EP1490673A2 - Procede et dispositif pour realiser et observer en permanence des reactions chimiques et/ou biologiques - Google Patents

Procede et dispositif pour realiser et observer en permanence des reactions chimiques et/ou biologiques

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Publication number
EP1490673A2
EP1490673A2 EP03718728A EP03718728A EP1490673A2 EP 1490673 A2 EP1490673 A2 EP 1490673A2 EP 03718728 A EP03718728 A EP 03718728A EP 03718728 A EP03718728 A EP 03718728A EP 1490673 A2 EP1490673 A2 EP 1490673A2
Authority
EP
European Patent Office
Prior art keywords
reaction
continuous
monitoring unit
chemical
selective
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Withdrawn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
EP03718728A
Other languages
German (de)
English (en)
Inventor
Stefan Spichiger
Ursula Spichiger-Keller
Gleb Zhylyak
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.)
C-Cit AG
Original Assignee
C-Cit AG
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 C-Cit AG filed Critical C-Cit AG
Publication of EP1490673A2 publication Critical patent/EP1490673A2/fr
Withdrawn legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Rigid containers without fluid transport within
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0006—Controlling or regulating processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/023—Sending and receiving of information, e.g. using Bluetooth®
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28—Electrolytic cell components
    • G01N27/30—Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood

Definitions

  • the present invention relates to a device for carrying out and continuously monitoring chemical and or biological reactions, comprising a reaction vessel and a monitoring unit, the monitoring unit permitting the continuous selective molecular recognition of a reaction participant of a chemical and / or biological reaction.
  • the present invention further comprises a method for the continuous monitoring of chemical and / or biological reactions by means of a device according to the invention, and a computer program for carrying out the method according to the invention.
  • FIA systems flow-injection-analysis
  • these systems comprising a complex fluid flow system with pumps and valves, and traditional analytical determination methods with reagents or ion-selective electrodes at the end of a flow system use as detectors.
  • Amperometric or voltammetric systems of the prior art include, for example, biosensors and miniaturized, modified electrodes such as "glassy carbon” or graphite -Electrodes (Kalcher, K. et al, Z. Electroanalysis 7/1 (1995), pp. 5-22).
  • Ion-selective transistors based on ISFETs are also known (Schindler, JG et al, Biomedtech 36/11 (1991) pp.271-280). All of the aforementioned systems can, as already explained above, only be used in so-called flow-through devices, as described, for example, in CH 692120 A5. This means that selective continuous determination of parameters, for example, of only one reaction participant is not possible.
  • oxygen, carbon dioxide and pH values can be measured by fluorescence emission with optical sensors.
  • An amperometric glucose sensor is also known from Medisense. These devices have sensors with several different selective layers, the combination of which ultimately leads to the selectivity of these sensors.
  • Steps that must be carried out today to take a sample from a reactor and analyze it are as follows:
  • a device which comprises a reaction vessel with an inlet and a cutout, a monitoring unit being arranged in the cutout, the monitoring unit being arranged in the areas which are arranged in the interior of the reaction vessel permeable membrane, and wherein the monitoring unit comprises a region which enables the continuous selective in situ detection of a reaction participant during the chemical and / or biological reaction and further comprises means for the continuous conversion of the selective detection by means of detection means into a measurement variable, the region and the conversion means are formed as a single layer.
  • the area and the conversion means are formed as a single layer.
  • the detection and conversion (transduction) step can thus take place in a single layer and information losses due to a possible spatial separation between selective detection means and conversion means are avoided.
  • the structure of the layer is selected, adapted and selectable, and also interchangeable, to the particular chemical and / or biological reaction.
  • a reaction vessel can be used for a large number of different reactions with different layers.
  • the layer can be porous or non-porous. It can also be in the form of an insoluble paste with conversion and / or recognition agents distributed therein.
  • the layer is a porous polymer layer (for example polypropylene, ethylene, PVC and other suitable polymers).
