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Keywords:

  • ambient mass spectrometry;
  • plasma;
  • corona discharge;
  • glow discharge;
  • dielectric barrier discharge;
  • microwave induced discharge

Abstract

  1. Top of page
  2. Abstract
  3. I INTRODUCTION
  4. II PLASMA-BASED TECHNIQUES
  5. III APPLICATIONS OF PLASMA-BASED TECHNIQUES
  6. IV SUMMARY AND OUTLOOK
  7. V ABBREVIATIONS
  8. ACKNOWLEDGEMENTS
  9. REFERENCES
  10. Biographies

Plasma-based ambient mass spectrometry is emerging as a frontier technology for direct analysis of sample that employs low-energy plasma as the ionization reagent. The versatile sources of ambient mass spectrometry (MS) can be classified according to the plasma formation approaches; namely, corona discharge, glow discharge, dielectric barrier discharge, and microwave-induced discharge. These techniques allow pretreatment-free detection of samples, ranging from biological materials (e.g., flies, bacteria, plants, tissues, peptides, metabolites, and lipids) to pharmaceuticals, food-stuffs, polymers, chemical warfare reagents, and daily-use chemicals. In most cases, plasma-based ambient MS performs well as a qualitative tool and as an analyzer for semi-quantitation. Herein, we provide an overview of the key concepts, mechanisms, and applications of plasma-based ambient MS techniques, and discuss the challenges and outlook. © 2013 Wiley Periodicals, Inc. Mass Spec Rev 34: 449–473, 2015.

I INTRODUCTION

  1. Top of page
  2. Abstract
  3. I INTRODUCTION
  4. II PLASMA-BASED TECHNIQUES
  5. III APPLICATIONS OF PLASMA-BASED TECHNIQUES
  6. IV SUMMARY AND OUTLOOK
  7. V ABBREVIATIONS
  8. ACKNOWLEDGEMENTS
  9. REFERENCES
  10. Biographies

Mass spectrometry is one of the primary research tools in analytical science, and is recognized as a useful tool for sensitive and specific trace identification of chemical compounds. For practical purposes, traditional chromatography-coupled techniques, such as GC/MS and LC/MS, might be brought to bear on the problem that draws the GC/LC run-off into the mass spectrometer. However, the techniques above have limits to detect complex compounds because the complicated sample pretreatments and severe vacuum need. Because electrospray ionization (ESI) was introduced to merge sample ionization and introduction to the high vacuum environment required for MS detection (Whitehouse et al., 1985; Fenn et al., 1990), the so-called atmospheric pressure ionization (API) techniques have boomed over the past two decades. The ESI source nebulizes the solution that flows from the capillary tube to create a fine spray of charged droplets under conditions where solvent evaporation occurs when the droplets traverse the atmospheric interface to introduce molecular ions into the vacuum system. Atmospheric pressure matrix-assisted laser desorption ionization (AP-MALDI) (Laiko, Baldwin, & Burlingame, 2000a; Laiko, Moyer, & Cotter, 2000b), first reported in 2000, is now among the most-common commercially available API sources. AP-MALDI enables a condensed-phase sample to be examined under atmospheric pressure conditions. Other API sources, such as atmospheric pressure chemical ionization (APCI) (Lane, 1982) and atmospheric pressure photoionization (APPI) (Robb, Covey, & Bruins, 2000), employ corona discharge or illumination, respectively, to ionize sample and transfer the ionized species into the analyzer. Whereas traditional API sources have decreased detection time by a large margin compared with chromatograph-coupled MS techniques, extensive sample-preparation steps, where the sample is dissolved in or coated with a specially selected matrix that is amenable to the analytical system, are still required. The problem was not solved until Cooks reported desorption electrospray ionization (DESI) for the first time in 2004 (Takats et al., 2004), and soon in 2005, Cody et al. introduced another ambient MS source named direct analysis in real time (DART) (Cody et al., 2005). Then, the 8-year period has attracted considerable attention to develop various types of ambient ionization/desorption sources for MS analysis (Venter, Nefliu, & Cooks, 2008; Ifa et al., 2010; Weston, 2010; Harris, Galhena, & Fernández, 2011). These new ambient MS techniques have simplified the mass spectrometric analytical procedure, and bridged the gap between the ambient environment of samples and the vacuum condition inside the mass spectrometer, thus to enhance the analytical efficiency.

A Ambient Mass Spectrometry

Ambient mass spectrometry is defined as mass spectrometric analysis without any sample preparation step, to allow direct sampling and ionization of sample at ambient environment (Venter et al., 2008). Noting that ambient ionization is different from API in several ways: (a) Ambient ionization should enable sample ionization (and even desorption) in ambient environment without any enclosure, whereas in API samples are ionized under atmospheric pressure state in enclosed cabins. (b) Ambient MS allows the sample of interest to be ionized without any sample-preparation steps, apart from some cases that need internal standards for quantitative analysis or other challenging applications, such as analysis of pesticides with FAPA (Jecklin et al., 2008), DART and DESI (Schurek et al., 2008), etc. (c) Ambient MS techniques enable high-throughput analysis where sample is placed directly between the ionization source and MS inlet to ignore the sample's state, and to reduce total analysis time <5 s (Ifa et al., 2010). (d) Ambient ionization/desorption sources are placed inline or incline with the MS inlet, whereas any linked unit is absent; thus, they are interfaceable to most types of mass spectrometers by simply demounting the original API sources. Although the boundary between API and ambient MS is getting fussy with the development of technology, the four tips above are still obvious when it comes to the most common techniques.

Ambient MS sources continue to be reported by substantial numbers of research papers, so that it is necessary to summarize the works regularly. Herein, we make a list of the ambient MS sources from the year 2004 to now in Table 1. When considering the different sources, it is very confusing to note that some techniques are named quite disparate even though their characteristics are similar. Examples lie in techniques with name changed from desorption sonic spray ionization (DeSSI) (Haddad, Sparrapan, & Eberlin, 2006) to easy ambient sonic spray ionization (EASI) (Haddad et al., 2008); surface-sampling probe (SSP) (Ford & Van Berkel, 2004) to sealing surface sampling probe (SSSP) (Luftmann, 2004); helium atmospheric pressure glow-discharge ionization (HAPGDI) (Andrade et al., 2006) to flowing atmospheric-pressure afterglow (FAPA) (Schilling et al., 2010); and low-temperature plasma (LTP) (Harper et al., 2008) to plasma pencil atmospheric mass spectrometry (PPAMS) (Stein et al., 2012). As suggested in previous reviews, researchers tried to categorize the ambient desorption ionization sources in several ways: (a) according to the ionization/post-ionization method (Venter, Nefliu, & Cooks, 2008; Chen et al., 2009a), and (b) how the facilities are organized; for example, spray and solid–liquid extraction-based techniques, plasma-based techniques, laser desorption/ablation techniques, acoustic desorption methods, etc. (Harris, Galhena, & Fernández, 2011). (c) Based upon the proposed desorption mechanisms that comprised principally thermal desorption, laser desorption and momentum desorption (Van Berkel et al., 2008b) (d) distinguish the excitation procedure of analytes (Huang et al., 2011b). It would seem that separating sources by the desorption steps is difficult, because thermal desorption and momentum desorption are involved in almost all sources, and in some cases the desorption step cannot be clearly separated from the ionization progress, like those in DBDI, LTP, DESI, EASI, etc. However, if we take desorption mechanisms into consideration to classify different sources might also help. Here, we present the summary obeying the first way because it is clearer when talking about the plasma-base techniques. In this way, the ambient MS sources are divided mainly into four parts, where the spray-based techniques and the plasma-based techniques dominate.

Table 1. List of ambient MS techniquesThumbnail image of

B Spray-Based Ambient MS Techniques

What is common in ESI-related techniques is that analyte molecules are transported into the mass spectrometer in the form of evaporating charged solvent droplets after first desorption from the sample surface. In the case of DESI, a fine spray of charged droplets created by an electrospray emitter is directed at the sample surface, where it delivers the secondary droplets into the MS inlet after a droplet pick-up process. The droplet pick-up process involves an interaction, where the impacting solvent droplet contacts with the wet sample surface to cause ejection of secondary solvent droplets that contain the dissolved analyte. For a root outline of the other spray-based sources, see Table 1. These techniques access compounds with masses as high as 66 kDa (Takáts, Wiseman, & Cooks, 2005; Shin et al., 2007; Ifa et al., 2008), and aim mainly at biochemical applications such as proteomics (Myung et al., 2006; Shin et al., 2007), metabonomics (Chen et al., 2007a; Wiseman et al., 2010), bioimaging (Girod et al., 2010).

C Plasma-Based Ambient MS Techniques

Looking around the ambient MS-correlated publications for the past few years, plasma-based sources are “hot.” By now, there have been DART (Cody et al., 2005), ASAP (McEwen, McKay, & Larsen, 2005), DAPCI (Takats et al., 2005), HAPGDI (Andrade et al., 2006), or FAPA (Andrade et al., 2008a, 2008b), DBDI (Na et al., 2007b), PADI (Ratcliffe et al., 2007), DAPPI (Haapala et al., 2007), SACI (Crotti & Traldi, 2009), LTP/PPAMS (Harper et al., 2008), DCBI (Li et al., 2010), microhollow cathode discharge microplasma (Symonds et al., 2010), MFGDP (Ding et al., 2013), and MIPI (Zhan et al., 2013). Figure 1 summarizes the number of publications related to plasma-based sources and total ambient MS sources respectively from 2004 to 2013, and shows the rapid development of plasma-based sources with the ambient ion sources booming.

image

Figure 1. The number of publications related to plasma-based sources and total ambient MS sources respectively from 2004 to 2012. The data were calculated according to the SciFinder. Publication number of the plasma-based ambient MS was the sum total of nine plasma-based sources with the search keys to be “direct analysis in real time,” “atmospheric solid analysis probe,” etc., respectively, while the search key for ambient MS was “ambient mass spectrometry.”

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Quite different from spray techniques, plasma-based sources employ various modes of electro-discharge instead of charged droplets to generate plasma gas that contains radicals, excited/metastable state atoms, and electrons. The carrier gas is often helium or argon. In most cases, the plasma gas is directed towards the samples, with optional secondary heating of the plasma gas stream to enhance desorption (Shelley et al., 2009). It is proposed that chemical and chemi-ionization are both involved in the ionization process. More details about the mechanisms will be discussed in the following paragraphs.

