Article pubs.acs.org/ac
Ambient Aerodynamic Desorption/Ionization Method for Microparticle Mass Measurement Caiqiao Xiong,† Xiaoyu Zhou,† Jianing Wang,† Ning Zhang,† Wen-Ping Peng,‡ Huan-Cheng Chang,§ and Zongxiu Nie*,† †
Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, China and Beijing National Laboratory for Molecular Sciences, Beijing 100190, China ‡ Department of Physics, National Dong Hwa University, Shoufeng, Hualien 97401, Taiwan § Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 106, Taiwan ABSTRACT: An ambient desorption/ionization method, named aerodynamic desorption (AD), was proposed for the in situ rapid mass measurement of microparticles. The AD method exploited the discontinuous atmospheric pressure interface (DAPI) to generate a pulsed airflow, which was used to desorb the microparticles under atmospheric pressure. Various microparticles, e.g., bacteria, cell, polystyrene, synthetic diamond, and silica particles, with different size and surface component were successfully desorbed. Similar to that in the conventional laser-induced acoustic desorption (LIAD) method, these microparticles were desorbed as precharged ions in the AD process and the charge number was largely relevant to the particle size. However, compared with LIAD, the sensitivity of the AD method was higher. A lower concentration of particles was required for the analysis. In addition, the construction and sampling process of AD source were much simpler. All types of liquid, solid, or/and gaseous samples can be directly sampled under ambient condition. As a demonstration of this AD method, the in situ mass analysis of red blood cells (RBCs) and E. coli bacteria were carried out using a homemade ambient AD mass spectrometer consisting of AD source, QIT mass analyzer, and charge detector. Their mass and mass distributions were obtained successfully.
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virus produced by ESI needs special caution. MALDI has been demonstrated as a useful technique for the laser desorption of polystyrene and intact bacterial particles,7,21−23 but it is not so applicable for viruses and cells that do not have a rigid wall. When these particles are mixed with the matrix and subsequently ablated by the laser, they can disintegrate easily. In contrast, LIAD is a much more general desorption/ ionization method for microparticles. In the LIAD method, the particles were loaded on a Si wafer devoid of any organic matrix and desorbed by the laser ablation at the backside of the sample plate. Such treatment can effectively avoid the disintegration effect of particles without the rigid wall in MALDI. In addition, because of no aerosol production, LIAD is much safer than ESI for virus analysis. However, the sample preparation and a vacuum environment are still required in LIAD, which severely limits its applications for the in situ fast measurement of microparticles. Ambient desorption/ionization methods,24−30 proliferated from desorption electrospray ionization (DESI)31 and direct analysis in real time (DART),32 require no or minimal sample preparation and thus allow the rapid analysis of samples or objects in their native state in the open environment. They greatly simplify the process of ion transfer in MS, increase the speed of MS analysis, and bring the MS into the “real world”.25
icroparticles with nanometer or micrometer size, such as aerosols, cells, finely divided materials, etc., play important roles in our natural environment, which involves air pollution, medicine, healthy, material synthesis, and processing.1,2 Generally, these microparticles always exhibit diverse functions according to their properties, e.g., mass, volume, density, etc. Among these properties, mass is a basic one that can provide the information of both volume and density and is thus of great importance for the characterization and identification of microparticles.1−3 Mass spectrometry (MS) has been a powerful technique for the mass analysis of various molecules and mixtures.4 More recently, the mass measurement of microparticles has been achieved using different MS techniques, including time-of-flight (TOF),5−7 ion mobility,8 and quadrupole ion trap (QIT).9 These mass measurements have been used to evaluate the condensation and evaporation of aerosol particles,10 distinguish the normal and abnormal cells,11−13 study the endocytosis by cells,14 interpret the assembling of virus,6−8,15 determine the specific surface area and size distribution of particle materials,16 etc. Prior to the analysis in MS, microparticles must be desorbed/ ionized. The ion sources that enable mass spectrometric detection of microparticles are the soft ionization methods including electrospray ionization (ESI),17 matrix-assisted laser desorption/ionization (MALDI),18 and the laser-induced acoustic desorption (LIAD)19,20 method. Various viruses have been evaporated and ionized by ESI.5,6,8 However, because of the infectious nature of these nanoscale particles, the aerosol of © 2013 American Chemical Society
