Microscopic-scale magnetic recording of brain neuronal electrical activity using a diamond quantum sensor

At a Glance

Metadata	Details
Publication Date	2023-07-31
Journal	Scientific Reports
Authors	Nikolaj Winther Hansen, James L. Webb, Luca Troise, Christoffer Olsson, Leo Tomasevic
Institutions	Technical University of Denmark, Hvidovre Hospital
Citations	14
Analysis	Full AI Review Included

Executive Summary

This analysis summarizes the microscopic-scale magnetic recording of neuronal electrical activity using a diamond quantum sensor, focusing on engineering and material science aspects.

Core Achievement: Demonstrated the first microscopic-scale biomagnetic recording of action potential propagation (Compound Action Potential, cAP) in fragile, living mammalian brain tissue (mouse corpus callosum).
Sensor Performance: Achieved a high magnetic field sensitivity of 50 pT/√Hz with a wide sensing bandwidth of 10 kHz, sufficient to resolve fast neural signal components (S1 and S2).
Methodology: Utilizes passive, remote sensing based on Optically Detected Magnetic Resonance (ODMR) of Nitrogen-Vacancy (NV) color centers in a CVD-grown diamond layer.
Biocompatibility & Non-Invasiveness: The technique is entirely passive, avoiding direct interaction with the tissue, eliminating the need for invasive electrodes, voltage-sensitive dyes, or genetic modification.
Material Design: The sensor uses a 20 µm thick CVD-overgrown layer doped with ~5 ppm ¹⁴N on a [100] electronic-grade diamond substrate, optimized for high NV density near the surface.
Pharmacological Validation: Successfully performed in situ pharmacology by monitoring the dose-dependent inhibition of action potentials using the sodium channel blocker Tetrodotoxin (TTX).
Future Prospect: Opens a new avenue for microscopic imaging of electrical activity in living mammalian brain tissue with high spatial resolution, leveraging the consistent density of NV centers.

Technical Specifications

Parameter	Value	Unit	Context
Magnetic Field Sensitivity	50	pT/√Hz	Achieved using NV ensemble.
Sensing Bandwidth (f_-3dB)	10	kHz	Determined by lock-in time constant (10 µs).
Diamond Substrate Size	2 x 2 x 0.5	mm³	Electronic-grade, [100] oriented.
CVD Overgrowth Thickness	20	µm	Layer containing NV centers.
Nitrogen Doping Concentration	~5	ppm	¹⁴N doping in the CVD layer.
NV Conversion Irradiation	2.8	MeV	Proton irradiation energy.
Annealing Temperature	800	°C	Performed in an inert atmosphere.
ODMR Linewidth (Single NV Axis)	1	MHz	Resonance quality.
ODMR Contrast (Single NV Axis)	1.5	%	Fluorescence change.
Pump Laser Wavelength	532	nm	Green laser (Coherent Verdi G2).
Pump Laser Power	1.2 - 1.4	W	Coupled into the diamond at Brewster’s angle (67°).
Static Bias Field (B₀)	1.5	mT	Applied parallel to diamond [110] direction.
Microwave Frequency Range	2.7 - 3	GHz	Used for spin transition.
Lock-in Modulation Frequency	33.3	kHz	Used for lock-in detection.
Sample-Sensor Distance	~60	µm	Separation maintained by Kapton insulating layer.
Tissue Bath Temperature	25	°C	Maintained stably for up to 24 hours.
Sensing Volume (Approximate)	300 x 100 x 20	µm³	Defined by laser spot size and NV layer depth.

