokerne und 3,21 ± 0,27 für dizentrische Chromosomen nochmal deutlich höher. Die signifikante Erhöhung der Induktion von Chromosomenaberrationen alleine durch die Fokussierung der Protonen und damit der räumlichen Dosisverteilung zeigt, dass die räumliche Dosisverteilung für den RBE maßgeblich ist. Die Experimente stellen somit die erste experimentelle Bestätigung der Grundannahme des Local Effect Models dar, welches in der Tumortherapie mit schweren Ionen zur Modellierung des RBE für die Dosisplanung verwendet wird. Rechnungen mit dem Local Effect Model III zeigen jedoch, dass dieses den RBE für die Endpunkte der Chromosomenaberrationen für die drei Bestrahlungsmodi zwar qualitativ, nicht aber quantitativ beschreiben kann.
BibTeX:
	@phdthesis{Greubel2013diss,
	  author = {Greubel, Christoph},
	  title = {Einfluss der zeitlichen und räumlichen Fokussierung auf die strahlenbiologische Wirksamkeit von Protonen.},
	  school = {Universität der Bundeswehr München},
	  year = {2013},
	  url = {http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:706-3415}
	}
	
High-accuracy fluence determination in ion beams using fluorescent nuclear track detectors
J.-M. Osinga, M. Akselrod, R. Herrmann, V. Hable, G. Dollinger, O. Jäkel and S. Greilich; Radiation Measurements 56 (2013) 294-298.
Abstract: We present an approach to use Al2O3:C,Mg-based fluorescent nuclear track detectors (FNTDs) and confocal laser scanning microscopy as a semiautomatic tool for fluence measurements in clinical ion beams. The method was found to cover a linear energy transfer (LET) range from at least L?(Al2O3) = 0.5 keV/?m to 61,000 keV/?m with a detection efficiency ?99.83% (20 MeV protons) at particle fluences up to at least 5 × 107 per cm2. Our technique allows to determine the spatial fluence distribution on a microscopic scale and enables detailed track-by-track comparison studies between different fluence detectors.
BibTeX:
	@article{Osinga2013,
	  author = {Osinga, J.-M. and Akselrod, M.S. and Herrmann, R. and Hable, V. and Dollinger, G. and Jäkel, O. and Greilich, S.},
	  title = {High-accuracy fluence determination in ion beams using fluorescent nuclear track detectors},
	  booktitle = {Proceedings of the 8th International Conference on Luminescent Detectors and Transformers of Ionizing Radiation (LUMDETR 2012)},
	  journal = {Radiation Measurements},
	  year = {2013},
	  volume = {56},
	  pages = {294--298},
	  url = {http://www.sciencedirect.com/science/article/pii/S1350448713000589},
	  doi = {http://doi.org/10.1016/j.radmeas.2013.01.035}
	}
	
3D-microscopy of hydrogen in tungsten
K. Peeper, M. Moser, P. Reichart, E. Markina, M. Mayer, S. Lindig, M. Balden and G. Dollinger; Journal of Nuclear Materials 438, Supplement (0) (2013) S887-S890.
Abstract: The mapping of hydrogen distributions in 3 dimensions and its correlation with structural features allow further insight into mechanisms of hydrogen trapping in tungsten. We studied hydrogen distributions in 25 ?m thick polycrystalline tungsten foils by 3D hydrogen microscopy using a proton-proton-scattering method. Two types of tungsten samples were prepared: (i) at 1200 K annealed foils and using 1.8 MeV implantation energy (ii) at 2000 K annealed foils using 200 eV implantation energy. It has been found that large variations of surface hydrogen contamination occur within different samples. Nevertheless, a statistically significant variation of the hydrogen content across grain boundaries has been observed.
BibTeX:
	@article{Peeper2013,
	  author = {Peeper, K. and Moser, M. and Reichart, P. and Markina, E. and Mayer, M. and Lindig, S. and Balden, M. and Dollinger, G.},
	  title = {3D-microscopy of hydrogen in tungsten},
	  booktitle = {Proceedings of the 20th International Conference on Plasma-Surface Interactions in Controlled Fusion Devices},
	  journal = {Journal of Nuclear Materials},
	  year = {2013},
	  volume = {438, Supplement},
	  number = {0},
	  pages = {S887--S890},
	  url = {http://www.sciencedirect.com/science/article/pii/S0022311513002006},
	  doi = {http://doi.org/10.1016/j.jnucmat.2013.01.192}
	}
	
Hydrogen microscopy - Distribution of hydrogen in buckled niobium hydrogen thin films
S. Wagner, M. Moser, C. Greubel, K. Peeper, P. Reichart, A. Pundt and G. Dollinger; International Journal of Hydrogen Energy 38 (31) (2013) 13822-13830.
Abstract: Hydrogen absorption in thin metal films clamped to rigid substrates results in mechanical stress that changes the hydrogen's chemical potential by ??H(?) = ?1.124? kJ/molH for ? measured in [GPa]. In this paper we show that local stress relaxation by the detachment of niobium hydrogen thin films from the substrate affects the chemical potential on the local scale: using coincident proton-proton scattering at a proton microprobe, the hydrogen concentration is determined with ?m resolution, revealing that hydrogen is not homogenously distributed in the film. The local hydrogen solubility of the film changes with its local stress state, mapping the buckled film fraction. In niobium hydrogen thin films loaded up to nominal concentrations in the two-phase coexistence region, the clamped film fraction remains in the solid solution phase, while the buckles represent the hydride phase. These results are compared to a simple model taking the stress impact on the chemical potential into account.
BibTeX:
	@article{Wagner2013,
	  author = {Wagner, Stefan and Moser, Marcus and Greubel, Christoph and Peeper, Katrin and Reichart, Patrick and Pundt, Astrid and Dollinger, Günther},
	  title = {Hydrogen microscopy - Distribution of hydrogen in buckled niobium hydrogen thin films},
	  journal = {International Journal of Hydrogen Energy},
	  year = {2013},
	  volume = {38},
	  number = {31},
	  pages = {13822--13830},
	  url = {http://www.sciencedirect.com/science/article/pii/S0360319913019137},
	  doi = {http://doi.org/10.1016/j.ijhydene.2013.08.006}
	}
	
Reduced side effects by proton microchannel radiotherapy: Study in a human skin model
O. Zlobinskaya, S. Girst, C. Greubel, V. Hable, C. Siebenwirth, D. Walsh, G. Multhoff, J. Wilkens, T. Schmid and G. Dollinger; Radiation and Environmental Biophysics 52 (1) (2013) 123-133.
Abstract: The application of a microchannel proton irradiation was compared to homogeneous irradiation in a three-dimensional human skin model. The goal is to minimize the risk of normal tissue damage by microchannel irradiation, while preserving local tumor control through a homogeneous irradiation of the tumor that is achieved because of beam widening with increasing track length. 20 MeV protons were administered to the skin models in 10- or 50-?m-wide irradiation channels on a quadratic raster with distances of 500 ?m between each channel (center to center) applying an average dose of 2 Gy. For comparison, other samples were irradiated homogeneously at the same average dose. Normal tissue viability was significantly enhanced after microchannel proton irradiation compared to homogeneous irradiation. Levels of inflammatory parameters, such as Interleukin-6, TGF-Beta, and Pro-MMP1, were significantly lower in the supernatant of the human skin tissue after microchannel irradiation than after homogeneous irradiation. The genetic damage as determined by the measurement of micronuclei in keratinocytes also differed significantly. This difference was quantified via dose modification factors (DMF) describing the effect of each irradiation mode relative to homogeneous X-ray irradiation, so that the DMF of 1.21 ± 0.20 after homogeneous proton irradiation was reduced to 0.23 ± 0.11 and 0.40 ± 0.12 after microchannel irradiation using 10- and 50-?m-wide channels, respectively. Our data indicate that proton microchannel irradiation maintains cell viability while significantly reducing inflammatory responses and genetic damage compared to homogeneous irradiation, and thus might improve protection of normal tissue after irradiation.
BibTeX:
	@article{Zlobinskaya2013,
	  author = {Zlobinskaya, O. and Girst, S. and Greubel, C. and Hable, V. and Siebenwirth, C. and Walsh, D.W.M. and Multhoff, G. and Wilkens, J.J. and Schmid, T.E. and Dollinger, G.},
	  title = {Reduced side effects by proton microchannel radiotherapy: Study in a human skin model},
	  booktitle = {Radiation and Environmental Biophysics},
	  journal = {Radiation and Environmental Biophysics},
	  year = {2013},
	  volume = {52},
	  number = {1},
	  pages = {123--133},
	  url = {http://link.springer.com/article/10.1007%2Fs00411-012-0450-9},
	  doi = {http://doi.org/10.1007/s00411-012-0450-9}
	}
	

2012

A laser-driven nanosecond proton source for radiobiological studies
J. Bin, K. Allinger, W. Assmann, G. Dollinger, G.A. Drexler, A.A. Friedl, D. Habs, P. Hilz, R. Hoerlein, N. Humble, S. Karsch, K. Khrennikov, D. Kiefer, F. Krausz, W. Ma, D. Michalski, M. Molls, S. Raith, S. Reinhardt, B. Roeper, T.E. Schmid, T. Tajima, J. Wenz, O. Zlobinskaya, J. Schreiber and J.J. Wilkens; Applied Physics Letters 101 (24) (2012) 243701.
Abstract: Ion beams are relevant for radiobiological studies and for tumor therapy. In contrast to conventional accelerators, laser-driven ion acceleration offers a potentially more compact and cost-effective means of delivering ions for radiotherapy. Here, we show that by combining advanced acceleration using nanometer thin targets and beam transport, truly nanosecond quasi-monoenergetic proton bunches can be generated with a table-top laser system, delivering single shot doses up to 7Gy to living cells. Although in their infancy, laser-ion accelerators allow studying fast radiobiological processes as demonstrated here by measurements of the relative biological effectiveness of nanosecond proton bunches in human tumor cells.
BibTeX:
	@article{Bin2012,
	  author = {Bin, Jianhui and Allinger, Klaus and Assmann, Walter and Dollinger, Guenther and Drexler, Guido A. and Friedl, Anna A. and Habs, Dieter and Hilz, Peter and Hoerlein, Rainer and Humble, Nicole and Karsch, Stefan and Khrennikov, Konstantin and Kiefer, Daniel and Krausz, Ferenc and Ma, Wenjun and Michalski, Doerte and Molls, Michael and Raith, Sebastian and Reinhardt, Sabine and Roeper, Barbara and Schmid, Thomas E. and Tajima, Toshiki and Wenz, Johannes and Zlobinskaya, Olga and Schreiber, Joerg and Wilkens, Jan J.},
	  title = {A laser-driven nanosecond proton source for radiobiological studies},
	  journal = {Applied Physics Letters},
	  year = {2012},
	  volume = {101},
	  number = {24},
	  pages = {243701},
	  url = {http://link.aip.org/link/doi/10.1063/1.4769372},
	  doi = {http://doi.org/10.1063/1.4769372}
	}
	
Recruitment kinetics of DNA repair proteins Mdc1 and Rad52 but not 53BP1 depend on damage complexity
V. Hable, G.A. Drexler, T. Brüning, C. Burgdorf, C. Greubel, A. Derer, J. Seel, H. Strickfaden, T. Cremer, A.A. Friedl and G. Dollinger; PLoS One 7 (7) (2012) e41943.
Abstract: The recruitment kinetics of double-strand break (DSB) signaling and repair proteins Mdc1, 53BP1 and Rad52 into radiation-induced foci was studied by live-cell fluorescence microscopy after ion microirradiation. To investigate the influence of damage density and complexity on recruitment kinetics, which cannot be done by UV laser irradiation used in former studies, we utilized 43 MeV carbon ions with high linear energy transfer per ion (LET = 370 keV/?m) to create a large fraction of clustered DSBs, thus forming complex DNA damage, and 20 MeV protons with low LET (LET = 2.6 keV/?m) to create mainly isolated DSBs. Kinetics for all three proteins was characterized by a time lag period T0 after irradiation, during which no foci are formed. Subsequently, the proteins accumulate into foci with characteristic mean recruitment times ?1. Mdc1 accumulates faster (T0 = 17±2 s, ?1 = 98±11 s) than 53BP1 (T0 = 77±7 s, ?1 = 310±60 s) after high LET irradiation. However, recruitment of Mdc1 slows down (T0 = 73±16 s, ?1 = 1050±270 s) after low LET irradiation. The recruitment kinetics of Rad52 is slower than that of Mdc1, but exhibits the same dependence on LET. In contrast, the mean recruitment time ?1 of 53BP1 remains almost constant when varying LET. Comparison to literature data on Mdc1 recruitment after UV laser irradiation shows that this rather resembles recruitment after high than low LET ionizing radiation. So this work shows that damage quality has a large influence on repair processes and has to be considered when comparing different studies.
BibTeX:
	@article{Hable2012,
	  author = {Hable, Volker and Drexler, Guido A. and Brüning, Tino and Burgdorf, Christian and Greubel, Christoph and Derer, Anja and Seel, Judith and Strickfaden, Hilmar and Cremer, Thomas and Friedl, Anna A. and Dollinger, Günther},
	  title = {Recruitment kinetics of DNA repair proteins Mdc1 and Rad52 but not 53BP1 depend on damage complexity},
	  journal = {PLoS One},
	  year = {2012},
	  volume = {7},
	  number = {7},
	  pages = {e41943},
	  url = {http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0041943},
	  doi = {http://doi.org/10.1371/journal.pone.0041943}
	}
	
Ultrahigh gain AlGaN/GaN high energy radiation detectors
J.D. Howgate, M. Hofstetter, S.J. Schoell, M. Schmid, S. Schäfer, I. Zizak, V. Hable, C. Greubel, G. Dollinger, S. Thalhammer, M. Stutzmann and I.D. Sharp; physica status solidi (a) 209 (8) (2012) 1562-1567.
Abstract: Due to its remarkable tolerance to high energy ionizing radiation, GaN has recently attracted attention as a promising material for dosimetry applications. However, materials issues that lead to persistent photoconductivity, poor sensitivity, and requirements for large operational voltages have been hurdles to realization of the full potential of this material. Here we demonstrate that the introduction of a two-dimensional electron gas channel, through the addition of AlGaN/GaN heterointerfaces, can be used to create intrinsic amplification of the number of electrons that can be collected from single ionization events, yielding exceptionally large sensitivities in ultralow dose rate regimes. Furthermore, anomalous photo-responses, which severely limit response times of GaN-based devices, can be eliminated using these heterostructures. Measurements using focused monochromatic synchrotron radiation at 1-20 keV, as well as focused 20 MeV protons, reveal that these devices provide the capability for high sensitivity and resolution real time monitoring, which is competitive with and complementary to state-of-the-art detectors. Therefore, AlGaN/GaN heterostructure devices are extremely promising for future applications in fields ranging from high energy physics to medical imaging.
BibTeX:
	@article{Howgate2012,
	  author = {Howgate, J. D. and Hofstetter, M. and Schoell, S. J. and Schmid, M. and Schäfer, S. and Zizak, I. and Hable, V. and Greubel, C. and Dollinger, G. and Thalhammer, S. and Stutzmann, M. and Sharp, I. D.},
	  title = {Ultrahigh gain AlGaN/GaN high energy radiation detectors},
	  journal = {physica status solidi (a)},
	  year = {2012},
	  volume = {209},
	  number = {8},
	  pages = {1562--1567},
	  url = {http://onlinelibrary.wiley.com/doi/10.1002/pssa.201228097/abstract},
	  doi = {http://doi.org/10.1002/pssa.201228097}
	}
	
High brilliance multicusp ion source for hydrogen microscopy at SNAKE
M. Moser, P. Reichart, W. Carli, C. Greubel, K. Peeper, P. Hartung and G. Dollinger; Nuclear Instruments and Methods in Physics Research Section B 273 (2012) 226-230.
Abstract: In order to improve the lateral resolution of the 3D hydrogen microscopy by proton-proton scattering at the Munich microprobe SNAKE, we have installed a new multicusp ion source for negative hydrogen ions manufactured by HVEE at the Munich 14 MV tandem accelerator that boosts the proton beam brilliance with the potential to reduce the beam diameter at the focal plane of SNAKE. We measured a beam brilliance B = 27 A m -2 rad -2 eV -1 directly behind the ion source that is at the space charge limit for conventional ion sources. After preacceleration to in total 180 keV beam energy we measure a slightly reduced beam brilliance of B = 10 ?A mm -2 mrad -2 MeV -1. For injection into the tandem accelerator, the extracted H --current of the multicusp source of 1 mA is reduced to about 10 ?A because of radiation safety regulations and heating problems at the object slits of SNAKE. Due to beam oscillations and influences of the terminal stripper of the tandem we measured a reduced beam brilliance of 0.8 ?A mm -2 mrad -2 MeV -1 in front of SNAKE at 25 MeV but still being nearly 10 times larger than measured with any other ion source.
BibTeX:
	@article{Moser2012,
	  author = {Moser, M. and Reichart, P. and Carli, W. and Greubel, C. and Peeper, K. and Hartung, P. and Dollinger, G.},
	  title = {High brilliance multicusp ion source for hydrogen microscopy at SNAKE},
	  booktitle = {20th International Conference on Ion Beam Analysis},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2012},
	  volume = {273},
	  pages = {226--230},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X11007257},
	  doi = {http://doi.org/10.1016/j.nimb.2011.07.081}
	}
	
Non-Rutherford backscattering microscopy using 25 MeV protons
K. Peeper, M. Moser, P. Reichart and G. Dollinger; Nuclear Instruments and Methods in Physics Research Section B 273 (2012) 254-257.
Abstract: Protons at energies between 10 and 25 MeV are a very sensitive probe for hydrogen using coincident proton-proton scattering with the possibility for depth profiling samples up to several 100 ?m thickness. At the Munich microprobe SNAKE we have developed this method for sensitive 3D hydrogen microscopy [1]. In parallel to sensitive 3D hydrogen microscopy by proton-proton scattering we introduce a non-Rutherford backscattering analysis utilizing 25 MeV protons in order to obtain 3D depth profiles of all major elements. We present energy spectra of backscattered protons at various thin and thick film samples of pure elements which we use as fingerprints to analyse more complex materials like minerals or metals. It is due to the low stopping power of the high energy protons that the depth profiles of several elements do not or do only partially overlap when analysing freestanding samples with thicknesses in the 100 ?m range. The merit of our method is that signals of the light elements may not be affected by heavier matrix elements. Analysing thin films smaller than 5 ?m we have achieved a mass resolution of ?A/A?1/28 for non-overlapping mass signals utilizing a 5 mm thick Si(Li)-detector.
BibTeX:
	@article{Peeper2012,
	  author = {Peeper, K. and Moser, M. and Reichart, P. and Dollinger, G.},
	  title = {Non-Rutherford backscattering microscopy using 25 MeV protons},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2012},
	  volume = {273},
	  pages = {254--257},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X11007324},
	  doi = {http://doi.org/10.1016/j.nimb.2011.07.088}
	}
	
Super resolution microscopy of repair foci after ion irradiation of human HeLa cells
Judith (Seel) Reindl; Masters-Thesis, Ludwigs-Maximilians-Universität München, 2012.
Abstract: High LET (linear energy transfer) irradiation of living cells using heavy ions generates a high amount of DNA double-strand breaks (DSB) in close vicinity to each other along the ion track. Various repair proteins cluster to the damage sites, such as gH2AX and 53BP1, forming so-called repair foci of a gross size of about 1 µm. Due to the fact that one focus covers more than one DSB, a fine-structure within the focus can be expected. First indications for such a fine-structure were found in wide field images of
cells taken one hour after irradiation with 55MeV carbon ions in a 5x5 µm matrix performed at the ion microprobe SNAKE. While a typical focus with the diameter of about 1 µm can be easily resolved using a conventional fluorescence microscope, its substructures cannot be resolved due to the diffraction limit of about 250 nm in conventional fluorescence microscopy. Therefore, for analyzing foci fine-structures systematically, super-resolution microscopy techniques like structured illumination microscopy (SIM), stimulation emission depletion microscopy (STED) or localization microscopy (SPDM) which provide a lateral resolution of about 130 nm (SIM) to 50 nm (SPDM) fwhm are utilized. Since with these techniques the lateral resolution is even better than the z-resolution we used an irradiation configuration, where the cells are irradiated at a small angle to the image plane. Thus, the complete ion track appears as a line within one layer of a 3D microscope image. Due to these improvements the super resolution images clearly indicate a fine-structure when e. g. 53BP1 is stained with two colors.
For quantification of the results the Pearson correlation coefficient is calculated for a pixel wise shift in x-direction as well as in y-direction of one color channel with respect to the other (Van Steensel approach). This proves the existence of a fine-structure of a scale of about 200-230 nm, which becomes obvious by an extra correlation peak with a fwhm of this size. Using the same Van Steensel approach with images where one color marks 53BP1 and the other gH2AX, it can be shown that there is no total correlation of the fine-structure between 53BP1 and gH2AX on the small scale.
Using the product of the difference of the mean (PDM) for 2D profiles the images where one protein is labeled with two colors show large regions with total correlation of the to color channels and only small regions at the rim of the focus with no total correlation. In addition, in the PDM approach two different damage markers each labeled in one color show colocalisation in small regions inside the focus but anticorrelation in the outer regions of the focus. These analysis lead to different results:
first of all a single repair marker seems to cluster systematically to the damage site and not in a random way. Secondly 53BP1 and gH2AX cluster in a different way and therefore no full colocalisation can be reached.
With this experimental and analytical methods it is possible to determine the way of clustering to DSB of one single DNA damage marker to clarify the structure of a DSB and the structure of the chromatin architecture as well as the comparison of two
damage markers to get deeper understanding to the interaction of repair markers and repair proteins and at the end decode the way of DNA repair.
BibTeX:
	@mastersthesis{Reindl2012ma,
	  author = {Reindl, Judith (Seel)},
	  title = {Super resolution microscopy of repair foci after ion irradiation of human HeLa cells},
	  school = {Ludwigs-Maximilians-Universität München},
	  year = {2012}
	}
	
