Light microscopes use the visible light spectrum passed through magnifying lenses to capture images of specimens. They are especially useful in biological research because you can see details without destroying specimens and can be used to image live specimens. Maintaining the cellular structure of those specimens, however, has been a challenge.
The best way to preserve cellular structures is to fast-freeze the specimens and maintain their frozen state at a temperature below -140°C, also known as cryogenic conditions. Conventional high-resolution imaging uses liquid immersion objective lenses – a lens coated in fluid, changing the way light travels through it. But the liquid on the lens freezes in these conditions and the high resolution images cannot be achieved.
CLF researchers led by Lin Wang and Marisa Martin-Fernandez found a different kind of lens that allowed them to increase the resolution of their images to the best yet achieved in this kind of microscopy. The lenses – known as superSILs – are ball-shaped with a flat edge, slightly thicker than the radius of the ball. These combined with standard dry lenses mean that specimens can be preserved cryogenically and result in images with a high level of detail at the sub-cellular level.
They zoomed in on the detail of the images even further by marking specific proteins in bacterial samples with fluorescent stains. This high precision imaging could reveal more about the relationship between the architecture of the cells and its proteins.
The new technique is a simple and inexpensive way of investigating cell biology, and even uses off-the-shelf components that could be used in any non-specialist laboratory. But it also brings light microscopy closer to the revealing the level of detail usually achieved with electron microscopy. Scientists may be able to combine the two to look at cells and study molecular structures and functions in even greater detail.
The more we know about these kinds of biological specimens, the more we can learn about how microbes develop resistance to drugs, potential biological sources of new drugs, and even about how to design and construct biological parts, devices and systems.