Until recently, it was standard practice for liquid samples containing particulate residues to undergo proper acid digestion before analysis with inductively coupled plasma mass spectrometry (ICP-MS). With this approach, the recorded ICP-MS data reflect the bulk particle population. In 2003, Degueldre demonstrated that ICP-MS can also quantitatively detect individual particles and introduced the concept of single particle (sp)ICP-MS [1]. spICP-MS measures the mass of recorded elements in individual particles and total particle number concentration, and it offers much lower detection limits (< ug particles/kg) than other techniques. The size of an individual particle can be estimated from the recorded mass if the density and shape are known. The ICP-MS signal generated by a single particle is very short in duration (fractions of a millisecond). With a scanning mass analyzer (e.g., quadrupole or magnetic sector), it is not possible to record an entire sweep of elements from this transient signal, and measurements commonly target one or two elements within the particles. Using a time-of-flight mass analyzer, which simultaneously measures all elements at high speed, it is possible to measure the complete multi-element composition of a particle. Today, spICP-MS is most commonly applied for characterization of inorganic nanoparticles and for studying their impact on the environment [2] and living systems [3], but it is not limited to these fields. For example, analysis of individual micro- and nanoparticles in ambient aerosols is another interesting application [4].
How does single particle ICP-MS work?
Single particle ICP-MS analysis has two main requirements:
· The particle number concentration in the sample is very low to reduce the probability of simultaneously introducing multiple particles into the ICP-MS
· The mass analyzer is operated with a dwell /integration time of < 2 milliseconds to observe individual particle detection events
Practically, any liquid sample introduction system can be used, with some being more efficient for particle transport and ionization than others. The particle suspension is usually diluted to the concentration of 105 – 106 particles/ml, depending on the MS hardware configuration. When the number of particles in the sample is low enough, only one particle will enter the ICP at a time. Once in the plasma, a particle is vaporized, atomized and ionized, forming a cloud of elemental ions. The generated ions are directed from the ICP toward the mass analyzer through a pressure-reduction interface that reconciles the pressure difference between the atmospheric-pressure ICP and the low pressure (e.g., 10-6 mbar) mass analyzer. Ion optics are used to efficiently transmit ions to the mass analyzer. The mass analyzer uses electric and/or magnetic fields to separate ions according to their mass-to-charge ratio (m/Q) before they strike a detector. The generated data show the number of ions recorded at each m/Q. The m/Q can be used to determine the elemental identity of an ion, and the number of ions to determine element concentration. The cloud of elemental ions created from a single particle in the ICP source will generate a very fast transient signal (signal spike), with total duration that is a fraction of a millisecond. The mass analyzer must therefore be able to make a very fast measurement to detect these ions. As mentioned, scanning analyzers will generally target one or two elements, whereas TOF mass analyzers are able to record the entire mass spectrum (all m/Q values) for each particle. For any recorded isotope (m/Q value), the total ion signal observed during the duration of the transient particle signal is proportional to the mass of that element in the particle. The frequency of particle events (transient signal spikes) detected by the ICP-MS is proportional to the particle number concentration in the introduced liquid sample. Continuous signal regions that do not contain spikes (single particle detection events) represents the concentration of the sample fraction present in dissolved form.
To ensure that recorded mass spectral data contain signals from single particles, the mass analyzer must be operated with short dwell/integration times [5]. As dwell/integration times increase, the number of recorded events containing the summed signal of two or more successively sampled particles increases, biasing the results. Acquiring data with high temporal resolution also increases the achieved signal-to-noise ratio (SNR): the less noise (particle free data) that is co-integrated with the particle, the better the SNR, and the lower the size detection limit is. Size detection limits achievable with spICP-MS are isotope specific and are typically in the range of 10 nm to a few hundreds of nm.
