Development of Efficient table-top laser-produced plasma sources for Water-Window

项目概述：生物标本的成像必须在高时空分辨率下进行，同时避免对标本造成损伤。目前的技术，如光学显微镜和透射电子显微镜（TEM），是生物医学研究/研究中有价值和广泛使用的工具，但有局限性。例如，光学显微镜的分辨率不如使用短波长的光所能获得的分辨率高。对于TEM，样品制备是繁琐的，并且有改变样品结构的风险。在水窗波长区域（= 2.3 - 4.4 nm）操作的显微镜提供高分辨率和大聚焦深度，从而能够进行微层析成像。这个波长下的显微镜在水和富含碳的组织（如蛋白质和脂类）之间提供了强烈的自然对比。最近，使用同步辐射的水窗显微镜显示了冷冻细胞的高分辨率三维断层成像的巨大潜力。然而，基于同步加速器的光源的有限可及性和高昂的费用极大地限制了WW显微镜在生物医学研究中的作用。只有在各种医学实验室和研究机构广泛使用WW显微镜时，WW显微镜的全部潜力才能实现。在本项目中，我们提出了一种基于激光产生等离子体（LPP）光源的高效桌面水窗透射x射线显微镜（TXM）辐射源。基于lpp的WW-TXM系统需要高效、稳定、无碎片的软x射线源。LPP光源是WW-TXM可行的光源，但由于其将激光能量转化为可用的软x射线光的效率相对较低，迄今为止受到限制。低效率的LPP光源导致较长的曝光时间成像的生物样品。这意味着高效或高转换效率（CE，从激光能量到WW辐射的转换）LPP源是使用它们作为WWW-TXM源的先决条件。LPP的CE取决于许多激光和目标的特性，确定最佳参数以获得最佳CE是非常具有挑战性的。这只能通过建模和实验工作的结合来实现。我们将利用我们最先进的辐射和原子物理模拟工具来识别产生高效软X射线源的激光和光源特性，并指导开发新型光源的实验活动。该项目将在水窗区域开发出价格合理的桌面软x射线光源，这将对生物医学研究和细胞生物学领域产生重大影响。

DESCRIPTION (provided by applicant): Project Summary Imaging of biological specimens must be performed with high spatial and temporal resolution, while at the same time avoiding damage to the sample. Present techniques, such as optical microscopy and transmission electron microscopy (TEM), are valuable and widely-used tools in biomedical studies/research, but have limitations. For example, the resolution of optical microscopy is not as high as that which can be obtained using short-wavelength light. For TEM, sample preparation is tedious and risks altering the sample structure. A microscope operating in the water-window wavelength region (= 2.3 - 4.4 nm) provides high resolution as well as a large depth of focus, which enables performing micro-tomography. Microscopy at this wavelength provides a strong natural contrast between water and carbon-rich tissues such as proteins and lipids. Very recently water-window microscopes using synchrotron radiation showed great potential for high resolution three-dimensional tomographic images of frozen cells. However, the limited accessibility and large expense associated with synchrotron-based sources significantly limits the role of WW microscopy in biomedical research. The full potential of WW microscopy will only be realized if it becomes widely accessible to a broad variety of medical laboratories and research facilities. In this project, we propose to develop an efficient, table-top water-window radiation source for transmission X-ray microscope (TXM) based on laser- produced plasma (LPP) light source. LPP-based WW-TXM systems require a soft X-ray source that is efficient, stable and debris free. LPP sources are viable light sources for WW-TXM, but up to now have been limited by their relatively low poor efficiency in converting laser energy into useable soft X-ray light. Low efficiency of LPP sources leads to longer exposure time for imaging of a biological sample. It implies efficient or high conversion efficiency (CE, conversion from laser energy to WW radiation) LPP sources are prerequisite for using them as a source for WWW-TXM. CE of a LPP depends on numerous laser and target characteristics and it is very challenging to identify optimum parameters for obtaining optimum CE. This can be attained only through a combination of modeling and experimental work. We will use our state-of-the-art radiation and atomic physics simulation tools to identify laser and source characteristics that produce highly efficient soft X- ray sources, and guide the experimental campaign for developing novel light sources. This project will lead to affordable, table-top soft X-ray light source in the water-window region that will be of significant benefit to the fields of biomedical research and cell biology. PUBLIC HEALTH RELEVANCE (provided by applicant): Project Narrative Images of biological cells are fundamental in many areas of medical and biological research. We propose to develop an efficient table-top light source instrument for water-window Transmission X-ray microscope (WW-TXM). Compact WW-TXM can provide highly detailed, high contrast images of carbon based structures in biological cells, while minimizing the impact of the water based growing medium, will ensure that this exciting technique is readily available to the maximum number of researchers.