DE102007017681A1 - Device for determining activity of enzymes in liquid test sample containing enzyme and enzyme inhibitor, comprises chromatography column, which contains substrate and substance bound to substrate - Google Patents
Device for determining activity of enzymes in liquid test sample containing enzyme and enzyme inhibitor, comprises chromatography column, which contains substrate and substance bound to substrate Download PDFInfo
- Publication number
- DE102007017681A1 DE102007017681A1 DE102007017681A DE102007017681A DE102007017681A1 DE 102007017681 A1 DE102007017681 A1 DE 102007017681A1 DE 102007017681 A DE102007017681 A DE 102007017681A DE 102007017681 A DE102007017681 A DE 102007017681A DE 102007017681 A1 DE102007017681 A1 DE 102007017681A1
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- measuring
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6408—Fluorescence; Phosphorescence with measurement of decay time, time resolved fluorescence
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
-
- 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
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/30—Control of physical parameters of the fluid carrier of temperature
-
- 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
- G01N30/74—Optical detectors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/645—Specially adapted constructive features of fluorimeters
- G01N2021/6463—Optics
- G01N2021/6467—Axial flow and illumination
-
- 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
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/30—Control of physical parameters of the fluid carrier of temperature
- G01N2030/3007—Control of physical parameters of the fluid carrier of temperature same temperature for whole column
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2201/00—Features of devices classified in G01N21/00
- G01N2201/06—Illumination; Optics
- G01N2201/064—Stray light conditioning
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
Description
Es
ist eine derartige Vorrichtung und Verfahren aus der
Dabei wird die Enzymaktivität gemessen, indem die Messprobe zuvor über eine Durchfluss- oder Durchlaufsäule gegeben wird, auf welcher der Probe die Inhibitoren entzogen werden, die das Enzym binden. Danach wird das inhibitorfreie Enzym in eine Messzelle gegeben, welche den Anstieg der Konzentration mindestens eines Spaltprodukts eines Substrats über der Zeit misst.there the enzyme activity is measured by passing the sample over a flow or flow column is given on which of the sample the inhibitors are deprived of the enzyme tie. Thereafter, the inhibitor-free enzyme is added to a measuring cell, which increases the concentration of at least one cleavage product of a substrate over time.
In der Messzelle wird bei dieser vorbekannten Methode ein Substrat zur Flüssigkeit, die aus der Säule eluiert wird (also möglichst inhibitorfrei und damit der Messung der Gesamtaktivität des Enzyms zugänglich), gegeben. Das solchermaßen freie Enzym spaltet das Substrat und das Spaltprodukt kann gemessen werden, bzw. die Konzentration dieses Spaltprodukts wird zeitlich ermittelt, und der Intensitätszuwachs ermittelt: Dieser ist ein Maß für die Gesamtaktivität des Enzyms, vor allem sobald er zeitlich konstant ist.In the measuring cell is a substrate in this prior art method to the liquid which is eluted from the column (ie as inhibitor-free and thus the measurement of Total activity of the enzyme available). The thus free enzyme cleaves the substrate and the Cleavage product can be measured, or the concentration of this cleavage product is determined in time, and determines the increase in intensity: This is a measure of the overall activity of the enzyme, especially once it is constant over time.
Das o. g. Thema soll insbesondere bei proteolytischen Enzymen, vor allem bei Cystein-Proteinasen, für die Diagnose und auch für die Therapie von malignen Tumoren zum Tragen kommen. In einer Messprobe sind Enzym-Inhibitor-Komplexe, und die proteolytischen Enzyme sind in vivo durch Bindung von Inhibitoren in ihrer Enzymaktivität überwiegend gehemmt.The o. g. Subject should be especially in proteolytic enzymes, especially in cysteine proteinases, for diagnosis and also for the therapy of malignant tumors come to fruition. In a test sample are enzyme-inhibitor complexes, and are the proteolytic enzymes inhibited in vivo by binding of inhibitors in their enzyme activity predominantly.
