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Analytical Validation of a Portable Mass Spectrometer Featuring Interchangeable, Ambient Ionization Sources for High Throughput Forensic Evidence Screening

  • Zachary E. Lawton
  • Angelica Traub
  • William L. Fatigante
  • Jose Mancias
  • Adam E. O’Leary
  • Seth E. Hall
  • Jamie R. Wieland
  • Herbert Oberacher
  • Michael C. Gizzi
  • Christopher C. MulliganEmail author
Focus: Honoring R. G. Cooks' Election to the National Academy of Sciences: Research Article

Abstract

Forensic evidentiary backlogs are indicative of the growing need for cost-effective, high-throughput instrumental methods. One such emerging technology that shows high promise in meeting this demand while also allowing on-site forensic investigation is portable mass spectrometric (MS) instrumentation, particularly that which enables the coupling to ambient ionization techniques. While the benefits of rapid, on-site screening of contraband can be anticipated, the inherent legal implications of field-collected data necessitates that the analytical performance of technology employed be commensurate with accepted techniques. To this end, comprehensive analytical validation studies are required before broad incorporation by forensic practitioners can be considered, and are the focus of this work. Pertinent performance characteristics such as throughput, selectivity, accuracy/precision, method robustness, and ruggedness have been investigated. Reliability in the form of false positive/negative response rates is also assessed, examining the effect of variables such as user training and experience level. To provide flexibility toward broad chemical evidence analysis, a suite of rapidly-interchangeable ion sources has been developed and characterized through the analysis of common illicit chemicals and emerging threats like substituted phenethylamines.

Graphical Abstract

Keywords

Analytical validation Ambient ionization Portable mass spectrometer Forensics Forensic evidence Desorption electrospray ionization Paper spray ionization Atmospheric pressure chemical ionization SWGDRUG 

Introduction

Controlled substance analysis plays a major role in both the typical workload and the substantial evidence backlog that burdens the public forensic laboratory system and impedes ongoing criminal investigations and judicial processing [1, 2]. A review of the 2009 Census for Publicly Funded Forensic Labs from the Bureau of Justice Statistics [3] shows that controlled substance requests were second only to forensic biology (e.g., serological screening, DNA analysis) in magnitude, accounting for 33% of all work requests. For county and municipal labs, drug evidence attributed to the highest workload, highlighting the burden of this routine casework at the local level. Of the overall backlog of evidence reported (i.e., ~ 1.2 million requests), forensic biology accounted for ~75%, with controlled substance attributing to a more modest 12%. Though novel training [4] and funding initiatives [5] have helped to contend with the demand, forensic biology has proven to be indispensable for suspect identification, leading to a significant level of outsourcing to private labs [6, 7]. While the development of higher performance analytical methods is seen as a means of accommodating the increasing number of these requests [8, 9], so too are techniques that reduce the impact of other types of forensic evidence [5, 10], allowing the reallocation of resources towards the more laborious biological analyses.

Given its implications on the typical lab workload, increasing the throughput of routine drug evidence analysis is of interest. While established laboratory-based methods for drug investigation (e.g., hyphenated mass spectrometric (MS), spectroscopy, etc.) are known for their accuracy, broad applicability, and court admissibility [8, 11, 12], throughput is hindered by the required preparative steps and overall duty cycle. Ambient MS techniques [13, 14], which increase sample throughput by forgoing extensive sample preparations, have shown proficiency in forensic chemical analysis [15, 16, 17], with recent reports involving the analysis of biofluids [18, 19], explosives [20], adulterated foodstuffs [21], mind-altering plant-based evidence [22], and simultaneous molecular/elemental composition [23]. Specific techniques like desorption electrospray ionization (DESI) [24], direct analysis in real time (DART) [25], and paper spray ionization (PSI) [26, 27] have shown utility in both trace and bulk drug evidence analysis, particularly in combatting the rise of “designer drugs” evidence and accommodating associated paraphernalia [28].

Field testing offers an inherent increase in throughput by alleviating the need for evidence transport to off-site forensic laboratories, while also providing timely information to law enforcement and forensic practitioners for establishing criminal intent and expediting investigations. Field-based processing of chemical evidence has been mostly relegated to presumptive colorimetric testing [29, 30], and while stalwart examples like the Scott (cocaine) and Marquis (opiates, amphetamines) tests are commonly implemented, they have elevated false positive rates due to circumstantial ambiguity in observed color changes [31], and lack of overall chemical specificity [32]. Several portable detection technologies have been recently investigated for forensic analysis, including Raman spectroscopy [33], near infrared spectroscopy (NIR) [34], and X-ray fluorescence microscopy (XRF). Several portable MS systems featuring membrane introduction or GC separations have been reported [35, 36], including the novel application of vehicle-mounted systems for spatial location of clandestine methamphetamine labs via volatile effluent mapping by Verbeck and co-workers [37], and although commercial products are available [38], they have yet to be broadly incorporated into forensic investigation and have preparative constraints similar to their lab-based counterparts.

