Holographic Nanoscale Microscopy Allows Watching Living Cells in 3D

Real time observation, of living cells, in 3D, and at the nanoscale - this are the incredible and groundbreaking features of a new holographic microscopy prototype developed by two young scientists at the Swiss Technology University EPFL.

In the world of microscopy, "this advance is almost comparable to the leap from photography to live television." Going beyond conventional microscopes by using a low-intensity laser for scanning combined with advanced computational image processing, it can acquire images of living cells in just a minute (and becoming much faster still as it is further developed) at a resolution of less than 100 nanometers — without using contrast dyes or fluorescents, to avoid distortion by the presence of foreign substances.

Being able to capture a living cell from every angle like this lays the groundwork for a whole new field of investigation. “We can observe in real time the reaction of a cell that is subjected to any kind of stimulus,” explains researcher Yann Cotte.

By making a film of a growing neuron and the birth of a synapse, caught over the course of an hour at a rate of one image per minute, the two young researcher demonstrated the potential of their method and managed to be featured in an editorial in the prestigious journal Nature Photonics. This work was carried out in collaboration with the Neuroenergetics and cellular dynamics laboratory in EPFL’s Brain Mind Institute, directed by Pierre Magistretti.

“Because we used a low-intensity laser, the influence of the light or heat on the cell is minimal. Our technique thus allows us to observe a cell while still keeping it alive for a long period of time.”continues Cotte. "This opens up all kinds of new opportunities, such as studying the effects of pharmaceutical substances at the scale of the individual cell, for example.”

As the laser scans the sample, numerous images extracted by holography are captured by a digital camera, assembled by a computer and “deconvoluted” to eliminate noise.

Afterwards, the assembled three-dimensional image of the cell can be virtually “sliced” to expose its internal elements, such as the nucleus, genetic material and organelles.

The researchers, who are already creating their startup tech company, have high ambitions and aim to develop their system to the point where it could deliver these kinds of observations in vivo, without the need for removing tissue, using portable devices.

Paper:
Yann Cotte et al., Marker-free phase nanoscopy, Nature Photonics, 2013, DOI: 10.1038/nphoton.2012.329