PSMA@Ag复合微球的制备及其在MALDI-MS分析小分子化合物中的应用研究

基质辅助激光解吸电离质谱(MALDI-MS)作为一种有力的分析手段,在生物分子分析中有着广泛的应用,但很难应用于分子量小于500的待测物的分析。该文利用聚多巴胺修饰还原法制备了核壳结构的聚苯乙烯-马来酸酐共聚物@银纳米壳层(PSMA@Ag)复合微球。采用傅立叶红外光谱法验证了聚多巴胺(PDA)的成功修饰。结合扫描电子显微镜(SEM)和紫外-可见光谱(UV-Vis)分析结果,发现Ag纳米壳层成功地包覆在PSMA微球的表面。将制备的PSMA@Ag复合微球作为辅助基质直接应用于MALDI-MS,成功地从0.5μL待测物样品中检测到2 pmol脯氨酸(M_w=115)和1 pmol丝氨酸(M_w=105)。研究结果证明PSMA@Ag微球对MALDI的离子化过程有促进作用,为解决MALDI-MS在分析小分子待测物时背景噪声过大,信号无法分辨的问题提供了一个有效途径。     

双步激光解析/激光电离质谱法及其应用的新进展

激光光电离技术已广泛应用于质谱领域.基于单束激光的基质辅助激光解析(MALDI)质谱分析方法,已成为质谱分析生物大分子的标准方法之一.本文介绍的是另一种新的激光质谱分析方法:双步激光解析/激光电离质谱法(L2MS),与MALDI相比,该方法不需要加入与样品形成共结晶的基质,同时可通过独立地改变两束激光的光强和波长达到优...     

Spatially resolved ultra-trace analysis of elements combining resonance ionization with a MALDI-TOF spectrometer

A combined setup for spatially resolved mass analysis of trace amounts of elements and macromolecules is presented. Using a MALDI-TOF mass spectrometer, a laser spectroscopic setup for resonant ionization of neutral atoms has been implemented. This allows for an efficient and selective detection of trace elements by means of resonance ionization mass spectrometry (RIMS). The instrumental scheme is described, and methodological developments are presented. In a first application pure, laser desorption/ionization with TOF-MS was used to measure mass distributions of cosmic nanodiamonds. For further applications regarding the spatially resolved ultra-trace analysis of elements in solid samples, an implanted target was used to characterize both laser desorption/ionization and laser desorption/resonance ionization for the detection of trace elements within. A perspective of the setup is given and future investigations are outlined.     

Mass spectrometric analysis of low molecular mass polyesters by laser desorption/ionization on porous silicon

A low molecular mass polyester was analyzed by desorption/ionization on porous silicon (DIOS) mass spectrometry. The results were compared with those of matrix-assisted laser desorption ionization (MALDI) mass spectrometry using matrixes of alpha-cyano-4-hydroxycinnamic acid (CHCA) and 10,15,20-tetrakis(pentafluorophenyl)porphyrin (F20TPP). The CHCA matrix was not suitable for characterization of low molecular mass components of the polyester because the matrix-related ions interfered with the component ions. On the other hand, the F20TPP matrix showed no interference because no matrix-related ions appeared below m/z 822. However, the solvent selection for determining optimal conditions of sample preparation was limited, because F20TPP does not dissolve readily in any of the available organic solvents. In the DIOS spectra, the polymer ions were observed at high sensitivity without a contaminating ion. No matrix is needed for DIOS spectra of low molecular mass polyesters, facilitating sample preparation and selectivity of a precursor ion in post-source decay measurements.     

Mass spectrometry based cellular phosphoinositides profiling and phospholipid analysis: A brief review

Phospholipids are key components of cellular membrane and signaling. Among cellular phospholipids, phosphoinositides, phosphorylated derivatives of phosphatidylinositol are important as a participant in essential metabolic processes in animals. However, due to its low abundance in cells and tissues, it is difficult to identify the composition of phosphoinositides. Recent advances in mass spectrometric techniques, combined with established separation methods, have allowed the rapid and sensitive detection and quantification of a variety of lipid species including phosphoinositides. In this mini review, we briefly introduce progress in profiling of cellular phosphoinositides using mass spectrometry. We also summarize current progress of matrices development for the analysis of cellular phospholipids using matrix-assisted laser desorption/ionization mass spectrometry. The phosphoinositides profiling and phospholipids imaging will help us to understand how they function in a biological system and will provide a powerful tool for elucidating the mechanism of diseases such as diabetes, cancer and neurodegenerative diseases. The investigation of cellular phospholipids including phosphoinositides using electrospray ionization mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry will suggest new insights on human diseases, and on clinical application through drug development of lipid related diseases.     

