Imaging of Surface Charge and the Mechanism of Desorption

Oct 19, 2009 - Distributions of charge deposited on surfaces in desorption electrospray ionization mass spectrometry (DESI-MS) were investigated using...
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J. Phys. Chem. C 2010, 114, 5331–5337

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Imaging of Surface Charge and the Mechanism of Desorption Electrospray Ionization Mass Spectrometry† Liang Gao,‡ Guangtao Li,‡ Jobin Cyriac,‡ Zongxiu Nie,‡ and R. Graham Cooks*,‡,§ Department of Chemistry, Purdue UniVersity, West Lafayette, Indiana 47907 and Center for Analytical Instrumentation DeVelopment, Purdue UniVersity, West Lafayette, Indiana 47907 ReceiVed: May 27, 2009; ReVised Manuscript ReceiVed: September 11, 2009

Distributions of charge deposited on surfaces in desorption electrospray ionization mass spectrometry (DESIMS) were investigated using a static charge measurement apparatus, which gives an output voltage proportional to the local surface charge density. By scanning the probe along the surface and taking measurements at fixed intervals, a contour image of relative charge density reflecting the charge distribution on the surface can be plotted. Through the measured charge distribution and the derived charge density gradient, the motion of charged droplets in the DESI experiment can be inferred. Measurements taken under various DESI operating conditions, including spray pressure, angle, flow rate, and sprayer tip-to-surface distance, show that charge is spread over an area of a few square centimeters under typical conditions; effective desorption occurs from a much smaller area (∼1 mm2) of highest charge density. Higher sheath gas pressures and smaller sprayer tip-to-surface distances lead to concentration of charge distribution into a smaller area, whereas smaller spray angles favor charge distribution over a larger area. The appearance of the highest charge density in front of the DESI sprayer tip and near the MS inlet suggests that charged droplets are moved toward the MS inlet by pneumatic forces and by the vacuum suction, in agreement with results of earlier simulations. The present observations are consistent with previous studies using other techniques and support the accepted droplet splashing DESI mechanism. Introduction Desorption electrospray ionization (DESI) is an ambient ionization method that allows chemical analysis of materials on surfaces with minimal or no prior sample preparation.1,2 In DESI-MS, charged solvent droplets formed in an electrospray plume are pneumatically propelled onto the surface to be investigated. Analyte molecules on the surface dissolve in a thin film of deposited solution and are incorporated in the secondary droplets released by the splash produced as incoming primary droplets impact the thin liquid film.3 Subsequent desolvation occurs by processes that parallel those in electrospray ionization. Loose parallels can be drawn between the ambient ionization process of DESI and the vacuum momentum transfer (sputtering) process that characterizes secondary ion mass spectrometry.4 Since its introduction in 2004, DESI has been evaluated for applicability in numerous areas, including pharmaceutical analysis,5-7 forensic analysis,6,8,9 chemical and biochemical imaging,10-15 natural product characterization,1,16,17 polymer analysis,18 and glycomics,19 as well as bacteria,20,21 protein,22,23 and explosives24 detection. Investigations into the DESI mechanism have been conducted using a variety of methods. Primary and secondary droplet sizes and velocities have been measured as a function of operating conditions, and the influence of these factors on signal intensities has been studied via a phase Doppler particle analysis method.25 It was found that droplet velocities and signal intensities are determined mainly by sheath gas pressure and distance between †

Part of the “Barbara J. Garrison Festschrift”. * To whom correspondence should be addressed. Phone: 765-494-5262. Fax: 765-494-9421. E-mail: [email protected]. ‡ Department of Chemistry. § Center for Analytical Instrumentation Development.

