IDSimF: An Open-Source Framework for the Simulation of Molecular Ion Dynamics in Mass Spectrometry and Ion Mobility Spectrometry.

The development of mass spectrometric and ion mobility devices heavily depends on a comprehensive understanding of the behavior of ions within such systems. Therefore, numerical modeling of ion paths helps to optimize and verify existing devices, and contributes to the development of innovative ion optical systems and multipole geometries. This Article introduces IDSimF (Ion Dynamics Simulation Framework), an open-source simulation tool tailored to the nonrelativistic dynamics of molecular ions in mass and ion mobility spectrometry applications. Addressing limitations in existing software packages, as for example SIMION, OpenFOAM, and COMSOL, IDSimF offers a specialized platform for simulating ion trajectories in electric fields. IDSimF efficiently accounts for space charge effects and considers various ion-neutral collision models while handling chemical kinetics. The framework is highly modular with reduced user input configuration complexity and aims to support simulation efforts in development and optimization of in mass spectrometers.

Observation of charged droplets from electrospray ionization (ESI) plumes in API mass spectrometers.

Electrospray ionization (ESI) generates bare analyte ions from charged droplets, which result from spraying a liquid in a strong electric field. Experimental observations available in the literature suggest that at least a significant fraction of the initially generated droplets remain large, have long lifetimes, and can thus aspirate into the inlet system of an atmospheric pressure ionization mass spectrometer (API-MS). We report on the observation of fragment signatures from charged droplets penetrating deeply the vacuum stages of three commercial mass spectrometer systems with largely different ion source and spray configurations. Charged droplets can pass through the ion source and pressure reduction stages and even into the mass analyzer region. Since droplet signatures were found in all investigated instruments, the incorporation of charged droplets is considered a general phenomenon occurring with common spray conditions in ESI sources.

Charge Retention/Charge Depletion in ESI-MS: Experimental Evidence.

The effects of liquid and gas phase additives (chemical modifiers) on the ion signal distribution for Substance P (SP), recorded with a nanoelectrospray setup, are evaluated. Depletion of the higher charge state of Substance P ([SP+3H]3+) is observed with polar protic gas phase modifiers. This is attributed to their ability to form larger hydrogen-bonded clusters, whose proton affinity increases with cluster size. These clusters are able to deprotonate the higher charge state. "Supercharging agents" (SCAs) as well as aprotic polar gas phase modifiers, which promote the retention of the higher charge state of Substance P, do not form such large clusters under the given conditions and are therefore not able to deprotonate Substance P. Both SCAs and aprotic modifiers form clusters with the higher charge state, leading to stabilization of the charge. Whereas supercharging agents have low vapor pressures and are therefore enriched in late-stage electrospray droplets, the gas phase modifiers are volatile organic solvents. Collision induced dissociation experiments revealed that the addition of a modifier significantly delays the droplet evaporation and ion release process. This indicates that the droplet takes up the gas phase modifier to a certain extent (accommodation). Depending on the modifier's properties either charge depletion or retention may eventually be promoted.

Charge Retention/Charge Depletion in ESI-MS: Theoretical Rationale.

Gas phase modification in ESI-MS can significantly alter the charge state distribution of small peptides and proteins. The preceding paper presented a systematic experimental study on this topic using Substance P and proposed a charge retention/charge depletion mechanism, explaining different gas- and liquid-phase modifications [Thinius et al. J. Am. Soc. Mass Spec. 2020, 10.1021/jasms.9b00044]. In this work, we aim to support this rational by theoretical investigations on the proton transfer processes from (multiply) charged analytes toward solvent clusters. As model systems we use small (di)amines as analytes and methanol (MeOH) and acetonitrile (ACN) as gas phase modifiers. The calculations are supported by a set of experiments using (di)amines, to bridge the gap between the present model system and Substance P used in the preceding study. Upon calculation of the thermochemical stability as well as the proton transfer pathways, we find that both ACN and MeOH form stable adduct clusters at the protonation site. MeOH can form large clusters through a chain of H-bridges, eventually lowering the barriers for proton transfer to an extent that charge transfer from the analyte to the MeOH cluster becomes feasible. ACN, however, cannot form H-bridged structures due to its aprotic nature. Hence, the charge is retained at the original protonation site, i.e., the analyte. The investigation confirms the proposed charge retention/charge depletion model. Thus, adding aprotic solvent vapors to the gas phase of an ESI source more likely yields higher charge states than using protic compounds.

