WO1981000304A1 - A method and apparatus for indicating the presence of substances which,in a chemical reaction,generate or consume gas - Google Patents

A method and apparatus for indicating the presence of substances which,in a chemical reaction,generate or consume gas Download PDF

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Publication number
WO1981000304A1
WO1981000304A1 PCT/SE1980/000193 SE8000193W WO8100304A1 WO 1981000304 A1 WO1981000304 A1 WO 1981000304A1 SE 8000193 W SE8000193 W SE 8000193W WO 8100304 A1 WO8100304 A1 WO 8100304A1
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Prior art keywords
gas
detector
reaction
recited
detectable
Prior art date
Application number
PCT/SE1980/000193
Other languages
French (fr)
Inventor
I Lundstroem
B Danielsson
K Mosbach
L Stiblert
Original Assignee
I Lundstroem
B Danielsson
K Mosbach
L Stiblert
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Filing date
Publication date
Application filed by I Lundstroem, B Danielsson, K Mosbach, L Stiblert filed Critical I Lundstroem
Publication of WO1981000304A1 publication Critical patent/WO1981000304A1/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M21/00—Bioreactors or fermenters specially adapted for specific uses
    • C12M21/18—Apparatus specially designed for the use of free, immobilized or carrier-bound enzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/32—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of substances in solution
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/34—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas
    • 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
    • C12Q1/26—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
    • C12Q1/32—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase involving dehydrogenase
    • 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
    • C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • G01N2333/978—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • G01N2333/98—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in linear amides (3.5.1)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • G01N2333/978—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • G01N2333/986—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in cyclic amides (3.5.2), e.g. beta-lactamase (penicillinase, 3.5.2.6), creatinine amidohydrolase (creatininase, EC 3.5.2.10), N-methylhydantoinase (3.5.2.6)

