EP0980515A1 - Dispositif de detection de biomolecules et de substances dissoutes dans des liquides - Google Patents

Dispositif de detection de biomolecules et de substances dissoutes dans des liquides

Info

Publication number
EP0980515A1
EP0980515A1 EP98924275A EP98924275A EP0980515A1 EP 0980515 A1 EP0980515 A1 EP 0980515A1 EP 98924275 A EP98924275 A EP 98924275A EP 98924275 A EP98924275 A EP 98924275A EP 0980515 A1 EP0980515 A1 EP 0980515A1
Authority
EP
European Patent Office
Prior art keywords
unit
analysis unit
sampling
processes
sampling system
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Withdrawn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
EP98924275A
Other languages
German (de)
English (en)
Inventor
Albet Stumpf
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of EP0980515A1 publication Critical patent/EP0980515A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/22—Devices for withdrawing samples in the gaseous state
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/405—Concentrating samples by adsorption or absorption
    • 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
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02E—REDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION
    • Y02E50/00—Technologies for the production of fuel of non-fossil origin
    • Y02E50/30—Fuel from waste, e.g. synthetic alcohol or diesel

Definitions

  • the present invention relates to a device for determining biomolecules and solutes in liquids, comprising a sampling system which can be brought into direct contact with the liquid to be analyzed within a vessel, in particular within a bioreactor, and an analysis unit.
  • the invention relates to a novel device with which biomolecules and solutes in liquids of sterile processes can be determined qualitatively and quantitatively and which represents a compact combination of a sampling system and an analysis unit, which takes place immediately after the sampling and thus quasi simultaneous measurement and at the same time a reduction of the infection risk to a minimum.
  • the device is suitable for use in all areas in which bioprocesses, in particular biotechnological and enzyme-technological production processes, are involved and high demands are placed on sterile process conditions.
  • the advantages of the invention can therefore be used in particular in food production, the production of pharmaceuticals, carboxylic acids, solvents, enzymes and amino acids, in processes of environmental biotechnology and in the production of active substances with recombinant cells or enzymes.
  • both the sampling system and the actual measuring unit are located outside the reactor.
  • Sampling and processing usually takes place using separation processes such as microfiltration, dialysis, electrolysis and gas diffusion; alternatively, the sample solution can also be freed from microorganisms and undissolved parts by the action of degrading enzymes, such as proteases.
  • the sample which has been prepared and possibly adapted to the corresponding analysis method, is then fed to the actual analysis unit.
  • a sterilisable sampling system integrated in the reactor for example a sterilisable membrane module
  • sampling and measurement take place spatially separated from one another in conventional systems.
  • the transfer of the sample from the reactor to a measuring unit not only results in a considerable risk of infection, but also in one unwanted time delay.
  • drastic changes in the sample to be measured can sometimes occur, which lead to incorrect analysis results and therefore do not allow meaningful control of the culture liquid in the reactor.
  • the immersion dialyzer described therein comprises a removable dialysis head with membrane holder and inlet and return channels extending through the dialysis head, as well as a mounting tube detachably connected to the dialysis head, through which the immersion dialyzer can be attached to the fermenter or a bypass.
  • a buffer solution previously supplied via the feed lines to the membrane which now contains the dialyzable materials from the culture liquid, can be withdrawn via a return line and then via tubes which connect the immersion dialyzer to an analysis device, an analysis unit, for example one automatic analyzer.
  • an analysis unit for example one automatic analyzer.
  • German Offenlegungsschrift 195 33 510 discloses a probe for removing dissolved gases or volatile components from liquids in order to determine their concentration in these liquids.
  • the device disclosed in this citation embodies a combination of a probe and a sensor, apart from the fact that the sensor used is exclusively designed for the quantification of gases, such as tin dioxide, and for this purpose it meets special requirements must not mention sterile processes and their particular problems and requirements at any point.
  • the object of the present invention is therefore to provide a probe suitable for the sterile process control, which overcomes the disadvantages of conventional control instruments, in particular shortens the time between sampling and the presence of the analysis result and reduces or completely excludes the risk of infection to a minimum.
  • the device according to the invention for the determination of biomolecules and solutes in liquids of sterile processes, which is a combination probe in which a sampling system in direct contact with the liquid to be analyzed within a bioreactor and an analysis unit as a compact Unit are present and as such are connected to the bioreactor.
  • the device can also be used to control processes in other vessels, e.g. Whirlpools are used in brewing processes etc.
  • the term "bioreactor” is not limited to classic fermenters in the context of this invention, but rather generally includes vessels in which material conversions taking place in liquids can be measured and monitored.
  • the device After the device according to the invention has been connected to the bioreactor, which can be carried out in a conventional manner, for example by means of a thread, the device can be subjected to a sterilization treatment together with the bioreactor.
  • the device can be sterilized both in a liquid and with steam at usual temperatures, usually at least 120 ° C.
  • the device more precisely the analysis unit arranged outside the bioreactor, can be equipped with one or more biosensors. After the sensor has been calibrated, the device is immediately ready for operation.
  • biosensors are to be understood in the usual sense, i.e. as a combination of bioactive components, e.g. immobilized biocatalysts, and a physical or physicochemical sensor (transducer) that delivers a signal in the presence of substrate as a measure of the substrate content.
  • bioactive components e.g. immobilized biocatalysts
  • transducer a physical or physicochemical sensor
  • the bioactive components are analytes that are able to "recognize” the substance to be analyzed.
  • Receptors, antibodies, enzymes, organelles, tissue sections or whole prokaryotic or eukaryotic cells are suitable for specific recognition.
  • Enzyme sensors, immunosensors and microbial sensors are currently commercially available.
  • biosensor is suitable for use in the combination probe according to the invention.
  • the bioactive component only has to be in a form that enables use in the analysis unit of the device.
  • conventional biosensors are available in the form of chips, measuring modules, bio-capsules or the like. on.
  • bioaffinity sensors can be used who usually use dyes, lectins, antibodies or hormone receptors for specific recognition.
  • the changes caused by the binding or complex formation are displayed as measurable quantities.
