Advances in drug discovery over the past twenty years have resulted in increased life expectancy and, ironically, have contributed to a 140% increase in EU healthcare costs, with patients suffering from diseases, such as cancer and dementia, now living longer. There is an ever-increasing need to understand disease causation and transmission mechanisms so these diseases can be prevented rather than just better-managed. Changes in a cell’s shape and in the shape of its internal organelle, are important influencers on the cell signalling mechanisms that underpin disease causation. For this reason, 3D imaging of the internal structure of whole, intact, cells is playing an increasingly important role in helping scientists to understand diseases. The only technology available today that can image through and measure the whole substructure of a cell, without needing to slice it or stain it, is soft x-ray microscopy (SXM). The problem is that the illumination required for a soft x-ray microscope is currently only available at four football-stadium sized facilities, called synchrotrons, and scientists have to queue for up to twelve months to get access to these. Despite this limitation, a small number of scientists have persisted with using the SXM technique and have made some very noteworthy breakthroughs in understanding disease causation and transmission. SiriusXT’s innovation has been to develop and patent a miniaturised soft x-ray source, allowing it to build the first commercial, lab-scale, microscope. This breakthrough idea is revolutionising the cell imaging market by opening up access for a proven imaging modality to a target niche market of 3,000 organisations. Project LICENT, aims to make a significant impact in helping reduce drug development and healthcare delivery costs. In so doing, it addresses specific objectives under the Horizon 2020 policy priority of ‘Societal Challenges’, which fall under the challenge of ‘Health, Demographic Change and Well Being’

The EVEREST project is a pioneering consortium in Extracellular Vesicle (EVs) research, bringing together 22 institutions from 11 countries, including 3 UK partners. This interdisciplinary consortium is distinguished by an ambitious plan for over 285 months of staff exchanges, engaging at least 81 fellows. Research-Innovation programme is structured into four pivotal work packages: 1. Combining Expertise and Resources for Advancing Standardised Characterisation and Isolation of EVs: Focused on harmonizing methods for EV isolation across diverse tissues and samples, enhancing the consistency and reliability of EV research. 2. Jointly Investigating EVs in Health or Disease, and Enhancing Translational Biomarker Discovery: Concentrated on exploring the roles of EVs in various health conditions and diseases, with a particular emphasis on identifying and validating new biomarkers for diagnostic and prognostic applications. 3. Uniting Capacities, Advancing EV-Based Therapeutics or Drug Delivery: Dedicated to developing innovative EV-based treatments and drug delivery mechanisms, targeting key health challenges like cancer and cardiovascular diseases. 4. Catalysing commercial development of EV-based technologies: Aiming to bridge the gap between research and practical application, this work package focuses on preparing EV-based solutions for large-scale production and market introduction. At its core, EVEREST is committed to significantly enhancing the capabilities of participating institutions and fostering career advancement for involved fellows. By positioning EVs as critical tools for biomarker discovery and therapeutic applications, the project aims to make substantial contributions to personalized medicine and improved health outcomes, ultimately translating research breakthroughs into clinical practice.

The cost of influenza virus care in the EU was approx. €29 billion in 2018, or 2% of total healthcare costs. The costs to EU state governments for dealing with the Covid-19 virus could be 50 times that of influenza, effectively doubling normal healthcare costs. The EU needs to be better prepared to quickly develop vaccines and drugs to deal with future outbreaks but this can only be achieved with a full understanding of disease pathways. The central idea in project CoCID is that changes in the size and structure of cellular organelle, as any disease infiltrates a cell, are seen as early warning indicators of that disease. The only technology available today that can image through a whole cell, measuring organelle size and structure, is soft x-ray microscopy (SXM). The problem is that the illumination required for a soft x-ray microscope is currently only available at four football-stadium sized facilities, called synchrotrons, and only 2% of the disease research community have access. The challenge addressed by project CoCID is to make SXM available to the wider disease research and drug discovery community, while also showing how technology improvements enhance its ability to revolutionise cell structure imaging. SiriusXT’s breakthrough innovation is its ability to miniaturize the synchrotron into a small chamber that will easily fit on a laboratory bench, providing the same type of soft x-ray illumination as the synchrotron. This novel and patented innovation, based on a laser-produced plasma (LPP) design, will give researchers 24/7 access to this imaging modality in their own labs. To demonstrate impact, the scope of the project has been narrowed to focus only on diseases relating to viral and bacterial infection, allowing a consortium of leading virologists and imaging experts to collaborate in elucidating the cellular origins of viral infection in a range of applications while increasing the EU’s readiness for future viral pandemics.

Development of a Confined, Optically Enhanced X-ray Imaging Source for Tomography (COEXIST). This project aims to leverage fundamental physics research to enhance the soft X-ray emission of a laser produced plasma light source, which is core to the development of a table-top soft X-ray tomograph (SXT) system. Soft X-ray light sources from a laser produced plasma is an emerging technology in table-top sub-cellular imaging, capable of providing high-contrast, whole cell (~ 15-micron penetration depth), natural (fully hydrated), 3-dimensional, high-resolution (< 25 nm) tomographs. Table top SXT systems are potentially a key research tool for future drug discovery and disease research, which currently rely on successful synchrotron beam-times applications for such images. Despite the potential, a fundamental drawback of table-top SXTs, when compared to synchrotron sources, is the relative brightness and thus the sample exposure time for imaging. The COEXIST project proposes to halve acquisition time of the SiriusXT soft X-ray light source and in turn improve image resolution, by increasing the laser plasma source brightness by up to a factor of ten This increase will be achieved via a combination of laser pre-pulsing, magnetic confinement and debris mitigation, technologies which have been proven via fundamental research, but have yet to emerge into a commercial SXT tool.

The aim of SMILE is to support SiriusXT in moving a prototype of its soft x-ray microscope (SXT100) from prototype to commercial product through addressing ease-of-assembly, manufacturing scale-up, serviceability, customer pilots, regulatory pathways and business model requirements. The disruptive innovation delivered by SMILE is to open up the market for soft x-ray imaging from approx. 100 users today to an immediate target addressable market of over 3,000 disease research and drug discovery organisations by reducing the cost of the microscope assembly by a factor of over 200 (from over €500 million to €2.5 million) and miniaturizing its size, by a factor of 5,000 (from 15,000m2 area to approx. 3m2). Soft x-ray imaging is the only means available today of generating high resolution, high contrast, 3D images of the internal structure of whole biological cells in their near-natural state. Cell researchers currently spend approx. €500m annually on electron and optical microscopes in order to increase their understanding of subcellular structure and how this relates to disease progression and therapy, however neither of these technologies is capable of imaging the whole internal cell structure. The SXT100 gives disease research and drug discovery organisations daily access to a soft x-ray microscope in their own labs, rather than having to queue for often more than six months to get a few hours of access to one of only four synchrotron locations around the world where a suitable soft x-ray source and microscope exists today. The SXT100 will not only increase a researcher’s productivity 100-fold, in the number of biological cells they can image, but it also allows them to carry out a range of disease progression studies, not possible today because of the restricted access to these synchrotron microscopes. SMILE is predicted to have a significant impact in addressing the EU/global challenge in reducing the cost of healthcare delivery and developing cures for disease.