MALDI-TOF and MALDI-FTICR imaging mass spectrometry of methamphetamine incorporated into hair

A new approach is described for imaging mass spectrometry (IMS) of methamphetamine (MA) incorporated into human hair using matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF) and MALDI-Fourier transform ion cyclotron resonance (FTICR). A longitudinal section of a lengthwise manually-cut single human hair shaft from a chronic MA user was directly analyzed by MALDI-TOF-IMS after deposited with α-Cyano-4-hydroxycinnamic acid matrix. A barcode-like image, which was most probably generated with repeated intakes of MA, was for the first time obtained by monitoring MA-specific product ion in the selected reaction monitoring mode. Laser beam scan lengthwise-cut hair shafts gave only poor mass spectra of MA, probably due to the loss of MA and/or the thermal denaturation of hair. The identity of MA detected in hair was further confirmed by MALDI-FTICR mass spectrometry. A combination with ultra-high resolution mass spectrometry by FTICR provided indisputable identification of MA. The MALDI-FTICR-IMS of another hair shaft from the same MA user also provided a barcode-like image by monitoring the protonated molecule of MA with ultra-high resolution. The two barcode-like images exhibited a close resemblance. Thus, MALDI-IMS can offer a new perspective: 'imaging hair analyses for drugs'.     

Advanced glycation end products: a highly complex set of biologically relevant compounds detected by mass spectrometry

Structural information on 'AGE-peptides,' a class of substances belonging to advanced glycation end products (AGE) and originating by proteolysis of glycated proteins, was gained through various analytical approaches on the mixture produced by proteinase K digestion of in vitro glycated bovine serum albumin. Both matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and high-performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS) were employed, and the results were compared with those from conventional spectroscopic methods (UV, fluorescence, gel permeation). The data acquired by the various techniques all depict the digestion mixtures as highly complex, with components exhibiting molecular mass in the range 300-3500 Da. In the analysis of HPLC/ESI-MS data, identification of AGE-peptides was facilitated by 3D mapping. Structural information was gained by means of multiple mass spectrometric experiments.     

Composition of Laprol-373 and Products of Its Reaction with 2,4-Toluylene Diisocyanate

The composition of oligoethers that are components of Laprol-373 and of products of their reaction with 2,4-toluylene diisocyanate were studied by matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF).     

Evaluation of a new matrix-free laser desorption/ionization method through statistic studies: comparison of the DIAMS (desorption/ionization on self-assembled monolayer surface) method with the MALDI and TGFA-LDI techniques

This work demonstrates that the desorption/ionization on self-assembled monolayer surface (DIAMS) mass spectrometry, a recent matrix-free laser desorption/ionization (LDI) method based on an organic target plate, is as statistically repeatable and reproducible as matrix assisted laser desorption ionization (MALDI) and thin gold film-assisted laser desorption/ionization (TGFA-LDI) mass spectrometries. On lipophilic DIAMS of target plates with a mixture of glycerides, repeatability/reproducibility has been estimated at 15 and 30% and the relative detection limit has been evaluated at 0.3 and 3 pmol, with and without NaI respectively. Salicylic acid and its d(6)-isomer analysis confirm the applicability of the DIAMS method in the detection of compounds of low molecular weight.     

硅纳米结构对表面辅助激光解吸/电离质谱检测性能的提高

本文总结了多种构筑硅纳米结构的方法, 综述了近年来利用硅纳米结构提高表面辅助激光解吸/电离质谱(SALDI-MS)性能的研究工作, 展望了利用功能化的硅纳米结构表面进一步提高激光解吸/电离(LDI)效率的前景.     

