Tiny mirrors enable MEANS microscopy

Examining cell structures that are just a fraction of a micrometre in size has long proved difficult, but an international team of researchers has developed a unique new way of looking inside cells using tiny mirrors.

According to Professor Dayong Jin, from the University of Technology Sydney, “This simple technology is allowing us to see the details of cells that have never been seen before.”

The problem has been achieving workable microscope resolution in the z-axis, which has traditionally been inferior to the resolution achievable in the x- and y-axes. The team’s answer has been to grow cells on mirrors, rather than glass slides, and image them using super-resolution microscopy. The mirror allows the researchers to create interference patterns as light waves pass through the cell and are then reflected back. These interference patterns allow for a vast improvement in z-axis resolution.

“A single cell is about 10 micrometres, inside that is a nuclear core about 5 micrometres, and inside that are tiny holes, called ‘nuclear pore complex’, that as a gate regulates the messenger biomolecules, but measure between one-fiftieth and one-twentieth of a micrometre,” explained Professor Jin. “With this super-resolution microscopy, we are able to see the details of those tiny holes.’

Getting a better view of how these micron-scale structures behave and communicate is a great leap forward, according to Peking University’s Professor Peng Xi.

“Previously, the vision of biologists was blurred by the large axial and lateral resolution,” he said. “This was like reading newspapers printed on transparent plastic; many layers were overlapped. By placing a mirror beneath the specimen, we can generate a narrowed focal spot so there is only one layer of the newspaper to read, so that every word becomes crystal clear.”

The task of adapting existing biological techniques to grow cells on tiny custom-made mirrors fell to Professor Phil Santangelo from Georgia Tech and Emory University, with help from graduate students Eric Alonas and Hao Xie. The team has dubbed their new technique ‘MEANS (mirror-enhanced, axial-narrowing, super-resolution) microscopy’.

The development of MEANS microscopy was reported in the journal Light: Science & Applications.

Image credit: Vanessa Valenzuela Davie.