Nitrogen-vacancy (NV) centers in diamond provide a versatile quantum sensing platform for biological imaging through magnetic field detection, offering unlimited photostability and the ability to perform long-term observations without photobleaching or phototoxicity. However, conventional stage-top incubators are incompatible with the unique requirements for NV widefield magnetometry to study cellular dynamics. Here, we present a purpose-built compact incubation platform that maintains precise environmental control of temperature, CO$_2$ atmosphere, and humidity while accommodating the complex constraints of NV widefield microscopy. The system employs a 3D-printed biocompatible chamber with integrated heating elements, temperature control, and humidified gas flow to create a stable physiological environment directly on the diamond sensing surface. We demonstrate sustained viability and proliferation of HT29 colorectal cancer cells over 90 hours of continuous incubation, with successful magnetic field imaging of immunomagnetically labeled cells after extended cultivation periods. This incubation platform enables long-term cultivation and real-time monitoring of biological samples on NV widefield magnetometry platforms, opening new possibilities for studying dynamic cellular processes using quantum sensing technologies.
Nitrogen-vacancy (NV) centers in diamond provide a versatile quantum sensing platform for biological imaging through magnetic field detection, offering unlimited photostability and the ability to perform long-term observations without photobleaching or phototoxicity. However, conventional stage-top incubators are incompatible with the unique requirements for NV widefield magnetometry to study cellular dynamics. Here, we present a purpose-built compact incubation platform that maintains precise environmental control of temperature, CO2 atmosphere, and humidity while accommodating the complex constraints of NV widefield microscopy. The system employs a 3D-printed biocompatible chamber with integrated heating elements, temperature control, and humidified gas flow to create a stable physiological environment directly on the diamond sensing surface. We demonstrate sustained viability and proliferation of HT29 colorectal cancer cells over 90 hours of continuous incubation, with successful magnetic field imaging of immunomagnetically labeled cells after extended cultivation periods. This incubation platform enables long-term cultivation and real-time monitoring of biological samples on NV widefield magnetometry platforms, opening new possibilities for studying dynamic cellular processes using quantum sensing technologies.
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.
Live-cell imaging of cellular and tissue samples relies predominantly on optical modalities, such as fluorescence, confocal, and multiphoton microscopy, in which cellular information is encoded in emitted photons. Photons scatter and attenuate in biological samples, restricting depth resolution, while the excitation light required to produce them induces photodamage that perturbs the very biology under observation. Magnetic fields, by contrast, traverse biological samples without attenuation at cellular length scales, but the imaging modality that extracts the encoded information, magnetic resonance imaging, cannot resolve individual cells. Here we present Quantum Cell Monitoring (QCM), a widefield nitrogen-vacancy magnetometry platform that encodes single-cell information in stray magnetic fields rather than emitted photons and reads it out at subcellular resolution. Integrated with a specialized live-cell incubator, QCM tracks magnetically labeled living cancer for up to 72 h through their individual magnetic field signatures. It captures single-cell mitosis and morphological remodeling, as well as cell cluster formation, splitting, and migration even within dense regions where brightfield contrast collapses. By shifting the carrier of single-cell information from propagating optical photons to static magnetic stray fields, QCM decouples cell from cellular optical accessibility and auto-fluorescence, enabling sustained live-cell observation in regimes inaccessible to optical microscopy.
In modern-day quantum metrology, quantum sensors are widely employed to detect weak magnetic fields or nanoscale signals. Quantum devices, exploiting quantum coherence, are inevitably connected to physical constants and can achieve accuracy, repeatability, and precision approaching fundamental limits. As a result, these sensors have shown utility in a wide range of research domains spanning both science and technology. A rapidly emerging quantum sensing platform employs atomic-scale defects in crystals. In particular, magnetometry using nitrogen-vacancy (NV) color centers in diamond has garnered increasing interest. NV systems possess a combination of remarkable properties, optical addressability, long coherence times, and biocompatibility. Sensors based on NV centers excel in spatial resolution and magnetic sensitivity. These diamond-based sensors promise comparable combination of high spatial resolution and magnetic sensitivity without cryogenic operation. The above properties of NV magnetometers promise increasingly integrated quantum measurement technology, as a result, they have been extensively developed with various protocols and find use in numerous applications spanning materials characterization, nuclear magnetic resonance (NMR), condensed matter physics, paleomagnetism, neuroscience and living systems biology, and industrial vector magnetometry. In this chapter, NV centers are explored for magnetic sensing in a number of contexts. In general, we introduce novel regimes for magnetic-field probes with NV ensembles. Specifically, NV centers are developed for sensitive magnetometers for applications where microwaves (MWs) are prohibitively invasive and operations need to be carried out under zero ambient magnetic field. The primary goal of our discussion is to improve the utility of these NV center-based magnetometers.
Wide-field nitrogen-vacancy (NV) magnetic imaging at cryogenic temperatures requires microwave excitation and reliable knowledge of the temperature near the sensing region. Here, we report an integrated diamond quantum-sensing platform combining an ensemble of NV centers with a boron-doped diamond (BDD) microwave antenna and thermometer formed on the same diamond substrate. The BDD antenna provides microwave excitation for optically detected magnetic resonance measurements, and the BDD thermometer monitors the thermal environment near the NV sensing region. The BDD thermometer detected laser-induced local heating that was not clearly resolved by a stage-mounted thermometer. Using this platform, we imaged the temperature-dependent Meissner response of multiple cuprate superconductors while recording the temperature. These results demonstrate that the integrated BDD--NV platform provides a practical approach for cryogenic wide-field magnetic imaging with integrated microwave delivery and local thermometry.
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.
We report progress toward a CMOS-integrated quantum diamond biosensing platform that combines nitrogen-vacancy (NV) centers in diamond with a custom 40 nm CMOS Single-Photon Avalanche Diode (SPAD) array. The system integrates on-chip active quenching and digital readout with external FPGA-based photon counting, compact microwave delivery, and practical optical excitation and collection schemes to support widefield optically detected magnetic resonance (ODMR). System-level design considerations spanning fluorescence collection efficiency, detector count-rate capability, and microwave homogeneity are analyzed with biological compatibility and scalability in mind. Using superparamagnetic iron oxide nanoparticle (SPION)-labeled HEK293T cells as a representative use case, simple dipole-field estimates indicate that sub-μT sensitivity is required to resolve ODMR shifts within typical ensemble linewidths. Based on the proposed architecture and efficiency analysis, a magnetic field sensitivity of approximately 90 nT/Hz per pixel is estimated. These results outline a practical path from optics-heavy quantum diamond microscopes toward compact, CMOS-integrated NV-based biosensors for quantitative magnetic imaging in complex biological environments.