Anal. Chem. 2008, 80, 7460–7466
Desorption and Ionization Mechanisms in Desorption Atmospheric Pressure Photoionization Laura Luosuja ¨ rvi,† Ville Arvola,‡ Markus Haapala,‡ Jaroslav Po ´ l,‡ Ville Saarela,§ Sami Franssila,§ †,‡ ‡ ,‡ Tapio Kotiaho, Risto Kostiainen, and Tiina J. Kauppila* Laboratory of Analytical Chemistry, Department of Chemistry, and Division of Pharmaceutical Chemistry, Faculty of Pharmacy, FI-00014 University of Helsinki, Finland, and Department of Micro and Nanosciences, Helsinki University of Technology, P.O. Box 3500, FI-02015 TKK, Finland The factors influencing desorption and ionization in newly developed desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS) were studied. Redirecting the DAPPI spray was observed to further improve the versatility of the technique: for dilute samples, parallel spray with increased analyte signal was found to be the best suited, while for more concentrated samples, the orthogonal spray with less risk for contamination is recommended. The suitability of various spray solvents and sampling surface materials was tested for a variety of analytes with different polarities and molecular weights. As in atmospheric pressure photoionization, the analytes formed [M + H]+, [M - H]-, M+•, M-•, [M - H + O]-, or [M - 2H + 2O]- ions depending on the analyte, spray solvent, and ionization mode. In positive ion mode, anisole and toluene as spray solvents promoted the formation of M+• ions and were therefore best suited for the analysis of nonpolar compounds (anthracene, benzo[a]pyrene, and tetracyclone). Acetone and hexane were optimal spray solvents for polar compounds (MDMA, testosterone, and verapamil) since they produced intensive [M + H]+ ion peaks of the analytes. In negative ion mode, the type of spray solvent affected the signal intensity, but not the ion composition. M-• ions were formed from 1,4-dinitrobenzene, and [M - H + O]- and [M 2H + 2O]- ions from 1,4-naphthoquinone, whereas acidic compounds (naphthoic acid and paracetamol) formed [M - H]- ions. The tested sampling surfaces included various materials with different thermal conductivities. The materials with low thermal conductivity, i.e., polymers like poly(methyl methacrylate) and poly(tetrafluoroethylene) (Teflon) were found to be the best, since they enable localized heating of the sampling surface, which was found to be essential for efficient analyte desorption. Nevertheless, the sampling surface material did not affect the ionization mechanisms. Direct desorption/ionization techniques for mass spectrometry (MS) have gained a lot of interest during recent years. Several * To whom correspondence should be addressed. E-mail: tiina.kauppila@ helsinki.fi. Tel: +358-9-19159169. Fax: +358-9-19159556, † Laboratory of Analytical Chemistry, Department of Chemistry, University of Helsinki. ‡ Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki. § Helsinki University of Technology.
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techniques, such as desorption electrospray ionization1 among others,2-6 offer the possibility for fast and simple direct analysis of surfaces. In these techniques, the ionization takes place at ambient conditions and sample preparation or separation prior to mass spectrometric analysis is unnecessary. In addition to simple analysis, these ambient ionization techniques can be used with portable mass spectrometers,7-9 which makes them even more attractive. Desorption atmospheric pressure photoionization (DAPPI)10,11 is a novel direct desorption/ionization technique for MS that combines the advantages of atmospheric pressure photoionization (APPI)12,13 with the possibility of fast surface analysis. A heated jet of mixed nebulizer gas and spray solvent vapor, produced by a microchip nebulizer, desorbs solid analytes from the surface, after which the ionization of the analytes takes place through