Low LET protons focused to submicrometer shows enhanced radiobiological effectiveness
T.E. Schmid, C. Greubel, V. Hable, O. Zlobinskaya, D. Michalski, S. Girst, C. Siebenwirth, E. Schmid, M. Molls, G. Multhoff and G. Dollinger; Physics in Medicine and Biology 57 (19) (2012) 5889-5907.
Abstract: This study shows that enhanced radiobiological effectiveness (RBE) values can be generated focusing low linear energy transfer (LET) radiation and thus changing the microdose distribution. 20 MeV protons (LET = 2.65 keV µm ?1 ) are focused to submicrometer diameter at the ion microprobe superconducting nanoprobe for applied nuclear (Kern) physics experiments of the Munich tandem accelerator. The RBE values, as determined by measuring micronuclei (RBE MN = 1.48 ± 0.07) and dicentrics (RBE D = 1.92 ± 0.15), in human–hamster hybrid (A L ) cells are significantly higher when 117 protons were focused to a submicrometer irradiation field within a 5.4 × 5.4 µm 2 matrix compared to quasi homogeneous in a 1 × 1 µm 2 matrix applied protons (RBE MN = 1.28 ± 0.07; RBE D = 1.41 ± 0.14) at the same average dose of 1.7 Gy. The RBE values are normalized to standard 70 kV (dicentrics) or 200 kV (micronuclei) x-ray irradiation. The 117 protons applied per point deposit the same amount of energy like a 12 C ion with 55 MeV total energy (4.48 MeV u ?1 ). The enhancements are about half of that obtained for 12 C ions (RBE MN = 2.20 ± 0.06 and RBE D = 3.21 ± 0.10) and they are attributed to intertrack interactions of the induced damages. The measured RBE values show differences from predictions of the local effect model (LEM III) that is used to calculate RBE values for irradiation plans to treat tumors with high LET particles.
BibTeX:
	@article{Schmid2012,
	  author = {Schmid, T. E. and Greubel, C. and Hable, V. and Zlobinskaya, O. and Michalski, D. and Girst, S. and Siebenwirth, C. and Schmid, E. and Molls, M. and Multhoff, G. and Dollinger, G.},
	  title = {Low LET protons focused to submicrometer shows enhanced radiobiological effectiveness},
	  journal = {Physics in Medicine and Biology},
	  year = {2012},
	  volume = {57},
	  number = {19},
	  pages = {5889-5907},
	  url = {http://stacks.iop.org/0031-9155/57/i=19/a=5889},
	  doi = {http://doi.org/10.1088/0031-9155/57/19/5889}
	}
	
Brillanzverlust durch die Kohlenstoffstripperfolie beim Strahltransport im Garchinger Tandembeschleuniger
Benedikt Urban; Bachelors-Thesis, Universität der Bundeswehr München, 2012.
Abstract: Die Verteilung von Wasserstoff in Materialien ist ein technisch äußerst relevanter Forschungsgegenstand der Materialphysik. Am SNAKE können mittels Proton- Proton Streuung Wasserstoffverteilungen in Materialien quantitativ bestimmt werden.
Einzigartig ist, dass Wasserstoffverteilungen an Strukturen im mm-Bereich aufgelöst werden können. Die laterale Auflösung (Strahldurchmesser) des bestehenden Systems beträgt derzeit ca. 1 mm. Um diese zu verbessern, wurde eine hochbrillante Ionenquelle aufgebaut, die bei besserer Strahlqualität gleichen Ionenstrom an der Probe zur Verfügung stellt.
Nach Inbetriebnahme und ersten Messungen wurde festgestellt, dass sich ein erheblicher Verlust der Brillanz einstellt und somit Einbußen bei der Strahlauflösung. Die Brillanz am Experiment ist um einen Faktor 20 schlechter als die Ausgangsbrillanz. Es gilt zu untersuchen, inwieweit eine Steigerung der Brillanz durch Variation des Strahleinschusses in den Beschleuniger möglich ist. Im Rahmen dieser Arbeit soll ein vorhandenes Simulationsprogramm sowie existierende Strahltransportrechnungen auf die Strahleigenschaften der nun hochbrillanten Quelle adaptiert werden. Auf dieser Basis sollen die Transporteigenschaften mit existierenden Messungen verglichen und validiert werden.
Ziel dieser Arbeit ist es, das benötigte Phasenraumvolumen direkt vor der Stripperfolie zu bestimmen, als Folge des nötigen Phasenraums am SNAKE. In einem weiteren Schritt ist es mithilfe des genauen Phasenraumvolumens möglich, die Brillanzverschlechterung aufgrund der Kleinwinkelstreuung beim Umladungsprozess im Inneren des Terminals nachzuvollziehen und den Strahlengang diesbezüglich zu optimieren.
BibTeX:
	@mastersthesis{Urban2012ba,
	  author = {Urban, Benedikt},
	  title = {Brillanzverlust durch die Kohlenstoffstripperfolie beim Strahltransport im Garchinger Tandembeschleuniger},
	  school = {Universität der Bundeswehr München},
	  year = {2012}
	}
	
Design und Simulation eines temperaturstabilisierten Schlitzsystems für den Transport eines hochbrillanten Protonen-Mikrostrahls
Thomas Vallentin; Bachelors-Thesis, Universität der Bundeswehr München, 2012.
Abstract: Die Verteilung von Wasserstoff in Materialien ist ein technisch äußerst relevanter Forschungsgegenstand der Materialphysik. Am Experiment SNAKE können mittels Proton-Proton Streuung Wasserstoffverteilungen in Materialien quantitativ bestimmt
werden. Einzigartig ist, dass Wasserstoffverteilungen an Strukturen im µm-Bereich aufgelöst werden können. Die laterale Auflösung (Strahldurchmesser) des bestehenden Systems beträgt derzeit ca. 1 µm. Um diese zu verbessern wurde eine hochbrilliante Ionenquelle aufgebaut, die bei besserer Strahlqualität gleichen Ionenstrom an der Probe zur Verfügung stellt. Dies führt zur thermischen Überlastung des aktuell verwendeten Mikroschlitzsystems, welches maÿgeblich für die erreichbare Auflösung verantwortlich ist.
Ziel dieser Arbeit ist es mittels Finite-Elemente-Simulationen die Anforderungen an ein neues Mikroschlitzsytem unter maximaler Strahllast zu untersuchen. Das System muss 10 µA Strahlstrom und Protonen mit Energien von bis zu 25 MeV standhalten.
Auf Grund der nötigen Empfindlichkeit des Systems wird besonders auf die Unsicherheitsabschätzung der Randbedingungen eingegangen. Als kritischer Punkt stellte sich die hochgenaue Strahlstrommessung im nano-Ampere Bereich heraus, die bei hohen Temperaturen an den Mikroschlitzen zur Tandemreglung benötigt wird. Als idealer Werkstoff zeigte sich Aluminiumnitrid (AlN), welches eine hohe Wärmeleitfähigkeit von bis zu k = 180W/(mK) und ein gutes Isolationsvermögen mit rho_v = 5 x 10^5
Ohm m bei Schlitztemperaturen Diese Arbeit zeigt, dass die Anforderungen an das neue Mikroschlitzsystem erfüllt werden können. Dabei kann unter Betracht aller Einflussgrößen eine sehr geringe Unschärfe der Objektgröÿe von Durch den Einsatz dieses neu definierten Mikroschlitzsystems wird eine Erhöhung der Auflösungen in den sub-µm-Bereich erwartet.
BibTeX:
	@mastersthesis{Vallentin2012ba,
	  author = {Vallentin, Thomas},
	  title = {Design und Simulation eines temperaturstabilisierten Schlitzsystems für den Transport eines hochbrillanten Protonen-Mikrostrahls},
	  school = {Universität der Bundeswehr München},
	  year = {2012}
	}
	
Induction and repair of DNA double-strand breaks assessed by gamma-H2AX foci after irradiation with pulsed or continuous proton beams
O. Zlobinskaya, G. Dollinger, D. Michalski, V. Hable, C. Greubel, G. Du, G. Multhoff, B. Röper, M. Molls and T.E. Schmid; Radiation and Environmental Biophysics 51 (1) (2012) 23-32.
Abstract: In particle tumor therapy including beam scanning at accelerators, the dose per voxel is delivered within about 100 ms. In contrast, the new technology of laser plasma acceleration will produce ultimately shorter particle packages that deliver the dose within a nanosecond. Here, possible differences for relative biological effectiveness in creating DNA double-strand breaks in pulsed or continuous irradiation mode are studied. HeLa cells were irradiated with 1 or 5 Gy of 20-MeV protons at the Munich tandem accelerator, either at continuous mode (100 ms), or applying a single pulse of 1-ns duration. Cells were fixed 1 h after 1-Gy irradiation and 24 h after 5-Gy irradiation, respectively. A dose–effect curve based on five doses of X-rays was taken as reference. The total number of phosphorylated histone H2AX (gamma-H2AX) foci per cell was determined using a custom-made software macro for gamma-H2AX foci counting. For 1 h after 1-Gy 20-MeV proton exposures, values for the relative biological effectiveness (RBE) of 0.97 ± 0.19 for pulsed and 1.13 ± 0.21 for continuous irradiations were obtained in the first experiment 1.13 ± 0.09 and 1.16 ± 0.09 in the second experiment. After 5 Gy and 24 h, RBE values of 0.99 ± 0.29 and 0.91 ± 0.23 were calculated, respectively. Based on the gamma-H2AX foci numbers obtained, no significant differences in RBE between pulsed and continuous proton irradiation in HeLa cells were detected. These results are well in line with our data on micronucleus induction in HeLa cells.
BibTeX:
	@article{Zlobinskaya2012,
	  author = {Zlobinskaya, O. and Dollinger, G. and Michalski, D. and Hable, V. and Greubel, C. and Du, G. and Multhoff, G. and Röper, B. and Molls, M. and Schmid, T. E.},
	  title = {Induction and repair of DNA double-strand breaks assessed by gamma-H2AX foci after irradiation with pulsed or continuous proton beams},
	  journal = {Radiation and Environmental Biophysics},
	  year = {2012},
	  volume = {51},
	  number = {1},
	  pages = {23--32},
	  url = {http://link.springer.com/article/10.1007%2Fs00411-011-0398-1},
	  doi = {http://doi.org/10.1007/s00411-011-0398-1}
	}
	

2011

Survival of tumor cells after proton irradiation with ultra-high dose rates
S. Auer, V. Hable, C. Greubel, G.A. Drexler, T.E. Schmid, C. Belka, G. Dollinger and A.A. Friedl; Radiation Oncology 6 (1) (2011) 139.
Abstract: Background Laser acceleration of protons and heavy ions may in the future be used in radiation therapy. Laser-driven particle beams are pulsed and ultra high dose rates of >109 Gy s-1may be achieved. Here we compare the radiobiological effects of pulsed and continuous proton beams. Methods The ion microbeam SNAKE at the Munich tandem accelerator was used to directly compare a pulsed and a continuous 20 MeV proton beam, which delivered a dose of 3 Gy to a HeLa cell monolayer within
BibTeX:
	@article{Auer2011,
	  author = {Auer, Susanne and Hable, Volker and Greubel, Christoph and Drexler, Guido A. and Schmid, Thomas E. and Belka, Claus and Dollinger, Günther and Friedl, Anna A.},
	  title = {Survival of tumor cells after proton irradiation with ultra-high dose rates},
	  journal = {Radiation Oncology},
	  year = {2011},
	  volume = {6},
	  number = {1},
	  pages = {139},
	  url = {http://ro-journal.biomedcentral.com/articles/10.1186/1748-717X-6-139},
	  doi = {http://doi.org/10.1186/1748-717X-6-139}
	}
	
Spatial Dynamics of DNA Damage Response Protein Foci along the Ion Trajectory of High-LET Particles
G. Du, G.A. Drexler, W. Friedland, C. Greubel, V. Hable, R. Krücken, A. Kugler, L. Tonelli, A.A. Friedl and G. Dollinger; Radiation Research 176 (6) (2011) 706-715.
Abstract: High-linear energy transfer (LET) ion irradiation of cell nuclei induces complex and severe DNA lesions, and foci of repair proteins are formed densely along the ion trajectory. To efficiently discriminate the densely distributed/overlapping foci along the ion trajectory, a focus recognition algorithm called FociPicker3D based on a local fraction thresholding technique was developed. We analyzed high-resolution 3D immunofluorescence microscopic focus images and obtained the kinetics and spatial development of ?-H2AX, 53BP1 and phospho-NBS1 foci in BJ1-hTERT cells irradiated with 55 MeV carbon ions and compared the results with the dynamics of double-strand break (DSB) distributions simulated using the PARTRAC model. Clusters consisting of several foci were observed along the ion trajectory after irradiation. The spatial dynamics of the protein foci supports that the foci clusters are not formed by neighboring foci but instead originate from the DSB cluster damage induced by high-LET radiations.
BibTeX:
	@article{Du2011,
	  author = {Du, Guanghua and Drexler, Guido A. and Friedland, Werner and Greubel, Christoph and Hable, Volker and Krücken, Reiner and Kugler, Alexandra and Tonelli, Laura and Friedl, Anna A. and Dollinger, Günther},
	  title = {Spatial Dynamics of DNA Damage Response Protein Foci along the Ion Trajectory of High-LET Particles},
	  booktitle = {Radiation Research},
	  journal = {Radiation Research},
	  year = {2011},
	  volume = {176},
	  number = {6},
	  pages = {706--715},
	  url = {http://www.bioone.org/doi/10.1667/RR2592.1},
	  doi = {http://doi.org/10.1667/RR2592.1}
	}
	
Anomalous subdiffusion of DNA repair protein foci after ion microirradiation.
Stefanie Girst; Diplomarbeit, Technische Universität München, 2011.
Abstract: DNA repair processes, starting after the irradiation of cell nuclei, can be made visible by tagging DNA repair proteins (here MDC1) with the green fluorescent protein GFP, so that microscopic accumulations of the repair proteins ( at the ion-induced
damages (mostly DNA double-strand breaks) can be observed and analyzed "live" under a fluorescence microscope.
The aim of this work is to determine the dynamics of the MDC1-foci in the nucleus. Living U2OS osteosarcoma cells were irradiated in a 5x5 µm^2 matrix pattern with one carbon ion (43MeV) per point or 32 protons (20 MeV) respectively at the ion microprobe SNAKE at the Munich 14MV Tandem accelerator. The relative movement (i.e. the distance) of neighboring foci within the living cells was monitored over several hours "online" at the irradiation site at SNAKE. This relative measure is more robust against cell movement than absolute position determination. The distribution of the change of distance dl between two foci in a time interval dt is a measure for the underlying diffusion. The square of its standard deviation sigma^2(dt) is in general described by
sigma^2(dt) = G*dt^a, with a = 1 for normal, a The diffusion data gathered in the performed experiments are in agreement with an anomalous subdiffusion. The anomalous diffusion exponent found is a = 0.50 +/- 0.04 for both proton and carbon irradiation on a time scale of dt =10 s till 10 000 s,
indicating that the degree of anomality does not depend on the density of double-strand breaks. The transport coefficient G and thus the apparent and the instantaneous diffusion coefficient, however, were clearly bigger in proton-irradiated cell nuclei
(G = (7+/-2)x10^(-3) µm^2/s^0.5) than in those irradiated with the higher-LET carbon ions (G = (3 +/- 1) x 10^(-3) µm^2/s^0.5). This probably arises from the fact that protons produce isolated double-strand breaks (DSBs) which move faster than the larger number of DSBs that form the foci in a carbon ion track.
BibTeX:
	@mastersthesis{Girst2011da,
	  author = {Girst, Stefanie},
	  title = {Anomalous subdiffusion of DNA repair protein foci after ion microirradiation.},
	  school = {Technische Universität München},
	  year = {2011}
	}
	
Scanning irradiation device for mice in vivo with pulsed and continuous proton beams
C. Greubel, W. Assmann, C. Burgdorf, G. Dollinger, G. Du, V. Hable, A. Hapfelmeier, R. Hertenberger, P. Kneschaurek, D. Michalski, M. Molls, S. Reinhardt, B. Röper, S. Schell, T.E. Schmid, C. Siebenwirth, T. Wenzl, O. Zlobinskaya and J.J. Wilkens; Radiation and Environmental Biophysics 50 (3) (2011) 339-344.
Abstract: A technical set-up for irradiation of subcutaneous tumours in mice with nanosecond-pulsed proton beams or continuous proton beams is described and was successfully used in a first experiment to explore future potential of laser-driven particle beams, which are pulsed due to the acceleration process, for radiation therapy. The chosen concept uses a microbeam approach. By focusing the beam to approximately 100 × 100 ?m2, the necessary fluence of 109 protons per cm2 to deliver a dose of 20 Gy with one-nanosecond shot in the Bragg peak of 23 MeV protons is achieved. Electrical and mechanical beam scanning combines rapid dose delivery with large scan ranges. Aluminium sheets one millimetre in front of the target are used as beam energy degrader, necessary for adjusting the depth–dose profile. The required procedures for treatment planning and dose verification are presented. In a first experiment, 24 tumours in mice were successfully irradiated with 23 MeV protons and a single dose of 20 Gy in pulsed or continuous mode with dose differences between both modes of 10%. So far, no significant difference in tumour growth delay was observed.
BibTeX:
	@article{Greubel2011,
	  author = {Greubel, Christoph and Assmann, Walter and Burgdorf, Christian and Dollinger, Günther and Du, Guanghua and Hable, Volker and Hapfelmeier, Alexander and Hertenberger, Ralf and Kneschaurek, Peter and Michalski, Dörte and Molls, Michael and Reinhardt, Sabine and Röper, Barbara and Schell, Stefan and Schmid, Thomas E. and Siebenwirth, Christian and Wenzl, Tatiana and Zlobinskaya, Olga and Wilkens, Jan J.},
	  title = {Scanning irradiation device for mice in vivo with pulsed and continuous proton beams},
	  journal = {Radiation and Environmental Biophysics},
	  year = {2011},
	  volume = {50},
	  number = {3},
	  pages = {339--344},
	  url = {http://link.springer.com/article/10.1007%2Fs00411-011-0365-x},
	  doi = {http://doi.org/10.1007/s00411-011-0365-x}
	}
	