In comparison with spray-based sources, because plasma-based sources ionize samples in a softer way, their mass spectra are dominated by [M+H]+ in the positive mode and [M−H] in the negative mode with few multi-charged, fragmented, or alkali-metal adducted ions. At the same time, on this basis, previous studies (Andrade et al., 2008a; Wang et al., 2012a) suggest that the plasma-based sources do apply to molecules of weak or moderate polarity, whereas the effective mass range from several hundred Dalton to ca, 1 kDa. However, a study that combined DESI and DART, termed desorption electrospray/metastable-induced ionization (DEMI) (Nyadong, Galhena, & Fernández, 2009), has largely broadened the mass range of analytes.

As to the applications, plasma-based sources have played an important role in various fields, including biochemical analysis, mass spectrometry imaging, forensics and chemical warfare reagents, food safety, environmental monitoring, controlled substances, and pharmaceutical diagnosis.

Described here is a summary of the implementation, characterization, application, and current trends of plasma-based ambient MS ionization/desorption sources. The plasma-based techniques are classified according to their discharge types and an overview of each type and the plasma-participated mechanisms will be followed by a more-detailed description of each technique, with emphasis on the implementation and some new developments. The third section will deal with diverse applications of the plasma-based techniques. Finally, challenges, outlook, and the summary are discussed.

II PLASMA-BASED TECHNIQUES

  1. Top of page
  2. Abstract
  3. I INTRODUCTION
  4. II PLASMA-BASED TECHNIQUES
  5. III APPLICATIONS OF PLASMA-BASED TECHNIQUES
  6. IV SUMMARY AND OUTLOOK
  7. V ABBREVIATIONS
  8. ACKNOWLEDGEMENTS
  9. REFERENCES
  10. Biographies

As shown in the title, this section focuses on flourishing plasma-based ambient MS sources. These techniques have the common characteristics that plasma is involved, either in the ionization step or the desorption step, and sometimes even in both. In general, the main differences of various plasma-based MS sources lay in the way how the working gas is discharged and what kind of reaction reagent ions are involved in ionization/desorption. The conditions under which discharge is performed have been an issue because diverse current–voltage curves (I–V) might cause changes of the discharge properties, which will lead to variation of instrumentation and ionization/desorption mechanisms. For a better comprehension of different kinds of plasma-based techniques, an overview of their basic principles and key ionization/desorption progress is described in Table 2, and in the following paragraphs, the various sources would be discussed in an order of the discharge form according to the table.

Table 2. Plasma-based ambient MS methodsThumbnail image of
  •  aDART and FAPA could also be operated in glow discharge mode.

  •  bNA means that data are not announced in recent studies.

  • A Corona Discharge-Based Techniques

    Corona discharge employs a common two-electrodes configuration, where the cathode is in the form of a wire (Raizer, 1997). As a high negative voltage is applied to the wire cathode at atmospheric pressure, the uneven electric field constrains the main ionization process to an area around the cathode where a lighting crown appears. During the discharge, the positive ions are accelerated towards the cathode to cause secondary electron emission, and the electrons will form a high-energy stream which moves into the plasma and give rise to inelastic collisions with the heavy particles. Hence reactant species can be formed via ionization, excitation, and dissociation (Bogaerts et al., 2002). For corona discharge-based ambient sources, such as DART, DAPCI, DSA, and DCBI, plasma is generated in the discharge chamber and would impact the sample surface after ejection from the chamber, whereas for ASAP, the analytes desorbed through the collision with hot gas undergo a corona discharge in the enclosed APCI cabinet.

    As the analyte molecules are desorbed via thermal and momentum mechanisms, the ionization process is induced through interact between the reactive species and the analytes. The reactive species of the plasma gas are mainly highly excited nitrogen for N2 plasma or metastable helium atoms (He*) for helium plasma gas. He* is believed to induce Penning Ionization of ambient molecules (Andrade et al., 2008a) and the analytes (M) (Cody, Laramée, & Durst, 2005):

    • display math

    In the positive-ion mode, water clusters generated via ion-molecule reactions and Penning Ionization are the main impurities in the mass spectrogram, where the most abundant species is H5O2+ (Shelley et al., 2009). Such clusters serve as proton donors and can protonate analyte molecules that have a higher proton affinity (Nicol, Sunner, & Kebarle, 1988):

    • display math

    In the negative-ion mode, O2 ions are presumed to serve as the active reaction agent. Supported by Dzidic et al. (1975), O2 is a strong base that enables proton abstraction for a wide array of compounds to form [M−H]. Another main products, M, is supposed to be formed through a reaction cascade as below:

    • display math

    The reactions of oxygen/water cluster ions dominant the negative-ion formation mechanisms (Cody, Laramée, & Durst, 2005). However, inferring from the highly similar products of DART and APPI (Song et al., 2009), one can conclude that some other mechanisms of ion formation also have function: electron capture, electron capture dissociation, deprotonation, and anion attachment. In summary, discussed above are the fundamental mechanisms of the corona discharge-based sources. Moreover, the instrumentation and characteristic about each of these techniques are commented in further detail below.

    1 Direct Analysis in Real Time

    Direct analysis in real time (DART) is placed in front of other techniques because it is the first and the only currently commercially available plasma-based ambient MS source. DART relies on a corona-to-glow transitional discharge to produce a plasma (Shelley et al., 2009). What is different from other plasma-based techniques is that the ionic species generated in the plasma source are selectively removed by a grid electrode to prevent ion-ion combination. Over the past several years, attention has been given to the hot topics of fundamental studies on reaction mechanisms.

    In a basic DART source, a gas flow, typically helium or nitrogen, enters a tube divided into three segments (Fig. 2). The gas first flows through a chamber, where a corona discharge is generated between a needle electrode and a first perforated-plate electrode. Carrying ions, electrons, and excited-state species, the plasma gas can be manipulated with a second perforated electrode to remove ions unwanted in the stream. In the third section, the gas stream is heated and subsequently passes through a final grid electrode, which repels ions and removes oppositely charged species. After ejection from the source, the ionizing neutral gas can either be directed towards the mass spectrometer orifice, or impact the sample surface at an angle suitable to reflect desorbing ions into the MS inlet. In general, the sample is inserted between the source outlet and the orifice gap of 5–25 mm; however, this condition is not critical because ions can be observed with this source as far away as 1 m from the mass spectrometer. Typically, the needle electrode is added with a positive potential of 1–5 kV, and the counter electrode (first perforated disk electrode) is grounded. The potential set to the second perforated electrode and the grid electrode is in accordance with the polarity of the detective ionic species. Typical values of the two electrodes are ±100 and ±250 V, respectively; however, a study suggested that the values could be set to zero (Kratzer, Mester, & Sturgeon, 2011). The source employs an insulator cap at the transmitting terminal of the tube to protect sample and the MS orifice from any high-voltage damage. The stream flow rate is adjusted to ca, 1 L min−1 and the gas temperature might be heated selectively from room temperature up to 250°C (Cody et al., 2005).

    image

    Figure 2. Schematic of the DART source. Reprinted with permission from Cody, Laramée, and Durst (2005), copyright 2005 [American Chemical Society].

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    The corona discharge operated with He or N2 produces electronically excited (metastable) species that contain excited/metastable atoms, ions, and electrons. The heated plasma gas passes through the heating chamber with the unwanted ions repelled with a grid electrode before ejection to the outside. Only neutral species are allowed out of the source. When hitting the sample surface, analyte molecules are desorbed via thermal mechanisms and the collision with plasma stream just as has been talked about above.

    2 Atmospheric Pressure Solid Analysis Probe, Desorption Atmospheric Pressure Chemical Ionization, and Axion Direct Sample Analysis

    Described in this section, are three ambient MS sources that are performed by simple modification of a conventional APCI/ESI ion source (Fig. 3): the atmospheric pressure solid analysis probe (ASAP), desorption atmospheric pressure chemical ionization (DAPCI), and the Perkin Elmer AxION direct sample analysis source (DSA). ASAP was first introduced by McEwen, McKay, and Larsen (2005) and McEwen and Gutteridge (2007) with a modification to allow insertion of a borosilicate capillary melting-point tube into the enclosed APCI cabinet. (Semi)Volatile solid or liquid samples dipped at the top end of the glass tube are thus rapidly thermally desorbed by the hot gas (or droplet stream) from the heated nebulizer. The following ionization is performed with a high-voltage corona discharge, similar to APCI. ASAP shows primary advantage over DESI and DART by the ability to be used in conjunction with any commercial atmospheric pressure mass spectrometry (McEwen, McKay, & Larsen, 2005). Research that compared the performance of ESI, APCI, and ASAP on detection of standard drug compounds revealed that ASAP is available to ionize both polar and nonpolar compounds (Petucci & Diffendal, 2008), and is the source of all others for medium polarity compounds with a mass range below 1,000 Da (McEwen, McKay, & Larsen, 2005). It is highly interesting that a combination of ASAP and DESI that used the complementary nature as well as the ease of conversion of both techniques has successfully broadened the selective range of analytes, neglecting their polarity and volatility (Lloyd, Harron, & McEwen, 2009).

    image

    Figure 3. Schematic of (A) ASAP ion source, reprinted with permission from Petucci and Diffendal (2008), copyright 2008 [Wiley] and (B) DAPCI, reprinted with permission from Song and Cooks (2006), copyright 2006 [Wiley], (C) the Direct Sample Analysis source.

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    DAPCI is defined by Cooks' group with the initial configuration implemented by replacement of the DESI source with an APCI-like corona discharge (Takats et al., 2005). It is similar to ASAP in most parts, but gaseous reagent ions generated with atmospheric pressure corona discharge directly impact the solid sample to result in desorption and APCI-resembled ionization. The ionization mechanisms are established to be similar to other APCI sources, whereas presently there are no results that we are well aware of the desorption mechanisms. It is believed that thermal desorption dominates when the sheath gas is heated (Williams et al., 2006; Van Berkel et al., 2008b); however, ion impacts and static-charge buildup occur when heat is absent (Chen et al., 2007b). DAPCI is much more sensitive for analytes of moderate polarity due to its close relationship with APCI, as supported by the detection of pharmaceuticals compared with DESI (Williams & Scrivens, 2005). The analysis performance of solventless DAPCI shows no obvious difference with ASAP; however, DAPCI with solvent is suggested to be more effective than DESI and DART in the case of common drugs and samples of biological origin (Williams et al., 2006).