Received: December 9, 2012 Accepted: March 27, 2013 Published: March 27, 2013 4370
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entrance of capillary 1 to ensure high desorption efficiency. If the particles have a rigid wall, they could also be directly analyzed by dropping the suspension (about 3 μL) in capillary 1. The inhaled suspension can be dried quickly in vacuum. Then, the particles adsorbed on capillary 2 were desorbed by the AD method. In this case, the desorption efficiency can be improved by beating the capillary wall.39 The QIT used for mass analysis consists of a hyperbolic ring electrode and two hyperbolic end-cap electrodes. The radius of the ring electrode is 10 mm. The distance d between the ion entrance orifice (3 mm in diameter) of QIT drilled on the endcap electrode and the exit of capillary 2 is about 5 mm. The ions that fell into the QIT were trapped with helium as buffer gas. A semiconductor laser (532 nm) was used to illuminate the trapped particles, and the scattered light of particles was monitored by a CCD (not shown in Figure 1a). The pressure was measured by a thermocouple gage. When DAPI was open for 9 ms, the pressure in the manifold increased rapidly from 2.6 to 2.8 Pa. After DAPI was closed, the pressure would gradually drop back to 2.6 Pa in about 10 s due to the evacuation of a mechanical pump (TRP-1). The QIT was operated in an axial mass-selective instability mode by scanning the trap driving frequency.22,40 When the particles were ejected from QIT, the image charge induced by particles was collected by the Faraday disk in the center of charge detector, and the voltage signal can be converted to the charge number Z on each particle.11 The microparticles analyzed in this work include 3 μm polystyrene size standards (NIST SRM 1692), 1 μm polystyrene size standards (NIST SRM 1690), 3 μm poly divinylbenzene/styrene spheres with pore size of 300 Å (UniPS 3-300, Suzhou Nanomicro Technology Company Limited, China), BSA coated 3 μm poly divinylbenzene/styrene spheres with pore size of 300 Å (the coating of BSA was achieved by incubating the particles with BSA solution for 3 h at the room temperature, and the amount of adsorption is about 150 mg/g determined from the difference between the initial and the final BSA concentration in the supernatant), 3 μm synthetic diamond (Huan Sukan Ultrahard Materials Co., Ltd., China), 5 μm porous silica particles with pore size of 100 Å, and C18 (octadecyldimethylsilane), Ph (phenyldimethylchlorosilane), and CN (cyanoethyldimethylchlorosilane) bonded 5 μm porous silica particles with pore size of 100 Å (Agela Technologies Inc., China), human red blood cells (RBCs, taken from hospital), and E.coli K-12 bacteria (Sigma). In our experiments, only RBCs and E.coli K-12 bacteria required minimal sample preparations. The RBCs were fixed by 0.25% (v/v) glutaraldehyde in PBS for 1 h. Then, the fixed RBCs were thoroughly washed with deionized water and resuspended in distilled water at a concentration of about 1 × 107 particles/mL. E. coli K-12 bacteria were purified by repeated centrifugation in deionized water and prepared as a suspension at a concentration of about 1 × 1010 particles/mL. The dry powder of 3 μm poly divinylbenzene/styrene spheres, 5 μm silica particles, and C18, Ph, and CN bonded 5 μm silica particles and the suspension of RBCs were smeared on the silica wafer. E.coli bacteria and 1 μm polystyrene microsphere suspensions were directly dropped in capillary 1. The 3 μm polystyrene size standards were analyzed by both of the sampling methods. Between the sampling of different microparticles, the channel of DAPI was cleaned by opening the pinch valve repeatedly until no particle was monitored by CCD. In addition, this cleaning process can be assisted by
In these ambient methods, the analytes embedded in a substrate are usually desorbed and ionized using energetic charged aqueous droplets, gas phase ions, or metastable atoms. Low energy, intact small and macromolecular ions can be produced. Nevertheless, the microparticles with ultrahigh mass (>5 MDa) and high desorption energy are difficult to splash off from a surface under the bombardment of charged particles.24,25 In this Article, we proposed an aerodynamic desorption (AD) method that allow the soft desorption/ionization of intact microparticles under ambient condition. A pulsed high speed airflow generated by a discontinuous atmospheric interface (DAPI)33−36 was used to desorb microparticles of interest. By coupling the AD source with a QIT mass analyzer and a charge detector, an ambient AD mass spectrometry was constructed. In our experiments, the distance between AD source and QIT mass analyzer was first optimized. Then, the desorption/ionization capability and sensitivity of the AD method were analyzed and compared with that of the LIAD method. Finally, the ambient AD mass spectrometry was used for the in situ analysis of human red blood cells (RBCs) and E. coli bacteria.
