The use of mass defect in modern mass spectrometry

Mass defect is defined as the difference between a compound's exact mass and its nominal mass. This concept has been increasingly used in mass spectrometry over the years, mainly due to the growing use of high resolution mass spectrometers capable of exact mass measurements in many application areas in analytical and bioanalytical chemistry. This article is meant as an introduction to the different uses of mass defect in applications using modern MS instrumentation. Visualizing complex mass spectra may be simplified with the concept of Kendrick mass by plotting nominal mass as a function of Kendrick mass defect, based on hydrocarbons subunits, as well as slight variations on this theme. Mass defect filtering of complex MS data has been used for selectively detecting compounds of interest, including drugs and their metabolites or endogenous compounds such as peptides and small molecule metabolites. Several strategies have been applied for labeling analytes with reagents containing unique mass defect features, thus shifting molecules into a less noisy area in the mass spectrum, thus increasing their detectability, especially in the area of proteomics. All these concepts will be covered to introduce the interested reader to the plethora of possibilities of mass defect analysis of high resolution mass spectra.     

Atomic spectrometry and atomic mass spectrometry in bioanalytical chemistry

Abstract

Atomic spectrometry and atomic mass spectrometric (MS) techniques have been playing crucial roles in the field of biosciences. They detect elements with relatively high sensitivities and are thus applicable to a wide range of analytical targets. In the past decade, determination of bio-relevant metallic elements continues to be of interest, while particularly noteworthy are methods developed for small molecules, peptides, proteins, nucleic acids and even cells that well exploited the bio-analytical strengths of atomic spectrometry and atomic MS, either in a direct or indirect manner. Quantitation, as well as speciation and imaging analyses are all involved. The present review aims to assimilate recent advances in bio-analysis utilizing atomic spectrometry and atomic MS, primarily covering the period of 2013–2018, in an attempt to provide readers insight into the developing trends of this research frontier. Followed by concluding remarks and perspectives, the applications are divided into the following four catalogs: (i) toxicologically important metal-containing species, with an emphasis on quantitative and imaging analysis; (ii) quantitation of biomolecules using naturally occurring heteroatoms; (iii) exogenous metal ion or nanoparticle tagging-based strategies in bioassays; and (iv) label-free detection of biomolecules.     

Accurate mass spectrometry of trapped ions

The Penning trap Ion Cyclotron Resonance (ICR) method we use to weigh atomic masses is reviewed, and our plans for future measurements, new methods, and apparatus improvements are discussed. Our ultimate goal is to develop a new technique for measuring atomic masses with an accuracy of a few parts in 10¹². We will do this by comparing the cyclotron frequencies of two simultaneously trapped ions. In order to successfully implement this new method we are developing a quieter, more sensitive DC SQUID-based detector and a new more harmonic trap, and we plan to use our classical squeezing techniques to reduce the effects of thermal noise. With our improved apparatus we will weigh Cs and Rb to help determine the fine structure constant α, weigh ²⁹Si and ³⁰Si as part of the current effort to replace the artifact kilogram standard with a Si crystal containing a known number of atoms, and measure the ³H-³He mass difference to help set a limit on the mass of the electron neutrino. Our higher accuracy will also enable us to ``weigh' the neutron capture gamma rays of <sup>28</sup>Si, <sup>32</sup>S, and <sup>48</sup>Ti to help determine the molar Planck constant N<sub>A</sub>h and the fine structure constant α. Finally, with a mass measurement accuracy \sim 10<sup>-12</sup> we will be able to ``weigh' chemical bonds. This revised version was published online in August 2006 with corrections to the Cover Date.     

High-accuracy mass spectrometry with stored ions

Like few other parameters, the mass of an atom, and its inherent connection with the atomic and nuclear binding energy is a fundamental property, a unique fingerprint of the atomic nucleus. Each nuclide comes with its own mass value different from all others. For short-lived exotic atomic nuclei the importance of its mass ranges from the verification of nuclear models to a test of the Standard Model, in particular with regard to the weak interaction and the unitarity of the Cabibbo–Kobayashi–Maskawa quark mixing matrix. In addition, accurate mass values are important for a variety of applications that extend beyond nuclear physics. Mass measurements on stable atoms now reach a relative uncertainty of about 10^-11${10}^{-11}$. This extreme accuracy contributes, among other things, to metrology, for example the determination of fundamental constants and a new definition of the kilogram, and to tests of quantum electrodynamics and fundamental charge, parity, and time reversal symmetry. The introduction of Penning traps and storage rings into the field of mass spectrometry has made this method a prime choice for high-accuracy measurements on short-lived and stable nuclides. This is reflected in the large number of traps in operation, under construction, or planned world-wide. With the development and application of proper cooling and detection methods the trapping technique has the potential to provide the highest sensitivity and accuracy, even for very short-lived nuclides far from stability. This review describes the basics and recent progress made in ion trapping, cooling, and detection for high-accuracy mass measurements with emphasis on Penning traps. Special attention is devoted to the applications of accurate mass values in different fields of physics.     

