On- and Off-Line Coupling of Separation Techniques to Ambient Ionization Mass Spectrometry

Sep 30, 2011

A review of recent research related to the coupling of ambient ionization mass spectrometry (MS) with various separation techniques is presented. Ambient ionization, referring to a mode of atmospheric pressure ion generation in which sample introduction is segregated from the generation of ionizing radiation under ambient conditions, has generated a great deal of interest in recent years. A plethora of techniques incorporating spray-based and chemical ionization–based source designs have been demonstrated for analysis of analytes from headspace, solution, and solid samples. An overview of some of the more common techniques is given, especially in light of their potential for coupling with different modes of separation, in both on- and off-line formats. This is an emerging area of research that has a strong potential for novel applications, especially given the capability for generating sensitive mass spectral signals from complex samples. In many cases, however, the possibility for coupling efficient separations with current ambient ionization MS exists, but more work remains to comprehensively demonstrate the effectiveness of such hyphenated techniques so that they can be used routinely.

This review highlights the combination, or potential combination, of various separation methods with ambient ionization mass spectrometry (MS) (1). The coupling of separation devices with MS has been recognized as an extremely useful approach for real-world samples analysis, in which complex mixtures are the norm. Typical liquid-phase separation techniques, including high performance liquid chromatography (HPLC), thin-layer chromatography (TLC), and capillary electrophoresis (CE), have been successfully combined with various MS interfaces, such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) to create high performance analytical methods (2). Ambient ionization refers to several relatively new ionization techniques that are rapidly advancing toward use in many fields for direct in-situ screening of analytes with minimal or no sample preparation. The popularity of these new ionization techniques is indicated by the explosive growth of the new designs and applications in this area. The ability to separate and independently optimize the sample introduction and the ionizing radiation provides significant advantages compared to more-traditional ionization techniques. Even so, without removing large background interferences, we should be aware that high-resolution and mass-accurate mass detectors are required to unambiguously discriminate the target mass from background noise. This is why additional hyphenation of ambient ionization with separation devices can promote these new techniques for wider applications. Significant advances can be found with these hyphenated techniques, compared with traditional coupling combinations (for example, HPLC and ESI), to a large extent; however, relatively few demonstrations and applications of this promising technology currently exist.

From the standpoint of separation science, factors that can restrict the range of the analysis in current separation–MS combinations still exist in various aspects. For example, nonvolatile buffers such as borate and phosphate that are adopted for better separation in chromatography can cause ion suppression in ESI (3). Also, nonpolar solvents, typically used in normal-phase liquid chromatography, are poorly compatible with ESI due to their low conductivity or low dielectric constants (4). On the contrary, this is another regime where ambient ionization sources could broaden the compatibility between separations and MS. With respect to matrix tolerance and samples present in non-ESI-friendly solvents, some ambient ionization techniques have been shown to provide a higher tolerance to such conditions, compared with traditional atmospheric pressure ionization (5).

Here, we cover the developments and trends of recent research achievements in ambient ionization techniques. Some popular cases will be illustrated with regard to experimental arrangements, mechanisms of ionization, and applications. Following this, some successful combinations between ambient ionization and separation techniques will be narrated. Finally, the potential for this coupling in future work to handle complex sample analysis will be discussed.