EP0876605A1 - Probenahmesystem für fluidische und in fluiden enthaltene analyte sowie verfahren zu seiner herstellung - Google Patents
Probenahmesystem für fluidische und in fluiden enthaltene analyte sowie verfahren zu seiner herstellungInfo
- Publication number
- EP0876605A1 EP0876605A1 EP97914106A EP97914106A EP0876605A1 EP 0876605 A1 EP0876605 A1 EP 0876605A1 EP 97914106 A EP97914106 A EP 97914106A EP 97914106 A EP97914106 A EP 97914106A EP 0876605 A1 EP0876605 A1 EP 0876605A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- membrane
- sampling system
- channel
- carrier
- cover
- 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- Withdrawn
Links
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
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- 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
- G01N27/3272—Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels
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- 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
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
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- 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
- B01L2300/0645—Electrodes
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- 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
- B01L2300/0654—Lenses; Optical fibres
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- 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
- B01L2300/0681—Filter
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- 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
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
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- 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
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0825—Test strips
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- 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
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0887—Laminated structure
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
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- 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
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
-
- 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
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T29/00—Metal working
- Y10T29/49—Method of mechanical manufacture
- Y10T29/49002—Electrical device making
- Y10T29/49117—Conductor or circuit manufacturing
- Y10T29/49124—On flat or curved insulated base, e.g., printed circuit, etc.
- Y10T29/49155—Manufacturing circuit on or in base
Definitions
- the invention relates to a sampling system and a method for its production. Such systems can be used simply and universally in chemical and biochemical analysis.
- electrochemical sensors are used to determine substance concentrations in liquids (cf. F. Oehme: Chemical sensors, Vieweg Verlag, Braunschweig, 1991).
- Flow systems of this type have the particular advantage that not only the liquid measuring medium but also calibration liquids can be pumped through the system alternately, so that the sensors can be calibrated regularly.
- a disadvantage of the prior art is that flow analysis systems in silicon technology can only be implemented at low unit costs if quantities of more than 100,000 are required per year. The same applies to the microdialysis needle, which is currently still being manufactured using manual techniques.
- connection technology for flow sensors and microdialysis needles has not been developed to such an extent that hose and channel connections for the liquid measuring medium can be produced at reasonable cost without widening the cross section and dead volume.
- the object of this invention is therefore to provide a sampling system which is simple in construction, can be used universally and alone and in combination and can be produced with little effort.
- the sampling system designed according to the invention for fluid or analytes contained in fluids consists of a flat carrier into which various openings are made, through which the respective fluid enters a channel and then again can leave.
- the channel is at least partially covered by a cover on the side opposite the carrier.
- a membrane permeable to the analyte is used, which at least partially covers the channel on its open upper side. The areas left free from the cover can be used for taking the analyte or for direct measurement there.
- the channel can also be formed directly in the carrier.
- a channel carrier If a channel carrier is used, it is favorable to provide it with additional openings which correspond in the assembled state of the sampling system designed according to the invention to the openings already mentioned in the carrier.
- the sampling system designed according to the invention has a very simple structure and can be used universally for the various measuring tasks. It is thus possible to take a sample, to separate the analyte to be determined from the carrier fluid and to take it for a subsequent analysis.
- the sampling system can, however, also be used in direct combination with sensor elements and, for example, substance concentrations of a specific analyte can be carried out directly on the sampling system.
- the simple structure and, consequently, the very cost-effective production are particularly advantageous here.
- An example of a sampling system designed according to the invention can be constructed such that a carrier 1 with at least two openings 4, 5 is firmly connected to a channel carrier 6 with at least two openings 9, 10 and at least one channel 11, and the channel carrier 6 with at least one membrane 12 is firmly connected and the membrane 12 is firmly connected to a cover 13 and through the openings 4, 5 and 9, 10 the analyte or a carrier liquid or carrier gas containing it are fed to the channel 11 can, which flows through this channel and can take up the analyte which is in contact with the membrane 12 permeable for this analyte at the uncovered area 14 of the membrane 12, and the analyte or also the carrier liquid containing it the channel can be guided past the openings 16, 17 in the cover 13, in which electrochemical or optical sensor elements can be inserted for which substance concentrations or ion activities can be measured.
