In-vitro Recordings of Neural Magnetic Activity From the Auditory Brainstem Using Color Centers in Diamond - A Simulation Study

At a Glance

Metadata	Details
Publication Date	2021-05-13
Journal	Frontiers in Neuroscience
Authors	Mürsel Karadas, Christoffer Olsson, Nikolaj Winther Hansen, Jean‐Françóis Perrier, James L. Webb
Institutions	Technical University of Denmark, University of Copenhagen
Citations	5
Analysis	Full AI Review Included

Technical Documentation & Analysis: NV-Diamond Neuromagnetometry

Research Paper: In-vitro Recordings of Neural Magnetic Activity From the Auditory Brainstem Using Color Centers in Diamond: A Simulation Study (Karadas et al., 2021)

Executive Summary

This simulation study validates the feasibility and defines the material requirements for using Nitrogen-Vacancy (NV) center magnetometry in MPCVD diamond to image neural activity in vitro.

Core Application: High-resolution 2D magnetic imaging of fast action potentials (APs) traveling along the auditory brainstem pathway (VCN-MNTB) in rodent brain slices.
Signal Strength: Peak magnetic fields were simulated at ~0.5 nT (electrical stimulation) and ~0.1 nT (optical stimulation) for the more likely scenario of 1,250 active cells.
Resolution Challenge: Achieving high spatial resolution imaging of individual APs requires next-generation NV sensors with an area-normalized sensitivity of 10 nT µm or better.
Current Feasibility: Existing NV sensors (sensitivity ~1,520 nT µm) are already capable of sensing spatially averaged, cumulated neural signals from larger parts of the pathway, serving as a promising intermediate step.
Material Requirement: Success hinges on high-quality Single Crystal Diamond (SCD) with precisely controlled NV-center density, ultra-low surface roughness, and custom geometry.
6CCVD Value: 6CCVD provides the necessary Optical Grade SCD and advanced fabrication services (precision thickness, polishing, custom metalization) required to manufacture both current and next-generation NV-diamond quantum sensors.

Technical Specifications

The following hard data points were extracted from the simulation study, defining the performance metrics and physical constraints for NV-diamond sensor development in this application.

Parameter	Value	Unit	Context
Peak Magnetic Field (Electrical Stim)	~0.5	nT	Estimated for 1,250 MNTB cells
Peak Magnetic Field (Optical Stim)	~0.1	nT	Estimated for 1,250 MNTB cells
Required Area-Normalized Sensitivity	10	nT µm	Necessary for high-resolution AP reconstruction
Existing Area-Normalized Sensitivity	1,520	nT µm	Based on 5 µm NV layer, 10 kHz sampling
Active Brain Slice Thickness	300	µm	Rodent brainstem slice model
Sensor Distance to Active Layer	25	µm	Distance from diamond surface to active tissue
Assumed NV Layer Thickness	5	µm	Used in sensitivity calculation
Optical Stimulation Wavelength	473	nm	Channelrhodopsin-2 (ChR2) excitation
Max Temperature Rise (Pulsed Stim)	<2	°C	Worst-case scenario (4 W/mm², 40 Hz)
NV-Center Sensitivity (Reported)	pT/Hz^1/2 and below	pT/Hz^1/2	Achieved by existing sensors at ambient temperature

Key Methodologies

The simulation relied on precise modeling of neural dynamics and light/magnetic field propagation, highlighting critical material and geometric requirements for the diamond sensor platform.

Cellular Modeling: The auditory pathway (GBC-MNTB) was modeled using the cable equation in NEURON software, incorporating realistic neural morphologies and ion channel dynamics (Na⁺, K⁺, Ca²⁺, I_h).
NV-Center Sensor Model: A planar NV sensor was assumed, placed 25 µm from the active 300 µm brain slice layer. The NV layer thickness was assumed to be 5 µm.
Optical Stimulation (Optogenetics): Optogenetic excitation was modeled using a four-state Channelrhodopsin-2 (ChR2) kinetic model, driven by 473 nm light.
Light Distribution Modeling: The Kubelka-Munk (KM) model was primarily used to estimate light irradiance in the tissue, crucial for determining the activation rate of ChR2 channels.
Thermal Analysis (Worst-Case): Monte Carlo simulations were used to provide worst-case irradiance estimates, which were then input into the simplified Pennes bioheat equation to confirm that temperature rise remained below 2°C during pulsed stimulation.
Magnetic Field Calculation: The extracellular magnetic fields (B) and local field potentials (LFP) were calculated using a forward modeling scheme, accounting for axial and transmembrane currents.
Stimulation Parameters:
- Electrical: Intracellular current injections (5 nA) or extracellular monopolar stimulation (100 µA, 100 µs) via a simulated TiN electrode.
- Optical: Light probe (0.2 mm diameter, NA 0.37) with source irradiance up to 4 W/mm² and pulse durations of 3 ms.

6CCVD Solutions & Capabilities

6CCVD is uniquely positioned to supply the advanced MPCVD diamond materials and fabrication services necessary to replicate this research and accelerate the development of next-generation NV-diamond quantum sensors.

Applicable Materials

To achieve the high sensitivity and low noise required for NV-center magnetometry, the material must be of the highest quality.