    The Perkin Elmer AxION direct sample analysis (DSA) system, exhibited in the 61st ASMS Conference (Anon, 2013), is a commercial ambient technique based on APCI. This novel ion source is consisted of a removable sealed cover, which enables enclosed system to prevent background laboratory contamination, a sample holding system, and a reagent ion generator. As the core component of DSA, the reagent ion generator employs a patented field-free APCI-like design where the corona pin is embedded inside the spray needle (see Fig. 3C), and sits directly in the path of heat nitrogen gas, thus all the neutral reagent molecules can be ionized inside the probe, to provide true molecular ions instead of metastale ions. After ejected from the probe, the reagent ions directly impact the sample surface to create a rich stream of analyte ions that is drawn into the MS detector. Compared with conventional APCI source, the sensitivity of DSA is five times higher. Samples with little or no pretreatment can be detected horizontally under the downward-facing nozzle (for solutions) or vertically between the horizontal nozzle and the MS inlet.

    Based on ESI/APCI-like characteristics, ASAP and DAPCI have proven to be suitable for detection of various analytes not possible with ESI and APCI-MS. Such applications include explosives and other chemical-warfare reagents (Takats et al., 2005; Chen et al., 2007b), agrochemicals (Chen et al., 2007b), agricultural products (Huang et al., 2011a), biological tissues (Wu et al., 2009), pharmaceuticals (Petucci & Diffendal, 2008), metabolites and consumed chemicals (Chen et al., 2007b), foodstuffs (Yang et al., 2009a; Pi et al., 2011), polymers (Trimpin, Wijerathne, & McEwen, 2009), etc. As to DSA, detection of gas, solid, powder, tablets, liquids, and samples on the surface of notes have been shown, moreover, this commercial source is supposed to have potential applications in the fields of tobacco, food safety, medicine, forensic medicine, and disease screening.

    3 Desorption Corona-Beam Ionization

    Desorption corona-beam ionization (DCBI), shown in Figure 4, is another ambient MS technique that employs corona discharge to induce ionization (Wang et al., 2010). DCBI shares some common features with its close relative, DART; helium is used as the plasma gas, and a heating section is included in the source construction. The differences lie in: (a) plasma generated in the discharge is visible as a pale purple corona beam outside the needle electrode; (b) plasma interacts directly with the sample surface. The visible plasma makes DCBI a source easier for sample alignment than DART, DAPCI, and ASAP. As what is inferred in other plasma-based techniques (McEwen, McKay, & Larsen, 2005; Symonds et al., 2010), the main limit of DCBI is the available molecular mass range <600 Da. This limit could be ascribed to the weak volatility of high-mass analytes when thermal desorption dominates desorption. The relationship between desorption temperature and heater temperature was calculated under two certain flow rates. Results showed that the heat transfer between the heater and the gas was more efficient at lower heater temperature, whereas energy transfer from gas molecules mainly caused sample heated in high temperature (above 150°C). Detection of TNT in the negative-mode exhibited a spectrum of abundant M, [M−H], [M−NO] ions, to indicate that electron capture, dissociative electron capture, and proton transfer are involved in the formation of negative ions. As to positive-ion mode, Penning ionization induced with metastable helium was responsible for formation of M+, whereas proton transfer generated [M+H]+.

    image

    Figure 4. Schematic of DBCI. Reprinted with permission from Wang et al. (2010), copyright 2010 [Royal Society of Chemistry].

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    DCBI ionites solid and liquid samples such as pesticides, explosives, pharmaceuticals, food additives, estrogens, and veterinary additives (Li et al., 2010; Wang et al., 2010, 2012a). By coupling DCBI with PDMS substrates, solid-phase microextraction of pesticides is enabled, so that the analytical performance of this technique was enhanced in the detection limit (μg L−1)and sample detection range (Li et al., 2010). Although quantification analysis of liquid samples is always limited in terms of co-evaporation of sample and matrix, analytically useful results have been obtained with room temperature ionic liquids (RTILS) as matrix instead of water (Wang et al., 2012a). Recently, experiments carried out to detect intermediates of Leuckart reaction with DCBI-MS indicates that this technique has promise in intermediate monitoring in some thermal reactions (Xu et al., 2012). Another promising role of DCBI in further study lies in the area of special analysis due to its visible plasma, which have not been reported for other corona-discharge sources.

    B Glow Discharge-Based Techniques

    Apart from corona discharge, there also exist other ambient sources that generate plasma through glow discharge. In general, glow discharge employs a simple two-electrode configuration where a few hundred volts are applied to the electrodes to cause breakdown of the gas and produce the ions, electrons, and other species that are useful for subsequent ionization (Harrison et al., 1986). The glow-discharge based techniques vary according to the type of power supply, the dimension of discharge space, and the shape of the electrodes. With a dc voltage supplied to a pin-to-plate or pin-to-capillary electrode pairs, we get FAPA; keep the distance between the plate electrodes below 1 mm, MFGDP is obtained; Punch a hole across the cathode and gather the glow into the hole, here is MHCD-microplasma; apply a radio frequency voltage between two electrodes with one of which covered with dielectric materials, a PADI chamber is almost accomplished.

    In contrast of those ambient techniques use corona discharge, the glow-discharge based sources always feature by low voltage (usually a few hundred volts) and high current (up to tens of mA). The low energy of the plasmas allows close contact between the plasma plume and the analytes with few surface injuries. During the contact, momentum desorption is more likely to occur than thermal desorption due to the low plasma temperature except FAPA (Shelley, Chan, & Hieftje, 2012). The ionization mechanisms are quite likely to the APCI-like techniques with Penning ionization, proton transfer, and charge transfer leading in the positive-ion mode, whereas proton abstraction, anion attachment, electron capture dominate the negative mode.

    4 Flowing Atmospheric-Pressure Afterglow

    Flowing atmospheric-pressure afterglow (FAPA) was first reported by Andrade et al. in 2006 with the former name helium atmospheric-pressure glow discharge (HAPGD). Different from DART, this source mainly employs glow discharge to generate the plasma, which induces a direct plasma-sample interaction in close proximity to the source.

    In an early study (Andrade et al., 2008a,2008b), the working gas, generally helium, is passed through a pin-to-plate constructed chamber, where a direct current glow-to-arc discharge is generated. In quantitative and qualitative terms, the original FAPA design exhibited some drawbacks: background levels were high with cluttered background spectra in the negative-ion mode, and significant oxidation of aromatic analytes. The ion-suppression effects also limited detection sensitivity because no predissociation steps are involved in the ambient MS sources. Contrast experiments of FAPA, DART, and LTP (Shelley & Hieftje, 2010b) showed that ionization suppression followed the order FAPA < DART < LTP, whereas the internal-energy deposition was LTP > FAPA > DART. In a recent study, Shelley, Wiley, and Hieftje (2011) presented a variant of the FAPA, which used a pin-to-capillary geometry (Fig. 5). The new configuration successfully reduced background signals in positive- and negative-ionization modes by 89% and 99%, respectively, and improved detection limit to amol level.

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    Figure 5. Schematic of the pin-to-capillary constructed FAPA source. Reprinted with permission from Shelley et al. (2011), copyright 2011 [American Chemical Society].

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    Chemical and chemi-ionization mechanisms are both proposed to occur simultaneously in FAPA. The background spectra dominated by water clusters, O2+, NO+, and N2+ (Shelley et al., 2009) indicated that charge-transfer reactions accompanied with Penning ionization of moisture and N2 could easily occur. As suggested in an optical study (Shelley, Chan, & Hieftje, 2012), helium excimer and similar species, including He*, He2* and He2+, could contribute significantly to reactive-reagent formation and analyte ionization. Rotational temperature of OH and N2+ were determined (Chan et al., 2011; Shelley, Chan, & Hieftje, 2012), with the former as low as below 500 K and the latter reached a maximum of 860 K. It could be inferred that the higher N2+ temperature is due to charge-transfer ionization of N2+ with He2+. Moreover, it was found that the polarity of the electrodes affects the formation of reactive species, and thus decides the detective sensitivity. Experiments carried out on opposite polarities of the pin exhibits better sensitivity in a pin-negative configuration because the low-energy electrons are abundant at the anode; that factor will promote enough He* and He2+. IR thermography experiments that compared the thermal effects of the corona-to-glow and glow-to-arc discharges showed that the plasma stream in FAPA mode was much hotter than that in the DART mode (∼235°C vs. ∼55°C). The higher thermal effect of FAPA is supposed to yield more-efficient desorption and thus increase detection sensitivity of volatile species. However, similar to what has been postulated in those spray-techs (Takáts, Wiseman, & Cooks, 2004, 2005; Haddad, Sparrapan, & Eberlin, 2006), reactive desorption through water clusters and other ionic species might play a more-important role in desorption of solid samples (Andrade et al., 2008b).

    5 Plasma-Assisted Desorption/Ionization

    Developed in 2007, plasma-assisted desorption/ionization (PADI) (Ratcliffe et al., 2007) created nonthermal plasma in helium gas by applying a radio frequency voltage between two electrodes with one of which was covered with dielectric materials (see Fig. 6). Plasma ejected from the source is directed to the sample surface and could be seen in the form of a plasma plume so that it can aim the stream at the analytes. In contrast to DART and the corona discharge sources, PADI employs a nonthermal atmospheric glow discharge characterized by lower operating voltage and higher discharge current. The total power applied is less than 5 W, which leads to a plasma temperature close to that of the ambient environment; however, the accurate value is not determined yet. PADI enables the plasma to interact with thermal unstable substances directly because the flow does not heat the sample as in FAPA and there is no extra heating setup.

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    Figure 6. Schematic of the PADI source. Reprinted with permission from Ratcliffe et al. (2007), copyright 2007 [American Chemical Society].

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    Studies that contrast analytical performances of PADI and DESI (Ratcliffe et al., 2007; Salter et al., 2011) show some main differences between the two sources: (a) DESI utilizes an electrospray for the ionization/desorption of analytes, whereas PADI employs nonthermal glow discharge plasma gas for these processes. (b) Several operational parameters related to the DESI source should be optimized for effective detection, including the high voltage applied to the ESI, solvent flow rate, distances to the MS inlet, and the angles between the sample (Takats et al., 2005). However, PADI is less angle-dependent with the main care on the input power. (c) In terms of morphological damage, DESI is gentler than PADI because PADI damaged the analyte surface after a few seconds, whereas DESI produced negligible damage. (d) Although the two sources generated similar data on a comparable time scale, PADI spectra could display less fragmentation and higher signal intensity than DESI. Ratcliffe et al. (2007) supposed that PADI is potentially a softer ionization technique for some analytes like paracetamol and anadin extra, however, DESI could produce simpler spectra when it goes to some personal care products (Salter et al., 2011).

    Ionization mechanisms in the positive-ion mode are similar to those in DART and FAPA (Chan et al., 2011). A combination of direct electron impact ionization, metastable helium-induced Penning ionization, and charge transfer is suggested to contribute to M+, [M+H]+, and water clusters in the spectra. The negative-ionization process is in agreement with that of the other APCI-related techniques (Ratcliffe et al., 2007; McEwen & Larsen, 2009; Song et al., 2009). [M−H] ions are produced through proton abstraction with reactive reagent such as O2. Other negative species are not yet fully stated in the literature. As to desorption, it is believed that mechanisms that include energy transfer from He*, ion impact, and radical-surface interactions play a part. Further research into the detailed ionization/desorption process is required.