Echtzeitbeobachtung schneller Reaktionskinetiken in lebenden Zellen nach Ionenmikrobestrahlung
Volker Hable; Dissertation, Universität der Bundeswehr München, 2011.
Abstract: Diese Arbeit beschreibt den Aufbau einer Lebendzellmikroskopieumgebung am Rasterionenmikroskop SNAKE, welches am Münchner 14 MV Tandembeschleuniger installiert ist. An dessen Zellbestrahlungsplatz können lebende Zellen mit Protonen und Schwerionen unter Lebendbedingungen mit einer Genauigkeit von ca. 0,5 µm und mit genau definierter Dosis bestrahlt werden. Die nach der Bestrahlung im Zellkern ablaufenden Reparaturvorgänge können durch eine mikroskopische Betrachtung der an der Reparatur beteiligten Proteine analysiert werden. Hierfür ist die Markierung dieser Proteine mittels Fluoreszenzfarbstoffen nötig. Dazu werden die Zellen auf gentechnischem Wege so verändert, dass an Proteine, die an der Reparatur der ioneninduzierten Schäden beteiligt sind, Fluoreszenzproteine (z. B. GFP, green fluorescent protein) angehängt werden. Mikroskopische Proteinanlagerungen an die Schadensorte, sogenannte Foci, können mit dem im Rahmen dieser Arbeit realisierten Aufbau unmittelbar nach und sogar während der Bestrahlung "online“ analysiert werden. Ein kommerziell erhältliches Fluoreszenzmikroskop (Zeiss Axiovert 200M) wurde hierzu am Bestrahlungsplatz angebracht. An dessen Probentisch befinden sich die Zellen während der Bestrahlung und der nachfolgenden Mikroskopie unter optimalen Umgebungsbedingungen in neu entwickelten Zellkulturgefäßen. Erste Experimente an dem neuen Aufbau dienten der Untersuchung von Kinetiken (= zeitlicher Ablauf der Focibildung) der Proteine Mdc1, 53BP1 und Rad52. Nach Applizierung einer mittleren Dosis von 4,4 Gy mit 55 MeV Kohlenstoffionen mit einem linearen Energietransfer LET = 310 keV/µm beginnt Mdc1 nach T0 = 17 ± 2 s mit der Anlagerung an die Schadensorte. Dies geschieht mit einer Zeitkonstante t = 98 ± 11 s. Wird dieselbe Dosis mit 20 MeV Protonen appliziert (LET = 2,65 keV/µm), läuft die Focibildung langsamer ab (T0 = 73 ± 16 s, t = 1050 ± 270 s). Eine höhere Bestrahlungsdosis durch Erhöhung der pro Punkt applizierten Protonen beschleunigt die Kinetik. Die Zeitkonstanten des Proteins 53BP1 weisen keine solch ausgeprägte Abhängigkeit von der Bestrahlungsart auf. Für alle Bestrahlungsbedingungen liegt hier T0 in der Größenordnung von 100 s und t in der Größenordnung von 300 s. Das nur qualitativ betrachtete Reparaturprotein Rad52 zeigt eine deutlich langsamere Kinetik, die allerdings wieder stark von der Dosis und vom LET der Strahlung abhängt. Während bereits ca. zehn Minuten nach Bestrahlung mit 4,7 Gy mit 55 MeV Kohlenstoffionen erste Foci sichtbar werden, dauert deren Erscheinen nach Applizierung von 5,7 Gy durch 20 MeV Protonen (117 Protonen pro Punkt) ca. drei Stunden. Eine Erhöhung der pro Punkt applizierten Protonenzahl auf 256 (und somit der Dosis auf 12 Gy) verkürzt diese Zeit auf ca. eine Stunde. Eine weitere Verdopplung von Protonenzahl und Dosis führt zu einem Sichtbarwerden der Foci nach weniger als zehn Minuten.
BibTeX:
	@phdthesis{Hable2011diss,
	  author = {Hable, Volker},
	  title = {Echtzeitbeobachtung schneller Reaktionskinetiken in lebenden Zellen nach Ionenmikrobestrahlung},
	  school = {Universität der Bundeswehr München},
	  year = {2011},
	  url = {http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:706-2487}
	}
	
Subdiffusion von DNS-Doppelstrangbrüchen unter dem Einfluss von Zellkernverformungen
Michael Haum; Bachelors-Thesis, Universität der Bundeswehr München, 2011.
Abstract: Die Untersuchung von Schäden an biologischem Material durch ionisierende Strahlung stellt immer noch ein großes Forschungsgebiet von Medizin und Biologie dar. Insbesondere die Reparaturvorgänge nach der Schädigung der DNS im Zellkern werfen noch viele offene Fragen auf, dabei vor allem die der gefährlichsten Doppelstrangbrüche (DSB). Für ein besseres Verständnis der raumzeitlichen Dynamik der DSB wurden lebende Zellen am Münchner 14 MV Tandembeschleuniger mit 43 MeV Kohlenstoff-Ionen beschossen, um so die DNS gezielt zu schädigen und die erzeugten DSB über die sich dort gebildeten fluoreszenzmarkierten Reparaturproteincluster („Foci“) zu beobachten.
Für die Analyse der Dynamik wurde die zeitliche Änderung der Abstände benachbarter Foci ( l?5?m ) herangezogen. Die Standardabweichung der Abstandsänderung über ein Zeitintervall dt kann mit der Gleichung sigma^2= G * dt^a beschrieben werden, die eine Aussage über die Art der Diffusion macht. Es zeigte sich, dass der Diffusionsexponent mit a=0,49±0,05 deutlich kleiner ist als der einer normalen Diffusion ( a=1 ) und der Transportkoeffizient bei G=(1,7± 0,6) x 10^(?3) ?m^2/s^0,49 liegt, sodass der Bewegung eine anomale Subdiffusion zugrunde liegt [S. Girst, 2011]. Durch die Betrachtung der Abstände anstelle von absoluten Positionen soll ausgeschlossen werden, dass eine Bewegung oder Deformation der gesamten Zelle unbeabsichtigt
in die Auswertung mit einfließt.
Ziel dieser Arbeit war es zu untersuchen, ob auch bei der Auswertung von größeren Foci-Abständen eine anomale Subdiffusion vorliegt. Hierfür wurden die Abstandsänderungen eines Foci zu seinem übernächsten Nachbarn ( l?10?m ) herangezogen. Es ergab sich, dass auch hier eine anomale Subdiffusion vorliegt, mit dem Diffusionsexponenten a=0,58± 0,03 und dem Transportkoeffizienten G=(1,6± 0,3) x 10^(?3) ?m^2 /s^0,58 . Trotz des größeren Diffusionsexponenten liegt auch nach dieser Auswertung eine anomale Subdiffusion vor, sodass das für kleine Abstände gefundene Ergebnis bestätigt wird. Der größere Diffusionsexponent ist allerdings ein Hinweis darauf, dass sich bei großen Foci-Abständen eine Verformung der Zelle in der Auswertung stärker
bemerkbar macht.
BibTeX:
	@mastersthesis{Haum2011ba,
	  author = {Haum, Michael},
	  title = {Subdiffusion von DNS-Doppelstrangbrüchen unter dem Einfluss von Zellkernverformungen},
	  school = {Universität der Bundeswehr München},
	  year = {2011}
	}
	
Differential proton-proton scattering cross section for energies between 1.9 MeV and 50 MeV
M. Moser, P. Reichart, C. Greubel and G. Dollinger; Nuclear Instruments and Methods in Physics Research Section B 269 (20) (2011) 2217-2228.
Abstract: We present a phase shift analysis of differential elastic proton-proton scattering cross sections (d?/d?) pp in the energy range from 1.9 MeV to 50 MeV and laboratory scattering angles ?lab= 15-75°. That results in an accurate representation of the experimental data by an analytical function (?red2=1.95). The average statistical error of the resulting data fit is 0.2%. The evaluation is representing the experimental data better than the evaluated cross section by the framework of the R-matrix theory as available from the ENDF database (?red2=6.98). For a fast evaluation we extract an E,?-matrix for (d?/d?) pp with a negligible interpolation error. These data may be used for data evaluation when using proton-proton scattering for hydrogen detection in material analysis.
BibTeX:
	@article{Moser2011,
	  author = {Moser, M. and Reichart, P. and Greubel, C. and Dollinger, G.},
	  title = {Differential proton-proton scattering cross section for energies between 1.9 MeV and 50 MeV},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2011},
	  volume = {269},
	  number = {20},
	  pages = {2217--2228},
	  note = {12th International Conference on Nuclear Microprobe Technology and Applications},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X1100200X},
	  doi = {http://doi.org/10.1016/j.nimb.2011.02.017}
	}
	
Differential Proton-Proton Scattering Cross Section for energies between 1.9 MeV and 50 MeV
Marcus Moser; Masters-Thesis, Hochschule München, 2011.
Abstract: We present a phase shift analysis of differential elastic proton-proton scattering cross sections (d?/dO)_pp in the energy range from 1.9 MeV to 50 MeV and laboratory scattering angles ?_lab = 15 . . . 75. It results in an accurate representation of the experimental data by an analytical function for (d?/dO)_pp (E, ?). The average statistical error of the resulting data fit is 0.2%. For a fast evaluation we extract an [E, ?]-matrix for (d?/dO)_pp with a negligible interpolation error smaller than 0.02%. This data may be relevant for data evaluation for hydrogen analysis when using proton-proton scattering.
BibTeX:
	@mastersthesis{Moser2011ma,
	  author = {Moser, Marcus},
	  title = {Differential Proton-Proton Scattering Cross Section for energies between 1.9 MeV and 50 MeV},
	  school = {Hochschule München},
	  year = {2011}
	}
	
Eine hochbrillante Multicusp H-/D- Ionenquelle am Münchener Tandembeschleuniger.
Marcus Moser; Studienarbeit, Hochschule München, 2011.
Abstract: Proton-proton scattering at the Munich microprobe SNAKE gives the unique possibility for sensitive 3D hydrogen microscopy [1]. We have installed a new multicusp ion source for negative hydrogen ions manufactured by HVEE [2] at the Munich tandem accelerator. The aim is boosting the proton beam brightness and hence optimizing the microprobe's lateral resolution and its sensitivity in hydrogen detection. The source operates at the space charge limit at its extraction site and therefore enables an optimum emittance of 15-20 Am^(?2)rad^(?2)eV^(?1) and brightness at the principal limit for conventional ion sources. The emittance is two orders of magnitude larger than that of the ECR source that was used before in combination with charge exchange for negative hydrogen production. For injection into the tandem accelerator, the extraction current of up to 1.5 mA H? is reduced to about 10 ?A. Thus, we only accelerate the high brightness core of the beam that is further restricted in size and divergence by micro slit systems in front of SNAKE. We present the performance of the installed source and show the beam characteristics at the focal plane of SNAKE. In addition we show first 3D hydrogen microscopy on geological samples with a new multi-strip detector matrix consisting of four 5x5 cm^2, 1 mm thick strip detectors in a configuration parallel to the beam. The new detector setup enables us to use up to 25 MeV of incoming protons stopping all scattered protons from proton-proton scattering in the detector.
BibTeX:
	@thesis{Moser2011sa,
	  author = {Moser, Marcus},
	  title = {Eine hochbrillante Multicusp H-/D- Ionenquelle am Münchener Tandembeschleuniger.},
	  school = {Hochschule München},
	  year = {2011}
	}
	
The effectiveness of 20 MeV protons at nanosecond pulse lengths in producing chromosome aberrations in human-hamster hybrid cells
T.E. Schmid, G. Dollinger, V. Hable, C. Greubel, O. Zlobinskaya, D. Michalski, S. Auer, A.A. Friedl, E. Schmid, M. Molls and B. Röper; Radiation Research 175 (6) (2011) 719-727.
Abstract: Laser accelerated radiotherapy is a potential cancer treatment with proton and carbon-ion beams that is currently under development. Ultra-fast high-energy laser pulses will accelerate ion beams that deliver their dose to a patient in a “pulsed mode” that is expected to differ from conventional irradiation by increasing the dose delivery rate to a tissue voxel by approximately 8 orders of magnitude. In two independently performed experiments at the ion microprobe SNAKE of the 14 MV Munich tandem accelerator, AL cells were exposed either to protons with 1-ns pulse durations or to protons applied over 150 ms in continuous irradiation mode. A slightly but consistently lower aberration yield was observed for the pulsed compared to the continuous mode of proton irradiation. This difference was not statistically significant when each aberration type was analyzed separately (P values between 0.61 and 0.85 in experiment I and P values between 0.32 and 0.64 in experiment II). However, excluding the total aberrations, which were not analyzed as independent radiation-induced effects, the mean ratio of the yields of dicentrics, centric rings and excess acentrics scored together showed (with 95% CI) a significant difference of 0.90 (0.81; 0.98) between the pulsed and the continuous irradiation modes. A similar tendency was also determined for the corresponding RBE values relative to 70 kV X rays. Since the different findings for the comparisons of individual chromosome aberration types and combined comparisons could be explained by different sample sizes with the consequence that the individual comparisons had less statistical power to identify a difference, it can be concluded that 20 MeV protons may be slightly less effective in the pulsed mode.
BibTeX:
	@article{Schmid2011,
	  author = {Schmid, T. E. and Dollinger, G. and Hable, V. and Greubel, C. and Zlobinskaya, O. and Michalski, D. and Auer, S. and Friedl, A. A. and Schmid, E. and Molls, M. and Röper, B.},
	  title = {The effectiveness of 20 MeV protons at nanosecond pulse lengths in producing chromosome aberrations in human-hamster hybrid cells},
	  booktitle = {Radiation Research},
	  journal = {Radiation Research},
	  year = {2011},
	  volume = {175},
	  number = {6},
	  pages = {719--727},
	  url = {http://www.bioone.org/doi/10.1667/RR2465.1},
	  doi = {http://doi.org/10.1667/RR2465.1}
	}
	
Double-strand break-induced transcriptional silencing is associated with loss of tri-methylation at H3K4
D. Seiler, J. Rouquette, V. Schmid, H. Strickfaden, C. Ottmann, G. Drexler, B. Mazurek, C. Greubel, V. Hable, G. Dollinger, T. Cremer and A. Friedl; Chromosome Research 19 (7) (2011) 883-899.
Abstract: Epigenetic alterations induced by ionizing radiation may contribute to radiation carcinogenesis. To detect relative accumulations or losses of constitutive post-translational histone modifications in chromatin regions surrounding DNA double-strand breaks (DSB), we developed a method based on ion microirradiation and correlation of the signal intensities after immunofluorescence detection of the histone modification in question and the DSB marker ?-H2AX. We observed after ionizing irradiation markers for transcriptional silencing, such as accumulation of H3K27me3 and loss of active RNA polymerase II, at chromatin regions labeled by ?-H2AX. Confocal microscopy of whole nuclei and of ultrathin nuclear sections revealed that the histone modification H3K4me3, which labels transcriptionally active regions, is underrepresented in ?-H2AX foci. While some exclusion of H3K4me3 is already evident at the earliest time amenable to this kind of analysis, the anti-correlation apparently increases with time after irradiation, suggesting an active removal process. Focal accumulation of the H3K4me3 demethylase, JARID1A, was observed at damaged regions inflicted by laser irradiation, suggesting involvement of this enzyme in the DNA damage response. Since no accumulation of the repressive mark H3K9me2 was found at damaged sites, we suggest that DSB-induced transcriptional silencing resembles polycomb-mediated silencing rather than heterochromatic silencing.
BibTeX:
	@article{Seiler2011,
	  author = {Seiler, D.M. and Rouquette, J. and Schmid, V.J. and Strickfaden, H. and Ottmann, C. and Drexler, G.A. and Mazurek, B. and Greubel, C. and Hable, V. and Dollinger, G. and Cremer, T. and Friedl, A.A.},
	  title = {Double-strand break-induced transcriptional silencing is associated with loss of tri-methylation at H3K4},
	  journal = {Chromosome Research},
	  year = {2011},
	  volume = {19},
	  number = {7},
	  pages = {883--899},
	  url = {http://link.springer.com/article/10.1007%2Fs10577-011-9244-1},
	  doi = {http://doi.org/10.1007/s10577-011-9244-1}
	}
	

2010

Quantitative Analyse der LET- und Strahlungsdosisabhängigkeit von Proteinkinetiken nach Ionenmikrobestrahlung
Christian Burgdorf; Diplomarbeit, Universität der Bundeswehr München, 2010.
Abstract: In dieser Arbeit wurde eine quantitative Analyse von Proteinkinetiken nach Ionenmikrobestrahlung hinsichtlich einer LET- und Strahlungsdosisabhängigkeit durchgeführt.
Zur Auswertung der ablaufenden Reparaturprozesse wurden die mit dem Rasterionenmikroskop SNAKE fluoreszenzmikroskopisch aufgenommenen Zeitserien analysiert. In diesen Zeitserien bildeten sich in bestrahlten Bereichen innerhalb von verschiedenen Zeitintervallen Foci aus. Diese Foci beschreiben Orte, in denen sich die Konzentration von Proteinen erhöht, was mit der Anlagerung von Reparaturproteinen an beschädigten DNA-Sequenzen gleich zusetzen ist. Bei Beobachtung dieser Focibildung wurde des Weiteren deutlich, dass die Foci mit den Bestrahlungsorten kolokalisieren.
In dieser Arbeit wurden die Kinetiken der Proteine MDC1 und 53BP1 mit Hilfe von Helligkeitsmessungen ihrer Foci ausgewertet. Eine entwickelte Modellfunktion wurde an die gemessenen Helligkeitsverläufe angepasst. Die Proteinanlagerung und der Proteinabbau wurden mit Hilfe von zwei Zeitkonstanten Tau_1 und Tau_2 charakterisiert. Eine mögliche zeitliche Verzögerung beim Start des Reparaturvorganges konnte mit einem Zeitoffset T0 modelliert werden.
Zum Abschluss der Helligkeitsmessungen wurden probenübergeifend einzelne Bestrahlungsexperimente zusammengefasst, die unter gleichen biophysikalischen Bedingungen durchgeführt wurden. Die Klassifizierung erfolgte nach der verwendeten Strahlungsart und -dosis sowie nach dem untersuchten Reparaturprotein.
Hinsichtlich einer LET- und Strahlungsdosisabhängigkeit konnten für das Reparaturprotein MDC1 nach 20MeV H+, wie auch bei einer 55MeV C+ Bestrahlung, Abhängigkeiten festgestellt werden. Dabei zeigte sich für die Bestrahlung mit H+, dass die Erhöhung der Strahlungsdosis von 4,8 Gy auf 12,05 Gy (Faktor 2,5) eine Beschleunigung der Anlagerungszeit Tau_1,( 4,8 Gy) = 1052 ± 272 s zu Tau_1,(12,05 Gy) = 522 ± 148 s zur Folge hatte. Das Starten der Reparaturprozesse hingegen war nahezu konstant nach einem Zeitoffset von
T0,(4,8 Gy) = 73 ± 16 s und T0,(12,05 Gy) = 80 ± 11 s.
Für die Zeitkonstanten nach 55MeV C+ Bestrahlung zeigte sich ein ähnliches Bild, wobei deutlich wurde, dass weitaus geringere Strahlungsdosen nötig waren, um vergleichsweise schnelle Reaktionen für die Proteinanlagerung zu erreichen. Die Zeit für den Anlagerungsprozess wurde mit steigender Strahlungsdosis weiter verringert. Bei einer Dosis von 3,1Gy betrug Tau_1,(3,1 Gy) = 218 ± 55 s, die sich bei der Dosis von 4,4 Gy auf Tau_1,(4,4 Gy) = 98 ± 11 s verringerte. Eine signifikante Dosisabhängigkeit für die Offset-Zeiten
T0 konnte nicht bestimmt werden (T0,(3,1 Gy) = 14 ± 4 s, T0,(4,4 Gy) = 17 ± 2 s).
Die Auswertung des zweiten Reparaturproteins 53BP1 erbrachte für die Bestrahlung mit 20MeV H+ keine linearen Dosisabhängigkeiten. Die Werte für die Zeitkonstanten Tau_1 liegen in niedrigen (3,4 Gy) und hohen Strahlungsdosisbereichen (13,7 Gy) nahezu konstant
bei Tau_1,(3,4 Gy) = 237 ± 33 s und Tau_1,(13,7 Gy) = 226 ± 60 s. Für den mittleren Dosisbereich ist mit Tau_1,(6,9 Gy) = 460 ± 100 s die benötigte Zeit für die Proteinanlagerung doppelt so groß. Derselbe Effekt ist auch bei der Offset-Zeit T0 zu erkennen (T0, 3,4 Gy = 118 ± 14 s, T0, 6,9 Gy = 160 ± 12 s, T0, 13,7 Gy = 120 ± 22 s).
Die Auswertung des 53BP1 nach 55 MeVC+ Bestrahlung erbrachte ein Tau_1,(6,3 Gy) = 375 ± 58 s und einen Zeitoffset T0,(6,3 Gy) = 89 ± 8 s. Dabei wurde deutlich, dass sich die Zeitkonstanten für unterschiedliche Strahlungsarten trotz einer ähnlichen applizierten Strahlungsdosis stark unterschieden. Dennoch zeigte sich, wie bei der Untersuchung von MDC1, dass 55MeV C+ bestrahlte 53BP1 Proben eine schnellere Reaktion zeigten.
BibTeX:
	@mastersthesis{Burgdorf2010da,
	  author = {Burgdorf, Christian},
	  title = {Quantitative Analyse der LET- und Strahlungsdosisabhängigkeit von Proteinkinetiken nach Ionenmikrobestrahlung},
	  school = {Universität der Bundeswehr München},
	  year = {2010}
	}
	
Life cell micro-irradiation
G. Dollinger; Nuclear Physics News 20 (3) (2010) 27-32.
Abstract: A main subject of modern experiments in radiobiology is the detailed investigation of the biological response on a microscopic scale when a living organism is irradiated by ionizing radiation. As known for long, a DNA double strand break (DSB) is one of the most harmful threats that can be induced by ionizing radiation (Figure 1a). Thus, the response of cells to DSBs on a microscopic scale interests in view of cell surveillance strategies. There are already a lot of proteins known that are omnipresent in cell nuclei and that are involved in the repair of DSBs. Some of them cluster around a DSB forming a “repair focus” (Figure 1b). The spatio-temporal development of the repair processes and the interaction of the different proteins within repair pathways are to a large extent still unknown. A precise irradiation of cells by means of a nuclear microprobe, for example, using SNAKE ( S uperconducting N anoscope for A pplied nuclear ( K ern-) physics E xperiments) at the Munich tandem accelerator, is an ideal tool to perform accurate radiobiological experiments and to investigate cell surveillance strategies in general [1].
BibTeX:
	@article{Dollinger2010,
	  author = {Dollinger, G.},
	  title = {Life cell micro-irradiation},
	  journal = {Nuclear Physics News},
	  year = {2010},
	  volume = {20},
	  number = {3},
	  pages = {27--32},
	  note = {cited By (since 1996)0},
	  url = {http://www.nupecc.org/index.php?display=npn/issues},
	  doi = {http://doi.org/10.1080/10619127.2010.506125}
	}
	
Differences in the kinetics of ?-H2AX fluorescence decay after exposure to low and high LET radiation
T.E. Schmid, G. Dollinger, W. Beisker, V. Hable, C. Greubel, S. Auer, A. Mittag, A. Tarnok, A.A. Friedl, M. Molls and B. Röper; International Journal of Radiation Biology 86 (8) (2010) 682-691.
Abstract: Purpose:
In order to obtain more insight into heavy ion tumour therapy, some features of the underlying molecular mechanisms controlling the cellular response to high linear energy transfer (LET) radiation are currently analysed.

