Oxford–ZEISS Centre to advance live-cell imaging for drug discovery

The Oxford-ZEISS Centre of Excellence in Biomedical Imaging (Oxford-ZEISS CoE) and ZEISS have entered a proof-of-principle stage in the product development of a new cutting-edge imaging technology, capable of systematically measuring the behaviour of drugs in cells and tissues, which has the potential to revolutionise the testing of new medicines for safety and effectiveness.

In the 12-month proof-of-principle phase, the Oxford-ZEISS CoE and ZEISS R&D will be joined by three partners from academia and three partners from the pharmaceutical industry to test the drug-profiling applications of the innovative Selective Plane Illumination Lattice Light Sheet Microscopy (SPI LLSM) technology in cells, organoids and tissue biopsies.

The state-of-the-art SPI LLSM method uses ultrathin, non-diffracting light sheets to visualise drug interactions within 3D cell culture models and was patented by the Oxford-ZEISS CoE and ZEISS through Oxford University Innovation (OUI).

The novel technique was developed at the Oxford-ZEISS CoE as a solution to the limitations of existing imaging methods, such as fluorescence correlation spectroscopy (FCS), to address the need for a fast, reliable, and high-resolution technology that can measure and characterise how drugs behave in standardised biological models.

Previously, the working principle of Selective Plane Illumination Lattice Light Sheet Microscopy was successfully demonstrated in solution assays and cell culture models, which are widely used as standard platforms in early-stage drug discovery.

With the help of ZEISS R&D, the Oxford-ZEISS CoE will team up with partners from academia and industry to expand the drug-screening applications of the proprietary SPI LLSM technology to patient-derived tissue biopsies from the Oxford Tissue Banks and organoids, tiny, three-dimensional lab-grown versions of human organs.

The initial development of the SPI LLSM imaging method at the Oxford-ZEISS CoE was led by Professor Marco Fritzsche, Dr Narain Karedla, and Assistant Professor Falk Schneider.

Professor Marco Fritzsche, Scientific Director of the Oxford-ZEISS CoE, said: 'This innovation finally allows us to observe 3D reaction-diffusion dynamics in physiologically relevant organoids and tissue biopsies. If successful, this technology has the potential to transform today's drug-screening technology.'

The Oxford-ZEISS CoE team behind the project aims to study the applications of SPI LLSM in disease-specific organoids in cancer and autoimmune disease contexts. The results of the 12-month alpha-testing study will inform the commercialisation of the novel imaging method, with the aim of making it widely available and accessible for academic research and pharmaceutical drug discovery.

The Oxford-ZEISS Centre of Excellence in Biomedical Imaging, leading the project, opened in February 2024 and was established through a strategic partnership between the Kennedy Institute of Rheumatology and the Institute for Developmental & Regenerative Medicine at the University of Oxford.

With a vision to build a future-proof imaging facility with constantly evolving technical excellence, the Centre is driven by novel biological research questions and supported by direct ZEISS Research & Development input from the industrial microscopy leader ZEISS.

Professor Paul Riley, Director of the Institute of Developmental & Regenerative Medicine, said: 'The SPI LLSM technology is transformational in enabling live imaging of cell behaviours in a 3D tissue or organ context and as such the applications are boundless, including disease modelling and drug screening as priority areas within the IDRM and the Oxford-ZEISS Centre.'

Professor Michael Dustin, Director of Research at the Kennedy Institute of Rheumatology, said: 'This novel approach should revolutionise the development of tumor penetrating biologics and nanoparticles.'

The proof-of-principle phase aims to validate the transformative SPI LLSM imaging technology and make it usable at scale in high-impact research addressing major biomedical challenges. If successful, SPI LLSM has the potential to replace conventional confocal microscopy and become the new gold standard for live-cell imaging.