EP1285249A1 - Procede et dispositif pour determiner la concentration d'analytes - Google Patents
Procede et dispositif pour determiner la concentration d'analytesInfo
- Publication number
- EP1285249A1 EP1285249A1 EP01938233A EP01938233A EP1285249A1 EP 1285249 A1 EP1285249 A1 EP 1285249A1 EP 01938233 A EP01938233 A EP 01938233A EP 01938233 A EP01938233 A EP 01938233A EP 1285249 A1 EP1285249 A1 EP 1285249A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- detector
- diffusion
- medium
- analyte
- sampling
- 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- Withdrawn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
- 239000012491 analyte Substances 0.000 title claims abstract description 70
- 238000000034 method Methods 0.000 title claims abstract description 43
- 238000009792 diffusion process Methods 0.000 claims abstract description 117
- 238000005070 sampling Methods 0.000 claims abstract description 79
- 239000012530 fluid Substances 0.000 claims abstract description 41
- 239000012528 membrane Substances 0.000 claims abstract description 19
- 239000007788 liquid Substances 0.000 claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims description 29
- 238000005259 measurement Methods 0.000 claims description 29
- 238000004458 analytical method Methods 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 11
- 238000011144 upstream manufacturing Methods 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 238000001514 detection method Methods 0.000 claims description 6
- 238000011156 evaluation Methods 0.000 claims description 6
- 238000002474 experimental method Methods 0.000 claims description 6
- 230000002123 temporal effect Effects 0.000 claims description 6
- 238000012360 testing method Methods 0.000 claims description 6
- 230000002452 interceptive effect Effects 0.000 claims description 5
- 239000000758 substrate Substances 0.000 claims description 4
- 238000009530 blood pressure measurement Methods 0.000 claims description 2
- 238000012937 correction Methods 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000000523 sample Substances 0.000 abstract description 19
- 238000000502 dialysis Methods 0.000 description 9
- 230000002950 deficient Effects 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000011157 data evaluation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 206010013496 Disturbance in attention Diseases 0.000 description 1
- 108010093096 Immobilized Enzymes Proteins 0.000 description 1
- 108010085603 SFLLRNPND Proteins 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
- G01N35/085—Flow Injection Analysis
-
- 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
- G01N1/10—Devices for withdrawing samples in the liquid or fluent state
- G01N1/14—Suction devices, e.g. pumps; Ejector devices
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
- G01N35/1097—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers characterised by the valves
Definitions
- the present invention relates to a method for the determination of substrate and product concentrations in liquid and / or gaseous media, in which several samples of at least one substance to be analyzed - the analyte - in several sampling sections by time-controlled diffusion of the at least one analyte between the respective medium and a diffusion medium, which is fed to the sampling sections through fluid line sections by means of at least one pump, is removed via semipermeable membranes and then the diffusion medium is transported from the sampling sections to at least one detector, while the new diffusion medium is supplied, and is analyzed by the latter to determine the analyte concentration, the pump works continuously and the diffusion medium is alternately supplied to the fluid line sections via a multi-way or multi-way valve arrangement upstream of the sampling sections. Furthermore, the invention relates to a device for performing the method.
- BESTATIGUNGSKOPIE technology it is necessary and desirable to simultaneously measure the concentration of certain substances in a large number of reaction batches, with online analysis in particular being of particular importance.
- Known approaches in this connection consist in assigning a sensor arrangement with a complete measuring section to each reaction container, sensors being used which can be introduced directly into the reaction vessel or into a fluid stream escaping from it.
- the prerequisite here is that the sensor can come into direct contact with the medium in which the concentration of a substance is to be measured, ie is not attacked by the medium, and furthermore the boundary conditions, for example the pH value and the temperature direct application and in the undiluted medium allow a sufficiently precise measurement.
