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SCIEX was very proud to have an illustration of the Acoustic Ejection Mass Spectrometry (AEMS) technology that powers the Echo® MS system on the front cover of the Journal of the American Society for Mass Spectrometry in January 2023. The associated article—Ultrahigh-Throughput Intact Protein Analysis with Acoustic Ejection Mass Spectrometry—was co-authored by scientists from SCIEX and Merck.

According to co-author Chang Liu, Staff Research Scientist at SCIEX, “the results in this work demonstrate high-quality and high-throughput intact protein analysis with the AEMS technology. The platform could be potentially applied widely in drug discovery workflows such as the identification of covalent binders, the ADCs characterizations, and the mAb QC.”¹

This statement raised a question for me: What has the Echo® MS system done for the pharma industry?

How is the Echo® MS system being used?

It didn’t take long for me to find lots of journal articles demonstrating the use of this system in the pharma industry. In a Journal of Pharmaceutical Analysis article, Current status and future directions of high-throughput ADME screening in drug discovery, Wilson Shou of Bristol-Myers Squibb highlighted the importance of HT-ADME screening in drug development and the role mass spectrometry plays. Shou pointed out that high-quality ADME data early in the drug development process reduces attrition later in the development of drug candidates, saving drug companies time and money, and making the treatments patients need available sooner.

Table 2 in the article (reproduced below) shows how well the Echo® MS system can provide high-quality data and save time compared to other commercially available systems.²

Table 2. Comparison of high-throughput MS analysis approaches. SPE: solid phase extraction; LDI: laser desorption ionization; AMI: acoustic mist ionization; AE: acoustic ejection.

In an SLAS Discovery article, A high-throughput screening assay for mutant isocitrate dehydrogenase 1 using acoustic droplet ejection mass spectrometry, Elisabeth Speckmeier et al. of Sanofi, Integrated Drug Discovery, detailed the development of a method for a mutant IDH1 using the Echo® MS system. The IDH1 gene is of interest because it is found in several types of cancer, such as myelodysplastic syndromes, acute myelogenous leukemia and brain cancer.

According to Speckmeier et al., “we have established a label-free enzymatic assay ADE-MS as a large-scale HTS-capable assay readout. Single-concentration incubations and 57 concentration–response curves showed high reproducibility and analytical performance comparable to the established fluorescence label-based assay readout, but with slightly lower Z-prime and fluctuating S/IC.”³

In another SLAS Discovery article, Acoustic Ejection Mass Spectrometry: A Fully Automatable Technology for High-Throughput Screening in Drug Discovery, Roman P. Simon et al. of Drug Discovery Sciences, Boehringer Ingelheim Pharma, reported on the implementation of a biochemical assay to identify small-molecule inhibitors: cyclic guanosine monophosphate–adenosine monophosphate (GMP-AMP) synthase (cGAS). Simon et al. concluded that “altogether, the established ADE-OPI-MS [Echo® MS system] platform fills in a current technological gap by adding ESI-based MS to the label-free high-throughput readout portfolio.”⁴

What is the Echo® MS system? 

The Echo® MS system uses Acoustic Ejection Mass Spectrometry (AEMS). Samples are placed into a well plate that is held in the autosampler of the Echo® MS module and sound energy is applied to the bottom of each well individually. The sound energy causes a reproducible droplet to be ejected from the well, allowing the sample to travel to the Open Port Interface (OPI) before making its way to the source of the mass spectrometer. From this point, the droplet is ionized using electrospray ionization (ESI), and it is ready for detection.

This ejection process has several benefits, including speed and contactless sampling. Combining this approach with mass spectrometry enables speed without compromising on data quality. For a peek at the Echo® MS system in action, watch this video.

References:

¹ Zacharias, AO et al. Ultrahigh-Throughput Intact Protein Analysis with Acoustic Ejection Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2023, 34(1): 4–9. https://doi.org/10.1021/jasms.2c00276

² Shou, WZ. Current status and future directions of high-throughput ADME screening in drug discovery. J Pharm Anal. 2020, 10(3): 201–208. https://doi.org/10.1016/j.jpha.2020.05.004

³ Speckmeier, E et al. A high-throughput screening assay for mutant isocitrate dehydrogenase 1 using acoustic droplet ejection mass spectrometry. SLAS Discov. 2022, 27(5): 298–305. https://doi.org/10.1016/j.slasd.2022.04.002

4 Simon, RP et al. Acoustic Ejection Mass Spectrometry: A Fully Automatable Technology for High-Throughput Screening in Drug Discovery. SLAS Discov. 2021, 26(8): 961–973.  https://doi.org/10.1177/24725552211028135