Personalized medicine, which identifies effective treatments via the sub-cellular characterization of disease and its response to treatments, has been identified as key approach to improving clinical treatment effectiveness, quality of care, and reduce the financial burden. A significant barrier to mainstream personal medicine is rising research cost in drug discovery. The average R&D cost of pre-clinical drug discovery has recently risen to over $1 billion. A resource intensive, yet critical step, in pre-clinical R&D is imaging of a pharmaceutical’s sub-cellular effect on in-vitro biological cells. Sub-cellular imaging is traditionally performed using Transmission Electron Microscopy (TEM) and/or Visible Microscopy, but these techniques have been complimented with Cryo-TEM, Super-Resolution Fluorescence Microscopy (SRFM) and the newly emerging cryogenic Soft X-ray Tomography (Cryo-SXT). State-of-the-art Cryo-SXT is capable providing high-contrast, high-resolution, whole cell, natural (hydrated) 3D images of biological samples.
Two distinct soft X-ray (SXR) sources are presently available to researchers; (1) high brilliance synchrotron sources - which can provide 3D images within minutes, but require the submission and approval of proposals months in advance and (2) Nitrogen laser plasma sources - relatively compact user systems, but rely on bespoke complex laser system making commercial deployment extremely challenging. SiriusXT is currently developing a commercial, table-top, high brightness, laser-plasma based, SXR source capable of delivering high-resolution 3D images in 10s of minutes. Such a source effectively shrinks the capabilities of a synchrotron into the footprint and cost of a traditional user microscope systems (e.g. TEM).
The COEXIST project identified scope to enhance the imaging capabilities of table-top SXT. The primary scientific goal of COEXIST was to leverage fundamental research to develop innovative enhancements for SiriusXT’s soft X-ray commercial microscope beyond state-of-the-art. These enhancements aimed to considerably reduce image acquisition times and strengthen SiriusXT’s soft X-ray microscope’s position as a powerful tool for scientific research, thus narrowing the performance gap between synchrotron and table-top sources.
The COEXIST research succeeded in developing, integrating, and validating light-source and system enhancements for SiriusXT’s SXT. These R&D enhancements were instrumental in the delivery of the first SXR images from SiriusXT’s prototype system. In addition, exploratory research conducted as part of COEXIST project discovered avenues to deliver further SXT system improvements. As a whole, the COEXIST project delivered significant improvements to a state-of-the-art imaging platform, with the potential to benefit and accelerate whole sectors of research which utilize imaging, these include, but are not limited to; drug discovery, disease treatment/prevention and applied/industrial microbiology.
