Advancing Liquid Atmospheric Pressure Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Toward Ultrahigh-Throughput Analysis.

Henriette Krenkel,Rainer Cramer,Cristian Piras,Evita Hartmane,Jeffery Brown,Michael Morris

doi:10.1021/acs.analchem.9b05202

Abstract

Label-free high-throughput screening using mass spectrometry has the potential to provide rapid large-scale sample analysis at a speed of more than one sample per second. Such speed is important for compound library, assay and future clinical screening of millions of samples within a reasonable time frame. Herein, we present a liquid atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) setup for high-throughput large-scale sample analysis (>5 samples per second) for three substance classes (peptides, antibiotics, and lipids). Liquid support matrices (LSM) were used for the analysis of standard substances as well as complex biological fluids (milk). Throughput and analytical robustness were mainly dependent on the complexity of the sample composition and the current limitations of the commercial hardware. However, the ultimate limits of liquid AP-MALDI in sample throughput can be conservatively estimated to be beyond 10–20 samples per second. This level of analytical speed is highly competitive compared with other label-free MS methods, including electrospray ionization and solid state MALDI, as well as MS methods using multiplexing by labeling, which in principle can also be used in combination with liquid AP-MALDI MS.

Highlights

Label-free high-throughput screening using mass spectrometry has the potential to provide rapid large-scale sample analysis at a speed of more than one sample per second
Bradykinin was selected as a peptidic analyte standard for the proof of principle of high-throughput analysis using liquid atmospheric pressure (AP)-matrixassisted laser desorption/ionization (MALDI) mass spectrometry (MS)
As the plate moved at a constant speed across each row, the MALDI samples were irradiated by the laser only for a fraction of the time

Summary

Introduction

Label-free high-throughput screening using mass spectrometry has the potential to provide rapid large-scale sample analysis at a speed of more than one sample per second. Solid MALDI samples were prepared by mixing matrix solution with analyte solution at a ratio of 1:1 (v/v), spotting 1 μL of the mixture onto the target plate and leaving it to dry at room temperature.

Results

Conclusion