photoionization and gas-phase ion-molecule reactions as in APPI. DAPPI is simple, easy to operate, it enables the analysis of, for example, tablets in seconds, and the range of potential analytes can be varied with the selection of spray solvent. The desorption/ ionization mechanism in DAPPI has been proposed to be a combination of thermal and chemical processes: thermal desorption of the analytes from the surface and subsequent dopantassisted photoionization in gas phase.10 Since the exact DAPPI mechanism remains unknown, it is now studied in more detail. In this study, we explore a number of factors influencing the desorption and ionization in DAPPI. Microfluidic jet impinging (1) Takats, Z.; Wiseman, J. M.; Gologan, B.; Cooks, R. G. Science 2004, 306, 471–473. (2) Wei, J.; Buriak, J. M.; Siuzdak, G. Nature 1999, 399, 243–246. (3) Cody, R. B.; Laramee, J. A.; Durst, H. D. Anal. Chem. 2005, 77, 2297– 2302. (4) Shiea, J.; Huang, M. Z.; Hsu, H. J.; Lee, C. Y.; Yuan, C. H.; Beech, I.; Sunner, J. Rapid Commun. Mass Spectrom. 2005, 19, 3701–3704. (5) McEwen, C. N.; McKay, R. G.; Larsen, B. S. Anal. Chem. 2005, 77, 7826– 7831. (6) Haddad, R.; Sparrapan, R.; Eberlin, M. N. Rapid Commun. Mass Spectrom. 2006, 20, 2901–2905. (7) Mulligan, C. C.; Justes, D. R.; Noll, R. J.; Sanders, N. L.; Laughlin, B. C.; Cooks, R. G. Analyst 2006, 131, 556–567. (8) Mulligan, C. C.; Talaty, N.; Cooks, R. G. Chem. Commun. 2006, 16, 1709– 1711. (9) Keil, A.; Talaty, N.; Janfelt, C.; Noll, R. J.; Gao, L.; Ouyang, Z.; Cooks, R. G. Anal. Chem. 2007, 79, 7734–7739. (10) Haapala, M.; Pol, J.; Saarela, V.; Arvola, V.; Kotiaho, T.; Ketola, R. A.; Franssila, S.; Kauppila, T. J.; Kostiainen, R. Anal. Chem. 2007, 79, 7867– 7872. (11) Kauppila, T. J.; Arvola, V.; Haapala, M.; Pol, J.; Aalberg, L.; Saarela, V.; Franssila, S.; Kotiaho, T.; Kostiainen, R. Rapid Commun. Mass Spectrom. 2008, 22, 979–985. (12) Robb, D. B.; Covey, T. R.; Bruins, A. P. Anal. Chem. 2000, 72, 3653–3659. (13) Syage, J. A.; Short, L. C.; Cai, S.-S. LCGC 2008, 26, 286–296. 10.1021/ac801186x CCC: $40.75 2008 American Chemical Society Published on Web 09/06/2008
Table 1. Sampling Surfaces Tested with DAPPI-MS sample plate material (thickness) aluminum (3.0 mm) aluminum foil (15 µm) copy/print paper filter paper microscope glass slide kitchen paper poly(methyl methacrylate) (PMMA) poly(tetrafluoroethylene) (PTFE, Teflon) silicon (0.5 mm) thin-layer chromatography (TLC) plates
manufacturer Tibnor Ltd., Espoo, Finland Metsa¨ Tissue, Ma¨ntta¨, Finland UPM Kymmene, Kuusankoski, Finland Schleicher & Schuell GmbH, Dassel, Germany Menzel GmbH + Co KG, Braunschweig, Germany Metsa¨ Tissue, Ma¨ntta¨, Finland Vink Finland Ltd., Kerava, Finland Vink Finland Ltd., Kerava, Finland Okmetic, Vantaa, Finland Merck KGaA, Darmstadt, Germany
geometry and thermal characteristics of the DAPPI surfaces are studied, as well as chemical issues such as spray solvent composition, and the ionization in both positive and negative ion modes. EXPERIMENTAL SECTION Chemicals. Water was purified with Milli-Q water purifying system (Millipore, Molsheim, France). HPLC grade acetone, hexane, and methanol were purchased from Mallinckrodt Baker B.V. (Deventer, The Netherlands), HPLC grade 2-propanol and toluene from Labscan Ltd. (Dublin, Ireland), and anisole (>99.9%) and testosterone from Fluka Chemie GmbH (Buchs, Switzerland). Anthracene, benzo[a]pyrene, 1,4-dinitrobenzene, naphthoquinone, naphthoic acid, tetracyclone, and verapamil hydrochloride were purchased from Sigma-Aldrich (Steinheim, Germany), and paracetamol was from Merck (Darmstadt, Germany). Methylenedioxymethamphetamine (MDMA) 1 mg/mL solution in methanol was obtained from United Laboratories Ltd. (Helsinki, Finland). All the analytes, except MDMA, were dissolved in methanol to form 10 mM stock solutions. Working solutions (1 µM for testosterone, 10 µM for MDMA and verapamil, 20 