- Carrier 1 and the channel carrier 6 consist of a material inert to the analyte and the carrier fluid, for example made of plastic (polyvinyl chloride (PVC), polyethylene (PE), polyoxymethylene (POM), polycarbonate (PC), ethylene / propylene cop. (EPDM), polyvinyl nylidene chloride (PVDC), polychlorotrifluoroethylene, polyvinyl butyral (PVB), cellulose acetate (CA), polypropylene (PP), polymethyl methacrylate (PMMA), polyamide (PA), tetrafluoroethylene / hexafluoropropylene cop.
- plastic polyvinyl chloride
- PE polyethylene
- POM polyoxymethylene
- PC polycarbonate
- EPDM polyvinyl nylidene chloride
- PVDC polychlorotrifluoroethylene
- PVB polyvinyl butyral
- CA cellulose acetate
- PP polypropylene
- FEP polytetrafluoroethylene
- PF Phenol-formaldehyde
- EP epoxy
- PUR polyurethane
- polyester UP
- silicone melamine-formaldehyde
- UF urea-formaldehyde
- Capton aniline-formaldehyde
- the carrier 1 can also be made of glass, ceramic or silicon. The same applies to the channel carrier 6.
- the openings 4, 5 and 9, 10 in the carrier 1 and in the channel carrier 6 as well as the channel 11 are produced in such a way that the carrier 1 and / or the channel carrier 6 by injection molding, pressing techniques or the LIGA process with these Structures are produced, or these structures subsequently by cutting, punching, milling, drilling, etching, laser cutting, spark erosion or the like getting produced.
- the typical dimensions of the carrier 1 are 1 to 10 cm for the length, 0.5 to 5 cm for the width and 0.1 to 1 mm for the thickness. The same or similar sizes apply to the channel support 6.
- the openings 4, 5 and 9, 10 have diameters between 0.1 and 10 mm.
- the width of the channel 11 is between 0.1 and 10 mm.
- ger 6 can be carried out according to the state of the art by gluing, welding or laminating (for plastics) or gluing (for glass, ceramic, silicon) or anodic bonding (for glass on silicon).
- the membrane 12 is designed as a dialysis membrane, gas-permeable membrane, lattice or fabric made of plastic, paper or textile fibers. Their thickness is between 10 and 1000 ⁇ m.
- the following materials can be used for dialysis membranes: polycarbonate, cellulose acetate, cellulose hydrate, cuprophan, Thomapor, regenerated cellulose, polyacrylonitrile, polysulfone, polyamide, polymethyl methacrylate or the like.
- the following materials can be used for a gas-permeable membrane: polyvinyl chloride (PVC), polyethylene (PE), polyoxymethylene (POM), polycarbonate (PC), ethylene / propylene cop. (EPDM), polyvinylidene chloride (PVDC), polychlorotrifluoroethylene , Polyvinyl butyral (PVB), cellulose acetate (CA), polypropylene (PP), polymethyl methacrylate (PMMA), polyamide (PA), tetrafluoroethylene / hexafluoropropylene cop.
- PVC polyvinyl chloride
- PE polyethylene
- POM polyoxymethylene
- PC polycarbonate
- EPDM polyvinylidene chloride
- PVDC polychlorotrifluoroethylene
- PVB polyvinyl butyral
- CA cellulose acetate
- PP polypropylene
- PMMA polymethyl methacrylate
- PA polyamide
- FEP polytetrafluoroethylene
- PF phenol-formaldehyde
- EP epoxy
- PUR polyurethane
- polyester UP
- silicone melamine-formaldehyde
- UF urea-formaldehyde
- Capton calcium phosphate
- the fixed connection between membrane 12 and channel support 6 can be made according to the prior art by gluing, welding or laminating.
- the cover 13 is produced by the same or similar methods as the carrier 1 and is firmly connected to the membrane by gluing, welding or laminating in such a way that the cover 13 is completely or partially covered.
