Traditional intracellular quantum sensing platforms—ranging from nitrogen-vacancy centers in nanodiamonds to semiconductor quantum dots and genetically encoded fluorescent probes—have long faced intrinsic limitations. These include heterogeneous material properties causing inconsistent sensor responses, challenges in achieving absolute thermometric accuracy amid cellular complexity, and biocompatibility issues that compromise cellular viability or sensor stability. The newly developed MoQNs surmount these obstacles by integrating pentacene molecular spin qubits embedded within para-terphenyl nanocrystals, themselves coated in the biocompatible surfactant Pluronic F127, yielding nanoscale sensors with molecular-level uniformity and preserved quantum coherence in physiological conditions.

Contrast to defect-based solid-state quantum sensors, which rely on vacancy creation in rigid crystalline lattices and suffer from spectral variability, MoQNs circumvent these pitfalls by embedding molecular spin qubits into nanocrystalline hosts without inducing defects. This careful materials engineering drastically reduces particle-to-particle heterogeneity in resonance spectra and consequently enhances the reliability of absolute temperature readings at single-particle resolution inside living cells. Crucially, the team confirmed that MoQNs can be internalized by living cells without detriment to membrane integrity, metabolic function, or cell-cycle dynamics, affirming their suitability for live-cell quantum sensing studies.

The quantum functionalities of these molecular sensors manifest robustly within intracellular environments. The researchers demonstrated continuous-wave optically detected magnetic resonance (ODMR) detection alongside hallmark quantum phenomena such as Rabi oscillations and spin-echo coherence measurements, alongside T1 spin relaxation analysis. To further refine thermometric sensitivity, they molecularly engineered the ODMR spectral profile by incorporating fully deuterated pentacene variants, termed dMoQNs, which fine-tune electron-nuclear spin interactions and mitigate decoherence.

Harnessing the enhanced dMoQNs, the team achieved absolute temperature sensing within the cytoplasm of living cancer cells with exceptional precision. Their observations consistently revealed that intracellular temperature exceeds that of extracellular media, and importantly, this temperature elevation varies spatially within the cytoplasm—a finding that underscores previously unappreciated thermal heterogeneity at the nanoscale within living cells. Extending these studies to the cellular nucleus, the researchers successfully delivered dMoQNs into nuclear compartments, presenting the first maps of absolute temperature distribution within subnuclear domains. These data reveal localized thermal microenvironments, suggesting intricate thermoregulation mechanisms active at the organelle level.

Beyond temperature mapping, the MoQN platform exhibits striking versatility by detecting radical-related spin species within living cancer cells. Upon treating cells with hydrogen peroxide to induce oxidative stress, the sensors detected localized variations in spin relaxation and coherence signatures in both cytoplasmic and nuclear regions. This capability heralds a new frontier in intracellular redox biology, where MoQNs can provide real-time, spatially resolved insights into radical-mediated biochemical processes, potentially illuminating pathways of oxidative damage and signaling that are pivotal in cancer progression and therapy resistance.

This research thus presents MoQNs as a chemically adaptable quantum sensing platform, combining nanoscale spatial resolution, molecular-level tunability, and full biocompatibility. By preserving quantum coherence under physiological conditions and enabling absolute thermometry along with radical spin detection in live cells, MoQNs chart a course towards advanced, minimally invasive bio-quantum measurements. Such innovations promise to unlock new dimensions in intracellular thermodynamics, biochemical microenvironment sensing, and augment the toolkit for future quantum-biological investigations and medical diagnostics.

Dr. Hitoshi Ishiwata, who leads the Quantum Bioengineering Team at QST and also holds a professorship at Chiba University’s Center of Quantum Life Science for Structural Therapeutics (cQUEST), emphasized the significance of this leap: “This work shows that MoQNs can operate directly inside living cells while maintaining the precision needed for absolute thermometry. We believe this opens a new route toward quantitative quantum measurement of intracellular environments.” His pioneering research integrates nanoscale quantum technologies to interrogate biological processes with label-free, high-resolution acuity.