the sprayer tip and surface. Computational fluid dynamics was used to model atmospheric droplet transport and droplet-thin film (surface) collisions; these data indicated that analytes contained within a thin liquid film can be released in secondary droplets generated and picked up by a high velocity primary droplet collision.26,27 The internal energy distributions of typical ions generated by DESI were measured by a thermometer-ion method,28,29 and they proved to be similar to that of electrospray ionization (ESI) and electrosonic spray ionization; this result supports an ESI-like desolvation mechanism for DESI after the splash that creates the analyte-bearing secondary droplets. The angled electrospray solvent plume forms an elliptical impact region on the surface being analyzed by DESI-MS.3,30 To date, the investigation of the DESI impact region has been performed mostly through observation of the area wetted and by recording mass spectra as a function of the position and spatial distribution of the analyte.3,30-33 The occurrence of surface charging in DESI has been inferred from time-dependent capacitive effects which depend strongly on the nature of the surface;34 however, the charge distribution within the impact region has not been documented. In this study, a static charge detection apparatus was built and used to image the distribution of surface charge in DESI-MS. The effects of DESI operating conditions on local charge distributions were elucidated. Since charges are deposited through charged droplets in DESI-MS, the motion and distribution of charged droplets was also inferred by the charge distribution and the spatial variation of charge density. Experimental Section Static charge measurement devices in various configurations have been used in many applications across science.35-39 Charge detection is usually realized by measuring an induced potential

10.1021/jp904960t  2010 American Chemical Society Published on Web 10/19/2009

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Figure 1. (a) Configuration of the surface charge imaging device, including a capacitive probe, an enhanced mode MOSFET, a power supply, and a current amplifier. (b) Surface charge imaging stage in which the surface charge distribution on a PTFE surface is obtained by scanning the capacitive probe in the XY plane, as shown in the figure and taking measurements at fixed intervals. (c) Theoretical model of the charge measurement setup. (d) Diagram of the DESI source and definition of geometric parameters.

generated on a capacitive probe, thus allowing the quantity of charge in a localized area to be evaluated. Such a surface charge measurement device (Figure 1a) was built for this study. The apparatus included a DC power supply, a current amplifier (Keithley 428, Keithley Instruments, Inc., Cleveland, OH), an oscilloscope, an enhanced mode N-channel MOSFET (IRF 530N), a 1 kΩ current limiting resistor, and a capacitive scanning probe, which was made of a 3-cm-long BNC coaxial cable. The probe center electrode, a copper wire 0.7 mm in diameter, protruded 0.5 mm from the grounded shield. When the scanning probe is close to the charged surface being measured, an image charge is induced on the probe, and this generates a potential difference between the center electrode and ground, which is also the MOSFET gate-to-source voltage. The MOSFET drain-to-source conductance as well as the drainto-source current is controlled by the gate-to-source voltage. Therefore, the gate-to-source voltage and the quantity of static charge can be estimated by measuring the drain-to-source current. In the apparatus of Figure 1a, the drain-to-source current was converted to voltage by the current amplifier in a ratio of 106 V/A and measured using an oscilloscope. The MOSFET circuit was selected because the MOSFET gate has an extremely large input resistance and draws almost no current, thus allowing small amounts of static charge to be measured. As shown in Figure 1b, the charge imaging stage consisted of an electrical grounded stainless steel substrate on which was placed the planar surface to be measured and a 3-dimensional moving stage to which the scanning probe was attached. The probe was always perpendicular to the surface during measurement. After charges were deposited onto the surface by DESI, the scanning probe was adjusted so that it was about 0.5 mm away from the surface and aligned with the top left corner of the area to be measured. The capacitive probe was then rastered across the XY plane from the top left corner to the bottom right corner of the area, as shown in Figure 1b. Measurements were taken at 1 mm intervals in both directions during scanning, which resulted in a matrix whose elements correspond to measured voltages at each position. Typically, it took about 8 min to obtain a surface charge distribution image after charges had been deposited onto the surface. A contour image of surface charge distribution could then be plotted.

A theoretical model of the measurement apparatus is shown in Figure 1c. Csg is the capacitance between the surface charge to be measured and electrical ground; Csp is the capacitance between surface charge and the scanning probe center electrode; Cpg is the capacitance between the center electrode and ground, including the capacitance of the BNC cable and the MOSFET gate-to-source capacitance; U0 is the induced voltage between the center electrode and ground, which is also the MOSFET gate-to-source voltage. The relationship between Q, the quantity of surface charge, which can also be represented as the product of surface charge density σ and area A, and the voltage U0 can be described by eq 1:35,36

U0(Csp + Cpg) Q ) ⇒ Q ) σA ) CspCpg Csp Csg + Csp + Cpg CsgCsp + CsgCpg + CspCpg U0 Csp

(1)

