Nanospray desorption electrospray ionization
Nanospray desorption electrospray ionization is an ambient pressure ionization technique used in mass spectrometry for chemical analysis of organic molecules. In this technique, analytes are desorbed into a liquid bridge formed between two capillaries and the sampling surface. Unlike [Desorption Electrospray ionization|electrospray ionization|desorption electrospray ionization (DESI)], from which nano-DESI is derived, nano-DESI makes use of a secondary capillary, which improves the sampling efficiency.
Principle of operation
The typical nano-DESI probe setup consists of two fused silica capillaries – primary capillary, which supplies solvent and maintains a liquid bridge, and secondary capillary, which transports the dissolved analyte to the mass spectrometer. High voltage is applied between the inlet of the mass spectrometer and the primary capillary, creating a self-aspirating nanospray. The liquid bridge is maintained by continuous flow of the solvent and the contact area between the solvent bridge and sample surface can be controlled by changing the solvent flow rate, varying the diameter of the utilized capillaries and regulating the distance between the sample and the nano-DESI probe. In this way, the spatial resolution in mass spectrometry imaging applications can be improved, with typical resolution ranging between 100–150 μm.
Pneumatically-assisted nano-DESI
To enhance sensitivity, the secondary capillary of the nano-DESI probe can be equipped with a nebulizer, which takes benefit of the Venturi effect, facilitating the aspiration of the liquid. This enables the secondary probe to be longer, while still maintaining stable electrospray. The probe can be incorporated into a 3D printed cassette, creating a plug and play device.
Applications
By continuously scanning a surface, such as tissue section, nano-DESI can be used for imaging. By carefully choosing the experimental conditions, such as the nano-DESI solvent, additives, and the ionization mode we can map the distribution of a wide variety of complex molecules on different surfaces. A few examples to mention are proteins, lipids, small metabolites, drugs or even the distribution of endogenous alkali metals. Nano-DESI has been applied for localized analysis of complex molecules and imaging of tissue sections, microbial communities and environmental samples.
Single-cell analysis
By decreasing the inner diameter of the primary and secondary capillaries, spatial resolution can be decreased to 20x20 μm or even smaller facilitating the analysis of individual cells. This way even various proteoforms can be measured in single cells as well as global and spatial metabolomics.