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BACKGROUND: The extremely fast delivery of doses with ultra high dose rate (UHDR) beams necessitates the investigation of novel approaches for real-time dosimetry and beam monitoring. This aspect is fundamental in the perspective of the clinical application of FLASH radiotherapy (FLASH-RT), as conventional dosimeters tend to saturate at such extreme dose rates. PURPOSE: This study aims to experimentally characterize newly developed silicon carbide (SiC) detectors of various active volumes at UHDRs and systematically assesses their response to establish their suitability for dosimetry in FLASH-RT. METHODS: SiC PiN junction detectors, recently realized and provided by STLab company, with different active areas (ranging from 4.5 to 10 mm2) and thicknesses (10-20 µm), were irradiated using 9 MeV UHDR pulsed electron beams accelerated by the ElectronFLASH linac at the Centro Pisano for FLASH Radiotherapy (CPFR). The linearity of the SiC response as a function of the delivered dose per pulse (DPP), which in turn corresponds to a specific instantaneous dose rate, was studied under various experimental conditions by measuring the produced charge within the SiC active layer with an electrometer. Due to the extremely high peak currents, an external customized electronic RC circuit was built and used in conjunction with the electrometer to avoid saturation. RESULTS: The study revealed a linear response for the different SiC detectors employed up to 21 Gy/pulse for SiC detectors with 4.5 mm2/10 µm active area and thickness. These values correspond to a maximum instantaneous dose rate of 5.5 MGy/s and are indicative of the maximum achievable monitored DPP and instantaneous dose rate of the linac used during the measurements. CONCLUSIONS: The results clearly demonstrate that the developed devices exhibit a dose-rate independent response even under extreme instantaneous dose rates and dose per pulse values. A systematic study of the SiC response was also performed as a function of the applied voltage bias, demonstrating the reliability of these dosimeters with UHDR also without any applied voltage. This demonstrates the great potential of SiC detectors for accurate dosimetry in the context of FLASH-RT.
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In recent times, ion implantation has received increasing interest for novel applications related to deterministic material doping on the nanoscale, primarily for the fabrication of solid-state quantum devices. For such applications, precise information concerning the number of implanted ions and their final position within the implanted sample is crucial. In this work, we present an innovative method for the detection of single ions of MeV energy by using a sub-micrometer ultra-thin silicon carbide sensor operated as an in-beam counter of transmitted ions. The SiC sensor signals, when compared to a Passivated Implanted Planar Silicon detector signal, exhibited a 96.5% ion-detection confidence, demonstrating that the membrane sensors can be utilized for high-fidelity ion counting. Furthermore, we assessed the angular straggling of transmitted ions due to the interaction with the SiC sensor, employing the scanning knife-edge method of a focused ion microbeam. The lateral dimension of the ion beam with and without the membrane sensor was compared to the SRIM calculations. The results were used to discuss the potential of such experimental geometry in deterministic ion-implantation schemes as well as other applications.
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Objective.Carbon is an ion species of significant radiobiological interest, particularly in view of its use in cancer radiotherapy, where its large Relative Biological Efficiency is often exploited to overcome radio resistance. A growing interest in highly pulsed carbon delivery has arisen in the context of the development of the FLASH radiotherapy approach, with recent studies carried out at dose rates of 40 Gy s-1. Laser acceleration methods, producing ultrashort ion bursts, can now enable the delivery of Gy-level doses of carbon ions at ultra-high dose rates (UHDRs), exceeding 109Gy s-1. While studies at such extreme dose rate have been carried out so far using low LET particles such as electrons and protons, the radiobiology of high-LET, UHDR ions has not yet been explored. Here, we report the first application of laser-accelerated carbon ions generated by focussing 1020W cm-2intense lasers on 10-25 nm carbon targets, to irradiate radioresistant patient-derived Glioblastoma stem like cells (GSCs).Approach.We exposed GSCs to 1 Gy of 9.5 ± 0.5 MeV/n carbon ions delivered in a single ultra-short (â¼400-picosecond) pulse, at a dose rate of 2 × 109Gy s-1, generated using the ASTRA GEMINI laser of the Central Laser Facility at the Rutherford Appleton Laboratory, Didcot, Oxfordshire, UK. We quantified carbon ion-induced DNA double strand break (DSB) damage using the 53BP1 foci formation assay and used 225 kVp x-rays as a reference radiation.Main Results.Laser-accelerated carbon ions induced complex DNA DSB damage, as seen through persistent 53BP1 foci (11.5 ± 0.4 foci/cell/Gy) at 24 h and significantly larger foci (1.69 ± 0.07µm2) than x-rays induced ones (0.63 ± 0.02µm2). The relative foci induction value for laser-driven carbon ions relative to conventional x-rays was 3.2 ± 0.3 at 24 h post-irradiation also confirming the complex nature of the induced damage.Significance.Our study demonstrates the feasibility of radiobiology investigations at unprecedented dose rates using laser-accelerated high-LET carbon ions in clinically relevant models.
