Abstract: Relative quantification of metabolites by Electrospray Ionization Mass Spectrometry (ESI-MS) requiring a mechanism for simultaneous analysis of multiple analytes in two or more samples. Labeling reagents that are reactive to particular compound classes and differ only in their isotopic compositions facilitate relative quantification. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules. Heavy and light isotopic forms of formaldehyde and cholamine were also synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as found in biological samples. The labeled end-products are positively charged under normal acidic conditions involving conventional Liquid Chromatography Mass Spectrometry (LC/MS) applications.

Abstract: Described herein are methods and systems which enable a unique platform for analyte quantitation. The methods and systems relate to determining the amount of interference in a precursor ion isolation window resulting from an impurity. Once the level of impurity is determined, several methods can be employed to reduce the amount of interference in a subsequent MS/MS spectrum. The methods and systems described herein enable increased quantitation accuracy while maintaining high levels of throughput.

Abstract: Described herein are mass spectrometry systems and methods which improve the accuracy of isobaric tag-based quantification by alleviating the pervasive problem of precursor interference and co-isolation of impurities through gas-phase purification. During the gas-phase purification, the mass-to-charge ratios of precursor ions within at least a selected range are selectively changed allowing ions having similar unmodified mass-to-charge ratios to be separated before further isolation, fragmentation or analysis.

Abstract: Described herein are mass spectrometry systems and methods which utilize a dynamic a new data acquisition/instrument control methodology. These systems and methods employ novel artificial intelligence algorithms to greatly increase quantitative and/or identification accuracy during data acquisition. In an embodiment, the algorithms can adapt the instrument methods and systems during data acquisition to direct data acquisition resources to increase quantitative or identification accuracy of target analytes, such as proteins, peptides, and peptide fragments.

Abstract: Various mass spectroscopy-based methods are provided to improve protein sequencing by detecting z-type product ions generated from the protein. A polypeptide is introduced to a mass spectrometer, and in particular c- and z-type product ions that are generated by selectively fragmenting the polypeptide. The z-type product ions are distinguished from the c-type product ions and the mass-to-charge ratio of at least a portion of the z-type product ions are determined. From the mass of the z-type product ions, a putative chemical composition is identified for at least a portion of the z-type product ions, c-type product ions, or both, which is used to determine polypeptide compositions. Further provided are various methods for reducing spectral noise, instrument calibration and database searching and verification.

Abstract: The present invention relates to a new method for fragmenting ions in a mass spectrometer through the use of electron transfer dissociation, and for performing sequence analysis of peptides and proteins by mass spectrometry. In the case of peptides, the invention promotes fragmentation along the peptide backbone and makes it possible to deduce the amino acid sequence of the sample, including modified amino acid residues, through the use of an RF field device.

Abstract: Methods and apparatus for data-dependent mass spectrometric MS/MS or MSn analysis are disclosed. The methods may include determination of the charge state of an ion species of interest, followed by automated selection of a dissociation type (e.g., CAD, ETD, or ETD followed by a non-dissociative charge reduction or collisional activation) based at least partially on the determined charge state. The ion species of interest is then dissociated in accordance with the selected dissociation type, and an MS/MS or MSn spectrum of the resultant product ions may be acquired.

Abstract: Described herein are methods and systems related to the use of the pre-existing ion injection pathway of a mass spectrometer to perform beam-type collision-activated dissociation, as well as other dissociation methods. Following injection and selection of a particular ion type or population, that population can be fragmented using the pre-existing ion injection pathway or inlet of a mass spectrometer. This is achieved by transmitting the ions back along the ion injection pathway. As the ions pass into the higher pressure regions located in or near the atmospheric pressure inlet, the ions are fragmented and then trapped. Following fragmentation and trapping, the ions can either be re-injected into the primary ion selection device or sent on to a secondary mass analyzer.

Abstract: Relative quantification of metabolites by Electrospray Ionization Mass Spectrometry (ESI-MS) requiring a mechanism for simultaneous analysis of multiple analytes in two or more samples. Labeling reagents that are reactive to particular compound classes and differ only in their isotopic compositions facilitate relative quantification. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules. Heavy and light isotopic forms of formaldehyde and cholamine were also synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as found in biological samples. The labeled end-products are positively charged under normal acidic conditions involving conventional Liquid Chromatography Mass Spectrometry (LC/MS) applications.

Abstract: Described herein are methods and systems which enable a unique platform for analyte quantitation. The methods and systems relate to determining the amount of interference in a precursor ion isolation window resulting from an impurity. Once the level of impurity is determined, several methods can be employed to reduce the amount of interference in a subsequent MS/MS spectrum. The methods and systems described herein enable increased quantitation accuracy while maintaining high levels of throughput.

