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Droplet Assisted Inlet Ionization for Online Analysis of Airborne Nanoparticles Andrew J. Horan, Michael J Apsokardu, and Murray V Johnston Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.6b04718 • Publication Date (Web): 24 Dec 2016 Downloaded from http://pubs.acs.org on December 28, 2016
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Analytical Chemistry
Droplet Assisted Inlet Ionization for Online Analysis of Airborne Nanoparticles Andrew J. Horan, Michael J. Apsokardu, Murray V. Johnston* Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States ABSTRACT: Airborne nanoparticles play a key role in climate effects as well as impacting human health. Their small mass and complex chemical composition represent significant challenges for analysis. This work introduces a new ionization method, Droplet Assisted Inlet Ionization (DAII), where aqueous droplets are produced from airborne nanoparticles. When these droplets enter the mass spectrometer through a heated inlet, rapid vaporization leads to the formation of molecular ions. The method is demonstrated with test aerosols consisting of polypropylene glycol (PPG), angiotensin II, bovine serum albumin and the “thermometer” compound p-methoxybenzylpyridinium chloride. High quality spectra were obtained from PPG particles down to 13 nm in diameter and sampled masses in the low pictogram range. These correspond to aerosol number and mass concentrations smaller than 1000 particles/cm3 and 100 ng/m3 respectively, and a time resolution on the order of seconds. Fragmentation of the thermometer ion using DAII was inlet temperature dependent and similar in magnitude to that observed with a conventional ESI source on the same instrument. DAII should be applicable to other types of aerosols including workplace aerosols and those produced for drug delivery by inhalation.
INTRODUCTION Recent years have seen rapid development of techniques for the analysis of atmospherically relevant aerosols1,2. These advancements are needed to bridge the knowledge gap with regard to predicting the composition and fate of ambient aerosols and how they impact climate and human health3. While these methods provide varying degrees of quantification and chemical characterization for specific combinations of particle size and composition, a need still exists for methods to characterize airborne nanoparticles, defined here as those with a diameter of 100nm or less4,5. The methods most widely used for online airborne nanoparticle characterization are the Nano Aerosol Mass Spectrometer (NAMS)6 and the Thermal Desorption Chemical Ionization Mass Spectrometer (TDCIMS)7. NAMS provides a quantitative measure of the elemental composition, while TDCIMS provides a semi-quantitative measure of the molecular composition. Both have excellent time resolution for capturing rapid changes in composition, and when deployed together can provide a fairly comprehensive view of ambient particle composition8. Additional insight into the organic molecular composition of atmospheric aerosol can be gained through offline analysis of collected samples by electrospray ionization (ESI)911 . When coupled with high performance mass spectrometry, hundreds to thousands of molecular species can be characterized. Recently, several groups have reported methods for online characterization of airborne particles by an extractive ESI technique 12-14. In this approach, aerosol flows around an electrospray plume. Molecular species are extracted into the charged droplets and ions are formed in a similar manner to conventional ESI12. While quite promising for ambient measurements, it is not clear whether these methods have the requisite sensitivity for nanoparticle analysis. Recently, a new class of ionization methods have been developed where ions are formed within the inlet of the mass spectrometer (Inlet Ionization)15. In one such method, Solvent Assisted Inlet Ionization (SAII), analyte solution is flowed directly into a heated capillary inlet where the liquid flow breaks into droplets and the droplets disintegrate in a
manner that produces ions similar to ESI16. While the mechanism of ion formation is not fully understood, it is thought to be similar to certain aspects of ESI (droplet charging, desolvation and Coulombic fission). SAII and most other inlet ionization methods share the characteristics of rapid sample heating in a high (near ambient) pressure region followed by a steep pressure gradient into a vacuum15,17. This work introduces a new ionization method, Droplet Assisted Inlet Ionization (DAII), that builds on previous inlet ionization studies. The basic idea is to generate aqueous droplets from airborne nanoparticles. When these droplets enter the heated capillary under conditions similar to SAII, ions are formed and subsequently mass analyzed. Initial results and future prospects are presented. EXPERIMENTAL METHODS The experimental setup, shown in Figure 1a, includes an atomizer to generate test aerosols, a Nano Aerosol SamplerConcentrator (NAS-c) to generate aqueous droplets from nanoparticles, and a heated capillary into the mass spectrometer. Test Aerosols. Polydisperse aerosols were generated from 5µM-5mM aqueous solutions of analyte with an atomizer (Model ATM226, TOPAS, Dresden, Germany). Bovine serum albumin (BSA, 66.9kDa, Sigma, St. Louis, MO), angiotensin II and polypropylene glycol (PPG, Mn 425, Sigma, St. Louis, MO) were