The pursuit of the high throughput drug analysis has led to the coupling of ambient ionization methods to field-portable MS instrumentation [39, 40], allowing rapid and flexible screening of controlled substances and other contraband while enjoying the discriminating power of MS analysis. Reported applications demonstrate the utility of specific ambient MS techniques in this arena, allowing the direct analysis of utilized surface swabs [24], trace residues [41], bulk evidence [42], and highly complex sample matrices [26, 43]. Furthermore, implementing automated spectral library searching and chemical identification on said systems can alleviate the need for field-based data interpretation, allowing the use by nontechnical operators [44].

While the benefit of rapid, on-site screening of contraband via can be anticipated (e.g., expedited criminal investigations, decreased chain-of-custody and sample degradation issues, reduced evidence load on off-site laboratories), adoption of this technology will be contingent on its overall analytical performance given the inherent legal ramifications of collected data. To this end, validation studies that follow standard practices [45] and recommendations from gatekeepers like the Scientific Working Group for the Analysis of Seized Drugs (SWGDRUG) [46] are required to ensure subsequent court admissibility. While broad validation efforts have been undertaken for ambient ionization methods conducted on lab-scale MS instrumentation, such as the work of Gurdak and co-workers at National Physical Laboratory (NPL) in assessing inter-laboratory repeatability and constancy of DESI-MS [47], similar efforts utilizing portable MS systems for forensic applications have been limited to categorical assessments like limits of detection (LOD) and linearity [48, 49]. Cooks and co-workers have assessed LODs for explosives residues [50, 51] and drugs of abuse [52] using their lineage of miniaturized MS systems, as well as demonstrated quantitative toxicological analysis of biofluids [53, 54]. Other reports have evaluated selectivity and throughput of drug evidence screening using commercially available systems [24, 42].

Herein, we report an extensive analytical validation of a portable MS system featuring interchangeable, ambient ionization sources for on-site drug evidence screening. Following SWGDRUG recommendations [46], specific performance characteristics assessed included selectivity, accuracy/precision, method robustness, ruggedness, and detection limit. Reliability in the form of false positive/negative response rates determined from large datasets are reported, examining the effect of user training, experience level, and environmental factors stemming from field usage. Furthermore, the utility and throughput afforded from the implementation of rapidly interchangeable, ambient ionization sources is investigated as a means to combat the rigor and variable nature of crime scene processing

Experimental

Samples and Sample Preparation

For these studies, analytical standards of target analytes were purchased from Cerilliant Corp. (Round Rock, TX, USA) in 1000 ppm (1.0 mg/mL) concentrations, and stock solutions of known concentration were prepared via serial dilution in methanol. To produce surface residues of known mass, 1 μL aliquots of these known composition solutions were spotted onto substrates of interest and allowed to dry. Limit of detection (LOD) studies were performed from four substrates of forensic interest: glass (e.g., microscope slide), a brass key, a plastic bag (polyethylene), and textured laminate countertop purchased from local distributors.

Solutions were analyzed as-is for ESI-MS analysis or spotted onto porous Teflon well slides (Prosolia Inc., Indianapolis IN, USA), dried, and subsequently analyzed for DESI-MS. For PSI analysis, MQuant paper-based testing strips (EMD Millipore Corp., Billerica, MA, USA) with one end cut into an isosceles triangle served as the ionization substrate. These testing strips feature a plastic backing behind the paper substrate, which provides rigidity for direct, dip sampling of condensed phases or surface swabbing with minimal deformation of the triangular shape, which is critical for spray quality and duration during analysis. For surface swabbing, the PSI substrate is pre-wetted with 2 μL of methanol to enhance recovery, used to probe the surface of interest, and then directly analyzed. All spray-based ionization sources utilized a spray solvent of 1:1 methanol/water with 0.1% formic acid.

