Rapid and Sensitive Chemical Analysis of Individual Picolitre Droplets by Mass Spectrometry

Abstract

Aerosol droplets are unique microcompartments containing microscopic amounts of material and exhibiting surprising chemical reactivity. Although a diverse set of tools exists to characterize the chemical composition of individual submicron particles in air, comparatively fewer approaches can chemically analyze individual, airborne picolitre droplets. We describe a novel approach for mass spectrometric analysis of individual aqueous picolitre droplets (∼2-180 pL volume) containing down to ∼1 pg analyte mass per droplet. Individual droplets are generated using a microdroplet dispenser, imparted a small amount of net charge, and guided to the inlet of a high-resolution mass spectrometer using a linear quadrupole-electrodynamic balance. Analyte molecules within the aqueous droplet are ionized using droplet assisted ionization, where droplet breakup within the mass spectrometer inlet leads to generation of molecular ions. This single droplet mass spectrometry approach is demonstrated for small molecules and proteins. The approach generates clean mass spectra, permits timing of droplet delivery for chemical analysis, and, by avoiding a separate ionization stage, avoids potential artifacts arising from current electrospray-based approaches for picolitre droplet analysis. It is anticipated this approach will permit exploration of the factors governing accelerated chemical reactions in aerosol droplets and will be suitable for sensitive analysis of particularly precious samples in different application domains.

Figure 1

A schematic of the SDMS experimental setup. The inset images are (a) a photograph of five droplets stacked in the quadrupole and (b) an example brightfield image of a droplet trapped in the quadrupole.

Figure 2

(a) Example chromatogram recorded for 39 pL droplets containing 320 μM angiotensin II, delivered to the MS at 1 Hz. The red line indicates a signal that is 20% of the largest measured signal. (b) A close-up of the same chromatogram, showing each droplet is analyzed within around one 0.1 s scan, with baseline resolution between sequential droplets.

Figure 3

Example angiotensin II (320 μM) mass spectra (a) for a single 39 pL droplet and (b) integrated over 5 droplets. The gray shaded region in (a) corresponds to a TIC < 100.

Figure 4

Comparison of angiotensin II signal integrated over 60 s using the SDMS approach and ESI.

Figure 5

Measured ion count and ion yield as a function of (a) analyte concentration (droplet volume held constant at 58 pL) and (b) droplet volume (analyte concentration held constant at 320 μM). The black dashed lines indicate a log–log relationship between ion count and (a) analyte concentration and (b) droplet volume.

Figure 6

Example 60 s myoglobin mass spectra for (a) SDMS (50 μm droplet diameter, 10 μM + 0.1% formic acid) and (b) ESI (1 μM + 0.1% formic acid).