Es ist Aufgabe der vorliegenden Anmeldung, eine Vorrichtung und eine Methode zu finden, die für die Alltagspraxis, z. B. von Arztpraxen bzw. kleinen ärztlichen Labors oder u. U. auch für Notfallsituationen bei relativ einfacher Handhabung ausreichend genaue Messwerte als Prognostikfaktor (für Therapieentscheidungen) oder Marker (für Diagnosezwecke) liefert. Ferner liegt die Aufgabe zugrunde, eingangs genannte Vorrichtung und Methode zu rationalisieren.It Object of the present application, a device and a To find a method that is suitable for everyday practice, eg. B. from Medical practices or small medical laboratories or u. U. also for emergency situations with relatively easy handling sufficiently accurate measured values as a prognostic factor (for Therapy decisions) or markers (for diagnostic purposes) supplies. Furthermore, the object is based, mentioned device and streamline method.
Die Lösung dieser Aufgabe geschieht mit den Mitteln des Anspruchs 1 oder 2 oder 3. Weiterbildungen dienen Maßnahmen, die in den Unteransprüchen definiert sind.The Solution of this task is done with the means of the claim 1 or 2 or 3. trainings serve measures that are defined in the subclaims.
In
den
Die
Dabei
ist eine austauschbare Affinitäts-Chromatographiesäule
Das
Volumen
Ein
Elutionspuffer vom ca. 100–103fachen Volumen
der Messprobe wird danach mittels einer zweiten Spritze
Eine
erste Vorgehensweise ist folgende: Man belässt die Messprobe
mit einem Teil des Elutionspuffers in der Säule
Bei
der ersten Methode ist das Ventil
Eine
zweite alternative Maßnahme besteht darin, dass die Messprobe
mit Hilfe des zugegebenen Säulenpuffers von oben nach unten
durch die Säule wandert mit einer Geschwindigkeit die gewährleistet,
dass auf diesem Weg der Inhibitor von allen in der Messprobe enthaltenen
Enzym-Inhibitorkomplexen auf die auf der Säule immobilisierte
Substanz übergeht, die den Inhibitor stärker bindet
als es das Enzym tut. Das ist quasi eine Wanderungsinkubation. Dadurch
wird das freie Enzym eluiert und die Elutionslösung fließt
nach unten in das Modul B gemäß
Auch
hier wird ein Verwertungsvolumen anfangs (wie in
Das
Modul A in
Die
Temperierung der Affinitäts-Chromatographiesäule
Die
Messung der Enzymaktivität in Modul B erfolgt temperiert
bei 37°C (für humanmedizinische Zwecke), (wozu
eine Zusatzeinrichtung für die Konstanthaltung der Temperatur
zweckmäßigerweise wiederum mittels Peltierelementen
dienlich ist: Thermostat
Im
einfachsten Fall ist auch die Küvette
Die
Teile
Die
Verdünnung des Eluats mit Messpuffer kann für
ein gutes Messergebnis sehr vorteilhaft, evtl. notwendig sein. Die
Kombination von Laserdiode und/oder Fotodiode direkt an der Messküvette
führt zu einer hohen Nachweisgrenze. Im einfachsten Fall der
In
In
Der
Tubus
Die
Pumpe
Für
die Ermittlung des Verwertungsvolumens wird die Verdünnung
der Probe nach dem Durchlauf durch die Säule
Nach
Durchfluss durch den Kanal
Der
Behälter
Er
kann eine Fluoreszenzküvette sein, wobei im Modul B eine
Laserdiode
Diese
Laserstrahlung aus
Unterhalb
der Fluoreszenzküvette
Die
Messkurve für die emittierte Fluoreszenzintensität
in
Im
einfachsten Fall ist das Modul A eine Wegwert-Chromatographiesäule,
in welche oben eine erste Einmalspritze mit der Messprobe eingeführt
wird, danach eine 2. Spritze mit dem Säulenpuffer, der
Ausgang
Im einfachsten Fall ist Modul B eine mit Messpuffer und weiteren Ingredientien, wie z. B. ein nicht ionisches Tensid und Dithiothreitol oder Cystein, aufbereitete billige Wegwerfpackung.in the the simplest case is module B with measuring buffer and other ingredients, such as A nonionic surfactant and dithiothreitol or cysteine, recycled cheap disposable pack.
