Electrical engineers at the University of California San Diego have developed a technology that improves the resolution of an ordinary light microscope so that finer structures and details in living cells can be observed directly.

The technology turns a conventional light microscope into a so-called super-resolution microscope. It’s a specially developed material that shortens the wavelength of light when it illuminates the sample – this shrunken light essentially enables the microscope to image with higher resolution.

“This material converts low-resolution light into high-resolution light,” says Zhaowei Liu, professor of electrical and computer engineering at UC San Diego. “It’s very simple and easy to use. Simply place a sample on the material and then place the whole thing under a normal microscope – no complex modifications required. “

The work that is in. has been published Nature communication, overcomes a major limitation of conventional light microscopes: low resolution. Light microscopes are useful for imaging living cells, but they cannot be used to see anything smaller. Conventional light microscopes have a resolution limit of 200 nanometers, which means that objects closer than this distance are not viewed as separate objects. And while there are more powerful tools like electron microscopes that have the resolution to see subcellular structures, they cannot be used to image living cells because the samples must be placed in a vacuum chamber.

“The biggest challenge is to find a technology that has a very high resolution and is also safe for living cells,” said Liu.

The technology developed by Liu’s team combines both properties. It can be used to image living subcellular structures with a conventional light microscope with a resolution of up to 40 nanometers.

The technology consists of a slide coated with a type of light-shrinking material called hyperbolic metamaterial. It consists of nanometer-thin alternating layers of silver and quartz glass. As light penetrates, its wavelengths shorten and scatter to create a series of random high resolution speckle patterns. When a specimen is mounted on the slide, this series of speckled light patterns illuminate it in different ways. This creates a series of low resolution images, all of which are captured and then stitched together by a reconstruction algorithm to produce a high resolution image.

The researchers tested their technology using a commercial inverted microscope. They were able to image fine features such as actin filaments in fluorescently labeled Cos-7 cells – features that are not clearly visible with the microscope itself. The technology also enabled researchers to clearly distinguish tiny fluorescent spheres and quantum dots spaced 40 to 80 nanometers apart.

Super-resolution technology has great potential for high-speed operation, the researchers said. Their goal is to integrate high speed, super resolution and low phototoxicity into one system for imaging living cells.

Liu’s team is now expanding the technology to create high-resolution images in three-dimensional space. This current paper shows that the technology can produce high resolution images in a two-dimensional plane. Liu’s team previously published a paper showing that this technology is also capable of imaging with ultra-high axial resolution (around 2 nanometers). Now they are working on combining the two.


Title of the article: “Metamaterial Assisted Illumination Nanoscopy via Random Super-Resolution Speckles”. Co-authors are: Yeon Ui Lee *, Junxiang Zhao *, Qian Ma *, Larousse Khosravi Khorashad, Clara Posner, Guangru Li, G. Bimananda M. Wisna, Zachary Burns and Jin Zhang, UC San Diego.

* These authors contributed equally to this work

This work was supported by the Gordon and Betty Moore Foundation and the National Institutes of Health (R35 CA197622). This work was done in part on the San Diego Nanotechnology Infrastructure (SDNI) of UC San Diego, a member of the National Nanotechnology Coordinated Infrastructure supported by the National Science Foundation (Grant ECCS-1542148).


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