Key Methodologies

Diamond Material Synthesis: A [100] oriented electronic-grade diamond was overgrown using Chemical Vapor Deposition (CVD) to create a 20 µm thick layer doped with approximately 5 ppm of ¹⁴N.
NV Center Creation: Nitrogen-Vacancy (NV) centers were formed by 2.8 MeV proton irradiation near the top surface of the CVD layer, followed by annealing at 800 °C in an inert atmosphere.
Thermal and Electrical Isolation: The diamond was mounted in an aluminum nitride heatsink. A 16 µm thick aluminum foil (secondary heatsink/reflector) and a 50 µm Kapton tape layer (electrical insulator) separated the diamond from the biological sample.
Optical Pumping Setup: A 532 nm green laser (1.2-1.4 W) was coupled into the diamond from beneath at Brewster’s angle (67°). The light was focused to a 300 x 100 µm spot, ensuring the pump light was entirely contained within the diamond and did not interact with the tissue or solution bath.
Magnetic Resonance Control: A continuous wave ODMR scheme was employed using two microwave generators tuned to the spin transition (2.7-3 GHz) and ¹⁴N hyperfine transitions (2.16 MHz). Microwaves were modulated at 33.3 kHz for lock-in detection.
Sample Preparation and Placement: 400 µm thick coronal mouse brain slices (corpus callosum) were kept alive in a chilled, carbogenated Artificial Cerebrospinal Fluid (ACSF) bath at a stable 25 °C, positioned ~60 µm above the NV sensing volume.
Signal Validation: Neuronal activity was induced electrically (0.2-0.8 mA current pulses) and simultaneously recorded using the passive NV quantum sensor and an invasive AgCl coated silver electrode (Local Field Potential, LFP) for direct comparison and validation.
Data Processing: Raw data was filtered to remove electrical mains noise (50/150 Hz) and non-stationary sources. A three-stage filtering process included time-domain artifact subtraction, frequency-domain notch filtering, and inverse Fourier transform to extract and average 100 ms epochs centered on stimulation triggers.

Commercial Applications

Quantum Sensing Technology: Manufacturing and sale of high-performance, solid-state magnetometers based on NV-diamond ensembles for industrial and research applications requiring high sensitivity (pT/√Hz) and wide bandwidth (kHz).
Biomedical Imaging and Diagnostics: Development of non-invasive microscopic imaging systems for functional analysis of fragile biological tissues, particularly for studying early onset mechanisms of neurodegenerative diseases (e.g., MS, Alzheimer’s) in animal models.
Drug Screening Platforms: Creation of high-throughput, non-contact platforms for pharmacological testing, allowing researchers to monitor the real-time effects of drugs (like ion channel blockers) on neuronal or cardiac electrical activity in situ.
Advanced CVD Diamond Materials: Production of custom-engineered electronic-grade diamond substrates and CVD overgrowth layers with precise control over nitrogen doping concentration (e.g., 5 ppm ¹⁴N) and NV creation protocols (irradiation/annealing) for quantum applications.
Bioelectronic Interface Technology: Supply of biocompatible, robust diamond sensor chips for integration into complex biological environments where traditional electrodes or optical probes are unsuitable due to invasiveness or phototoxicity.

View Original Abstract

Abstract Quantum sensors using solid state qubits have demonstrated outstanding sensitivity, beyond that possible using classical devices. In particular, those based on colour centres in diamond have demonstrated high sensitivity to magnetic field through exploiting the field-dependent emission of fluorescence under coherent control using microwaves. Given the highly biocompatible nature of diamond, sensing from biological samples is a key interdisciplinary application. In particular, the microscopic-scale study of living systems can be possible through recording of temperature and biomagnetic field. In this work, we use such a quantum sensor to demonstrate such microscopic-scale recording of electrical activity from neurons in fragile living brain tissue. By recording weak magnetic field induced by ionic currents in mouse corpus callosum axons, we accurately recover signals from neuronal action potential propagation while demonstrating in situ pharmacology. Our sensor allows recording of the electrical activity in neural circuits, disruption of which can shed light on the mechanisms of disease emergence. Unlike existing techniques for recording activity, which can require potentially damaging direct interaction, our sensing is entirely passive and remote from the sample. Our results open a promising new avenue for the microscopic recording of neuronal signals, offering the eventual prospect of microscopic imaging of electrical activity in the living mammalian brain.

Tech Support

Original Source

DOI: https://doi.org/10.1038/s41598-023-39539-y