The slide that will revolutionize fluorescence microscopy
Scientists at EPFL Neuchâtel have developed a new type of slide for fluorescence microscopy. They can increase the amount of light obtained by up to 25 times compared with conventional slides. Capable of amplifying and directing light, these slides target a wide range of applications, from early diagnosis to high-speed archiving of pathology samples.
For scientists, the transparent glass slides on which samples are placed for microscopic observation are practically part of our heritage. And with good reason: this microscopic element has remained virtually unchanged for almost 200 years.
Researchers at EPFL's Institute of Microtechnology in Neuchâtel have come up with an alternative. They have developed a new type of slide whose coating "structures" the light, thereby increasing the sensitivity of the microscope by up to 25 times.
This technology is designed for fluorescence microscopy, widely used, for example, in the diagnosis of cancers, autoimmune diseases, allergies and DNA sequencing. Thanks to its optical capabilities, the slide can detect very small amounts of light. This makes it possible to make early diagnoses, identify cancer subtypes more quickly, or archive pathology samples at high speed. "In an ideal situation, we could detect the presence of a single molecule on one of our slides, where 25 would be needed on a standard slide", illustrates researcher Nicolas Descharmes.
The technology has been patented, and the blades have already been successfully used by scientists in various fields. They are also about to be tested by several companies. The researchers have received support from EPFL, the Gebert Rüf Foundation and Innosuisse. They plan to create a start-up in the coming months. This will enable them to enter the industrial development phase and make the technology available to hospital laboratories and diagnostic suppliers.
Recover 100% of light and more
Fluorescence microscopy is based on the physical property of certain molecules - known as fluorophores - to emit light at a certain wavelength (known as the emission wavelength) in response to the absorption of light of a shorter wavelength (known as the excitation wavelength). Fluorescence enables the visualization of elements (naturally fluorescent or previously labeled with a fluorophore) that would otherwise be impossible to detect using standard microscopy.
Fluorescence microscopy on glass slides, however, has two main shortcomings. Firstly, the amount of light emitted by fluorophores is often low. Secondly, much of the light emitted by the sample is lost in the slide, making it unusable. As a result, it is sometimes difficult - if not impossible - to detect certain molecules, unless they are present in significant quantities.
An optical mille-feuille
Featuring a mille-feuille structure, this new slide has the ability to control the electromagnetic environment of the sample. In particular, it increases the amount of light emitted by the fluorophores and redirects all the light to the detector. The resulting images are therefore clearer than before, or can be acquired much more rapidly, as required.
"What I saw was extremely promising," says Séverine Lorrain, a collaborator at UNIL's Protein Analysis Facility, who works to detect proteins in samples. "I was clearly impressed by the efficiency of this surface, which amplifies the fluorescence signal. This could enable me to avoid, in my protocols, the signal amplification step, which often generates an increase in background noise."
Jessica Sordet-Dessimoz, head of the Histology Technology Platform at EPFL, agrees: "The surface of these slides improves visualization of the fluorescent signal and reduces the exposure time required. This could prove very useful for applications such as cyclic immunofluorescence."
Early diagnosis
The two researchers are targeting several key applications, such as the early identification of certain types of cancer, or simplifying the reading and archiving of histopathological slides - typically used for biopsy analysis. "At the moment, scanning traditional slides with fluorescence is extremely time-consuming, as the signals are weak. Our slides could clearly be useful in this field", assures Raphaël Barbey. He is currently working on industrializing the production of these slides with another Neuchâtel technology flagship - the CSEM (Centre Suisse d'Electronique et de Microtechnique).
"The challenge now is to get users to agree to swap some of their usual slides for our new ones," adds the researcher. In the field of fluorescence microscopy, slides have hardly ever evolved: "Almost every element of a microscope has been optimized, on a regular basis, over the last few decades. Light sources have become ever more powerful, cameras ever more sensitive and objectives ever better. Surprisingly, the slide is the forgotten element. What we are proposing represents a clear break with this constant evolution. The great appeal of our approach lies in the fact that it involves a relatively minor change for the user, but has a major impact on performance".
Nicolas Descharmes is currently employed by the Photovoltaics and Thin Film Electronics Laboratory (PV-Lab) at EPFL (Neuchâtel), while Raphael Barbey works at CSEM (Neuchâtel).
Author: Laure-Anne Pessina - Source: EPFL