  • the layer can also be a conventional MOSFET, MISFET or ISFET (metal oxide or ion selective field effective transistor). Further the layer can consist of metal oxides or mixed metal oxides or of metals such as Pt, Pd, Au, Ag, Cu or their alloys with one another.
  • the continuous in-situ measurement can avoid the risk of contamination by opening the reaction vessels, taking samples and falsifying samples by taking samples and transporting them to the analytical laboratory. This also completely avoids the late detection of changes in the composition of culture media, particularly in the case of biological reactions.
  • the permeable membrane is designed as a semipermeable membrane, so that the reaction participant to be followed can diffuse only in one direction towards the monitoring unit.
  • the semipermeable membrane prevents any reaction / follow-up reaction products of the reactant, which may be caused by the selective recognition process, from diffusing back into the reaction medium.
  • a biological reaction is understood to mean reactions between biological substances and / or living beings, that is to say, for example, animal, microbiological and plant cell cultures.
  • chemical reactions are reactions between chemical compounds which lead to a chemical and or physical change in the starting materials.
  • reaction participant encompasses starting materials, intermediates and products of biological and chemical reactions.
  • Monitoring unit is understood above to mean a sensor system that is based on potentiometric, amperometric, voltammetric or optical measurement techniques.
  • the area that enables the continuous selective recognition of a reaction participant is constructed such that only a single reaction participant can be selectively recognized. This completely eliminates any disruptions that may result from the detection of two reaction participants, for example, or their interaction, which could lead to a falsification of the reaction result. This will e.g. achieved in that only the specifically acting detection means, such as Enzymes, chromophores, ionophores, metal oxides, metals etc. are arranged / distributed in the area.
  • selective recognition is understood to mean that the region selectively recognizes only molecules / atoms in the form of charged molecules / atoms (ions) or as non-charged molecules or chemical and / or biological compounds.
  • This area preferably has detection means which enable the selective detection of only a single reaction participant.
  • this area enables a fast, selective, reversible recognition reaction, since only in this way is it possible to precisely determine the substances / reaction participants to be determined.
  • fast means a time span from a few ms to s, preferably 0.5-10 s.
  • the area can preferably be regenerated quickly.
  • "fast” means a period of a few ms to 10 minutes for regenerability.
  • the regeneration is preferably carried out after the end of the chemical and / or biological reaction carried out. In some reactions, however, regeneration can also take place during the course of the reaction.
  • the detection takes place selectively, the target substance (the reaction participant) being preferred to accompanying substances, ie the other reaction participants.
  • This so-called selectivity principle can be based on distribution equilibria or typical chemical interactions between selected reaction participants and at least one recognition component. As stated above, it is reversible and / or regenerable according to the timing of the continuous monitoring / measuring system.
  • this area also has means for the continuous conversion (transduction) of the selective detection, which was carried out by means of the detection means, into a measurement variable.
  • a conversion or transduction refers to a step or a sequence of steps which, induced / triggered by the selective recognition, causes the formation of a measurement quantity which is generally quantifiable or detectable. The conversion step depends on the measurement method used. In the case of an optical measurement, the measured absorption / absorbance, reflection, the refractive index or their change is detected and converted into a signal.
  • the chemical potential formed is converted into an electrical potential that is measured by an electrode / contact with an electrode.
  • An amperometric measurement method generates or consumes electrons (oxidation and reduction), which are removed or supplied via an electrode or contact with an electrode, so that the current flow changes and is accessible for measurement.
  • the formation of the measured variable is the result of the recognition with its selectivity principle, which is typical for him, and the subsequent conversion.
  • the measurement variable can already be formed as a result of the change in the distribution equilibrium due to the detection and selectivity principle (potentiometry, IR spectroscopy) or through coupling of auxiliary substances (e.g. indicators)
  • this layer is arranged between the membrane and the monitoring unit. It is further preferred that the conversion means continuously transmit the acquired quantifiable measurement variables to a transmission device, which in turn transmits them to a data acquisition device.
