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.
Mass
spectrometry (MS) allows for automated analysis of complex
samples at high resolution without the need for labeling/derivatization.
Liquid atmospheric pressure matrix-assisted laser desorption/ionization
(LAP-MALDI) enables rapid sample preparation and MS analysis using
microtiter-plate formats and high-performing mass spectrometers. We
present a step change in high-speed, large-scale MS sample analysis
of peptides at 20 samples/s and an enzymatic assay at 40 samples/s,
i.e., an order of magnitude faster than current MS platforms. LAP-MALDI
requires only low amounts of sample volume (<2 μL), of which
only a fraction (<1%) is typically consumed, and allows for multiplexing
and high-speed MS/MS analysis, demonstrated at ∼10 samples/s.
Its high ion signal stability and similarity to electrospray ionization
enables CVs below 10% and the analysis of multiply charged peptide
ions at these extreme speeds. LAP-MALDI MS fulfills the speed requirements
for large-scale population diagnostics and compound screening with
the potential of analyzing >1 million samples per day.
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