Definitions

  • the present invention relates to a method and an apparatus for indicating the presence of substances which, in a chemical reaction, generate or consume detectable gas.
  • an ion-selective elec ⁇ trode in combination with a gas-permeable membrane can be used for measuring the amount of ammonia which is generated in certain enzymatic reactions. In this case, the electrode is kept in a buffer solution.
  • an apparatus having an ion-selective elec ⁇ trode placed above a thin air gap in a reaction vessel may be used. In these prior art cases, the concentra ⁇ tion of a certain ion is measured, and not the generated gas itself. These prior art methods are not particularly sensitive or rapid, and they restrict the number of gases or reactions which can be studied.
  • those substances whose presence is to be indicated are caused to react for the generation or consumption of detectable gas, whereafter the detectable gas, if such is present, is caused to pass a gas detector which is selectively responsive to the detectable gas.
  • This measurement method is not electrochemical, but is characterized in that the generated (or rest of the consumed) gas is detected by means of a catalytically active detector in the gas phase.
  • the present invention also relates to an apparatus for carrying out the novel method.
  • This apparatus comprises a reaction vessel and a gas detector disposed in conjunction therewith, the detector being sensitive to the detectable gas.
  • an enzyme is caused to act on a carrier for the enzyme, a gas, such as, for example, hydrogen, ammonia or hydrogen sulfide, bein generated.
  • a gas such as, for example, hydrogen, ammonia or hydrogen sulfide
  • This gas is then caused to pass a detector which is sensitive precisely to the gas in question.
  • Suitable gas detectors are so-called Pd-MOS-structures which are responsive to hydrogen-containing gases, but other gas detectors may also be used, such as for example a (warm) platinum thread, a semiconducting metal oxide (ZnO, Sn0 2 etc) , or an oscillating piezoelectric crystal.
  • H 2 9 2 can also be detected by means of the apparatus according to the present invention.
  • the method andapparatus according to the present invention may be applied to a semiconductor sensor based on silicon, the current strength of the sensor changing in the presence of, for example, ammonia
  • a carrier gas i.e. air
  • This is particularly favorable when the invention is used to indicate the consumption of a gas in a reaction. In such an instance, a minor amount of the gas which is being consumed is introduced into a carrier gas which, after the reaction, is caused to pass the detector which then determines the amount of remaining reacting gas in the carrier gas.
  • the gas detector may be disposed directly above the surface of a solution in which, for example, enzyme and carrier are allowed to react. The detector then responds to the gas which is released in the enzymatic reaction and is dissipated out into the air gap above the solution.
  • an immobilized enzyme is caused to react on a carrier in a through flow cell, in which the detector is disposed in an air gap above the liquid flow.
  • an immobilized enzyme may be disposed closely.adjacent the detector, for example by being chemically coupled to the detector.
  • the apparatus and the method according to the present invention may apart from in enzymatic reactions, also be used in reactions in which are included micro ⁇ organisms which generate or consume gases. Of particular interest in this context are microorganisms which develop hydrogen gas and methane gas.
  • microorganisms which develop hydrogen gas and methane gas.
  • FIG. 1-3 show three different embodiments of the apparatus according to the present invention, also called an enzyme transistor ?
  • Fig 4A and B schematically show illustrations of hydrogen-sensitive detectors
  • Fig 5 shows a calibrating diagram for ammonia obtained with a detector according to Fig 4
  • Fig 6 shows a curve of the response of the detector to a reaction in which urea is hydrolized by means of urease;
  • Fig 7 illustrates the hydrogen gas production from 5 Clostridium aceto butylicum as a function of time.
  • Fig 8 shows a standard curve for NADH
  • Fig 9 shows a standard curve for NAD .
  • Fig 1 illustrates an apparatus comprising a gas-sensitive detector disposed above the 10 surface of a solution in which an enzyme and a carrier- therefor are located.
  • the detector responds to the gas which is released in the enzymatic reaction and which is diffused out into the air gap above the solutio
  • Fig 2 shows an apparatus in which a carrier gas is 15 allowed to pass a solution with reactants, whereafter the carrier gas, entraining gas from the reaction, passes a gas detector.
  • This apparatus is also suitable for use when it is desirable to study a gas-consuming reaction, a minor amount of the gas which is to react 20 being introduced into the carrier gas. The amount of remaining gas in the carrier gas is thereafter measured by the gas detector.
  • Fig 3 illustrates a through-flow cell for reaction between an immobilized enzyme and a carrier in which 25 the detector is disposed above the liquid flow in some part of the cell.
  • OMPI -structure These hydrogen-sensitive Pd-MOS-structures have been described, int al, in Swedish patent specifi ⁇ cation 7411342-4.
  • Fig 4 schematically illustrates two embodiments of these structures.
  • hydrogen-containing gases H-, H 3 , H 2 S etc
  • Fig. 4B a shift of the current-voltage curve along the voltage axis.
  • This shift which may be of the order of magnitude of 0.5 V, may readily be measured.
  • This type of detector has a response, shown in Fig. 5, to ammonia, which has been generated by the reaction between NH.C1 and NaOH in an apparatus according to Fig. 1.
  • Fig 6 -structure in an apparatus according to Fig 1, is shown in Fig 6.
  • the slope of the curve (the broken line in Fig 6) may be used to determine the amount of urea which was present in the measurement cell. This slope is unambiguously determined by the urea concentration. Urea concentrations of as little as 0.1 mM may easily be determined in this manner.
  • the signal from a Pd-MOS-structure was compared with the signal from an enzyme transistor in which the Pd-MOS-structure was used as a gas sensor in an apparatus according to Fig 3.
  • the reaction which was studied was deimination of creatinine by means of immobilized creatininase.
  • the correlation between the signals from the enzyme transistor and the gas detector was very good.
  • Fig 8 illustrates a standard curve for NADH, in which 2.5 ml samples of varying concentrations were introduced into the buffer flow.
  • the tower contained immobilized hydrogen dehydrogenase of a volume of 1 ml.
  • the amount of generated hydrogen gas is expressed as ppm in the carrier gas.
  • Fig 9 illustrates a standard curve for NAD , in which 2.5 ml samples of varying concentrations were introduced into the buffer flow.
  • the tower contained immobilized hydrogen dehydrogenase of a volume of 1 ml.
  • the amount of hydrogen gas present in the buffer corres ⁇ ponds to 100 ppm in the carrier gas flow.