  • So-called metabolism sensors which are based on the specific detection of substrates and their chemical conversion to corresponding products, are also particularly suitable. These include enzyme electrodes, organelle sensors, microbial sensors and generally sensors based on biocatalytically active materials. A coupled analysis method with several enzymes is also often indicated, which may also include the detection of cofactors.
  • biosensors of the biomimetic type can be used, simulate the function of sensory organs and recode physical signals such as strain or light into chemical signals.
  • enzymatic and immunological methods can be coupled with one another, especially if particularly low concentrations of a substance are to be determined. The so-called ELISA detection (enzyme-linked immunosorbent assay) should be mentioned here.
  • bioactive substance in particular a receptor, antibody or enzyme
  • the analyte can be bound directly to the transducer surface or applied directly to the electronic element that converts or amplifies the signals.
  • Numerous biosensors which are arranged for the detection of various substances and are suitable for use in the device according to the invention, are already available. Buchholz K. and Kasche V., for example, in “Biocatalysts and Enzyme Technology", VCH, Weinheim, 1997, provide a current overview, particularly with regard to affinity biosensors.
  • the device according to the invention can be sterilized together with the bioreactor, only those materials can be used for its production which can be subjected to a sterilization treatment and preferably withstand temperatures of at least 120 ° C. and particularly preferably up to 150 ° C.
  • the materials used should be resistant to oxidation and corrosion.
  • all parts of the device that are to be subjected to a sterilization treatment must withstand the resulting sterilization pressure, which can be up to 1.5 bar.
  • Further requirements for the materials used for the production result from the fact that the sampling unit is in direct contact with the liquid to be analyzed in the bioreactor. At least the sampling unit should therefore have an inert surface.
  • Sterilizable and inert materials include stainless steel and plastics, especially polytetrafluoroethylene.
  • the sampling unit can have a conventional structure and, for example, in the form of the German one
  • the device according to the invention comprises at least two channels, a feed and a return channel, which extend from the end of the contact with the liquid to be analyzed in the bioreactor Extend the sampling unit through the entire device, ie in any case beyond the sampling unit into the analysis unit.
  • the sample taken is preferably led to the biosensor.
  • Sampling can take place via a dialysis membrane which is attached to the end of the unit which projects into the reactor.
  • the dialysis membrane is preferably part of a dialysis head which is detachably connected to the part of the device which is connected to the wall of the bioreactor.
  • the dialysis head also has at least two channels incorporated therein (feed and return channels), which are detachably connected to the channels or lines of the device.
  • feed and return channels A tight and tight connection of the dialysis head with the rest of the device can be achieved, for example, by ring grooves at the lower end of the dialysis head, into which rubber or plastic O-rings can be inserted.
  • the channels or lines of the device can be connected to the channels of the dialysis head, for example via plug-in or threaded connections.
  • the front end of the sampling unit - the front of the dialysis head when using a removable dialysis head - can be provided planar and possibly with a raised edge area, but preferably has a conically shaped and more preferably a rounded tip.
  • the tip can have longitudinal and transverse grooves for better distribution of the buffer solution in contact with the membrane.
  • the front end of the sampling unit - if a removable dialysis head is used, the front end of the dialysis head - has membrane membrane in the form of one or more ring grooves running around the circumference of the unit or dialysis head, into which rubber O-rings can be inserted. which define the dialysis membrane pulled over the tip of the sampling unit or the dialysis head.
  • the grooves should not have any sharp edges that could damage the sensitive dialysis membrane.
  • the dialysis membrane is thus removably attached to the front end of the sampling unit, preferably at the front end of the removable dialysis head, by means of a membrane holder.
  • the channels extending through the device and possibly the removable dialysis head are preferably arranged in such a way that they end at different points on the tip of the device or dialysis head, as a result of which the buffer solution guided past the dialysis membrane covers as large an area as possible.
  • the channels and the lines connected to them usually have an inside diameter of 0.1 to 3 mm and preferably between 0.8 and 1.3 mm.
  • ultrafiltration or microfiltration membranes can also be used.
  • In-situ filters are also particularly suitable for the removal of dissolved gases, but also for the removal of high-molecular compounds.
  • Any suitable membrane can be used as the membrane, for example membranes made of cellulose or plastics, Teflon, PVC, silicone, generally ceramic or polymeric membranes.
  • the sampling unit or the removable dialysis head additionally has one Dialysis membrane on a depth filter, which is particularly suitable for sampling higher and lower molecular weight substances.
  • a depth filter in combination with a pulsation method, by means of which turbulent flows are generated over the surface of the filter, through which the filter surface is cleared of deposits. This prevents the filter from being clogged, particularly at high media densities.
  • the use of a pulsation method allows sampling even over a long period of time, despite the high density.
  • the filter can also be kept free by the temporary or continuous generation of vibrations or oscillations of the part of the apparatus projecting into the reactor or a part thereof.
  • the device comprises at least three channels, i.e. at least one feed and return channel for dialysis and at least one further channel through which the filtrate is led from the filter into the part of the device outside the reactor becomes. If the depth filter is used alone, the device only has to have at least one channel which feeds the filtered sample to the analysis unit, and preferably there to the biosensor.
  • the device according to the invention is preferably sterilized together with the fermenter in the installed state, when a sensitive membrane is used, it must be protected against bursting by pressure overlay. This is done by closing the interior of the bioreactor during the sterilization phase one or more valves arranged in the device is closed to the outside.
  • This so-called in-situ bridge ensures that the pressure builds up equally on both sides of the membrane during sterilization, so that there is no fear of damage to the membrane.
  • the pressure overlay achieved by the in-situ bridge is removed by opening the valve or valves.
  • the in-situ bridge should not only be used when using membranes, but also when using filters for pressure overlay, in order to prevent the filter from clogging or sticking during the sterilization treatment.
  • the in-situ bridge can be brought about by any suitable valve, for example a shut-off valve, changeover / diverter valve, for example a 3-way valve, stamped valve, in the form of a solenoid, pneumatic or manually operated valve.
  • a shut-off valve for example a 3-way valve, stamped valve
