WO2000005580A2 - Methode de determination du report d'un analyte - Google Patents

Methode de determination du report d'un analyte Download PDF

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Publication number
WO2000005580A2
WO2000005580A2 PCT/EP1999/005332 EP9905332W WO0005580A2 WO 2000005580 A2 WO2000005580 A2 WO 2000005580A2 EP 9905332 W EP9905332 W EP 9905332W WO 0005580 A2 WO0005580 A2 WO 0005580A2
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WIPO (PCT)
Prior art keywords
analyte
over
carry
model
assay
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Application number
PCT/EP1999/005332
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English (en)
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WO2000005580A8 (fr
WO2000005580A3 (fr
Inventor
Thomas Augustinus Maria Beumer
Wilhelmus Marinus Carpay
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Akzo Nobel NV
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Akzo Nobel NV
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Priority to AU52876/99A priority Critical patent/AU5287699A/en
Publication of WO2000005580A2 publication Critical patent/WO2000005580A2/fr
Publication of WO2000005580A3 publication Critical patent/WO2000005580A3/fr
Anticipated expiration legal-status Critical
Publication of WO2000005580A8 publication Critical patent/WO2000005580A8/fr
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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
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material

Definitions

  • Immuno assays like Enzyme Linked Sorbent Assays (ELISA) generally make use of a highly specific, immobilized capture molecules to concentrate the analyte(-s) of interest onto a solid phase. Due to the high affinity of the chemical compounds it is possible to detect, even quantify, very low concentrations of particular biomolecules in a complex environment like serum or plasma. If the compound of interest is present in the sample (this sample is to cause a so called positive test result), the concentration variation that naturally occurs is large.
  • ELISA Enzyme Linked Sorbent Assays
  • Typical examples are the pregancy hormone hCG that is known to occur in ranges from less than lU/1 up to more than 100,000U/1, and the Hepatitis-B antigen (HBsAg) that is found from less then 0.01 up to much more than 100,000U/ml.
  • hCG pregancy hormone
  • HBsAg Hepatitis-B antigen
  • any suspectedly reactive sample causes a sequence of costly actions, varying from re-testing the non-reactive sample with even more refined and expensive test systems up to complete disposal of the precious donated material. This is all done to rigidly reduce any risk of transferring diseases like Hepatitis- B or HIV into people who need transfusion of blood components.
  • Typical contact based carry-over fractions in sample distribution and 'washing' equipment range from 100 down to 0.1 ppm. With the above examples of occuring concentration ranges it is easy to see that samples of the highest reactivity undoubtedly cause a positive reaction in the next sample, even if that is known to be negative. This amount of transferred reactive material depends on the intrinsic design of the instrument (materials, geometry) and is to some extent subject to its use (between-run washing procedures).
  • the present invention relates to a method of determining the carry-over of an analyte in an assay comprising consecutive transfer of analyte-comprising samples by the same transferring means.
  • Such a method is generally known in the art and comprises the steps of
  • [A] ⁇ m the concentration of analyte measured in the first container
  • [ A] 2m the concentration of analyte measured in the second container
  • [A] 2l the theoretical concentration of analyte in the second container, i.e. the concentration of analyte expected without carry-over.
  • the second liquid solution usually does not contain any analyte, [A] 2t , is usually zero.
  • the determination of the concentration analyte ([A]) may be direct or indirect. In the latter case a relative concentration is determined, as will usually be the case when the analyte is an enzyme, and the amount of substrate converted (or product formed) is a measure of the enzyme concentration.
  • Absolute concentrations may be determined by preparing a dilution series of the analyte at a known concentration, which dilution series serves as a calibration curve for the determination of the absolute concentration.
  • the carry-over depends on the particular assay performed, including the assay protocol and the characteristics of the type of apparatus used for transferring samples. Therefore the carry-over is determined, in practice, by using a strongly positive sample tested earlier, which is rather undefined. If this strongly positive sample does not comprise analyte in the maximum concentration that a sample may comprise, the carryover may erroneously be assumed to be satisfactorily low. Thus, accurate determination of the carry-over is impeded, not in the least because assays are often optimized for maximum sensitivity and, as an adverse consequence, show a poor linearity between a signal generated and the analyte concentration.
  • a further disadvantage is that the determination of the carry-over is costly due to the use of expensive assay reagents and rather time consuming, taking an hour or more, for each different assay or assay protocol, that is.
  • the object of the present invention is to overcome the above disadvantages.
  • C 3 the ratio between the temperature of the second rinse solution used between transfers of the model analyte and the temperature of the first rinse solution used in the assay;
  • model analyte which may be very cheap, it is possible to establish a model carry-over which is characteristic for many of the parameters determining the carry-over for a particular assay.
  • This model carry-over is corrected for the particular assay to be performed, most conveniently using data, that is correction factor C or at least one member thereof, supplied by the manufacturer of the assay.
  • the model carry-over can be determined very quickly, typically within 5 to 30 minutes.
