Scanning Quadrupole Research Articles

Experimental Investigation of a Digital Quadrupole Inductively Coupled Plasma Mass Spectrometer for Elemental Analysis.

We describe the development and initial characterization of a digital waveform scanning quadrupole mass filter (digital QMF) used for inductively coupled plasma mass spectrometry (ICP-MS). Unlike a conventional voltage scanning QMF, in the digital QMF, the frequency of the digital waveform is scanned to filter ions with different m/z through the quadrupole, and m/z is proportional to 1/f2. In digital QMF, the duty cycle of the digital waveform driving the quadrupole is modified such that stability regions of interest are accessible for mass analysis with no DC voltage applied. Here, we evaluate the performance of our digital ICP-QMS instrument at several duty cycles and corresponding stability zones: from zone 1 to zone 3,2. We demonstrate that, regardless of the stability zone used, frequency vs m/z calibration matches theory. For lower-order stability zones, the mass range of the analyzer is limited by the high-frequency waveform required; however, at zone 3,2, we demonstrate a mass range from at least 40 to 232 Th, which covers most of the elemental mass range. Similar to the conventional QMF, higher stability regions of the digital QMF can yield a higher resolution. We obtained the best resolution for our current instrument at zone 3,2 with a 62.50/37.50 duty cycle. The resolution at full-width at 10% peak height (R10%) was 1200 and 1100 for 115In+ and 232Th+, respectively. Lower pole bias yielded a R10% of 1400 for 40Ar+. Resolution and sensitivity comparisons indicate that higher q values and higher duty cycles lead to enhanced resolution, but lower sensitivity. Our results validate the operation of digital quadrupole ICP-MS and suggest that, with continuous improvement of electronics and instrumentation, a high resolution digital waveform scanning ICP-QMS for elemental analysis is possible.

A non-targeted analysis workflow for the identification of organic contaminants in a sludge water based on fragmentation matching score and metadata

ABSTRACT Non-targeted analysis (NTA) methods have been increasingly used to discover organic contaminants in environmental samples. The identification efficiency of conventional NTA workflow is often very low due to many factors such as low fragmentation score between experimental MS2 data and reference MS2 data/in-silico MS2 data. Additionally, the prioritisation of possible candidates is also challenging due to the large number of candidates obtained from MS acquisitions. In this study, a multiplatform data processing workflow applicable to non-targeted LC-MS data is proposed to improve the identification accuracy of organic contaminants in water. This workflow consists of (1) scanning quadrupole data-independent acquisition (SONAR) to acquire relatively clean MS1 and MS2 data, (2) data deconvolution using Progenesis QI Software to filter/select the appropriate ions (MS1 data), (3) the selected MS1 data matching against U.S. EPA Chemistry Dashboard to get a list of the environmentally related candidates with metadata (e.g., data sources, toxicity, and exposure), (4) experimental MS2 data matching against in-silico fragmentation data of the obtained candidate by MetFrag to obtain a fragmentation score, (5) compound identification through ranking the candidates by MetFrag based on fragmentation score and metadata. The identification efficiency of the metadata-based NTA workflow was evaluated using a 33-component mixture of chemicals in a complex sludge water. Out of 33 spiked compounds, 26 compounds had been identified using the defined NTA workflow. Most of the 26 identified compounds were recognized as 1st hit of the candidates obtained from the library searching. Overall, the incorporation of fragmentation score and metadata to rank the candidates has significantly improved the accuracy of the organic contaminant identification in the sludge water, compared to the conventional NTA workflow based solely on the fragmentation score.

A comprehensive LFQ benchmark dataset on modern day acquisition strategies in proteomics

In the last decade, a revolution in liquid chromatography-mass spectrometry (LC-MS) based proteomics was unfolded with the introduction of dozens of novel instruments that incorporate additional data dimensions through innovative acquisition methodologies, in turn inspiring specialized data analysis pipelines. Simultaneously, a growing number of proteomics datasets have been made publicly available through data repositories such as ProteomeXchange, Zenodo and Skyline Panorama. However, developing algorithms to mine this data and assessing the performance on different platforms is currently hampered by the lack of a single benchmark experimental design. Therefore, we acquired a hybrid proteome mixture on different instrument platforms and in all currently available families of data acquisition. Here, we present a comprehensive Data-Dependent and Data-Independent Acquisition (DDA/DIA) dataset acquired using several of the most commonly used current day instrumental platforms. The dataset consists of over 700 LC-MS runs, including adequate replicates allowing robust statistics and covering over nearly 10 different data formats, including scanning quadrupole and ion mobility enabled acquisitions. Datasets are available via ProteomeXchange (PXD028735).