Portable MS System and “Plug and Play” Style Ionization Sources

For these studies, a FLIR Systems AI-MS 1.2 cylindrical ion trap (CIT) mass spectrometer (FLIR Mass Spectrometry, West Lafayette, IN, USA) ruggedized for field use was implemented for all data collection and validation studies. As previously reported [24, 26, 44], this system features a capillary-based atmospheric pressure inlet for coupling to ambient ionization methods, while providing analyte confirmation via MS/MS. Cartridge-based helium CID damping gas, syringe pump solvent delivery, and the high voltage supply needed for all investigated ionization sources are incorporated into the instrumental design. Nebulizing gas for ESI and DESI is supplied by a small self-contained breath apparatus (SCBA) tank during field use. Dimensions (60 × 50 × 40 cm, L × W × H) and weight (~45 kg) of this field-ready system are well-suited for on-site criminal investigations and CSI applications.

For maximum flexibility towards the broad forensic evidence screening, a centralized mounting/positioning system that allows rapid interchangeability of a suite of traditional and ambient ionization sources was constructed for use on the AI-MS 1.2; further detail on the design and construction of the rail system and associated ionization sources can be found in the Supplementary Material. Each modular ionization source was designed for quick coupling/disconnection to instrumental voltage and solvent lines and minimal user manipulation to simplify overall operation for nontechnical users. Ion sources were selected to enable the rapid screening of condensed phases, residues, and gas-phase species, including ESI and DESI via a factory-mounted, dual function spray chamber, PSI, paper cone spray ionization (PCSI) [55], and direct air sampling-atmospheric pressure chemical ionization (APCI). The included sources required no external power requirements other than that built-in to AI-MS 1.2 system. For brevity, explicit experimental detail for each ionization method can be found in the Supplemental Material.

Comparison to a Standard Mass Spectral Reference Library

To assess selectivity of the AI-MS 1.2 in identifying forensic analytes, base MS and MS/MS spectra data were compared with both recent literature and a widely accepted reference library, the ‘Wiley Registry of Tandem Mass Spectral Data, MSforID’ (Wiley: Hoboken, NJ, USA) [56]. The library was developed on QqTOF instrumentation (Qstar XL; AB Sciex) using ESI in positive and negative ion mode, with the detailed instrumental parameters utilized reported previously [57, 58]. To date, the published version of the library contains 12,122 spectra of 1208 compounds. The library version used in this publication covered more than 1700 entries.

Pertinent MS/MS spectral information (i.e., precursor ion m/z, fragment ion(s) m/z, relative ion intensities) was submitted for compound identification with the MSforID library search program [58, 59]. The search algorithm determines the degree of similarity between a sample spectrum and library spectra, expressed as a ‘relative average match probability’ (ramp). High compound-specific ramp-values indicate high similarity between the unknown and the reference compound, and the substance with the highest ramp-values is considered to represent the unknown compound. The correctness of each putatively positive match was then checked by expert reviewing.

Results and Discussion

The validation plan implemented for the FLIR AI-MS 1.2 was constructed to include performance characteristics delineated in recent SWGDRUG recommendations [46] for seized drug analysis methodologies. Specific categories incorporated were throughput, selectivity of analyte identification, accuracy/precision (i.e., repeatability, inter-user reproducibility, and error rate), method robustness, environmental ruggedness, and detection limit. Further description of each validation category can be found in Figure S-1 of the Supplemental Materials.

Throughput and Utility of “Plug and Play” Style Ionization Sources

Ambient MS methods reported to date are diverse in terms of the analyte desorption and ionization mechanisms and minor preparative steps that are employed [60]; therefore, certain techniques are inherently better suited for specific analysis scenarios (e.g., analytes present, complexity and phase of matrix, surface geometry). For instance, the paper substrate employed in PSI-MS makes it naturally applicable to surface swabbing [26], and flexibility of positioning for DART-MS is convenient for rapid introduction of solid samples [42]. To maximize the utility of portable MS screening of forensic evidence, a centralized mounting/positioning system that allows rapid interchanging and operation of a suite of traditional and ambient ion sources (i.e., ESI, DESI, PSI, PCSI, and APCI) was developed and assessed in terms of utility and throughput; the mounting system and constructed ion sources are detailed in Supplementary Figure S-1. The interchangeable aspect of these sources allows the user to select the optimal ionization method for the evidence in question, while allowing broad coverage of solid, liquid, and gas-phase evidence types.