Converting the recorded signal intensity to element mass and converting the frequency of particle events to particle number concentration both require proper calibration. Calibration based on reference particles is most straightforward, but it is not readily applicable due to lack of these materials. Therefore, Pace et al. [6] proposed an alternative calibration procedure using element standard solutions and a protocol for determining particle transport efficiency and detection efficiency. Though this approach is being utilized in many analytical laboratories, different calibration concepts are also reported in the literature [7].
Ultra-pure water is the most ICP-MS-compatible solvent for single particle analysis and it gives the best detection limits, however, it is not practical for all systems. Single particle analysis can also be conducted in more complex matrices either after sample dilution or after particle extraction [8], [9].
Multi-element single particle ICP-MS
Single particle analysis using ICP-MS with quadrupole or sector-field mass analyzers is limited to simple systems – single-element metal- or oxide-particles – because these mass analyzers can only record the signal of one or two isotopes during the short duration of the particle detection event. In contrast, time-of-flight mass analyzers, such as that used in the TOFWERK icpTOF, can record the signals of all isotopes for each individual particle. So, in addition to reporting element mass and number concentration, TOF-based instruments can characterize the multi-element composition of particles. This unique capability is very useful for the analysis of composite nanoparticles, those applications are growing quickly. Also, pristine, simple particles frequently undergo compositional transformations after exposure to a complex environment, which might change their behavior and interaction pathways. Multi-element single particle ICP-MS provides a means to study these processes.
Production of nanoparticles is rapidly increasing, rising concerns about their negative impact on the environment and living system – including humans. However, the concentrations of engineered nanomaterials already released into the environment are still very small compared to concentrations of natural particles of similar composition. The detection of these manufactured particles is critical for predicting their future impact, but identification of a low concentration analyte in a complex background is very challenging. Fingerprinting of individual particles using multi-element spICP-MS analysis has recently been proposed as a possible approach to this problem. For example, the method has successfully been applied for tracing engineered CeO2 nanoparticles in the high background of natural Ce-containing particles in soils [2].
Further Reading
1. Degueldre, C. and P.Y. Favarger, Colloid analysis by single particle inductively coupled plasma-mass spectroscopy: a feasibility study. Colloids Surf., A, 2003. 217(1-3): p. 137-142.
2. Praetorius, A., et al., Single-particle multi-element fingerprinting (spMEF) using inductively-coupled plasma time-of-flight mass spectrometry (ICP-TOFMS) to identify engineered nanoparticles against the elevated natural background in soils. Environ. Sci.: Nano, 2017. 4(2): p. 307-314.
3. Scanlan, L.D., et al., Silver Nanowire Exposure Results in Internalization and Toxicity to Daphnia magna. ACS Nano, 2013. 7(12): p. 10681-10694.
4. Suzuki, Y., et al., Real-time monitoring and determination of Pb in a single airborne nanoparticle. Journal of Analytical Atomic Spectrometry, 2010. 25(7): p. 947-949.
5. Hineman, A. and C. Stephan, Effect of dwell time on single particle inductively coupled plasma mass spectrometry data acquisition quality. Journal of Analytical Atomic Spectrometry, 2014. 29(7): p. 1252-1257.
6. Pace, H.E., et al., Determining Transport Efficiency for the Purpose of Counting and Sizing Nanoparticles via Single Particle Inductively Coupled Plasma Mass Spectrometry. Analytical Chemistry, 2011. 83(24): p. 9361-9369.
7. Gschwind, S., et al., Capabilities of inductively coupled plasma mass spectrometry for the detection of nanoparticles carried by monodisperse microdroplets. Journal of Analytical Atomic Spectrometry, 2011. 26(6): p. 1166-1174.
8. Peters, R.B., et al., Development and validation of single particle ICP-MS for sizing and quantitative determination of nano-silver in chicken meat. Analytical and Bioanalytical Chemistry, 2014. 406(16): p. 3875-3885.
9. Mitrano, D.M., et al., Detecting nanoparticulate silver using single-particle inductively coupled plasma-mass spectrometry. Environmental Toxicology and Chemistry, 2012. 31(1): p. 115-121.