Impact of Measurement Protocol on ICP-MS Data Quality Objectives: Part II

The first part of this article focused on the fundamental principles of a scanning quadrupole and how measurement protocol can be optimized based on the data quality objectives of the analysis and in particular the compromise between limit of detection and sample throughput. Part 2 looks at different ways to assess detection capability when processing continuous signals generated by a conventional sample introduction system, and also transient signals produced by different types of sampling methods such as chromatographic separation techniques and nanoparticle size studies.

Data-Independent Identification of Suspected Organic Pollutants Using Gas Chromatography-Atmospheric Pressure Chemical Ionization-Mass Spectrometry.

The identity of an unknown environmental pollutant is reflected by the mass and dissociation chemistry of its (quasi)molecular ion. Gas chromatography-atmospheric pressure chemical ionization-mass spectrometry (GC-APCI-MS) increases the yield of molecular ions (compared to conventional electron ionization) by collisional cooling. Scanning quadrupole data-independent acquisition (SQDIA) permits unbiased, unattended selection of (quasi)molecular ions and acquisition of structure-diagnostic collision-induced dissociation mass spectra, while minimizing interferences, by sequentially cycling a quadrupole isolation window through the m/z range. This study reports on the development of a suspect screening method based on industrial compounds with bioaccumulation potential. A comparison of false and correct identifications in a mixed standard containing 30 analytes suggests that SQDIA results in a markedly lower false-positive rate than standard DIA: 5 for SQDIA and 82 for DIA. Electronic waste dust was analyzed using GC and quadrupole time-of-flight MS with APCI and SQDIA acquisition. A total of 52 brominated, chlorinated, and organophosphorus compounds were identified by suspect screening; 15 unique elemental compositions were identified using nontargeted screening; 17 compounds were confirmed using standards and others identified to confidence levels 2, 3, or 4. SQDIA reduced false-positive identifications, compared to experiments without quadrupole isolation. False positives also varied by class: 20% for Br, 37% for Cl, 75% for P, and >99% for all other classes. The structure proposal of a previously reported halogenated compound was revisited. The results underline the utility of GC-SQDIA experiments that provide information on both the (quasi)molecular ions and its dissociation products for a more confident structural assignment.

Effect of polyvinylpyrrolidone on the catalytic properties of Pd/γ-Fe2O3 in phenylacetylene hydrogenation

Maghemite nanoparticles modified with polyvinylpyrrolidone were synthesized using the chemical co-precipitation method. Palladium ions have then been immobilized on the PVP/γ-Fe2O3 magnetic support. The Pd-PVP/γ-Fe2O3 catalyst obtained was characterized using X-ray diffraction, thermogravimetry coupled with differential scanning calorimetry and quadrupole mass spectrometry, scanning electron microscopy combined with energy dispersive X-ray analysis, transmission electron microscopy, nitrogen adsorption–desorption and vibrating sample magnetometry. Morphology, microstructure, particle sizes and textural properties of the Pd-PVP/γ-Fe2O3 were compared with those of the unmodified Pd/γ-Fe2O3 catalyst, synthesized using the same method. The polymer has affected the size of γ-Fe2O3 nanoparticles and their agglomeration, forming compact microstructure with decreased mesopores (4.5 nm). Palladium nanoparticles with size of 3–5 nm were found both on the surface of the PVP/γ-Fe2O3 particles (6–10 nm) and inside the pores formed by them. The Pd-PVP/γ-Fe2O3 has demonstrated improved catalytic properties in phenylacetylene hydrogenation under mild conditions of 40 °C and 0.1 MPa, compared to Pd/γ-Fe2O3 and similar catalysts prepared using polyethylene glycol and pectin. The hydrogenation rate of C–C triple bond on Pd-PVP/γ-Fe2O3 achieved 2.8 × 10–6 mol s−1 and selectivity to styrene was 92%. The catalyst showed weak ferromagnetic and soft magnetic properties (MS = 51 emu g−1, Mr = 5.4 emu g−1, and HC = 71 Oe) and, therefore, can be easily recovered with an external magnet and reused for at least 11 runs without significant degradation in the catalytic activity.

