Development of an ESI-HiKE-IMS reference platform for IMS to investigate field-dependent effects such as fragmentation, cluster association and dissociation, and to determine the alpha functions of larger analyte molecules

• Applicant: Professor Dr.-Ing. Stefan Zimmermann
• Subject Area: Measurement Systems
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 546921154

Compared to mass spectrometry, ion mobility spectrometry is an almost orthogonal separation technique, so that ion mobility spectrometers (IMS) are increasingly being coupled with mass spectrometers (MS) to provide an additional dimension of separation. Such IMS-MS are particularly important in the analysis of biochemical samples such as lipids, sugars, metabolites and peptides, where electrospray ionization (ESI) is usually used. Unlike the mass-to-charge ratio, the ion mobility is not independent of the device parameters. In particular, the ion mobility depends on the reduced electric field strength E/N, which is described by the ion-specific alpha function. Furthermore, field-dependent processes such as fragmentation, cluster association and dissociation are possible. The IMS established in MS today, such as TWIMS, TIMS and DMS, use high, time-varying electric fields due to the separation principle or for ion focusing, so that the ion mobility and alpha function as well as other field-dependent processes cannot be determined directly. In practice, calibration methods are used to approximate the ion mobility. However, the error can be significant, as the measurement results cannot be interpreted correctly and the error of ion mobility cannot be minimized without understanding and quantifying the ion-specific, field-dependent processes. Therefore, this project aims to develop a reference platform that can be used to investigate ion mobility and field-dependent processes at defined E/N over a very wide E/N range. The high kinetic energy ion mobility spectrometer (HiKE-IMS) developed in previous work serves as the basis, but is not yet designed for analyzing larger molecules such as lipids, sugars, metabolites and peptides. For this reason, the first ESI-HiKE-IMS with E/N range up to 120 Td is to be developed. In this context, a new approach using high E/N in the evaporation region of the HiKE-IMS for accelerated evaporation of the charged droplets generated by ESI is to be investigated. For a detailed analysis of the present ion species and their charge states, the ESI-HiKE-IMS is to be coupled to an MS via an ion interface that is as energy-neutral as possible. The relevant standards for TWIMS, TIMS and DMS are then to be experimentally characterized with this ESI-HiKE-IMS-MS. In order to demonstrate the potential of the ESI-HiKE-IMS as a reference platform, the first question to be addressed is the possible error when calibrating TWIMS with ions of different charge states. Therefore, the field-dependent ion mobilities of suitable substances in different charge states are to be determined and compared with each other.

• DFG Programme: Research Grants