Matrix-free methods for laser desorption/ionization mass spectrometry

Matrix assisted laser desorption/ionization (MALDI) is a soft ionization mass spectrometric method that has become a preeminent technique in the analysis of a wide variety of compounds including polymers and proteins. The main drawback of MALDI is that it is difficult to analyze low molecular weight compounds (<1,000 m/z) because the matrix that allows MALDI to work interferes in this mass range. In recent years there has been considerable interest in developing laser desorption/ionization (LDI) techniques for the analysis of small molecules. This review examines the approaches to matrix-free LDI mass spectrometry including desorption/ionization on silicon (DIOS), sol-gels, and carbon-based microstructures. For the purposes of this review matrix-free methods are defined as those that do not require matrix to be mixed with the analyte and therefore does not require co-crystallization. The review will also examine mechanisms of ionization and applications of matrix-free LDI-MS.     

激光共振电离质谱计用光入射系统的研制

针对NINT3000质谱计的结构特点,利用高斯光学理论,推导出双透镜系统光学参数传递方程,并以此为依据设计出一套光学系统和光路调整装置,实现了激光束在离子源腔内的精确定位和聚集,焦斑半径为160μm,调节精度为10μm。目前,该系统已经安装在激光共振电离质谱计上,并实现了镥的单色双光子共振电离。     

Protein sequence information by matrix-assisted laser desorption/ionization in-source decay mass spectrometry

Proteins from biological samples are often identified by mass spectrometry (MS) with the two following "bottom-up" approaches: peptide mass fingerprinting or peptide sequence tag. Nevertheless, these strategies are time-consuming (digestion, liquid chromatography step, desalting step), the N- (or C-) terminal information often lacks and post-translational modifications (PTMs) are hardly observed. The in-source decay (ISD) occurring in a matrix assisted laser desorption/ionization (MALDI) source appears an interesting analytical tool to obtain N-terminal sequence, to identify proteins and to characterize PTMs by a "top-down" strategy. The goal of this review deals with the usefulness of the ISD technique in MALDI source in proteomics fields. In the first part, the ISD principle is explained and in the second part, the use of ISD in proteomic studies is discussed for protein identification and sequence characterization.     

基质辅助激光解吸电离飞行时间质谱法分析核糖核酸酶

应用基质辅助激光解吸电离飞行时间质谱法(MALD I-TOF-MS)成功地对核糖核酸酶相对分子量进行测定。探讨三种不同基质对其分析结果的影响,实验中发现α-氰基-4-羟基肉桂酸是适宜的基质,该方法是传统生物方法无法比拟的。     

Surface-assisted laser desorption/ionization mass spectrometry imaging: A review

In the last decades, surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) has attracted increasing interest due to its unique capabilities, achievable through the nanostructured substrates used to promote the analyte desorption/ionization. While the most widely recognized asset of SALDI-MS is the untargeted analysis of small molecules, this technique also offers the possibility of targeted approaches. In particular, the implementation of SALDI-MS imaging (SALDI-MSI), which is the focus of this review, opens up new opportunities. After a brief discussion of the nomenclature and the fundamental mechanisms associated with this technique, which are still highly controversial, the analytical strategies to perform SALDI-MSI are extensively discussed. Emphasis is placed on the sample preparation but also on the selection of the nanosubstrate (in terms of chemical composition and morphology) as well as its functionalization possibilities for the selective analysis of specific compounds in targeted approaches. Subsequently, some selected applications of SALDI-MSI in various fields (i.e., biomedical, biological, environmental, and forensic) are presented. The strengths and the remaining limitations of SALDI-MSI are finally summarized in the conclusion and some perspectives of this technique, which has a bright future, are proposed in this section.     

Femtosecond laser ablation elemental mass spectrometry

Laser ablation mass spectrometry (LA-MS) has always been an interesting method for the elemental analysis of solid samples. Chemical analysis with a laser requires small amounts of material. Depending on the analytical detection system, subpicogram quantities may be sufficient. In addition, a focused laser beam permits the spatial characterization of heterogeneity in solid samples typically with micrometer resolution in terms of lateral and depth dimensions. With the advent of high-energy, ultra-short pulse lasers, new possibilities arise. The task of this review is to discuss the principle differences between the ablation process of short (>1 ps) and ultra-short (<1 ps) pulses. Based on the timescales and the energy balance of the process that underlies an ablation event, it will be shown that ultra-short pulses are less thermal and cause less collateral damages than longer pulses. The confinement of the pulse energy to the focal region guarantees a better spatial resolution in all dimensions and improves the analytical figures of merit (e.g., fractionation). Applications that demonstrate these features and that will be presented are in-depth profiling of multi-layer samples and the elemental analysis of biological materials.     

