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WO1989004967A1 - Procede et appareil d'analyse chimique - Google Patents

Procede et appareil d'analyse chimique Download PDF

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Publication number
WO1989004967A1
WO1989004967A1 PCT/DK1988/000191 DK8800191W WO8904967A1 WO 1989004967 A1 WO1989004967 A1 WO 1989004967A1 DK 8800191 W DK8800191 W DK 8800191W WO 8904967 A1 WO8904967 A1 WO 8904967A1
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WO
WIPO (PCT)
Prior art keywords
analyte
fluid
concentration
sample
urea
Prior art date
Application number
PCT/DK1988/000191
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English (en)
Inventor
Bo Arne Petersson
Original Assignee
Radiometer A/S
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 Radiometer A/S filed Critical Radiometer A/S
Publication of WO1989004967A1 publication Critical patent/WO1989004967A1/fr

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Classifications

    • 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
    • C12Q1/001—Enzyme electrodes
    • C12Q1/005—Enzyme electrodes involving specific analytes or enzymes
    • C12Q1/006—Enzyme electrodes involving specific analytes or enzymes for glucose
    • 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
    • C12Q1/001—Enzyme electrodes
    • C12Q1/005—Enzyme electrodes involving specific analytes or enzymes
    • 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
    • C12Q1/58—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving urea or urease