Materials and methods:
We analysed the decay of the integrated fluorescence intensity of ?-H2AX (phosphorylated histone H2AX) which is thought to reflect the repair kinetics of radiation-induced DNA double-strand breaks (DSB) using Laser-Scanning-Cytometry. Asynchronous human HeLa cells were irradiated with a single dose of either 1.89 Gy of 55 MeV carbon ions or 5 Gy of 70 kV X-rays.

Results:
Measurements of the ?-H2AX-intensities from 15–60?min resulted in a 16 % decrease for carbon ions and in a 43 % decrease for X-rays. After 21?h, the decrease was 77 % for carbon ions and 85 % for X-rays. The corresponding time-effect relationship was fitted by a bi-exponential function showing a fast and a slow component with identical half-life values for both radiation qualities being 24?±?4?min and 13.9?±?0.7?h, respectively. Apparent differences in the kinetics following high and low LET irradiation could completely be attributed to quantitative differences in their contributions, with the slow component being responsible for 47 % of the repair after exposure to X-rays as compared to 80 % after carbon ion irradiation.

Conclusion:
?-H2AX loss kinetics follows a bi-exponential decline with two definite decay times independent of LET. The higher contribution of the slow component determined for carbon ion exposure is thought to reflect the increased amount of complex DSB induced by high LET radiation.

BibTeX:
	@article{Schmid2010,
	  author = {Schmid, Thomas E. and Dollinger, Günther and Beisker, Wolfgang and Hable, Volker and Greubel, Christoph and Auer, Susanne and Mittag, Anja and Tarnok, Attila and Friedl, Anna A. and Molls, Michael and Röper, Barbara},
	  title = {Differences in the kinetics of ?-H2AX fluorescence decay after exposure to low and high LET radiation},
	  journal = {International Journal of Radiation Biology},
	  year = {2010},
	  volume = {86},
	  number = {8},
	  pages = {682--691},
	  note = {PMID: 20569192},
	  url = {http://informahealthcare.com/doi/abs/10.3109/09553001003734543},
	  doi = {http://doi.org/10.3109/09553001003734543}
	}
	
Relative biological effectiveness of pulsed and continuous 20 MeV protons for micronucleus induction in 3D human reconstructed skin tissue
T.E. Schmid, G. Dollinger, V. Hable, C. Greubel, O. Zlobinskaya, D. Michalski, M. Molls and B. Röper; Radiotherapy and Oncology 95 (1) (2010) 66-72.
Abstract: Background and purpose: Laser accelerated radiotherapy is a prospect for cancer treatment with proton and/or carbon ion beams that is currently under fast development. In principal, ultra fast, high-energy laser pulses will lead to a "pulsed" delivery of the induced ion beam with pulse durations of 1 ns and below, whereas conventional proton beams deriving from a cyclotron or synchrotron apply the dose within 100 ms ("continuous"). Materials and methods: A simulation of both irradiation modes could be established at the Munich tandem accelerator with a 20 MeV proton beam, and a wide-field fast scanning system was implemented that allowed for application of up to 5 Gy per tissue voxel in a single pulse. The relative biological effectiveness (RBE) of pulsed and continuous modes of irradiation with 20 MeV protons relative to the reference radiation 70 kV X-rays was examined in a human tissue model (3D human reconstructed skin, EpiDermFT™) which preserves the three-dimensional geometric arrangement and communication of cells present in tissues in vivo. Using the induction of micronuclei (MN) in keratinocytes as the biological endpoint, the RBE was calculated as the ratio between the dose of 70 kV X-rays and 3 Gy of 20 MeV protons (pulsed or continuous) which produced equal response. Results: For pulsed and continuous 20 MV proton exposures of the human skin model, RBE values of 1.08 ± 0.20 and 1.22 ± 0.15 versus 70 kV X-rays were obtained in a first experiment and 1.00 ± 0.14 and 1.13 ± 0.14 in a second experiment during distinct beam access times, respectively. The ?10% difference in RBE between the respective irradiation modes in both experiments was associated with large uncertainties which were not statistically significant (p ? 0.5). Conclusion: These findings represent an important step on the way towards application of laser-accelerated protons for clinical radiotherapy. Further clinically relevant endpoints in normal and tumor tissue have to be evaluated.
BibTeX:
	@article{Schmid2010a,
	  author = {Schmid, Thomas E. and Dollinger, Günther and Hable, Volker and Greubel, Christoph and Zlobinskaya, Olga and Michalski, Dörte and Molls, Michael and Röper, Barbara},
	  title = {Relative biological effectiveness of pulsed and continuous 20 MeV protons for micronucleus induction in 3D human reconstructed skin tissue},
	  journal = {Radiotherapy and Oncology},
	  year = {2010},
	  volume = {95},
	  number = {1},
	  pages = {66--72},
	  url = {http://www.sciencedirect.com/science/article/pii/S0167814010001623},
	  doi = {http://doi.org/10.1016/j.radonc.2010.03.010}
	}
	
Tumorbestrahlung mit gepulsten und kontinuierlichen Protonen am Mausmodell.
Christian Siebenwirth; Diplomarbeit, Technische Universität München, 2010.
Abstract: Zur Qualifizierung der Tumortherapie mit gepulsten Protonenstrahlen mit Pulsbreiten von 1 ns, wie sie bei der Laserbeschleunigung erzeugt werden, wurden am Münchner 14 MV Tandembeschleuniger menschliche Tumore am Mausmodell mit 20 Gy bestrahlt. Anhand des Parameters der Tumorwachstumsverzögerung wurde überprüft, ob ein Unterschied in der relativen biologischen Wirksamkeit (RBW) zwischen Protonenstrahlung, die ihre Dosis in Pulsen der Breite von 1 ns applizieren, und kontinuierlicher Protonenbestrahlung auftritt.
Da es noch keine laserbeschleunigten Ionenstrahlen in hinreichender Qualität gibt, um eine Tumorbestrahlung durchzuführen, wurde am Rasterionenmikroskop SNAKE ein laserbeschleunigter Protonenstrahl simuliert. Dazu wurde das 5 MHz Pulsungssystem des Tandembeschleunigers verwendet, das ein 23 MeV Protonenstrahl mit einer Pulsbreite von 1 ns erzeugt. Durch die Fokussierung des Strahls an SNAKE auf einen Durchmesser von 100 ?m konnte in einem einzelnen Puls eine Ionenstrahldichte von 10^9 Protonen/cm² erreicht werden und so eine Dosis von 20 Gy mit einem Puls im Target deponiert werden. Die Strahlflecke wurden in lateraler Richtung durch Strahlablenkung und Bewegen des Tumors inklusive Maus zu einem homogenen Feld von ca. 1 cm² zusammengesetzt. Die homogene Tiefendosis wurde mittels Aluminiumplättchen als diskrete Energieabsorber kurz vor dem Target verwirklicht. So besaß das homogen bestrahlte Gesamtvolumen eine Tiefe von 4,8 mm und einen Durchmesser von 9 mm. Durch die Realisierung der kontinuierlichen Protonenbestrahlung am selben Gerät, wurden systematische Fehler im Vergleich der beiden Bestrahlungsarten minimiert.
Zur Kontrolle der Protonenfluenz diente ein vor dem Tumor platzierter Gafchromic EBT2 Film, der in Abhängigkeit von der durch die Protonen deponierten Dosis verdunkelt. Damit konnte die Dosis der gepulsten und kontinuierlichen Bestrahlung mit einer relativen Genauigkeit von 3 % rekonstruiert werden.
Es wurden insgesamt 11 XF354 und 12 FaDu Tumore bestrahlt, davon 12 im gepulsten und 11 im kontinuierlichen Modus. Die sich aus der Dosisrekonstruktion ergebende mittlere Tiefendosis lag für die gepulsten Bestrahlungen durchschnittlich bei 17,6 Gy mit einer Breite von 0,2 Gy bzw. für die kontinuierliche Bestrahlung bei 19,6 Gy mit einer Breite von 0,3 Gy. Annähernd die Hälfte des 10 % Dosisunterschieds zwischen gepulst und kontinuierlicher Bestrahlung konnten auf systematische Fehler der Bestrahlungsdurchführung und der Dosisrekonstruktion zurückgeführt werden. Diese sind
in zukünftigen Experimenten einfach zu korrigieren. Die andere Hälfte liegt vermutlich in der Strahlstrommessung begründet und sollte nach näheren Untersuchungen ebenfalls reduziert werden können.
Bei den XF354 Tumoren erreichte ein Tumor je Bestrahlungsmodus das dreifache Bestrahlungsvolumen, das für die Wachstumsverzögerung als Bezugspunkt dient, wobei die Wachstumsverzögerung 103 d für die gepulste und 35 d für die kontinuierliche Bestrahlung ergab. Die übrigen Tumore wurden kontrolliert, wodurch sich wegen der geringen Statistik keine Aussage über eine unterschiedliche RBW treffen lässt. Für die FaDu Tumore konnte eine mittlere Wachstumsverzögerung von (34 ± 4) d aus fünf gepulst bestrahlten und (36 ± 4) d aus vier kontinuierlich bestrahlten nicht kontrollierten Tumoren bestimmt werden.
Die gewonnenen Ergebnisse zeigen keinen signifikanten Unterschied bezüglich der Tumorwachstumsverzögerung von gepulster und kontinuierlicher Protonenbestrahlung.
BibTeX:
	@mastersthesis{Siebenwirth2010da,
	  author = {Siebenwirth, Christian},
	  title = {Tumorbestrahlung mit gepulsten und kontinuierlichen Protonen am Mausmodell.},
	  school = {Technische Universität München},
	  year = {2010}
	}
	

2009

Nanosecond pulsed proton microbeam
G. Dollinger, A. Bergmaier, V. Hable, R. Hertenberger, C. Greubel, A. Hauptner and P. Reichart; Nuclear Instruments and Methods in Physics Research Section B 267 (12-13) (2009) 2008-2012.
Abstract: We show the preparation of a pulsed 20 MeV proton beam at the Munich tandem accelerator which offers a fluence of more than 1 × 10e9 protons/cm2 being deposited in a beam spot smaller than 100 ?m in diameter and within a time span of 0.9 ns fwhm. Such a beam is produced by an ECR type proton source using charge exchange in cesium vapor to obtain a beam of negative hydrogen of high brightness that is bunched, chopped, accelerated and then focused by the superconducting multipole lens of the microprobe SNAKE. Single beam pulses are generated in order to irradiate cell samples or tissue and to measure their biological effect in comparison to continuous proton or X-ray irradiation.
BibTeX:
	@article{Dollinger2009,
	  author = {Dollinger, G. and Bergmaier, A. and Hable, V. and Hertenberger, R. and Greubel, C. and Hauptner, A. and Reichart, P.},
	  title = {Nanosecond pulsed proton microbeam},
	  booktitle = {Proceedings of the 11th International Conference on Nuclear Microprobe Technology and Applications and the 3rd International Workshop on Proton Beam Writing},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2009},
	  volume = {267},
	  number = {12-13},
	  pages = {2008--2012},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X09003310},
	  doi = {http://doi.org/10.1016/j.nimb.2009.03.006}
	}
	
The live cell irradiation and observation setup at SNAKE
V. Hable, C. Greubel, A. Bergmaier, P. Reichart, A. Hauptner, R. Krücken, H. Strickfaden, S. Dietzel, T. Cremer, G. Drexler, A. Friedl and G. Dollinger; Nuclear Instruments and Methods in Physics Research Section B 267 (12-13) (2009) 2090-2097.
Abstract: We describe a new setup at the ion microprobe SNAKE (Superconducting Nanoscope for Applied nuclear (Kern-) physics Experiments) at the Munich 14 MV Tandem accelerator that facilitates both living cell irradiation with sub micrometer resolution and online optical imaging of the cells before and after irradiation by state of the art phase contrast and fluorescence microscopy. The cells are kept at standard cell growth conditions at 37 °C in cell culture medium. After irradiation it is possible to switch from single ion irradiation conditions to cell observation within 0.5 s. First experiments were performed targeting substructures of a cell nucleus that were tagged by TexasRed labeled nucleotides incorporated in the cellular DNA by 55 MeV single carbon ion irradiation. In addition we show first online sequences of short time kinetics of Mdc1 protein accumulation in the vicinity of double strand breaks after carbon ion irradiation.
BibTeX:
	@article{Hable2009,
	  author = {Hable, V. and Greubel, C. and Bergmaier, A. and Reichart, P. and Hauptner, A. and Krücken, R. and Strickfaden, H. and Dietzel, S. and Cremer, T. and Drexler, G.A. and Friedl, A.A. and Dollinger, G.},
	  title = {The live cell irradiation and observation setup at SNAKE},
	  booktitle = {Proceedings of the 11th International Conference on Nuclear Microprobe Technology and Applications and the 3rd International Workshop on Proton Beam Writing},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2009},
	  volume = {267},
	  number = {12-13},
	  pages = {2090--2097},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X09003504},
	  doi = {http://doi.org/10.1016/j.nimb.2009.03.071}
	}
	
Hydrogen Analysis by Proton-Proton Scattering
P. Reichart and G. Dollinger; In: Y. Wang and M. Nastasi (Eds.), Handbook of Modern Ion Beam Materials Analysis (2nd Ed.) , Chapter 9 , p. 187-206 , Materials Research Society , 2009.
BibTeX:
	@incollection{Reichart2009,
	  author = {Reichart, P. and Dollinger, G.},
	  title = {Hydrogen Analysis by Proton-Proton Scattering},
	  booktitle = {Handbook of Modern Ion Beam Materials Analysis (2nd Ed.)},
	  publisher = {Materials Research Society},
	  year = {2009},
	  pages = {187--206},
	  edition = {2nd},
	  editor = {Y. Wang and M. Nastasi},
	  url = {http://www.mrs.org/ibh2}
	}
	
Proton–Proton Scattering Cross Sections
P. Reichart and G. Dollinger; In: Y. Wang and M. Nastasi (Eds.), Handbook of Modern Ion Beam Materials Analysis (2nd Ed.) Appendices , Chapter 14 , p. 229-254 , Materials Research Society , 2009.
BibTeX:
	@incollection{Reichart2009a,
	  author = {Reichart, P. and Dollinger, G.},
	  title = {Proton–Proton Scattering Cross Sections},
	  booktitle = {Handbook of Modern Ion Beam Materials Analysis (2nd Ed.) Appendices},
	  publisher = {Materials Research Society},
	  year = {2009},
	  pages = {229--254},
	  edition = {2nd},
	  editor = {Y. Wang and M. Nastasi},
	  url = {http://www.mrs.org/ibh2}
	}
	
No Evidence for a Different RBE between Pulsed and Continuous 20 MeV Protons
T.E. Schmid, G. Dollinger, A. Hauptner, V. Hable, C. Greubel, S. Auer, A.A. Friedl, M. Molls and B. Röper; Radiation Research 172 (5) (2009) 567-574.
Abstract: To obtain greater insight into the future potential of tumor radiotherapy using proton beams generated from high-intensity lasers, it is important to characterize the ionization quality of the new beams by measuring the relative biological effectiveness (RBE) under conditions where the full dose at one irradiation site will be deposited by a few proton pulses less than 1 ns in duration. HeLa cells attached to a Mylar foil were irradiated with 70 kV X rays to obtain a reference dose–response curve or with 3 Gy of 20 MeV protons at the Munich tandem accelerator (Garching), either using a continuous mode where a cell sample was irradiated within a 100-ms time span or using a pulsed mode where radiation was given in a single proton pulse of about 1 ns. After irradiation cytochalasin B was added; 24 h later cells were fixed and stained with acridine orange and micronuclei were counted. The X-ray dose–response curve for the production of micronuclei in HeLa cells followed a linear-quadratic model. The corresponding RBE values for 20 MeV protons in pulsed and continuous irradiation modes were 1.07 ± 0.08 and 1.06 ± 0.10 in the first proton experiment and 1.09 ± 0.08 and 1.05 ± 0.11 in the second, respectively. There was no evidence for a difference in the RBE for pulsed and continuous irradiation of HeLa cells with 20 MeV protons.
BibTeX:
	@article{Schmid2009,
	  author = {Schmid, T. E. and Dollinger, G. and Hauptner, A. and Hable, V. and Greubel, C. and Auer, S. and Friedl, A. A. and Molls, M. and Röper, B.},
	  title = {No Evidence for a Different RBE between Pulsed and Continuous 20 MeV Protons},
	  booktitle = {Radiation Research},
	  journal = {Radiation Research},
	  year = {2009},
	  volume = {172},
	  number = {5},
	  pages = {567--574},
	  note = {cited By (since 1996)18},
	  url = {http://www.bioone.org/doi/10.1667/RR1539.1},
	  doi = {http://doi.org/10.1667/RR1539.1}
	}
	
IR calibrations for water determination in olivine, r-GeO2, and SiO2 polymorphs
S.-M. Thomas, M. Koch-Müller, P. Reichart, D. Rhede, R. Thomas, R. Wirth and S. Matsyuk; Physics and Chemistry of Minerals 36 (2009) 489-509.
Abstract: Mineral-specific IR absorption coefficients were calculated for natural and synthetic olivine, SiO2 polymorphs, and GeO2 with specific isolated OH point defects using quantitative data from independent techniques such as proton–proton scattering, confocal Raman spectroscopy, and secondary ion mass spectrometry. Moreover, we present a routine to detect OH traces in anisotropic minerals using Raman spectroscopy combined with the ‘‘Comparator Technique’’. In case of olivine and the SiO2 system, it turns out that the magnitude of e for one structure is independent of the type of OH point defect and therewith the peak position (quartz e = 89,000 ± 15,000 l mol^-1_H2O cm^-2), but it varies as a function of structure (coesite e = 214,000 ± 14,000 l mol-1 H2O cm-2; stishovite e = 485,000 ± 109,000 l mol-1 H2O cm-2). Evaluation of data from this study confirms that not using mineral-specific IR calibrations for the OH quantification in nominally anhydrous minerals leads to inaccurate estimations of OH concentrations, which constitute the basis for modeling the Earth’s deep water cycle.
BibTeX:
	@article{Thomas2009,
	  author = {Thomas, Sylvia-Monique and Koch-Müller, Monika and Reichart, Patrick and Rhede, Dieter and Thomas, Rainer and Wirth, Richard and Matsyuk, Stanislav},
	  title = {IR calibrations for water determination in olivine, r-GeO2, and SiO2 polymorphs},
	  journal = {Physics and Chemistry of Minerals},
	  year = {2009},
	  volume = {36},
	  pages = {489--509},
	  url = {http://link.springer.com/article/10.1007%2Fs00269-009-0295-1},
	  doi = {http://doi.org/10.1007/s00269-009-0295-1}
	}
	
