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Technical Note
Rapid Characterization of Chemical Compounds in Liquid and Solid States
Using Thermal Desorption Electrospray Ionization Mass Spectrometry
Min-Zong Huang, Chi-Chang Zhou, De-Lin Liu, Siou-Sian Jhang, Sy-Chyi Cheng, and Jentaie Shiea
Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/ac401364k • Publication Date (Web): 03 Sep 2013
Downloaded from http://pubs.acs.org on September 7, 2013

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Page 1 of 29 Analytical Chemistry

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11 Rapid Characterization of Chemical Compounds in
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13 Liquid and Solid States Using Thermal Desorption
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16 Electrospray Ionization Mass Spectrometry
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24 Min-Zong Huang1,*; Chi-Chang Zhou1; De-Lin Liu1; Siou-Sian Jhang1; Sy-Chyi
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26 Cheng1; Jentaie Shiea1,2,*
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31 1.
Department of Chemistry, National Sun Yat-Sen University, Kaohsiung, Taiwan
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34 Department of Medicinal and applied Chemistry, National Medical University,
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36 Kaohsiung, Taiwan
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44 *: To whom correspondence should be addressed,
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47 Dr. Jentaie Shiea, jetea@mail.nsysu.edu.tw;
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50 Dr. Min-Zong Huang, minzong38@gmail.com
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Department of Chemistry, National Sun Yat-Sen University, Kaohsiung, 80424
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54 Taiwan. Tel./Fax: +886-7-5253933.
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4 Abstract
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6 Rapid characterization of thermally stable chemical compounds in solid or liquid
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8 states is achieved through thermal desorption electrospray ionization mass
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10 spectrometry (TD-ESI/MS). A feature of this technique is that sampling, desorption,
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12 ionization and mass spectrometric detection are four separate events with respect to
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time and location. A metal probe was used to sample analytes in their solid or liquid
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17 states. The probe was then inserted in a preheated oven to thermally desorb the
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19 analytes on the probe. The desorbed analytes were carried by a nitrogen gas stream
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21 into an ESI plume, where analyte ions were formed via interactions with charged
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23 solvent species generated in the ESI plume. The analyte ions were subsequently
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25 detected by a mass analyzer attached to the TD-ESI source. Quantification of
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acetaminophen in aqueous solutions using TD-ESI/MS was also performed in which a
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30 linear response for acetaminophen was obtained between 25-500 ppb (R2=0.9978).
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32 The standard deviation for a reproducibility test for ten liquid samples was 9.6 %.
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34 Since sample preparation for TD-ESI/MS is unnecessary, a typical analysis can be
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36 completed in less than 10 seconds. Analytes such as the active ingredients in
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38 over-the-counter drugs were rapidly characterized regardless of the different physical
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properties of said drugs, which included liquid eye drops, viscous cold syrup solution,
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43 ointment cream, and a drug tablet. This approach was also used to detect trace
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45 chemical compounds in illicit drugs and explosives, in which samples were obtained
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47 from the surfaces of a cell phone, piece of luggage made from hard plastic, business
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49 card, and wooden desk.
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54 Keywords:
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56 Ambient ionization, thermal desorption, electrospray ionization, post-ionization
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4 Introduction
5 The development of ambient ionization techniques has been attributed to a
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7 revolutionary improvement in mass spectrometry in recent times. This research area
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10 has rapidly evolved, and these techniques have become one of the most versatile and
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12 informative analytical tools for investigating analytes in different states of matter.
