Abstract: A system comprises: (1) a central location comprising: (a) computer storage media having one or more databases thereon; and (b) one or more computers configured to communicate with the computer storage media: and (2) a plurality of sites, each site comprising: (a) an analytical apparatus; and (b) a site computer system comprising program instructions operable to generate a collection of apparatus signatures, each apparatus signature comprising a collection of data relating to the operation of the analytical apparatus at a time when said signature is generated, wherein the one or more computers at the central location are configured to store each collection of signatures in the one or more databases. In embodiments, each site computer system stores the plurality of apparatus signatures generated at the respective site and transmits the stored apparatus signatures to the one or more computers at the central location.

Abstract: Real-time search (RTS) for mass spectrometry is described. In one instance, precursor ions generated from a sample are introduced into a mass spectrometer during an introduction period. The precursor ions are fragmented to form product ions, and a mass spectrum is acquired. During the introduction period, scores indicating the similarity between the mass spectrum and a candidate mass spectrum are identified. Based on the distribution of the scores, an action is performed.

Abstract: A method is described that involves simplification of UVPD mass spectra and comprises selecting precursor ions for UVPD fragmentation, performing UVPD fragmentation on selected precursor ions to give UVPD fragment ions. PTR may then be performed on the UVPD fragment ions with optional ion parking to yield charge-state reduced UVPD fragment ions. The UVPD-PTR steps may be repeated above n times where n=1 to 50. Ion parking may enhance the intensity of selected lower fragment ion charge states or to increase the intensity of peaks in selected m/z ranges. After a number of PTR-UVPD iterations, fragment ions are mass analyzed. The method provides a way of simplifying UVPD mass spectral product ions by lowering fragment ion charge states and spreading out resulting product ions in m/z mass spectral space when compared to using UVPD fragmentation alone.

Abstract: A method for analyzing a sample includes trapping a first ion packet in a first segment of a multi-segment reaction cell; trapping a second ion packet in a second segment of the multi-segment reaction cell; and trapping a third ion packet in a third segment of the multi-segment reaction cell. At least one of the first, second, and third ion packets includes precursor ions, and at least another one of the first, second, and third ion packets includes reagent ions. The method further includes mixing the first, second, and third ion packets within the reaction cell to cause a reaction between the precursor ions and the reagent ions to form product ions.

Abstract: A method is described that involves simplification of UVPD mass spectra and comprises selecting precursor ions for UVPD fragmentation, performing UVPD fragmentation on selected precursor ions to give UVPD fragment ions. PTR may then be performed on the UVPD fragment ions with optional ion parking to yield charge-state reduced UVPD fragment ions. The UVPD-PTR steps may be repeated above n times where n=1 to 50. Ion parking may enhance the intensity of selected lower fragment ion charge states or to increase the intensity of peaks in selected m/z ranges. After a number of PTR-UVPD iterations, fragment ions are mass analyzed. The method provides a way of simplifying UVPD mass spectral product ions by lowering fragment ion charge states and spreading out resulting product ions in m/z mass spectral space when compared to using UVPD fragmentation alone.

Abstract: A hybrid mass spectrometer design and architecture, and methods of operating mass spectrometers are disclosed. According to one operating method, an analysis time is determined for each one of a plurality of ion species to be analyzed in an ordered sequence, and an injection time is calculated for at least some of the ion species based on an analysis time of a preceding ion species in the ordered list. The method enables more efficient utilization of analyzer time.

Abstract: A mass spectrometry method comprises: acquiring a series of survey mass spectra of first-generation ions generated from a sample; acquiring a series of fragment-ion mass spectra, each being a record of a respective set of fragment-ion species generated by fragmentation of a respective subset of the first-generation ions within a respective mass-to-charge isolation range; adjusting mass spectrometer operational parameters used to acquire a later one of the survey mass spectra based on results of an earlier one of the survey mass spectra; dividing the acquired series of fragment-ion mass spectra into a first group wherein an appearance of a fragment-ion species correlates with the appearance of a first-generation ion species observed in a survey mass spectrum and a second group wherein no obvious correlation is observed between fragment-ion species and first-generation ion species; and mathematically processing the spectra of the first and second groups by different mathematical procedures.