Development of a C18 Supercritical Fluid Chromatography-Tandem Mass Spectrometry Methodology for the Analysis of Very-Long-Chain Polyunsaturated Fatty Acid Lipid Matrices and Its Application to Fish Oil Substitutes Derived from Genetically Modified Oilseeds in the Aquaculture Sector.

Lipidomics methodologies traditionally utilize either reverse phase- or hydrophilic interaction liquid chromatography-type separations; however, supercritical fluid chromatography can offer a rapid normal phase type separation while reducing the dependence on organic solvents. However, normal phase type lipid separations typically lack pronounced intraclass separation, which is problematic for complex lipidomes containing very-long-chain polyunsaturated fatty acids, especially those from genetically modified organisms. A high-strength silica C18 method was developed, which benefitted from discrete class separation, as well as displaying intraclass selectivity sufficient for profiling flesh of salmon fed with a diet supplemented with oil from the genetically engineered oilseed Camelina sativa, a terrestrial oilseed with a fish oil-type profile. Salmon fed a diet containing this Camelina oil were found to have flesh enriched in triacylglycerols and phospholipids containing 18:3, 20:5, and 22:6, whereas salmon fed the control diet were differentiated by shorter chain plant-type fatty acids integrated within complex lipids. Coupled with active scanning quadrupole technology, data acquisition was enhanced, allowing for fragmentation data to be acquired in a data independent fashion, permitting acyl chain identification of resolved isomers. Therefore, we have developed a method, which is amenable for lipidomics studies of complex lipidomes, specifically those altered by synthetic biology approaches.

A Bottom-Up Approach for Data Mining in Bioaromatization of Beers Using Flow-Modulated Comprehensive Two-Dimensional Gas Chromatography/Mass Spectrometry

In this study, we report the combination of comprehensive two-dimensional gas chromatography (GC×GC) with multivariate pattern recognition through template matching for the assignment of the contribution of Brazilian Ale 02 yeast strain to the aroma profile of beer compared with the traditional Nottingham yeast. Volatile organic compounds (VOC) from two beer samples, which were fermented with these yeast strains were sampled using headspace solid-phase microextraction (HS-SPME). The aroma profiles from both beer samples were obtained using GC×GC coupled to a fast scanning quadrupole mass spectrometer. Data processing performed through multiway principal components analysis succeeded in separating both beer samples based on yeast strain. The execution of a simple and reliable procedure succeeded and identified 46 compounds as relevant for sample classification. Furthermore, the bottom-up approach spotted compounds found exclusively in the beer sample fermented with the Brazilian yeast, highlighting the bioaromatization properties introduced to the aroma profile by this yeast strain.

Transverse Twiss parameter measurement with space charge in CADS Injector I

The test stand of CADS Injector Ⅰ is built at the Institute of High Energy Physics(IHEP). The 3.2 MeV, 10 mA beam from the RFQ will be transported and matched by medium energy transport line (MEBT1) to the superconductive accelerating section. To minimize the beam loss from mismatch, the Twiss parameters at the exit of RFQ should be got. The method of scanning quadrupole strength with wire scanner is used in CADS Injector Ⅰ. As to the data process, the traditional method based on matrix will bring errors for high intensity accelerators, especially at low energy when the space charge force is very strong. This paper introduces the traditional method and the new method considering space charge effect, which is based on MOGA. The result proves that the space charge should be considered when calculating the Twiss parameters for high intensity low energy accelerators.

Scanning Quadrupole Data-Independent Acquisition, Part A: Qualitative and Quantitative Characterization.

A novel data-independent acquisition (DIA) method incorporating a scanning quadrupole in front of a collision cell and orthogonal acceleration time-of-flight mass analyzer is described. The method has been characterized for the qualitative and quantitative label-free proteomic analysis of complex biological samples. The principle of the scanning quadrupole DIA method is discussed, and analytical instrument characteristics, such as the quadrupole transmission width, scan/integration time, and chromatographic separation, have been optimized in relation to sample complexity for a number of different model proteomes of varying complexity and dynamic range including human plasma, cell lines, and bacteria. In addition, the technological merits over existing DIA approaches are described and contrasted. The qualitative and semiquantitative performance of the method is illustrated for the analysis of relatively simple protein digest mixtures and a well-characterized human cell line sample using untargeted and targeted search strategies. Finally, the results from a human cell line were compared against publicly available data that used similar chromatographic conditions but were acquired with DDA technology and alternative mass analyzer systems. Qualitative comparison showed excellent concordance of results with >90% overlap of the detected proteins.

