Thermal microscopy investigates individual living cells

30 Dec 2015

French heat-mapping project can detect and identify various disease conditions.

Researchers in France have adapted active thermography camera technology, which enables night-vision equipment and the thermal imaging of buildings, for example, to create a thermal microscope that produces “heat maps” of single cells. This process helps in the understanding of the thermal behavior of the cells and could be used to detect diseased conditions at the sub-cell scale, they say. The work has just been reported in Applied Physics Letters.

Thermal properties of cells regulate their ability to store, transport or exchange heat with their environment. So gaining control of these properties is of great interest for optimizing cryopreservation -- the process of freezing and storing blood or tissues, which is also used when transporting organs for transplants. Cell activity influences thermal properties, and at the tissue level this explains why infected wounds feel warm to the touch. Cancer cells, in particular, contain a thermal signature that reflects a higher metabolism than those of healthy cells. This feature is useful for grading tumors and can be used to complement classical histological analysis.

The research team, led by the University of Bordeaux, said, that the first step of their work involved growing cells on top of a nanometric titanium sheet. Titanium was selected because it is the main constituent of bone implants. Thomas Dehoux, a researcher at CNRS, the French National Centre for Scientific Research, commented, “We flash heat the titanium sheet by only a few degrees with a micrometric laser spot. We heat this spot to image the temperature variations on the bottom side of the sheet. If there is no cell on the other side, the heat remains in the titanium sheet and the temperature increases.” Conversely, if there is a cell on the other side it will absorb heat and create a cold spot on the sheet.

The temperature variations involved are quite small and occur on a tiny micron-sized spot so the researchers cannot rely on a standard thermometer. Instead, they measure the titanium sheet's deformation upon heating, by thermo-optical means.

Thermal camera + laser sensing

"When the temperature is high – without a cell present on the reverse side – the metal sheet dilates locally and creates a bump,” said Dehoux. “When the temperature decreases, indicating that a cell has been probed – then the sheet's profile returns to normal. We arre able to detect this effect with a second laser beam that's deflected by the movement of the lower surface, which gives us unprecedented sensitivity.”

Each part of the cell absorbs heat differently, due to the inhomogeneities in its thermal properties. "This allows us to see through the metal sheet and produce a thermal image of the cell," Dehoux added.While many existing modalities exploit differences in optical properties to image cells, most use fluorescent marking to increase contrast. Such images reveal the structure and molecular composition of the cell, but provide no useful details about its thermal properties.

The significance of the team's model is that it provides an image of a single cell with micrometer resolution via a contrast based on the cell's thermal properties. "Before now, no such image has ever been produced -- it's like looking at cells with night-vision goggles," said Dehoux. In terms of wider applications, the team expects that the technique can serve as a new tool to perform histological analysis and detect diseased cells within samples of human patient tissue. "It might also reveal new information about the behavior of cells because we will be able to observe them with greater contrast," said Dehoux.

What's next for the team? Since this is the first time images of this nature have been produced, the technique could benefit from further optimization. “In particular, we want to improve its acquisition time and sensitivity to enable observation of cells in real time,” said Dehoux. "We would also like to test the effect of anti-cancer drugs on the thermal properties of cells to see if new thermal strategies can be defined to stop cancer."

About the Author

Matthew Peach is a contributing editor to optics.org.