Nano-electrospray spray capillaries

Fig. 11.5. Nano-electrospray (a) SEM micrograph of the open end of a glass nanoESI capillary having a 2-pm aperture, (b) microscopic view of the spray from a nanoESI capillary as provided by observations optics. By courtesy of New Objective, Woburn, MA.

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. 

Finally, (nano)electrospray deposition can be used to deposit the analytes onto different kinds of predeposited matrix layers. MALDI sample preparations where the analyte solution is deposited on top of a previously prepared matrix layer are generally termed sandwich methods. The base layer of matrix may be prepared either by the standard dried droplet technique or by thin layer preparation. For (nano)electrospray deposition of peptides, for example, a 10 M solution is sprayed from a (nano)electrospray capillary onto the solid matrix layer. The advantage of nanoelectrospray over conventional electrospray is that very small droplets are formed, which arrive at the target as dry particles, and thus, do not wet and redissolve the matrix surface [41]. 

The ionspray (ISP, or pneumatically assisted electrospray) LC-MS interface offers all the benefits of electrospray ionisation with the additional advantages of accommodating a wide liquid flow range (up to 1 rnl.rnin ) and improved ion current stability [536]. In most LC-MS applications, one aims at introducing the highest possible flow-rate to the interface. While early ESI interfaces show best performance at 5-l() iLrnin, ion-spray interfaces are optimised for flow-rates between 50 and 200 xLmin 1. A gradient capillary HPLC system (320 xm i.d., 3-5 xLmin 1) is ideally suited for direct coupling to an electrospray mass spectrometer [537]. In sample-limited cases, nano-ISP interfaces are applied which can efficiently be operated at sub-p,Lmin 1 flow-rates [538,539]. These flow-rates are directly compatible with micro- and capillary HPLC systems, and with other separation techniques (CE, CEC). 

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