Mussel eyes as a model for new microscope objectives [1]

Neuroscientists at the University of Zurich have developed innovative lenses for light microscopy that use mirrors instead of lenses. They were inspired by astronomical telescopes on the one hand and the eyes of scallops on the other. This is because some species of shellfish can see. Scallops, for example, have up to 200 eyes, which help them to recognize predators such as approaching starfish. However, the scallop eye differs considerably from the human eye. While in humans the combination of cornea and lens creates an image on the retina, in scallops a hemispherical mirror focuses the light.

Generating images with mirrors instead of lenses is particularly common in astronomical telescopes in order to capture as much light as possible from planets, stars and galaxies. In the "Schmidt telescope", which was developed in the 1930s by Bernhard Schmidt (1879-1935) and is still used in many observatories today, a thin corrective lens is combined with a large spherical mirror.

In the study of the biological microcosm, mirror objectives are rarely encountered. Most microscope objectives are so compact that they can easily be assembled from many lenses. For the highest image quality, 10 to 15 lenses made of different types of glass are required, which must be precisely polished and accurately aligned. Such lenses are therefore very expensive.

In addition to their complex structure, many commercial lenses have the disadvantage that they are usually only designed for a specific immersion medium such as air, water or oil. A new objective must therefore be purchased for samples in different immersion media. In recent years, so-called clearing methods, which can make tissue samples transparent, have aroused great interest in biology and pathology: instead of laboriously cutting a mouse brain into extremely thin slices, for example, it can be made transparent as a whole with the aid of clearing techniques. In pathology, the hope is that clearing will allow biopsy samples to be examined more efficiently in order to diagnose malignant tissue changes such as tumors earlier. Unfortunately, however, most clearing techniques use immersion media that are not compatible with conventional microscope objectives. Significant advantages of clearing for research therefore remain partially unused.

UZH neuroscientist and amateur astronomer Dr. Fabian Voigt realized that it is possible to fill a Schmidt telescope with a liquid immersion medium and shrink it to the size of a microscope [2]. The resulting "Schmidt objective" is thus a miniature telescope, so to speak, that has been placed under water and still delivers a sharp image. It can deliver excellent image quality in any homogeneous liquid and also in air. This means that a single Schmidt objective is compatible with many different clearing techniques. The reason for this unusual property is that a mirror is used instead of lenses and the corrective lens is specially adapted. A spherical mirror focuses the light at the same point, regardless of whether it is immersed in liquid or in the air.

Researchers have used the Schmidt lens to examine prototype samples of mouse brains, tadpoles and chicken embryos. Cleared human brain samples were also analyzed and neuronal activity was measured in the brains of young living zebrafish larvae. With equivalent or better image quality, such microscope objectives are less expensive than conventional ones.

Literature

[1] www.uzh.ch
[2] Fabian Voigt et al.: Reflective multi-immersion microscope objectives inspired by the Schmidt telescope, Nature Biotechnology, March 30, 2023, Doi: s41587-023-01717-8