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EXPERIMENTAL SECTION The experimental setup is as shown in Figure 1a. It consists of an AD ion source, a QIT mass analyzer,37 and a charge
Figure 1. (a) Experimental setup consisting of an AD ion source, a QIT mass analyzer, and a charge detector. (b) Schematic of AD process. The microparticles will be desorbed by aerodynamic force and inhaled into the mass spectrometer when DAPI was open.
detector.11,20 The channel in DAPI contains two capillaries: Teflon capillary 1 (i.d. of 0.04 in., o.d. of 1/16 in., and a length of 1.5 cm) and the stainless steel capillary 2 (i.d. of 0.02 in., o.d. of 1/16 in., and a length of 20 cm). Capillaries 1 and 2 were connected to each other via a silicone tube (i.d. of 1/16 in., o.d. of 1/8 in., and a length of 3 cm). The close/open status of the silicone tube was controlled by a pinch valve (390NC24330, ASCO Valve Inc., Florham Park, NJ) which was driven by a 0/ 24 V pulse dc signal. As shown in Figure 1b, the DAPI was usually closed to keep the high vacuum in the mass spectrometer. When it was opened briefly (for 9 ms), gas would enter the vacuum chamber rapidly due to the high pressure difference.35 When the gas passed the sample, the microparticles can be pulled in the airflow and desorbed according to the Bernoulli principle.38 Then, the desorbed particles were synchronously carried into the mass analyzer. The powder or suspension of analyzed microparticles was loaded on a silica wafer. After the suspension (10 μL) was dried in air, the silica wafer was held within 3 mm away from the 4371
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adding about 5 μL of ethanol or water in capillary 1. For the mass analysis of these microparticles, a 600 V ac voltage (zeroto-peak) was applied on the ring electrode with end-cap electrodes electrically grounded. The frequency of ac field was scanned linearly in 5 s, and the range of frequency scan was from 450 to 150 Hz for 3 μm polymer particles, 5 μm silica particles, and RBCs, from 1400 to 700 Hz for 1 μm polystyrene, and from 3000 to 800 Hz for E.coli. After several hundreds of particles were measured, both the mean mass and the mass distribution can be obtained by fitting the mass histogram with a Gaussian profile.11−13
entrance of QIT. Figure 3 shows the mass and charge distributions of 3 μm polystyrene size standards with different
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RESULTS AND DISCUSSION Figure 2a shows a typical single-scan mass spectrum of 3 μm polystyrene size standards. About 10 peaks are observed, and
Figure 3. Mass and charge distributions of 3 μm polystyrene size standards with d = 5 mm (a, b) and d = 7 mm (c, d), respectively, where d is the distance between the exit of capillary 2 and the entrance of QIT shown in Figure 1a.
