Single-spin Quantum Sensing Technology For Single-cell Nuclear Magnetic Resonance

Single-cell research is crucial for revealing heterogeneity masked by large cell populations.For instance,early detection of cancer cells prior to their widespread proliferation enables the initiation of therapeutic interventions at a more preliminary stage.However,an ideal detection method requires providing high-resolution,multilevel,comprehensive information while maintaining cell viability,and so far,no technology has achieved this goal perfectly.Nuclear magnetic resonance(NMR)offers a noninvasive approach for rapidly and accurately obtaining quantitative information about molecular structures,chemical environments,dynamics,and interactions.Since the 1950s,NMR spectroscopy has been widely applied to the analysis of cells and tissues,revealing rich information about intracellular molecules at the atomic scale.However,conventional NMR lacks high-resolution spatial information,preventing the detection of cellular heterogeneity.Single-cell NMR demands extremely high sensitivity and spatial resolution,even surpassing the energy resolution limit(ERL),which presents the most significant challenge.Nitrogen-vacancy(NV)centers in diamond,as atomic-scale single-spin quantum probes,have the potential to achieve single-cell NMR.However,due to the complexity of the solid-state lattice,the manipulation fidelity of NV centers at room temperature is insufficient for single-cell NMR measurements.In this thesis,we improved the optically detected magnetic resonance(ODMR)platform,developed high-fidelity quantum manipulation methods,achieved high-sensitivity and high-resolution magnetic measurements,and successfully detected single-cell scale NMR signals.This research is conducted in four progressive stages as follows:1.This study improved the ODMR platform and especially developed combined magnet and radiofrequency coil techniques,achieving uniform static magnetic fields and radiofrequency fields within a limited space to meet the requirements of single-cell NMR.Stability is crucial for high-precision detection;therefore,experimental conditions such as temperature and magnetic fields were optimized.To verify the platform’s stability,the first identity test experiment for single NV centers in diamond was conducted,achieving frequency measurement accuracy at the Hz-precision level.2.This study refined the entire quantum sensing process,achieving 97.74(18)%electron spin initialization fidelity,98.94(3)%charge state initialization fidelity,99.920(7)%non-local gate control fidelity,and 99.14(4)%readout fidelity.Besides,the magnetic measurements beyond the standard quantum limit were achieved for the first time in solid-state spin systems.3.The main drawbacks of near-surface NV centers,such as short coherence time,low initialization fidelity,and low readout efficiency,were addressed by integrating various quantum techniques,including real-time feedback charge state initialization,dynamical decoupling based on shaped pulses,and repetitive readout techniques,to achieve a significant sensitivity improvement.The magnetic sensitivity reached 0.5 nT·Hz-1/2 for single NV centers above 30 nm depth,which corresponds to an energy resolution below the ERL,laying the foundation for single-cell NMR.4.Leveraging these technical advancements,we successfully detected single-cell scale(micrometer)NMR sample signals and further measured the nuclear spin relaxation process,which will enable future studies of single-cell heterogeneity and singlecell NMR imaging.