    6 Microplasma-Based Ionization Source

    Although corona discharge, glow discharge, and dielectric barrier discharge have been largely applied to various ambient MS sources, the issue of so-called microplasma is not so well-exploited in this field, despite its prominence in spectrographic analysis and surface treatment (Foest, Schmidt, & Becker, 2006; Miclea & Franzke, 2007; Becker et al., 2010). Microplasma owns a size where at least one dimension is 1 mm. The feature that it is stable in high pressure and its low temperature (around 300 K) (Foest, Schmidt, & Becker, 2006) makes it promising in the design of mass spectrum ion source (Brede et al., 1998; Vautz, Michels, & Franzke, 2008). However, it was not until 2010 that Symonds et al. demonstrated the first use of a microplasma-based ambient ionization MS source (Symonds et al., 2010). This device used a microhollow cathode discharge (MHCD) configuration, where plasma is generated in a cavity that employed a Si–SiO2–Al layered structure (Fig. 7). Ultrahigh purity helium was the plasma gas at a flow rate of 0.28 L min−1. The negative DC potential applied to the Al electrode was held constant between −300 and −350 V, and the current was typically maintained at ∼30 μA. The plasma source was held ∼1 cm away from the MS inlet to allow the plasma stream to directly hit the sample, which was placed ∼1 to 5 mm from the inlet. This novel source was effective in detection of gas, liquid, and solid samples with a MW below 500 Da. Four possible plasma processes occur in the positive-mode ionization step that consisted of proton transfer from water clusters, electron-impact ionization, photoionization, and Penning ionization induced by metastable helium. Among the four mechanisms, proton transfer was believed to dominate, with H3O+ the main protonated reagent. According to the abundant [M−H] and [M−C2H2O] ions in the negative-mode spectrum of acetylsalicylic acid, the negative-mode ionization mechanism seemed mainly to be proton abstraction. In terms of desorption, thermal desorption was not so effective because of the nonthermal characteristic of microplasma. Although the desorption mechanism was not well-studied in that report, it was considered that momentum desorption played a role.

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    Figure 7. Schematic of the microplasma ion source: (a) spatial arrangement of the inlet capillary with respect to the ion source, (b) cross-sectional schematic of the microplasma chip, (c) photograph of continous discharge observed within the discharge cavity. Reprinted with permission from (Symonds et al., 2010), copyright 2009 [American Chemical Society].

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    Recently, a newly designed microplasma-based ion source for ambient mass spectrometry, called micro-fabricated glow discharge plasma (MFGDP) (Ding et al., 2013), has been developed. This novel device has a simple configuration, where two platinum electrodes are set face to face in an alumina ceramic-constructed discharge chamber. The cross-sectional area of the carrier gas (Ar) channel is ca. 1 mm2. In the working state, cold Ar/He plasma, with temperature similar to those produced in LTP probe, is generated and maintained by DC micro glow discharge with an average power supply under 4 W. By adjusting the discharge current, the MFGDP source could be applied to compounds with molecular mass that range from tens to below 2,000 Da, mostly in the positive mode. For qualitative analysis, gas, liquids, solid, and complex real samples such as tobacco and OTC tablets, are feasible. For quantitative analysis, detection limits of solution and dry dots are calculated to be in the level of nM and fg mm−2, respectively. The mechanisms of ionization and desorption are still under research; the authors suggest that Penning ionization, proton-transfer reaction, and momentum desorption play a role.

    The microplasma-based ambient ionization MS source exhibits distinct advantages and disadvantages over other ambient sources in that it could be operated under very low power supply (<4 W) whereas electrode sputter cannot be avoided. Former studies have showed promising role of microplasma in the development of portable analytical instrument (Eijkel, Stoeri, & Manz, 2000; Jin, Su, & Duan, 2000) and there are also other ambient sources reported to be successfully assembled to pint-sized mass spectrometer (Mulligan, Talaty, & Cooks, 2006; Soparawalla et al., 2011; Dalgleish et al., 2012). We suggest that further consideration of the microplasma-based source be considered for the design of a new-type microplasma ionization source that could effectively neglect the electrode contamination and are possible in combination with portable mass spectrometer.

    C Dielectric Barrier Discharge-Based Techniques

    Dielectric barrier discharge (DBD) is a kind of gas electrical discharge with a dielectric inserted into the discharge space. The operation of the DBDs demands an ac voltage because the insulating dielectric cannot pass a dc current (Kogelschatz, 2003). In order to transport current in the discharge gap the power has to be high enough to cause the gas breakdown so that an amplitude of 1–100 kV and a frequency of a few Hz to MHz (Bogaerts et al., 2002) is always required. DBDs are different from APGDs that the former generate a heterogeneous breakdown where a large number of microdischarges exist, whereas the APGDs are generally homogeneous (Kogelschatz, Eliasson, & Egli, 1999). The microdischarges, observed as numerous fast pulse current filaments that live a lifetime of <10 sec, form the discharge current with a electric current density as large as 0.1–1 kA/cm2. Because microdischarge causes an ambient gas temperature up to <300 K, the plasma is characterized by low temperature.

    First used to generate ozone, various applications of the DBDs have been reported in atomic/molecular emission spectroscopy, excimer UV lamps, and other optical fields (Kogelschatz, 2003; Franzke, 2009). In the mean time, further combinations of DBD and the ambient MS have also been developed. By now, there are mainly two types of ambient MS sources based on DBD, namely, DBDI and LTP.

    Zhang et al. published an interesting series of papers that delineated new applications of DBD as an ambient MS source, named dielectric barrier discharge ionization (DBDI) (Na et al., 2007a,2007b). The initial research of DBDI employed a pin-to-plane configuration (see Fig. 8A), where a glass slide is inserted between the electrodes to function as the dielectric material and object stage. Helium or argon flows through the hollow needle, and an alternating voltage (20.3 kHz, up to 4.5 kVp-p) is applied between the two electrodes to form a stable plasma through the discharge space. The analytes on the glass slide surface are, therefore, desorbed and ionized with the plasma. In the low-temperature plasma (LTP) probe (Harper et al., 2008), regarded as a variant of DBDI, a glass tube serves as the electric material to separate the outer copper tape electrode and the internal grounded electrode (Fig. 8B). He, Ar, N2, or air could serve as the discharge gas to flow through the glass tube, and to transport the plasma torch (visible in He and Ar) directly in contact with the sample. LTP generally operates at a temperature as low as 30°C, whereas a modestly elevated temperature could enhance the signal to analyze trace compounds in complex matrices (Huang, Ouyang, & Cooks, 2009). LTP has some key advantages over other ambient techniques in that it has access to analytes of any surface with no thermal or other damage to the sample (Wiley et al., 2010), along with the ability of fragmentation control through the relative location of electrodes (Harper et al., 2008). A new version of the DBD-type source published recently is the so-called plasma pencil atmospheric mass spectrometry (PPAMS) (Stein et al., 2012). It is actually a LTP-similar source to desorb and ionize species from liquid or solid samples. Advice is that categorizing the LTP probe and PPAMS into one class.

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    Figure 8. Schematic of (A) the DBDI source, reprinted with permission from Na et al. (2007a), copyright 2007 [Wiley] and (B) the LTP source, reprinted with permission from Harper et al. (2008), copyright 2008 [American Chemical Society].

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    DBDI and LTP share some main features in ionization and desorption mechanisms. The positive-ion mode generally produces [M+H]+ and M+, whereas the negative-ion mode mainly generates [M−H] and M. However, to detect explosives such as TNT, RDX, and PETN (Na et al., 2007a; Zhang et al., 2009), it was found that [M−NO], [M−NO2], [M+NO3], and [M+NO2] dominate the spectra. There has been a common acknowledgement that Penning ionization of ambient nitrogen by He* is the major mechanism to generate N2+ (Andrade et al., 2008a; Schilling et al., 2009), which is suggested to be a key intermediate for the ionization step. Study by Chan et al. (2011) summarized the reaction mechanisms responsible for ionic species formation in the LTP afterglow, and emphasized formation of N2+ through charge transfer from He2+ to N2. Although the competitive relationship between Penning ionization and charge transfer is not yet clearly stated, the minimum contribution of charge transfer from He2+is determined to be 30%. In the desorption process, a thermal-desorption mechanism is essential, as supported by the increasing signal with heat (Van Berkel et al., 2008b; Wiley et al., 2010).

    LTP/DBDI-MS has been applied to several fields; for example, explosives (Na et al., 2007a; Zhang et al., 2009; Garcia-Reyes et al., 2010), agrochemical residues (Wiley et al., 2010; Soparawalla et al., 2011), pharmaceuticals and controlled substances (Jackson et al., 2010; Kratzer, Mester, & Sturgeon, 2011), biochemicals (Zhang et al., 2011a; Zhang, Tao, & Cooks, 2011b), and daily used chemicals (Salter et al., 2011). The unique characteristics of LTP that it can work well with air and be suitable for any sample surface make the novel technique promising in portable instrument development (Soparawalla et al., 2011; Dalgleish et al., 2012). There is still space for further study that differentiates the ionization/desorption processes between the two techniques.

    D Microwave-Induced Plasma-Based Techniques

    Developed in the mid-1950s, microwave-induced plasma (MIP) has been designed into several configurations, including the TM 010 resonator introduced by Beenakker (1976), TE 101 resonant structure according to Matusiewicz (1992), surface-wave propagation, so-called Surfatron, described by Hubert, Moisan, and Ricard (1979), Selby and Hieftje in succession (Mark Selby, 1987), and microwave plasma torch (Perez et al., 2010) described by Jin et al. (1991).