d values. When d = 5 mm, a mild corona discharge in the ion trap was induced by the entered gas.43 As shown in Figure 3a,b, the mass histogram of 3 μm polystyrene size standards can be perfectly fitted with a Gaussian profile. The charge number on most analyzed particles ranged from 5000 to 10 000 e. When d was increased to 7 mm, the strong gas expansion effect at the exit of capillary 235 reduced the gas entering the trap. The corona discharge was not observed, and the precharged microparticles desorbed by the AD method were analyzed directly. As a result, plenty of precharged particle clusters weighed more than 1.2 × 1013 Da and charges of more than 10 000 e were observed (Figure 3c,d). These results implied that the mild corona discharge would be beneficial for the further dispersion of microparticles after they were desorbed by the AD method, and the complexity of the spectrum resulting from particle clusters was avoided. Nevertheless, when the exit of DAPI capillary is too close to the entrance of QIT (d < 3 mm), stronger gas flow and discharge would harm the trapping of ions in QIT and resulted in fewer particles that could be detected.35 Therefore, d = 5 mm was selected as an optimized value for 3 μm polystyrene size standards. Besides polystyrene, various other microparticles (their names were listed in Figure 4) can be desorbed and ionized by the AD method. It was found that, when the distance d was about 5 mm (5 mm ± 1 mm), a mild discharge would always be induced by the entered gas,43 and good mass and charge distributions similar to Figure 3a,b can be obtained for different microparticles. Figure 4 shows the charge distribution of different microparticles desorbed by the AD method, and the results were compared with that obtained by the LIAD method. These microparticles can be divided into two groups: 3 μm size group including polystyrene size standards (NIST SRM 1692), poly divinylbenzene/styrene spheres (UniPS 3-300), BSA coated 3 μm poly divinylbenzene/styrene spheres (UniPS 3-300+BSA), and synthetic diamond and 5 μm size group including silica particles, and C18, Ph, and CN bonded silica particles. From Figure 4, it can be seen that the charge number obtained by the
Figure 2. (a) Typical single-scan mass spectrum of 3 μm polystyrene size standards. Each peak indicates a single particle. The mass of each particle was calculated from simultaneous measurement of m/Z and Z. (b) Mass histogram of 3 μm polystyrene size standards.
each peak indicates a particle with specific m/Z value determined by the ejection frequency. The peak height represents the charge number Z derived from the amplitude at charge detector. Figure 2b shows the corresponding mass histogram of 3 μm polystyrene size standards, which have a certified mean diameter of 2.982 μm and a corresponding mole mass of 0.88× 1013 Da with density 1.055 g/cm3. This mass value was used to calibrate to our instrument and ensure its accuracy.41,42 The determined mass distribution was characterized by a coefficient of variation (CV, defined as the ratio of SD to the mean). The values of CV were determined as 16.6% and 18.3% when the suspension of 3 μm polystyrene spheres were loaded on the sample plate and directly dropped in capillary 1, respectively. Theoretically, the observed mass distribution profile is a result of convolution of the source and the instrumental functions. Assuming that both functions are Gaussian, it has:12 SD2 = SDs 2 + SDi 2
(1)
where SD, SDs, and SDi are the standard deviation of the observed mass distribution, the source function, and the instrumental function, respectively. Since the intrinsic standard mass variation of the polystyrene size standard is only 1.6%, the observed mass distribution width 16.6% and 18.3% represents the mass resolution of the mass spectrometer.12 These results are similar to that obtained in our previous study using LIAD ion source,12,16 which demonstrates the soft desorption/ ionization capability of the AD method and the good performance of ambient AD mass spectrometry. The performance of the AD method was optimized by adjusting the distance, d, between the DAPI capillary and the 4372
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Figure 5. Averaged peak number in the mass spectrum as a function of the concentration of microparticles.
Figure 4. Charge distribution of different microparticles generated by the AD method (black) and the LIAD method (red). The analyzed microparticles are 3 μm polystyrene size standards (NIST SRM 1692), 3 μm poly divinylbenzene/styrene spheres with pore size of 300 Å (UniPS 3-300), BSA coated 3 μm poly divinylbenzene/styrene spheres with pore size of 300 Å (UniPS 3-300+BSA), 3 μm synthetic diamond, 5 μm porous silica particles with pore size of 100 Å, and C18, Ph, and CN bonded 5 μm porous silica particles with pore size of 100 Å.
