Reactive Charged Droplets for Reduction of Matrix Effects in Electrospray Ionization Mass Spectrometry

Kulyk, Dmytro S.; Miller, Colbert; Badu‐Tawiah, Abraham K.

doi:10.1021/acs.analchem.5b02943

Cited by 34 publications

(42 citation statements)

References 44 publications

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“…In 2007, Armstrong (Armstrong et al, 2007) could in principle detect 25 AAs without derivatization since all of them are usually well ionized. ESI (see chapter 4) as method of choice for gentle biomolecule ionization and fragmentation was applied (Kulyk et al, 2015). For improving the specificity of the measurement, a MRM protocol was engaged that allows identification of specific precursor-toproduct ion transitions (Armstrong et al, 2007).…”

Section: Prospects and Limitations Of Lc-ms Without Derivatizationmentioning

confidence: 99%

The why and how of amino acid analytics in cancer diagnostics and therapy

Manig

Kuhne

Neubeck

et al. 2017

Journal of Biotechnology

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Pathological alterations in cell functions are frequently accompanied by metabolic reprogramming including modifications in amino acid metabolism. Amino acid detection is thus integral to the diagnosis of many hereditary metabolic diseases. The development of malignant diseases as metabolic disorders comes along with a complex dysregulation of genetic and epigenetic factors affecting metabolic enzymes. Cancer cells might transiently or permanently become auxotrophic for non-essential or semi-essential amino acids such as asparagine or arginine. Also, transformed cells are often more susceptible to local shortage of essential amino acids such as methionine than normal tissues. This offers new points of attacking unique metabolic features in cancer cells. To better understand these processes, highly sensitive methods for amino acid detection and quantification are required. Our review summarizes the main methodologies for amino acid detection with a particular focus on applications in biomedicine and cancer, provides a historical overview of the methodological pre-requisites in amino acid analytics. We compare classical and modern approaches such as the combination of gas chromatography and liquid chromatography with mass spectrometry (GC-MS/LC-MS). The latter is increasingly applied in clinical routine. We therefore illustrate an LC-MS workflow for analyzing arginine and methionine as well as their precursors and analogs in biological material. Pitfalls during protocol development are discussed, but LC-MS emerges as a reliable and sensitive tool for the detection of amino acids in biological matrices. Quantification is challenging, but of particular interest in cancer research as targeting arginine and methionine turnover in cancer cells represent novel treatment strategies.

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Section: Prospects and Limitations Of Lc-ms Without Derivatizationmentioning

confidence: 99%

The why and how of amino acid analytics in cancer diagnostics and therapy

Manig

Kuhne

Neubeck

et al. 2017

Journal of Biotechnology

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“…Multiple charged droplets are found in a number of highly diverse environments such as thunderclouds, 1 ink-jet printing, 2 mass spectrometry ionization methods, [3][4][5][6][7][8][9][10][11] and in the emerging area of aerosol micro-reactors. [12][13][14][15][16][17][18][19] The relation of the structure of a multiple charged droplet to the ion-ejection mechanisms has been a central question in mass spectrometry and atmospheric chemistry. The problem is significant because the (simple) ion-ejection may determine the charge state of macroions that are detected in native mass spectrometry.…”

Section: Introductionmentioning

confidence: 99%

The Relation Between Ejection Mechanism and Ion Abundance in the Electric Double Layer of Drops

Kwan¹,

O'Dwyer²,

Laur³

et al. 2021

Preprint

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The composition of outer drop layers has been associated with distinct chemical reactivity. We use atomistic modeling to examine how the composition of the surface excess charge layer (SECL) is related to the ejection mechanisms of ions. Even though the drop disintegration is inherently a non-equilibrium process we find that the equilibrium ion distribution in SECL predicts the ions that are ejected. The escape of the ions in aqueous drops takes place from conical protrusions that are global drop deformations and their appearance is independent of the location of a single ion. Our results are consistent with the equilibrium partition model, which associates the mass spectrum with the distribution of analytes in the drop’s double electric layer. We present evidence that atomistic simulations of minute nano-drops cannot distinguish Rayleigh fission from the ion evaporation mechanism.

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“…In a series of articles we dissect the droplet structure using atomistic modeling with the aim to find the mechanisms of charging of macromolecules in spray-based methods used in native mass spectrometry and explain the acceleration of reactions in microdrops. [25][26][27][28][29][30] In previous research we computed ion distribution profiles and compared them with our analytical theory that combines main factors that determine these distributions. 31 These factors include a decay length of the ion distribution that arises from the solution of non-linear Poisson-Boltzmann (NPB) equation for a rigid spherical droplet, shape fluctuations and the size of the ions.…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization of the Surface Excess Charge Layer in Droplets

Kwan¹,

Consta²

2020

Preprint

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<div>Charged droplets play a central role in native mass spectrometry, atmospheric aerosols and in serving as micro-reactors for accelerating chemical reactions. The surface excess charge layer (SECL) in droplets has often been associated with distinct chemistry. Using molecular simulations for droplets with Na+ and Cl- ions we have found that this layer is ≈ 1.5−1.7 nm thick and depending on the droplet size it includes 33%-55% of the total number of ions. Here, we examine the eﬀect of droplet size and nature of ions in the structure of SECL by using molecular dynamics. We ﬁnd that in the presence of simple ions the thickness of the surface excess charge layer is invariant not only with respect to droplet size but also with respect to the nature of the simple ions and it is not sensitive to ﬁne details of different force ﬁelds used in our simulations.</div><div> In the presence of macroions the SECL may extend to 2.0. nm. For the same droplet size, iodide and model H3O+ ions show considerably higher concentration than the sodium and chloride ions. In nano-drops, the SECL does not have the highest concentration of ions. We identify the maximum ion concentration region that may overlap with SECL in nano-drops. We also ﬁnd that the differences in the average water dipole orientation in the presence of cations and anions in this layer are reﬂected in the charge distributions. Within the surface charge layer, the number of hydrogen bonds reduces gradually relative to the droplet interior where the number of hydrogen bonds is on the average 2.9 for droplets of diameter < 4 nm and 3.5 for larger droplets. The decrease in the number of hydrogen bonds from the interior to the surface is less pronounced in larger droplets. In droplets with diameter < 4 nm and high concentration of ions the charge of the ions is not compensated only by the solvent polarization charge but by the total charge that also includes the other free charge. This ﬁnding shows exceptions to the commonly made assumption that the solvent compensates the charge of the ions in solvents with very high dielectric constant. The study provides molecular insight into the bi-layer droplet structure assumed in the equilibrium partitioning model (EPM) of C. Enke and assesses critical assumptions of the Iribarne-Thomson model for the ion-evaporation mechanism. We suggest the extension of the bi-layer droplet structure in EPM to include the maximum ion concentration region that may not coincide with SECL in nanodrops. We compute the ion concentrations in SECL, which are those that should enter the kinetic equation in the ion-evaporation mechanism, instead of the overall drop ion concentration that has been used thus far.<br></div>

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Reactive Charged Droplets for Reduction of Matrix Effects in Electrospray Ionization Mass Spectrometry

Cited by 34 publications

References 44 publications

The why and how of amino acid analytics in cancer diagnostics and therapy

The why and how of amino acid analytics in cancer diagnostics and therapy

The Relation Between Ejection Mechanism and Ion Abundance in the Electric Double Layer of Drops

Molecular Characterization of the Surface Excess Charge Layer in Droplets

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