## 6 Cellular Basis of Laser-driven Radiation Therapy
### Laser-driven Radiation in Radiobiological Studies  
In 2012 the RBE of electrons and protons was addressed [23; 100; 108; 109] and the overall results show no significant differences in radiobiological response for _in vitro_ cell experiments between pulsed laser-accelerated and conventional clinical electron beams. Much the same conclusion has been drawn in comparisons between protons from laser-driven and conventional accelerator sources. At this point we also address the potential use of laser-driven radiation with ultra-high dose rates in future radiobiological studies. A basic cellular radiobiological agenda will confirm the usefulness of laser-accelerated ion irradiation with effects similar to those generated with conventional accelerators. Although radiobiological effects which originate from DNA damage are less likely to exhibit any ultra-high dose effects, various biological endpoints derived from non-DNA targets or multi-cellular phenomena may indeed reveal dose rate issues. However, we expect that, under any circumstances, the ionized/excited molecules or radicals generated at biologically relevant doses should interact with one another to cause ultra-high dose rate effects. The use of microbeams to reduce the spatial distance between the tracks could increase the possibility of such interactions. One of the promising directions using laser-driven radiation may also involve studies of very fast physiochemical processes that take place within the picosecond to nanosecond timescale after irradiation of biomolecules. Real Time Identification of Healthy and Cancerous Tissue Using Laser Desorption Ionization Mass Spectrometry  
In the 1980-1990s high intensity laser driven ionization and fragmentation mass spectrometry was developed for the ultra-sensitive detection particularly of molecules [110]. The applications were principally for the sensitive detection of explosives, drugs of abuse and environmental pollutants. Most hydrocarbon and bio-molecules when irradiated by an intense laser beam fragment into moieties which are characteristic of that molecule but which usually contain hydrogen, carbon, oxygen, nitrogen and other atoms in certain proportions. During the last few years [PERSON] and his team [111, 112, 113, 114, 115] realized that this technology could also be used to distinguish between healthy and diseased cancerous tissue during the removal of malignant tumors which can potentially enable surgery with greater precision and reduce the likelihood of further surgery. In particular a neurosurgery challenge is the distinction of where a brain tumor ends and healthy tissue begins. This procedure could be carried out in real time. In Figure 21 the fragmentation patterns of certain tissues are shown and it can be seen from B and C the ratios of certain masses around 700 amu are different for healthy and diseased tissue. The fragmentation patterns can be induced by either lasers or electrical high temperatures. The ratios of the principal components (the highest mass peaks) are measured and it is found that the variance of any specific tissue (healthy or diseased) is smaller than the variance between tissue types (healthy or diseased). Figure 21: This figure shows the fragmentation pattern of human tissues both healthy and diseased. There are certain prominent mass peaks which are called principal components and it is found that the principal components of healthy and diseased tissues are sufficiently different to be used as a diagnostic technique. Reproduced from [115]. Copyright 2013, American Association for the Advancement of Science. A tumor is shown in Figure 22 below surrounded by healthy tissue. **Figure 22.** This figure shows a tumor (in blue) surrounded by healthy tissue (in green). Reproduced from [116]. Copyright 2013, American Association for the Advancement of Science.