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14 This state-of-the-art technology is usually defined as mass spectrometric analysis that
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16 requires little or no sample preparation, where sample ionization is performed under
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ambient conditions, allowing for rapid, real-time, and high-throughput analysis of a
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21 wide range of substances.1-5
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23 Based on differences in their analytical processes, ambient ionization techniques
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25 can be classified into two categories. The first category includes techniques that
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27 impact the sample surface with small droplets or plasma for both analyte desorption
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30 and ionization; desorption electrospray ionization (DESI),6 easy ambient sonic-spray
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32 ionization (EASI),7-8 and direct analysis in real time (DART)9 are three techniques
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34 that are in this category. The second category includes two-step ionization, where
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36 analytes generated by lasers, shockwaves, thermal heat, or nebulizers are post-ionized
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via interactions with charged species generated by electrospray ionization (ESI),
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41 atmospheric pressure chemical ionization (APCI) or atmospheric pressure
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43 photoionization (APPI); techniques in this category include fused-droplet electrospray
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45 ionization (FD-ESI),10-11 electrospray laser desorption ionization (ELDI),12-14
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atmospheric solids analysis probe (ASAP),15 laser diode thermal desorption (LDTD),
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49 16
50 and other related techniques.17-20
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52 Given the different characteristics of ambient ionization techniques, use of these
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54 techniques depends on the nature of the analyte. For instance, FD-ESI is useful for
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56 characterizing both volatile and non-volatile compounds in solution.21-22 In ELDI
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3 and LIAD-ESI, a pulsed laser is used to irradiate the sample in order to
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5 improve production of nonvolatile analytes.23-24 However, for the analysis of
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thermally stable compounds, analytes can be more efficiently generated by thermally
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10 heating large amounts of samples so the detection sensitivity can be increased.
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12 Several examples of techniques using thermal heating together with ESI for
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14 post-ionization are given below. First, gas chromatography-electrospray ionization
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16 (GC-ESI), where the gaseous analyte eluted from GC column is conducted into an
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19 ESI plume for ionization.21 Second, electrospray-assisted pyrolysis ionization mass
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21 spectrometry (ESA-Py/MS) is used to characterize pyrolytic products from a
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23 pyrolyzer.25 Third, atmospheric pressure-thermal desorption (AP-TD) is coupled with
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25 electrospray ionization mass spectrometry to analyze thermally desorbed neutrals,
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where a heated test tube with sample is placed in close proximity to an enclosed
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30 pneumatically-assisted ESI spray plume. This technique is applied to the analysis of
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32 volatile compounds in complex matrices like Bacillus spores.26 Fourth, thermal
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34 desorption-based ambient mass spectrometry (TDAMS) is used to analyze small
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36 organic analytes from complex samples without any sample pretreatment, where
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39 thermal desorption is induced by using an NIR diode laser beam to irradiate multiple
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41 self-assembled layers of gold nanoparticles, after which the desorbed analytes of
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43 small organics were post-ionized via electrospray ionization.27 Fifth, a technique
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45 known as atmospheric pressure thermal desorption proximal probe coupled with
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electrospray post-ionization is used for the direct mass spectrometric analysis of a
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50 diverse set of compounds separated on various high-performance thin-layer
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52 chromatography (HPTLC) plates. Thermal desorption is accomplished by placing a
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54 heated metal probe close to or in contact with the surface of TLC plate. Desorbed
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56 species are drawn into the ESI plume for post-ionization and mass spectrometric
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3 detection.28 Finally, a technique was recently developed that couples a
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5 nanometer-sized heated probe for thermal desorption with electrospray ionization
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mass spectrometry for sampling and ionizing analytes on surfaces. Here, a 30 nm
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10 diameter nano-thermal analysis (nano-TA) probe tip in an atomic force microscope
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12 (AFM) was coupled via a vapor transfer line and ESI interface; the thermally
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14 desorbed material was then transferred to the mass spectrometer from the AFM tip
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16 area. 29-30
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19 Unfortunately, switching between samples during analyses is time-consuming
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21 when using the cramped analytical setup of existing techniques that couples thermal
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23 desorption to electrospray ionization. In addition, the sampling apparatuses are always
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25 attached to the ion sources so that analyte carry-over poses a serious problem between
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each analysis. Furthermore, due to the cramped analytical space of the ion sources, it
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30 is difficult for these techniques to analyze analytes from oversized or immovable
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32 objects. To overcome these problems, a simple, ease-of-operation and cost-effective
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34 TD-ESI technique was developed. The efficiency of qualitative and quantitative
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36 assays using this thermal desorption-electrospray ionization mass spectrometry
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39 (TD-ESI/MS) was evaluated.
