Molecular spin sensor takes the temperature of cancer cells
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Heating up Measurement of the spin states of a nanoparticle within the nucleus of a living cell reveals the internal temperature of that cell. (Courtesy: Shutterstock/Inna Bigun) Researchers in Japan have succeeded in measuring the temperature inside living cells with high precision using a new class of biocompatible quantum nanosensor – something that has been difficult to do until now even. If improved, the nanosensor could be used to characterize a wide range of biological phenomena and so help in disease diagnosis, they say. Recent years have seen the advent of a new generation of nanoscale quantum sensors that can detect the tiny magnetic fields of biological systems. Some of these sensors rely on photons and others on electrons or spin defects – typically diamond specially engineered with nitrogen–vacancy (NV) defects. This material is made by removing two carbon atoms from the diamond lattice and replacing one with a nitrogen atom. The other “hole” is left empty, thereby creating a vacancy or defect. The spin state of the defect is influenced by the local magnetic field that can be “read out” from the way it fluoresces. While a powerful tool, and biocompatible, this type of quantum sensor does suffer from certain limits. For one, it can be structurally inhomogeneous, which affects how it detects temperature and other physical or chemical parameters inside biological cells. A more homogenous structure Even though the new molecular quantum nanosensor (MoQN) works in the same way as these conventional devices, it does not suffer from this problem, explain Nobuhiro Yanai of the University of Tokyo and Hitoshi Ishiwata of the National Institutes for Quantum Science and Technology (QST), who led this research effort. This is because it has a more homogenous structure and does not contain any defects. Instead, it is made by embedding molecular spin qubits, in this case fabricated from pentacene, in nanocrystals of para-terphenyl. This design makes the structure uniform on a molecular scale and preserves the quantum coherence of the spin qubits. It is then coated with Pluronic F127, which is a biocompatible surfactant. By detecting the spin direction of the “excited triplet state” of the pentacene qubits using a technique known as optically detected magnetic resonance (OMDR), the researchers can precisely determine the temperature of the qubits’ surroundings from the OMDR peak position. When they tested their method inside the cytoplasm of cancer cells in vivo, they found that the intracellular temperature was consistently higher than the surrounding medium. Yanai says he embarked on this study after reading about the work of Sam Bayliss’ group at the UK’s University of Glasgow, and Ashok Ajoy’s group at the University of California, Berkeley in the US on OMDR in pentacene-doped para-terphenyl crystals. He says he immediately got the idea that nanocrystals of this material could be used for quantum sensing inside cells. This was because his group had already developed such nanocrystals for a different purpose in previous research. Ensuring biocompatibility “I then spoke with Hitoshi Ishiwata, who is an expert in quantum sensing using NV centres,” he recalls. “While many molecular qubits have been developed to date, there had been no examples demonstrating their sensing ability within living cells.” The project required materials science expertise, he tells Physics World, and in particular, finding out how to reduce the material to the nanoscale and ensuring it was biocompatible. “We already knew that nanodiamonds are good quantum sensors for temperature measurements, but I had noticed a practical limitation: their ODMR spectra often vary significantly from particle to particle,” he says. “This spectral dispersion can introduce errors, especially when trying to perform precise measurements at the single-particle level.” Replacing hydrogen with deuterium The researchers thought they had overcome this problem during the first run of their experiments because they found that different particles showed identical OMDR spectra. However, their joy quickly waned when they observed that the spectra were still broadened by hyperfine interactions between the pentacene-doped para-terphenyl molecules’ electron spins and hydrogen nuclear spins. Quantum sensors benefit from miniaturized ultrahigh vacuum Read more To improve the spectral resolution, Ishiwata says he suggested chemically modifying the molecule by replacing the hydrogen in it with deuterium. And the technique worked: “the hyperfine broadening was strongly suppressed, allowing us to determine the OMDR spectra much more precisely.” These findings, which are detailed in Science Advances, show that MoQNs are a chemically versatile platform for quantum sensing in living cells and that they can operate directly inside them while maintaining the precision needed for absolute thermometry, he says. Their appeal also lies in in the fact that their structures can be easily modified. It will not all be plain sailing, however, adds Yanai. MoQNs cannot yet target specific organelles within cells, so endowing them with this targeting capability is an important future challenge. “What is more, their size has been limited to around 200 nm so far, so creating smaller MoQN particles will be crucial,” he says. Want to read more? Registration is free, quick and easy Note: The verification e-mail to complete your account registration should arrive immediately. However, in some cases it takes longer. Don't forget to check your spam folder. If you haven't received the e-mail in 24 hours, please contact customerservices@ioppublishing.org. E-mail Address Register