Researchers at the National Institutes for Quantum Science and Technology (QST), Japan, and The University of Tokyo, Japan, in collaboration with Kyushu University, Japan, have developed a new class of biocompatible molecular quantum nanosensors (MoQNs) that operate inside living cells. The study demonstrates that these nanosensors enable absolute temperature measurements with subcellular spatial resolution and detect radical-related spin signals in both the cytoplasm and nucleus of living cancer cells. The study finding was published in the journal Science Advances on April 29, 2026.
Quantitatively mapping physical and chemical states inside living cells remains a major challenge in modern biology. Existing intracellular quantum sensors, including nanodiamonds, quantum dots, and fluorescent proteins, can be powerful but often face limitations in material heterogeneity, thermometric specificity, or biocompatibility.
To overcome these issues, the research team developed MoQNs based on pentacene molecular spin qubits embedded in para-terphenyl nanocrystals and coated with the biocompatible surfactant Pluronic F127. This design provides molecular-level uniformity while preserving quantum coherence under physiological conditions.
Unlike conventional solid-state quantum sensors that rely on defect formation inside hard crystals, MoQNs are built by introducing molecular qubits into host nanocrystals without creating vacancies. This markedly reduced spectral variability from particle to particle and improved the reliability of single-particle absolute temperature measurements inside cells. The team first confirmed that MoQNs can be introduced into living cells while preserving viability. Across multiple assays, cells containing MoQNs maintained plasma membrane integrity, metabolic activity, and cell-cycle progression, indicating that the particles are compatible with live-cell measurements.
The researchers then demonstrated that MoQNs retain quantum functionality inside cells, including continuous-wave optically detected magnetic resonance (ODMR) detection, Rabi oscillations, spin-echo measurements, and T1 relaxometry. To improve thermometric precision, they further engineered the ODMR spectrum of the quantum sensors at the molecular level by tuning electron–nuclear interactions through the incorporation of fully deuterated pentacene, thereby creating dMoQNs.
Using dMoQNs, the team achieved absolute temperature sensing inside the cytoplasm of living cancer cells with high precision. They also found that intracellular temperature was consistently higher than the surrounding medium in a location-dependent manner. The researchers next extended the method to organelle-specific measurements. By delivering dMoQNs into the nuclei of living cancer cells, they were able to map absolute temperature at multiple intranuclear positions and observed localized thermal heterogeneity within the nucleus.
Beyond temperature sensing, the MoQN platform also enabled detection of radical-related external spins inside living cells. After inducing radical-generating conditions with hydrogen peroxide, the researchers observed spot-dependent changes in spin relaxation and coherence in both the cytoplasm and nucleus, indicating that the sensors can report on intracellular redox-associated environments as well as temperature.
Together, these findings establish MoQNs as a chemically versatile platform for quantum sensing in living cells.
"This work shows that MoQNs can operate directly inside living cells while maintaining the precision needed for absolute thermometry," said Dr. Ishiwata, Team Leader of the Quantum Bioengineering Team at QST. "We believe this opens a new route toward quantitative quantum measurement of intracellular environments."
By combining molecular-level tunability, biocompatibility, and robust spin readout under physiological conditions, MoQNs open new opportunities for nanoscale thermometry, intracellular biochemical sensing, and future quantum-enabled biological and medical measurements.
Reference
DOI: https://doi.org/10.1126/sciadv.aeb5422
About the National Institutes for Quantum Science and Technology, Japan
The National Institutes for Quantum Science and Technology (QST) was established in April 2016 to promote quantum science and technology in a comprehensive and integrated manner. The new organization was formed from the merger of the National Institute of Radiological Sciences (NIRS) with certain operations that were previously undertaken by the Japan Atomic Energy Agency (JAEA).
QST is committed to advancing quantum science and technology, creating world-leading research and development platforms, and exploring new fields, thereby achieving significant academic, social, and economic impacts.
Website: https://www.qst.go.jp/site/qst-english/
About Dr. Hitoshi Ishiwata from the National Institutes for Quantum Science and Technology, Japan
Dr. Hitoshi Ishiwata works at the Institute for Quantum Life Science (iQLS), QST, Japan, and is also an Associate Professor at Chiba University's Center of Quantum Life Science for Structural Therapeutics (cQUEST). His research focuses on developing nanoscale quantum sensors—such as NV centers in diamond and molecular quantum nanosensors—for label-free, high-resolution measurements inside living cells. He has published widely in this area, with more than 30 papers and over 1,000 citations, on topics including intracellular thermometry, radical quantification, and lipid membrane analysis using quantum sensing. He has received multiple awards including the Early Career Award in Biophysics (2021) and the NDNC Silver Best Oral Award (2021).
Funding information
This work was supported by JST FOREST Program (JPMJFR224K); JST CREST Program (JPMJCR22E4 and JPMJCR23I6); JSPS KAKENHI (JP23H00304 and JP24K23089); the Council for Science, Technology and Innovation (CSTI), Cross-ministerial Strategic Innovation Promotion Program (SIP) "Promoting the application of advanced quantum technology platforms to social issues" (funding agency: QST); the MEXT Quantum Leap Flagship Program (MEXT Q-LEAP, JPMXS0120330644); and research grants from the Murata Science and Education Foundation.