  • the position of the valve within the device possibly within the combination of device and dialysis head, only has to meet the requirement that the opening / closing of the valve on the part of the device lying outside the bioreactor after connecting the device to the bioreactor or can generally be accomplished from outside the reactor.
  • the locking within the device can, however, also take place within the part of the device which projects into the reactor.
  • the inlet and return channels or lines of the device are connected at the rear end of the analysis unit with suitable lines, for example rubber or plastic hoses.
  • suitable lines for example rubber or plastic hoses.
  • These can include the supply of liquids, especially buffer solutions, and the removal of the samples, serve, for example, for additional analysis devices. If a sample is not to be supplied to the biosensor, or is not to be supplied entirely, but rather, in whole or in part, is to be passed directly to an analysis device (eg mass spectrometer or flow injection analysis) outside the device according to the invention, this can be done via additional lines or discharge lines and corresponding valves within the part of the device present outside the reactor can be reached.
  • an analysis device eg mass spectrometer or flow injection analysis
  • the buffer solution of suitable composition required for dialysis and / or filtration is fed via the feed lines into the feed channels and from there to the front end of the sampling unit.
  • the dialysable or filterable substances present in the medium to be analyzed are taken up in the buffer stream via dialysis or filtration and then transported to the analysis unit via the return channels and lines.
  • the buffer stream can also be passed directly to an analyzer present outside the device.
  • the flow rate of the buffer stream can be regulated so that the substances to be determined are in equilibrium on both sides of the membrane or the filter.
  • the analysis unit of the device can be supplemented by a temperature device in order to compensate for temperature changes and to be able to counteract erroneous measurement results caused thereby.
  • the temperature can be regulated, for example, by a cooling coil or jacket cooling.
  • the device can be supplemented by an ultrasonic unit for cell disruption connected between the removal and analysis unit.
  • an ultrasonic unit for cell disruption connected between the removal and analysis unit. This enables the analysis of intracellular substances such as enzymes and other substances that have not been removed from the cells.
  • the analysis unit can be supplemented by a movable, preferably hinged casing.
  • a partial or complete sheathing of the front end of the sampling unit or of the dialysis head can, for example, be fan-shaped or (semi) bowl-shaped.
  • the casing lies tightly against the front end of the sampling unit or the dialysis head and can then be brought out and folded down by a device present outside the reactor.
  • the casing also fulfills a protective function for the sensitive membrane or filter when closed.
  • the device in particular the one or more biosensor units, is connected to a computer unit which enables continuous process monitoring and control.
  • the analysis data obtained can be forwarded by means of remote data transmission, which enables online monitoring and control of the process.
  • the particular advantage of the device according to the invention namely real-time measurement without the usual delays between sampling and analysis, comes into play in particular.
  • the signals generated by a plurality of biosensors are transmitted directly to a computer unit and recorded and evaluated in complex form.
  • the combination probe according to the invention enables the determination and analysis of all substances which can be separated from the medium by dialysis and / or filtration. This results in a particularly wide range of possible applications.
  • dissolved substances e.g.
  • undissolved substances e.g. proteins, enzymes, antibodies
  • breweries and distilleries e.g. for the determination of sugar, alcohol, carbon dioxide etc.
  • environmental biotechnology wastewater and exhaust gas purification, water treatment, biogas and sewage treatment plants
  • food production processes yeast production, cheese, dairy products
  • production of pharmaceuticals Carboxylic acids, solvents, proteins, enzymes, amino acids, in fish farming and water protection, in petrochemical and in general in chemical processes.
  • the device according to the invention can be used in all processes in which dialysable and / or filterable substances are to be detected, the device being particularly suitable for processes with high demands on sterile process conditions, such as, for example, methods for cultivating mammalian cells for the Production of high-quality pharmaceutical active ingredients and the active ingredient production with recombinant cells.
  • FIG. 1 shows a schematic sectional view of a first embodiment of the device according to the invention
  • FIG. 1 shows an embodiment of the combination probe according to the invention, which comprises a sampling unit (3) with a dialysis head (2) and an analysis unit (8), including the biosensor unit (9), which is in the installed state outside the bioreactor.
  • the device can be attached to the bioreactor by means of a screw thread (4).
  • the dialysis head (2) comprises a membrane (1) which is placed around the edge area and part of the dialysis head and is held on the dialysis head with the aid of a rubber ring.
  • An inlet channel (6a) and a return channel (7a) are incorporated at a distance from one another via the dialysis head, via which the buffer solution required for dialysis is supplied or removed. These channels (6a, 7a) are connected to the feed and return channels (6, 7) which extend through the sampling unit (3) to the analysis unit (8).
  • the buffer solution is fed to the dialysis membrane via the feed channels (6, 6a) and drawn off into the analysis unit via the return channels (7, 7a).
  • a buffer space is formed under the membrane (1), which is connected to the analysis unit (8) or the biosensor unit (9) comprised by the analysis unit via the feed and return channels mentioned.
  • the outer end of the device is formed by a screw cap (10) which closes off the analysis unit and ensures a firm and tight assembly of the device.
  • the analysis unit is equipped with a cover (11) located above the biosensor unit, which enables simple use of a biosensor, for example in the form of a chip or another biosensor module. The possibility of sterilizing the device together with the bioreactor is ensured by an in-situ bridge caused by a shut-off valve (5).
  • Fig. 2 shows the schematic view of a second Embodiment of the combination probe according to the invention, in which the sampling unit (3) comprises a depth filter (13) in addition to a dialysis membrane (1).
  • the head of the sampling unit comprising the membrane (1) and the depth filter (13)
  • a protective grille (12) is protected by a protective grille (12).
  • a buffer solution is fed to the dialysis membrane (1) via the feed line (6) and passed to the analysis unit (8) via the return line (7).
  • the buffer solution can be fed to the biosensor unit (9) by a corresponding setting of a 3-way valve (17) or can be fed via a return line (16) directly to an analysis device outside the device.
  • the biosensor unit is connected to a computer unit via a line (15).
  • the depth filter (13) is connected to the biosensor unit via a channel (14) through which the filtrate is conducted from the sampling unit to the analysis unit.
  • a channel (14) through which the filtrate is conducted from the sampling unit to the analysis unit.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