Laser ablation‐inductively coupled plasma mass spectrometry in archaeometric research

Laser ablation‐inductively coupled plasma mass spectrometry (LA‐ICPMS) is a solid sampling technique in continuous expansion in all types of research fields in which direct multi‐elemental or isotopic analysis is required. In particular, this technique shows unique characteristics that made its use recommended in many archaeometric applications, where valuable solid artifacts are often the target samples, because it offers flexibility to achieve spatially resolved information with high detection power and a wide linear range, in a fast and straightforward way, and with minimal sample damage. The current review provides a systematic survey of publications that reported the use of LA‐ICPMS in an archaeological context, highlights its main capabilities and limitations and discusses the most relevant parameters that influence the performance of this technique for this type of application. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:55–78, 2010     

负热电离飞行时间质谱仪及其用于硼酸中硼同位素比值的测定

在自行研制的热电离飞行时间质谱仪(TI-TOF-MS)基础上,通过对仪器的重新设计和电源的改造,研制了负离子热电离飞行时间质谱仪(NTI-TOF-MS)。文中介绍NTI-TOF-MS仪器的结构及性能特点,通过对仪器性能进行测试,获得了仪器的分辨率,仪器在m/z为219amu处的分辨率为1369。文中应用NTI-TOF-MS法测量了核纯级硼酸样品中硼的同位素比值,测量的结果为¹⁰B/¹¹B=0.2403±0.0007。     

Ambient ionization mass spectrometry applied to new psychoactive substance analysis

In the past decade a plethora of drugs with similar effects to controlled psychoactive drugs, like cannabis, amfetamine (amphetamine), or lysergic acid diethylamide, have been synthesized. These drugs can collectively be classified under the term new psychoactive substances (NPS) and are used for recreational purposes. The novelty of the substances, alongside the rapid rate of emergence and structural variability, makes their detection as well as their legal control highly challenging, increasing the demand for rapid and easy-to-use analytical techniques for their detection and identification. Therefore, interest in ambient ionization mass spectrometry applied to NPS has grown in recent years, which is largely because it is relatively fast and simple to use and has a low operating cost. This review aims to provide a critique of the suitability of current ambient ionization techniques for the analysis of NPS in the forensic and clinical toxicology fields. Consideration is given to analytical performance and ease of implementation, including ionization efficiency, selectivity, sensitivity, quantification, analyte chemistry, molecular coverage, validation, and practicality.     

Electron ionization time-of-flight mass spectrometry: historical review and current applications

This review presents an overview of electron ionization time-of-flight mass spectroscopy (EITOFMS), beginning with its early development to the employment of modern high-resolution electron ionization sources. The EITOFMS is demonstrated to be ideally suited for analytical and basic chemical physics studies. Studies of the formation of positive ions by electron ionization time-of-flight mass spectroscopy have been responsible for many of the known ionization potentials of molecules and radicals, as well as accepted bond dissociation energies for ions and neutral molecules. The application of TOFMS has been particularly important in the area of negative ion physics and chemistry. A wide variety of negative ion properties have been discovered and studied by using these methods including: autodetachment lifetimes, metastable dissociation, Rydberg electron transfer reactions and field detachment, SF(6) Scavenger method for detecting temporary negative ion states, and many others.     

Aerosol laser time-of-flight mass spectrometer for the on-line measurement of secondary organic aerosol in smog chamber

An aerosol laser time of flight mass spectrometer (ALTOFMS) that can be used for real-time measurement of the size and composition of individual aerosol particles has been designed and utilized to provide on-line measurement of secondary organic aerosol (SOA) particles resulted from Cl-initiated oxidation of toluene in smog chamber. Both the size and chemical compositions of individual aerosol particles were obtained in real-time. According to a large number of single aerosol diameters and mass spectra, the size distribution and chemical composition of aerosol were determined statistically. Experimental results indicate that aerosol particles produced from Cl-initiated oxidation of toluene were predominantly in the form of PM 2.5 particles, and nine positive laser desorption/ionization mass spectra peaks: m/z 18, 29, 30, 44, 46, 52, 65, 77, and 94 may come from the fragment ions of the products of the SOA: aromatic aldehydes, aromatic acids, phenolic compounds, and nitrogenated organic compounds. These results were in good agreement with those ones from previous Cl-initiated oxidation of toluene. These were demonstrated that ALTOFMS is a useful tool to reveal the formation and transformation processes of SOA particles in smog chamber.     

