Ionization Nano spray

In 2008, easy ambient sonic-spray ionization mass spectrometry (EASI-MS), originally named desorption sonic spray ionization (DeSSI), was coupled with TLC [69], later with HPTLC [70]. An acidic mixture of methanol and water was sprayed at a maximum flow rate of 15 pL/min coaxial with the supersonic nebulizing gas set at 30 bar. The spray beam of the homemade easy ambient sonic-spray ionization (EASI) source was mounted on the supplied nano-electrospray ionization (nano-ESI) source and directed in a 30-degree angle onto the plate. Without any voltage or heating, just the impact of a high velocity spray served to extract and desorb analytes from the TLC surface and softly ionize them. 

The nano-electrospray (nanoES) source is essentially a miniaturized version of the ES source. This technique allows very small amounts of sample to be ionized efficiently at nanoliters per minute flow rates and it involves loading sample volumes of 1-2 pi into a gold-coated capillary needle, which is introduced to the ion source. Alternatively for on-line nanoLC-MS experiments the end of the nanoLC column serves as the nanospray needle. The nanoES source disperses the liquid analyte entirely by electrostatic means [27] and does not require assistance such as solvent pumps or nebulizing gas. This improves sample desolvation and ionization and sample loading can be made to last 30 minutes or more. Also, the creation of nanodroplets means a high surface area to volume ratio allowing the efficient use of the sample without losses. Additionally, the introduction of the Z-spray ion source on some instruments has enabled an increase in sensitivity. In a Z-spray ion source, the analyte ions follow a Z-shaped trajectory between the inlet tube to the final skimmer which differs from the linear trajectory of a conventional inlet. This allows ions to be diverted from neutral molecules such as solvents and buffers, resulting in enhanced sensitivity. 

Methods Ambient ionization methods, of which there are now over 20, e.g., desorption electrospray ionization (DESI), desorption atmospheric pressure chemical ionization (DAPC), desorption atmospheric pressme photo-ionization (DAPPI), and direct analysis in real time (DART), are now joined by paper spray, a method where ESI is initiated at the pointed tip of a piece of filter paper. A drop of blood ( 15 pi) is dried on the paper, and then the paper is moistened with 25 pi of a solvent suited to both the extraction of the analytes from the blood and the ESI process (e.g., 90% methanol 10% water with either 100 ppm acetic acid or 200 ppm sodium acetate). When the paper is exposed to high voltage (3-5 kV) while held close ( 5 mm) to the entrance of the mass analyzer, a spray (similar to electrospray) is induced at the tip of the paper as capillary action carries extracted compounds through the paper (Figure 4.5). The spray is maintained for 30-90 s at a flow rate comparable to that used in nano-electrospray. 

Fisher, C.M., Kharlamova, A., McLuckey, S.A. (2014) Affecting Protein Charge State Distributions in Nano-electrospray Ionization via In-spray Solution Mixing Using Theta Capillaries. Anal. Chem. 86 4581-4588. 

Another instrumental development is based on the fact that the generation of smaller droplets is more favorable in terms of droplet evaporation during ESI, of sensitivity and the abihty to preserve non-covalent molecular associates. Thus, nanoelectrospray ionization (nESI) has been developed [68], where the analyte is sprayed from a gold-coated fused-silica capillary with a tip diameter of 1-5 pm rather than from capillaries with a 100-150-pm tips that are used in conventional (pneumatically assisted) ESI. In nESI, flow-rates as low as 20 nl/min can be nebulized. Thus, gentler operating conditions (temperature, gas flows, needle voltage) can be achieved. In order to more readily implement nESI in LC-MS operation, integrated chip-based nano-LC-nESI devices have also been developed [69]. 

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