selected as test compounds since they are non-volatile, commonly used as standards in ESI and well examined using inlet ionization techniques16,18-20. The polydisperse aerosols generated in this manner typically had a mode diameter on the order of 80 nm with a geometric standard deviation of 20nm as measured with a Scanning Mobility Particle Sizer (TSI Inc., Shoreview, MN). Monodisperse aerosols were obtained by placing a differential mobility analyzer and classifier (Model 3080, TSI, Shoreview, Minnesota) just after the atomizer. Depending upon analyte concentration in solution and whether or not size selection was performed, the test aerosols had particle diameters between 10 and 200 nm and mass concentrations between 10 ng/m3 and 1000 µg/m3. Droplet Formation. An aerosol flow of 1 liter per minute (Lpm) was sent into a Nano Aerosol Sampler operated
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in concentration mode (NAS-c). The sampler was custom designed and built by Aerosol Dynamics Inc. (Berkeley, CA). This device uses a water-based condensation method21 to either sample particles into a small collection well or to concentrate them into an outlet air flow. In concentration mode, a 7fold increase in aerosol concentration is achieved by growing individual particles 10nm dia. and above in a 1 Lpm inlet air flow into aqueous micro-droplets that are focused into an exit flow of about 0.14 Lpm. Figure 1b illustrates the droplet formation process. The aerosol flows through a growth tube surrounded by a water-soaked wick. After the aerosol passes through a “conditioner” region at 5˚C, it enters a slightly heated “initiator” region at 28˚C where the air becomes saturated with water vapor. Depending on particle composition, a small amount of water is taken up into the particle in this region. The aerosol then enters a cooled “moderator” region at 10˚C, where the temperature decrease creates a supersaturated vapor. In this region, water condenses on the particles to produce droplets. According to the manufacturer, the droplet size distribution exiting the moderator (not measured in this experiment) depends on aerosol number concentration and is typically in the 1-3 µm dia. range. Heated Capillary. The interface to a Waters SYNAPT G2-S Quadrupole Ion Mobility Time-of-Flight mass spectrometer was modified by replacing the manufacturer’s sample cone and cone gas assembly with a stainless steel capillary tube 54 mm in length, 1mm O.D. and 0.5 mm I.D. The tube was inserted into one entrance of a 50mm long, doubleholed ceramic insulator (Omega, Swedesboro, NJ). A thermocouple probe was inserted into the second hole of the insulator. To heat the capillary, 24-gauge NiChrome wire was coiled around the insulator and coated with a high temperature cement (Omegabond 600, Omega, Swedesboro, NJ). The high temperature cement served the dual purpose of securing the NiChrome coil to the ceramic tube as well as providing further insulation. The entire assembly could be heated up to a maximum of 950˚C. Under normal operation at 850˚C, the measured air flow drawn through the capillary from atmospheric pressure into the vacuum of the instrument (1x10-4 mbar at the capillary exit) was 1.6 standard Lpm as measured by a Gilibrator-2 (Sensidyne, St. Petersburg, FL). Since this was greater than the exit air flow of the NAS-c, makeup air was required. The exit flow of the NAS-c was connected to a 3-way Swage-Lok tee union. The second port of the tee was connected to house air (30% Relative Humidity, RH) at a flowrate of 1.4Lpm, which was used in this work, though provision was made to insert a HEPA filter and/or to use zero air. The third port on the tee was connected to an 8 mm long copper tube (1.8mm O.D., 1mm I.D.) which fit snugly over the exposed tip of the capillary. Mass Spectrometry. ESI spectra were obtained by direct infusion of analyte solutions at a concentration of 0.1 µg/µL in 50/50 acetonitrile/water with 0.1% formic acid using a syringe pump set to 10µL/min. The source settings were optimized based on the electrospray of a 0.01µg/µL CsI/NaI standard (Waters) as follows: sample capillary voltage at 3.4kV, sample cone at 40V, source block at 100˚C, and desolvation region at 200˚C. DAII spectra were obtained with all of the previously mentioned ESI settings switched off and a capillary temperature of 850˚C. The heating and voltage controls on the source
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assembly of the SYNAPT were all set to zero so that the temperature of the capillary could be controlled externally. For these initial studies, the ion mobility separation capability of the mass spectrometer was not utilized and the instrument was exclusively used in Time-Of-Flight mode. Unless otherwise specified, the mass spectrometer was run in continuum / positive ion / resolution mode with spectra processed as 20 second summations using the Waters MassLynx software. Thermal Desorption Chemical Ionization (TDCI) was performed using a direct insertion probe on a Waters GCT Premier instrument. The temperature was ramped to the maximum setting of 650˚C using methane as the reagent gas. Materials. p-Methoxybenzylpyridinium chloride was synthesized via a well-established method22 of combining pyridine with 4-methoxybenzyl chloride (both Sigma, St. Louis, MO) at 60˚C for 3 hours. The resulting solid was filtered, allowed to dry, and then used to make solutions as needed without further purification.
