Controlling Charge States of Large Ions

Scalf, Mark; Westphall, Michael S.; Krause, Joern; Kaufman, Stanley L.; Smith, Lloyd M.

doi:10.1126/science.283.5399.194

Cited by 164 publications

(177 citation statements)

References 28 publications

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“…ES-MS methods have difficulty measuring high molecular weight proteins and the presence of more than one charge state can complicate data interpretation [45].…”

Section: 2polymers and Proteinsmentioning

confidence: 99%

Electrospray–differential mobility analysis of bionanoparticles

Guha

Tarlov

et al. 2012

Trends in Biotechnology

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The growth of the multibillion dollar bionanoparticle industry has spurred the development of new physical characterization methods. One such method, electrospraydifferential mobility analysis (ES-DMA) constitutes an electrospray for aerosolization of bionanoparticles (such as viruses, gold-nanoparticles, proteins, nanoparticle-protein complexes) and an ion mobility method that operates at atmospheric conditions, and separates bionanoparticles spatially. This dissertation identifies some relevant "problem" areas for ES-DMA by reviewing selected applications.Some such problems are: proteins while passing through ES capillaries are found to interact with it and thus produce time dependent size distributions. Further, it is thought that adsorbed proteins may subsequently desorb and influence size distributions with the ES-DMA which may concomitantly affect quantification of aggregates. These artifacts are studied systematically and it is demonstrated that ES-DMA can quantify adsorption-desorption of complex protein mixtures at high shear rates. Further, it is shown that desorbing proteins do not have a significant effect on size distributions. Another artifact of the ES takes place during the aersolization process. Two units (called monomers) of a bionanoparticle may get encapsulated in the same ES droplet and upon drying of the droplet create artificial dimers thus affecting quantification with ES-DMA. Assuming Poisson distribution, this thesis provides a systematic approach that can be undertaken to eliminate this artifact. A third artifact arises from the low sensitivity of the DMA to size increase. When a ligand (for e.g. protein) adsorbs to a bionanoparticle it creates an increase in the size of the later, which can be used to quantify the amount of ligand adsorbed per bionanoparticle. As ligands can change conformations upon adsorption, using ES-DMA for such applications may be flawed. This issue has been identified and a solution has been provided by integrating a mass analyzer after the ES-DMA.After correcting for these artifacts, this dissertation delves into characterization of different types of bionanoparticles and demonstrates that ES-DMA has several advantages over other traditional techniques such as transmission electron microscopy, size exclusion chromatography, analytical ultracentrifugation, dynamic light scattering and plaque assay and thus has immense potential to become a process analytical technique in biomanufacturing environments. ELECTROSPRAY-DIFFERENTIAL MOBILITY ANALYSIS OF BIONANOPARTICLES

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“…ES-MS methods have difficulty measuring high molecular weight proteins and the presence of more than one charge state can complicate data interpretation [45].…”

Section: 2polymers and Proteinsmentioning

confidence: 99%

Electrospray–differential mobility analysis of bionanoparticles

Guha

Tarlov

et al. 2012

Trends in Biotechnology

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“…In 1999, Smith and coworkers reported charge reduction of biopolymer ions formed via electrospray with the use of atmospheric pressure ion/ion reactions [21]. The instrument used in the original study contained three basic components: ESI source; a charge neutralization chamber, as shown in Figure 2; and an orthogonal TOF mass spectrometer [22].…”

Section: Atmospheric Pressure Ion/ion Reactions Followed By Mass Analmentioning

confidence: 99%

Evolution of instrumentation for the study of gas-phase ion/ion chemistry via mass spectrometry

