Abstract: A method for manipulating ions in an ion trap includes storing ions, spatially compressing, and ejecting selected ions according to mass-to-charge ratio. An ion trap includes an injection port, an arm having a first and a second end for confining and spatially compressing the ions, and an ejection port for ejecting the ions from the second end. The arm includes two pairs of opposing electrodes, which provide a quadrupole electric field potential at any cross-section of the ion trap. The distance between opposing electrodes and the cross-sectional area of the electrodes increases from the first to second end. The electrodes may be tapered cylindrical rods or of hyperbolic cross-section. Ions selected for ejection are spatially compressed into a region at the second (wider) end. The ion trap may include one arm, with either orthogonal or axial ejection, or two arms with a central insert for orthogonal ejection.

Abstract: Method is described for sequencing polypeptides by forming peptide ladders comprising a series of polypeptides in which adjacent members of the series vary by one amino acid residue and determining the identity and position of each amino acid in the polypeptide by mass spectroscopy.

Abstract: Disclosed are compositions and methods for sensitive detection of one or multiple analytes. In general, the methods involve the use of special label components, referred to as reporter signals, that can be associated with, incorporated into, or otherwise linked to the analytes. In some embodiments, the reporter signals can be altered such that the altered forms of different reporter signals can be distinguished from each other. In some embodiments, sets of reporter signals can be used where two or more of the reporter signals in a set have one or more common properties that allow the reporter signals having the common property to be distinguished and/or separated from other molecules lacking the common property.

Abstract: Method is described for sequencing polypeptides by forming peptide ladders comprising a series of polypeptides in which adjacent members of the series vary by one amino acid residue and determining the identity and position of each amino acid in the polypeptide by mass spectroscopy.

Abstract: The present invention is a method for accurately comparing the levels of cellular components, such as proteins, present in samples which differ in some respect from each other using mass spectroscopy and isotopic labeling. A first sample of biological matter, such as cells, is cultured in a first medium and a second sample of the same biological matter is cultured in a second medium, wherein at least one isotope in the second medium has a different abundance than the abundance of the same isotope in the first medium. One of the samples is modulated, such as by treatment with a bacteria, a virus, a drug, hormone, a chemical or an environmental stimulus. The samples are combined and at least one protein is removed. The removed protein is subjected to mass spectroscopy to develop a mass spectrum. A ratio is computed between the peak intensities of at least one closely spaced pair of peaks to determine the relative abundance of the protein in each sample.

Abstract: A method and apparatus for increasing the signal-to-noise ratio in a range of mass-to-charge ratios of a mass spectrum. Initially ions of interest and background ions having mass-to-charge ratios within the range of mass-to-charge ratios are generated. The ions of interest and the background ions are then subjected to an activation energy sufficient to cause dissociation of background ions to an extent greater than the dissociation of the ions of interest. The dissociation of the background ions causes the background ions to have mass-to-charge ratios that fall outside of the range of mass-to-charge ratios. The mass-to-charge ratios of the ions of interest are then detected.

Abstract: The present invention is a method for accurately comparing the levels of cellular components, such as proteins, present in samples which differ in some respect from each other using mass spectroscopy and isotopic labeling. A first sample of biological matter, such as cells, is cultured in a first medium and a second sample of the same biological matter is cultured in a second medium, wherein at least one isotope in the second medium has a different abundance than the abundance of the same isotope in the first medium. One of the samples is modulated, such as by treatment with a bacteria, a virus, a drug, hormone, a chemical or an environmental stimulus. The samples are combined and at least one protein is removed. The removed protein is subjected to mass spectroscopy to develop a mass spectrum. A ratio is computed between the peak intensities of at least one closely spaced pair of peaks to determine the relative abundance of the protein in each sample.

Abstract: Method is described for sequencing polypeptides by forming peptide ladders comprising a series of polypeptides in which adjacent members of the series vary by one amino acid residue and determining the identity and position of each amino acid in the polypeptide by mass spectroscopy.

Abstract: A method and apparatus for increasing the signal-to-noise ratio in a range of mass-to-charge ratios of a mass spectrum. Initially ions of interest and background ions having mass-to-charge ratios within the range of mass-to-charge ratios are generated. The ions of interest and the background ions are then subjected to an activation energy sufficient to cause dissociation of background ions to an extent greater than the dissociation of the ions of interest. The dissociation of the background ions causes the background ions to have mass-to-charge ratios that fall outside of the range of mass-to-charge ratios. The mass-to-charge ratios of the ions of interest are then detected.

Abstract: Disclosed are compositions and methods for sensitive detection of one or multiple analytes. In general, the methods involve the use of special label components, referred to as reporter signals, that can be associated with, incorporated into, or otherwise linked to the analytes. In some embodiments, the reporter signals can be altered such that the altered forms of different reporter signals can be distinguished from each other. In some embodiments, sets of reporter signals can be used where two or more of the reporter signals in a set have one or more common properties that allow the reporter signals having the common property to be distinguished and/or separated from other molecules lacking the common property.

