Acoustic ejection mass spectrometry: fundamentals and applications in high-throughput drug discovery

ABSTRACT

Introduction

Acoustic ejection mass spectrometry (AEMS) is an electrospray ionization-mass spectrometry (ESI-MS) based analytical platform that provides high analytical throughput and data quality. It has been applied in numerous drug discovery workflows, such as high-throughput screening (HTS), absorption, distribution, metabolism, and excretion (ADME) profiling, pharmacokinetics (PK) analysis, compound quality control (QC), and the high throughput readout of medical chemistry samples.

Areas covered

This paper introduces the working principle of AEMS technology. The analytical performance, system tuning and method development workflows, and representative applications on high-throughput drug discovery assays are introduced.

Expert opinion

The fast sample readout speed, high reproducibility, wide compound coverage, minimum carryover, and the tolerance to complex sample matrices of AEMS have demonstrated its advantages over other technologies in this field, with broad applicability to a diverse range of drug discovery workflows. However, the current platform still has challenges for some assays due to having less sensitivity compared with liquid chromatography-mass spectrometry (LC-MS), and the lack of chromatographic separation for isomeric interferences. Despite the remaining hurdles, AEMS is becoming an attractive high-throughput analytical platform in drug discovery. Additional system developments would enable its further adoption in the future.

KEYWORDS:

• High-throughput analysis
• mass spectrometry
• acoustic dropout ejection
• sampling interface
• drug discovery

Article highlights

• AEMS is a high-throughput technology that could deliver the similar data quality as LC-MS while providing >10 times sample readout speed and consumes 1000 times less sample.

• AEMS separates the sampling event from the ionization process, so that the benefits of both ambient ionization technologies such as high analytical throughput and simplified sample preparation, and the advantages of the classic ionization method of MS (e.g. ESI) including high sensitivity, reproducibility, and wide compound coverage, could be maintained simultaneously.

• The in-line matrix dilution of AEMS reduces the ionization suppression in many drug discovery assays, which significantly simplify the sample preparation and method development effort.

• The system tuning protocols and the method development workflows are outlined in this review.

• The AEMS technology has demonstrated the wide applicability in high-throughput drug discovery workflows.

Declaration of Interest

C Liu is an employee of SCIEX, the commercial provider of ECHO® MS AEMS technology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.