  • the data is transmitted wirelessly. This avoids complex cabling systems and further increases the simplicity of the system.
  • the transmission device is only loosely connected to the transmission unit. It is thereby achieved that the transmission device can be removed from the monitoring unit at any time, so that the reaction vessel used can be disposed of with the basic components of the monitoring unit, while the generally more expensive transmission device can continue to be used for further devices according to the invention.
  • the object of the present invention is further achieved in that a method for continuous in-situ monitoring of chemical and biological reactions is provided using an apparatus according to the invention.
  • the method according to the invention comprises the following steps.
  • a computer program for carrying out the invention 'ate procedure available, the computer program converts the data acquired in the data acquisition unit in a chemical and / or physical size of the measured reactant.
  • Figure 1 shows the schematic representation of a device according to the invention
  • FIG. 2 shows the schematic cross section through an amperometric monitoring unit
  • Figure 3 shows the schematic cross section through an optical monitoring unit
  • FIG. 4 shows the schematic cross section through a potentiometric monitoring unit
  • FIG. 5 shows the schematic cross section through a further embodiment of a potentiometric monitoring unit
  • FIG. 6 shows the schematic cross section through a further embodiment for an amperometric monitoring unit
  • Figure 7 shows the schematic representation of a further embodiment of a device according to the invention.
  • FIG. 1 shows a device 100 according to the invention, comprising a reaction vessel 110 with an inlet 111.
  • the reaction vessel can be made of any material. In the case of single-use reaction vessels which are thrown away after the end of the reaction, an inexpensive plastic or glass is preferably used.
  • a reaction medium 140 is also shown schematically in FIG. 1, which comprises the reaction participants for a chemical and / or biological reaction.
  • the monitoring unit 120 is arranged in a cutout 112 in the reaction vessel 110. You can be attached via seals, or, for. B. can also be cast in reaction vessels made of plastic or glass. Otherwise, the type of attachment, for. B. glue etc. arbitrarily selectable and adapted to the reaction type.
  • the monitoring unit 120 is wholly or partly in contact with the inside of the reaction vessel 110 or with the reaction medium 140 through a semipermeable membrane 121, which can be made of cellulose, a cellulose derivative or another suitable material known to the person skilled in the art.
  • the monitoring unit 120 is preferably completely immersed in the reaction medium. In the monitoring unit 120 there is an area 130, a freely selectable and exchangeable so-called “molecular recognition layer” 130, which enables the selective recognition of a single reaction participant of a desired reaction.
  • This recognition layer 130 is in contact with a conversion means 131, which converts the data obtained by means of the recognition layer 130 into a physical measurement variable.
  • the detection layer and the conversion means 131 form a single component of the device according to the invention.
  • the conversion means 131 is in contact with a transmission device 132, which further transmits the measurement variables thus obtained to a data acquisition device 150, for example by radio.
  • the contact can also z. B. electrically such as about metal electrodes, wires or via suitable optical means. It goes without saying that the data can of course be transmitted from the transmission device 132 to the data acquisition device by means of a cable or radio, also via an interposed handheld device, which then further transfers the collected data to another data acquisition device, for example a server or a network.
  • the radio head can thus be removed after the end of the reaction and can be used again in a new one-way reaction vessel, while the used reaction vessel can be thrown away.
  • This also enables a more cost-effective, standardized production of devices according to the invention, since only a few replaceable and reusable expensive radio heads are required and the design of the device according to the invention can thus be considerably simplified.
  • the entire monitoring unit 120 is miniaturized in such a way that it is designed as a sensor chip which can have one or more monitoring units 120 and / or can have all or part of the components described above.
  • FIG. 2 shows a schematic cross section, not to scale, through a monitoring unit 200 based on the amperometric measuring principle (hereinafter referred to as amperometric sensor) for installation in a reaction vessel. More precisely, in the present case it is a glucose sensor, the general principle of which is described in CH 692 120 A5, for example.
