Extension of the two-dimensional mass channel cluster plot method to fast separations utilizing low thermal mass gas chromatography with time-of-flight mass spectrometry

Implementation of a data reduction and visualization method for use with high-speed gas chromatography and time-of-flight mass spectrometry (GC-TOFMS) is reported. The method, called the “2D m/z cluster method” facilitates analyte detection, deconvolution, and identification, by accurately measuring peak widths and retention times using a fast TOFMS sampling frequency (500 Hz). Characteristics and requirements for high speed GC are taken into consideration: fast separations with narrow peak widths and high peak capacity, rapid data collection rate, and effective peak deconvolution. Transitioning from standard GC (10–60+ minute separations) to fast GC (1–10 min separations) required consideration of how to properly analyze the data. This report validates use of the 2D m/z cluster method with newly developed GC technology that produces ultra-fast separations (∼1 min) with narrow analyte peak widths. Low thermal mass gas chromatography (LTM-GC) operated at a heating rate of 250 °C/min coupled to a LECO Pegasus III TOFMS analyzed a 115 component test mixture in 120 s with peak widths-at-base, w_b (4σ), of 350 ms (average) to produce a separation with a high peak capacity, n_c ∼ 340 (at unit resolution R_s = 1). The 2D m/z cluster method is shown to separate overlapped analytes to a limiting R_s ∼ 0.03, so the effective peak capacity was increased nearly 30-fold to n_c ∼10,000 in the 120 s separation. The method, when coupled with LTM-GC-TOFMS, is demonstrated to provide unambiguous peak rank (i.e. the number of analytes per overlapped peak in the total ion current (TIC)), by visualizing locations of pure and chromatographically overlapped m/z. Hence, peak deconvolution and identification using MCR-ALS (multivariate curve resolution – alternating least squares) is demonstrated.     

Utility of peak shape analyses in determining unresolved interferences in exact mass measurements at low resolution

Low resolution methods can provide exact mass data comparable to that obtained with high resolution instrumentation and offer potential advantages in throughput and robustness. However, low resolution exact mass techniques have realized limited use largely because of the possibility of errors caused by unresolved interferences. Here the utility of statistical peak shape analysis for determining unresolved interferences at low resolution is considered. Equations describing the effect of unresolved interferences on statistical peak shape parameters are developed and used to investigate the extent to which evaluations of peak shape can be used to reduce the likelihood of mass measurement errors. Peak shape analysis is shown to be a highly effective and sensitive method of determining unresolved interferences. Mass measurement errors resulting from undetermined interferences are found to increase with increasing relative abundance of the interfering peak, to increase with decreasing resolution, and to increase with decreasing precision in the intensity measurement. At low resolution, undetermined interferences as small as a few percent relative abundance can produce mass measurement errors in excess of 5 ppm. Peak shape analyses alone do not appear adequate to eliminate the risk of significant mass measurement errors resulting from unresolved interferences at low resolution.     

Chemometric evaluation of time-of-flight secondary ion mass spectrometry data of minerals in the frame of future in situ analyses of cometary material by COSIMA onboard ROSETTA

Chemometric data evaluation methods for time-of-flight secondary ion mass spectrometry (TOF-SIMS) have been tested for the characterization and classification of minerals. Potential applications of these methods include the expected data from cometary material to be measured by the COSIMA instrument onboard the ESA mission ROSETTA in the year 2014. Samples of the minerals serpentine, enstatite, olivine, and talc have been used as proxies for minerals existing in extraterrestrial matter. High mass resolution TOF-SIMS data allow the selection of peaks from inorganic ions relevant for minerals. Multivariate cluster analysis of peak intensity data by principal components analysis and the new method CORICO showed a good separation of the mineral classes. Classification by k nearest-neighbor classification (KNN) or binary decision trees (CART method) results in more than 90% correct class assignments in a leave-one-out cross validation.     