    Initial results on the use of MIP have been presented for optical emission & absorption spectrometry (Foest, Schmidt, & Becker, 2006; Jin, Duan, & Olivares, 1997; Jankowski, 2001) and inorganic mass spectrometry (Su, Duan, & Jin, 2000) where it serves as the excitation source or ionization source, respectively. However, here in our group, we first employ MIP as an ambient MS source, namely microwave-induced plasma desorption ionization (MIPDI; Zhan et al., 2013). The MIPDI source is constructed in a Surfatron structure, where non-equilibrium microwave-induced argon or helium plasma is generated at a microwave frequency of 2,450 MHz. Analytes deposited on the surface of poly(tetrafluoroethylene) (PTFE) or quartz slide after HF etching are suggested to be ionized through a proton transfer and charge transfer reaction, and thermally desorbed by the relatively high plasma temperature. The mass spectra show protonated or deprotonated molecule ions of [M+H]+ or [M−H] as well as their adduct ion species in the positive- or negative-ion modes. To be distinguished from other plasma-based MS source, the MIPDI-MS could manage polymer (e.g., PEG 800) analysis with a mw up to 1,000 Da. It is capable of determining solid, liquid, gaseous sample in pg range including both pure chemicals and complex real samples such as over-the-counter drugs. Mass spectra compared with those obtained with ESI source are approximately the same, except for the more-abundant fragment species peaks exhibited in the MIPDI spectra. Furthermore, the simple construction, reduced gas flow rate, and ability to sustain plasmas with alternative gases for high efficiency to desorb and ionize analytes directly from samples surface in their ambient environment make MIPDI a promising ionization source for ambient mass spectrometry.

    In another paper that combines MIP with ambient MS (Zhang et al., 2013), a dual-flow design was introduced for better modify the plasma jet shape. Different from other plasma-based techniques, the background of the Ar-induced MPT is dominated by NH4+, (H2O)NH4+, and (H2O)2NH4+ instead of (H2O)nH+. It is found that the drying gas (nitrogen) from the mass spectrometer plays an important role in the formation of [M+NH4]+ and [M+H]+. The MPT-MS was used to obtain full-scan mass spectra of OTC medicines, to directly detect the allicin in garlic, and to monitor nicotine in exhaled breath after smoking. The microwave-induced plasma-based techniques share the main advantages of easy optimization, solvent-free, and no pretreatment with other plasma-based techniques. However, extra work on the design of the microwave chamber is demanded to prevent the operators from any microwave radiation injury.

    III APPLICATIONS OF PLASMA-BASED TECHNIQUES

    1. Top of page
    2. Abstract
    3. I INTRODUCTION
    4. II PLASMA-BASED TECHNIQUES
    5. III APPLICATIONS OF PLASMA-BASED TECHNIQUES
    6. IV SUMMARY AND OUTLOOK
    7. V ABBREVIATIONS
    8. ACKNOWLEDGEMENTS
    9. REFERENCES
    10. Biographies

    Plasma-based ambient ionization/desorption mass spectrometry has been very popular in analytical science and evolved as an effective analytical method for biochemical, pharmaceutical, forensics, and modern life chemistry. A substantial numbers of research papers focus on the use of ambient MS techniques (Weston, 2010; Harris, Galhena, & Fernández, 2011; Nemes & Vertes, 2012), and reports about applications of these techniques continue to grow. It is difficult to make a full-scale summary of the diverse applications; hence, here we just present below some of the most common fields in recent years. What should be pointed out is that some of subjects overlap. The major application areas of each plasma-based technique are shown in Table 3.

    Table 3. The major application areas of each plasma-based technique*Thumbnail image of
  • *

    This table only summarizes the major application area of the common plasma-based techniques, so that some rare areas and derived techniques might not be mentioned.

  • A Bioanalysis

    Although mass spectrometry continues to have an important role in the study of biological analysis, plasma-based ambient MS techniques, with their high sensitivity and simple operation, are used effectively in the field of metabolomics, proteomics, and biological tissue analysis.

    For metabolite analysis, urine and serum are two mostly used matrixes. The use of plasma-based ambient MS methods for drug metabolite analysis in urine has generated several reports in the literature, including the use of DART to detect ranitidine and its derivants in human urine 5 h after ingestion (Cody, Laramée, & Durst, 2005), detect ibuprofen metabolites with DAPCI (Williams et al., 2006), and investigation of Levaquin from untreated urine of a patient (Lloyd, Harron, & McEwen, 2009) with ASAP. A study used ASAP-MS/MS to detect the β-agonist in porcine urine (Wang et al., 2012b). By combining ASAP with solid-phase extraction procedures for analyte enrichment and matrix-effect suppression, the study reported a detection limit of 13β-agonist below 0.2 ng mL−1 and the R2 value of the calibration curves above 0.98. Zhou, McDonald, and Fernández (2010) managed human serum metabolomic fingerprinting with DART coupled with a time-of-flight (TOF) MS and hybrid quadrupole TOF (Q-TOF) MS. It was found that the detectable mass range and number of metabolites were expanded respectively from around 100 to 1,500 and m/z 100–300 to m/z 100–800 in serum derivatized with MSTFA/TMCS (N-trimethylsilyl-N-methyltrifluoroacetamide/trimethylchlorosilane) reagent mixture compared with that underivatized. The repeatability recorded for the total ion signal was from 4.1% to 4.5%, whereas that recorded for single peak was around 18%. DART-MS combined with solid-phase microextraction was used for blood analysis, where a 5 μL sampling volume of blood spots that contained diazepam was deposited on a PAN-over C18-PAN coating (Mirnaghi & Pawliszyn, 2012). The extracted blood spot-DART-MS was said to clean up the interfering matrix with the linearity correlation of calibration curve increased from 0.9899 up to 0.9987 compared with that with bare mesh, and the LOQ was obtained at 1 μg mL−1.

    The capability of plasma-based ambient mass spectrometry to determinate the biochemicals or metabolic process in a living body or other complex biological samples has been demonstrated by several groups. ASAP has been proven to be effective to monitor the ergosterol pathway of ustilago maydis; the fungus cells added with different inhibitors were directly inserted into the hot nitrogen stream of the source (McEwen & Gutteridge, 2007). Whatever step of the ergosterol pathway was interrupted by the inhibitor could be determined from the corresponding intermediates that dominated the mass spectrum. Watts et al. (2011), who used DART-MS to detect secondary metabolites from fungal hyphae, identified two novel chlorinated metabolites and biosynthesized two new brominated analogues. With use of PCA and LTP-MS, different bacterial species (B. subtilis, S. aureus, E. coli, and Salmonella) and 11 out of 13 Salmonella strains were well-distinguished via the characteristic fatty acid ethyl esters (Zhang et al., 2011a). DAPCI-MS has also been used for biological sample analysis with examples as following two papers: differentiate dry sea cucumber from different geographic areas through direct determination of the sea cucumber slices (Wu et al., 2009); detect sinapine in radish taproot (Huang et al., 2011a). Up to now, the reported techniques, DART, ASAP, DAPCI, and LTP, are limited to small molecules in tissues, body fluids, and low-grade organisms. The challenge remains to develop more ambient MS techniques to determine biological molecules of a wide mass range in multiple biological matrixes.

    As with other application areas of the plasma-based ambient MS techniques, there is still much research not included in this paper; examples lie in the following: structure analysis, where DART were used to obtain the structure information of synthetic cannabinoids (Musah et al., 2012) and peptides (Sanchez et al., 2011), LTP was used to determine the double-bond position in unsaturated fatty acids and esters (Zhang et al., 2011b); polymer analysis, to detect low molecular weight synthetic polymers, poly(ethylene glycol) and poly(styrene) with ASAP (Smith, Cameron, & Mosely, 2012).

    B Ambient Ionization Mass Spectrometry Imaging

    Ambient ionization mass spectrometry imaging (MSI) is a newly developed member of the MSI family that allows direct ionization of natural state samples at atmospheric pressure outside the mass spectrometer. Confined by the fundamental nature of ambient ionization source, ambient ionization MSI is limited to a mw <2,000 Da with a spatial resolution that ranges from tens to hundreds microns (Sampson & Muddiman, 2009; Girod et al., 2010; Nemes & Vertes, 2012). As for plasma-based techniques, the large plasma plume (>1 mm) always make trouble in direct high resolution imaging issues. However, the plasma-based sources has been shown to be useful for imaging when coupled with a high spatial resolution desorption method such as a laser (Shelley, Ray, & Hieftje, 2008). Although much of the new work in this area focus on biological imaging with DESI, SIMS, MALDI, and laser-assisted techniques, there is also research directed toward in situ/in vivo mapping the distribution of chemicals in various materials.

    Through coupling laser ablation to a pin-to-plate constructed FAPA source (Shelley, Ray, & Hieftje, 2008), Shelley et al. successfully mapped lidocaine and caffeine in turkey and celery tissue, respectively. With the laser ablation configuration, depth information of 2.7 mm with an average resolution of 36 mm was obtained on an Excedrin Migraine tablets. With 2-D imaging, inkjet printer loading ink doped with caffeine was used to print the Indiana University logo, which was scanned with a laser, ionized with a FAPA source, and finally recorded the time trace for m/z 195 to accomplish imaging (Fig. 9A). The total time cost with LA-FAPA imaging is less than 30 min, with a spacial resolution of 63 μm (horizontal) and 178 μm (vertical). Although the preliminary study shows that imaging with LA-FAPA is limited to analytes that produce ionic species with a mw <1,000 Da, it is promising in ambient MSI with further improvement on device arrangement.

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    Figure 9. A: Imaging of the Indiana university logo printed on paper with caffeine-doped ink, using LA-FAPA-MS, reprinted with permission from Shelley, Ray, and Hieftje (2008), copyright 2008 [American Chemical Society]. B: Using DART for direct analysis of profile cuticular compounds from virgin male and female flies with the living flies being held by a vacuum applied through a pipette tip and probed with a metal pin, reprinted with permission from Yew, Cody, and Kravitz (2008), copyright 2008 [National Academy of Sciences, U.S.A.]. C: Imaging of an egg slice containing melamine using DAPCI-MS/MS and the corresponding real photo, reprinted with permission from Yang et al. (2009b), copyright 2009 [Elsevier]. D: Employing LTP-MS for imaging of calligraphy and the inkpads of seals, picture, reprinted with permission from Liu et al. (2010b), copyright 2010 [Wiley].

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    Although it has been possible to characterize chemical compounds in insects with GC-MS, the limitations of this method always lie in lethality of the living beings and time-consumption. However, the efficient use of DART to analyze cuticular hydrocarbons on an awake behaving fly has been demonstrated with merits that allow low-destructive in vivo analysis and high throughput (Yew, Cody, & Kravitz, 2008). In order to decrease damage and spatial variation, vacuum suspension was introduced to attach the fly; also non-invasive probes were used for sampling, as has been showed in Figure 9B. The female and male flies were compared by the kind and intensity of cutibular hydrocarbons in the mass spectrogram. The different spectrogram obtained from the lateral thorax and the anal–genital region of individual male flies showed spatial differences in the expression of hydrocarbons. In addition, by comparing the spectrogram before and after copulation, DART-MSI was proved to enable normal physiological behavior of flies in parallel with bioanalysis. The author focused further study in DART-MSI on quantitative and structure analysis of the cuticular substances.