from a healthy female adult and a patient with iron deficiency anemia, and E. coli K-12 bacteria were carried out. These bioparticles cover the mass range from 1 × 1010 to 1 × 1014 Da or the size range from about 1 to 10 μm. Figure 6 shows the
AD method (black histogram) was similar to that obtained by LIAD method (red histogram). The charge number for different microparticles was mainly related to their particle sizes.20 With the increment of particle size from 3 to 5 μm, the mean charge number on microparticles was also increased from about 6000 to 8000. For the microparticles with the same size, although they might have different skeleton molecules (e.g., 3 μm polystyrene, poly divinylbenzene/styrene spheres, and synthetic diamond) or be modified using different chemical reagents (e.g., 3 μm poly divinylbenzene/styrene spheres with and without BSA adsorption and C18, Ph, and CN bonded 5 μm silica particles), the charge number would not be influenced significantly. Compared with the size of the laser spot (about 0.5 mm) in the LIAD method, the diameter of capillary 1 (1.016 mm) aiming at sample in AD source was much larger. As a result, more particles could be desorbed in every AD process and the sensitivity of AD method should be higher. As a demonstration for quantitative analysis, the suspensions of 3 μm polystyrene size standards at concentrations from 2 × 107 to 8 × 108 particles/mL were analyzed, and the peak numbers in the mass spectrum, average of 10 repeated measurements, were counted. Figure 5 shows the plot of averaged peak number versus the concentration of microparticles. It can be seen that the averaged peak number of the AD method (black line) was about twice as much as that of the LIAD method (red line). When the particle concentration was lower than 2 × 108, a linear relationship between averaged peak number and the microparticle concentration would be found. The fitted curves for the AD method and the LIAD method were y = 2.83 × 10−8x + 4.11 (R2 = 0.99) and y = 1.39 × 10−8x + 2.04 (R2 = 0.97), respectively. It was demonstrated that the sensitivity of the AD method was higher indeed. If the limit of detection (LOD) was defined as the microparticle concentration at which only 1 peak was in the mass spectrum, it should be lower than 1 × 107 particles/mL for the AD method. Using the ambient AD mass spectrometry, the mass analysis of the human red blood cells (RBCs), which were collected
Figure 6. Mass histograms of human red blood cells. The two data sets are those of normal (red) and anemic (blue) red blood cells.
mass histograms of normal (red) and anemic (blue) RBCs. The former gave a mean mass of 1.83 × 1013 Da (30.4 pg) with an intrinsic mass distribution CVs of 19.6% calculated using eq 1. This measured mass matched closely with the value of mean corpuscular hemoglobin (MCH) 28.6 pg obtained by the automated hematology analyzer. In comparison, the mean mass of anemic RBCs was significantly lower at 1.49 × 1013 Da (24.7 pg, MCH = 22.8 pg), and the mass distribution was broader as CVs = 31.7%. The ability to distinguish these two types of RBCs confirmed the utility of this method for clinical diagnosis. Considering that the mass of E. coli K-12 bacteria was much smaller than that of 3 μm polystyrene spheres, the accuracy of mass spectrometry was recalibrated using 1 μm polystyrene size standards with a known mass of 2.38 × 1011 Da19 prior to the mass measurement. Figure 7a shows the mass profile of 1 μm polystyrene spheres. Its mass distribution was determined as CV = 18.9%. Figure 7b shows the mass histogram of E. coli K12 bacteria. It gave a mean mass of 2.55 × 1011 Da (423 fg) with a mass distribution CVs of 31.3%. The determined mean mass was about 5 times as much as its dry mass 83.5 fg determined by the light scattering method.19,23 This result implied that the particles detected in our work are bacteria clusters with an average cell number of 5. The detection of 4373
