Mobility separation

In a solution without chiral selectors, enantiomers cannot be distinguished from each other through their electrophoretic mobility. Separation can, however, be achieved when the buffer solution contains certain chiral compounds. The chiral compounds used to distinguish enantiomers are referred to as selectors. 

IM-TOF MALDI positive ion mode Full-scan MS Ion mobility separation (29)... 

Trim P, Henson C, Avery J, McEwen A, Snel M, Claude E, Marshall P, West A, Princivalle A, Clench M (2008) Matrix-assisted laser desorption/ionization-ion mobility separation-mass spectrometry imaging of vinblastine in whole body tissue sections. Anal Chem 80 8628-8634. doi 10.1021/ac8015467... 

Briefly, a solution of the polymer s uIlple is introduced at the interface between a leading electrolyte of high effective mobility and a trailing electrolyte of low effective mobility. Ssunple ions of different electrophoretic mobilities separate into individual zones with the zone order in direct relation to their effective mobilities. The zones migrate past an on-column potential-gradient or conductivity detector with a response that is proportional to the effective mobility and eunount of Ion present. 

Ion mobility can add an extra dimension of separation when coupled to a mass analyzer. Ion mobility spectrometry (IMS) separates ions according to their interactions with a buffer gas, in addition to differences in their m/z ratios. This can provide separation of ions (i.e., isobaric or conformational isomers), which cannot be accomplished using traditional mass analyzers. It can also be used to reduce interfering chemical noise. Ion mobility separates ions based on how long they take to migrate... 

Pringle SD, Giles K, Wildgoose JL, et al., An investigation of the mobility separation of some peptide and protein ions using a new hybrid quadrupole/travelling wave IMS/oa-ToF instrument, Int. J. Mass Spectrom. 2007 261(1) 1-12. 

Because IMS is a method that separates gas phase ions through collisions with a buffer gas, all analytes must be transported from the sample matrix and converted to a gas phase ion before ion mobility separation and detection can be performed. Thus, the type of introduction method largely depends on the physical characteristics of the analyte. The remainder of this chapter is divided into four sections based on the characteristics of the sample vapor, semivolatile, aqueous, and solid. While these categories are somewhat arbitrary with significant sample overlap, it is useful to think of volatile samples as those compounds that exist or partially exist as vapors under ambient temperature and pressure semivolatile samples as those compounds that can be volatilized but have vapor pressures too low to detect by IMS under ambient temperature and pressure aqueous samples as those compounds that are not volatile but can be dissolved in water and solid samples as compounds not in a solution. Table 3.1 lists a number of example analytes according to the categories discussed in this chapter. 

Papanastasiou, D. Wollnik, H. Rico, G. Tadjimukhamedov, F. Mueller, W. Eiceman, G. A., Differential mobility separation of ions using a rectangular asymmetric waveform, J. Phys. Chem. A 2008, 112, 3638-3645. 

The process of converting a swarm of gas phase ions into an electrical signal that provides both arrival time information and amplitude information is known as ion detection. The ion detector is typically located after the ion mobility separation cell and has a number of ideal requisites to accomplish the transduction of mobility-separated ions in a manner that minimizes loss of sensitivity and IMS resolving power. 

AMBIENT DETECTION OF MOBILITY-SEPARATED IONS 7.2.1 Faraday Cup and Faraday Plate Detectors... 

In a cloud chamber detector, ions at atmospheric pressure are electrically focused into a cloud chamber filled with cold water or octane vapors. The presence of the ion serves as the nucleus for the formation of small droplets that can scatter light from a laser beam passing through the cloud chamber. When mobility-separated ions entered the cloud chamber, perturbation in the laser light due to the formation of ion-nucleated particles was detected by a PMT. When the chamber was supersaturated with water, the scattered light intensity increased in the presence of ions, but when the chamber was supersaturated with octane, the intensity decreased in the presence of ions. Mobility spectra of difluorodibromomethane have been reported using cloud chamber detection." ... 

The resolution of an ion mobility separation depends on both the resolving power Rp and the separation selectivity a of the IMS system. Resolution R determines how well two peaks, with drift times of tj and t2 and peak widths of Wj and W2 can be separated from one another and is defined as... 

FIGURE 8.9 Selectivity induced by cation adduction. Ion mobility separation of methyl-p-D-galactopyranoside from its isomer methyl-a-D-galactopyranoside using different cation adducts. (From Dwivedi et al., Rapid resolution of carbohydrate isomers by electrospray ionization ambient pressure ion mobility spectrometry-time-of-flight mass spectrometry (ESI-APIMS-TOFMS), J. Am. Soc. Mass Spectrom. 2007, 18, 1163-1175. With permission.)... 

In summary, ion mobility separations occur by a variety of methods. In all cases, there is an instrumental scan parameter that controls the separation of the ion. For example, in the drift tube spectrometers, it is the arrival time of the ion for the aspiration spectrometers, it is the position of the faraday plates for the mobility analyzers, it is the strength of the orthogonal voltage and for the DMSs, it is the compensation voltage. The relative value of these scan parameters for two ions is called the separation factor a, and the resolving power of a spectrometer is determined by the ratio of the scan parameter to the width of the scan parameters for a packet of ions. 

After mobility separation, the ions exit the ion mobility drift tube and are shaped into a ribbon trajectory with a combination of Einzel and DC-quadrupole lenses so that the ion beam traverses the 25-cm long focusing region and passes through a 1.6 X 12.7 mm slit into the source region of a TOF-MS. 

After mobility separation, ions are transferred to a third traveling wave cell similar to the first cell of the triwave assembly and operating as an ion transfer lens or as a CID cell. Finally, the ions are transferred into a high-resolution TOF-MS. Thus, many types of analyses can be performed with this single instrument. It can operate simply as an IMS-TOF or a Q-TOF, but it can also operate as a Q-IMS-TOF or, in its most powerful mode, as a Q-IMS-CID-TOF. 

An example of IMS-TrapMS analysis is shown in Figure 9.12. Spectrum 1 illustrates the ion mobility separation of three isomers (hesperidin, neohesperidin, and rutin) adducted with silver. Spectrum 2 shows the overlaid ion mobility spectra of the respective standards. Through the use of single-mobility monitoring, the ions contained in the drift time windows (a), (b), and (c) were fragmented to produce the mass spectra shown in 1(a), 1(b), and 1(c), respectively. Shown in bold text in 1(a) and 1(b), the ions 409 and 411 may be used to confirm the presence of either hesperidin or neohesperidin. However, the IMS separation prior to mass analysis is necessary to distinguish conclusively among the three isomers. 

More complex samples can be analyzed when IMS is coupled to MS. One example is the use of a Synapt traveling wave (TW) IMS for the metabolite profiling of leflunomide (LEF) and acetaminophen (APAP). Compared with quantitative (Q) TOF-MS and Q-TRAP-MS, the ability to provide mobility separation of the MS ... 

Thus, IMS can serve as a stand-alone instrument in medical and biological applications for which only limited information from a small number of compounds is required. Ion mobility separation can be used to preseparate or filter interfering compounds prior to MS analysis or serve as a means of distinguishing between isomers based on structural differences. As mentioned, mobility data can also be used to determine the stereoscopic conformation of macromolecules and can thus serve as a means for assessing their biologic activity. 

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