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4 Experimental section
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6 Methanol (HPLC-grade) and acetic acid (reagent-grade) were purchased from
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8 Merck (Darmstadt, Germany) and J. T. Baker (Phillipsburg, NJ, USA), respectively.
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10 Distilled deionized water (purified by a Milli-Q plus apparatus; Millipore, Molsheim,
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12 France) was used to prepare the standard sample solutions. Acetaminophen was
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purchased from Sigma (St Louis, MO, USA), while diluted
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17 3,4-methylenedioxy-N-methamphetamine (MDMA), codeine, 2,4,6-trinitrotoluene
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19 (TNT), and trinitrohexahydro-1,3,5-triazine (RDX) standard solutions were purchased
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21 from Cerilliant Inc. (Round Rock, TX, US). All chemicals were used without further
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23 purification. Over-the-counter pharmaceutical samples (i.e., eye drops, cold syrup,
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25 Ledernin ointment, and Viagra tablet) were obtained from local stores.
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Acetaminophen solutions with concentrations from 25 ppb to 500 ppb were
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30 prepared in methanol and water (1:1, v/v) solutions for quantification tests. Each data
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32 point was the average obtained from triplicate experiments. An acetaminophen
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34 solution with a concentration of 500 ppb was used for reproducibility tests. In order to
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36 detect trace amounts of chemicals on various object surfaces, standard solutions
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38 including MDMA, codeine, TNT and RDX were spread onto different surfaces (such
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as those of a business card, wooden desk, cell phone, and a piece of hard plastic
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43 luggage) and dried in an area of approximately 9 mm2 prior to analysis. The
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45 concentrations of those surfaces were approximately 50-100 ng/cm2.
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4 TD-ESI instrument:
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6 Figure 1a shows a photograph of the TD-ESI source developed in this study. The
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8 TD-ESI source comprised of a direct probe (DP), thermal desorption unit, and
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10 electrospray ionization device. First, the direct probe (DP) was used for sampling
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12 analytes in solution or on solid surfaces. For liquid samples, a stainless steel
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inoculating loop serving as a probe (2 mm in diameter) was used to obtain
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17 approximately 2 µL of sample solution for each analysis (Figure 2a). For viscous
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19 solutions or solid samples, a straight fine needle (350 µm in diameter) was used to
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21 either collect analytes of viscous solutions or sweep five times across solid surfaces to
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23 obtain analytes. Second, the function of the thermal desorption unit was to vaporize
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25 samples on the DP and introduce desorbed analytes into the ESI plume through a
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quartz tube with single taper (OD= 6 mm, ID= 4 mm, Length= 80 mm) so that
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30 effective sample ionization can take place. In addition, an opening in the thermal
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32 desorption unit was created when the direct probe was removed from the unit to
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34 sample analytes. The thermal desorption unit was sealed after the direct probe was
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36 placed back on the thermal desorption unit for analysis of sample analytes on the
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38 probe. Third, an electrospray ionization device was used for post-ionizing desorbed
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analytes. The high voltage and solvent flow rate required to generate an electrospray
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43 plume were 5 kV and 2.5 µL/min, respectively. The ESI solution was a methanol and
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45 water mixture (1:1, v/v) containing 0.1% acetic acid, and was delivered through a
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47 fused-silica spray capillary (ID= 100 µm, OD= 375 µm, Polymicro, Phoenix, AZ) into
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49 the mass inlet of the mass spectrometer. The TD-ESI source was attached to a triple
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quadruple mass spectrometer (Agilent 6410) to detect the analyte ions. To obtain a
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54 stable solvent and analyte ion signal, the electrospray capillary was aligned to the MS
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56 inlet and the distance from the exit of the TD tube to the electrospray capillary (d1)
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58 was kept at 8 mm, while the distance from the MS inlet to the electrospray capillary
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4 (d2) was 5 mm (Figure 1b). The temperature in the thermal desorption unit was set at
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6 250 ℃ and was measured by a thermistor installed in the source. The flow rate of the
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8 nitrogen gas used to deliver desorbed analytes into the ESI plume was 0.8 L/min.
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4 Results and Discussion
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6 The field of ambient mass spectrometry encompasses many different techniques.