Direct profiling of saccharides,organic acids and anthocyanins in fruits using electrospray droplet impact/secondary ion mass spectrometry

Electrospray droplet impact (EDI)/secondary ion mass spectrometry (SIMS) is a new desorption/ionization technique for mass spectrometry in which highly charged water clusters produced from atmospheric‐pressure electrospray are accelerated in vacuum by several kV and impact on the sample deposited on the metal substrate. In this study, we applied EDI/SIMS directly to fruits, such as bananas, strawberries, grapes and apples. The major components in the fruits – fructose, glucose, sucrose and organic acids – could be observed with strong signal intensities. EDI/SIMS was also applied to the analysis of different regions of strawberries and apples. Compared with matrix‐assisted laser desorption/ionization (MALDI), ion signals with lower background signals could be obtained, particularly for the low molecular weight analytes. Copyright © 2010 John Wiley & Sons, Ltd.     

Can crude oils be distinguished by different component distribution obtained by laser desorption ionization mass spectrometry and evaluated by chemometrics?

Fourteen different crude oil samples were analyzed as collected by mass spectrometry. For two of them the results obtained by means of different techniques, i.e. electrospray ionization, atmospheric pressure chemical ionization, laser desorption/ionization, were compared. The latter technique leads to the best results: even if unable to give specific information on heteroatom-containing components, it allows a general view to be obtained of the panorama of the oil composition in terms of molecular weight distribution. The statistical evaluation of the mass spectrometry data by multivariate techniques, such as cluster analysis (Average Linkage) and correspondence analysis, allows evidence for the differences and similarities among the crude oils under study.     

Porous polymer monolith for surface-enhanced laser desorption/ionization time-of-flight mass spectrometry of small molecules

Porous poly(butyl methacrylate-co-ethylene dimethacrylate), poly(benzyl methacrylate-co-ethylene dimethacrylate), and poly(styrene-co-divinylbenzene) monoliths have been prepared on the top of standard sample plates used for matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and the modified plates were used for laser desorption/ionization mass spectrometry (LDI-MS). The hydrophobic porous surface of these monoliths enables the transfer of sufficient energy to the analyte to induce desorption and ionization prior to TOFMS analysis. Both UV and thermally initiated polymerization using a mask or circular openings in a thin gasket have been used to define spot locations matching those of the MALDI plates. The desorption/ionization ability of the monolithic materials depends on the applied laser power, the solvent used for sample preparation, and the pore size of the monoliths. The monolithic matrices are very stable and can be used even after long storage times in a typical laboratory environment without observing any deterioration of their properties. The performance of the monolithic material is demonstrated with the mass analysis of several small molecules including drugs, explosives, and acid labile compounds. The macroporous spots also enable the archiving of samples.     

Analysis of amphetamines and fentanyls by atmospheric pressure desorption/ionization on silicon mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry and its application to forensic analysis of drug seizures

The suitability of atmospheric pressure desorption/ionization on silicon mass spectrometry (AP-DIOS-MS) and matrix-assisted laser desorption ionization mass spectrometry (AP-MALDI-MS) for the identification of amphetamines and fentanyls in forensic samples was studied. With both ionization techniques, the mass spectra recorded showed abundant protonated molecules, and the background did not disturb the analysis. The use of tandem mass spectrometry (MS/MS) allowed unambiguous identification of the amphetamines and fentanyls. AP-DIOS-MS/MS and AP-MALDI-MS/MS were also successfully applied to the identification of authentic compounds from drug seizures. Common diluents and tablet materials did not disturb the analysis and compounds were unequivocally identified. The limits of detection (LODs) for amphetamines and fentanyls with AP-DIOS-MS/MS were 1-3 pmol, indicating excellent sensitivity of the method. The LODs with AP-MALDI-MS/MS were about 5-10 times higher.     