Figure 1a depicts the throughput of interchanging between the simplified ion sources in order to process differing evidence types. Increases in the total ion count denote the usage of each ion source for a minimum of 30 s, and a return to baseline depicts the time required for source switching, coupling of solvent and voltage connections, and needed positioning. Overall, five distinct sample/source combinations were able to be processed in less than 6 min total, generating characteristic spectral data for each scenario, as seen in Figure 1b through f. Ambient MS data collected upon the FLIR AI-MS 1.2 commonly exhibits significant in-source fragmentation (i.e., inadvertent fragmentation prior to initiating MS/MS scan modes) [24, 44], similar to other portable [61] and lab-scale MS instrumentation [62] capable of sampling externally-generated ions. This in-source fragmentation can be varied, but rarely eliminated, by manipulating ion optic potentials in the high pressure regions of the vacuum system (e.g., tube lens/skimmer assembly) [63] and minimizing thermal dissociation (e.g., inlet capillary temperature) [64]. Specific detail regarding the in-source fragmentation pathways observed can be seen in the Supplemental Materials. Of note, the high spectral intensity for the PSI analysis required a 30× demagnification to scale correspondingly with the other data. The higher sensitivity of PSI-MS is attributed to more efficient collection of analyte ions due to its coaxial positioning relative to the MS inlet capillary; this is further supported by the comparative detection limit studies summarized in Table 4. Given the rigor and variable nature of crime scene processing, the throughput and applicability demonstrated could be well suited for rapidly establishing probative value of evidence at hand.
Figure 1

(a) Total ion chromatogram depicting five successive, yet discrete, ion source/sample combinations, with the rise in ion signal corresponding to the onset and duration of said analysis. A return to baseline represents the time needed to physically interchange between sources, including reattachment of voltage and solvent lines, if needed. Completing five diverse experiments in less than 6 min eludes to the throughput and utility of the instrumental platform; (b)–(f) corresponding MS data collected during said analyses

Selectivity of Analyte Identification

The FLIR AI-MS 1.2 and other trap-based portable MS systems [41, 42] have demonstrated high spectral congruency when compared with lab-grade instrumentation for most traditional forensic chemicals [24] and, so, enjoy the selectivity afforded to MS analysis. Incorporation of tandem MS data in analyte identification even allows discernment from complex matrices [26, 43]. Previous work towards establishing spectral congruence and selectivity compared blind portable MS/MS data to a widely accepted reference library, the ‘Wiley Registry of Tandem Mass Spectral Data, MSforID’, returning the correct identification for over 30 forensic analytes and evidentiary samples [44]. While this shows selectivity towards traditional drugs of abuse, extension towards novel psychoactive substances (NPS) [28], particularly those that are structurally similar and even isomeric, must be assessed.

To determine spectral congruence and selectivity towards novel illicit drugs, MS/MS spectra for a selection of substituted phenethylamines and N-(2-methoxy)benzyl (NBOMe) derivatives was compared to reference spectra contained in the MSforID database. Library search results returned the most probable identification, reported in Table 1, and a representative visual comparison of sample and reference spectra for 2C-T2 can be seen in Supplementary Figure S-7. Although a majority of analytes were correctly identified, a few discrepancies are observed that serve to exemplify potential issues with NPS analysis and the comparison of spectral data between mass analyzer types. The incorrect matches for both 2C-D (Supplementary Figure S-8A) and 2C-T4 (Supplementary Figure S-8B) are other isomeric psychoactive compounds that have proven difficult to discern even on high performance LC-MS instrumentation [65], as they yield simplistic MS/MS data that is distinguishable only by minor differences in relative abundance. For instance, MS/MS for chain isomers 2C-T4 and 2C-T7 is marked only by the loss of an amidogen radical (17 Da).
Table 1

Summary of Library Searching Results Obtained for FLIR AI-MS 1.2 MS/MS Data

Ion trap instrumentation is known to produce a low number of compound-specific fragments, as resonant excitation-collision induced dissociation (CID) commonly produces product ions too cool to undergo further fragmentation and low-mass fragment ions are inefficiently trapped [66]. The combination of inter-analyzer differences, variable CID energies and a low number of compound-specific transitions has been shown to hinder accurate identification via library searching [67], which led to the misidentification of 25I-NBOMe.

Of note, MS/MS spectra obtained from NBOMe derivatives using the CIT of the AI-MS 1.2 demonstrated much higher complexity compared to that contained in the Wiley Registry of Tandem MS Data (Supplementary Figure S-8C), although there have been similar reports in recent literature [28, 68, 69]. It has been asserted that the addition of the N-(2-methoxy)benzyl group to the 2C-phenethylamine structure (another electron donating aromatic ring, as seen in Supplementary Figure S-8C) creates more favorable sites for dissociation that can occur along the –C-C-N-C- linkage chain, specifically C–C bond cleavage between the α- and β-carbon atoms on the ethylene bridge [68, 69]. The complexity and intensity to which these fragmentation patterns are seen is highly dependent on the MS/MS conditions utilized [44], which leads to the inter-instrument variations reported [66, 70]. While NBOMe derivatives may represent a special case due to the number of low abundance transitions seen, instrument-specific spectral databases [71] may be more prudent in scenarios where automated chemical identification is needed, but variability is a concern.

