EP0161299A1 - Sensor for chemical analysis - Google Patents

Sensor for chemical analysis

Info

Publication number
EP0161299A1
EP0161299A1 EP19840904205 EP84904205A EP0161299A1 EP 0161299 A1 EP0161299 A1 EP 0161299A1 EP 19840904205 EP19840904205 EP 19840904205 EP 84904205 A EP84904205 A EP 84904205A EP 0161299 A1 EP0161299 A1 EP 0161299A1
Authority
EP
European Patent Office
Prior art keywords
membrane
electrode
liquid flow
sensor
analysis
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP19840904205
Other languages
German (de)
French (fr)
Inventor
Sven-Olof Enfors
Niel Fredrik Cleland
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of EP0161299A1 publication Critical patent/EP0161299A1/en
Withdrawn legal-status Critical Current

Links

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

Definitions

  • the present invention relates to a system in which a measuring chamber has been brought into connection with the sensitive surface of an analysis electrode.
  • the measuring chamber which together with the analysis electrode is submerged in the sample solution and is spaced from the latter by means of a membrane of a cer ⁇ tain permeability, is continuously flushed through by a liquid flow emanating from a specific outer reservoir.
  • a membrane of a cer ⁇ tain permeability is continuously flushed through by a liquid flow emanating from a specific outer reservoir.
  • the electrochemical analysis electrodes may be di- vided up into ion-selective and membrane electrodes, where the ion-selective ones measure a specific elect ⁇ rochemical reaction on their sensitive surface and the membrane electrodes have a gas-permeable membrane which only allows gas molecules to pass into the electrolyte solution.
  • the ion-selective electrode type are pH and NH.
  • -electrodes and examples of the membrane type are NH-. and O ⁇ -electrodes.
  • In practice problems may arise with these electrode types when measuring in samples of wholly or partly undefined contents. The problem may be illustrated with an example. In determin ⁇ ing NH.
  • a lon-selective NH. electrode cannot be used due to its sensitivity to K and other ions which are known to be present in the medium.
  • a membrane electrode for deter- mining the percentage of NH_. cannot either be used since at pH 7.0 almost all NH-, is present as NH. according to the equation
  • the present invention allows direct measuring of the NH. content in the sample by placing in connection with the gas-permeable membrane of a NH-. electrode a ion-permeable membrane and laying between these mem- branes a flow of a buffer solution which holds so high a pH that the desired part of the NH. ions diffusing into the measuring chamber are converted into NH, form.
  • This principle may be used in all systems of the type
  • HA H + A (g) where it is desired to change an environmental para ⁇ meter such as e.g. pH or buffer capacity from those prevailing in the sample but still perform a not sample- destroying analysis with a sensor placed in the sample.
  • the present invention may also be applied to other ⁇ es of chemical reactions, e.g. redox reactions.
  • An ⁇ other advantage is that, if it is desired to analyse percentages exceeding the measuring range of the elect- trode in question, it is possible by a suitable choice of flow rate of the external buffer to create a direct, continuous dilution of the analysis substance inside the membrane adjacent the sensor surface. Thus it is possible to obtain an optional measuring range in the instrument by adjustment of the liquid flow.
  • the system can be used solely to create a vari ⁇ able measuring range in a certain electrode.
  • other liquids and membranes than those mentioned above may be used in dependence upon the desired application.
  • One may, for instance, let a reagent be contained in a constant percentage in the liquid flow in order to react with the analysis substance and form a measurable product.
  • the principle for an electrochemical analysis electrode constructed according to the present inven ⁇ tion will appear from the following (see Fig. 1).
  • (1) is an electrochemical sensor over the sensi- tive surface of which a membrane (2) has been mounted so that a liquid flow (F) is allowed to pass the mea ⁇ suring chamber (3) thus formed, through tubes (4) adap ⁇ ted therefor.
  • An adjustable pump (5) drives the flow which comes from a specific reservoir (6).
  • the analysis substance diffuses from the sample through the membrane (2) into the measuring chamber (3) where, after dilution and possibly chemical conversion, the percentage is measured with the sensor (1) and the re- suit is obtained with the aid of the electronics (7).
  • Enzyme electrodes have been the object of great, interest during the last decade (ref). They consist (see Fig.
  • Electrode (2) in principle of an electrochemical sensor of membrane or ion-selective type (1) on the sensitive surface of which one has mounted one or more immobi ⁇ lized enzymes in the form of a membrane or on a carrier (2) and separated this from the sample solution by means of a semi-permeable membrane (3).
  • the electrode signals is recorded in the electronics (4).
  • the electrode (1) is chosen so that one of the reactants or products of the enzyme reaction will form analysis substance for the electrode.
  • An enzyme reaction follows the formula A + H 2 0 + 0 2 E Z > C + H 2 0 2 and the substance A is that which is of interest to determine.
  • a and C are complicated organic substances which cannot be measured directly electro ⁇ chemically.
  • 0- and H-0- being stoichiometri- cally related with A, can be measured with rescpect- ively a membrane and an ion-selected electrode. In this case therefore one of these electrodes are chosen as sensor ( (1) in Fig. 2).
  • Certain disadvantages are en ⁇ tailed with enzyme electrodes: sensitivity to environ ⁇ mental parameters such as e.g. pH, sensitivity to de- naturating substances, product inhibition due to in ⁇ creased product percentages inside the enzyme layer etc.
  • the present invention permits elimination of these disadvantages in that it makes it possible, by means of the flow system described above and an appropriate choice of liquid in the flow (F), to create optimum conditions for enzyme inside the measuring chamber even if the conditions in the sample are very unfavourable. Moreover, possibilities are provided, in the same way as described above, for simply varying the measuring range for the enzyme electrode.
  • the principle for an enzyme electrode built ac ⁇ cording to the present invention appears from the fol ⁇ lowing (see Fig. 3).
  • Fig. 3 A shows the build-up of the measuring chamber when the enzyme functions-as "active membrane", i.e. the analysis substance must diffuse -through a membrane with immobilized enzyme (1) while being transformed before it reaches the measuring chamber and the sensor ( (2) and (3) respectively).
  • Fig. 3 B shows the situation when the enzyme (4) is contained immobilized in the chamber (2) and the sample is .. spaced from the measuring chamber by means of a membrane (1).
  • the present invention may, in the same way as de ⁇ scribed above, also be applied to other electrode sys ⁇ tems with active and passive membranes, e.g. microbial electrodes and antigen-antibody- and carbohydrate-lec- tine electrodes etc.
  • active and passive membranes e.g. microbial electrodes and antigen-antibody- and carbohydrate-lec- tine electrodes etc.
  • a reagent accompany the liquid flow (F), which reagent takes part in the enzyme reaction while forming coloured or otherwise characteristic substances which then may be detected optically or in another way.
  • Fig. 4 shows the electrode flow I as a function of the glucose concentration when the present invention has been applied to a glucose-sen ⁇ sitive enzyme electrode in 4 different flows (F) .

