Differential Ion Mobility Separations in up to 100 % Helium Using Microchips

The performance of differential IMS (FAIMS) analyzers is much enhanced by gases comprising He, especially He/N₂ mixtures. However, electrical breakdown has limited the He fraction to ~50 %–75 %, depending on the field strength. By the Paschen law, the threshold field for breakdown increases at shorter distances. This allows FAIMS using chips with microscopic channels to utilize much stronger field intensities (E) than “full-size” analyzers with wider gaps. Here we show that those chips can employ higher He fractions up to 100 %. Use of He-rich gases improves the resolution and resolution/sensitivity balance substantially, although less than for full-size analyzers. The optimum He fraction is ~80 %, in line with first-principles theory. Hence, one can now measure the dependences of ion mobility on E in pure He, where ion-molecule cross section calculations are much more tractable than in other gases that form deeper and more complex interaction potentials. This capability may facilitate quantitative modeling of high-field ion mobility behavior and, thus, FAIMS separation properties, which would enable a priori extraction of structural information about the ions.

Implementation of Dipolar Resonant Excitation for Collision Induced Dissociation with Ion Mobility/Time-of-Flight MS

An ion mobility/time-of-flight mass spectrometer (IMS/TOF MS) platform that allows for resonant excitation collision induced dissociation (CID) is presented. Highly efficient, mass-resolved fragmentation without additional excitation of product ions was accomplished and over-fragmentation common in beam-type CID experiments was alleviated. A quadrupole ion guide was modified to apply a dipolar AC signal across a pair of rods for resonant excitation. The method was characterized with singly protonated methionine enkephalin and triply protonated peptide angiotensin I, yielding maximum CID efficiencies of 44 % and 84 %, respectively. The Mathieu q_x,y parameter was set at 0.707 for these experiments to maximize pseudopotential well depths and CID efficiencies. Resonant excitation CID was compared with beam-type CID for the peptide mixture. The ability to apply resonant waveforms in mobility-resolved windows is demonstrated with a peptide mixture yielding fragmentation over a range of mass-to-charge (m/z) ratios within a single IMS-MS analysis.

Electrochemically controlled solid-phase micro-extraction of proline using a nanostructured film of polypyrrole, and its determination by ion mobility spectrometry

We report on a fast, simple and accurate method for the determination of proline in urine samples by employing a nanostructured film of conducting polypyrrole for electrochemically controlled solid-phase microextraction, and ion mobility spectrometry (IMS) for detection. This method has the advantages of simple sample preparation and a sensitivity of IMS to proline that is higher than that for other amino acids. The calibration curve is linear in the range of 0.5–60 μg L^?1 (4–521 nmol L^?1), and the detection limit is 0.2 μg L^?1. The electrochemical potentials for uptake and release were optimized. The method was successfully applied to the clean-up and quantitation of trace amounts of proline in urine samples.

Lanthanoid complexes with thenoyltrifluoroacetone and 4-tert-butylcalix[4]arene-tetraacetic acid tetraethyl ester: synergistic extraction and separation

The solvent extraction of fourteen lanthanoid ions with thenoyltrifluoroacetone (HTTA) in combination with tetraethyl 4-tert-butylcalix[4]arene-tetraacetic acid tetraethyl ester (S) from a perchlorate medium at constant ionic strength was investigated. The extracted species were identified as the Ln(TTA)₃·S complexes by slope analysis. Equilibrium constants, parameters for extraction, and the synergistic and separation factors between two adjacent Ln(III) ions were determined.

Traveling Wave Ion Mobility Mass Spectrometry and Ab Initio Calculations of Phosphoric Acid Clusters

