arXiv2016
A key challenge for neuroscience is noninvasive, label-free sensing of action potential (AP) dynamics in whole organisms with single-neuron resolution. Here, we present a new approach to this problem: using nitrogen-vacancy (NV) quantum defects in diamond to measure the time-dependent magnetic fields produced by single-neuron APs. Our technique has a unique combination of features: (i) it is noninvasive, as the light that probes the NV sensors stays within the biocompatible diamond chip and does not enter the organism, enabling activity monitoring over extended periods; (ii) it is label-free and should be widely applicable to most organisms; (iii) it provides high spatial and temporal resolution, allowing precise measurement of the AP waveforms and conduction velocities of individual neurons; (iv) it directly determines AP propagation direction through the inherent sensitivity of NVs to the associated AP magnetic field vector; (v) it is applicable to neurons located within optically opaque tissue or whole organisms, through which magnetic fields pass largely unperturbed; and (vi) it is easy-to-use, scalable, and can be integrated with existing techniques such as wide-field and superresolution imaging. We demonstrate our method using excised single neurons from two invertebrate species, marine worm and squid; and then by single-neuron AP magnetic sensing exterior to whole, live, opaque marine worms for extended periods with no adverse effect. The results lay the groundwork for real-time, noninvasive 3D magnetic mapping of functional neuronal networks, ultimately with synapse-scale (~10 nm) resolution and circuit-scale (~1 cm) field-of-view.