Das Ventil ist dann unerlässlich, wenn man die Messprobe im Durchflussverfahren aus der Säule eluiert, denn dann wird man einen ersten Teil des Eluats verwerfen. Es ist aber auch dann unerlässlich, wenn man die Probe auf der Säule eine Zeit lang inkubiert; denn dazu muss man nach dem Auftragen der Probe auf die Säule danach einen gewissen Teil des Säulenpuffers in die Säule lassen und unten auslassen; dadurch sickert die Messprobe in die Säule ein und die Enzym-Inhibitorkomplexe der Messprobe finden so möglichst alle Kontakt mit der auf der Säule immobilisierten Substanz, die den Inhibitor besser bindet,The valve is essential if you elute the sample from the column in the flow process, because then you will discard a first part of the eluate. It is also essential to incubate the sample on the column for a while; because you have to do this after applying the sample to the column afterwards a certain part leave the column buffer in the column and drain below; As a result, the test sample seeps into the column and the enzyme-inhibitor complexes of the test sample find as much contact as possible with the substance immobilized on the column, which binds the inhibitor better.
Während
in der Anordnung gemäß
Dadurch
ist unterhalb der Messküvette
In diesen Figurenbeschreibungen sind identische Ziffern für gleich wirkende oder identische Teile verwendet. Außerdem wird Modul A als ebenes Schnittbild dargestellt, während Modul B in räumlicher Darstellung gezeigt ist.In these figure descriptions are identical numbers for identical or identical parts used. Furthermore Module A is shown as a flat sectional image, while Module B is shown in a spatial representation.
Das
Verfahren, das gemäß
Gemäß
Eine
weitere, hier nicht dargestellte Variante sieht vor, dass im Modul
A (in die Säule
Bei
dieser niedrigen Temperatur würde die an sich unerwünschte
Reaktion zwischen Enzym und Substrat noch vernachlässigbar
sein, so dass das Substrat schon in Modul A dazugegeben werden könnte.
Die Messung könnte wie bei
ZITATE ENTHALTEN IN DER BESCHREIBUNGQUOTES INCLUDE IN THE DESCRIPTION
Diese Liste der vom Anmelder aufgeführten Dokumente wurde automatisiert erzeugt und ist ausschließlich zur besseren Information des Lesers aufgenommen. Die Liste ist nicht Bestandteil der deutschen Patent- bzw. Gebrauchsmusteranmeldung. Das DPMA übernimmt keinerlei Haftung für etwaige Fehler oder Auslassungen.This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.