Theoretical and experimental study of the achievable separation power in resistive‐glass atmospheric pressure ion mobility spectrometry

We present a detailed investigation of the performance of our previously reported nanoelectrospray high‐resolution resistive‐glass atmospheric pressure drift tube ion mobility spectrometer constructed with monolithic resistive‐glass desolvation and drift regions. Using experimental spectral data and theoretical pulse width and diffusion variables, we compare theoretical and experimental resolving powers achievable under a variety of field strengths and ion gate pulse widths. The effects of instrumental and operational parameters on the resolution achievable in chromatographic terms are also discussed. Following characterization of the separation power of the instrument, experimental spectral peak width data is fitted by a least‐squares procedure to a pre‐existing semi‐empirical model developed to study contributions to peak width other than initial pulse width and diffusional broadening. The model suggests possible contributions to the final measured peak width from electric field inhomogeneity and minor contributions from instrumental parameters such as anode size, anode‐to‐anode grid distance and drift gas flow rate. The model also reveals an unexpected ion gate width dependence on the final measured peak width that we attribute to non‐ideal performance of the Bradbury‐Nielsen ion gate and limitations in the design of our pulsing‐electronics. Copyright © 2010 John Wiley & Sons, Ltd.     

Efficiency for close geometries and extended sources of a p-type germanium detector with low-energy sensitivity

Typically, germanium detectors designed to have good sensitivity to low-energy photons and good efficiency at high energies are constructed from n-type crystals with a boron-implanted outer contact. These detectors usually exhibit inferior resolution and peak shape compared to ones made from p-type crystals. To overcome the resolution and peak-shape deficiencies, a new method of construction of a germanium detector element was developed. This has resulted in a gamma-ray detector with high sensitivity to photon energies from 14 keV to 2 MeV, while maintaining good resolution and peak shape over this energy range. Efficiency measurements, done according to the draft IEEE 325-2004 standard, show efficiencies typical of a GMX or n-type detector at low energies. The detectors are of large diameter suitable for counting extended samples such as filter papers. The Gaussian peak shape and good resolution typical of a GEM or p-type are maintained for the high count rates and peak separation needed for activation analysis.     

Optimisation of high-performance liquid chromatography with diode array detection using an automatic peak tracking procedure based on augmented iterative target transformation factor analysis

An automated method for the optimisation of high-performance liquid chromatography is developed. First of all, the sample of interest is analysed with various eluent compositions. All obtained data are combined into one augmented data matrix. Subsequently, augmented iterative target transformation factor analysis performs the integrated tasks of curve resolution and peak tracking. Since this type of curve resolution processes all data at once, it can deal with strong peak overlap and reveal the correspondence of compounds between runs, i.e. peak tracking. The retention time and peak width at half height for each component of the sample are determined for every eluent composition. Next, models are built for the retention time and the peak width at half height. These models are used to predict the resolution and the analysis time for each point in factor space. Finally, a multi-criterion decision-making method, Pareto optimality, is used to find the optimum. The method completes all calculations within a few minutes and without user intervention. By means of this procedure, a mixture of three benzodiazepines is successfully separated using a ternary mobile phase. There are two requirements for the automated optimisation method to work correctly. Firstly, all components of the sample must have sufficiently different spectra. Secondly, each compound should have the same spectrum under all experimental conditions.     

On the use of computer assisted resolution of non-separable peaks in a congener specific polybrominated diphenyl ether capillary gas chromatographic analysis

The use of computer assisted deconvolution for chromatographically not separated peaks in the analysis of polybrominated diphenyl ethers (PBDEs) by capillary gas chromatography (CGC) was studied. Twenty-two not separated clusters containing 48 overlapped PBDEs were registered in the separation of a sample containing 122 PBDE congeners on a semipolar poly(8%-phenyl-92%-dimethyl)siloxane column. There were only two clusters in which overlapped PBDEs differ in the number of bromine atoms {PBDE 126(5Br) co-elutes with 154(6Br) and PBDE 105(5Br) co-elutes with 144(6Br)} and therefore their mass spectra could be successfully used for deconvolution purposes. In 22 other clusters 46 isomeric PBDEs with identical mass spectra overlapped and for their resolution a computer assisted deconvolution procedure using a commercial available program was used. A published procedure for the estimation of minimum number of peaks in a peak cluster for which the data found by deconvolution are reliable, has been adapted. Using this procedure, for eight overlapped PBDE full peak data (single peak retention times and peak areas) were extracted.     