- All sensor elements can be integrated into the openings 16, 17 of the cover 13, which can be realized small enough and are known, for example, from F. Oehme: Chemical sensors, Vieweg Verlag, Braunschweig, 1991 or from DE 41 15 414.
- the particular advantages of this invention lie in the fact that chemical and biochemical sensors in multi-sensor arrangements together with flow channels and microdialysis elements can be realized as a unit in such a way that they can be produced with little effort.
- the device can be used to take the sample and measure substance concentrations with the help of integrated sensors.
- the flow arrangement makes it possible to regularly calibrate the sensors with the aid of calibration liquids. With a small channel cross section, the system can be used on the principle of microdialysis due to the capillary throttling effect.
- FIGS. 1 to 22 Exemplary embodiments of the invention are shown in FIGS. 1 to 22.
- 1 a layer structure of a first example of a sampling system into which sensor elements can be integrated
- 2 a sampling system according to FIG. 1
- 3 a sensor element of a sampling system which can be integrated into openings
- 4 a second exemplary embodiment of a sampling system with an ion-selective sensor element
- 5 a third exemplary embodiment of a sampling system with a biosensor element
- 6 shows a fourth exemplary embodiment of a sampling system with a sensor element for measuring gases dissolved in liquids
- 7 a fifth exemplary embodiment of a sampling system with a glucose sensor
- 8 an electrode carrier according to FIG. 7
- 9 a sampling system according to FIG. 7 with glucose sensor
- 10 a sampling system of a sixth exemplary embodiment with an additional channel end;
- Fig. 11 a seventh embodiment of a
- Sampling system 12: a sampling system according to an eighth exemplary embodiment; 13: a sampling system of a ninth exemplary embodiment with an additional membrane; 14: a sampling system in an eleventh embodiment with an external connection of sensor elements; 15: a sampling system in a twelfth exemplary embodiment; Fig. 16: a sampling system in a thirteenth
- Embodiment 17 a sampling system in a fourteenth exemplary embodiment, into which sensor elements can be integrated; 18: a sampling system as a fifth exemplary embodiment, in which sensor elements can be integrated; Fig. 19: a sampling system in a sixteenth
- FIG. 1 shows the layer sequence of a sampling unit in which sensor elements can be integrated.
- FIG. 2 shows the layer structure after the various planes have been joined and firmly connected.
- Sensor elements such as are known, for example, from DE 41 15 414 can be integrated into the openings 16, 17 of the cover 13.
- Such a sensor element is shown in FIG. 3.
- an ion-selective membrane 18 is in direct contact with a noble metal derivation 19 made of silver.
- This sensor element is inserted into the opening 16 of the cover 13 in such a way that the ion-selective membrane 18 is in direct contact with the membrane 12 and the noble metal derivative 19 contacts through the opening 16 with a contact pin from the outside and with a measuring device electronics can be connected.
- the sensor element according to FIG. 3 can then additionally be fixed with an adhesive on the surface of the cover 13 in such a way that the noble metal derivative remains free of adhesive.
- the membrane 12 can be covered in the opening 16 with a thin hydrogel film (for example HEMA), which is used as a solution in the membrane, before the sensor element is inserted Opening (16) is filled, after formation of the hydrogel film, the sensor element according to Figure 3 is used.
- a thin hydrogel film for example HEMA
- a reference electrode is inserted into the opening 17 and is constructed in the same way as the sensor element according to FIG. 3.
- the layer 18 in FIG. 3 consists of a KCl gel and the layer 19 consists of a chloridized silver film.
- carrier 1, channel carrier 6 and cover 13 are produced from a 150 ⁇ m thick laminating film by punching out. This film consists of polyethylene and polyester and is commercially available under the name CODOR film.
- the membrane 12 is a 20 to 100 ⁇ m, preferably 50 ⁇ m thick dialysis membrane made of polycarbonate.
- the carrier 1, the channel carrier 6, the membrane 12 and the cover 13 are firmly connected by lamination at 125 ° C.
- a carrier liquid for example a saline solution
- the carrier liquid leaves the arrangement via the opening 4 in the carrier 1.
- the surface 14 of the membrane 12 not covered by the cover 13 is brought into direct contact with the liquid measuring medium, for example, by immersion and the analyte can be removed there.
