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The masses of the exotic calcium isotopes .sup.53Ca and .sup.54Ca measured by a multi-reflection time-of-flight method confirm predictions of calculations including nuclear three-body interactions. Exotic calcium isotopes weighed The calcium atom provides an ideal system for the study of nuclear shell evolution, from the valley of stability to the limits of existence. Although predictions for the masses of the neutron-rich isotopes .sup.51Ca and .sup.52Ca have been tested by direct measurements, it is an open question as to how nuclear masses evolve for heavier calcium isotopes. Frank Wienholtz and colleagues report the mass determination of the exotic calcium isotopes .sup.53Ca and .sup.54Ca, using a multi-reflection time-of-flight mass spectrometer. The results provide key information for theoretical models and show that a description of extreme neutron-rich nuclei can be closely connected to a deeper understanding of nuclear forces. The properties of exotic nuclei on the verge of existence play a fundamental part in our understanding of nuclear interactions.sup.1. Exceedingly neutron-rich nuclei become sensitive to new aspects of nuclear forces.sup.2. Calcium, with its doubly magic isotopes .sup.40Ca and .sup.48Ca, is an ideal test for nuclear shell evolution, from the valley of stability to the limits of existence. With a closed proton shell, the calcium isotopes mark the frontier for calculations with three-nucleon forces from chiral effective field theory.sup.3,4,5,6. Whereas predictions for the masses of .sup.51Ca and .sup.52Ca have been validated by direct measurements.sup.4, it is an open question as to how nuclear masses evolve for heavier calcium isotopes. Here we report the mass determination of the exotic calcium isotopes .sup.53Ca and .sup.54Ca, using the multi-reflection time-of-flight mass spectrometer.sup.7 of ISOLTRAP at CERN. The measured masses unambiguously establish a prominent shell closure at neutron number N = 32, in excellent agreement with our theoretical calculations. These results increase our understanding of neutron-rich matter and pin down the subtle components of nuclear forces that are at the forefront of theoretical developments constrained by quantum chromodynamics.sup.8., Author(s): F. Wienholtz [sup.1] , D. Beck [sup.2] , K. Blaum [sup.3] , Ch. Borgmann [sup.3] , M. Breitenfeldt [sup.4] , R. B. Cakirli [sup.3] [sup.5] , S. George [sup.1] [...]

The design and fabrication of various nanoscale architectures for the effective MALDI-TOF MS analysis of surface-confined DNA are reported. The nanoscale architectures are derived from layer-by-layer assemblies of negatively charged nanoparticles and positively charged polymers. An important finding is that porous structures comprising bottom Si[O.sub.2] nanoparticle layers and top Au nanoparticle layers enable the observation of both covalently bound (with Au--S bond) and hybridized oligonucleotides. The achievement of this unprecedented detection capability is attributed to the unique combination of a nanoporous dielectric film and discrete noble metal nanoparticles. The conclusion is supported by control experiments performed on a variety of single and multilayered Au nanoparticle structures, where only the hybridized oligonucleotides in a two- or three-strand system could be detected. 10.1021/ac901815v

A newly developed high irradianee laser ionization orthogonal time-of-flight mass spectrometer (LI-O-TOFMS) was employed for the elemental analysis of residues, which were prepared by evaporating mixed salt solutions. The residues were first characterized in terms of shape and elemental distribution. In TOFMS detection, all of the metal elements in the residue can be observed in the spectra. Relative sensitivity coefficients for different elements were within 1 order of magnitude, which meets semiquantitative analysis criteria. By calculating the individual masses from the ablated area due to a single laser shot, the absolute detection limit reached 7 x [10.sup.-15], g fur most metal elements. The results indicate that LI-O-TOFMS is capable of performing ultratrace elemental qualification and quantification, with an absolute limit of detection and an absolute limit of quantitation at the femtogram level. 10.1021/ac901615k

