Thermo Finnigan LLC

Dh Technologies Development Pte. Ltd.

Robert Alois Grothe, Jr

Justin Blethrow

Alan E Schoen

Iman Mohtashemi

Systems and methods for filtering a continuous beam of ions are provided. An acceleration electric field is applied to a continuous beam of ions using an accelerator to produce an accelerated beam of ions. A field is applied to the accelerated beam to separate ions in time and space using a deflector producing a separated beam of ions. The field applied by the deflector is a rotating field or a circulant rastering field. The rotating field can be a rotating magnetic or electric field. Only accept those ions from the separated beam whose m/z values lie within a range centered around a target m/z value using an aperture. The aperture can include a pinhole aperture in a rotating disk or an annular aperture in a first stationary disk, a second deflector, and a pinhole aperture in the center of a second stationary disk.

Mass filtering of ions using a rotating field

Systems and methods are provided for time-of-flight analysis of a continuous beam of ions by a detector array. A sample is ionized using an ion source to produce a continuous beam of ions. An electric field is applied to the continuous beam of ions using an accelerator to produce an accelerated beam of ions. A rotating magnetic and/or electric field is applied to the accelerated beam to separate ions with different mass-to-charge ratios over an area of a two-dimensional detector using a deflector located between the accelerator and the two-dimensional detector. An arrival time and a two-dimensional arrival position of each ion of the accelerated beam are recorded using the two-dimensional detector. Alternatively, an electric field that is periodic with time is applied in order to sweep the accelerated beam over a periodically repeating path on the two-dimensional rectangular detector.

Time-of-flight analysis of a continuous beam of ions by a detector array

A method for detecting a list of known biopolymer molecules comprises: calculating, for each biopolymer, a respective list of oligomer molecules predicted to be produced by chemical processing; calculating, for each oligomer molecule, a respective predicted chromatographic elution time period; assigning, for each biopolymer molecule, one or more selected oligomer molecules to be detected, wherein the selecting is performed using weighted selection probabilities determined from the predicted elution times; scheduling a plurality of oligomer detection events of a detection system, wherein each oligomer detection event corresponds to a respective one of the predicted elution time periods; performing the chemical reaction or processing of the sample to generate a processed sample; introducing the processed sample into a chromatographic system; introducing any eluting oligomers into the detection system; and operating the detection system so as to search for each of the selected oligomer molecules in accordance with the scheduled detection events.

Methods for mass spectrometric biopolymer analysis using optimized weighted oligomer scheduling

A novel scanning method of a mass spectrometer apparatus is introduced so as to relate by simple time shifts, rather than time dilations, the component signal ('peak') from each ion even to an arbitrary reference signal produced by a desired homogeneous population of ions. Such a method and system, as introduced herein, is enabled in a novel fashion by scanning exponentially the RF and DC voltages on a quadrupole mass filter versus time while maintaining the RF and DC in constant proportion to each other. In such a novel mode of operation, ion intensity as a function of time is the convolution of a fixed peak shape response with the underlying (unknown) distribution of discrete mass-to-charge ratios (mass spectrum). As a result, the mass distribution can be reconstructed by deconvolution, producing a mass spectrum with enhanced sensitivity and mass resolving power.

Exponential scan mode for quadrupole mass spectrometers to generate super-resolved mass spectra

Disclosed herein are isobaric labeling reagent sets useful for multiplexed quantitation of peptides. The isobaric labeling reagent sets include a collection of at least two isobaric labeling reagents having first and second reporter groups with the same nominal mass but different isotopic substitutions and consequently different exact masses. Mass spectrometric analysis of the labeled samples is performed using a mass analyzer, such as an Orbitrap mass analyzer, capable of adequately resolving the ions of the first and second reporter groups. Reagent sets of the foregoing description may provide a degree of multiplexing in reporter ion quantitation experiments that is expanded relative to conventional labeling reagent sets, thereby reducing the number of chromatographic runs required for analysis and improving sample throughput.

Method for highly multiplexed quantitation of peptides by mass spectrometry and labeling reagent sets therefor

Method for highly multiplexed quantitation of peptides by mass spectrometry and mass labels therefor

A novel method and mass spectrometer apparatus is introduced to spatially and temporally resolve images of one or more ion exit patterns of a multipole instrument. In particular, the methods and structures of the present invention measures the ion current as a function of time and spatial displacement in the beam cross-section of a quadrupole mass filter via an arrayed detector. The linearity of the detected quadrupole ion current in combination with it reproducible spatial-temporal structure enables the deconvolution of the contributions of signals from individual ion species in complex mixtures where both sensitivity and mass resolving power are essential.

Quadrupole mass spectrometer with enhanced sensitivity and mass resolving power

Methods of tandem mass spectrometry are disclosed, characterized by: providing a mixture of precursor ions comprising a plurality of individually isolated ion types of respective selected m/z ratios; estimating an elemental composition for each precursor ion type based on its respective m/z ratio; generating a sample of fragment ions comprising a plurality of fragment ion types by fragmenting the plurality of precursor ion types of the mixture; generating a mass spectrum of the fragment ion types to determine a respective m/z ratio or m/z ratio range for each respective fragment ion type; estimating an elemental composition for each fragment ion type based on its respective m/z ratio or m/z ratio range; and calculating probabilities, for each precursor ion type, that a fragment ion type or a pair of fragment ion types was derived from said precursor ion type.

Methods and systems for matching product ions to precursor ions

Methods of tandem mass spectrometry (MS/MS) for use in a mass spectrometer are disclosed, the methods characterized by the steps of: (a) providing a sample of precursor ions comprising a plurality of ion types, each ion type comprising a respective range of masses; (b) generating a mass spectrum of the precursor ions using the mass spectrometer so as to determine a respective mass value or mass value range for each of the precursor ion types; (c) estimating an elemental composition for each of the precursor ion types based on the mass value or mass value range determined for each respective ion type; (d) generating a sample of fragment ions comprising plurality of fragment ion types by fragmenting the plurality of precursor ion types within the mass spectrometer; (d) generating a mass spectrum of the fragment ion types so as to determine a respective mass value or mass value range for each respective fragment ion type; (e) estimating an elemental composition for each of the fragment ion types based on the mass value or mass value range determined for each respective fragment ion type; and (f) calculating a set of probability values for each precursor ion type, each probability value representing a probability that a respective fragment ion type or a respective pair of fragment ion types was derived from the precursor ion type. Some embodiments may include a step (g) of generating a synthetic MS/MS spectrum for each respective precursor ion type based on the calculated probability values.

Growing community of inventors

Campbell, CA, United States of America

Robert Alois Grothe, Jr