Positive and negative ion electrospray mass spectra obtained from 50 mM phosphoric acid solutions presented a large number of phosphoric acid clusters: [(H₃PO₄)_n?+?zH] ^z+ or [(H₃PO₄)_n – zH] ^z– , with n up to 200 and z up to 4 for positively charged clusters, and n up to 270 and z up to 7 for negatively charged cluster ions. Ion mobility experiments allowed very explicit separation of the different charge states. Because of the increased pressures involved in ion mobility experiments, dissociation to smaller clusters was observed both in the trap and transfer areas. Voltages along the ion path could be optimized so as to minimize this effect, which can be directly associated with the cleavage of hydrogen bonds. Having excluded the ion mobility times that resulted from dissociated ions, each cluster ion appeared at a single drift time. These drift times showed a linear progression with the number of phosphoric atoms for cluster ions of the same charge state. Cross section calculations were carried out with MOBCAL on DFT optimized geometries with different hydrogen locations and with three types of atomic charges. DFT geometry optimizations yielded roughly spherical structures. Our results for nitrogen gas interaction cross sections showed that values were dependent on the atomic charges definition used in the MOBCAL calculation. This pinpointed the necessity to define a clear theoretical framework before any comparative interpretations can be attempted with uncharacterized compounds.

Solvent induced phenomena in a dendronized linear polymer

The properties of a dendronized linear polymer (DP) in dilute solutions depending on solvent quality and temperature are described. The polymer has a contour length of L _c?=?1,060 nm. The sample of the fourth generation (PG4) was analyzed in the thermodynamically good solvents dioxane, chloroform, and methanol. The wormlike macromolecule has a persistence length l _p?=?7 nm in dioxane and a cross-section radius determined by small angle X-ray scattering (SAXS) of R _{c (SAXS)}?=?2.8 nm. The bulk density of PG4 determined by SAXS was compared with solution density. Evidence for substantial swelling of the cross-section was found. Toluene acts as a thermodynamically poor solvent (θ solvent). Above the θ temperature T _θ , a strong temperature dependence of the size and the Young’s modulus E was observed. Following Odijk, E/k _B T ～1 was found. Below T _θ , a regime characterized by unswelling of the wormlike chains was observed. The results suggest that DPs can be described as soft colloid filaments, which are subject to commonly observed interactions in colloidal systems. A phase diagram indicates a regime below T _θ in which fluctuations of osmotic pressure inside the filaments result in periodic undulation of the chains. In summary, introducing a dense dendritic shell around the backbone converts conventional polymers into molecular colloids.

Electromagnetic induction-assisted heating as a new method for on-line cloud point extraction of cadmium from water samples

We report on a novel method for on-line cloud point extraction (CPE) for preconcentration of cadmium ions. It is based on electromagnetic induction-assisted heating (EMIH) of iron particles in a packed bed contained in a quartz tube that acts as an on-line CPE enrichment column. The cadmium complex of 1-(2-pyridylazo)-2-naphthol is quantitatively retained by the column under the cloud point temperature with the help of EMIH. The column was then eluted with alcoholic borax buffer at room temperature and on-line coupled to FAAS. Under optimum conditions, the limit of detection (3 s_b/b) and limit of quantification (10 s_b/b) are 0.21 μg?L^?1 and 0.70 μg?L^?1 of Cd(II), respectively, and the relative standard deviation is 3.8 % (for n?=?8; at 20 ng?mL^?1). An enhancement factor of 76 is typically achieved. The correlation coefficient of the calibration graph using the present method was 0.9986. The method was successfully applied to determine Cd(II) in water samples

The Effective Temperature of Ions Stored in a Linear Quadrupole Ion Trap Mass Spectrometer

The extent of internal energy deposition into ions upon storage, radial ejection, and detection using a linear quadrupole ion trap mass spectrometer is investigated as a function of ion size (m/z 59 to 810) using seven ion-molecule thermometer reactions that have well characterized reaction entropies and enthalpies. The average effective temperatures of the reactants and products of the ion-molecule reactions, which were obtained from ion-molecule equilibrium measurements, range from 295 to 350 K and do not depend significantly on the number of trapped ions, m/z value, ion trap q _z value, reaction enthalpy/entropy, or the number of vibrational degrees of freedom for the seven reactions investigated. The average of the effective temperature values obtained for all seven thermometer reactions is 318?±?23 K, which indicates that linear quadrupole ion trap mass spectrometers can be used to study the structure(s) and reactivity of ions at near ambient temperature.

157 nm Photodissociation of Dipeptide Ions Containing N-Terminal Arginine

Twenty singly-charged dipeptide ions with N-terminal arginine were photodissociated using 157 nm light in both a linear ion-trap mass spectrometer and a MALDI-TOF-TOF mass spectrometer. Analogous to previous work on dipeptides containing C-terminal arginine, this set of samples enabled insights into the photofragmentation propensities associated with individual residues. In addition to familiar products such as a-, d-, and immonium ions, m₂ and m₂+13 ions were also observed. Certain side chains tended to cleave between their β and γ carbons without necessarily forming d- or w-type ions, and a few other ions were produced by the high-energy fragmentation of multiple bonds.