Ambient pressure ion mobility time-of-flight mass spectrometry (IMMS) has recently emerged as a rapid and efficient analytical technique for applications to metabolomics. Ah important application of metabolomics is to monitor metabolome shifts caused by stress due to toxin exposure, nutritional changes, or disease. The research presented in this paper uses IMMS to monitor metabolic changes in rat lymph fluid caused by dietary stresses over time. Extracts of metabolites found in the lymph fluid collected from dietary stressed rats were subjected to analysis by electrospray (ESI) IMMS operated both in positive and negative ion detection mode. Metabolites detected were tentatively identified based on their mass to charge ratio (m/z). In one sample, 1180 reproducible tentative metabolite ions were detected in negative mode and 1900 reproducible tentative metobolite ions detected in positive mode. Only biologically reproducible ions, defined as metabolite ions that were measured in different rats under the same treatment, were analyzed to reduce the complexity of the data. A metabolite peak list including m/z, mobility, and intensity generated for each metabolome was used to perform principle component analysis (PCA). Dynamic changes in metabolomes were investigated using principle components PC1 and PC2 that described 62% of the variation of the system in positive mode and 81% of the variation of the system in negative mode. Analysis of variance (ANOVA) was performed for PC 1 and PC2 and means were statistically evaluated. Profiles of intensifies were compared for tentative metabolite ions detected at different times before and after the rats were fed to identify the metabolites that were changing the most. Mobility-mass correlation curves (MMCC) were investigated for the different classes of compounds.

Mass spectrometry imaging has been used to map liver biopsies of several patients suffering from nonalcoholic fatty liver disease. This steatosis is characterized by an accumulation of triacylglycerols and diacylglycerols in the liver. Using time-of-flight-secondary ion mass spectrometry (TOF-SIMS) with a bismuth cluster ion source, it has been possible to map lipids in situ at the micrometer scale and to simultaneously characterize their molecular distribution on liver sections. Accumulation of triacylglycerols, diacylgiycerols, monoacylglycerols, fatty acids, with the apparition of myristic acid, together with a dramatic depletion of vitamin E and a selective macrovacuolar localization of cholesterol are observed in steatosis areas of fatty livers compared to control livers. These ion species are concentrated in small vesicles having a size of a few micrometers. Moreover, very fine differences in lipid localizations, depending on alkyl acid chain lengths of diacylglycerols and fatty acids, have been found after careful scrutiny of the ion images. Finally, TOF-SIMS has revealed lipid zonation in the normal human liver and accumulation of very similar lipids to those detected in areas of the fatty livers, which are not characterized as steatotic ones by the histological control performed on serial tissue sections.

A microsecond-pulsed direct current glow discharge (GD) was interfaced and synchronized to a time-of-flight mass spectrometer MS(TOF) for time-gated generation and detection of elemental, structural, and molecular ions. In this way, sequential collection of the mass spectra at different temporal regimes occurring during the GD pulse cycle is allowed. The capabilities of this setup were explored using bromochloromethane as model analyte. A simple GD chamber, developed in our laboratory and characterized by a low plasma volume minimizing dilution of the sample but showing great robustness to the entrance of organic compounds in the microsecond-pulsed plasma, has been used. An exhaustive analytical characterization of the GD-MS(TOF) prototype has been performed. Calibration curves for bromochloromethane observed at the different time regimes of the GD pulse cycle (that is, for elemental, fragment, and molecular ions from the analyte) showed very good linearity for the measurement of the different involved ions, with precisions in the range of 7-13% (relative standard deviation). Actual detection limits obtained for bromochloromethane were in the range of 1-3 [micro]g/L for elements monitoring in the GD pulse 'prepeak', in the range of 11-13 [micro]g/L when monitoring analyte fragments in the plateau, and about 238 [micro]g/L when measuring the molecular peak in the afterpeak regime.

Capillary enzymatic microreactors containing trypsin and endoproteinase LysC immobilized on a porous polymer monolith have been prepared and used for the characterization and identification of proteins such as cytochrome c, bovine serum albumin, and high-molecular weight human immunoglobulin G. The hydrophilicity of diol functionalities originating from the hydrolyzed poly(giycidyl methacrylate-co-ethylene dimethacrylate) monolith was not sufficient to avoid adsorption of hydrophobic albumin in a highly aqueous mobile phase. Therefore, this monolith was first hydrophilized via photografting of poly(ethylene glycol) methacrylate followed by photografting of a 4-vinyl-2,2-dimethylazlactone to provide the pore surface with reactive functionalities required for immobilization. This new approach reduced the undesired nonspecific adsorption of proteins and peptides and facilitated control of both the enzyme immobilization and protein digestion processes. The enzymatic reactors were coupled off-line with MALDI/TOF MS and/or on-line with ESI/TOF MS. Experimental conditions for digestion were optimized using cytochrome c and bovine serum albumin as model proteins. The optimized reactors were then integrated into a multidimensional system comprised of a monolithic capillary enzyme reactor, an in-line nanoLC separation of peptides using a poly(lauryl methacrylate-co-ethylene dimethacrylate) monolithic column, and ESI/ TOF MS. With the use of this system, immunogiobulin G was digested at room temperature in 6 min to an extent similar to that achieved with soluble enzyme at 37[degrees]C after 24 h.

