WO1995002067A1 - Procede ameliore de quantification de l'acide nucleique - Google Patents

Procede ameliore de quantification de l'acide nucleique Download PDF

Info

Publication number
WO1995002067A1
WO1995002067A1 PCT/EP1994/002295 EP9402295W WO9502067A1 WO 1995002067 A1 WO1995002067 A1 WO 1995002067A1 EP 9402295 W EP9402295 W EP 9402295W WO 9502067 A1 WO9502067 A1 WO 9502067A1
Authority
WO
WIPO (PCT)
Prior art keywords
nucleic acid
sample
analyte
amounts
constructs
Prior art date
Application number
PCT/EP1994/002295
Other languages
English (en)
Inventor
Marinus Gerardus Johannes Beuningen
Tim Kievits
Thomas Augustinus Maria Beumer
Original Assignee
Akzo Nobel N.V.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Akzo Nobel N.V. filed Critical Akzo Nobel N.V.
Priority to JP50383695A priority Critical patent/JP3594598B2/ja
Priority to KR1019950700919A priority patent/KR100312800B1/ko
Priority to DE69417863T priority patent/DE69417863T2/de
Priority to DK94924750T priority patent/DK0662156T3/da
Priority to EP94924750A priority patent/EP0662156B1/fr
Priority to CA002143857A priority patent/CA2143857C/fr
Priority to AU74928/94A priority patent/AU668659B2/en
Publication of WO1995002067A1 publication Critical patent/WO1995002067A1/fr
Priority to FI951082A priority patent/FI112094B/fi
Priority to GR990401631T priority patent/GR3030554T3/el

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844Nucleic acid amplification reactions
    • C12Q1/6865Promoter-based amplification, e.g. nucleic acid sequence amplification [NASBA], self-sustained sequence replication [3SR] or transcription-based amplification system [TAS]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844Nucleic acid amplification reactions
    • C12Q1/6851Quantitative amplification
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/70Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
    • C12Q1/701Specific hybridization probes
    • C12Q1/702Specific hybridization probes for retroviruses
    • C12Q1/703Viruses associated with AIDS

Definitions

  • each construct being distinguishable from the analyte nucleic acid and capable of being co-amplified with the analyte nucleic acid
  • reaction aliquots, each of a known volume, to each of which nucleic acid constructs are added in different ranges of amounts. Preferably, in that case, to each reaction volume the same nucleic acid constructs are added. If, for example, two reactions are used, a "low-range” reaction and a “high range” reaction can be carried out. For example, when the ranges of nucleic acid
  • Contaminations with about 100-1000 molecules will slightly influence the internal calibration line and will only interfere with the calculation of the amount of analyte nucleic acid molecules present in the sample if the amount of analyte molecules in the sample is less than 1000 molecules. Contaminations with more than 1000 molecules will alter the calibration line and the outcome of the calculation.
  • log (Q/A) log (Q/A)
  • nucleic acid amplification procedure may be added, said quantity expected to be within the same range as the expected amount of analyte nucleic acid present in said sample, subjecting the sample to a nucleic acid amplification procedure, using
  • pGEM3Q C ⁇ gag3 Q C -RNA
  • SP6 RNA polymerase SP6 RNA polymerase
  • the cloned inserts of pGEM3p24 and pGEM3Q A were recloned into vector pGEM4 creating pGEM4p24 and pGEM4Q A .
  • Using these plasmids in vitro RNA was made using T7 RNA polymerase (Sambrook, 1989).
  • the length of the in vitro RNA is 1514 nucleotides for plasmids pGEM3p24 (WT-RNA) and pGEM3Q A (Q A -RNA) and 1090 nucleotides for plasmids
  • the number of amplification reactions can be decreased with the method according to the invention where several distinguishable internal standards are spiked into one amplification.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Virology (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • AIDS & HIV (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La présente invention se rapporte à un procédé amélioré de quantification de l'acide nucléique qui peut être effectué avec une dose minime déclenchant l'amplification de l'acide nucléique. Selon l'invention, le procédé de quantification de l'acide nucléique d'un analyte dans un échantillon consiste à: ajouter à l'échantillon différentes quantités respectives de produits de recombinaison différents d'acide nucléique, chaque produit de recombinaison pouvant se distinguer de l'acide nucléique de l'analyte et pouvant être co-amplifié avec l'acide nucléique de l'analyte; soumettre l'échantillon à une procédure d'amplification de l'acide nucléique en utilisant des réactifs d'amplification capables de réagir à la fois avec l'acide nucléique de l'analyte et les produits de recombinaison de l'acide nucléique; détecter les quantités relatives d'agents d'amplification dérivés de l'acide nucléique de l'analyte et de chaque produit de recombinaison de l'acide nucléique; calculer la quantité d'acide nucléique de l'analyte à partir de ces quantités relatives. Chaque produit de recombinaison de l'acide nucléique est différent; les produits de recombinaison de l'acide nucléique peuvent se distinguer les uns des autres et de l'acide nucléique de l'analyte. Les produits de recombinaison de l'acide nucléique se ressemblent, et ressemblent aussi à l'acide nucléique de l'analyte, en ce qu'ils sont tous capables de réagir aux mêmes réactifs d'amplification.
PCT/EP1994/002295 1993-07-09 1994-07-08 Procede ameliore de quantification de l'acide nucleique WO1995002067A1 (fr)