Assessment of Accuracy and Precision

Overall Instrument and User-Specific Error Rates

To ensure a statistically-relevant population of data for determination of error rate, a dataset consisting of over 1400 replicates of both positive and negative control samples was collected and analyzed. For these studies, cocaine was selected as the analyte of interest; “positive” control samples were comprised of 200 ng of cocaine, deposited directly onto a MQuant testing strip (for PSI analysis) or a glass slide (for DESI analysis) and directly analyzed, whereas “negative” control samples involved the same substrate with no cocaine present. A blank sample (identical substrate) was tested between each control to assess carryover and hygiene. In these studies, a cocaine “detection” signified the presence of both the precursor ion for cocaine, [M + H]+ (m/z 304), in base MS spectra and characteristic fragment (m/z 182) in subsequent MS/MS spectra observed at an intensity of at least three times the signal-to-noise level. The m/z 182 fragment, although characteristic, was the only transition observed for the cocaine precursor, serving as the identifying ion signature. Table 2 provides the detection and false positive rates attained in this study, controlling for the ionization source utilized. PSI was selected for a more intensive study, as its source design incorporates flexibility in user positioning and, consequently, has a higher susceptibility for user error over the static nature of the DESI source.
Table 2

FLIR AI-MS 1.2 Error Rates, Controlling for Ion Source, User Experience, and Education Level

 

Detection rate (%)a

False positive rate (%)b

Overall FLIR AI-MS

98.87 (1412)

0.14 (1412)

PSI-MS

99.01 (1212)

0.17 (1212)

DESI-MS

98.80 (200)

0.00 (200)

Breakdown of PSI-MS error rate

Trained user operation

 Graduate students

99.84 (610)

0.00 (610)

 Undergraduate students

99.20 (250)

0.00 (250)

 High School graduate

97.96 (245)

0.41 (245)

During training period

  

 Undergraduate and High School students

94.81 (77)

0.00 (77)

Other users (untrained)

 Ph.D. candidate (Analytical Chemistry)

100.00 (10)

0.00 (10)

 Undergraduate w/o AC coursework

100.00 (10)

0.00 (10)

 Police Academy graduate

100.00 (10)

10.00 (10)

Breakdown of DESI-MS error rate

Trained user operation

  

 Graduate students

98.00 (200)

0.00 (200)

aDetection rate = percentage of positive samples analyzed that were accurately detected (i.e., true positive rate).

bFalse positive rate = percentage of negative samples that returned an incorrect detection.

Sample size, n, given in the parentheses.

User-specific variables are also of interest, as educational background and level of on-instrument training could vary depending on which first responder groups utilize said instrumentation. An educationally diverse selection of users was chosen for this study, including M.S. in Chemistry candidates, B.S. in Chemistry undergraduates (with and without formal analytical chemistry coursework), Ph.D. (Analytical Chemistry) candidates, high school students with only introductory chemistry knowledge, and a recent police academy graduate with little coursework in the general physical sciences. Instrument-specific experience was controlled by examining error rates during and after the initial training period.

When examining the error rate breakdowns shown in Table 2, better outcomes can be realized by users following the formal training period and after instrument-specific experience is gained. This can be observed in Figure 2a and b, which depict the average and range of maximum peak heights observed for replicate experiments obtained during and after formal training sessions, as well as the daily sample throughput (i.e., min/sample); for this, the observed datapoint represents the average value from replicate analyses, with the provided bar depicting the maximum and minimum intensity observed for that day, and daily sample throughput (min/sample) is indicated above each range. The effect of cumulative experience can be seen herein, particularly in regards to sample throughput, but also to a lesser extent for the daily average and maximum spectral intensity obtained. As seen in Figure 2a, the high school student user struggled to reproducibly acquire high intensity data shortly after the training period, but did trend to better outcomes after several days of continued usage. The benefit of past experience with chemical instrumentation through pertinent coursework and hands-on usage is seen by the comparable data obtained during and after training for an undergraduate Chemistry major user (Figure 2b). This data, in contrast, is marked by fairly reproducible average and maximum signal intensities obtained directly after formal training; similar observations were made for other users in this demographic. Sample throughput can also be considered as a metric of overall comfort with the methodology, and both user groups exhibited higher throughputs as the level of method-specific experience increased. Further comparison of user experience is presented in Figure 2c, which compares the performance of a graduate student highly experienced with the AI-MS 1.2 platform (i.e., over 1000 uses) and an undergraduate in the post-training phase. The performance of other untrained users seen in Table 2 does show that decent outcomes can still be realized without rigorous training experiences, though, alluding to the overall simplicity of ambient MS methods. Of note, even when relatively low signal intensities are acquired (as observed in Figure 2a and c), a positive detection of cocaine was still obtained.
Figure 2

