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Design of a focusing high-energy heavy ion microbeam system at the JAERI AVF cyclotron
Nuclear Instruments and Methods in Physics Research B 210 (2003) 54–58 www.elsevier.com/locate/nimb
Design of a focusing high-energy heavy ion microbeam system at the JAERI AVF cyclotron M. Oikawa a,*, T. Kamiya a, M. Fukuda a, S. Okumura a, H. Inoue b, S. Masuno c, S. Umemiya d, Y. Oshiyama e, Y. Taira e a
Advanced Radiation Technology Center, Japan Atomic Energy Research Institute (JAERI), 1233 Watanuki-machi, Takasaki, Gunma 370-1292, Japan b Mitsubishi Electric Corporation, 1-1-2 Wadasaki-cho, Hyogo-ku, Kobe 652-8555, Japan c Mitsubishi Electric Engineering Corporation, 1-1-2 Wadasaki-cho, Hyogo-ku, Kobe 652-8555, Japan d World Engineering Corporation, 945-4 Higashi-Naganuma, Inagi, Tokyo 206-0802, Japan e Peritec Corporation, 1-17-2 Kataoka-machi, Takasaki, Gunma 370-0862, Japan
Abstract For bio-medical applications of single-ion hit techniques such as radio-microsurgery, a focused high-energy heavy ion microbeam was designed and installed as a vertical beam line connected to the AVF cyclotron (K ¼ 110) facility at JAERI Takasaki. By extracting a heavy ion microbeam into atmosphere, living cells can be irradiated with an accuracy smaller than typical cellular sizes. In addition, a high-speed automatic targeting and single-ion irradiation system was combined with a two-dimensional microbeam scanning system allowing more than 1000 targets per minute to be hit within a set field of view. Such high speeds targeting is necessary when examining statistically significant trends in cell irradiation studies within feasible time constraints. A real-time single-ion hit position detecting system was also designed to further increase the reliability of such irradiations. Ó 2003 Elsevier B.V. All rights reserved. PACS: 01.50.My; 41.75.Ak; 61.80.Jh Keywords: Microbeam; Single-ion hit; Focusing lens; Bio-medical application
1. Introduction For microbeam applications in biomedical science such as radio microsurgery, high-energy single-ion hit irradiation techniques with a spatial resolution of around the 1 lm level are required for striking particular sites within intracellular *
Corresponding author. Tel.: +81-27-346-9659; fax: +81-27346-9690. E-mail address: [email protected] (M. Oikawa).
structure. The ability to do so presents a powerful tool for research into the effects of radiation on single celled structures and is routinely performed at several facilities using 3–5 MeV hydrogen or helium ions from electrostatic accelerators [1,2]. At the TIARA facility (Takasaki Ion accelerators for Advanced Radiation Applications) of JAERI Takasaki [3], a focused high-energy heavy ion scanning microbeam system was designed and installed on a vertical beam line of the AVF cyclotron accelerator (K ¼ 110, Model 930, Sumitomo
0168-583X/$ - see front matter Ó 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0168-583X(03)01007-3
M. Oikawa et al. / Nucl. Instr. and Meth. in Phys. Res. B 210 (2003) 54–58
Heavy Industries, Ltd.) for external-beam singlecell irradiation using the single-ion hit technique. The advantage of this new system compared to those currently in operation, is that very high linear energy transfer (LET) ionization tracks can be generated in biological media using ions of more than 10 MeV/u in energy. A vertical microbeam line is also advantageous since it reduces problems associated with cell movements under gravity and hence overall target complexity as compared with a horizontal system such as the one at GSI [4], where additional techniques are required to maintain cell position. Prior to this work, a collimated microbeam and single-ion hit system has already been developed on a separate vertical beam line at TIARA [5] and cell irradiation experiments have been performed using this system [6]. However, this existing system is limited by its spatial resolution and irradiation speed, which are 10 lm and 2 sample positions per minute, due to ion scattering from the edge of the final collimator and the time required for stage manipulation and sample positioning, respectively. This line does however; possess a fully automated single-ion hit system [5]. The new system uses a set of quadruplet quadrupole magnets for focusing with an accuracy of around 1 lm. To reduce the contribution of chromatic aberration in determining the overall spot size, it is necessary to minimize the energy spread DE=E to less than 104 for typical heavy ion beams provided by the cyclotron (generally the energy spread is usually >103 ). To ensure a highly stable voltage during the acceleration phase, a flat top (FT) acceleration technique was introduced into the cyclotron RF system [7]. The system also has an X , Y beam scanner, so that a larger number of micron-scaled samples like biological cells can be irradiated in single-ion mode to improve statistics as mentioned before. A thin film window was used to extract beam into atmosphere. The problem of scattering can be ignored if the window is thin enough and samples are set as close to the window as physically possible. In actual cell irradiation experiments, it is necessary to detect the cell to be irradiated as well as the striking single ions as efficiently and precisely as possible. To reduce the exposure time per cell and increase
55
throughput for large batches where high reliability is required, a real-time single-ion hit position detection system was also required. This paper reports on the new microbeam system and describes methods to perform the above requirements.
