Development of Cyclotron Beam Technology for Applications...

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Development of Cyclotron Beam Technology for Applications in Materials Science and Biotechnology at JAERI-TIARA Y. Ohara, K. Arakawa, M. Fukuda, T. Kamiya, S. Kurashima, Y. Nakamura, S. Okumura, M. Saidoh, and S. Tajima Takasaki Radiation Chemistry Research Establishment, Japan Atomic Energy Research Institute, 1233 Watanuki, Takasaki, Gunma, 370-1292 JAPAN Abstract. Recent progress of cyclotron ion beam development for applications in materials science and biotechnology at the ion-irradiation research facility TIARA of the Japan Atomic Energy Research Institute(JAERI) is overviewed. The AVF cyclotron in TIARA can accelerate protons and heavy ions up to 90 MeV and 27.5 MeV/n, respectively. In order to conform to the requirement of a reliable tuning of microbeam formation, the cyclotron beam current has been stabilized by controlling the temperature of the magnet yoke and pole within +/-0.5 o and hence by decreasing the variation of the magnetic field B/B below 10 -5 . A heavy ion microbeam with energy of hundreds MeV is a significantly useful probe for researches on biofunctional elucidation in biotechnology. Production of the microbeam with spot size as small as 1µm by quadrupole lenses requires the energy spread of the beam E/E < 2 x 10 -4 . In order to minimize the energy spread of the cyclotron beam, the fifth-harmonic voltage waveform has been successfully superposed on the fundamental one to make energy gain uniform. INTRODUCTION Applications of energetic ion beams with MeV- range energies were initiated more than 50 years ago in the medical use for the cancer treatment and the RI production, while application researches for materials science and biotechnology using the MeV ion beams have been broadened far later, in the 1990s. Particularly, the MeV microbeam has become a useful probe for analytical and biological studies. Microbeam irradiation and single ion hit is useful for the localized irradiation, which can be applied to inactivation of microscopic region of a cell and cell surgery technique. Microbeams are also useful for analysis of living organisms using secondarily-produced radiations such as X-rays and gamma-rays, which are applied to PIXE (Particle Induced X-ray Emission) analysis and nuclear reaction analysis (NRA), respectively. These analyses have been possible with an accuracy of 1µm, since a microbeam with the spot size as small as 1µm can be produced from several MV electrostatic accelerators. On the other hand, energetic heavy ion beams with energy of several hundred MeV transfer their energy to materials or living organisms with high-density ionization and excitation along the trajectory, which results in microscopically nonuniform dose delivery. This characteristic is fundamental to induce unique mutation and local inactivation in living organisms efficiently. However, the spot size of high energy heavy ion beams from a cyclotron is still about ten times larger compared to the beams from an electrostatic accelerator. In order to evolve radiation applications based on these useful characteristics of energetic ion beams, the ion-irradiation research facility TIARA (Takasaki Ion Accelerators for Advanced Radiation Application) was completed at JAERI in 1993, followed by intensive R&D activities in materials science and biotechnology[1]. The present paper overviews the recent progress on ion beam development at TIARA to realize a cyclotron microbeam with diameter of 1µm as small as the cell nucleus. CYCLOTRON FACILITY The TIARA facility consists of four accelerators: a K110 AVF cyclotron, a 3-MV tandem accelerator, a 3- MV single-ended accelerator and a 400-kV ion implanter. The accelerator complex provides a variety of ion species from proton to bismuth ions with a wide range of ion energy from 10keV to several hundred MeV. The AVF cyclotron can accelerate a proton and heavy ions up to 90 MeV and 27.5 MeV/n, respectively. The main parameters of the cyclotron are shown in Table 1. The cyclotron is equipped with ten horizontal beam courses and four vertical branch beam courses as

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Development of Cyclotron Beam Technology for Applications in Materials Science and Biotechnology at JAERI-TIARA

Y. Ohara, K. Arakawa, M. Fukuda, T. Kamiya, S. Kurashima,

Y. Nakamura, S. Okumura, M. Saidoh, and S. Tajima

Takasaki Radiation Chemistry Research Establishment, Japan Atomic Energy Research Institute, 1233 Watanuki, Takasaki, Gunma, 370-1292 JAPAN