- the measuring ions diffuse through the dialysis membrane 12, reach the carrier liquid flow in the channel 11 and are transported to the sensor element, which is located in the opening 16 of the cover 13.
- the ion-selective membrane 18 of the sensor element according to FIG. 3 is thus in contact with the measuring medium via the dialysis membrane.
- a potential difference is formed between the measuring solution and the ion-selective membrane, which can be measured between the metal leads 19 of the sensor element or the reference electrode with the aid of a high-resistance millivolt meter.
- FIG. 4 shows an arrangement according to FIGS. 1 and 2 in section.
- no sensor element according to FIG. 3 is inserted into the opening 16 of the cover 13.
- a 0.1 to 1 ⁇ m thick noble metal film 20, 21 (for example made of silver) is applied to the cover 13 using vapor deposition, sputtering or screen printing technology (both noble metal films 20 , 21) are made of the same material and are connected to each other).
- a membrane solution for example made of PVC or silicone with ion carriers, is now introduced into the opening 16 with the aid of a micropipette or an automatic dispenser.
- Such membrane solutions include also known from F.
- the membrane 22 After the sensor membrane 22 has solidified by evaporation of the solvent or by crosslinking under UV light, this arrangement acts as an ion-selective sensor element. A similar element can be introduced into the opening 17 as a reference electrode.
- the membrane 22 is designed as a KC1 gel and the metal film 20, 21 as a silver film, the surface of which is chloridated.
- FIG. 5 A third exemplary embodiment is shown in FIG. 5. This representation corresponds to the representation in FIG. 4. However, an additional membrane 23 is introduced here. If this membrane 23 is designed as a gel layer with an enzyme (for example the enzyme urease) and the membrane 22 is designed as a pH-sensitive or ammonium-selective membrane, a biosen sensor element for the measurement of urea concentrations. Both membranes 22 and 23 can be filled into the opening 16 from the liquid phase and solidified one after the other, as stated above.
- the reference electrode is designed in the same way as in the second exemplary embodiment (FIG. 4).
- FIG. 6 a sensor element for the measurement of dissolved gases in liquids is shown.
- the structure is similar to that shown in Figure 4.
- an additional gas-permeable membrane 24 is laminated between membrane 12 and cover 13 in FIG. 6.
- This gas-permeable membrane consists, for example, of a 50 ⁇ m thick PTFE film.
- the noble metal films 20, 21 are not made of the same material and are not connected to one another for the design of an oxygen sensor of the Clark type.
- the noble metal film 20 consists, for example, of platinum (cathode) and the noble metal film 21 of silver, the surface of which is chloridized (Ag / AgCl anode).
- the membrane 22 is designed as a KCl gel.
- the oxygen can diffuse through the dialysis membrane 12 and the gas-permeable membrane 24 to the platinum cathode, where it is converted electrochemically and an electrical current flows between the Pt cathode 20 and Ag / AgCl anode 21, as described by Clark Oxygen sensor is known.
- FIG. 7 shows a layer sequence according to FIG. 1.
- the electrode carrier 25 has a platinum layer 26 and a silver film 27 coated with the aid of the above-mentioned methods. Both films 26, 27 have layer thicknesses between 0.1 and 1 ⁇ m. The surface of the silver film 27 is converted into silver chloride when the sensor element is in operation.
- the electrode body 25 with the noble metal film 26 is shown enlarged in section in FIG.
- the electrode body is provided with small holes 28, the diameters of which are between 50 and 1000 ⁇ m.
- FIG. 9 also shows the assembled configuration in
- the gel layer 31 consists, for example, of polyvinyl alcohol (PVA) and is introduced and solidified by pouring a solution into the opening 16 of the carrier 13, as is known from DE 44 08 352.
- PVA polyvinyl alcohol
- the enzyme glucose oxidase is immobilized in it.
- a KCl gel is filled into the opening 17 for the realization of a reference electrode.
- an electrical voltage (typically 600 mV) is applied to the electrode carrier 25 with the aid of two contact pins through the openings 29, 30 in the cover 13 between the Pt 26 and Ag / AgCl electrodes 27 and in
- An electrical current is measured as a function of the glucose concentration.