Zitierte PatentliteraturCited patent literature
- - WO 97/00969 [0001] WO 97/00969 [0001]
Claims (6)
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102007017681A DE102007017681A1 (en) | 2007-04-14 | 2007-04-14 | Device for determining activity of enzymes in liquid test sample containing enzyme and enzyme inhibitor, comprises chromatography column, which contains substrate and substance bound to substrate |
DE102007057388A DE102007057388A1 (en) | 2007-04-14 | 2007-11-27 | Apparatus and method for measuring the activity of enzymes after inhibitor withdrawal |
DE102008036329A DE102008036329A1 (en) | 2007-04-14 | 2008-07-07 | Protease activity determination in biological samples and liquid test sample, e.g. blood sample and blood serum, involves withdrawing protease from test sample of protease inhibitor by bringing test sample in contact with support material |
DE102008034120A DE102008034120A1 (en) | 2007-04-14 | 2008-07-21 | Protease activity determination in biological samples and liquid test sample, e.g. blood sample and blood serum, involves withdrawing protease from test sample of protease inhibitor by bringing test sample in contact with support material |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102007017681A DE102007017681A1 (en) | 2007-04-14 | 2007-04-14 | Device for determining activity of enzymes in liquid test sample containing enzyme and enzyme inhibitor, comprises chromatography column, which contains substrate and substance bound to substrate |
Publications (1)
Publication Number | Publication Date |
---|---|
DE102007017681A1 true DE102007017681A1 (en) | 2009-01-08 |
Family
ID=40092118
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE102007017681A Withdrawn DE102007017681A1 (en) | 2007-04-14 | 2007-04-14 | Device for determining activity of enzymes in liquid test sample containing enzyme and enzyme inhibitor, comprises chromatography column, which contains substrate and substance bound to substrate |
DE102007057388A Ceased DE102007057388A1 (en) | 2007-04-14 | 2007-11-27 | Apparatus and method for measuring the activity of enzymes after inhibitor withdrawal |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE102007057388A Ceased DE102007057388A1 (en) | 2007-04-14 | 2007-11-27 | Apparatus and method for measuring the activity of enzymes after inhibitor withdrawal |
Country Status (1)
Country | Link |
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DE (2) | DE102007017681A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102007057388A1 (en) | 2007-04-14 | 2009-05-28 | Papst Licensing Gmbh & Co. Kg | Apparatus and method for measuring the activity of enzymes after inhibitor withdrawal |
DE102009004371A1 (en) | 2009-01-08 | 2010-07-15 | Papst Licensing Gmbh & Co. Kg | Apparatus and method for measuring the activity of enzymes after inhibitor withdrawal |
US8759019B2 (en) | 2007-07-06 | 2014-06-24 | Papst Licensing Gmbh & Co. Kg | Method for measuring the activity of proteases |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3838011A (en) * | 1971-06-18 | 1974-09-24 | Boehringer Mannheim Gmbh | Process and apparatus for the quantitative determination of an enzymatically reactive substance |
DE2526558A1 (en) * | 1975-06-13 | 1976-12-30 | Boehringer Mannheim Gmbh | PROCEDURE FOR ENZYMATIC ANALYSIS |
US4169765A (en) * | 1977-09-14 | 1979-10-02 | Technicon Instruments Corp. | Apparatus for the quantitative determination of α-amylase |
US4762617A (en) * | 1987-01-15 | 1988-08-09 | The United States Of America As Represented By The United States Department Of Energy | Size-exclusion chromatography system for macromolecular interaction analysis |
DD283867A5 (en) * | 1988-05-25 | 1990-10-24 | Boehringer Mannheim Gmbh,De | PROCESS FOR DETERMINING AN IMMUNOLOGICALLY DETECTABLE SUBSTANCE AND REACTION GEFA SUITABLE FOR IT |
US5133937A (en) * | 1989-06-01 | 1992-07-28 | Iniziative Marittime, 1991 S.R.L. | Analysis system having a removable reaction cartridge and temperature control |