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Genetics & Genomics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)

Abstract

Electrode d'analyse comportant un détecteur sur la surface sensible duquel a été appliqué un écoulement liquide variable dans lequel la substance à analyser diffuse à travers une membrane semi-perméable en liaison avec la surface de l'électrode. En modifiant la composition et la vitesse de l'écoulement liquide, on obtient d'une part la modification adéquate de la substance à analyser, par exemple la dissociation et d'autre part l'optimalisation de l'environnement chimique entourant la surface du détecteur, par exemple pour une réaction enzymatique. Il est en outre possible de faire varier la fourchette de mesure en modifiant la concentration de la substance à analyser par la modification de la vitesse de l'écoulement de liquide.Analysis electrode comprising a detector on the sensitive surface of which a variable liquid flow has been applied in which the substance to be analyzed diffuses through a semi-permeable membrane in connection with the surface of the electrode. By modifying the composition and the speed of the liquid flow, one obtains on the one hand the adequate modification of the substance to be analyzed, for example the dissociation and on the other hand the optimization of the chemical environment surrounding the surface of the detector , for example for an enzymatic reaction. It is also possible to vary the measurement range by modifying the concentration of the substance to be analyzed by modifying the speed of the liquid flow.

Description

SENSOR FOR CHEMICAL ANALYSIS
The present invention relates to a system in which a measuring chamber has been brought into connection with the sensitive surface of an analysis electrode. The measuring chamber, which together with the analysis electrode is submerged in the sample solution and is spaced from the latter by means of a membrane of a cer¬ tain permeability, is continuously flushed through by a liquid flow emanating from a specific outer reservoir. Among existing analysis electrodes those which are noticed in the first place today are the electrochemi¬ cal ones, the so-called enzyme electrodes and the mic- robial electrodes. Also so-called solid-state electrodes are coming into use.
The electrochemical analysis electrodes may be di- vided up into ion-selective and membrane electrodes, where the ion-selective ones measure a specific elect¬ rochemical reaction on their sensitive surface and the membrane electrodes have a gas-permeable membrane which only allows gas molecules to pass into the electrolyte solution. Examples of the ion-selective electrode type are pH and NH. -electrodes and examples of the membrane type are NH-. and O^-electrodes. In practice problems may arise with these electrode types when measuring in samples of wholly or partly undefined contents. The problem may be illustrated with an example. In determin¬ ing NH. in a sample from a fermentation (pH = 7.0) a lon-selective NH. electrode cannot be used due to its sensitivity to K and other ions which are known to be present in the medium. A membrane electrode for deter- mining the percentage of NH_. cannot either be used since at pH 7.0 almost all NH-, is present as NH. according to the equation
NH.+ ==* NH., + H+ fpΛK: = 9.3. The present invention allows direct measuring of the NH. content in the sample by placing in connection with the gas-permeable membrane of a NH-. electrode a ion-permeable membrane and laying between these mem- branes a flow of a buffer solution which holds so high a pH that the desired part of the NH. ions diffusing into the measuring chamber are converted into NH, form. This principle may be used in all systems of the type
HA+ -s≤ HA =*=* H+ + A~ and