  • the amperometric sensor 200 has a sensor body 203, for example on the polysulfone.
  • the material itself can be selected as desired, it should only be resistant or inert to the reactions taking place or the reaction medium and not be electrically conductive.
  • a guide channel 211 there is a selective layer structure 208.
  • the deflection element consists of a platinum wire 205 which is in direct contact with the layer structure 208.
  • the layer structure 208 can also be designed as a paste. According to Korell, U .; Spichiger, UE Electroanalysis 6 (1994) 305-315 or Korell, U .; Spichiger, UE Anal. Chem. 66 (1994) 510-515. It contains an enzyme as a recognition component, TTF / TCNQ as mediators and silicone oil as a bulk medium. The redox-active enzyme is introduced into the paste and shows an optimal lifespan in this environment. The bulk of the paste serves as a reservoir from which active enzyme can be supplied. The paste can be placed in the recess in the head section of the sensor module. The surface forms the sensor field where the sample and the selective layer structure are in contact with each other.
  • the selective layer structure 208 comprises at least one component that effects the selectivity of the sensor element, i.e. the preferred detection of the target substance or a group of target substances over accompanying substances allows.
  • the selectivity can be brought about by molecular recognition of the target substance, the reaction participant or by the partition of the substance between the reaction participant and the sensor element (by means of a distribution equilibrium).
  • the selective layer structure can contain auxiliary substances which are necessary for the formation of the layer and / or support, catalyze and / or reduce the influence of interference, as well as optionally a further component which is responsible for the transduction step.
  • the layer structure includes the possibility of combining the selective layer with auxiliary layers which, for example, ensure biocompatibility and / or form the separation between gaseous, neutral and charged substances and / or form a diffusion barrier.
  • the layer structure can contain both more or less lipophilic / apolar as well as more or less hydrophilic / polar layers as well as micelles or reverse micelles.
  • the washing out of components in the sample / specimen is prevented, for example, by high lipophilicity of the components in the case where there is an aqueous sample / aqueous specimen or by immobilization of individual components.
  • the selective layer structure is preferably attached so that it is easily removable or replaceable, e.g. B. is only connected to the sensor body by suitable fastening elements, such as grooves, clamps etc.
  • the layer structure is thus given a certain flexibility ("flexibility") with which it can compensate for any tensions that may occur. It can, for example, only be clamped between the two by fastening the sensor body to the membrane, or it can adhere to the sensor body through adhesive forces.
  • the selective layer structure can be applied on a suitable carrier, for example on a planar waveguide, on an optical fiber, on a reflecting layer, or on a diffusion barrier and can also be offered as a "disposable layer" and used in a module. (Disposable layers or disposable waveguides with target-analyte selective layers.) If a sensor element or a layer structure is used up, you can either only the selective element but also parts of the monitoring unit or the entire monitoring unit are replaced.
  • thermostatting of the amperometric sensor can optionally be provided.
  • the above-mentioned paste can e.g. inserted in the form of a tablet of adjusted viscosity into the head part, placed on a sensor field or inserted with the exchangeable platinum wire.
  • the guide channel 21 1 can consist zone by zone of a platinum tube which simultaneously forms the counter electrode and the guide channel.
  • the amperometric sensor 200 also has a reference module, preferably consisting of a "free-flow free-diffusion" electrode, which has proven to be extremely robust and low-interference in continuous operation.
  • This reference module consists of a recess 207 in the sensor body 203, which has the electrolyte solution for the reference electrode 206, which preferably consists of silver wire.
  • the recess 207 is connected via a capillary 210 to the inside of the reaction vessel, not shown.
  • the capillary can of course also be replaced by other suitable devices such as e.g. a diaphragm etc. to be replaced.