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8 Examples include ELDI, DESI, and DART. However, to be efficiently analyzed by
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10 these ambient ion sources, the sample needs to be placed in the ionization source,
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12 which is problematic during analysis of an oversized or irregularly-shaped sample due
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to the spatial limitations of the setup. Thus, a TD-ESI source was developed to
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17 overcome this issue in order to analyze analytes on and from any kind of object
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19 regardless of sample size.
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21 The operation of the TD-ESI developed in this study is similar to that of a direct
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23 insertion probe (DIP) used in an electron impact ionization (EI) source, where the
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25 sample (while adsorbed on a probe in its liquid or solid state) is introduced into the EI
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source so that analytes are thermally desorbed and ionized by electron impact. In
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30 TD-ESI, analytes thermally desorbed from the probe are delivered by a hot nitrogen
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32 gas stream and enter an electrospray plume, reacting with charged solvent species to
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34 form analyte ions. These ions are either formed through ion-molecule reactions
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36 between analytes and charged solvent ions (e.g., H+, CH3OH2+, or H3O+), or through
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38 analyte fusion with charged solvent droplets so that analyte ions are generated from
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newly-formed charged droplets after ESI. Since the analytes are desorbed inside a
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43 closed heated oven and delivered into ESI plume by a nitrogen gas stream for
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45 post-ionization, it is favorable to reduce diffusion effects and concentrate these
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47 analytes during desorption and ionization rather than analyzing them in an open space.
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49 Furthermore, the ionization efficiency would be enhanced due to an increase in
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reaction times and collision probabilities in a closed space. In addition, such an ion
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54 source design can also prevent environmental inferences. Figure 1c shows the
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56 TD-ESI desorption and ionization processes.
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58 Five separate analytical steps- sampling, desorption, ionization, ion detection and
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4 probe cleaning- are usually involved in a TD-ESI/MS analysis (Figure 2). To sample
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6 a liquid, a stainless steel inoculating loop (diameter: 2 mm) was dipped in and rapidly
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8 removed from the sample solution to obtain approximately 2 µL of solution (see the
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10 insert in Figure 2a). A straight fine needle was used to sample viscous solutions. By
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12 dipping and rapidly removing the probe from the solution, a small amount of the
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sample solution would remain on the probe. The same needle probe can also be used
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17 to sample solids by sweeping the loop across sample surfaces for a couple times. The
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19 probe was then inserted into a preheated oven so that analytes would be thermally
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21 desorbed and separated from the sample matrix. They were then carried by a nitrogen
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23 gas stream into an electrospray plume to be ionized and subsequently detected (see
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25 Figures 2b and 2c).
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Since these analytical processes are performed without sample pretreatment
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30 under atmospheric pressure, the time required to complete a TD-ESI/MS analysis is
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32 short, requiring less than 10 seconds. In addition, the probe is made of stainless steel
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34 so that any residues on the probe can be easily removed by burning the probe with a
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36 gas torch for a few seconds (see Figure 2d); the same procedure can be used to
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38 remove residues inside the desorption unit.
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Desorption and ionization performance in a TD-ESI source is affected by several
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43 parameters, such as (1) source geometry, i.e. the distance between the end of the
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45 thermal desorption tube and the ESI plume (d1), and the distance between the ESI
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47 capillary and the entrance of the MS inlet (d2) (Figure 1b); (2) desorption unit
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49 settings, i.e. desorption temperature and carrier gas flow rate and (3) electrospray
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settings, i.e. solvent flow rate and ESI voltage. To obtain optimal operating
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54 parameters for TD-ESI, a standard solution of acetaminophen (m/z 152) was used as a
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56 testing sample. The dependence of analyte ion signal intensity on d1 and d2 is shown
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4 in Figures 3a and b. The highest analyte ion signal was obtained while d1 and d2 were
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6 set as 8 mm and 5 mm, respectively.
