CA2488584C - Methods, mixtures, kits and compositions pertaining to analyte determination - Google Patents
Methods, mixtures, kits and compositions pertaining to analyte determination Download PDFInfo
- Publication number
- CA2488584C CA2488584C CA2488584A CA2488584A CA2488584C CA 2488584 C CA2488584 C CA 2488584C CA 2488584 A CA2488584 A CA 2488584A CA 2488584 A CA2488584 A CA 2488584A CA 2488584 C CA2488584 C CA 2488584C
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- Canada
- Prior art keywords
- group
- reporter
- linker
- alkyl
- analyte
- Prior art date
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Classifications
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- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
- G01N33/6848—Methods of protein analysis involving mass spectrometry
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/531—Production of immunochemical test materials
- G01N33/532—Production of labelled immunochemicals
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
- G01N33/6842—Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2458/00—Labels used in chemical analysis of biological material
- G01N2458/15—Non-radioactive isotope labels, e.g. for detection by mass spectrometry
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- 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.]
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- 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]
- Y10T436/145555—Hetero-N
-
- 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]
- Y10T436/145555—Hetero-N
- Y10T436/147777—Plural nitrogen in the same ring [e.g., barbituates, creatinine, 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
- Y10T436/24—Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
Landscapes
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Hematology (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Bioinformatics & Computational Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Biophysics (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Optics & Photonics (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US44361203P | 2003-01-30 | 2003-01-30 | |
| US60/443,612 | 2003-01-30 | ||
| PCT/US2004/002077 WO2004070352A2 (en) | 2003-01-30 | 2004-01-27 | Methods, mixtures, kits and compositions pertaining to analyte determination |
Publications (2)
| Publication Number | Publication Date |
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| CA2488584A1 CA2488584A1 (en) | 2004-08-19 |
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Families Citing this family (86)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60003177T2 (de) * | 1999-03-18 | 2004-05-06 | 602531 British Columbia Ltd., Vancouver | Dateneingabe für personalrechnergeräte |
| AU6770800A (en) * | 1999-08-13 | 2001-03-13 | Yale University | Analysis of sequence tags with hairpin primers |
| US20020106648A1 (en) * | 2000-05-05 | 2002-08-08 | Lizardi Paul M. | Highly multiplexed reporter carrier systems |
| US6835545B2 (en) | 2000-05-08 | 2004-12-28 | President And Fellows Of Harvard College | Methods, products and treatments for diabetes |
| CA2419159A1 (en) * | 2000-08-11 | 2002-02-21 | Agilix Corporation | Ultra-sensitive detection systems |
| AU2004209401A1 (en) | 2003-01-30 | 2004-08-19 | Applied Biosystems, Llc. | Methods, mixtures, kits and compositions pertaining to analyte determination |
| GB0306756D0 (en) * | 2003-03-24 | 2003-04-30 | Xzillion Gmbh & Co Kg | Mass labels |
| CA2542941C (en) * | 2003-11-26 | 2013-02-12 | Applera Corporation | Analysis of mass spectral data in the quiet zones and label selection therefor |