  • a platinum button 204 is arranged in the electrode body 203 connected to a platinum wire 209, which together form the counterelectrode.
  • the monitoring unit 200 further comprises a transmission device 201, which is designed as a radio head for the wireless transmission of measurement data obtained. It is therefore sufficient if only the sensor body 203 is attached in the reaction vessel (not shown here). The expensive radio head 201 can therefore advantageously always be used again.
  • the platinum wire 205 of the measuring electrode, as well as the silver wire 206 of the reference electrode and a platinum button 212 for connection to the platinum wire 209 are fastened to the radio head 201 and can therefore always be reused. Of course, a fixed connection using a cable is also possible instead of the radio head.
  • Hgur ⁇ shows a schematic cross section through an optical monitoring unit 300. This consists of a wireless radio head 302 similar to that shown in FIG. 2 for transmitting the measurement results to a data acquisition device, not shown here.
  • the latter is in loose contact with the sensor body 301 permanently installed in the reaction vessel (not shown), which has a selective layer structure 303, which is connected to the radio button 302, for example, via a platinum wire 304 arranged in a guide channel 305, an optical fiber or via another suitable transmission medium is.
  • the selective layer structure comprises a suitable ligand, or else a mixture of different ligands.
  • the selective layer structure was synthesized, for example, on the basis of known nitrite and chloride-selective ligands (Nitritionophore I, Fluka Chemie AG, Buchs, Switzerland; chloride-selective ligand ETH 9033, synthesis at the center for chemical sensors).
  • an H + -selective chromoionophore (chromoionophore I, II and VI for nitrite; chromoionophore III for chloride, Fluka Chemie AG, Buchs, Switzerland) with the nitrite or chloride-selective ligand and, where this is necessary for charge compensation , dissolved together with anionic lipophilic excipients in a DOS plasticized PVC layer.
  • the change in absorbance as a result of the co-extraction of the anion together with H + from the buffered sample solution is determined photometrically and follows the change in the concentration of the anion.
  • the measuring range is between 0.5 and 5000 mg kg - 1 , chloride is discriminated with a selectivity factor of 10 " 2 - 9 (molar units).
  • the implementation of several optode layers for the determination of nitrite in one system is also possible.
  • the nitrite-selective membrane with chromoionophore VI as an indicator shows a luminescence emission in the visible range of the spectrum and can therefore also be used as a luminescence-active layer.
  • the measured variable can be formed, for example, by measurements in ATR mode (attenuated reflection), by measurements of changes in refractive index, by measuring the luminescence decay time or by deriving the luminescence emission.
  • the light energy required for this can be radiated in from outside the module via an optical fiber or the light source can be integrated into the sensor head 302, for example, by implementing diodes.
  • a detector diode can also be integrated into the sensor head 302.
  • a wireless radio connection a cable connection from the sensor / monitoring device to the data acquisition device (not shown in the figure) is also possible here.
  • FIG. 4 shows the schematic section, not to scale, through a potentiometric monitoring unit 400, also referred to below as a potentiometric sensor.
  • the potentiometric sensor also has a wireless radio head 401, to which the measuring electrode 404 and the reference electrode 403 are attached. This also ensures good reusability.
  • the selective layer structure 405 is placed on a sensor field and is in contact with the reaction medium at this point via a membrane, not shown.
  • Base part 402 and head part 401 can be produced independently of one another and can be joined / closed after the layer structure has been introduced.
  • the base part 402 contains the sensor element with the layer structure 405, a recess 406 which is connected to the reaction medium via a capillary 407.
  • the radio head has the discharge device or the discharge element 404, as well as the electrode 403.
  • a connection via cable from the sensor / monitoring device to a data acquisition device (not shown in the figure) is also possible here.
  • FIG. 5 shows a further schematic cross-section, not to scale, through a potentiometric monitoring unit 500, also referred to below as a potentiometric flat sensor.
