Live imaging module for organoids

Project Information

LiveOrg

Grant agreement ID: 101138640

DOI

10.3030/101138640

Project closed

EC signature date 30 November 2023

Start date 1 January 2024

End date 30 June 2025

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France

Periodic Reporting for period 1 - LiveOrg (Live imaging module for organoids)

Reporting period: 2024-01-01 to 2025-06-30

Summary of the context and overall objectives of the project

The increased use of organoids (22% growth rate market) creates a new need: methods of rapid high throughput screening of the organoids for quality control in the case where they are to be used as graft tissues or in drug screening trials, while at the same time not damaging the organoids so that they may be used for graft, or followed up long term for therapy efficacy evaluation or disease modeling applications. Current imaging methods for organoids do not meet this need as they are invasive and cause damage to the sample. Our team of experts in optics and biology propose a modular solution to live image 2D and 3D cell models with an unprecedented resolution and without use of any kind of marker over a multiple week time span. Dynamic Full Field Optical Coherence Tomography (DFFOCT) is a non-invasive, 3D, label free, live, long term, high resolution, modular imaging system, for which we own two patents. It is an interferometric technique where the image contrast is generated by movements of subcellular organelles such as mitochondria, producing a quantitative colormap linked to cell activity. The present Proof of Concept project “LiveOrg” seeks to valorise the live imaging method developed for retinal organoids in ERC Consolidator “Optoretina”, and disseminate this technology to a wide audience outwith the retina, including cancer, neurology, gastroenterology, hematology, and development. The LiveOrg project specifically aims to design, construct and install DFFOCT modules; and acquire and analyse data with these modules in concertation with key opinion leaders to disseminate results. Thanks to this project, we anticipate that we may attract interest from investors which would fund the startup created during the project period, and potentially from known microscope manufacturers who could distribute our modules, or to whom we could license our patents.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

LiveOrg aims to disseminate DFFOCT technology to new applications and make the technology commercially available. The original workplan to achieve these goals was to hire an engineer to duplicate the DFFOCT device and place new modules in a number of labs with different applications. The team have instead progressed towards the same goal with a different strategy.
In the first phase of the project realized in January-July 2024, the future commercial module needs were defined by enlisting the help of a subcontractor, expert in industrial prototyping.
Based on the result of this process, the team decided to subcontract the building of the duplicate modules in order to benefit from industrial expertise in moving from a lab research device to a first commercial prototype device, rather than hiring an engineer. The team studied offers from multiple subcontractors to decide who was most suited to the project, and set to work with the chosen subcontractor in November 2024, with a first device becoming available in June 2025. This prototype device is ready to install in other labs at the end of the LiveOrg project and is possible to duplicate in a repeatable, cost-effective manner. In addition to this prototype which unites all of the optomechanical elements of the design, a second subcontractor, expert in electronic and information technology design, delivered a custom interface to complete the module that allows rapid and efficient data acquisition and processing.
In parallel to the development of the prototype module, the team decided to perform the dissemination aspect of the technology into new application domains both by diversifying internal collaborations at the Vision Institute to work on new samples and with new teams, and also by inviting interested external researchers to come to Paris to look at the samples of their interest on the DFFOCT demonstrator at the Vision Institute. This was an effective approach in terms of both cost and community building, as the external researchers interested in the technology were able to visit the existing microscope, meet the team, and spend time discussing the images and their interpretation, for only the cost of their own travel, rather than needing to send our equipment and staff to remote sites.
In addition to continuing imaging in the organoid types declared in the initial project, these explorative proof of concept imaging experiments that have been realised include
• mouse intestinal organoids,
• live zebrafish in early development,
• fibroblast cell imaging, which lead to a new microscope design, patented, specific to imaging of flat 2D samples located close to the coverglass,
• organoid model of retinitis pigmentosa generated from patient iPSCs
• corneal organoids
• tissue models including skin, cartilage and conjunctiva models to look at goblet cells
In terms of dissemination, in addition to participating in biology experiments which will lead to peer reviewed publications by the visiting collaborators, we created a logo and website for the startup founded during the project duration. Lutèce Dynamics was created in August 2024 and has so far been successful in attracting public awards and funding from BPI France, and is now moving towards investor fundraising. Several pre-sales have been made internationally. The website https://lutecedynamics.com/ and logo created thanks to the LiveOrg project have contributed to Lutèce Dynamics success in portraying a professional appearance to investors and clients.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

While we are aware that we will require all of the aspects listed (further research, demonstration, access to markets and finance, commercialisation, IPR support, internationalisation, supportive regulatory and standardisation framework), we are satisfied to have already made major steps in all of these directions since the beginning of LiveOrg, thanks to the boost given to the project by the ERC POC funding. We have successfully created a startup, with an online identity (website and logo), an optomechanical and electronic custom prototype for duplication, and have produced data and research results with multiple visiting research teams on a wide variety of samples. These initial data have led to several pre-sales internationally. We have also been successful in attracting further funding, including recognition of our valorization via BPI France awards and project grants, along with progress towards attracting investor capital. The dissemination of our label free, non invasive, 3D live imaging microscope appears to be on the path to adoption in the research community, which we hope will lead to the larger market of pharmaceutical research in the coming years.