Bringing Random Illumination Microscopy to the community
How do you turn an innovative microscopy prototype into an operational tool accessible to the research community? France-BioImaging supported the transfer of the Random Illumination Microscopy (RIM) technique from Toulouse to Rennes by enabling both the project and the recruitment of engineer Nina Soler.
In this interview, Nina shares how this technology transfer was implemented at the MRic facility, and how RIM is now opening new possibilities for live super-resolution imaging.
Could you briefly introduce yourself?
I completed a PhD in cell biology, where I investigated microtubule dynamics within the mitotic spindle in C. elegans. This work allowed me to develop strong expertise in image processing and quantitative analysis. I then aimed to broaden my skill set by specializing in super-resolution light microscopy.
Supported by France-BioImaging funding, I joined the MRic core facility in Rennes to transfer the RIM technique and make it accessible for independent use by researchers. I am currently part of the MRic electronic unit, where I am working on the development of CLEM approaches.
What was your role in this project?
I was in charge of optimizing system parameters and refining data acquisition workflows. I also contributed to improving the prototype’s usability, enabling biologists to operate the system independently.
Briefly, what is RIM? What makes it particularly interesting compared to other super-resolution techniques?
RIM combines speckle wide-field illumination and a new statistical approach based on the covariance, the variance, and the standard deviation. RIM is based on the use of speckle patterns, which arise naturally from laser interference. In practice, the laser beam is directed onto a spatial light modulator (SLM), where random phase patterns are applied. When combined with the intrinsic speckle field, these patterns create a series of random illumination fronts that sequentially cover the sample.
From the resulting dataset, a super-resolution image can be reconstructed by exploiting the statistical invariance of the speckle patterns. Its key advantage is the ability to image living samples, thanks to its rapid acquisition and low phototoxicity, while also supporting deep imaging enabled by the unique properties of speckle illumination.
This project is based on a technology transfer from Toulouse. Could you explain how this was initiated and implemented?
An initial prototype of the microscope was developed at the Toulouse facility (LICT Core facility). This innovative approach quickly generated strong interest among research teams in Rennes, leading to a project proposal in 2020 to establish the system locally. However, due to limited personnel availability in Toulouse, a funding application was submitted to France-BioImaging in 2023 to support the full transfer and optimization of the technique in Rennes.
What were the main steps involved in setting up the RIM system at MRic?
We first assembled the prototype and acquired the required optical components. The setup was carried out by Gilles Le Marchand, co–first author of the study1. We then ensured proper alignment and optimized the system to achieve high-quality speckle illumination. I subsequently developed the system’s metrology and prepared a user manual so that biologists could operate it independently. Finally, the system was validated in collaboration with research teams using their own biological samples.
Which aspects of the system proved to be the most challenging to reproduce in a core facility environment?
Optimization was the most challenging stage. During this phase, Gilles and I worked closely together: I evaluated the system from a biological perspective, while he, as the optics specialist, fine-tuned the setup to achieve the highest possible illumination quality.
What does this technology bring to the platform’s users?
This technology enables users to perform super-resolution imaging on living organisms, something that was previously impossible on this platform at this acquisition speed.
How do you support users in getting started with the system, both for acquisition and reconstruction?
Core facility engineers provide training on the system, covering both the use of the microscope and the reconstruction process. A user manual is always available to help users get started with the system. Afterward, the engineers remain available to assist users in optimizing the acquisition and reconstruction parameters for their samples.
Why is it important to share and pool innovations across imaging platforms?
The goal is to enable as many biologists as possible to address their research questions by drawing on the technical and technological expertise of the platform engineers.
Do you see potential developments toward other modalities?
RIM is highly compatible with multimodal approaches.
It can be combined with:
- multi-color imaging
- 3D acquisition
- time-resolved imaging (xyzt)
These perspectives open the door to increasingly rich and comprehensive datasets, bridging spatial and temporal scales.
(1) Soler, N., L. Marchand, G., Dutertre, S., et al. 2026. “Implementation and Optimization of a Random Illumination Microscope: towards Robustness for Microscopy Core Facility.” Biology of the Cell118, no. 3: e70060. https://doi.org/10.1111/boc.70060