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8 The parameters from thermal desorption unit including desorption temperature
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10 and carrier gas flow rate affect the degree of analyte molecules formation and
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12 efficiency of their transfer from desorption unit to ESI plume. The dependence of the
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analyte ion signal on the desorption temperature and carrier gas flow rate are shown in
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17 Figures 3c and d. Analyte ion signals increased when the desorption temperature
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19 ranged from 100 to 350 ℃, while signals remained constant even at 400 ℃. The
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21 results suggested acetaminophen was efficiently desorbed between 350 and 400 ℃
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23 without decomposition. However, different trends were found for acetaminophen
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25 when the carrier gas flow rate was adjusted. The analyte ion signal intensity rapidly
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increased when the carrier gas flow rate was increased a maximum of 0.8 L/min but
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30 decreased when the flow rate was increased beyond this point. A higher carrier gas
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32 flow rate decreases the probability for analyte molecules to interact with charged
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34 solvent species in the ESI plume and therefore decreases analyte ion signal intensity.
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36 Electrospray parameters also affect the analyte ion intensity. The effects of high
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38 voltage and solvent flow rate on the acetaminophen ion signal are shown in Figures
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3e and f. The analyte ion signal was obtained as the on-set voltage (i.e., 4 kV) for
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43 generating the electrospray was reached. The anaiyte ion signal remained unchanged
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45 even after further increase in voltage. The ESI solvent flow rate affects the stability of
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47 the electrospray plume as well as the formation of charged solvent species like
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49 protons, cluster solvent ions and charged droplets. Higher solvent flow rates may
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result in unstable and inefficient ionization of samples because the large droplets
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54 formed degrade the performance of the mass spectrometer.31 In this study, the
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4 resulting in low ionization efficiencies and analyte ion intensities. The optimum
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6 operating parameters of the TD-ESI are listed in Table1.
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8 Figure 4a shows the extracted ion chromatogram (EIC) for ten consecutive
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10 analyses of the acetaminophen solution with a concentration of 500 ppb using the
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12 optimum operating parameters for TD-ESI. The analyte ion was detected immediately
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after the sample probe was inserted in the TD-ESI source. The peak areas from the
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17 extracted ion chromatograms for m/z 152 were used to evaluate the reproducibility
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19 tests. The standard deviation calculated from the ten analyses was 9.6% (n=10). To
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21 determine the detection limit and linearity of quantification, acetaminophen solutions
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23 with different concentrations ranging from 25 to 500 ppb were analyzed. The
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25 calibration curve (R2=0.9978) is shown in Figure 4b, which indicated that the
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detection limit of TD-ESI for acetaminophen is below 25 ppb.
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30 To demonstrate the usability of TD-ESI/MS for the analysis of different types of
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32 samples, the technique was used to characterize the active ingredients in different
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34 types of pharmaceutical products formulated as clear liquids, viscous liquid-syrups,
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36 ointments, and solid tablets. Figure 5a shows TD-ESI mass spectrum of eye drops
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38 analyzed in positive mode. The dominant ion signal in the mass spectrum belonged to
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the protonated sulfamethoxazle ion (m/z 254), an active ingredient in eye drops.
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43 TD-ESI/MS was also used to characterize active ingredients in cold syrup, in which
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45 cold syrup contained acetaminophen (14.94 mg/mL), dl-methylephedrine
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47 hydrochloride (0.49 mg/mL), caffeine (1.8 mg/mL), and chlorpheniramine maleate
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49 (0.124 mg/mL). Since the cold syrup sample was quite viscous and the concentrations
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of its active ingredients were high, the inoculating loop normally used for the sample
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54 probe was replaced with a straight fine needle to avoid sampling too many analytes.