Aminoacyl-tRNA protein transferases catalyze the post-translational addition of amino acids to proteins. The eubacterial leucyl/phenylalanyl-tRNA-protein transferase (L/F transferase) catalyzes the transfer of leucine or phenylalanine from their respective aminoacylated tRNAs to the N-termini of substrate proteins possessing an N-terminal lysine or arginine amino acid. Conventional assays to quantify L/F transferase activity involve measuring radioactive amino acid incorporation into substrate proteins. We have developed a quantitative matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry procedure to measure the enzymatic activity of L/F transferase. The procedure utilizes stable isotope labeled substrate and internal standard peptides. The method is used to determine the kinetic parameters of [k.sub.cat] and [K.sub.m] for the enzymatic transfer of phenylalanine and three unnatural amino acid derivatives from an aminoacyl-tRNA to a peptide substrate.

A method for performing untargeted metabolomic analysis of human serum has been developed based on protein precipitation followed by Ultra Performance Liquid Chromatography and Time-of-Flight mass spectrometry (UPLC--TOF-MS). This method was specifically designed to fulfill the requirements of a long-term metabolomic study, spanning more than 3 years, and it was subsequently thoroughly evaluated for robustness and repeatability. We describe here the observed drift in instrumental performance over time and its improvement with adjustment of the length of analytical block. The optimal setup for our purpose was further validated against a set of serum samples from 30 healthy individuals. We also assessed the reproducibility of chromatographic columns with the same chemistry of stationary phase from the same manufacturer but from different production batches. The results have allowed the authors to prepare SOPs for 'fit for purpose' long-term UPLC--MS metabolomic studies, such as are being employed in the HUSERMET project. This method allows the acquisition of data and subsequent comparison of data collected across many months or years.

Samples of polydisperse gold nanoclusters (AuNCs) protected with monolayers of N-acetyl-L-cysteine (NAC) have been chromatographically separated by a C18 column (4.6 mm x 250 mm) using a gradient elution program with a mobile phase of methanol (MeOH)/water containing tetrabutylammonium fluoride ([Bu.sub.4][N.sup.+][F.sup.-]) and sodium chloride. The effects of ([Bu.sub.4][N.sup.+][F.sup.-]) and MeOH on the separation have been investigated in detail. In conjunction with absorbance-based, fluorescence, and electrochemical detectors, the elution order of these water-soluble AuNCs is confirmed according to their core size in an ascending order. The onset oxidation potential closely follows the core size of AuNC. The separated fractions from high-performance liquid chromatography (HPLC) were collected and analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry to determine the number of Au atoms in the fractions. The sizes of AuNCs in some selected HPLC fractions were also assessed by transmission electron microscopy and high-resolution transmission electron microscopy. Photoluminescence spectra of the fractions show that the luminescent shift in the visible/near-infrared region does not follow with the core size of AuNC. More importantly, the proposed HPLC methodology has been successfully applied to analyze various polydisperse AuNC products synthesized from different gold-to-ligand mole ratios (Au/ NAC) and reaction temperatures. The results confirm that larger Au/NAC and higher temperature will produce larger core size AuNCs products with narrower dispersity. In addition, AuNC samples obtained from various synthesis reaction times were analyzed by our HPLC methodology, demonstrating that the reaction's behavior follows the nucleation--growth--disintegration process.

Phosphorylation is one of the most important posttranslational modifications of proteins, which modulates a wide range of biological functions and activities of proteins. The phosphorylation of proteins is also associated with the pathway of cancer cells. We have previously enriched the low molecular weight proteome from human plasma based on the combination of size exclusion and adsorption mechanism by using highly ordered mesoporous silica particles. Herein, highly ordered mesoporous silica particles were modified with titanium phosphonate to selectively capture the phosphopeptides from complex peptide and protein mixtures. The limit of detection for phosphopeptides from [beta]-casein and standard phosphopeptide spiked in human serum was as low as 1.25 fmol based on MALDI-TOFMS detection. The modified mesoporous silica particles were further used to enrich phosphopeptides from serum of hepatocellular carcinoma patients and healthy individuals and then analyzed with MALDI-TOFMS. The combination of isobaric tagging for relative and absolute quantitation labeling with MALDI-TOFMS/MS was further applied to validate the serum phosphopeptide profiling result of MALDI-TOFMS. The profiling of the serum phosphopeptides between the cancer patients and healthy persons was distinguishingly different, which indicated the potential ability of this technique for cancer diagnosis and biomarker discovery. The approach developed here would be applicable to other biological samples and a wide variety of diseases.