DE4314981A1 (en) * | 1992-05-15 | 1993-12-02 | Lange Gmbh Dr Bruno | Measuring biochemical oxygen@ demand - using a cuvette which is coated with polymer-immobilised bio-catalyst |
WO1997000969A1 (en) | 1995-06-20 | 1997-01-09 | Johannes Schumacher | Process and device for determining the activity of enzymes in liquids, or the concentration and/or activity of inhibitors in liquids |
US5919419A (en) * | 1994-02-22 | 1999-07-06 | Orion-yhtyma Oy | Analyzer cuvette, method and diagnostic test kit for determination of analytes in whole blood samples |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4294923A (en) * | 1979-04-23 | 1981-10-13 | Smith Robert E | Substrates and method for determining enzymes |
US7416854B2 (en) * | 2004-01-22 | 2008-08-26 | Promega Corporation | Luminogenic and nonluminogenic multiplex assay |
DE102007017681A1 (en) | 2007-04-14 | 2009-01-08 | Papst Licensing Gmbh & Co. Kg | Device for determining activity of enzymes in liquid test sample containing enzyme and enzyme inhibitor, comprises chromatography column, which contains substrate and substance bound to substrate |
-
2007
- 2007-04-14 DE DE102007017681A patent/DE102007017681A1/en not_active Withdrawn
- 2007-11-27 DE DE102007057388A patent/DE102007057388A1/en not_active Ceased
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3838011A (en) * | 1971-06-18 | 1974-09-24 | Boehringer Mannheim Gmbh | Process and apparatus for the quantitative determination of an enzymatically reactive substance |
DE2526558A1 (en) * | 1975-06-13 | 1976-12-30 | Boehringer Mannheim Gmbh | PROCEDURE FOR ENZYMATIC ANALYSIS |
US4169765A (en) * | 1977-09-14 | 1979-10-02 | Technicon Instruments Corp. | Apparatus for the quantitative determination of α-amylase |
US4762617A (en) * | 1987-01-15 | 1988-08-09 | The United States Of America As Represented By The United States Department Of Energy | Size-exclusion chromatography system for macromolecular interaction analysis |
DD283867A5 (en) * | 1988-05-25 | 1990-10-24 | Boehringer Mannheim Gmbh,De | PROCESS FOR DETERMINING AN IMMUNOLOGICALLY DETECTABLE SUBSTANCE AND REACTION GEFA SUITABLE FOR IT |
US5133937A (en) * | 1989-06-01 | 1992-07-28 | Iniziative Marittime, 1991 S.R.L. | Analysis system having a removable reaction cartridge and temperature control |
DE4314981A1 (en) * | 1992-05-15 | 1993-12-02 | Lange Gmbh Dr Bruno | Measuring biochemical oxygen@ demand - using a cuvette which is coated with polymer-immobilised bio-catalyst |
US5919419A (en) * | 1994-02-22 | 1999-07-06 | Orion-yhtyma Oy | Analyzer cuvette, method and diagnostic test kit for determination of analytes in whole blood samples |
WO1997000969A1 (en) | 1995-06-20 | 1997-01-09 | Johannes Schumacher | Process and device for determining the activity of enzymes in liquids, or the concentration and/or activity of inhibitors in liquids |
Non-Patent Citations (2)
Title |
---|
SCHROEDER,R.R.,et.al.:Enzyme-Selective Detector Sy stems for High-Pressure Liquid-Chromatography. In: Journal of Chromatography, Vol. 134,1977,S.83-90;; * |
SCHROEDER,R.R.,et.al.:Enzyme-Selective Detector Sy stems for High-Pressure Liquid-Chromatography.In:J ournal of Chromatography, Vol.134,1977,S.83-90; |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102007057388A1 (en) | 2007-04-14 | 2009-05-28 | Papst Licensing Gmbh & Co. Kg | Apparatus and method for measuring the activity of enzymes after inhibitor withdrawal |
US8759019B2 (en) | 2007-07-06 | 2014-06-24 | Papst Licensing Gmbh & Co. Kg | Method for measuring the activity of proteases |
DE102009004371A1 (en) | 2009-01-08 | 2010-07-15 | Papst Licensing Gmbh & Co. Kg | Apparatus and method for measuring the activity of enzymes after inhibitor withdrawal |
US8945863B2 (en) | 2009-01-08 | 2015-02-03 | Papst Licensing Gmbh & Co. Kg | Method for measuring the activity of cathepsin B after de-inhibition |
Also Published As
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---|---|
DE102007057388A1 (en) | 2009-05-28 |
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R005 | Application deemed withdrawn due to failure to request examination |
Effective date: 20140415 |