Abstract

Method of indicating the presence of a detectable gas in gas-generating or gas-consuming reactions, by the use of a hydrogen and ammonia sensitive, palladium coated semiconductor device (Pd-MOS-FET). The measurements are carried out in the gas phase in a gas detector which is disposed in association with the reaction vessel in which the reaction which is to be studied takes place. A particular study has been made of enzymatic reactions in which hydrogen and/or ammonia are generated by the action of the enzyme urease on urea and creatininase on creatinine.

Description

A METHOD AND APPARATUS FOR INDICATING THE PRESENCE OF SUBSTANCES WHICH, IN A CHEMICAL REACTION, GENERATE OR
CONSUME GAS
The present invention relates to a method and an apparatus for indicating the presence of substances which, in a chemical reaction, generate or consume detectable gas. It is known in this art that an ion-selective elec¬ trode in combination with a gas-permeable membrane can be used for measuring the amount of ammonia which is generated in certain enzymatic reactions. In this case, the electrode is kept in a buffer solution. It is also known that an apparatus having an ion-selective elec¬ trode placed above a thin air gap in a reaction vessel may be used. In these prior art cases, the concentra¬ tion of a certain ion is measured, and not the generated gas itself. These prior art methods are not particularly sensitive or rapid, and they restrict the number of gases or reactions which can be studied.
A new method and a new apparatus for indicating the presence of substances which, in a chemical reaction, generate or consume detectable gas have now been developed, these constituting the subject matter of the present invention.
In the method according to the present invention, those substances whose presence is to be indicated are caused to react for the generation or consumption of detectable gas, whereafter the detectable gas, if such is present, is caused to pass a gas detector which is selectively responsive to the detectable gas. This measurement method is not electrochemical, but is characterized in that the generated (or rest of the consumed) gas is detected by means of a catalytically active detector in the gas phase. As a result, a greater degree of flexibility will be attained as regards the number of gases (the number of reactions) which can be studied, and, in many cases,, a superior level of sensitivity and rapidity in relation to that which can be achieved using prior art methods.
The present invention also relates to an apparatus for carrying out the novel method. This apparatus comprises a reaction vessel and a gas detector disposed in conjunction therewith, the detector being sensitive to the detectable gas.
In a particularly preferred embodiment of the method according to the invention, an enzyme is caused to act on a carrier for the enzyme, a gas, such as, for example, hydrogen, ammonia or hydrogen sulfide, bein generated. This gas is then caused to pass a detector which is sensitive precisely to the gas in question. Suitable gas detectors are so-called Pd-MOS-structures which are responsive to hydrogen-containing gases, but other gas detectors may also be used, such as for example a (warm) platinum thread, a semiconducting metal oxide (ZnO, Sn02 etc) , or an oscillating piezoelectric crystal.
H292 can also be detected by means of the apparatus according to the present invention. Furthermore, the method andapparatus according to the present invention may be applied to a semiconductor sensor based on silicon, the current strength of the sensor changing in the presence of, for example, ammonia In certain cases, it may be advisable to have a carrier gas (i.e. air) flow through the reaction vessel. This is particularly favorable when the invention is used to indicate the consumption of a gas in a reaction. In such an instance, a minor amount of the gas which is being consumed is introduced into a carrier gas which, after the reaction, is caused to pass the detector which then determines the amount of remaining reacting gas in the carrier gas.
O P In certain cases, it may also be necessary to decompose the gas in question before it reaches the sensor element in the detector. Such a decomposition stage is considered as forming part of the concept of a gas detector.
The gas detector may be disposed directly above the surface of a solution in which, for example, enzyme and carrier are allowed to react. The detector then responds to the gas which is released in the enzymatic reaction and is dissipated out into the air gap above the solution.
In another embodiment of a present invention, an immobilized enzyme is caused to react on a carrier in a through flow cell, in which the detector is disposed in an air gap above the liquid flow.
Furthermore, an immobilized enzyme may be disposed closely.adjacent the detector, for example by being chemically coupled to the detector.
The apparatus and the method according to the present invention may apart from in enzymatic reactions, also be used in reactions in which are included micro¬ organisms which generate or consume gases. Of particular interest in this context are microorganisms which develop hydrogen gas and methane gas. The nature of the present invention in its aspect will be more readily understood from the following brief description of the accompanying drawings, and discussion relating thereto.
