Sheath flow

Extremely low level detection work is being performed ia analytical chemistry laboratories. Detection of rhodamine 6G at 50 yoctomole (50 x lO " mol) has been reported usiag a sheath flow cuvette for fluorescence detection foUowiag capiUary electrophoresis (9). This represeats 30 molecules of rhodamine, a highly fluoresceat molecule (see Electhoseparations, electrophoresis Spectroscopy, optical). 

Two high-voltage power supplies are used to drive the separation. The first power supply applies high voltage through a platinum electrode to the injection buffer reservoir for the first dimension separation. The second power supply applies potential to the interface through its buffer reservoir. The sheath flow cuvette is held at ground potential. 

After this prerun, the voltage is programmed to periodically pulse a plug of analyte into the interface. This fraction is then drawn into the second capillary for further separation. In our current configuration, the separation window in the CSE dimension is roughly 200 s in duration, and roughly 200 pulses of 1 s duration are required for the contents of the CSE capillary to be transferred to the second dimension. A constant potential is applied across the second dimension capillary, typically 10,000-20,000 V. Under this constant voltage, any analyte present within the interface is driven into the second dimension capillary for separation. Detection is by laser-induced fluorescence in a postcolumn sheath-flow cuvette. 

Electrospray ionization (ESI) is ideally suited as a detection technique for the online interfacing of liquid-phase separations (HPLC and CE) to MS, because it facilitates the transfer of analytes from the liquid phase of the HPLC or CE column to the gas phase of the MS. Also, it allows the detection of high molecular weight species, such as peptides. Three interface designs have been developed in the past 18 years for coupling CE with MS. The first CE-MS interface, coaxial sheath flow, was introduced by Smith and his group in 1987 (Olivares et al., 1987) and was improved upon in later work (Smith et al., 1988). Coaxial sheath flow is formed using two concentric metal capillaries, whereby the CE terminus and the makeup flow line are inserted into the... 

Munson MS, Hasenbank MS, Fu E, Yager P (2004) Suppression of non-specific adsorption using sheath flow. Lab Chip 4 438 145 Munson MS, Hawkins KR, Hasenbank MS, Yager P (2005) Diffusion-based analysis in a sheath flow microchannel the sheath flow T-sensor. Lab Chip 5 856-862... 

For capillary zone electrophoresis (CZE) mass spectrometry coupling, another modification of an ESI interface has been developed. This interface uses a sheath flow of liquid to make the electrical contact at the CZE terminus, thus defining both the CZE and electrospray field gradients. This way, the composition of the electro sprayed liquid can be controlled independently of the CZE buffer, thereby providing operation with buffers that could not be used previously, e.g., aqueous and high ionic strength buffers. In addition, the interface operation becomes independent of the CZE flow rate. [62]... 

With the work of Fenn and co-workers, liquid chromatography—electrospray interfaces for mass spectrometers were developed in 1984. Subsequently, the Pacific Northwest Laboratory began work in the area of CE—ESI—MS under the direction of Richard Smith and published the initial paper describing on-line CE—MS in 1987. Initial interface designs involved removing the polyimide at the end of the capillary in favor of a layer of silver for electrical contact. This interface was limited due to below optimum flow rates and limited lifetime of the metallized capillary. The introduction of the sheath flow design dramatically improved the CE—MS results. In lieu of being connected to a standard outlet buffer, the CE—MS interface used the outlet end of electrophoretic capillary connected directly to the electrospray mass spectrometer. 

Huggins, T. G., and Henion, J. D. (1993). Capillary electrophoresis/mass spectrometry determination of inorganic ions using and ion spray-sheath flow interface. Electrophoresis 14, 531 — 539. 

With the coaxial interface, initially reported by Smith et al., the problem of irregular droplets formation is circumvented by using a sheath flow in the pL/min range surrounding the CE capillary and mixing with the CE buffer at the tip of the separation capillary. It provides electrical contact at the outlet end of the separation capillary, appropriate flow, and solvent conditions for ionization and evaporation, independent on the nature of the CE buffer solution. It is the most commonly used interface and can be easily implemented. Furthermore,... 

FIGURE I Experimental setup for CE ESI/MS with a coaxial sheath-flow interface. 

Lord et al. analyzed a mixture of steroids by CEC-ESI/MS and interfaced externally tapered CEC columns in both sheathless and sheath-flow arrangement. Sensitivity was found 20-fold higher in the sheathless configuration. The same conclusion was drawn by Warriner et ah, who evaluated CEC-nanospray/MS vs. CEC-microspray/MS with an ion trap using five corticosteroids. Cahours et al. used CEC-ESI/MS for a drug metabolism study and obtained a simultaneous baseline separation of flunitrazepam and its major metabolites. For CEC-ESI/MS coupling, the commercially available packed-CEC column was connected... 

FIGURE 6 Schematic representation of different interfaces for chip CE-ESI/MS (A) spray directly from the chip, (B) liquid-junction capillary interface, (C) gold-coated capillary interface, and (D) coaxial sheath-flow configuration. Reprinted from reference 410 with permission from Elsevier Science B.V. 

Liu, C. C., Jong, R., and Covey, T. (2003). Coupling of a large-size capillary column with an electrospray mass spectrometer. A reliable and sensitive sheath flow capillary electrophoresis-mass spectrometry interface.. Chromatogr. A 1013, 9-18. 

A mouthpiece. The mouthpiece may be used to control the direction of the aerosol cloud in the mouth and throat, in order to reduce drug deposition in the oropharyngeal cavities. De Boer et al. [55] use a so-called sheath flow to reduce mouth deposition. 

The electrolyte composition and pH should not be too detrimental. Aspects such as pressure, temperature, and injection technique may have an influence. Concerning the interface, the sheath flow should be optimized with respect to composition, pH, and flow rate. Furthermore, the positions of the fused-silica capillary as well as the API probe need to be carefully optimized. The mixing volume at the tip of the capillary must be kept at a minimum to avoid postcolumn band broadening caused by diffusion. 

The unintended negative effects of high buffer-salt concentrations on the efficiency of the electrospray can be significantly reduced by adding an appropriate sheath liquid, thus usually improving the spray stability. However, since the sheath liquid acts as the terminal buffer reservoir, it must contain an electrolyte in order to maintain an efficient electrophoretic separation. Therefore, any choice of sheath flow composition represents a compromise between separation efficiency and spray stability. 

Many authors claim that the dilution by the sheath flow would not significantly affect the detection sensitivity, because it is completely evaporated in the spray process. Moreover, it has been discussed that in this layered-flow approach, preferably the inner layer of the spray enters the collector opening. If this were true, the composition of sheath liquid would be less important. Anyhow, it has to be stated that there is a dilution problem in the sheath-flow approach. In addition, it has been proven many times that ESI is a concentration-sensitive, not mass-sensitive, process. Knowing this, it makes sense to reduce the sheath liquid flow rate to the minimum required for stable spray conditions. 

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