Mass Spectrometry,Review of the Basics: Ionization

Abstract: Mass spectrometry (MS) has become an integral tool in life sciences. The first step in MS analysis is ion formation (ionization). Many ionization methods currently exist; electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) are the most commonly used. ESI relies on the formation of charged droplets releasing ions from the surface (ion evaporation model) or via complete solvent evaporation (charge residual model). MALDI ionization, however, is facilitated via laser energy and the use of a matrix. Despite wide use, ESI cannot efficiently ionize nonpolar compounds. Atmospheric pressure chemical ionization (APCI) and atmospheric pressure photo ionization (APPI) are better suited for such tasks. APPI requires photon energy and a dopant, whereas APCI is similar to chemical ionization. In 2004, ambient MS was introduced in which ionization occurs at the sample in its native form. Desorption electrospray ionization (DESI) and direct analysis in real time (DART) are the most widely used methods. In this mini-review, we provide an overview of the main ionization methods and the mechanisms of ion formation. This article is educational and intended for students/researchers who are not very familiar with MS and would like to learn the basics; it is not for MS experts.     

Electrostatic field and charge distribution in small charged dielectric droplets

The charge distribution in small dielectric droplets is calculated on the basis of continuum medium approximation. There are considered charged liquid spherical droplets of methanol in the range of nanometer sizes. The problem is solved by the following way. We find the free energy of some ion in dielectric droplet, which is a function of distribution of other ions in the droplet. The probability of location of the ion in some element of volume in the droplet is a function of its free energy in this element of volume. The same approach can be applied to other ions in the droplet. The obtained charge distribution differs considerably from the surface distribution. The curve of the charge distribution in the droplet as a function of radius has maximum near the surface. Relative concentration of charges in the vicinity of the center of the droplet does not equal to zero, and it is the higher, the less is the total charge of the droplet. According to the estimates the model is applicable if the droplet radius is larger than 10 nm.     

Shape oscillations and stability of charged microdroplets

Classical Rayleigh theory predicts an instability of a surface charged liquid sphere, when the Coulomb energy E(C) exceeds twice the surface energy E(S). Previously, electrified liquid droplets have been found to disintegrate at a fissility X=E(C)/2E(S) well below one, however. We determine the stability of charged droplets in an electrodynamic levitator by observing the amplitude and phase of their quadrupolar shape oscillations as a function of the fissility. With this novel approach, which does not rely on an independent determination of the charge and surface tension of the droplets, we are able to confirm for the first time the Rayleigh limit of stability at X=1 for micrometer sized droplets of ethylene glycol.     

Modeling simple-jet mode electrohydrodynamic-atomization droplets' trajectories and spray pattern for a single nozzle system

Electrohydrodynamic atomization (EHDA), or simply Electrospraying is the process of influencing the breakup of a liquid into droplets by using a strong electric field. There can be different modes of Electrospraying depending, basically, on the created electric field strength and the liquid flowrate, for a specified liquid. Among these modes, the so-called cone-jet mode is the most explored one. This is due to its ability to produce highly charged monodisperse droplets in the nano- to micro-meter size range. Another mode of interest, which can also produce monodisperse droplets is the simple-jet mode. This mode is less explored when compared to the former. Within the papers that were explored by the authors, Agostinho et al. (2012) were the first authors to carefully investigate and characterize this mode. In their work, the authors reported about the influence of the electric field and the liquid flowrate on the droplets' size and spray dispersion. They also pointed out that the charge on these droplets can be expressed as a certain percentage of their Rayleigh limit.So far, there has been no model proposed to describe the droplets' trajectories in the simple-jet mode. This paper describes the design and the implementation of a physical model for determining the droplet trajectories in this mode. The model is done, specifically, for a single nozzle/ring-up configuration. It is a two-dimensional model, which solves the force balance equation for each droplet breaking up from the jet. It takes into consideration; the initial droplet velocity, the force of gravity, the electric field force, the inter-droplet coulombic force and the drag force. The droplets' deformation and reorientation were hypothesized, from observations, to play a major role in initiating the droplets' dispersion. They were simulated by implementing periodic displacements on the droplets' center of charge from its center of mass. The calculated droplets' trajectories' envelope angle was fitted to the experimental envelope angle by adjusting the droplet charge around the values that were reported by Agostinho et al. (2012). The model was validated by comparing the shapes of the theoretical and experimental sprays.The model offers new possibilities of modeling the droplets' trajectories in complex geometries, and of introducing additional forces to manipulate their trajectories in the simple-jet mode.     

