Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/04—Preparation or injection of sample to be analysed
  • G01N30/06—Preparation
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/62—Detectors specially adapted therefor
  • G01N30/72—Mass spectrometers
  • G01N30/7233—Mass spectrometers interfaced to liquid or supercritical fluid chromatograph
• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
  • H01J49/00—Particle spectrometers or separator tubes
  • H01J49/0009—Calibration of the apparatus
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/04—Preparation or injection of sample to be analysed
  • G01N2030/042—Standards
  • G01N2030/045—Standards internal
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T436/00—Chemistry: analytical and immunological testing
  • Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T436/00—Chemistry: analytical and immunological testing
  • Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
  • Y10T436/142222—Hetero-O [e.g., ascorbic acid, etc.]
  • Y10T436/143333—Saccharide [e.g., DNA, etc.]
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T436/00—Chemistry: analytical and immunological testing
  • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation

Definitions

• the system also contains a mass spectroscopy analysis system comprising a mass spectrometer capable of detecting analyte derivatives, a first derivatizing agent useful for derivatizing analytes in a sample to form analyte derivatives in the sample comprising AccQTagTM or a functional derivative thereof , and reagents capable of producing a plurality of analyte derivative standards comprising AccQTagTM or a functional derivative thereof that have been labeled with a radioactive or stable isotope.
• the number of analyte derivative standards is greater than 10, e.g., greater than 15, e.g., greater than 20.
• an increase in the accuracy of analyte quantification refers to an improvement in obtaining a measured value that is closer to the actual or true value. This improvement may be identified/described by reference to a percent increase in accuracy with respect to the accuracy obtainable using existing methods of measurement that utilize mass spectroscopy of a plurality of analytes. .
• Amino acid analogs include modified forms of naturally and non-naturally occurring amino acids. Such modifications can include, for example, substitution or replacement of chemical groups and moieties on the amino acid or by derivitization of the amino acid.
• Amino acid mimetics include, for example, organic structures that exhibit functionally similar properties such as charge and charge spacing characteristic of the reference amino acid. For example, an organic structure that mimics lysine (Lys or K) would have a positive charge moiety located in similar molecular space and having the same degree of mobility as the ⁇ -amino group of the side chain of the naturally occurring Lys amino acid. Mimetics also include constrained structures so as to maintain optimal spacing and charge interactions of the amino acid or of the amino acid functional groups.
• analyte refers to any chemical or biological compound or substance that is subject to the analysis of the invention capable of derivatization according to the methods of the invention.
• Analytes of the invention include, but are not limited to, small organic compounds, amino acids, peptides, polypeptides, proteins, nucleic acids, polynucleotides, biomarkers, synthetic or natural polymers, or any combination or mixture thereof.
• the analyte is a primary or secondary amino acid.
• analyte as used throughout the specification may be interpreted in its singular or plural form.
• AccQTagTM, PicoTag® or a functional derivative thereof.
• Functional derivatives of derivatizing agents AccQTagTM and PicoTag® include modifications of the chemical structure of the AccQTagTM and PicoTag® reagents that would not substantially affect the ability of these reagents to perform their intended function, i.e., derivatization and utility in detection according to the methods of the invention.
• internal standard describes a collection of one or more functionalized chemical or biological compounds or substances, e.g., one or more analytes functionalized with another moiety in order to convert such compounds or substances into a derivative thereof.
• Internal standards of the invention are present in known concentrations and added to the sample to form a sample mixture. The addition of the internal standard allows for the detection of and comparison between the known concentrations of one or more known analytes, with the unknown concentrations of analytes in the original sample.
• the internal standards of the present invention provide a novel way to measure the absolute quantity of a plurality of analytes in sample using a response factor calculation.
• mobile phase is art-recognized, and describes a liquid solvent system used to carry a compound of interest into contact with a solid phase (e.g., a solid phase in a solid phase extraction (SPE) cartridge or HPLC column) and to elute a compound of interest from the solid phase.
• a solid phase e.g., a solid phase in a solid phase extraction (SPE) cartridge or HPLC column
• non-volatile salts describes salts present in the mobile phase which are substantially non-volatile under conditions used for removing mobile phase solvents when interfacing a liquid chromatography system with a mass spectrometer.
• precision is art-recognized and describes the reproducibility of a result. It is measured by comparison of successive values obtained for a measurement to the prior values, where more precise measurements (or those with greater precision) will be demonstrated by successive measurements that are more consistently closer to the prior measurements.
• specimen may also be a microbiological specimen, which may be derived from a culture of the microorganisms, including those cultured from a specimen from an individual.