    DAPCI-MS can manage biological imaging via detection of the concentration distribution of melamine in cooked egg slices (Yang et al., 2009b). Experimental data were recorded for the characteristic fragment of melamine (m/z 127) at m/z 85. Figure 9C shows the MS/MS image of an egg slice and its corresponding real photo. Result showed that melamine was unevenly distributed in the egg and concentrated in the egg white rather than the yolk. The spatial resolution of DAPCI-MS imaging was calculated to be 0.6 mm2. In the meanwhile, the experiment offered relative high reproducibility with an RSD of 1.3% for six parallel tests. Other reports on DAPCI-MS imaging have not found yet, whereas developing this technique in more imaging fields is encouraging.

    As for imaging of art work, LTP has a main advantage over other spray-related and laser-assisted techniques in that it allows a nondestructive and in situ scan due to its low-temperature and spray-free characteristics. Zhang's group has published a highly interesting application of LTP-MS imaging Chinese calligraphy, and distinguished genuine and counterfeit seals (Liu et al., 2010b), see Figure 9(d). In this work, the non-destructive characteristic of LTP imaging was confirmed with SEM photographs. The spatial resolution, which was around 250 μm in horizontal direction, could be determined by adjusting the size of LTP probe, the gas flow rate, and the surface-scanning rate. The identification function of LTP worked well in terms of different imaging patterns and MS fingerprints of genuine and counterfeit seals. Encouraged by the good performance of LTP-MSI in the study above, use of this technique in a wider range of art-authentication is under consideration.

    C Pharmaceuticals and Drugs

    Because the pharmaceutical industry is both one part of a national economy, and a cure, prevention, health care, family planning of the social welfare undertakings, it has occupied an important part for analytical chemistry for a long time. This viewpoint is supported by the phenomenon that almost all kinds of ambient MS sources have been used to detect of pharmaceuticals and illicit drugs. Among the most-common pharmaceuticals detected are Aspirin, Paracetamol, Ibuprofen, and Loratadine.

    Cody, Laramée, and Durst (2005) first introduced DART to detect intact painkiller tablet, acetaminophen and oxycodone were clearly recognized in the form of protonated molecule ions from the mass spectra. For real samples, ranitidine in human urine was presented as [M+H]+ ions hours after taking the corresponding medicine. Other biofluids, such as saliva and blood, were also studied. After being put into commercial operation, DART was widely used in drug detection with more or less development on the instrument or testing method. Grange et al. accomplished quick quantification of 11 drugs with cotton swab wipe samples, home-made field sample carrier, and autosampler to a DART-TOFMS (Grange & Sovocool, 2011). DART-MS was also applied in forensics (Steiner & Larson, 2009). It was presumed that the orifice voltage has a proportion relationship with fragmentation, and, therefore, affected the isomer identification. Compared with GC-MS data, the AccuTOF-DART offered more sufficient data about the drugs due to its high-throughput and high-speed characteristics. In another case that combined thin layer chromatography (TLC) with forensic drug detection with AccuTOF-DART (Howlett & Steiner, 2011), the gas-heater temperature, proportion of developing solution (glycerin), and orifice voltage were optimized to the value of 325°C, 1:25, and 190 V to improve reproducibility and to obtain effective identification. Three pharmaceutical preparations (oxycodone with acetaminophen, hydrocodone with acetaminophen, and codeine with acetaminophen) were analyzed as protonated molecule ion peaks in the spectra within a reproducibility criterion of ±5 mDa. To strengthen the application of DART as a routine confirmation tool, collision-induced dissociation (CID) was used to provide structural information that was useful to characterize various analogs of cannabinoid, including those contained in real herbal (Musah et al., 2012). In this work, the core structural of five synthetic cannabinoids could be deduced from the precursor ions and key product ions with typical abundance. There is hardly space here to do justice to the richness of the various reports about the application of DART in pharmaceutical industry (Chernetsova & Morlock, 2011).

    The drug analysis ability of DART and DAPCI was proved through a comparison experiment of DESI, DART, and DAPCI (Williams et al., 2006). The results showed that DAPCI was more effective than the others for medium to low polarity compounds, whereas DART worked well with weakly polar gaseous samples. Another comparative analysis was made among DESI, DART, and ASAP (Petucci & Diffendal, 2008). An outstanding feature of ASAP in drug discovery is that it is available to identify polar and nonpolar compounds. OTC medicine, such as Paracetamol, Excedrin, Tylenol, and Claritin, were also detected with DCBI (Wang et al., 2010) and microplasma (Symonds et al., 2010) in a tablet. In the latter technique, LODs of the active pharmaceutical ingredients in the finished medicine were calculated to be 0.4–14.3 ng mm−2, whereas values of the same API differed in different medicine. As to in situ detection, Jackson et al. (2010) tried to analyze drugs of abuse in biofluids with LTP. In their experiments, salvia and urine were chosen as the biological matrices to successfully detect 14 drug standards with negligible matrix effects. Semi-quantitative results were obtained, where R2 values could always be above 0.99 and the linear dynamic range was as high as 105 for methadone. LTP also exhibited capability to analyze real samples, including monitoring caffeine metabolism in urine and identifying cocaine in hair extract.

    In very quantitative terms, matrix effects and irreproducible sampling position yield difficulties. To avoid the first problem, Wang et al. (2012a) have largely improved the quantitative performance of DCBI through use of room temperature ionic liquids (RTILs), [BMIM]BF4, as the matrix. The use of a non-volatile RTILs matrix decrease the fluctuation of analyte desorption caused by co-evaporation, and therefore dramatically decreases the RSD to <3% compared with 14.3% achieved with a water matrix. Satisfactory quantification results were also presented, where R2 of the Setastine and Triprolidine regression curve reached 0.9999, with an LOD of several hundred picograms. There are other researchers who improve the quantitative performance of ambient ionization/desorption MS sources. By coupling a “drop-on-demand” (DOD) aerosol generator to FAPA-MS (Schaper et al., 2012), quantification could be achieved without any internal standards. The DOD reproducibly introduced a very small volume droplet, which was tunable into the afterglow region of FAPA, and to therefore release the matrix effects and avoid error from sampling. Experimental results show good reproducibility versus what was obtained from probe-type FAPA; RSD was 4% vs. 35%. For real sample analysis, raw urine doped with five drugs and metabolites was under detection with a final LOD that ranged from 0.04 (Methadone) to 1.3 μg mL−1 (Benzoylecgonine). Due to the nature characteristic of the ambient MS sources that they work with no or little pretreatment, they are hardly comparable with the GC/LC coupled techniques in precision. Urgent attention and considerable further work is still required to develop methods that can quantify analytes and not ignore configuration identification.

    D Chemical Reaction Monitoring

    Optimization of chemical reactions via real-time monitoring substrates and products has been of some concern. Ambient mass spectrometry is now used extensively by several research groups in the field of reaction monitoring due to its real-time sampling, high analytical speed, and high specificity. The basic reaction-monitoring process follows the order that reaction substances are first sampled from the reaction system to the ambient MS source for ionization, and delivered to the MS detector for analysis. According to the continuity of sampling, reaction monitoring can be divided into off-line and on-line versions (Ma, Zhang, & Zhang, 2012). Here we focus on examples of reaction monitoring with some plasma-based ambient MS sources, DART, LTP, and DCBI.

    DART off-line monitored the synthetic transformations, including N-methylation of an indole and a debenzylation reaction (Petucci et al., 2007). To monitor the methylation of indole, 2 μL of a diluted reaction mixture in 1 mL of MeOH was attached to the end of a capillary tube for sampling. Ratios of reactant- and product-ion signal intensities calculated from the mass spectra matched well with those obtained from the UV spectra of LC/UV/ESI-MS during a total reaction time of 16 h (Fig. 10). The match of mass spectral data and UV spectra was also found in the case of debenzylation by similar detection methods.

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    Figure 10. Total diode array chromatograms for the reaction monitoring of an indole converting to an N-methylindole via LC/UV/ESI-MS: UV spectra at (a) 0 min, (b) 20 min, (c) 40 min, (d) 80 min, (e) 140 min, and (f) 16 h; mass spectral data for the protonated indole (m/z = 254), and protonated N-methylindole (m/z = 268), generated via DART/MS (350°C) at (g) 0 min, (h) 20 min, (i) 40 min, (j) 80 min, (k) 140 min, and (l) 16 h. Reprinted with permission from Petucci et al. (2007), copyright 2007 [American Chemical Society].

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    Cho and coworkers (Cho et al., 2011) have employed automatic sample introduction with success for the DART-MS quantitative monitoring of a model batch slurry reaction that coupled 2-amino-4,6-dimethylpyrimidine (ADP) and methyl 2-(isocyanatosulfonyl) benzoate (MIB) for synthesis of sulfometuron methyl ester (SME) in xylenes. The introduction of automatic sampling device impressed the RSD to 6–30% compared with manual method.

    Another application of DART in reaction monitoring falls in solid-phase organic synthesis (SPOS) of an on-bead Heck coupling between aryl iodide and methyl acrylate (Sanchez et al., 2011). DART-MS was used to analyze beads that contained reactants and products at several time points. The time-trace graph showed, that the ion intensity of the starting material declined with the reaction time, and that of the products increased. Such tendency was confirmed by a parallel NMR examination of the starting material/product ratio on the same beads. The authors suggest that DART is suited to monitor starting material and product ions than to identify side reaction because compounds of the latter are hardly known. Both reports we mention above employed DART as an off-line reaction monitoring method because of the time-point detection; further research in this field demand some instrumental or sampling development that enable on-line monitoring.

    Zhang's group realized real-time monitoring of organic reactions with LTP (Ma et al., 2009). In their design, reactants could be added at any time into the reaction container, which was mounted perpendicularly to the LTP probe. The reactants, intermediates, and products from the surface of the reaction solution could be continuously desorbed and ionized with the plasma as the reaction proceeded. Recently, another plasma-based technique, DCBI, was reported to monitor on-going multi-step chemical reactions (Xu et al., 2012). As a thermal-exciting reaction, the Leukart reaction cannot start without the heat corona beam of DCBI. From the vantage point of real-time detection of substances in a reaction system, DCBI corroborated the reaction mechanism via detection of effective intermediates. Moreover, it seemed that gas flow rate and plasma temperature would affect the kind and intensity of intermediates in the mass spectra such that the reaction process could be controlled to some extent by adjustment of the DCBI operation parameters. Other plasma-based techniques have not been applied in reaction monitoring, even though they share some common features with the three methods discussed above. The challenge remains to develop methods that could improve resolution and flexibility of sampling of ambient MS, and also to introduce new techniques that are suitable for on-line and off-line monitoring.