Formation of cations and anions upon electron interaction with (doped) helium droplets

Superfluid helium droplets have provided a new perspective for studying electron induced chemistry at extremely low temperatures. Helium droplets represent an ideal environment for the formation of novel and exotic agglomerates of atoms and molecules. Mass spectrometry can be used to detect the resulting ions formed upon electron ionization and electron attachment to doped droplets. In the case of electron ionization a helium atom of the droplet is ionized initially and after few resonant charge transfer reactions between helium atoms the charge finally localises on the dopant. An alternative process is Penning ionization of the dopant, where the scattered electron first electronically excites a helium atom on the surface of the droplet. The attachment of a low energy electron leads to formation of an electron bubble inside the droplet which decays by autodetachment or localization on a dopant, if present in the droplet. In the present minireview a general overview about the field of electron scattering with doped helium droplets is given and a presentation of important recent results related to these electron collision studies is given as well.     

Nebulizing conditions of pneumatic electrospray ionization significantly influence electrolyte effects on compound measurement

Composition of mobile phase can greatly influence the success of electrospray ionization (ESI)-interfaced liquid chromatography-mass spectrometry analysis. To investigate the relationship between formic-acid-based modification of mobile phase and ESI nebulizing conditions, an API 4000 ESI source and a TSQ Quantum one were compared under the same chromatographic conditions. Ginkgo terpene lactones and flavonols were measured in plasma, which involved using ascorbic acid to circumvent cross-interference between the analytes. ESI responses to using formic acid included changes in signal intensity, matrix effect, and upper limit of quantification. Significant disparities in the responses were observed between the two ESI sources, suggesting that the use of electrolyte modifier in liquid chromatography mobile phase and the pneumatic nebulization for ESI should be properly balanced to accomplish optimal ESI-based analysis. The distribution of unpaired ions toward the surface of the initial droplet was assumed to be an important step in the pneumatic ESI process. When using the electrolyte in mobile phase, a too fast droplet reduction by rapid-heating-assisted pneumatic nebulization could negatively decrease the time available for the unpaired ions to migrate from droplet interior to its surface. Ascorbic acid was identified as a major interfering substance for the bioanalytical assay; the interference mechanism might be associated with hindering the unpaired analyte ions from distributing toward the droplet surface rather than outcompeting the analyte ions for the limited excess charge on droplets surface. The current work extends the knowledge base of pneumatic ESI, which has implication for optimal use of the ESI-interfaced liquid chromatography-mass spectrometry technique.     

General solvation motifs of a charged linear macroion in an aqueous droplet

ABSTRACT

We explore the solvation patterns of a charged rigid and semi-rigid linear macroion in an aqueous droplet. The solvation patterns are summarised in an empirical ‘phase diagram’ on the parameter space defined by the length of the macroion and its charge density. In the study, we employ molecular dynamics and atomistic modelling. The macroion is represented by a positively charged carbon nanotube. Linear macroion-solvent interactions in droplets are distinct from those of spherical ions because of the interplay among several factors such as the tendency of the solvent to form spherical droplets in order to minimise the surface energy, the constraint on the charge of a spherical droplet imposed by the Rayleigh limit, the solvation energy of the macroion and its length. The combination of all these factors may lead to a variety of solvent distributions along the rigid rod such as asymmetric solvation of the linear macroion, formation of spiky ‘star’-like distribution of solvent, partial wetting of the rod by a droplet. The study provides insight into the solvation of macroions in droplets with applications in electrosprayed macroions and atmospheric aerosols. We also propose a possible path of generating a sequence of nanoparticles of different shapes (spheres, multi-point stars) along a linear macromolecule by exploiting the various solvation patterns.     

On the mechanism of liquid metal ion sources

We have developed a theoretical model of liquid metal ion source operation which consistently explains the shape and size of the ion emitting region, the mechanism of ion formation and properties of the ion beam. We find that field evaporation is the main current generating mechanism and that field evaporation and subsequent postionization produce the doubly and higher charged ions. Field ionization of thermally evaporated neutrals may make a significant, but not dominant, contribution to the current of singly charged ions. Our model is consistent with experimental results on energy spread, energy deficit and charge state ratios and we are able to explain the stability of the emitted ion current.     

The shrinking instability of toroidal liquid droplets in the Stokes flow regime

We analyze the stability and dynamics of toroidal liquid droplets. In addition to the Rayleigh instabilities akin to those of a cylindrical droplet there is a shrinking instability that is unique to the topology of the torus and dominates in the limit that the aspect ratio is near one (fat tori). We first find an analytic expression for the pressure distribution inside the droplet. We then determine the velocity field in the bulk fluid, in the Stokes flow regime, by solving the biharmonic equation for the stream function. The flow pattern in the external fluid is analyzed qualitatively by exploiting symmetries. This elucidates the detailed nature of the shrinking mode and the swelling of the cross-section following from incompressibility. Finally the shrinking rate of fat toroidal droplets is derived by energy conservation.     