Priority Applications (9)

Application Number Priority Date Filing Date Title
JP50383695A JP3594598B2 (ja) 1993-07-09 1994-07-08 改良された核酸定量方法
KR1019950700919A KR100312800B1 (ko) 1993-07-09 1994-07-08 핵산의정량방법
DE69417863T DE69417863T2 (de) 1993-07-09 1994-07-08 Verbessertes verfahren für die quantifizierung von nukleinsäuren
DK94924750T DK0662156T3 (da) 1993-07-09 1994-07-08 Forbedret fremgangsmåde til kvantificering af nukleinsyre
EP94924750A EP0662156B1 (fr) 1993-07-09 1994-07-08 Procede ameliore de quantification de l'acide nucleique
CA002143857A CA2143857C (fr) 1993-07-09 1994-07-08 Methode amelioree pour le dosage de l'acide nucleique
AU74928/94A AU668659B2 (en) 1993-07-09 1994-07-08 Improved method for the quantification of nucleic acid
FI951082A FI112094B (fi) 1993-07-09 1995-03-08 Parannettu menetelmä nukleiinihapon kvantitoimiseksi
GR990401631T GR3030554T3 (en) 1993-07-09 1999-06-17 Improved method for the quantification of nucleic acid.

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP93202015.9 1993-07-09
EP93202015 1993-07-09
EP93203424 1993-12-06
EP93203424.2 1993-12-06

Publications (1)

Publication Number Publication Date
WO1995002067A1 true WO1995002067A1 (fr) 1995-01-19

Family

ID=26133903

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1994/002295 WO1995002067A1 (fr) 1993-07-09 1994-07-08 Procede ameliore de quantification de l'acide nucleique

Country Status (10)

Country Link
JP (1) JP3594598B2 (fr)
KR (1) KR100312800B1 (fr)
AT (1) ATE178946T1 (fr)
AU (1) AU668659B2 (fr)
CA (1) CA2143857C (fr)
DE (1) DE69417863T2 (fr)
DK (1) DK0662156T3 (fr)
ES (1) ES2131699T3 (fr)
FI (1) FI112094B (fr)
WO (1) WO1995002067A1 (fr)

