History of LC-MS interfaces

Over 30 years of liquid chromatography-mass spectrometry (LC-MS) research has resulted in a considerable number of different interfaces (Ch. 3.2). A variety of LC-MS interfaces have been proposed and built in the various research laboratories, and some of them have been adapted by instmment manufacturers and became commercially available. With the advent in the early 1990 s of interfaces based on atmospheric-pressure ionization (API), most of these interfaces have become obsolete. However, in order to appreciate LC-MS, one carmot simply ignore these earlier developments. This chapter is devoted to the older LC-MS interfaces, which is certainly important in understanding the histoiy and development of LC-MS. Attention is paid to principles, instrumentation, and application of the capillary inlet, pneumatic vacuum nebulizers, the moving-belt interface, direct liquid introduction, continuous-flow fast-atom bombardment interfaces, thermospray, and the particle-beam interface. More elaborate discussions on these interfaces can be found in previous editions of this book. 

The theory of capillary inlet interfacing has been discussed by Tal roze et al. [1-3] and others [7, 13-14]. The flow of a hqttid through the capillary tube into the mass spectrometric vacuiun system is the result of several coimterbalancing effects the capillary forces and the inlet pressure of the hqttid which drives the liquid into the MS on one hand, and the vapottr pressure of the liqttid on the other. The flow-rate (mVs) of liquid entering the MS vacuiun system can be calculated from  

The practical value of this equation is limited because in most cases liquid mixtures are used, and because the temperature is not corrstant over the tube but is higher at the ion source side. Nevertheless, the equation is useful for gaining insight in the processes and the important experimental parameters. 

In practical sitnations, the evaporation will always take place inside the capillary. This has corrsequences for the practical applicability. Nonvolatile imprrrities in the liquid stream precipitate at the position of the liquid-vapotu interface and will ultimately block the inlet capillary. The most important group of nonvolatile components in the solvent stream is the analyte from the LC colttmn. Therefore, the capillary irrlet interface has a very narrow applicability range, limited to rather volatile analytes, i.e., rather nonpolar compotmds with a molecttlar mass below ca. 400 Da [11], which are also readily amenable to GC-MS analysis. 

In a pnerrmatic nebulizer, a high-speed gas flow is used to mechanically disrapt the hqrrid srrrface and to form small droplets which are subsequently dispersed by the gas to avoid droplet coagrrlation. Pnerrmatic nebrrlizers are widely used in various LC-MS interface strategies, especially coaxial nebulizers. 

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The history of LC-MS has been recently described [2] and will not be repeated here in detail. It is worthwhile to note, however, the following dates, qnoted in this reference, when the interfaces to be described in snbseqnent parts of this chapter became available commercially ... 

Different mass analyzers may impose unique technical requirements when interfaced to LC. Understanding the operating principles and technical properties of both LC/MS interfaces and mass analyzers is deemed beneficial. A brief overview of the history of the development of LC/MS interfaces is given in Section II, which is followed in Section III by a summary of working principles and characteristics of commonly used mass analyzers. 

Besides the history of LC-MS that Niessen [1] rendered he gave an excellent description of these types of interfaces and their different principles of operation. Moreover, he extensively discussed LC-MS interfacing strategies as combined with these different types of interfaces. 

Capillary HPLC-MS has been reported as a confirmatory tool for the analysis of synthetic dyes [585], but has not been considered as a general means for structural information (degradant identification, structural elucidation or unequivocal confirmation) positive identification of minor components (trace component MW, degradation products and by-products, structural information, thermolabile components) or identification of degradation components (MW even at 0.01 % level, simultaneous mass and retention time data, more specific and much higher resolution than PDA). Successful application of LC-MS for additive verification purposes relies heavily and depends greatly on the quality of a MS library. Meanwhile, MB, DLI, CF-FAB, and TSP interfaces belong to history [440]. 

For a number of years (1987-1992), thermospray LC-MS was the most frequently applied interface for LC-MS. It has demonstrated its applicability in both qualitative and quantitative analysis in various application areas. With the advent of the more robust LC-MS interfaces, based on atmospheric-pressure ionization, the use of thermospray interfacing and ionization rapidly decreased. The newer technology pointed out the limitations of the thermospray system, e.g. in the analysis of thermolabile compounds, ionic compounds, high molecular-mass compounds, as well as in robustness and user-friendliness. Therefore, thermospray as an ionization and interface technique for LC-MS is now history. Thermospray nebulization will continue to be used, e.g. in nebulization for ICP-MS. 

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