Time-Resolved Micro Liquid Desorption Mass Spectrometry: Mechanism, Features, and Kinetic Applications

Liquid water beam desorption mass spectrometry is an intriguing technique to isolate charged molecular aggregates directly from the liquid phase and to analyze them employing sensitive mass spectrometry. The liquid phase in this approach consists of a 10 µm diameter free liquid filament in vacuum which is irradiated by a focussed infrared laser pulse resonant with the OH-stretch vibration of bulk water. Depending upon the laser wavelength, charged (e.g. protonated) macromolecules are isolated from solution through a still poorly characterized mechanism. After the gentle liquid-to-vacuum transfer the low-charge-state aggregates are analyzed using time-of-flight mass spectrometry. A recent variant of the technique uses high performance liquid chromatography valves for local liquid injections of samples in the liquid carrier beam, which enables very low sample consumption and high speed sample analysis. In this review we summarize recent work to characterize the ‘desorption’ or ion isolation mechanism in this type of experiment. A decisive and interesting feature of micro liquid beam desorption mass spectrometry is that — under certain conditions — the gas-phase mass signal for a large number of small as well as supramolecular systems displays a surprisingly linear response on the solution concentration over many orders of magnitude, even for mixtures and complex body fluids. This feature and the all-liquid state nature of the technique makes this technique a solution-type spectroscopy that enables real kinetic studies involving (bio)polymers in solution without the need for internal standards. Two applications of the technique monitoring enzyme digestion of proteins and protein aggregation of an amyloid model system are highlighted, both displaying its potential for monitoring biokinetics in solution.