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Making tissue stretchable, compressible, and nearly indestructible

Chemical process called ELAST allows labeling probes to infuse more quickly, and makes samples tough enough for repeated handling

 

by David Orenstein

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A new technology called ELAST transforms tissues, such as this slab of human brain, to make them reversibly stretchable or compressible, as well as much more durable. This allows them to be repeatedly stretched out or squished down thin for much faster infusion of labeling probes, which labs use to highlight cells or molecules under the microscope.

Photo courtesy of the Chung Lab

When there’s a vexing problem to be solved, people sometimes offer metaphorical advice such as “stretching the mind” or engaging in “flexible” thinking, but in confronting a problem facing many biomedical research labs, a team of MIT researchers has engineered a solution that is much more literal. To make imaging cells and molecules in brain and other large tissues easier while also making samples tough enough for years of handling in the lab, they have come up with a chemical process that makes tissue stretchable, compressible, and pretty much indestructible.

“ELAST” technology, described in a new paper in Nature Methods, provides scientists a very fast way to fluorescently label cells, proteins, genetic material, and other molecules within brains, kidneys, lungs, hearts, and other organs. That’s because when such tissues can be stretched out or squished down thin, labeling probes can infuse them far more rapidly. Several demonstrations in the paper show that even after repeated expansions or compressions to speed up labeling, tissues snap back to their original form unaltered except for the new labels.

The lab of Kwanghun Chung, an associate professor of chemical engineering and a member of MIT’s Institute for Medical Engineering and Science, and Picower Institute for Learning and Memory, developed ELAST amid work on a five-year project, funded by the National Institutes of Health, to make the most comprehensive map yet of the entire human brain. That requires being able to label and scan every fine cellular and molecular detail in the thickest slabs possible to preserve 3D structure. It also means the lab must be able to keep samples perfectly intact for years, even as they must accomplish numerous individual rounds of labeling quickly and efficiently. Each round of labeling — maybe a particular kind of neuron one day, or a key protein the next — will tell them something new about how the brain is structured and how it works.

“When people donate their brain, it is like they are donating a library,” says Chung. “Each one contains a library worth of information. You cannot access all the books in the library at the same time. We have to repeatedly be able to access the library without damaging it. Each of these brains is an extremely precious resource.”

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By growing photo-sensitive nanowires in the aluminum membrane of their artificial retina, researchers were able to closely mimic a biological human eye.Hongrui Jiang/Nature

If human eyes are the window to the soul, then what lies inside robotic eyes?

While scientists behind new research in biomimetic eyes may not be interested in the soul of their creation, improvements in robotic eyes could bring them closer than ever to their biological counterparts.

 

By embedding light-sensitive receptors directly into the surface of a 3D sphere the researchers could design robotic eyes with a sensitivity much closer to that of biological human eyes.

 

The researchers also gave these robotic eyes an upgrade, making them even quicker to react to light and potentially even better at resolving images than the real deal. Say goodbye to blind spots.

In research published Wednesday in the journal Nature, researchers describe why the human eye is such a sought-after target.

 

"Biological eyes are arguably the most important sensing organ for most of the animals on this planet. In fact, our brains acquire more than 80 percent of information about our surroundings via our eyes," write the authors. "Particularly, the domed shape of the retina has the merit of reducing the complexity of optical systems by directly compensating the aberration from the curved focal plane. Mimicking human eyes, artificial vision systems are just as essential in autonomous technologies such as robotics."

The work was done by scientists at the Hong Kong University of Science and Technology, UC Berkeley, and the Lawrence Berkeley National Laboratory.

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