Abstract An attempt towards an experimental set up which could provide the experimental data on correlation processes occurred simultaneously in two distanced DNA targets within a charged particle track is presented. A modified Jet Counter nanodosemeter was used in two experiments with carbon ions with mean energies of 52 and 23 MeV. The probability distributions of the correlated pairs of ionisation clusters produced in two neighbouring sensitive volumes are presented. A question of potential new descriptors of radiation quality is raised. INTRODUCTION Experimental nanodosimetry is aimed at direct measurement of the ionisation clusters created by a track of a single ionising particle in a nanometric volume equivalent to DNA segments. The target volume can be irradiated directly by a projectile or placed at some distance from the track core where clusters of ions are created only by secondary electrons. Such experiments provide the ionisation cluster-size distributions in the single nanometre sites and could be called 1D. There are numbers of reports(1–5) describing such 1D experiments for different kinds of charged particles. New descriptors of radiation quality can be derived from such distributions, e.g. the probability of creating two or more ionisations in a single nanometric volume F2. As shown by Grosswendt, by means of MC simulations, for a liquid water cylindrical target (2.3 nm in diameter and 3.4 nm in height) irradiated with a rectangular homogeneous particle beam of cross section 4.6 × 6.8 nm2, F2 correlates to the probability of creating double strand breaks in plasmid SV40 viral DNA(6). However, a new kind of nanodosimetric experiment could aid to better understand the formation of more complex DNA damage and consequent biological outcomes. In contrast with the conclusion formulated by Simmons and Watt(7), that individual delta rays from heavy particle tracks have negligible effect on the induction of damage, the attention was here focused on the contribution of the secondary electrons in the close penumbra region and its correlations with primary events. The role of the track penumbra, is of particular interest as it is considered to play an important role in whole balance of radiation damage. It has to be highlighted that all events within a short segment of a single track are correlated in space and time. Such correlation would be responsible for the synergetic effects of delta electrons. It seems that the data which include angular and distance dependence of ionisation events in close proximity of the track core are needed. The experimental data on spatial correlation between the ionisation events within a track may be potentially linked with complex DNA damage probability. It is especially interesting in cases of particle radiotherapy where complex DNA breakage contributes significantly to radiation damage of living cells. An attempt towards an experimental set-up which could provide the experimental data on correlation processes occurring simultaneously in two separated DNA targets within a charged particle track is presented. The first results for carbon ions are presented and discussed here. As the ionisations created within a single track are mutually correlated the whole experiment has been named ‘spatially correlated ionisation clusters’. MATERIALS AND METHODS The Jet Counter (JC) device used in this study has been specially modified for simultaneous measurements of ionisation clusters in two neighbouring sensitive volumes (SVs). However, general design and performance has not changed. Schematic view of JC is presented in Figure 1. It consists of an interaction chamber (IC), where a SV with simulated nanometre-size target is obtained by gas expansion (gas jet) from a reservoir R by a pulse operating a piezoelectric valve PZ with a repetition rate of 1–8 Hz. The gas jet density is monitored with 1 keV electron beam at the projectiles beam height (see Ref.(8) for details) and assumed to be constant in whole IC during peak plateau. The basis for this assumption is a large diameter to length ratio of the IC, so the effects of the flow viscosity are negligible. Also, the duration of the plateau (~400 μs) is sufficient to uniformly fill whole IC volume. Gas molecules ionised by single projectiles form ionisation clusters of different size (different number of ions). The time and amplitude of each detected ion and projectile is recorded on an event-by-event basis (event means each single crossing of a projectile through IC). Figure 1. View largeDownload slide Schematic view of JC, not to scale. The G1 grid is optional and if present it is placed inside IC. Figure 1. View largeDownload slide Schematic view of JC, not to scale. The G1 grid is optional and if present it is placed inside IC. The detailed scheme of the IC is shown in Figure 2. The chamber is cylindrical, 10 mm in diameter, and lined with 1 mg/cm2 Mylar (Al covered both sides). The height of IC is adjustable and equal 10 or 20 mm. Figure 2. View largeDownload slide Detailed scheme of the interaction chamber of the JC in two sensitive volume experiment. Separation grid G1 consists of two wires 4 mm apart and parallel to a projectile path. Extraction grid G2 is a ring with two wires 8 mm apart also parallel to a projectile path. Figure 2. View largeDownload slide Detailed scheme of the interaction chamber of the JC in two sensitive volume experiment. Separation grid G1 consists of two wires 4 mm apart and parallel to a projectile path. Extraction grid G2 is a ring with two wires 8 mm apart also parallel to a projectile path. For more detailed description and performance tests of JC, see Refs.