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0714988A2 (fr) * 1994-09-26 1996-06-05 IMMUNO Aktiengesellschaft Procédé pour quantifier d'acides nucléiques
EP0722508A1 (fr) * 1993-09-22 1996-07-24 Igen, Inc. Dosage d'acides nucleiques electrochimioluminescents par replication de sequences auto-entretenues
EP0747488A1 (fr) * 1995-06-07 1996-12-11 Gen-Probe Incorporated Procédés et trousse des détection des taux de pre-amplification d'une séquence cible d'acide nucléique à partir des taux de post-amplification des produits
WO1997012058A1 (fr) * 1995-09-26 1997-04-03 Dynal A/S Procede de quantification d'acide nucleique consistant a utiliser plusieurs acides nucleiques concurrents
US5705365A (en) * 1995-06-07 1998-01-06 Gen-Probe Incorporated Kits for determining pre-amplification levels of a nucleic acid target sequence from post-amplification levels of product
WO1998000547A1 (fr) * 1996-07-03 1998-01-08 Ambion, Inc. Preparation et utilisation d'arn resistant a la ribonuclease
US5710029A (en) * 1995-06-07 1998-01-20 Gen-Probe Incorporated Methods for determining pre-amplification levels of a nucleic acid target sequence from post-amplification levels of product
WO1998041650A2 (fr) * 1997-03-18 1998-09-24 Visible Genetics Inc. Procede et trousse de quantification et de sequençage d'acide nucleique d'analytes d'acide nucleique dans un echantillon
FR2765590A1 (fr) * 1997-07-01 1999-01-08 Pasteur Institut Methode de semi-quantification d'alleles
US5919625A (en) * 1996-07-03 1999-07-06 Ambion, Inc. Ribonuclease resistant viral RNA standards
WO2000000638A2 (fr) * 1998-06-26 2000-01-06 Akzo Nobel N.V. Marquage d'amplicons d'arn produits au moyen d'une amplification fondee sur la transcription
EP1013776A1 (fr) * 1998-12-22 2000-06-28 Universiteit van Amsterdam Méthode sensible d'essai pour la détection ou pour la quantification d'acide nucléique de cytomégalovirus humain
WO2000046401A1 (fr) * 1999-02-03 2000-08-10 Lgc (Teddington) Limited Materiau de reference pour amplification d'acide nucleique
WO2001007661A2 (fr) * 1999-07-23 2001-02-01 Gen-Probe Incorporated Methode d'amplification de polynucleotides
WO2001046463A2 (fr) * 1999-12-22 2001-06-28 Baxter Aktiengesellschaft Methodes de preparation et d'utilisation d'etalons internes destines a des dosages par amplification de l'acide nucleique
EP1319716A1 (fr) * 2000-09-22 2003-06-18 Hitachi, Ltd. Procede d'analyse d'acide nucleique
EP1352091A2 (fr) * 2000-12-22 2003-10-15 Cepheid Compositions et procedes permettant la surveillance interne totale de la reaction par amplification
US7972778B2 (en) 1997-04-17 2011-07-05 Applied Biosystems, Llc Method for detecting the presence of a single target nucleic acid in a sample
WO2012114312A3 (fr) * 2011-02-25 2012-11-01 Novartis Ag Témoin positif interne exogène
US8889405B2 (en) 2009-09-16 2014-11-18 Seiko Epson Corporation Biochip and target DNA quantitative method

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5564795B2 (ja) * 2009-01-06 2014-08-06 株式会社島津製作所 Dna定量方法、及び遺伝子解析方法
KR102108855B1 (ko) 2017-10-30 2020-05-12 한국표준과학연구원 안정동위원소 표지 핵산을 내부표준물질로 활용하는 핵산 정량 방법 및 이의 용도

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0303459A2 (fr) * 1987-08-11 1989-02-15 The President And Fellows Of Harvard College Séquenage multiplexe
EP0525882A1 (fr) * 1991-08-02 1993-02-03 Akzo Nobel N.V. Quantification d'acides nucléiques
WO1993010257A1 (fr) * 1991-11-15 1993-05-27 Institut National De La Sante Et De La Recherche Medicale (Inserm) Procede de determination de la quantite d'un fragment d'adn d'interet par une methode d'amplification enzymatique d'adn

Patent Citations (3)

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EP0303459A2 (fr) * 1987-08-11 1989-02-15 The President And Fellows Of Harvard College Séquenage multiplexe
EP0525882A1 (fr) * 1991-08-02 1993-02-03 Akzo Nobel N.V. Quantification d'acides nucléiques
WO1993010257A1 (fr) * 1991-11-15 1993-05-27 Institut National De La Sante Et De La Recherche Medicale (Inserm) Procede de determination de la quantite d'un fragment d'adn d'interet par une methode d'amplification enzymatique d'adn

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APOSTOLAKOS ET AL., ANALYTICAL BIOCHEMISTRY, vol. 213, September 1993 (1993-09-01), NEW YORK US, pages 277 - 284 *
GEMEN ET AL., JOURNAL OF VIROLOGICAL METHODS, vol. 43, July 1993 (1993-07-01), AMSTERDAM NL, pages 177 - 188 *