Separation of sarcosine and L-alanine isomers using corona discharge ion mobility spectrometry

The capability of corona discharge ion mobility spectrometry (CD-IMS) for separation and quantification of sarcosine and L-alanine isomers has been evaluated for the first time. Although these two compounds have the same mass and m/z values in mass spectrometer, ion mobility spectrometry was able to separate and determine them. Variables including carrier gas flow rate, injection and cell temperatures were optimized. The reduced mobilities (K ₀) of sarcosine and L-alanine were 1.96 and 1.83, respectively, based on the reduced mobility of nicotinamide. At the optimized conditions the detection limit of sarcosine and L-alanine were 0.7 and 0.9 μg/mL, respectively. The relative standard deviation (RSD) was found to be 6%. Furthermore, a sample injection port of a gas chromatograph was also modified to introduce solvent-free samples into the IMS.     

Polythiophene-coated Fe3O4 nanoparticles as a selective adsorbent for magnetic solid-phase extraction of silver(I), gold(III), copper(II) and palladium(II)

We have developed a fast method for sensitive extraction and determination of the metal ions silver(I), gold(III), copper(II) and palladium(II). Fe₃O₄ magnetic nanoparticles were modified with polythiophene and used for extraction the metal ions without a chelating agent. Following extraction, the ions were determined by flow injection inductively coupled plasma optical emission spectrometry. The influence of sample pH, type and volume of eluent, amount of adsorbent, sample volume and time of adsorption and desorption were optimized. Under the optimum conditions, the calibration plots are linear in the 0.75 to 100 μg L^?1 concentration range (R²?>?0.998), limits of detection in the range from 0.2 to 2.0 μg L^?1, and enhancement factors in the range from 70 to 129. Precisions, expressed as relative standard deviations, are lower than 4.2 %. The applicability of the method was demonstrated by the successful analysis of tap water, mineral water, and river water.

Solution Dependence of the Collisional Activation of Ubiquitin [M + 7H]7+ Ions

The solution dependence of gas-phase unfolding for ubiquitin [M + 7H]⁷⁺ ions has been studied by ion mobility spectrometry-mass spectrometry (IMS-MS). Different acidic water:methanol solutions are used to favor the native (N), more helical (A), or unfolded (U) solution states of ubiquitin. Unfolding of gas-phase ubiquitin ions is achieved by collisional heating and newly formed structures are examined by IMS. With an activation voltage of 100 V, a selected distribution of compact structures unfolds, forming three resolvable elongated states (E1-E3). The relative populations of these elongated structures depend strongly on the solution composition. Activation of compact ions from aqueous solutions known to favor N-state ubiquitin produces mostly the E1 type elongated state, whereas activation of compact ions from methanol containing solutions that populate A-state ubiquitin favors the E3 elongated state. Presumably, this difference arises because of differences in precursor ion structures emerging from solution. Thus, it appears that information about solution populations can be retained after ionization, selection, and activation to produce the elongated states. These data as well as others are discussed. Figure

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In-situ decorated gold nanoparticles on polyaniline with enhanced electrocatalysis toward dopamine

Gold nanoparticles were in-situ decorated on top of a polyaniline film (GNPs–PANI) via the direct electroreduction of the adsorbed AuCl ₄ ^- ions on a glassy carbon electrode that previously was coated with PANI by electropolymerization. The GNPs–PANI composite and the performance of the resultant sensors were investigated in some detail. The sensor was applied to the oxidation of dopamine (DA) with improved catalytic activity. Its catalytic current showed wide linear response toward dopamine ranging from 3 to 115 μM, with a low detection limit of 0.8 μM (S/N=3). In addition, the sensor exhibits easy-operation, fast response to dopamine, as well as excellent reproducibility and stability.