    E Foodstuffs and Daily Chemicals

    In recent years, food safety has become a topic with international impact due to the high-speed development of economy. The major factors that influence the food safety include pesticide and chemical fertilizer residues in fruits and vegetable, excess and illegal food additives in food industry, inferior raw food materials, and heavy-metal contamination. Plasma-based ambient MS sources function well in food-quality detection due to the features of pre-treatment free, high-throughput, in situ and invasive detection.

    DART, the first and most mature plasma-based ambient MS technique, is highly desirable for food quality detection. Furthermore, the use of DART-MS for fragrance industry has been described (Haefliger & Jeckelmann, 2007). With the detection limit around 100 pg, DART could semi-quantify or identify fragrance deposited on a complex matrix, including smelling strips, fabric, and hair. Another trial in this study confirmed the ability of DART to detect taste-refreshing compounds in chewing gum. Some efforts were made into the rapid screening of strobilurin fungicides in wheat grains in <1 min (Schurek et al., 2008). Good quantitative performance was obtained through a simple ethyl-acetate extraction and addition of prochloraz as the internal standard. Vaclavik et al. (2010b) made quantitative analysis of multiple mycotoxins in cereals with DART coupled to high resolution mass spectrometry. Two calibration approaches, matrix-matched standards calibration and 13C internal standard calibration, were used for quantification with the optimal calibration levels (LCLs) that ranges from 50 to 150 μg kg−1 estimated for particular analyte. In an attempt to combine single-drop liquid–liquid–liquid microextraction (SD-LLLME) with DART (Bai, Zhang, & Liu, 2012), six phytohormones, including indole-3-acetic acid (IAA), indole-3-butyric acid (IBA), jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), and gibberellin A(3) (GA(3)), were quantified with good linearity and sensitivity (the R2 were 0.991–0.996, detection limits were 0.65–72 ng mL−1). When used to test endogenous phytohormones in juice, satisfactory recoveries were obtained; the whole test time was <30 min. An accurate method that couples DART with orbitrap high-resolution mass spectrometry was used to establish the distinction of Chinese and Japanese star anise via identification of anisatin in raw materials (Shen et al., 2012). Herbal teas were also studied to determine anisatin by extracting 2 μL of prepared tea. Several reports have dealt with detection of contamination from food packaging, including rapid screening of additives in food packaging (Ackerman, Noonan, & Begley, 2009), and identification of addictives from PVC lid gaskets for fear that the harmful compounds would migrate into the foodstuffs (Rothenbacher & Schwack, 2010). Other studies include quantitative analysis of caffeine in coffee samples (Danhelova et al., 2012) and 5-hydroxymethylfurfural in honey (Chernetsova & Morlock, 2012), authentication of animal fats (Vaclavik et al., 2011), recognition of beer brand (Cajka et al., 2010), melamine analysis (Dane & Cody, 2010; Vaclavik et al., 2010a), identification of characteristic component in olive oil (Garcia-Reyes et al., 2009), allium (Block et al., 2010; Kubec et al., 2010), etc. Presented here are not the whole about the various applications of DART in foodstuff because of space constraints of this section, anyone who demands a detail review about this field can go for reference (Hajslova, Cajka, & Vaclavik, 2011).

    Apart from DART, considerable studies have also been published on DAPCI, FAPA, DBDI, and LTP. In the work of Chen et al. (2007b) sudan dyes in tomato sauce were detected semiquantitatively with DAPCI. Successful identification of atrazine (10 pg) on the surface of an unripe pumpkin was achieved, with easily recognizable peaks in the spectrum. Other samples, such as putrescine and cadaverine in spoiled fish meat were also successfully identified. DAPCI also provides a practical way to screen melamine in milk products within a few seconds (Yang et al., 2009a). The linear dynamic range was found to be 105 for authentic melamine standards, powdered milk, and liquid milk, whereas LOD (3.4 × 10−15 g mm−2) for the first sample was much lower than the latter two (1.6 × 10−11 g mm−2 and 1.3 × 10−12 g mm−2, respectively). The author ascribed this phenomenon to the interaction between melamine and the matrix. Further, DAPCI-MS combined with Principal Component Analysis (PCA) has been employed with success by Pi et al. (2011) to differentiate various kind of Fructus schisandrae acquired by different growing environment, geographic areas, and processed methods. The capability of APGD-MS/MS to identify 10 pesticides in fruit juices and on skin of fruits and vegetables with LODs in the low ppb range has been demonstrated (Jecklin et al., 2008). Despite the poor reproducibility of this method, APGD-MS was expected to be an effective fast screening tool for labeling control of the bio-/organic food. Analogous agrichemicals analysis has been performed with LTP-MS (Wiley et al., 2010). Thirteen multi-class agrichemicals were directly detected on fruit peels and fruit/vegetable extracts, to yield the detection limit in pictogram range. The combination of a handheld mass spectrometry and LTP might play a large role in the in situ analysis of complex samples. For example, in the rapid detection of diphenylamine (DPA) directly in apple and orange (Soparawalla et al., 2011), the compounds on the fruit skin and inside the fruit were identified from their CID spectra. Depth profile of the DPA concentration distribution in the apple was obtained. The handheld MS could achieve collision-induced dissociation to the stage of MS5 to offer accurate results for identification. This method did not go well with quantification partly due to the crude treating processes. García-Reyes et al. (2009) adopted LTP to determine free fatty acids, phenolics, and volatiles in raw olive oil. The characteristics of fast detection and quantification make LTP-MS promising in quality control and authentication of virgin olive oil. A recently developed methodology (Gilbert-Lopez et al., 2012), LC/DBDI-MS, where DBDI serves as the ionization source instead of conventional ESI and APCI, has made foodstuff analysis in the LODs of low ng L−1 to μg kg−1 more available. This methodology used olive oil extract as the matrix for multiclass contaminants, including polycyclic aromatic hydrocarbons, organochlorine pesticides, polar pesticides, emerging contaminants, and controlled drugs to offer appropriate performance with good linearity and minor matrix effect. Comparative studies with APCI and ESI predicted the expanding application of LC/DBDI-MS in food testing. Although the quantification performances of ambient ionization techniques are still inferior to LC/GC-MS in most cases, their advantages of high sensitivity, simple sampling process, and fast detection can offset the defect to some extent.

    F Explosives

    Explosive detection has turned to a worldwide concern in recent years due to the increasingly serious international armed conflicts and terrorism. For homeland security and residents' personal safety, people paid more attention to detection and identification of explosives with physical and chemical technologies, among which ambient MS technology is of clear advantage in trace explosive determination.

    As to plasma-based ambient MS methods, this capability has been shown in DART, DAPCI, FAPA, DBDI, and LTP. For example with DART (Rowell et al., 2012), seven common explosives, including TATP, Tetryl, TNT, TNG, PETN, RDX, and HMX, presented in spiked latent marks have been tested in pg range. In the study, the explosives were successfully detected on several surfaces such as finger, paper, plastic bag, metal drink can, wood laminate, adhesive tape, and white ceramic tile to demonstrate DART-MS an effective explosive detector. The capability of DAPCI in explosive detection was first confirmed by Cooks and coworkers (Takats et al., 2005; Song & Cooks, 2006). In a latter application (Song & Cooks, 2006), DAPCI and APCI were used to detect nitro-aromatic explosives by monitoring their ion/molecule reaction products ([M+CN], [M+CH2CN], [M+OH], [M+OOH]) with reagent ions produced from acetonitrile and air. DAPCI has also been used for peroxide-based explosives that involve HMTD and TATP (Cotte-Rodriguez et al., 2008), where 15 ng of each explosive deposited on paper in a total area of 1 cm2 was detected with or without ammonium acetate added as dopant to the carrier gas (N2). Zhang and coworkers have reported the application of DBDI to detect trace amounts of explosives on solid surfaces (Na et al., 2007a) with limit of detection in the 1 ng to pg range. The experiment setup includes a pin-to-plate configuration DBD source and He used as the plasma gas at the flow rate of 150 mL min−1, although Ar, N2, and air also worked. The matrices have little influence on the detective performance because the RSD to detect TNT on five different matrices is 5.57%. The use of LTP to analyze RDX, TNT, and PTEE with a limit of detection at 5 pg has been described (Harper et al., 2008). Zhang et al. (2009) soon improved the LOD of the same explosives to the low fg range on conductive and non-conductive substrates. Further illustrations of ultra-trace amount analyses of more than 13 common explosives and explosives-related compounds have established a place for LTP-MS in this field (Garcia-Reyes et al., 2010). An initial result on the combination of a portable mass spectrometer to LTP for in situ trace explosive analysis has been presented recently (Dalgleish et al., 2012). This trial permitted the detection of 100 ng of PETN, RDX, and Tetryl only in 1 min with air supplied by a small diaphragm pump that served as the working gas. As mentioned earlier (Shelley, Wiley, & Hieftje, 2011), the pin-to-capillary configuration FAPA has also been used to identify PETN and latent fingerprint of RDX, the low amol to fmol detection limits, easily identified mass spectra make this novel method attractive for homeland security applications. However, applications of those ambient MS methods in the field of explosive detection are still under development, because few reports have dealt with the linear issue of quantification.

    G Environmental Analysis

    The merits of high speed and throughput, high sensitivity, free of LC separation, and simple operation make ambient MS techniques attractive in applications of sophisticated environmental analysis. Derivatizations have been laid in the fields of water monitoring, indoor environmental monitoring, air quantity test, poisonous reagent detection, etc. DART-MS performed well in the identification and quantification of the chemical warfare agents GA, GB, VX, and HD (Nilles, Connell, & Durst, 2009). The R2 value of all the calibration curves made from 7 to 21 points were above 0.99 with the presence of internal standards. This technique can also be used to determine organometallic compounds of As, Fe, Hg, Pb, Se, and Sn from the headspace vapor from the pure sample or their toluene solutions with He or N2 (Borges et al., 2009). The interesting results showed that dimer was preferred in the N2 gas in contrast to He. As for complicated aromatics or compounds that contain aromatic rings, Domin et al. (Domin et al., 2010) reported the use of DART to detect insoluble polycyclic aromatic compounds, Haunschmidt et al. (2010) determined seven organic UV filters in water with polydimethylsiloxane-coated stir bars for extraction. The DART-MS in the latter case was believed to be a suitable semi-quantitative method with the detection limit of 4-MBC in deionized water as low as 20 ng L−1 and the repeatability from 5% (for 4-MBC) to 30% (for BM-DBM). A study of pesticides in water used DCBI-MS with SPME-alike poly-dimethylsiloxane substrate to microextract compounds in solution samples has been mentioned in the preceding text (Li et al., 2010). Spectra of pesticides in spiked river samples at mg L−1 level were obtained that contained the corresponding [M+H]+ peaks of five analytes. Each of the [M+H]+ peaks was confirmed with MS2 spectra.

