INSPIRE: Compact X-Ray Laser in "Water Window" and Microscopy of Cell Membranes

这个多学科INSPIRE奖的最终目标是实现一种新的、非常高分辨率的显微镜，这种显微镜能够通过使用比普通可见光更有能量的光来观察生物细胞内部，但不像传统医学x射线使用的光那么有能量。具体来说，这个项目试图产生和使用“软x射线”光，在光的每次振荡（波长3.4和4.0 nm）中，这种光将传播30到40亿分之一米。这些波长落在所谓的“水窗”（2.3-4.4纳米），在这个窗口中，水是透明的，但细胞的许多其他部分却不是。利用这些波长的光，人们可以透过细胞内部的水，以高分辨率清晰地看到细胞的功能部分。关键的启用工具被称为x射线激光器（XRL），该项目旨在生产一种足够小且价格合理的工具，可以广泛用于在自然环境中对活的生物细胞进行成像。这项工作是基于使用高电荷离子，原子的大部分电子被去除。这个项目的目标是通过对天然细胞膜成像来展示新的XRL的实用性。这项工作由美国国家科学基金会综合活动办公室、原子、分子和光学实验物理项目、美国国家科学基金会/美国能源部基础等离子体科学与工程伙伴关系、生物研究仪器开发项目和生物理事会新兴前沿办公室共同资助。最近，在4.0nm的复合x射线激光器中首次展示了高增益，这一结果激发了利用4.0nm的XRL与红外场直接在复合XRL的倒置介质中有效产生阿秒脉冲的新思路。这个想法是在德克萨斯农工大学（TAMU）基于量子光学的理论基础上发展起来的，作为INSPIRE项目的一部分，在普林斯顿大学提出了这个想法的实验测试。预计XRL用于生物成像的实际应用要求激光脉冲的能量为每脉冲2 - 4微焦耳。因此，这个项目的关键问题将是寻找大的XRL光束强度放大。这种搜索的自然延伸将是在另一个水窗波长产生高XRL光束强度，在这种情况下为3.4nm。通过使用Schwarzschild多层涂覆物镜和高灵敏度二维电荷耦合器件探测器，细胞的辐射暴露将保持在较低的水平，从而允许对活细胞进行成像。

The ultimate goal of this multidisciplinary INSPIRE award is to enable a new, very high resolution microscope which is able to see inside biological cells by using light which is more energetic than ordinary visible light, but not as energetic as the light used in conventional medical x-rays. In specific, this project seeks to produce and use "soft x-ray" light that will travel between 3 and 4 billionths of a meter during each oscillation of the light (wavelengths 3.4 and 4.0 nm). These wavelengths fall in the so-called "water window" (2.3-4.4 nm) in which water is transparent, but many other parts of cells are not. Using light with these wavelengths allows one to see through the water inside cells to clearly visualize the functional parts of the cells in high resolution. The key enabling tool is called an X-ray laser (XRL), and this project seeks to produce one that is sufficiently small and affordable that it can be put into widespread use to image live biological cells in their natural environment. The work is based on the use of highly charged ions, atoms which have most of their electrons removed. Included in this project is the goal of demonstrating the utility of the new XRL by imaging natural cell membranes. This work is co-funded by the NSF Office of Integrative Activities, the Atomic, Molecular, and Optical Experimental Physics Program, the NSF/DOE Partnership in Basic Plasma Science and Engineering, the Instrument Development for Biological Research Program, and the Emerging Frontiers Office of the Biology Directorate.Recently, high gain was demonstrated for the first time in a recombination X-ray laser at 4.0nm This result stimulated a new idea to efficiently generate attosecond pulses by utilizing an XRL at 4.0 nm in combination with an infrared (IR) field directly in the inverted media of a recombination XRL. This idea was developed theoretically at Texas A&M University (TAMU) based on quantum optics and is proposed here to test this idea experimentally at Princeton as part of this INSPIRE project. It is expected that the practical application of an XRL for biological imaging requires the laser pulses to have an energy of 2 - 4 micro-Joules of energy per pulse. Therefore the crucial issue for this project will be the search for large XRL beam intensity amplification. The natural extension of this search will be the generation of high XRL beam intensity at another water window wavelength, in this case 3.4nm. By using a Schwarzschild multilayer coated objective and a high sensitivity two dimensional charge-coupled device detector, the cell radiation exposure will be kept low to allow the imaging of live cells.