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.     

基体辅助激光解吸电离飞行时间质谱用于人参皂甙Rg3的定量分析

考察了基体辅助激光解吸电离时间飞行质谱用于人参皂甙Rg     

基于纳米材料的表面辅助激光解吸离子化质谱研究

基质辅助激光解吸离子化质谱(MALDI-MS)作为一种常规的分析表征方法主要用于生物大分子的分析,如蛋白质、多肽、多糖及核酸等.然而,MALDI-MS中使用的有机小分子基质在低分子量区会产生背景干扰,很难分析小分子量化合物(m/z < 700).最近,基于纳米材料的免有机基质的激光解吸离子化质谱(又称为表面辅助激光解吸离子化质谱,SALDI-MS)有效解决了上述问题.SALDI-MS分析中使用的起到能量转移作用的纳米材料在低分子量区间不会产生背景干扰峰,可以将分析对象由大分子扩展到小分子.另外,SALDI-MS还具有许多其他优点,如样品制备简单、信噪比高、耐盐性好、基底表面信号重复性好及可实现样品的定量分析等,显示了较好的应用前景.本文综述了研究较多的四大类纳米材料在SALDI-MS分析、检测及成像方面的应用,包括碳纳米材料(富勒烯、碳纳米管、石墨烯及氧化石墨烯)、硅纳米材料(多孔硅、硅纳米纤维、硅纳米粒子)、其他材料纳米粒子(包括金属纳米粒子、金属氧化物纳米粒子、无机盐纳米粒子及量子点等)及纳米杂化多孔材料,详细介绍了最近的一些研究进展;并讨论了纳米材料在SALDI-MS应用中的能量转移机理.最后,讨论了该领域未来的研究内容和方向以及亟待研究的重要问题.     

Meso-四(对烷氧苯基)卟啉金属银配合物的激光解吸电离飞行时间质谱表征

通过激光解吸电离飞行时间质谱对meso-四(对烷氧苯基)卟啉金属银配合物进行了表征.样品溶解在氯仿中,以正离子方式记录谱图,结果发现除了产生目标化合物分子离子峰外,没有任何碎片峰.激光解吸电离飞行时间质谱是表征这种meso-四(对烷氧苯基)卟啉金属银配合物有效的方法.     

稠环齐聚物结构的激光解吸电离飞行时间质谱表征

应用激光解吸电离飞行时间质谱对几种不同结构的吡嗪稠环齐聚物进行了表征.样品溶解在二甲基亚砜中,以正离子方式记录谱图,结果发现除了产生目标化合物的质子化的分子离子峰外,还产生了少量的碎片分子离子峰.结果表明激光解吸电离飞行时间质谱能有效地、快速准确地给出这类化合物的分子离子峰,为吡嗪类稠环齐聚物的研究提供了有效的表征方法.     

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。     

MALDI-TOF-MS在生物化学和高分子化学中的应用

基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)这一先进技术是80年代末发展起来的一个质谱学分支,它的诞生无疑为国内诸多领域注入了一丝新鲜的活力.自从带基质的激光解吸电离飞行时间质谱技术问世以来,具有良好的"软电离"性质对杂质的包容性以及可直接分析混合物而无需预先分离等特点,已广泛地应用于生物化学、高分子化学、有机化学、金属有机化学、药学等领域,显示出独特的潜力和应用前景.本文讨论了MALDI-TOF-MS技术在生物化学和高分子化学领域中的应用.     

基质辅助激光解吸电离飞行时间质谱研究2: 四硫 富瓦烯化合物

采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS),对四硫富瓦烯化合物进行质谱表征。在所用的实验条件下,样品很容易解吸电离生成单电荷分子离子,得到单同位素分辨的质谱图。26种实际样品的质谱分析结果表明;MALDI-TOF-MS可以比其它质谱方法更有效、更方便地用于此类化合物的质谱分析,解决了此类化合物不易进行质谱鉴定的难题。     

基质辅助激光解吸电离飞行时间质谱研究2: 四硫 富瓦烯化合物

采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS),对四硫富瓦烯化合物进行质谱表征。在所用的实验条件下,样品很容易解吸电离生成单电荷分子离子,得到单同位素分辨的质谱图。26种实际样品的质谱分析结果表明;MALDI-TOF-MS可以比其它质谱方法更有效、更方便地用于此类化合物的质谱分析,解决了此类化合物不易进行质谱鉴定的难题。     

基质辅助激光解吸电离飞行时间质谱研究Ⅱ.四硫富瓦烯化合物

采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS),对四硫富瓦烯化合物进行质谱表征.在所用的实验条件下,样品很容易解吸电离生成单电荷分子离子,得到单同位素分辨的质谱图.26种实际样品的质谱分析结果表明:MALDI-TOF-MS可以比其它质谱方法更有效、更方便地用于此类化合物的质谱分析,解决了此类化合物不易进行质谱鉴定的难题.     

