A new optical technique for accurately mapping the temperature distribution within single cells looks set to provide important insights into their thermodynamics and aid the development of photothermal cancer therapies (Nano Lett. 12, 2107–2111; 2012).

The scheme, developed by scientists from the Institute of Photonic Sciences (ICFO) and the Catalan Institution for Research and Advanced Studies (ICREA) in Barcelona, Spain, and the Institut Fresnel in Marseille, France, makes use of green fluorescent protein (GFP) as a thermal probe. Temperature measurements are made by monitoring the polarization anisotropy of fluorescence from GFP, which is known to be temperature-dependent. As the temperature rises, increased Brownian rotational motion of the cells reduces the polarization anisotropy of their light emission.

Credit: ICFO

“As with most chemical reactions, many intercellular processes such as gene expression and cell division, for example, are exothermic,” explained Romain Quidant, a researcher from ICFO involved in the study. “The possibility of measuring intracellular temperature could be the basis of the development of a quite unexplored field: thermal biology at the single-cell level.”

The researchers tested their technique with HeLa and U-87 MG cancer cells that had been transfected with GFP and were surrounded by photothermally heated gold nanorods. The study employed a confocal microscope equipped with two laser sources: an infrared laser for heating the nanorods and a blue laser to excite the GFP. Results showed that intracellular measurements with a spatial resolution of 300 nm and a temperature accuracy of 0.4 °C are possible. The approach is also non-invasive, provides fast read-out and allows data to be collected with a time resolution of 20 ms.

The researchers are now investigating strategies for improving the accuracy and resolution of the method and are thinking of applying it to in vivo measurements.

“The intracellular temperature mapping of single cells will help to explain the thermodynamics of different cell organelles,” commented Quidant. “This information could be extremely important to monitor and thus further understand, for example, the increased production of heat of cancer cells over normal cells.”