Ambient mass spectrometry has been used for the analysis of strobilurin residues in wheat. The use of this novel, challenging technique, employing a direct analysis in a real time (DART) ion-source coupled with a time-of-flight mass spectrometer (TOF MS) and a desorption electrospray ionization (DESI) source coupled with a linear ion trap tandem MS (LIT MS'), permitted a direct screen of the occurrence of target fungicides in treated grains in less than 1 min. For quantification purpose by DART-TOF MS, an ethyl acetate extract had to be prepared. With the use of a prochloraz as an internal standard, the performance characteristics obtained by repeated analyses of extract, spiked at 50 [micro]g [kg.sup.-1] with six strobilurins (azoxystrobin, picoxystrobin, dimoxystrobin, kresoxim-methyl, pyraclostrobin, and trifloxystrobin), were in the following range: recoveries 78-92%, repeatability (RSD) 8-15%, linearity ([R.sup.2]) 0.9900-0.9978. The analysis of wheat with incurred strobilurin residues demonstrated good trueness of data generated by the DART-TOF MS method; the results were in a good agreement with those obtained by the conventional approach, i.e., by the QuEChERS sample handling procedure followed by identification/quantification employing high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Tandem mass spectrometry using DESI-LIT [MS.sup.n] provided a sufficient number of product ions for confirmation of the identity of azoxystrobin and pyraclostrobin in incurred wheat samples.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) can be utilized to map the distribution of various molecules on a surface with submicrometer resolution. Much of its biological application has been in the study of membrane lipids, such as phospholipids and cholesterol. Cholesterol is a particularly interesting molecule due to its involvement in numerous biological processes. For many studies, the effectiveness of chemical mapping is limited by low signal intensity from various biomolecules. Because of the high energy nature of the SIMS ionization process, many molecules are identified by detection of characteristic fragments. Commonly, fragments of a molecule are identified using standard samples, and those fragments are used to map the location of the molecule. In this work, MS/MS data obtained from a prototype [C.sub.60.sup.+]/quadrupole time-of-flight mass spectrometer was used in conjunction with indium LMIG imaging to map previously unrecognized cholesterol fragments in single cells. A model system of J774 macrophages doped with cholesterol was used to show that these fragments are derived from cholesterol in cell imaging experiments. Examination of relative quantification experiments reveals that m/z 147 is the most specific diagnostic fragment and offers a 3-fold signal enhancement. These findings greatly increase the prospects for cholesterol mapping experiments in biological samples, particularly with single cell experiments. In addition, these findings demonstrate the wealth of information that is hidden in the traditional TOF-SIMS spectrum.

Although the current literature has recorded many reports of identifying components from herbal preparations, all of them were largely limited to target components. This paper provides a novel and generally applicable approach to identifying nontarget components from herbal preparations, based on the use of liquid chromatography ion trap time-of-flight mass spectrometry (LC/MS-IT-TOF). A simple program was originally developed for searching the common diagnostic ions from all experimentally generated ions. The components sharing the exact same ions (mass error < 5 mDa) were classified into a family. All families were then connected into a coherent network by the bridging components that are present in two or more families. With the benefit from such a network, it is feasible to sequentially characterize the structures of all diagnostic ions once a single component has been de novo identified. The structures of the diagnostic ions could then be used as 'a priori' information for selecting the exact candidates containing the substructures of the corresponding diagnostic ions from the primary database hits. This strategy enables a nearly 7-fold narrowing of the database hits and thus substantially enhances the analytical efficiency and sharpness. With the use of such an approach, 43 out of 53 components incorporated into the network have been successfully identified from the test herbal preparation. For the rest, components failed to be identified using this approach; a complementary approach to screening by sequential loss of specific chemical groups, proposed from the accurate mass differences between fragments, was established to narrow the database hits. All of the 87 peaks detected have been successfully identified by combining the use of both approaches except failed to differentiate some isomers. The presently developed approach and methodology would be useful for the identifications of complicated nontarget components from various complex mixtures such as herbal preparations, biological, and environmental samples.

