Acoustic Mist Ionization Platform for Direct and Contactless Ultrahigh-Throughput Mass Spectrometry Analysis of Liquid Samples

Abstract

Mass spectrometry (MS) has many advantages as a quantitative detection technology for applications within drug discovery. However, current methods of liquid sample introduction to a detector are slow and limit the use of mass spectrometry for kinetic and high-throughput applications. We present the development of an acoustic mist ionization (AMI) interface capable of contactless nanoliter-scale "infusion" of up to three individual samples per second into the mass detector. Installing simple plate handling automation allowed us to reach a throughput of 100 000 samples per day on a single mass spectrometer. We applied AMI-MS to identify inhibitors of a human histone deacetylase from AstraZeneca's collection of 2 million small molecules and measured their half-maximal inhibitory concentration. The speed, sensitivity, simplicity, robustness, and consumption of nanoliter volumes of sample suggest that this technology will have a major impact across many areas of basic and applied research.

Translational Metabolomics: Current Challenges and Future Opportunities

“…Furthermore, the choice of chromatographic separation does have an impact on the types of measured compounds and the biochemical pathways, as reverse phase approaches are better for non-polar components like flavonoids and fatty acids, while normal phase approaches are better for polar compounds like nucleotides and sugars. Advances in analytical instrumentation are slowly making progress in this area, continually expanding the scope of metabolites which can be measured using a single method [96]. The combined use of NMR and mass spectrometry (MS) technologies are gaining more interest in the recent years to obtain much wider coverage of metabolites (Figure 1) [97,98,99,100,101,102].…”

Ultrahigh-Throughput ESI-MS: Sampling Pushed to Six Samples per Second by Acoustic Ejection Mass Spectrometry

“…[17] This approach was recently used to identify inhibitors of a human histone deacetylase at a throughput of 100,000 samples per day. [17] However, this approach ejects a steady mist of droplets directly in the gas stream of a transfer capillary. Thus, in absence of any active self-cleaning of the droplet intake and any dilution effect into a carrier liquid, the risk of probe contamination and ion suppression effects is present.…”

“…Additionally, this specific mist-ionization technique has limitations such as an individual ionization characteristic and interor intrawell signal deviations of 25% that can just be lowered to 3.5% when isotope labeled standards were used. [17] Recent adaptations of OPI-ESI-MS used modified versions of the ATS-G4P (EDC Biosystems, Fremont, California, USA) or the ECHO 555 liquid handler, both equipped with an OPI (SCIEX, Concord, Canada). In both systems, the acoustic transducer ejects precise sample droplets of an accurate low nanoliter volume vertically out of 384-or 1536-well plates filled with only 1.5-50 µL of sample liquid.…”

Integration of Acoustic Liquid Handling into Quantitative Analysis of Biological Matrix Samples

“…16 Acoustic liquid handlers are widely used in the pharmaceutical industry with applications extending from highthroughput screening in compound management to gene expression sequencing, genomic and epigenetic assays, and cell-based assays. [17][18][19][20][21][22][23] Acoustic liquid handlers accurately deliver small volumes (nL-µL) of multiple fluid types with dynamic viscosity profiling. 1,24,25 Acoustic droplet ejection (ADE) has been thoroughly described elsewhere.…”