Development of a hard X-ray microfocus source for radiobiological applications

开发用于放射生物学应用的硬 X 射线微焦点源

• 批准号: EP/I005714/1
• 负责人: Giuseppe Schettino
• 金额: $ 13.27万
• 依托单位: Queen's University Belfast
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FI005714%2F1
• 关键词: Development; hard; ray; microfocus; source

The project aims to develop a unique compact high energy (5-25 keV) X-ray microbeam facility by integrating recent developments in X-ray production and glass capillary optics with single cell targeting and analysis technique. The facility will represent an exquisite tool to investigate risks and responses of simple and complex biological samples to a type of ionizing radiation widely used in our society (from medical diagnostic and therapeutic applications to nuclear and enviromental levels) in an unprecedented way. The fine resolution, wide energy range, brightness and compact size will make this facility unique and appealing not just for radiobiological applications. Such a goal will be realised by improving commercially available X-ray sources and adopting glass capillary devices to focus X-rays into micron and submicron diameter spots. Source improvements will be mainly directed to increasing the source brightness (i.e. X-ray production) while reducing the effective X-ray source (< 10 micron diameter). Target cooling options (diamond heat spreaders and Peltier units) will also be considered to increase the output flux and producing therefore a point-like, very bright lab bench X-ray source. By exploiting the total reflection that occurs at shallow incident angles, glass capillary devices will then able to focus hard X-rays into a fine spot through multiple internal reflections. Specifically, we aim to deliver ~1 Gy/sec into sub-micron spots. Finally, the developed hard X-ray microfocus probe will be integrated into an existing single-cell irradiation facility. Such a system consists of a 3-axis micropositioning stage (0.25 micron resolution) coupled to an epi-fluorescent microscope and controlled by in house developed software to automatically locate biological cellular and sub-cellular targets and align them with a specific radiation probe.Radiobiological microbeams are facilities able to deliver a specific dose of radiation to single cells or part of them and subsequently assess the damage induced and the effect caused. As such, microbeams are unique tools to precisely investigate effects of radiation on biological samples and the complex pathways that regulate cellular response to radiation insult. Despite the importance of a deterministic irradiation experiment has been recognised since the early 1950's, only with the technological advances of the last couple of decades has it been possible to develop sophisticated microbeam. Over such a period, microbeam have significantly contributed to our knowledge in radiation biology providing critical insights which have and are being exploited for radiotherapy and radioprotection purposes. Currently most of the microbeam facilities worldwide use charged particles and only 3 employ soft X-rays (<5 keV). On the other hand, hard X-rays (>5 keV) are particularly interesting due to their attenuation characteristics, the pattern of ionization/damage induced and their wide use in modern society (from diagnostic equipment to natural and man-made background levels).The hard X-ray microbeam will be used for wide range of radiobiological experiments aimed to study the effects and risks associated with exposure to very low doses of sparsely ionizing radiation. In particular, the ability to target individual cells within a selected populations or indeed a complex 3D tissue structure will provide a valuable asset for the investigation of the bystander effect (i.e. radiation effects expressed in cells not being directly exposed but in contact or proximity of irradiated samples). Moreover, sub-nuclear organelles (i.e. mitochondria) and individual chromosomes can be targeted in order to investigate their radioresistance and address specific questions about their functionality. Finally, our findings and expertise in developing high energy X-ray microfocus could also be beneficial to the X-ray microscopy and spectroscopy communities.

该项目旨在通过将 X 射线产生和玻璃毛细管光学器件的最新发展与单细胞靶向和分析技术相结合，开发一种独特的紧凑型高能 (5-25 keV) X 射线微束设施。该设施将成为一种精致的工具，以前所未有的方式研究简单和复杂的生物样本对我们社会广泛使用的一种电离辐射（从医学诊断和治疗应用到核和环境水平）的风险和反应。精细的分辨率、宽的能量范围、亮度和紧凑的尺寸将使该设施独特且不仅对放射生物学应用具有吸引力。这一目标将通过改进商用X射线源并采用玻璃毛细管装置将X射线聚焦成微米和亚微米直径的光斑来实现。源改进将主要针对增加源亮度（即 X 射线产生），同时减少有效 X 射线源（< 10 微米直径）。目标冷却选项（金刚石散热器和珀耳帖装置）也将被考虑以增加输出通量，从而产生点状、非常明亮的实验室台式 X 射线源。通过利用浅入射角发生的全反射，玻璃毛细管装置将能够通过多次内反射将硬 X 射线聚焦成一个细点。具体来说，我们的目标是将约 1 Gy/秒传输到亚微米点。最后，开发的硬X射线微焦点探头将集成到现有的单细胞辐照设施中。这样的系统由与落射荧光显微镜耦合的 3 轴微定位台（0.25 微米分辨率）组成，并由内部开发的软件控制，自动定位生物细胞和亚细胞目标，并将它们与特定的辐射探针对齐。放射生物微束是能够向单个细胞或其中一部分传递特定剂量的辐射，随后评估引起的损伤和损伤的设施。 造成的影响。因此，微束是精确研究辐射对生物样本的影响以及调节细胞对辐射损伤反应的复杂途径的独特工具。尽管自 20 世纪 50 年代初以来人们就认识到确定性辐照实验的重要性，但只有随着过去几十年的技术进步，才有可能开发出复杂的微束。在此期间，微束对我们在辐射生物学方面的知识做出了重大贡献，提供了重要的见解，这些见解已经或正在被用于放射治疗和辐射防护目的。目前，全球大多数微束设施都使用带电粒子，只有 3 个使用软 X 射线（<5 keV）。另一方面，硬 X 射线 (>5 keV) 由于其衰减特性、电离/损伤模式及其在现代社会的广泛使用（从诊断设备到自然和人造背景水平）而特别令人感兴趣。硬 X 射线微束将用于广泛的放射生物学实验，旨在研究与暴露于极低剂量的稀疏电离辐射相关的影响和风险。特别是，针对选定群体内的单个细胞或实际上复杂的 3D 组织结构的能力将为旁观者效应（即未直接暴露但接触或接近受辐射样品的细胞中表达的辐射效应）的研究提供宝贵的资产。此外，可以靶向亚核细胞器（即线粒体）和单个染色体，以研究它们的辐射抗性并解决有关其功能的具体问题。最后，我们在开发高能 X 射线微焦点方面的发现和专业知识也可能有益于 X 射线显微镜和光谱学界。

项目成果

Imaging and radiation effects of gold nanoparticles in tumour cells.

• DOI: 10.1038/srep19442
• 发表时间: 2016-01-20
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: McQuaid HN;Muir MF;Taggart LE;McMahon SJ;Coulter JA;Hyland WB;Jain S;Butterworth KT;Schettino G;Prise KM;Hirst DG;Botchway SW;Currell FJ
• 通讯作者: Currell FJ