Scanning Quadrupole Data-Independent Acquisition, Part B: Application to the Analysis of the Calcineurin-Interacting Proteins during Treatment of Aspergillus fumigatus with Azole and Echinocandin Antifungal Drugs.

Calcineurin is a critical cell-signaling protein that orchestrates growth, stress response, virulence, and antifungal drug resistance in several fungal pathogens. Blocking calcineurin signaling increases the efficacy of several currently available antifungals and suppresses drug resistance. We demonstrate the application of a novel scanning quadrupole DIA method for the analysis of changes in the proteins coimmunoprecipitated with calcineurin during therapeutic antifungal drug treatments of the deadly human fungal pathogen Aspergillus fumigatus. Our experimental design afforded an assessment of the precision of the method as demonstrated by peptide- and protein-centric analysis from eight replicates of the study pool QC samples. Two distinct classes of clinically relevant antifungal drugs that are guideline recommended for the treatment of invasive "aspergillosis" caused by Aspergillus fumigatus, the azoles (voriconazole) and the echinocandins (caspofungin and micafungin), which specifically target the fungal plasma membrane and the fungal cell wall, respectively, were chosen to distinguish variations occurring in the proteins coimmunoprecipitated with calcineurin. Novel potential interactors were identified in response to the different drug treatments that are indicative of the possible role for calcineurin in regulating these effectors. Notably, treatment with voriconazole showed increased immunoprecipitation of key proteins involved in membrane ergosterol biosynthesis with calcineurin. In contrast, echinocandin (caspofungin or micafungin) treatments caused increased immunoprecipitation of proteins involved in cell-wall biosynthesis and septation. Furthermore, abundant coimmunoprecipitation of ribosomal proteins with calcineurin occurred exclusively in echinocandins treatment, indicating reprogramming of cellular growth mechanisms during different antifungal drug treatments. While variations in the observed calcineurin immunoprecipitated proteins may also be due to changes in their expression levels under different drug treatments, this study suggests an important role for calcineurin-dependent cellular mechanisms in response to antifungal treatment of A. fumigatus that warrants future studies.

Lipid profiling of complex biological mixtures by liquid chromatography/mass spectrometry using a novel scanning quadrupole data-independent acquisition strategy.

A novel data-independent acquisition method is detailed that incorporates a scanning quadrupole in front of an orthogonal acceleration time-of-flight (TOF) mass analyser. This approach is described and the attributes are compared and contrasted to other DIA approaches. Specific application of the method to both targeted and untargeted lipidomic identification strategies is discussed, with data from both shotgun and LC separated lipidomics experiments presented. The benefits of the fast quadrupole scanning technique are highlighted, and include improvements in speed and specificity for complex mixtures providing high quality qualitative and quantitative data. In particular the high specificity afforded by the scanning quadrupole improves qualitative information for lipid identification.

Faster, More Reproducible DESI-MS for Biological Tissue Imaging

A new, more robust sprayer for desorption electrospray ionization (DESI) mass spectrometry imaging is presented. The main source of variability in DESI is thought to be the uncontrolled variability of various geometric parameters of the sprayer, primarily the position of the solvent capillary, or more specifically, its positioning within the gas capillary or nozzle. If the solvent capillary is off-center, the sprayer becomes asymmetrical, making the geometry difficult to control and compromising reproducibility. If the stiffness, tip quality, and positioning of the capillary are improved, sprayer reproducibility can be improved by an order of magnitude. The quality of the improved sprayer and its potential for high spatial resolution imaging are demonstrated on human colorectal tissue samples by acquisition of images at pixel sizes of 100, 50, and 20 μm, which corresponds to a lateral resolution of 40–60 μm, similar to the best values published in the literature. The high sensitivity of the sprayer also allows combination with a fast scanning quadrupole time-of-flight mass spectrometer. This provides up to 30 times faster DESI acquisition, reducing the overall acquisition time for a 10 mm × 10 mm rat brain sample to approximately 1 h. Although some spectral information is lost with increasing analysis speed, the resulting data can still be used to classify tissue types on the basis of a previously constructed model. This is particularly interesting for clinical applications, where fast, reliable diagnosis is required.Graphical ᅟ

Successive Resonances for Ion Ejection at Arbitrary Frequencies in an Ion Trap.