In addition to the fundamental scientific advancements, this study lays foundational groundwork for practical applications spanning biomedical research, drug development, and clinical diagnostics. The ability to accurately measure intracellular temperature gradients and radical species could provide insights into cellular metabolism, stress responses, and disease mechanisms at unparalleled resolutions. It broadens the horizon for quantum-enabled investigations into the physicochemical landscapes that govern cell function and pathology.

The development of MoQNs is supported by a synthesis of cutting-edge chemistry, quantum physics, and nanotechnology. Pentacene molecules, selected for their favorable spin properties, are embedded into para-terphenyl nanocrystals engineered for optimal quantum coherence. The surface coating with Pluronic F127 imparts biocompatibility and colloidal stability, facilitating cellular uptake without cytotoxicity. This interdisciplinary approach exemplifies how strategic molecular design can overcome the historical limitations of intracellular quantum sensors.

Furthermore, the study showcases the adaptability of molecular quantum nanosensors to modifications such as deuteration to enhance performance. By carefully tuning electron-nuclear spin interactions, the researchers improved the ODMR spectral resolution and thermometric precision. This molecular engineering underscores the unique advantage of MoQNs over conventional solid-state quantum sensors, whose characteristics are often fixed by crystal defects and difficult to manipulate post-synthesis.

In conclusion, the MoQN platform represents a transformative leap in intracellular sensing technologies. It offers reliable, high-fidelity quantum measurements directly inside living cells, enabling biological discoveries and medical advancements previously out of reach. As quantum technologies integrate increasingly with life sciences, tools like MoQNs are poised to become indispensable for exploring the nanoscale frontiers of cell biology and for developing innovative quantum-assisted diagnostics and therapeutics.

Subject of Research: Cells

Article Title: Molecular Quantum Nanosensors Functioning in Living Cells

News Publication Date: 29-Apr-2026

Web References:
https://doi.org/10.1126/sciadv.aeb5422
https://www.qst.go.jp/site/qst-english/

References:
DOI: 10.1126/sciadv.aeb5422

Image Credits:
National Institutes for Quantum Science and Technology, Japan

Keywords

Quantum sensing, molecular quantum nanosensors, intracellular thermometry, spin detection, living cancer cells, pentacene molecular spin qubits, para-terphenyl nanocrystals, biocompatible quantum sensors, optically detected magnetic resonance, Rabi oscillations, spin-echo, T1 relaxometry, molecular engineering, oxidative stress sensing, nanoscale thermodynamics, quantum bioengineering

The heart of this technological leap lies in its ability to simultaneously image eight focal planes across a vertical span of 5 micrometers while covering a lateral area of 50 by 50 micrometers. Traditional wide-field microscopes capture a single focal plane at a time, constraining observations to flat, two-dimensional sections which omit critical depth information intrinsic to biological function. By integrating a beam-splitting prism into the optical path, the system effectively partitions the emitted fluorescence into multiple depth-resolved images captured concurrently. This allows real-time, volumetric acquisition without necessitating mechanical scanning along the z-axis, thereby preserving temporal resolution essential for dynamic biological phenomena.

The microscope’s design capitalizes on the Coherent Verdi G5 laser source, whose stable, high-intensity illumination ensures robust excitation of the nitrogen-vacancy (NV) centers in the nanodiamonds. These NV centers, renowned for their quantum coherence even in ambient conditions, serve as atomic-scale sensors that respond to minute variations in magnetic and electric fields, temperature, and strain with exceptional sensitivity. Coupled with a high numerical aperture objective (Olympus LUCPLFLN40X), the system optimizes photon collection efficiency, critical for maintaining signal integrity across multiple focal depths.