µM for anthracene, benzo[a]pyrene, and tetracyclone, 50 µM for 1,4dinitrobenzene, naphthoquinone, naphthoic acid, and paracetamol) were prepared in water/methanol (50/50, v/v). One microliter of working sample was applied per one sample spot. The Tylenol Cold tablets were from McNeil PPC Inc. (Fort Washington, PA) and were used as such. Fabrication of the Microchip. The API microchips consisted of two glass plates, which were bonded together by fusion bonding. A detailed description of the fabrication process has been presented elsewhere.14 The microchips featured an insertion channel for spray solvent capillary, an inlet for spray gas connection, and a heated mixing channel. Deactivated silica capillary (50 µm i.d., 220 µm o.d.) for spray solvent introduction was attached with epoxy glue (Duralco 4703, Cotronics Corp., Brooklyn, NY) and a Nanoport fluidic connector (Upchurch Scientific Inc., Oak Harbor, WA) for spray gas tubing with an adhesive ring. (14) Saarela, V.; Haapala, M.; Kostiainen, R.; Kotiaho, T.; Franssila, S. Lab. Chip 2007, 7, 644–646.
Figure 1. DAPPI parallel (a) and orthogonal (b) experiment setups. The heated jet desorbs the analytes from the surface, after which the analytes are ionized in gas phase by photons emitted by the krypton discharge lamp, and the analytes are finally introduced to the MS through a capillary extension. The x and y distances of the sample spot from the capillary extension tip and the angle between the microchip and the sampling surface were optimized. The optimal angle was 45°, and the optimal sample spot distances were x ) 3 mm and y ) 0 mm in the parallel setup (a), and x ) 1 mm and y ) 3 mm in the orthogonal setup (b). In (b), the position of the UV lamp is shown with a dashed line.
Sample Plates. A wide range of sample plate materials were tested (Table 1). Bulk materials were used as such, and thin foils (aluminum and papers) were attached on a poly(methyl methacrylate) (PMMA) plate with double-sided tape (Scotch, CergyPontoise, France) to make the handling of the foils easier. The sample plate size was ∼3.5 cm × 1.5 cm. The distance between the sample spots on the sample plates was ∼7 mm. Mass Spectrometer and Ion Source. The DAPPI ion source geometry and setup is depicted in Figure 1. Conventional ion source of a Bruker Esquire 3000+ ion trap mass spectrometer (Bruker Daltonik GmbH, Bremen, Germany) was replaced by a Nanospray stand (Proxeon Biosystems A/S, Odense, Denmark). The spray shield of the MS was replaced by a capillary extension part (Agilent Technologies, Santa Clara, CA). The position of the microchip and the sample plate for DAPPI were adjusted with xyz-stages (Proxeon Biosystems A/S, Odense, Denmark), which were attached to the Nanospray stand and placed in front of the capillary extension. A krypton discharge UV lamp (10.0 eV with small amount of 10.6 eV, Cathodeon, Cambridge, England) was placed above the sample plate. Drying gas flow from the MS flushed the tip of the capillary extension (nitrogen from liquid nitrogen, AGA, Espoo, Finland). Nebulizer gas (nitrogen from liquid nitrogen, AGA) was introduced to the microchip through a Nanoport connector and heated in the meandering channel. Spray solvent was introduced to the microchip through a silica capillary and vaporized and mixed with preheated nebulizer gas in the microchip nebulizing channel. The basic MS and microchip parameters were adapted from Haapala et al.:10 capillary voltage -4000 V, drying gas flow rate 4 L/min, drying gas temperature 285 °C, nebulizer gas flow rate through microchip 180 mL/min, spray solvent flow rate 10 µL/min, and microchip heating power 4.5 W. The MS was controlled with esquireControl software (Version 5.3, Build 11). RESULTS AND DISCUSSION Ion Source Configuration. Table 2 shows the most important microchip and mass spectrometer parameters optimized for DAPPI-MS operation. This includes the parallel and orthogonal configurations of the ion source as shown in Figure 1a and b, respectively. The distances x and y of the sample spot from the MS inlet and the angle between the nebulizer microchip and the Analytical Chemistry, Vol. 80, No. 19, October 1, 2008