- FIG. 1 A sixth exemplary embodiment is shown in FIG. This configuration corresponds to the illustration in FIG. 1. However, an additional channel 11 ′′ is introduced into the channel carrier 6 ′ here. Through the openings 32 and 33, a calibration liquid can be supplied to the sensor element, which is located in the opening 16.
- FIG. 11 shows a seventh exemplary embodiment based on FIG. 1.
- the openings 16, 17 in the cover 13 are replaced by the openings 34, 35 which are located in the carrier 1 ′′.
- a sensor element according to FIG. 3 and a reference electrode are inserted into these openings.
- FIG. 12 An eighth exemplary embodiment is shown in FIG. 12 based on FIG. 1.
- the membrane 37 (it replaces the membrane 12) only partially covers the channel support 6.
- the cover 38 is made larger and has a window 41 through which the measuring medium can be brought into contact with the membrane 37.
- sensor elements and reference electrodes can be implemented in the openings 39, 40.
- FIG. 12 A ninth exemplary embodiment is shown in FIG.
- a further membrane 42 (for example made of PTFE) is introduced here which is gas permeable.
- a sensor for dissolved oxygen can be implemented in the opening 39.
- Tenth embodiment It is also possible to make the membrane 42 in FIG. 13 from a thin PVC film to produce and fill in the openings 39, 40 with a solution for producing an ion-selective PVC membrane and thus to form an ion-selective sensor element analogously to the exemplary embodiment two.
- FIG. 14 An eleventh embodiment is shown in FIG. 14. In contrast to the first exemplary embodiment, no sensor elements and reference electrodes are produced in openings in the cover (13 in FIG. 1, 36 in FIG. 14). This device serves as
- FIG. 15 in contrast to FIG. 1, the carrier and the channel carrier (1 and 6 in FIG. 1) are joined to form a unit 43.
- This carrier 43 consists for example of PVC and is 5 mm thick.
- the openings 44, 45 go over the entire thickness; the channel 46 has a depth of 1 mm.
- the thirteenth exemplary embodiment shows a configuration according to FIG. 15 in FIG. 16.
- a sampling layer 47 is additionally glued onto the membrane 12.
- This layer 47 consists of filter paper that can hold a drop of the liquid medium.
- FIG. 17 shows a fourteenth exemplary embodiment.
- a flow arrangement is shown which consists of a support 48, a channel support 51, a membrane 55 (dialysis membrane or gas-permeable membrane) and a cover 56, in the openings 57, 58, 59 of which, as stated above, sensor elements and reference electrodes can be inserted nen.
- the arrangement works like a sensor flow cell, to which the liquid measuring medium is fed through the opening 49 and withdrawn again through the opening 50.
- FIG. 18 shows a fifteenth exemplary embodiment based on FIG. 17. However, the membrane 55 is missing in FIG. 18. Sensor elements according to FIG. 3 can be inserted into the openings 57, 58, 59.
- FIG. 19 A sixteenth embodiment is shown in FIG. 19 as a layer sequence. All layers are firmly connected again.
- a liquid measuring medium is fed through the opening 64 in the carrier 63 to the channel 69 and withdrawn again via the opening 65.
- the measuring medium flows through the channel 69 in the channel carrier 66.
- the liquid measuring medium is in contact with a reactive material which is introduced into the channel-shaped opening (reaction path 74) in the cover 71.
- Sensor elements and reference electrodes which measure the substance concentration before and after the reaction zone, are again introduced in the openings 72, 73.
- a polymer, gel or hydrogel with immobilized enzymes, antibodies or microorganisms can be used as the reactive material. If, for example, there are oxygen-consuming microorganisms in the reaction zone and the sensor elements in the openings 72, 73 are designed as oxygen sensors, a sensor system for the biological oxygen requirement can be implemented.
- An arrangement according to FIG. 4 is shown in FIG. Here, the inflow and outflow of the carrier liquid is realized with the aid of a plastic block 76 with at least one channel 77, which is sealed against the carrier 1 with the aid of an O-ring 78.