| EP1916527A1 (en) * | 2003-11-26 | 2008-04-30 | Applera Corporation | Analysis of mass spectral data in the quiet zones |
| US20050147985A1 (en) * | 2004-01-05 | 2005-07-07 | Applera Corporation | Mixtures of isobarically labeled analytes and fragments ions derived therefrom |
| JP4832312B2 (ja) * | 2004-01-05 | 2011-12-07 | ディーエイチ テクノロジーズ デベロップメント プライベート リミテッド | 標識試薬および標識化分析物の混合物を含む、標識試薬、標識化分析物、およびそれらに由来するフラグメントイオン、ならびにそれらの分析方法 |
| US20050148087A1 (en) | 2004-01-05 | 2005-07-07 | Applera Corporation | Isobarically labeled analytes and fragment ions derived therefrom |
| US20050148771A1 (en) * | 2004-01-05 | 2005-07-07 | Applera Corporation. | Active esters of N-substituted piperazine acetic acids, including isotopically enriched versions thereof |
| JP4613320B2 (ja) | 2004-03-01 | 2011-01-19 | ディーエイチ テクノロジーズ デベロップメント プライベート リミテッド | 結合特性に基づく分析物の特徴の決定 |
| EP1766413A2 (en) * | 2004-05-19 | 2007-03-28 | Applera Corporation | Expression quantification using mass spectrometry |
| US20080206737A1 (en) * | 2004-05-19 | 2008-08-28 | Hunter Christie L | Expression quantification using mass spectrometry |
| US20070054345A1 (en) | 2004-05-19 | 2007-03-08 | Hunter Christie L | Expression quantification using mass spectrometry |
| US8335652B2 (en) * | 2004-06-23 | 2012-12-18 | Yougene Corp. | Self-improving identification method |
| US20050287574A1 (en) * | 2004-06-23 | 2005-12-29 | Medtronic, Inc. | Genetic diagnostic method for SCD risk stratification |
| US8027791B2 (en) * | 2004-06-23 | 2011-09-27 | Medtronic, Inc. | Self-improving classification system |
| US20060172319A1 (en) * | 2004-07-12 | 2006-08-03 | Applera Corporation | Mass tags for quantitative analyses |
| US20070048752A1 (en) * | 2004-07-12 | 2007-03-01 | Applera Corporation | Mass tags for quantitative analyses |
| CA2838007A1 (en) * | 2004-11-15 | 2006-05-26 | University Of North Dakota | A method for single oxygen atom incorporation into digested peptides using peptidases |
| WO2006086098A2 (en) * | 2005-01-06 | 2006-08-17 | President And Fellows Of Harvard College | Mass spectrometric methods and products |
| US20070207555A1 (en) * | 2005-02-03 | 2007-09-06 | Cesar Guerra | Ultra-sensitive detection systems using multidimension signals |
| US20060183238A1 (en) * | 2005-02-09 | 2006-08-17 | Applera Corporation | Amine-containing compound analysis methods |
| US20070037286A1 (en) * | 2005-02-09 | 2007-02-15 | Subhasish Purkayastha | Thyroxine-containing compound analysis methods |
| JP4242358B2 (ja) | 2005-03-14 | 2009-03-25 | ホシザキ電機株式会社 | 断熱箱体及びその製造方法 |
| DE102005015005A1 (de) * | 2005-04-01 | 2006-10-05 | Qiagen Gmbh | Verfahren zur Behandlung einer Biomoleküle enthaltenden Probe |
| DE602006014846D1 (de) | 2005-09-15 | 2010-07-22 | Alk Abello As | Verfahren zur quantifizierung von allergenen |
| US20080318327A1 (en) * | 2006-01-05 | 2008-12-25 | Ge Healthcare Bio-Sciences Ab | Kit and Method for Mass Labelling |
| US8975404B2 (en) | 2006-01-24 | 2015-03-10 | Dh Technologies Development Pte. Ltd. | Labeling reagents for analyte determination and methods and compounds used in making the same |
| US20070185346A1 (en) * | 2006-02-03 | 2007-08-09 | Vaidya Niteen A | Kit for automated resolving agent selection and method thereof |
| US7982070B2 (en) | 2006-03-21 | 2011-07-19 | Wisconsin Alumni Research Foundation | Ionizable isotopic labeling reagents for relative quantification by mass spectrometry |
| CN101454488A (zh) * | 2006-05-26 | 2009-06-10 | 阿普里拉股份有限公司 | 用于羟基化化合物的标签试剂和方法 |
