SARS-CoV-2 Quantum Sensor Based on Nitrogen-Vacancy Centers in Diamond

At a Glance

Metadata	Details
Publication Date	2021-12-16
Journal	Nano Letters
Authors	Changhao Li, Rouhollah Soleyman, Mohammad Kohandel, Paola Cappellaro
Institutions	University of Waterloo, Massachusetts Institute of Technology
Citations	94
Analysis	Full AI Review Included

SARS-CoV-2 Quantum Sensor: Technical Analysis and 6CCVD Material Solutions

This document analyzes the research paper “SARS-CoV-2 quantum sensor based on nitrogen-vacancy centers in diamond” (arXiv:2111.05472v1) and outlines how 6CCVD’s advanced MPCVD diamond materials and engineering services can support the replication, optimization, and scaling of this quantum biosensing technology.

Executive Summary

The research proposes a highly sensitive, rapid, and scalable quantum sensor for SARS-CoV-2 RNA detection utilizing Nitrogen-Vacancy (NV) centers in nanodiamonds (NDs).

Core Mechanism: Detection relies on monitoring the NV spin relaxation time (T₁), which is quenched by the proximity of Gadolinium (Gd³⁺) complexes attached to the ND surface via complementary DNA (c-DNA).
Detection Principle: Viral RNA hybridization causes the Gd³⁺ complexes to detach and diffuse, resulting in a measurable increase in T₁ and photoluminescence (PL) yield.
Superior Performance: The proposed method achieves a sensitivity down to a few hundreds of viral RNA copies, significantly surpassing the performance of standard RT-PCR.
Low False Negative Rate (FNR): Numerical simulations predict an FNR of less than 1%, compared to FNRs often exceeding 25% for RT-PCR, making it highly accurate for early diagnosis.
Scalability and Speed: The sensor is fast (1-second measurement window) and scalable for high-throughput diagnosis using ensembles of NDs integrated into microfluidic devices.
Material Requirement: Success hinges on high-quality, engineered diamond material with precisely controlled NV centers and optimized surface chemistry to mitigate charge noise.

Technical Specifications

The following hard data points were extracted from the theoretical model and simulation results:

Parameter	Value	Unit	Context
NV Center Zero-Field Splitting (ω₀/2π)	2.87	GHz	Triplet ground state separation
Minimum Detectable RNA Copies (Single NV)	100	Copies	In 1-second integration time (optimal conditions)
Minimum Detectable RNA Copies (Ensemble, 10 NDs)	< 500	Copies	Required for > 99.6% accuracy
False Negative Rate (FNR)	< 1	%	Achievable with ensemble measurements
Optimal Ensemble Accuracy	0.996 ± 0.003	N/A	Achieved with 10 ND average
NV Center Initialization/Readout Wavelength	532	nm	Green laser excitation
NV Center Emission Wavelength	637	nm	Red fluorescence readout
Typical ND Diameter (d)	15 - 40	nm	Used in simulations
Optimal Dark Time (τ)	200	µs	Used for ensemble PL measurement
Surface Gd³⁺ Density (n)	0.1	nm^-2	Average density used in simulations

Key Methodologies

The proposed diagnosis protocol relies on precise material engineering and quantum readout techniques:

Sample Preparation: Viral RNA is isolated and purified from an upper respiratory sample (e.g., swab). Reverse transcription and nucleic acid amplification (RT-PCR) are not required due to the sensor’s high sensitivity.
Nanodiamond Functionalization: Nanodiamonds containing NV centers are coated non-covalently with cationic polymers (e.g., Polyethyleneimine, PEI).
c-DNA/Gd³⁺ Complex Attachment: Complementary DNA (c-DNA) sequences, specific to SARS-CoV-2 RNA, are attached to the PEI coating. These c-DNA strands are complexed with paramagnetic Gadolinium (Gd³⁺) chelators (e.g., DOTA-Gd³⁺).
Magnetic Noise Quenching: The proximity of the Gd³⁺ complexes to the NV centers induces strong transverse magnetic noise, efficiently quenching the NV spin relaxation time (T₁).
Viral RNA Detection: When viral RNA is introduced, strong RNA-DNA hybridization occurs, causing the c-DNA-DOTA-Gd³⁺ complex to detach from the ND surface and diffuse freely in the solution.
Optical Readout: The detachment reduces the magnetic noise felt by the NV centers, leading to a measurable increase in T₁ and a corresponding increase in photoluminescence (PL) intensity after a fixed dark time (τ). This change is monitored optically using a confocal microscope or CCD camera.
Ensemble Measurement: To achieve high accuracy and mitigate parameter variations (ND size, NV position), the fluorescence signal is averaged across an ensemble of NDs, significantly reducing the FNR.

