Improving Resolution of Single Nanoparticles Using ICP-MS and Shorter Dwell Times

Improving Single-Nanoparticle ICP-MS Resolution Using Shorter Dwell Times (50 s) — Technical Overview

Significance of the topic

Single-particle ICP-MS (spICP-MS) is a key analytical technique for characterizing engineered nanoparticles (sNPs, < 100 nm) used across industry and research. High temporal resolution of transient ion signals from individual particles is essential to obtain accurate particle-size distributions and number concentrations. In critical applications such as semiconductor process control, detection of sub-10 nm contaminants can determine product yield; in environmental and biological matrices, precise nanoparticle measurement supports exposure and risk assessment. Improved temporal resolution reduces event overlap and increases confidence in distinguishing individual particle events.

Objectives and overview of the study

The study evaluated the performance benefits and trade-offs of operating an Agilent 9500 ICP-QQQ in single-particle mode with a reduced dwell time of 50 s versus the common 100 s setting. Goals were to determine whether 50 s dwell time yields sharper, better-resolved nanoparticle signals, to compare measured mean particle sizes and distributions against certified TEM values, and to assess the practical implications for data acquisition and processing workload.

Methodology and sample preparation

Key experimental elements:

• Nanoparticle standards: Seven suspensions from nanoComposix: Au (30, 60, 100 nm), Pt (50, 70 nm), and SiO2 (500, 1000 nm).
• Ionic standards: Aqueous Au, Pt, and Si ionic standards diluted from 1000 ppm stocks to evaluate instrumental sensitivity and to correct for element-specific response.
• Nebulization efficiency: Determined from the 60 nm Au material and applied to convert Pt and SiO2 signals to equivalent particle sizes with sensitivity correction from ionic standards.
• Data acquisition: Rapid Multi-Element Nanoparticle Analysis mode (Agilent OpenLab Single Nanoparticle Application Module) to sequentially collect multi-element data in a single sample uptake.

Instrumentation used

Instrumentation and configuration details summarized from the study:

• ICP-MS: Agilent 9500 Triple Quadrupole ICP-MS (ICP-QQQ) in single-particle mode, standard Ni sampling/cones and u-lens.
• Torch: Quartz torch fitted with a 1.5 mm inner-diameter injector to minimize ion-cluster diffusion and sharpen transient peaks.
• Operating conditions of note: RF power ~1550 W, sampling depth ~10 mm, nebulizer gas flow ~0.96 L/min, lens voltages set by autotune, no collision/reaction gas used during NP mode.
• Software: OpenLab ICP-MS with the Single Nanoparticle Application Module; multithreaded CPU-based processing to handle increased data volumes from shorter dwell times.
• Optional components cited: Single nanoparticle module (part number G5714A) and 1.5 mm torch for 9500 ICP-MS (part number M5150-67012).

Results and discussion — peak shape and event resolution

Key findings:

• Peak sharpness: Using a 50 s dwell time produced noticeably sharper and better-resolved transient peaks for single nanoparticle events compared with data binned at 100 s. Individual particle peaks that were merged at 100 s became separable at 50 s.
• Event overlap (coincidence): Shorter dwell times reduce the probability that two particles arriving close in time will be recorded as a single event, which otherwise leads to a positive bias in apparent particle size and a negative bias in particle number concentration.
• Signal-to-noise considerations: Sampling over shorter intervals reduces both peak sampling duration and background sampling, which lowers S/N per data point. This can reduce detection efficiency for very small or low-signal particles that were detectable at longer dwell times.

Results and discussion — particle size and distributions

Comparative performance:

• Mean sizes: For all tested Au, Pt, and SiO2 materials the mean particle sizes measured with a 50 s dwell time were consistent with manufacturer-certified TEM values and matched results obtained with 100 s dwell time within stated uncertainties.
• Distributions: Particle size distributions for a 57 6 nm Au material were near-normal and centered around ~60 nm for both 50 and 100 s acquisitions, with slight skew toward the lower size range consistent with the certificate of analysis.
• Large particles: For larger SiO2 standards (500 and 1000 nm), measured mean diameters at 50 s agreed with certified sizes and with 100 s results, demonstrating applicability across a wide size range.

Practical trade-offs and data handling

Operational implications:

• Data volume: Halving dwell time approximately doubles the number of data points, increasing storage and processing demand. Multithreaded analysis software is required to maintain practical analysis times for large datasets.
• Flexibility: The 50 s option adds analytical flexibility for samples with unexpectedly high particle counts, potentially reducing the need for additional dilutions.
• Analytical limits: While 50 s improves temporal resolution and reduces coincidence, analysts must weigh gains in peak separation against potential loss of sensitivity for the smallest particles due to decreased S/N per dwell.

Benefits and practical applications

Practical advantages demonstrated in the study:

• Improved resolution of closely spaced nanoparticle events enables more accurate particle counts and reduces size-distribution bias from coincident events.
• Compatibility with multi-element sequential acquisition reduces sample handling and contamination risk by measuring multiple analytes in a single uptake.
• Maintains consistency with certified TEM sizes, indicating that higher temporal resolution does not compromise accuracy for mean-size determination when appropriate corrections (nebulization efficiency, ionic sensitivity) are applied.
• Useful in semiconductor process monitoring, environmental/food/biological nanoparticle surveillance, and research requiring detection of low-frequency but critical particle events.

Future trends and opportunities for use

Anticipated developments and applications:

• Hardware evolution: Further improvements to ion optics, detector electronics, and faster ADCs will continue to enable even shorter dwell times with improved S/N.
• Real-time processing: On-instrument or GPU-accelerated real-time deconvolution and event discrimination will mitigate the processing burden of high-rate data streams.
• Advanced data analysis: Machine-learning algorithms to deconvolve overlapping events and to improve detection of low-S/N particles are likely to enhance sensitivity at short dwell times.
• Standardization and uncertainty quantification: Broader adoption will drive standards for reporting dwell-time-dependent uncertainties and best practices for nebulization-efficiency calibration.
• Expanded sample types: Demonstrated robustness suggests wider application to organic solvents, complex matrices, and regulatory monitoring where improved temporal resolution is beneficial.

Conclusion

Operating the Agilent 9500 ICP-QQQ in single-particle mode with a 50 s dwell time yields improved temporal resolution and peak separation compared with a 100 s dwell time while producing mean particle sizes and distributions consistent with certified TEM values. The shorter dwell time reduces event coincidence and improves confidence in particle counting, at the cost of increased data volume and potentially reduced S/N for the smallest particles. The combination of optimized hardware (torch injector, robust plasma), instrument tuning, and multithreaded software processing makes 50 s a practical option that expands analytical flexibility for demanding nanoparticle measurements.

References

1. Waegeneers N., et al. Estimation of the Uncertainties Related to the Measurement of the Size and Quantities of Individual Silver Nanoparticles in Confectionery. Materials. 2019;12(17):2677. DOI: 10.3390/ma12172677.
2. Agilent Technologies. Multielement Nanoparticle Analysis of Semiconductor Process Chemicals Using spICP-QQQ. Agilent publication 5994-0987EN.
3. Agilent Technologies. Analysis of Nanoparticles in Organic Reagents by Agilent 8900 ICP-QQQ in spICP-MS Mode. Agilent publication 5994-1306EN.
4. Agilent Technologies. Analysis of 15 nm Iron Nanoparticles in Organic Solvents by spICP-MS. Agilent publication 5994-1747EN.
5. Agilent Technologies. Extending ICP-MS Capabilities to Detect Nanoparticles in Food. Agilent publication 5994-1748EN.