Simultaneous fragmentation of multiple ions using IMS drift time dependent collision energies

Abstract

Ion mobility spectrometry coupled with mass spectrometry (IMS-MS) was utilized to evaluate an ion collision energy ramping technique that simultaneously fragments a variety of species. To evaluate this technique, the fragmentation patterns of a mixture of ions ranging in mass, charge state, and drift time were analyzed to determine their optimal fragmentation conditions. The precursor ions were pulsed into the IMS-MS instrument and separated in the IMS drift cell based on mobility differences. Two differentially pumped short quadrupoles were used to focus the ions exiting the drift cell, and fragmentation was induced by collision induced dissociation (CID) between the conductance limiting orifice behind the second short quadrupole and before the first octopole in the mass spectrometer. To explore the fragmentation spectrum of each precursor ion, the bias voltages for the short quadrupoles and conductance limiting orifices were increased from 0 to 50 V above nonfragmentation voltage settings. An approximately linear correlation was observed between the optimal fragmentation voltage for each ion and its specific drift time, so a linear voltage gradient was employed to supply less collision energy to high mobility ions (e.g., small conformations or higher charge state ions) and more to low mobility ions. Fragmentation efficiencies were found to be similar for different ions when the fragmentation voltage was linearly ramped with drift time, but varied drastically when only a single voltage was used. [7,8] and carbohydrates. [9, 10] While tandem MS has successfully been applied to a range of difficult sequence and structural problems, [11,12] its application to highly complex samples has been limited by the general need for the selection of specific precursor species for each fragmentation experiment. This allows the fragment ions to be correctly assigned to their corresponding precursor ion in a mixture, but creates a severe MS "under sampling" problem in untargeted analyses especially for online liquid chromatography (LC)-MS examinations of small-volume samples. Developing methods to simultaneously fragment all ions in a complex sample is very appealing; however, difficulties arise because distinct species generally require differing amounts of collisional excitation depending on their mass, [13] charge state [14], and structure [15,16].Typically, if only one collision energy is utilized, both under-fragmentation and over-fragmentation (which corresponds to the sequential dissociation of the initial higher m/z dissociation products to yield often less informative lower m/z products) contribute excessively in the acquired spectrum.Multiplexed MS/MS approaches, which dissociate multiple ions simultaneously, have been studied to increase the throughput of LC-MS/MS analyses. Currently, these approaches either use a single collision energy for fragmentation [17,18] or alternate between a low and high collision energy (MS E ) [19]. Since both fragmentation approaches are unable to optimize the collision energy of the d...

A novel approach to collision-induced dissociation (CID) for ion mobility-mass spectrometry experiments

“…CID of peptide ions was demonstrated for several model peptides and peptides from a proteolytic digest. It is also possible to obtain spectra over a range of applied voltages to enhance ion signal of all fragments, similar to the technique described recently by Smith and coworkers [9]; although a single optimized voltage is generally sufficient to produce fragment ions over the entire m/z range of interest. For example, a 400 V drop across region II of the interface was sufficient to generate all of the fragment ions for fibrinopeptide A between 1400 and 100 m/z that are observed over a range of voltage settings.…”

“…Additionally, Waters Corporation has introduced an rf ion guide as an interface for their traveling-wave mobility cell that is CID capable [15,16]. Smith and coworkers have also demonstrated CID of mobility-separated ions using a ramped voltage gradient between two short quadrupoles [9]. Here, we describe a different approach to IM-CID-MS that is compatible with MALDI and periodic-field drift cells.…”

“…That is, the ion mobility spectrometry (IMS) separation provides a temporal correlation between the precursor and product ions, circumventing the need to pre-select each precursor mass of interest [1,9,10]. A number of fragmentation techniques have been previously developed with IM-MS; including photodissociation [11], surface-induced dissociation (SID) [12,13], and collision-induced dissociation (CID) [10,14].…”

An Ion Mobility/Ion Trap/Photodissociation Instrument for Characterization of Ion Structure

“…IMS techniques [34][35][36][37] and theory [38][39][40][41][42][43] as well as the instrumentation utilized to obtain IMS measurements [2,5,7,15,[44][45][46][47][48][49][50][51][52][53][54][55][56] have been described in detail elsewhere. Here, a detailed description of the new instrumentation is provided.…”

High performance ion mobility spectrometry as a fast and low cost green analytical technology part I: analysis of nutritional supplements

“…On the other hand, ion mobility spectrometry (IMS) has been shown to provide faster separation and higher throughput for analyzing a large variety of semi-volatile compounds, such as chemical warfare agents [5,50,51], explosives [4,24,29,54], and environmental contaminants [10,14,58]. IMS has also proven amenable to separating non-volatile compounds such as illicit drugs [28, 35, 39-41, 49, 59], pharmaceuticals [15,34,37,43,52,53], over-thecounter drugs [18], and biological molecules [6,32,48,56] once they are introduced into the gas phase. The growing use of IMS derives from it inherently being a rapid, low cost, sensitive analytical method where the separation of the ions is typically completed in 20 to 50 ms using a neutral drift gas at atmospheric pressure with resolving power comparable to LC with minimal solvent use [2].…”