In life sciences,the ability to measure the distribution of biomolecules inside a cell in situ is an important investigative goal.Among a variety of techniques,scientists have used magnetic imaging(MI)based on the nitrogen vacancy center(NV)in diamonds as a powerful tool in biomolecular research.However,nanoscale imaging of intracellular proteins has remained a challenge thus far.In a recent study now published in Science Advances,Pengfei Wang and colleagues at the interdisciplinary departments of physics,biomacromolecules,quantum information and life sciences in China,used ferritin proteins to demonstrate the MI realization of endogenous proteins in a single cell,using the nitrogen-vacancy(NV)center as the sensor.They imaged intracellular ferritins and ferritin-containing organelles using MI and correlative electron microscopy to pave the way for nanoscale magnetic imaging(MI)of intracellular proteins.

　　Increasing existing spatial resolution of biomedical imaging is required to achieve ongoing demands in medical imaging,and therefore,among a variety of techniques,magnetic imaging is of broad interest at present.Magnetic resonance imaging(MRI)is widely used to quantify the distribution of nuclear spins but conventional MRI can only reach a resolution of 1µm in nuclear spin imaging where the resolution is limited by electrical detection sensitivity.Scientists have developed a series of techniques to break this resolution barrier,including a superconducting quantum interference device and magnetic resonance force microscopy.Nevertheless,these reports require a cryogenic environment and high vacuum for imaging,limiting the experimental implementation and its translation to clinical practice.

　　A recently developed quantum sensing method based on the nitrogen vacancy center in diamond has radically pushed the boundary of MI techniques at the nanoscale to detect organic molecules and proteins in the lab.Scientists have combined quantum sensing with NV centers and scanning probe microscopy to demonstrate nanoscale MRI for single electron spin and small nuclear spin ensemble while using the NV center as a biocompatible magnetometer to noninvasively image ferromagnetic particles within cells at the subcellular scale(0.4µm).For example,depolarization of the NV center can be used as a wideband magnetometer to detect and measure fluctuating noise from metal ions and nuclear spins.However,such imaging of single proteins via MI at the nanoscale has not been reported in the single cell thus far.

　　The work will contribute to clinical diagnostics to determine biomarker-based iron storage and release in cells.This will include studies on the regulatory mechanisms of iron metabolism during the progression of hemochromatosis,anemia,liver cirrhosis and Alzheimer's disease.Wang et al.propose to extend the approach in situ to other cellular components with paramagnetic signals,including magnetic molecules,metalloproteins and special spin-labelled proteins.The scientists envision that further studies will explore additional targets suitable for high-resolution MI and correlated TEM imaging techniques,with optical microscopy detection incorporated to the experimental setup to extend the work and determine protein nuclear spin MRI as well as perform three-dimensional cell tomography.

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