- Many sensors do not meet these technical requirements. For example, in the case of sensors with immobilized enzymes, the instability of the enzyme, especially at higher temperatures (steam sterilization) and the limited measuring range, prevent direct application. For these reasons, the detectors are arranged outside the reaction vessels in known online analysis devices.
- Sampling is carried out regularly by taking media volumes from the reaction containers to be sampled and feeding them to an analysis device or detector via transport lines. Frequent volume removal is only possible in containers in which the volume withdrawn is very small compared to the reaction volume. The means that with this sampling strategy the frequency and the extent of the sampling depend on the reaction volume and is directly limited by it.
- DE 197 29 492 A1 proposes to carry out the sampling by time-controlled diffusion of the analyte from the medium to be sampled into an acceptor liquid via dialysis tubes.
- concentration of the analyte in the diffusion medium and thus the sampling is controlled via the diffusion time.
- This procedure has the advantage that only molecules are removed from the medium, but no volume of media. Sampling is therefore only limited by the total amount of substance and not by the reaction volume.
- the acceptor liquid is transported through the system by means of a pump. This is switched off after the dialysis tubing has been filled with fresh acceptor liquid, so that analytes which are present in higher concentrations in the reaction area are diffusively absorbed into the acceptor liquid via the wall of the dialysis tubing.
- This procedure therefore requires control of the pump, which must be switched on and off, and, in addition, control of valves which may be arranged in the sampling sections.
- Talanta, Vol. 49 (1999) pp it is proposed in Talanta, Vol. 49 (1999) pp.
- the object of the invention is therefore to develop a method of the type mentioned at the outset in such a way that rows of analysis can be carried out effectively with little effort.
- detector and the pump are additionally connected by a bypass line, which is connected in particular to the valve arrangement, and the diffusion medium is fed continuously to the detector via the fluid line sections and the bypass line.
- a bypass line is thus provided, via which diffusion medium is guided from the pump past the sampling sections to the detector.
- This bypass can also be via the Multi or multi-way valve arrangement and alternatively to the sampling sections can be controlled.
- the diffusion medium can be passed through this bypass line if no sampling section is to be flowed through. In this way, the pump can run, it is no longer necessary to switch it on and off. It is also possible to inject a 'standard medium in the diffusion medium in the region of the bypass and transporting that segment by connecting the bypass to the detector. If this procedure is carried out repeatedly before and during the test period, drift phenomena of the detector can be corrected.
- rinsing liquid can be fed to the detector via the bypass line.
- a particularly efficient sampling is achieved if in the parallel sampling sections the diffusion or sampling time of a section is at least the measurement time of all other parallel sampling sections necessary for signal detection in the detector.
- the diffusion times are thus coordinated in such a way that the measurements for the other sampling sections can be carried out simultaneously one after the other during the sampling in a section and then the measurement of the sample can then directly follow the diffusion. This results in particularly high effectiveness and flexibility.
- a pressure measurement is carried out in the line for the diffusion medium upstream of the sampling sections in order to detect a fault in a line section.
- check valves or alternatively a further multi-way or multi-valve arrangement can be provided downstream of the sampling sections, which prevents a diffusion medium from flowing back from the sampling section into another sampling section.
- several detectors can be provided connected in series for the simultaneous measurement of different analytes. Since experience has shown that the detectors can also fail or drift strongly, it can also be expedient to provide a plurality of detectors for the same analyte in parallel sections, which can be switched in if a detector fails.
- different detectors can also be connected in parallel via a multi-way or multi-valve arrangement, which opens up the possibility of determining different analytes at different times. Such an interconnection is useful, for example, in the case of detectors which influence one another in their measuring methods.
- the device can contain a sample preparation module connected upstream of the detector, which module either absorbs interfering components from the diffusion medium (for example activated carbon) or reactively converts them into a non-interfering chemical form.
- a sample preparation module connected upstream of the detector, which module either absorbs interfering components from the diffusion medium (for example activated carbon) or reactively converts them into a non-interfering chemical form.