Abstract. Recent progress of cyclotron ion beam development for applications in materials science and biotechnology at the ion-irradiation research facility TIARA of the Japan Atomic Energy Research Institute(JAERI) is overviewed. The AVF cyclotron in TIARA can accelerate protons and heavy ions up to 90 MeV and 27.5 MeV/n, respectively. In order to conform to the requirement of a reliable tuning of microbeam formation, the cyclotron beam current has been stabilized by controlling the temperature of the magnet yoke and pole within +/-0.5o and hence by decreasing the variation of the magnetic field ∆B/B below 10-5. A heavy ion microbeam with energy of hundreds MeV is a significantly useful probe for researches on biofunctional elucidation in biotechnology. Production of the microbeam with spot size as small as 1µm by quadrupole lenses requires the energy spread of the beam ∆E/E < 2 x 10-4. In order to minimize the energy spread of the cyclotron beam, the fifth-harmonic voltage waveform has been successfully superposed on the fundamental one to make energy gain uniform.

INTRODUCTION

Applications of energetic ion beams with MeV-range energies were initiated more than 50 years ago in the medical use for the cancer treatment and the RI production, while application researches for materials science and biotechnology using the MeV ion beams have been broadened far later, in the 1990s. Particularly, the MeV microbeam has become a useful probe for analytical and biological studies. Microbeam irradiation and single ion hit is useful for the localized irradiation, which can be applied to inactivation of microscopic region of a cell and cell surgery technique. Microbeams are also useful for analysis of living organisms using secondarily-produced radiations such as X-rays and gamma-rays, which are applied to PIXE (Particle Induced X-ray Emission) analysis and nuclear reaction analysis (NRA), respectively. These analyses have been possible with an accuracy of 1µm, since a microbeam with the spot size as small as 1µm can be produced from several MV electrostatic accelerators.

On the other hand, energetic heavy ion beams with energy of several hundred MeV transfer their energy to materials or living organisms with high-density ionization and excitation along the trajectory, which results in microscopically nonuniform dose delivery. This characteristic is fundamental to induce unique mutation and local inactivation in living organisms efficiently. However, the spot size of high energy

heavy ion beams from a cyclotron is still about ten times larger compared to the beams from an electrostatic accelerator.

In order to evolve radiation applications based on these useful characteristics of energetic ion beams, the ion-irradiation research facility TIARA (Takasaki Ion Accelerators for Advanced Radiation Application) was completed at JAERI in 1993, followed by intensive R&D activities in materials science and biotechnology[1].

The present paper overviews the recent progress on ion beam development at TIARA to realize a cyclotron microbeam with diameter of 1µm as small as the cell nucleus. CYCLOTRON FACILITY

The TIARA facility consists of four accelerators: a

K110 AVF cyclotron, a 3-MV tandem accelerator, a 3-MV single-ended accelerator and a 400-kV ion implanter. The accelerator complex provides a variety of ion species from proton to bismuth ions with a wide range of ion energy from 10keV to several hundred MeV. The AVF cyclotron can accelerate a proton and heavy ions up to 90 MeV and 27.5 MeV/n, respectively. The main parameters of the cyclotron are shown in Table 1.

The cyclotron is equipped with ten horizontal beam courses and four vertical branch beam courses as

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shown in Fig.1. In a vertical beam course, an apparatus for local irradiation of a single living cell is installed, in which a very low current high-energy heavy-ion microbeam is formed by a collimation system and finally extracted into the air through a bottom micro-aperture. In another vertical beam course, a new apparatus with a quadruplet of quadrupole lenses has been installed to realize a microbeam with the spot size of 1µm.

TABLE 1. Main parameters of the JAERI cyclotron K-number : 110 Extraction radius : 92.3 cm Number of sectors : 4 Angle and number of dees : 86o and 2 RF frequency : 11~22 MHz Harmonic number : 1, 2, 3 Maximum average magnetic field : 16.7 kG .