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REFERENCES
(1) Heal, M. R.; Kumar, P.; Harrison, R. M. Chem. Soc. Rev. 2012, 41, 6606−6630. (2) DeCarlo, P. F.; Slowik, J. G.; Worsnop, D. R.; Davidovits, P.; Jimenez, J. L. Aerosol Sci. Technol. 2004, 38, 1185−1205. (3) Bryan, A. K.; Goranov, A.; Amon, A.; Manalis, S. R. Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 999−1004. (4) Hoffmann, E. D.; Stroobant, V. Mass spectrometry principles and applications, 3rd ed.; John Wiley &Sons, Ltd: Hoboken, NJ, 2007. (5) Tito, M. A.; Tars, K.; Valegard, K.; Hajdu, J.; Robinson, C. V. J. Am. Chem. Soc. 2000, 122, 3550−3551. (6) Fuerstenau, S. D.; Benner, W. H.; Thomas, J. J.; Brugidou, C.; Bothner, B.; Siuzdak, G. Angew. Chem., Int. Ed. 2001, 40, 542−544. (7) Aksenov, A. A.; Bier, M. E. J. Am. Soc. Mass Spectrom. 2008, 19, 219−230. (8) Uetrecht, C.; Heck, A. J. R. Angew. Chem., Int. Ed. 2011, 50, 8248−8262. (9) Chang, H.-C. Annu. Rev. Anal. Chem. 2009, 2, 169−185. (10) Davis, E. J. Aerosol Sci. Technol. 1997, 26, 212−254. (11) Peng, W.-P.; Lin, H.-C.; Lin, H.-H.; Chu, M.-L.; Yu, A. L.; Chang, H.-C.; Chen, C.-H. Angew. Chem., Int. Ed. 2007, 46, 3865− 3869. (12) Nie, Z. X.; Cui, F. P.; Tzeng, Y.-K.; Chang, H.-C.; Chu, M.-L.; Lin, H.-C.; Chen, C.-H.; Lin, H.-H.; Yu, A. L. Anal. Chem. 2007, 79, 7401−7407. (13) Zhu, Z. Q.; Xiong, C. Q.; Xu, G. P.; Liu, H.; Zhou, X. Y.; Chen, R.; Peng, W.-P.; Nie, Z. X. Analyst 2011, 136, 1305−1309. (14) Lin, H.-C.; Lin, H.-H.; Kao, C.-Y.; Yu, A. L.; Peng, W.-P.; Chen, C.-H. Angew. Chem., Int. Ed. 2010, 49, 3460−3464. (15) Nie, Z. X.; Tzeng, Y.-K.; Chang, H.-C.; Chiu, C.-C.; Chang, C.Y.; Chang, C.-M.; Tao, M.-H. Angew. Chem., Int. Ed. 2006, 45, 8131− 8134. (16) Xiong, C. Q.; Zhou, X. Y.; Chen, R.; Zhang, Y. M.; Peng, W.-P.; Nie, Z. X.; Chang, H.-C.; Liu, H. W.; Chen, Y. Anal. Chem. 2011, 83, 5400−5406. (17) Wong, S. F.; Meng, C. K.; Fenn, J. B. J. Phys. Chem. 1988, 92, 546−550. (18) Tanaka, K.; Waki, H.; Ido, Y.; Akita, S.; Yoshida, Y.; Yoshida, T. Rapid Commun. Mass Spectrom. 1988, 2, 151−153. (19) Peng, W.-P.; Yang, Y.-C.; Kang, M.-W.; Tzeng, Y.-K.; Nie, Z. X.; Chang, H.-C.; Chang, W.; Chen, C.-H. Angew. Chem., Int. Ed. 2006, 45, 1423−1426. (20) Peng, W.-P.; Lin, H.-C.; Chu, M.-L.; Chang, H.-C.; Lin, H.-H.; Yu, A. L.; Chen, C.-H. Anal. Chem. 2008, 80, 2524−2530. (21) Cai, Y.; Peng, W.-P.; Kuo, S.-J.; Sabu, S.; Han, C.-C.; Chang, H.C. Anal. Chem. 2002, 74, 4434−4440. (22) Cai, Y.; Peng, W.-P.; Chang, H.-C. Anal. Chem. 2003, 75, 1805− 1811. (23) Peng, W.-P.; Yang, Y.-C.; Kang, M.-W.; Lee, Y. T.; Chang, H.-C. J. Am. Chem. Soc. 2004, 126, 11766−11767. (24) Weston, D. J. Analyst 2010, 135, 661−668. (25) Alberici, R. M.; Simas, R. C.; Sanvido, G. B.; Romão, W.; Lalli, P. M.; Benassi, M.; Cunha, I. B. S.; Eberlin, M. N. Anal. Bioanal. Chem. 2010, 398, 265−294. (26) Harris, G. A.; Galhena, A. S.; Fernández, F. M. Anal. Chem. 2011, 83, 4508−4538. (27) Ifa, D. R.; Wu, C.; Ouyang, Z.; Cooks, R. G. Analyst 2010, 135, 669−681. (28) Chen, H.; Gamez, G.; Zenobi, R. J. Am. Soc. Mass Spectrom. 2009, 20, 1947−1963. (29) Cooks, R. G.; Ouyang, Z.; Takats, Z.; Wiseman, J. M. Science 2006, 311, 1566−1570. (30) Ma, X. X.; Zhang, S. C.; Zhang, X. R. TrAC 2012, 35, 50−66. (31) Takats, Z.; Wiseman, J. M.; Gologan, B.; Cooks, R. G. Science 2004, 306, 471−473. (32) Cody, R. B.; Laramee, J. A.; Durst, H. D. Anal. Chem. 2005, 77, 2297−2302. (33) Gao, L.; Cooks, R. G.; Ouyang, Z. Anal. Chem. 2008, 80, 4026− 4032.
