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

这笔NSERC联盟COVID-19赠款将支持和加速工艺技术研究，以及时制造纳米级X射线波带片，作为设计和识别抗COVID-19药物和/或疫苗的分析工具。 除了对当前流行病的短期应对措施，如社交距离和有效检测，更根本和更长期的方法需要开发有效的免疫和/或治疗药物。除了筛选现有药物用于新冠肺炎治疗外，更有针对性的分析方法将通过直接结构匹配得出SARS-CoV-2病毒的分子结构和强效药物所需的分子结构。这种最先进的药物设计方法应用来自同步加速器光源的软X射线进行纳米分辨断层扫描。这种技术重建了三维结构，例如，生物分子，如潜在的药物，因此允许优化与SARS-Cov-2病毒的结构和功能匹配。所需的空间分辨率是通过产生纳米聚焦的X射线束来获得的，迄今为止，只能使用波带片作为衍射聚焦元件来获得。波带片是世界范围内研究的热点。衍射效率和光谱响应在很大程度上取决于制造方法，每件成本可能高达40，000美元。波带片是非常脆弱的，因此，在某些方面，被视为消耗品。 合适的波带片的可用性构成了Covid-19药物分析的瓶颈，拟议的研究旨在用基于软X射线光刻（XRL）的更快的并行图案化技术取代缓慢和串行的传统纳米纤维技术。应用纳米工具公司(ANT)，埃德蒙顿，波带片制造的全球领导者之一，是与阿肯巴赫博士的小组，在萨斯喀彻温大学的XRL专家，在加拿大光源开发一个相关的波带片制造过程。

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.