- the diffusion medium for example activated carbon
- there are also detectors that require a sample preparation module so that the analyte is converted into a detectable form for example enzyme or color reactions and photometric measurement method.
- a diffusion medium is preferably used which is essentially free of the analytes to be detected, so that the concentration gradient across the semi-permeable membranes from the medium to be sampled to the diffusion medium. ion medium is high.
- the analyte concentration in the medium to be sampled falls below the detection limit of a detector, it can also make sense to use a diffusion medium which contains a known concentration of the analyte or analytes which is above the low concentration in the medium. Then, in the area of the sampling section, the analyte diffuses into the medium and the concentration loss is measured over the diffusion time in the diffusion medium and used to determine the analyte concentration in the medium to be sampled.
- the diffusion medium can be disposed of after the analysis has been carried out. Alternatively, it is also possible to collect the samples in an automatic fraction collector for later off-line analysis.
- the components of a sample are quantified by the supply line to the corresponding detectors. Since the measurement of the diffusively obtained sample segment is a relative measurement method, the measurement signals from unknown concentrations can only be determined in comparison with a standard mixture sampled by diffusion under practical conditions.
- the provision of a standard solution in which a further semipermeable membrane is immersed separately from the other sampling points, as is known from DE 197 29 492 AI, is not sufficient for such a calibration if the selected semipermeable membranes do not have exactly the same properties as for example the same length, surface and have wall thickness.
- the semipermeable membranes are immersed in media of known analyte concentration for calibration and that measurement data sets are created on the basis of which the measurement results supplied by the detector are evaluated to determine the analyte concentration.
- Standard concentrations can also be set directly in the reaction containers, in particular in the case of sterile requirements. This prevents frequent media changes and expensive sterilization measures in the containers.
- known concentrations of at least one analyte are adjusted into the preferably analyte-free medium by adding correspondingly calculated volumes of a concentrated standard mixture of the analyte. This results in a concentration that is known from the metering.
- the reaction containers are sampled in the manner described above and corresponding measurement data records are created. A further metering of standard mixture into the reaction medium and subsequent measurement can be repeated until the maximum concentration of the analyte desired by the user is reached. In this way, the expected measuring range of the analyte can be covered during the experiment.
- the detector used can already be set internally or pre-calibrated so that it directly determines the analyte concentrations in the samples passed through, which were obtained by the diffusion in the sampling sections, ie the device delivers the analyte concentration present in the diffusion medium without further conversion.
- the device delivers the analyte concentration present in the diffusion medium without further conversion.
- the detector can provide a temporal concentration distribution or a temporal distribution of a signal proportional to the concentration, the calibration and a corresponding evaluation of the detector signals then being used to draw conclusions about the analyte concentration in the sample medium.
- the maximum rise in the leading edge of the detector signal, the signal maximum, the area under the signal curve or the increased baseline after the flow of the peak maximum, which results from the diffusion of the analyte at a constant flow (volume flow) into the diffusion medium, can be used for the evaluation.
- a change in the ratio of the signal maximum to the baseline in the outflow of the detector signals are determined and a change in the diffusion properties of the semipermeable membranes is deduced therefrom and a corresponding correction factor is determined and taken into account in the further execution.
- any drift caused by changes in the diffusion properties for example due to blockages or deposits (fouling), can be taken into account via the data evaluation.
- the single figure shows a schematic representation of a device for determining substrate and product concentrations in liquid and / or gas. medium 2.
- the device has a plurality of reaction containers 1, each of which contains a gaseous or liquid medium 2 to be analyzed.
- the reaction vessels 1 can be shaking flasks, for example, which are kept in constant motion.
- the analysis is intended to measure the concentrations of substances, of educts or of reaction products, hereinafter referred to as analytes, within the medium.
- each reaction container 1 at least one sampling module 3 is inserted, which has a semipermeable membrane 4, which here is in the form of a dialysis tube and is completely immersed in the medium 2 contained in the reaction container 1.
