Nanoscale sensing and imaging in biology using the nitrogen-vacancy center in diamond

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Introduction The nitrogen-vacancy (NV) center in diamond has emerged as an important system for quantum sensing applications. This atomic-level defect displays a remarkable range of properties, including sustained fluorescence,1 long quantum coherence times under ambient conditions,2 and demonstrated biocompatibility.3–5 Nanoscale ambient magnetometry using single NV spins has been demonstrated experimentally in controlled environments6–8 with reported AC sensitivities2 of 4 nT Hz–1/2. Wide-field imaging using NV emsembles9 has recently demonstrated sensitivity10 at 100 nT Hz–1/2. By implementing dynamical decoupling control, it may be possible to extend the sensitivity even further (e.g., to the pT Hz–1/2 level using the Uhrig scheme).11 Optical absorption-based techniques at low temperatures (75 K) also show great promise with demonstrated sensitivities down to 7 nT Hz–1/2.12 For random magnetic field fluctuations in biological contexts, it has been proposed that probing the quantum decoherence time of the NV system in situ could enable direct noninvasive monitoring of processes at the nanoscale.13,14 In this article, we review some recent work on applications of NV magnetometry in biology, such as fluorescence tracking, noninvasive ion-channel detection, and neuronal network imaging, and discuss the opportunities and potential for nanoscale tracking, sensing, and imaging.

The NV center as a fluorescent biomarker in vitro and in vivo Fluorescent nanoparticles have been lighting the way in biology for decades, providing great insight into the complex processes and mechanisms occurring at the intracellular level. Modern biomarkers exist in many forms, such as fluorescent proteins, organic dyes, quantum dots, and single molecules, and while these markers have been effective in illuminating biological processes, they often lack the desirable feature of photostability over arbitrarily long time scales. Over the past decade, there has been significant interest in the fluorescent properties offered by a new family of biomarkers in the form of optical defects in diamond. Color centers in diamond are photostable down to crystal sizes 10 hours) indicated that one ND was rotating while the other was relatively fixed in space (Figure 4b). Also, in a first attempt at decoherence sensing in this environment, the T2 time of the NV centers was monitored, showing a change over the lifetime of the cell (Figure 4c). In a separate experiment, a NV-ND in a HeLa cell was tracked, and the ODMR spectrum was measured continuously (Figure 4d). From the change in Zeeman splitting, it was shown that the orientation of such a ND could be determined to within an accuracy of 1 degree in a fluorescence acquisition time of order of 100 ms.

Conclusion Recent progress on both theoretical and experimental fronts indicates that the nitrogen-vacancy (NV) system has a fortuitous convergence of physical properties that make it ideal for biological imaging and detection applications. The first experiments in NV nanobiomagnetometry demonstrate that the combination