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Courtesy of Allen Institute (file doc)

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Using technology originally designed for defect detection in electronics manufacturing, scientists have built a one-of-a-kind microscope for capturing brain images at incredible resolution.

Known as the 'ExA-SPIM' microscope, its ability to provide unprecedented details could advance our understanding of the brain's enigmatic structures and neurological functions.

Recent advances in tissue processing, labeling, and fluorescence microscopy offer exceptional insights into cell and tissue structures at sub-diffraction resolutions and near single-molecule sensitivity.

It's advancements like these that keep on driving discoveries in various biological fields, including neuroscience.

That said, to enable molecular imaging across three-dimensional samples across the scales biological tissues exhibit —nanometers to centimeters— new microscopes with larger fields of view and higher imaging throughput are required.

A higher imaging throughput means the system can acquire images more quickly, allowing more data to be generated and analyzed in a shorter period.

With this context in mind, Adam Glaser, Ph.D., and his colleagues at the Allen Institute in Seattle, U.S., created a new expansion-assisted selective plane illumination microscope (ExA-SPIM).

Essentially, the microscope utilizes a plane of laser light to penetrate tissue samples, eliminating the need for cutting them into smaller sections.

Watch how the team put together ExA-SPIM in this time-lapse video:

The microscope produces images that allow scientists to examine individual neurons and their connections within the entire mouse brain, roughly the size of a jellybean and containing approximately 80 million neurons.

Impressively, they could image specific features, such as corticospinal neurons in the motor cortex of macaque monkeys and trace axons in human white matter.

The researchers utilized special fluorescent tags to highlight specific neurons for observation under the microscope.

Allen Institute/ YouTube

According to a press release, the new machine is "a kind of light-sheet microscope," an emerging technology that employs two-dimensional (2D) light planes to illuminate tissues or cells with remarkable precision.

In ExA-SPIM's case, these 2D images are stitched together to create a three-dimensional view of entire mouse brains.

Furthermore, the technology incorporates elements from the electronics manufacturing industry, including defect detection cameras. These cameras were originally designed to identify minute imperfections in LED chips on conveyor belts in electronics factories.

The result of this camera tech integration into the new microscope systems is high-resolution imaging at a rapid pace.

A study— yet to be peer-reviewed— highlighting the microscope's latest results was published in the preprint Biorxiv and can be found here.

Study abstract:

Recent advances in tissue processing, labeling, and fluorescence microscopy are providing unprecedented views of the structure of cells and tissues at sub-diffraction resolutions and near single molecule sensitivity, driving discoveries in diverse fields of biology, including neuroscience. Biological tissue is organized over scales of nanometers to centimeters. Harnessing molecular imaging across three-dimensional samples on this scale requires new types of microscopes with larger fields of view and working distance, as well as higher imaging throughput. We present a new expansion-assisted selective plane illumination microscope (ExA-SPIM) with diffraction-limited and aberration-free performance over a large field of view (85 mm2) and working distance (35 mm). Combined with new tissue clearing and expansion methods, the microscope allows nanoscale imaging of centimeter-scale samples, including entire mouse brains, with diffraction-limited resolutions and high contrast without sectioning. We illustrate ExA-SPIM by reconstructing individual neurons across the mouse brain, imaging cortico-spinal neurons in the macaque motor cortex, and tracing axons in human white matter.