2. Detail of high-energy heavy ion microbeam system The schematic of the microbeam line is shown in Fig. 1. As noted earlier all samples are mounted on the atmosphere side of a thin film window at the rear of the chamber. A high-energy heavy ion beam from the cyclotron is deflected 90° with a bending magnet and lead into a vertical beam line. The slit systems forming object and aperture are also indicated in Fig. 1. The microslits used to form the micron-sized object are composed of two wedged shape slits that cross perpendicularly to one another on the beam axis (made by Technisches B€ uro S. Fischer with a minimum slit aperture <1 lm and maximum aperture of 150 lm). Divergence defining slits are composed of four ordinary slit chips. The motion of each slit is controlled by a stepper-motor-driven precision stage (positional resolution of 0.5 lm). In order to monitor the beam profile or current passing through each slit system, a beam viewer and Faraday cup are installed on a single diagnostic rod manipulated by a two-step pneumatic actuator. For beam viewing, a CaF2 (Eu) scintillator having a high luminescence efficiency of 50 compared to that of NaI(Tl) 1 0 0 was chosen, resulting in beam currents as low as 100 fA being observed on a high sensitivity camera. The focusing lens is a quadruplet of quadrupole magnets with a bore radius of 15 mm and mechanical pole length of 150 mm as shown in Fig. 2. The lenses are configured to converge, diverge, converge and diverging with the both the first and fourth lenses and second and third lenses, coupled. The working distance is 300 mm resulting in a horizontal and vertical demagnification of 5. So as to minimize irregularities in the quadrupole fields, an assembly tolerance of 50 lm was set during manufacturing. Such a small tolerance is also necessary for reducing the
56
M. Oikawa et al. / Nucl. Instr. and Meth. in Phys. Res. B 210 (2003) 54–58
Fig. 1. Schematic view of microbeam system on the vertical beam line of the AVF cyclotron.
risk of geometrical misalignment of the magnet poles, or yokes, as there is no means for adjusting each magnets relative position. The magnet current supplies are stabilized to DI=I values of less than 1 105 so as to maintain a stable beam spot focus. Air-core coils placed just above the first focusing element are used to either target the beam, or, scan the beam over a 1 mm 1 mm area of the sample in the case of the most rigid beam being used.
3. Outline of the real-time single-ion hit detection system Fig. 3 shows an outline of the real-time singleion hit position detecting system, combined with
the automated single cell irradiation system both developed in previous work [5]. In order to obtain the exact position of each single-ion hit, the flash of luminescence from a scintillator placed under the sample is observed by an optical microscope and super high sensitivity CCD camera and superimposed over a sample image collected by the same camera and magnification. However, as shown in previous studies, the intensity of the CCD signal from such faint luminescence is lower than background noise. In order to reduce noise from the luminescence image, single-ion detection signals have been used to define the CCD acquisition times thereby further eliminating the effects of scattered ions or irregular ion injection. X , Y scanning control signals are also used to limit the active region of the CCD to the target position.
M. Oikawa et al. / Nucl. Instr. and Meth. in Phys. Res. B 210 (2003) 54–58
57
4. Summary A focusing high-energy heavy ion microbeam system has been designed and installed on a vertical beam line of the TIARA AVF cyclotron accelerator. Optimization of the microbeam focusing system was performed using 260 MeV Ne7þ accelerated with the FT technique in the second stage of the development for the minimum beam size of 1 lm. A real-time single-ion hit position detection system has been designed and requires further investigation to be fully optimized. We obtained the prospect in which the single-ion hit position detecting is possible by using the particular camera configuration in the preliminary examinations. The final goal for this development will be to establish a high-speed automated single cell irradiation system and combine it with the real-time single-ion hit position detecting system. Fig. 2. Quadruplet quadrupole magnet.
