Nanomagnetic particles for SQUID-based magnetically labeled immunoassay
Nanomagnetic Particles for SQUID-based Magnetically Labeled Immunoassay
Abstract
With the increasing importance of SQUID-based magnetically labeled immunoassay, the study on the synthesis of controllable sizes of magnetic nanoparticles plays a role to promote the accuracy of the immunoassay.
In this work, Fe₃O₄ nano-particles coated with a suitable bio-probe (biotin) are synthesized through chemical co-precipitation process to probe the bio-target (avidin). Through the synthesis developed here, the particle hydrodynamic diameter can be adjusted from 30 to 90 nm, which provide candidates for probing various bio-targets in the future.
The amount of the magnetically labeled avidin is then analyzed via measuring the saturated magnetization or the remanence of the sample by using a SQUID magnetometer.
🔬 Key Research Achievements
- SQUID-Based Detection: Utilizes superconducting quantum interference device (SQUID) magnetometry for ultra-sensitive detection of magnetically labeled biomolecules
- Controllable Particle Size: Synthesized Fe₃O₄ nanoparticles with adjustable hydrodynamic diameter ranging from 30 to 90 nm
- Biotin Coating: Nanoparticles functionalized with biotin as bio-probe for specific recognition of avidin bio-target
- Chemical Co-precipitation Method: Reliable synthesis process for producing magnetic nanoparticles with controlled properties
- Multiple Bio-target Capability: Size range provides candidates for probing various bio-targets beyond avidin
- Dual Detection Methods: Quantification via saturated magnetization or remanence measurements using SQUID
- Enhanced Accuracy: Controllable nanoparticle synthesis promotes improved accuracy in immunoassay applications
- Biotin-Avidin Model System: Demonstrates feasibility using well-characterized biotin-avidin interaction
Technical Specifications
Sensitive Detection Capability
Material Characteristics
Research Background
SQUID-Based Magnetically Labeled Immunoassay
SQUID (Superconducting Quantum Interference Device) magnetometry represents one of the most sensitive techniques for detecting magnetic fields. When applied to immunoassay, SQUID-based detection offers several advantages over conventional optical or electrochemical methods:
- Ultra-high Sensitivity: SQUID can detect extremely small magnetic moments, enabling detection of trace amounts of target biomolecules
- No Optical Interference: Unlike fluorescence-based methods, magnetic detection is not affected by sample turbidity or color
- No Background Signal: Biological samples are generally non-magnetic, providing zero background
- Quantitative Analysis: Direct correlation between magnetic signal and number of labeled molecules
- Room Temperature Operation: Modern SQUID systems can operate at accessible temperatures
Importance of Controllable Nanoparticle Size
The synthesis of magnetic nanoparticles with controllable sizes is crucial for optimizing immunoassay performance:
- Magnetic Properties: Particle size directly affects magnetic moment and magnetization behavior
- Binding Efficiency: Optimal size ensures efficient binding to target biomolecules
- Surface Area: Particle size influences the number of bio-probes that can be conjugated
- Detection Sensitivity: Properly sized particles maximize SQUID detection signal
- Bio-target Specificity: Different bio-targets may require different optimal particle sizes
The 30-90 nm range explored in this work provides flexibility for targeting various biomolecules with different molecular weights and sizes.
Biotin-Avidin Interaction
The biotin-avidin system is one of the strongest non-covalent interactions in nature and serves as an ideal model for immunoassay development:
- High Affinity: Dissociation constant (Kd) ~ 10⁻¹⁵ M, one of the strongest known biological interactions
- Specificity: Avidin has four biotin-binding sites with high specificity
- Stability: Interaction stable under various pH and temperature conditions
- Well-Characterized: Extensively studied system with known kinetics and thermodynamics
- Versatile Platform: Can be extended to other biomolecular recognition systems
Synthesis and Detection Methodology
Nanoparticle Synthesis
The Fe₃O₄ magnetic nanoparticles are synthesized through chemical co-precipitation process with specific modifications to control particle size:
1. Chemical Co-precipitation Process
- Controlled mixing of ferrous (Fe²⁺) and ferric (Fe³⁺) salt solutions
- Addition of base solution to precipitate Fe₃O₄
- Precise control of reaction parameters (temperature, pH, concentration)
- Adjustment of synthesis conditions to achieve target particle size
2. Size Control Mechanism
- Variation of precursor concentration affects nucleation rate
- Temperature control influences particle growth kinetics
- Reaction time adjustment determines final particle size
- pH control affects precipitation rate and particle uniformity
3. Biotin Functionalization
- Surface modification of Fe₃O₄ nanoparticles with biotin
- Chemical conjugation ensures stable biotin attachment
- Biotin coating provides specific recognition capability for avidin
- Maintains magnetic properties while adding biological functionality
SQUID Magnetometry Detection
The amount of magnetically labeled avidin is quantified using SQUID magnetometer through two measurement approaches:
1. Saturated Magnetization Measurement
- Sample exposed to strong external magnetic field
- All magnetic moments align with field direction
- Saturated magnetization directly proportional to number of magnetic particles
- Provides quantitative measure of bound avidin-biotin complexes
2. Remanence Measurement
- Residual magnetization after removing external field
- Sensitive to particle size and magnetic properties
- Alternative quantification method for labeled biomolecules
- Can provide information about particle aggregation state
Advantages of This Approach
- Size Tunability: 30-90 nm range covers multiple application requirements
- Reproducible Synthesis: Chemical co-precipitation provides consistent results
- High Sensitivity: SQUID detection enables ultra-low detection limits
- Quantitative Analysis: Direct correlation between magnetic signal and target concentration
- Versatile Platform: Extendable to various bio-recognition systems beyond biotin-avidin
🏥 Applications and Future Prospects
Current Application: Biotin-Avidin Detection
This research demonstrates the feasibility of SQUID-based magnetically labeled immunoassay using the biotin-avidin model system. The strong and specific biotin-avidin interaction validates the detection principle and establishes performance benchmarks.
