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

Abstract

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.

A novel approach to analyze membrane proteins by laser mass spectrometry: From protein subunits to the integral complex

“…In the older version of the LILBID technique, based on continuous liquid beams, which are still applied presently [27,28], a large consumption of analyte excluded application to the mass analysis of biomolecules of low availability. The new version, however, now uses liquid droplets [19], which minimizes the analyte consumption by orders of magnitude.…”

The function and performance of aqueous aerosol devices for inhalation therapy

“…drug particle size of nanosuspension) can influence the jet break‐up characteristics . Nevertheless, EHDA is a gentle technique that can be successfully used in the ionization of macromolecules for analysis with mass spectroscopy . Not surprisingly, large biomolecules are aerosolized with this mechanism without suffering thermal degradation, even at high concentrations of protein solutions .…”

A Complex Catalytic Reaction Caught in the Act: Intermediates and Products Sampling Online by Liquid μ‐Beam Mass Spectrometry and Theoretical Modeling

“…Details of the approach and technology employing al iquid microbeam in combination with mass spectrometry are given in the Experimental Sectiona nd in recent publicationso fo ur group. [7,9,[12][13][14]25] The main components of the setup are at hin liquid beam,a nI Rl aser,a nd ar eflectron-typem asss pectrometer.T he liquid beam is ejectedi nto ah igh vacuum through a2 0mmq uartz nozzle driven by an HPLC pump. The IR laser excites the OH-stretch vibration of water molecules and thus heats up and disperses the liquid m-water beam containing the sample from the reaction vessel.…”

“…[11] In contrast, mass spectrometry (MS) is very specific and highly sensitive but often lacks time resolution and the ability to sample the liquid state directly.The invention and application of electrospray ionization mass spectrometry (ESI) [4] and IR liquid-beam desorption MS have openedu pt he possibility to sample reactive systems in the liquid phase online. [12,13] For the latter,alinear response of the MS signal on the analyte concentration has been found, [9,14] which is advantageous and superior for quantitative evaluation of kinetic experiments. Extractive electrospray ionization mass spectrometry (EESI-MS)f or real-time monitoring of organic chemical reactions was demonstrated recently.…”