Buffer gas additives (modifiers/shift reagents) in ion mobility spectrometry: Applications, predictions of mobility shifts, and influence of interaction energy and structure.

Ion mobility spectrometry (IMS) is an analytical technique used for fast and sensitive detection of illegal substances in customs and airports, diagnosis of diseases through detection of metabolites in breath, fundamental studies in physics and chemistry, space exploration, and many more applications. Ion mobility spectrometry separates ions in the gas-phase drifting under an electric field according to their size to charge ratio. Ion mobility spectrometry disadvantages are false positives that delay transportation, compromise patient's health and other negative issues when IMS is used for detection. To prevent false positives, IMS measures the ion mobilities in 2 different conditions, in pure buffer gas or when shift reagents (SRs) are introduced in this gas, providing 2 different characteristic properties of the ion and increasing the chances of right identification. Mobility shifts with the introduction of SRs in the buffer gas are due to clustering of analyte ions with SRs. Effective SRs are polar volatile compounds with free electron pairs with a tendency to form clusters with the analyte ion. Formation of clusters is favored by formation of stable analyte ion-SR hydrogen bonds, high analytes' proton affinity, and low steric hindrance in the ion charge while stabilization of ion charge by resonance may disfavor it. Inductive effects and the number of adduction sites also affect cluster formation. The prediction of IMS separations of overlapping peaks is important because it simplifies a trial and error procedure. Doping experiments to simplify IMS spectra by changing the ion-analyte reactions forming the so-called alternative reactant ions are not considered in this review and techniques other than drift tube IMS are marginally covered.