Future Bio-target Applications
The controllable particle size range (30-90 nm) provides candidates for probing various bio-targets:
- Protein Detection: Antibodies, enzymes, cytokines, hormones
- Cancer Biomarkers: PSA, CEA, AFP, CA-125, and other tumor markers
- Infectious Disease Diagnostics: Viral antigens, bacterial toxins, pathogen-specific antibodies
- Cardiac Markers: Troponin, myoglobin, CK-MB for heart disease diagnosis
- Nucleic Acid Detection: DNA/RNA sequences for genetic testing
- Small Molecule Detection: Drugs, hormones, toxins, environmental contaminants
Advantages for Immunoassay Applications
- Ultra-high Sensitivity: Detection of femtomolar to picomolar concentrations
- Wide Dynamic Range: Several orders of magnitude concentration range
- Minimal Sample Preparation: Direct detection in complex biological matrices
- Rapid Detection: Fast magnetic measurements compared to optical methods
- Automation Potential: Compatible with automated analytical systems
- Cost-Effective: Reusable SQUID sensor reduces per-test costs
Clinical and Research Impact
- Early Disease Detection: Ultra-sensitive detection enables identification of disease at earlier stages
- Point-of-Care Testing: Potential for miniaturized SQUID systems for field use
- Personalized Medicine: Monitoring individual biomarker profiles for tailored treatments
- Drug Development: Screening and validation of therapeutic targets
- Environmental Monitoring: Detection of pollutants and contaminants
Advantages and Innovation
Technical Innovations
- Controllable Synthesis: Systematic approach to adjust particle size from 30 to 90 nm
- SQUID Integration: Application of superconducting sensor technology to immunoassay
- Dual Measurement Methods: Both saturation magnetization and remanence for validation
- Bio-functionalization: Successful biotin coating maintains both magnetic and biological properties
Comparison with Conventional Immunoassay Methods
- vs. ELISA: Higher sensitivity, no optical interference, no enzymatic amplification needed
- vs. Fluorescence: No photobleaching, no background fluorescence, works in opaque samples
- vs. Electrochemical: No electrode fouling, simpler sample handling, wider dynamic range
- vs. Radioimmunoassay: No radioactive materials, safer handling, longer shelf life
Significance for Immunoassay Field
This research demonstrates that controlling magnetic nanoparticle size enhances the accuracy and versatility of SQUID-based immunoassays. The ability to adjust particle diameter according to specific bio-target requirements represents an important step toward optimized magnetic biosensing platforms.
How to Cite This Article
H.E. Horng, S.Y. Yang, Y.W. Huang, W.Q. Jiang, C.-Y. Hong, and H.C. Yang, "Nanomagnetic particles for SQUID-based magnetically labeled immunoassay," IEEE Trans. Appl. Supercond., vol. 15, no. 2, pp. 668-671, June 2005. doi: 10.1109/TASC.2005.849995
BibTeX:
@article{Horng2005,
title={Nanomagnetic particles for SQUID-based magnetically labeled immunoassay},
author={Horng, H.E. and Yang, S.Y. and Huang, Y.W. and Jiang, W.Q. and Hong, C.-Y. and Yang, H.C.},
journal={IEEE Transactions on Applied Superconductivity},
volume={15},
number={2},
pages={668--671},
year={2005},
month={June},
publisher={IEEE},
doi={10.1109/TASC.2005.849995}
}
Related Resources & Further Reading
Keywords & Search Terms
SQUID magnetometer • Magnetically labeled immunoassay • Fe₃O₄ nanoparticles • Biotin • Avidin • Magnetic nanoparticles • Chemical co-precipitation • Superconducting quantum interference device • Biosensing • Magnetic biosensor • Biotin-avidin interaction • Saturated magnetization • Remanence • Nanomagnetic particles • Immunoassay accuracy • Controllable particle size
