Soft X-ray Laser for Imaging DNA in Vivo

描述（由申请人提供）：该项目的目标是建立和测试一个前所未有的桌面连续波软x射线激光器（CW- sxl）系统。它的波长正好落在水窗口（2.3 nm - 4.3 nm），因此DNA和DNA结合蛋白可以在体内成像，而不会被细胞或细胞核周围的水层所掩盖。DNA损伤和修复过程的动态可以被连续或快照跟踪。这种SXL不依赖于需要建筑物大小的太瓦（TW）激光系统的电子碰撞泵浦方案，也不依赖于由于非线性（或多光子吸收）过程而效率较低的高谐波产生（HHG）方案。我们的SXL系统利用高效的电荷交换（CEX）泵浦方案在高电荷离子（HCI）系统中实现电子居数反转。随着HCI电荷态的增加，CEX碰撞截面增大。从紧凑的电子回旋共振（ECR）离子源中提取hci。它们在与激光腔长度正交的相互作用腔中与靶原子相互作用。由于耗尽的基态离子（灰）可以漂移出激光腔区，这种配置使得连续波激光首次在x射线激光社区中成为可能。此外，通过在带正电荷的HCI光束上施加一个激发电场，可以实现超快（纳秒）脉冲模式下的激光操作。近年来，多层镀膜x射线反射镜制造技术和纳米分辨率运动控制技术的进步使得类似可见激光的谐振腔成为可能。这保证了我们的SXL的高增益长度产品和高光束质量。美国国立卫生研究院（NIH）的使命是追求生命系统行为的基本知识和应用这些知识以延长健康生命的科学。我们创造性和创新性的CW-SXL的开发及其应用将导致对人类dna作为一个生命系统的分子水平的理解。CW-SXL显微镜可以在高分辨率3d成像激光扫描共聚焦显微镜（LSCM）下抑制活dna的转录和复制，从而延长健康寿命。这种生物手术可以可靠地抑制癌细胞的快速生长：通过控制化疗。物理光学公司（POC）在x射线成像、开发x射线准直器、镜头和数码摄影方面具有重要的专业知识。在第一阶段，将构建一个缩小的ECR离子源，并在连续波模式下提取大量的软x射线光子。这种非相干光束在乳腺癌的早期检测中有现成的应用。将建立并测试一个装有准正入射激光反射镜的软x射线激光腔。在第二阶段，将从放大的紧凑ECR离子源中提取选定的HCI束。提取的HCI光束将进行质量分析并引入相互作用室，目标原子与HCI相互作用以实现种群反转（或负温度）HCI系统。一种新型CW-SXL系统将在为期两年的第二阶段结束时准备好进行演示。公共卫生相关性：拟议的软x射线激光器将能够产生波长短至几纳米的相干光。它将允许蛋白质成像，例如DNA，在体内，这反过来将彻底改变研究方法，以抑制癌细胞的转录和复制。x射线激光的另一个应用是对软组织进行超高分辨率成像，用于乳房x光检查，以早期发现乳腺癌。

DESCRIPTION (provided by applicant): The goal of this project is to build and test an unprecedented tabletop CW soft X-ray laser (CW-SXL) system. Its wavelength will fall exactly in the water window (2.3 nm - 4.3 nm), so DNA and DNA-binding proteins can be imaged in vivo without being obscured by layers of water surrounding cells or cell nuclei. The dynamics of the DNA damage-and-repair processes can be tracked continuously or by snapshots. This SXL does not rely on the electron-collision pumping scheme that would require a building-size terawatt (TW) laser system, nor on the high harmonic generation (HHG) scheme where efficiency is low due to the nonlinear (or multi-photon absorption) process. Our SXL system utilizes an efficient charge-exchange (CEX) pumping scheme to achieve electron population inversion in the highly-charged ion (HCI) system. The cross section of CEX collision increases as the charge state of HCI increases. HCIs are extracted from a compact electron cyclotron resonance (ECR) ion source. They are interacted with target atoms in an interaction chamber directed orthogonal to the length of laser cavity. This configuration makes CW laser operation possible for the first time in X-ray laser communities because the used-up ground state ions (ash) can be drifted out of the laser cavity region. Furthermore, laser operation in the ultrafast (nanosecond) pulse mode is feasible by applying a kicker electric field on the positively-charged HCI beam. Recent advancements in multi-layer coating X-ray mirror fabrication technology and nano-meter resolution motion control technology have made a visible-laser like resonance cavity possible. This guarantees a high gain-length product and high beam quality for our SXL. The mission of the National Institute of Health (NIH) is stated as science in pursuit of fundamental knowledge about the behavior of living systems and application of that knowledge to extend healthy life. Development of our creative and innovative CW-SXL and its application will lead to a molecular level understanding of human DNAs as a living system. The CW-SXL microscope can extend healthy life because one can inhibit the transcription and replication of living DNAs under high-resolution 3D-imaging: with laser scanning confocal microscopy (LSCM). Such biological operations can reliably inhibit rapid growth of cancer cells: with controlled chemotherapy. Physical Optics Corporation (POC) has significant expertise in X-ray imaging, developing X-ray collimators, lenses, and digital photography. In Phase I, a scaled-down ECR ion source will be constructed and copious soft X-ray photons will be extracted in CW mode. This incoherent beam has a ready application for early detection of breast cancer. A soft X-ray laser cavity equipped with quasi-normal incidence laser mirrors will be built and tested. In Phase II, a selected HCI beam will be extracted from the scaled-up, yet compact ECR ion source. Extracted HCI beams will be mass analyzed and introduced into an interaction chamber, where target atoms interact with HCIs to achieve a population inverted (or negative temperature) HCI system. A novel CW-SXL system will be ready for demonstration by the end of the two-year Phase II period. PUBLIC HEALTH RELEVANCE: The proposed soft X-ray laser will be able to generate coherent light at a wavelength as short as a few nanometers. It will allow imaging of proteins, DNA for instance, in vivo, which, in turn, will revolutionize research on methods to inhibit the transcription and replication of cancer cells. Another application of the X-ray laser is ultrahigh resolution imaging of soft tissues to be applied in mammography for the early detection of breast cancer.