- the dialysis tubes 4 are arranged in the manner of a parallel connection and are connected via fluid lines 5 on the inlet side to a pump 6 and on the outlet side to a detector 7.
- the pump 6 is connected to a storage container 8 for receiving a diffusion medium suitable for diffusion sampling, which can be gaseous or liquid depending on the physical state of the medium 2 to be sampled.
- a bubble trap 9 is provided downstream of the pump 6 and is used to remove bubbles from liquid diffusion medium.
- a pressure sensor 10 is provided which measures the line pressure.
- the fluid line section 5a coming from the pump 3 opens into a media distributor 11, on the outlet side of which the parallel fluid line sections 5b with the sample Take modules 3 are connected, and between the media distributor 11 and the sampling modules 3, a multi-valve arrangement 12 is provided, through which the parallel fluid line sections 5b can be opened for a flow of diffusion medium or closed to prevent such a flow.
- the sampling modules 3 open via the parallel fluid line sections 5b into a media collection module 13, which has an outlet 5c on the outlet side, which leads to the detector 7 and an outlet behind it into a suitable waste reservoir 14 or another type of discharge for the diffusion medium.
- a sample preparation module 16 which absorbs interfering components from the diffusion medium or reactively converts them into a non-interfering chemical form, is provided in the flow 5c, viewed in the direction of flow, in front of the detector 7. Alternatively or additionally, the sample preparation module 16 can also serve to convert the analyte into a form that can be detected by the detector 7.
- the signal output of the detector 7 is connected via a measuring amplifier 17 to a computer 18 which evaluates the measuring signals coming from the detector 7 and also controls the valves of the multi-valve arrangement 12 and the delivery speed of the pump 6.
- Ren check valves 19 are provided, which should prevent leakage in a fluid line section 5b that diffusion medium, which comes from a sampling module 3, instead of back to the detector 7 flows back into the defective line section 5b.
- a bypass line 20 is connected via a further valve of the multi-valve arrangement 12, through which diffusion medium can be guided from the pump 6 past the sampling sections 5b to the detector 7.
- the baseline (baseline) of the detector 7 can be determined when fresh diffusion agent flows through it, or the detector 7 can be rinsed with a rinsing medium using, for example, another pump which is only connected to the bypass 20.
- the bypass additionally provides the possibility of introducing a sample segment of a standard mixture, which is contained in a storage container 22, into the flow of the diffusion medium via a three / two-way valve 21 or another type of injection valve.
- a suitable diffusion medium is pumped into the system until the fluid lines 5 and the dialysis tubes 4 are completely filled with the diffusion medium.
- sampling is carried out in each case by closing the valve of the multi-valve arrangement 12 upstream of the corresponding fluid line section 5b while the pump 6 is continuously operating, so that the diffusion medium rests in the sampling module 3 of this fluid line section 5b. This state is maintained for a predetermined period of time so that the concentrations of the analyte in the medium to be sampled, which is contained in the reaction container 1, and the diffusion medium are equalized by diffusion.
- an amount of analyte which is characteristic of the concentration of the analyte in the medium accumulates in the diffusion medium within the predetermined time period. If the analyte concentration in the diffusion medium is higher, analyte depletion takes place in the opposite way due to the diffusion taking place. In contrast to filtration, it is advantageously achieved that the volume of the medium contained in the reaction container 1 remains essentially unchanged.
- this fluid line section 5b is opened again, so that the diffusion medium contained in the dialysis tube 4, enriched or depleted with analyte, is transported to the detector 7 and at the same time new diffusion medium flows into the fluid line section 5b.
- the sample segment is analyzed when flowing through the detector 7, the detector 7 emitting measurement signals to the computer, which the correspond to the respective concentrations of the analyte in the assigned reaction containers 1. The manner in which the evaluation is carried out will be explained below.