Optical Grade Single Crystal Diamond (SCD): This is the essential material for NV-center quantum sensors. 6CCVD provides high-purity, low-strain SCD necessary to maximize the spin coherence time (T₂*) and optical transparency required for Optically Detected Magnetic Resonance (ODMR).
Controlled Nitrogen Doping: The paper notes that NV-center density (nnv ~ 1ppm) is a limiting factor. 6CCVD offers precise control over nitrogen incorporation during MPCVD growth, enabling the creation of custom-doped SCD layers optimized for specific NV-center concentrations and layer depths (e.g., the 5 µm layer assumed in the model).

Customization Potential

The success of this application relies on integrating the diamond sensor into a complex biological setup, requiring precise geometry, surface quality, and integrated components.

Research Requirement / Challenge	6CCVD Solution & Capability	Technical Specification
Precision NV Layer Thickness	Custom SCD Thickness Control	SCD layers available from 0.1 µm up to 500 µm, allowing precise engineering of the active 5 µm NV layer depth.
Wide-Field Imaging Arrays	Large Area PCD Substrates	Polycrystalline Diamond (PCD) plates/wafers available up to 125mm diameter, ideal for scaling up wide-field sensor arrays.
Optimal Optical Interface	Ultra-Low Roughness Polishing	SCD polishing to Ra < 1 nm and inch-size PCD polishing to Ra < 5 nm. Essential for minimizing light scattering (both excitation and fluorescence collection) and ensuring close proximity (25 µm) to the tissue slice.
Integrated Electrodes/Shielding	Custom Metalization Services	Internal capability for depositing thin films (Au, Pt, Pd, Ti, W, Cu). This supports the integration of microelectrodes (e.g., the TiN electrode mentioned) or reflective shielding layers required for the optical setup.
Robust Sensor Platform	Thick Substrates	SCD or PCD substrates available up to 10 mm thick for robust mechanical and thermal stability in complex experimental setups.

Engineering Support

The transition from simulation (predicting 10 nT µm sensitivity is needed) to physical realization requires deep material science expertise.

6CCVD’s in-house PhD engineering team specializes in optimizing MPCVD diamond growth parameters (purity, strain, nitrogen concentration) specifically for Quantum Sensing and Neuromagnetometry applications. We provide consultation on material selection, doping profiles, and surface preparation to help researchers achieve the necessary sensitivity improvements (two orders of magnitude) required for next-generation NV sensors capable of high-resolution AP imaging.

Call to Action: For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly. We ship globally (DDU default, DDP available).

View Original Abstract

Magnetometry based on nitrogen-vacancy (NV) centers in diamond is a novel technique capable of measuring magnetic fields with high sensitivity and high spatial resolution. With the further advancements of these sensors, they may open up novel approaches for the 2D imaging of neural signals in vitro . In the present study, we investigate the feasibility of NV-based imaging by numerically simulating the magnetic signal from the auditory pathway of a rodent brainstem slice (ventral cochlear nucleus, VCN, to the medial trapezoid body, MNTB) as stimulated by both electric and optic stimulation. The resulting signal from these two stimulation methods are evaluated and compared. A realistic pathway model was created based on published data of the neural morphologies and channel dynamics of the globular bushy cells in the VCN and their axonal projections to the principal cells in the MNTB. The pathway dynamics in response to optic and electric stimulation and the emitted magnetic fields were estimated using the cable equation. For simulating the optic stimulation, the light distribution in brain tissue was numerically estimated and used to model the optogenetic neural excitation based on a four state channelrhodopsin-2 (ChR2) model. The corresponding heating was also estimated, using the bio-heat equation and was found to be low (&lt;2°C) even at excessively strong optic signals. A peak magnetic field strength of ∼0.5 and ∼0.1 nT was calculated from the auditory brainstem pathway after electrical and optical stimulation, respectively. By increasing the stimulating light intensity four-fold (far exceeding commonly used intensities) the peak magnetic signal strength only increased to 0.2 nT. Thus, while optogenetic stimulation would be favorable to avoid artefacts in the recordings, electric stimulation achieves higher peak fields. The present simulation study predicts that high-resolution magnetic imaging of the action potentials traveling along the auditory brainstem pathway will only be possible for next generation NV sensors. However, the existing sensors already have sufficient sensitivity to support the magnetic sensing of cumulated neural signals sampled from larger parts of the pathway, which might be a promising intermediate step toward further maturing this novel technology.

Tech Support

Original Source

DOI: https://doi.org/10.3389/fnins.2021.643614

References

2009 - Diamonds with a high density of nitrogen-vacancy centers for magnetometry applications. [Crossref]
2010 - Temperature dependence of the nitrogen-vacancy magnetic resonance in diamond. [Crossref]
2013 - Light scattering properties vary across different regions of the adult mouse brain. [Crossref]
2007 - An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. [Crossref]
2013 - Theoretical principles underlying optical stimulation of myelinated axons expressing channelrhodopsin-2. [Crossref]
2008 - Nanoscale imaging magnetometry with diamond spins under ambient conditions. [Crossref]
2009 - Ultralong spin coherence time in isotopically engineered diamond. [Crossref]
1995 - Pre- and postsynaptic glutamate receptors at a giant excitatory synapse in rat auditory brainstem slices. [Crossref]
2020 - Sensitivity optimization for NV-diamond magnetometry. [Crossref]
2016 - Optical magnetic detection of single-neuron action potentials using quantum defects in diamond. [Crossref]