EPFL brings structured illumination capability to standard microscopes

06 Mar 2024

Add-on module allows cheaper 3D super-resolution imaging of cells, organoids and embryos.

A project at Swiss research center EPFL has designed an add-on unit intended to bring structured light capability to a standard optical microscope.

Described in Nature Communications, the design principles behind the modification have been released in open-access format, allowing them to be applied to as many potential applications as possible.

Structured illumination microscopy (SIM) involves acquiring multiple images of a sample under different patterns of light, and computationally reconstructing a picture of the target.

Since the optical data is sourced from intensity variations in multiple dimensions, this reconstructed image can achieve a higher resolution than the diffraction limited capability of the observing system using basic illumination.

SIM has been applied in several bioimaging applications, such as the project at University of Colorado Boulder that applied the technique to mouse brain imaging and delivered the illumination patterns via a coherent fiber bundle in a miniaturized microscope. However, cost and availability constraints mean that SIM imaging remains out of reach for many applications.

EPFL aimed to develop a way to transform a standard optical microscope into a high-resolution SIM device using inexpensive, commercially available components. Building on previous EPFL work on more complex and cumbersome platforms, the projet aimed to design a compact SIM alternative suitable for non-experts to use without expensive upkeep and maintenance.

"We sourced electronic components of the kind used to make the video projectors you see in classrooms," said Georg Fantner from EPFL's Laboratory for Bio-and Nano-Instrumentation (LBNI). "We altered and arranged them, so they were capable of projecting a light pattern onto a sample."

Making super-resolution microscopy a daily tool

The team's "openSIM" add-on module includes high-power LEDs illuminating a liquid-crystal-on-silicon spatial light modulator (SLM), which generates the pattern to be projected on the sample. A software interface brings together on-the-fly control of pattern, illumination color and light intensity, according to EPFL's published paper.

In trials using bacteria, mouse intestinal organoids and zebrafish embryos, the openSIM was able to seamlessly integrate with existing complex microscopy systems, said EPFL, and improve the quality of microscopy images in terms of resolution and optical sectioning.

After a positive reception from researchers at EPFL who tested out the system, the LBNI team is now aiming to bring its work to a wider group of scientists and build a community of users to share their experiences.

"As the openSIM is a versatile tool with a well-documented assembly, simple maintenance, and linked to an open-source community, we believe that it has the potential to make super-resolution microscopy not only a cutting-edge technique but also a daily tool for biological research," commented EPFL.