A new method for measuring lung deposition efficiency of airborne nanoparticles in a single breath

Abstract

Assessment of respiratory tract deposition of nanoparticles is a key link to understanding their health impacts. An instrument was developed to measure respiratory tract deposition of nanoparticles in a single breath. Monodisperse nanoparticles are generated, inhaled and sampled from a determined volumetric lung depth after a controlled residence time in the lung. The instrument was characterized for sensitivity to inter-subject variability, particle size (22, 50, 75 and 100 nm) and breath-holding time (3-20 s) in a group of seven healthy subjects. The measured particle recovery had an inter-subject variability 26-50 times larger than the measurement uncertainty and the results for various particle sizes and breath-holding times were in accordance with the theory for Brownian diffusion and values calculated from the Multiple-Path Particle Dosimetry model. The recovery was found to be determined by residence time and particle size, while respiratory flow-rate had minor importance in the studied range 1-10 L/s. The instrument will be used to investigate deposition of nanoparticles in patients with respiratory disease. The fast and precise measurement allows for both diagnostic applications, where the disease may be identified based on particle recovery, and for studies with controlled delivery of aerosol-based nanomedicine to specific regions of the lungs.

Figure 1. Schematic illustration of the instrument.

The aerosol is produced with an electrospray aerosol generator (E-spray), size selected with a differential mobility analyser (DMA) and transferred into an aerosol reservoir where it is diluted and mixed with particle free air. Aerosol from the distal airspaces is sampled into a separate volume and the particle concentration in inhaled and exhaled aerosol is measured with a condensation particle counter (CPC).

Figure 2

(Upper panel) Typical breathing pattern during measurements. From beginning of the measurement (min 30 s) to point (I), the subject breathed particle free air. Thereafter, the subject exhaled to residual volume. At point (II) the four-way valve switched and the subject inhaled particles from the aerosol reservoir. Between points (III) and (IV), all valves were closed and the subject held his breath. After a set period of time, at point (IV), the valve switched again and the subject exhaled into the sample collector. Once the determined sample volume was collected the valve to the sample collector was closed (V) and the subject exhaled to waste. (Lower panel) The measured particle number concentration during a typical measurement. The particle concentration in the aerosol reservoir was monitored until the exhaled sample was collected. Subsequently the exhaled aerosol concentration was measured. The particle recovery, R, was calculated from the mean values for the particle concentrations in inhaled and exhaled aerosols corrected for particle losses in the apparatus.

Figure 3. The recovery, R, for three particle sizes at varying breath-holding times.

Data are for one subject. Standard deviations show variations between three or more measurements (most of the error bars are too small to be visible on this scale).

Figure 4. Observed recovery for 50 nm particles with different flow rates (1.2–10.6 L/s) at 7 s and 10 s breath-holding times, plotted as a function of total residence time.

The data shows that there is correlation between recovery and total residence time (Pearson’s correlation coefficient = 0.94).

Figure 5. Observed recovery for 50 nm particles at different flow-rates (1.2–10.6 L/s) with 7 s and 10 s breath-holding times (the same data as shown in Fig. 4), plotted as a function of flow-rate.

No correlation was found between flow-rate and recovery.

Figure 6. Particle recovery (R) for seven subjects, normalized to 10 s residence time in the lung, compared to calculation with the MPPD model.

The variability between the subjects is 26–50 times larger than the measurement precision.

Figure 7. Observed and modelled values for penetration efficiencies, i.e. recovery, in the inhalation system for various particle sizes and flow rates.