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MIT Scientists Work Out How To Shrink Objects 1,000 Times Smaller

A few years ago scientists came up with a technique known as expansion microscopy. It involves embedding tissue into a hydrogel and then expanding it to allow for high-resolution imaging with a regular microscope. They thought up the technique in order to do high-resolution imaging of brain tissue; and now, hundreds of research groups in biology and medicine are using expansion microscopy. It became such a popular method because it enables 3-D visualization of cells and tissues by using ordinary hardware.

The same scientists decided to adapt this technique, but this time to shrink things instead of enlarging them. The experiment proved successful as they were able to create large-scale objects, then embed them in expanded hydrogels, and shrink them to the nanoscale. They termed this reverse process ‘implosion fabrication’.

“It’s a way of putting nearly any kind of material into a 3-D pattern with nanoscale precision,” says Edward Boyden, the Y. Eva Tan Professor in Neurotechnology and an associate professor of biological engineering and of brain and cognitive sciences at MIT. He and graduate students Daniel Oran and Samuel Rodriques worked on this project together then wrote a research paper detailing the study in the Dec. 13 issue of Science. Boyden is also a member of MIT’s Media Lab, McGovern Institute for Brain Research, and Koch Institute for Integrative Cancer Research.

“People have been trying to invent better equipment to make smaller nanomaterials for years, but we realized that if you just use existing systems and embed your materials in this gel, you can shrink them down to the nanoscale, without distorting the patterns,” Rodriques says.

This is certainly a “thinking outside the box” idea. To produce three-dimensional objects at very small scales with precision is one of the most difficult things for engineers. Implosion fabrication is a brilliant solution from another angle. Instead of making something small, just make it big then shrink it! The system produces 3-D structures one-thousandth the size of the originals.

Implosion fabrication relies on shrinking a pre-made scaffold structure. To do so, a highly absorbent polyacrylate, commonly used in disposable nappies, is used to create a larger sized scaffold of the structure they want to fabricate. Within this solution is fluorescein. Next, a laser is used to bind the fluorescein molecules to the polyacrylate scaffold. To do so they use two-photon microscopy because it allows for precise targeting of points deep within a structure; thus enabling the fluorescein molecules to be attached to specific locations within the gel.

Those molecules are now like anchor points for whatever material the researchers wanted to shrink to the nanoscale. “You attach the anchors where you want with light, and later you can attach whatever you want to the anchors,“ researcher Edward Boyden said in an MIT news release. “It could be a quantum dot, it could be a piece of DNA, it could be a gold nanoparticle.“ Then an acid is used to dehydrated the polyacrylate scaffold which causes the material attached to the polyacrylate to shrink in an even way to a thousandth of its original size.

“It’s a bit like film photography — a latent image is formed by exposing a sensitive material in a gel to light. Then, you can develop that latent image into a real image by attaching another material, silver, afterwards. In this way implosion fabrication can create all sorts of structures, including gradients, unconnected structures, and multi-material patterns,” Oran says.

The best part about all this is that the technique uses equipment that many biology and materials science labs already have, making it widely accessible for researchers who want to try it. “With a laser you can already find in many biology labs, you can scan a pattern, then deposit metals, semiconductors, or DNA, and then shrink it down,” Boyden says.

The researchers are very excited about this discovery saying they see no limit to the technique’s possible applications. From optics to medicine to robotics, the possibilities for use of implosion fabrication span many fields. “There are all kinds of things you can do with this,” Boyden said. “Democratizing nanofabrication could open up frontiers we can’t yet imagine.”

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