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56 As shown in Figure 5b, protonated ion signals for the active ingredients in cold syrup
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58 - acetaminophen (m/z 152), methylephedrine hydrochloride (m/z 180), caffeine (m/z
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4 195) and chlorpheniramine maleate (m/z 275) were detected on the TD-ESI mass
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6 spectrum. The variations in the ion intensities of the detected analytes may be due to
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8 their low ionization efficiencies and matrix effects from complex mixtures. However,
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10 the relative intensities of these four compounds obtained by TD-ESI/MS were similar
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12 to those obtained by ESI/MS, in which the sample was diluted at least 10 times before
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analysis in the latter (data not shown). An ointment (Ledernin) containing econazol
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17 nitrate as the active ingredient was also examined by TD-ESI/MS using a fine needle
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19 probe. The mass spectrum showed predominant signals characteristic of tri-chlorine
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21 isotopic signatures, where the peak for protonated econazol is observed at m/z 381
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23 and its isotope peaks appear at m/z 383, m/z 385 and m/z 387 with an abundance ratio
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25 of 27:27:9:1. The relative intensities of these isotopes is in good agreement with the
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expected Cl3 isotopic ratio (Figure 5c.). A tablet containing sildenafil citrate (Viagra)
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30 as the active ingredient was analyzed by TD-ESI/MS. The sample was collected by
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32 sweeping the tablet surface with a straight fine needle. The protonated sildenafil ion
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34 (m/z 475) was detected as the predominant ion peak on the TD-ESI mass spectrum
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36 (Figure 5d).
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38 There is an increasing need to rapidly identify trace chemical compounds on
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various surfaces for forensics or homeland security. The use of TD-ESI/MS as a tool
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43 for rapidly characterizing trace chemical compounds on various surfaces was
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45 conducted using MDMA (50 ng/cm2), codeine (50 ng/cm2), TNT (100 ng/cm2) and
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47 RDX (100 ng/cm2); these compounds were applied on the surfaces of a business card,
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49 wooden desk, cell phone, and piece of hard plastic luggage, respectively. A fine
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needle probe was swept across the surface of the object for sampling. Figure 6
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54 displays the mass spectra of the samples analyzed by TD-ESI/MS. The TD-ESI mass
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56 spectra of MDMA (on a business card) and codeine (on a wooden desk) are shown in
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4 detected at m/z 194 and 304, respectively. Additionally, a fragment ion signal at m/z
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6 163 indicating the loss of CH3NH2 was observed in the MDMA mass spectra. In short,
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8 the mass spectra for MDMA and codeine are similar to those obtained with other
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10 ambient ionization techniques.32-33 TD-ESI/MS analysis in the negative ion mode
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12 detected TNT and RDX applied on cell phones and pieces of hard plastic luggage,
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respectively (Figures 6c-6d). As seen in Figure 6c, the major ions for TNT in the
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17 mass spectrum are at m/z 227 and m/z 226, which correspond to the negative M˙and
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19 [M-H] ions. Fragment ions detected at m/z 210 ([M-OH]) and m/z 197 ([M-NO])
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21 were the thermal decompositional products from the TD-ESI procedure. RDX ions at
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23 m/z 268 ([M+NO]) and m/z 221 ([M-H]) were detected; many ions were also
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25 detected at m/z 157, 171, 199, 241, 255, 283, 299, 311 and 319. These ions were
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formed by the reaction of the solvent species in electrospray. These ion signals are in
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30 accordance with previous reports that used electrospray ionization (ESI) and
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32 atmospheric pressure chemical ionization (APCI). 34-35
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36 Conclusion
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38 TD-ESI/MS provides a simple analytical strategy for characterizing thermally
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stable chemical compounds through ambient ionization. The principle of the
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43 technique involves separate sampling, desorption, ionization and detection stages. The
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45 operation protocol of the technique is as follows: (1) use of a direct probe to collect
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47 samples in their solid or liquid states, regardless of sample size; (2) thermal
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49 desorption for characterizing thermally stable and volatile compounds; and (3)
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ionization through interactions between desorbed analytes and charged solvent
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54 species in the ESI plume. Samples with different types of viscosities (including
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56 liquids, syrups, ointments, and solids) were directly analyzed without extraction and
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58 separation. Although sampling, desorption, ionization and detection are separate
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4 events, the analytical time required to complete a typical TD-ESI/MS analysis takes
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6 only a few seconds. In addition, compared to other ambient ion sources such as DESI,
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8 DART and ELDI, the sample is usually placed in the ion source. The use of a direct
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10 sampling probe in TD-ESI/MS is suitable for the analysis of chemical compounds
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12 present on surfaces of over-sized or immovable objects. A linear response in the range
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of 25-500 ppb and a standard deviation less than 10 % for liquid samples suggests
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17 TD-ESI/MS is also useful for quantitative analysis. These features make the technique
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19 particularly useful for screening a large number of samples.