High resolution measurements of kinetic energy release distributions of neon, argon, and krypton cluster ions using a three sector field mass spectrometer

Using a newly constructed three sector field mass spectrometer (resulting in a BE1E2 field configuration) we have measured the kinetic energy release distributions of neon, argon, and krypton cluster ions. In the present study we used the first two sectors, B and E1, constituting a high resolution mass spectrometer, to select the parent ions in terms of mass, charge, and energy, and studied the decay of those ions in the third field free region. Due to the improved mass resolution we were able to extend earlier studies carried out with a two sector field machine, where an upper size limit arose from the fact that several isotopomers contribute to a decaying parent ion beam when the cluster size exceeds a certain value. Furthermore we developed a new data analysis. It allows us to model also fragment ion peaks that are a superposition of different decay reactions and thus we can determine the average kinetic energy release for all decay reactions of a given cluster ion. In a further step we used these results to determine the binding energies of cluster ions Rg(n) (n> or =10) by applying finite heat bath theory. The smaller sizes have not been included in this analysis, because the validity of finite heat bath theory becomes questionable below n approximately 10. The present average kinetic energy releases and binding energies are compared with other experiments and various calculations.     

Utilizing a constant peak width transform for isothermal gas chromatography

A computational approach to partially address the general elution problem (GEP), and better visualize, isothermal gas chromatograms is reported. The theoretical computational approach is developed and applied experimentally. We report a high speed temporally increasing boxcar summation (TIBS) transform that, when applied to the raw isothermal GC data, converts the chromatographic data from the initial time domain (in which the peak widths in isothermal GC increase as a function of their retention factors, k), to a data point based domain in which all peaks have the same peak width in terms of number of points in the final data vector, which aides in preprocessing and data analysis, while minimizing data storage size. By applying the TIBS transform, the resulting GC chromatogram (initially collected isothermally), appears with an x-axis point scale as if it were instrumentally collected using a suitable temperature program. A high speed GC isothermal separation with a test mixture containing 10 compounds had a run time of ～25 s. The peak at a retention factor k ～0.7 had a peak width of ～55 ms, while the last eluting peak at k ～89 (i.e., retention time of ～22 s) had a peak width of ～2000 ms. Application of the TIBS transform increased the peak height of the last eluting peak 45-fold, and S/N ～20-fold. All peaks in the transformed test mixture chromatogram had the width of an unretained peak, in terms of number of data points. A simulated chromatogram at unit resolution, studied using the TIBS transform, provided additional insight into the benefits of the algorithm.     

Multivariate curve resolution in liquid chromatography—resolving two-way multi-component data using a Varimax extended rotation

The Varimax extended rotations (VER) have been proposed as a new method to mathematically resolve severely overlapped peaks in chromatographic experiments that produce bilinear data. VER employs a four-step procedure to determine the relative concentration and identity of the components that comprise a severely overlapped chromatographic peak. In the first step, the data are pre-processed to ensure that they are in a form suitable for multivariate curve resolution. The second step involves principal component analysis, which reduces the dimensionality of the data matrix while simultaneously retaining the information present in the data. In the third step, a new coordinate system is developed for the data using a Varimax rotation followed by a so-called extended rotation, which assists in identifying the so-called pure regions in the peak. Identifying these regions is crucial to rotating the concentration and spectral matrices towards a solution. The fourth step utilizes alternating least squares (ALS) to improve the estimates of the concentration and spectral profiles of each component. Results from real and simulated data are used to illustrate the efficacy and simplicity of the proposed method.     