RECENT PROGRESS

In order to realize the irradiation of countable number of ions with the spatial resolution as well as the targeting resolution of 1µm, we have conducted R&D on (1)stabilization of the cyclotron beam current, (2)single-ion hit / lens focusing system, and (3)flat-top acceleration system. The recent progresses on these development activities are described in the following sub-sections. Stabilization of the cyclotron beam current

It is well known in many cyclotrons in the world

that beam intensity gradually decreases after the start of operation. Since the start of the cyclotron routine operation at TIARA in 1991, we have experienced a rapid decrease of beam intensity during several tens of hours after the cyclotron was excited. The reason has been identified to be the fact that the magnetic field strength of the cyclotron drifts by the order of 10-4 due to a small change in temperature of the magnet yoke by several degrees[2]. We analyzed the data of the magnet temperature and the magnetic field of the cyclotron, and made heat conduction simulation with a computer code. It has turned out as a result that the small change of the temperature is due to the heat conduction from the main coil and the trim coils. In order to shield or reduce the heat conduction to the yoke and the pole, a water jacket has been mounted between the main coil and the yoke(See Fig.2), and the averaged temperature of the inlet and outlet coolant to the trim coils and the water jacket has been controlled so as to keep the yoke temperature constant within +/-0.5o. Consequently, the temperature change of the magnet has been reduced to one tenth of the previous

one, and the variation of the magnetic field ∆B/B has been suppressed to less than 1 x 10-5, and hence the beam intensity has become satisfactorily steady as shown in Fig.3 [2]. The stabilization has led to great advantages in tuning the microbeam formation.

Yoke

MagnetPole

Trim CoilsMain Coil

Water Jacket

Sector

FIGURE 2. Cross sectional view of one fourth of the cyclotron magnet. The heat conduction from the main coil and the trim coils to the magnet yoke and the pole is suppressed by the water jacket and the trim coils with temperature control of the coolant.

FIGURE 3. Variation of the beam current with and without the temperature control of the magnet yoke.

FIGURE 1. Layout of AVF cyclotron and its beam courses in the TIARA accelerator complex.

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Single-ion hit / Lens focusing system

A single-ion hit technique is useful to introduce a large radiation effect to a specific local area of various biological cells with a countable number of ions. This technique has originally been developed at several facilities to hit individual cells in atmospheric conditions for biomedical applications, though the beam energies are limited to several MeV[3,4,5]. At TIARA, the fundamental technology of single-ion hit was established at the heavy ion microbeam system installed in the 3MV tandem accelerator facility[6].

This technique has been introduced to a high-energy microbeam system in a vertical beamline of the AVF cyclotron[7]. A schematic diagram of the single-ion hit system is shown in Fig.4. The beams have been collimated to about 10µm in diameter with a set of apertures. More than 95% of the collimated ions were within the mono-energetic peak and delivered to the aimed local area with targeting accuracy of 85-90%. The system is equipped with a single-ion detector using a plastic scintillation counter and a fast beam switcher in the injection line of the cyclotron. The scintillation counter occupies one of the ports on the objective lens revolver for the optical microscope observing samples on the stage, and detects single ions passing through a thin target such as biological cells. The single-ion hits on the target can be realized by setting the beam switcher 'enable' after completing the single-ion detection. The spatial resolution of the present system is ~10µm, as shown in Fig.5.

In order to realize the spatial and targeting resolution of 1µm, a new system has been introduced instead of a collimation system[8]. In the new system, an ion beam is collimated with a set of slits and further

focused by a quadruplet of quadrupole magnetic lenses, as shown in Fig.6 schematically. The resolution will be reduced to 1 µm coupled with the flat-top acceleration system. Flat-top acceleration

Production of a microbeam with a spot size of 1µm in diameter using the focusing lens requires the energy spread of the beam ∆E/E < 2 x 10-4 , to minimize an effect of chromatic aberrations in the lenses. The energy spread of the cyclotron beam depends on a waveform of an acceleration voltage and beam phase acceptance of the cyclotron. The typical energy spread of the cyclotron beam is around 1 x 10-3 in an ordinary acceleration mode using a sinusoidal voltage waveform. However, the energy spread can be reduced by utilizing a flattop waveform for uniform energy gain, which can be generated by superimposing the third- or fifth-harmonic voltage waveform on the fundamental one [9,10].

We have designed an additional coaxial cavity to generate the fifth-harmonic voltage, coupled to the main resonator of one-fourth wavelength coaxial type

Ion Source

Vertical BeamLine

The Orbit of High-Energy Heavy Ion

Sample StageSingle-IonScintillator

Fast Beam Switch

Single-Ion HitMeasurement Module

Collimator

Particle DetectorParticle Detectoror Objective Lensor Objective Lens

BeamAttenuator

Micro Aperture

AVF Cyclotron

FIGURE 4. Conceptual scheme of the real-time single ion hit system.