Xia

McLuckey

2008

J. Am. Soc. Mass Spectrom.

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The scope of gas-phase ion/ion chemistry accessible to mass spectrometry is largely defined by the available tools. Due to the development of novel instrumentation, a wide range of reaction phenomenologies has been noted, many of which have been studied extensively and exploited for analytical applications. This perspective presents the development of mass spectrometry-based instrumentation for the study of the gas-phase ion/ion chemistry in which at least one of the reactants is multiply charged. The instrument evolution is presented within the context of three essential elements required for any ion/ion reaction study: the ionization source(s), the reaction vessel or environment, and the mass analyzer. Ionization source arrangements have included source combinations that allow for reactions between multiply charged ions of one polarity and singly charged ions of opposite polarity, arrangements that enable the study of reactions of multiply charged ions of opposite polarity and, most recently, arrangements that allow for ion formation from more than two ion sources. Gas-phase ion/ion reaction studies have been performed at near atmospheric pressure in flow reactor designs and within electrodynamic ion traps operated in the mTorr range. With ion trap as a reaction vessel, ionization and reaction processes can be independently optimized and ion/ion reactions can be implemented within the context of MS n experiments. Spatial separation of the reaction vessel from the mass analyzer allows for the use of any form of mass analysis in conjunction with ion/ion reactions. Time-of-flight mass analysis, for example, has provided significant improvements in mass analysis figures of merit relative to mass filters and ion traps. The development and evaluation of new tools has clearly been a central activity and contributor to the dramatic advances in the capabilities of mass spectrometry over the past several decades. In this perspective, we relate the evolution of instrumentation for research activities focused on the study and use of ion/ion reactions and offer it as one example of many where progress in an area of science is intimately related to and dependent on the development of instrumentation. It is provided in appreciation for the inspirational example of creativity in instrumentation development [1] provided by Cooks over the years. Electrospray ionization (ESI) [2], among its many contributions, enabled the development of macro-molecule ion/ ion chemistry as a research area. The multiple-charging phenomenon associated with electrospray makes possible the generation of multiply charged reactant ions. This capability leads to the possibility that at least one ion/ion reaction product can retain charge, which makes such a product directly amenable to study with mass spectrometry. In the past two decades, significant progress has been made in understanding and exploring the gas-phase ion/ion chemistry of high mass multiply charged ions. A variety of potential analytical applications have been developed accordingly. Co...

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“…The second approach is to admit the ions of opposite polarity into an electrodynamic ion trap for subsequent mutual storage and reaction. The former approach has employed a spray ionization method as one of the ion sources and either a discharge [12][13][14], radioactive source [15,16], or another spray ionizer [17] as the second ion source. In this approach, the ion sources have been operated simultaneously and, in general, continuously.…”

mentioning

confidence: 99%

A pulsed triple ionization source for sequential ion/ion reactions in an electrodynamic ion trap

Liang

Han

Xia

et al. 2007

J. Am. Soc. Mass Spectrom.

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A pulsed triple ionization source, using a common atmosphere/vacuum interface and ion path, has been developed to generate different types of ions for sequential ion/ion reaction experiments in a linear ion trap-based tandem mass spectrometer. The triple ionization source typically consists of a nano-electrospray emitter for analyte formation and two other emitters, an electrospray emitter and an atmospheric pressure chemical ionization emitter or a second nano-electrospray emitter for formation of the two different reagent ions. The three emitters are positioned in a parallel fashion close to the sampling orifice of the tandem mass spectrometer. The potentials applied to each emitter are sequentially pulsed so that desired ions are generated separately in time and space. Sequential ion/ion reactions take place after analyte ions of interest and different set of reagent ions are sequentially injected into a linear ion trap, where axial trapping is effected by applying an auxiliary radio frequency voltage to the end lenses. The pulsed triple ionization source allows independent optimization of each emitter and can be readily coupled to any atmospheric pressure ionization interface with no need for instrument modifications, provided the potentials required to transmit the ion polarity of interest can be synchronized with the emitter potentials. Several sequential ion/ion reactions examples are demonstrated to illustrate the analytical usefulness of the triple ionization source in the study of gas-phase ion/ion chemistry. . Electron-transfer reactions appear to be a highly useful means for deriving the primary structure information of peptides and proteins [7][8][9][10][11].Most ion/ion reaction studies involving biomolecules are conducted in one of two ways. The first approach is to mix the oppositely charged reactant ions at or near atmospheric pressure before sampling ions into a mass spectrometer. The second approach is to admit the ions of opposite polarity into an electrodynamic ion trap for subsequent mutual storage and reaction. The former approach has employed a spray ionization method as one of the ion sources and either a discharge [12][13][14], radioactive source [15,16], or another spray ionizer [17] as the second ion source. In this approach, the ion sources have been operated simultaneously and, in general, continuously. This approach avoids the need for instrument modification to accommodate an additional ion source interface but it is not conducive to MS n studies. In the latter approach, electrodynamic ion traps, either a quadrupole ion trap or a linear ion trap (LIT), are used as reaction vessels for ion/ion reactions due to their ability to store oppositelycharged ions simultaneously [18] as well as their ion isolation and MS n functionalities [19].Sequential ion/ion reactions have been found to be useful in a number of applications in the analysis of peptides and proteins. One example is the increase of the absolute charge state of a polypeptide ion, which has been achieved via two sequential i...

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Controlling Charge States of Large Ions

Cited by 164 publications

References 28 publications

Electrospray–differential mobility analysis of bionanoparticles

Electrospray–differential mobility analysis of bionanoparticles

Evolution of instrumentation for the study of gas-phase ion/ion chemistry via mass spectrometry

A pulsed triple ionization source for sequential ion/ion reactions in an electrodynamic ion trap

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