Development of a resolution metric for comprehensive two-dimensional chromatography

A new resolution metric for two-dimensional chromatography is proposed and tested. This resolution measurement is based on the concept of the (one-dimensional) valley-to-peak ratio, which has been adapted and modified for two-dimensional chromatography. Two questions are considered related to the computation of the resolution of a given (two-dimensional) peak. First, the concept of peak neighbourhood is revised, since it changes drastically from one- to two-dimensional chromatography. In a chromatogram resulting from a two-dimensional analysis, one peak may be surrounded by more than two neighbouring peaks. However, the neighbouring peaks can be remote from the peak or some interfering peaks may be in between. In these cases, it is not meaningful to compute the resolution between them. A method is proposed to determine whether a resolution measurement between two two-dimensional peaks is reasonable. Second, a measurement of the valley-to-peak ratio in two-dimensional chromatography is proposed. The measurement is based on the concept of the saddle point (which is defined for two-dimensional surface plots). A study of the correlation of the valley-to-peak ratio with the error obtained for quantification is presented. The new metric can be used as an estimator of the quantification errors. Also, valley-to-peak ratios can be calculated for one or more target peak(s) to estimate the separation quality of the entire chromatogram. This makes the proposed measurement suitable for optimisation purposes. Although the algorithm was developed for GC x GC, preliminary studies suggested that its application to other two-dimensional separation methods (e.g. LC x LC) should only require minor modification (if any).     

Deconvolution of isobaric interferences in mass spectra

The concept of isobar deconvolution using the mass domain and signal intensity based domains is described. The intensity domain-based approach employs the reconstruction of the observed isotope pattern from the isolated patterns of the isobaric species. The quantitative information is adjusted with the use of the least squares algorithm. The mass domain-based approach employs signal deconvolution by forming Gaussian components for which the peak width and position can be predicted a priori. The latter method is applicable to medium resolution instruments, such as TOF-MS, while the pattern reconstruction approach is applicable also to low resolution instrumentation, such as quadrupole-based ICP-MS or GC/MS. An example of CH(z)Se (z = 0-4) cluster analysis in dimethyl diselenide mass spectra is given to illustrate the concepts underlying both approaches.     

A wavelet‐PCA method saves high mass resolution information in data treatment of SIMS molecular depth profiles

A detailed depth characterization of multilayered polymeric systems is a very attractive topic. Currently, the use of cluster primary ion beams in time‐of‐flight secondary ion mass spectrometry allows molecular depth profiling of organic and polymeric materials. Because typical raw data may contain thousands of peaks, the amount of information to manage grows rapidly and widely, so that data reduction techniques become indispensable in order to extract the most significant information from the given dataset. Here, we show how the wavelet‐based signal processing technique can be applied to the compression of the giant raw data acquired during time‐of‐flight secondary ion mass spectrometry molecular depth‐profiling experiments. We tested the approach on data acquired by analyzing a model sample consisting of polyelectrolyte‐based multilayers spin‐cast on silicon. Numerous wavelet mother functions and several compression levels were investigated. We propose some estimators of the filtering quality in order to find the highest ‘safe’ approximation value in terms of peaks area modification, signal to noise ratio, and mass resolution retention. The compression procedure allowed to obtain a dataset straightforwardly ‘manageable’ without any peak‐picking procedure or detailed peak integration. Moreover, we show that multivariate analysis, namely, principal component analysis, can be successfully combined to the results of the wavelet‐filtering, providing a simple and reliable method for extracting the relevant information from raw datasets. Copyright © 2016 John Wiley & Sons, Ltd.     

Designing polymer matrix for microchip-based double-stranded DNA capillary electrophoresis

An optimization strategy for ternary solvent-strength gradient elution RP chromatography is described in which a two-dimensional model of gradient time (2 levels) against ternary proportions of organic modifiers (4 levels) was constructed. From the resolution surface the optimum ratio of organic modifiers could be selected. Excellent retention time and acceptable peak width and resolution simulations were obtained. The separation could be further optimized from the same input data by using a standard one-dimensional model in order to optimize for gradient slope, duration and shape. Excellent retention time and acceptable peak width and resolution simulations were obtained (< 1, 2 and 6% error, respectively).     