Inter-day repeatability plots for (a) high school and (b) undergraduate chemistry major users showing PSI-MS results obtained during training (shaded blue) and post-training. Each date-stamped datapoint expresses the average of the maximum peak heights obtained from multiple analyses of cocaine positive controls, and bars visualizing the range of peak heights obtained on that day are included. Average throughput (in min/sample) for each period of operation is included above each datapoint. (c) Intra-day reproducibility plot assessed between two users (graduate versus undergraduate), plotting the maximum peak height obtained for all cocaine positive standards analyzed. Zones corresponding to historically low, medium, and high intensity are denoted by dashed red lines, and the number of samples falling within for each user is reported. Of note, even when relatively low signal intensities are obtained, a positive detection of cocaine was still obtained

The PSI-MS methodology produced a true positive detection rate of 99.01% and false positive detection rate of 0.17%. Although the samples investigated in this study were simplistic in nature compared to traditional forensic evidence, the error rates obtained suggest that reliable field-based chemical evidence screening can be accomplished even when operated by nontechnical users. Overall system reliability, incorporating all PSI and DESI-MS error rate investigations, modestly alters these rates to 98.87% and 0.14%, respectively. Specific errors observed throughout the study for each user are reported in Supplementary Table S-2, with a majority pertaining to rectifiable systematic errors (e.g., improper positioning/sample loading, poor preparation of the PSI substrate, neglecting hygiene protocols and method blanks), suggesting that even better outcomes could be realized after extensive experience is gained.

Repeatability, Inter-User Reproducibility, and Ion Source Comparison

Figure 3 depicts average and range trends for all cocaine positive controls analyzed by trained users (n = 1070), broken down by date of analysis and user (color-coded for visualization) in order to examine both inter-day and intra-user trends. While data collected via PSI-MS is marked by substantial variation in spectral intensity, even for highly experienced users (i.e., graduate students A and B), some trends can be observed. In examining the user-specific plots found in Supplementary Table S-9, maximum signals obtained and repeatability (i.e., test-retest variability of a single user) are lower for users with minimal instrument-specific experience. The effect of experience level, in terms of education, instrument familiarity, and training, on user-to-user reproducibility can be insinuated from Figure 2c and Figure 3. Ultimately, while repeatability is modest and user-to-user reproducibility can be impacted by experience and training, there is only a minor effect of overall reliability of qualitative assessments. Source-specific variability was also examined, reported in Figure S-10. While overall signal was shown to be highly variable for both DESI and PSI, average and maximum signals obtained by PSI are markedly higher. This is attributed to the desorption/ionization mechanism employed by DESI-MS, which requires the collection of secondary analyte ions liberated from a surface of interest [60]. Portable MS systems commonly employ miniaturized vacuum systems, and the reduced conductance of the inlet capillary makes efficient collection of non-proximity ion plumes desorbed from surfaces more problematic compared with PSI and traditional ESI sources that employ coaxial alignment.
Figure 3

Variability plot of all PSI-MS analyses of cocaine positive control samples completed by trained users (n = 1070), showing inter-day and intra-user trends. Each date-stamped datapoint expresses the average of the maximum peak heights obtained from multiple analyses, color-coded to identify the specific user. Bars visualizing the range of peak heights obtained on that day are included. Although the inherent variability of PSI-MS is apparent, the effect of education level and cumulative experience on average and maximum peak height can be seen

Method Robustness for PSI-MS

Although PSI-MS is a flexible technique, several variables have been identified as affecting the quality of spectral data collected and subsequent instrumental hygiene, including substrate positioning in reference to the inlet capillary, paper imperfections stemming from manual cutting of the triangular tip, and, to a lesser extent, the amount of solvent and voltage applied to induce spray ionization. To assess the robustness of these method-specific variables, a systematic study of spatial positioning and ionization parameters was undertaken. Figure 4 provides a graphical representation of the three-dimensional positioning of variables examined in reference to the inlet capillary of the AI-MS 1.2.
Figure 4