  • Each of the members determining the correction factor C may be determined empirically or theoretically, and separately or as a combination of one or more other factors. For example, if the rinsing duration between different samples in the assay differs from that when establishing the model carry-over, the member C5 may account for this difference, but the consequence of this different duration may be established by a manufacturer of an assay for a particular analyte together with other differences such as those determined by one or more of the members Ci to C 4 , without any need to deter- mine each member separately.
  • C 5 may be used to correct for, for example, a different inner diameter of a needle of an apparatus used to transfer solutions, time during which is rinsed and any other factor affecting the carry-over.
  • an enzyme-comprising analyte is used as the model analyte.
  • model carry-over may be determined using other methods, such as those employing a radioactive, fluorescent or chemiluminescent analyte, for example fluorescein-labelled bovine serum albumin, an enzyme-comprising analyte offers the advantageous possibility of enhanced sensitivity due to the enzymatic activity of the label If hazardous labels are used, such as radioactive labels, determination of the carry-over increases the amount of radioactive waste to be disposed of
  • a radioactive, fluorescent or chemiluminescent analyte for example fluorescein-labelled bovine serum albumin
  • an enzyme-comprising analyte offers the advantageous possibility of enhanced sensitivity due to the enzymatic activity of the label If hazardous labels are used, such as radioactive labels, determination of the carry-over increases the amount of radioactive waste to be disposed of
  • the method according to the invention is characterized in that an adsorption preventing blocking agent is present at a concentration in excess of the model analyte.
  • an adsorption preventing blocking agent is present at a concentration in excess of the model analyte.
  • the blocking agent such as bovine serum albumin, casein or polyethylene glycol (PEG)
  • PEG polyethylene glycol
  • the preferred assay for which the carry-over is established is an immunoassay
  • the enzyme used for determining the carry-over is preferably the same as in the assay This eliminates the need to use different reagents for detecting the enzyme when determining the model carry- over
  • horseradish peroxidase is used as the enzyme label
  • the enzyme label may be a carrier-bound enzyme label, the carrier for example being bovine serum albumin
  • the model analyte is used at a concentration of at least e t , where nest — l*m Alo / r ac0 wherein
  • F m a multiplication factor of at least 10;
  • Aiow lowest concentration of model analyte detectable
  • Faco acceptable carry-over factor
  • the acceptable carry-over factor F ac0 depends on the particular assay, such as an immunoassay, to be performed.
  • the F aco can easily be established by calculating the ratio between a) the threshold concentration, i.e. - in case the analyte, for example a virus such as HIV, should not be present, the concentration of analyte at which a sample is considered positive, and
  • a carry-over is determined with an analyte-comprising standard solution provided with an assay kit is used, the standard solution with the highest concentration of analyte is used.
  • the assay usually is aimed at determining the presence of an analyte at a concentration just above the detection limit, the highest concentration in the standard solution provided with the assay kit is often considerably lower than the highest concentration of analyte that may be present in a sample.
  • a typical commercially available assay kit for hepatitis B comprises a standard solution of about 5 units antigen per ml, whereas a sample containing a high concentration of antigen may comprise 100,000 to 1 ,000,000 units per ml.
  • the molecular weight of the model- analyte is generally approximately equal to and or smaller than, for example, 0,7 times the molecular weight of the analyte, preferably 0,5 times or less and more preferably 0,3 times or less.
  • the invention also relates to a solution suitable for determination of a model carry-over, said solution comprising a model analyte chosen from the group of enzymes, fluorescent molecules, molecules comprising a fluorescent, radio-active, enzyme or chemiluminescent label, together with an effective concentration of an adsorption- preventing agent.
  • a solution suitable for determination of a model carry-over comprising a model analyte chosen from the group of enzymes, fluorescent molecules, molecules comprising a fluorescent, radio-active, enzyme or chemiluminescent label, together with an effective concentration of an adsorption- preventing agent.
  • a solution improves quality assurance procedures, allowing in addition people from different laboratories to more easily compare their results.
  • a person skilled in the art can easily determine the effective concentration for a particular adsorption- preventing agent, such as polyethylene glycol or a protein such as bovine serum albumin. As long as a higher concentration of the adsorption-preventing agent results in a larger signal, the effective concentration is not reached.
  • the invention relates to the use of a correction value specific for a particular assay for correcting a model carry-over value determined using a standardized method to obtain a carry-over value for the particular assay.
  • the particular assay is preferably an immunoassay.
  • a model analyte and a standardized method for determining the carry-over with that particular model analyte results in a model carry-over, which comprises particulars such as characteristics of an apparatus for dispensing sample and reagent solutions, as well as those regarding the model analyte.
  • a manufacturer of a particular assay can determine a correction factor, which can be used to correct the model carry-over resulting in the carry-over for that particular assay.
  • HRP horseradish peroxidase
  • NHS normal human serum
  • HSA human serum albumin