Abstract: A method for analyzing a sample includes trapping a first ion packet in a first segment of a multi-segment reaction cell; trapping a second ion packet in a second segment of the multi-segment reaction cell; and trapping a third ion packet in a third segment of the multi-segment reaction cell. At least one of the first, second, and third ion packets includes precursor ions, and at least another one of the first, second, and third ion packets includes reagent ions. The method further includes mixing the first, second, and third ion packets within the reaction cell to cause a reaction between the precursor ions and the reagent ions to form product ions.

Abstract: A hybrid mass spectrometer design and architecture, and methods of operating mass spectrometers are disclosed. According to one operating method, an analysis time is determined for each one of a plurality of ion species to be analyzed in an ordered sequence, and an injection time is calculated for at least some of the ion species based on an analysis time of a preceding ion species in the ordered list. The method enables more efficient utilization of analyzer time.

Abstract: A hybrid mass spectrometer design and architecture, and methods of operating mass spectrometers are disclosed. According to one operating method, an analysis time is determined for each one of a plurality of ion species to be analyzed in an ordered sequence, and an injection time is calculated for at least some of the ion species based on an analysis time of a preceding ion species in the ordered list. The method enables more efficient utilization of analyzer time.

Abstract: A method of obtaining and analyzing a mass spectrum of a sample comprising components is characterized by: setting values of a first energy level and a second energy level; chromatographically separating the components; ionizing a portion of the separated components to create precursor ions; introducing a first portion of the precursor ions into a collision or reaction cell and generating a first sub-population of ions corresponding to the first energy level; introducing a second portion of the precursor ions into the cell and generating a second sub-population of ions corresponding to the second energy level; transferring a mixture of the first and second sub-populations of ions into a mass analyzer; producing an analysis of the ions of the mixture; varying the value of at least one of the first and the second energy levels according to a pre-determined cyclical variation; repeating various above steps; and analyzing the time-variation of the analyses.

Abstract: A set of two or more types of isobaric tags is described where each tag in the set includes a mass-labeling group and a mass-normalizing group. The mass-labeling group includes a reactive group configured to form a first bond to a functional group of an analyte. The mass-normalizing group is attached to the mass-labeling group via a second bond. The first bond is configured to be stable when subjected to a dissociative energy level from a mass spectrometer so that the first bond does not cleave. When subjected to the same dissociative energy level, the second bond is configured to cleave that liberates the mass-normalizing groups. The tag is configured to form a charged mass-labeled analyte when the second bond is cleaved.

Abstract: The instrument initially assesses the purity of a given candidate parent. If the candidate parent is contaminated with an isobaric signal(s), it promptly focuses on the alternative charge state(s) for the same neutral mass. Specifically for every peptide mass there are almost universally several charge states (usually 1-4 for tryptic peptides) present in the ESI spectrum. An optional step may be used for more complex situations where alternative (lower) charge states are not evident in the spectrum. In this case, proton transfer is performed on a higher charge state. Next, if the reduced ion parent is isobarically pure, a higher energy collisionally activated dissociation is performed on the reduced ion parent. Alternatively, a dedicated targeted isolation can be performed for low abundant precursors at calculated m/z if they fall below LOD of the analyzer full scan.

Abstract: A method for acquiring and analyzing polypeptide mass spectra comprising: creating first and second sets of fragmented ions using first and second fragmentation techniques; obtaining mass spectra of the first and second sets of fragmented ions; searching a database of fragments of a first fragment pair type and of a second fragment pair type to respectively provide a set of M ranked and a set of N ranked best matching polypeptide sequences; subtracting synthetic spectra corresponding to each of the M and N ranked sequences from the mass spectra to provide first and second sets of modified mass spectra; searching the database of fragments of the second fragment pair type and of the first fragment pair type to provide third and fourth sets of polypeptide sequences providing best matches to the first and second sets of modified spectra, respectively; and creating a cumulative ranking of the third and fourth sets.