A novel in-line surface-induced dissociation (SID) device was designed and implemented in a commercial QTOF instrument (Waters/Micromass QTOF II). This new setup allows efficient SID for a broad range of molecules. It also allows direct comparison with conventional collision-induced dissociation (CID) on the same instrument, taking advantage of the characteristics of QTOF instrumentation, including extended mass range, improved sensitivity, and better resolution compared with quadrupole analyzers and ion traps. Various peptides and a noncovalent protein complex have been electrosprayed and analyzed with the new SID setup. Here we present SID of leucine enkephalin, fibrinopeptide A, melittin, insulin chain-B, and a noncovalent protein complex from wheat, heat shock protein 16.9. The SID spectra were also compared to CID spectra. With the SID setup installed, ion transmission proved to be efficient. SID fragmentation patterns of peptides are, in general, similar to CID, with differences in the relative intensities of some peaks such as immonium ions, backbone cleavage b- versus y-type ions, and y- versus y-N[H.sub.3] ions, suggesting enhanced accessibility to high-energy/secondary fragmentation channels with SID. Furthermore, these results demonstrate that the in-line SID setup is a valid substitute for CID, with potential advantages for activation of singly/multiply charged peptides and larger species such as noncovalent protein complexes.

Ion velocity distribution (IVD) and ion charge state distribution of silver ions in a plasma beam emitted by two compact, serially connected, and simultaneously operating vacuum arcs were measured using a dynamic time-of-flight diagnostics. The anode and cathode of each arc were made of two strips of silver layers pasted on an alumina wafer and separated by a narrow 100-[micro]m gap. The two arcs were laterally separated by 0.015 m and located on the same horizontal plane, emitting two plasma plums, which merged into a single one and is few centimeters away from the arcs. Each arc was ignited by high-voltage breakdown on the alumina surface gap by 3-[micro]s 100-A current. The IVD of the merged plasma beam was analyzed 0.7 m away from the arcs and compared with that of the ions emitted by a single arc. When only a single arc was active, the plasma beam consisted of more than 90% of Ag ions with an average velocity of = (0.7 - 0.8) * [10.sub.4] m/s and charge state z = 1. About 10% of the beam ion population consisted of oxygen and carbon. When the two arcs operated simultaneously, the form of the IVD was significantly different, containing a second peak with a velocity of = (1.15 - 1.25) * [10.sub.4] m/s, which is significantly higher than that observed with a single arc. However, the integrated ion charge in the merged beam was lower by 30% from the sum of the ion charge obtained from the plasma of each arc. It was found that the observed phenomena were correlated with a formation of conducting channel between the cathode of the first serially connected arc and the anode of the second arc, which is occurring when the plasma plums are expanding from the two arcs merged. When a physical barrier was inserted between the two arcs to prevent a contact between the two expanding plums, the observed plasma shunting did not occur, although the two beams merged in space beyond the barrier, as before. The effect on the IVD due to arc transfer from the first cathode to the second arc anode is currently being investigated. Index Terms--Ion charge state distribution (ICSD), ion energy distribution (IED), silver, time-of-flight (TOF) measurements, vacuum arcs.

Microcystins (MCs) are a growing problem in drinking water supplies worldwide. Common analytical techniques used to determine MC concentrations have several shortcomings, including extensive sample handling and lengthy analysis times. A simple, rapid method for quantitation of MCs by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is presented. Four potential internal standards were tested, including an [.sup.15N]-labeled MC. For MC-LR in mixed standard solutions, a linear range of 0.11-5.0 [micro]M ([R.sup.2] = 0.98) was achieved, with a method detection limit (MDL) of 0.015 [micro]M. Matrix effects due to extracted cell components decreased the MC-LR linear range slightly to 0.195.0 [micro]M ([R.sup.2] = 0.99), with MDL = 0.058 [micro]M. Extensive analysis of possible internal standards indicates that nodularin was preferred over [[[.sup.15N].sub.10]-microcystin-YR or angiotensin I. The ionization efficiency and analyte-analyte suppression for four MCs of varying polarity are presented; the three polar congeners exhibited good ionization efficiency and acceptable levels of analyte-analyte suppression. These results indicate that MALDITOF MS represents a viable alternative for the quantitative measurement of MCs in field samples.

