title: Selective ion filtering by digital thresholding: a method to unwind complex ESI-mass spectra and eliminate signals from low molecular weight chemical noise.
abstract: In this work, we present a simple method by which to preferentially detect either high molecular weight or low molecular weight ions generated by electrospray ionization. This approach, termed selective ion filtering by digital thresholding (SIFdT) is demonstrated on a commercial ESI-TOF instrument that employs a fast digitizer coupled to a microchannel plate detector. The digital representation of each individual scan is digitally filtered prior to spectral coaddition. As larger, more highly charged ions induce a more intense response than low molecular weight singly charged species, a digital threshold can be set that precludes the detection of singly charged species yet permits the efficient detection of larger, more highly charged species. In this work, we demonstrate the applicability of this approach to eliminate low molecular weight chemical noise in ESI-TOF spectra of oligonucleotide and protein ions, demonstrate improved dynamic range for analyte solutions containing high levels of low MW constituents, and show that spectra acquired at different digital thresholds can be subtracted to yield spectra of low molecular weight constituents with improved mass measurement accuracies. A notional scheme is presented in which an alternative digitization approach is employed using multiple differentially thresholded data streams to allow improved internal mass calibration and higher resolution ion partitioning.
authors.affiliation: Ibis Division of Isis Pharmaceuticals, 1891 Rutherford Road, Carlsbad, California 92008, USA. shofstad@isisph.com
authors.forename: Steven A
authors.initials: SA
authors.lastname: Hofstadler
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Drader
authors.forename: Amy
authors.initials: A
authors.lastname: Schink
mesh_terms: D006801:Humans; D008970:Molecular Weight; D009841:Oligonucleotides / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D012815:Signal Processing, Computer-Assisted; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D009841:Oligonucleotides; D011506:Proteins