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Purpose: To optimize geometries of ultrahigh dose rate proton FLASH beam positioning devices for various multi-well cell culture microplates.
Methods: Monte Carlo simulations were employed to design and evaluate custom positioning devices with the goal to maximize the number of wells per plate receiving homogeneous doses. The goal was to enable reproducible beam delivery to different wells on a single plate, increasing efficiency and reducing cost. Shapes, sizes and positions of air spaces, range shifters and indexing devices were optimized to ensure dose homogeneity inside wells of interest, while minimizing stray radiation to neighboring wells. Four designs of microplates were chosen for this project, 96-well-plates, 24-well-plates, 384-well-plates and 4-well-chambers. Each design requires a different positioning mechanism and beam delivery geometry addressing the lateral extent of the dose profiles. Proton beams with a 20 mm wide SOBP and a diameter of 20 mm were simulated for various combinations of beam ranges and air gaps. Custom designed collimators with integrated range shifters and range compensators were used to provide homogeneous dose profiles. Out-of-field doses, which lead to inacceptable conditions in neighboring wells, were addressed by either spacing the beam centers sufficiently wide apart or collimating the beams.
Results: The dose profiles in the wells of interest were associated with systematic and statistical uncertainties, amounting to minimum and maximum values of -3.2% to +2.5% (sigma<1.2%) for the 96-well-plate; -3.4% to +3.2% for the 24-well-plate (sigma<1.9%); -1.5% to +2.2% (sigma<1%) for the 384-well-plate and -2% to +2.2% (sigma<1,5%) for the 4-well-chamber. Aside from the 24-well-plates, which can be fully used, the number of wells with homogeneous dose is 24 for 96-well- plates, 168 for 384-well-plates, and 2 for the 4-well-chambers.
Conclusion: In conclusion, we applied the Monte Carlo technique to design optimized multi-well-plate irradiation geometries, enabling efficient high content/high throughput in-vitro experiments.
Funding Support, Disclosures, and Conflict of Interest: Dr. Kiminori Iga is an employee of HITACHI Ltd.
Not Applicable / None Entered.