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Table 2. Optimized Ion Source, Microchip, and MS Parameters and Optimal Sample Spot Distances (Figure 1) parameter parallel setup; sample x position parallel setup; sample y position orthogonal setup; sample x position orthogonal setup; sample y position angle between the microchip and the sample plate vertical distance of the microchip tip from the sample plate microchip heating power spray solvent flow rate nebulizer gas flow rate drying gas flow rate drying gas temperature
optimal value
range 2-4 mm -1 to 1 mm 1-3 mm
3 mm 0 mm 1 mm
2-4 mm
3 mm
40-55°
45°
not optimizeda
3 mm
1.5-5.0 W 2-20 µL/min 60-300 mL/min 4-8 L/min 250-350 °C
4.5 W 10 µL/min 180 mL/min 4 L/min 285 °C
a The vertical distance of the microchip tip from the sample plate is not crucial since the plume produced by the microchip is confined and narrow with a diameter of 1 mm.27
Scheme 1. Ionization Reactions in Positive Ion DAPPI (Reactions 1-3) and Negative Ion DAPPI (Reactions 1, 4-9)a 20,30
a
S stands for solvent and M for analyte molecule.
sample plate (Figure 1) were optimized to give maximum analyte signal intensity (Table 2). Both orthogonal and parallel configurations of the nebulizer chip spray were found to be functional with proper positioning. However, in the analysis of concentrated (i.e., tablets) or otherwise dirty samples, the parallel setup was suspected to cause more contamination and memory effect than the orthogonal setup, since the plume of the nebulizer chip was directed toward the MS interior. This phenomenon was demonstrated by analyzing a series of identical Tylenol Cold tablets and clean PMMA plates after each tablet. In the parallel setup, the analyte ion intensities were observed to be higher than those in the orthogonal setup, and a considerable cumulative memory effect from the clean PMMA plates was observed due to contamination. The orthogonal configuration is therefore recommended for the analysis of concentrated samples. However, the parallel setup was used in the rest of the experiments, since contamination was not an issue with the diluted samples used here. Additionally, adjusting the sample spot position was less complicated with the parallel setup, and due to that, it produced a more repeatable signal. Spray Solvents. Previously, acetone, toluene, acetone/toluene (50/50, v/v), methanol/toluene (50/50, v/v), and acetone/ methanol (50/50, v/v) have been tested as spray solvents in DAPPI.10 Acetone and toluene showed the best performance for 7462
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the neutral (anthracene and testosterone) and basic (MDMA and verapamil) analytes. In this study, more solvents were tested, and a wider range of analytes (Table 3) were analyzed in positive and negative ion modes. Anthracene, benzo[a]pyrene, MDMA, testosterone, tetracyclone, and verapamil were analyzed in positive ion mode and 1,4-dinitrobenzene, naphthoic acid, naphthoquinone, and paracetamol in negative ion mode. The set of compounds was chosen so that it represents polar and nonpolar compounds, different ionization routes, different ionization energies, proton affinities, electron affinities, and gas-phase acidities. PMMA sample plates were used in solvent comparison, since they produce relatively high analyte signal intensities. PTFE produced more intensive peaks, but the repeatability of the peak area was better with PMMA. The main ionization reactions are presented in Scheme 1. (a) Positive Ion Mode. When anisole or toluene was used as the spray solvent, the nonpolar anthracene, benzo[a]pyrene, and tetracyclone