α粒子微束定点照射--细胞的放射生物学效应及精确性分析

进行微束试验的关键是能够精确地控制照射的粒子数和将粒子准确地射入受照射位点.该研究通过对哥伦比亚大学单粒子微束装置在精确性、准确性以及各项指标的分析发现该装置可精确地控制照射粒子数,精确率为98.4%.同时,它可将α粒子准确地射入受照射位点,束半径为34,达到设计4的标准.在对细胞特定位点如细胞质照射上,粒子击中细胞质至少一个位点的概率为90%,在这一过程中的偶然核击中率,对大多数照射剂量(8个粒子)均小于0.8%.应用该微束装置的放射生物学研究发现单个α粒子仅导致大约20%的致死率,其存活率曲线类似于用常规照射获得的平均粒子存活曲线.诱变试验首次证实单个α粒子在AL细胞的CD59基因位点可诱导出比对照高出3倍数量的诱变子,诱变率随粒子数的增加而增加.这一结果不同于常规照射中,诱变率在高剂量照射后下降的结论.     

单粒子微束装置的研究

介绍了一种用于生物学研究中细胞精确定位辐照的装置———单粒子微束装置的研究进展情况和发展目标。     

复旦大学单粒子微束研制进展

建设了一基于复旦大学2×3 MV串列加速器的单粒子微束装置。离子束经分析磁铁30°水平偏转传输后再经90°偏转磁铁竖直上行至辐照终端,以内径1.5 μm的毛细玻璃管微准直器获取离子微束。采用薄膜闪烁体结合光电倍增管的探测结构对微束离子进行精确探测和计数,并以高压静电偏转开关快速关断束流以实现对离子数目的精确控制。目前实验已获得在质子能量为3 MeV时,能散（能量分布曲线中半高宽FWHM）<60 keV、束分辨<2.2 μm、定量照射精度>95%的质子微束。本文对复旦大学单粒子微束的束流管道设计、微束获取、束开关及单粒子探测等核心环节的研制进展进行介绍。     

粒子微束辐射生物学效应研究进展

粒子微束能够将单个或精确数目的粒子定点、定位射人靶目标,使得辐射生物学效应的研究由定性走向了定量。本文介绍了辐射目标靶研究,以及低剂量辐射生物学效应、低剂量辐射旁效应和重离子微束辐射生物学效应的研究进展。现代精确粒子微束的建立,有助于进一步研究低剂量辐射和空间辐射等生物学效应。     

微束单细胞照射的研究和发展

了解低剂量辐射效应等辐射生物学基本问题的关键是研究单一粒子与生物体的相互作用。然而 ,由于粒子在能量、径迹上的随机分布 ,这种单一粒子与生物体的相互作用很难在实验室中用常规照射的方法进行。微束的发展 ,特别是单粒子微束通过将精确数量的粒子准确地射入细胞或细胞的特定位置为回答这些问题提供了一个直接 ,有用的手段。该文论述了微束的历史 ,现状和未来发展 ,以及微束在辐射生物学研究中的应用。     

单粒子微束品质优化装置研制的设想

对影响单粒子微束装置束品质的因素进行了全面分析,并提出了一种优化单粒子微束装置束品质的方 法——用束流发射度精确测量与粒子束聚焦自动调节装置改进单粒子微束装置瞄准器出口束斑。     

单粒子微束辐照装置的束流光学计算

利用束流光学计算程序TRANSPORT和TURTLE对基于2×3MV串列静电加速器的单粒子微束细胞精确照射装置的束流传输光学进行了一阶近似计算,得到了包括束流包络、束流相图、束斑大小及束流发散程度的相关数据。计算结果表明,对于能量1.5MeV,经2mm×2mm狭缝入射且初始发散角x’～y’≤3mrad的典型质子束流,通过优化光学元件的参数,在束线末端可获得束径x<0.2cm,y<0.3cm,发散角x’<4.8mrad,y’<6.5mrad的准平行束流,达到了微准直器获取单粒子微束所需的束流品质。计算结果为束线系统优化和束流调试工作提供了必要的参考依据。     

应用单细胞微凝胶电泳技术检测成纤维细胞的放射敏感性

应用单细胞微凝胶电泳（SCGE）技术以及噻唑蓝（MTT）比色法检测辐射诱发的成纤维细胞系AT5BIVA和GM637的初始DNA双链断裂数及断裂后的修复与细胞放射敏感性之间的关系。结果表明,AT5BIVA细胞系的放射敏感性显著高于GM637。两种细胞系的初始DNA双链断裂数均随剂量的增加而增加,呈显著的剂量效应关系,在给定的剂量点,辐射诱发的AT5BIVA细胞系的初始DNA双链断裂数显著高于GM637。AT5BIVA细胞系对辐射诱发的DNA双链断裂的修复能力小于GM637。结果提示,辐射诱发的初始DNA双链断裂数及断裂后的修复与细胞的放射敏感性均有一定的相关性,作为细胞放射敏感性预测指标具有很大的应用潜势。     

早期微束的发展及其在细胞辐射生物学中的应用

介绍了研究细胞辐射生物学效应的早期微束装置 ,总结了在单细胞定位定量辐射中所得到的一系列研究成果 ,并分析了这些微束装置存在的局限性 ,为微束装置的设计提供了借鉴和参考。     

33 重离子微束辐照装置

采用针孔准直技术，在HI-13串列加速器上建立了微电子器件单粒子效应重离子微束辐照装置。该装置主要由5个主要部分组成：产生微束装置、定位装置、样品运动控制装置、束流注量检测装置和单粒子效应测量装置组成。图1为装置的平面布局图。     