Development of an ion activation stage for atmospheric pressure ionization sources.

RATIONALE: The ion-molecule chemistry in typical atmospheric pressure ion sources is essentially thermodynamically controlled. Methods relying on gas-phase protonation reactions, e.g. atmospheric pressure chemical ionization (APCI), thus suffer from the low reactivity of the equilibrated reagent ion population, which is mostly [H + (H2O)n](+). Reagent ion activation to yield reactive species such as H3O(+) is largely uncontrolled in commercial API mass spectrometers. METHODS: The ion activation stage (IAS) is realized as an ion 'tunnel' device. The 30-electrode geometry has an octagonal cross section and an inner diameter of 10 mm. The tunnel is mounted in a vacuum chamber, which directly attaches to the first pumping stage of API mass spectrometers. The effluent from a typical inlet capillary is expanding into the IAS. Reagent ions are generated at atmospheric pressure. Mass spectrometric analysis is performed with quadrupole and time-of-flight instruments. RESULTS: The performance of the IAS is demonstrated by the controlled activation of the initially equilibrated proton-bound water cluster system. It is shown that a gradual increase in the RF voltage amplitude applied to the electrode structure leads to a reproducible shift of the cluster distribution along with clearly discernible protonation thresholds of selected analytes. Increasing the radiofrequency (RF) voltage from zero to maximum values does not change the average ion residence time within the IAS. CONCLUSIONS: We have developed an IAS for operation in the intermediate (1-10 mbar) regime in the ion transfer region of API mass spectrometers. This stage is fully compatible with the recently introduced cAPCI method, which relies on the operation of a liquid point electrode generating very clean and stable thermal distributions of [H + (H2O)n] clusters. The IAS allows controlled ion activation by increasing the ion temperature, which is demonstrated by selective analyte protonation.

Capillary atmospheric pressure chemical ionization using liquid point electrodes.

RATIONALE: Atmospheric pressure chemical ionization (APCI) sources operated with point to plane DC discharges ('Coronas') frequently suffer from point electrode degradation and potentially lead to oxidation and/or fragmentation of the generated analyte ions. It is postulated that these adverse effects are caused by the interaction of these ions with the discharge chemistry as well as en route to the mass analyzer region. METHODS: The corona discharge metal point electrode is replaced by the conically shaped liquid effluent evolving from a fused-silica capillary, which is analogous but not identical to the Taylor cone formation in electrospray ionization. The liquid consisting of either pure water or water containing 0.1 %V formic acid is fed via a nano-flow delivery stage at typical flow rates between 1-800 µL/h. The liquid flow is continuously replenishing the surface of the point electrode. The source is directly coupled to the inlet capillary of appropriate mass spectrometers, e.g., the Bruker Daltonics and Agilent varieties. RESULTS: The actively pumped liquid flow is supplying a constant amount of the reagent gas (H2O) to the corona region in the 20 ppmV to 30 %V range, leading to controlled, very stable operation of the source. The typical light emission observed for corona discharges is in very close proximity to the aqueous surface. Analyte protonation is the dominating ionization pathway. The degree of primary analyte fragmentation is extremely low. CONCLUSIONS: We have developed a novel atmospheric pressure chemical ionization source designed for the hyphenation of nano-flow liquid chromatography and gas chromatography with atmospheric pressure ionization mass spectrometry. The proposed reaction mechanism including the electrochemistry occurring in the source along with formation of protonated analyte molecules via collision-induced dissociation (CID) is in full accord with the experimental results. The system exhibits an extremely stable performance over prolonged operation times, sole generation of protonated molecules, and low degree of analyte ion fragmentation.