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4 Reference
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7 (1) Cooks, R. G.; Ouyang, Z.; Takats, Z.; Wiseman, J. M. Science 2006, 311,
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13 (2) Alberici, R. M.; Simas, R. C.; Sanvido, G. B.; Romao, W.; Lalli, P. M.; Benassi,
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M.; Cunha, I. B. S.; Eberlin, M. N. Anal. Bioanal. Chem. 2010, 398, 265-294.
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21 Chem. 2010, 3, 43-65.
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24 (4) Van Berkel, G. J.; Pasilis, S. P.; Ovchinnikova, O. J. Mass Spectrom. 2008, 43,
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30 (5) Huang, M. Z.; Cheng, S. C.; Cho, Y. T.; Shiea, J. Anal. Chim. Acta 2011, 702,
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33 1-15.
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36 (6) Takats, Z.; Wiseman, J. M.; Gologan, B.; Cooks, R. G. Science 2004, 306,
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42 (7) Haddad, R.; Sparrapan, R.; Kotiaho, T.; Eberlin, M. N. Anal. Chem. 2008, 80,
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50 20, 2901-2905.
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53 (9) Cody, R. B.; Laramee, J. A.; Durst, H. D. Anal. Chem. 2005, 77, 2297-2302.
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56 (10) Lee, C. C.; Chang, D. Y.; Jeng, J.; Shiea, J. J. Mass Spectrom. 2002, 37, 115-117.
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4 (11) Shiea, J.; Chang, D. Y.; Lin, C. H.; Jiang, S. J. Anal. Chem. 2001, 73, 4983-4987.
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7 (12) Shiea, J.; Huang, M. Z.; Hsu, H. J.; Lee, C. Y.; Yuan, C. H.; Beech, I.; Sunner, J.
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10 Rapid Commun. Mass Spectrom. 2005, 19, 3701-3704.
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13 (13) Huang, M. Z.; Hsu, H. J.; Lee, L. Y.; Jeng, J. Y.; Shiea, L. T. J. Proteome Res.
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21 Rapid Commun. Mass Spectrom. 2007, 21, 1767-1775.
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24 (15) McEwen, C. N.; McKay, R. G.; Larsen, B. S. Anal. Chem. 2005, 77. 7826-7831.
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27 (16) Wu, J.; Hughes, C. S.; Picard, P.; Letarte, S.; Gaudreault, M.; Levesque, J. F.;
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30 Nicoll-Griffith, D. A.; Bateman, K. P. Anal. Chem. 2007, 79. 4657-65.
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33 (17) Cheng, S. C.; Cheng, T. L.; Chang, H. C.; Shiea, J. Anal. Chem. 2009, 81,
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39 (18) Carter, J. F.; Sleeman, R.; Burton, I. F. A.; Roberts, D. J. Analyst 1999, 124,
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(19) Popov, I. A.; Chen, H.; Kharybin, O. N.; Nikolaev, E. N.; Cooks, R. G. Chem
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50 (20) Jorabchi, K.; Hanold, K.; Syage, J. Anal. Bioanal. Chem. 2012, 23 (DOI
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4 (22) Shieh, I. F.; Lee, C. Y.; Shiea, J. J. Proteome Res. 2005, 4, 606-612.
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7 (23) Huang, M. Z.; Jhang, S. S.; Cheng, C. N.; Cheng, S. C.; Shiea, J. Analyst 2010,
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10 135, 759-766.
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13 (24) Huang, M. Z.; Cheng, S. C.; Jhang, S. S.; Chou, C. C.; Cheng, C. N.; Shiea, J.;
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Popov, I. A.; Nikolaev, E. N. Int. J. Mass Spectrom. 2012, 325, 172-182.
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24 (26) Basile, F.; Zhang, S. F.; Shin, Y. S.; Drolet, B. Analyst 2010, 135, 797-803.