Ce dispositif de détection de biomolécules et de substances dissoutes dans des liquides comprend un système (3) de prélèvement d'échantillons qui peut être mis en contact direct avec le liquide à analyser à l'intérieur d'un récipient, notamment un bioréacteur, ainsi qu'une unité d'analyse (8). L'invention concerne notamment un dispositif d'un type nouveau qui permet de déterminer qualitativement et quantitativement des biomolécules et des substances dissoutes dans des liquides utilisés dans des processus stériles, et qui associe dans un dispositif compact un système de prélèvement d'échantillons et une unité d'analyse. On peut ainsi mesurer l'échantillon dès qu'il est prélevé et réduire le risque d'infection au minimum. Ce dispositif est utile dans tous les domaines dans lesquels des processus biologiques, notamment des processus de production biotechnologiques et enzymatiques, sont impliqués et des exigences strictes de stérilité s'imposent. L'invention est particulièrement avantageuse dans l'industrie alimentaire, pharmaceutique et chimique, pour mettre en oeuvre des procédés de biotechnologie de l'environnement et de production de principes actifs avec des cellules ou des enzymes recombinants.
EP98924275A 1997-05-05 1998-05-04 Dispositif de detection de biomolecules et de substances dissoutes dans des liquides Withdrawn EP0980515A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19718828 1997-05-05
DE19718828 1997-05-05
PCT/EP1998/002625 WO1998050774A1 (fr) 1997-05-05 1998-05-04 Dispositif de detection de biomolecules et de substances dissoutes dans des liquides