Figure 1. (a) Experimental setup for DAII including an atomizer to generate test aerosols (bracketed in red), the nanoaerosol sampler-concentrator (NAS-c) to generate aqueous droplets from nanoparticles, and the heated capillary attached to the inlet of the mass spectrometer. (b) Schematic of the three temperature regions inside the NAS-c where incoming nanoparticles are activated and grown into micro-droplets. The initiator region is saturated with water vapor, which creates a supersaturation in the moderator region.
RESULTS AND DISCUSSION For PPG (Figure 2) and angiotensin II (Figure S-1), the positive ions produced by DAII included protonated, sodiated, and potassiated adducts, with charge state distributions similar to those generated by other inlet ionization methods and traditional ESI. PPG showed only singly charged ions ([M+H]+, [M+Na]+, and [M+K]+), while angiotensin showed
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Analytical Chemistry
both singly and doubly charged ions ([M+H]+ and [M+2H]2+). Relative to ESI, DAII produced a higher fraction of metal cationized adducts (mostly sodiated), though it is not clear whether this is an intrinsic characteristic of the method or a consequence of trace metal contamination in the atomizer and/or the water supply to the NAS-c. Figure 2 illustrates the excellent sensitivity of DAII for PPG aerosol. This spectrum was obtained from a 10 second summation, corresponding to a total of 7 pg sampled into the mass spectrometer. The aerosol was size selected at 23 nm, and the number and mass concentrations sampled into the NAS-c are typical of ambient aerosol in this size range during new particle formation events4,23. (High quality spectra were obtained down to the smallest particle size examined, 13 nm.) ESI of this PPG sample showed a similar intensity distribution of oligomer ions, indicating that thermal decomposition in the DAII interface did not occur. The lack of decomposition in DAII was reinforced by thermal decomposition chemical ionization experiments, for which molecular ions could not be observed at any temperature studied. ESI gave mostly protonated adducts and normalizing the signal to mass flow showed that it was 4 orders of magnitude less sensitive than DAII for this sample. We did not explore whether the ESI sensitivity could be increased by adding metal ions to the electrosprayed solution or switching to a nanospray source.
served at temperatures below 400˚C, and the ion count remained weak until a temperature of 700˚C was reached. The signal continued to increase with increasing temperature up to 950˚C. Temperatures above this were not examined due to physical constraints of the apparatus. The capilllary temperature required for efficient DAII is much higher than that for liquid-flow inlet ionization techniques such as SAII, where the optimum temperature is typically between 200-425˚C.16,24 Furthermore, no decomposition products were observed even though PPG is known to decompose at temperatures well below 800˚C. The high temperature and lack of decomposition may be the consequence of the very short residence time of aerosol inside the DAII heated capillary (on the order of 0.1 ms) relative to SAII where the analyte residence time is determined in part by a slow liquid flow rate into the capillary.25.
Figure 3. Total ion count from PPG aerosol vs. DAII capillary temperature. The higher signal variation above 750˚C is caused
by instability of the temperature controller used in the initial experiments. (For simplicity, temperature variations are not shown in this plot.)