This equation shows that the induced voltage, U0, is proportional to the quantity of charge, Q, and charge density, σ, when all capacitance values (except those that depend on surface charge) are constant; this condition can be maintained by keeping a constant probe-to-surface distance during the measurement. The MOSFET drain-to-source current can also be made proportional to the voltage U0, provided it is located in a selected working range of the MOSFET. Thus, the measured voltage is proportional to the charge quantity and density at the measurement position. The exact values of all parameters appearing in eq 1 need to be calculated or measured only if quantitative data are desired. Otherwise, the measured voltages and their relative intensity across the surface can give a good representation of the relative charge distribution on the surface. Therefore, data are presented in arbitrary units without converting to the actual density of surface charge. It should be further noted that the center electrode voltage needs to be offset to achieve the selected working range by transferring a certain amount of static charge to the probe electrode (done by connecting the center electrode to a voltage source close to the

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Figure 2. (a) Voltages measured as a result of positive surface charges plotted against the scanning probe to surface distance on log-log scale. (b) Line plot of charging showing shape expected from angled spray (55° spray angle, 100 psi sheath gas pressure and 2 µL/min flow rate) and the persistence over a period of time.

threshold voltage, the amount depending on the exact properties of the selected MOSFET) before making the actual measurement. A standard DESI source allowing adjustment in sheath gas pressure, spray angle, and solvent flow rate was used in the experiment (Figure 1d). A potential of +4 kV was applied to form the electrospray, which used as solvent 1:1 methanol/water solution and (in some experiments done to visualize the area of solvent deposition) 10 ppm Rhodamine B solution prepared in 1:1 methanol/water with 1% acetic acid. Polytetrafluoroethylene (PTFE), 2 cm by 2 cm sheets with a thickness of 1 mm, were used as the surface for all experiments because of the excellent insulation property of this material and its extensive use as a substrate in DESI-MS. Surfaces were cleaned using methanol and dried in nitrogen gas to decrease the influence of pre-existing static charges. Prior to each experiment, blank measurements were conducted to ensure that the measured voltage was constant across the surface. Results and Discussion In a preliminary experiment, the charge detection capability of the apparatus was examined. A positively charged PTFE sheet was prepared by electrospraying 1:1 methanol/water solvent onto the surface in the positive ion mode. Then the scanning probe was adjusted to approach the spray impact region of the PTFE surface gradually to take measurements. The voltages measured were recorded and plotted versus the probe electrode-to-surface distance on a log-log scale, as shown in Figure 2a. As expected, the voltage increases as the probe approaches the surface with approximately an r-1 power dependence on the probe to surface distance because of the increase of capacitance, Csp, as the distance decreases. The result qualitatively verifies the charge detection capability of the apparatus. The rate of discharge was measured by performing a line scan on a charged PTFE surface along the line oriented as indicated in Figure 2b, then waiting 20 min and repeating this scan. The data show only a slight drop in voltage over this period; the signal observed is consistent with the spray pattern illustrated. Note that this result is particular to the PTFE surface studied; discharge occurs more or less rapidly with other surfaces. The surface charge distribution established by DESI under normal operating conditions was measured. The 1:1 methanol/ water solvent was sprayed onto a PTFE sheet surface at a flow rate of 2 µL/min for 1 min with a spray angle of 55° to the surface, a sheath gas pressure of 100 psi, and 3 mm sprayer tip-to-surface distance. The resulting charge density contour