  • the potentiometric flat sensor 500 has a wireless radio head 501, on which contacts 502, 503 and 504 for producing an electrically conductive contact with the electrodes, the measuring electrode 510 and the reference electrode 1 1 oeresugi sin ⁇ .
  • ⁇ s-on ⁇ a ⁇ _. ⁇ ⁇ is not always e ⁇ oroe ⁇ ich and can be omitted if necessary
  • the measuring and reference electrodes 510 and 51 1 are applied to a sensor body 505 as thin films.
  • the application to the sensor body 505 can be carried out, for example, by printing (inkjet printer, rollers, printing forms, etc.), doctor blades, CVD (chemical vapor deposition), sputtering or other suitable application methods.
  • the sensor body 505 consists, for example, of polyethylene, polypropylene, copolymers of ethylene, propylene or other suitable, essentially chemically resistant plastics, such as, for example, polybutadiene, polybutadiene styrene copolymers and the like.
  • the thickness of the plastic carrier is between 0.1 to 4 mm, preferably from 0.2 to 1.5 mm.
  • the electrodes 510 and 511 consist essentially of carbon or graphite with various chemical additives, e.g. Particles or powders of conductive substances, such as Ag, Pt, Pd, Au, Cu and their salts, as well as suitable conductive metal oxides.
  • conductive substances such as Ag, Pt, Pd, Au, Cu and their salts, as well as suitable conductive metal oxides.
  • silver and / or silver chloride is added to the carbon in order to improve the conductivity.
  • the rod-shaped printed electrodes 510 and 51 1 run out on the underside of the sensor body 505 in enlarged, preferably circular or rectangular areas 506 and 507.
  • the electrodes preferably consist of carbon, or else of Ag, Pt, Cu, Au or alloys and mixtures thereof.
  • the molecular recognition layer which is not shown in FIG. 5, is applied to the circular end 506 on the measuring electrode 510.
  • the ends of the electrodes are not enlarged.
  • the paste described in FIG. 2 can be used as the molecular recognition layer.
  • the detection means or the material of the detection layer for example the ionophore, the enzyme etc.
  • the detection means or the material of the detection layer is added directly to the electrode material mixture before being applied to the sensor body and is thus integrated into the electrode. Subsequent application is therefore not necessary in this case, although it is of course not excluded.
  • a second plastic film 512 made of the same material as the plastic film 505 is applied to the first plastic film 505 and sealed, so that there is no space between the two plastic carriers 505 and 512, respectively which liquid can possibly penetrate and distort the measurement can.
  • the application of the second undisturbed layer does not take place over the entire length of the plastic film 505, but only over about 2 thirds of the total area. This is represented by the line with reference number 513 in FIG. 5. Openings 508 and 509 are cut into the second plastic layer 512 at the location of the enlarged ends of the measuring or reference electrodes 510 and 511 in order to enable a measurement.
  • FIG. 6 shows a further schematic section, not to scale, through an amperometric monitoring unit 600, also referred to below as an amperometric flat sensor.
  • the amperometric flat sensor 600 initially also has a radio head 601, as explained above, with contacts 602, 603 and 604. It is particularly important that the contacts are corrosion-resistant or that they are protected against corrosion in a suitable manner (casing and the like).
  • the second part of the amperometric flat sensor 600 consists of a plastic carrier (film) 605, which essentially consists of the same material and has the same dimensions and properties as the one shown in FIG.
  • Three electrodes 608, 606 and 607 are arranged on the plastic carrier 605, which likewise consist, for example, of carbon with additions of, for example, silver or silver chloride and are printed on the plastic body 605. It goes without saying that other application methods, as discussed for example in relation to FIG. 5, can also be applied to the amperometric flat sensor in FIG. 6.
  • the amperometric flat sensor 600 has a reference electrode 606 and a counter electrode 608.
  • the measuring electrode 607 and the reference or counter electrode 606 and 608 likewise have widened, preferably circular ends 611, 610 and 612 at the lower end.
