Anal. Chem. 1994,615, 3005-3012
Hyperthermal Surface Ionization as a New Interfacing Approach in Liquid Chromatography/Mass Spectrometry A. P. Tinke, W. M. A. Niessen,' U. R. TJaden, and J. van der Greef Division of Analytical Chemistty, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands
A hyperthermal surface ionization (HSI) interface is constructed for the coupling of liquid chromatography (LC) and mass spectrometry (MS). A liquid stream of 0.1-10 pL.min-' is nebulized in a low molecular mass camer gas of either hydrogen or helium. After expansion of the gas mixture into an expansion chamber, which is held at a background pressure of 0.5 Pa, a supersonic molecular beam is sampled with a skimmer into the vacuum of the mass spectrometer. Collision of the supersonic molecular beam with a platinum, tungsten, or rhenium surface leads to the formation of ions. These ions have been analyzed with a quadrupole analyzer. SensitiveLC/ HSI-MS detectionis illustrated for a mixture of some polycyclic aromatic hydrocarbons. With HSI, an up to 10-fold better ion intensity is obtained compared to electron impact. The significantly lower chemical noise in HSI leads to on-column detection limits of less than 200 pg.
The coupling of liquid chromatography (LC) and mass spectrometry (MS) is a powerful tool in compound analysis.' A variety of LC/MS interfaces has become commercially available, because the large amount of solvent used for the separation in LC is incompatible with the vacuum of the MS. Each interface has its limitations with respect to the polarity, composition, and flow rate of the mobile phase, as well as to the molecular mass and polarity of the analyte molecules. Until now, there has been no universal interface, and as a result, the LC/MS analysis of each class of analytes requires its own particular approach. The particle beam (PB) interface is generally used for the analysis of low molecular mass and nonpolar compounds at mobile phase flow rates of 0.1-1 mL-min-l. The LC/PB-MS system suffers from a lack of sensitivity, which can be explained by the poor analyte transmission of the nozzle-skimmer configuration of the interface at low concentration levels and by the limited ionization efficiency under electron impact (EI) and chemical ionization (CI) conditions. For example, the ionization efficiency under standard E1 conditions is assumed to be merely 0.01%.2 For the electrospray (ESP) nebulization of LC effluents, very high ionization efficiencies up to 100% can be ~ b t a i n e d . ~As a result, LC/ESP-MS is generally applied as a very sensitive LC/MS technique for the analysis of both polar and ionic compounds. However, the poor (1) Niessen, W. M. A.; van der Greef, J. Liquid Chromatography Mass Spectromefry; Chromatographic Science Series 58; Marcel Dekker, Inc.: New York, 1993. (2) Chapman, J. R. Practical Organic Mass Spectrometry; John Wiley & Sons: Chichester, England, 1985. (3) Mann, M. Org. Mass Specrrom. 1990, 25, 575.
0003-2700/94/0366-3005$04.50/0 0 1994 Amerlcan Chemical Society
transmission characteristics of the interface explain the still limited sensitivity. As there is a growing need for highly sensitive LC/MS procedures, it is of vital importance that a lot of effort is put into techniques, that combine a high analyte transmission to the MS with a high ionization efficiency. A totally different approach in improving the LC/MS sensitivity is the use of surface ionization (SI). Ionization efficiencies exceeding 1% can be achieved by the collision of a hyperthermal or supersonic molecular beam with a surface like platinum or r h e n i ~ m . This ~ so-called hyperthermal surface ionization (HSI) was first described by Amira@ for the coupling of GC and MS. Because the PB interface' is generally believed to create a high-velocity beam of molecule aggregates by the expansion of both the mobile phase and the nebulization gas into the momentum separator of the interface, the potential of surface ionization in combination with particle beam mass spectrometry has been investigateda8 The surface ionization of tetraalkylammonium salts offers low picogram detection limits, which compete well with LC/ESP-MS detection limits. However, the applicability of surface ionization as an ionization technique for neutral compounds in LC/PB-MS is limited, because the increase in kineticenergy resulting from the expansion of the