In the accompanying drawings: Figs. 1-3 show three different embodiments of the apparatus according to the present invention, also called an enzyme transistor?
. Fig 4A and B schematically show illustrations of hydrogen-sensitive detectors; Fig 5 shows a calibrating diagram for ammonia obtained with a detector according to Fig 4; 4 Fig 6 shows a curve of the response of the detector to a reaction in which urea is hydrolized by means of urease;
Fig 7 illustrates the hydrogen gas production from 5 Clostridium aceto butylicum as a function of time.; Fig 8 shows a standard curve for NADH; and Fig 9 shows a standard curve for NAD . More precisely. Fig 1 illustrates an apparatus comprising a gas-sensitive detector disposed above the 10 surface of a solution in which an enzyme and a carrier- therefor are located. Here, the detector responds to the gas which is released in the enzymatic reaction and which is diffused out into the air gap above the solutio Fig 2 shows an apparatus in which a carrier gas is 15 allowed to pass a solution with reactants, whereafter the carrier gas, entraining gas from the reaction, passes a gas detector. This apparatus is also suitable for use when it is desirable to study a gas-consuming reaction, a minor amount of the gas which is to react 20 being introduced into the carrier gas. The amount of remaining gas in the carrier gas is thereafter measured by the gas detector.
Fig 3 illustrates a through-flow cell for reaction between an immobilized enzyme and a carrier in which 25 the detector is disposed above the liquid flow in some part of the cell.
The invention will now be described in greater detail below by means of the following examples which are not intended to restrict the spirit and scope of 30 the present invention as are apparatent from the appende claims. EXAMPLE .1
The reaction between urea and urease, during which ammonia is generated, was studied. As gas detector, use 35 was made of a hydrogen and ammonia sensitive Pd-MOS-
OMPI -structure . These hydrogen-sensitive Pd-MOS-structures have been described, int al, in Swedish patent specifi¬ cation 7411342-4. Fig 4 schematically illustrates two embodiments of these structures. In the first instance, Fig 4A, hydrogen-containing gases (H-, H3, H2S etc) realize a shift of the capacitance-voltage curve along the voltage axis, and in the second case, Fig. 4B, a shift of the current-voltage curve along the voltage axis. This shift, which may be of the order of magnitude of 0.5 V, may readily be measured. This type of detector has a response, shown in Fig. 5, to ammonia, which has been generated by the reaction between NH.C1 and NaOH in an apparatus according to Fig. 1.
EXAMPLE 2 Urease (0.5 I.U) was added to a solution containing urea (1 M urea in 1 ml 0.1 M Tris-HCl. pH 8.5). After 6 min., the reaction was stopped by the addition of HgCl„ . The response from the hydrogen-sensitive Pd-MOS-
-structure in an apparatus according to Fig 1, is shown in Fig 6. The slope of the curve (the broken line in Fig 6) may be used to determine the amount of urea which was present in the measurement cell. This slope is unambiguously determined by the urea concentration. Urea concentrations of as little as 0.1 mM may easily be determined in this manner.
No attempt at optimation was made in the experiment, for which reason it is probable that a much higher degree of sensitivity can be attained. EXAMPLE 3
The signal from a Pd-MOS-structure was compared with the signal from an enzyme transistor in which the Pd-MOS-structure was used as a gas sensor in an apparatus according to Fig 3. The reaction which was studied was deimination of creatinine by means of immobilized creatininase. The correlation between the signals from the enzyme transistor and the gas detector was very good.
O PI EXAMPLE 4
A Pd-MOS-capacitance provided as gas sensor accor¬ ding to Fig 3 was used continuously to follow the H2 generation from a 5 ml tower packed with immobilized (on balls of alginate gel) Clostridium acetobutylicum under anaerobic conditions. The buffer flow through the tower was 0.3 ml/min and generated gas was diluted 10 times prior to analysis. The thus obtained H~ generation is illustrated in Fig 7. Finally, mention might be made of a further interes ting field of application of the present invention, namely the use of the enzyme hydrogen dehydrogenase (E.C.I.12.1.2) which provides the possibility to study reactions in which hydrogen and the coenzymes NAD(P) participate. EXAMPLE 5
Fig 8 illustrates a standard curve for NADH, in which 2.5 ml samples of varying concentrations were introduced into the buffer flow. The tower contained immobilized hydrogen dehydrogenase of a volume of 1 ml. The amount of generated hydrogen gas is expressed as ppm in the carrier gas.
Fig 9 illustrates a standard curve for NAD , in which 2.5 ml samples of varying concentrations were introduced into the buffer flow. The tower contained immobilized hydrogen dehydrogenase of a volume of 1 ml. The amount of hydrogen gas present in the buffer corres¬ ponds to 100 ppm in the carrier gas flow.
OUP

