Taking A Cell’s Temperature

Nanoscale thermometry has untold possible uses for biology, from basic research on how heat flows in living systems to controlling gene expression with temperature. Researchers use a number of techniques for biological thermal sensing, including Raman spectroscopy and detection of fluorescing proteins. But all have problems, such as low sensitivity or the inability to make highly localized measurements.

Now, a group led by physics professor Mikhail D. Lukin and chemistry professor Hongkun Park at Harvard University have harnessed a common defect in diamonds to develop an improved approach for nanometer-scale thermometry in biological systems (Nature 2013, DOI: 10.1038/nature12373).

In some diamonds, two adjacent carbons are replaced by a nitrogen and an empty spot called a nitrogen vacancy center. Minuscule temperature changes strain the lattice of such diamonds, which affects the quantum spin properties of the local defect and modifies its fluorescence properties. These changes can then be detected.

The group used microwave pulses to manipulate a diamond-lattice defect’s spin states, and from resulting changes in fluorescence, researchers determined corresponding temperature variations. The method, they found, is capable of detecting temperature changes as small as 1.8 mK in areas as small as 200 nm across.

The team then tested the thermometer in a living human cell, an embryonic fibroblast. They inserted nanodiamonds and gold nanoparticles into the cell. Laser light heated the gold nanoparticles, and the group monitored temperature gradients throughout the cell by observing changes in the nanodiamonds’ fluorescence.

“I like this technique very much,” says Xinwei Wang, a mechanical engineering professor at Iowa State University, noting that in addition to being very sensitive, the technique’s spatial resolution is comparable or superior to that of widely used Raman techniques.

“This kind of sensitivity is extremely important when diagnosing thermal responses and studying chemical reactions in biosystems at the cellular level,” Wang says.

Konstantin V. Sokolov, a physics professor at the University of Texas, Houston, calls the work “a precious solution” to the problem of measuring temperatures in biological systems on the nanometer scale.

With improvement, the team says the technique may make it possible to observe real-time biological activity with subcell resolution.