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Nature Communications

Quantum-sensing-based super-resolution live cell microenvironment imaging

Yuxian Lu, Yibo Yang, Ke Xu, Zihan Mao, Lu Yin, Yang Xu, Zengrong Zhou, Xin Wang, Chi Zhang, Wenxin Zhu, Jiandong Feng

Published Oct 10, 2026• 0 citations
Publisher

Abstract

Direct monitoring the multifaceted intracellular microenvironment is fundamental for deciphering localized cellular behavior and function. However, performing nanoscale spatiotemporal sensing of the dynamic physiochemical environment within a live cell has remained challenging, mainly limited by the lack of robust, biocompatible method which satisfies the requirements for spatiotemporal resolution, sensitivity, multi-physical sensing capability and long-term viability. Here we present a super-resolution-based quantum biosensing approach, namely Super-resolution Multi-physical field Imaging with Deconvolution, implemented in our custom-built setup which integrates nitrogen vacancy center-based quantum sensing with structured illumination microscopy. This enables quantitative, super-resolved, and long-term tracking of intracellular physical fields, featuring spatial resolution of 136 nm, temporal resolution of 150 ms, and field of view of 180×180 μm2. We further perform super-resolution multimodal imaging in a live cell, revealing the spatially heterogeneous reactive oxygen species dynamics under external stimulation. Our work enables the dynamic assessment of localized physiochemical dynamics under super-resolution quantum biosensing. This work presents a super-resolution quantum biosensing approach by integrating nitrogen vacancy (NV) center-based quantum nanodiamond sensors with structured illumination microscopy, which achieves super-resolution multi-physical imaging within live cells.