(8, 9). The idea of the spatial correlation measurements The idea of the spatial correlation measurements is schematically explained in Figure 3. Each act of primary ionisation created in volume V1 may be correlated with an ionisation created in volume V2 by secondary electrons released by the same particle. The main requirement for the nanodosemeter used in such experiments is to create conditions to count ions created in both volumes independently. Figure 3. View largeDownload slide Arrangement of sensitive volumes (dashed) in ionisation spatial correlation measurements. Grey balls represent ions created by heavy charged particle. Figure 3. View largeDownload slide Arrangement of sensitive volumes (dashed) in ionisation spatial correlation measurements. Grey balls represent ions created by heavy charged particle. Ionisation clusters of positively charged ions created by a projectile in an IC filled with gas are guided from their place of birth to the detector. Therefore, the drift time of an ion depends on the place where that ion was created. Recording the drift time for each ion allows an estimate to be made of the place of origin of the ion. These data are used for the investigation of correlations between number of ions created in two separated volumes within a track of a charged particle. In the proposed experiment V1 is placed in a track core region and V2 in the penumbra, thus a strong correlation is expected as many of ions in V2 are produced (directly or indirectly) by secondary particles originating in V1. The main issue is the diffusion of ions, which may produce very high background in the V2, as there may be as high as 20–50 times more ions created in V1. The experiment is meant to study correlation of ionisations, thus information about place of origin of each ion cannot be uncertain. Proposed solution is presented in the next sub-section. Some other geometries than that presented in Figure 3 can also be considered. If both volumes are placed outside the track core, than much weaker correlation is expected as the region where most of secondary electrons originate is not observed. Another option is to place volumes along the projectile trajectory, however, there would be very high background of independent ionisation events created directly by the projectile. Modifications of the IC for correlation measurements In case of using two SVs which are needed for correlation measurements, the longer, 20 mm, version of IC was used. Also, IC was modified with the addition of an electric grid G1 made of two very thin gold wires. Very low potential (a few volts) applied to the G1 grid and its low geometrical cross section (2 × 10−3 mm2 for each wire) provide transparency for secondary electrons of energies higher than ionisation potential for molecular nitrogen (~15.5 eV). Still, the grid can modify the drift time of ions created in different parts of the IC. The potential on G1 should be high enough to stop ions in V1 as long as it is polarised. Different potential values was applied to G1 grid to determine how they affect drift time spectrum of ions. As one can see in Figure 4, the first part of spectrum is practically not affected by the G1 potential value except small acceleration. These ions are considered to be created below G1 grid in volume V2. Figure 4. View largeDownload slide Ions drift time spectra for constant potentials on G1 grid measured for 3.8 MeV alpha particles (the same target size as in experiments with carbon ions). Figure 4. View largeDownload slide Ions drift time spectra for constant potentials on G1 grid measured for 3.8 MeV alpha particles (the same target size as in experiments with carbon ions). Constant potential on G1 grid is not suitable to perform simultaneous measurement in both volumes. To independently count ions created in each volume the grid is polarised only for several microseconds after a projectile triggers the system. This way most of ions from V1 are not lost, but only delayed (Figure 5). The time and polarisation amplitude has to be carefully chosen to achieve as short a delay as possible, but sufficient to create a clear minimum in the drift time spectrum, which allows to distinguish ions created above and below G1. Too large a delay may lead to significant recombination of ions. A compromise between separation and efficiency of ion counting must be found. Figure 5. View largeDownload slide Ions drift time spectrum in two SV experiment. Ions counted during first 40 μs are considered to be created in the second volume V2. Ions created after 41 μs till 180 μs are considered to be created in volume V1. Figure 5. View largeDownload slide Ions drift time spectrum in two SV