image is shown in Figure 3a, which also shows the approximate projection of the DESI sprayer capillary onto the surface. The region of maximum charge distribution, symmetrical about the direction of spray and elliptical in shape, was observed to cover an area of a few square centimeters. The region in front of the sprayer tip has the highest charge density, and the charge density gradually decreases as the distance from the sprayer tip increases. It decreases slowly along the spray direction and rapidly in the reverse direction. This is consistent with the fact that charged droplets are most likely to move with the pneumatic force along the spray direction; hence, higher charge density is observed in this direction. Charge density gradients, represented by arrows, are plotted in the same figure to allow visualization of charge density variation across the surface. The arrow lengths and directions represent gradient magnitude and direction, respectively. A contour image of charge density gradient magnitude (Figure 3b), was plotted to help further the understanding of the charge distribution and the motion of charged droplets that produces it. To explain, charges are deposited by charged droplets. Hence, the charge distribution directly reflects the spatial distribution of charged droplets, and the motion of droplets projected onto the surface can be traced by the charge density and its variation, Charge density should be higher in places to which more charged droplets have access and lower in places less accessible to them. There are no features of the data to indicate significant charge flow across the surface during or after deposition; all the data are consistent, qualitatively, with the vapor phase motion of droplets measured in laser tomography experiments25 and simulated in computational fluid dynamics simulations.26,27 For this reason, the gradient magnitude of charge density is smaller in directions across the surface that droplets intend to move to, and it is larger in directions where the opposite holds. Therefore, the contours in the gradient magnitude contour diagram map out the motion of droplets parallel to the surface plane. In Figure 3b, the contours stretch radially outward from the sprayer tip and extend along the surface indicating the directions of motion of the charged droplets. The most effective desorption and ionization area in DESIMS is a few square millimeters in size and is located in the center of the spray impact region.3,30 To determine whether the desorption area corresponds to that of highest charge density, the prepared Rhodamine B solution was electrosprayed using the same DESI conditions for 1 min. The contour image recorded is shown in Figure 4a along with an optical picture (Figure 4b) of the rectangle area in Figure 4a taken with an

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Figure 3. (a) Contour image of charge density on a PTFE surface after methanol-water solution was electrosprayed on surface by DESI. (b) Contour image of charge density gradient magnitude shown in Figure 2a.

Figure 4. (a) Contour image of charge density on a PTFE surface after Rhodamine B solution was electrosprayed on surface for 1 min. (b) Optical image of the rectangular area in Figure 4(a) taken by Olympus BX51 optical microscope, showing the desorption area.

Olympus BX51 optical microscope, showing the size of the desorption area. It was confirmed that the desorption area was within the highest charge density region by comparing their locations. The boundary area of the PTFE sheet showing low charge density was sliced off and analyzed using a custombuilt secondary ion mass spectrometer (SIMS).40 A peak at m/z 443 along with other fragments at lower mass range with low intensities confirms the presence of Rhodamine B. This observation verifies that charges are distributed by arriving droplets over a much larger area than that from which analyte is desorbed. This is easily understandable as a consequence of the fact that droplet impact is a necessary but insufficient condition for successful analyte ionization. According to the accepted DESI mechanism, ionization requires formation of a thin liquid film on the surface onto which energetic primary droplets must impact. Both these factors become less likely as one moves away from the central area of highest primary droplet flux. It is interesting to note that the Rhodamine B distribution forms a “coffee ring”. It would appear that in this region, solvent flows freely; however, the size of the region is too small to

establish whether it is accompanied by charge flow. The region has an area (in this particular experiment) of ∼0.5 mm2. This is much smaller than the area of elevated charge that is some hundreds of square millimeters. It is comparable to the wetted area observed by visualization experiments measured as 0.4 mm2, and it is also comparable to the area of a few square millimeters from which ionization has been measured by depositing samples into small areas and measuring the resulting mass spectra. These comparisons are consistent with the droplet “pick-up” mechanism of DESI. In particular, the data suggest that charging occurs on droplet deposition, but that a much smaller area within the charged region has a liquid surface film of solvent and that analyte is desorbed from this small region. Next, the influence of DESI sheath gas pressure, spray angle, solvent flow rate and sprayer tip-to-surface distance on charge distribution was investigated. The 1:1 methanol/water solution was first sprayed at a 2 µL/min flow rate with a 55° spray angle and a 1.5 mm sprayer tip-to-surface distance for 30 s with sheath gas pressure of 130 and 60 psi. Corresponding images obtained are shown in Figure 5a and b. Images given in Figure 5c and d

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Figure 5. Contour image of charge density on a PTFE surface after 1:1 methanol/water solution was sprayed onto the surface by DESI with different sheath gas pressures, spray angles, and solvent flow rates: (a) 55° spray angle, 130 psi sheath gas pressure, and 2 µL/min flow rate; (b) 55° spray angle, 60 psi sheath gas pressure, and 2 µL/min flow rate; (c) 30° spray angle, 100 psi sheath gas pressure, and 2 µL/min flow rate; (d) 90° spray angle, 100 psi sheath gas pressure, and 2 µL/min flow rate; (e) 55° spray angle, 100 psi sheath gas pressure, and 1 µL/min flow rate; and (f) 55° spray angle, 100 psi sheath gas pressure and 5 µL/min flow rate.

