公开(公告)号：US20160086780A1

公开(公告)日：2016-03-24

申请号：US14891084

申请日：2014-05-14

Applicant: McMaster University

Inventor： Philip Britz-McKibbin

IPC: H01J49/00 ,  H01J49/04 ,  H01J49/16 ,  G01N27/447

CPC classification number: G01N27/44782 ,  G01N27/447 ,  G01N27/4473 ,  G01N27/44743 ,  G01N30/7266 ,  H01J49/0027 ,  H01J49/0404 ,  H01J49/165

Abstract: Various embodiments illustrating a multiplexed method for high throughput screening of ions in biological samples within a single capillary when using capillary electrophoresis mass spectrometry (CE-MS) are illustrated. The method includes sequential injection of multiple sample segments in series within a single capillary, the sample segments being separated by a spacer plug of buffer, and multiplexed analysis of the sample segments simultaneously within a single capillary electrophoresis (CE) run. The method also includes application of voltage to the single capillary subsequent to sequential injection and zonal separation of polar metabolites within each sample segment by CE such that each analyte zone migrates within its characteristic electrophoretic mobility offset in time by the spacer. The incorporation of a quality control/reference sample and the use of dilution patterning with specific injection configurations also enables encoding of information temporally for enhanced data processing with quality assurance.

Abstract translation: 示出了当使用毛细管电泳质谱（CE-MS）时，单个毛细管内的生物样品中离子生物样品的高通量筛选的多路复用方法。 该方法包括在单个毛细管内连续注射多个样品片段，样品片段由缓冲液的间隔塞隔开，并在单个毛细管电泳（CE）运行中同时对样品片段进行多重分析。 该方法还包括在CE之间顺序注射和每个样品区段内的极性代谢物的区域分离之后，向单个毛细管施加电压，使得每个分析物区域在其特征电泳迁移率偏移期间通过间隔物在时间上迁移。 质量控制/参考样品的并入以及使用具有特定注射配置的稀释图案化也可以使信息在时间上进行编码，从而提高质量保证的数据处理能力。

公开(公告)号：US09490110B2

公开(公告)日：2016-11-08

申请号：US14891084

申请日：2014-05-14

Applicant: McMaster University

Inventor： Philip Britz-McKibbin

IPC: H01J49/26 ,  H01J49/00 ,  G01N27/447 ,  H01J49/04 ,  H01J49/16

CPC classification number: G01N27/44782 ,  G01N27/447 ,  G01N27/4473 ,  G01N27/44743 ,  G01N30/7266 ,  H01J49/0027 ,  H01J49/0404 ,  H01J49/165

Abstract: Various embodiments illustrating a multiplexed method for high throughput screening of ions in biological samples within a single capillary when using capillary electrophoresis mass spectrometry (CE-MS) are illustrated. The method includes sequential injection of multiple sample segments in series within a single capillary, the sample segments being separated by a spacer plug of buffer, and multiplexed analysis of the sample segments simultaneously within a single capillary electrophoresis (CE) run. The method also includes application of voltage to the single capillary subsequent to sequential injection and zonal separation of polar metabolites within each sample segment by CE such that each analyte zone migrates within its characteristic electrophoretic mobility offset in time by the spacer. The incorporation of a quality control/reference sample and the use of dilution patterning with specific injection configurations also enables encoding of information temporally for enhanced data processing with quality assurance.

Abstract translation: 示出了当使用毛细管电泳质谱（CE-MS）时，单个毛细管内的生物样品中离子生物样品的高通量筛选的多路复用方法。 该方法包括在单个毛细管内连续注射多个样品片段，样品片段由缓冲液的间隔塞隔开，并在单个毛细管电泳（CE）运行中同时对样品片段进行多重分析。 该方法还包括在CE之间顺序注射和每个样品区段内的极性代谢物的区域分离之后，向单个毛细管施加电压，使得每个分析物区域在其特征电泳迁移率偏移期间通过间隔物在时间上迁移。 质量控制/参考样品的并入以及使用具有特定注射配置的稀释图案化也可以使信息在时间上进行编码，从而提高质量保证的数据处理能力。