Graphical depictions of spatial positioning variables examined for PSI-MS method robustness. (a) 3-Dimensional representation of the spatial (X, Y, Z) axes in relation to MS inlet capillary. (b) Positioning increments (in mm) for the X- and Y-axis. (c) Side view representation of Z-axis PSI substrate positioning in relation to the MS inlet

For this study, maximum ion signal, signal duration, and sample-to-sample hygiene was determined for triplicate analyses of 200 ng cocaine samples at each variable increment. Table 3 provides both the operational and optimal values subsequently established for PSI analysis; “operational” values represent those that can hinder spectral characteristics, but still provide data that is satisfactory for analyte detection/identification. Supplementary Figure S-11 and the corresponding Supplemental Material show representative experimental data regarding the effect of X, Y, Z positioning on spray duration, as well as a detailed experimental design. Given the variability of spectral intensity observed via PSI-MS (as seen in Figure 2 and Figure 3), spray duration served as a better indicator of proper positioning.
Table 3

Method Robustness for PSI-MS Positioning and Ionization Variables

Positioning parameters (mm)

 

Operational

Optimal

X - axis

0.00 to 0.80

0.00 ± 0.40

Y - axis

–0.80 to 0.40

– 0.40 to 0.00

Z - axis

2.00 to 3.25

2.00

Ionization parameters

 

Operational

Optimal

Voltage (kV)

3.00 to 4.00

3.75 to 4.00

Solvent (μL)

1.50 to 2.50

2.00

Spatial positioning studies showed that satisfactory spectral data can be collected as long as the pinnacle of the PSI substrate aligns within the outer diameter of the inlet capillary (Figure 4b), with more optimal signals stemming from alignment within the boundaries of the inner diameter. The only exception observed arises during horizontal positioning (Y-axis), as the plastic backing of the PSI substrate interferes with the generation of an effective Taylor cone when it resides in the line of sight between the paper triangle and inlet capillary (0.4 to 0.8 mm). Placement outside of the capillary face (i.e., past 0.80 mm on X, Y axes) did not produce reliable signals and, so, is not recommended for operation.

Optimization of voltage applied to induce ionization provided values that coincide well with those reported in literature [60]. Interestingly, spray solvent volume was shown to highly influence experimental outcomes, which is of note given that PSI in the current embodiment requires user deposition of solvent. Small volumes (e.g., 1.50 μL) provided successful detection, but with markedly lower spray duration and higher spray instability due to incomplete saturation of the paper substrate. This, in turn, could increase the frequency of false negative errors in the field setting. Aliquots greater than 2.50 μL produced considerable solvent build-up on the paper substrate, which had the predilection to sputter larger droplets directly into the inlet capillary, increasing the chance of sample carryover from condensed phases like bulk powder and false positives errors. An optimal value of 2.00 μL was found to provide reliable spray duration and ion intensity for routine experimentation.

The factory ESI/DESI combination source employed on the AI-MS 1.2 has been previously characterized in terms of method variables and reported elsewhere [24], and its static nature mostly alleviates source positioning issues. Sample positioning, however, still remains critical to effectively desorb and subsequently sample analyte ions into capillary-based inlet systems.

Ruggedness Towards Field Implementation

Ruggedness towards external factors naturally entails the consideration of field implementation, which is especially pertinent for application to routine law enforcement (e.g., traffic control stops) and crime scene processing. An initial assessment of environmental factors affecting on-site analysis was conducted during late Spring/Summer 2016, tracking meteorological data (i.e., ambient temperature and humidity) with an AcuRite weather station (model VN1TXCA2; Chaney Instrument Co., Lake Geneva, WI, USA) in tandem with the analysis of positive cocaine control samples (n = 140). Although only a modest range of seasonally-dependent temperatures was examined, data collected was marked by slight reductions in both minimum and average durations obtained as temperature increased, as shown in Supplementary Figure S-12. Of note, a significant portion of the false negative errors obtained on the AI-MS 1.2 (S-2) coincided with the increased temperatures, potentially stemming from poor spray characteristics. The overall effect of humidity was inconclusive. Given that PSI-MS is commonly operated as an open-air source, other factors such as wind direction/speed and dew point (for night operations) may be found relevant upon further investigation.

