Periodic Reporting for period 1 - TriScanner (Next-gen fluorescence imaging for research and theranostics)
Período documentado: 2023-06-01 hasta 2024-11-30
Fluorescence microscopy is key technique in the life sciences because it offers an unmatched sensitivity, selectively, and non-invasiveness. In addition to their deep embedding in all academic research environments, fluorescence microscopes are also commonly used in industry for research purposes and in clinical diagnostics such as pathology. Around this need a commercial ecosystem has developed encompassing major and well-known companies such as Zeiss, Nikon, Evident (formerly Olympus), Leica, etc., and also several innovative start-ups targeting specific optical applications.
Developments in fluorescence microscopy have enabled much of our current knowledge. However, the technique is now severely challenged by the need to deliver fast imaging of multicellular systems. Such samples are rapidly becoming the norm because biological systems are highly heterogeneous and so must be studied with high resolutions and in large numbers. This includes not only animals and tissues but increasingly also samples such as organoids, tissue-like mimics that can be grown in the lab from patient materials and that faithfully recapitulate the tissue’s physiology. This technology offers exceptional potential because many organoids can be grown from e.g. single tumor biopsies, in order to assess the potential of personalized treatments, leading to its selection as ‘Method of the Year 2017’ by the journal Nature Methods. However, while such samples can be created rapidly and in large numbers, the current gold standard in fluorescence microscopy takes hours to measure even a tiny 1 mm3 region of a sample, drastically limiting the experimental space that can be explored because only a very low number of such samples can be imaged in a reasonable time. The same bottlenecks are encountered also in other highly innovative methodologies such as spatial transcriptomics, which are revolutionizing our understanding of life, but are crucially held back by the lack of suitably powerful imaging methodologies.
More generally, this bottleneck affects all studies of multicellular systems, including the many crucial fields that depend on this, such as neurobiology, embryo- and organogenesis, cell differentiation, cell signalling, cellular and tissue ageing and morphogenesis, cancer research, as well as the study of many other diseases and disorders. Living systems are structured by necessity, and we have little choice but to include this structuring in our experiments.
Several efforts have tried to address this limitation However, all of these technical solutions suffer from two or more of the following limitations: slow acquisitions and/or low throughput, low resolution and low sensitivity, and high complexity and cost. In addition to the technical limitations, the high costs also complicate the deployment of such techniques at scale, which is essential for their routine use in innovative diagnostics and therapies (‘theranostics’).
Overall, the lack of powerful and fast fluorescence imaging is a major bottleneck holding back not only research but also the deployment of innovative methodologies based on e.g. spatial ‘omics’ and organoids, despite the many research and health benefits that the routine application of such methodologies would entail.
Based on the innovative research performed as part of my ERC Grant ‘NanoCellActivity’, we have developed the ‘TriScan’, a novel type of fluorescence microscope that can easily image hundreds of times faster than conventional imaging, while also delivering an outstanding (single-molecule) sensitivity and spatial resolution. The design is also inherently compatible with high-throughput imaging.
The goal of this project is to explore the commercialization of this design. We will develop a demonstrator instrument, benchmarking its performance under a range of settings, and will demonstrate it's performance to stakeholders. In parallel, we will develop a business plan and IP strategy for further valorization.
Developments in fluorescence microscopy have enabled much of our current knowledge. However, the technique is now severely challenged by the need to deliver fast imaging of multicellular systems. Such samples are rapidly becoming the norm because biological systems are highly heterogeneous and so must be studied with high resolutions and in large numbers. This includes not only animals and tissues but increasingly also samples such as organoids, tissue-like mimics that can be grown in the lab from patient materials and that faithfully recapitulate the tissue’s physiology. This technology offers exceptional potential because many organoids can be grown from e.g. single tumor biopsies, in order to assess the potential of personalized treatments, leading to its selection as ‘Method of the Year 2017’ by the journal Nature Methods. However, while such samples can be created rapidly and in large numbers, the current gold standard in fluorescence microscopy takes hours to measure even a tiny 1 mm3 region of a sample, drastically limiting the experimental space that can be explored because only a very low number of such samples can be imaged in a reasonable time. The same bottlenecks are encountered also in other highly innovative methodologies such as spatial transcriptomics, which are revolutionizing our understanding of life, but are crucially held back by the lack of suitably powerful imaging methodologies.
More generally, this bottleneck affects all studies of multicellular systems, including the many crucial fields that depend on this, such as neurobiology, embryo- and organogenesis, cell differentiation, cell signalling, cellular and tissue ageing and morphogenesis, cancer research, as well as the study of many other diseases and disorders. Living systems are structured by necessity, and we have little choice but to include this structuring in our experiments.
Several efforts have tried to address this limitation However, all of these technical solutions suffer from two or more of the following limitations: slow acquisitions and/or low throughput, low resolution and low sensitivity, and high complexity and cost. In addition to the technical limitations, the high costs also complicate the deployment of such techniques at scale, which is essential for their routine use in innovative diagnostics and therapies (‘theranostics’).
Overall, the lack of powerful and fast fluorescence imaging is a major bottleneck holding back not only research but also the deployment of innovative methodologies based on e.g. spatial ‘omics’ and organoids, despite the many research and health benefits that the routine application of such methodologies would entail.
Based on the innovative research performed as part of my ERC Grant ‘NanoCellActivity’, we have developed the ‘TriScan’, a novel type of fluorescence microscope that can easily image hundreds of times faster than conventional imaging, while also delivering an outstanding (single-molecule) sensitivity and spatial resolution. The design is also inherently compatible with high-throughput imaging.
The goal of this project is to explore the commercialization of this design. We will develop a demonstrator instrument, benchmarking its performance under a range of settings, and will demonstrate it's performance to stakeholders. In parallel, we will develop a business plan and IP strategy for further valorization.
We have developed an optimized prototype microscope and have applied it to a range of settings and samples, including both fast 3D and highly-sensitive single-molecule experiments. We have also developed electronics and software to provide powerful acquisition possibilities in combination with high ease of use. In parallel, we have developed and are developing a miniaturized version of the design, aiming to create a low-footprint and comparatively inexpensive layout suitable for at-scale deployment. The resulting performance of the demonstrator was showcased at multiple meetings and events. We collaborated with LRD on furthering the business case and development roadmap for the design.
A key priority is a showcased demonstration of our instrument in a peer-reviewer publication, for which a preprint is available but will be updated. A next step is to perform a full stability analysis of the design in order to identify factors that may impede or compromise the long-term performance. On the business side, we will need to update and assemble a full business plan a we converge on a more final prototype.