showed mainly M+• ions formed by charge exchange (Scheme 1, reactions 1 and 2; Figure 2a). With methanol/toluene (50/50, v/v) or hexane as the spray solvents, benzo[a]pyrene and tetracyclone showed [M + H]+ ions formed by proton transfer (Scheme 1, reactions 1 and 3). With acetone and 2-propanol, only tetracyclone was ionized, forming [M + H]+ ions by proton transfer. The polar MDMA, testosterone, and verapamil showed [M + H]+ ions with all the spray solvents. However, the verapamil mass spectrum was dominated by the fragment ion peak [M - C9H11O2]+ at m/z 303 instead of [M + H]+ ion at m/z 455 when anisole or toluene was used. Anisole and toluene have relatively low ionization energies, and they easily form radical cations (Table 4; Scheme 1, reaction 1), which react through charge exchange with the analytes to produce M+• analyte ions, if the ionization energy of the analyte is lower than that of the solvent (Table 3; Scheme 1, reaction 2). Therefore, the analytes with relatively low ionization energies (anthracene, benzo[a]pyrene, and tetracyclone) show radical cations, M+•, when anisole or toluene are used. On the contrary, if the analyte has a higher proton affinity than the solvent, solvent-originated reactant ions donate protons to the analytes (MDMA, testosterone, and verapamil) to produce protonated molecular ions, [M + H]+ (Scheme 1, reaction 3). Acetone, 2-propanol, methanol, methanol/ toluene, and hexane produce proton-donating reactant ions (Table 4), and therefore, [M + H]+ ions are observed with these solvents, except for low PA anthracene, as the result of proton-transfer reactions. Of the nonpolar compounds, the PA of benzo[a]pyrene is probably higher than that of anthracene due to a higher amount of conjugated carbon rings in the molecular structure and thus a higher amount of delocalized π-electrons. Therefore, [M + H]+ ions were seen in the benzo[a]pyrene but not in the anthracene spectra. A similar argument probably holds for tetracyclone as well. (b) Negative Ion Mode. In negative ion mode, the same ions were observed with all the spray solvents (Figure 2). 1,4Dinitrobenzene showed M-• ions formed by electron capture (Scheme 1, reaction 6) or charge exchange with superoxide radical (Scheme 1, reactions 1, 4, and 5). 1,4-Naphthoquinone showed [M - H + O]- and [M - 2H + 2O]- ions. Formation of this kind of oxidization products from substituted aromatic compounds (reactions 1, 4, and 8) in negative atmospheric pressure ionization
Table 3. Ionization Energies (IE), Proton Affinities (PA), Electron Affinities (EA), Gas-Phase Acidities, and Monoisotopic Masses of the Studied Compounds28 compound
IE (eV)
anisole acetone hexane 2-propanol methanol toluene anthracene benzo[a]pyrene 1,4-dinitrobenzene MDMA naphthoic acid 1,4-naphthoquinone paracetamol testosterone tetracyclone verapamil oxygen, O2
8.2 9.7 10.1 10.2 10.8 8.8 7.4 7.1 10.5
PA (kJ mol-1)
EA (eV)
gas-phase acidity, ∆Gacid (kJ mol-1)
840 812
1648 1515
793 754 784 877
1543 1565 1567 0.55 0.81 2.00
9.5 7.6
1.80
1370 1607
0.45
1450 (HO2•)
92529 98029 421
12.1
Mmonoisotopic (g/mol) 108.1 58.0 86.1 60.1 32.0 92.1 178.1 252.1 168.0 193.1 172.1 158.0 151.1 288.2 384.2 454.3 32.0
Table 4. Reactant Ions Formed from the Studied Spray Solventsa m/z (relative intensity, %) solvent acetone anisole hexane
reactant ions in negative ion mode
methanol/toluene
59 (100), 81 (27) 108 (100) 99 (100), 117 (29), 115 (15), 101 (13), 59 (13) 121 (100), 61 (63), 103 (28),43 (20), 79 (19), 38 (19) 88 (100)
toluene
92 (100)
2-propanol
a
reactant ions in positive ion mode
107 (100), 59 (37), 108 (20), 121 (18) 93 (100), 59 (44), 115 (20) 101 (100), 58 (47), 73 (44), 59 (34), 97 (31) 103 (100) 107 (100), 113 (65), 72 (51), 89 (49), 59 (45), 99 (45), 73 (44), 124 (44) 107 (100)
PMMA sampling surface, solvent flow rate 10 µL/min in positive ion mode, and 20 µL/min in negative ion mode.