Infrared pulsed fiber laser-produced silver-109-nanoparticles for laser desorption/ionization mass spectrometry of amino acids

Application of monoisotopic cationic ¹⁰⁹Ag nanoparticles (¹⁰⁹AgNPs) obtained by pulsed fiber laser (PFL) 2D galvo-scanner (GS) laser generated nanomaterial (LGN) for both high resolution laser desorption/ionization mass spectrometry and mass spectrometry imaging of amino acids is presented. Four amino acids, alanine, isoleucine, lysine, and phenylalanine were used as test compounds for quantification with matrix-assisted laser desorption/ionization mas (MALDI)-type mass spectrometer. Comparison of commonly made manual measurements with semiautomatic mass spectrometry imaging (MSI) was performed providing very interesting findings. Amino acids were directly tested in 1 000 000-fold concentration change conditions ranging from 1 mg/ml to 1 ng/ml, which equates to 500 ng to 500 fg of amino acid per measurement spot. Methods were also tested on samples of human blood plasma for quantification of endogenous amino acids.     

Coupling two-step laser desorption/ionization with aerosol time-of-flight mass spectrometry for the analysis of individual organic particles

Analysis of organic compounds in aerosol particles using real-time single particle techniques is difficult because of extensive fragmentation that occurs in the laser desorption/ionization step. In an effort to avoid such fragmentation processes, we coupled a “soft” two-step laser desorption/ionization technique (L2MS) with aerosol time-of-flight mass spectrometry (ATOFMS). In these studies, we find this combination preserves intact organic molecules while providing the real-time mass spectra of suspended aerosol particles. Mass spectra of particles analyzed by one-step desorption mass spectrometry and L2MS are presented for comparison. These include 2,4-dihydroxybenzoic acid as a test case and wood and cigarette combustion particles as real world examples. This is the first published demonstration of L2MS performed on single particles not deposited on a substrate prior to analysis.     

MALDI-TOF MS测定多肽类聚合物相对分子质量的条件优化

本文用基质辅助激光解吸电离飞行时间质谱来测定多肽类聚合物的相对分子质量,对基质、溶剂以及添加阳离子条件进行了优化。     

Silver‐109‐based laser desorption/ionization mass spectrometry method for detection and quantification of amino acids

A new methodology applicable for both high‐resolution laser desorption/ionization mass spectrometry and mass spectrometry imaging of amino acids is presented. The matrix‐assisted laser desorption ionization‐type target containing monoisotopic cationic ¹⁰⁹Ag nanoparticles (¹⁰⁹AgNPs) was used for rapid mass spectrometry measurements of 11 amino acids of different chemical properties. Amino acids were directly tested in 100,000‐fold concentration change conditions ranging from 100 μg/mL to 1 ng/mL which equates to 50 ng to 500 fg of amino acid per measurement spot. Limit of detection values obtained suggest that presented method/target system is among the fastest and most sensitive ones in laser mass spectrometry. Mass spectrometry imaging of spots of human blood plasma spiked with amino acids showed their surface distribution allowing optimization of quantitative measurements.     

X-ray ionization and fragmentation for use with time-of-flight mass spectrometry

In this paper, we introduce laser desorption X-ray ionization for producing ions from the previously undetected neutral species present during laser desorption mass spectrometry. Studies involving the laser desorption of simple sugars were conducted to illustrate the differences between spectra with and without the X-ray source. Ionization was made possible by placing a 200 mCi Am X-ray source directly into the ionization chamber of a time-of-flight mass spectrometer.     

Detection and characterization by high-performance liquid chromatography and mass spectrometry of two truncated goat alphas2-caseins

The identification and characterization of truncated forms of goat alphas2-Cn variants A and E are reported. The two proteins, which have experimental Mr values of 24 183 and 24 227 Da, were detected as minor components in a goat milk sample from an autochthonous breed of southern Italy, 'Rossa Mediterranea', by reversed-phase high-performance liquid chromatography/electrospray ionization mass spectrometry (RP-HPLC/ESI-MS). Characterization of the amino acid sequences, performed by coupling trypsin digestion with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), RP-HPLC/ESI-MS and tandem mass spectrometry (MS/MS), demonstrated that the polypeptide chains correspond to the 1-204 sequence of mature alphas2-Cn variant A (component with Mr of 24 183 Da) and E (component with Mr of 24 227 Da), respectively. These components seem to be the product of a differential splicing of pre-messenger RNA during the translation process of the alphas2-Cn variants A and E.