Tech Compare: Light Sheet vs. Super Resolution Microscopy for Live-cell Imaging

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Hepatocyte spheroid, imaged with Lightsheet Z.1. Image cropped. Credit: ZEISS Microscopy via Flickr Commons, CC BY-NC-ND 2.0. Sample courtesy of TNG Weiquan John, Ng Huck Hui, Genome Institute of Singapore. Original Image

Live-cell imaging enables researchers to observe the intricate dynamic changes that are essential to the development and function of organisms, observations that can ultimately lead to a better understanding of human health and disease, and aid in the development of effective therapies for cancer, autoimmune disease, cardiovascular disease, neurological disorders and more. Live cell imaging comes with unique challenges compared with imaging of fixed and cleared biological samples, including the need for high temporal resolution and methods that minimize toxicity to the sample, including phototoxicity.

Two microscopy techniques that have grown popular for live-cell imaging in recent years are light sheet fluorescence microscopy (LSFM) and super resolution microscopy, each offering their own advantages over other techniques like standard wide-field fluorescence microscopy and confocal microscopy. Each of these techniques also involve their own limitations and technological requirements that must be weighed when considering a method for your own live-cell imaging experiments. This article will provide summaries of both approaches to live-cell microscopy, highlight some of their key differences and help bring you a step closer to understanding which method is best suited for your specific application.

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