高能聚焦质子束无掩模刻写方法研究初步

在中国科学院上海应用物理研究所的扫描质子微探针装置上,研制了图形化扫描器,同时研究了适合质子束刻写的光刻胶制备、显影、定影技术.在此基础上,开展高能聚焦质子束无掩模刻写实验,在厚度约11μm的PMMA光刻胶上刻写出高纵横比的任意图案,取得了初步质子刻写结果,为进一步开展质子纳米束刻写奠定基础.     

Proton beam writing of microstructures at the ion nanoprobe LIPSION

Proton beam writing (PBW) is a direct writing technique which allows the creation of three-dimensional structures with a high aspect ratio in the micrometer and nanometer range in photoresist materials without the use of templates. At the high-energy ion nanoprobe LIPSION of the University of Leipzig this technique was established recently. In this article the latest results concerning this topic are presented. PBW was successfully performed with the positive resist polymethyl methacrylate (PMMA) which is now used at LIPSION in addition to the negative resist SU-8. With the new data acquisition system MICRODAS being commissioned, a new scan program was developed and tested which is dedicated to the creation of arbitrarily shaped structures. Squares with dimensions down to 1.2 μm were created in SU-8 at LIPSION. Furthermore, Ni grids were produced by electroplating, using templates written in PMMA resist. In addition, first structures for studying the growing behavior of Bragg reflectors and the optical characterisation of ZnO nanowhiskers were produced by PBW.     

Proton beam writing of long, arbitrary structures for micro/nano photonics and fluidics applications

The last decade has seen proton beam writing maturing into a versatile lithographic technique able to produce sub-100 nm, high aspect ratio structures with smooth side walls. However, many applications in the fields of photonics and fluidics require the fabrication of structures with high spatial resolution that extends over several centimetres. This cannot be achieved by purely magnetic or electrostatic beam scanning due to the large off-axis beam aberrations in high demagnification systems. As a result, this has limited us to producing long straight structures using a combination of beam and stage scanning. In this work we have: (1) developed an algorithm to include any arbitrary pattern into the writing process by using a more versatile combination of beam and stage scanning while (2) incorporating the use of the ubiquitous AutoCAD DXF (drawing exchange format) into the design process. We demonstrate the capability of this approach in fabricating structures such as Y-splitters, Mach-Zehnder modulators and microfluidic channels that are over several centimetres in length, in polymer. We also present optimisation of such parameters as scanning speed and scanning loops to improve on the surface roughness of the structures. This work opens up new possibilities of using CAD software in PBW for microphotonics and fluidics device fabrication.     

Proton beam micromachined resolution standards for nuclear microprobes

The quest for smaller spot sizes has long been the goal of many nuclear microprobe groups worldwide, and consequently there is a need for good quality resolution standards. Such standards have to be consistent with the accurate measurement of state-of-the-art nuclear microbeam spot sizes, i.e. 400 nm for high current applications such as Rutherford backscattering spectrometry and proton-induced X-ray emission, and 100 nm for low current applications such as scanning transmission ion microscopy or ion beam-induced charge. The criteria for constructing a good quality nuclear microprobe resolution standard is therefore demanding: the standard has to be three dimensional with a smooth surface, have an edge definition better than the state-of-the-art beam spot resolutions, and exhibit vertical side walls. Proton beam micromachining (PBM) is a new technique of high potential for the manufacture of precise 3D microstructures. Recent developments have shown that metallic microstructures (nickel and copper) can be formed from these microshapes. Prototype nickel PBM resolution standards have been manufactured at the Research Centre for Nuclear Microscopy, NUS and these new standards are far superior to the 2000 mesh gold grids currently in use by many groups in terms of surface smoothness, vertical walls and edge definition. Results of beam resolution tests using the new PBM standards with the OM2000 microprobe end station/HVEE Singletron system have yielded spot sizes of 290 nm×450 nm for a 50 pA beam of 2 MeV protons.     

Micro-fluidic target chamber machined by proton beam writing for the in situ analysis of gas absorption in synthetic crystals

