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Researchers Overcome Longstanding Challenges in Microscopy

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Researchers at Delft University of Technology have made a significant advance in light microscopy, addressing a long-standing issue of sample distortion in biological imaging. Traditionally, scientists believed that the distortion—where samples appear flatter than their true shape—was a constant factor. However, this new study demonstrates that the distortion is actually depth-dependent, confirming a prediction made by Nobel laureate Stefan Hell in the 1990s. The research team, including PhD candidate Daan Boltje and postdoc Ernest van der Wee, developed a web tool that allows researchers to calculate the correct depth of biological samples accurately, countering the previous assumptions based on a constant scaling factor.

When viewing samples, light rays are disturbed depending on their medium, causing depth measurements to appear smaller. The new calculations and experiments indicate that this effect intensifies closer to the lens. The web tool enables users to input specific experimental parameters to obtain a depth-dependent scaling factor, allowing for more precise analysis of proteins and other biological structures. This enhanced precision reduces time and costs in complex microscopy studies, ultimately aiding in the understanding of abnormalities and diseases by allowing researchers to focus on correctly targeting relevant proteins.

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