公开(公告)号：US10426751B2

公开(公告)日：2019-10-01

申请号：US15542225

申请日：2016-01-08

Applicant: MCMASTER UNIVERSITY

Inventor： Philip Britz-McKibbin

IPC: A61K31/215 ,  A61K31/192 ,  C12Q1/26

Abstract: A method of restoring activity in phenylalanine hydroxylase is provided. The method comprises exposing the phenylalanine hydroxylase to shikimic acid, a functionally equivalent analog thereof, a pharmaceutically acceptable salt of shikimic acid or analog thereof, or combinations thereof. A method of screening for allosteric activators for a target enzyme is also provided comprising the steps of: denaturing the target enzyme with a first chaotropic agent to yield denatured enzyme, incubating the denatured enzyme with a candidate compound under denaturing conditions to allow enzyme refolding, and assaying enzyme activity in the presence of enzyme substrate and a candidate compound; and if enzyme activity of the denatured enzyme was restored in step i) by at least about 10% of residual enzyme activity, denaturing the target enzyme with a second chaotropic agent to yield denatured enzyme, incubating the denatured enzyme with the candidate compound under non-denaturing conditions to allow enzyme refolding, and assaying enzyme activity in the presence of enzyme substrate and the candidate compound, wherein an increase in enzyme activity of at least about 10% of residual enzyme activity indicates that the candidate compound is an allosteric activator of the target enzyme.

公开(公告)号：US10054566B2

公开(公告)日：2018-08-21

申请号：US15293775

申请日：2016-10-14

Applicant: McMaster University

Inventor： Philip Britz-McKibbin

IPC: G01N27/447 ,  H01J49/04 ,  H01J49/16 ,  H01J49/00

CPC classification number: G01N27/44782 ,  G01N27/447 ,  G01N27/4473 ,  G01N27/44743 ,  G01N30/7266 ,  H01J49/0027 ,  H01J49/0404 ,  H01J49/165

Abstract: Various embodiments illustrating a multiplexed method for high throughput screening of ions in biological samples within a single capillary when using capillary electrophoresis mass spectrometry (CE-MS) are illustrated. The method includes sequential injection of multiple sample segments in series within a single capillary, the sample segments being separated by a spacer plug of buffer, and multiplexed analysis of the sample segments simultaneously within a single capillary electrophoresis (CE) run. The method also includes application of voltage to the single capillary subsequent to sequential injection and zonal separation of polar metabolites within each sample segment by CE such that each analyte zone migrates within its characteristic electrophoretic mobility offset in time by the spacer. The incorporation of a quality control/reference sample and the use of dilution patterning with specific injection configurations also enables encoding of information temporally for enhanced data processing with quality assurance.

公开(公告)号：US10768183B2

公开(公告)日：2020-09-08

申请号：US15361216

申请日：2016-11-25

Applicant: McMaster University

Inventor： Philip Britz-McKibbin

IPC: G01N33/68 ,  G01N33/50 ,  G01N27/447 ,  A23L33/10 ,  A23L33/00 ,  G16H50/20 ,  G16H50/30

Abstract: A method of diagnosing cystic fibrosis in a human subject is provided. The method includes the steps of: i) determining in a biological sample from the subject the level of one or more metabolic biomarkers; ii) comparing the level of the biomarker to a control level and determining the difference between the biomarker level and the control level; and iii) determining that the subject has cystic fibrosis or a related disorder when the difference in the level of the biomarker in the sample is statistically different from the control level.

公开(公告)号：US20180064672A1

公开(公告)日：2018-03-08

申请号：US15542225

申请日：2016-01-08

Applicant: MCMASTER UNIVERSITY

Inventor： Philip Britz-McKibbin

IPC: A61K31/215 ,  A61K31/192 ,  C12Q1/26

CPC classification number: A61K31/215 ,  A61K31/19 ,  A61K31/191 ,  A61K31/192 ,  A61K31/519 ,  A61K38/51 ,  A61P3/00 ,  A61P43/00 ,  C12Q1/00 ,  C12Q1/26 ,  C12Y114/16001 ,  A61K2300/00

Abstract: A method of restoring activity in phenylalanine hydroxylase is provided. The method comprises exposing the phenylalanine hydroxylase to shikimic acid, a functionally equivalent analogue thereof, a pharmaceutically acceptable salt of shikimic acid or analogue thereof, or combinations thereof. A method of screening for allosteric activators for a target enzyme is also provided comprising the steps of: denaturing the target enzyme with a first chaotropic agent to yield denatured enzyme, incubating the denatured enzyme with a candidate compound under denaturing conditions to allow enzyme refolding, and assaying enzyme activity in the presence of enzyme substrate and a candidate compound; and if enzyme activity of the denatured enzyme was restored in step i) by at least about 10% of residual enzyme activity, denaturing the target enzyme with a second chaotropic agent to yield denatured enzyme, incubating the denatured enzyme with the candidate compound under non-denaturing conditions to allow enzyme refolding, and assaying enzyme activity in the presence of enzyme substrate and the candidate compound, wherein an increase in enzyme activity of at least about 10% of residual enzyme activity indicates that the candidate compound is an allosteric activator of the target enzyme.