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Biochemistry (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La présente invention concerne une méthode de détermination du report d'un analyte dans un dosage comprenant le transfert consécutif d'échantillons contenant l'analyte par les mêmes moyens de transfert. Selon l'invention, un analyte modèle est utilisé pour déterminer un modèle de report, ledit modèle de report étant représentatif des nombreux paramètres déterminant le report d'un dosage particulier. Pour déterminer le report pour un dosage particulier, le modèle de report est corrigé avec un facteur de correction C fourni par le fabricant du dosage.
PCT/EP1999/005332 1998-07-24 1999-07-19 Methode de determination du report d'un analyte Ceased WO2000005580A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU52876/99A AU5287699A (en) 1998-07-24 1999-07-19 Method of determining the carry-over of an analyte

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP98202488.7 1998-07-24
EP98202488 1998-07-24

Publications (3)

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WO2000005580A2 true WO2000005580A2 (fr) 2000-02-03
WO2000005580A3 WO2000005580A3 (fr) 2000-08-24
WO2000005580A8 WO2000005580A8 (fr) 2001-02-08

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002049764A1 (fr) * 2000-12-21 2002-06-27 Dade Behring Marburg Gmbh Procede pour eviter la contamination de materiel d'echantillonnage negatif par des echantillons contenant des analytes, par utilisation de machines automatiques de pippetage

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59108942A (ja) * 1982-12-14 1984-06-23 Fuji Photo Film Co Ltd シ−ト状分析要素を用いる定量方法
FI901924A7 (fi) * 1988-08-30 1990-04-17 Cholestech Corp Itsekorjaava määrityslaitteisto ja -menetelmä
JPH05505108A (ja) * 1990-03-01 1993-08-05 バクスター、ダイアグノスティックス、インコーポレイテッド 反応副生成物を酵素アッセイのための校正試薬として使用する方法
EP0650044A3 (fr) * 1993-04-02 1996-06-19 Hitachi Chemical Co Ltd Méthode analytique de chémiluminescence.

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002049764A1 (fr) * 2000-12-21 2002-06-27 Dade Behring Marburg Gmbh Procede pour eviter la contamination de materiel d'echantillonnage negatif par des echantillons contenant des analytes, par utilisation de machines automatiques de pippetage
US7169613B2 (en) 2000-12-21 2007-01-30 Dade Behring Marburg Gmbh Method for avoiding the contamination of negative sampling material by samples containing analytes during the use of automatic pipette machines
US7534617B2 (en) 2000-12-21 2009-05-19 Siemens Healthcare Diagnostics Products Gmbh Methods for avoiding contamination of negative sample material with analyte-containing samples when using pipetting robots

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Publication number Publication date
AU5287699A (en) 2000-02-14
WO2000005580A8 (fr) 2001-02-08
WO2000005580A3 (fr) 2000-08-24

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