Definitions

  • the methods according to the invention has the features of claim 1 or claim 2 or claim 3.
  • the preferred embodiments have the features of claims 4-9.
  • the analyte sensor may be an electrochemical sensor, an optical sensor or any other suitable sensor means.
  • the fluid element is stationary and is held by any suitable support means, such as a porous or fibrous member in the shape of a film, a sheet, a block, a cylinder or any other suitable shape, e.g. a ceramic pin or a thread, a hydrophilic or porous membrane, a gelled structure etc..
  • a suitable support means such as a porous or fibrous member in the shape of a film, a sheet, a block, a cylinder or any other suitable shape, e.g. a ceramic pin or a thread, a hydrophilic or porous membrane, a gelled structure etc.
  • the chemical composition of the fluid element may be maintained by conditioning the fluid element with the carrier fluid prior to the contact with each individual sample.
  • the fluid element is preferably an aqueous composition.
  • the analyzer according to the present invention has the features of claim 10 and the preferred embodiments have the features of claims 11-13.
  • the analyzer according to the invention is an analyzer with a sample inlet, a sample conduit, a sensor means arranged proximate to a test location of the sample conduit and a sample outlet and further with support means for the fluid element arranged between the actual fluid sample under test and the sensor means.
  • the sample may be fed to the analyzer in any conventional manner, e.g. by injection or aspiration.
  • the sample is transported through the analyzer by $ means of a flowing carrier fluid.
  • the carrier fluid may constitute the conditioning medium of controlled chemical composition.
  • There may be direct contact between the sample and the carrier fluid or there may be a plug of an immiscible fluid such as a plug of oil or of gas separating sample and carrier fluid.
  • the analyzer may be of the conventional flow injection analyzer type.
  • the analyzer will be able to handle in series more than 30 samples per hour.
  • Fig. 1(b) shows an exploded view of a gas diffusion/detection unit shown in Fig. 1(a).
  • Fig. 2 shows a calibration graph for urea?
  • Fig. 3 shows a FIA manifold for the detection of wea using an ion-selective electrode
  • Fig. 4 shows a FIA manifold for the detection of glucose or lactate
  • a miniaturized flow injection system for the assay of urea in undiluted whole blood is described. Based on the optical determination of o ammonia, the system incorporates a flow cell combining gas diffusion and optosensing, the separating barrier betweeen the donor and accepting streams consisting of a sandwich of a hydrophilic membrane between which is contained a s gel of covalently immobilized urease.
  • the sample urea content is quantified by the colour change of an acid-base indicator contained within the acceptor stream. Within the physiological range the measurement is not affected by variations in 0 the pH value, the buffering capacity or the
  • Urea is the final product of human protein metabolism. Determination of blood urea makes it posible to trace and follow changes in protein ° and amino acid composition, and the concentration of urea in blood is an important index of renal, function. In clinical chemistry blood urea is traditionally asayed in the serum or plasma fraction, yet the ultimate goal is to perform the measurement in the original sample matrix since this requires a minimum of manipulations, and hence a shorter time to obtain the analytical result, such an apparoach furthermore facilitates the possibility of continuous monitoring. Besides, the importance to confine manual handling of blood samples has been emphasised in recent years due to increased occurrence of contagious diseases.
  • Urea is frequently determined by the indophenol colorimetric method (5), yet most of the work reported in the literature has been devoted to development and use of enzyme electrodes.
  • the nonactin/monactin electrode (2) provides poor o selectivity for ammonium ions over potassium, but the interference can be compensated for by introducing a second ammonium selective electrode for NH- and K background detection (4).
  • Sensing of the pH changes generated in a 5 urease-gel, wrapped around a pH electrode, is another approach (6-8). This type of ammonia sensor yields excellent selectivity for ammonia over ions in the solution (9), yet besides being pH sensitive its response is rather slow.
  • a o hybride urea sensor consisting of an immobilized layer of nitrifying bacteria with ultimate detection of oxygen with an oxygen electrode has been reported (10).
  • An ammonia sensitive In/Pd MOS capacitor (11-13) has been suggested as an s alternative to the ammonia gas electrode with the added advantage of being inexpensive.
  • the gas diffusion/detection unit (Fig. lb) was constructed of black PVC.
  • the unit comprises two separate parts (A and B) between which, when assembled by four screws, the membrane sandwich is contained.
  • part A Into part A is milled a 1 x 1 x 20 mm groove communicating with two perpendicularly drilled holes (0,5 mm ID) serving as in- (I) and outlets (0) for the acceptor stream.
  • part B embodies a 1 x 1 x 10 mm groove served by in- and outlets for the donor stream.
  • the membrane sandwich consists of a gas permeable membrane (G) ⁇ Celgard 2500, hydrophobic polypropylene polymer, thickness 25 ⁇ m, pore size 0.004 ⁇ i , Celanese, Belgium), and an enzyme membrane (M) (see below).
  • G gas permeable membrane
  • M enzyme membrane
  • the optical measurement of the colour of the acid-base indicator is effected by reflectance, the nontransparent white gas permeable membrane serving as a reflecting opaque background, which, in order to further improve the reflected signal, is supplemented by the incorporaration of a thin foil of gold (GF) placed opposite the optical fibre.
  • GF thin foil of gold
  • the signal from the optical fibre photometer was sent to a recorder (Radiometer Servograph REC 61, furnished with a REA-112 high-sensitivity interface), the peak height at peak maximum serving as the analytical readout.
  • aqueous urea standards in the range 1-35.0 mM used for calibrating the system were prepared by o appropriate dilutions with 0.01 M phosphate buffer of pH 7.2 of a 35.0 mM stock solution made by dissolving 2.102 g of urea (Riedel-de Haen) in 1 1 of 0.01 M phosphate buffer of pH 7.2.