Abstract: The present invention is directed to methods of merging spectral data resulting from collision fragmentation processes, such as, for example, Pulsed Q Dissociation (PQD), high-energy collision-induced dissociation (HCD), electron transfer disassociation (ETD), collision-induced dissociation (CID), and photo-dissociation processes, such as, but not limited to, infrared multi-photon photo-dissociation (IRMPD), to provide the desired qualitative and quantitative information on a single peptide. By merging such ETD, CID, or IRMPD scans with corresponding HCD scans that are obtained on the same precursor, the quality of the resulting spectrum is increased so as to provide more confident identification of peptides and correspondingly the quantification is enhanced because the HCD method of the MS/MS spectrum produces higher abundances of detectable reporter ions. Such methods, as disclosed herein, are especially applicable for peptides which experience predominant neutral loss in the ion trap, e.g., phosphorylated.

Abstract: A method of obtaining and analyzing a mass spectrum of a sample comprising components is characterized by: setting values of a first energy level and a second energy level; chromatographically separating the components; ionizing a portion of the separated components to create precursor ions; introducing a first portion of the precursor ions into a collision or reaction cell and generating a first sub-population of ions corresponding to the first energy level; introducing a second portion of the precursor ions into the cell and generating a second sub-population of ions corresponding to the second energy level; transferring a mixture of the first and second sub-populations of ions into a mass analyzer; producing an analysis of the ions of the mixture; varying the value of at least one of the first and the second energy levels according to a pre-determined cyclical variation; repeating various above steps; and analyzing the time-variation of the analyses.

Abstract: A method for acquiring and analyzing polypeptide mass spectra comprising: creating first and second sets of fragmented ions using first and second fragmentation techniques; obtaining mass spectra of the first and second sets of fragmented ions; searching a database of fragments of a first fragment pair type and of a second fragment pair type to respectively provide a set of M ranked and a set of N ranked best matching polypeptide sequences; subtracting synthetic spectra corresponding to each of the M and N ranked sequences from the mass spectra to provide first and second sets of modified mass spectra; searching the database of fragments of the second fragment pair type and of the first fragment pair type to provide third and fourth sets of polypeptide sequences providing best matches to the first and second sets of modified spectra, respectively; and creating a cumulative ranking of the third and fourth sets.

Abstract: The present invention is directed to methods of merging spectral data resulting from collision fragmentation processes, such as, for example, Pulsed Q Dissociation (PQD), high-energy collision-induced dissociation (HCD), electron transfer disassociation (ETD), collision-induced dissociation (CID), and photo-dissociation processes, such as, but not limited to, infrared multi-photon photo-dissociation (IRMPD), to provide the desired qualitative and quantitative information on a single peptide. By merging such ETD, CID, or IRMPD scans with corresponding HCD scans that are obtained on the same precursor, the quality of the resulting spectrum is increased so as to provide more confident identification of peptides and correspondingly the quantification is enhanced because the HCD method of the MS/MS spectrum produces higher abundances of detectable reporter ions. Such methods, as disclosed herein, are especially applicable for peptides which experience predominant neutral loss in the ion trap, e.g., phosphorylated.

Abstract: A method is disclosed for data-dependent neutral loss analysis of biomolecules and other materials in a hybrid mass spectrometer. Candidate product ions are selected by identifying peaks in a MS/MS spectrum acquired in a first mass analyzer that exhibit a specified nominal neutral loss value, which may be representative of the mass of a peptide modification, such as phosphate. High mass accuracy MS and MS/MS spectra acquired at a second mass analyzer, such as an FTICR or Orbitrap, are processed to determine if the mass difference between a candidate product ion and its corresponding precursor matches an accurate neutral loss value. In one embodiment, MS3 analysis is performed only on the candidate product ions that satisfy the accurate mass neutral loss value test.

Abstract: A method is disclosed for data-dependent neutral loss analysis of biomolecules and other materials in a hybrid mass spectrometer. Candidate product ions are selected by identifying peaks in a MS/MS spectrum acquired in a first mass analyzer that exhibit a specified nominal neutral loss value, which may be representative of the mass of a peptide modification, such as phosphate. High mass accuracy MS and MS/MS spectra acquired at a second mass analyzer, such as an FTICR or Orbitrap, are processed to determine if the mass difference between a candidate product ion and its corresponding precursor matches an accurate neutral loss value. In one embodiment, MS3 analysis is performed only on the candidate product ions that satisfy the accurate mass neutral loss value test.