show the experimental results conducted with the same setup, where 100 psi sheath gas pressure and 30° and 90° spray angle were used. In Figure 5e and f, a 55° spray angle and 100 psi sheath gas pressure were applied, and solvent was sprayed for 10 s at a flow rate of 1 and 5 µL/min respectively. By comparison of Figure 5a and b, it was observed that charges were better focused using the higher sheath gas pressure. The charge density drops rapidly from the desorption area to boundary areas with a higher sheath gas pressure. The result is consistent with the previous observations that at higher sheath gas pressure, the primary droplets traveling at higher velocities are confined to a smaller spot, whereas poorly focused larger droplets with lower velocities are produced as a result of the inefficient nebulization at lower sheath gas pressure.25,33 Similar poorly focused charge distributions were observed when a larger sprayer tip-to-surface distance (3 mm) was used in a separate experiment. In both Figure 5c and d, charges are well-focused, which shows that charge focusing is not influenced by the spray angle. However, using a smaller spray angle, droplets can be spread farther on the surface along the direction of the spray. In Figure 5e and f, charges were distributed into only a small area, since only a small amount of solvent was sprayed onto the surface. However, the charge distribution is symmetrical in Figure 5e and asymmetrical in Figure 5f. A possible reason for the difference is that more secondary droplets can be generated to distribute charges along the direction of spray using a larger solvent flow rate. Otherwise, the shape of contours should be similar in the two figures if only primary droplets are considered. Thus, one can speculate that a higher signal intensity can be obtained in DESI-MS with a higher solvent flow rate, since more analyte can be extracted and picked up by the larger amount of solvent and released in the secondary droplets, an expectation verified in previous studies.3 In DESI-MS, desorbed secondary droplets from the sample surface are extracted by suction into the mass spectrometer, and

this force too directly influences the charge analysis result. The effect of the mass spectrometer vacuum on charge distribution was studied by placing the PTFE surface and the DESI sprayer in front of the inlet of a Thermo Finnigan LTQ mass spectrometer as in normal operation. A 55° spray angle, 100 psi sheath gas pressure, and 1.5 mm sprayer tip-to-surface distance were applied. The MS inlet was about 5 mm away from the sprayer tip and 1 mm from the surface, and the collection angle was about 5°. A 1:1 methanol/water solution was sprayed to the surface for 1 min at a flow rate of 3 µL/ min. The surface charge density was measured, and the resultant contour image is shown in Figure 6a (direction of spray is from top to bottom). Interestingly, two charge centers now appear in the charge density image. One falls in the desorption area established in the earlier experiments, located right in front of the sprayer tip, and the other occurs in front of the MS inlet. It was also observed that charges mostly accumulated in the area between the sprayer tip and the MS inlet, leaving very few charges elsewhere. The appearance of the second charge center is obviously a product of the presence of the MS vacuum and is not due to the potential on the MS inlet. That is, droplets were forced to move toward the MS inlet by gas flow caused by the MS vacuum, which generated the second charge center This was verified in a separate experiment in which the PTFE surface and DESI sprayer were placed in front of the inlet of the mass spectrometer. However, the vacuum inlet to the mass spectrometer was blocked so that only its electrical fields could influence the charge distribution. (Spray direction is from top to bottom and the mass spectrometer capillary inlet voltage is +130 V; a 55° spray angle, 100 psi sheath gas pressure, and 1.5 mm sprayer tip-to-surface distance were applied. The MS inlet was ∼5 mm away from the sprayer tip and 1 mm from the surface, and the collection angle was ∼5°. A 1:1 methanol/ water solution was sprayed to the surface for 1 minute at a flow rate of 3 µL/min.) The resulting surface charge distribution

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Figure 6. (a) Contour image of charge density on a PTFE surface after methanol-water solution was electrosprayed on the surface by DESI with presence of the MS vacuum and a 5° collection angle. Spray direction is from the top to the bottom in the image. (b) Contour image of charge density gradient shown in Figure 6a. (c) Contour image of charge density on a PTFE surface after methanol-water solution was electrosprayed onto the surface by DESI in the presence of the MS vacuum and a 45° collection angle. Spray direction is from the top to the bottom in the image. (d) Contour image of charge density gradient shown in Figure 6c.