experiment. Ions counted during first 40 μs are considered to be created in the second volume V2. Ions created after 41 μs till 180 μs are considered to be created in volume V1. The following voltages and delay time was used in the experiment—G1 was polarised up to +5 V in the ready state and switched to potential of IC walls (0 V) 11 μs after projectile interaction (switching time ~0.5 μs). G2 was polarised to −12 V. Other guiding grids where also polarised like in the single volume experiments(9). The resulting ions drift time spectrum is shown in Figure 5. A deep minimum has been obtained at ~40.5 μs, but some overlap is still present. To reduce the influence of this overlapping region ions arrived between 40 and 41 μs were not included in the analysis. This choice is supported by analysis presented in Figure 6. Contribution of ions created in V1 in the region before 40 μs is estimated to be lower than 2%. Contribution of ions created in V2 in the region after 41 μs is below 0.1%. Efficiency of ion detection is estimated to be equal 65% for V1 and 80% for V2. Estimation is based on the comparison with Monte Carlo simulations and previous experiments(9) and is independent of considered radiation qualities. Figure 6. View largeDownload slide Drift time spectrum of ions created in the IC. Fitted curve is composed of two skew normal distribution density functions. Ions in gray region was rejected in analysis. Figure 6. View largeDownload slide Drift time spectrum of ions created in the IC. Fitted curve is composed of two skew normal distribution density functions. Ions in gray region was rejected in analysis. To test whether the modification of IC has not distorted measurements, a comparison with previous well-tested set-up(8, 9) containing only V1 has been made. ICSDs measured before and after the modification are shown in Figure 7. Also, due to known drop in efficiency expected ICSDs were calculated based on previous data (assuming radiation quality independent efficiency ratio). Good agreement of the actual and expected results indicates the correct operation of the device. Also, even assuming highest possible energy transfer to secondary electrons equal 5 eV for most of their energy spectrum the effect will be negligible, so the main side-effect of the modification is efficiency drop in the V1. Figure 7. View largeDownload slide Single-site ICSDs from V1 measured before and after modifications of IC. Gray lines show expected distributions. Figure 7. View largeDownload slide Single-site ICSDs from V1 measured before and after modifications of IC. Gray lines show expected distributions. Experiments with carbon ions The experiments were performed at Heavy Ion Laboratory University of Warsaw with 52 and 23 MeV carbon ion beams (using nitrogen gas as a target). The shape of each simulated nanometric volume was cylindrical 0.32 μg/cm2 in diameter and 0.32 μg/cm2 in height, which corresponds to ~3.2 nm at water density scale. The distance between centres of volumes was equal to 0.32 μg/cm2. As the mean number of ionisations depends linearly on the efficiency and to some extent linearly on the target size, the more accurate scaling is ~2.1 nm for V1 and 2.6 nm for V2. More detailed considerations of the equivalent scale in nanodosimetric measurements can be found in Ref.(10). The first volume was irradiated directly (placed in the track core region) and the second one was placed perpendicularly to the projectile path. RESULTS AND DISCUSSION In the nanodosimetric measurements with a single SV the major result is an ionisation cluster-size probability distribution Pν(V, Q) for creating exactly ν ions in the volume V for given radiation quality Q. In the case of two SVs a probability Pν,μ(V1, V2, Q) that exactly ν ions are created in V1 and μ ions are created in V2 is measured. Figure 8 shows the 2D cluster-size distributions for the carbon ions as the results of the ‘correlation’ experiments. Distributions are normalised to: ∑ν=0∞∑μ=0∞Pν,μ(V1,V2,Q)=1. (1) Figure 8. View largeDownload slide ICSD for pairs of clusters created in volume V1 and V2 for 23 MeV (top) and 52 MeV (bottom) carbon ions. ν and μ are the cluster-sizes in the first and second sensitive volume, respectively. No unfolding applied. Pairs of clusters with μ > 6 are not presented due to low statistic. Figure 8. View largeDownload slide ICSD for pairs of clusters created in volume V1 and V2 for 23 MeV (top) and 52 MeV (bottom) carbon ions. ν and μ are the cluster-sizes in the first and second sensitive volume, respectively. No unfolding applied. Pairs of clusters with μ > 6 are not presented due to low statistic. These ICSDs were obtained for two energies in the Bragg peak region. The parameter F2 is the probability of creating two or more ions in a single volume: F2(V,Q)=∑ν=2∞Pν(V,Q). (2) In the case of a two SV experiment one can also estimate the cumulative probability F2,2 as follows: F2,2(V1,V2,Q)=∑ν=2∞∑μ=2∞Pν,μ(V1,V2,Q). (3) It can be expected that the F2,2 value is correlated with the cross sections for complex damage like multi-double strand brakes. From the data presented in Figure 8 we can derive the expected (mean) number of ionisations