Field ionization mass spectrometry of organic compounds

A review is given on field ionization mass spectrometry of organic compounds. Four different subjects are treated and illustrated by means of significant examples: Experimental techniques, surface reactions induced by high electric fields, the kinetics of fast unimolecular decompositions of ions, and qualitative and quantitative analyses of organic compounds by field desorption methods.     

Parts-per-billion detection with electron-gas secondary-neutral mass spectrometry

Post-ionization of sputtered neutral atoms by means of the electron component of a special low-pressure plasma (‘electron gas’) and detection of these ions in a high-transmission double-focusing mass spectrometer provide a bulk detection efficiency in the low parts-per-billion (ppb ≡ 10⁻⁹) range. This is demonstrated for 12 trace elements in a Cu standard (with concentrations in the low and sub-ppm range) and a Te-doped GaAs specimen. The Te isotope with the lowest natural abundance (¹²⁰Te) corresponds to an atomic concentration of 2.85 ppb and is identified at a signal level of 2 counts/s, while the (mass-independent) background amounts to < 0.1 counts/s. For both specimens, measured intensities exhibit a close one-to-one correlation with the atomic concentrations extending over a range of nearly nine orders of magnitude.     

Gas-flow assisted ion transfer for mass spectrometry

Methods and devices that use gas flows to collect ions and transfer them over long distances for mass spectrometric analysis have been developed. Gas flows derived from the ionization source itself or provided by means of additional pumping were used to generate a laminar flow inside cylindrical tube. Hydrodynamic simulations and experimental tests demonstrate that laminar flow can transfer ions over long distance. The typical angular discrimination effects encountered when sampling ions from ambient ionization sources are minimized, and the sampling of relatively large surface areas is demonstrated with desorption electrospray ionization (DESI). Ion transfer over 6 m has been achieved and its application to multiplexed chemical analysis is demonstrated on samples at locations remote from the mass spectrometer.     

A quantum sensor for high-performance mass spectrometry

A novel device, called quantum sensor, has been conceived to measure the mass of a single ion with ultimate accuracy and unprecedented sensitivity while the ion is stored and cooled in a trap. The quantum sensor consists of a single calcium ion as sensor, which is laser cooled to mK temperatures and stored in a second trap connected to the trap for the ion under study by a common endcap. The cyclotron motion of the ion under investigation is transformed into axial motion along the magnetic field lines and coupled to the sensor ion by the image current induced in the common endcap. The axial motion of the sensor ion in turn is monitored spatially resolved by its fluorescence light. In this way the detection of phonons can be upgraded to a detection of photons. This device will allow one to overcome recent limitations in high-precision mass spectrometry.     

Quantitative secondary ion mass spectrometry of fluorocarbon polymers

Secondary ion mass spectrometry (SIMS) is used to measure quantitatively the thickness of thin (6–160 Å) polyperfluoroether films on silicon and gold surfaces. Linear relationship between ellipsometrically measured thicknesses and integrated SIMS signals is demonstrated. Time dependence of SIMS signals indicates that the polymeric films have a uniform thickness down to the thinnest layers studied. In the lower limit, the fluorocarbon polymers have extended, flat conformation due to polymer-substrate interactions. Sputtering yield and effective sputtering depth of oxygen ions are determined for these liquid polymers. It is also shown that organic adsorbates reside between the solid surface and the low surface tension fluorocarbon films.     

Ion-cyclotron-resonance mass spectrometry with a microwave plasmasource

The feasibility of coupling an electron-cyclotron-resonance (ECR) plasma-processing reactor directly to an omegatron mass spectrometer is demonstrated. The ECR plasma is created in a chamber that is coupled to the omegatron through a small, grounded orifice. Ions created in the ECR chamber flow along the magnetic field into the omegatron analysis cell, and the mass spectrum of these ions is recovered. Using this technique the mass spectra of both single-component (He) and two-component (N₂ and N) ECR plasmas were measured. The mass resolution as a function of the omegatron excitation voltage for He and N₂ plasmas was obtained and found to compare well to theoretical calculations     