The application of a recently developed direct coupling of high-performance thin-layer chromatography (HPTLC) and infrared matrix-assisted laser desorption/ionization orthogonal extracting time-of-flight mass spectrometry (Dreisewerd, K.; Muthing, J.; Rohlfing, A.; Meisen, I.; Vukelic, Z.; Peter-Katalinic, J.; Hillenkamp, F.; Berkenkamp, S. Anal. Chem. 2005, 77, 4098-4107) to the analysis of phospholipid mixtures is demonstrated. Mixtures of six phospholipid types were exemplarily analyzed. The sensitivity was found to be in the range between about 10 and 150 pmol of material spotted for HPTLC, depending on phospholipid acidity, [R.sub.f] value, and ion polarity. The lateral resolution of the analysis is on the order of the laser focus diameter of about 220 x 300 [micro][m.sup.2], allowing differentiation between phospholipid species of different acyl chain composition within one single HPTLC band, which were undistiguishable by a mere visual assessment. Analyte diffusion due to the addition of glycerol to the HPTLC plate was found to be--if at all notable--of only minor importance.

A database of 5448 peptide tandem mass spectra acquired in a quadrupole time-of-flight mass spectrometer was generated for peptides derived from proteins digested with trypsin. Peptides were identified from their mass spectra by the Mascot algorithm. Statistical models were then used to investigate factors influencing the abundance of ions formed. Separate models were formulated for b and y ions as it was thought that different factors may influence the formation of each type of ion. Several factors were found to have a highly significant influence on the abundance of ions formed. These include the actual mass of the ion formed after fragmentation as well as the location of the cleavage. The composition of the fragmenting peptide was also found to be important, and amino acids either side of the fragmentation site influenced the abundance of ions produced. To increase understanding of fragmentation mechanisms, the effect of several physicochemical properties of these residues was also investigated in a separate model. In conclusion, the models formulated for b and y ions provide useful characterization of the abundance of ions formed, and this information could be used to develop improved algorithms for peptide identification.

A series of model systems of poly(dimethylsiloxane) (PDMS) of molecular mass 2400 Da and low polydispersity (1.09) were prepared using the Langmuir-Blodgett technique to investigate the effects of tertiary structure on the ion formation probability in time-of-flight secondary ion mass spectrometry (TOF-SIMS). Using data from the measured surface pressure--area isotherm for PDMS ordered monolayer, films were transferred to silver mirror substrates from the various regions in the isotherm where structural changes are observed. Two particular conformations of the polymer are examined here: a linear caterpillar-like structure and a coiled helical structure. Reflection absorption Fourier transform infrared spectroscopic analysis indicates structural changes for the films related to adjustments to the orientation of the polymeric backbone consistent with the formation of two distinct structures. The polymeric changes translate into differences in ion formation probability of fragments in both the low (1000 Da) mass range. Data are also presented to analyze how tertiary structure may affect the apparent polydispersity index calculated from the TOF-SIMS spectra.

The time-of-flight secondary ion mass spectrometry and reflection absorption infrared spectroscopy were used to determine the properties of supercooled liquid water and the mechanism of crystallization. The supercooled water is found to contain two phases and undergoes immediate crystallization and dissolution of LiCl.

Functionalized magnetic nanoparticles (MNPs) were synthesized to serve as laser desorption/ionization elements as well as solid-phase extraction probes for simultaneous enrichment and detection of small molecules in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. Two laser-absorbing matrices were each conjugated onto MNP to give MNP@matrix which provided high ionization efficiency and background-free detection in MS leading to unambiguous identification of target small molecules in a complex mixture. MNP@matrix was demonstrated to serve as a general matrix-free additive in MALDI-TOF MS analysis of structurally distinct small molecules. Also, MNP@matrix provides a simple, rapid, and reliable quantitative assay for small molecules by mass without either the use of an internal standard or an isotopic labeling tag. Furthermore, the affinity extraction of small molecules from complex biofluid was achieved by probe protein-conjugated MNP@matrix without laborious purification. We demonstrated that a nanoprobe-based assay is a cost-effective, rapid, and accurate platform for robotic screening of small molecules.

The simple, ballistic time-of-flight equation for the maximum altitude of a vertically launched rocket neglects the effects of atmospheric drag. We show that the error introduced by using this equation to estimate the maximum altitude is typically less than 1% because of the effective cancellations of timing errors during the ascent and descent of the rocket. [DOI: 10.1119/1.2673110]

The time-of-flight mass spectroscopy was used to study the interaction of [C.sub.2][H.sub.5]X, I-[C.sub.3][H.sub.7]X, I-[C.sub.4[H.sub.9]X (where X = I, Br, Cl). The dependence of the laser intensity of the ratio of the doubly charged halogen ions to the singly charged ones has shown that the molecular coupling with the laser field increases with the molecular size.