- the membrane material 22 is sealed with an encapsulation layer 75 made of epoxy resin.
- FIG. 21 shows an arrangement according to FIG. 2, which is needle-shaped at the tip.
- the width of the needle probe is 0.1 to 5 mm.
- the channel 80 of the channel carrier can be seen under the membrane 79.
- sensor elements and reference electrodes are used in the openings 86, 87 of the cover 85.
- the carrier liquid can be supplied and discharged through the openings 88, 89.
- This needle-shaped design is suitable, for example, for piercing tissue.
- FIG. 22 shows a further exemplary embodiment of a sampling system designed according to the invention.
- the essential structure corresponds to the example already explained in the description of FIG. 4.
- At least one electrode 90 was additionally arranged in the channel 11 in order to achieve an electrochemical conversion there.
- the electrode (s) 90 can be applied, for example, by a known thin-film or screen printing method.
- Electrode (s) there is also a possibility (not shown in FIG. 22) of removing the electrode (s) from the side of the membrane opposite channel 11 12 to arrange.
- This electrode (s) can be applied, for example, as a metallic paste.
- the electrochemical conversion that can be achieved in this way allows a further improvement in the isolation of the analyte to be determined.
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- Chemical Kinetics & Catalysis (AREA)
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- Pathology (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
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- Investigating Or Analysing Biological Materials (AREA)
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Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19602861A DE19602861C2 (de) | 1996-01-28 | 1996-01-28 | Probenahmesystem für in Trägerflüssigkeiten enthaltene Analyte sowie Verfahren zu seiner Herstellung |
DE19602861 | 1996-01-28 | ||
PCT/DE1997/000192 WO1997027475A1 (de) | 1996-01-28 | 1997-01-28 | Probenahmesystem für fluidische und in fluiden enthaltene analyte sowie verfahren zu seiner herstellung |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0876605A1 true EP0876605A1 (de) | 1998-11-11 |
Family
ID=7783802
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP97914106A Withdrawn EP0876605A1 (de) | 1996-01-28 | 1997-01-28 | Probenahmesystem für fluidische und in fluiden enthaltene analyte sowie verfahren zu seiner herstellung |
Country Status (5)
Country | Link |
---|---|
US (1) | US6287438B1 (ja) |
EP (1) | EP0876605A1 (ja) |
JP (1) | JP2000505194A (ja) |
DE (1) | DE19602861C2 (ja) |
WO (1) | WO1997027475A1 (ja) |
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CN114728286A (zh) * | 2019-11-22 | 2022-07-08 | 皇家飞利浦有限公司 | 用于夹持活检组织的新型多功能流体装置 |
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DE19747875A1 (de) * | 1997-10-20 | 1999-05-06 | Meinhard Prof Dr Knoll | Verfahren zum Messen veränderlicher Größen und Vorrichtung zum Durchführen des Verfahrens |
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AU2001274558A1 (en) * | 2000-06-20 | 2002-01-02 | Kawamura Institute Of Chemical Research | Microdevice having multilayer structure and method for fabricating the same |
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US6572745B2 (en) * | 2001-03-23 | 2003-06-03 | Virotek, L.L.C. | Electrochemical sensor and method thereof |
US20030216677A1 (en) * | 2002-05-15 | 2003-11-20 | Li Pan | Biosensor for dialysis therapy |
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US7235164B2 (en) | 2002-10-18 | 2007-06-26 | Eksigent Technologies, Llc | Electrokinetic pump having capacitive electrodes |