Publications (1)

Publication Number Publication Date
EP0980515A1 true EP0980515A1 (fr) 2000-02-23

Family

ID=7828598

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98924275A Withdrawn EP0980515A1 (fr) 1997-05-05 1998-05-04 Dispositif de detection de biomolecules et de substances dissoutes dans des liquides

Country Status (4)

Country Link
EP (1) EP0980515A1 (fr)
AU (1) AU7652698A (fr)
DE (2) DE19880595D2 (fr)
WO (1) WO1998050774A1 (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0989404B1 (fr) 1998-09-23 2008-06-25 WTW Wissenschaftlich-Technische Werkstätten GmbH & Co. KG Dispositif d'analyse d'eau et des eaux usées
DE102006045558A1 (de) * 2006-09-25 2008-04-03 Rwo Gmbh Wasseraufbereitungsanlage
DE102011085749B3 (de) * 2011-11-04 2013-02-21 Ums Gmbh Fluiddiffusionsmessvorrichtung
DE102019117446A1 (de) * 2019-06-27 2020-12-31 Schott Ag Multi-Sensor-Komponente zur Bioprozesskontrolle

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2650730C2 (de) * 1976-11-05 1979-03-29 Boehringer Mannheim Gmbh, 6800 Mannheim Tauchdialysator
DE2734247C2 (de) * 1977-07-29 1984-07-19 Fresenius AG, 6380 Bad Homburg Vorrichtung zur fortlaufenden chemischen Analyse im lebenden Körper
DE3516080A1 (de) * 1985-05-04 1986-11-06 Proton AG, Zug Probeentnahmesonde
CH673536A5 (fr) * 1986-03-04 1990-03-15 Ingold W Dr Ag
US5089112A (en) * 1989-03-20 1992-02-18 Associated Universities, Inc. Electrochemical biosensor based on immobilized enzymes and redox polymers
DE4028356A1 (de) * 1989-09-06 1991-03-07 Sartorius Gmbh Verfahren zur herstellung einer mikrofiltrationsmembran und nach diesem verfahren erhaltene membran
CA2011297A1 (fr) * 1990-03-01 1991-09-01 Anton G. Meiering Detecteur d'ethanol pour le controle informatise de la fermentation
AU6645494A (en) * 1993-04-29 1994-11-21 Danfoss A/S Device for analyzing a fluid medium
GB2289339B (en) * 1994-05-12 1998-09-16 Cambridge Life Sciences Flow-through electrochemical biosensor
DE19530886C1 (de) * 1995-08-11 1996-10-02 Inst Bioprozess Analysenmesst Vorrichtung zur sterilen Entnahme von Proben über eine Filtermembran
DE19533510C2 (de) * 1995-08-30 1997-07-24 Dirk Dr Thamm Vorrichtung zur Entnahme und Bestimmung gelöster Komponenten in Flüssigkeiten oder Gasen