公开(公告)号：US20170199203A1

公开(公告)日：2017-07-13

申请号：US15361216

申请日：2016-11-25

Applicant: McMaster University

Inventor： Philip Britz-McKibbin

IPC: G01N33/68 ,  G06F19/00 ,  A23L33/00 ,  G01N33/50 ,  A23L33/10

CPC classification number: G01N33/6893 ,  A23L33/10 ,  A23L33/40 ,  A23V2002/00 ,  G01N27/4473 ,  G01N33/50 ,  G01N33/6806 ,  G01N2560/00 ,  G01N2570/00 ,  G01N2800/382 ,  G01N2800/52 ,  G16H50/20 ,  G16H50/30

Abstract: A novel method of diagnosing cystic fibrosis in a human subject is provided. The method includes the steps of: i) determining in a biological sample from the subject the level of one or more metabolic biomarkers; ii) comparing the level of the biomarker to a control level and determining the difference between the biomarker level and the control level; and iii) determining that the subject has cystic fibrosis or a related disorder when the difference in the level of the biomarker in the sample is statistically different from the control level.

公开(公告)号：US20230015257A1

公开(公告)日：2023-01-19

申请号：US17784979

申请日：2020-12-13

Applicant: McMaster University

Inventor： Philip Britz-McKibbin ,  Nikhil Pai

IPC: G01N33/68

Abstract: Methods of diagnosing Crohn’s disease and ulcerative colitis in subjects is provided based on the determination of metabolites in urine samples, such as serine, hypoxanthine, kynurenine, threonine, dimethylglycine, tryptophan, indoxylsul-fate, phenylacetylglutamine, sialic acid, 5-hydroxy-6-indolyl-o-sulfate, 5-(Δ-carboxybutyl) homocysteine, and/or an anion having m/ z:RMT:polarity of 345.1553:0.770:n, or determination of metabolites in stool samples, such as ketodeoxycholic acid, cholic acid, choline, tryptophan, trimethyllysine, serine, butyric acid, lactic acid, hypoxanthine and/or guanine.

公开(公告)号：US10234421B2

公开(公告)日：2019-03-19

申请号：US15281205

申请日：2016-09-30

Applicant: McMaster University

Inventor： Philip Britz-McKibbin

IPC: G01N27/447 ,  G01N33/02 ,  G01N33/14 ,  G01N33/18 ,  G01N33/48 ,  G01N33/483 ,  G01N33/49 ,  G01N33/50 ,  G01N33/487 ,  G01N33/493

Abstract: The present application is directed to the use of electrophoresis with UV detection in the determination of iodine nutritional status in human biological specimens, specifically for monitoring iodine deficiency/inadequacy in large-scale epidemiological studies. In particular, the present application is directed to a method for determining iodide and iodide uptake inhibitors in a human biological sample when using sample self-stacking with capillary electrophoresis and UV detection.

公开(公告)号：US20170146486A1

公开(公告)日：2017-05-25

申请号：US15281205

申请日：2016-09-30

Applicant: McMaster University

Inventor： Philip Britz-McKibbin

IPC: G01N27/447 ,  G01N33/493 ,  G01N33/49 ,  G01N33/487

CPC classification number: G01N27/44773 ,  G01N27/44721 ,  G01N27/44747 ,  G01N33/48707 ,  G01N33/49 ,  G01N33/493

Abstract: The present application is directed to the use of electrophoresis with UV detection in the determination of iodine nutritional status in human biological specimens, specifically for monitoring iodine deficiency/inadequacy in large-scale epidemiological studies. In particular, the present application is directed to a method for determining iodide and iodide uptake inhibitors in a human biological sample when using sample self-stacking with capillary electrophoresis and UV detection.