Optical magnetic detection of single-neuron action potentials using quantum defects in diamond

Significance We demonstrate noninvasive detection of action potentials with single-neuron sensitivity, including in whole organisms. Our sensor is composed of quantum defects within a diamond chip, which detect time-varying magnetic fields generated by action potentials. The sensor is biocompatible and can be brought into close proximity to the organism without adverse effect, allowing for long-term observation and superior resolution of neuron magnetic fields. Optical magnetic detection with quantum defects also provides information about action potential propagation that is not easily available with existing methods. The quantum diamond technique requires no labeling or genetic modification, allows submillisecond time resolution, does not bleach, and senses through opaque tissue. With further development, we expect micrometer-scale magnetic imaging of a variety of neuronal phenomena. Magnetic fields from neuronal action potentials (APs) pass largely unperturbed through biological tissue, allowing magnetic measurements of AP dynamics to be performed extracellularly or even outside intact organisms. To date, however, magnetic techniques for sensing neuronal activity have either operated at the macroscale with coarse spatial and/or temporal resolution—e.g., magnetic resonance imaging methods and magnetoencephalography—or been restricted to biophysics studies of excised neurons probed with cryogenic or bulky detectors that do not provide single-neuron spatial resolution and are not scalable to functional networks or intact organisms. Here, we show that AP magnetic sensing can be realized with both single-neuron sensitivity and intact organism applicability using optically probed nitrogen-vacancy (NV) quantum defects in diamond, operated under ambient conditions and with the NV diamond sensor in close proximity (∼10 µm) to the biological sample. We demonstrate this method for excised single neurons from marine worm and squid, and then exterior to intact, optically opaque marine worms for extended periods and with no observed adverse effect on the animal. NV diamond magnetometry is noninvasive and label-free and does not cause photodamage. The method provides precise measurement of AP waveforms from individual neurons, as well as magnetic field correlates of the AP conduction velocity, and directly determines the AP propagation direction through the inherent sensitivity of NVs to the associated AP magnetic field vector.