Fundamental studies on droplet throughput and the analysis of single cells using a downward-pointing ICP-time-of-flight mass spectrometer

Capabilities of the downwardly oriented inductively coupled plasma mass spectrometer (ICP-MS) recently reported (Vonderach et al. 2021) were studied using a time-of-flight mass spectrometer (TOFMS) yielding benefits for the fast detection of short transient signals containing multi-element information. The previously reported sample inlet configuration for the analysis of microdroplets was equipped with two extra gas inlets for the supply of argon and helium, which enabled a more precise optimization of the sample introduction and operating conditions of the plasma. Furthermore, the sample supply system was operated at elevated temperatures to enhance the desolvation of the droplets prior to their introduction into the plasma. Transient droplet signals with frequencies of up to 1000 Hz were recorded for 74 μm (diameter) sized droplets. The upper detectable droplet size was limited by the droplet generator used and was measured at 93 μm (diameter). The droplets served as the transporter for biological cells so that the described setup could be used to analyze single cells. Mouse lung cells embedded into droplets were detected successfully according to their Cs droplet tracer, Ir nucleus marker, surface markers and the phosphorus content. Transient signals were recorded at a time resolution of 33 μs in order to investigate the signal structure of single droplet-cell events containing multiple elements. Signals between 200-400 μs (FW base) and ≤100 μs (FWHM) in duration were measured. To ensure that the droplet formation process did not affect the sampled cells, different types of cells were localized within the droplets using optical inspection directly after droplet formation and it was possible to observe that cells remained intact with random sampling. The results indicate that a downward-pointing ICP-MS in combination with the microdroplet-based approach can be considered as an alternative to commonly used ICP-MS systems for single cell analysis, and might be suitable for online coupling to flow cytometry. A downward inductively coupled plasma (ICP) was coupled to a time-of-flight mass spectrometer (TOFMS) and monodisperse microdroplets were used to study its capabilities and analyze single biological cells.