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27 (27) Lin, J. Y.; Chen, T. Y.; Chen, J. Y.; Chen, Y. C. Analyst 2010, 135. 2668-2675.
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30 (28) Van Berkel, G. J.; Ovchinnikova, O. S. Rapid Commun. Mass Spectrom. 2010, 24,
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33 1721-1729.
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36 (29) Van Berkel, G. J.; Ovchinnikova, O. S.; Kertesz, V. Anal. Chem. 2011, 83,
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39 598-603.
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42 (30) Ovchinnikova, O. S.; Nikiforov, M. P.; Bradshaw, J. A.; Jesse, S.; Van Berkel, G.
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J. Acs Nano 2011, 5, 5526-5531.
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(31) Schmidt, A.; Karas, M.; Dulks, T. J. Am. Soc. Mass Spectrom. 2003, 14, 492–
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50 500.
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53 (32) Talaty, N.; Mulligan, C. C.; Justes, D. R.; Jackson, A. U.; Noll, R. J.; Cooks, R. G.
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56 Analyst 2008, 133, 1532-1540.
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4 (33) Brewer, T. M.; Verkouteren, J. R. Rapid Commun Mass Spectrom. 2011, 25,
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7 2407-2417.
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10 (34) Yinon, J.; McClellan, J. E.; Yost, R. A. Rapid Commun. Mass Spectrom. 1997, 11,
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13 1961-1970.
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(35) Song, Y. S.; Cooks, R. G. Rapid Commun. Mass Spectrom. 2006, 20, 3130-3138.
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8 Table 1 Summary of optimal parameters in TD-ESI
9 Parameter Optimal setting
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Distance between quartz tube and ESI capillary 8 mm
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12 Distance between ESI capillary and MS inlet 5 mm
13 Desorption temperature 250-350 ℃a
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15 Carrier gas flow rate 0.8 L/min
16 Electrospray high voltage 5 kV
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18 Electrospray solvent flow rate 2.5 µL/min
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20 a
21 The desorption temperature depends on the target analyte. In this study, the optimal
22 desorption is around 350 ℃ for acetaminophen.
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4 Figure Legends
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6 Figure 1. Photographs of (a) TD-ESI source coupled to a triple quadrupole mass
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8 spectrometer, (b) the inside of the TD-ESI source, showing the mixing of desorbed
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10 analytes with the electrospray plume, and (c) schematic illustrations of desorption and
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12 ionization process in the TD-ESI source. Charged solvent droplets (acidic MeOH
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solution) are generated by electrospray; analytes in their liquid or solid states on the
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17 probe are desorbed via thermal heating, after which the desorbed analytes enter the
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19 electrospray plume to react with charged solvent species to form analyte ions in order
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21 to enter the MS inlet for detection.
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25 Figure 2. TD-ESI/MS involves four independent analytical steps: (a) sampling with a
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probe (the right panel shows two types of probes) (b) insertion of the probe in the
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30 TD-ESI unit for desorption via thermal heating and post-ionization via electrospray;
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32 (c) detecting analytes with a mass spectrometer, and (d) cleaning the probe by burning
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34 it with a torch.
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38 Figure 3. Dependence of signal intensity for acetaminophen ions on the (a) distance
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between quartz tube and ESI capillary (d1 in Fig.1), (b) distance between ESI
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43 capillary and the MS inlet (d2 in Fig.1), (c) desorption temperature, (d) carrier gas
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45 flow rate, (e) high ESI voltage, and (f) ESI solvent flow rate.
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49 Figure 4. (a) Extracted ion chromatogram (m/z 152) for ten consecutive
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acetaminophen analyses via TD-ESI and (b) A linear response for acetaminophen (R2
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54 =0.9978) in the 25 – 500 ppb range. The error bars represent the standard deviation of
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12 Figure 6. TD-ESI mass spectra of chemical compounds on different surfaces: (a)
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46 schematic illustrations of desorption and ionization process in the TD-ESI source. Charged solvent droplets
47 (acidic MeOH solution) are generated by electrospray; analytes in their liquid or solid states on the probe are
48 desorbed via thermal heating, after which the desorbed analytes enter the electrospray plume to react with
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