Quantitative characterization of silica nanoparticles by asymmetric flow FFF‑MALS‑ICP‑QQQ using the Agilent 8800 ICP‑QQQ

Significance of the Topic

The reliable quantification and size characterization of silica nanoparticles (NPs) is critical in food, environmental and industrial applications due to their widespread use as additives, in consumer products and emerging biomedical technologies.

Growing concerns about long-term health and safety effects of synthetic amorphous silica drive the need for robust analytical methods that can separate, size and quantify nanoparticles with high specificity and sensitivity.

Objectives and Study Overview

This study presents a novel on-line coupling of asymmetric flow field-flow fractionation (A4F) with multi-angle light scattering (MALS) and triple quadrupole inductively coupled plasma mass spectrometry (ICP-QQQ) for quantitative characterization of silica NPs.

Key aims:

• Separate silica NPs in the 20–200 nm size range by A4F.
• Determine particle size via MALS and calibration using known monodisperse standards.
• Quantify silicon mass in each size fraction using Agilent 8800 ICP-QQQ in O₂ MS/MS mass-shift mode to avoid polyatomic interferences.

Methodology and Instrumentation

The A4F separation used a regenerated cellulose membrane and stepped cross-flow conditions to resolve particle sizes from 20 to 180 nm.
The MALS detector measured the radius of gyration (r_g), converted to hydrodynamic diameter (d_h) via the relation r_g/r_h = 0.775.
ICP-QQQ operated in MS/MS mass-shift mode with O₂ gas to convert Si⁺ to SiO⁺, enabling interference-free detection of m/z 44, 45 and 46.
Calibration strategies included:

• Pre-channel calibration with monodisperse silica standards to relate elution time to size and mass.
• Post-channel calibration with ionic silicon standards for comparison.

Used Instrumentation

• Postnova AF2000 MT asymmetric flow FFF system with 350 µm spacer and 10 kDa membrane.
• Postnova 3621 MALS detector (flat channel, 280 mm length).
• Agilent 8800 Triple Quadrupole ICP-MS with octopole CRC, platinum injector, PFA concentric nebulizer and cooled double-pass spray chamber.

Main Results and Discussion

Polyatomic interferences on Si (e.g. 14N14N⁺ at m/z 28) were eliminated by O₂ mass-shift, yielding linear calibration (R² > 0.999) and limits of detection down to 0.09 µg/L Si.
Hydrodynamic diameters measured by MALS and FFF-ICP-QQQ agreed with certified reference values within experimental uncertainties.
Recovery studies on ERM-FD100 (bovine liver) and a 140 nm silica test sample demonstrated accurate size and mass determination, with pre-channel calibration providing the most reliable quantification.
Background Si from the FFF eluent (due to surfactant FL-70) was identified and quantified, suggesting improved performance by reducing eluent contamination.

Benefits and Practical Applications

• Simultaneous size and element-specific quantitative analysis supports quality control of nano-formulated products.
• The method addresses regulatory needs by providing traceable measurements across the nano-range.
• Suitable for food safety assessments, environmental fate studies and nanotoxicology research.

Future Trends and Possibilities

• Applying isotope dilution with isotopically enriched silica NPs for absolute quantification.
• Extension to complex matrices (food, biological fluids) with tailored sample preparation.
• Integration with orthogonal detectors (e.g. fluorescence, UV) to broaden characterization capabilities.

Conclusion

The on-line A4F-MALS-ICP-QQQ method enables accurate separation, sizing and quantification of silica nanoparticles over a 20–200 nm range.
Mass-shift ICP-QQQ provides interference-free silicon detection, while dual calibration strategies enhance confidence in particle mass measurements.
This approach meets emerging regulatory and research demands for robust nanoparticle analysis.

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