5µm

FIGURE 5. Image of forty Ar ions with energy of 460MeV on CR-39 using a collimation type single-ion hit system.

Slits

Beam Scanner

Steering Magnet

Sample Stage

Quadruplet ofQuadrupole

Magnets

Optical Microscopeand CCD Camera

Vertical beamline

FIGURE 6. A new microbeam system based on a quadruplet of quadrupole magnetic lens focusing.

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as shown in Fig.7 [11]. A frequency range of the fifth harmonics from 55 to 110MHz is covered in the flattop acceleration system. In a power test, we successfully generated the fifth-harmonic voltage waveform and observed the flat-top voltage waveform as shown in Fig.8 [12], by picking up an acceleration voltage signal with an electrode capacitively coupled to the edge of a dee electrode. CONCLUSIONS

A heavy-ion microbeam with energy of hundreds

MeV is a significantly useful tool for research in biology and biotechnology. In order to conform to the research of the biofunction in cellular level for biology or medicine, a single-ion hit system for the cyclotron has been developed for the first time at TIARA. The system can irradiate a countable number of ions with the spatial and targeting resolution of 10µm using a micro-aperture collimation system. The development is based on the successful stabilization of the cyclotron beam current, which allows easy and reliable tuning of

the microbeam formation. In order to realize the spatial and targeting resolution of 1µm, which corresponds to the size of a cell nucleus, a new lens focusing system and a flat-top acceleration system have been developed. An initial test of these systems has started and high energy heavy ions like a 260MeV 20Ne7+ ion will be available in 2003 as a first microbeam with a spot size of 1µm. ACKNOWLEDGMENTS

The authors would like to acknowledge all the staffs of the cyclotron group and beam engineering laboratory and also Dr. Y. Sudo for their continuous assistance and support. REFERENCES 1. Tanaka, R., et al., "JAERI AVF Cyclotron for Research of

Advanced Radiation Technology,", Proc. 12th Int. Conf. on Cyclotrons and their Applications, Berlin, Germany, 1989, p.556

2. Okumura, S., et al., "Temperature Control of a Cyclotron Magnet for Stabilization of the JAERI AVF Cyclotron Beam,", Proc. 16th Int. Conf. on Cyclotrons and their Applications, East Lansing, Michigan, USA, May 13-17, 2001, pp.330-332.

3. Folkard, M., et al., Nucl. Instr. and Meth. B130,270(1997). 4. Geard, R., et al., Nucl. Instr. and Meth. B54, 411 (1991). 5. Braby, L.A., Scanning Microsc. 6, 167 (1992). 6. Kamiya, T., Suda, T., and Tanaka, R., Nucl. Instr. and

Meth. B118, 423-425 (1996). 7. Kamiya, T., et al., Nucl. Instr. and Meth in Physics

Research B181, 27-31 (2001). 8. Oikawa, M., et al., "Development of a focusing high-

energy heavy ion microbeam system at the JAERI AVF Cyclotron,", 8th Int. Conf. on Nuclear Microprobe Technology & Applications, Takasaki, Japan, Sep.8-13, 2002, P1-15.

9. Bischof, B., IEEE Trans. Nucl. Sci. NS-26, 2186(1979). 10.Conradie, J.L., et al., "A Flat-Top Acceleration Systems

for the NAC Light Ion Injector Cyclotron,", Proc. 14th Int. Conf. On Cyclotrons and their Applications, Cape Town, South Africa, 1995, p.249.

11. Kurashima, S., et al., " Design of the Flat-top Acceleration System for the JAERI AVF Cyclotron", Proc. 16th Int. Conf. on Cyclotrons and their Applications, East Lansing, Michigan, USA, May 13-17, 2001, pp.303-305.

12. Fukuda, M., et al., "An energy spread minimization system for microbeam generation in the JAERI AVF cyclotron", 8th Int. Conf. on Nuclear Microprobe Technology & Applications, Takasaki, Japan, Sep.8-13, 2002, P1-15.

FIGURE 8. The flat-top dee voltage waveform (upper)and the fifth-harmonic one (lower) observed with thepickup electrode at the fundamental frequency of17.475MHz and the fundamental voltage of 25 kV in apower test.

FIGURE 7. The flat-top cavity mounted on the mainresonator of the TIARA AVF cyclotron.

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