Figure 2. DAII mass spectrum of monodisperse PPG aerosol (23 nm dia. particles, 900 particles/cm3, 70 ng/m3 entering the NASc). This spectrum is a 10 s summation, which corresponds to a total of 7 pg sampled into the heated capillary (850˚C).
To test whether or not droplet formation was required, the DAII experiment was repeated in two ways. First, the NAS-c was bypassed by sending the PPG aerosol directly into the heated capillary. Second, a drying tube filled with dessicant around the outer edges of the aerosol flow was inserted between the NAS-c and the entrance to the capillary. In both cases, the PPG signal was reduced by 2-3 orders of magnitude when normalized to the mass flow of analyte into the mass spectrometer. While aqueous droplets were not absolutely required for ion formation, they did greatly enhance the ionization efficiency. A similar effect has been observed with other inlet ionization techniques17. Figure 3 shows the capillary temperature dependence of the DAII ion signal for PPG aerosol. No signal was ob-
To further assess the possibility of thermal decomposition inside the capillary, DAII was performed with a pmethoxybenzylpyridinium salt (p-OCH3) that has been previously employed as a thermometer ion to study the energetics of other inlet ionization methods25. Thermal excitation during ion formation and analysis is described by the survival yield,26,27, which is defined as the molecular ion signal divided by the sum of the molecular and fragment ion signals. First, p-OCH3 solution was infused directly into the ESI source. Depending on the tuning of the voltages and temperature in the source, the SY could be as low as 1% or as high as 10%. Under normal ESI operating conditions recommended by the instrument manufacturer, the survival yield was 4%. The salt was then aerosolized and analyzed by DAII (Figure S-2). Under normal operating conditions (850˚C) the SY was 5-6%, suggesting that ionization by DAII is no harsher than conventional ESI for this analyte and that ion decomposition is determined by characteristics of the manufacturer inlet to the mass spectrometer rather than the heated capillary. Increasing the capillary temperature in DAII caused a decrease of the SY to 1% at 900˚C and finally complete fragmentation at 950˚C. Thus, successful application of DAII requires a balance between sensitivity (higher temperature) and fragmentation (lower temperature), and it may be that the optimum
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temperature corresponds to a situation where the analyte is fully desolvated at the capillary exit but not before. The ability to impart multiple charges by DAII was investigated by analyzing BSA aerosol (Figure S-3a). The peak of the charge envelope corresponded a charge state of +25, indicating that desolvation and fission of each droplet resulted in the formation of many charges. When analyzed by ESI on this same mass spectrometer (Figure S-3b), the average charge state was higher (+45) than DAII. When the integrated signal intensity was normalized to mass flow, DAII was found to be one order of magnitude more sensitive than ESI for this compound. CONCLUSIONS AND FUTURE WORK In its current form, DAII is able to characterize airborne nanoparticles with sufficient sensitivity for application to ambient aerosol as well as laboratory experiments. For all analytes studied, the signal response was found to be strongly dependent on the presence/absence of water in the particles. Our initial work shows that signal intensity qualitatively scales with analyte mass flow through the capillary. A more detailed study is needed to determine how particle size affects analyte charging and hence sensitivity. While this work was performed with a Q-IMS-TOF instrument, inlet ionization methods are transferrable to a wide variety of instrumental platforms28. The focus of this work has been to develop new analytical methodology for ambient aerosol characterization. However, other applications can be envisioned. For example, there is a need for real-time molecular characterization of workplace aerosols29 and aerosol-delivered pharmaceuticals30. The initial results presented here suggest that DAII will be applicable to a wide range of aerosol applications.
SUPPORTING INFORMATION Three figures as referenced in the manuscript.
AUTHOR INFORMATION Corresponding Author *Email:
[email protected] ACKNOWLEDGMENTS The authors thank Bryan Bzdek, Nicholas Chubatyi, Charles McEwen and Sarah Trimpin for helpful comments and suggestions throughout this work. This work was supported by the National Science Foundation under Grant No. CHE 1408455.