Detection Limit Comparisons

While both DESI and PSI have been shown to be capable of attaining low-level detection limits using portable instrumentation, source-to-source comparisons could prove useful in selecting the appropriate method for the trace evidence of interest. Using a selection of forensically-relevant chemicals, LODs were established using PSI (surface swabbing) and direct DESI analysis for residues deposited onto surfaces of evidentiary value (shown in Supplementary Figure S-13). As seen in Table 4, PSI LODs ranged in the low to mid-nanogram (ng) range, with DESI limits determined to be an order of magnitude or higher in most cases. Mild surface and ionization efficiency effects across both sources can be seen, particularly for surfaces with more geometric complexity or those prone to movement during analysis. Particularly for DESI, the static nature of the ion source can hinder the investigation of non-flat surfaces, making surface swabbing PSI more appealing. Representative LODs stemming from APCI analysis of low concentration vapors of flammable organic solvents were also collected (Supplementary Table S-3), demonstrating trace gas analysis capability of the AI-MS 1.2 system.
Table 4

LODs for PSI and DESI-MS Analysis of Surface-Bound Residues

 

Compound

Glass slide

Brass key

Polyethylene bag

Countertop

PSI

Cocaine

20

25

20

35

Codeine

25

35

25

45

Methamphetamine

5.0

6.5

7.0

20

2C-B

55

60

65

85

25B-NBOMe

300

330

335

345

DESI

Cocaine

250

600

350

300

Codeine

300

700

650

450

Methamphetamine

300

700

400

450

2C-B

250

550

400

400

25B-NBOMe

800

1250

1050

950

Conclusions

In the present work, the novelty of an ambient sampling, field-portable mass spectrometer featuring interchangeable, ambient ionization sources for high throughput forensic investigation was demonstrated, while addressing the practical obstacles that surround field-based forensic evidence screening (e.g., applicability to diverse sample matrices and emerging threats, quality and reliability of evidentiary data collected, and data collection by nontechnical operators). While recent advances in the fields of ambient and portable mass spectrometry have intrinsic value in combatting the growing forensic evidentiary backlog, this work represents the first multi-category analytical validation of a field-ready system. Validation categories examined, particularly selectivity, error rate, and ruggedness, will assist in meeting the demands of the Daubert standard for future admissibility of field-collected MS data.

While collected data exhibited variability in regards to the spectral intensity observed, the reliability of detection was shown to be relatively unaffected when investigating low-complexity samples. Although previous reports have shown the AI-MS 1.2 platform to be capable of accurately identifying street drugs [24] and clandestine drug manufacturing paraphernalia [26], further work involving associated error rate is pertinent. Interestingly, user-specific variables, such as education and training, were shown to affect experimental outcomes. It is anticipated that the categorical breakdown of user-specific error rates presented will prove to be beneficial in determining the most effective approach and duration of training for nontechnical operators. Incorporation of internal quality control standards into the needed spray solvent and monitoring of ion source spray current could enhance outcomes for novice users. Initial ruggedness studies regarding field usage scenarios suggest that meteorological variables could be of interest, such as ambient temperature. Future investigations controlling for daily meteorological phenomenon (i.e., dew point), extreme weather, harsh environments, and the potential of operator duress in unsafe usage scenarios could be of value to the first response community.

Notes

Acknowledgments

This project was supported by Award nos. 2011-DN-BX-K552 and 2015-IJ-CX-K011, awarded by the National Institute of Justice, Office of Justice Programs, U.S. Department of Justice. The opinions, findings, and conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect those of the Department of Justice. Molecular assignments for fragmentation spectra were made for select compounds with assistance from high resolution MS instrumentation acquired through support by the National Science Foundation MRI Program under Grant no. CHE 1337497. The authors would also like to thank Cerilliant Corp. for supplying the substituted phenethylamine and NBOMe derivative standards utilized in this work.

Supplementary material

13361_2016_1562_MOESM1_ESM.pdf (1.2 mb)
ESM 1 (PDF 1253 kb)

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Copyright information

© American Society for Mass Spectrometry 2016

Authors and Affiliations

  • Zachary E. Lawton
    • 1
  • Angelica Traub
    • 1
  • William L. Fatigante
    • 1
  • Jose Mancias
    • 1
  • Adam E. O’Leary
    • 1
  • Seth E. Hall
    • 1
  • Jamie R. Wieland
    • 2
  • Herbert Oberacher
    • 3
  • Michael C. Gizzi
    • 4
  • Christopher C. Mulligan
    • 1
    Email author
  1. 1.Department of ChemistryIllinois State UniversityNormalUSA
  2. 2.Department of Management and Quantitative MethodsIllinois State UniversityNormalUSA
  3. 3.Institute of Legal Medicine and Core Facility MetabolomicsInnsbruck Medical UniversityInnsbruckAustria
  4. 4.Department of Criminal Justice SciencesIllinois State UniversityNormalUSA

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