How do you take a worm’s temperature? With a quantum thermometer of course. This is exactly what researchers have achieved using devices containing nanodiamonds with nitrogen-vacancy (NV) defect centres, the magnetic resonances of which change with temperature. The new technique could be important for a range of clinical applications.

You may ask, why take the temperature of a worm? One of the reasons is that the temperature within a living organism is a direct measure of the biological activities happening inside. Going down to the submicron-scale temperature range, as in this new work, should provide detailed information on cellular and molecular activities. This could be important for clinical applications such as imaging brain sub-tissue structures, visualizing tumour heterogeneity and mapping adipocytes, to cite just three examples. It is, however, no easy task to reduce the size of biocompatible thermometers down to this small scale.

Recent years have the seen the emergence of light-emitting nanothermometers – such as thermoresponsive molecular probes and nanoparticles – that could overcome this technical limitation. Most devices made thus far, however, are not robust enough for long-term use and can only monitor temperature changes over relatively long periods (hours). They are also not completely biocompatible.

Nanodiamond quantum thermometers

The nanodiamond quantum thermometers employed in the new study are promising in many respects. The probes are made of nanodiamond, which naturally contains defects, known as NV centres. These occur when two adjacent carbon atoms in a diamond lattice are replaced with a nitrogen atom and an empty lattice site.

The nitrogen has an extra electron that remains unpaired and so behaves as an isolated spin. This spin can be “up” or “down” or in a superposition of the two. Its state can be probed by illuminating the diamond with laser light and recording the intensity and frequencies of the emitted fluorescence.

NVs in nanodiamonds are ideal as biological probes because they are non-toxic, photostable, have surfaces that can be functionalized and can be easily inserted into living cells. They are also isolated from their surroundings, which means that their quantum behaviour is not immediately affected by surrounding thermal fluctuations, and can detect the very weak magnetic fields that come from nearby electronic or nuclear spins. They can thus be used as highly-sensitive magnetic resonance probes capable of monitoring local spin changes in a material over distances of a few tens of nanometres. And, in contrast to conventional magnetic resonance imaging (MRI) techniques in biology, in which millions of spins are required to produce a measurable signal, the NV defects can detect individual target spins with nanoscale spatial precision.

Healthy worms vs worms with a fever

In their experiments, Masazumi Fujiwara of Osaka City University in Japan and colleagues functionalized the surfaces of the nanodiamonds with polymer structures and injected them into C. elegans nematode worms (one of the most popular animal models in biology). The sensor began by reading the base “healthy” temperature of the creatures as a frequency shift of the optically detected magnetic resonance of the NV defect centres.

Since the nanodiamonds move much more quickly inside a worm than in cultured cells, the researchers developed a fast particle-tracking algorithm. They also included an error-correction filter that takes into account the worm’s body structure, which can cause substantial fluctuations in the intensity of the fluorescent light emitted and can create temperature-measurement artefacts.

Next, the team, who report their work in Science Advances, induced an artificial “fever” in the worms by stimulating their mitochondria with a chemical. Their sensor successfully recorded this temperature increase with a precision of around ±0.22°C.

“It was fascinating to see quantum technology work so well in live animals and I never imagined that the temperatures of tiny worms less than 1 mm in size could deviate from the norm and develop into a fever,” says Fujiwara. “Our results are an important milestone that will guide the future direction of quantum sensing as it shows how it contributes to biology.”