title: Alternative approaches to infrared multiphoton dissociation in an external ion reservoir.
abstract: In this work we present variations on in-hexapole infrared multiphoton dissociation (IRMPD) for the characterization of modified oligonucleotides using an ESI-FTICR spectrometer. We demonstrate that IRMPD in the external ion reservoir provides a comprehensive series of fragments allowing thorough characterization of a wide range of oligonucleotides containing alternative backbones and 2' substitutions. An alternative pulse sequence is presented that allows alternating MS and IRMPD MS/MS spectra to be acquired on a chromatographic timescale without loss in ionization duty cycle. Ions are excited to a larger cyclotron radius such that they "dodge" the IR laser beam that travels through the center of the trapped ion cell and impinges on the external ion reservoir creating IRMPD fragments that will be detected in the next scan. An alternative approach for directing IR radiation into the external ion reservoir using a hollow fiber waveguide as a photon conduit is presented. This approach offers a simple and robust alternative to the previously utilized on-axis scheme and may allow effective implementation with lower power lasers owing to the inherent increase in power density achieved by focusing the nascent laser beam into the hollow fiber waveguide.
authors.affiliation: Ibis Therapeutics, a Division of Isis Pharmaceuticals, Carlsbad, California 92008, USA. shofsatd@isisph.com
authors.forename: Steven A
authors.initials: SA
authors.lastname: Hofstadler
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Drader
authors.forename: Hans
authors.initials: H
authors.lastname: Gaus
authors.forename: James C
authors.initials: JC
authors.lastname: Hannis
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Sannes-Lowery
mesh_terms: D002851:Chromatography, High Pressure Liquid; D017357:Cyclotrons; D005583:Fourier Analysis; D007259:Infrared Rays; D007834:Lasers; D013058:Mass Spectrometry; D009841:Oligonucleotides / Q000737:chemistry*; D017785:Photons
chemical_list: D009841:Oligonucleotides