Subject(s)
DNA Breaks, Double-Stranded , Protons , Humans , Cells, Cultured , Ions , DNA , Lasers , Carbon/therapeutic useABSTRACT
Silicon carbide (SiC), thanks to its material properties similar to diamond and its industrial maturity close to silicon, represents an ideal candidate for several harsh-environment sensing applications, where sensors must withstand high particle irradiation and/or high operational temperatures. In this study, to explore the radiation tolerance of SiC sensors to multiple damaging processes, both at room and high temperature, we used the Ion Microprobe Chamber installed at the Ruder Boskovic Institute (Zagreb, Croatia), which made it possible to expose small areas within the same device to different ion beams, thus evaluating and comparing effects within a single device. The sensors tested, developed jointly by STLab and SenSiC, are PIN diodes with ultrathin free-standing membranes, realized by means of a recently developed doping-selective electrochemical etching. In this work, we report on the changes of the charge transport properties, specifically in terms of the charge collection efficiency (CCE), with respect to multiple localized proton irradiations, performed at both room temperature (RT) and 500 °C.
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BACKGROUND: There is currently significant interest in assessing the role of oxygen in the radiobiological effects at ultra-high dose rates. Oxygen modulation is postulated to play a role in the enhanced sparing effect observed in FLASH radiotherapy, where particles are delivered at 40-1000 Gy/s. Furthermore, the development of laser-driven accelerators now enables radiobiology experiments in extreme regimes where dose rates can exceed 109 Gy/s, and predicted oxygen depletion effects on cellular response can be tested. Access to appropriate experimental enviroments, allowing measurements under controlled oxygenation conditions, is a key requirement for these studies. We report on the development and application of a bespoke portable hypoxia chamber specifically designed for experiments employing laser-driven sources, but also suitable for comparator studies under FLASH and conventional irradiation conditions. MATERIALS AND METHODS: We used oxygen concentration measurements to test the induction of hypoxia and the maintenance capacity of the chambers. Cellular hypoxia induction was verified using hypoxia inducible factor-1α immunostaining. Calibrated radiochromic films and GEANT-4 simulations verified the dosimetry variations inside and outside the chambers. We irradiated hypoxic human skin fibroblasts (AG01522B) cells with laser-driven protons, conventional protons and reference 225 kVp X-rays to quantify DNA DSB damage and repair under hypoxia. We further measured the oxygen enhancement ratio for cell survival after X-ray exposure in normal fibroblast and radioresistant patient- derived GBM stem cells. RESULTS: Oxygen measurements showed that our chambers maintained a radiobiological hypoxic environment for at least 45 min and pathological hypoxia for up to 24 h after disconnecting the chambers from the gas supply. We observed a significant reduction in the 53BP1 foci induced by laser-driven protons, conventional protons and X-rays in the hypoxic cells compared to normoxic cells at 30 min post-irradiation. Under hypoxic irradiations, the Laser-driven protons induced significant residual DNA DSB damage in hypoxic AG01522B cells compared to the conventional dose rate protons suggesting an important impact of these extremely high dose-rate exposures. We obtained an oxygen enhancement ratio (OER) of 2.1 ± 0.1 and 2.5 ± 0.1 respectively for the AG01522B and patient-derived GBM stem cells for X-ray irradiation using our hypoxia chambers. CONCLUSION: We demonstrated the design and application of portable hypoxia chambers for studying cellular radiobiological endpoints after exposure to laser-driven protons at ultra-high dose, conventional protons and X-rays. Suitable levels of reduced oxygen concentration could be maintained in the absence of external gassing to quantify hypoxic effects. The data obtained provided indication of an enhanced residual DNA DSB damage under hypoxic conditions at ultra-high dose rate compared to the conventional protons or X-rays.
Subject(s)
Protons , Radiobiology , DNA/radiation effects , Humans , Hypoxia , Lasers , OxygenABSTRACT
The nuclear reaction known as proton-boron fusion has been triggered by a subnanosecond laser system focused onto a thick boron nitride target at modest laser intensity (â¼10^{16}W/cm^{2}), resulting in a record yield of generated α particles. The estimated value of α particles emitted per laser pulse is around 10^{11}, thus orders of magnitude higher than any other experimental result previously reported. The accelerated α-particle stream shows unique features in terms of kinetic energy (up to 10 MeV), pulse duration (â¼10 ns), and peak current (â¼2 A) at 1 m from the source, promising potential applications of such neutronless nuclear fusion reactions. We have used a beam-driven fusion scheme to explain the total number of α particles generated in the nuclear reaction. In this model, protons accelerated inside the plasma, moving forward into the bulk of the target, can interact with ^{11}B atoms, thus efficiently triggering fusion reactions. An overview of literature results obtained with different laser parameters, experimental setups, and target compositions is reported and discussed.
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[This corrects the article on p. 223 in vol. 7, PMID: 28971066.].
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The CATANA proton therapy center was the first Italian clinical facility making use of energetic (62 MeV) proton beams for the radioactive treatment of solid tumors. Since the date of the first patient treatment in 2002, 294 patients have been successful treated whose majority was affected by choroidal and iris melanomas. In this paper, we report on the current clinical and physical status of the CATANA facility describing the last dosimetric studies and reporting on the last patient follow-up results. The last part of the paper is dedicated to the description of the INFN-LNS ongoing activities on the realization of a beamline for the transport of laser-accelerated ion beams for future applications. The ELIMED (ELI-Beamlines MEDical and multidisciplinary applications) project is introduced and the main scientific aspects will be described.