High Resolution MALDI Imaging Mass Spectrometry of Retinal Tissue Lipids

Matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) has the ability to provide an enormous amount of information on the abundances and spatial distributions of molecules within biological tissues. The rapid progress in the development of this technology significantly improves our ability to analyze smaller and smaller areas and features within tissues. The mammalian eye has evolved over millions of years to become an essential asset for survival, providing important sensory input of an organism’s surroundings. The highly complex sensory retina of the eye is comprised of numerous cell types organized into specific layers with varying dimensions, the thinnest of which is the 10 μm retinal pigment epithelium (RPE). This single cell layer and the photoreceptor layer contain the complex biochemical machinery required to convert photons of light into electrical signals that are transported to the brain by axons of retinal ganglion cells. Diseases of the retina, including age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy, occur when the functions of these cells are interrupted by molecular processes that are not fully understood. In this report, we demonstrate the use of high spatial resolution MALDI IMS and FT-ICR tandem mass spectrometry in the Abca4 ^–/– knockout mouse model of Stargardt disease, a juvenile onset form of macular degeneration. The spatial distributions and identity of lipid and retinoid metabolites are shown to be unique to specific retinal cell layers.

Collision-Induced Dissociation Fragmentation Inside Disulfide C-Terminal Loops of Natural Non-Tryptic Peptides

Collision-induced dissociation (CID) spectra of long non-tryptic peptides are usually quite complicated and rather difficult to interpret. Disulfide bond formed by two cysteine residues at C-terminus of frog skin peptides precludes one to determine sequence inside the forming loop. Thereby, chemical modification of S–S bonds is often used in “bottom up” sequencing approach. However, low-energy CID spectra of natural non-tryptic peptides with C-terminal disulfide cycle demonstrate an unusual fragmentation route, which may be used to elucidate the “hidden” C-terminal sequence. Low charge state protonated molecules experience peptide bond cleavage at the N-terminus of C-terminal cysteine. The forming isomeric acyclic ions serve as precursors for a series of b-type ions revealing sequence inside former disulfide cycle. The reaction is preferable for peptides with basic lysine residues inside the cycle. It may also be activated by acidic protons of Asp and Glu residues neighboring the loop. The observed cleavages may be quite competitive, revealing the sequence inside disulfide cycle, although S–S bond rupture does not occur in this case.

Moving-window two-dimensional correlation infrared spectroscopy study on structural variations of partially hydrolyzed poly(vinyl alcohol)

In the present study, the molecular chain changes and structural transitions of partially hydrolyzed poly(vinyl alcohol) (PVA) having a 12 mol% acetate unit were analyzed by moving-window two-dimensional (MW2D) correlation infrared spectroscopy combined with differential scanning calorimetry and thermogravimetric analysis. The results show the glass-transition temperature (T _g ) of PVA is clearly distinguished by MW2D correlation infrared spectroscopy, and the acetate groups start to be eliminated around the melting temperature, whereas the free water molecules in PVA are eliminated above T _g. The correlation movements of the O–H stretching modes, including the free hydroxyl groups and the hydrogen bonds, are clearly determined using MW2D correlation infrared spectroscopy. The spectral variations in the C=O stretching region caused by the elimination of the acetate unit from polymer chains are also discussed on the basis of the results of the MW2D correlation analysis. Such results cannot be obtained by traditional infrared spectroscopy owing to the complex overlapping peaks.

Preconcentration of trace cadmium ion using magnetic graphene nanoparticles as an efficient adsorbent

Graphene-based magnetic nanoparticles (G-Fe₃O₄) were prepared and used as an effective adsorbent for the solid-phase extraction of trace quantities of cadmium from water and vegetable samples. The method avoids some of the time-consuming steps associated with traditional solid phase extraction. The excellent sorption property of the G-Fe₃O₄ system is attributed to π - π stacking interaction and hydrophobic interactions between graphene and the Cd-PAN complex. The effects of pH, the amount of G–Fe₃O₄, extraction time, type and volume of eluent, desorption time and interfering ions on the extraction efficiency were optimized. The preconcentration factor is 200. Cd(II) was then quantified by flame atomic absorption spectrometry with a detection limit of 0.32 ng mL^?1. The relative standard deviation (at 50 ng mL^?1; for n?=?10) is 2.45 %. The method has a linear analytical range from 1.1 to 150 ng mL^?1, and the recoveries in case of real samples are in the range between 93.1 % and 102.3 %.

