The study was published in the journal Nature Communications.
This technology turns traditional light microscopes into so-called ultra-resolution microscopes. It incorporates a specially designed material that shortens the wavelength of light while illuminating the sample – it is this shrinking light that essentially allows the microscope to take images at higher resolutions. “This material converts low-resolution light into high-resolution light,” said Zhaowei Liu, professor of electrical and computer engineering at the University of California, San Diego. “It is very simple and easy to use. Just place the sample on the material, then place it all under a normal microscope – no complicated adjustments required.”
The work overcomes a significant limitation of conventional light microscopy: low resolution. Optical microscopes are useful for imaging living cells, but they cannot be used to see anything smaller. Conventional optical microscopes have a resolution limit of 200 nanometers, which means that any object close to this distance will not be observed as a separate object. And although there are more powerful instruments, such as electron microscopes, that can accurately see subcellular structures, they cannot be used to image living cells because the sample must be placed in a vacuum. “The main challenge is to find a technology that is high resolution and also safe for living cells,” Liu said.
The technology developed by Liu’s team combines both features. With it, conventional optical microscopy can be used to image living subcellular structures at a resolution of up to 40 nm. This technique consists of microscopic slides covered with a type of light-retracting material called a hyperbolic metamaterial. It consists of a nanometer-thick layer of silver and silica glass. As light passes, its wavelengths shorten and scatter to produce a series of high-resolution, random grainy patterns.
When a sample is mounted on a slide, it is illuminated in various ways by this series of highlight patterns. This creates a series of low-resolution images, all of which are captured and then combined with a reconstruction algorithm to produce a high-resolution image. The researchers tested their technology using a commercial inverted microscope. They were able to depict tiny features, such as actin filaments, in fluorescence-labeled Cos-7 cells—features that could not be clearly distinguished using the same microscope. The technique also allows the researchers to clearly distinguish between tiny fluorescent beads and quantum dots that are 40 to 80 nanometers apart.
The researchers say the ultra-fine technology has great potential for high-speed operation. Their goal is to combine high speed, ultra-high resolution, and low phototoxicity into a single live cell imaging system. Liu’s team is now extending the technology to perform high-resolution imaging in 3D space. The current paper demonstrates that this technique can produce high-resolution images in a two-dimensional plane. Liu’s team previously published a paper showing that the technology is also capable of imaging at very high axial resolution (about 2 nanometers). They are now working to bring the two together.
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