in the second SV as a function of a cluster size in the second SV: E[μ](ν)=(∑μ=0∞μPν,μ)/∑μ=0∞Pν,μ. (4) Each ionisation in V1 is an additional source of secondary electrons, which may contribute to μ value. This contribution is on average the same, so a linear dependence is expected (Figure 9). Figure 9. View largeDownload slide The dependence of the mean cluster-size E[μ] in V2 on the cluster-size ν in V1. Linear dependence is fitted. Figure 9. View largeDownload slide The dependence of the mean cluster-size E[μ] in V2 on the cluster-size ν in V1. Linear dependence is fitted. The difference in slope coefficient may indicate its dependence on radiation quality. An offset parameter seen in Figure 9 represents probability of observing ions created in V2, when no ions created in V1 were detected. It has non-zero value for two reasons. The first one is that JC is not 100% efficient in detecting ions, so there is some probability that an electron was created in V1, but the associated ion was not detected. The second reason is the presence of electrons originating outside V1. The first one should not be present in an ideal detector, whereas the second reason is an inherent feature of a track of a charged particle. Without correlation measurements one can only estimate the average ICSD in V2. For both considered radiation qualities F2 (as defined in Eq. 2) in the first SV V1 is very close to 1 (P(ν = 0) + P(ν = 1) ≪ 1, see Figure 7), which means that the radiobiological cross-section for DSBs is expected to be effectively saturated. Additionally due to fact that multiple ionisations in the penumbra acts synergically it may be considered as a contribution increasing the cross section for complex damage. CONCLUSIONS Correlated ionisation spectra—a new kind of nanodosimetric measurements in multiple nanometric SVs is proposed. First results such 2D ionisation cluster-size spectra have been obtained for carbon ion beams using modified JC device. The new measurement technique can potentially provide an answer to the question about the importance of secondary electrons to the overall efficiency of creating complex DNA damage. However, further investigations are needed to account for all possible side-effects of the proposed technique to ensure reliability of this new kind of data. A comparison with another system is advised. ACKNOWLEDGEMENTS The authors thank Z. Szefliński for assistance in the beam facility and E. Jaworska, A. Dudziński for their technical assistance during the experiments. REFERENCES 1 Conte , V. , Selva , A. , Colautti , P. , Hilgers , G. , Rabus , H. , Bantsar , A. , Pietrzak , M. and Pszona , S. Nanodosimetry: towards a new concept of radiation quality . Radiat. Prot. Dosim. ( 2017 ) doi:10.1093/rpd/ncx175 . 2 Pszona , S. , Kula , J. and Marjańska , S. A new method for measuring ion clusters produced by charged particles in nanometre track sections of DNA size . Nucl. Instrum. Methods A 447 ( 3 ), 601 – 607 ( 2000 ). Google Scholar CrossRef Search ADS 3 Garty , G. , Shchemelinin , S. , Breskin , A. , Chechik , R. , Assaf , G. , Orion , I. , Bashkirov , V. , Schulte , R. and Grosswendt , B. The performance of a novel ion-counting nanodosimeter . Nucl. Instrum. Methods A 492 ( 1 ), 212 – 235 ( 2002 ). Google Scholar CrossRef Search ADS 4 De Nardo , L. , Colautti , P. , Conte , V. , Baek , W. Y. , Grosswendt , B. and Tornielli , G. Ionization-cluster distributions of alpha-particles in nanometric volumes of propane: measurement and calculation . Radiat. Environ. Biophys. 41 ( 4 ), 235 – 256 ( 2002 ). Google Scholar PubMed 5 Grosswendt , B. and Pszona , S. The track structure of alpha-particles from the point of view of ionization-cluster formation in ‘nanometric’ volumes of nitrogen . Radiat. Environ. Biophys. 41 ( 2 ), 91 – 102 ( 2002 ). Google Scholar CrossRef Search ADS PubMed 6 Grosswendt , B. From macro to nanodosimetry: limits of the absorbed-dose concept and definition of new quantities. In: Workshop on Uncertainty Assessment in Computational Dosimetry, Bologna, 8–10 October 2007 . 7 Simmons , J. A. and Watt , D. E. Radiation Protection Dosimetry: A Radical Reappraisal ( Wisconsin, USA : Med. Phys. Publ. ) pp. 70 – 77 ( 1999 ) ISBN 978-0944838877. 8 Bantsar , A. Ionization cluster size distributions created by low energy electrons and alpha particles in nanometric track segment in gases. PhD thesis, arXiv:1207.6893 ( 2011 ). 9 Bantsar , A. , Colautti , P. , Conte , V. , Hilgers , G. , Pietrzak , M. , Pszona , S. , Rabus , H. and Selva , A. State of the art of instrumentation in experimental nanodosimetry . Radiat. Prot. Dosim. ( 2017 ) doi:10.1093/rpd/ncx263 . 10 Grosswendt , B. , De Nardo , L. , Colautti , P. , Pszona , S. , Conte , V. and Tornielli , G. Experimental equivalent cluster-size distributions in nanometric volumes of liquid water . Radiat. Prot. Dosim. 110 ( 1–4 ), 851 – 857 ( 2004 ). Google Scholar CrossRef Search ADS © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: email@example.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)
Radiation Protection Dosimetry – Oxford University Press
Published: Aug 1, 2018
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