HA H + A (g) where it is desired to change an environmental para¬ meter such as e.g. pH or buffer capacity from those prevailing in the sample but still perform a not sample- destroying analysis with a sensor placed in the sample. The present invention may also be applied to other ^ es of chemical reactions, e.g. redox reactions. An¬ other advantage is that, if it is desired to analyse percentages exceeding the measuring range of the elect- trode in question, it is possible by a suitable choice of flow rate of the external buffer to create a direct, continuous dilution of the analysis substance inside the membrane adjacent the sensor surface. Thus it is possible to obtain an optional measuring range in the instrument by adjustment of the liquid flow. In other words, the system can be used solely to create a vari¬ able measuring range in a certain electrode. Also other liquids and membranes than those mentioned above may be used in dependence upon the desired application. One may, for instance, let a reagent be contained in a constant percentage in the liquid flow in order to react with the analysis substance and form a measurable product. The principle for an electrochemical analysis electrode constructed according to the present inven¬ tion will appear from the following (see Fig. 1).
(1) is an electrochemical sensor over the sensi- tive surface of which a membrane (2) has been mounted so that a liquid flow (F) is allowed to pass the mea¬ suring chamber (3) thus formed, through tubes (4) adap¬ ted therefor. An adjustable pump (5) drives the flow which comes from a specific reservoir (6). When the analysis substance diffuses from the sample through the membrane (2) into the measuring chamber (3) where, after dilution and possibly chemical conversion, the percentage is measured with the sensor (1) and the re- suit is obtained with the aid of the electronics (7). Enzyme electrodes have been the object of great, interest during the last decade (ref). They consist (see Fig. 2) in principle of an electrochemical sensor of membrane or ion-selective type (1) on the sensitive surface of which one has mounted one or more immobi¬ lized enzymes in the form of a membrane or on a carrier (2) and separated this from the sample solution by means of a semi-permeable membrane (3). The electrode signals is recorded in the electronics (4). The electrode (1) is chosen so that one of the reactants or products of the enzyme reaction will form analysis substance for the electrode.
Ex. An enzyme reaction follows the formula A + H20 + 02 E Z > C + H202 and the substance A is that which is of interest to determine. However, A and C are complicated organic substances which cannot be measured directly electro¬ chemically. However, 0- and H-0-, being stoichiometri- cally related with A, can be measured with rescpect- ively a membrane and an ion-selected electrode. In this case therefore one of these electrodes are chosen as sensor ( (1) in Fig. 2). Certain disadvantages are en¬ tailed with enzyme electrodes: sensitivity to environ¬ mental parameters such as e.g. pH, sensitivity to de- naturating substances, product inhibition due to in¬ creased product percentages inside the enzyme layer etc. The present invention permits elimination of these disadvantages in that it makes it possible, by means of the flow system described above and an appropriate choice of liquid in the flow (F), to create optimum conditions for enzyme inside the measuring chamber even if the conditions in the sample are very unfavourable. Moreover, possibilities are provided, in the same way as described above, for simply varying the measuring range for the enzyme electrode. The principle for an enzyme electrode built ac¬ cording to the present invention appears from the fol¬ lowing (see Fig. 3). Fig. 3 A shows the build-up of the measuring chamber when the enzyme functions-as "active membrane", i.e. the analysis substance must diffuse -through a membrane with immobilized enzyme (1) while being transformed before it reaches the measuring chamber and the sensor ( (2) and (3) respectively). Fig. 3 B shows the situation when the enzyme (4) is contained immobilized in the chamber (2) and the sample is .. spaced from the measuring chamber by means of a membrane (1).
The present invention may, in the same way as de¬ scribed above, also be applied to other electrode sys¬ tems with active and passive membranes, e.g. microbial electrodes and antigen-antibody- and carbohydrate-lec- tine electrodes etc. One may let a reagent accompany the liquid flow (F), which reagent takes part in the enzyme reaction while forming coloured or otherwise characteristic substances which then may be detected optically or in another way. Fig. 4 shows the electrode flow I as a function of the glucose concentration when the present invention has been applied to a glucose-sen¬ sitive enzyme electrode in 4 different flows (F) .
Reference.
Guilbault, G.G.
Enz. Microb. Technol, 2, 258 (1980).
OAIP "