  • the selective layer for example in the form of a paste, as explained above, is also applied to the measuring electrode 607 or the circular end 610.
  • the selective layer is not shown in FIG. 6.
  • a second plastic layer 615 preferably also in the form of a plastic film, which is made of the same material as the plastic body, is applied to the printed electrode 606, 607, 608 and the sensor body 605.
  • This second protective film 615 is not applied over the entire length of the sensor body, but only on two thirds of the area, what for example in the present case is represented by reference number 616.
  • the second film 615 can also have a different chemical composition than the first film 605.
  • the two plastic films 605 and 615 are welded to one another or bonded to one another so airtight that no liquid or gaseous substances can penetrate possibly falsify the measurement.
  • circular cutouts are likewise punched into the protective film 615 with the reference numerals 614, 612 and 613. This also enables measurement in the medium.
  • FIG. 7 shows a further embodiment of the device according to the invention.
  • FIG. 7a shows a device 700 according to the invention, comprising a reaction vessel 701 with an inlet 702.
  • the reaction vessel consists of any material, but preferably plastic, for example poly (meth) acrylates and their derivatives. Of course, any other material that is largely chemically inert can also be used within the scope of the present invention.
  • a reaction medium 703 is also shown schematically, which comprises the reaction participants for a chemical and / or biological reaction.
  • the monitoring unit 707 is arranged in a recess 704.
  • the monitoring unit 707 is arranged in a further vessel 705, which is designed as a membrane.
  • This membrane has essentially the same chemical composition as described above. In particular, it is a relatively dimensionally stable cellulose membrane. However, it can also contain other chemical substances, for example plastics, which bring about even greater stiffening and increased strength. In general, if the membrane does not have sufficient rigidity, it is applied to a lattice structure made of chemically inert material, which defines the space and shape of the vessel 705.
  • the monitoring unit 707 is, for example, an amperometric sensor with three electrodes 708, 709 and 710 which, as explained above in FIGS.
  • the monitoring unit is therefore a sensor as shown in FIGS. 5 and 6.
  • the sensor 707 also has a radio head 711.
  • the sensor element 707 can thus be inserted into the vessel 705, which also acts as a membrane.
  • the reaction medium 703 can diffuse through the membrane or exclusively To measure it, so for example a first selectivity can be selected via the type of membrane 705.
  • the reaction participant to be measured is then subsequently measured on the selective layer structure 706.
  • FIG. 7b shows essentially the same device 730 as shown in FIG. 7a, but the device 730 shows the situation during the measurement.
  • the membrane 705 or the entire monitoring unit 707 is completely sunk in the recess 704 and is partially immersed in the reaction medium 703, so that a reaction participant can be measured selectively and continuously on the selective layer structure 706.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

L'invention concerne un dispositif pour réaliser et observer en permanence in situ des réactions chimiques et/ou biologiques. Ce dispositif comprend un réacteur, dans lequel est installée fixe une unité de surveillance, qui permet l'identification moléculaire sélective et continue d'un seul agent réactif. La présente invention porte également sur un procédé pour l'identification in situ sélective et continue d'agents réactifs dans des réactions chimiques et/ou biologiques, ainsi que sur un programme informatique pour réaliser ce procédé.
EP03718728A 2002-04-03 2003-04-03 Procede et dispositif pour realiser et observer en permanence des reactions chimiques et/ou biologiques Withdrawn EP1490673A2 (fr)

Applications Claiming Priority (3)

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PCT/EP2003/003502 WO2003082469A2 (fr) 2002-04-03 2003-04-03 Procede et dispositif pour realiser et observer en permanence des reactions chimiques et/ou biologiques

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AU2003222794A1 (en) 2003-10-13
WO2003082469A2 (fr) 2003-10-09
AU2003222794A8 (en) 2003-10-13
DE10214713A1 (de) 2003-10-30
WO2003082469A3 (fr) 2003-12-24

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