Abstract: A method of generating a frequency distribution of scores comprising: a) generating mass data for a biological molecule; b) generating mass data for a series of random hypothetical biological molecules; c) calculating a frequency distribution of high similarity scores between mass data of each molecule generated in steps a and b.

Abstract: Disclosed are a composition and a method for a multiplexing-optimized reporter system. The system is designed for the simultaneous detection of dozens or even hundreds of analytes. The analytes may be present on the surface of cells in suspension, on the surface of cytology smears, on the surface of histological sections, on the surface of DNA microarrays, on the surface of protein microarrays, on the surface of beads, or any other situation where complex samples need to be studied. The disclosed composition accomplishes this detection by associating specific binding molecules—which interact with desired targets—with numerous tag molecules in a carrier. The numerous tag molecules can be detected and effectively amplify the signal generated from targets.

Abstract: A method for determining the probability that a biological molecule identification is incorrect for a chosen significance level is provided. The method includes comparing experimental mass data of an unknown biological molecule with theoretical mass data and calculating a score for each comparison; selecting at least two scores from the scores to form a primary data set; generating artificial data sets from the primary data set; calculating a sample mean for each artificial data set; estimating population mean and population standard deviation from the sample means wherein the population is based on the distribution underlying the primary dataset; computing a Z score from the population mean and population standard deviation for each score to standardize the scores; choosing a significance level; and comparing a test Z score to a Z score of the chosen significance level to determine the probability that the biological molecule identification is incorrect.

Abstract: The present invention is a method for accurately comparing the levels of cellular components, such as proteins, present in samples which differ in some respect from each other using mass spectroscopy and isotopic labeling. A first sample of biological matter, such as cells, is cultured in a first medium and a second sample of the same biological matter is cultured in a second medium, wherein at least one isotope in the second medium has a different abundance than the abundance of the same isotope in the first medium. One of the samples is modulated, such as by treatment with a bacteria, a virus, a drug, hormone, a chemical or an environmental stimulus. The samples are combined and at least one protein is removed. The removed protein is subjected to mass spectroscopy to develop a mass spectrum. A ratio is computed between the peak intensities of at least one closely spaced pair of peaks to determine the relative abundance of the protein in each sample.

Abstract: A method for evaluating the performance of biopolymer identification algorithms, the method comprising a) generating noise and signal distributions, wherein the noise distribution comprises identification results obtained from the search of a database for arbitrarily generated sets of database mass data and wherein the signal distribution comprises identification results obtained from the search of a database for arbitrarily generated sets of database mass data which comprises mass data of a particular biopolymer of the database designated as a signal biopolymer; and b) calculating a performance index from the distributions which evaluates the performance of the algorithm.

Abstract: Method is described for sequencing polypeptides by forming peptide ladders comprising a series of polypeptides in which adjacent members of the series vary by one amino acid residue and determining the identity and position of each amino acid in the polypeptide by mass spectroscopy.

Abstract: A method of increasing the sensitivity and efficiency of MALDI-MS analysis of an oligosaccharide which comprises derivatization, prior to analysis by MALDI-MS, of said oligosaccharide by efficient ligation to a basic aminooxyacetylpeptide by oxime formation reaction to result in the formation of a glycoconjugate.

Abstract: Methods of producing biopolymer ladders and their use to obtain structural information about the biopolymer. The ladders are produced by setting up catalytic cleavage and terminating reactions at the end of biopolymer molecules. The terminating reactions terminate cleavage of a percentage of the biopolymer molecules at each round of cleavage.

Abstract: Improved techniques are provided for DNA sequencing, and particularly for sequencing of the entire human genome. Different base-specific reactions are utilized to use different sets of DNA fragments from a piece of DNA of unknown sequence. Each of the different sets of DNA fragments has a common origin and terminates at a particular base along the unknown sequence. The molecular weight of the DNA fragments in each of the different sets is detected by a matrix assisted laser absorption mass spectrometer to determine the sequence of the different bases in the DNA. The methods and apparatus of the present invention provide a relatively simple and low cost technique which may be automated to sequence thousands of gene bases per hour, and eliminates the tedious and time consuming gel electrophoresis separation technique conventionally used to determine the masses of DNA fragments.

Abstract: Improved techniques are provided for DNA sequencing, and particularly for sequencing of the entire human genome. Different base-specific reactions are utilized to use different sets of DNA fragments from a piece of DNA of unknown sequence. Each of the different sets of DNA fragments has a common origin and terminates at a particular base along the unknown sequence. The molecular weight of the DNA fragments in each of the different sets is detected by a matrix assisted laser absorption mass spectrometer to determine the sequence of the different bases in the DNA. The methods and apparatus of the present invention provide a relatively simple and low cost technique which may be automated to sequence thousands of gene bases per hour, and eliminates the tedious and time consuming gel electrophoresis separation technique conventionally used to determine the masses of DNA fragments.