An experiment was carried out by subjecting molecular clusters of B[Br.sub.3] (Boron tribromide) to electron ionization and mass analysis in a reflectron time-of flight mass spectrometer. The results have predicted that fragment ions smaller than B[Br.sub.3.sup.+] undergo reactions with neutral B[Br.sub.3] molecules to form covalently bound adduct species that function as core ions within the clusters.

Phospho- and glycolipids contained in the plasma membrane of neuronal tissue were profiled by direct infrared laser desorption/ionization orthogonal time-of-flight mass spectrometry (IR-LDI-o-TOF-MS), performed on cryosected native slices generated from rat brain. About 100 different detected lipid species are putatively assigned based on their molecular weight. Spraying of potassium acetate onto the slices was found to facilitate data interpretation in positive ion mode by reducing residual sodium adduct ion intensities. Coating the slices with matrix and using an ultraviolet laser for UV-MALDI-o-TOF-MS extends the analysis to peptides and small proteins but induces analyte diffusion. Peptides and partially cleaved proteins derived from proteolytic digests were recorded after incubation of native sections with trypsin and subsequent coating of the slices with MALDI matrix.

Ion mobility spectrometry (IMS) coupled to orthogonal time-of-flight mass spectrometry (TOF) has shown significant promise for the characterization of complex biological mixtures. The enormous complexity of biological samples (e.g., from proteomics) and the need for both biological and technical analysis replicates imposes major challenges for multidimensional separation platforms with regard to both sensitivity and sample throughput. A major potential attraction of the IMS-TOF MS platform is separation speeds exceeding that of conventional condensed-phase separations by orders of magnitude. Known limitations of the IMS-TOF MS platforms that presently mitigate this attraction include the need for extensive signal averaging due to factors that include significant ion losses in the IMS-TOF interface and an ion utilization efficiency of less than ~1% with continuous ion sources (e.g., ESI). We have developed a new multiplexed ESI-IMS-TOF mass spectrometer that enables lossless ion transmission through the IMS-TOF as well as a utilization efficiency of >50% for ions from the ESI source. Initial results with a mixture of peptides show a ~10-fold increase in signal-to-noise ratio with the multiplexed approach compared to a signal averaging approach, with no reduction in either IMS or TOF MS resolution.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) using buckminsterfullerene ([C.sub.60]) as the primary ion source has the ability to generate chemical images of surfaces with high sensitivities and minimal chemical damage. We studied the application of [C.sub.60.sup.+] to depth profile a biological cell surface in a controlled manner and to subsequently image the revealed subsurfaces, in order to generate three-dimensional molecular images of the biological system. Such an analytical tool not only enables the surface localization of molecular species to be mapped but also enables the biomolecular distribution as a function of depth to be investigated with minimal sample preparation/intervention. Here we demonstrate the technique with a freeze-dried Xenopus laevis oocyte, which is a single cell. A [C.sub.60.sup.+] ion beam was used with computer-controlled analyses and etch cycles. Mass spectra derived from the surface revealed peaks corresponding to cholesterol (m/z 369) and other lipids at m/z 540-570 and 800-1000, in the positive ion mode, and lipid fatty acid side chains (e.g., m/z 255) in the negative ion mode. To our knowledge, this is the first demonstration of the 3D biomolecular imaging within an actual biological system using TOF-SIMS.

A general relationship is derived for the abundance of an imperfect dendrimer with a given number of missing constitutional repeating units in the two outmost layers. The relationship is used in the interpretation of the MALDI TOF mass spectrum of the second-generation carbosilane dendrimer prepared by the iterative divergent method. The model quantitatively describes the spectrum of the dendrimer and correctly predicts the MALDI TOF mass spectrum of its first-generation precursor. Thus, the use of well-resolved MALDI TOF mass spectra for assessing the purity of low-generation dendrimers with uniform end groups is substantiated for carbosilane dendrimers and to lesser extent for dendrimers in general.

The article analyses the flatband voltage shift of ruthenium (Ru) gated metal-oxide-semiconductor stacks and its effects on the formation of thin Ru oxide layer at the dielectric interface after a thermal treatment with oxygen. It reveals that an increase in the voltage shifts for Ru gated stacks is the result of the formation of the thin Ru-oxide layer, which is found to be thermodynamically very much similar to the bulk Ru[O.sub.2].