Abstract: Relative quantification of metabolites by Electrospray Ionization Mass Spectrometry (ESI-MS) requiring a mechanism for simultaneous analysis of multiple analytes in two or more samples. Labeling reagents that are reactive to particular compound classes and differ only in their isotopic kit facilitating relative quantification and providing tangible evidence for the existence of specific functional groups. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules, such as biological samples. Heavy and light isotopic forms of formaldehyde and cholamine were also synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as found in biological samples. Advantageously, the labeled end-products are positively charged under normal acidic conditions involving conventional Liquid Chromatography Mass Spectrometry (LC/MS) applications.

Abstract: The present invention provides methods for enhancing the fragmentation of peptides for mass spectrometry by modifying the peptides with a tagging reagent containing a functional group, such as a tertiary amine, having a greater gas-phase basicity than the amide backbone of the peptide. These high gas-phase basicity functional groups are attached to a peptide by reacting the tagging reagent to one or more available carboxylic acid groups of the peptide. Linking these high gas-phase functional groups to the peptides leads to higher charge state ions from electrospray ionization mass spectrometry (ESI-MS), which fragment more extensively during fragmentation techniques, particularly non-ergodic fragmentation techniques such as electron capture dissociation (ECD) and electron transfer dissociation (ETD).

Abstract: The present invention relates to a new method for identifying polypeptides by deducing the amino acid sequence of the carboxy and amino termini by a mass spectrometer analysis. The method comprises the steps of dissociating highly charged peptide precursor ions (e.g., z>4) using electron transfer dissociation inducing anions followed by removal of those reagents and introduction of a second, proton transfer inducing anion type. The second PTR reaction duration is adjusted to convert the ETD products to primarily the +1 charge-state to reduce the highly charged c and z-type fragments, producing an m/z spectrum containing a series of c and z-type fragment ions that are easily interpreted to reveal the sequence of the amino and carboxy terminus, respectively.

Abstract: The present invention relates to a new method for fragmenting ions in a mass spectrometer through the use of electron transfer dissociation, and for performing sequence analysis of peptides and proteins by mass spectrometry. In the case of peptides, the invention promotes fragmentation along the peptide backbone and makes it possible to deduce the amino acid sequence of the sample, including modified amino acid residues, through the use of an RF field device.

Abstract: Various mass spectroscopy-based methods are provided to improve protein sequencing by detecting z-type product ions generated from the protein. A polypeptide is introduced to a mass spectrometer, and in particular c- and z-type product ions that are generated by selectively fragmenting the polypeptide. The z-type product ions are distinguished from the c-type product ions and the mass-to-charge ratio of at least a portion of the z-type product ions are determined. From the mass of the z-type product ions, a putative chemical composition is identified for at least a portion of the z-type product ions, c-type product ions, or both, which is used to determine polypeptide compositions. Further provided are various methods for reducing spectral noise, instrument calibration and database searching and verification.

Abstract: The present invention relates to a new method for fragmenting ions in a mass spectrometer through the use of electron transfer dissociation, and for performing sequence analysis of peptides and proteins by mass spectrometry. In the case of peptides, the invention promotes fragmentation along the peptide backbone and makes it possible to deduce the amino acid sequence of the sample, including modified amino acid residues, through the use of an RF field device.

Abstract: The subject invention provides improved methods for injecting ions into a quadrupole ion trap mass spectrometer (QIT-MS). The methods of the subject invention are applicable to procedures involving atmospheric pressure laser desorption (AP-LD) of a sample to be investigated. Specifically, the subject invention involves controlling the pulse frequency of the laser such that the laser pulses are synchronized with changes in radiofrequency (RF) amplitude levels of the QIT-MS. Advantageously, by utilizing the methods of the subject invention it is possible to improve the accuracy and reproducibility of the results while improving duty cycle and reducing sample consumption.

Abstract: The subject invention pertains to a methods and devices for ionizing a sample material. The subject invention also relates to an ionization source and to a method of sampling gas-phase ions from a sample. An ionization source in accordance with the subject invention can be used in conjunction with mass spectrometry or other sampling techniques. The subject invention can utilize a means for desorbing gas-phase ions and neutral molecules from a sample and a means to generate reagent ions where the reagent ions ionize the desorbed neutral molecules so as to increase the population of gas-phase ions. The subject invention can incorporate laser radiation for desorbing gas-phase ions and neutral molecules from a sample. In a specific embodiment, the subject invention provides an ionization source that uses a pulsed laser for desorption, so as to produce a population of desorbed neutral molecules from a sample, as well as a number of gas-phase sample ions.

Abstract: The subject invention pertains to a methods and devices for ionizing a sample material. The subject invention also relates to an ionization source and to a method of sampling gas-phase ions from a sample. An ionization source in accordance with the subject invention can be used in conjunction with mass spectrometry or other sampling techniques. The subject invention can utilize a means for desorbing gas-phase ions and neutral molecules from a sample and a means to generate reagent ions where the reagent ions ionize the desorbed neutral molecules so as to increase the population of gas-phase ions. The subject invention can incorporate laser radiation for desorbing gas-phase ions and neutral molecules from a sample. In a specific embodiment, the subject invention provides an ionization source that uses a pulsed laser for desorption, so as to produce a population of desorbed neutral molecules from a sample, as well as a number of gas-phase sample ions.