Using a conventional light microscope, engineers at the Massachusetts Institute of Technology (MIT) have developed a method for imaging biological samples with an accuracy of 10 nanometers.
A new low-cost imaging method from MIT engineers will allow scientists to image viruses and possibly even individual biomolecules. It is based on expansion microscopy. This approach involves embedding biological samples in a hydrogel and then expanding them before being visualized with a microscope. For a new imaging method, researchers have developed a new type of hydrogel. Its peculiarity is that it supports a more uniform configuration. In turn, this allows tiny biological structures to be displayed with greater accuracy.
This degree of precision will help in the study of the basic molecular interactions that make life possible, explains Edward Boyden, a professor at MIT.
Laboratories around the world have started using expansion microscopy since Boyden’s lab first introduced it in 2015. With this technique, researchers physically enlarge their samples to about four times their linear size before rendering them. This allows them to create high-resolution images without expensive equipment.
In a paper published in 2017, Boyden’s lab demonstrated a resolution of about 20 nanometers using a process in which samples were expanded twice before imaging. This approach, as well as earlier versions of expansion microscopy, are based on an absorbent polymer made from sodium polyacrylate. These gels swell when exposed to water. However, one of their critical limitations is that they are not completely uniform in structure or density. This unevenness leads to slight distortion of the sample shape during its expansion, which limits the achievable accuracy.
To overcome this, MIT has developed a new gel, tetragel, which forms a more predictable structure. By combining tetrahedral molecules of polyethylene glycol with tetrahedral sodium polyacrylates, scientists were able to create a lattice structure. It is much more homogeneous than the free radical-synthesized sodium polyacrylate hydrogels previously used.
Scientists have demonstrated the accuracy of the new imaging approach by using it to expand particles of herpes simplex virus type 1 (HSV-1). They have a characteristic spherical shape. After expanding the viral particles, the researchers compared the shapes to the shapes obtained using electron microscopy. It turned out that the distortion was much lower than in previous versions of expanding microscopy. This made it possible to achieve an accuracy of about 10 nanometers.