• the analytes or compounds present in the mixture may include, for example, small organic molecules (such as pharmaceuticals or pharmaceutical candidates, typically having a molecular weight of less than 1000), amino acids, proteins, peptides or polypeptides (e.g.
• the analytes are selected from the group consisting of amino acids, polypeptides, and mixture thereof.
• the analytes are selected from the group consisting of amino acids and mixtures thereof, e.g., a primary or secondary amino acid.
• This amino acid may be, for example, selected from the group consisting of known natural and non-natural amino acids.
• any method for modifying the amino-terminus of a polypeptide may also be used.
• other methods for modifying the N-terminus are well known to those skilled in the art (see, for example, Brancia et al., Electrophoresis 22:552 559 (2001); Hoving et al., Anal. Chem. 72:1006 1014 (2000); Munchbach et al., Anal. Chem. 72:4047 4057 (2000), each of which is incorporated herein by reference).
• a PicoTag® reagent Waters Corporation, Milford, MA
• PITC phenylisothiocyanate
• the system also contains a mass spectroscopy analysis system comprising a mass spectrometer capable of detecting analyte derivatives, a first derivatizing agent useful for derivatizing analytes in a sample to form analyte derivatives in the sample comprising AccQTagTM or a functional derivative thereof , and a plurality of analyte derivative standards comprising AccQTagTM or a functional derivative thereof that have been labeled with an isotope.
• the isotope is a radioactive isotope.
• the isotope is a stable isotope, e.g., selected from the group consisting of 13 C, 15 N, and 2 H.
• the number of analyte derivative standards is greater than 5, e.g., greater than 10, e.g., greater than 15, e.g., greater than 20. In certain embodiments, the analyte derivative standard is between 5 and 40, e.g., between 5 and 30, e.g., between 10 and 30, e.g., between 10 and 25, e.g., between 10 and 20.
• Another aspect of the invention is directed to a liquid chromatography/mass spectroscopy system for quantitatively analyzing the amount of a plurality of analytes in a sample.
• the system contains a chromatographic analysis system comprising a chromatographic column and a pump for pumping at least one mobile phase through the chromatographic column.
• the size of the column can be selected according to factors such as the amount of sample to be analyzed or purified.
• an HPLC column having a diameter of about 3 mm to about 20 mm may be used.
• a microbore column, capillary column, or nanocolumn may be used.
• the chromatographic separation is performed using a column selected from the group consisting of a microbore column, a capillary column, a preparative column, or a nanocolumn.
• Reversed phase chromatography utilizes a non-polar stationary phase in conjunction with more polar, largely aqueous mobile phases.
• ion-exchange chromatography retention of the sample on the stationary phase is controlled through the interaction of charged analytes with oppositely charged functional groups on the stationary phase surface. Because both the sample components and the stationary phase could contain either cation or anion exchange groups (and possibly both) these separations are strongly influenced by changes in mobile phase pH and/or ionic strength. In the case of ion-exchange separations, raising or lowering the pH and/or ionic strength of the mobile phase results in either an increase or a decrease in the elution strength of the mobile phase, depending on the pKa of the sample and whether the stationary phase is a cation or anion exchanger.
• the methods of the invention can be readily adapted to automation. For example, automated sampling, robotics, or any suitable automation methods can be applied to methods of the invention, if desired. Since all the reactions can be done easily in an automated fashion, the methods of the invention would allow for a high throughput sample preparation. hi addition, since there is virtually no sample handling such as transferring steps, loss of captured molecules is minimized, thus improving the yield of molecule recovery. The captured molecules can also be extensively washed to remove non-captured sample molecules or any regents since the captured sample molecules remain bound to the solid support during the wash steps. The methods of the invention can be used to capture essentially all of a class or multiple classes of molecules from a sample, or a portion of the molecules from a sample, as desired.
• novel equivalents to number values provided herein are intended to include number values that are one or two integers removed from the number provided herein, e.g., wherein the number of analytes in the sample is greater than 20 is also intended to include 18, 19, 21 , and 22.

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• Chemical & Material Sciences (AREA)
• Analytical Chemistry (AREA)
• Physics & Mathematics (AREA)
• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Biochemistry (AREA)
• General Health & Medical Sciences (AREA)
• General Physics & Mathematics (AREA)
• Immunology (AREA)
• Pathology (AREA)
• Other Investigation Or Analysis Of Materials By Electrical Means (AREA)

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Cited By (15)

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Citations (3)

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• 2008
  • 2008-11-20 JP JP2010534957A patent/JP2011504596A/ja active Pending
  • 2008-11-20 EP EP08855298A patent/EP2215460A4/en not_active Withdrawn
  • 2008-11-20 WO PCT/US2008/012938 patent/WO2009070233A1/en not_active Ceased
  • 2008-11-20 US US12/676,011 patent/US20100285593A1/en not_active Abandoned
• 2012
  • 2012-12-07 US US13/708,252 patent/US20130102478A1/en not_active Abandoned

Patent Citations (3)

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