Measurement of trace atmospheric species by chemical ionization mass spectrometry: speciation of reactive nitrogen and future directions

Chemical ionization mass spectrometry (CIMS) has proven to be a powerful method for sensitive, fast time response (t approximately 1 sec) measurements of various atmospheric compounds with limits of detection (LOD) of the order of tens of pptv and lower. The rapid time response of CIMS is particularly well suited for airborne measurements and its application has largely grown out of airborne measurements in the stratosphere and upper troposphere. This work reviews some of the advances in CIMS technology that have occurred in the past decade. In particular, CIMS methods for selective measurement of reactive nitrogen species (e.g., HNO3, HO2NO2, PAN, and NH3) in the lower atmosphere (altitudes approximately 0-8 km) are described. In addition, recent developments in CIMS technology for the selective measurement of gas-phase hydroperoxides and aerosol chemical composition are briefly described.     

The laser ball bar: a new instrument for machine tool metrology

Current techniques for mapping the volumetric positioning errors of machine tools are time and labor intensive. To address these shortcomings, a linear displacement measuring device is introduced to rapidly and easily determine tool positions via trilateration. The laser ball bar (LBB) consists of a laser interferometer aligned within a telescoping ball bar. The design of the device is discussed and an error budget is developed to estimate its predicted accuracy. Results of repeatability and linear accuracy test of the assembled prototype LBB are given. The LBB is used to map the volumetric errors of a two-axis turning center. Comparison of the LBB error map and the error map obtained through parametric error measurements shows the LBB can accurately map the machine errors in a timely manner.     

Bioimaging of metals by laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS)

The distribution analysis of (essential, beneficial, or toxic) metals (e.g., Cu, Fe, Zn, Pb, and others), metalloids, and non‐metals in biological tissues is of key interest in life science. Over the past few years, the development and application of several imaging mass spectrometric techniques has been rapidly growing in biology and medicine. Especially, in brain research metalloproteins are in the focus of targeted therapy approaches of neurodegenerative diseases such as Alzheimer's and Parkinson's disease, or stroke, or tumor growth. Laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) using double‐focusing sector field (LA‐ICP‐SFMS) or quadrupole‐based mass spectrometers (LA‐ICP‐QMS) has been successfully applied as a powerful imaging (mapping) technique to produce quantitative images of detailed regionally specific element distributions in thin tissue sections of human or rodent brain. Imaging LA‐ICP‐QMS was also applied to investigate metal distributions in plant and animal sections to study, for example, the uptake and transport of nutrient and toxic elements or environmental contamination. The combination of imaging LA‐ICP‐MS of metals with proteomic studies using biomolecular mass spectrometry identifies metal‐containing proteins and also phosphoproteins. Metal‐containing proteins were imaged in a two‐dimensional gel after electrophoretic separation of proteins (SDS or Blue Native PAGE). Recent progress in LA‐ICP‐MS imaging as a stand‐alone technique and in combination with MALDI/ESI‐MS for selected life science applications is summarized. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:156–175, 2010     

Accurate measure of laser irradiance threshold for near-infrared photo-oxidation with a modified confocal microscope

Femtosecond mode‐locked lasers are now being used routinely in multiphoton fluorescence and autofluorescence spectroscopy, are just beginning to be used in refractive surgery, and may be used in the future diagnosis of skin cancer. Pulses from these lasers induce non‐linear effects in resultant tissue interactions. Using a modified confocal microscope with dispersion compensation and accurate measurements of beam diameter, a very low threshold was measured for photochemical oxidation in cultured cells. The measured threshold showed non‐linear photo‐oxidation at a peak irradiance and photon‐flux density of 8.4 × 10⁸ W cm^?2 and 3.4 × 10²⁷ photons cm^?2 s^?1, respectively (90‐fs pulse). The impact of these findings is significant to those using ultrashort lasers because they provide a tangible reference point (microscope‐independent) for the generation of photo‐oxidative stress in laser‐exposed tissues, and because they highlight the importance of dispersion compensation in minimizing collateral tissue damage.