- sampling by diffusion between the medium 2 contained in the respective reaction container 1 and the diffusion medium can take place in all sampling modules 3 and an analysis can then be carried out by the segment of the diffusion medium which has been subjected to diffusion in the sampling module 3 , transported to the detector 7 and analyzed as it flows through it.
- the analysis of the sample segments obtained in the individual sampling sections takes place alternately one after the other, ie with a time delay.
- the measuring times are determined in such a way that the measuring or transport time in one of the parallel fluid line sections 5b is equal to the sum of the diffusion times of the other parallel lines, or vice versa Way, the diffusion or sampling time of a section is at least the measurement time necessary for signal detection in the detector of all other parallel sampling sections.
- the diffusion times, on the one hand, and the measuring times, on the other hand are coordinated with one another in such a way that, with the exception of a few delays due to circuitry, one of the parallel fluid line sections 5b flows continuously and accordingly the segment of the diffusion medium that was previously exposed to diffusion is analyzed.
- the detector can already be internally set or precalibrated so that it directly determines the analyte concentrations in the samples passed through from the sampling modules 3, i.e. it delivers the analyte concentration present in the diffusion medium without further conversion. On the basis of these analyte concentrations, it is possible arithmetically to draw conclusions about the analyte concentration contained in the medium being sampled on the basis of series of measurements obtained in the course of a calibration carried out beforehand.
- the detector can provide a temporal distribution of the concentration of the sample in the flow (residence time curve) or a temporal distribution of a signal proportional to the concentration.
- a conclusion can be drawn on the analyte concentration in the sample medium based on the signal supplied by the detector, various properties such as the peak maximum, a slope of the leading edge, the surface being used for the evaluation below the curve, the baseline in the downstream of the curve etc. can be used. Since such analysis methods are known in principle, we shall not go into them in detail. For the sake of completeness, reference is made to the disclosure content of DE 197 29 492 AI in this regard.
- the analyte concentration in the diffusion medium is measured and the unknown analyte concentration in the sample medium 2 is then deduced. Since this is a relative measuring method, a pre-calibration must be carried out in which the analyte concentration in the diffusion medium is related to the analyte concentration in the medium 2 to be sampled.
- each sampling module 3 is immersed in at least one medium with a known analyte concentration. With the same diffusion times and different settings of a device as in the planned experiment, the measurement is now carried out in each connected sampling module 3. As a result, a set of measurement data for each analyte is now assigned to each sampling module 3. The relationship between the concentration in the reaction container to be sampled and the response to the detector when the sample obtained by diffusion is transported through the detector is used to evaluate the signals obtained online in the experiment by the computer.
- the pre-calibration can also be carried out directly in the reaction containers 1, in which a certain volume of a concentrated standard analyte mixture of known construction, which is preferably mixed with the medium to be sampled, is mixed with a preferably analyte-free medium in order to dilute other constituents to prevent the medium from being added. This results in a concentration that is known from the metering. Then the reaction containers 1 are sampled in the manner described above and the measurement data are recorded. A further metering of the standard analyte mixture into the medium to be sampled and subsequent measurement can be repeated until the maximum analyte concentration desired by the user is reached. In this way, the expected measuring range of the analyte can be covered during the experiment.
- an intermediate calibration can be carried out via the bypass 20 during the test.
- the sampling module arranged in a bypass or in a further parallel section can be immersed in a standard mixture during the test and sampled at regular intervals for recalibration with the same diffusion time.
- the leakage detection is evident in the case of liquids, but not, for example, in the case of gases.
- the pressure sensor 10 By installing the pressure sensor 10, malfunctions in the line can be detected. This is based on the consideration that the line pressure in the parallel fluid line sections 5b when flowing through the parallel sections and the bypass 20 is in a range of values characteristic of the device. If the pressure when flowing through a fluid line section 5b lies outside this range, there is a fault and the defective section 5b can be uncoupled, i. H. are no longer flowed through. Specifically, there is a leak if the pressure is too low and there is a blockage if the pressure is too high.