Many synthetic crystals used for chemical and industrial applications have special internal structures, e.g. nano-pores, which allow separating different gases and fluids. Ion beam analytical methods can be used to study the gas diffusion and absorption in these materials in situ and to visualize their inner surfaces which affect these processes. For this purpose, a small target chamber was constructed in PMMA (polymethyl methacrylate) using proton beam writing (PBW). This micro-fluidic structure enables the establishment of a defined atmosphere around a crystal and allows the simultaneous ion beam analysis. In order to confine the gas from the high vacuum in the measurement chamber Si₃N₄-windows of 200 nm thickness were thermally bonded to the structured PMMA block yielding a closed target chamber with the possibility to accomplish PIXE and RBS measurements. In addition, two capillaries were connected to the chamber for gas inlet and evacuation. First tests showed that the construction is leak-proof and allows to establish a defined atmosphere. After that, the Argon gas diffusion into Zn(tbip)-crystals was studied. These measurements have shown unexpectedly high nickel concentrations in the host crystal which reduces the Argon density in these areas after absorption, because the Ni atoms decrease the pore size by replacing Zn-atoms in the Zn(tbip)-lattice. It could be demonstrated that gas diffusion and absorption in organic crystals can be studied in situ with high lateral resolution using ion beam analysis in a dedicated target chamber machined by PBW.     

Fabrication of smooth silicon optical devices using proton beam writing

This work gives a brief review of proton beam writing and electrochemical etching process for the fabrication of smooth optical devices in bulk silicon. Various types of structures such as silicon-on-oxidized porous silicon waveguides, waveguide grating and disk resonators have been produced. Optical characterization has been carried out on the waveguides for both TE and TM polarization using free space coupling at 1.55 μm. Various fabrication and processing parameters have been optimized in order to reduce the propagation loss to approximately 1 dB/cm. A surface smoothening technique based on controlled oxidation has also been used to achieve an RMS roughness better than 3 nm.     

Proton beam writing and electroplating for the fabrication of high aspect ratio Au microstructures

We present an approach to fabricate tall high aspect ratio Au microstructures by means of proton beam direct writing. Combining proton beam direct writing and electroplating, we successfully produced gold structures with sub-micrometer lateral dimensions, structure heights in excess of 11 μm, and aspect ratios over 28. Sidewall quality of the Au structures was improved by lowering the process temperature to 20 °C when developing PMMA patterns with GG developer. The application of such structures as X-ray masks for deep X-ray lithography with synchrotron radiation was demonstrated.     

Creation of 3D microsculptures in PMMA by multiple angle proton irradiation

In recent years the technique of proton beam writing has established itself as a versatile method for the creation of microstructures in resist materials. While these structures can be almost arbitrary in two dimensions, the creation of genuine 3D structures remains a challenge.At the LIPSION accelerator facility a new approach has been developed which combines aspects of ion beam tomography, so far solely an analysis method, with proton beam writing. Key element is the targeted irradiation from multiple angles in order to obtain a much broader range of 3D microstructures than has hitherto been possible.PMMA columns with a diameter of ∼90 μm were used as raw material and placed in an upright position on top of a rotational axis. Using 2.25 MeV protons patterns corresponding to the silhouettes of the desired structures were written from two or more directions. In a subsequent step of chemical etching irradiated portions were dissolved, leaving behind the finished 3D sculpture.Various objects have been created. For the demonstration of the method a 70 μm high model of the Eiffel tower has been sculpted by irradiation from two angles. Using irradiation from three angles a 40 μm wide screw with right-handed thread could be crafted which might find applications in micromachining. Also, a cage structure with a pore size of ca. 20 μm was written with the intention to use it as a scaffold for the growth of biological cells.     

The front-end electronics design of dose monitors for beam delivery system of Shanghai Advanced Proton Therapy Facility

A front-end electronics of dose monitor has been developed for measuring irradiation dose to the patient in Shanghai Advanced Proton Therapy Facility.The parallel plate ionization chamber is used for the dose monitoring.Unlike the traditional method of recycling capacitor integration and voltage-to-frequency conversion,this dose monitor electronics uses the trans-impedance amplifier and analog-to-digital conversion method.It performs satisfactorily,with the integral nonlinearity of less than ±0.04 nA in the range of-400 to 50 nA and the resolution of about±0.6 nA.     

Development of function-graded proton exchange membrane for PEFC using heavy ion beam irradiation

The graded energy deposition of heavy ion beam irradiation to polymeric materials was utilized to synthesize a novel proton exchange membrane (PEM) with the graded density of sulfonic acid groups toward the thickness direction. Stacked Poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP) films were irradiated by Xe⁵⁴⁺ ion beam with the energy of 6 MeV/u under a vacuum condition. The induced trapped radicals by the irradiation were measured by electron spin resonance (ESR) spectroscopy. Irradiated films were grafted with styrene monomer and then sulfonated. X-ray photo-electron spectroscopy (XPS) spectra showed that the densities of sulfonic acid groups were controlled for injection “Surface” and transmit “Back” sides of the fabricated PEM. The membrane electrode assembly (MEA) fabricated by the function-graded PEM showed improved fuel cell performance in terms of voltage stability. It was expected that the function-graded PEM could control the graded concentration of sulfonic acid groups in PEM.     