  • Immobilized Enzyme Membranes 40 mg of urease from "jack beans” (E.C. 3.5.1.5, Sigma, 70 U/mg) and 30 mg of bovine serum o albumine were completely dissolved in 0.3 ml of phosphate buffer (10 mM, pH 7.2) and 20 11 of glutaraldehyde (25% aqueous solution) was added.
  • a controlled dispersion of the sample zone while it is passing through the system towards the s detector is essential in Flow Injection
  • the sensing process in fact, occurs in two steps: In the first step, where the injected sample is in contact with the enzyme layer, the degradation of urea to ammonium takes place.
  • the first step where the injected sample is in contact with the enzyme layer, the degradation of urea to ammonium takes place.
  • the amount of ammonia ultimately diffusing into the acceptor stream of the system in Fig. 1 is of such magnitude that 5 the ensuing absorbance change registered by the optical system is sufficient to obtain a reliable signal.
  • additional signal enhancement may be o obtained by operating the donor stream and especially the acceptor stream in a stopped-flow mode (14) .
  • Assay of Standards, Plasma and Whole Blood Samples For actual urea assays the FIA manifold depicted in Fig. la was used. A typical calibration graph obtained with a series of aqueous urea standards is shown in Fig. 2.
  • the dynamic measuring range is 0-35 mM urea with a linear range from 0 to 6 mM urea (the normal physiological range).
  • the curvature of the calibration plot might be due to several factors. In order to obtain a linear relationship between the urea concentration and the recorded absorbance signal the following two conditions must be fulfilled:
  • the activity of the membrane sandwich remained constant during at least one week of continuous daily operation, upon which some deterioration in the measured signal appeared.
  • Urea in whole blood, enzymatically degraded by immobilized urease followed by colorimetric detection of the ammonia generated can be 5 determined in a FIA system provided that the dispersion coefficient of the injected sample at the point of quantification is as close to unity as possible. With this condition fulfilled, the analytical readout is independent of any ° variations in the pH, the buffering capacity and the hematocrit level of individual samples.
  • ABSTRACT 5 A flow injection system for the assay of urea in undiluted whole blood is described. Quantification of urea is achieved by means of an ammonium ion-selective electrode furnished with a membrane incorporating immobilized urease o measuring the enzymatically generated ammonium which is directly related to the concentration of the urea. The interference from potassium is reduced by adjusting the potassium concentration in the carrier stream and in the aqueous s calibration solutions to 4.0 mM. However, a complete elimination of this interference is achieved by measuring the actual potassium concentration in the respective sample using an external instrument, thus mathematically 0 correcting for the additional contribution to the signal due to the presence of K .
  • the linear measuring range is 1-40 mM urea with a sample frequency of 40 h ⁇ and a standard deviation of 1% for whole blood samples.
  • the result of the 5 measurement is obtained within 25 sec. from the time of injection. Variations in the hematocrit level of the sample has no effect on the measurement.
  • the method is in excellent agreement with the one used routinely at a local 0 County Hospital.
  • the sensor is stable for more than 30 days.
  • Enzyme sensors or electrodes as they are conventionably called, consists of an electrode covered with a membrane layer containing one or possibly more enzymes. This type of electrodes have proved to be useful in biochemical analysis and have been developed for a variety of substrates. The enzyme catalyses the reaction of the substrate to be measured by generating or o consuming species for which the inner sensor is selective. In most cases, covalently immobilized rather than physically entrapped enzymes are preferred, because covalent immobilization techniques generally offers increased stability 5 of the enzyme activity. Enzyme electrodes have the advantage of being simple, reliable, essentially reagentless and sensitive, besides being highly selective due to the inherent selectivety of the enzymes.
  • nonactin/monactin electrode used provides poor selectivity for.ammonium ions over potassium.
  • An urea electrode of similar composition was used by Yasuda et.al. (2) in conjunction with a FIA system, where the interference from potassium was compensated for by using an additional ammonium ion-selective electrode (without enzyme) for K detection. This system proved to be s linear in the range 3.6-107 mM urea. However, attempts to determine urea in whole blood was impeded due to influence by the hematocrit level of the sample.
  • the FIA manifold therefore should, for pratical assays, 5 be operated at a D-value as close as possible to 1, that is, the distance between the injection port and the detection position should be minimized (3, 4).
  • E standard electrode potential 0 (temperature dependent)
  • R is the gas constant
  • T is the absolute temperature (K)
  • F is the Faraday constant
  • ax is the ion activity - ⁇ .
  • y J x denotes the activity - ⁇ coefficient which is governed by the total ionic strength, I, of the sample.
  • the ionic strength is defined as:
  • c. concentration of each ionic species present in the sample and z. is the charge of each ionic species present in the sample.
  • the activity coefficient can, up to an ionic
  • a and B are general constants assuming a value of 0.5115 and 0.3291 respectively at 25 C and a is the specific ion size parameter.
  • Kxi. values When.Kxi. values are known, it is p e ossible to compensate for interferences by making appropriate calculations. However, it must be remembered that the K value is not a constant. It varies to some degree with the concentration level of the primary ion (analyte) and of the interfering species, sample composition, time and temperature.
  • K 1. from electrode to electrode was evaluated with and without the incorporation of an enzyme membrane using 5 different electrodes (ASE.-ASAg).
  • the K. value was only determined in the range 1-10 M urea and 1-10 mM ammonium. At higher concentration levels the interference from potasiu is of less importance. As expected, the "naked" ASE can be made very reproducible (cf. Table 2) owing to the uniformity of the PVC ion-selective membranes. TABLE 2 Determination of K. as a function of the
  • Kx indicates the K value at an urea concentration of x mM
