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Biological Effectiveness of Ion Beam for In Vitro Cell Irradiations

ABSTRACT: Despite numerous ion beam irradiation of cell experiments performed over the past five decades, the relationship between the biological effectiveness of ion beams and the physical characteristics of the ion beam remains unclear. Using 1,118 sets of in vitro cell survival experiments with ion beam irradiation, compiled by the Particle Irradiation Data Ensemble (PIDE) project, the relationship between cell survival and the fluence and linear energy transfer (LET) of the ion beam was established. Unlike previous studies, the closed-form analytical function is independent of photon irradiation and takes a universal form across all ion and cell species. A new understanding of the biological effectiveness of ion beams is crucial for predicting tumor response and toxicities in ion beam radiation therapy, along with radiation protection for high-LET ion beams with low fluence.

SUBMITTER: Li H

PROVIDER: S-EPMC9278697 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHelium (4He) ion beam therapy provides favorable biophysical characteristics compared to currently administered particle therapies, i.e., reduced lateral scattering and enhanced biological damage to deep-seated tumors like heavier ions, while simultaneously lessened particle fragmentation in distal healthy tissues as observed with lighter protons. Despite these biophysical advantages, raster-scanning 4He ion therapy remains poorly explored e.g., clinical translational is hampered by the lack of reliable and robust estimation of physical and radiobiological uncertainties. Therefore, prior to the upcoming 4He ion therapy program at the Heidelberg Ion-beam Therapy Center (HIT), we aimed to characterize the biophysical phenomena of 4He ion beams and various aspects of the associated models for clinical integration.MethodsCharacterization of biological effect for 4He ion beams was performed in both homogenous and patient-like treatment scenarios using innovative models for estimation of relative biological effectiveness (RBE) in silico and their experimental validation using clonogenic cell survival as the gold-standard surrogate. Towards translation of RBE models in patients, the first GPU-based treatment planning system (non-commercial) for raster-scanning 4He ion beams was devised in-house (FRoG).ResultsOur data indicate clinically relevant uncertainty of ±5-10% across different model simulations, highlighting their distinct biological and computational methodologies. The in vitro surrogate for highly radio-resistant tissues presented large RBE variability and uncertainty within the clinical dose range.ConclusionsExisting phenomenological and mechanistic/biophysical models were successfully integrated and validated in both Monte Carlo and GPU-accelerated analytical platforms against in vitro experiments, and tested using pristine peaks and clinical fields in highly radio-resistant tissues where models exhibit the greatest RBE uncertainty. Together, these efforts mark an important step towards clinical translation of raster-scanning 4He ion beam therapy to the clinic.

Project description:Microelectrode material and cell culture medium have significant roles in the signal-to-noise ratio and cell well-being in in vitro electrophysiological studies. Here, we report an ion beam assisted e-beam deposition (IBAD) based process as an alternative titanium nitride (TiN) deposition method for sputtering in the fabrication of state-of-the-art TiN microelectrode arrays (MEAs). The effects of evaporation and nitrogen flow rates were evaluated while developing the IBAD TiN deposition process. Moreover, the produced IBAD TiN microelectrodes were characterized by impedance, charge transfer capacity (CTC) and noise measurements for electrical properties, AFM and SEM for topological imaging, and EDS for material composition. The impedance (at 1 kHz) of brand new 30 μm IBAD TiN microelectrodes was found to be double but still below 100 kΩ compared with commercial reference MEAs with sputtered TiN microelectrodes of the same size. On the contrary, the noise level of IBAD TiN MEAs was lower compared with that of commercial sputtered TiN MEAs in equal conditions. In CTC IBAD TiN electrodes (3.3 mC/cm2) also outperformed the sputtered counterparts (2.0 mC/cm2). To verify the suitability of IBAD TiN microelectrodes for cell measurements, human pluripotent stem cell (hPSC)-derived neuronal networks were cultured on IBAD TiN MEAs and commercial sputtered TiN MEAs in two different media: neural differentiation medium (NDM) and BrainPhys (BPH). The effect of cell culture media to hPSC derived neuronal networks was evaluated to gain more stable and more active networks. Higher spontaneous activity levels were measured from the neuronal networks cultured in BPH compared with those in NDM in both MEA types. However, BPH caused more problems in cell survival in long-term cultures by inducing neuronal network retraction and clump formation after 1-2 weeks. In addition, BPH was found to corrode the Si3N4 insulator layer more than NDM medium. The developed IBAD TiN process gives MEA manufacturers more choices to choose which method to use to deposit TiN electrodes and the medium evaluation results remind that not only electrode material but also insulator layer and cell culturing medium have crucial role in successful long term MEA measurements.

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Biological Effectiveness of Ion Beam for In Vitro Cell Irradiations

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