Measurement techniques for respiratory tract deposition of airborne nanoparticles: a critical review

Abstract

Determination of the respiratory tract deposition of airborne particles is critical for risk assessment of air pollution, inhaled drug delivery, and understanding of respiratory disease. With the advent of nanotechnology, there has been an increasing interest in the measurement of pulmonary deposition of nanoparticles because of their unique properties in inhalation toxicology and medicine. Over the last century, around 50 studies have presented experimental data on lung deposition of nanoparticles (typical diameter≤100 nm, but here≤300 nm). These data show a considerable variability, partly due to differences in the applied methodologies. In this study, we review the experimental techniques for measuring respiratory tract deposition of nano-sized particles, analyze critical experimental design aspects causing measurement uncertainties, and suggest methodologies for future studies. It is shown that, although particle detection techniques have developed with time, the overall methodology in respiratory tract deposition experiments has not seen similar progress. Available experience from previous research has often not been incorporated, and some methodological design aspects that were overlooked in 30-70% of all studies may have biased the experimental data. This has contributed to a significant uncertainty on the absolute value of the lung deposition fraction of nanoparticles. We estimate the impact of the design aspects on obtained data, discuss solutions to minimize errors, and highlight gaps in the available experimental set of data.

Keywords: NSAM; aerosol; dosimetry; engineered nanoparticles; health; inhalation; lung deposition; pulmonary; ultrafine particles.

FIG. 1.

Total and regional deposition fractions (DFs) of aerosol particles in the range 1–1,000 nm according to the MPPD model. The values are averages for relaxed nose breathing in men and women (tidal volume, 0.75 L and 0.464 L; breathing frequency, 12 min^–1 and 14 min^–1).

FIG. 2.

Size-resolved total DF as a function of particle density (0.0001–20 g/cm³). Data are calculated with the ICRP model for a sitting male adult (nose breathing; tidal volume, 0.75 L; breathing frequency, 12 min^–1).⁽⁵⁾ For small enough particles, DF is independent of particle density (diffusion-dominated regime). The upper limit of the diffusion-dominated regime is between 100 and 600 nm for densities between 20 and 0.5 g/cm³. For a density of 1–2 g/cm³ (typical for ambient particles), the upper size limit of the diffusion-dominated regime is about 300 nm, because at this size DF is twice the value of the zero density line (here: 0.0001 g/cm³), which represents DF due to diffusion only.

FIG. 3.

Schematic pictures of the two major types of inhalation systems used. The flow-through type (left) is the most common, but several groups have also used bag systems (right). Some critical parts usually needed are shown in the left part of the figure: heating of the exhaled aerosol, flow meter, and drying of the particles before the detector.

FIG. 4.

The error occurring if assuming that the DF of a polydisperse aerosol represented that of a monodisperse. Here the relative error in DF (i.e., ΔDF/DF) is depicted as a function of particle diameter for different GSD values (1.2–2.5). The calculations were performed based on DF data generated by the ICRP model (LUDEP v. 1.96; ICRP⁽⁵⁾) for a nose-breathing, sitting male (12 breaths/min; tidal volume, 0.75 L; constant air flow rate, 18 L/min) assuming spherical particles with unit density. It is evident that, for particle diameters below 50 nm, polydispersity does not have a major effect (<8% bias in the measured DF), whereas it introduces an almost 100% error near 500 nm for GSD=2.5. Maintaining less than 8% bias in DF over the entire submicrometer size range requires GSD<1.3.

FIG. 5.

The number of critical design aspects that potentially may have led to a bias in the published experiments (A, B, C, and D refer to items in Table 1). The average for each decade is shown. In total, 40 studies measuring particles below 300 nm in diameter were included. It is important to note that this figure is based solely on information given by the authors of the reviewed studies. As it is likely that some design aspects were addressed properly, but not explicitly mentioned in the studies, this figure presents a “worst case” scenario. Criteria and explanations for each design aspect are found in the Appendix.

FIG. 6.

The fraction of all studies that may be biased because of not appropriately accommodating the critical design aspects introduced above (see Section 4; A, aerosol properties; B, inhalation system; C, particle detection; D, aerosol polydispersity). Black and white indicate design aspects that, if not considered, lead to an overestimate and underestimate of DF, respectively. Gray refers to design aspects that may cause an error in both directions depending on the specific operational conditions. It is important to note that this figure is based solely on information given by the authors of the reviewed studies. As it is likely that some design aspects were addressed properly, but not explicitly mentioned in the studies, this figure presents a “worst case” scenario. Criteria and explanations for each design aspect are found in the Appendix.

FIG. 7.

Inhaled size distribution and the exhaled distribution as calculated by the ICRP model (tidal volume, 0.750 L; breathing frequency, 12 min^–1). A presumed 5% negative size shift of the exhaled distribution due to, for instance, evaporation or agglomerate restructuring is also shown. If the size-shifted exhaled distribution is used to calculate the DF, an error will occur as shown in Figure 8.

FIG. 8.

Error caused by 1% and 5% size shifts of the exhaled size distribution from Figure 7. The erroneous deposition curves are calculated by using size-shifted exhaled distributions (ICRP model; tidal volume, 0.75 L; breathing frequency, 12 min^–1).