## 3 Applications with J-KAREN Laser System
### Radiation Biology with Laser-Accelerated Proton Beams  
It has been widely recognized that the use of particle ion beams in cancer radiotherapy has the physical advantage of delivering longitudinally a more localized dose deposition associated with the well-known Bragg peak phenomenon [96]. However, the high capital cost of ion beam radiotherapy (IBRT) facilities remains a primary hurdle to a more widespread access to this treatment modality. Recently, high-intensity lasers have been suggested as a potential, cost-saving alternative [97] to conventional ion accelerators for the radiotherapy. However, we must pose the fundamental question, \"How does the biological effect of laser-accelerated ions compare to that of ions generated by conventional facilities?\" We must address this basic question because some characteristics of a laser-driven ion beam significantly differ from those delivered by a more conventional accelerator. For example, one unique feature of a laser-driven proton source is the potential for extremely high current in a single ion bunch by virtue of both high bunch charge and short duration. **Figure 19.** DNA double-strand breaks [98] induced by the irradiation of laser-accelerated protons with 20 Gy, indicated with the green signals. To address the fundamental question we have developed a laser-driven ion irradiation apparatus [98, 99, 100], which was the first attempt to investigate the radiobiological effects for laser-accelerated ions. For example, we have demonstrated DNA double-strand breaking of human cancer cells (as seen in Figure 19) by laser-driven proton bunches of short duration and high single bunch current. The latest configuration [100] of the beam line is seen in Figure 20. The J-KAREN laser system [11] at JAEA provided the intense laser pulses for target irradiation. Laser pulses of 1 J energy and 45 fs duration are focused to an intensity of \(\sim\)5 \(\times\) 10\({}^{19}\) onto a polyimide target foil of 7.5-\(\upmu\)m-thick. Compatible with the 1 Hz laser repetition-rate a new target area is provided for each pulse by advancing the foil tape with a servomotor. At the foil source the initial proton spectrum is continuous with a 4 MeV maximum kinetic energy. The proton beam line consists of four dipole magnets. Each dipole magnet consists of a pair of rectangular permanent magnets, generating a central magnetic field of 0.78 T. The second and third magnetic fields are parallel with each other and oriented antiparallel to the first and fourth ones. Protons are collimated by an entrance pinhole and laterally displaced from the target normal axis in the midplane (midway between the second and third magnets) by the first two magnets. Proton energy and energy spread is set by a movable 5 mm diameter pinhole that is located in this midplane. The final two magnets steer protons back to the target normal axis. The transverse beam profile is adjusted by a pinhole. Protons are finally extracted from vacuum into air through a thin polyimide window of 7.5-\(\upmu\)m-thickness and 10 mm diameter. The proton energy spectrum transported through the beam line is measured with online single bunch Time-of-Flight (TOF) spectrometry [101]. The results are shown in Figure 21, where single-shot spectra obtained with 1-Hz repetition rate are individually shown in gray and the averaged spectrum is displayed in black. One can see that the intensity peak is stable at 2.25 MeV with the energy spread of 0.66 MeV (FWHM). Figure 20: Experimental setup of the laser-driven quasi-monoenrgetic beam line [100]. Cultured cancer cells from the human salivary gland (HSG cells) were used for all cell experiments. HSG cells are purchased from Human Science Research Resource Bank (HSGc-C5, JCRB 1070). Using a colony formation assay, we have determined the value of relative biological effectiveness: RBE, which is one of the most important parameters in radiation biology. The cell survival ratio was measured 13 days after the cell irradiation by counting the number of cells that formed cell colonies.