Quantum Sensing of Lanthandie Binding Tags with Relaxometer of NV Center in Diamond
At a Glance
Section titled âAt a Glanceâ| Metadata | Details |
|---|---|
| Publication Date | 2025-05-06 |
| Journal | Advanced Optical Materials |
| Authors | Zibo Gao, Zhengzhi Jiang, Qiyu Liang, Ruihua He, Van Cuong |
| Institutions | Jilin Agricultural University, Jilin University |
| Analysis | Full AI Review Included |
Technical Documentation & Analysis: Quantum Relaxometry for Biomarker Detection
Section titled âTechnical Documentation & Analysis: Quantum Relaxometry for Biomarker DetectionâThis documentation analyzes the research demonstrating high-sensitivity biomolecule detection using ensemble Nitrogen-Vacancy (NV) center relaxometry in diamond, providing technical specifications and outlining how 6CCVDâs advanced MPCVD diamond materials and engineering services can support and advance this critical quantum sensing application.
Executive Summary
Section titled âExecutive Summaryâ- Core Achievement: Successful demonstration of a low-cost, background fluorescence-free immunomagnetic assay utilizing ensemble NV centers in diamond for highly sensitive biomolecule detection.
- Sensing Mechanism: The method exploits the magnetic noise generated by Gadolinium (GdÂłâș)-loaded Lanthanide Binding Tags (LBTs) to disrupt the NV centerâs T1 spin relaxation time.
- High Sensitivity: Achieved a detection limit of approximately 1 pmol for the Receptor-Binding Domain (RBD) of the SARS-CoV-2 spike protein, comparable to or surpassing many magnetic and optical detection methods.
- Material Requirements: Requires high-quality Single Crystal Diamond (SCD) with a precisely controlled near-surface ensemble NV layer, necessitating ultra-smooth polishing and rigorous chemical functionalization (APTES silanization, BSA passivation).
- Scalability & Adaptability: The platform is readily adaptable for detecting diverse biological entities by simply replacing the functionalization antibody and LBT nanobody, offering significant potential for medical diagnostics and research.
- 6CCVD Value: 6CCVD provides the necessary foundation: ultra-pure, optical-grade SCD substrates with Ra < 1 nm polishing, custom thickness control for optimal NV depth, and integrated metalization capabilities for on-chip microwave delivery.
Technical Specifications
Section titled âTechnical SpecificationsâThe following table summarizes the critical quantitative parameters and performance metrics extracted from the research on NV center relaxometry for LBT detection.
| Parameter | Value | Unit | Context |
|---|---|---|---|
| Target Detection Limit (RBD) | ~1 | pmol | Sensitivity threshold for SARS-CoV-2 RBD protein. |
| LBT Detection Limit (GdÂłâș) | 25 | fmol | Direct detection capability of LBTs on silanized surface. |
| T1 Relaxation Time (Baseline) | 3.02 | ms | T1 value on silanized diamond surface (0 fmol LBTs). |
| T1 Relaxation Time (Max Load) | 0.77 | ms | T1 value after adsorption of 73.5 fmol LBTs. |
| T1-RBD Linear Slope | -0.05 ± 0.0015 | ms/pmol | Observed linear relationship between T1 response and RBD concentration. |
| Zero Field Splitting (D) | ~2.87 | GHz | Energy gap between |
| Optical Initialization Wavelength | Green Laser | N/A | Used to pump NV centers into the |
| Diamond Pickling Temperature | 210 | °C | Required for diamond surface cleaning (H2SO4:HNO3 mixture, 8 hours). |
| Silanization Temperature | 50 | °C | Required for APTES functionalization (16 hours). |
Key Methodologies
Section titled âKey MethodologiesâThe successful implementation of the NV relaxometer relies on precise diamond surface preparation and a multi-step immunomagnetic assay sequence.
- Initial Diamond Cleaning & Hydroxylation:
- Diamond cleaned with 2M NaOH, Acetone, and IPA via ultrasonic treatment.
- Pickling in 1:1 H2SO4:HNO3 at 210 °C for 8 hours.
- Hydroxylation via Piranha solution (3:1 H2SO4:H2O2) at 75 °C for 45 minutes to create surface -OH groups.
- Surface Silanization:
- Hydroxylated diamond incubated in 2% 3-Aminopropyltriethoxysilane (APTES) in 98% toluene at 50 °C for 16 hours.
- This introduces amine (NH2) functional groups for subsequent biomolecule attachment.
- Antibody Immobilization & Passivation:
- RBD polyclonal antibodies coated onto the silanized surface (electrostatic interaction).
- Bovine Serum Albumin (BSA) applied (3% solution) to passivate remaining unbound sites, preventing false positives.