兔血管内皮细胞、平滑肌细胞酸性成纤维细胞生长因子受体的分析

为了解不同增殖时期血管内皮细胞（ＥＣ）、平滑肌细胞（ＳＭＣ）表面酸性成纤维细胞生长因子（ａＦＧＦ）受体的变化,并探讨ａＦＧＦ促血管内皮细胞和平滑肌细胞增殖作用的机制,以氯胺－Ｔ法＾１２５Ｉ标记的ａＦＧＦ为配体,用放射配体分析法研究静止期、增殖期血管ＥＣ、ＳＭＣ表面ａＦＧＦ受体表达的变化。结果表明,增殖期血管ＥＣ、ＳＭＣ表面ａＦＧＦ受体数量及亲和力较静止期明显增加,受体数量增加３－４倍,亲和力增加１     

On the comparison of three methods of assessing beam quality for broad beam in vitro cell irradiation

The interaction of charged particles with living matter has recently attracted increasing interest in the field of biomedical applications such as hadron therapy, radioprotection and space radiation biology. Particle accelerators are particularly useful in this area.In vitro radiobiological studies with a broad beam configuration require beam homogeneity. The goal is to produce a dose distribution given to a cell population that is as close to uniform as possible.In this paper, we compare the results of three devices used to assess the beam quality for broad beam irradiation: a passivated implanted planar silicon (PIPS) particle detector, a position-sensitive solid state detector, which is camera-like, and a solid state nuclear track detector (CR39).The first device is a PIPS detector of 300 μm nominal depletion depth and an entrance window with a thickness of about 500 Å. It is collimated with a 0.5 mm aperture and mounted in air on an XY moving table as close as possible to the exit window of the beam line.The second device is a CMOS position-sensitive detector (technological process 0.6 μm AMS CUA), 112 × 112 pixels, with 153 × 153 μm² pixel size. It allows the user to rapidly obtain dose uniformity over a surface of 1 × 1 cm². During uniformity and dose rate assessment it is placed in air at the PIPS location.For both detectors, beam profile was obtained for various proton fluxes (from ∼5 × 10⁴ to 10⁶ particles cm⁻² s⁻¹). Preliminary tests were made with CR39 using 4 MeV He⁺⁺ ions.Results are analysed using Poisson distribution and cell hit probability.     

Experimental determination of the absorbed dose to water in a scanned proton beam using a water calorimeter and an ionization chamber

The absorbed dose to water is the reference physical quantity for the energy absorbed in tissue when exposed to beams of ionizing radiation in radiotherapy. The SI unit of absorbed dose to water is the gray (Gy = 1 J/kg). Ionization chambers are used as the dosimeters of choice in the clinical environment because they show a high reproducibility and are easy to use. However, ionization chambers have to be calibrated in order to convert the measured electrical charge into absorbed dose to water. In addition, protocols require these conversion factors to be SI traceable to a primary standard of absorbed dose to water. We present experimental results where the ionization chamber used for the dosimetry for the scanned proton beam facility at PSI is compared with the direct determination of absorbed dose to water from the METAS primary standard water calorimeter. The agreement of 3.2% of the dose values measured by the two techniques are within their respective statistical uncertainties.     

Optimization of GEANT4 settings for Proton Pencil Beam Scanning simulations using GATE

This study reports the investigation of different GEANT4 settings for proton therapy applications in the context of Treatment Planning System comparisons. The GEANT4.9.2 release was used through the GATE platform. We focused on the Pencil Beam Scanning delivery technique, which allows for intensity modulated proton therapy applications. The most relevant options and parameters (range cut, step size, database binning) for the simulation that influence the dose deposition were investigated, in order to determine a robust, accurate and efficient simulation environment. In this perspective, simulations of depth-dose profiles and transverse profiles at different depths and energies between 100 and 230 MeV have been assessed against reference measurements in water and PMMA. These measurements were performed in Essen, Germany, with the IBA dedicated Pencil Beam Scanning system, using Bragg-peak chambers and radiochromic films. GEANT4 simulations were also compared to the PHITS.2.14 and MCNPX.2.5.0 Monte Carlo codes. Depth-dose simulations reached 0.3 mm range accuracy compared to NIST CSDA ranges, with a dose agreement of about 1% over a set of five different energies. The transverse profiles simulated using the different Monte Carlo codes showed discrepancies, with up to 15% difference in beam widening between GEANT4 and MCNPX in water. A 8% difference between the GEANT4 multiple scattering and single scattering algorithms was observed. The simulations showed the inability of reproducing the measured transverse dose spreading with depth in PMMA, corroborating the fact that GEANT4 underestimates the lateral dose spreading. GATE was found to be a very convenient simulation environment to perform this study. A reference physics-list and an optimized parameters-list have been proposed. Satisfactory agreement against depth-dose profiles measurements was obtained. The simulation of transverse profiles using different Monte Carlo codes showed significant deviations. This point is crucial for Pencil Beam Scanning delivery simulations and suggests that the GEANT4 multiple scattering algorithm should be revised.     