液滴发生器系统中流速及振荡频率的确定

 根据Rayleigh流体不稳定原理,确定了射流振荡波频率范围,分析了充电偏转过程,推导出了每滴液滴的充电量和受偏转电场偏转的电场力的大小。在压强为0.02,0.03,0.04,0.05,0.06 MPa下测量了喷射孔孔径分别为0.10,0.11,0.15 mm的射流初始速率,确定了最佳偏转振荡频率与射流初始速率和充电环长度的关系表达式。     

Investigations of Droplet‐Plasma Interaction using Multi‐Dimensional Coupled Model

Recently developed multi‐dimensional coupled fluid‐droplet model is used to investigate the behavior of complex interaction between the liquid precursor droplets and atmospheric pressure plasma (APP). The significance of this droplet‐plasma interaction is not well understood under diverse realm of working conditions in two‐phase flow. In this study, we explain the implication of vaporization of liquid droplets in APP which are subsequently responsible to control major characteristics of surface coating depositions. Coalescence of water droplets is more dominant than Hexamethyldisiloxane (HMDSO) droplets because of its sluggish rate of evaporation. A disparity in the performance of evaporation is identified in two independent mediums, such as gas mixture and discharge plasma using HMDSO precursor. The length of evaporation of droplets is amplified by an increment of gas flow rate indicating with a reduction in the gas temperature and electron mean energy. In particular, the spatio‐temporal density distributions of charged particles show a clear pattern in which the typical nitrogen impurity ions are primarily effective as compared to other helium ionic species along the pulse of droplets in APP. Finally, we contrast the behavior of discharge species in the pure helium and He‐N2 gas mixtures revealing the importance of stepwise and Penning ionization processes. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

超声波电喷推力器羽流中和特性研究

超声波电喷推力器主要应用在小卫星(10 kg)平台,为解决该类型推力器的羽流在中和过程中产生的推力偏角以及能效低的问题,对超声波电喷推力器的羽流中和过程进行数值研究.为实现电喷推力器羽流特有物理过程的仿真,建立了一种带电液滴中和模型(NECD模型),对电子-正电液滴的中和过程进行捕捉,包括带电粒子的输运过程、电子液滴碰撞过程以及液滴的破碎与重组等过程;为验证模型的可行性和精度,开展推力测量和羽流高速照相试验,以工况相同试验和仿真结果进行对比.结果显示,该模型的综合计算误差在20%左右,在不同工况下可以和试验值形成趋势上的符合.基于该计算模型,对放电功率为2 W、放电电流为2 m A的超声波电喷推力器进行羽流输运过程的数值模拟,获得表征羽流中和特性的几种参数分布,包括数密度、电荷密度、液滴体积大小等,并统计出各类能耗所占比例,解释了推力偏角和能效低问题的内在机理以及为相应优化提供参考.     

微尺度下锥形微操作探针表面液滴形成的研究（英）

基于液滴的转移方法可实现微操作任务中微对象的拾取,锥形操作探针则常作为一种毛细力微操作执行工具。主要研究在空气冷凝模式下锥形探针端面的液滴形成。建立了微液滴形成的数学模型,主要包括初始液滴的形成、液滴的合并和液滴的移动,研究了影响操作液滴的关键参数,分析表明:过冷度决定最小液滴半径。对单液滴的生长机制进行理论分析,并通过数值求解的方法模拟了锥形操作探针端面的液滴形成。搭建实验测试平台,实验研究了微尺度下锥形微操作探针端面的液滴形成。实验结果表明:在空气冷凝模式下,操作探针端面能够形成微液滴。经过初始液滴的形成,液滴的合并和移动等过程最终可形成稳定的微液滴,且不同锥顶角下液滴的形成呈现多样化。     

Catching proteins in liquid helium droplets

An experimental approach is presented that allows for the incorporation of large mass-to-charge ratio selected ions in liquid helium droplets. It is demonstrated that droplets can be efficiently doped with a mass-to-charge ratio selected amino acid as well as with the much bigger m ≈ 12,000 amu protein cytochrome C in selected charge states. The sizes of the ion-doped droplets are determined via electrostatic deflection. Under the experimental conditions employed, the observed droplet sizes are very large and range, depending on the incorporated ion, from 101? helium atoms for protonated phenylalanine to 1012 helium atoms for cytochrome C. As a possible explanation, a simple model based on the size and internal energy dependence of the pickup efficiency is given.     

Electrosprayed droplet impact/secondary ion mass spectrometry

A new ionization method, electrosprayed droplet impact ionization (EDI), has been developed for mass spectrometry. The charged droplets formed by electrospraying 1 M acetic acid aqueous solution are sampled through an orifice with a diameter of 400 μm into the first vacuum chamber, transported into a quadrupole ion guide and accelerated by 10 kV after exiting the ion guide. The m/z of the primary droplet projectiles range from 10 000 to 50 000. The droplets impact on a dry solid sample deposited on a stainless steel substrate. No matrix was used for the sample preparation. The secondary ions formed by the impact are transported to a second quadrupole ion guide and mass-analyzed by an orthogonal TOF-MS. Intense molecular-related ions are detected for drugs, amino acids, peptides and proteins. EDI is found to be very sensitive to molecules present near the surface of the sample.     