- the predetermined sampling time (diffusion time) in the dialysis tubing 4 will be less than the concentration adjustment without these Occupancy.
- This error can be identified by evaluating the detector signals and can be included in the concentration calculation with the original calibration values as an online corrector.
- the signal which is recorded when a detector 7 flows through it is e.g. B. a peak that does not return to the baseline level when flowing with pure diffusion medium.
- the signal approaches a level that arises when the diffusion medium flows through the sampling module 3 through the diffusion when flowing through (effect of a contact time - and thus flow-dependent diffusion). In this way, the accumulation in the diffusion medium is known at two different diffusion times. By comparing these two values and changing their relationship to one another, the changes in the diffusion properties, ie the fouling, on the measurements can be taken into account and corrected arithmetically.
- a single detector 7 is used. Since such a detector 7 can also fail or drift strongly, several detectors can optionally be provided for the same analyte, which can optionally be switched on or off, for example if a detector 7 fails. Optionally, different detectors can also be connected in parallel, for example via a multi-way or multi-valve arrangement, so that different analytes can be analyzed at different times. Such an interconnection is, for example, at Detectors useful, which influence each other in their measurement procedures.
- the device described above works in a very efficient manner, since a measurement can be carried out practically continuously in the detector 7 provided, with the individual parallel sampling sections 5b being opened and / or opened for transporting diffusion medium in a simple manner by actuating the multi-valve arrangement 12 when the pump 6 is operating continuously be closed during the diffusion period.
- the multi-valve arrangement 12 it is also possible to use several pumps for the diffusion medium.
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- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
L'invention concerne un procédé pour déterminer la concentration d'analytes dans des liquides et/ou des gaz. Selon ce procédé, plusieurs échantillons d'au moins un analyte sont prélevés par l'intermédiaire de membranes semi-perméables (2) dans plusieurs sections de prélèvement d'échantillons (3), par diffusion de l'analyte, régulée dans le temps, entre le milieu concerné et un milieu de diffusion qui est acheminé aux sections de prélèvement d'échantillons (3) par l'intermédiaire de tronçons de conduites de fluide (5a, 5b) au moyen d'au moins une pompe (6). Ensuite, tout en renouvelant l'apport de milieu de diffusion, on transporte le milieu de diffusion entre les sections de prélèvement d'échantillons (3) et au moins un détecteur (7) où il est analysé. La pompe (6) fonctionne en continu et le milieu de diffusion est acheminé de façon alternée aux tronçons de conduites de fluide (5b) par l'intermédiaire d'un ensemble multisoupape ou d'un ensemble soupape à plusieurs voies (12) monté en amont des sections de prélèvement d'échantillons (3). L'invention est caractérisée en ce que le milieu de diffusion peut être acheminé en continu au détecteur (7) par l'intermédiaire des tronçons de conduites de fluide (5b) et de la conduite de dérivation (20).
