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。     

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。     

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。     

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。     

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。     

用锥形玻璃毛细管聚焦获取MeV能量He~+微米离子束

用锥形玻璃毛细管聚焦离子束方法获取微米离子束成本低、使用方便,我们制备了出口口径35-110μm不等的多种锥形玻璃毛细管,并用其在2×1.7 MV串列加速器上获得了出射束流密度比入射束流密度大的MeV能量He~+微离子束。用金硅面垒探测器(SBD)测量在毛细管与入射束夹角不同条件下出射的微米束的能谱,并对锥形玻璃毛细管聚束的机制做初步定性讨论。     

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。     

同步辐射硬X射线微束技术

同步辐射硬X射线微束(微探针)技术是目前很多学科领域的主流分析技术,本文介绍了同步辐射硬X射线的各种微束技术以及微束的应用研究情况,阐述了各种微束技术的基本聚焦原理,并对其优势和不足以及发展状况作了简要的概述.     

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1.5 MeV,经2 mm×2 mm狭缝入射且初始发散角x'～y'≤3mrad的典型质子束...     

一氧化氮在亚细胞结构精确照射诱导旁效应中的作用

研究了肿瘤细胞的亚结构在荷能离子照射下所诱导的旁效应及其信号分子.以氦离子微束装置所产生的精确数量离子定位照射神经胶质瘤细胞T98G细胞核或细胞质,检测细胞染色体损伤和胞内一氧化氮(Nitric Oxide,NO)自由基的产额,探索NO清除剂对它们的影响,并以(Diethylamine nitric oxide,DEANO)研究NO的细胞效应.结果表明,无论是细胞核照射还是细胞质照射,只要1个细胞受到1个离子的照射,就可通过损伤的级联放大形成辐射旁效应,引起周围数十个细胞的损伤.对比核、质照射的生物效应,细胞核照射比细胞质照射具有更加显著的直接作用,但这两种照射所诱导的旁效应程度却相当.而NO自由基清除剂c-PTIO(2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide)可抑制旁效应的产生.NO分子探针DAF-FM(4-amino-5-methylamino-2',7'-difluorofluorescein diacetate)原位检测表明,即使只有1%的细胞核或细胞质受到单离子照射,具有NO阴性表达的细胞百分数增加了30%,使NO引起的细胞荧光密度增加15%.DEANO实验表明,NO可引起细胞微核的产生.因此,NO是亚细胞结构照射引起旁效应的一个重要信号因子.     

Application of heavy-ion microbeam system at Kyoto University: Energy response for imaging plate by single ion irradiation

A heavy-ion microbeam system for cell irradiation has been developed using an accelerator at Kyoto University. We have successfully developed proton-, carbon-, fluorine- and silicon-beams in order to irradiate a micro-meter sized area with ion counting, especially single ion irradiation. In the heavy-ion microbeam system, an imaging plate (IP) was utilized for beam diagnostics on the irradiation. The IP is widely used for radiography studies in biology. However, there are a few studies on the low linear energy transfer (LET) by single ions, i.e., low-intensity exposure. Thus we have investigated the energy response for the IP, which can be utilized for microbeam diagnostics.     

细胞质受照射的遗传损伤效应

通过使用精确单粒子微束装置照射人与中国仓鼠杂交AL细胞细胞质,显示α粒子照射细胞质只有轻微的致死率,照射16个α粒子后仍有76％的细胞可以存活。诱变试验结果发现,尽管单个α粒子照射细胞质在CD59基因位点诱变频率较低,但8个或多于8个α粒子可诱导出高于未受照射对照3倍的诱变频率聚合酶链式反应（PCR）分析发现,照射细胞质诱导的CD59^-基因突变子其11号染色体上Wilms肿瘤（WT）、过氧化氢酶（CAT）、（H－rasRAS)、甲状旁腺激素（PTH）、（脱脂蛋白－A1 APO－A1）等基因缺失率很小,其突变谱类似于自发突变子的突变谱。DMSO或BSO处理细胞的研究显示,自由基清除剂DMSO可降低照射细胞质所诱发的CD59基因突变频率;与此相反,能与细胞内的谷胱甘肽结合的BSO可增加突变频率。结果表明,自由基很可能是照射细胞质诱发突变的主要原因之一。此外,用IF7单克隆抗体进行的8－羟基脱氧鸟苷免疫过氧化物酶染色反应发现照射细胞质可在核内引起DNA的氧化损伤。     

Microbeam complex at TIARA: Technologies to meet a wide range of applications

Since 1990 R&Ds of microbeam technology has been progressed at the TIARA facility of JAEA Takasaki. In order to meet a wide variety of ion beam applications, analysis, radiation effect studies, or fabrication in regions of micro- or nano-structures, three different types of ion microbeam systems were developed. In these systems, high-spatial resolutions have been achieved and techniques of micro-PIXE, single ion hit and particle beam writing (PBW) were also developed for these applications. Microbeams, on the other hand, require the highest quality of beams from the accelerators, the cyclotron in particular, which was an important part of the microbeam technology of TIARA. In this paper, the latest progress of the ion microbeam technology and applications are summarized and a future prospect of them is discussed.     

Design of a single ion hit facility

The aim of this project is to develop a new system for single ion irradiation of cells for genetic and cell biology studies. This charged particle focused microbeam system will provide a fully computer controlled irradiation facility with submicron (subcellular) resolution and will open many new avenues into studies of radiobiological mechanisms. In the first stage of this project a system for single ion detection has been developed. A thin diamond window has been tested as vacuum/atmosphere window and as a possible source of secondary electrons and/or photons for single ion detection. A detection efficiency of 97% has been achieved.     

Cell Locating with the Image Analysis System of the CAS-LIBB Single-Particle Microbeam Facility

A single-particle microbeam facility has been constructed at the Key Laboratory ofIon Beam Bioengineering (LIBB), Chinese Academy of Sciences (CAS). At the CAS-LIBB microbeam facility, we have developed protocols to place exact numbers of charged particles through nuclear centroids of cells, at defined positions in the cytoplasm relative to the nucleus, and through defined fractions of cells in a population. In this paper, we address the methods for nucleus, cytoplasm and bystander (either a single or an exact number of ions is delivered to a certain percentage of cells in a population to study the bystander effects of radiation) irradiation in detail from theprecision of target finding and cell locating in the image analysis system. Moreover, for cells touching slightly in an image, a watershed method is used to separate these touching objects;after that, the number of objects in an image is counted accurately and the irradiation points are located precisely.     

Strain-ageing in zirconium-oxygen alloys

The parameters affecting the strain-ageing of zirconium-oxygen alloys have been investigated. Strainageing was found to be limited to a temperature range between 200 and 500°C. Transmission electron microscopy has shown that strain-ageing is associated with the formation of a dense dislocation cell structure. Segregation of oxygen atoms to these cell walls is proposed as the mechanism of strain-ageing in zirconium-oxygen alloys. The low-temperature strength and strain-ageing response is attributed to the presence of interstitial oxygen pairs which have an asymmetric strain field and so can interact with both edge and screw dislocations. The effect of neutron irradiation on the strain-ageing response is consistent with some form of interstitial trapping by radiation induced defects.