Landau–Ginzburg theory for ‘star’-shaped droplets

ABSTRACT

Molecular simulations have shown that when a nano-drop comprising a single spherical central ion and a dielectric solvent is charged above a well-defined threshold, it acquires a stable star morphology. A linear continuum model of the ‘star’-shapes comprised electrostatic and surface energy is not sufficient to describe these shapes. We employ combined molecular dynamics, continuum electrostatics and macroscopic modelling in order to construct a unified free energy functional that describes the observed star-shaped droplets. We demonstrate that the Landau free energy coupled to the third-order Steinhardt invariant mimics the shapes of droplets detected in molecular simulations. Using the maximum likelihood technique we build a universal free energy functional that describes droplets for a range of Rayleigh fissility parameter. The analysis of the macroscopic free energy demonstrates the origin of the finite amplitude perturbations just above the Rayleigh limit. We argue that the presence of the finite amplitude perturbations precludes the use of the small parameter perturbation method for the analysis of the shapes above the Rayleigh limit of the corresponding spherical shape.     

Ionization probability of sputtered particles as a function of their energy: Part II. Positive Si ions

In this paper we represent the experimental ionization probability of sputtered silicon atoms as a function of their energy, which has been obtained for positive Si⁺ ions sputtered from silicon by O₂⁺ ion beam. To explain the experimental data, we have considered ionization of an outgoing atom at a critical distance from the surface, which occurs due to the electron transition between this atom and the surface, and suggested the formation of a local surface charge with the polarity opposite to that of the outgoing ion that has just been formed. Then we have considered the interaction between those two charges, outgoing ion, and surface charge as a process of the particle passage through a spherical potential barrier; as a result, we have obtained the theoretical energy distribution of secondary ions. Together with the well-known Sigmund-Thompson energy distribution of sputtered atoms, the obtained ion energy distribution allowed us to derive the equation for the secondary ion yield versus the sputtered particle energy. Both equations derived have exhibited a quite good correlation with our experimental results and also with a large number of published experimental data.     

Simulations of coulombic fission of charged inviscid drops

We present boundary-integral simulations of the evolution of critically charged droplets. For such droplets, small perturbations are unstable and eventually lead to the formation of a lemon-shaped drop with very sharp tips. For perfectly conducting drops, the tip forms a self-similar cone shape with a subtended angle identical to that of a Taylor cone, and quantities such as pressure and velocity diverge in time with power-law scaling. In contrast, when charge transport is described by a finite conductivity, we find that small progeny drops are formed at the tips, whose size decreases as the conductivity is increased. These small progeny drops are of nearly critical charge, and are precursors to the emission of a sustained flow of liquid from the tips as observed in experiments of isolated charged drops.     

Correlations to predict droplet size in ultrasonic atomisation.

In conventional two fluid nozzles, the high velocity air imparts its energy to the liquid and disrupts the liquid sheet into droplets. If the energy for liquid sheet fragmentation can be supplied by the use of ultrasonic energy, finer droplets with high sphericity and uniform size distribution can be achieved. The other advantage of ultrasound induced atomisation process is the lower momentum associated with ejected droplets compared to the momentum carried by the droplets formed using conventional nozzles. This has advantage in coating and granulation processes. An ultrasonic probe sonicator was designed with a facility for liquid feed arrangement and was used to atomise the liquid into droplets. An ingenious method of droplet measurement was attempted by capturing the droplets on a filter paper (size variation with regard to wicking was uniform in all cases) and these are subjected to image analysis to obtain the droplet sizes. This procedure was evaluated by high-speed photography of droplets ejected at one particular experimental condition and these were image analysed. The correlations proposed in the literature to predict droplet sizes using ultrasound do not take into account all the relevant parameters. In this work, a truly universal correlation is proposed which accounts for the effects of physico-chemical properties of the liquid (flow rate, viscosity, density and surface tension), and ultrasonic properties like amplitude, frequency and the area of vibrating surface. The significant contribution of this work is to define dimensionless numbers incorporating ultrasonic parameters, taking cue from the conventional numbers that define the significance of different forces involved in droplet formation. The universal correlations proposed are robust and can be used for designing ultrasonic atomisers for different applications. Among the correlations proposed here, those ones that are based on the dimensionless numbers and Davies approach predict droplet sizes within acceptable limits of deviation. Also, an empirical correlation from experimental data has been proposed in this work.