Resolution of the Embedded Chromatographic Peaks by Modified Orthogonal Projection Resolution and Entropy Maximization Method

ABSTRACT

The embedded chromatographic peaks usually can not be completely resolved by conventional multivariate resolution methods. The resolution condition of a certain component in two-way data is first reviewed. A modified orthogonal projection resolution (OPR) algorithm and new entropy maximization (EM) method are then proposed to resolve embedded chromatographic peaks in this paper. The modified OPR algorithm performs more precisely than conventional orthogonal projection resolution algorithm in resolving the chromatography of minor peak. The entropy criterion defined on the differential chromatography could obtain an approximate solution in resolution of the major chromatographic peak. Simulated and real data show that the modified OPR and entropy maximization (EM) methods perform well in solving the embedded problem.     

Inner chromatogram projection (ICP) for resolution of GC-MS data with embedded chromatographic peaks

The chromatographic peak located inside another peak in the time direction is called an embedded or inner peak in contradistinction with the embedding peak, which is called an outer peak. The chemical components corresponding to inner and outer peaks are called inner and outer components, respectively. This special case of co-eluting chromatograms was investigated using chemometric approaches taking GC-MS as an example. A novel method, named inner chromatogram projection (ICP), for resolution of GC-MS data with embedded chromatographic peaks is derived. Orthogonal projection resolution is first utilized to obtain the chromatographic profile of the inner component. Projection of the two-way data matrix columnwise-normalized along the time direction to the normalized profile of the inner component found is subsequently performed to find the selective m/z points, if they exist, which represent the chromatogram of the outer component by itself. With the profiles obtained, the mass spectra can easily be found by means of a least-squares procedure. The results for both simulated data and real samples demonstrate that the proposed method is capable of achieving satisfactory resolution performance not affected by the shapes of chromatograms and the relative positions of the components involved.     

Richardson–Lucy deconvolution of reflection electron energy loss spectra

A procedure for deconvolving the energy spread introduced by the primary beam and the analyzer in a reflection electron energy loss spectrum (REELS) has been developed. The procedure is based on the Richardson–Lucy (RL) algorithm. The approach has been successfully tested on experimental spectra by comparison with spectra with an inherent high‐energy resolution. As a typical result, it was found that the effective energy resolution of spectra with a full width half maximum (FWHM) of the elastic peak of ～1.5 eV in the raw experimental data can be reduced to ～0.7 eV in the deconvoluted spectra. Copyright © 2009 John Wiley & Sons, Ltd.     

直观推导式演进特征投影法对环境样本中多环芳烃的定性定量分析

基于新近发展的直观推导式演进特征投影法(HELP), 本文提出了一个对二维数据进行同时定性定量的分析方法, 并将其成功地用于环境样本中多环芳烃化合物定量解析。对于一维色谱难以定量的重叠峰, HELP方法充分利用色谱、光谱两方面的选择性信息, 得到了具有真实物理意义的唯一解。在定性分辨结果的基础上, 本文还提出了三种可能的定量方法。这种二维数据的解析新方法, 能大幅度地降低对色谱分离条件的要求, 可直接用于复杂实际样本的定性定量分析。     

Size of elementary clusters and process period in silver nanoparticle formation

The time dependence of small-angle X-ray scattering (SAXS) curves for silver nanoparticle formation was followed in situ at a time resolution of 0.18 ms, which is 3 orders of magnitude higher than that used in previous reports (ca. 100 ms). The starting materials were silver nitrate solutions that were reacted with reducing solutions containing trisodium citrate. The SAXS analyses showed that silver nanoparticles were formed in three distinct periods from a peak diameter of ca. 0.7 nm (corresponding to the size of a Ag(13) cluster) during the nucleation and the early growth period. The Ag(13) clusters are most likely elementary clusters that agglomerate to form silver nanoparticles.