DOI
10.1038/s41467-026-78321-2

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Direct monitoring the multifaceted intracellular microenvironment is fundamental for deciphering localized cellular behavior and function. However, performing nanoscale spatiotemporal sensing of the dynamic physiochemical environment within a live cell has remained challenging, mainly limited by the lack of robust, biocompatible method which satisfies the requirements for spatiotemporal resolution, sensitivity, multi-physical sensing capability and long-term viability. Here we present a super-resolution-based quantum biosensing approach, namely Super-resolution Multi-physical field Imaging with Deconvolution, implemented in our custom-built setup which integrates nitrogen vacancy center-based quantum sensing with structured illumination microscopy. This enables quantitative, super-resolved, and long-term tracking of intracellular physical fields, featuring spatial resolution of 136 nm, temporal resolution of 150 ms, and field of view of 180×180 μm2. We further perform super-resolution multimodal imaging in a live cell, revealing the spatially heterogeneous reactive oxygen species dynamics under external stimulation. Our work enables the dynamic assessment of localized physiochemical dynamics under super-resolution quantum biosensing. This work presents a super-resolution quantum biosensing approach by integrating nitrogen vacancy (NV) center-based quantum nanodiamond sensors with structured illumination microscopy, which achieves super-resolution multi-physical imaging within live cells.
Wide-field quantum sensing and imaging with solid-state spins has attracted wide interest for its ability to detect relative physical quantities with high sensitivity at nanoscale. However, the optical diffraction limit hinders the improvement in spatial resolution. In this work, we utilize blind structured illumination microscopy to perform wide-field quantum sensing with nitrogen-vacancy (NV) center in diamond. Without the requirement of prior knowledge of excitation light field, the spatial resolution of NV centers imaging is enhanced by 1.8-fold in comparison with conventional microscopy. Combined with spin manipulation and detection, super-resolution NV center sensing is subsequently performed to reveal the optical and electrical properties of nanodevice. The high spatial resolution and feasibility of this work will promote the applications of quantum sensing in nanoscience.
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Quantum sensing using nitrogen-vacancy (NV) centers in diamond has emerged as a powerful platform for detecting ultra-low magnetic fields under ambient conditions. Owing to their long spin coherence times, optical addressability, and compatibility with aqueous environments, it has found widespread applications in biosensing and bio-imaging. This review presents the fundamental principles and recent advances in NV-based quantum magnetometry for biosensing applications, with a particular focus on measurements in aqueous medium and at cellular and molecular length scales. We discuss the underlying spin physics of NV centers and highlight two primary detection modalities: optically detected magnetic resonance (ODMR) and T1 relaxometry-based sensing and how these approaches aids in the detection of both static magnetic fields and dynamic magnetic noise arising from biological processes. The review explores key application areas, including nanoscale nuclear magnetic resonance (NMR), monitoring of neural activity, detection of abnormal or rogue cells using NV-based platforms etc. In addition, strategies for enhancing sensitivity, such as surface functionalization of nanodiamonds, femtosecond (fs) laser-written photonic structures, and integration with microfluidic and lab-on-chip systems have also been discussed in depth. We also address the critical challenges, including surface-induced decoherence, charge-state instability, and signal-to-noise limitations in biofluids associated with NV-based biosensing applications. Finally, we outline future prospects, highlighting how NV-based magnetic biosensing provides a promising pathway for translating quantum sensing technologies into practical biomedical applications.
The NV defect center in diamond forms a pseudo-atomic quantum system with discreet optically excitable transitions between ground and excited states in the gap between valence and conduction bands, making the NV center a deep-level defect center in diamond. For the negatively charged NV center (NV-), both the ground and excited states are spin triplets (S=1) and coupling between optical and spin states provides unique opportunities for optical detection of magnetic resonance (ODMR) and quantum metrology under ambient conditions. As an atomically sized point defect that is stable in single nanodiamonds as small as a few nanometers, the NV center enables spin based imaging of temperature, electric fields, magnetic fields and mechanical strain with nanoscale spatial resolution. Made of carbon, nanodiamonds are also ideal nanoparticles for use in biological systems, exhibiting extremely low cytotoxicity, no photo bleaching and exceptional contrast in transmission electron and light microscopy. With the ability to act as both a passive, non perturbing sensor (e.g. a diamagnetic material used for sensing magnetic fields) and a connection point for two way, direct coupling of far field optics to NV−^-− spins and indirectly to the highly localized neighborhood of atoms, electronic states and phonon modes in the local vicinity, NV diamond provides a route to nanoscale field sensing and spin based optical microscopy. These sensors are also stable in nanodiamonds. For nanoparticles, the reduction in particle diameter dramatically enhances the proportion of the material that is surface exposed, enhancing any surface related properties. Nitrogen Vacancy centers in nanodiamonds provide another example of material properties that vary with particle size. In chapter 5, evidence that modulation of nanodiamonds fluorescent emissions by electrical perturbations in their surrouding environment allows transduction of local electrodynamics into a far field optical signal capable of mapping action potentials in cardiomyocytes in presented. The unifying theme for all of the work presented in this dissertation is to enable the use of magnetic resonance signals and interactions for imaging and sensing in previously inaccessible regimes. The specific focus is on methods and techniques to enable nanoscale physical sensing and functional imaging in live tissues, with the ultimate aim to lay the predicate for the combination of both without compromise.
Nitrogen-vacancy (NV) centres are exceptional solid-state quantum sensors with optically addressable spins. With room-temperature operability and biocompatibility, functionalised NV centres in nanodiamonds facilitate atomic-scale tracking and real-time monitoring of physical and chemical properties within living systems [1]. Conventionally, these systems work by addressing stochastically-positioned defects with a complex bulk-optic microscope [2] or using a single scanning probe, limited in scalability and the ability to capture spatial and temporal information simultaneously.
High spatial resolution and low perturbation are required for mapping the electromagnetic field at the nanoscale, to provide crucial information about local light-matter interaction. Using optical superresolution microscopy for detection via a nitrogen-vacancy center in diamond, this work demonstrates far-field noninvasive sensing of the local electromagnetic field with high accuracy and a spatial resolution of approximately 50 nm. As the nitrogen-vacancy center is sensitive to various physical quantities, a multifunctional far-field quantum nanoscope is anticipated.