  • a typical calibration graph is obtained with a series of aqueous urea standards. At urea 5 concentrations higher than 40 mM the calibration graph is no longer lineari The curvature of the calibration plot at concentrations above 40 M urea might be due to several factors.
  • the following three conditions must be fulfilled: (a) The kinetics of the urease enzyme has to follow that of pseudo-first order reaction conditions, i.e. the amount of urease must be in excess and CureaD « K-, s (Michaelis-Menten constant).
  • the coefficient of variation for 10 measurements l o of a blood sample was 1.06%.
  • the correlation coefficient is 0.999. up to - 15% can occur. Even though the actual determinations of the potassium have been made in a static system, there is no reason, whatsoever, that a FIA system similar to that used for the derermination of urea, should not be used in conjunction with a potassium ion-selective electrode, thus making a parallel determination of these two analytes.
  • a computer controlled flow ' injection system for the assay of D-glucose and L-lactic acid in undiluted plasma is described. Quantification of glucose/lactate is achieved by coupling of an immobilized glucose oxidase/lactate oxidase enzyme membrane with an amperometric electrode, thus measuring the enzymatically generated hydrogen peroxide, which is directly related to the concentration of glucose/lactate.
  • the amperometric electrodee consists of a platinum anode, to which a potential of +600 mV is applied, and a Ag/AgCl cathode. The diameter of the exposed electrode surface is 2.5 mm. The linear range is 0-40 mM and 0-10 mM for glucose and lactic acid respectively.
  • the sample ffrreeqquueennccyy i iss 66C0 h with a standard deviation of less than 1.5%.
  • Analysis of blood glucose are used to detect hyper- and hypo-glycaemia, both of which can result from a variety of different disorders, many of them of endocrine origin.
  • hyperglycaemia is diabetes mellitus, and elderly patients may present in hyperosmolar non-ketotic coma with blood glucose levels as high as 60 mmol/L.
  • serial blood glucose levels are required to monitor diabetes on treatment, and to detect and ultimately to prevent gestational hyperglycaemia which although not necessarily harmful to the mother, may be damaging to the foetus (1) .
  • the arterial lactate concentration is now recognized as a very good indicator of severity and prognosis (2, 3).
  • the increases in blood lactate are due to a critical reduction in oxygen delivery such that aerobic metabolism through the Krebs cycle cannot be sustained.
  • the severity of the defect in oxygen delivery is proportional to the increase in lactate generated through the emergency pathway of glucose metabolism from pyruvate.
  • Samples (25 ⁇ l ) were injected into the single line FIA system depicted in Fig. 4 by means of a 5 rotary valve operated by a step motor.
  • the distance between,the injection port and the 10 JJ.1 flow cell (FC) was made as short as possible in order to ensure minimum dispersion of the sample zone.
  • a special designed electrode comprising a central 0.4 mm diameter platinum working electrode with an outer 2.5 mm-diameter silver ring as the reference electrode was polarized at + 600 mV and used for hydrogen peroxide detection.
  • the electrode system was connected to a home-built potentiostat and the current intensity as a function of time was recorded by a BBC computer from Acorn DFS utilizing the built-in analogue to digital facility.
  • the carrier stream 0 was propelled by means of a Radiometer A/S ABU80 syringe pump (PI) at 1.0 ml/min.
  • PI Radiometer A/S ABU80 syringe pump
  • the BBC computer facilitated the data aquisition and the operation of the sampling pump, the syringe pump and the injection valve.
  • the isotonic phosphate buffer used as carrier stream was prepared by dissolving 1.12 g of NaEDTA, 1.84 g NaBenzoate, 3.04 g NaH 2 P0 4 , 13.80 g Na 2 HP0 4 and 5.44 g NaCl in 2 1 of distilled water.
  • Aqueous glucose and lactate standards were prepared from stock solutions containing 100 mM glucose and 100 mM lactate respectively.
  • high rejective glucose or high rejective lactate membranes (3.0 mm diameter) purchased from Yellow Springs Instrument Co. was placed on the electrode tip and fixed with an outer polycarbonate membrane (Nucleopore, 5 ⁇ m thick, 0.08 urn pore size) held with an o-ring.
  • control of the sampling and syringe pump 5) presentation of data i.e. the concentration in mM, the time of peak maximum and the sample no.
  • Eqn. (11) is not valid for enzyme systems which require additional cosubstrate(s) or coenzyme(s). Nevertheless eqn. (11) has proved 5 to be a very useful approximation as long as the cosubstrate(s) or coenzyme(s) are in excess. In order to obtain a linear relationship between the glucose or the lactate concentration and the recorded signal the two following conditions must be fulfilled:
  • a typical calibration run is obtained with a series of aqueous glucose standards. It is worth while to notice that the result of the analysis is completed within 5 sec. from the time of injection.
  • the linear range is 0-40 mM glucose with a sample frequency of 60 h " and a standard deviation of less than 1.5%.
  • a potential of 600-650 mV is chosen because the current is not affected by small changes of the potential in this range.
  • a potential of +300 V can be used in conjunction with a three electrode system.
  • the high rejective glucose oxidase membrane was then replaced with a high rejection lactate oxidase membrane, and a series of 11 blood plasma samples, supplied by the Copenhagen County 5 Hospital in Herlev (CCHH), were assayed in order to compare the FIA method with the YSI lactate analyzer.
  • a FIA system has been applied for detection of glucose and lactate in plasma using an amperometric electrode with detection of enzymatically generated hydrogen peroxide.
  • the analysis is completed within 5 sec. and there is no interference from other species.
  • the linear range is 0-40 mM glucose and 0-10 mM lactate with aa ssaammppllee ffrreeqquueennccyy ooff 6600 hh ⁇ and a standard deviation of less than 1.5%.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
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  • Physics & Mathematics (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
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  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Emergency Medicine (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

