Thermal Contrast Technique Reveals Cell Characteristics

A label-free technique based on a thermoelastic lens has been used to capture images of single cells with 2-μm resolution. The method could be used to perform histological analysis and for disease detection in tissue samples.

Researchers from the University of Bordeaux created the microscope system, which uses the thermal properties of cell samples as a contrast mechanism for imaging, much like the thermography cameras used in night vision goggles and for thermal imaging of buildings. Their goal was to produce heat maps of single cells, offering insight into the thermal behavior of the cells or even detecting disease conditions at the subcell scale.

On the top, a classical phase-contrast image of a cell obtained via a standard microscope. On the bottom, a thermal image of the same cell recorded with a thermal imaging device. Courtesy of the University of Bordeaux.

Thermal properties of cells regulate their ability to store, transport or exchange heat with their environment. Cell activity influences thermal properties; at the tissue level, this explains why infected wounds feel warm to the touch.

Cancer cells, in particular, contain a thermal signature that reflects higher metabolism than that of healthy cells. This feature is useful for grading tumors and can be used to complement classical histological analysis.

The first step of Bordeaux team's work involved growing cells atop a nanometric titanium sheet.

"We flash-heat the titanium sheet by only a few degrees with a micrometric laser spot," said Thomas Dehoux, a researcher at CNRS, the French National Centre for Scientific Research. "You might say we 'heat the 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 were quite small. To measure them, the researchers observed how the titanium sheet bulged upon heating.

"When the temperature is high — without a cell on the other side — the metal sheet dilates locally and creates a bump," Dehoux said. "When the temperature decreases — a cell is probed — the sheet's profile returns to normal. We're able to detect this effect with a second laser beam that's deflected by the movement of the bottom surface, which gives us unprecedented sensitivity."

Each part of a cell absorbs heat differently, due to inhomogeneities in thermal properties, which allowed the researchers to see through the metal sheet and produce a thermal image of the cell.

To investigate the thermorheological behavior of cells, the researchers also performed simultaneous acoustic imaging using an inverted optoacoustic microscope. Acoustic impedances extracted from the these images supported the effusivity data obtained from the thermal images.

The research was published in Applied Physics Letters (doi: 10.1063/1.4938998).