Claims

1. Analysis electrode including a sensor, c h a ¬ r a c t e r i z e d in that a variable liquid flow has been disposed in the vicinity of the sensitive sur¬ face thereof and that this liquid flow has been spaced from the sample solution by means of a membrane.
2. Analysis electrode according to claim 1, c h a r a c t e r i z e d in that said membrane is a semi-permeable or gas-permeable membrane.
3. Analysis electrode according to claim 1, c h a r a c t e r i z e d in that said membrane con¬ tains one or more of the following components: proteins, enzymes, other active substances, organelles or micro¬ organisms.
4. Analysis electrode according to claim 1, c h a r a c t e r i z e d in that said measuring cham¬ ber contains an immobilized preparation of one or more of the following components: proteins, enzymes, other active substances, organelles or micro-organisms.
EP19840904205 1983-11-03 1984-11-02 Sensor for chemical analysis Withdrawn EP0161299A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE8306050 1983-11-03
SE8306050A SE8306050D0 (en) 1983-11-03 1983-11-03 SENSOR OF CHEMICAL ANALYSIS

Publications (1)

Publication Number Publication Date
EP0161299A1 true EP0161299A1 (en) 1985-11-21

Family

ID=20353170

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19840904205 Withdrawn EP0161299A1 (en) 1983-11-03 1984-11-02 Sensor for chemical analysis

Country Status (4)

Country Link
EP (1) EP0161299A1 (en)
JP (1) JPS61500330A (en)
SE (1) SE8306050D0 (en)
WO (1) WO1985002017A1 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5278048A (en) * 1988-10-21 1994-01-11 Molecular Devices Corporation Methods for detecting the effect of cell affecting agents on living cells
WO1990004645A1 (en) * 1988-10-21 1990-05-03 Molecular Devices Corporation Methods and apparatus for detecting the effect of cell affecting agents on living cells
US5607565A (en) * 1995-03-27 1997-03-04 Coulter Corporation Apparatus for measuring analytes in a fluid sample
JP2002330752A (en) * 2001-05-08 2002-11-19 Sanden Corp Apparatus for counting number of microorganisms
GB201003720D0 (en) 2010-03-08 2010-04-21 Octens Bvba Ion-selective electrode

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE397731B (en) * 1975-03-27 1977-11-14 Servochem STERILIZABLE AND REGENERATABLE ENZYME ELECTRODE AND WAY TO PRODUCE THE SAME
DE2714379A1 (en) * 1977-03-31 1978-10-05 Eschweiler & Co Gas partial pressure sensor - uses electrode enclosed by hollow sleeve with pervious membrane across its end
US4490234A (en) * 1982-02-22 1984-12-25 Beckman Instruments, Inc. Method for measuring ionic concentration utilizing an ion-sensing electrode

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8502017A1 *

Also Published As

Publication number Publication date
WO1985002017A1 (en) 1985-05-09
SE8306050L (en) 1985-05-04
SE8306050D0 (en) 1983-11-03
JPS61500330A (en) 1986-02-27

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