Figure 7. Mass histograms of (a) 1 μm polystyrene size standards and (b) E. coli bacteria (ca, 1.0 μm long and 0.5 μm diameter).
single bacteria particle was mainly limited by the high electronic background (about 600 e) of charge detector used in our work. By analyzing the charge distribution of detected bacteria clusters, it was found that the mean charge number on a single bacteria particle was about 700 e which was slightly higher than the electronic noise of the charge detector.11,20 Only the bacteria clusters with enough charges can be detected in the experiments. Therefore, in order to achieve the characterization of bacteria, virus, and inhaled aerosol particles, which are usually smaller than 1 μm and harmful to human health, the noise of the charge detector should be lowered.44,45 In addition, considering that the mass difference between strains of bacteria or viruses caused by a genetic mutant or post-translational modification may be very small, their identification should be based on the gene or protein characterization,46 and the mass analysis of the whole particle should be coupled with the MS characterization of particle chemical composition in the future research.
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CONCLUSION In summary, an ambient AD method was developed for the in situ mass analysis of microparticles. It utilizes a high speed airflow instead of a laser to achieve the soft desorption/ ionization of intact microparticles. Various microparticles can be desorbed as precharged ions. The charge number mainly depends on the particle size, regardless of the particle component. Compared with the conventional LIAD method, the AD method can provide higher sensitivity. More importantly, the sampling process in the AD method is greatly simplified. All types of liquid, solid, or/and gaseous microparticles can be sampled in their native state. Therefore, the possible use of the AD source for its adaptation to a hand-held particle mass spectrometer can be predicted.
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Article
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was supported by grants from Innovation Method Fund of China (Grant No.2012IM030400), the National Natural Sciences Foundation of China (Grant Nos. 21127901, 20927006, and 21175139), and Chinese Academy of Sciences. 4374
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(34) Gao, L.; Li, G. T.; Nie, Z. X.; Duncan, J.; Ouyang, Z.; Cooks, R. G. Int. J. Mass Spectrom. 2009, 283, 30−34. (35) Xu, W.; Charipar, N.; Kirleis, M. A.; Xia, Y.; Ouyang, Z. Anal. Chem. 2010, 82, 6584−6592. (36) Huang, G. M.; Li, G. T.; Ducan, J.; Ouyang, Z.; Cooks, R. G. Angew. Chem., Int. Ed. 2011, 50, 1−5. (37) March, R. E.; Hughes, R. J. Quadrupole Storage Mass Spectrometry; Wiley: New York, 1989; Chapter 2. (38) Serway, R. A.; Jewett, J. W. Physics for scientists and engineers with modern physics, 8th ed.; Cengage Learning: Belmont, CA, 2010; Chapter 14. (39) McEwen, C. N.; Pagnotti, V. S.; Inutan, E. D.; Trimpin, S. Anal. Chem. 2010, 82, 9164−9168. (40) Schlunegger, U. P.; Stoeckli, M.; Caprioli, R. M. Rapid Commun. Mass Spectrom. 1999, 13, 1792. (41) Peng, W.-P.; Yang, Y.-C.; Liu, C.-W.; Chang, H.-C. Anal. Chem. 2005, 77, 7084−7089. (42) Nie, Z. X.; Cui, F. P.; Chu, M.-L.; Chen, C.-H.; Chang, H.-C.; Cai, Y. Int. J. Mass Spectrom. 2008, 270, 8−15. (43) Gao, L.; Song, Q. Y.; Noll, R. J.; Duncan, J.; Cooks, R. G.; Ouyang, Z. J. Mass Spectrom. 2007, 42, 675−680. (44) Contino, N. C.; Pierson, E. E.; Keifer, D. Z.; Jarrold, M. F. J. Am. Soc. Mass Spectrom. 2013, 24, 101−108. (45) Choi, M. C.; Lee, J. M.; Lee, S. G.; Choi, S. H.; Choi, Y. S.; Lee, K. J.; Kim, S. Y.; Kim, H. S.; Stahl, S. Anal. Chem. 2012, 84, 10543− 10548. (46) Trauger, S. A.; Junker, T.; Siuzdak, G. Top. Curr. Chem. 2003, 225, 265−282.
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