Le procédé et l'appareil décrit servent à l'analyse chimique d'échantillons à matrice variable. Les échantillons sont transportés en série par un fluide porteur. En un point au moins est amené un élément fluide dont la composition chimique est maintenue sensiblement constante à la suite de l'exposition de l'élément fluide au fluide porteur avant et après l'exposition de l'élément fluide à chaque échantillon.
PCT/DK1988/000191 1987-11-27 1988-11-24 Procede et appareil d'analyse chimique WO1989004967A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DK6225/87 1987-11-27
DK622587A DK622587D0 (da) 1987-11-27 1987-11-27 Fremgangsmaade og apparat til kemisk analyse

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WO1989004967A1 true WO1989004967A1 (fr) 1989-06-01

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0670491A2 (fr) * 1994-03-02 1995-09-06 Centro De Estudios E Investigacion Del Agua Procédé et dispositif pour mesurer la concentration d'ammonium total dans un milieu liquide

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0120202A2 (fr) * 1983-01-21 1984-10-03 Hitachi, Ltd. Senseur électrochimique capable de déterminer la concentration en péroxyde d'hydrogène et analyseur équipé de ce senseur

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0120202A2 (fr) * 1983-01-21 1984-10-03 Hitachi, Ltd. Senseur électrochimique capable de déterminer la concentration en péroxyde d'hydrogène et analyseur équipé de ce senseur

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
Analyst, Vol. 109, January 1984, K. YASUDA et al: "Determination of Urea in Whole Blood using a Urea Electrode with an Immobilised Urease Membrane", pages 61-64, see the whole document *
Analytical Chemistry, Vol. 58, No. 6, May 1986, B. OLSSON et al: "Theory and Application of Diffusion - Limited Amperometric Enzyme Electrod Detection in Flow Injection Analysis of Glucose", pages 1046-1052, see especially results and discussion. *
CHEMICAL ABSTRACTS, Vol. 106, No. 5, 2 February 1987, F. SCHELLER et al: "Flow Injection analysis of Lactate and Lactatedehydrogenas using an Enzym Membrane in Conjunction with a Modified Electrode", Abstract Number 29536X & Anal. Lett., 1986, Vol. 19 (15-16), pages 1691-703, Abstract. *
Dialog Informational Services, File 305, Analytical Abstracts, Acces. No. 47-08-D-00105, F. WINQVIST et al: "Determination of Urea with an Ammonia-Gas-Sensitive Semiconductor Device in Combination with Urease" & Anal. Chem. Acta, Vol. 163, pages 143-149, September 1984, Abstract. *
Dialog Informational Services, File 305, Analytical Abstracts, Acces. No. 50-08-D-00172, B. PETERSSON et al: "Determination of Urea in Undiluted Blood Samples by Flow Injection Analysis using Optosensing" & Anal. Lett., Vol. 20 (12), December 1987, pages 1977-1994, Abstract *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0670491A2 (fr) * 1994-03-02 1995-09-06 Centro De Estudios E Investigacion Del Agua Procédé et dispositif pour mesurer la concentration d'ammonium total dans un milieu liquide
EP0670491A3 (fr) * 1994-03-02 1996-05-15 Estudios E Invest Del Agua Procédé et dispositif pour mesurer la concentration d'ammonium total dans un milieu liquide.

Also Published As

Publication number Publication date
EP0389545A1 (fr) 1990-10-03
DK622587D0 (da) 1987-11-27

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