应用激光质谱法选择探测一氧化碳

此文解决了激光质谱法中从含同质量数的N2分子的混合气体中选择CO分子这一问题,由于用紫外266nm激光不能从含N2分子的混合气体中选择CO分子,因此采用了可见激光来探测,发现用可见激光430～435nm的激光能成功地将CO分子选择探测出来。此外还着重分析了在可见波段和266nm激光下产生CO+离子的机理：在可见光波段443.55nm所对应的共振峰是CO分子吸收3光子的激光能量与A1Π态的振动量子数为2的振动态共振产生的;434.3nm所对应的共振峰是CO分子吸收3光子的激光能量与A1Π态的振动量子数为3的振动态共振产生的;CO分子吸收两光子的266nm激光能量与A1Π态第7振动态的某一高转动态相共振,处于该振动态的CO分子再继续吸收一个光子的266nm激光的能量至其电离态电离产生CO+离子。     

Investigation of trace laser mass p-dichlorobenzene using spectrometry

The time-of-flight mass spectrum （TOFMS） relative to the resonant two-photon ionization of gas phase p- dichlorobenzene was obtained in the wavelength range of 240 - 250 nm by a home-made system. A special design was made to reduce the effect of memory on the inner wall of the sample inlet system suitable for the investigation of semi-volatile organic compound. In this wavelength range, p-dichlorobenzene molecules firstly absorbed one photon to be excited from the ground state ^1Ag（So） to the first excited state ^1B2u （S1）, then absorbed another photon to be ionized. The relationship between the signal intensity of p-dichlorobenzene molecular ion C6H4^35Cl2^＋ at 248-nm wavelength and the laser power was given. The 1.52 power index of C6H4^35Cl2^＋ was a typical identification of the 3/2 power law. The relationship between the ion signal intensity of C6H4^35Cl2^＋ and the sample concentration was close to a linear one in the ppm（V/V） range, which led to a detection limit of 125 ppb（V/V） for p-dichlorobenzene.     

Differentiation of aminomethyl corrole isomers by mass spectrometry

Two new isomeric aminomethyl corrole derivatives of [5,10,15-tris(pentafluorophenyl)corrolato]gallium(III) were synthesized with pyridine (py) molecules as axial ligands. When investigated by electrospray ionization mass spectrometry, in the positive and the negative ion modes, these compounds showed an unusual gas-phase behavior that could be used for their differentiation. In the positive ion mode, the differentiation was achieved through the formation of diagnostic fragment ions formed from [M-py?+?H](+) precursors, by (CH(3) )(2) NH and HF losses. An unusual addition of water to the main fragment ions provides an alternative route for isomer identification. Semi-empirical calculations were performed to elucidate the structures and stabilities of the main ionic species formed in the positive ion mode. In the negative ion mode isomer discrimination is accomplished via the fragmentation of the methoxide adduct ions [M-py?+?CH(3) O](-) through (CH(3) )(2) N(.) and HF losses.     

The contribution of mass spectrometry to the biosciences

This paper provides a personal perspective on the recent development of mass spectrometry, arguing that these developments are increasingly driven by the research demands of the life sciences. Within that context, the analytical requirements of proteomics (the determination of the protein constituents of a cell or organism) provide useful examples of the need for very high sensitivity, selectivity to match the required analytical outcomes, rigorous quantification (both relative and absolute) of individual components, and quantitative definition of cellular processes.     

Investigation of trace p-dichlorobenzene using laser mass spectrometry

The time-of-flight mass spectrum (TOFMS) relative to the resonant two-photon ionization of gas phase pdichlorobcnzene was obtained in the wavelength range of 240 - 250 nm by a home-made system. A special design was made to reduce the effect of memory on the inner wall of the sample inlet system suitable for the investigation of semi-volatile organic compound. In this wavelength range, p-dichlorobenzene molecules firstly absorbed one photon to be excited from the ground state 1A9(So) to the first excited state 1B2u (S1), then absorbcd another photon to be ionized. The relationship between the signal intensity of p-dichlorobenzene molccular ion C6H435Cl at 248-nm wavelength and the laser power was given. The 1.52 power index of C6H435Cl2 was a typical identification of the 3/2 power law. The relationship between the ion signal intensity of C6H435Cl and the sample concentration was close to a linear one in the ppm(V/V) range, which led to a detection limit of 125 ppb(V/V) for p-dichlorobenzene.     

Penning trap mass spectrometry for nuclear structure studies

High-precision mass measurements as performed at the Penning trap mass spectrometer ISOLTRAP at ISOLDE/CERN are an important contribution to the investigation of nuclear structure. Precise nuclear masses with less than 0.1 ppm relative mass uncertainty allow stringent tests of mass models and formulae that are used to predict mass values of nuclides far from the valley of stability. Furthermore, an investigation of nuclear structure effects like shell or sub-shell closures, deformations, and halos is possible. In addition to a sophisticated experimental setup for precise mass measurements, a radioactive ion-beam facility that delivers a large variety of short-lived nuclides with sufficient yield is required. An overview of the results from the mass spectrometer ISOLTRAP is given and its limits and possibilities are described.