Dh Technologies Development Pte. Ltd.

Mds Inc.

The University of British Columbia

Applera Corporation

Mds Analytical Technologies, a Business Unit of Mds Inc.

Applied Biosystems, LLC

Dh Technologies Pte. Ltd.

Mds Inc., Doing Business As Mds Sciex

Bruce Andrew Collings

Mircea Guna

Frank Londry

Bruce A Thomson

Donald J Douglas

William R Stott

Pascal Martin

Alexandre V Loboda

James Walter Hager

Hassan Javaheri

Martian Daniel Dima

Yves J C Leblanc

Thomas R Covey

Bradley B Schneider

Yves Le Blanc

Gordana Ivosev

Jennifer M Campbell

William Ronald Stott

Stephen Bruce Locke

Zhaohui Du

Lars Konermann

Wiliam R Stott

In one aspect, a method of modulating transmission of ions in a mass spectrometer is disclosed, which comprises generating an ion beam comprising a plurality of ions, directing the ion beam to an ion optic positioned in the path of the ion beam, wherein the ion optic includes at least one opening through which the ions can pass, and applying one or more voltage pulses at a selected duty cycle to said ion optic so as to obtain a desired attenuation of brightness of the ion beam passing through the ion optic, where a pulse width of said voltage pulses at said selected duty cycle is determined by identifying a pulse width on a calibration normalized ion intensity versus pulse width relation for said ions that corresponds to said desired attenuation on an ideal normalized ion intensity versus pulse width relation for said ions.

Increased dynamic range for the attenuation of an ion beam

Apparatus and methods for controlling contamination of components contained within the high-vacuum chambers of mass spectrometer systems are provided. The apparatus and methods employ a beam of neutral gas injected in a contra-flow configuration to incoming particle stream from the ionization chamber. The contra-flow can be in the directly opposite counter-flow direction (e.g., 180 degrees) or at a cross-flow angle to the incoming ion stream (e.g., flowing at an angle between about 10 degrees and 170 degrees). The contra-flow disrupts the axial gas flow and diverts neutral molecules and other undesirable contaminants before they reach the high vacuum stages (e.g., beyond the IQ0 orifice) of the spectrometer. By reducing the transmission of contaminants into the sensitive components housed deep within the mass spectrometer, the present invention can increase throughput, improve robustness, and/or decrease the downtime typically required to vent/disassemble/clean the fouled components.

Apparatus and methods for reduced neutral contamination in a mass spectrometer

Methods and apparatus are disclosed for reducing ion reflections between multipole segments in a mass spectrometer by matching the effective potential between the two segments. Mass spectrometers having at least two multipole segments separated from each other along a longitudinal axis of the mass spectrometer such that a boundary region exists through which ions are drawn from an upstream segment to a downstream segment, and wherein each multipole segment further includes a set of spaced-apart rod-shaped electrodes disposed around the longitudinal axis and having a field radius defined by an inscribed circle between the innermost portions of each electrode. Effective potential matching can be achieved by either supplying RF signals of different amplitudes to each segment and/or by modifying the field strength of the segments. In one embodiment, the multipole segments are configured such that the upstream multipole segment has a smaller field radius than the downstream segment.

Effective potential matching at boundaries of segmented quadrupoles in a mass spectrometer

Systems and methods are provided to perform sequential windowed acquisition of mass spectrometry data. A mass range and a mass window width parameter are received for a sample. A plurality of ions from the sample that are within the mass range are collected in an ion trap of a mass spectrometer. Two or more mass adjacent or overlapping windows are calculated to span the mass range using the mass window width parameter. Ions within each mass window are ejected from the ion trap. A mass spectrum is then detected from the ejected ions of the each mass window with a mass analyzer of the mass spectrometer, producing a collection of mass spectra for the mass range. The two or more mass windows can all have the same width, can all have different widths, or can have at least two mass windows with different widths.

Systems and methods for sequential windowed acquisition across a mass range using an ion trap

Systems and methods are provided for multiplexed precursor ion selection using a filtered noise field (FNF). Two or more different precursor ions are selected using a processor. The processor calculates an FNF waveform. The calculated FNF waveform is applied to a continuous beam of ions using the processor. The processors sends information to a mass spectrometer, which includes an ion source that provides the continuous beam of ions and a first quadrupole that receives the continuous beam of ions, so that the first quadrupole applies the calculated FNF waveform to the continuous beam of ions. The first quadrupole applies the calculated FNF waveform to the continuous beam of ions by applying the calculated FNF waveform between pairs of rods or between pairs of auxiliary electrodes placed between rods.

Multiplexing of ions for improved sensitivity

An electron multiplier is positioned relative to at least one dynode to direct a beam of secondary particles from the at least one dynode to a collector area of the electron multiplier and not to a channel area of the electron multiplier for a range of electron multiplier voltages applied by one or more voltage sources to the electron multiplier and for a dynode voltage applied by the one or more voltage sources to the at least one dynode. The electron multiplier includes an aperture with an entrance cone and walls of the entrance cone comprise the collector area and an apex of the entrance cone comprises the channel area. An electron multiplier voltage of the range of electron multiplier voltages is applied to the electron multiplier and the dynode voltage is applied to the at least one dynode using the one or more voltage sources.

