A New ICP-MS Configuration for Single Cell Analysis
For most of the ICP-MS-based techniques, the sample introduction is still considered as Achilles heel due to low or incomplete sample transport. [1] Highly efficient micro-flow nebulizer and microdroplet dispenser have been developed showing acceptable performance for a multiplicity of applications, although efficiency and throughput still need to be improved. Especially in the field of single cell analysis, the introduction efficiencies of the aforementioned sample introduction systems tend to decrease significantly with the cell size. [2][3] Low total masses and small sample sizes (ranging between several microns down to several nanometers) face high uptake rates and low transport efficiencies, which makes single particle and cell analyses challenging. Since every cell line shows a certain average size and size distribution, any type of sample loss goes hand in hand with the loss of information.
In this work, two sample introduction approaches shall be presented both featuring the highest transport efficiencies, i.e. 100%. Chinese Hamster Ovary (CHO) cells (13 μm) and other eukaryotic cells (10-20 μm) were successfully transported via monodisperse droplets and analyzed using time-resolved single cell ICP-MS. Every sampled cell was embedded into a droplet with the help of a so-called Autodrop Pipette (microdrop Technologies GmbH, Germany) emitting monodisperse droplets at selectable size in the range from 50 to 90 μm. The droplets were directly introduced into a vertically oriented low-temperature desolvation system, a so-called falling tube using an Ar-He mixture as a carrier and drying gas. [4] In the first approach, the low-temperature desolvation system was directly coupled with a downwards-pointing vertical ICP enabling a gravitation-assisted sample introduction for ICP-MS. In the second approach, additional make-up gas (up to 0.8 L/min of additional Ar) was used to transport the evaporated droplets horizontally into a state-of-the-art ICP. In comparison, the downwards-pointing vertical ICP did not require additional make-up gas and the droplets reached the plasma independent of the initial droplet size, the droplet evaporation or the cell size. The presented in-house developed prototype shows great promise for future single cell analysis studies.
[1] John W. Olesik, Patrick. J. Gray, Journal of Analytical Atomic Spectrometry, 2012, 27, 1143-1155
[2] Shin-ichi Miyashita et al., Journal of Analytical Atomic Spectrometry, 2014, 29, 1598-1606
[3] Kaori Shigeta et al., Journal of Analytical Atomic Spectrometry, 2013, 28, 637-645
[4] Sabrina Gschwind et al., Journal of Analytical Atomic Spectrometry, 2011, 26, 1166-1174