    DBDI-MS was used to examine H2O2 in ambient air (Chen et al., 2009b). The spectra in the negative mode mainly recorded the m/z 66 peak, which corresponded to cluster ions [H2O2]O2 formed between aqueous solution of 0.03% H2O2 and O2 from the ambient air.

    Although ambient MS continues to be a workhorse technique of molecular analysis, a hydride generation (HG)-FAPA system enabled the detection of gas phase elemental (As, Sb, Ge) species with a well-designed gaseous sample introduction/separation section (Schilling et al., 2009). The spectra showed atomic and molecular peaks including the elements, their hydrides, oxide species and clusters with the detection limits of As species being below 10 ppb. GC-FAPA-MS can act as a precise technique to detect chemical warfare agents and herbicides (Shelley & Hieftje, 2010a), which heavily reduced the matrix effects by the transient mini sampling amount. Apart from the good reproducibility (<5%) and low detection limit (<6 fmol for a mixture of herbicides), analyte identification was accomplished with the molecular and structural information offered by first-stage collision-induced dissociation (CID) during the timescale of a chromatographic peak.

    PADI-MS has been reported to determine personal care products (PCP) direct from fixed fibroblast cells isolated from human skin (Salter et al., 2011). The performance compared with DESI showed that PADI had access to linear and highly cyclized polysiloxanes in the spectra of three anti-aging creams, whereas DESI was mostly for the [NH4]+adducts of cyclic siloxane D6.

    IV SUMMARY AND OUTLOOK

    1. Top of page
    2. Abstract
    3. I INTRODUCTION
    4. II PLASMA-BASED TECHNIQUES
    5. III APPLICATIONS OF PLASMA-BASED TECHNIQUES
    6. IV SUMMARY AND OUTLOOK
    7. V ABBREVIATIONS
    8. ACKNOWLEDGEMENTS
    9. REFERENCES
    10. Biographies

    The novel plasma-based ambient MS techniques described herein are characterized by soft ionization mode, high analysis speed, no or little pretreatment requirement, ambient experimental environment, accurate identification and semi-quantification, and universal applicability. In such devices, positive ions of analytes are mainly produced through Penning ionization induced by a metastable noble gas, He*, Ar*, and protonation induced by moisture in the atmospheric environment; negative ionization mechanisms include ion-molecule reaction between ambient O2 and analytes, electron capture, electron capture dissociation, deprotonation, and anion attachment. As to desorption process, thermal desorption plays a role in most techniques, whereas in LTP, where the temperature of plasma gas is below 30°C, momentum desorption dominates. For an in-depth knowledge of the mechanisms, several papers delve into root causes of a single source alone (Song et al., 2009; Chan et al., 2011; Shelley, Chan, & Hieftje, 2012), or make comparison of different ambient sources via optical and thermal methods (Shelley et al., 2009; Kratzer, Mester, & Sturgeon, 2011). There have been several methods to classify these techniques according to the mechanisms whereas in this paper, we divide them into four parts due to the plasma-formation approaches that contain corona discharge, glow discharge, dielectric barrier discharge, and microwave-induced plasma. What should be noticed is that techniques from different columns of the table might have similar performance in the analysis procedure.

    The plasma-based ambient MS techniques are versatile in the detection of gas, liquid, and solid samples. These techniques have allowed a wide range of applications such as the cases listed in this paper: pharmaceuticals and drug analysis, food safety, chemical reaction monitoring, structure identification, mass spectrometry imaging, explosive detection, environmental monitoring, biochemical analysis, polymer determination, etc. The ability of identification has been well-demonstrated in applications above, but problems can arise with quantification, where internal standards are required in most cases and the reproducibility is poor compared with chromatograpy-related mass spectrometry. Efforts have been made to optimize sampling methods: change sampling ways from manual to automated in order to improve the reproducibility (Schaper et al., 2012), employ extraction steps to decrease matrix interference and increase sensitivity (Li et al., 2010; Bai, Zhang, & Liu, 2012; Mirnaghi & Pawliszyn, 2012), adopt a special matrix to minimize fluctuation of analyte evaporation and improve quantification precision (Wang et al., 2012a), combine chromatograph to the ambient MS source for pre-separation (McEwen, McKay, & Larsen, 2005; Gilbert-Lopez et al., 2012). The field of plasma-based ambient mass spectrometry is flourishing rapidly with a deepening understanding of the foundation. Although perhaps driven initially by the aim to develop new application fields, the pursuit of non-destructive, low-temperature, plasma-based source affords the possibility to mini-type device construction. One of the general tendencies of the ambient MS science is to bring the instrument out of the laboratory for convenient, quick, and sensitive analysis of substance around our daily life. In this way, confirmation based on the combination of a hand-held mass spectrometer seems practical (Soparawalla et al., 2011; Dalgleish et al., 2012), whereas energy-saving, air-driving, miniature ambient MS sources are pursued.

    V ABBREVIATIONS

    1. Top of page
    2. Abstract
    3. I INTRODUCTION
    4. II PLASMA-BASED TECHNIQUES
    5. III APPLICATIONS OF PLASMA-BASED TECHNIQUES
    6. IV SUMMARY AND OUTLOOK
    7. V ABBREVIATIONS
    8. ACKNOWLEDGEMENTS
    9. REFERENCES
    10. Biographies
    APCI

    atmospheric pressure chemical ionization

    API

    atmospheric pressure ionization

    APPI

    atmospheric pressure photo ionization

    APLDI

    atmospheric pressure laser desorption/ionization

    AP-MALDI

    atmospheric pressure matrix-assisted laser desorption ionization

    APTDI

    atmospheric pressure thermal desorption ionization

    ASAP

    atmospheric solids analysis probe

    CID

    collision-induced desorption

    DAPCI

    desorption atmospheric pressure chemical ionization

    DAPPI

    desorption atmospheric pressure photo-ionization

    DART

    direct analysis in real time

    DBDI

    dielectric barrier desorption ionization

    DCBI

    desorption corona-beam ionization

    DEMI

    desorption electrospray/metastable-induced ionization

    DESI

    desorption electrospray ionization

    DESSI

    desorption sonic spray ionization

    DICE

    desorption ionization by charge exchange

    DSA

    direct sample analysis source

    EASI

    easy ambient sonic spray ionization

    EESI

    extractive electrospray ionization

    ELDI

    electrospray-assisted laser desorption ionization

    ESI

    electrospray ionization

    FAPA

    flowing atmospheric-pressure afterglow

    FD-ESI

    fused droplet electrospray ionization

    HAPGDI

    helium atmospheric pressure glow discharge ionization

    IR-LADESI

    infrared laser ablation electrospray ionization

    IR-LAMICI

    infrared laser ablation metastable-induced chemical ionization

    JEDI

    jet desorption ionization

    LAESI

    laser ablation electrospray ionization

    LDESI

    laser desorption electrospray ionization

    LDTD

    laser diode thermal desorption

    LIAD-ESI

    laser-induced acoustic desorption-electrospray ionization

    LMJ-SSP

    liquid microjunction surface-sampling probe

    LTP

    low temperature plasma

    MALDESI

    matrix-assisted laser desorption electrospray ionization

    MFGDP

    micro-fabricated glow discharge plasma

    MICROPLASMA-MS

    microplasma discharge ionization

    MIPDI

    microwave-induced plasma desorption ionization

    MS

    mass spectrometry

    NANOEESI

    nano-extractive electrospray ionization

    ND-EESI

    neutral desorption extractive electrospray ionization

    PADI

    plasma-assisted desorption ionization

    PESI

    probe electrospray ionization

    PCA

    principle component analysis

    PPAMS

    plasma pencil atmospheric mass spectrometry

    SACI

    surface activated chemical ionization

    SSP

    surface sampling probe

    SSSP

    scaling surface-sample probe

    TD/APCI

    thermal desorption/atmospheric pressure chemical ionization

    ACKNOWLEDGEMENTS

    1. Top of page
    2. Abstract
    3. I INTRODUCTION
    4. II PLASMA-BASED TECHNIQUES
    5. III APPLICATIONS OF PLASMA-BASED TECHNIQUES
    6. IV SUMMARY AND OUTLOOK
    7. V ABBREVIATIONS
    8. ACKNOWLEDGEMENTS
    9. REFERENCES
    10. Biographies

    The authors are grateful to the support from the Research Center of Analytical Instrumentation of Sichuan University for providing all the materials demanded to write this review.

    REFERENCES

    1. Top of page
    2. Abstract
    3. I INTRODUCTION
    4. II PLASMA-BASED TECHNIQUES
    5. III APPLICATIONS OF PLASMA-BASED TECHNIQUES
    6. IV SUMMARY AND OUTLOOK
    7. V ABBREVIATIONS
    8. ACKNOWLEDGEMENTS
    9. REFERENCES
    10. Biographies

    Biographies

    1. Top of page
    2. Abstract
    3. I INTRODUCTION
    4. II PLASMA-BASED TECHNIQUES
    5. III APPLICATIONS OF PLASMA-BASED TECHNIQUES
    6. IV SUMMARY AND OUTLOOK
    7. V ABBREVIATIONS
    8. ACKNOWLEDGEMENTS
    9. REFERENCES
    10. Biographies
    • Image of creator

      Xuelu Ding was born in 1989 in Chengdu, China. She accomplished her undergraduate studies in the department of Chemistry at Sichuan University, obtaining a B.Sc. degree in Chemistry in 2012. Presently she is going on to take higher level M.Sc. programs in the Research Center of Analytical Instrumentation at Sichuan University. Her interests lie in the field of mass spectrometry, especially the development of ambient ionization/desorption MS techniques.

    • Image of creator

      Yixiang Duan received his B.S. degree from Fudan University and M.S. degree in analytical chemistry from Changchun Institute of Applied Chemistry, Chinese Academy of Science in 1988 and Ph.D. degree in analytical chemistry jointly from Jilin University, China, and Indiana University, USA in 1994. Then he did his postdoctoral research at Los Alamos National Laboratory. From 1997 to 2010, he was a Principal Investigator and Staff Scientist with the Chemical Diagnostics and Engineering Group, Los Alamos National Laboratory. He is currently a National Special Professor and Director of Research Centre of Analytical Instrumentation, Sichuan University, China. His current research interests include mass spectrometry, molecular spectrometry, noninvasive medical diagnostics, novel analytical instrumentation, as well as various applications of surface chemistry to nanomaterials, nanoscience, and biological science.