Device for improved detection of ions in mass spectrometry

Systems and methods are provided for selecting and fragmenting a first precursor ion in an MS3 experiment. One or more first excitation parameters are calculated that define a first dipole excitation using a processor. The first dipole excitation is used to select a first precursor ion and fragment the first precursor ion to produce a second precursor ion. The first dipole excitation is applied to the continuous beam of ions by sending a first set of data including the first excitation parameters to a mass spectrometer. The first set of data is sent so that a first quadrupole applies the first dipole excitation to a continuous beam of ions. The mass spectrometer includes an ion source that provides the continuous beam of ions and the first quadrupole that receives the continuous beam of ions and is adapted to apply dipole excitation to the continuous beam of ions.

[object Object]

Systems and methods are provided to perform dead time correction. An observed ion count rate is obtained using a non-paralyzable detection system of a mass spectrometer. The detection system includes an ion detector, a comparator/discriminator, a mono-stable circuit and a counter. The non-paralyzable detection system exhibits dead time extension at high count rates. The extension of the dead time occurs because the mono-stable circuit requires a rising edge to trigger and can only be triggered again after the output pulse from the comparator/discriminator has gone low. This allows a second comparator/discriminator pulse arriving just before the end of the dead time started by a first comparator/discriminator pulse to extend the dead time to the trailing edge of the second comparator/discriminator pulse. A true ion count rate is calculated by performing dead time correction of the observed ion count rate.

High dynamic range detector correction algorithm

Systems, devices, circuits, and methods are provided for an improved mass spectrometry detection system that comprises an ion source and a detector that operate at opposite polarities. In some embodiments, the system can comprise a positive and negative multiplier, each of which can be configured to provide voltage to each of the ion source and the detector. In some embodiments, the system can comprise switches that allow the change between positive and negative polarities for the ion source or detector to occur quickly. A variety of embodiments of systems, devices, circuits, and methods in conjunction with the disclosures are provided.

Fast switching, dual polarity, dual output high voltage power supply

Methods for improved separation of ions from an ion trap employing a combination of low pressure and low amplitude ion excitation, including methods for removing, from an ion trap ion population, ions having a m/z value neighboring that of an ion of interest, mass spectrometry methods providing improved resolution of ion detection, and programmable apparatus programmed with instructions therefor.

High resolution excitation/isolation of ions in a low pressure linear ion trap

Methods for fragmenting ions in an ion trap are described. These methods involve a) selecting parent ions for fragmentation; b) retaining the parent ions within the ion trap for a retention time interval, the ion trap having an operating pressure of less than about 1&#xd7;10&#x2212;4 Torr; c) providing a RF trapping voltage to the ion trap to provide a Mathieu stability parameter q at an excitement level during an excitement time interval within the retention time interval; d) providing a resonant excitation voltage to the ion trap during the excitement time interval to excite and fragment the parent ions; e) providing a non-steady-state pressure increase of at least 10% of the operating pressure within the ion trap by delivering a neutral gas into the ion trap for at least a portion of the retention time interval to raise the pressure in the ion trap to a varying first elevated-pressure in the range between about 6&#xd7;10&#x2212;5 Torr to about 5&#xd7;10&#x2212;4 Torr for a first elevated-pressure duration; and f) within the retention time interval and after the excitement time interval, terminating the resonant excitation voltage and changing the RF trapping voltage applied to the ion trap to reduce the Mathieu stability parameter q to a hold level less than the excitement level to retain fragments of the parent ions within the ion trap. The excitation time interval and the first elevated-pressure duration substantially overlap in time.

Method of operating a linear ion trap to provide low pressure short time high amplitude excitation with pulsed pressure

Methods for fragmenting ions retained in an ion trap are described. In various embodiments, a non-steady-state pressure of a neutral collision gas of less than about 5&#xd7;10Torr and an excitation amplitude of less than about 500 mV (peak to ground) is used to fragment ions with greater than about 80% fragmentation efficiency. In various embodiments, duration of ion excitation is greater than about 25 ms.

Methods for fragmenting ions in a linear ion trap

Methods for cooling ions retained in an ion trap are described. In various embodiments, a cooling gas is delivered into a linear ion trap causing a non-steady state pressure elevation in at least a portion of the trap above about 8&#xd7;10Torr for a duration less than the ion-retention time. In various embodiments, the duration of pressure elevation can be based upon a period of time required for an ion to lose a desired amount of its kinetic energy.

Method for cooling ions in a linear ion trap

A novel curved collision cell for a mass spectrometer is described. The collision cell includes a straight section having a length that is selected to cause a precursor ion entering the straight section to lose a desired amount of kinetic energy such that when the precursor ion enters the curved section of the collision cell the precursor ion will tend to neither escape nor contact the collision cell, and thereby tending to survive its passage within the curved portion.

Growing community of inventors

Bradford, Canada

Bruce Andrew Collings