Monte-Carlo study of induced radioactivity in probe for low-energy proton beam

Induced radionuclides generated from the probe which is bombarded by proton beam will turn the detector into a typical external irradiation radiation source. Thus, it is beneficial for developing radiation protection to calculate the types and the activities of radionuclides. Here we applied both a theoretical analysis and a Monte-Carlo method to compute the induced radioactivity in a copper probe irradiated by proton beam. Various kinds of radionuclides saturation activity obtained by these two different methods were compared. The comparisons of the results cast by the two methods show the similar saturation activities for ⁶³Zn and ⁶⁵Zn. However, the Monte-Carlo method conducted by the software FLUKA is able to provide a more complete consideration on nuclear reaction, and to calculate both the direct and indirect radioactivity under different irradiation time. Furthermore, by employing the FLUKA Monte-Carlo program, the induced radioactivity of three types of probe materials (Cu, Ta and W) under low-energy (below 20 MeV) proton beam irradiated were also separately simulated and tantalum is considered as the best material for low-energy proton interceptive diagnostics probe due to the higher energy threshold of nuclear reaction and the lower radioactivity.     

MLFC在质子单粒子效应实验束流诊断中的应用

对宇航微电子器件进行抗质子辐射性能评估时,常利用加速器产生的质子束流来测量其质子单粒子效应截面曲线（σ-E曲线）。基于北京HI-13串列加速器重离子辐照装置,研制了适用于质子能量测量的多叶法拉第筒（MLFC）,为今后开展质子单粒子效应辐照实验奠定基础。测试结果表明,研制的MLFC既可测量质子能量和束流强度,也能测量质子束流的能量纯度,这对判定束流是否符合实验要求及调束非常实用。     

Ion beam characterization of advanced luminescent materials for application in radiation effects microscopy

The ion photon emission microscope (IPEM) is a technique developed at Sandia National Laboratories (SNL) to study radiation effects in integrated circuits with high energy, heavy ions, such as those produced by the 88” cyclotron at Lawrence Berkeley National Laboratory (LBNL). In this method, an ion-luminescent film is used to produce photons from the point of ion impact. The photons emitted due to an ion impact are imaged on a position-sensitive detector to determine the location of a single event effect (SEE). Due to stringent resolution, intensity, wavelength, decay time, and radiation tolerance demands, an engineered material with very specific properties is required to act as the luminescent film. The requirements for this material are extensive. It must produce a high enough induced luminescent intensity so at least one photon is detected per ion hit. The emission wavelength must match the sensitivity of the detector used, and the luminescent decay time must be short enough to limit accidental coincidences. In addition, the material must be easy to handle and its luminescent properties must be tolerant to radiation damage. Materials studied for this application include plastic scintillators, GaN and GaN/InGaN quantum well structures, and lanthanide-activated ceramic phosphors. Results from characterization studies on these materials will be presented; including photoluminescence, cathodoluminescence, ion beam induced luminescence, luminescent decay times, and radiation damage. Results indicate that the ceramic phosphors are currently proving to be the ideal material for IPEM investigations.     

MG132联合X射线对非小细胞肺癌生长转移和凋亡的影响

探讨蛋白酶体抑制剂MG132联合X射线对非小细胞肺癌H1299细胞生长、转移侵袭和细胞凋亡的影响及机制。采用MTT法检测不同MG132浓度不同时间处理后肺癌H1299细胞的增殖;Transwell小室实验测定肺癌细胞的迁移和侵袭能力;流式细胞术测定肺癌细胞的凋亡;Western—blot法测定蛋白表达水平。结果表明,MG132能明显抑制H1299细胞的生长,并呈现剂量-效应和处理时间-效应关系;MG132在无毒性剂量下联合X射线可显著抑制H1299细胞的迁移及侵袭能力,并明显诱导细胞凋亡;MG132能明显降低H1299细胞的基质金属蛋白酶-2、-9的表达水平,降低抗凋亡蛋白Bcl-2的表达水平,同时增加凋亡蛋白Bax的表达水平。提示MG132可以显著抑制人非小细胞肺癌H1299细胞的生长,且在无毒性剂量下联合X射线可以明显降低癌细胞转移和侵袭能力,能显著加强X射线诱导的细胞凋亡作用。