mobile phase into the momentum separator of the interface is too low to induce efficient ionization. In order to achieve proper expansion conditions and to study the applicability of HSI in LC/MS interfacing, an HSI interface has been constructed. Since supersonic molecular beams are difficult to generate with the standard nozzleskimmer configuration of the PB interface, a modified configuration with much better expansion characteristics has been designed. Since the LC mobile phase liquid may unfavorably affect the expansion conditions and thus the final beam characteristics, special interest has been paid to the effect of introducing a liquid stream in a low mass carrier gas like helium or hydrogen. Finally, LC/HSI-MS has been demonstrated for the analysis of polycyclic aromatic hydrocarbons. A comparison between the sensitivity achieved under HSI and standard E1 conditions has been made. THEORETICAL CONSI DERATIONS (Hyperthermal) Surface Ionization. Under so-called thermal surface ionization (TSI) conditions, analyte molecules (4) Overbosch, E. G. Surface Ionization of Hyperthermal Alkali Atoms. Thesis, Eindhoven, The Netherlands, 1980. ( 5 ) Danon, A.; Amirav, A. Isr. J. Chem. 1989, 29, 443. (6) Amirav, A. Org. Mass Spectrom. 1991, 26, 1. (7) Willoughby, R. C.; Browner, R. F. Anal. Chem. 1984,56, 2626. (8) Tinke, A. P.; van der Hoeven, R. A. M.; Niessen, W. M. A,; Tjaden, U. R.; van der Greef,J. J. Chromatogr. 1993, 647, 63.
Analytkal Chemistry, Vol. 66,No. 19, October 1, 1994 3005
first adsorb on a surface and subsequently desorb either as neutral or as charged species. For neutral species, the number of positive ions that desorb from a surface is predicted by the Saha-Langmuir e q u a t i ~ n : ~ J ~
n+ = A exp [Te] (4 - IP) -
no
where n+/no is the ratio of the number of positive ions and neutral molecules evaporating from the surface, A is the ratio of the statistical weights of the ionic and neutral states of the compound, 4 is the surface work function, IP is the ionization potential of the analyte, k is the Boltzmann constant, Tis the absolute temperature of the surface, and e is the electron charge. Generally, TSI offers a low ionization yield for neutral compounds with a high ionization potential, which explains its limited analytical and mass spectrometric applicability. So far, TSI has been used, for example, in the analysis of quaternary ammonium salts,11-14 but its applicability is mainly restricted to thermionic e m i s s i ~ n and ~ ~ Jto~ the detection of low IP alkali or rare earth metal atoms. Under hyperthermal surface ionization (HSI) conditions, ions are generated from analyte molecules with supersonic velocities after collision with metal surfaces such as platinum or rhenium. The ionization probability in HSI differs from TSI, since the kinetic energy of the molecules is used to bridge the (6 - IP) energy gap in the Saha-Langmuir equation. Amirav and Danon6J7 described HSI as potentially the most universal, ultrasensitive ionization technique with tunable selectivity in both negative and positive ion modes due to (a) very high ionization probabilities exceeding 1% (b) the absence of background from the vacuum chamber molecules since they do not posses the required hyperthermal energy, and (c) the appearance of only a single molecular ion or fragment for many molecules. In the experiments of Amirav and cow o r k e r ~a~gas ~ ,chromatography ~~ (GC) system was coupled to the MS by means of an HSI interface. To our knowledge, the use of an HSI interface for the coupling of LC and MS has not been reported. Supersonic Expansion. The adiabatic expansion of a gas into vacuum is a very useful technique to cool molecules. This phenomenon can be explained by the conversion of random thermal energy into directed flow kinetic energy. In practice, the adiabatic expansion of a gas through a so-called nozzle into a low-pressure region results in the formation of an atomic or molecular beam with supersonic v e l o ~ i t y . ~ ~ ~ ~ ~
0.1-0.01 Pa
Figure 1. Schematic representation of a Fenn-type supersonic molecular beam source.18
Ideal expansion conditions are obtained in a zero-pressure environment. However, since there is always a residual gas pressure maintained in the expansion region, these ideal expansion conditions can never be arranged. Semiideal expansion conditions can be obtained at a low background pressure (