Differences in gamma-H2AX foci formation after irradiation with continuous and pulsed proton beams
O. Zlobinskaya, T. Schmid, G. Dollinger, V. Hable, C. Greubel, D. Michalski, J. Wilkens, G. Du, M. Molls and B. Röper; In: , O. Dössel and W.C. Schlegel (Eds.), IFMBE Proceedings 25 (2009) 142-145 , Springer International Publishing AG.
Abstract: Introduction: Classical particle accelerators offer proton pulses of some milliseconds duration. In contrast, the new technology of the high-intensity laser acceleration will produce ultimately shorter particle packages (up to one nanosecond) with substantially lower pulse frequency and higher pulse-dose achievement. Very little is known about the relative biological effectiveness (RBE) of this new beam quality, which could be a possible future application in radiation oncology. In our present study we investigate possible differences based on quantitative analysis of ?-H2AX fluorescence - a known marker of DNA double strand breaks (DSBs). Methods: HeLa cells were irradiated with 1 Gy of 20 MeV protons at the Munich tandem accelerator, either at continuous mode (100 ms), or at pulsed mode with a single pulse of 1 ns duration. A dose-effect-curve based on five doses of 75 kV x-rays served for reference. The total number of ?-H2AX foci per cell was determined using a self-developed macro (ImageJ, NIH, USA). Results: Quantitative analysis of ?-H2AX fluorescence revealed no significant difference (p=0.16) in yield of foci formation after irradiation with pulsed or continuous proton beams. ?-H2AX data for cell samples exposed to 1 Gy of 20 MeV protons at pulsed or continuous irradiation modes were 23.29 ± 2.04 and 26.54 ± 2.54 foci per cell, respectively. The corresponding RBE values for 20 MeV protons were 0.96 ± 0.18 and 1.13 ± 0.21 (p=0.21) for pulsed and continuous irradiation modes. However, the percentage of foci smaller than 5-10 pixels was slightly decreased and foci tended to cluster after irradiation with pulsed protons. Conclusions: Based on ?-H2AX foci formation no significant difference in the RBE between pulsed and continuous proton irradiation beams in HeLa cells has been detected so far. These results are well in line with our data on micronucleus induction in HeLa cells.
BibTeX:
	@inproceedings{Zlobinskaya2009,
	  author = {Zlobinskaya, O. and Schmid, T.E. and Dollinger, G. and Hable, V. and Greubel, C. and Michalski, D. and Wilkens, J. and Du, G. and Molls, M. and Röper, B.},
	  title = {Differences in gamma-H2AX foci formation after irradiation with continuous and pulsed proton beams},
	  booktitle = {IFMBE Proceedings},
	  publisher = {Springer International Publishing AG},
	  year = {2009},
	  volume = {25},
	  number = {3},
	  pages = {142--145},
	  editor = {Olaf Dössel and Wolfgang C. Schlegel},
	  note = {World Congress on Medical Physics and Biomedical Engineering: Radiation Protection and Dosimetry, Biological Effects of Radiation; Munich; Germany; 7 September 2009 through 12 September 2009;},
	  url = {http://link.springer.com/book/10.1007/978-3-642-03902-7},
	  doi = {http://doi.org/10.1007/978-3-642-03902-7}
	}
	

2008

Quantitative Analyse von Proteinkinetiken nach Bestrahlung lebender Zellen mit energetischen Schwerionen am Rasterionenmikroskop SNAKE
Tino Brüning; Diplomarbeit, Universität der Bundeswehr München, 2008.
BibTeX:
	@mastersthesis{Bruening2008da,
	  author = {Brüning, Tino},
	  title = {Quantitative Analyse von Proteinkinetiken nach Bestrahlung lebender Zellen mit energetischen Schwerionen am Rasterionenmikroskop SNAKE},
	  school = {Universität der Bundeswehr München},
	  year = {2008}
	}
	
Realisierung einer Schnittstelle für die externe Steuerung der Software AxioVision 4.6.3 in Verbindung mit dem Rasterionenmikroskop SNAKE
Christian Burgdorf; Studienarbeit, Universität der Bundeswehr München, 2008.
BibTeX:
	@thesis{Burgdorf2008sa,
	  author = {Burgdorf, Christian},
	  title = {Realisierung einer Schnittstelle für die externe Steuerung der Software AxioVision 4.6.3 in Verbindung mit dem Rasterionenmikroskop SNAKE},
	  school = {Universität der Bundeswehr München},
	  year = {2008}
	}
	
Water in natural olivine—determined by proton-proton scattering analysis
J. Gose, P. Reichart, G. Dollinger and E. Schmädicke; American Mineralogist 93 (10) (2008) 1613-1619.
Abstract: Here we present water concentration data for olivine from different host rocks, measured with a nuclear technique using proton-proton scattering. This method, which is used here for the first time on olivine, is very powerful for determining trace amounts of water. The studied olivine specimens differ in their H2O contents, ranging from 4 to 51 wt ppm (=10–117 atom ppm H). The lowest concentrations are found in olivine from spinel peridotite xenoliths, the highest concentrations in olivine from alpine-type peridotite; the contents of an ophiolitic and a hydrothermal olivine are intermediate. Infrared spectroscopy was applied to ensure that the measured water contents stem solely from hydroxyl defects in the mineral structure. The infrared spectra differ from sample to sample. Five of six olivine specimens show absorption bands typical of hydroxyl groups associated with Ti defects. These olivines differ in their Ti contents by two orders of magnitude. However, a correlation of water and Ti content was not observed.
BibTeX:
	@article{Gose2008,
	  author = {Gose, Jürgen and Reichart, Patrick and Dollinger, Günther and Schmädicke, Esther},
	  title = {Water in natural olivine—determined by proton-proton scattering analysis},
	  journal = {American Mineralogist},
	  year = {2008},
	  volume = {93},
	  number = {10},
	  pages = {1613-1619},
	  url = {http://ammin.geoscienceworld.org/content/93/10/1613.abstract},
	  doi = {http://doi.org/10.2138/am.2008.2835}
	}
	
Quantitative analysis of DNA-damage response factors after sequential ion microirradiation
C. Greubel, V. Hable, G.A. Drexler, A. Hauptner, S. Dietzel, H. Strickfaden, I. Baur, R. Krücken, T. Cremer, A.A. Friedl and G. Dollinger; Radiation and Environmental Biophysics 47 (4) (2008) 415-422.
Abstract: Several proteins are known to form foci at DNA sites damaged by ionizing radiation. We study DNA damage response by immunofluorescence microscopy after microirradiation of cells with energetic ions. By using microirradiation, it is possible to irradiate different regions on a single dish at different time-points and to differentiate between cells irradiated earlier and later. This allows to directly compare immunofluorescence intensities in both subsets of cells with little systematic error because both subsets are cultivated and stained under identical conditions. In addition, by using irradiation patterns such as crossing lines, it is possible to irradiate individual cells twice and to differentiate between immunofluorescence signals resulting from the cellular response to the earlier and to the later irradiation event. Here, we describe the quantitative evaluation of immunofluorescence intensities after sequential irradiation.
BibTeX:
	@article{Greubel2008,
	  author = {Greubel, Christoph and Hable, Volker and Drexler, Guido A. and Hauptner, Andreas and Dietzel, Steffen and Strickfaden, Hilmar and Baur, Iris and Krücken, Reiner and Cremer, Thomas and Friedl, Anna A. and Dollinger, Günther},
	  title = {Quantitative analysis of DNA-damage response factors after sequential ion microirradiation},
	  journal = {Radiation and Environmental Biophysics},
	  year = {2008},
	  volume = {47},
	  number = {4},
	  pages = {415--422},
	  url = {http://link.springer.com/article/10.1007%2Fs00411-008-0181-0},
	  doi = {http://doi.org/10.1007/s00411-008-0181-0}
	}
	
Competition effect in DNA damage response
C. Greubel, V. Hable, G. Drexler, A. Hauptner, S. Dietzel, H. Strickfaden, I. Baur, R. Krücken, T. Cremer, G. Dollinger and A. Friedl; Radiation and Environmental Biophysics 47 (4) (2008) 423-429.
Abstract: We have built an ion-microbeam for studies of the nuclear topography and kinetics of double-strand break repair at the single cell level. Here, we show that a first and a second, delayed single ion exposure at different nuclear sites led to comparable accumulations of phospho-ATM, ?-H2AX and Mdc1 at both earlier (e) and later (l) microirradiated sites. In contrast, accumulations of 53BP1 and the recombination protein Rad51 were strongly reduced at l-sites. This apparent competition effect is accompanied by a reduced amount of 53BP1 in undamaged areas of the irradiated nuclei. We suggest that a critically limited pool size combined with strong binding at irradiated sites leads to the exhaustion of unbound factors freely roaming the nuclear space. The undersupply of these factors at l-sites requires in addition a long-lasting binding at e-sites or a weaker binding at l-sites. The observed effects suggest that DNA damage response at individual nuclear sites depends on the time course of damage load. This may have implications for therapeutic radiation treatments.
BibTeX:
	@article{Greubel2008a,
	  author = {Greubel, C. and Hable, V. and Drexler, G.A. and Hauptner, A. and Dietzel, S. and Strickfaden, H. and Baur, I. and Krücken, R. and Cremer, T. and Dollinger, G. and Friedl, A.A.},
	  title = {Competition effect in DNA damage response},
	  journal = {Radiation and Environmental Biophysics},
	  year = {2008},
	  volume = {47},
	  number = {4},
	  pages = {423--429},
	  url = {http://link.springer.com/article/10.1007%2Fs00411-008-0182-z},
	  doi = {http://doi.org/10.1007/s00411-008-0182-z}
	}
	
Relative biological effectiveness (RBE) of 20 MeV protons for induction of micronuclei in HeLa cells at continuous and pulsed irradiation modes
T.E. Schmid, G. Dollinger, A. Hauptner, V. Hable, C. Greubel, A.A. Friedl, M. Molls and B. Röper; In: , M. Baumann (Ed.), Proceedings des 17. Symposiums Experimentelle Strahlentherapie und Klinische Strahlenbiologie : Dresden, 28. Februar - 01. März 2008 17 (2008) 105-108 , Inst. für Biophysik u. Strahlenbiologie.
BibTeX:
	@inproceedings{Schmid2008,
	  author = {Schmid, T. E. and Dollinger, G. and Hauptner, A. and Hable, V. and Greubel, C. and Friedl, A. A. and Molls, M. and Röper, B.},
	  title = {Relative biological effectiveness (RBE) of 20 MeV protons for induction of micronuclei in HeLa cells at continuous and pulsed irradiation modes},
	  booktitle = {Proceedings des 17. Symposiums Experimentelle Strahlentherapie und Klinische Strahlenbiologie : Dresden, 28. Februar - 01. März 2008},
	  publisher = {Inst. für Biophysik u. Strahlenbiologie},
	  year = {2008},
	  volume = {17},
	  number = {17},
	  pages = {105--108},
	  editor = {Baumann, Michael}
	}
	
Application of Raman spectroscopy to quantify trace water concentrations in glasses and garnets
S.-M. Thomas, R. Thomas, P. Davidson, P. Reichart, M. Koch-Müller and G. Dollinger; American Mineralogist 93 (10) (2008) 1550-1557.
Abstract: We present a new technique for the quantification of water in glasses down to the parts per million level, using confocal microRaman spectroscopy with the recently developed “Comparator Technique.” To test this method, we used a suite of glasses and gemstone-quality garnets with varying chemical compositions. Water contents were independently determined with proton-proton (pp) scattering and infrared (IR) spectroscopy. Moreover, water concentrations obtained for the garnets were compared to data from a study by Maldener et al. (2003) using nuclear reaction analysis (NRA). For each sample, we recorded Raman spectra in the frequency range from 3100 to 3750 cm?1 and standardized them using an independently well-characterized glass. In this paper, we demonstrate the usefulness of this technique for quantifying water concentrations in natural and synthetic glass samples and garnets, and verify its adaptability for concentrations from 40 wt ppm up to 40 wt% H2O. However, in the case of absorbing material (e.g., Fe-bearing samples), the suggested method needs to be modified to overcome problems due to heating and melting of those phases. Furthermore, we propose an integrated molar absorption coefficient for water in quartz glass, ?itot = 72 000 ± 12 000 Lmol?1H2Ocm?2, for quantitative IR spectroscopy that is higher than a previously reported value of Paterson (1982) or that predicted by the general calibration trend determined by Libowitzky and Rossman (1997).
BibTeX:
	@article{Thomas2008,
	  author = {Thomas, Sylvia-Monique and Thomas, Rainer and Davidson, Paul and Reichart, Patrick and Koch-Müller, Monika and Dollinger, Günther},
	  title = {Application of Raman spectroscopy to quantify trace water concentrations in glasses and garnets},
	  journal = {American Mineralogist},
	  year = {2008},
	  volume = {93},
	  number = {10},
	  pages = {1550-1557},
	  url = {http://ammin.geoscienceworld.org/content/93/10/1550.abstract},
	  doi = {http://doi.org/10.2138/am.2008.2834}
	}
	

2007

Entwicklung von Auswertemethoden zur Bestimmung von Proteinkinetiken nach Zellbestrahlungen am Rasterionenmikroskop SNAKE
Tino Brüning; Studienarbeit, Universität der Bundeswehr München, 2007.
BibTeX:
	@thesis{Bruening2007sa,
	  author = {Brüning, Tino},
	  title = {Entwicklung von Auswertemethoden zur Bestimmung von Proteinkinetiken nach Zellbestrahlungen am Rasterionenmikroskop SNAKE},
	  school = {Universität der Bundeswehr München},
	  year = {2007}
	}
	

2006

Hydrogen microscopy and analysis of DNA repair using focused high energy ion beams
G. Dollinger, A. Bergmaier, A. Hauptner, S. Dietzel, G. Drexler, C. Greubel, V. Hable, P. Reichart, R. Krücken, T. Cremer and A. Friedl; Nuclear Instruments and Methods in Physics Research Section B 249 (1-2) (2006) 270-277.
Abstract: The ion microprobe SNAKE (Supraleitendes Nanoskop für Angewandte Kernphysikalische Experimente) at the Munich 14 MV tandem accelerator achieves beam focussing by a superconducting quadrupole doublet and can make use of a broad range of ions and ion energies, i.e. 4-28 MeV protons or up to 250 MeV gold ions. Due to these ion beams, SNAKE is particularly attractive for ion beam analyses in various fields. Here we describe two main applications of SNAKE. One is the unique possibility to perform three-dimensional hydrogen microscopy by elastic proton-proton scattering utilizing high energy proton beams. The high proton energies allow the analysis of samples with a thickness in the 100 ?m range with micrometer resolution and a sensitivity better than 1 ppm. In a second application, SNAKE is used to analyse protein dynamics in cells by irradiating live cells with single focussed ions. Fluorescence from immunostained protein 53BP1 is used as biological track detector after irradiation of HeLa cells. It is used to examine the irradiated region in comparison with the targeted region. Observed patterns of fluorescence foci agree reasonably well with irradiation patterns, indicating an overall targeting accuracy of about 2 ?m while the beam spot size is less than 0.5 ?m in diameter. This performance shows successful adaptation of SNAKE for biological experiments where cells are targeted on a sub-cellular level by energetic ions.
BibTeX:
	@article{Dollinger2006,
	  author = {Dollinger, G. and Bergmaier, A. and Hauptner, A. and Dietzel, S. and Drexler, G.A. and Greubel, C. and Hable, V. and Reichart, P. and Krücken, R. and Cremer, T. and Friedl, A.A.},
	  title = {Hydrogen microscopy and analysis of DNA repair using focused high energy ion beams},
	  booktitle = {Proceedings of the Seventeenth International Conference on Ion Beam Analysis},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2006},
	  volume = {249},
	  number = {1-2},
	  pages = {270--277},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X06004587},
	  doi = {http://doi.org/10.1016/j.nimb.2006.04.012}
	}
	
Radiobiological Experiments at the Munich Microprobe SNAKE
A.A. Friedl, G.A. Drexler, M. Deutsch, H. Strickfaden, S. Dietzel, T. Cremer, A. Hauptner, R. Krücken, C. Greubel, V. Hable and G. Dollinger; In: Proceedings of the 7th International Workshop: Microbeam Probes of Cellular Radiation Response , Radiation Research 166 (2006) 668 , Radiation Research Society.
BibTeX:
	@inproceedings{Friedl2006,
	  author = {Friedl, A. A. and Drexler, G. A. and Deutsch, M. and Strickfaden, H. and Dietzel, S. and Cremer, T. and Hauptner, A. and Krücken, R. and Greubel, C. and Hable, V. and Dollinger, G.},
	  title = {Radiobiological Experiments at the Munich Microprobe SNAKE},
	  booktitle = {Proceedings of the 7th International Workshop: Microbeam Probes of Cellular Radiation Response},
	  journal = {Radiation Research},
	  publisher = {Radiation Research Society},
	  year = {2006},
	  volume = {166},
	  number = {4},
	  pages = {668},
	  url = {http://www.bioone.org/doi/abs/10.1667/RR0683.1},
	  doi = {http://doi.org/10.1667/RR0683.1}
	}
	
The Munich Microprobe SNAKE, a Single-Ion Cell Irradiation Facility
C. Greubel, V. Hable, G. Dollinger, A. Hauptner, R. Krücken, H. Strickfaden, S. Dietzel, T. Cremer, G.A. Drexler, M. Deutsch and A.A. Friedl; In: Proceedings of the 7th International Workshop: Microbeam Probes of Cellular Radiation Response , Radiation Research 166 (2006) 654 , Radiation Research Society.
BibTeX:
	@inproceedings{Greubel2006,
	  author = {Greubel, C. and Hable, V. and Dollinger, G. and Hauptner, A. and Krücken, R. and Strickfaden, H. and Dietzel, S. and Cremer, T. and Drexler, G. A. and Deutsch, M. and Friedl, A. A.},
	  title = {The Munich Microprobe SNAKE, a Single-Ion Cell Irradiation Facility},
	  booktitle = {Proceedings of the 7th International Workshop: Microbeam Probes of Cellular Radiation Response},
	  journal = {Radiation Research},
	  publisher = {Radiation Research Society},
	  year = {2006},
	  volume = {166},
	  number = {4},
	  pages = {654},
	  url = {http://www.bioone.org/doi/abs/10.1667/RR0683.1},
	  doi = {http://doi.org/10.1667/RR0683.1}
	}
	
Dynamics of DNA Repair Proteins after Directed Heavy-Ion Cell Irradiation.
V. Hable, G. Dollinger, C. Greubel, A. Hauptner, R. Krücken, S. Dietzel, T. Cremer, G.A. Drexler and A.A. Fried; In: Proceedings of the 7th International Workshop: Microbeam Probes of Cellular Radiation Response , Radiation Research 166 (2006) 676 , Radiation Research Society.
BibTeX:
	@inproceedings{Hable2006,
	  author = {Hable, V. and Dollinger, G. and Greubel, C. and Hauptner, A. and Krücken, R. and Dietzel, S. and Cremer, T. and Drexler, G. A. and Fried, A. A.},
	  title = {Dynamics of DNA Repair Proteins after Directed Heavy-Ion Cell Irradiation.},
	  booktitle = {Proceedings of the 7th International Workshop: Microbeam Probes of Cellular Radiation Response},
	  journal = {Radiation Research},
	  publisher = {Radiation Research Society},
	  year = {2006},
	  volume = {166},
	  number = {4},
	  pages = {676},
	  url = {http://www.bioone.org/doi/abs/10.1667/RR0683.1},
	  doi = {http://doi.org/10.1667/RR0683.1}
	}
	
Methods for quantitative evaluation of dynamics of repair proteins within irradiated cells
V. Hable, G. Dollinger, C. Greubel, A. Hauptner, R. Krücken, S. Dietzel, T. Cremer, G. Drexler, A. Friedl and R. Löwe; Nuclear Instruments and Methods in Physics Research Section B 245 (1) (2006) 298-301.
Abstract: Living HeLa cells are irradiated well directed with single 100 MeV oxygen ions by the superconducting ion microprobe SNAKE, the Superconducting Nanoscope for Applied Nuclear (=Kern-) Physics Experiments, at the Munich 14 MV tandem accelerator. Various proteins, which are involved directly or indirectly in repair processes, accumulate as clusters (so called foci) at DNA-double strand breaks (DSBs) induced by the ions. The spatiotemporal dynamics of these foci built by the phosphorylated histone ?-H2AX are studied. For this purpose cells are irradiated in line patterns. The ?-H2AX is made visible under the fluorescence microscope using immunofluorescence techniques. Quantitative analysis methods are developed to evaluate the data of the microscopic images in order to analyze movement of the foci and their changing size.
BibTeX:
	@article{Hable2006a,
	  author = {Hable, V. and Dollinger, G. and Greubel, C. and Hauptner, A. and Krücken, R. and Dietzel, S. and Cremer, T. and Drexler, G.A. and Friedl, A.A. and Löwe, R.},
	  title = {Methods for quantitative evaluation of dynamics of repair proteins within irradiated cells},
	  booktitle = {Proceedings of the Sixth International Symposium on Swift Heavy Ions in Matter (SHIM 2005)},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2006},
	  volume = {245},
	  number = {1},
	  pages = {298--301},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X05020628},
	  doi = {http://doi.org/10.1016/j.nimb.2005.11.118}
	}
	