| US8580534B2 (en) * | 2006-06-30 | 2013-11-12 | The University Of North Dakota | Method for incorporation of two oxygen atoms into digested peptides using peptidases |
| US8362242B2 (en) * | 2006-06-30 | 2013-01-29 | Dh Technologies Development Pte. Ltd. | Analyte determination utilizing mass tagging reagents comprising a non-encoded detectable label |
| US7906341B2 (en) * | 2006-06-30 | 2011-03-15 | Dh Technologies Development Pte, Ltd. | Methods, mixtures, kits and compositions pertaining to analyte determination |
| EP1918714A1 (en) * | 2006-11-02 | 2008-05-07 | Koninklijke Philips Electronics N.V. | Compounds and methods for double labelling of polypeptides to allow multiplexing in mass spectrometric analysis |
| EP1921081A1 (en) | 2006-11-06 | 2008-05-14 | Koninklijke Philips Electronics N.V. | Use of arylboronic acids in protein labelling |
| US7951608B2 (en) * | 2007-05-04 | 2011-05-31 | Perkinelmer Health Sciences, Inc. | Detecting succinylacetone |
| WO2009003188A2 (en) * | 2007-06-27 | 2008-12-31 | Cedars-Sinai Medical Center | N-terminal specific chemical labeling for proteomics applications |
| US20090028791A1 (en) * | 2007-07-25 | 2009-01-29 | Balatoni Julius A | Dichloroacetate Analogs as Imaging Agents |
| US7820964B2 (en) * | 2007-08-06 | 2010-10-26 | Metabolic Analyses, Inc | Method for generation and use of stable isotope patterns in mass spectral data |
| US7982180B2 (en) * | 2007-09-10 | 2011-07-19 | Dh Technologies Development Pte. Ltd. | Methods and systems for analysis and correction of mass spectrometer data |
| US8604692B2 (en) | 2007-11-06 | 2013-12-10 | Translational Therapeutics, Inc. | Mass spectrometry assay for eIF4E and eIF4E regulon activity |
| EP2212690A4 (en) * | 2007-11-06 | 2011-03-30 | Translational Therapeutics Inc | MASS SPECTROMETRY ANALYSIS OF THE ACTIVITY OF ELF4E AND ELF4E REGULON |
| US20110143956A1 (en) * | 2007-11-14 | 2011-06-16 | Medtronic, Inc. | Diagnostic Kits and Methods for SCD or SCA Therapy Selection |
| US20090136954A1 (en) * | 2007-11-14 | 2009-05-28 | Medtronic, Inc. | Genetic markers for scd or sca therapy selection |
| EP2108957A1 (en) * | 2008-04-07 | 2009-10-14 | Koninklijke Philips Electronics N.V. | Compounds and methods for the labelling and affinity-selection of proteins |
| GB0809488D0 (en) * | 2008-05-23 | 2008-07-02 | Electrophoretics Ltd | Mass spectrometric analysis |
| US8486712B2 (en) | 2009-03-10 | 2013-07-16 | University Of Maryland, College Park | Deuterium isobaric tag reagents for quantitative analysis |
| US8592216B2 (en) | 2009-04-15 | 2013-11-26 | Wisconsin Alumni Research Foundation | Labeling peptides with tertiary amines and other basic functional groups for improved mass spectrometric analysis |
| WO2010132546A2 (en) * | 2009-05-12 | 2010-11-18 | Medtronic, Inc. | Sca risk stratification by predicting patient response to anti-arrhythmics |
| US20110003395A1 (en) | 2009-05-31 | 2011-01-06 | Dh Technologies Development Pte. Ltd. | Specific analysis of analytes using reagent compounds, labeling strategies, and mass spectrometry workflow |
| GB0916881D0 (en) | 2009-09-25 | 2009-11-11 | Electrophoretics Ltd | Mass labels |
| US20110143445A1 (en) * | 2009-12-15 | 2011-06-16 | Dh Technologies Development Pte. Ltd. | Analysis of Amino Acids And Amine-Containing Compounds Using Tagging Reagents and LC-MS Workflow |
| US8309359B2 (en) * | 2010-01-15 | 2012-11-13 | California Institute Of Technology | Isobaric tags for analyte detection and quantification |
| EP2528443B1 (en) | 2010-01-25 | 2017-01-11 | DH Technologies Development Pte. Ltd. | Quantitative analysis of vitamin d3, vitamin d2, and metabolites thereof |
