Magnetic Microparticles in Clinical Applications
Selection, Quality Metrics and the Supplier Landscape for In-Vitro Diagnostics
Magnetic microparticles generally refer to superparamagnetic particles with diameters in the micrometre or nanometre range. Superparamagnetism means that in the presence of an external magnetic field the particles become magnetic and can be captured by an external magnet, while in the absence of a field they show no magnetism at all. Using this principle, scientists have developed magnetic microparticles of different sizes and with different functional groups for commercial applications.
The core of a magnetic microparticle is a magnetic material such as Fe, Ni, Co or Mn. The core is encapsulated in a hydrophilic polymer coating, a hydrophobic polymer coating or a silica coating, and various functional groups — such as carboxyl, amino, tosyl and hydroxyl — are attached to the outer surface by chemical synthesis. These groups can in turn be used to attach different proteins; linking streptavidin, for example, produces streptavidin (SA) magnetic microparticles. Alternatively, the polymer coating can be replaced with agarose, the most ideal natural polymer material in the field of protein separation and purification, to produce magnetic microparticles for a range of uses. Depending on the application, particle size can vary from 100 nm to 150 µm.
Because technical routes differ between manufacturers, other structural types of magnetic microparticles may also exist.
1. Selecting Magnetic Microparticles
The appropriate particle size is chosen according to the surface functional group and the intended application:
| Application | Typical functional groups | Typical particle size |
|---|---|---|
| Cell separation | Amino or carboxyl microparticles for cross-linking specific antibodies, for example in T-lymphocyte (CD4/CD8) sorting and identification | About 3 µm or 4.5 µm |
| Nucleic acid extraction | Silica-hydroxyl, amino or silica-carboxyl microparticles; widely used in nucleic acid diagnostic kits and prominent in COVID-19 nucleic acid testing | About 500 nm to 1.0 µm |
| Protein purification | Microparticles cross-linked with Protein A/G antibodies, carboxyl microparticles, amino microparticles, or agarose microparticles containing Protein A/G; used for antibody or antigen purification | About 1–3 µm; agarose types about 30–150 µm |
| Small-particle applications | Amino microparticles, used mainly for target identification and metabolic-property studies in biopharmaceuticals | About 200 nm |
| Immunoassay | Carboxyl, amino (as required), tosyl, streptavidin (SA) or FITC-antibody microparticles; commonly used in in-vitro diagnostic (IVD) reagent development | About 300 nm to 3.0 µm |
2. Key Quality Metrics
When selecting a suitable magnetic microparticle, the following indicators are generally considered:
01. Magnetic Responsiveness
This indicates the separation efficiency of the microparticles in an external magnetic field. In theory, larger particles respond faster and separate better.
02. Magnetic Suspension Stability
This checks whether the microparticles remain suspended within the specified time of the reaction system, maximising the reaction time available between antibody and antigen.
03. Non-Specific Adsorption
This indicates the ability of the microparticle surface to bind non-target antibodies or antigens, and whether the customer needs to perform manual blocking.
04. Stability
This tests whether the surface functional groups are bound firmly to the microparticle.
05. Lot-to-Lot Variation
This is a very important metric. Large lot-to-lot variation creates a considerable downstream testing workload.
06. Particle Size Uniformity
This metric reflects a manufacturer's process-control capability. Good control reduces large variation and well-to-well dropout.
07. Iron Leakage Rate
Exposed to strongly acidic conditions, any magnetic microparticle may leach iron, which affects magnetic responsiveness and therefore product quality.
08. Effective Binding Capacity
For SA microparticles, this evaluates the binding capacity for biotinylated antibodies. For carboxyl and amino microparticles, it evaluates the capacity to cross-link antibodies or antigens per unit volume of microparticles.
3. An Overview of Magnetic Microparticle Suppliers
Rapid technical development has driven the growth of the in-vitro diagnostics (IVD) industry, and has made an outstanding contribution to chemiluminescence immunoassay platforms in particular — supporting the upgrade from plate-based chemiluminescence to high-throughput, high-efficiency fully automated chemiluminescence. The technology began to emerge abroad in the 1990s, became widespread in China only from around 2005, and is now very mature.
Major International Suppliers of Immunomagnetic Microparticles
The main international suppliers of immunomagnetic microparticles include Roche (SA microparticles), Agilent (SA and carboxyl microparticles), Merck (amino and carboxyl microparticles), JSR (carboxyl, SA and tosyl microparticles), Thermo Fisher Scientific's Dynabeads series, and Ademtech of France (SA and carboxyl microparticles). Performance is generally good, but prices are relatively high, some manufacturers' products require lot-to-lot testing, and lead times are long.
Major Domestic Suppliers of Immunomagnetic Microparticles
The main domestic suppliers include Suzhou Beaver Biosciences (magnetic microparticles as its core business, with a broad portfolio), Suzhou Weidu Biotechnology (carboxyl and SA microparticles), Hangzhou Boyue Biotechnology (carboxyl and SA microparticles), Chongqing Bolanying Biotechnology (carboxyl, nucleic acid extraction and SA microparticles, among others) and Xiamen Puruimaige Biotechnology (carboxyl and SA microparticles). A number of newer manufacturers have also identified this niche market.
Conclusion
The preparation technology for magnetic microparticles, together with lot-to-lot variation control, has consistently been the key to microparticle quality. In immunology and molecular diagnostics, each manufacturer needs to select microparticles with the appropriate particle size and functional groups according to its own technical conditions and the compatibility of its instrument platform — preventing loss of magnetic response, ensuring the microparticles are mixed evenly, and maintaining liquid-phase reaction conditions as far as possible. In academic research, and particularly on molecular biology platforms, magnetic microparticles also have considerable scope, and can help advance the study of the life sciences.
References
[1] El-Toni AM, Habila MA, Labis JP, ALOthman ZA, Alhoshan M, Elzatahry AA, Zhang F. Design, synthesis and applications of core-shell, hollow core, and nanorattle multifunctional nanostructures. Nanoscale. 2016;8:2510.
[2] Guesdon JL, Avrameas S. J Immunol Methods. 1976;11:129.