Spatial Distribution of DNA Double-Strand Breaks from Ion Tracks
A. Hauptner, W. Friedland, S. Dietzel, G.A. Drexler, C. Greubel, V. Hable, H. Strickfaden, T. Cremer, A.A. Friedl, R. Krücken, H.G. Paretzke and G. Dollinger; In: P. Sigmund (Ed.), Ion Beam Science: Solved and Unsolved Problems , Vol. 52 , p. 59-85 , Royal Danish Academy of Sciences and Letter , 2006.
Abstract: Theoretical and experimental approaches are developed to investigate the spatial distribution of DNA damage induced by energetic ions in cell nuclei, with a special emphasis on DNA double-strand breaks (DSB). Using a phenomenological description for the relationship between energy dose and DSB induction, the total number of DSBs and their average number per unit pathlength can be calculated analytically for single ion tracks in cell nuclei. A simple approach to microscopic DNA damage description is offered by analytical representations which give the average energy dose in dependence of the radial distance from the ion track. However, the extreme fluctuations in the DNA damage per volume, which is due to the inhomogeneous ionisation events of the individual secondary electron paths and the structure of chromatin in the nucleus, make a true follow-up of the ionisation and excitation events desirable, e.g. by using Monte Carlo methods. The visualisation of DSBs by staining proteins which accumulate in large amounts at DSB repair sites, thus forming so-called foci, allows to analyse the spatial distribution of DSB sites under the fluorescence microscope. With this method, generally a much lower number of DSB sites along an ion track is observed than expected on basis of calculations. This observation hints at insufficient consideration of gross structures in the organisation of nuclear DNA or at a fast clustering of DSBs, possibly to form repair factories.
BibTeX:
	@incollection{Hauptner2006,
	  author = {Hauptner, A. and Friedland, W. and Dietzel, S. and Drexler, G. A. and Greubel, C. and Hable, V. and Strickfaden, H. and Cremer, T. and Friedl, A. A. and Krücken, R. and Paretzke, H. G. and Dollinger, G.},
	  title = {Spatial Distribution of DNA Double-Strand Breaks from Ion Tracks},
	  booktitle = {Ion Beam Science: Solved and Unsolved Problems},
	  publisher = {Royal Danish Academy of Sciences and Letter},
	  year = {2006},
	  volume = {52},
	  pages = {59--85},
	  editor = {P. Sigmund},
	  url = {http://www.sdu.dk/Bibliotek/matfys}
	}
	
DNA-repair protein distribution along the tracks of energetic ions
A. Hauptner, R. Krücken, C. Greubel, V. Hable, G. Dollinger, G. Drexler, M. Deutsch, R. Löwe, A. Friedl, S. Dietzel, H. Strickfaden and T. Cremer; Radiation Protection Dosimetry 122 (1-4) (2006) 147-149.
Abstract: A simple model of homogenous chromatin distribution in HeLa-cell nuclei suggests that the track of an energetic ion hits 30 nm chromatin fibers with a mean distance of 0.55 ?m. To test this assumption, living HeLa-cells were irradiated at the irradiation setup of the ion microprobe SNAKE using the ion beams provided by the Munich 14 MV tandem accelerator. After irradiation, the distribution of 53BP1 protein foci was studied by immunofluorescence. The observed 53BP1 distribution along the tracks of 29 MeV 7Li ions and 24 MeV 12C ions differed significantly from the expectations resulting from the simple chromatin model, suggesting that the biological track structure is determined by cell nuclear architecture with higher order organisation of chromatin.
BibTeX:
	@article{Hauptner2006a,
	  author = {Hauptner, A. and Krücken, R. and Greubel, C. and Hable, V. and Dollinger, G. and Drexler, G.A. and Deutsch, M. and Löwe, R. and Friedl, A.A. and Dietzel, S. and Strickfaden, H. and Cremer, T.},
	  title = {DNA-repair protein distribution along the tracks of energetic ions},
	  journal = {Radiation Protection Dosimetry},
	  year = {2006},
	  volume = {122},
	  number = {1-4},
	  pages = {147--149},
	  url = {http://rpd.oxfordjournals.org/content/122/1-4/147.abstract},
	  doi = {http://doi.org/10.1093/rpd/ncl420}
	}
	
Irradiation of living cells with single ions at the ion microprobe SNAKE
A. Hauptner, T. Cremer, M. Deutsch, S. Dietzel, G. Drexler, C. Greubel, V. Hable, R. Krücken, R. Löwe, H. Strickfaden, G. Dollinger and A. Friedl; Acta Physica Polonica A 109 (3) (2006) 273-278.
Abstract: The irradiation setup at the ion microprobe SNAKE is used to irradiate living cells with single energetic ions. The irradiation accuracy of 0.55 µm and respectively 0.40 µm allows to irradiate substructures of the cell nucleus. By the choice of ion atomic number and energy the irradiation can be performed with a damage density adjustable over more than three orders of magnitude. Immunofluorescence detection techniques show the distribution of proteins involved in the repair of DNA double-strand breaks. In one of the first experiments the kinetics of appearance of irradiation-induced foci in living HeLa cells was examined. In other experiments a new effect was detected which concerned the interaction between irradiation events performed at different time points within the same cell nucleus.
BibTeX:
	@article{Hauptner2006b,
	  author = {Hauptner, A. and Cremer, T. and Deutsch, M. and Dietzel, S. and Drexler, G.A. and Greubel, C. and Hable, V. and Krücken, R. and Löwe, R. and Strickfaden, H. and Dollinger, G. and Friedl, A.A.},
	  title = {Irradiation of living cells with single ions at the ion microprobe SNAKE},
	  journal = {Acta Physica Polonica A},
	  year = {2006},
	  volume = {109},
	  number = {3},
	  pages = {273--278},
	  note = {Proceedings of the XL Zakopane School of Physics, Zakopane 2005},
	  url = {http://przyrbwn.icm.edu.pl/APP/SPIS/a109-3.html},
	  doi = {0.12693/APhysPolA.109.273}
	}
	
Mikroskopisch genaue Zellbestrahlung mit hochenergetischen Ionen.
Andreas Hauptner; Dissertation, Technische Universität München, 2006.
Abstract: Im Rahmen der Arbeit wurde die physikalisch-biologische Schädigungswirkung von hochenergetischer Ionenstrahlung in Modell-Zellkernen auf mikroskopischer Ebene abgeschätzt. Zur Durchführung von Bestrahlungsexperimenten wurde am Rasterionenmikroskop SNAKE des Münchener 14 MV Tandembeschleunigers ein Einzel-Ionen-Bestrahlungsaufbau für lebende Zellen realisiert. An HeLa-Zellen konnten damit Bestrahlungen mit einer räumlichen Auflösung von 0,5 µm durchgeführt und mittels Immunofluoreszenz-Methoden Proteine nachgewiesen werden, die an der Reparatur von DNA-Doppelstrangbrüchen beteiligt sind. Dies ermöglichte das Studium der Chromatin-Dynamik an geschädigten Zellkernbereichen sowie die Charakterisierung eines neu entdeckten "Konkurrenzeffekts" der DNA-Reparatur nach fraktionierter Bestrahlung. Durch Änderung der Bestrahlungsgeometrie konnten Schädigungsereignisse in Form sogenannter Foci entlang von Ionenspuren mit hoher Auflösung untersucht und mit Modellrechnungen verglichen werden.
BibTeX:
	@phdthesis{Hauptner2006diss,
	  author = {Hauptner, Andreas},
	  title = {Mikroskopisch genaue Zellbestrahlung mit hochenergetischen Ionen.},
	  school = {Technische Universität München},
	  year = {2006},
	  url = {http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:91-diss20060915-1726116123}
	}
	
3D-Hydrogen analysis of ferromagnetic microstructures in proton irradiated graphite
P. Reichart, D. Spemann, A. Hauptner, A. Bergmaier, V. Hable, R. Hertenberger, C. Greubel, A. Setzer, G. Dollinger, D. Jamieson, T. Butz and P. Esquinazi; Nuclear Instruments and Methods in Physics Research Section B 249 (1-2) (2006) 286-291.
Abstract: Recently, magnetic order in highly oriented pyrolytic graphite (HOPG) induced by proton broad- and microbeam irradiation was discovered. Theoretical models propose that hydrogen could play a major role in the magnetism mechanism. We analysed the hydrogen distribution of pristine as well as irradiated HOPG samples, which were implanted to ?m-sized spots as well as extended areas with various doses of 2.25 MeV protons at the Leipzig microprobe LIPSION. For this we used the sensitive 3D hydrogen microscopy system at the Munich microprobe SNAKE. The background hydrogen level in pristine HOPG is determined to be less than 0.3 at-ppm. About 4.8 × 1015 H-atoms/cm2 are observed in the near-surface region (4 ?m depth resolution). The depth profiles of the implants show hydrogen located within a confined peak at the end of range, in agreement with SRIM Monte Carlo simulations, and no evidence of diffusion broadening along the c-axis. At the sample with microspots, up to 40 at.% of the implanted hydrogen is not detected, providing support for lateral hydrogen diffusion.
BibTeX:
	@article{Reichart2006,
	  author = {Reichart, P. and Spemann, D. and Hauptner, A. and Bergmaier, A. and Hable, V. and Hertenberger, R. and Greubel, C. and Setzer, A. and Dollinger, G. and Jamieson, D.N. and Butz, T. and Esquinazi, P.},
	  title = {3D-Hydrogen analysis of ferromagnetic microstructures in proton irradiated graphite},
	  booktitle = {Proceedings of the Seventeenth International Conference on Ion Beam Analysis},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2006},
	  volume = {249},
	  number = {1-2},
	  pages = {286--291},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X06004605},
	  doi = {http://doi.org/10.1016/j.nimb.2006.04.014}
	}
	

2005

Microirradiation of cells with energetic heavy ions
G. Dollinger, V. Hable, A. Hauptner, R. Krücken, P. Reichart, A. Friedl, G. Drexler, T. Cremer and S. Dietzel; Nuclear Instruments and Methods in Physics Research Section B 231 (1-4) (2005) 195-201.
Abstract: The ion microprobe SNAKE (superconducting nanoscope for applied nuclear (Kern) physics experiments) at the Munich 14 MV tandem accelerator achieves beam focusing by a superconducting quadrupole doublet and can make use of a broad range of ions and ion energies, from 20 MeV protons to 200 MeV gold ions. This allows to adjust the number of DNA single strand breaks (SSBs) and double strand breaks (DSBs) per ion and per cell nucleus from about 0.1 DSBs per ion to several 100 DSBs per ion. When irradiating with single 100 MeV 16O ions, the adapted setup permits a fwhm irradiation accuracy of 0.55 ?m in x-direction and 0.4 ?m in y-direction, as demonstrated by retrospective track etching of polycarbonate foils. The experiments point to investigate protein dynamics after targeted irradiation. As an example for such experiments we show a kind of three dimensional representation of foci of ?-H2AX which are visible 0.5 h after the irradiation with 100 MeV 16O ions took place. It shows the gross correlation with the irradiation pattern but also distinct deviations which are attributed to protein dynamics in the cell.
BibTeX:
	@article{Dollinger2005,
	  author = {Dollinger, G. and Hable, V. and Hauptner, A. and Krücken, R. and Reichart, P. and Friedl, A.A. and Drexler, G. and Cremer, T. and Dietzel, S.},
	  title = {Microirradiation of cells with energetic heavy ions},
	  booktitle = {Proceedings of the 9th International Conference on Nuclear Microprobe Technology and Applications},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2005},
	  volume = {231},
	  number = {1-4},
	  pages = {195--201},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X05000765},
	  doi = {http://doi.org/10.1016/j.nimb.2005.01.056}
	}
	
Three dimensional hydrogen microscopy in diamond
G. Dollinger, P. Reichart, A. Bergmaier, A. Hauptner and C. Wild; In: , S. Ashok, J. Chevallier, B.L. Sopori, M. Tabe and P. Kiesel (Ed.), Materials Research Society Symposium Proceedings 864 (2005) 541-547 , MRS, Warrendale, PA, United States.
Abstract: We introduce proton-proton scattering at a microprobe of 17 MeV protons to quantitatively image three dimensional hydrogen distributions in polycrystalline diamond at a lateral resolution better than 1 ?m and high sensitivity. The images show that most of the hydrogen of a ?110?-textured undoped polycrystalline diamond film is located at grain boundaries. The average amount of hydrogen is (8.1±1.5)·10 14 atoms/cm 2 along the grain boundaries which corresponds to about a third of a monolayer. The content within the grain is below the detection limit of 1.4-10 16 atoms/cm 2 (0.08 at-ppm).
BibTeX:
	@inproceedings{Dollinger2005a,
	  author = {Dollinger, G. and Reichart, P. and Bergmaier, A. and Hauptner, A. and Wild, C.},
	  title = {Three dimensional hydrogen microscopy in diamond},
	  booktitle = {Materials Research Society Symposium Proceedings},
	  publisher = {MRS, Warrendale, PA, United States},
	  year = {2005},
	  volume = {864},
	  pages = {541--547},
	  editor = {Ashok S., Chevallier J., Sopori B.L., Tabe M., Kiesel P.},
	  note = {cited By (since 1996)0},
	  url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-30544438196&partnerID=40&md5=4d513ce20703288ffbfba125377daf31}
	}
	
Dynamik der Verteilung von DNA-Reparaturfaktoren in lebenden Zellen nach fraktionierter Bestrahlung am Rasterionenmikroskop SNAKE
Christoph Greubel; Diplomarbeit, Technische Universität München, 2005.
BibTeX:
	@mastersthesis{Greubel2005da,
	  author = {Greubel, Christoph},
	  title = {Dynamik der Verteilung von DNA-Reparaturfaktoren in lebenden Zellen nach fraktionierter Bestrahlung am Rasterionenmikroskop SNAKE},
	  school = {Technische Universität München},
	  year = {2005}
	}
	

2004

Untersuchung der Dynamik von DNA-Reparaturproteinen nach Bestrahlung lebender Zellen am Rasterionenmikroskop SNAKE.
Volker Hable; Diplomarbeit, Technische Universität München, 2004.
Abstract: In dieser Arbeit wurde die Dynamik der Reparaturvorgänge von DNA-Schäden in biologischen Zellen nach Schwerionenbestrahlung untersucht. Dazu wurden lebende HeLa-Zellen am Rasterionenmikroskop SNAKE mit 100MeV Sauerstoff-Ionen des Münchner 14MV Tandembeschleuniger bestrahlt. Die dort installierte Bestrahlungseinrichtung ermöglicht es, Zellkernen eine definierte Anzahl von Ionen und somit eine definierte Dosis mikroskopisch genau zu applizieren. Die erreichbare Strahlauflösung konnte im Rahmen dieser Arbeit mittels einer 50 Hz-Pulsung in x auf 0.55?m fwhm und in y auf 0.40?m verbessert werden. Durch die Entwicklung mikrostrukturierter Zellträgerfolien wurde das Auffinden der bestrahlten Zellen deutlich erleichtert und somit erstmals Experimente zur gezielten Bestrahlung einzelner Zellkerne ermöglicht.
Die schwersten Schäden, die hochenergetische Ionen in Zellkernen bewirken, sind Doppelstrangbrüche der DNA. Zu deren Reparatur stehen der Zelle verschiedene Mechanismen zur Verfügung. An der Reparatur direkt oder indirekt beteiligte Proteine
wie gH2AX, 53BP1, Rad51 und Mdc1 werden an Doppelstrangbrüchen angehängt und bilden sogenannte Foci aus. Ihre Funktion und Dynamik wurde in dieser Arbeit untersucht. Mittels biochemischer Prozesse wurden diese Proteine nach der Bestrahlung
angefärbt und unter dem Fluoreszenzmikroskop in einer Fokusserie abgebildet. So gewonnene und rechnergestützt entfaltete, dreidimensionale Bilder lieferten die Grundlage für eine quantitative Auswertung der Proteinverteilungen, um so die Dynamik der
Reparaturproteine zu studieren.
In Zeitreihenstudien wurde in der Zellkernmitte innerhalb der ersten 2 – 4 Stunden nach Bestrahlung ein Anwachsen der Focigröße (fwhm) von 1.2?m auf 1.5?m bei gH2AX und von 0.8?m auf 1.1?m bei 53BP1 beobachtet. In den folgenden zwei Stunden
fällt sie wieder in etwa auf den Anfangswert ab, und bleibt über 24 Stunden nahezu konstant. Am Zellkernrand wächst die Größe der gH2AX-Foci von ebenfalls 1.2?m innerhalb der ersten Stunde um knapp 0.1?m an und fällt daraufhin auf ca. 0.8?m
ab.
Des weiteren wurde die Bewegung der geschädigten DNA im Zellkern untersucht. Die hierbei gewonnenen Ergebnisse sind mit dem Modell einer Diffusion verträglich. Die Diffusionskonstante ließ sich zu (7 · 10^(?7) ± 4 · 10^(?7))?m^2/s bestimmen. Dabei waren keine signifikanten Unterschiede zwischen Zellkernmitte und -rand erkennbar.
Darüber hinaus wurde durch markiertes Bestrahlen zu zwei verschiedenen Zeitpunkten festgestellt, dass in Zellkernen, die gerade Doppelstrangbrüche reparieren, neu hinzukommende Strahlenschäden eine Unterversorgung von Protein 53BP1 erleiden.
Dieser Effekt tritt auf, wenn die Zeitdauer zwischen den beiden Bestrahlungen unter einer Stunde liegt.
BibTeX:
	@mastersthesis{Hable2004da,
	  author = {Hable, Volker},
	  title = {Untersuchung der Dynamik von DNA-Reparaturproteinen nach Bestrahlung lebender Zellen am Rasterionenmikroskop SNAKE.},
	  school = {Technische Universität München},
	  year = {2004}
	}
	
Microirradiation of cells with energetic heavy ions
A. Hauptner, S. Dietzel, G.A. Drexler, P. Reichart, R. Krücken, T. Cremer, A.A. Friedl and G. Dollinger; Radiation and Environmental Biophysics 42 (4) (2004) 237-245.
Abstract: The ion microprobe SNAKE at the Munich 14 MV tandem accelerator achieves beam focussing by a superconducting quadrupole doublet and can make use of a broad range of ions and ion energies, from 20 MeV protons to 200 MeV gold ions. Because of these properties, SNAKE is particularly attractive for biological microbeam experiments. Here we describe the adaptation of SNAKE for microirradiation of cell samples. This includes enlarging of the focal distance in order to adjust the focal plane to the specimen stage of a microscope, construction of a beam exit window in a flexible nozzle and of a suitable cell containment, as well as development of procedures for on-line focussing of the beam, preparation of single ions and scanning by electrostatic deflection of the beam. When irradiating with single 100 MeV 16O ions, the adapted set-up permits an irradiation accuracy of 0.91 µm (full width at half maximum) in the x-direction and 1.60 µm in the y-direction, as demonstrated by retrospective track etching of polycarbonate foils. Accumulation of the repair protein Rad51, as detected by immunofluorescence, was used as a biological track detector after irradiation of HeLa cells with geometric patterns of counted ions. Observed patterns of fluorescence foci agreed reasonably well with irradiation patterns, indicating successful adaptation of SNAKE. In spite of single ion irradiation, we frequently observed split fluorescence foci which might be explained by small-scale chromatin movements.
BibTeX:
	@article{Hauptner2004,
	  author = {Hauptner, A. and Dietzel, S. and Drexler, G. A. and Reichart, P. and Krücken, R. and Cremer, T. and Friedl, A. A. and Dollinger, G.},
	  title = {Microirradiation of cells with energetic heavy ions},
	  journal = {Radiation and Environmental Biophysics},
	  year = {2004},
	  volume = {42},
	  number = {4},
	  pages = {237--245},
	  url = {http://link.springer.com/article/10.1007%2Fs00411-003-0222-7},
	  doi = {http://doi.org/10.1007/s00411-003-0222-7}
	}
	
The Munich Microprobe Setup for Single-Ion Irradiation of Cells
A. Hauptner, G. Dollinger, G. Datzmann, H.-J. Körner, R. Krücken and P. Reichart; In: Proceedings of the 6th International Workshop/12th L. H. Gray Workshop: Microbeam Probes of Cellular Radiation ResponseMarch 29–31, 2003 , Radiation Research 161 (2004) 98 , Radiation Research Society.
BibTeX:
	@inproceedings{Hauptner2004a,
	  author = {Hauptner, A. and Dollinger, G. and Datzmann, G. and Körner, H.-J. and Krücken, R. and Reichart, P.},
	  title = {The Munich Microprobe Setup for Single-Ion Irradiation of Cells},
	  booktitle = {Proceedings of the 6th International Workshop/12th L. H. Gray Workshop: Microbeam Probes of Cellular Radiation ResponseMarch 29–31, 2003},
	  journal = {Radiation Research},
	  publisher = {Radiation Research Society},
	  year = {2004},
	  volume = {161},
	  number = {1},
	  pages = {98},
	  url = {http://www.rrjournal.org/toc/rare/161/1},
	  doi = {http://doi.org/10.1667/RR3091}
	}
	