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(5) Bzdek, B. R.; Pennington, M. R.; Johnston, M. V. J. Aerosol Sci. 2012, 52, 109-120. (6) Wang, S.; Johnston, M. V. Int. J. Mass Spectrom. 2006, 258, 50-57. (7) Voisin, D.; Smith, J. N.; Sakurai, H.; McMurry, P. H.; Eisele, F. L. Aerosol Sci. Technol. 2003, 37, 471-475. (8) Bzdek, B. R.; Lawler, M. J.; Horan, A. J.; Pennington, M. R.; DePalma, J. W.; Zhao, J.; Smith, J. N.; Johnston, M. V. Geophys. Res. Lett. 2014, 41, 6045-6054. (9) Meade, L. E.; Riva, M.; Blomberg, M. Z.; Brock, A. K.; Qualters, E. M.; Siejack, R. A.; Ramakrishnan, K.; Surratt, J. D.; Kautzman, K. E. Atmos. Environ. 2016, 145, 405-414. (10) Vogel, A. L.; Schneider, J.; Müller-Tautges, C.; Klimach, T.; Hoffmann, T. Environ. Sci. Technol. 2016, 50, 10814-10822. (11) Kristensen, K.; Bilde, M.; Aalto, P. P.; Petäjä, T.; Glasius, M. Atmos. Environ. 2016, 130, 36-53. (12) Horan, A. J.; Gao, Y.; Hall, W. A.; Johnston, M. V. Anal. Chem. 2012, 84, 9253-9258. (13) Gallimore, P. J.; Kalberer, M. Environ. Sci. Technol. 2013, 47, 7324-7331. (14) Doezema, L. A.; Longin, T.; Cody, W.; Perraud, V.; Dawson, M. L.; Ezell, M. J.; Greaves, J.; Johnson, K. R.; Finlayson-Pitts, B. J. RSC Adv. 2012, 2, 2930-2938. (15) McEwen, C. N.; Pagnotti, V. S.; Inutan, E. D.; Trimpin, S. Anal. Chem. 2010, 82, 9164-9168. (16) Pagnotti, V. S.; Chubatyi, N. D.; McEwen, C. N. Anal. Chem. 2011, 83, 3981-3985. (17) Trimpin, S.; Wang, B.; Inutan, E. D.; Li, J.; Lietz, C. B.; Harron, A.; Pagnotti, V. S.; Sardelis, D.; McEwen, C. N. J. Am. Soc. Mass Spectrom. 2012, 23, 1644-1660. (18) Wang, B.; Trimpin, S. Anal. Chem. 2014, 86, 1000-1006. (19) Trimpin, S.; Inutan, E. D. J. Am. Soc. Mass Spectrom. 2013, 24, 722-732. (20) El-Baba, T. J.; Lutomski, C. A.; Wang, B.; Trimpin, S. Rapid Commun. Mass Spectrom. 2014, 28, 1175-1184. (21) Hering, S. V.; Stolzenburg, M. R. Aerosol Sci. Technol. 2005, 39, 428-436. (22) Naban-Maillet, J.; Lesage, D.; Bossée, A.; Gimbert, Y.; Sztáray, J.; Vékey, K.; Tabet, J.-C. J. Mass Spectrom. 2005, 40, 18. (23) Bzdek, B. R.; Horan, A. J.; Pennington, M. R.; DePalma, J. W.; Zhao, J.; Jen, C. N.; Hanson, D. R.; Smith, J. N.; McMurry, P. H.; Johnston, M. V. Faraday Discussions 2013, 165, 25-43. (24) Pagnotti, V. S.; Chakrabarty, S.; McEwen, C. N. J. Am. Soc. Mass Spectrom. 2013, 24, 186-192. (25) Fenner, M. A.; McEwen, C. N. Int. J. Mass Spectrom. 2015, 378, 107-112. (26) Greisch, J. F.; Gabelica, V.; Remacle, F.; De Pauw, E. Rapid Commun. Mass Spectrom. 2003, 17, 1847-1854. (27) Gabelica, V.; Pauw, E. D. Mss Spectrom. Rev. 2005, 24, 566587. (28) Hoang, K.; Pophristic, M.; Horan, A. J.; Johnston, M. V.; McEwen, C. N. J. Am. Soc. Mass Spectrom. 2016, 1-7. (29) Harper, M. J. Environ. Monit. 2006, 8, 598-604. (30) Morrical, B. D.; Balaxi, M.; Fergenson, D. Int. J. Pharm. 2015, 489, 11-17.
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