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

描述(申请人提供)：对生物标本进行成像的项目摘要必须具有高空间和时间分辨率，同时避免对样本造成损害。目前的技术，如光学显微镜和透射电子显微镜，在生物医学研究/研究中是有价值的和广泛使用的工具，但有局限性。例如，光学显微镜的分辨率不如使用短波长光所能获得的分辨率高。对于透射电子显微镜，样品制备是繁琐的，而且有改变样品结构的风险。在水窗口波长区域(=2.3-4.4 nm)工作的显微镜提供高分辨率以及大焦深，这使得能够进行微断层扫描。这一波长的显微镜在水和富含碳的组织(如蛋白质和脂肪)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高分辨率冷冻细胞三维层析成像的巨大潜力。然而，有限的可获得性和与基于同步加速器的源相关的巨额费用显著限制了WW显微镜在生物医学研究中的作用。只有当各种各样的医学实验室和研究机构都能广泛使用时，才能充分发挥万维网显微镜的潜力。在这个项目中，我们提出了一种基于激光产生等离子体(LPP)光源的透射式X射线显微镜(TXM)的高效桌面水窗辐射源。基于LPP的WW-TXM系统需要高效、稳定和无碎片的软X射线源。LPP光源是WW-TXM的可行光源，但到目前为止，由于LPP光源在将激光能量转化为可用软X射线光方面效率较低，因此受到了限制。低效率的LPP光源导致生物样品成像的曝光时间较长。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依赖于大量的激光和靶材特性，确定最佳的参数以获得最佳的CE是非常具有挑战性的。这只能通过建模和实验相结合的工作来实现。我们将使用我们最先进的辐射和原子物理模拟工具来确定产生高效软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。该项目将为生物医学研究和细胞生物学领域的生物医学研究和细胞生物学领域带来巨大的好处，这将导致在水窗口地区产生负担得起的桌面软X射线光源。 公共卫生相关性(由申请人提供)：生物细胞的项目叙事图像在医学和生物学研究的许多领域是基本的。我们提出了一种用于水窗透射式X射线显微镜(WW-TXM)的高效台式光源装置。紧凑型WW-TXM可以提供生物细胞中碳基结构的高细节、高对比度图像，同时将水基生长介质的影响降至最低，这将确保这项令人兴奋的技术随时可供最多的研究人员使用。

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.