Three-Dimensional Hydrogen Microscopy in Diamond
P. Reichart, G. Datzmann, A. Hauptner, R. Hertenberger, C. Wild and G. Dollinger; Science 306 (5701) (2004) 1537-1540.
Abstract: A microprobe of protons with an energy of 17 million electron volts is used to quantitatively image three-dimensional hydrogen distributions at a lateral resolution better than 1 micrometer with high sensitivity. Hydrogen images of a -textured undoped polycrystalline diamond film show that most of the hydrogen is located at grain boundaries. The average amount of hydrogen atoms along the grain boundaries is (8.1 ± 1.5) × 1014 per square centimeter, corresponding to about a third of a monolayer. The hydrogen content within the grain is below the experimental sensitivity of 1.4 × 1016 atoms per cubic centimeter (0.08 atomic parts per million). The data prove a low hydrogen content within chemical vapor deposition–grown diamond and the importance of hydrogen at grain boundaries, for example, with respect to electronic properties of polycrystalline diamond.
BibTeX:
	@article{Reichart2004,
	  author = {Reichart, P. and Datzmann, G. and Hauptner, A. and Hertenberger, R. and Wild, C. and Dollinger, G.},
	  title = {Three-Dimensional Hydrogen Microscopy in Diamond},
	  journal = {Science},
	  year = {2004},
	  volume = {306},
	  number = {5701},
	  pages = {1537-1540},
	  url = {http://www.sciencemag.org/content/306/5701/1537.abstract},
	  doi = {http://doi.org/10.1126/science.1102910}
	}
	
3D hydrogen microscopy with sub-ppm detection limit
P. Reichart, G. Dollinger, A. Bergmaier, G. Datzmann, A. Hauptner, H.-J. Körner and R. Krücken; Nuclear Instruments and Methods in Physics Research Section B 219-220 (1-4) (2004) 980-987.
Abstract: Coincident elastic proton-proton scattering at a 17 MeV microprobe is used to investigate hydrogen distributions on microscopic scale inside freestanding samples up to some 100 ?m thickness. Hydrogen imaging at atomic ppm level needs a total count rate of about 100 kHz of scattered protons in order to get sufficient statistics from the small fraction of coincident hydrogen signals. It is obtained using a highly segmented silicon strip detector of 2.3 sr for proton currents of less than 100 pA impinging on films thicker 10 ?m. A five level filter almost completely suppresses accidental coincidences. The sensitivity of this kind of 3D hydrogen microscopy is demonstrated by the analysis of a 55 ?m thick synthetic diamond layer showing a detection limit of 0.08 at-ppm hydrogen. In addition, the proposed depth resolution of 3-6 ?m is experimentally confirmed and a lateral resolution of 0.6 ?m full width half maximum is obtained at a significant hydrogen enhancement inside the layer.
BibTeX:
	@article{Reichart2004a,
	  author = {Reichart, P. and Dollinger, G. and Bergmaier, A. and Datzmann, G. and Hauptner, A. and Körner, H.-J. and Krücken, R.},
	  title = {3D hydrogen microscopy with sub-ppm detection limit},
	  booktitle = {Proceedings of the Sixteenth International Conference on Ion Beam Analysis},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2004},
	  volume = {219-220},
	  number = {1-4},
	  pages = {980--987},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X04002502},
	  doi = {http://doi.org/10.1016/j.nimb.2004.01.200}
	}
	
Dreidimensionale Wasserstoffmikroskopie mittels Proton-Proton-Streuung
Patrick Reichart; Dissertation, Technische Universität München, 2004.
Abstract: Mit der Methode der Proton-Proton-Streuung zum Wasserstoffnachweis wurde ein Verfahren entwickelt, um unter Einsatz eines fokussierten 17 MeV Protonenstrahls Wasserstoffverteilungen auf mikroskopischer Skala quantitativ mit einer sub-ppm Nachweisgrenze dreidimensional abzubilden. Die Realisierung am Rasterionenmikroskop SNAKE am Münchener 14 MV Tandembeschleuniger mit einem großen ringförmigen, segmentierten Detektor und einem komplexen Analysesystem ermöglicht eine Nachweisgrenze von 0.08 at-ppm bei einer lateralen Auflösung von 0.6 ?m und einer Tiefenauflösung besser als 5 ?m. Mit den hohen Protonenenergien können Proben bis einige 100 ?m untersucht werden. Damit konnte erstmals nachgewiesen werden, dass in künstlich hergestellten polykristallinen Diamantschichten der Wasserstoff hauptsächlich an den Korngrenzen lokalisiert ist. In weiteren Experimenten wird das Potential für zukünftige Anwendungen zur Untersuchung organischer Materialien oder innerer Grenzflächen demonstriert.
BibTeX:
	@phdthesis{Reichart2004diss,
	  author = {Reichart, Patrick},
	  title = {Dreidimensionale Wasserstoffmikroskopie mittels Proton-Proton-Streuung},
	  school = {Technische Universität München},
	  year = {2004},
	  url = {http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:91-diss2004030314833}
	}
	
Basic aspects of deep lithography with particles for the fabrication of micro-optical and micro-mechanical structures
B. Volckaerts, P. Vynck, M. Vervaeke, L. Cosentino, P. Finocchiaro, P. Reichart, G. Datzmann, A. Hauptner, G. Dollinger, A. Hermanne and H. Thienpont; In: , P. Daele and J. Mohr (Ed.), Proc. SPIE 5454, Micro-Optics: Fabrication, Packaging, and Integration 5454 (2004) 52-63 , SPIE.
Abstract: The strength of today's deep lithographic micro-machining technologies is their ability to fabricate monolithic building-blocks including optical and mechanical functionalities that can be precisely integrated in more complex photonic systems. In this contribution we present the physical aspects of Deep Lithography with ion Particles (DLP). We investigate the impact of the ion mass, energy and fluence on the developed surface profile to find the optimized irradiation conditions for different types of high aspect ratio micro-optical structures. To this aim, we develop a software program that combines the atomic interaction effects with the macroscopic beam specifications. We illustrate the correctness of our simulations with experimental data that we obtained in a collaboration established between the accelerator facilities at TUM, LNS and VUB. Finally, we review our findings and discuss the strengths and weaknesses of DLP with respect to Deep Lithography with X-rays (LIGA).
BibTeX:
	@inproceedings{Volckaerts2004,
	  author = {Volckaerts, B. and Vynck, P. and Vervaeke, M. and Cosentino, L. and Finocchiaro, P. and Reichart, P. and Datzmann, G. and Hauptner, A. and Dollinger, G. and Hermanne, A. and Thienpont, H.},
	  title = {Basic aspects of deep lithography with particles for the fabrication of micro-optical and micro-mechanical structures},
	  booktitle = {Proc. SPIE 5454, Micro-Optics: Fabrication, Packaging, and Integration},
	  publisher = {SPIE},
	  year = {2004},
	  volume = {5454},
	  number = {52},
	  pages = {52--63},
	  editor = {Daele P., Mohr J.},
	  note = {cited By (since 1996)0},
	  url = {http://proceedings.spiedigitallibrary.org/proceeding.aspx?articleid=845728},
	  doi = {http://doi.org/10.1117/12.547718}
	}
	

2003

The Munich ion microprobe: Characteristics and prospect
G. Dollinger, G. Datzmann, A. Hauptner, R. Hertenberger, H.-J. Körner, P. Reichart and B. Volckaerts; Nuclear Instruments and Methods in Physics Research Section B 210 (2003) 6-13.
Abstract: The newly developed ion microprobe SNAKE (superconducting nanoscope for applied nuclear (Kern-) physics experiments) has gone into routine operation at the Munich 14 MV tandem accelerator. It focuses ion beams, from protons to uranium, with energies that are about 10 times larger than they are available at standard nuclear microprobes. Lateral resolutions of ?x=1.6 ?m and ?y=1.2 ?m for x- and y-direction at full aperture and as low as ?x=600 nm and ?y=150 nm for a pencil beam have been achieved so far. The latter values are limited by positional drifts and 50 Hz oscillating fields which have become obvious in time resolved measurements.
SNAKE opens new possibilities for analysis of microstructured materials as well as materials modifications. The highlights are three dimensional hydrogen analysis using proton proton scattering, high resolution transmission energy loss measurements utilizing a magnetic spectrograph and materials modification with available high energy proton and heavy ion beams. Standard techniques like particle induced X-ray emission, elastic and inelastic scattering are also used for imaging. The paper summarizes some of the prospects using the enlarged range of available ion beams and ion energies.
BibTeX:
	@article{Dollinger2003,
	  author = {Dollinger, Günther and Datzmann, Gerd and Hauptner, Andreas and Hertenberger, Ralf and Körner, Hans-Joachim and Reichart, Patrick and Volckaerts, Bart},
	  title = {The Munich ion microprobe: Characteristics and prospect},
	  booktitle = {8th International Conference of Nuclear Microprobe Technology and Applications},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2003},
	  volume = {210},
	  pages = {6--13},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X03010012},
	  doi = {http://doi.org/10.1016/S0168-583X(03)01001-2}
	}
	
Three-dimensional hydrogen microscopy using a high-energy proton probe
G. Dollinger, P. Reichart, G. Datzmann, A. Hauptner and H.-J. Körner; Applied Physics Letters 82 (1) (2003) 148-150.
Abstract: It is a challenge to measure two-dimensional or three-dimensional (3D) hydrogen profiles on a micrometer scale. Quantitative hydrogen analyses of micrometer resolution are demonstrated utilizing proton–proton scattering at a high-energy proton microprobe. It has more than an-order-of-magnitude better position resolution and in addition higher sensitivity than any other technique for 3D hydrogen analyses. This type of hydrogen imaging opens plenty room to characterize microstructured materials, and semiconductor devices or objects in microbiology. The first hydrogen image obtained with a 10 MeV proton microprobe shows the hydrogen distribution of the microcapillary system being present in the wing of a mayfly and demonstrates the potential of the method.
BibTeX:
	@article{Dollinger2003a,
	  author = {Dollinger, G. and Reichart, P. and Datzmann, G. and Hauptner, A. and Körner, H.-J},
	  title = {Three-dimensional hydrogen microscopy using a high-energy proton probe},
	  journal = {Applied Physics Letters},
	  year = {2003},
	  volume = {82},
	  number = {1},
	  pages = {148--150},
	  url = {http://apl.aip.org/resource/1/applab/v82/i1/p148_s1},
	  doi = {http://doi.org/10.1063/1.1533111}
	}
	
Sensitive 3D hydrogen microscopy using high energy protons at SNAKE
P. Reichart, G. Dollinger, G. Datzmann, A. Hauptner, R. Hertenberger and H.J. Körner; Nuclear Instruments and Methods in Physics Research Section B 210 (2003) 135-141.
Abstract: The new ion microprobe SNAKE (Superconducting Nanoscope for Applied nuclear (Kern-) physics Experiments) is a tool to focus, beside heavy ions, 4-28 MeV protons to submicron beam spot size. This facility establishes a sensitive 3D microscopy of hydrogen distributions by elastic proton proton scattering. The high proton energy enables analysis at a target thickness up to some 100 ?m without significant reduction of the micrometer lateral resolution. The scattered projectile and recoiled target protons are detected in coincidence using an annular silicon strip detector. It covers scattering angles from 29° to 61° and a 2.3 sr solid angle of detection. The readout electronics with a 50 ns coincidence window allows an efficient reduction of accidental coincidence events even at some 10 kHz count rates. 3D hydrogen microscopy using 17 MeV proton proton scattering is tested successfully providing a ppm detection limit in a 55 ?m thick diamond plate. First measurements on CVD grown diamond show the possibility to investigate such low hydrogen content of the bulk region with micrometer lateral resolution.
BibTeX:
	@article{Reichart2003,
	  author = {Reichart, P. and Dollinger, G. and Datzmann, G. and Hauptner, A. and Hertenberger, R. and Körner, H. - J.},
	  title = {Sensitive 3D hydrogen microscopy using high energy protons at SNAKE},
	  booktitle = {8th International Conference of Nuclear Microprobe Technology and Applications},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2003},
	  volume = {210},
	  pages = {135--141},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X0301084X},
	  doi = {http://doi.org/10.1016/S0168-583X(03)01084-X}
	}
	

2002

Aufbau und Charakterisierung des Hochenergie Rasterionenmikroskops SNAKE
Gerd Datzmann; Dissertation, Technische Universität München, 2002.
Abstract: Im Rahmen der Arbeit wurde am Münchner Tandembeschleuniger das Hochenergie Rasterionenmikroskop SNAKE (Supraleitendes Nanoskop für Angewandte Kernphysikalische Experimente) aufgebaut und charakterisiert. Die speziell dafür entwickelte supraleitende Multipollinse kann Protonen- und Schwerionenstrahlen mit einem Masse-Energieprodukt bis 160 MeV×u auf Mikrometergröße und kleiner fokussieren. SNAKE ist ein vielseitiges Werkzeug für Materialanalyse und -modifikation. Einen Schwerpunkt bildet dabei eine quantitative dreidimensionale Wasserstoffanalytik
BibTeX:
	@phdthesis{Datzmann2002diss,
	  author = {Datzmann, Gerd},
	  title = {Aufbau und Charakterisierung des Hochenergie Rasterionenmikroskops SNAKE},
	  school = {Technische Universität München},
	  year = {2002},
	  url = {http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:91-diss2002050313488}
	}
	
Electron-stimulated hydrogen desorption from diamond surfaces and its influence on the low-pressure synthesis of diamond
C. Goeden and G. Dollinger; Applied Physics Letters 81 (26) (2002) 5027-5029.
Abstract: A total cross section ?D = (5±2.6)×10e?18?cm2 is measured for electron-stimulated desorption (ESD) of deuterium from a boron-doped, deuterated diamond(100) surface at 5 eV incident electron energy. This large ESD cross section means a significant contribution of ESD to hydrogen abstraction reactions in microwave-driven chemical vapor deposition of diamond. The ESD cross section decreases when changing to a nitrogen-doped diamond. This change is suggested to be the reason for the reported influence of small concentrations of nitrogen or boron added to the process gas on diamond growth.
BibTeX:
	@article{Goeden2002,
	  author = {Goeden, C. and Dollinger, G.},
	  title = {Electron-stimulated hydrogen desorption from diamond surfaces and its influence on the low-pressure synthesis of diamond},
	  journal = {Applied Physics Letters},
	  year = {2002},
	  volume = {81},
	  number = {26},
	  pages = {5027-5029},
	  url = {http://link.aip.org/link/?APL/81/5027/1},
	  doi = {http://doi.org/10.1063/1.1526460}
	}
	
Electron stimulated desorption of negative ions: A time-of-flight experiment
C. Goeden and G. Dollinger; Review of Scientific Instruments 73 (8) (2002) 3058-3064.
Abstract: We present a setup for stimulated desorption experiments of negative ions using low energy incident electrons and time-of-flight identification of the desorbed ions. It consists of a pulsed electron gun, an electrostatic focusing system, and a channel plate detector setup. Electron beams down to sub-eV energies can be used due to electrostatic shielding and the compensation of the earth’s magnetic field by a set of Helmholtz coils. The main advantage is the large acceptance for ions of all masses, energies, and desorption angles at the same time, which keeps measuring time reasonably short and allows us to gain information before degeneration of the irradiated sample occurs, even if weak desorption channels are investigated. We demonstrate the power of our setup with first results from a boron doped, (100)-oriented diamond sample, which is partly oxidized and partly hydrogenated with some water contaminations on it. Different binding states of oxygen are disclosed clearly by different desorption thresholds. The C–O binding on oxidized diamond forms a carbonyl group. The 1b_2 orbital of water can be seen in a O desorption threshold. The yield of negative hydrogen desorption shows a linear increase for incident electron energies higher than 13 eV. It results from a dipolar dissociation as has been published previously.
BibTeX:
	@article{Goeden2002a,
	  author = {Goeden, C. and Dollinger, G.},
	  title = {Electron stimulated desorption of negative ions: A time-of-flight experiment},
	  journal = {Review of Scientific Instruments},
	  year = {2002},
	  volume = {73},
	  number = {8},
	  pages = {3058-3064},
	  url = {http://link.aip.org/link/?RSI/73/3058/1},
	  doi = {http://doi.org/10.1063/1.1491030}
	}
	
Elektronisch stimulierte Wasserstoffdesorption von Diamantoberflächen
Christian Goeden; Dissertation, Technische Universität München, 2002.
Abstract: Im Rahmen dieser Arbeit wurden zwei Instrumente zur stimulierten Desorption (ESD) negativer und positiver Ionen von Festkörperoberflächen unter Elektronenbeschuß (Anregungsenergie 0.5 - 300 eV) aufgebaut und betrieben. Damit wurde die stimulierte Wasserstoffdesorption von Diamantoberflächen untersucht. Die Ergebnisse werden in Bezug auf die technische Verwendbarkeit des Prozesses zum Bau einer brillanten Ionenquelle dargestellt. Darüberhinaus zeigen die Ergebnisse einen signifikanten Einfluß von ESD-Prozessen auf die Diamant-Niederdrucksynthese. Der lange bekannte Einfluß der Dotierung auf das Wachstum wird damit erklärbar.
BibTeX:
	@phdthesis{Goeden2002diss,
	  author = {Goeden, Christian},
	  title = {Elektronisch stimulierte Wasserstoffdesorption von Diamantoberflächen},
	  school = {Technische Universität München},
	  year = {2002},
	  url = {http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:91-diss2002072313551}
	}
	
Design of the munich microprobe facility for single-ion irradiation of cells
A. Hauptner, G. Datzmann, G. Dollinger, H.-J. Körner, P. Reichart and O. Schmelmer; In: Proceedings of the 5th International Workshop: Microbeam Probes of Cellular Radiation Response , Radiation Research 158 (2002) 367 , Radiation Research Society.
BibTeX:
	@inproceedings{Hauptner2002,
	  author = {Hauptner, A. and Datzmann, G. and Dollinger, G. and Körner, H.-J. and Reichart, P. and Schmelmer, O.},
	  title = {Design of the munich microprobe facility for single-ion irradiation of cells},
	  booktitle = {Proceedings of the 5th International Workshop: Microbeam Probes of Cellular Radiation Response},
	  journal = {Radiation Research},
	  publisher = {Radiation Research Society},
	  year = {2002},
	  volume = {158},
	  number = {3},
	  pages = {367},
	  note = {Stresa, Lago Maggiore, Italy,May 26–27, 2001},
	  url = {http://www.rrjournal.org/toc/rare/158/3},
	  doi = {http://doi.org/10.1667/0033-7587(2002)158%5B0365:POTIWM%5D2.0.CO;2}
	}
	
Sensitive 3D hydrogen microscopy by proton proton scattering
P. Reichart, G. Dollinger, A. Bergmaier, G. Datzmann, A. Hauptner and H.-J. Körner; Nuclear Instruments and Methods in Physics Research Section B 197 (1-2) (2002) 134-149.
Abstract: Elastic proton proton scattering is a sensitive and fast method for hydrogen analysis. Utilising a nuclear microprobe it is actually the only technique for the absolute quantification of hydrogen distributions with micrometer or even better lateral resolution. High proton energies, e.g. 20 MeV, allow a wide field of applications since even materials, some 100 ?m thick, can be analysed. Irradiation damage is reduced to a minimum compared to all other known ion beam analysis techniques, because a large solid angle of detection of some stradian can be used and the nuclear scattering cross section for protons at these energies is enhanced nearly three orders of magnitudes compared to Coulomb scattering. As a consequence, a sensitivity in the ppm range for hydrogen microscopy is possible. However, the large solid angle of detection induces geometrical effects in the energy analysis which are kept within a physical limit by an angular resolution of 10 mrad e.g. by utilising an annular silicon strip detector of 2.3 sr solid angle of detection. Therefore, the third dimension is provided with a depth resolution better 10 ?m using the energy information of the scattered protons.
BibTeX:
	@article{Reichart2002,
	  author = {Reichart, P. and Dollinger, G. and Bergmaier, A. and Datzmann, G. and Hauptner, A. and Körner, H.-J.},
	  title = {Sensitive 3D hydrogen microscopy by proton proton scattering},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2002},
	  volume = {197},
	  number = {1-2},
	  pages = {134--149},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X02014799},
	  doi = {http://doi.org/10.1016/S0168-583X(02)01479-9}
	}
	

2001

The Munich microprobe SNAKE: First results using 20 MeV protons and 90 MeV sulfur ions
G. Datzmann, G. Dollinger, C. Goeden, A. Hauptner, H.-J. Körner, P. Reichart and O. Schmelmer; Nuclear Instruments and Methods in Physics Research Section B 181 (1-4) (2001) 20-26.
Abstract: The scanning ion microprobe called Superconducting Nanoscope for Applied nuclear (Kern) physics Experiments (SNAKE) is taken into operation at the Munich 15 MV tandem accelerator. During the first experiments 16 and 20 MeV protons as well as 90 MeV 32S ions were used to test all equipments. With a reduced divergence of the beam, an overall lateral resolution of 700 nm was achieved by scanning a gold grid with a focused 90 MeV sulfur beam and detecting transmitted ions. However, some field distortions at full acceptance of the lens were detected which derive from mechanical problems at higher coil currents. In addition to the beam characterisation experiments several new detector systems were tested. Analysing the 90 MeV sulfur beam by a magnetic spectrograph behind the target chamber in transmission geometry, an overall relative energy width of 3.8×10?5 fwhm was demonstrated.
BibTeX:
	@article{Datzmann2001,
	  author = {Datzmann, Gerd and Dollinger, Günther and Goeden, Christian and Hauptner, Andreas and Körner, Hans-Joachim and Reichart, Patrick and Schmelmer, Oliver},
	  title = {The Munich microprobe SNAKE: First results using 20 MeV protons and 90 MeV sulfur ions},
	  booktitle = {7th International Conference on Nuclear Microprobe Technology and Applications},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2001},
	  volume = {181},
	  number = {1-4},
	  pages = {20--26},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X01005493},
	  doi = {http://doi.org/10.1016/S0168-583X(01)00549-3}
	}
	