The use of successive resonances for ion ejection is demonstrated here as a method of scanning quadrupole ion traps with improvement in both resolution and sensitivity compared with single frequency resonance ejection. The conventional single frequency resonance ejection waveform is replaced with a dual-frequency waveform. The two included frequencies are spaced very closely and their relative amplitudes are adjusted so that the first frequency that ions encounter excites them to higher amplitudes where space charge effects are less prominent, thereby giving faster and more efficient ejection when the ions come into resonance with the second frequency. The method is applicable at any arbitrary frequency, unlike double and triple resonance methods. However, like double and triple resonance ejection, ejection using successive resonances requires the rf and AC waveforms to be phase-locked in order to retain mass accuracy and mass precision. The improved performance is seen in mass spectra acquired by rf amplitude scans (resonance ejection) as well as by secular frequency scans. Graphical Abstract ᅟ.

Selective Identification of Organic Iodine Compounds Using Liquid Chromatography–High Resolution Mass Spectrometry

A method to selectively and sensitively detect organic iodine compounds and identify their structures has been developed using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Using extracted ion chromatograms of product ions (iodine ion) collected on a rapid scanning quadrupole orbitrap mass spectrometer, the retention times of the unknown organic iodine compounds were determined, and the structural information were acquired according to the MS/MS experiments and the matching with reference standards. We have demonstrated the application of this method by identifying unknown organic iodine compounds in seaweed. A total of 28 possible organic iodine peaks were discovered, among them, the accurate mass and element composition of the corresponding precursor ions were identified for 12 peaks, and molecular structures were confirmed for 4 peaks, which were 3-iodo-L-tyrosine, 3,5-diiodo-L-tyrosine, 4-iodophenol, and 2-iodobenzoic acid. This method is expected to lead to the future discovery of new organic iodine compounds via LC-HRMS in different environmental samples, which is crucial for understanding the iodine biogeochemical cycling.

Liquid chromatography, in combination with a quadrupole time-of-flight instrument, with sequential window acquisition of all theoretical fragment-ion spectra acquisition: validated quantification of 39 antidepressants in whole blood as part of a simultaneous screening and quantification procedure.

Sequential window acquisition of all theoretical fragment ion spectra (SWATH) is a data independent acquisition (DIA) method for very fast scanning quadrupole time-of-flight (QTOF) instruments. SWATH repeatedly cycles through 28 consecutive 20 Da precursor isolation windows detecting all precursor ions and fragments MS ALL like and yet fast enough to generate more than 10 data points over the chromatographic peak. It was already shown in previous publications that SWATH, despite its wide Q1 windows, allows the identification of different substances and that SWATH has a higher identification rate than data dependent acquisition approaches. The aim of this study was a proof of concept study whether these same data sets can also enable validated quantification according to international guidelines, exemplified for 39 antidepressants. The validation included recovery, matrix effects, process efficiency, ion suppression, and enhancement of coeluting ions, selectivity, accuracy, precision, and stability. The method using SWATH acquisition proved to be selective, sensitive, accurate, and precise enough for 33 out of the 39 antidepressants. The applicability of SWATH for screening and validated quantification in the same run was successfully tested with authentic whole blood samples containing different antidepressants and other drugs thus proving the QUAL/QUAN abilities of SWATH. In an additional systematic investigation, it could be shown that calibration curves injected a few days after or before the actual sample can be used for quantification with acceptable accuracy.

Elemental Bioimaging by Means of Fast Scanning Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry.

