Development, characterization, and application of a charged particle microbeam for radiobiological research

Abstract

The goal of this work is to develop a charged-particle microbeam for use in radiobiological research at the MIT Laboratory for Accelerator Beam Applications (LABA). The purpose of this device is to precisely explore the radiation response of biological systems on a cellular and subcellular level, particularly in the area of temporal and spatial effects of radiation on in vitro systems. An accelerator-based 750 keV proton source was characterized and integrated into a laboratory-scale device that includes a deflection/gating system, single-particle detection system, imaging and positioning system, and a collimation system with two designed modes: a "charged-particle microslit" for delivering a -3 micron by 1 mm dose profile; and a pinhole aperture for delivering a -3 micron diameter pattern of radiation. The entire device measures less than 4 m, requires minimal radiation shielding, and utilizes a dedicated ion source. The charged particle microslit has been fully characterized and used to deliver a radiation pattern to a series of mammalian fibroblast cell monolayers that have subsequently been assayed for direct and indirect chemical effects of radiation, double-stranded DNA damage, and DNA repair protein localization. These studies will contribute to the understanding of the radiation-induced bystander effect, which is generally defined as the induction of biological effects in cells that are not directly traversed by ionizing radiation.

(cont.) Analysis of the range of assays performed on the microbeam-irradiated cells demonstrates that even though the physical radiation dose is confined to a subnuclear width (< 5 microns), in many cases the biological effects of the radiation extend for many cell widths (> 40 microns) and show dependence on the initial radiation dose delivered to the directly irradiated cells. As an experimental system, the LABA Microbeam was designed to be practically turn-key, and most applications require only one operator to perform. The LABA Microbeam represents a significant step towards a cost-effective and easily operated charged-particle microbeam appropriate for use as a standard laboratory research tool. Further work remains in automation of the microbeam subsystems and optimization/characterization of the pinhole-aperture collimator, as well as expanding the scope of the radiobiological assays performed using the charged-particle microslit.