Energy distribution of thermally emitted negative particles from type Ia diamond (100)
C. Goeden and G. Dollinger; Diamond and Related Materials 10 (3-7) (2001) 496-499.
Abstract: This study explores the electron emission of natural, nitrogen-doped diamond at elevated temperatures. The diamond was resistively heated up to 870°C. Accruing negatively charged particles where accelerated by a bias voltage of 30 V and the energy distribution is measured. The electrons are analysed by an electrostatic deflection resulting in an energy resolution of 70 meV. A hydrogen-free surface at a base pressure of 2.0×10?9 mbar shows a very small emission. The energy distribution has its maximum at 2.5 eV and a FWHM of 0.52 eV. Beside the main emission peak, some smaller features are observable at higher energies. An atomic hydrogen supply at 1.9×10?5 mbar increases the emission by a factor of 30. With some delay to the hydrogen supply, a new low energy peak appears. The increase in intensity during hydrogen adsorption is explained by the occurrence of a negative electron affinity (NEA) of the hydrogen-covered diamond surface. The low-energy feature might be due to hydrogen ions, either desorbing from the surface or from charge transfer during collisions of gas phase hydrogen with the diamond surface.
BibTeX:
	@article{Goeden2001,
	  author = {Goeden, C. and Dollinger, G.},
	  title = {Energy distribution of thermally emitted negative particles from type Ia diamond (100)},
	  booktitle = {11th European Conference on Diamond, Diamond-like Materials, Carbon Nanotubes, Nitrides and Silicon Carbide},
	  journal = {Diamond and Related Materials},
	  year = {2001},
	  volume = {10},
	  number = {3-7},
	  pages = {496--499},
	  url = {http://www.sciencedirect.com/science/article/pii/S0925963500004544},
	  doi = {http://doi.org/10.1016/S0925-9635(00)00454-4}
	}
	
Particle-induced X-ray emission using high energy ions with respect to microprobe application
O. Schmelmer, G. Dollinger, G. Datzmann, A. Hauptner, H.-J. Körner, P. Maier-Komor and P. Reichart; Nuclear Instruments and Methods in Physics Research Section B 179 (4) (2001) 469-479.
Abstract: Cross-sections for continuous and characteristic X-ray emission from heavy elements induced by 16 MeV protons and 70 MeV carbon ions are measured. The K- and L-line emission cross-sections are significantly increased compared to those of lower proton energies. The data are in satisfactory agreement with semi-empirical calculations for the proton beams while the experimental cross-sections for the 70 MeV carbon ions are up to one order of magnitude lower as calculated. The continuous X-ray background for protons can also be well described by theory taking into account the various sources of X-ray production by bremsstrahlung whereas again for carbon ions the background is overestimated by scaled theory. The sensitivity for particle-induced X-ray emission (PIXE) using high energy ions is within the same order of magnitude as that for the commonly used 1-3 MeV protons. However, 16 MeV proton beams may be better suited for PIXE analysis with submicron-sized beams due to the lower ion currents necessary from the increased X-ray production cross-sections and because the sample damage and lateral spread are reduced.
BibTeX:
	@article{Schmelmer2001,
	  author = {Schmelmer, O. and Dollinger, G. and Datzmann, G. and Hauptner, A. and Körner, H.-J. and Maier-Komor, P. and Reichart, P.},
	  title = {Particle-induced X-ray emission using high energy ions with respect to microprobe application},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {2001},
	  volume = {179},
	  number = {4},
	  pages = {469--479},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X01006085},
	  doi = {http://doi.org/10.1016/S0168-583X(01)00608-5}
	}
	
Ein Rasterionenmikroskop für hochenergetische Ionen
Oliver Schmelmer; Dissertation, Technische Universität München, 2001.
Abstract: Im Rahmen der Arbeit wurden am Münchener Tandem Beschleuniger wesentliche Komponenten des Rasterionenmikroskops SNAKE (Supraleitendes Nanoskop für Angewandte Kernphysikalische Experimente) zur Materialanalyse und -modifikation aufgebaut. SNAKE dient zur Fokussierung von hochenergetischen Ionenstrahlen auf einen Strahldurchmesser von 100 nm. Für den sensitiven Nachweis mittelschwerer bis schwerer Elemente (Z > 26) wurde das Potential der teilcheninduzierten Röntgenfluoreszenzanalyse (PIXE, Particle Induced X-ray Emission) mit 16 MeV Protonen und 70 MeV Kohlenstoffionen untersucht.
BibTeX:
	@phdthesis{Schmelmer2001diss,
	  author = {Schmelmer, Oliver},
	  title = {Ein Rasterionenmikroskop für hochenergetische Ionen},
	  school = {Technische Universität München},
	  year = {2001},
	  url = {http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:91-diss2001072513284}
	}
	

2000

Nanoprobe Capabilities Using 25 MeV Protons or 200 MeV Heavy Ions
G. Datzmann, G. Dollinger, C. Goeden, H.-J. Körner and O. Schmelmer; In: Proceedings of the 4th International Workshop: Microbeam Probes of Cellular Radiation Response1Killiney Bay, Dublin, Ireland, July 17--18, 1999 153 (2000) 220-238 , Radiation Research Society.
BibTeX:
	@inproceedings{Datzmann2000,
	  author = {Datzmann, G. and Dollinger, G. and Goeden, C. and Körner, H.-J. and Schmelmer, O.},
	  title = {Nanoprobe Capabilities Using 25 MeV Protons or 200 MeV Heavy Ions},
	  booktitle = {Proceedings of the 4th International Workshop: Microbeam Probes of Cellular Radiation Response1Killiney Bay, Dublin, Ireland, July 17--18, 1999},
	  publisher = {Radiation Research Society},
	  year = {2000},
	  volume = {153},
	  number = {2},
	  pages = {220--238},
	  url = {http://www.rrjournal.org/toc/rare/153/2},
	  doi = {http://doi.org/10.1667/0033-7587(2000)153%5B0220:POTIWM%5D2.0.CO;2}
	}
	
Electron stimulated desorption of negative hydrogen ions from diamond (100)
C. Goeden, G. Dollinger and P. Feulner; Diamond and Related Materials 9 (3-6) (2000) 1164-1166.
Abstract: The electron stimulated desorption of negatively charged hydrogen ions from diamond surfaces is studied with respect to an application as a bright ion source. Desorption of macroscopic currents of negative ions from a diamond surface by stimulated desorption has been demonstrated recently. To determine the dependence of the ionization cross-section on electron affinity, an oxygen covered diamond was used as a model system for positive electron affinity diamond. On this surface, different amounts of deuterium have been adsorbed. The D? ionization cross-section has been proven to vary by one order of magnitude between 3.5×10?18 cm2 and 5×10?19 cm2 with hydrogen coverage of the surface. The energy distribution of desorbed negative ions has been measured by an electrostatic analyser. For the measured broad energy distribution, an attempt of an explanation is made.
BibTeX:
	@article{Goeden2000,
	  author = {Goeden, C. and Dollinger, G. and Feulner, P.},
	  title = {Electron stimulated desorption of negative hydrogen ions from diamond (100)},
	  journal = {Diamond and Related Materials},
	  year = {2000},
	  volume = {9},
	  number = {3-6},
	  pages = {1164--1166},
	  url = {http://www.sciencedirect.com/science/article/pii/S0925963599002915},
	  doi = {http://doi.org/10.1016/S0925-9635(99)00291-5}
	}
	

1999

A superconducting multipole lens for focusing high energy ions
G. Datzmann, G. Dollinger, G. Hinderer and H.-J. Körner; Nuclear Instruments and Methods in Physics Research Section B 158 (1-4) (1999) 74-80.
Abstract: At the Munich 15 MV tandem accelerator a new two stage microprobe system Supraleitendes Nanoskop für Angewandte Kernphysikalische Experimente (SNAKE) is currently under construction. In contrast to existing facilities, it is projected to focus up to 30 MeV protons as well as heavy ions with maximum energies of 200 MeV q2/A to a submicron beam spot. In order to achieve this goal, a superconducting lens with inherent multipole corrections and special shaped edges with respect to fringe field calculations was designed. The introduction of superconductivity enables a pole tip field of 1.2 T at 10 mm bore radius and the possibility of auto correction mechanisms. An implemented electrostatic octupole for active field correction will have a maximum field strength in the same order of magnitude as the intrinsic magnetic octupole correction. For an analytical test of the novel concepts of this lens, a multipole detection device on the rotating coil principle has been built. It is capable of measuring small multipole contributions on a strong quadrupole field.
BibTeX:
	@article{Datzmann1999,
	  author = {Datzmann, G. and Dollinger, G. and Hinderer, G. and Körner, H.-J.},
	  title = {A superconducting multipole lens for focusing high energy ions},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {1999},
	  volume = {158},
	  number = {1-4},
	  pages = {74--80},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X99003080},
	  doi = {http://doi.org/10.1016/S0168-583X(99)00308-0}
	}
	
Electron stimulated desorption on diamond (100) as a negative hydrogen source
C. Goeden and G. Dollinger; Applied Surface Science 147 (1-4) (1999) 107-113.
Abstract: The electron-stimulated desorption of negatively charged hydrogen ions from diamond surfaces is studied with respect to an application as a bright ion source. Bombarding an (100)-oriented, boron-doped single crystal diamond with 40-?A electrons at energies up to 12 keV, a maximum ion current of 700 pA negative hydrogen is obtained. A supply of 1.0×10?4 mbar atomic deuterium results in a steady-state ion current of 30 pA. The ionization cross section has been proven to vary one order of magnitude between 3.5×10?18 cm2 and 5×10?19 cm2 with hydrogen coverage of the surface. This effect might be caused by the changing electron affinity of the diamond.
BibTeX:
	@article{Goeden1999,
	  author = {Goeden, C. and Dollinger, G.},
	  title = {Electron stimulated desorption on diamond (100) as a negative hydrogen source},
	  journal = {Applied Surface Science},
	  year = {1999},
	  volume = {147},
	  number = {1-4},
	  pages = {107--113},
	  url = {http://www.sciencedirect.com/science/article/pii/S0169433299000926},
	  doi = {http://doi.org/10.1016/S0169-4332(99)00092-6}
	}
	
Der 0°-Spektrograph am Raster-Ionenmikroskop SNAKE.
Andreas Hauptner; Diplomarbeit, Technische Universität München, 1999.
Abstract: Das Ziel dieser Arbeit bestand im Aufbau und der Inbetriebnahme des 0°-Spektrographen am Raster-Ionenmikroskop SNAKE. Dieses Instrument erweitert die vielfältigen Anwendungsmöglichkeiten des Ionenmikroskops um Transmissionsmessungen mit einer Energieauflösung im Bereich von dE/E   1 x 10^(-5). Dadurch werden sowohl Dickenmessungen mit Auflösungen bis zu einatomaren Schichten als auch ganz grundlegende Experimente möglich, die sich mit der Wechselwirkung zwischen hochenergetischen Ionen und Materie beschäftigen.
Die ionenoptischen Grundlagen des Spektrographen werden ausführlich behandelt. Der vertikale 90°-Magnet als zentrales Element erlaubt dabei eine ionenoptische Abbildung in die Fokalebene mit hoher Qualität. Um die projektierte Energieauflösung
zu erreichen, ist jedoch eine weitergehende, flexible Fokussierung des Ionenstrahls notwendig.
Daher wurde der Spektrograph durch zwei Quadrupol-Linsen vervollständigt.
Um den Spektrographen betreiben zu können, wurde ein CCD (charge coupled device) Zeilensensor als Fokalebenendetektor gewählt. Dieser bietet eine Ortsauflösung von 14µm. Seine prinzipielle Eignung für die Detektion sowohl von leichten wie auch
von schweren Ionen wurde experimentell mit 20 MeV Protonen und 90 MeV Schwefelionen nachgewiesen. Bei 20 MeV Protonen konnten dabei effektive Zählraten von ca. 100kHz erreicht werden. Es zeigte sich, dass die Strahlenbeständigkeit des CCD-
Detektors ausreicht, um auf einem Pixel des Detektors zwischen 10^7 und 10^8 Protonen nachzuweisen.
In ersten Experimenten konnte die Einsetzbarkeit des Spektrographen einschließlich des Fokalebenendetektors demonstriert werden.
Mit 20 MeV Protonen wurde eine relative Energieauflösung von dE_(FWHM)/E = 1.3 x 10^(-4) erreicht und Energieverlustmessungen an Goldfolien durchgeführt. Die Auflösung war hier noch durch den Strahl beschränkt.
In einer Strahlzeit mit 90 MeV Schwefelionen wurde eine relative Energieauflösung von dE_(FWHM)/E = 3.8 x 10^(-5) erreicht. Dadurch scheint die projektierte Energieauflösung und damit auch der Einsatz des 0°-Spektrographen für die geplanten Experimente in absehbarer Zeit möglich.
BibTeX:
	@mastersthesis{Hauptner1999da,
	  author = {Hauptner, Andreas},
	  title = {Der 0°-Spektrograph am Raster-Ionenmikroskop SNAKE.},
	  school = {Technische Universität München},
	  year = {1999}
	}
	
Entwicklung eines Detektors zur 3-dimensional ortsauflösenden Wasserstoffanalytik mittels Proton-Proton-Streuung.
Patrick Reichart; Diplomarbeit, Technische Universität München, 1999.
Abstract: Mit dem neuen Raster–Ionenmikroskop SNAKE (Supraleitendes Nanoskop für Angewandte Kernphysikalische Experimente) am Münchener 15MV Tandembeschleuniger wird eine Einrichtung zur Verfügung stehen, mit der 20MeV Protonen bei einem Strahlstrom von 100 pA auf einen Strahlfleck von 100 nm Durchmesser fokussiert werden können. Dies eröffnet die Möglichkeit eines sensitiven, 3–dimensionalen Nachweises von Wasserstoffverteilungen unter Anwendung der sogenannten Proton–Proton–Streuung. Dabei ermöglicht die koinzidente Detektion der gestreuten Projektilprotonen und der rückgestreuten Wasserstoffkerne in Transmissionsrichtung hinter der Probe einen untergrundfreien Nachweis der Proton–Proton–Streuereignisse.
In dieser Arbeit werden die wesentlichen Merkmale der Proton–Proton–Streuung für dieWasserstoffanalytik diskutiert und die experimentellen Anforderungen für ein sensitives Detektorsystem zur tiefenaufgelösten Wasserstoff–Mikroskopie erarbeitet.
Der große Vorteil der Methode ist die geringst mögliche Strahlenschädigung in der Wasserstoffanalytik mit Ionenstrahlen, aufgrund eines gegenüber reiner Coulombstreuung 500–fach überhöhten Streuquerschnitts bei hohen Protonenenergien.
Zusätzlich kann fast der komplette Raumwinkel hinter der Probe für einen Nachweis genutzt werden. Daher wird das Verhältnis des Nachweisquerschnitts zum Schädigungsquerschnitt größer als in irgendeiner vergleichbaren Ionenstrahl–Analysetechnik und eine Wasserstoffanalyse bei Konzentrationen unter 100 ppm oder die Analyse von biologischen Proben jeweils mit sub–?m–Auflösung möglich.
Tiefenprofile von Wasserstoffverteilungen können durch die Analyse der Summenenergie der beiden Protonen gewonnen werden. Durch die hohe Projektilenergie ist zudem eine Untersuchung von Schichtdicken über 200 ?m möglich.
In der Arbeit wurde ein Silizium–Streifendetektor mit 48 Streifen und 16 Sektoren aufgebaut, mit dem es möglich ist, einen Raumwinkel von 2.3 sr für die Proton–Proton–Streuung zu nutzen und gleichzeitig eine optimale Tiefenauflösung zu erreichen. Mit einer Winkelauflösung von unter 1° können die geometrischen Effekte so stark begrenzt werden, daß zur hohen lateralen Auflösung Tiefenauflösungen unter 10 ?m erzielt werden.
Die Signalauslese wurde unter Verwendung einer speziell angepaßten Vielkanal–Elektronik mit einer Integration in das Beschleuniger–Datenaufnahmesystem realisiert. In einem ersten Experiment konnte die Funktion des Detektorsystems und die Sensitivität der Methode demonstriert werden.
BibTeX:
	@mastersthesis{Reichart1999da,
	  author = {Reichart, Patrick},
	  title = {Entwicklung eines Detektors zur 3-dimensional ortsauflösenden Wasserstoffanalytik mittels Proton-Proton-Streuung.},
	  school = {Technische Universität München},
	  year = {1999}
	}
	
A novel high precision slit system
O. Schmelmer, G. Dollinger, G. Datzmann, C. Goeden and H.-J. Körner; Nuclear Instruments and Methods in Physics Research Section B 158 (1-4) (1999) 107-112.
Abstract: A new high precision slit system has been developed for the nano beam facility SNAKE (Supraleitendes Nanoskop für Angewandte Kernphysikalische Experimente) which is under construction at the Munich tandem accelerator. Cylindrically strained germanium wafers with a bending radius of 50 mm are used as optimized slit edges. High resolution and angle resolved energy distributions of the transmitted protons were measured by means of a Q3D magnetic spectrograph at incident energies of 20 MeV. The measurements revealed the expected strong correlation between small angle scattering and energy loss processes at the slits. Within SNAKE's angular acceptance the ratio of particles suffering energy loss by interacting with the slit and particles not interacting with the slit is less than 0.6% even for aperture widths of 2 ?m.
BibTeX:
	@article{Schmelmer1999,
	  author = {Schmelmer, O. and Dollinger, G. and Datzmann, G. and Goeden, C. and Körner, H.-J.},
	  title = {A novel high precision slit system},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {1999},
	  volume = {158},
	  number = {1-4},
	  pages = {107--112},
	  note = {cited By (since 1996)11},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X99003572},
	  doi = {http://doi.org/10.1016/S0168-583X(99)00357-2}
	}
	

1998

Aufbau einer Quelle hochbrillanter, negativer Ionen.
Christian Goeden; Diplomarbeit, Technische Universität München, 1998.
BibTeX:
	@mastersthesis{Goeden1998da,
	  author = {Goeden, Christian},
	  title = {Aufbau einer Quelle hochbrillanter, negativer Ionen.},
	  school = {Technische Universität München},
	  year = {1998}
	}
	

1997

Eine supraleitende Multipollinse zur Fokussierung hochenergetischer Ionen.
Gerd Datzmann; Diplomarbeit, Technische Universität München, 1997.
BibTeX:
	@mastersthesis{Datzmann1997da,
	  author = {Datzmann, Gerd},
	  title = {Eine supraleitende Multipollinse zur Fokussierung hochenergetischer Ionen.},
	  school = {Technische Universität München},
	  year = {1997}
	}
	
Design of the new superconducting microprobe system in Munich
G. Hinderer, G. Dollinger, G. Datzmann and H.-J. Körner; Nuclear Instruments and Methods in Physics Research Section B 130 (1-4) (1997) 51-56.
Abstract: At the Munich 15 MV tandem accelerator a new two-stage microprobe system is under construction. It will demagnify a beam spot by a factor 200 in both transversal directions for ions up to an energy of 200 MeV · q2/A. The second stage of the system is a superconducting quadrupole doublet lens, with overlayed 2n-poles, n = 4, 6 and 8. The multipole components of this lens have been determined by a ray tracing program with a special treatment of the fringing fields. As a result of these calculations, the overall geometrical aberrations at the focal point are 180 nm horizontally and 280 nm vertically at full angular acceptance (image coordinates ±9 and ±20 mrad, respectively). A main part of the superconducting lens is a central ceramic tube which defines the exact positions of the poles. Superconducting NbTi foils are used to shape the field to the desired one. Superconducting current loops automatically serve for a suppression of all odd harmonic field components.
BibTeX:
	@article{Hinderer1997,
	  author = {Hinderer, G. and Dollinger, G. and Datzmann, G. and Körner, H.-J.},
	  title = {Design of the new superconducting microprobe system in Munich},
	  booktitle = {5th International Conference of Nuclear Microprobe Technology and Applications},
	  journal = {Nuclear Instruments and Methods in Physics Research Section B},
	  year = {1997},
	  volume = {130},
	  number = {1-4},
	  pages = {51--56},
	  url = {http://www.sciencedirect.com/science/article/pii/S0168583X9700178X},
	  doi = {http://doi.org/10.1016/S0168-583X(97)00178-X}
	}
	

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