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9850774A1 *

Also Published As

Publication number Publication date
WO1998050774A1 (fr) 1998-11-12
DE19880595D2 (de) 2000-07-27
AU7652698A (en) 1998-11-27
DE19819857C2 (de) 2000-08-31
DE19819857A1 (de) 1998-11-12

Similar Documents

Publication Publication Date Title
WO2007121887A2 (fr) Système d'analyses de procédés à prélèvement stérile de matériaux sensibles mécaniquement, à partir d'un bioréacteur
DE69816663T2 (de) Vorrichtung zur bestimmung von analyten in lösungen
DE3516080C2 (fr)
EP2044438B1 (fr) Installation pour des mesures en ligne sur des cellules
EP2499232B1 (fr) Dispositif et procédé pour traiter un moyen de filtration
EP0995098B1 (fr) Procede et dispositif pour prelever en serie des echantillons
DE19819857C2 (de) Vorrichtung zur Bestimmung von Biomolekülen und gelösten Stoffen in Flüssigkeiten
EP0821231B1 (fr) Appareil pour l'analyse de liquides
EP0476595A2 (fr) Système pour l'analyse du type à injection dans un écoulement
EP0905229B1 (fr) Procédé et dispositif pour déterminer et surveiller l'état physiologique de cultures microbiennes
EP1285249A1 (fr) Procede et dispositif pour determiner la concentration d'analytes
DE19921999C2 (de) Vorrichtung und Verfahren zur Überwachung und Kontrolle von biologisch aktiven Fluiden
DE4417078A1 (de) Vorrichtung zum Mikroskopieren
DE102005059536B4 (de) Verfahren und Biochip zur Untersuchung einer biologischen Probe
DE19605753C2 (de) Verfahren und Vorrichtung zur Detektion von stoffwechselaktiven, unlädierten, ungestressten Mikroorganismen - quantitativ und qualitativ im "Sub-ppb-Bereich" innerhalb von Minuten
DE2828525A1 (de) Chemisches analyseverfahren und vorrichtung zu dessen ausfuehrung
WO2019110185A1 (fr) Dispositif et procédé d'analyse d'un milieu
DE19950341C1 (de) Vorrichtung zum Abscheiden von Mikroorganismen aus Mikroorganismen-enthaltenden Gasen und ihre Verwendung
DE2655265C3 (de) Verfahren zur automatischen Vorbereitung von aus Zellsuspensionen bestehenden Proben zum Zwecke der nachfolgenden Bestimmung intra- und/oder extrazellulärer Stoffe durch eine kontinuierlich aufeinanderfolgende Behandlung einer Mehrzahl von Proben
DE3519265A1 (de) Reaktorgekoppelte filtrationsanlage mit automatischem probeneinlass zur aufbereitung und analyse von proben aus fermentationsprozessen
DE102007034935B4 (de) Anordnung für Online-Messungen an Zellen
DE10134656B4 (de) Mobile Analytik zur VFA Bestimmung
DE19917955A1 (de) Verfahren und Vorrichtung zur Überwachung aerober umweltbiotechnologischer Prozesse
DE3811099A1 (de) Verfahren zum nachweis von verbindungen, die katalysiert durch oxidase elektronen aufnehmen oder abgeben koennen
WO2011085791A1 (fr) Procédé de préparation d'échantillons en ligne dans la zone de haute pression de hplc à l'aide d'ultrasons

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19991206

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: SI PAYMENT 19991206

GRAG Despatch of communication of intention to grant

Free format text: ORIGINAL CODE: EPIDOS AGRA

17Q First examination report despatched

Effective date: 20010209

GRAG Despatch of communication of intention to grant

Free format text: ORIGINAL CODE: EPIDOS AGRA

GRAH Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOS IGRA

GRAH Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOS IGRA

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20021203