One of the most common setups for elemental bioimaging, the hyphenation of a laser ablation (LA) system and an inductively coupled plasma mass spectrometer (ICP-MS), was expanded by adding full scan mass spectrometric information as another dimension of information. While most studies deal with the analysis of typically not more than up to 10 isotopes per scan cycle, a fast scanning quadrupole mass analyzer was utilized to record the full mass spectrum of interest in this work. Mass-to-charge ratios from 6 to 250 were observed within one cycle. Besides the x- and y-position on the ablated sample and the intensity, the m/z-ratio served as fourth variable for each pixel of the obtained data, closing thereby the gap between "inorganic" and "organic" mass spectrometric imaging techniques. The benefits of this approach include an improved control of interferences, the discovery of unexpected elemental distributions, the possibility to plot isotopic ratios, and to integrate the intensities of a certain number of mass channels recorded for each isotope, thus virtually increasing sensitivity. The respective data are presented for dried droplets as well as embedded animal and human tissue slices. Limits of detection were calculated and found to be in accordance with counting statistics. A dedicated software macro was developed for data manipulation prior to common evaluation and image creation.

Comprehensive two-dimensional gas chromatography with mass spectrometry applied to the analysis of volatiles in artichoke (Cynara scolymus L.) leaves

Artichoke (Cynara scolymus L.) is well known due to its medicinal properties and, as a result, a large number of studies have been conducted to determine the chemical constituents produced by the plant. However, investigations were mainly focused on the non-volatile compounds, while the volatile constituents remained largely neglected. This study was aimed at obtaining a deeper understanding of the volatile composition of artichoke. For this propose, comprehensive two-dimensional gas chromatography coupled to a rapid scanning quadrupole mass spectrometer (GC×GC/qMS) and retention indices were used to improve the chemical characterization of volatiles from leaves. A total of 130 compounds were found, 109 of which are reported for the first time in C. scolymus L., including oxygenated monoterpenes, sesquiterpenes, oxygenated sesquiterpenes, norisoprenoids, lactones, alcohols, ketones and aldehydes. The major compounds were 1-octen-3-one (3.85%), (E)-2-hexenal (3.75%), benzene acetaldehyde (2.90%), 2,2-dimethyl-4-pentenal (2.81%), β-ionone (1.94%), furfural (1.65%), (E)-β-damescenone (1.59%), α-methyl-γ-butirolactone (1.53%), benzaldehyde (1.47%) and dihydroactinidiolide (1.44%). The comprehensive GC×GC/qMS approach enabled a greater number of analytes to be identified, approximately four times higher than that obtained for GC/qMS. Additionally, the results imply that artichoke leaves are a potential source of volatile bioactive compounds.

Use of Narrow Mass-Window, High-Resolution Extracted Product Ion Chromatograms for the Sensitive and Selective Identification of Protein Modifications

Protein modifications, including oxidative modifications, glycosylations, and oxidized lipid-protein adducts, are becoming increasingly important as biomarkers and in understanding disease etiology. There has been a great deal of interest in mapping these on Apo B100 from low density lipoprotein (LDL). We have used extracted ion chromatograms of product ions generated using a very narrow mass window from high-resolution tandem mass spectrometric data collected on a rapid scanning quadrupole time-of-flight (QTOF) instrument, to selectively and sensitively detect modified peptides and identify the site and nature of a number of protein modifications in parallel. We have demonstrated the utility of this method by characterizing for the first time oxidized phospholipid adducts to LDL and human serum albumin and for the detection of glycosylation and kynurenin formation from the oxidation of tryptophan residues in LDL.

Evaluation of comprehensive two-dimensional gas chromatography coupled to rapid scanning quadrupole mass spectrometry for quantitative analysis

Comprehensive two-dimensional gas chromatography (GC×GC) is a powerful technique that provides excellent separation and identification of analytes in highly complex samples with considerable increase in GC peak capacities. However, since second dimension analyses are very fast, detectors with a rapid acquisition rate are required. Over the last years, quite a number of studies have discussed the potential and limitations of the combination GC×GC with a variety of quadrupole mass spectrometers. The present research focuses on the evaluation of qMS effectiveness at a 10,000-amu/s scan speed and 20-Hz scan frequency for the identification (full scan mode acquisition-TIC) and quantification (extracted ion chromatogram) of target pesticide residues in tomato samples. The following MS parameters have been evaluated: number of data points per peak, mass spectrum quality, peak skewing, and sensitivity. The validated proposed GC×GC/qMS method presented satisfactory results in terms of repeatability (coefficient of variation lower than 15%), accuracy (84–117%), and linearity (ranging from 25 to 500ng/g), while significant enhancement in sensitivity was observed (a factor of around 10) under scan conditions.