High surface area of porous silicon drives desorption of intact molecules

The surface structure of porous silicon used in desorption/ionization on porous silicon (DIOS) mass analysis is known to play a primary role in the desorption/ionization (D/I) process. In this study, mass spectrometry and scanning electron microscopy (SEM) are used to examine the correlation between intact ion generation with surface ablation and surface morphology. The DIOS process is found to be highly laser energy dependent and correlates directly with the appearance of surface ions (Si(n)(+) and OSiH(+)). A threshold laser energy for DIOS is observed (10 mJ/cm(2)), which supports that DIOS is driven by surface restructuring and is not a strictly thermal process. In addition, three DIOS regimes are observed that correspond to surface restructuring and melting. These results suggest that higher surface area silicon substrates may enhance DIOS performance. A recent example that fits into this mechanism is the surface of silicon nanowires, which has a high surface energy and concomitantly requires lower laser energy for analyte desorption.     

Oxidation of ferrocene derivatives in desorption/lonization on porous silicon.

In matrix-assisted laser desorption/ionization (MALDI), the true molecular structures of some analytes are not represented by the observed ions due to a redox reaction. In earlier reports, electron transfer from analyte to chemical matrix has been proposed for the oxidation of ferrocene derivatives in MALDI. To address such a redox phenomenon in laser desorption/ionization processes, two ferrocene derivatives, FcCH2CH2Fc and FcCH2NMe2 [Fc:(CsHs)Fe(CsH4)], were analyzed by a matrix-free method, desorption/ionization on porous silicon (DIOS). The oxidized species, Fc+CH2NMe2 and FcCH2CH2Fc+, were detected in the DIOS mass spectra. The results suggested that electron transfer from the analytes to the sample target occurs during the ionization process.     

Reduction of organic dyes in matrix-assisted laser desorption/ionization and desorption/ionization on porous silicon

Reduction of analytes in matrix-assisted laser desorption/ionization (MALDI) often obscures the actual determination of molecular structure. To address the redox reactions in laser desorption/ionization processes, the organic dyes Methylene Blue, Janus Green B, Crystal Violet and Rhodamine B were analyzed by MALDI or by desorption/ionization on porous silicon (DIOS). Susceptibility to reduction in MALDI was dependent on both the reduction potentials of analytes and the molar ratio of analyte to matrix molecules. Addition of Cu(II) ions as an electron scavenger suppressed the reduction of Methylene Blue in MALDI. The results suggested that electron transfer to analytes from the sample target and/or from the matrix contributed to the reduction. In DIOS, the reductions of organic dyes were more prominent than in MALDI, and were not prevented by Cu(II) ion doping, probably due to direct contact of the analytes with silicon which had little electric resistance.     

Laser desorption/ionization mass spectrometry on porous silica and alumina for peptide mass fingerprinting

We investigated a variant of desorption/ionization on porous silicon (DIOS) mass spectrometry utilizing an aqueous suspension of either porous silica gel or porous alumina (pore size of 60 and 90 A, respectively). Laser desorption/ionization (LDI) from samples directly deposited on a stainless steel surface without any inorganic substrates was also achieved. Synthetic peptides designed to cover large sequence diversity constituted our model compounds. Sample preparation, including material conditioning, peptide solubilization, and deposition protocol onto standard matrix-assisted laser desorption/ionization (MALDI) probe, as well as ionization source tuning were optimized to perform sensitive reproducible LDI analyses. The addition of either a cationizing agent or an alkali metal scavenger to the sample suspension allowed modification of the ionization output. Comparing hydrophilic silica gel to hydrophobic reversed-phase silica gel as well as increasing material pore size provided further insights into desorption/ionization processes. Furthermore, mixtures of peptides were analyzed to probe the spectral suppression phenomenon when no interfering organic matrix was present. The results gathered from synthetic peptide cocktails indicated that LDI mass spectrometry on silica gel or alumina constitutes a promising complementary method to MALDI in proteomics for peptide mass fingerprinting.     

Atmospheric pressure laser desorption/ionization on porous silicon

A recently developed commercial atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) source (MassTech, Inc.) was modified to adopt commercially available DIOS plates (Mass Consortium Corp.) for the studies of laser desorption from the surface of porous silicon under atmospheric pressure conditions. The feasibility of atmospheric pressure laser desorption/ionization from the surface of porous silicon (AP-DIOS) was demonstrated. The advantages of this new AP-DIOS technique include reasonably good sensitivity (subpicomole range for standard peptide mixtures), simplicity of sample preparation, uniformity of target spots and the absence of matrix peaks in the spectra. The AP-DIOS source was interfaced with a commercial ion trap (LCQ Classic, Thermo Finnigan) which additionally provides a unique MS(n) capability. The AP-DIOS spectrum of 250 fmol of unseparated tryptic digest of bovine serum albumin (BSA) was compared with that of AP-MALDI for the same compound. AP-DIOS offers significantly better coverage for the digest components in the mass range 200-1000 Da. The combined data of both techniques enabled us to nearly double the number of matched peaks in BSA digest analysis compared with AP-DIOS or AP-MALDI analysis separately.     

