SBIR-STTR Award

Relevance: Soft x-ray microscopy is a fast, high resolution imaging technique for hydrated biological cells that is limited today by the need to use synchrotron light, available only at the National Laboratories. This project's goal is to develop a soft x-ray microscope using a compact source of soft x-rays that can be used in small biological laboratories for the rapid analysis of cells for disease identification and drug discovery. Project Summary: Soft X-Ray microscopy, using light in the so-called 'water-window' between 2.3 and 4.4 nanometer (nm) wavelength, allows imaging of frozen-hydrated biological cells, with high contrast between carbon containing proteins and water, with resolution down to 15nm, and with rapid sample turnaround. Energetiq Technology has developed a novel light source technology called an electrodeless z-pinch xenon plasma source, originally for use in the semiconductor fabrication industry at 13.5nm wavelength, that could provide a source of soft x-rays that would enable a lab-scale soft x-ray microscope. The cost of a soft x-ray microscope would be comparable to an electron microscope, but with a sample to image collection time reduced by a factor of more than 100. The project includes collaboration with expert researchers at the NYS Wadsworth Lab and Lawrence Berkeley Lab to 1) develop a detailed model for a small lab-scale microscope including the required brightness and linewidth required for the imaging, 2) modify the previously developed 13.5nm electrodeless z-pinch source, use nitrogen or other gases in place of xenon and measure the actual brightness and linewidth for emission lines in the 2.3nm to 4.4nm range using specilized power and spectral monitors, and 3) optimize the light source to demonstrate that the electrodeless-z pinch approach can produce sufficient soft x-ray light to provide hydrated cell images in an acceptable time. Subsequent phases of this research will be to leverage the soft x-ray microcope technology already developed for use on the synchrotrons into the development of a cost effective lab-scale microscope. Such a soft x-ray microscope would enhance the study of, for example, cell motility, mitosis and vesicular transport. The microscope would allow the more rapid imaging of labeled molecular components in optimally preserved specimens, thereby increasing the pace of cellular research

Soft x-ray microscopy shows enormous promise as a technique for imaging cellular structures at resolutions well beyond what can be achieved in optical microscopes, and with much simpler sample preparation than is required for electron microscopy. In addition, the lower radiation dose required (compared to electron microscopy) allows tomographic investigation of subcellular structures in three dimensions. Existing synchrotron based microscopes have shown the potential of the soft x-ray microscope as a research tool, but they have the disadvantage of being tied to a massive light source at only a few national laboratories. A suitably bright, compact, low cost light source is the enabling innovation needed to realize a commercial biological soft x-ray microscope. Energetiq has developed a unique light source technology using an electrodeless, inductively coupled plasma to produce light in the soft x-ray range. The Energetiq light source can be used to generate light needed to illuminate and image biological specimens in a soft x-ray microscope. In Phase I Energetiq explored the capability of the light source in the "water window" range of wavelengths and determined that an x- ray microscope based on the light source is feasible. A "proof of principle" microscope will be constructed in Phase II. Biologists have a need to image whole biological cells both at high resolution and in their hydrated state. Currently available microscopes satisfy one of these requirements but not both. Soft x-ray microscopy in the so-called 'water window' allows resolution to 20nm for fully hydrated cell samples, and can produce 2-D and 3-D tomographic images. The ability to resolve sub cellular structures in hydrated cells, and to create those images in minutes rather than days, could lead to more rapid advances in drug discovery, disease diagnosis, disease treatment and better understanding of the fundamental cellular processes