Silicon nanopowder (5-50 nm) was applied as a matrix for the analysis of small molecules in laser desorption/ ionization mass spectrometry. In contrast with conventional matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry, the matrix background interference in the low mass range was significantly reduced. Effects of the particle size and sample preparation procedures on the background mass spectra and the analyte signal intensity have been investigated, and an optimized powder and sample preparation protocol was established. Several surface characterization tools have been applied as well. Both positive mode and negative mode laser desorption/ionization have been applied to different analytes including drugs, peptides, pesticides, acids, and others. Detection limits down to the low femtomole per microliter levels were achieved for propafenone and verapamil drugs. The method developed was found relatively tolerant to salt contamination, which allowed the direct analysis of morphine and propaphenone in untreated urine and triazine herbicides in a soil extract. The new silicon-nanoparticle-assisted laser desorption ionization method was found to be highly selective, which may be due to analyte-dependent precharging in solution, prior to vacuum laser desorption. Some aspects of the charge-transfer mechanism have been studied and discussed. In comparison with standard MALDI matrixes, the silicon nanopowder requires much lower laser fluence (contributing to a reduced background) has much better surface homogeneity, and is more tolerant to salt interference, which makes it an easily applicable practical tool at a potentially low cost.

The development of a new high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) is reported. The high-resolution capabilities of this instrument allow the direct separation of most ions from inorganic and organic species at the same nominal m/z, the quantification of several types of organic fragments ([C.sub.x][H.sub.y], [C.sub.x][H.sub.y][O.sub.z], [C.sub.x][H.sub.y][N.sub.p], [C.sub.x][H.sub.y][O.sub.z][N.sub.p]), and the direct identification of organic nitrogen and organosulfur content. This real-time instrument is field-deployable, and its high time resolution (0.5 Hz has been demonstrated) makes it well-suited for studies in which time resolution is critical, such as aircraft studies. The instrument has two ion optical modes: a single-reflection configuration offers higher sensitivity and lower resolving power (up to ~2100 at m/z 200), and a two-reflectron configuration yields higher resolving power (up to ~4300 at m/z 200) with lower sensitivity. The instrument also allows the determination of the size distributions of all ions. One-minute detection limits for submicrometer aerosol are

The surface of a styrene-b-isobutylene-b-styrene triblock copolymer, containing a solid-phase drug, was studied by time-of-flight secondary ion mass spectrometry employing 15-keV [Ga.sup.+] and 20-keV [C.sub.60.sup.+] ion sources. This polymer/drug system has direct application in the cardiac stent arena, where it has been used to treat restenosis or renarrowing of arterial walls after stent or angioplasty procedures. Overall, the results illustrate the successful use of a cluster ion beam for greatly enhancing the high-mass fragment ion and molecular ion intensities from the surface and bulk of the polymer system. The use of [C.sub.60.sup.+] also established the ability to remove common overlayers like poly(dimethylsiloxane), which was not possible using a [Ga.sup.+] ion source. Furthermore, the use of [C.sub.60.sup.+] allowed depth profiles to be obtained using primary ion dose densities in excess of 6 x [10.sup.14] [C.sub.60.sup.+]/[cm.sup.2]. Resultant sputter craters reached depths of ~2 [micro]m and possessed relatively flat bottoms without the need for sample rotation. AFM and profilometry studies support the relatively gentile removal of surface species via phase contrast and topographic imaging. In addition, the findings suggest that relatively high ion doses do not significantly alter the phase distribution or surface topography of the polymer surface; however, a slight increase in surface roughness was detected.

Sialylated glycopeptides contained in liquid chromatographic fractions of bovine [[alpha].sub.1]-glycoprotein tryptic digests were isolated from asialo peptides using capillary electrophoresis (CE). CE effluents were deposited directly onto a metallic target and analyzed using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. This method allowed the characterization of four N-glycosylation sites in the glycoprotein, and each site was observed as a set of sialylated peptide glycoforms. Tandem mass spectrometry was used to confirm peptide sequences and glycan content in glycoforms. The CE method developed for this study resulted in a very clear separation of the sialylated from the asialo content of glycoprotein digests and proved very useful in the determination of the nature and location of sialylated glycans along the protein chain. This article is the first report describing the use of on-target CE fraction collection using a MALDI removable sample concentrator.