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DE10360714A1 (de) * | 2003-12-19 | 2005-07-21 | TransMIT Gesellschaft für Technologietransfer mbH | Nachfüllbare Mikrosonde |
US7666285B1 (en) * | 2004-02-06 | 2010-02-23 | University Of Central Florida Research Foundation, Inc. | Portable water quality monitoring system |
SE527292C2 (sv) * | 2004-08-25 | 2006-02-07 | Chemel Ab | Kalibrerbar genomflödesdetektor |
US8224414B2 (en) | 2004-10-28 | 2012-07-17 | Echo Therapeutics, Inc. | System and method for analyte sampling and analysis with hydrogel |
WO2006050031A2 (en) * | 2004-10-28 | 2006-05-11 | Sontra Medical Corporation | System and method for analyte sampling and analysis with error correction |
CA2602259A1 (en) | 2005-03-29 | 2006-10-05 | Arkal Medical, Inc. | Devices, systems, methods and tools for continuous glucose monitoring |
CN101356441B (zh) * | 2005-10-25 | 2011-06-15 | 株式会社岛津制作所 | 流通池及其制造方法 |
WO2007062182A2 (en) | 2005-11-23 | 2007-05-31 | Eksigent Technologies, Llp | Electrokinetic pump designs and drug delivery systems |
US20080058726A1 (en) * | 2006-08-30 | 2008-03-06 | Arvind Jina | Methods and Apparatus Incorporating a Surface Penetration Device |
US7867592B2 (en) | 2007-01-30 | 2011-01-11 | Eksigent Technologies, Inc. | Methods, compositions and devices, including electroosmotic pumps, comprising coated porous surfaces |
RU2444980C2 (ru) | 2007-03-07 | 2012-03-20 | Эко Терапьютикс, Инк. | Трансдермальная система мониторинга аналита и способы детекции аналита |
US8858681B2 (en) * | 2007-04-23 | 2014-10-14 | W. L. Gore & Associates, Inc. | Patterned porous venting materials |
EP2027812A1 (de) * | 2007-08-24 | 2009-02-25 | F. Hoffman-la Roche AG | Verfahren zur Herstellung eines Mikrodialysekatheters und durch dieses hergestellter Mikrodialysekatheter |
WO2009076134A1 (en) | 2007-12-11 | 2009-06-18 | Eksigent Technologies, Llc | Electrokinetic pump with fixed stroke volume |
WO2012091540A1 (en) * | 2010-12-29 | 2012-07-05 | Mimos Berhad | Integrated microfluidics sensor |
DE102011009854A1 (de) * | 2011-02-01 | 2012-08-02 | Erwin Quarder Systemtechnik Gmbh | Sensoreinrichtung zur Messung von Eigenschaften von Analyten |
EP2704759A4 (en) | 2011-05-05 | 2015-06-03 | Eksigent Technologies Llc | COUPLING GEL FOR ELECTROCINETIC FLUID DISTRIBUTION SYSTEMS |
KR101325676B1 (ko) | 2011-12-02 | 2013-11-06 | 서강대학교산학협력단 | 미세채널 내의 이온선택성 멤브레인 형성방법 및 미세채널 장치 |
CN102631957B (zh) * | 2012-04-13 | 2014-06-25 | 北京大学 | 带有栅压调制功能的超薄封装微流体系统及其制备方法 |
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DE102016110696A1 (de) | 2016-06-10 | 2017-12-14 | Endress+Hauser Conducta Gmbh+Co. Kg | Verfahren zur Herstellung einer Sensorkappe mit einer Membran |
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-
1996
- 1996-01-28 DE DE19602861A patent/DE19602861C2/de not_active Expired - Fee Related
-
1997
- 1997-01-28 JP JP9526445A patent/JP2000505194A/ja active Pending
- 1997-01-28 WO PCT/DE1997/000192 patent/WO1997027475A1/de not_active Application Discontinuation
- 1997-01-28 US US09/117,077 patent/US6287438B1/en not_active Expired - Fee Related
- 1997-01-28 EP EP97914106A patent/EP0876605A1/de not_active Withdrawn
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Title |
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See references of WO9727475A1 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114728286A (zh) * | 2019-11-22 | 2022-07-08 | 皇家飞利浦有限公司 | 用于夹持活检组织的新型多功能流体装置 |
CN111604098A (zh) * | 2020-06-04 | 2020-09-01 | 天津德祥生物技术有限公司 | 侧面加样微流控芯片 |
Also Published As
Publication number | Publication date |
---|---|
JP2000505194A (ja) | 2000-04-25 |
DE19602861C2 (de) | 1997-12-11 |
DE19602861A1 (de) | 1997-07-31 |
WO1997027475A1 (de) | 1997-07-31 |
US6287438B1 (en) | 2001-09-11 |
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