| DE102011017084B4 (de) | 2010-04-14 | 2020-07-09 | Wisconsin Alumni Research Foundation | Massenspektrometriedaten-Erfassungsmodus zur Erzielung einer zuverlässigeren Proteinquantifizierung |
| CA2799750A1 (en) | 2010-05-17 | 2011-11-24 | The Uab Research Foundation | A general mass spectrometry assay using continuously eluting co-fractionating reporters of mass spectrometry detection efficiency |
| US8835361B2 (en) * | 2010-06-01 | 2014-09-16 | The Curators Of The University Of Missouri | High-throughput quantitation of crop seed proteins |
| WO2012027555A2 (en) | 2010-08-25 | 2012-03-01 | President And Fellows Of Harvard College | Glycated cd59 peptides, their preparation, and uses thereof |
| DE102011053684B4 (de) | 2010-09-17 | 2019-03-28 | Wisconsin Alumni Research Foundation | Verfahren zur Durchführung von strahlformstossaktivierter Dissoziation im bereits bestehenden Ioneninjektionspfad eines Massenspektrometers |
| JP5711948B2 (ja) * | 2010-12-02 | 2015-05-07 | 良雄 林 | 固相担持型ｓｈ基選択的標識試薬 |
| JP5454462B2 (ja) * | 2010-12-22 | 2014-03-26 | 株式会社島津製作所 | クロマトグラフ質量分析装置 |
| US8492163B2 (en) | 2011-01-31 | 2013-07-23 | Dh Technologies Development Pte. Ltd. | Methods, mixtures, kits and compositions pertaining to analyte determination |
| MX377572B (es) | 2011-02-10 | 2025-03-10 | Harvard College | Sustitutos de proteínas modificadas post-traduccionalmente y usos de los mismos. |
| US9040903B2 (en) | 2011-04-04 | 2015-05-26 | Wisconsin Alumni Research Foundation | Precursor selection using an artificial intelligence algorithm increases proteomic sample coverage and reproducibility |
| US9388132B2 (en) | 2011-09-15 | 2016-07-12 | Wisconsin Alumni Research Foundation | Isobaric tandem mass tags for quantitative proteomics and peptidomics |
| US9874575B2 (en) | 2012-01-20 | 2018-01-23 | Dh Technologies Development Pte. Ltd. | Analysis of estradiol and analytes with phenolic OH using labeling chemistry and LC-MSMS workflow |
| US9029086B2 (en) * | 2012-01-26 | 2015-05-12 | Masood Kamali Moghaddam | Detection of single and multimodal analytes |
| EP2850430B1 (en) | 2012-05-18 | 2017-04-19 | Dh Technologies Development Pte. Ltd. | Analysis of a panel of cerebrotendinous xanthomatosis biomarkers using site specific derivation and lc/ms/ms workflow |
| WO2014013051A1 (en) | 2012-07-19 | 2014-01-23 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Method of predicting or diagnosing an hepatic encephalopathy in patients with cirrhosis treated with transjugular intra-hepatic porto-systemic shunt (tips) |
| US9366678B2 (en) | 2012-10-25 | 2016-06-14 | Wisconsin Alumni Research Foundation | Neutron encoded mass tags for analyte quantification |
| GB201410523D0 (en) * | 2014-06-12 | 2014-07-30 | Electrophoretics Ltd | Mass labels |
| US20170089915A1 (en) * | 2015-09-30 | 2017-03-30 | Agilent Technologies, Inc. | Methods of analyte derivatization and enhanced soft ionization |
| GB201521903D0 (en) * | 2015-12-11 | 2016-01-27 | Electrophoretics Ltd | Isorbaric mass labels |
| CN109311803A (zh) * | 2016-06-29 | 2019-02-05 | 株式会社日立高新技术 | 酶反应及质量分析方法中使用的化合物 |
| WO2018141821A1 (en) | 2017-01-31 | 2018-08-09 | Roche Diagnostics Gmbh | Reagent for mass spectrometry |
| WO2019096852A1 (en) * | 2017-11-14 | 2019-05-23 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Uses of isobaric tags in mass spectrometry |
| JP7547315B2 (ja) * | 2018-07-24 | 2024-09-09 | エフ． ホフマン－ラ ロシュ アーゲー | 質量分析のための試薬 |
