Particle-beam systems

The particle beam system is a simple transport device, very similar to a two-stage jet separator. The solvent vapour is pumped away, while the analyte particles are concentrated in a beam and allowed to enter the mass spectrometric source. Here they are vapourized and ionized by electron impact. 

The APCI interface uses a heated nebulizer to form a fine spray of the HPLC eluate, which is much finer than the particle beam system but similar to that formed during thermospray. A cross-flow of heated nitrogen gas is used to facilitate the evaporation of solvent from the droplets. The resulting gas-phase sample molecules are ionized by collisions with solvent ions, which are formed by a corona discharge in the atmospheric pressure chamber. Molecular ions, M+ or M , and/or protonated or de-protonated molecules can be formed. The relative abundance of each type of ion depends upon the sample itself, the HPLC solvent, and the ion source parameters. Next, ions are drawn into the mass spectrometer analyzer for measurement through a narrow opening or skimmer, which helps the vacuum pumps to maintain very low pressure inside the analyzer while the APCI source remains at atmospheric pressure. 

The APCI interface uses a heated nebulizer to form a fine spray of the HPLC eluate, which is much finer than the particle beam system... 

The two stage momentum separator used in this interface is shown schematically in Figure 3 coupled to the combination Thermospray/EI source. This device is conceptually similar to those used in other MAGIC (2) or particle beam (3,4) interfaces. However, since most of the solvent vapor is removed in the gas diffusion cell, this separator is required primarily to remove sufficient helium to allow the standard MS pumping system to achieve the good vacuum required for El operation. The performance of this device can be optimized much more readily for separating helium from macroscopic particles than when copious quantities of condensible vapors are present as in the more conventional particle beam systems. 

The nebulization and evaporation processes used for the particle-beam interface have closely similar parallels with atmospheric-pressure ionization (API), thermospray (TS), plasmaspray (PS), and electrospray (ES) combined inlet/ionization systems (see Chapters 8, 9, and 11). In all of these systems, a stream of liquid, usually but not necessarily from an HPLC column, is first nebulized... 

It is worth noting that some of these methods are both an inlet system to the mass spectrometer and an ion source at the same time and are not used with conventional ion sources. Thus, with electrospray, the process of removing the liquid phase from the column eluant also produces ions of any emerging mixture components, and these are passed straight to the mass spectrometer analyzer no separate ion source is needed. The particle beam method is different in that the liquid phase is removed, and any residual mixture components are passed into a conventional ion source (often electron ionization). 

Even so, much effort was put into the development of such a system and this resulted in the introduction of the particle-beam interface, also known as the... 

Various transport type interfaces, such as SFC-MB-MS and SFC-PB-MS, have been developed. The particle-beam interface eliminates most of the mobile phase using a two-stage momentum separator with the moving-belt interface, the column effluent is deposited on a belt, which is heated to evaporate the mobile phase. These interfaces allow the chromatograph and the mass spectrometer to operate independently. By depositing the analyte on a belt, the flow-rate and composition of the mobile phase can be altered without regard to a deterioration in the system s performance within practical limits. Both El and Cl spectra can be obtained. Moving-belt SFE-SFC-MS" has been described. 

Two LC-MS systems were developed, based on nearly full removal of the solvent moving-belt [520] and particle-beam [521], Mechanical transport devices... 

LC-PB-MS is especially suited to NPLC systems. RPLC-PB-MS is limited to low-MW (<500 Da) additives. For higher masses, LC-API-MS (combined with tandem MS and the development of a specific mass library) is necessary. Coupling of LC via the particle-beam interface to QMS, QITMS and magnetic-sector instruments has been reported. In spite of the compatibility of PB-MS with conventional-size LC, microbore column (i.d. 1-2 mm) LC-PB-MS has also been developed. A well-optimised PB interface can provide a detection limit in the ng range for a full scan mode, and may be improved to pg for SIM analyses. 

Only the particle-beam interface produces El spectra for direct comparisons with computerized library spectra of fragmentation patterns. The other systems enable the relative molecular mass (RMM) of analytes up to 105 and above to be established. An example of an HPLC-APCI separation and identification of some benzodiazepine tranquillizers is shown in Figure 4.39. The most appropriate choice of LC-MS interface for a particular... 

Based on a new technology, particle beam enhanced liquid chromatography-mass spectrometry expands a chemist s ability to analyse a vast variety of substances. Electron impact spectra from the system are reproducible and can be searched against standard or custom libraries for positive compound identification. Chemical ionization spectra can also be produced. Simplicity is a key feature. A simple adjustment to the particle beam interface is all it takes. 

The different ways a particle beam liquid chromatography mass spectrometer can be configured reflect the versatility of the system in accommodating both the application and the availability of existing instrumentation. The system consists of these elements ... 

As in all processing steps, cleanliness of the exposure hardware is of paramount importance. Any particle that lands on the resist prior to exposure, will shield the film underneath the particle from the exposing radiation and give rise to opaque spots in the case of positive resist, or pinholes in the case of negative resists. Particulate contamination is especially troublesome with electron beam and ion beam systems where the probability of a particle landing on a substrate is increased relative to other techniques because of the much longer exposure times involved. 

Interfacing of solution-based separation techniques with mass spectrometry has historically been a challenge because of the incompatibility of the used solvent with the vacuum system. Standard electron impact (El) ionization with techniques such as particle beam require samples to be vaporized under high vacuum for ion formation to occur. 

Schreiner, J., C. Voigt, K. Mauersberger, P. McMurry, and P. Zie-mann, Aerodynamic Lens System for Producing Particle Beams at Stratospheric Pressures, Aerosol Sci. Technol., 29, 50-56 (1998). 

Patterns can be produced in a mask, and that mask used to define the pattern to be produced on the material to be exposed. Alternatively, particle beams can be deflected in patterns over the substrate to be exposed, and the patterns are produced by turning the beam off and on, changing its shape and size, or both. Regardless of how the pattern is produced, and regardless of the type of radiation used, there are some fundamental aspects of exposure that hold for all lithographic systems, and these are the topic of this chapter. 

At present, the most powerful and promising interfaces for drug residue analysis are die particle-beam (PB) interface that provides online EI mass spectra, the thermospray (TSP) interface diat works well with substances of medium polarity, and more recently the atmospheric pressure ionization (API) interfaces that have opened up important application areas of LC to LC-MS for ionizable compounds. Among die API interfaces, ESP and ISP appear to be the most versatile since diey are suitable for substances ranging from polar to ionic and from low to high molecular mass. ISP, in particular, is compatible with the flow rates used with conventional LC columns (70). In addition, both ESP and ISP appear to be valuable in terms of analyte detectability. These interfaces can further be supplemented by preanalyzer collision-induced dissociation (CID) or tandem MS as realized with the use of triple quadrupole systems. Complementary to ESP and ISP interfaces with respect to the analyte polarity is APCI with a heated nebulizer interface. This is a powerful interface for both structural confirmation and quantitative analysis. 

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