Preparation of porous n-type silicon sample plates for desorption/ionization on silicon mass spectrometry (DIOS-MS)

This study focuses on porous silicon (pSi) fabrication methods and properties for desorption ionization on silicon mass spectrometry (DIOS-MS). PSi was prepared using electrochemical etching of n-type silicon in HF-ethanol solution. Porous areas were defined by a double-sided illumination arrangement: front-side porous areas were masked by a stencil mask, eliminating the need for standard photolithography, and backside illumination was used for the backside ohmic contact. Backside illumination improved the uniformity of the porosified areas. Porosification conditions, surface derivatizations and storage conditions were explored to optimize pSi area, pore size and pore depth. Chemical derivatization of the pSi surfaces improved the DIOS-MS performance providing better ionization efficiency and signal stability with lower laser energy. Droplet spreading and drying patterns on pSi were also examined. Pore sizes of 50-200 nm were found to be optimal for droplet evaporation and pore filling with the sample liquid, as measured by DIOS efficiency. With DIOS, significantly better detection sensitivity was obtained (e.g. 150 fmol for midazolam) than with desorption ionization from a standard MALDI steel plate without matrix addition (30 pmol for midazolam). Also the noise that disturbs the detection of low-molecular weight compounds at m/z < 500 with MALDI could be clearly reduced with DIOS. Low background MS spectra and good detection sensitivity at the 100-150 fmol level for pharmaceutical compounds were achieved with DIOS-MS.     

Analysis of deprotonated acids with silicon nanoparticle-assisted laser desorption/ ionization mass spectrometry

Chemically modified silicon nanoparticles were applied for the laser desorption/negative ionization of small acids. A series of substituted sulfonic acids and fatty acids was studied. Compared to desorption ionization on porous silicon (DIOS) and other matrix-less laser desorption/ionization techniques, silicon nanoparticle-assisted laser desorption/ionization (SPALDI) mass spectrometry allows for the analysis of acids in the negative ion mode without the observation of multimers or cation adducts. Using SPALDI, detection limits of many acids reached levels down to 50 pmol/μl. SPALDI of fatty acids with unmodified silicon nanoparticles was compared to SPALDI using the fluoroalkyl silylated silicon powder, with the unmodified particles showing better sensitivity for fatty acids, but with more low-mass background due to impurities and surfactants in the untreated silicon powder. The fatty acids exhibited a size-dependent response in both SPALDI and unmodified SPALDI, showing a signal intensity increase with the chain length of the fatty acids (C12-C18), leveling off at chain lengths of C18-C22. The size effect may be due to the crystallization of long chain fatty acids on the silicon. This hypothesis was further explored and supported by SPALDI of several, similar sized, unsaturated fatty acids with various crystallinities. Fatty acids in milk lipids and tick nymph samples were directly detected and their concentration ratios were determined by SPALDI mass spectrometry without complicated and time-consuming purification and esterification required in the traditional analysis of fatty acids by gas chromatography (GC). These results suggest that SPALDI mass spectrometry has the potential application in fast screening for small acids in crude samples with minimal sample preparation.     

多孔硅表面的激光解吸离子化质谱

多孔硅表面的解吸离子化质谱是一种新的生物质谱分析方法。克服了MALDI-TOF-MS中的基体干扰,适合进行了小分子分析。提出了新的样品制备方法,可以扩大测定范围,消除吸附杂质的干扰。发现该方法与多孔硅的光致光特性及表面疏水性无关。具有纳米结构的多孔硅作为该方法中能量的接收器。利用DIOS方法分析了氨基酸、肽、蛋白、糖等样品。此方法用于环糊精合成产物的分析,也得到了较好的结果。     

Laser desorption/ionization on porous silicon mass spectrometry for accurately determining the molecular weight distribution of polymers evaluated using a certified polystyrene standard.

Desorption/ionization on porous silicon-mass spectrometry (DIOS-MS) is a novel soft ionization MS technique that does not require any matrix reagent, ideally resulting in fewer obstructive peaks in the lower mass region. In this study, the etching conditions of porous silicon spots as an ionization platform of DIOS-MS were investigated for determining the molecular weight distribution (MWD) of polymers. To evaluate the accuracy of DIOS mass spectra observed using porous silicon spots prepared under various etching conditions, a certified polystyrene (PS) standard sample with an average molecular weight of ca. 2400 was used as a model sample. By optimizing the etching conditions, the MWD of the PS sample could be accurately observed by DIOS-MS using both p-type and n-type porous silicon spots. Especially, in the case of a suitable n-type spot, an accurate peak distribution with very fewer obstructive background peaks could be observed using the minimum laser power, comparable to the conventional matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS).     

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.