Claims

1. A method of indicating the presence of substances which, in a chemical reaction, generate or consume detectable gas, wherein the substances are caused to react for the generation or consumption of detectable gas, whereafter the detectable gas, if such a present, is caused to pass a gas detector which is selectively sensitive to the detectable gas.
2. The method as recited in claim 1, wherein the reaction is carried out in a solution, and wherein the gas is caused to pass a gas detector placed above the surface of the solution.
3. The method as recited in claim 1, wherein the reaction is carried out in a through flow cell, the gas detector being placed in the outlet from the cell.
4. The method as recited in one or' ore of the preceding claims, wherein a carrier gas flow is used to lead the detectable gas from the reaction to the gas detector.
5. The method as recited in one or more of the preceding claims, wherein the detectable gas is hydrogen, ammonia, hydrogen sulfide or orther dissociable, hydro¬ gen-containing gas.
6. The method as recited in one or more of the preceding claims, wherein use is made of a Pd-MOS-struc- ture as gas detector.
7. The method as recited in one or more of the preceding claims, wherein the reaction takes place in the presence of an enzyme, such as urease, creatininase or hydrogen dehydrogenase.
8. The method as recited in one or more of the preceding claims, wherein the detectable gas is decomposed before being caused to pass the gas detector.
9. An apparatus for indicating the presence of substances which,, in a chemical reaction, generate or consume detectable gas, comprising a reaction vessel and a gas detector disposed in association therewith, the detector being sensitive to the detectable gas.
10. The apparatus as recited in claim 9, wherein the gas detector is disposed above the surface of a solution in which the reaction is carried out, in the outlet of a throughflow cell, or in a carrier gas flow which has passed the reaction vessel.
11. The apparatus as recited in claim 9 or 10, wherein the gas detector is a Pd-MOS-structure.
PCT/SE1980/000193 1979-07-24 1980-07-23 A method and apparatus for indicating the presence of substances which,in a chemical reaction,generate or consume gas WO1981000304A1 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0168200A2 (en) * 1984-07-04 1986-01-15 THORN EMI Patents Limited Gas sensor
EP0446972A2 (en) * 1990-02-15 1991-09-18 Akzo Nobel N.V. Device and methods for detecting microorganisms
US5162229A (en) * 1988-03-15 1992-11-10 Akzo N.V. Device and method for enhanced recovery and detection of microbial growth in the presence of antimicrobial substances
US5164796A (en) * 1988-03-15 1992-11-17 Akzo N.V. Apparatus and method for detection of microorganisms
US5217876A (en) * 1988-03-15 1993-06-08 Akzo N.V. Method for detecting microorganisms
US5518895A (en) * 1990-02-15 1996-05-21 Akzo N.V. Device for detecting microorganisms using piezoelectric means
US5858769A (en) * 1989-05-15 1999-01-12 Akzo Nobel N.V. Device for detecting microorganisms
EP0966045A1 (en) * 1997-06-11 1999-12-22 Micronas Intermetall GmbH Method of fabricating a semiconductor device having a structured metallisation
CN107064483A (en) * 2017-04-26 2017-08-18 上海健康医学院 A kind of double item rapid assay methods of serum urea nitrogen creatinine
US10525410B2 (en) 2013-01-22 2020-01-07 Stephen R. Temple Methods and equipment for treatment of odorous gas steams