The Progress of a Microbeam Facility in the Institute of Plasma Physics

The progress of a microbeam facility in the institute of Plasma Physics was discussed in this paper.This kind of equipment can supply single-particle beam which may be implanted into cells in micrometer-radius and measured by a new outstanding detector among global microbeam systems.Measurements by some plain targets showed that the highest current after the accelerator tube can be larger than 20μA ,the H2^ current before the second bending magnet is near 0.9μA ,the current after the second bending magnet is near 0.8μA,and the current of the beam line(after a 2-mm diameter aperture)is near 0.25nA which is enough for the single-particle microbeam experiment.It took scientists 3 months to do their microbeam experiment after setting up the qccelerator beam line and get the microbeam from this equipment.Two pre0collimators were installed between the 2-mm diameter aperture and the collimator to survey the beam.Tracks on the CR39 film ectched in the solution of NaOH showed that the beam can go through the collimator including a 10μm diameter aperture and the 3.5μm thick vacuum sealing film(Mylar).A new method,which is called optimization of the beam quality,was put forward in this paper,in order to get smaller diameter of beam-spot in microbeam system.     

The Experiment of Obtaining Micron Beam in the Single-Particle Microbeam Facility of the Institute of Plasma Physics

The Experiments, methods and results of obtaining micron beam in the Microbeam Facility of the Institute of Plasma Physics were discussed in this paper. The H2^ beam was accelerated by the Van de Graa/f electrostatic accelerator, and the collimator at the end of the beam line is a 60μm thick stainless steel chip. And as a result, particle tracks on the solid track probes (CR39 film) etched in the solution of NaOH showed that the beam can go through the collimator with a small aperure (2000, 300, 55, 30, or 10μm) and 3.5μm thick vacuum film(Mylar). Besides the CR39 method, the beam was measured by an energy spectrum detector after the 10μm diameter aperture and the 3.5 μm thick vacuum film too.     

Preliminary Study of the CAS-LIBB Single-Particle Microbeam Ⅱ Endstation： Ⅰ. Proposed Multi-Dimensional Quantitative Fluorescence Microscopy

Single-particle microbeam as a powerful tool can open a research field to find answers to many enigmas in radiobiology. A single-particle microbeam facility has been constructed at the Key Laboratory of Ion Beam Bioengineering （LIBB）, Chinese Academy of Sciences （CAS）, China. However there has been less research activities in this field concerning the original process of the interaction between low-energy ions and complicated organisms. To address this challenge, an in situ multi-dimensional quantitative fluorescence microscopy system combined with the CAS-LIBB single-particle microbeam II endstation is proposed. In this article, the rationale, logistics and development of many aspects of the proposed system are discussed.     

单离子束能量稳定性的改进

设计了旋转伏特计（Generating voltmeter,GVM）控制电路以稳定静电加速器终端高压,以提高单离子束能量稳定性、长时间工作稳定性和定位精度等束流品质。建立了简化模型计算束流能量不稳定性与单离子束束径的关系。测试结果表明,增加GVM控制后,单离子束稳定工作的时间可达6 h以上,单离子束束径约减小了10%。     

Improvement of the Energy Stability of the Single Ion Microbeam

Energy instability strongly affects the state and the beam size of the single ion microbeam. A facility based on the Generating Voltmeter was developed to improve the energy stability of the CAS-LIBB （Chinese Academy of Sciences, key laboratory of ion beam bioengineering） single ion microbeam. This paper presents the analysis of the energy＇ instability of the single ion microbeam. A simplified theoretical model is set up to calculate the relationship between the energy instability and the beam spot size. By using this technique, the energy instability is adjusted to about 1%. Stable run-time is over 6 hours. The radius of the single ion beam is reduced by 10% compared to the previous olin.     

Analysis and Optimization of Stability of CAS-LIBB Single Ion Microbeam

Single ion microbeam is the most advanced technology which can emit a single ion for precise localization. A single-ion microbeam facility has been constructed at the Key Laboratory of Ion Beam Bioengineering （LIBB）, Chinese Academy of Sciences （CAS）, with a spatial resolutions of about 5 μm. Based on CAS-LIBB microbeam, three key elements affecting the quality of the system are assessed： the size of beam spot, the energy range and the counting accuracy of implanting ions. Various contributions to the ion beam stability, including the ion source, the terminal voltage of electrostatic accelerator and the components in beam pipeline, are discussed. Analysis shows that the improvement of terminal voltage stability is the most important issue for future optimization of CAS-LIBB facility. Some preliminary investigations and project aimed at optimization and development are proposed as well.     

充气飞行时间探测方法分析

本工作涉及充气飞行时间探测器的工作原理和实验测量结果。在不同能量(64、48和33MeV)下,利用充气飞行时间探测方法对同量异位素³⁶S和³⁶Cl进行鉴别,并与用传统的ΔE－E方法在相同能量下的鉴别结果进行比较。实验结果表明,在入射能量较高（E_i＞40MeV）时,ΔE－E法的鉴别能力比充气飞行时间法的稍好些;在E_i＜40MeV时,充气飞行时间法的鉴别能力比ΔE－E法的好,入射能量为20～40MeV时,充气飞行时间法能明显将³⁶S和³⁶Cl区分出来。     

Design of the CAS-LIBB Single-Ion Microbeam Endstation Ⅱ

Cellular micro-irradiation is now recognized as a powerful technique to unveil the mechanisms of interaction between ionizing radiation and living cells or tissues. The single-ion microbeam （SIM） is uniquely capable of delivering precisely the predefined number of charged particles （precise doses of radiation） to specific individual cells or sub-cellular targets in situ. No active research in the field concerning the original process of the interaction between low-energy ions and complicated organisms has been reported yet. To address this challenge, the aim of the present design is to further wrestle with multi-dimensional quantitative information from living cells traversed by an exact number of ions real-time rather than endpoints, in the time scale from milliseconds to days.