Acknowledgements Single-ion detection signals are obtained using secondary electrons from the vacuum side of the beam exit window. Since CaF2 (Eu) has high optical transparency and non-deliquescency as well as luminescence efficiency it was obviously deemed the first candidate for use in this system.
Authors would like to thank Drs. T. Satoh and J.S. Laird for cooperating in these experiments and discussion. They would like to acknowledge all of the accelerator staff for their great help in carrying out experiments.
Fig. 3. Conceptual scheme of the real-time single-ion hit position detection system.
58
M. Oikawa et al. / Nucl. Instr. and Meth. in Phys. Res. B 210 (2003) 54–58
References [1] M. Folkard, B. Vojnovic, G. Schettino, M. Forsberg, G. Bowey, K.M. Prise, B.D. Michael, A.G. Michette, S.J. Pfauntsch, Nucl. Instr. and Meth. B 130 (1997) 270. [2] R. Geard, D.J. Brenner, G. Randers-Pehrson, S.A. Marino, Nucl. Instr. and Meth. B 54 (1991) 411. [3] R. Tanaka, Proc. 5th Japan–China Joint Symp. Accel. Nucl. Sci. Appl., Osaka, Japan, 1993, p. 201. [4] B.E. Fischer, M. Cholewa, H. Noguchi, Nucl. Instr. and Meth. B 181 (2001) 60.
[5] T. Kamiya, W. Yokota, Y. Kobayashi, M. Cholewa, M.S. Krochmal, G. Laken, I.D. Larsen, L. Fiddes, G. Parkhill, K. Dowsey, Nucl. Instr. and Meth. B 181 (2001) 27. [6] Y. Kobayashi, T. Funayama, M. Taguchi, S. Wada, M.Tanaka, T. Kamiya, W. Yokota, H. Watanabe, K.Yamamoto, TIARA Ann. Rep. 2000, JAERI-Review, 2001039 (2001) 73. [7] M. Fukuda, S. Kurashima, N. Miyawaki, S. Okumura, T. Kamiya, M. Oikawa, Y. Nakamura, T. Nara, T. Agematsu, I. Ishibori, K. Yoshida, W. Yokota, K. Arakawa, Y. Kumata, Y. Fukumoto, K. Saito, Nucl. Instr. and Meth. B, these proceedings. doi:10.1016/S0168-583X(03)01012-7.
Design of a focusing high-energy heavy ion microbeam system at the JAERI AVF cyclotron M. Oikawa a,*, T. Kamiya a, M. Fukuda a, S. Okumura a, H. Inoue b, S. Masuno c, S. Umemiya d, Y. Oshiyama e, Y. Taira e a
Advanced Radiation Technology Center, Japan Atomic Energy Research Institute (JAERI), 1233 Watanuki-machi, Takasaki, Gunma 370-1292, Japan b Mitsubishi Electric Corporation, 1-1-2 Wadasaki-cho, Hyogo-ku, Kobe 652-8555, Japan c Mitsubishi Electric Engineering Corporation, 1-1-2 Wadasaki-cho, Hyogo-ku, Kobe 652-8555, Japan d World Engineering Corporation, 945-4 Higashi-Naganuma, Inagi, Tokyo 206-0802, Japan e Peritec Corporation, 1-17-2 Kataoka-machi, Takasaki, Gunma 370-0862, Japan
Abstract For bio-medical applications of single-ion hit techniques such as radio-microsurgery, a focused high-energy heavy ion microbeam was designed and installed as a vertical beam line connected to the AVF cyclotron (K ¼ 110) facility at JAERI Takasaki. By extracting a heavy ion microbeam into atmosphere, living cells can be irradiated with an accuracy smaller than typical cellular sizes. In addition, a high-speed automatic targeting and single-ion irradiation system was combined with a two-dimensional microbeam scanning system allowing more than 1000 targets per minute to be hit within a set field of view. Such high speeds targeting is necessary when examining statistically significant trends in cell irradiation studies within feasible time constraints. A real-time single-ion hit position detecting system was also designed to further increase the reliability of such irradiations. Ó 2003 Elsevier B.V. All rights reserved. PACS: 01.50.My; 41.75.Ak; 61.80.Jh Keywords: Microbeam; Single-ion hit; Focusing lens; Bio-medical application
1. Introduction For microbeam applications in biomedical science such as radio microsurgery, high-energy single-ion hit irradiation techniques with a spatial resolution of around the 1 lm level are required for striking particular sites within intracellular *
Corresponding author. Tel.: +81-27-346-9659; fax: +81-27346-9690. E-mail address: [email protected] (M. Oikawa).