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2967764A (en) * 1958-04-24 1961-01-10 Technicon Instr Apparatus for analysis and other processing of fluids
US3111390A (en) * 1959-06-30 1963-11-19 Fisher Scientific Co Apparatus for blood gas analysis
CH435802A (en) * 1963-08-27 1967-05-15 Technicon Instr Device for the quantitative analysis of liquid samples for a vaporizable component contained in them
SE321369B (en) * 1964-08-12 1970-03-02 Technicon Instr
US3926734A (en) * 1973-12-21 1975-12-16 Owens Illinois Inc Urea analysis
US3948731A (en) * 1974-10-24 1976-04-06 Massachusetts Institute Of Technology Method and apparatus for measuring reactant concentrations and quantities
US3958942A (en) * 1974-03-14 1976-05-25 Evgeny Mikhailovich Brazhnikov Analyzer for determination of double bonds
SE390068B (en) * 1972-10-11 1976-11-29 Merck Patent Gmbh TEST STREAM REACTION CHAMBER DEVICE
US4020830A (en) * 1975-03-12 1977-05-03 The University Of Utah Selective chemical sensitive FET transducers
US4030979A (en) * 1975-12-10 1977-06-21 Walter H. Zuber, Jr. Method of detecting hydrogen-producing bacteria

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2967764A (en) * 1958-04-24 1961-01-10 Technicon Instr Apparatus for analysis and other processing of fluids
US3111390A (en) * 1959-06-30 1963-11-19 Fisher Scientific Co Apparatus for blood gas analysis
CH435802A (en) * 1963-08-27 1967-05-15 Technicon Instr Device for the quantitative analysis of liquid samples for a vaporizable component contained in them
SE321369B (en) * 1964-08-12 1970-03-02 Technicon Instr
SE390068B (en) * 1972-10-11 1976-11-29 Merck Patent Gmbh TEST STREAM REACTION CHAMBER DEVICE
US3926734A (en) * 1973-12-21 1975-12-16 Owens Illinois Inc Urea analysis
US3958942A (en) * 1974-03-14 1976-05-25 Evgeny Mikhailovich Brazhnikov Analyzer for determination of double bonds
US3948731A (en) * 1974-10-24 1976-04-06 Massachusetts Institute Of Technology Method and apparatus for measuring reactant concentrations and quantities
US4020830A (en) * 1975-03-12 1977-05-03 The University Of Utah Selective chemical sensitive FET transducers
US4020830B1 (en) * 1975-03-12 1984-09-04
US4030979A (en) * 1975-12-10 1977-06-21 Walter H. Zuber, Jr. Method of detecting hydrogen-producing bacteria

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Biomedical Applications of Immobilized Enzymes and Proteins, Ed. Chang T.M.S. Vol. 2 published 1977, p 207-28, weaver J.C."Possible Biomedical Applications of the volatile Enzyme product method" *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0168200A3 (en) * 1984-07-04 1987-08-12 Emi Limited Gas sensor
EP0168200A2 (en) * 1984-07-04 1986-01-15 THORN EMI Patents Limited Gas sensor
US5217876A (en) * 1988-03-15 1993-06-08 Akzo N.V. Method for detecting microorganisms
US5856175A (en) * 1988-03-15 1999-01-05 Akzo Nobel N.V. Device for detecting microorganisms
US5162229A (en) * 1988-03-15 1992-11-10 Akzo N.V. Device and method for enhanced recovery and detection of microbial growth in the presence of antimicrobial substances
US5164796A (en) * 1988-03-15 1992-11-17 Akzo N.V. Apparatus and method for detection of microorganisms
US5858769A (en) * 1989-05-15 1999-01-12 Akzo Nobel N.V. Device for detecting microorganisms
US5518895A (en) * 1990-02-15 1996-05-21 Akzo N.V. Device for detecting microorganisms using piezoelectric means
EP0446972A3 (en) * 1990-02-15 1992-06-03 Akzo N.V. Device and methods for detecting microorganisms
EP0446972A2 (en) * 1990-02-15 1991-09-18 Akzo Nobel N.V. Device and methods for detecting microorganisms
EP0966045A1 (en) * 1997-06-11 1999-12-22 Micronas Intermetall GmbH Method of fabricating a semiconductor device having a structured metallisation
US10525410B2 (en) 2013-01-22 2020-01-07 Stephen R. Temple Methods and equipment for treatment of odorous gas steams
CN107064483A (en) * 2017-04-26 2017-08-18 上海健康医学院 A kind of double item rapid assay methods of serum urea nitrogen creatinine

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