| BR112021001061A2 (pt) | 2018-07-24 | 2021-04-20 | F. Hoffmann-La Roche Ag | composto, composição, kit, aduto covalente, uso de um composto e método para a determinação de espectrometria de massa |
| WO2020020850A1 (en) * | 2018-07-24 | 2020-01-30 | F. Hoffmann-La Roche Ag | Reagent for mass spectrometry |
| CN112146967A (zh) * | 2019-06-28 | 2020-12-29 | Fei 公司 | 用于制备和递送用于带电粒子分析的生物样品的系统和方法 |
| EP3910341A1 (en) * | 2020-05-13 | 2021-11-17 | PreOmics GmbH | Sample preparation for mass spectrometry |
Family Cites Families (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3860581A (en) | 1972-12-27 | 1975-01-14 | American Home Prod | Preparation of 1,4-benzodiazepines |
| AU5940186A (en) | 1985-07-05 | 1987-01-08 | Institut Fur Pflanzenschutzforschung | 2, 6 - dimethyl - morpholine quartenary compounds |
| US4761415A (en) | 1986-08-28 | 1988-08-02 | Smithkline Beckman Corporation | Dopamine-β-hydroxylase inhibitors |
| JPH01125357A (ja) | 1987-11-06 | 1989-05-17 | Dainippon Pharmaceut Co Ltd | トリペプチドの誘導体 |
| US5800992A (en) * | 1989-06-07 | 1998-09-01 | Fodor; Stephen P.A. | Method of detecting nucleic acids |
| US5087815A (en) | 1989-11-08 | 1992-02-11 | Schultz J Albert | High resolution mass spectrometry of recoiled ions for isotopic and trace elemental analysis |
| US5252296A (en) * | 1990-05-15 | 1993-10-12 | Chiron Corporation | Method and apparatus for biopolymer synthesis |
| DK51092D0 (da) * | 1991-05-24 | 1992-04-15 | Ole Buchardt | Oligonucleotid-analoge betegnet pna, monomere synthoner og fremgangsmaade til fremstilling deraf samt anvendelser deraf |
| WO1993024834A1 (en) | 1992-05-29 | 1993-12-09 | The Rockefeller University | Method and product for the sequence determination of peptides using a mass spectrometer |
| GB9300883D0 (en) | 1993-01-18 | 1993-03-10 | Pfizer Ltd | Antiparasitic agents |
| AU7247896A (en) | 1995-09-29 | 1997-04-17 | Scripps Research Institute, The | Protein signature analysis |
| US6312893B1 (en) * | 1996-01-23 | 2001-11-06 | Qiagen Genomics, Inc. | Methods and compositions for determining the sequence of nucleic acid molecules |
| US6027890A (en) * | 1996-01-23 | 2000-02-22 | Rapigene, Inc. | Methods and compositions for enhancing sensitivity in the analysis of biological-based assays |
| US6613508B1 (en) | 1996-01-23 | 2003-09-02 | Qiagen Genomics, Inc. | Methods and compositions for analyzing nucleic acid molecules utilizing sizing techniques |
| EP0863858B1 (en) * | 1996-04-08 | 2004-02-04 | Glaxo Group Limited | Mass-based encoding and qualitative analysis of combinatorial libraries |
| US5780232A (en) * | 1996-05-28 | 1998-07-14 | Atom Sciences, Inc. | DNA sequencing, mapping, and diagnostic processes using hybridization and stable isotope labels of DNA |
| US6329180B1 (en) | 1996-09-13 | 2001-12-11 | Alex M. Garvin | Genetic analysis using peptide tagged in-vitro synthesized proteins |
| GB9620769D0 (en) | 1996-10-04 | 1996-11-20 | Brax Genomics Ltd | Nucleic acid sequencing |
| DE69723096T2 (de) | 1996-10-04 | 2004-05-06 | Dako A/S | Sonden zur detektion von mycobakterien |
| DE69735445T2 (de) | 1996-12-10 | 2006-08-10 | Sequenom, Inc., San Diego | Abspaltbare, nicht-flüchtige moleküle zur massenmarkierung |
| EP0979305B1 (en) | 1997-01-15 | 2006-09-27 | Xzillion GmbH & CO.KG | Mass label linked hybridisation probes |
| DE69817211T2 (de) | 1997-01-23 | 2004-06-03 | Xzillion Gmbh & Co. Kg | Charakterisierung von polypeptiden |
| IL133948A0 (en) | 1997-07-11 | 2001-04-30 | Brax Group Ltd | Characterising nucleic acids |
| CA2297158C (en) | 1997-07-22 | 2009-12-22 | Rapigene Inc. | Methods and compounds for analyzing nucleic acids by mass spectrometry |