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10024992 | 2000-05-22 | ||
DE10024992A DE10024992C2 (de) | 2000-05-22 | 2000-05-22 | Verfahren und Vorrichtung für die Bestimmung von Substrat- und Produktkonzentrationen in einem Medium |
PCT/EP2001/005890 WO2001090718A1 (fr) | 2000-05-22 | 2001-05-22 | Procede et dispositif pour determiner la concentration d'analytes |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1285249A1 true EP1285249A1 (fr) | 2003-02-26 |
Family
ID=7642913
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP01938233A Withdrawn EP1285249A1 (fr) | 2000-05-22 | 2001-05-22 | Procede et dispositif pour determiner la concentration d'analytes |
Country Status (4)
Country | Link |
---|---|
US (1) | US20040029170A1 (fr) |
EP (1) | EP1285249A1 (fr) |
DE (1) | DE10024992C2 (fr) |
WO (1) | WO2001090718A1 (fr) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10206999A1 (de) * | 2002-02-19 | 2003-08-28 | Forschungszentrum Juelich Gmbh | Verfahren zur Überwachung von technischen Trennprozessen sowie Meßeinrichtung zur Durchführung dieses Verfahrens |
DE10249771A1 (de) * | 2002-10-24 | 2004-05-13 | AMTEC-Anwendungszentrum für Mikrotechnologien Chemnitz GmbH | Verfahren und Vorrichtung zur Entnahme von flüssigen Proben aus einem oder mehreren Druckbehältern |
DE102007063440B4 (de) | 2007-12-21 | 2011-02-17 | Thomas Grimm | Screeningsystem zur Durchführung und direkten Analyse von biologischen, biochemischen und chemischen Synthese- und Umsetzungsreaktionen |
WO2012045047A2 (fr) | 2010-09-30 | 2012-04-05 | University Of Maryland Baltimore County | Système et procédé non invasifs de détection et de surveillance d'analyte |
CN103975055B (zh) | 2011-10-10 | 2016-05-04 | 德国达斯其普信息与程序技术有限公司 | 包括生物反应器的生物技术装置、用于生物反应器的排出气体温度控制装置以及用于处理生物技术装置中的排出气流的方法 |
DK2766468T3 (da) | 2011-10-10 | 2019-05-06 | Dasgip Information And Process Tech Gmbh | Fremgangsmåde til kontrolleret drift af en bioteknologisk indretning og bioreaktorsystemer |
WO2014011655A1 (fr) * | 2012-07-10 | 2014-01-16 | Anne Yaeger | Milieux de contact pour refroidisseurs à évaporation |
US20150093775A1 (en) * | 2013-07-08 | 2015-04-02 | Govind Rao | System and method for analyte sensing and monitoring |
KR102461233B1 (ko) * | 2015-06-26 | 2022-10-28 | 엘리멘탈 사이언티픽, 인코포레이티드 | 액체 샘플 수집을 위한 시스템 |
EP3199616B1 (fr) | 2016-01-29 | 2024-08-21 | Eppendorf SE | Dispositif de connexion a une voie |
CN113790936A (zh) * | 2021-09-28 | 2021-12-14 | 江苏核电有限公司 | 一种气体多点取样在线放射性测量系统及方法 |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4601881A (en) * | 1984-11-01 | 1986-07-22 | Allied Corporation | Liquid handling system |
US5252486A (en) * | 1990-10-15 | 1993-10-12 | Calgon Corporation | Flow injection analysis of total inorganic phosphate |
US5192984A (en) * | 1990-12-19 | 1993-03-09 | Environmental Analytical Systems, Inc. | Apparatus and method for determination of concentrations |
AU681765B2 (en) * | 1994-04-28 | 1997-09-04 | Mitsubishi Materials Corporation | Continuous flow analyzing method and apparatus |
US5766959A (en) * | 1996-05-24 | 1998-06-16 | The Dow Chemical Company | Method for determining a component using a liquid film or droplet |
DE19729492A1 (de) * | 1997-07-10 | 1999-02-11 | Forschungszentrum Juelich Gmbh | Verfahren und Vorrichtung zur Serienprobenahme |
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2000
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-
2001
- 2001-05-22 US US10/296,175 patent/US20040029170A1/en not_active Abandoned
- 2001-05-22 WO PCT/EP2001/005890 patent/WO2001090718A1/fr not_active Application Discontinuation
- 2001-05-22 EP EP01938233A patent/EP1285249A1/fr not_active Withdrawn
Non-Patent Citations (1)
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See references of WO0190718A1 * |
Also Published As
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WO2001090718A1 (fr) | 2001-11-29 |
US20040029170A1 (en) | 2004-02-12 |
DE10024992C2 (de) | 2002-09-19 |
DE10024992A1 (de) | 2001-12-06 |
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