Cited By (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0722508A1 (fr) * 1993-09-22 1996-07-24 Igen, Inc. Dosage d'acides nucleiques electrochimioluminescents par replication de sequences auto-entretenues
EP0722508A4 (fr) * 1993-09-22 1999-08-11 Igen Inc Dosage d'acides nucleiques electrochimioluminescents par replication de sequences auto-entretenues
EP0714988A2 (fr) * 1994-09-26 1996-06-05 IMMUNO Aktiengesellschaft Procédé pour quantifier d'acides nucléiques
EP0714988A3 (fr) * 1994-09-26 1997-04-16 Immuno Ag Procédé pour quantifier d'acides nucléiques
US5789153A (en) * 1994-09-26 1998-08-04 Immuno Aktiengesellschaft Method of quantitating nucleic acid
EP0747488A1 (fr) * 1995-06-07 1996-12-11 Gen-Probe Incorporated Procédés et trousse des détection des taux de pre-amplification d'une séquence cible d'acide nucléique à partir des taux de post-amplification des produits
WO1996040990A1 (fr) * 1995-06-07 1996-12-19 Gen-Probe Incorporated Procedes et trousses servant a determiner les niveaux de preamplification d'une sequence cible d'acides nucleiques a partir des niveaux de post-amplification du produit
US5705365A (en) * 1995-06-07 1998-01-06 Gen-Probe Incorporated Kits for determining pre-amplification levels of a nucleic acid target sequence from post-amplification levels of product
AU709292B2 (en) * 1995-06-07 1999-08-26 Gen-Probe Incorporated Methods and kits for determining pre-amplification levels of a nucleic acid target sequence from post-amplification levels of product
US5710029A (en) * 1995-06-07 1998-01-20 Gen-Probe Incorporated Methods for determining pre-amplification levels of a nucleic acid target sequence from post-amplification levels of product
WO1997012058A1 (fr) * 1995-09-26 1997-04-03 Dynal A/S Procede de quantification d'acide nucleique consistant a utiliser plusieurs acides nucleiques concurrents
US5919625A (en) * 1996-07-03 1999-07-06 Ambion, Inc. Ribonuclease resistant viral RNA standards
US6214982B1 (en) 1996-07-03 2001-04-10 Ambion Inc Ribonuclease resistant RNA preparation and utilization
US6399307B1 (en) 1996-07-03 2002-06-04 Ambion, Inc. Methods of quantifying viral load in an animal with a ribonuclease resistant RNA preparation
US7033749B2 (en) 1996-07-03 2006-04-25 Ambion, Inc. Ribonuclease resistant RNA preparation and utilization
WO1998000547A1 (fr) * 1996-07-03 1998-01-08 Ambion, Inc. Preparation et utilisation d'arn resistant a la ribonuclease
US5939262A (en) * 1996-07-03 1999-08-17 Ambion, Inc. Ribonuclease resistant RNA preparation and utilization
WO1998041650A2 (fr) * 1997-03-18 1998-09-24 Visible Genetics Inc. Procede et trousse de quantification et de sequençage d'acide nucleique d'analytes d'acide nucleique dans un echantillon
WO1998041650A3 (fr) * 1997-03-18 1999-01-14 Visible Genetics Inc Procede et trousse de quantification et de sequençage d'acide nucleique d'analytes d'acide nucleique dans un echantillon
US8859204B2 (en) 1997-04-17 2014-10-14 Applied Biosystems, Llc Method for detecting the presence of a target nucleic acid sequence in a sample
US8822183B2 (en) 1997-04-17 2014-09-02 Applied Biosystems, Llc Device for amplifying target nucleic acid
US8563275B2 (en) 1997-04-17 2013-10-22 Applied Biosystems, Llc Method and device for detecting the presence of a single target nucleic acid in a sample
US8551698B2 (en) 1997-04-17 2013-10-08 Applied Biosystems, Llc Method of loading sample into a microfluidic device
US8278071B2 (en) 1997-04-17 2012-10-02 Applied Biosystems, Llc Method for detecting the presence of a single target nucleic acid in a sample
US8257925B2 (en) 1997-04-17 2012-09-04 Applied Biosystems, Llc Method for detecting the presence of a single target nucleic acid in a sample