| GB9718921D0 (en) | 1997-09-05 | 1997-11-12 | Brax Genomics Ltd | Catalytically generated mass labels |
| EP1015632A1 (en) | 1997-09-15 | 2000-07-05 | Brax Group Limited | Characterising nucleic acid by mass spectrometry |
| GB9823646D0 (en) | 1997-12-19 | 1998-12-23 | Brax Genomics Ltd | Compounds for mass spectrometry |
| US6326479B1 (en) * | 1998-01-27 | 2001-12-04 | Boston Probes, Inc. | Synthetic polymers and methods, kits or compositions for modulating the solubility of same |
| US6428956B1 (en) * | 1998-03-02 | 2002-08-06 | Isis Pharmaceuticals, Inc. | Mass spectrometric methods for biomolecular screening |
| WO1999049293A2 (en) * | 1998-03-24 | 1999-09-30 | Boston Probes, Inc. | Methods, kits and compositions pertaining to detection complexes |
| EP1073767B1 (en) * | 1998-04-29 | 2009-11-25 | Boston Probes, Inc. | Methods, kits and compositions for detecting and quantitating target sequences |
| ATE253126T1 (de) * | 1998-08-25 | 2003-11-15 | Univ Washington | Schnelle quantitative analyse von proteinen oder proteinfunktionen in komplexen gemischen |
| US6270976B1 (en) * | 1998-09-15 | 2001-08-07 | Brax Group Limited | Characterizing nucleic acid by mass spectrometry |
| GB9821669D0 (en) | 1998-10-05 | 1998-12-02 | Glaxo Group Ltd | Chemical constructs and their uses |
| US6319476B1 (en) | 1999-03-02 | 2001-11-20 | Perseptive Biosystems, Inc. | Microfluidic connector |
| US6629040B1 (en) | 1999-03-19 | 2003-09-30 | University Of Washington | Isotope distribution encoded tags for protein identification |
| US6403309B1 (en) * | 1999-03-19 | 2002-06-11 | Valigen (Us), Inc. | Methods for detection of nucleic acid polymorphisms using peptide-labeled oligonucleotides and antibody arrays |
| AU6770800A (en) * | 1999-08-13 | 2001-03-13 | Yale University | Analysis of sequence tags with hairpin primers |
| US6472156B1 (en) | 1999-08-30 | 2002-10-29 | The University Of Utah | Homogeneous multiplex hybridization analysis by color and Tm |
| GB0006141D0 (en) * | 2000-03-14 | 2000-05-03 | Brax Group Ltd | Mass labels |
| AUPQ664300A0 (en) * | 2000-04-03 | 2000-05-04 | Proteome Systems Ltd | Macromolecule detection |
| US20020106648A1 (en) | 2000-05-05 | 2002-08-08 | Lizardi Paul M. | Highly multiplexed reporter carrier systems |
| CA2419159A1 (en) | 2000-08-11 | 2002-02-21 | Agilix Corporation | Ultra-sensitive detection systems |
| CA2426728A1 (en) | 2000-10-23 | 2002-06-13 | Genetics Institute, Llc. | Isotope-coded ionization-enhancing reagents (icier) for high-throughput protein identification and quantitation using matrix-assisted laser desorption ionization mass spectrometry |
| US20020090652A1 (en) * | 2000-12-22 | 2002-07-11 | Fu Emil Wei-Ming | Inverse labeling method for the rapid identification of marker/target proteins |
| US7045296B2 (en) * | 2001-05-08 | 2006-05-16 | Applera Corporation | Process for analyzing protein samples |
| GB0115581D0 (en) | 2001-06-26 | 2001-08-15 | Glaxo Group Ltd | Method of mass spectometry |
| GB0116143D0 (en) * | 2001-07-02 | 2001-08-22 | Amersham Pharm Biotech Uk Ltd | Chemical capture reagent |
| US7732378B2 (en) | 2001-09-14 | 2010-06-08 | Electrophoretics Limited | Mass labels |
| WO2003040288A2 (de) | 2001-11-09 | 2003-05-15 | Bayer Healthcare Ag | Isotopencodierte affinitätsmarker 3 |
| ES2284783T3 (es) * | 2001-11-16 | 2007-11-16 | Randox Laboratories Ltd. | Metodo y estuche para detectar, o determinar la cantidad de,metabolitos de fentanilo y metabolitos de analogos de fentanilo. |
| GB0130845D0 (en) | 2001-12-22 | 2002-02-06 | James Peter | Analysis |
