SARS-CoV-2 Quantum Sensor Based on Nitrogen-Vacancy Centers in Diamond
At a Glance
Section titled âAt a Glanceâ| 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 |
Executive Summary
Section titled âExecutive SummaryâThis analysis details a proposed hybrid quantum sensor utilizing Nitrogen-Vacancy (NV) centers in nanodiamonds (NDs) for the rapid and highly sensitive detection of SARS-CoV-2 RNA, offering a significant performance advantage over conventional methods like RT-PCR.
- Core Innovation: The sensor transduces the presence of viral RNA into a measurable change in the NV spin relaxation time (T1) by controlling the proximity of Gadolinium (Gd3+) magnetic complexes.
- Detection Mechanism: Complementary DNA (c-DNA) probes linked to Gd3+ are bound to the ND surface. Viral RNA hybridization causes the Gd3+ complexes to detach, reducing magnetic noise and increasing the NV T1 time, which is read out optically via photoluminescence (PL).
- High Sensitivity: Simulated performance shows a detection limit as low as a few hundreds of viral RNA copies (potentially 100 copies in optimal single-NV scenarios) without requiring nucleic acid amplification.
- Superior Accuracy: Ensemble measurements (averaging signals from multiple NDs) achieve a simulated False Negative Rate (FNR) of less than 1%, dramatically lower than the typical FNR of 25% or greater associated with RT-PCR.
- Speed and Scalability: The protocol is fast, requiring only a 1-second measurement time window, and is scalable for high-throughput diagnosis using microfluidic devices and CCD camera readout.
- Generalizability: The technology can be adapted to diagnose other RNA viruses (e.g., HIV, MERS) by changing the c-DNA probe sequence, and can be integrated with CRISPR technology for further sensitivity enhancement.
Technical Specifications
Section titled âTechnical Specificationsâ| Parameter | Value | Unit | Context |
|---|---|---|---|
| NV Zero-Field Splitting (omega0/2pi) | 2.87 | GHz | Triplet ground state separation. |
| Minimum Detectable RNA Copies | 100 - few hundreds | copies | Single NV sensor, 1s integration time (quantum sensitivity). |
| Ensemble False Negative Rate (FNR) | < 1 | % | Achieved with ensemble averaging (e.g., 10 NDs, Accuracy > 99.6%). |
| RT-PCR FNR (Comparison) | > 25 | % | Typical FNR for standard RT-PCR diagnosis. |
| Total Integration Time (T) | 1 | second | Time window used for sensitivity calculation. |
| ND Diameter (d) Range (Simulated) | 15 to 40 | nm | Diameters used in performance simulations. |
| Gd3+ Surface Density (n) (Average) | 0.1 | nm-2 | Density of c-DNA-DOTA-Gd3+ on ND surface. |
| Gd-ND Surface Distance (l) (Average) | 1.5 | nm | Distance between Gd complex and ND surface. |
| Diffusion Constant (D) | 10-9 | m2s-1 | Used to calculate free Gd diffusion volume. |
| NV Polarization/Readout Wavelength | 532 | nm | Green laser excitation for non-resonant spin initialization. |
| NV Fluorescence Wavelength | 637 | nm | Red fluorescence emission. |
Key Methodologies
Section titled âKey MethodologiesâThe proposed diagnosis relies on a magnetic noise transduction mechanism using functionalized nanodiamonds and optical readout of NV spin relaxation.
- Sample Acquisition and Purification: A sample (e.g., nasopharyngeal swab) is collected, followed by standard nucleic acid extraction and purification (e.g., using fast spin-columns) to isolate viral RNA. Reverse transcription and amplification are not required.
- Nanodiamond Functionalization: Nanodiamonds (NDs) containing NV centers are non-covalently coated with a cationic polymer, such as polyethyleneimine (PEI), which facilitates binding to nucleic acids.
- Probe Preparation and Attachment: Complementary DNA (c-DNA) sequences specific to the SARS-CoV-2 genome are synthesized and complexed with Gadolinium (Gd3+) chelators (e.g., DOTA-Gd3+). These magnetic complexes are then adsorbed onto the PEI-coated ND surface via electrostatic interactions.
- Sample Loading and Reaction: The functionalized NDs are loaded into microfluidic channels. The purified viral RNA sample is injected, allowing the RNA to interact with the surface-bound c-DNA-DOTA-Gd3+ probes.
- Magnetic Noise Transduction: If viral RNA is present, strong RNA-DNA hybridization occurs, causing the c-DNA-DOTA-Gd3+ complexes to detach from the ND surface and diffuse into the solution.
- Optical Readout: The NV centers are optically initialized using a 532 nm laser. The detachment of the Gd3+ complexes reduces the transverse magnetic noise felt by the NV spin, resulting in a longer longitudinal relaxation time (T1). The change in T1 is monitored by measuring the photoluminescence (PL) signal at a fixed dark wait time (tau).
- Ensemble Analysis: To overcome noise and parameter variations (ND size, NV position), the PL signal from an ensemble of NDs is measured simultaneously. A threshold is applied to the PL distribution to classify the sample as positive or negative, maximizing balanced accuracy (minimizing FNR and FPR).
Commercial Applications
Section titled âCommercial ApplicationsâThis technology is relevant across several high-tech sectors, particularly in advanced diagnostics and quantum sensing platforms.
- Infectious Disease Diagnostics:
- Rapid Viral Testing: Provides a fast, non-amplification-based method for detecting active viral infections (e.g., SARS-CoV-2, MERS, HIV).
- Epidemic Surveillance: Enables accurate, quantitative viral load estimation, crucial for tracking infectivity windows and modeling epidemic trajectories.
- Point-of-Care (POC) Devices: The low material cost, scalability, and optical readout simplify the system, making it suitable for portable diagnostic devices.
- Quantum Sensing and Metrology:
- Solid-State Quantum Sensors: Advances the use of NV centers and other solid-state defects (e.g., silicon-vacancy centers in silicon carbide) for highly sensitive magnetic and chemical sensing.
- Biosensing Platforms: Generalizable platform for detecting any nucleic acid (DNA or RNA) by designing specific complementary probes.
- Biotechnology and Nanomaterials:
- Biocompatible Nanomaterials: Utilizes functionalized nanodiamonds as stable, fluorescent, and biocompatible substrates, relevant for drug and gene delivery systems.
- CRISPR Integration: Provides a novel, highly sensitive readout mechanism for CRISPR-based diagnostics, potentially replacing fluorescent reporters with magnetic noise transduction.
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.