The interest in hadron therapy is growing fast thanks to the latest technological advances in accelerators and delivery technologies, to the development of more and more efficient and comprehensive treatment planning tools, and due to its increasing clinical adoption proving its efficacy. A precise and reliable beam quality assessment and an accurate and effective inclusion of the biological effectiveness of different radiation qualities are fundamental to exploit at best its advantages with respect to conventional radiotherapy. Currently, in clinical practice, the quality assurance (QA) is carried out by means of conventional dosimetry, while the biological effectiveness of the radiation is taken into account considering the Relative Biological Effectiveness (RBE). The RBE is considered a constant value for protons and it is estimated as a function of the absorbed dose in case of carbon ions. In this framework, microdosimetry could bring a significant improvement to both QA and RBE estimation. By measuring the energy deposited by the radiation into cellular or sub-cellular volumes, microdosimetry could provide a unique characterisation of the beam quality on one hand, and a direct link to radiobiology on the other. Different detectors have been developed for microdosimetry, from the more conventional tissue equivalent proportional counter (TEPC), silicon-based and diamond-based solid-state detectors, to ΔE-E telescope detectors, gas electrons multiplier (GEM), hybrid microdosimeters and a micro-bolometer based on Superconducting QUantum Interference Device (SQUID) technology. However, because of their different advantages and drawbacks, a standard device and an accredited experimental methodology have not been unequivocally identified yet. The establishment of accepted microdosimetry standard protocols and code of practice is needed before the technique could be employed in clinical practice. Hoping to help creating a solid ground on which future research, development and collaborations could be planned and inspired, a comprehensive state of the art of the detector technologies developed for microdosimetry is presented in this review, discussing their use in clinical hadron therapy conditions and considering their advantages and drawbacks.

Objectives. Microdosimetry is proving to be a reliable and powerful tool to be applied in different fields such as radiobiology, radiation protection and hadron therapy. However, accepted standard protocols and codes of practice are still missing. With this regard, a systematic and methodical uncertainty analysis is fundamental to build an accredited uncertainty budget of practical use. This work studied the contribution of counting statistics (i.e. number of events collected) to the final frequency-mean and dose-mean lineal energy uncertainties, aiming at providing guidelines for good experimental and simulation practice. The practical limitation of current technologies and the non-negligible probability of nuclear reactions require careful considerations and nonlinear approaches. Approach. Microdosimetric data were obtained by means of the particle tracking Monte Carlo code Geant4. The uncertainty analysis was carried out relying on a Monte Carlo based numerical analysis, as suggested by the BIPM's ‘Guide to the expression of uncertainty in measurement’. Final uncertainties were systematically investigated for proton, helium and carbon ions at an increasing number of detected events, for a range of different clinical-relevant beam energies. Main results. Rare events generated by nuclear interactions in the detector sensitive volume were found to massively degrade microdosimetric uncertainties unless a very high statistics is collected. The study showed an increasing impact of such events for increasing beam energy and lighter ions. For instance, in the entrance region of a 250 MeV proton beam, about 5 ∗ 10 ⁷ events need to be collected to obtain a dose-mean lineal energy uncertainty below 10%. Significance. The results of this study help define the necessary conditions to achieve appropriate statistics in computational microdosimetry, pointing out the importance of properly taking into account nuclear interaction events. Their impact on microdosimetric quantities and on their uncertainty is significant and cannot be overlooked, particularly when characterising clinical beams and radiobiological response. This work prepared the ground for deeper investigations involving dedicated experiments and for the development of a method to properly evaluate the counting statistics uncertainty contribution in the uncertainty budget, whose accuracy is fundamental for the clinical transition of microdosimetry.

Objective. Microdosimetry is gaining increasing interest in particle therapy. Thanks to the advancements in microdosimeter technologies and the increasing number of experimental studies carried out in hadron therapy frameworks, it is proving to be a reliable experimental technique for radiation quality characterisation, quality assurance, and radiobiology studies. However, considering the variety of detectors used for microdosimetry, it is important to ensure the consistency of microdosimetric results measured with different types of microdosimeters. Approach. This work presents a novel multi-thickness microdosimeter and a methodology to characterise the radiation quality of a clinical carbon-ion beam. The novel device is a diamond detector made of three sensitive volumes (SVs) of different thicknesses: 2, 6 and 12 µm. The SVs, which operate simultaneously, were accurately aligned and laterally positioned within 3 mm. This alignment allowed for a comparison of the results with a negligible impact of the SVs alignment and their lateral positioning, ensuring the homogeneity of the measured radiation quality. An experimental campaign was carried out at MedAustron using a carbon-ion beam of typical clinical energy (284.7 MeV u⁻¹). Main results. The measurement results allowed for a meticulous interpretation of its radiation quality, highlighting the effect of the SV thickness. The consistency of the microdosimetric spectra measured by detectors of different thicknesses is discussed by critically analysing the spectra and the differences observed. Significance. The methodology presented will be highly valuable for future experiments investigating the effects of the target volume size in radiobiology and could be easily adapted to the other particles employed in hadron therapy for clinical (i.e. protons) and for research purposes (e.g. helium, lithium and oxygen ions).

The increasing interest in hadron therapy has heightened the need for accurate and reliable methods to assess radiation quality and the biological effectiveness of particles used in treatment. Microdosimetry has emerged as a key tool for this, demonstrating its potential, reliability, and suitability. In this context, solid-state microdosimeters offer technological advantages over traditional Tissue-Equivalent Proportional Counters, and recent advancements have further improved their performance and reliability. However, one critical challenge in solid-state microdosimetry is the so-called 'border effect', which can impact measurement accuracy. In this study, the border effect in diamond microdosimeters was thoroughly studied using Ion Beam Induced Charge (IBIC) analysis. The research, relying on experiments conducted at the Surrey Ion Beam Centre, developed an effective method to characterise and quantify the border effect. Geant4 Monte Carlo simulations were also employed to assess the impact of the border effect under typical proton therapy conditions, with a specific model developed and validated to reproduce this effect in simulations. Results showed potential significant variations of up to 40% in ȳ_F and 20% in ȳ_D values, highlighting the importance of accurately characterising the border effect and encouraging further research to mitigate its influence on microdosimetry measurements.

The interest in microdosimetry is growing thanks to the advancement in microdosimetric technologies, improving detector performance and reliability. Herein, the fabrication and characterization of a novel diamond‐based microdosimeter are proposed. The microdosimeter consists of an array of single‐crystal diamond Schottky diodes about 1.5 μm thick connected in parallel. The detector prototypes are characterized using the ion beam‐induced charge technique, employing a 6 MeV carbon ions microbeam. Despite a good overall response, the first prototypes are affected by the “bridge effect”: a charge collection beneath the metallic bridges connecting the sensitive volumes (SVs), which alters the energy deposition spectrum. To mitigate the bridge effect, different technological solutions are explored: the selective growth of intrinsic diamond layers and the use of an insulating material such as photoresist. These second prototypes reveal a good SV spatial definition without any charge collection from the bridges and a good response homogeneity within the SVs ranging between 3% and 5% full‐width‐half‐maximum among the different prototypes. While the cell‐like thickness and lateral dimensions of SVs make the diamond microdosimeter array ideal for radiobiological applications, its array configuration can make it highly versatile to perform under different fluence rate conditions in particle therapy.