structure. The ability to do so presents a powerful tool for research into the effects of radiation on single celled structures and is routinely performed at several facilities using 3–5 MeV hydrogen or helium ions from electrostatic accelerators [1,2]. At the TIARA facility (Takasaki Ion accelerators for Advanced Radiation Applications) of JAERI Takasaki [3], a focused high-energy heavy ion scanning microbeam system was designed and installed on a vertical beam line of the AVF cyclotron accelerator (K ¼ 110, Model 930, Sumitomo
0168-583X/$ - see front matter Ó 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0168-583X(03)01007-3
M. Oikawa et al. / Nucl. Instr. and Meth. in Phys. Res. B 210 (2003) 54–58
Heavy Industries, Ltd.) for external-beam singlecell irradiation using the single-ion hit technique. The advantage of this new system compared to those currently in operation, is that very high linear energy transfer (LET) ionization tracks can be generated in biological media using ions of more than 10 MeV/u in energy. A vertical microbeam line is also advantageous since it reduces problems associated with cell movements under gravity and hence overall target complexity as compared with a horizontal system such as the one at GSI [4], where additional techniques are required to maintain cell position. Prior to this work, a collimated microbeam and single-ion hit system has already been developed on a separate vertical beam line at TIARA [5] and cell irradiation experiments have been performed using this system [6]. However, this existing system is limited by its spatial resolution and irradiation speed, which are 10 lm and 2 sample positions per minute, due to ion scattering from the edge of the final collimator and the time required for stage manipulation and sample positioning, respectively. This line does however; possess a fully automated single-ion hit system [5]. The new system uses a set of quadruplet quadrupole magnets for focusing with an accuracy of around 1 lm. To reduce the contribution of chromatic aberration in determining the overall spot size, it is necessary to minimize the energy spread DE=E to less than 104 for typical heavy ion beams provided by the cyclotron (generally the energy spread is usually >103 ). To ensure a highly stable voltage during the acceleration phase, a flat top (FT) acceleration technique was introduced into the cyclotron RF system [7]. The system also has an X , Y beam scanner, so that a larger number of micron-scaled samples like biological cells can be irradiated in single-ion mode to improve statistics as mentioned before. A thin film window was used to extract beam into atmosphere. The problem of scattering can be ignored if the window is thin enough and samples are set as close to the window as physically possible. In actual cell irradiation experiments, it is necessary to detect the cell to be irradiated as well as the striking single ions as efficiently and precisely as possible. To reduce the exposure time per cell and increase
55
throughput for large batches where high reliability is required, a real-time single-ion hit position detection system was also required. This paper reports on the new microbeam system and describes methods to perform the above requirements.
2. Detail of high-energy heavy ion microbeam system The schematic of the microbeam line is shown in Fig. 1. As noted earlier all samples are mounted on the atmosphere side of a thin film window at the rear of the chamber. A high-energy heavy ion beam from the cyclotron is deflected 90° with a bending magnet and lead into a vertical beam line. The slit systems forming object and aperture are also indicated in Fig. 1. The microslits used to form the micron-sized object are composed of two wedged shape slits that cross perpendicularly to one another on the beam axis (made by Technisches B€ uro S. Fischer with a minimum slit aperture <1 lm and maximum aperture of 150 lm). Divergence defining slits are composed of four ordinary slit chips. The motion of each slit is controlled by a stepper-motor-driven precision stage (positional resolution of 0.5 lm). In order to monitor the beam profile or current passing through each slit system, a beam viewer and Faraday cup are installed on a single diagnostic rod manipulated by a two-step pneumatic actuator. For beam viewing, a CaF2 (Eu) scintillator having a high luminescence efficiency of 50 compared to that of NaI(Tl) 1 0 0 was chosen, resulting in beam currents as low as 100 fA being observed on a high sensitivity camera. The focusing lens is a quadruplet of quadrupole magnets with a bore radius of 15 mm and mechanical pole length of 150 mm as shown in Fig. 2. The lenses are configured to converge, diverge, converge and diverging with the both the first and fourth lenses and second and third lenses, coupled. The working distance is 300 mm resulting in a horizontal and vertical demagnification of 5. So as to minimize irregularities in the quadrupole fields, an assembly tolerance of 50 lm was set during manufacturing. Such a small tolerance is also necessary for reducing the
56
M. Oikawa et al. / Nucl. Instr. and Meth. in Phys. Res. B 210 (2003) 54–58
Fig. 1. Schematic view of microbeam system on the vertical beam line of the AVF cyclotron.
risk of geometrical misalignment of the magnet poles, or yokes, as there is no means for adjusting each magnets relative position. The magnet current supplies are stabilized to DI=I values of less than 1 105 so as to maintain a stable beam spot focus. Air-core coils placed just above the first focusing element are used to either target the beam, or, scan the beam over a 1 mm 1 mm area of the sample in the case of the most rigid beam being used.