| WO2003078584A2 (en) | 2002-03-11 | 2003-09-25 | Thermo Finnigan, Llc | Identifying peptide modifications |
| DE60325847D1 (de) | 2002-03-11 | 2009-03-05 | Caprotec Bioanalytics Gmbh | Verbindungen und verfahren für die analyse des proteoms |
| AU2003259029A1 (en) | 2002-06-04 | 2003-12-19 | The Institute For Systems Biology | Methods for high throughput and quantitative proteome analysis |
| US7473535B2 (en) | 2002-08-20 | 2009-01-06 | The Institute For Systems Biology | Chemical reagents and methods for detection and quantification of proteins in complex mixtures |
| US7425451B2 (en) * | 2002-12-13 | 2008-09-16 | Agilent Technologies, Inc. | Triazine derivatives as universal peptide isotope tag reagents (U-PIT) |
| AU2004209401A1 (en) * | 2003-01-30 | 2004-08-19 | Applied Biosystems, Llc. | Methods, mixtures, kits and compositions pertaining to analyte determination |
| GB0306756D0 (en) | 2003-03-24 | 2003-04-30 | Xzillion Gmbh & Co Kg | Mass labels |
| US20050147985A1 (en) * | 2004-01-05 | 2005-07-07 | Applera Corporation | Mixtures of isobarically labeled analytes and fragments ions derived therefrom |
| US20050147982A1 (en) * | 2004-01-05 | 2005-07-07 | Applera Corporation | Mixtures of isobarically labeled analytes and fragments ions derived therefrom |
| US7355045B2 (en) * | 2004-01-05 | 2008-04-08 | Applera Corporation | Isotopically enriched N-substituted piperazine acetic acids and methods for the preparation thereof |
| US20050148087A1 (en) * | 2004-01-05 | 2005-07-07 | Applera Corporation | Isobarically labeled analytes and fragment ions derived therefrom |
| US20050148771A1 (en) | 2004-01-05 | 2005-07-07 | Applera Corporation. | Active esters of N-substituted piperazine acetic acids, including isotopically enriched versions thereof |
| US20060172319A1 (en) * | 2004-07-12 | 2006-08-03 | Applera Corporation | Mass tags for quantitative analyses |
-
2004
- 2004-01-27 AU AU2004209401A patent/AU2004209401A1/en not_active Abandoned
- 2004-01-27 CA CA2488584A patent/CA2488584C/en not_active Expired - Fee Related
- 2004-01-27 JP JP2006503013A patent/JP4613299B2/ja not_active Expired - Lifetime
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- 2004-01-27 US US10/765,267 patent/US7195751B2/en not_active Expired - Lifetime
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- 2008-11-28 AU AU2008250877A patent/AU2008250877A1/en not_active Abandoned
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- 2010-03-19 JP JP2010065164A patent/JP5503358B2/ja not_active Expired - Lifetime
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| US7910059B2 (en) | 2011-03-22 |
| ATE515702T1 (de) | 2011-07-15 |
| JP5503358B2 (ja) | 2014-05-28 |
| EP1588145A2 (en) | 2005-10-26 |
| US20060105416A1 (en) | 2006-05-18 |
| US7947513B2 (en) | 2011-05-24 |
| EP1588145B1 (en) | 2011-07-06 |
| US8679773B2 (en) | 2014-03-25 |
| US7195751B2 (en) | 2007-03-27 |
| US20080101989A1 (en) | 2008-05-01 |
| JP2010190902A (ja) | 2010-09-02 |
| WO2004070352A3 (en) | 2006-09-28 |
| WO2004070352A2 (en) | 2004-08-19 |
| JP2007525639A (ja) | 2007-09-06 |
| US20040219686A1 (en) | 2004-11-04 |
| AU2008250877A1 (en) | 2008-12-18 |
| US7799576B2 (en) | 2010-09-21 |
| US20040219685A1 (en) | 2004-11-04 |
| US20110217720A1 (en) | 2011-09-08 |
| JP4613299B2 (ja) | 2011-01-12 |
| CA2488584A1 (en) | 2004-08-19 |
| EP1588145A4 (en) | 2007-05-16 |
| US20040220412A1 (en) | 2004-11-04 |
| US20100112708A1 (en) | 2010-05-06 |
| AU2004209401A1 (en) | 2004-08-19 |
| US20110045516A1 (en) | 2011-02-24 |
| US20070141659A1 (en) | 2007-06-21 |
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