has been reported on several occasions, such as with chlorobenzenes, nitrobenzenes, polychlorinated biphenyls, polybrominated diphenyl ethers, and 1,4-naphthoquinone.15-22 The acidic naphthoic acid and paracetamol showed [M - H]- ions, which were formed through proton transfer with the superoxide radical (reactions 1, 4, and 7) or with another reactant ion. With the solvents and analytes studied in negative ion mode, the type of solvent was observed to affect only the intensity of the analyte ion signal but not the type of the ions formed. The ionization mechanism is proposed to be determined by the electron affinity and the gas-phase acidity of the analyte and the spray solvent (Table 3) and the signal intensity by the amount of ionizing electrons. The latter depends on the ionization energy (15) Fehsenfeld, F. C.; Ferguson, E. E. J. Chem. Phys. 1974, 61, 3181–3193. (16) Dzidic, I.; Carroll, D. I.; Stillwell, R. N.; Horning, E. C. Anal. Chem. 1975, 47, 1308–1312. (17) Horning, E. C.; Carroll, D. I.; Dzidic, I.; Lin, S.-N.; Stillwell, R. N.; Thenot, J.-P. J. Chromatogr. 1977, 142, 481–495. (18) Korfmacher, W. A.; Mitchum, R. K. Chemosphere 1983, 12, 1243–1249. (19) Basso, E.; Marotta, E.; Seraglia, R.; Tubaro, M.; Traldi, P. J. Mass Spectrom. 2003, 38, 1113–1115. (20) Kauppila, T. J.; Kotiaho, T.; Bruins, A. P.; Kostiainen, R. J. Am. Soc. Mass Spectrom. 2004, 15, 203–211. (21) Debrauwer, L.; Riu, A.; Jouahri, M.; Rathahao, E.; Jouanin, I.; Antignac, J. P.; Cariou, R.; Le Bize, B.; Zalko, D J. Chromatogr., A 2005, 1082, 98– 109. (22) Luosuja¨rvi, L.; Karikko, M. M.; Haapala, M.; Saarela, V.; Huhtala, S.; Franssila, S.; Kostiainen, R.; Kotiaho, T.; Kauppila, T. J. Rapid Commun. Mass Spectrom. 2008, 22, 425–431.
of the spray solvent, and with high IE solvents (hexane, 2-propanol, and methanol), the ionization is less efficient compared to that with low IE solvents (anisole, acetone, and toluene), which can be seen on the analyte signal intensities (Figure 2b). If the ionization energy of the spray solvent is higher than 10.0 eV, the majority of the photons emitted by the krypton discharge lamp are incapable of ionizing the solvent, and ionization is initiated only by the minority 10.6-eV photons. Sample Plate Materials. Several materials have been introduced as sampling surfaces in desorption ionization techniques.10,23-25 The selection of sampling surfaces has been reported to have a significant effect on sensitivity and selectivity of desorption electrospray ionization (DESI). In this study, a set of sampling surfaces was tested for DAPPI (Table 1), and polymers were observed to give the best analyte signal intensities. Interestingly, the performance of silicon wafer and porous silicon was poor, although in other desorption/ionization techniques, DESI23 and desorption/ionization on silicon,2 the performance of porous silicon has been reported to be good. Thus, additional experiments were carried out to clarify the role of sampling surfaces in the DAPPI process. Altogether six (23) Kauppila, T. J.; Talaty, N.; Salo, P. K.; Kotiaho, T.; Kostiainen, R.; Cooks, R. G. Rapid Commun. Mass Spectrom. 2006, 20, 2143–2150. (24) Kauppila, T. J.; Wiseman, J. M.; Ketola, R. A.; Kotiaho, T.; Cooks, R. G.; Kostiainen, R. Rapid Commun. Mass Spectrom. 2006, 20, 387–392. (25) Ifa, D. R.; Manicke, N. E.; Rusine, A. L.; Cooks, R. G. Rapid Commun. Mass Spectrom. 2008, 22, 503–510.