US8067159B2 (en) 1997-04-17 2011-11-29 Applied Biosystems, Llc Methods of detecting amplified product
US9506105B2 (en) 1997-04-17 2016-11-29 Applied Biosystems, Llc Device and method for amplifying target nucleic acid
US7972778B2 (en) 1997-04-17 2011-07-05 Applied Biosystems, Llc Method for detecting the presence of a single target nucleic acid in a sample
FR2765590A1 (fr) * 1997-07-01 1999-01-08 Pasteur Institut Methode de semi-quantification d'alleles
WO1999001575A1 (fr) * 1997-07-01 1999-01-14 Institut Pasteur De Lille Methode de semi-quantification d'alleles
WO2000000638A2 (fr) * 1998-06-26 2000-01-06 Akzo Nobel N.V. Marquage d'amplicons d'arn produits au moyen d'une amplification fondee sur la transcription
WO2000000638A3 (fr) * 1998-06-26 2000-04-20 Akzo Nobel Nv Marquage d'amplicons d'arn produits au moyen d'une amplification fondee sur la transcription
EP1013776A1 (fr) * 1998-12-22 2000-06-28 Universiteit van Amsterdam Méthode sensible d'essai pour la détection ou pour la quantification d'acide nucléique de cytomégalovirus humain
WO2000037678A1 (fr) * 1998-12-22 2000-06-29 Universiteit Van Amsterdam Analyse sensible destinee a la detection ou la quantification d'un acide nucleique du cytomegalovirus humain
WO2000046401A1 (fr) * 1999-02-03 2000-08-10 Lgc (Teddington) Limited Materiau de reference pour amplification d'acide nucleique
US6908735B2 (en) 1999-07-23 2005-06-21 Gen-Probe Incorporated Polynucleotide quantitation method
AU781570B2 (en) * 1999-07-23 2005-06-02 Gen-Probe Incorporated Polynucleotide amplification method
WO2001007661A2 (fr) * 1999-07-23 2001-02-01 Gen-Probe Incorporated Methode d'amplification de polynucleotides
WO2001007661A3 (fr) * 1999-07-23 2002-07-11 Gen Probe Inc Methode d'amplification de polynucleotides
WO2001046463A3 (fr) * 1999-12-22 2002-06-27 Baxter Ag Methodes de preparation et d'utilisation d'etalons internes destines a des dosages par amplification de l'acide nucleique
WO2001046463A2 (fr) * 1999-12-22 2001-06-28 Baxter Aktiengesellschaft Methodes de preparation et d'utilisation d'etalons internes destines a des dosages par amplification de l'acide nucleique
EP1319716A1 (fr) * 2000-09-22 2003-06-18 Hitachi, Ltd. Procede d'analyse d'acide nucleique
US7790368B1 (en) 2000-09-22 2010-09-07 Hitachi, Ltd. Method for analyzing nucleic acid
EP1319716A4 (fr) * 2000-09-22 2005-01-12 Hitachi Ltd Procede d'analyse d'acide nucleique
EP1352091A4 (fr) * 2000-12-22 2004-07-21 Cepheid Compositions et procedes permettant la surveillance interne totale de la reaction par amplification
EP1352091A2 (fr) * 2000-12-22 2003-10-15 Cepheid Compositions et procedes permettant la surveillance interne totale de la reaction par amplification
US8889405B2 (en) 2009-09-16 2014-11-18 Seiko Epson Corporation Biochip and target DNA quantitative method
US9388467B2 (en) 2009-09-16 2016-07-12 Seiko Epson Corporation Biochip and target DNA quantitative method
US9416418B2 (en) 2009-09-16 2016-08-16 Seiko Epson Corporation Biochip and target DNA quantitative method
WO2012114312A3 (fr) * 2011-02-25 2012-11-01 Novartis Ag Témoin positif interne exogène
US9580761B2 (en) 2011-02-25 2017-02-28 Novartis Ag Exogenous internal positive control

Also Published As

Publication number Publication date
AU668659B2 (en) 1996-05-09
JPH08501222A (ja) 1996-02-13
DK0662156T3 (da) 1999-10-25
FI951082A (fi) 1995-03-08
CA2143857A1 (fr) 1995-01-19
CA2143857C (fr) 2005-09-20
KR100312800B1 (ko) 2002-02-28
FI112094B (fi) 2003-10-31
FI951082A0 (fi) 1995-03-08
JP3594598B2 (ja) 2004-12-02
ES2131699T3 (es) 1999-08-01
AU7492894A (en) 1995-02-06
DE69417863T2 (de) 1999-10-07
ATE178946T1 (de) 1999-04-15
DE69417863D1 (de) 1999-05-20

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