Evidence for Sequence Scrambling in Collision-Induced Dissociation of y-Type Fragment Ions

Sequence scrambling from y-type fragment ions has not been previously reported. In a study designed to probe structural variations among b-type fragment ions, it was noted that y fragment ions might also yield sequence-scrambled ions. In this study, we examined the possibility and extent of sequence-scrambled fragment ion generation from collision-induced dissociation (CID) of y-type ions from four peptides (all containing basic residues near the C-terminus) including: AAAAHAA-NH₂ (where “A” denotes carbon thirteen (¹³C₁) isotope on the alanine carbonyl group), des-acetylated-α-melanocyte (SYSMEHFRWGKPV-NH₂), angiotensin II antipeptide (EGVYVHPV), and glu-fibrinopeptide b (EGVNDNEEGFFSAR). We investigated fragmentation patterns of 32 y-type fragment ions, including y fragment ions with different charge states (+1 to +3) and sizes (3 to 12 amino acids). Sequence-scrambled fragment ions were observed from ~50 % (16 out of 32) of the studied y-type ions. However, observed sequence-scrambled ions had low relative intensities from ~0.1 % to a maximum of ~12 %. We present and discuss potential mechanisms for generation of sequence-scrambled fragment ions. To the best of our knowledge, results on y fragment dissociation presented here provide the first experimental evidence for generation of sequence-scrambled fragments from CID of y ions through intermediate cyclic “b-type” ions.

Flash Desorption/Mass Spectrometry for the Analysis of Less- and Nonvolatile Samples Using a Linearly Driven Heated Metal Filament

In this paper, the important issue of the desorption of less- and nonvolatile compounds with minimal sample decomposition in ambient mass spectrometry is approached using ambient flash desorption mass spectrometry. The preheated stainless steel filament was driven down and up along the vertical axis in 0.3 s. At the lowest position, it touched the surface of the sample with an invasion depth of 0.1 mm in 50 ms (flash heating) and was removed from the surface (fast cooling). The heating rate corresponds to ~10⁴ °C/s at the filament temperature of 500 °C. The desorbed gaseous molecules were ionized by using a dielectric barrier discharge ion source, and the produced ions were detected by a time-of-flight (TOF) mass spectrometer. Less-volatile samples, such as pharmaceutical tablets, narcotics, explosives, and C₆₀ gave molecular and protonated molecule ions as major ions with thermal decomposition minimally suppressed. For synthetic polymers (PMMA, PLA, and PS), the mass spectra reflected their backbone structures because of the suppression of the sequential thermal decompositions of the primary products. The present technique appears to be suitable for high-throughput qualitative analyses of many types of solid samples in the range from a few ng to 10 μg with minimal sample consumption. Some contribution from tribodesorption in addition to thermal desorption was suggested for the desorption processes.

Coupling of a High-Resolution Ambient Pressure Drift Tube Ion Mobility Spectrometer to a Commercial Time-of-flight Mass Spectrometer

Ion mobility spectrometry provides information about molecular structures of ions. Hence, high resolving power allows separation of isomers which is of major interest in several applications. In this work, we couple our high-resolution ion mobility spectrometer (IMS) with a resolving power of R_p?=?100 to a time-of-flight mass spectrometer (TOF-MS). Besides, the benefit of an increased resolving power such an IMS-MS also helps analyzing and understanding the ionization processes in IMS. Usually, the coupling between IMS and TOF-MS is realized by synchronizing data acquisition of the IMS and MS resulting in two-dimensional data containing ion mobility and mass spectra. However, due to peak widths of less than 100 μs in our high-resolution IMS, this technique is not practicable due to significant peak broadening during the ion transfer into the MS and an insufficient data acquisition rate of the MS. Thus, a novel but simple interface between the IMS and MS has been designed which minimizes ion losses, allows recording of ion mobility at full IMS resolving power, and enables a shuttered transmission of ions into the MS. The interface is realized by replacing the Faraday plate used in IMS by a Faraday grid that is shielded by two additional aperture grids. For demonstration, positive product ions of benzene, toluene, and m-xylene in air are investigated. The IMS is equipped with a radioactive ³H source. Besides the well-known product ions M⁺ and M·NO⁺, a dimer ion is also observed for benzene and toluene, consisting of two molecules and three further hydrogen atoms.

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