6CCVD Solutions & Capabilities

This research highlights the critical need for high-purity, highly engineered diamond material to realize next-generation quantum sensors. 6CCVD is uniquely positioned to supply the foundational materials and customization services required to advance this technology from theoretical model to scalable diagnostic device.

Applicable Materials

The success of NV-based quantum sensing relies on the quality and purity of the host diamond lattice. 6CCVD provides the necessary high-purity MPCVD substrates for optimal NV creation and integration:

Optical Grade Single Crystal Diamond (SCD): Essential for creating high-coherence NV centers, whether through ion implantation into bulk substrates or as the source material for high-quality nanodiamond synthesis. Our SCD offers superior purity and low defect density, minimizing background noise (T_1,bulk) and maximizing quantum coherence.
High-Purity Polycrystalline Diamond (PCD): For large-area, high-throughput applications, our PCD wafers (up to 125mm diameter) provide a cost-effective, robust platform. While the paper focuses on NDs, future integration into microfluidic chips or alternative solid-state defects (like SiV in SiC, mentioned in the paper) benefits from the scalability of large-area PCD substrates.
Boron-Doped Diamond (BDD): Although not the primary material for NV sensing, BDD is crucial for electrochemical applications. If the sensor requires integrated microelectrodes for charge state control or fluidic manipulation, 6CCVD offers custom BDD films (0.1µm to 500µm thickness).

Customization Potential

The proposed sensor requires precise integration into microfluidic channels and controlled surface functionalization. 6CCVD’s advanced fabrication capabilities directly address these engineering challenges:

Research Requirement	6CCVD Customization Service	Technical Advantage
Scalability & Integration	Custom Plates/Wafers up to 125mm (PCD)	Enables high-throughput fabrication of large sensor arrays and microfluidic chips.
Precise Geometry	Custom Laser Cutting and Shaping	Provides substrates tailored to specific microfluidic channel designs or sensor geometries.
Surface Stability	Ultra-Low Roughness Polishing	SCD (Ra < 1nm) and Inch-size PCD (Ra < 5nm) ensures stable surface chemistry for PEI/c-DNA attachment and minimizes surface charge noise.
Electronic Integration	Custom Metalization Services	Internal capability for depositing Au, Pt, Pd, Ti, W, and Cu contacts, essential for integrating diamond sensors with external electronics or microfluidic heaters/actuators.
Thickness Control	SCD/PCD Films (0.1µm - 500µm)	Allows researchers to optimize film thickness for specific optical or quantum requirements, including thin films for enhanced surface sensitivity.

Engineering Support

The paper emphasizes that future optimization requires better engineering of NV-containing NDs and mitigation of surface charge noise. 6CCVD’s in-house PhD team specializes in MPCVD growth parameters, defect engineering, and surface termination.

Defect Optimization: Our experts can assist researchers in selecting the optimal SCD substrate specifications (e.g., nitrogen concentration, growth rate) to maximize the yield and coherence of NV centers, crucial for replicating or extending this quantum biosensing research.
Surface Mitigation: We offer consultation on surface preparation techniques to reduce the random surface charge noise that can degrade NV coherence, a key limitation discussed in the paper.

For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly.

View Original Abstract

The development of highly sensitive and rapid biosensing tools targeted to the highly contagious virus SARS-CoV-2 is critical to tackling the COVID-19 pandemic. Quantum sensors can play an important role because of their superior sensitivity and fast improvements in recent years. Here we propose a molecular transducer designed for nitrogen-vacancy (NV) centers in nanodiamonds, translating the presence of SARS-CoV-2 RNA into an unambiguous magnetic noise signal that can be optically read out. We evaluate the performance of the hybrid sensor, including its sensitivity and false negative rate, and compare it to widespread diagnostic methods. The proposed method is fast and promises to reach a sensitivity down to a few hundreds of RNA copies with false negative rate less than 1%. The proposed hybrid sensor can be further implemented with different solid-state defects and substrates, generalized to diagnose other RNA viruses, and integrated with CRISPR technology.

Tech Support

Original Source

DOI: https://doi.org/10.1021/acs.nanolett.1c02868