Lenses with mirrors instead of lenses: Researchers have developed novel microscope lenses for sophisticated insights into the microcosm. They used astronomical telescopes and the eyes of scallops as models. Since the innovative mirror lenses can "see clearly" in different media, they could advance a fascinating microscopy technique: They deliver high-resolution images of tissues embedded in liquid that have been made transparent by various substances.
The insights into the fascinating structures of tissues, nerves and other wonders of the microcosm are becoming ever more detailed. In light microscopy, lenses are still used, which are composed of many lenses in order to achieve the magnification effects. The top-of-the-range devices contain up to 15 such units made of different types of glass, which are polished and precisely aligned to produce the performance. Of course, this top optical technology has its price: the value of a lens in research microscopes can correspond to that of a mid-range car. In addition, an assortment of different lenses is often necessary. As a rule, a lens is only suitable for a specific so-called immersion medium in which the examination object is located. A different lens is required for air, water or oil, for example.
Insights into structures made transparent
However, the importance of this aspect has increased significantly in recent times. Because so-called clearing methods, which require certain immersion media to make tissue samples transparent, have found their way into research. This technique makes it possible, for example, to make larger nerve structures or pieces of tumor transparent as a whole and thus examine them. In pathology, "cleared" biopsy samples could make malignant tissue changes detectable earlier. So far, however, the concept has not been able to fully develop its potential, since most clearing methods require immersion media that are not compatible with conventional microscope lenses. In short: the development of more adaptable and cheaper lenses is in demand.
The researchers led by Fabian Voigt from Harvard University in Cambridge have dedicated themselves to this challenge. As they report, they found inspiration in nature - and precisely in creatures that most people would probably consider blind: mussels. But some species, like the scallop, use a whole set of pinpoint eyes to detect approaching predators. The highlight: They contain unusual biological technology. While in us the combination of cornea and lens creates an image on the retina, in scallops a hemispherical mirror focuses the light onto the sensitive cell tissue.
Miniaturized telescopes as lenses
In principle, this system is not new to the technology: the generation of images with mirrors instead of lenses is widespread in astronomical telescopes. The so-called "Schmidt telescope", which was developed in the 1930s and is still used in many observatories today, uses a large spherical mirror to focus the light from the cosmos. The system is only combined with a thin correction lens. This in turn means that scallops use tiny Schmidt telescopes to look through the liquid medium of their habitat in a certain way. So the scientists came up with the idea of converting this into a lens concept for microscopy.
Specifically, the approach was to fill a Schmidt telescope with a liquid immersion medium and then shrink it down to a small format so that it could be inserted into a microscope. This is exactly what the team apparently succeeded in doing, as the tests of their prototype showed. The innovative lens is ultimately a miniature Schmidt telescope: a mirror is used instead of lenses and only one correction lens is required. The spherical mirror focuses the light in the same place, regardless of whether the object is in the air or in special liquids. "It is possible to design this concept in such a way that it delivers excellent image quality in any homogeneous liquid and also in air. This makes it compatible with many different clearing techniques,” says Voigt.
To demonstrate the potential, the scientists examined a large number of samples with the lens prototype. For example, they were able to display cleared mouse brains, tadpoles, chicken embryos and human brain samples.
"In all cases, the image quality was equivalent or even better than with conventional lenses - even though the new lens consists of only two optical elements," says senior author Fritjof Helmchen from the University of Zurich. "Compared to classic lenses, which have around a dozen more lenses, it can therefore be manufactured much more cheaply," he emphasizes. "Ultimately, the scallops could have shown us the way to improved medical diagnostics," concludes Helmchen.
Source: University of Zurich, specialist article: Nature Biotechnology, doi: https://www.nature.com/articles/s41587-023-01717-8