- Target and Probe Binding (Sandwich Assay):
- Purified RBD target protein loaded onto the surface.
- GdÂłâș-containing LBTs (fused with anti-RBD nanobody) introduced, forming the specific antibody-RBD-LBT sandwich structure.
- T1 Relaxometry Measurement:
- Pulsed ODMR sequence used to measure the T1 spin relaxation time of the near-surface ensemble NV centers.
- The decrease in T1 is directly proportional to the magnetic noise generated by the bound GdÂłâș ions, quantifying the target concentration.
6CCVD Solutions & Capabilities
Section titled â6CCVD Solutions & Capabilitiesâ6CCVD is uniquely positioned to supply the foundational diamond materials and customization services required to replicate, optimize, and scale this advanced quantum biosensing platform.
Applicable Materials
Section titled âApplicable MaterialsâTo achieve the high sensitivity and low magnetic noise required for NV relaxometry, the following 6CCVD materials are essential:
- Optical Grade Single Crystal Diamond (SCD): Required for high-coherence quantum sensing. Our SCD plates offer low strain and high purity, crucial for maximizing the T1 spin lifetime (baseline 3.02 ms observed in the study).
- Custom Near-Surface NV Diamond: The experiment relies on ensemble NV centers near the surface for optimal magnetic coupling. 6CCVD offers custom SCD substrates with precise control over nitrogen concentration and post-growth processing (e.g., implantation and annealing) to achieve the required near-surface NV density and depth profile (e.g., 5-10 nm depth).
Customization Potential
Section titled âCustomization PotentialâThe complexity of the experimental setup (involving lightpipes and microwave antennas) demands highly customized diamond substrates.
| Research Requirement | 6CCVD Customization Service |
|---|---|
| Ultra-Smooth Surface for Functionalization | Precision Polishing: We guarantee SCD surfaces with roughness Ra < 1 nm. This ultra-smooth finish is critical for uniform chemical functionalization (APTES) and minimizing non-specific binding, directly impacting assay reliability. |
| Integration with Microwave Delivery | Custom Metalization: The study used an external double split ring antenna. For enhanced performance, 6CCVD offers in-house metalization (e.g., Ti/Pt/Au, W, Cu) to fabricate high-Q microwave transmission lines directly onto the diamond surface, enabling integrated quantum sensing chips. |
| Integration with Optical Components | Custom Dimensions & Shaping: We provide custom laser cutting and shaping services for SCD and PCD plates up to 125 mm. This allows the diamond substrate to be perfectly matched to specialized optical components, such as the hexagonal lightpipe (4mm aperture) used in the reported setup. |
| Scaling and High-Throughput | Large Area Polycrystalline Diamond (PCD): For future high-throughput screening applications, 6CCVD can supply large-area PCD wafers (up to 125 mm) with controlled NV density, offering a cost-effective alternative for ensemble sensing. |
Engineering Support
Section titled âEngineering Supportâ6CCVDâs in-house PhD team specializes in optimizing diamond material properties for quantum applications. We can assist researchers in material selection for similar NV Center Relaxometry and Immunomagnetic Biosensing projects, focusing on:
- Nitrogen Doping Optimization: Tailoring the initial nitrogen concentration to achieve the ideal ensemble NV density for maximum signal-to-noise ratio (SNR).
- Surface Termination: Advising on and providing specific surface terminations (e.g., oxygen or hydrogen) to enhance the stability and efficiency of subsequent chemical functionalization steps (hydroxylation, silanization).
- Advanced Polishing: Ensuring the surface quality meets the stringent requirements for biological assays and minimizes surface noise that degrades T1 coherence.
Call to Action: For custom specifications or material consultation regarding NV center substrates, surface functionalization, or integrated quantum sensing platforms, visit 6ccvd.com or contact our engineering team directly.
View Original Abstract
Abstract Lanthanide binding tags (LBTs) stand out as a prominent group of fluorescent probes that are extensively utilized in biological detection. However, research on LBTs has predominantly emphasized their fluorescence properties, which frequently compromised by background fluorescence noise. Investigating magnetic properties could optimize detection methodologies that offer enhanced sensitivity and specificity. This study measures the response of a relaxometer based on ensemble nitrogenâvacancy (NV) centers in diamond to various amounts of LBTs with gadolinium ions, determining the detection limit of LBTs to be 25 fmol. A detection scheme employing the NV relaxometer to detect specific binding between LBTs and target is then proposed and demonstrated. Specifically, the study assesses the relaxometerâs response to various concentrations of the interaction between the modified LBTs and ReceptorâBinding Domain (RBD) of SARSâCOVIDâ2 spike protein, with the detection threshold reaching â2 pmol. The research provides a potential application platform for biomarker detection under picomole concentration by using NV centers to detect the magnetism of LBTs.