Microbeam
A microbeam is a narrow beam of radiation, of micrometer or sub-micrometer dimensions. Together with integrated imaging techniques, microbeams allow precisely defined quantities of damage to be introduced at precisely defined locations. Thus, the microbeam is a tool for investigators to study intra- and inter-cellular mechanisms of damage signal transduction.
A schematic of microbeam operation is shown on the right. Essentially, an automated imaging system locates user-specified targets, and these targets are sequentially irradiated, one by one, with a highly-focused radiation beam. Targets can be single cells, sub-cellular locations, or precise locations in 3D tissues. Key features of a microbeam are throughput, precision, and accuracy. While irradiating targeted regions, the system must guarantee that adjacent locations receive no energy deposition.
The first microbeam facilities were developed in the mid-90s. These facilities were a response to challenges in studying radiobiological processes using broadbeam exposures. Microbeams were originally designed to address two main issues:
Additionally, microbeams were seen as ideal vehicles to investigate the mechanisms of radiation response.
At the time it was believed that radiation damage to cells was entirely the result of damage to DNA. Charged particle microbeams could probe the radiation sensitivity of the nucleus, which at the time appeared not to be uniformly sensitive. Experiments performed at microbeam facilities have since shown the existence of a bystander effect. A bystander effect is any biological response to radiation in cells or tissues that did not experience a radiation traversal. These "bystander" cells are neighbors of cells that have experienced a traversal. The mechanism for the bystander effect is believed to be due to cell-to-cell communication. The exact nature of this communication is an area of active research for many groups.
At the low doses of relevance to environmental radiation exposure, individual cells only rarely experience traversals by an ionizing particle and almost never experience more than one traversal. For example, in the case of domestic radon exposure, cancer risk estimation involves epidemiological studies of uranium miners. These miners inhale radon gas, which then undergoes radioactive decay, emitting an alpha particle This alpha particle traverses the cells of the bronchial epithelium, potentially causing cancer. The average lifetime radon exposure of these miners is high enough that cancer risk estimates are driven by data on individuals whose target bronchial cells are subjected to multiple alpha particle traversals. On the other hand, for an average house occupant, about 1 in 2,500 target bronchial cells will be exposed per year to a single alpha particle, but less than 1 in 107 of these cells will experience traversals by more than one particle. Therefore, in order to extrapolate from miner to environmental exposures, it is necessary to be able to extrapolate from the effects of multiple traversals to the effects of single traversals of a particle.
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