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Figure 3. Analyte signal intensities from different sampling surfaces. (a) Average intensities of the analytes in (a) positive and (b) negative ion mode. Spray solvents in positive ion mode: toluene for nonpolar compounds (anthracene, benzo[a]pyrene, tetracyclone), and acetone for polar compounds (MDMA, testosterone, verapamil). Spray solvent in negative ion mode: anisole.
Figure 2. Detected signal intensities of the analyte ions with six different spray solvents in (a) positive and (b) negative ion mode. All the samples were applied on a PMMA surface. Solvents: Ani, anisole; Ace, acetone; Hex, hexane; Pro, 2-propanol, M/T, methanol/toluene (50/50, v/v); and Tol, toluene.
sampling surfaces with different thermal conductivity, surface porosity, and thickness were analyzed: aluminum, aluminum foil, copy/ print paper, glass, PMMA, and PTFE. All the 10 test compounds (Table 3) were analyzed from these six surfaces. The spray solvents were chosen for the sampling surface study as follows: acetone was used for polar compounds in positive ion mode, since it showed the best overall ionization efficiency for polar compounds (Figure 2a). Toluene was used for nonpolar compounds in positive ion mode due to its ability to produce both M+• and [M + H]+ ions (Figure 2a). Anisole was used for all compounds in negative ion mode, since it produced a high analyte signal intensity (Figure 2b) and a low background. PMMA and PTFE were found to be the best materials for all the studied analytes (Figure 3), although PMMA was found more repeatable than PTFE. This was probably due to drifting of the sample droplets on the PTFE surface before drying, which complicated the sample spot adjustment for the DAPPI-MS analysis. Other thermal insulators, glass and paper, worked fairly well in positive ion mode, but in negative ion mode, their performance was poor. On glass and paper, the sample droplets 7464
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were observed to spread more than on PMMA and PTFE, and therefore, the narrow and confined jet from the microchip was probably unable to desorb the entire sample simultaneously as from the rest of the surfaces. The aluminum foil showed better performance than the thick aluminum sample plate, but on the whole, these metal substrates were not as good as the polymer substrates. The same reactant ions were observed in the spectra from all the surface materials (data not shown), suggesting that the surface material did not take part in the ionization process. Instead, the differences in the ionization efficiencies were thought to depend on physical factors. However, the aluminum foil showed relatively better performance in negative ion mode compared to positive ion mode, which may be due to the metal surface’s ability to release electrons (Scheme 1, reaction 9) and subsequently strengthen the ionization in negative ion mode, as has been proposed in APPI.19 The polymer plates were assumed to work best due to their low thermal conductivity, which caused the nebulizer plume to heat up the sample spot more efficiently. This hypothesis was supported by the better performance of the aluminum foil when compared to the thick aluminum plate. Moreover, small molecules (with low boiling points) were observed to desorb faster than larger molecules (i.e., verapamil < testosterone < MDMA), which supports the thermal desorption process.
Figure 4. Infrared thermography images of different surface materials after 15 s of heating by the microchip. The chip heating power was 4.5 W, acetone was used as the spray solvent, and the nebulizer gas (nitrogen) flow rate was 180 mL/min. (a) PMMA (thickness 3 mm), Tmax ∼ 300 °C; (b) aluminum foil (thickness 15 µm) on PMMA, Tmax ∼ 180 °C; (c) kitchen paper on PMMA, Tmax ∼ 300 °C; and (d) silicon (thickness 0.5 mm), Tmax < 100 °C. On PMMA (a), the other warm spot below the spot being sprayed is the position where the jet was directed before the recording.