Achieving nanometer-scale localization in three dimensions required the development of a sophisticated fluorescent particle positioning method based on Fourier-transform principles. By transforming spatial fluorescence distributions into frequency domain signatures, the algorithm deciphers subtle position-dependent phase shifts in the emitted light. This yields a lateral localization precision as fine as 9 nanometers and axial accuracy down to 12 nanometers—a remarkable feat surpassing the diffraction limits typical of conventional optical microscopy. The implementation of this computational approach enables precise tracking of individual intracellular nanodiamonds amidst the complex and heterogeneous cellular environment.

Experimental validation was conducted in mouse cardiomyocytes, where the researchers introduced FNDs as intracellular quantum probes. Utilizing the developed multi-plane microscope, they successfully performed correlated 3D mapping of these nanoparticles within the cellular architecture. Subsequent optically detected magnetic resonance (ODMR) measurements were performed on NV centers nestled inside the FNDs, revealing detailed local magnetic field distributions within the cytoplasm. This dual capability of spatial positioning combined with quantum sensing within living cells demonstrates a powerful new modality for biological investigation.

Importantly, the platform’s volumetric imaging capacity enables continuous single-particle tracking within a three-dimensional cellular context. This capability is pivotal for unraveling dynamic intracellular transport mechanisms, molecular interactions, and spatial heterogeneities at the nanoscale—domains previously obscured in two-dimensional snapshots. The potential to monitor magnetically sensitive quantum markers in living cells over time opens avenues for high-resolution studies of physiological and pathological processes with quantum-enhanced sensitivity.

Moreover, this work underscores the practical feasibility of applying wide-field quantum sensors beyond traditional physics laboratories into mainstream biomedical research. The non-invasive nature of FND probes, coupled with their biocompatibility and photostability, promotes long-term intracellular studies without compromising cell viability, overcoming limitations posed by organic fluorescent dyes prone to photobleaching. The ability to measure physical parameters like magnetic fields and temperature inside living cells with nanometric precision stands to revolutionize the diagnostic and therapeutic landscape.

The integration of a beam-splitting prism to simultaneously access multiple imaging planes marks a technical milestone in optical microscopy, bridging the gap between wide-field speed and confocal or multiphoton depth-sectioning resolution. This hybrid approach balances the need for rapid, high-throughput imaging with the spatial discrimination necessary to resolve complex intracellular environments. As quantum sensors evolve, coupling them with sophisticated microscopy architectures is fundamental to unlocking their full potential in life sciences.

This innovative platform’s implications extend far beyond cardiomyocytes. Its adaptability suggests potential applications in neuroscience, immunology, and cellular biomechanics, where spatially resolved quantum sensing could elucidate subtle physico-chemical cues critical for cellular function and signaling. Furthermore, the capability to perform in vivo quantum magnetic resonance measurements at subcellular resolution foreshadows transformative insights into diseases rooted in dysregulated ionic fluxes and magnetic field anomalies.

Looking ahead, continued refinement of this multi-plane quantum imaging system could involve scaling up imaging volume, enhancing temporal resolution, and integrating complementary contrast mechanisms. Implementing adaptive optics to correct sample-induced aberrations and deploying machine learning algorithms for real-time data processing may further boost localization performance and sensing fidelity. Such advancements will propel the platform toward routine application in complex biological models and clinical diagnostics.

In conclusion, this development in multi-plane wide-field microscopy coupled with quantum sensing via intracellular fluorescent nanodiamonds heralds a new era of nanoscale bioimaging. By capturing fast, volumetric, and quantum-sensitive observations within living cells, this technology bridges disciplines of quantum physics, optics, and cell biology, presenting unprecedented opportunities to decode the intricacies of life at the quantum frontier.

Subject of Research: Not applicable

Article Title: 3D positioning and optically detected magnetic resonance of intracellular fluorescent nanodiamonds using a multi-plane microscope

News Publication Date: 1-Feb-2026

Web References: http://dx.doi.org/10.52601/bpr.2025.250012

Image Credits: HIGHER EDUCATION PRESS

Keywords: Cell biology