3. Outline of the real-time single-ion hit detection system Fig. 3 shows an outline of the real-time singleion hit position detecting system, combined with
the automated single cell irradiation system both developed in previous work [5]. In order to obtain the exact position of each single-ion hit, the flash of luminescence from a scintillator placed under the sample is observed by an optical microscope and super high sensitivity CCD camera and superimposed over a sample image collected by the same camera and magnification. However, as shown in previous studies, the intensity of the CCD signal from such faint luminescence is lower than background noise. In order to reduce noise from the luminescence image, single-ion detection signals have been used to define the CCD acquisition times thereby further eliminating the effects of scattered ions or irregular ion injection. X , Y scanning control signals are also used to limit the active region of the CCD to the target position.
M. Oikawa et al. / Nucl. Instr. and Meth. in Phys. Res. B 210 (2003) 54–58
57
4. Summary A focusing high-energy heavy ion microbeam system has been designed and installed on a vertical beam line of the TIARA AVF cyclotron accelerator. Optimization of the microbeam focusing system was performed using 260 MeV Ne7þ accelerated with the FT technique in the second stage of the development for the minimum beam size of 1 lm. A real-time single-ion hit position detection system has been designed and requires further investigation to be fully optimized. We obtained the prospect in which the single-ion hit position detecting is possible by using the particular camera configuration in the preliminary examinations. The final goal for this development will be to establish a high-speed automated single cell irradiation system and combine it with the real-time single-ion hit position detecting system. Fig. 2. Quadruplet quadrupole magnet.
Acknowledgements Single-ion detection signals are obtained using secondary electrons from the vacuum side of the beam exit window. Since CaF2 (Eu) has high optical transparency and non-deliquescency as well as luminescence efficiency it was obviously deemed the first candidate for use in this system.
Authors would like to thank Drs. T. Satoh and J.S. Laird for cooperating in these experiments and discussion. They would like to acknowledge all of the accelerator staff for their great help in carrying out experiments.
Fig. 3. Conceptual scheme of the real-time single-ion hit position detection system.
58
M. Oikawa et al. / Nucl. Instr. and Meth. in Phys. Res. B 210 (2003) 54–58
References [1] M. Folkard, B. Vojnovic, G. Schettino, M. Forsberg, G. Bowey, K.M. Prise, B.D. Michael, A.G. Michette, S.J. Pfauntsch, Nucl. Instr. and Meth. B 130 (1997) 270. [2] R. Geard, D.J. Brenner, G. Randers-Pehrson, S.A. Marino, Nucl. Instr. and Meth. B 54 (1991) 411. [3] R. Tanaka, Proc. 5th Japan–China Joint Symp. Accel. Nucl. Sci. Appl., Osaka, Japan, 1993, p. 201. [4] B.E. Fischer, M. Cholewa, H. Noguchi, Nucl. Instr. and Meth. B 181 (2001) 60.
[5] T. Kamiya, W. Yokota, Y. Kobayashi, M. Cholewa, M.S. Krochmal, G. Laken, I.D. Larsen, L. Fiddes, G. Parkhill, K. Dowsey, Nucl. Instr. and Meth. B 181 (2001) 27. [6] Y. Kobayashi, T. Funayama, M. Taguchi, S. Wada, M.Tanaka, T. Kamiya, W. Yokota, H. Watanabe, K.Yamamoto, TIARA Ann. Rep. 2000, JAERI-Review, 2001039 (2001) 73. [7] M. Fukuda, S. Kurashima, N. Miyawaki, S. Okumura, T. Kamiya, M. Oikawa, Y. Nakamura, T. Nara, T. Agematsu, I. Ishibori, K. Yoshida, W. Yokota, K. Arakawa, Y. Kumata, Y. Fukumoto, K. Saito, Nucl. Instr. and Meth. B, these proceedings. doi:10.1016/S0168-583X(03)01012-7.