The local heating of the surface was further studied with thermal imaging26 of selected sampling surfaces under the microchip jet. The surface temperatures of the sampling surfaces after 15 s of spraying with the DAPPI chip are illustrated with thermographs (Figure 4). The differences between the materials with low (PMMA, kitchen paper) and high (aluminum foil, silicon) thermal conductivity can clearly be seen. Due to their lower thermal conductivity the polymer plates can be locally heated up to 300 °C, which seems to be an important factor for the effective desorption of the analytes in DAPPI. Figure 4a displays a hot spot on the PMMA sample plate, whereas on the aluminum foil, in Figure 4b, the heat is more widely and evenly spread due to the better thermal conductivity of aluminum. Kitchen paper can be heated to a temperature of 300 °C with DAPPI, as shown in Figure 4c, but on silicon, Figure 4d, the hot spot is hardly seen; instead, the whole silicon sample plate is slightly heated. This result and the signal intensities of the analytes from the different sampling ¨ stman, P.; Kotiaho, T.; Kostiainen, (26) Franssila, S.; Marttila, S.; Kolari, K.; O R.; Lehtiniemi, R.; Fager, C.-M.; Manninen, J. J. Microelectromech. Systems 2006, 15, 1251–1259. (27) Saarela, V.; Haapala, M.; Kostiainen, R.; Kotiaho, T.; Franssila, S. Proceedings of µTAS 2006 Conference 2006, 1, 152–154. (28) NIST Chemistry WebBook, NIST Standard Reference Database Number 69; Linstrom, P. J., Mallard, W. G., Eds.; National Institute of Standards and Technology: Gaithersburg, MD, 20899, June (http://webbook.nist.gov). ¨ stman, P.; Pakarinen, J. M.; Vainiotalo, P.; Franssila, S.; Kostiainen, R.; (29) O Kotiaho, T. Rapid Commun. Mass Spectrom. 2006, 20, 3669–3673. (30) Kauppila, T. J.; Kuuranne, T.; Meurer, E. C.; Eberlin, M. N.; Kotiaho, T.; Kostiainen, R. Anal. Chem. 2002, 74, 5470–5479.
materials support the hypothesis that due to the thermal desorption process the desorption efficiency in DAPPI is dependent on the thermal conductivity of the surface. It has to be taken into account that thermal imaging was carried out without the heated drying gas flow (Figure 1) from the mass spectrometer, which affects the absolute temperatures of the sample plate and the ionization zone. However, the relative differences between the sampling materials were clear. The effect of the solvent’s specific heat capacity was checked by thermal imaging with three spray solvents water/methanol (50:50, v/v), toluene, and acetone. The type of the solvent did not have any detectable effect on the heating rate and the final temperature of the sample plate. CONCLUSIONS DAPPI-MS is a powerful method for the fast analysis of analytes from solutions or solid samples like tablets. The desorption in DAPPI is a thermal process, and its efficiency is greatly determined by the thermal conductivity of the sampling surface, although it is likely that the size and polarity of the analyte also play a role. The ionization, however, takes place in the gas phase after the desorption through similar reactions as in atmospheric pressure photoionization. The ionization can be significantly affected by the selection of spray solvent. Low-polarity, low-proton affinity analytes can be ionized through charge exchange if solvents that form radical cations through photoionization are used as spray solvents, whereas spray solvents that form proton-donating reactant ions promote the ionization of Analytical Chemistry, Vol. 80, No. 19, October 1, 2008
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polar, high-proton affinity analytes through proton transfer. In negative ion DAPPI, the best ionization efficiency is achieved with spray solvents that have ionization energies below the energy of the VUV lamp photons and thus efficiently release thermal electrons in photoionization. The ionization efficiency in negative ion DAPPI could possibly be enhanced further using electron-releasing sampling materials.
and Microanalytical Systems, and the Academy of Finland for financial support. Dr. Reijo Lehtiniemi and Mr. Carl-Magnus Fager from Nokia Research Center (Helsinki, Finland) are acknowledged for their expertise and help in IR measurements.
ACKNOWLEDGMENT The authors thank the Finnish Funding Agency for Technology and Innovation (Tekes), the Graduate School of Chemical Sensors
Received for review June 12, 2008. Accepted July 28, 2008.
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