High-speed microscope illuminates biology

The Columbia team behind the revolutionary 3D SCAPE microscope announces today a new version of this high-speed imaging technology. In collaboration with scientists from around the world, they used SCAPE 2.0 to reveal previously unseen details of living creatures -- from neurons firing inside a wriggling worm to the 3D dynamics of the beating heart of a fish embryo, with far superior resolution and at speeds up to 30 times faster than their original demonstration.

These improvements to SCAPE promise to impact fields as wide ranging as genetics, cardiology and neuroscience.

Although imaging samples using sheets of light date back more 100 years, SCAPE's ingenuity lies in the way that it rapidly moves the light sheet and focuses the image of this sheet back to a stationary camera using a single moving mirror -- making it lightning fast and surprisingly simple. In addition, SCAPE is gentle on living samples because it uses only a fraction of the light that point-scanning microscopes would need to get images at comparable speeds. SCAPE achieves all this through a single, stationary objective lens, opening up space for a wide array of samples compared to conventional light-sheet microscopes that require complex sample chambers surrounded by many lenses.

SCAPE 2.0's improved resolution also enabled the team to image samples created using tissue clearing and tissue expansion. These methods let scientists see structures and connections deep inside intact samples, from whole mouse brains to tumors and human biopsies. Although these samples are not alive, they are very large and take a long time to image using standard microscopes. Today's paper demonstrates that SCAPE 2.0 could image these types of samples at record-breaking speeds. The researchers worked with Lambert Instruments, leveraging the company's ultra-fast HiCAM Fluo camera. This camera was used to capture images at more than 18,000 frames per second in the zebrafish embryo's beating heart. This new configuration opened the door to recording individual neurons firing in a freely moving C. elegans worms, giving the first view of an animal's complete nervous system in action. SCAPE 2.0's other upgrades include improved light efficiency, a larger field of view and much improved spatial resolution.

See:

Venkatakaushik Voleti, Kripa B. Patel, Wenze Li, et al. Real-time volumetric microscopy of in-vivo dynamics and large-scale samples with SCAPE 2.0. Nature Methods, 2019 DOI: 10.1038/s41592-019-0579-4

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology