High resolution zone plates fabricated by soft X-ray lithography for tomographic soft X-ray analysis applied in the designing and screening of potential Covid-19 drugs

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This NSERC Alliance COVID-19 grant will support and accelerate process technology research to enable the timely fabrication of nanometer-scale X-ray zone plates as analysis tools for the design and identification of drugs and/or vaccines against Covid-19. Beyond short-term responses to the current pandemic, such as social distancing and effective testing, a more fundamental and longer-term approach requires the development of an effective immunization and/or curing drug. Besides screening of existing drugs for additional use in Covid-19 treatment, a more targeted approach to analysis will derive the molecular structure of the SARS-CoV-2 virus and the required molecular structure of potent drugs through direct structural matching. This state-of-the art approach to the most advanced drug design applies soft X-rays from a synchrotron light source to perform nanometer-resolved tomography. This technique reconstructs the three-dimensional structure of, e.g., a biomolecule such as a potential drug, and hence allows optimization of the structural and functional fit with the SARS-Cov-2 virus. The required spatial resolution is obtained by producing a nano-focussed X-ray beam, which, to date, can only be obtained using zone plates as diffractive focussing elements. Zone plates are the subject of intense world-wide research efforts. Diffraction efficiency and spectral response strongly depend on the fabrication approach, and costs can be as high as $40,000 per piece. Zone plates are highly fragile and are, therefore, to a certain aspect, to be seen as consumables. The availability of suitable zone plates constitutes a bottleneck in Covid-19 drug analysis, and the proposed research aims at replacing a slow and serial conventional nanofabrication technology with a faster, parallel patterning technique based on soft X-ray lithography (XRL). Applied Nanotools Inc. (ANT), Edmonton, one of the global leaders in zone plate fabrication, is partnering with Dr. Achenbach's group, experts in XRL at the University of Saskatchewan, to develop a related zone plate fabrication process at the Canadian Light Source.