Soft X-ray Laser for Imaging DNA in Vivo

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.