Perkinelmer Health Sciences, Inc.

Analytica of Branford, Inc.

Craig M. Whitehouse

Welkie, David G.

Whitehouse, Craig M.

Lisa Cousins

David G. Welkie

Craig M Whitehouse

David G Welkie

Gholamreza Javahery

Sergey Rakov

Javahery Gholamreza

Apparatus and methods are provided that enable the interaction of low energy electrons and positrons with sample ions to facilitate electron capture dissociation (EGO) and positron capture dissociation (PGO), respectively, within multipole ion guide structures.

Fragmentation methods for mass spectrometry

Apparatus and methods are provided that enable the interaction of low energy electrons and positrons with sample ions to facilitate electron capture dissociation (EGO) and positron capture dissociation (PGO), respectively, within multipole ion guide structures. The apparatus and methods described herein allow EGO (and PCO) to be performed within multipole ion guides, either alone, or in combination with conventional ion fragmentation methods.

Apparatus and methods are provided that enable the interaction of low-energy electrons and positrons with sample ions to facilitate electron capture dissociation (ECD) and positron capture dissociation (PCD), respectively, within multipole ion guide structures. It has recently been discovered that fragmentation of protonated ions of many biomolecules via ECD often proceeds along fragmentation pathways not accessed by other dissociation methods, leading to molecular structure information not otherwise easily obtainable. However, such analyses have been limited to expensive Fourier transform ion cyclotron resonance (FTICR) mass spectrometers; the implementation of ECD within commonly-used multipole ion guide structures is problematic due to the disturbing effects of RF fields within such devices. The apparatus and methods described herein successfully overcome such difficulties, and allow ECD (and PCD) to be performed within multipole ion guides, either alone, or in combination with conventional ion fragmentation methods. Therefore, improved analytical performance and functionality of mass spectrometers that utilize multipole ion guides are provided.

A mass spectrometer includes an ion source and at least one vacuum stage, a means for delivering ions from the ion source to the vacuum stage, a collision cell, a detector, at least two multipole ion guide segments, and independent RF frequency and DC voltage sources applied to the multipole ion guide segments, the RF frequency and DC voltage sources being controlled independently of each other.

Mass spectrometry with segmented RF multiple ion guides in various pressure regions

Apparatus and methods are provided for trapping, manipulation and transferring ions along RF and DC potential surfaces and through RF ion guides potential wells are formed near RF-field generating surfaces due to the overlap of the radio-frequency (RF) fields and electrostatic fields created by static potentials applied to surrounding electrodes. Ions can be constrained and accumulated over time in such wells During confinement, ions may be subjected to various processes, such as accumulation, fragmentation, collisional cooling, focusing, mass-to-charge filtering, spatial separation ion mobility and chemical interactions, leading to improved performance in subsequent processing and analysis steps, such as mass analysis. Alternatively, the motion of ions may be better manipulated during confinement to improve the efficiency of their transport to specific locations, such as an entrance aperture into vacuum from atmospheric pressure or into a subsequent vacuum stage.

RF surfaces and RF ion guides

Apparatus and methods are provided for trapping, manipulation and transferring ions along RF and DC potential surfaces and through RF ion guides. Potential wells are formed near RF-field generating surfaces due to the overlap of the radio-frequency (RF) fields and electrostatic fields created by static potentials applied to surrounding electrodes. Ions can be constrained and accumulated over time in such wells. During confinement, ions may be subjected to various processes, such as accumulation, fragmentation, collisional cooling, focusing, mass-to-charge filtering, spatial separation ion mobility and chemical interactions, leading to improved performance in subsequent processing and analysis steps, such as mass analysis. Alternatively, the motion of ions may be better manipulated during confinement to improve the efficiency of their transport to specific locations, such as an entrance aperture into vacuum from atmospheric pressure or into a subsequent vacuum stage.

A mass spectrometer is configured with individual multipole ion guides, configured in an assembly in alignment along a common centerline wherein at least a portion of at least one multipole ion guide mounted in the assembly resides in a vacuum region with higher background pressure, and the other portion resides in a vacuum region with lower background pressure. Said multipole ion guides are operated in mass to charge selection and ion fragmentation modes, in either a high or low pressure region, said region being selected according to the optimum pressure or pressure gradient for the function performed. The diameter, lengths and applied frequencies and phases on these contiguous ion guides may be the same or may differ. A variety of MS and MS/MSanalysis functions can be achieved using a series of contiguous multipole ion guides operating in either higher background vacuum pressures, or along pressure gradients in the region where the pressure drops from high to low pressure, or in low pressure regions. Individual sets of RF, +/&#x2212;DC and resonant frequency waveform voltage supplies provide potentials to the rods of each multipole ion guide allowing the operation of ion transmission, ion trapping, mass to charge selection and ion fragmentation functions independently in each ion guide. The presence of background pressure maintained sufficiently high to cause ion to neutral gas collisions along a portion of each multiple ion guide linear assembly allows the conducting of Collisional Induced Dissociation (CID) fragmentation of ions by axially accelerating ions from one multipole ion guide into an adjacent ion guide. Alternatively ions can be fragmented in one or more multipole ion guides using resonant frequency excitation CID. A multiple multipole ion guide assembly can be configured as the primary mass analyzer in single or triple quadrupole mass analyzers with or without mass selective axial ejection. Alternatively, the multiple multipole ion guide linear assembly can be configured as part of a hybrid Time-Of-Flight, Magnetic Sector, Ion Trap or Fourier Transform mass analyzer.

Growing community of inventors

Branford, CT, United States of America

Lisa Cousins