shows only one charge center, proving that the pneumatic force associated with the sprayer dominates the motion of the droplets. The experiment was repeated with the mass spectrometer inlet capillary grounded, and similar results were obtained, which confirms that the electrical force has little influence. Next, the experiment shown in Figure 6a was repeated under the same conditions except a 45 degree collection angle was used. The image obtained is shown in Figure 6c. Two charge centers can still be observed in the image, but that of a higher charge density center is now located in front of the MS inlet rather than in the desorption area. This can be attributed to the low droplet pick-up efficiency caused by the large collection angle. Droplets moving toward the low pressure region developed by MS inlet were unable to be picked up efficiently by the mass spectrometer, subsequently creating a high charge density area in front of the MS inlet. The droplet motion projection in a plane parallel to the surface under the influence of vacuum suction is visualized in Figure 6b and d, which display the contour images of charge density gradient. The

contours show that droplets diverge from the end of the sprayer tip and converge to the MS inlet. The preferential direction is that directly connecting the sprayer tip and the MS inlet, where the smallest gradient magnitude can be observed. The rapidly increasing gradient magnitude behind MS inlet and around the center area further confirms that most droplets are confined to the center area between the sprayer tip and the MS inlet. These results demonstrate that charged droplets move toward the MS inlet under the influence of MS vacuum and that a smaller collection angle gives better droplet pick-up efficiency in DESIMS, consistent with experiment. Conclusion A static charge measurement apparatus was built with a capacitive probe and a MOSFET circuit. By scanning the capacitive probe along the surface and recording measurement data at a fixed interval, a contour image of surface charge density could be plotted and the motion of droplets could be inferred.

Imaging of Surface Charge, Mechanism of DESI-MS Charge distributions on the surface under various DESI conditions were measured, and the effects of sheath gas pressure, spray angle, solvent flow rate, sprayer tip to surface distance, MS vacuum, and MS collection angle were studied. The results show that charges are distributed to an area of a few square centimeters through charged droplets, and the DESI desorption area (typically a few square millimeters) has the highest charge density. Charges are better focused with higher sheath gas pressure and smaller spray tip to surface distance, smaller spray angles help to distribute charges to a larger area, and higher solvent flow rates enhance the generation of secondary droplets. In the presence of vacuum suction, droplets are forced to move toward the MS inlet, and a smaller collection angle gives better droplet pick-up efficiency. The observations can be wellexplained using the droplet mechanism of DESI, which simultaneously supports the droplet pick-up mechanism of DESI. There are several limitations that need to be addressed in the application of the charge imaging method. The apparatus can be used only to measure fixed charges of a given polarity so that charges resulting from plasma processes cannot be measured. In addition, in the measurement, charges not immediately beneath the probe electrode also induce image charges on the probe electrode so that both measurement accuracy and resolution are affected, blurring the recorded charge distribution. However, the effect of charge falls with a (1/r) dependence, and the shielding of the probe electrode minimize these effects. Improved performance could be obtained with a thinner central electrode, but this was not needed in this study. The conductivity of the surface influences measurement accuracy as well because of charge neutralization. It also should be mentioned that the measurement result reflects an integrated charge distribution on the surface over a period of time rather than the actual situation at any specific moment in DESI-MS. Nonetheless, the information obtained by surface charge imaging is still valuable for a better understanding of the fundamental mechanism underlying DESI, and this, in turn, allows the optimization of parameters for more advanced DESI applications, including DESI imaging and DESI large area analysis. It is also possible that the approach used here could prove useful in examining charging effects in other ambient ionization experiments. Acknowledgment. This research was supported by the Department of Energy, Office of Basic Energy Sciences. Liang Gao acknowledges a graduate fellowship from American Chemical Society Division of Analytical Chemistry, sponsored by Agilent Technologies, Inc. References and Notes (1) Takats, Z.; Wiseman, J. M.; Gologan, B.; Cooks, R. G. Science 2004, 306, 471. (2) Cooks, R. G.; Ouyang, Z.; Takats, Z.; Wiseman, J. M. Science 2006, 311, 1566. (3) Takats, Z.; Wiseman, J. M.; Cooks, R. G. J. Mass Spectrom. 2005, 40, 1261.

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