New High-Speed 3D Microscope—SCAPE—Gives Deeper View of Living Things

Microscopy system is faster, simpler, and cheaper

Opening new doors for biomedical and neuroscience research, Elizabeth Hillman, associate professor of biomedical engineering at Columbia Engineering and of radiology at Columbia University Medical Center (CUMC), has developed a new microscope that can image living things in 3D at very high speeds. In doing so, she has overcome some of the major hurdles faced by existing technologies, delivering 10 to 100 times faster 3D imaging speeds than laser scanning confocal, two-photon, and light-sheet microscopy. Hillman’s new approach uses a simple, single-objective imaging geometry that requires no sample mounting or translation, making it possible to image freely moving living samples. She calls the technique SCAPE, for swept confocally aligned planar excitation microscopy. Her study is published in the Advance Online Publication (AOP) on Nature Photonics’s website on January 19, 2015.

“The ability to perform real-time 3D imaging at cellular resolution in behaving organisms is a new frontier for biomedical and neuroscience research,” says Hillman, who is also a member of Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute. “With SCAPE, we can now image complex, living things, such as neurons firing in the rodent brain, crawling fruit fly larvae, and single cells in the zebrafish heart while the heart is actually beating spontaneously—this has not been possible until now.”

Highly aligned with the goals of President Obama’s BRAIN Initiative, SCAPE is a variation on light-sheet imaging, but, “It breaks all the rules,” says Hillman. While conventional light-sheet microscopes use two awkwardly positioned objective lenses, Hillman realized that she could use a single-objective lens, and then that she could sweep the light sheet to generate 3D images without moving the objective or the sample. “This combination makes SCAPE both fast and very simple to use, as well as surprisingly inexpensive,” she explains. “We think it will be transformative in bringing the ability to capture high-speed 3D cellular activity to a wide range of living samples.”

SCAPE is an urgently needed breakthrough.

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