DE102020113317A1 - Automatic sampling device and method for the automated provision of a sample for a qualitative and / or quantitative determination of an analyte - Google Patents

Abstract

The invention relates to an automatic sampling device (1) for taking liquid samples from a sample liquid present at a sampling point (12) of a body of water or a container, in particular water or waste water, for the qualitative or quantitative determination of at least one analyte contained in the sample liquid, in particular a biopolymer , comprising: a sample line (5) fluidically connectable to the sampling point (12); a pumping device (4); at least one sample container (8) fluidically connectable to the sample line (5); and control electronics (10) which are set up to fluidically connect the sample line (5) to the at least one sample container (8), so that a flow from the sampling point (12) through the sample line (5) into the sample container (8) extending fluid flow path is formed, and wherein the control electronics (10) are further set up to transport a predeterminable volume of the sample liquid as a liquid sample along the fluid flow path into the sample container (8) by means of the pump device (5), characterized in that the sampling device (1 ) Has means (14, 17) for concentrating and / or extracting the analyte present in the liquid sample.

Description

The invention relates to an automatic sampling device and a method for the automated provision of a sample for a qualitative and / or quantitative determination of an analyte comprising a biopolymer in a sample liquid, in particular in water or wastewater. The invention also relates to a measuring system for the qualitative or quantitative determination of the analyte, which comprises the automatic sampling device, and a method for the qualitative or quantitative determination of the analyte in the sample liquid.

The analyte can be a bioparticle and / or a biopolymer, e.g. DNA, RNA, a protein, a virus, a virus component, a bacterium or a bacterial component, or an anthropogenic trace substance or micropollutant, e.g. a pesticide, drug, personal care product or their breakdown products or Metabolites.

From S. Mallapaty, How sewage could reveal true scale of coronavirus outbreak, Nature, Vol. 580, 2020, p. 176, it is known that virus components, e.g. RNA, can be detected in the municipal sewage of an area in which virus infections are currently occurring . The detection of such virus components is carried out by manually taking water samples from a sewage treatment plant and then examining them in the laboratory. The laboratory examination usually initially comprises complex preparatory procedures for the concentration and / or extraction of the analyte in order to provide a sample suitable for the qualitative or quantitative analysis. The sample produced in this way is then analyzed using an immunological method or a method based on quantitative real-time PCR (English technical term: real-time quantitative PCR or qPCR for short). This procedure is not suitable for systematic monitoring of wastewater, which could serve as the basis for an early warning system even for extensive geographical areas, e.g. for a large number of municipalities or districts, since the associated time and personnel expenditure is very high.

The object of the invention is to provide a device and a method that allow systematic monitoring of water or wastewater for the occurrence of certain analytes, for example biopolymers or bioparticles, such as viruses, virus components, bacteria, bacterial components, proteins, DNA or RNA , or anthropogenic micropollutants.

The object is achieved by the automatic sampling device according to claim 1, the measuring system according to claim 12, the method for the automated provision of a sample according to claim 16 and the method for the qualitative or quantitative determination of at least one analyte according to claim 23 specified.

• eine mit der Probenentnahmestelle fluidisch verbindbare Probenleitung;
• eine Pumpeinrichtung;
• mindestens einen mit der Probenleitung fluidisch verbindbaren Probenbehälter; und eine Steuerelektronik, die dazu eingerichtet ist, die Probenleitung fluidisch mit dem mindestens einen Probenbehälter zu verbinden, so dass ein sich von der Probenentnahmestelle durch die Probenleitung in den Probenbehälter erstreckender Fluidströmungspfad gebildet wird,
• und wobei die Steuerelektronik weiter dazu eingerichtet ist, mittels der Pumpeinrichtung ein vorgebbares Volumen der Probenflüssigkeit als Flüssigkeitsprobe entlang des Fluidströmungspfads in den Probenbehälter zu transportieren,
• wobei die Probenentnahmevorrichtung Mittel zur Aufkonzentrierung und/oder Extraktion des in der Flüssigkeitsprobe vorliegenden Analyten aufweist.

The automatic sampling device according to the invention for taking liquid samples from a sample liquid present at a sampling point of a body of water or a container, in particular water or waste water, for the qualitative or quantitative determination of at least one analyte contained in the sample liquid, in particular a biopolymer, comprises:

• a sample line fluidically connectable to the sampling point;
• a pumping device;
• at least one sample container that can be fluidically connected to the sample line; and control electronics which are set up to fluidically connect the sample line to the at least one sample container, so that a fluid flow path is formed that extends from the sampling point through the sample line into the sample container,
• and wherein the control electronics are further set up to transport a predeterminable volume of the sample liquid as a liquid sample along the fluid flow path into the sample container by means of the pump device,
• wherein the sampling device has means for concentrating and / or extracting the analyte present in the liquid sample.

By concentrating and / or extracting the analyte present in the sample liquid by means of the sampling device, a sample prepared for a subsequent quantitative or qualitative determination can be made available with a volume that is significantly reduced compared to the liquid sample originally taken from the sampling point. This makes it easier to transport the sample to be examined to a laboratory for further analysis. The sample obtained by concentration and / or extraction is also advantageously suitable for, in particular automated, transfer to an analysis device. The removal of the liquid sample and the concentration or extraction can advantageously be carried out partially or completely automatically by means of the sampling device. This allows systematic monitoring of the sample liquid for the presence of the analyte at a single sampling point or also at a large number of Sampling sites in an extensive geographic area.

A qualitative determination of the analyte is understood here and below to mean a method in which it is determined whether the analyte is present in the liquid sample. A quantitative determination also includes the determination of a value representing the concentration of the analyte in the liquid sample.

The device can be set up to concentrate and / or extract one or more analytes to be determined. The at least one analyte can be a bioparticle or a biopolymer, for example DNA, RNA, a protein, a virus, a virus component, a bacterium or a bacterial component, or an anthropogenic trace substance or micropollutant, e.g. a pesticide, drug, personal care product or its degradation product Metabolite.

The sample liquid can be waste water, water present in a body of water or water, in particular drinking water, in a supply network. The aforementioned sampling point can be, for example, a point on or in a body of water. A container containing the sample liquid can be a pipe through which the sample liquid flows, or an open basin or channel. Correspondingly, the sampling point can also be arranged on or in a pipeline through which the sample liquid flows, fluidly connected or connectable to the sample line, e.g. in a water supply network or in a sewage network, or on or in a basin, e.g. in a local or communal sewage treatment plant be. The sampling point can be, for example, a point in the area of the inlet of a sewage treatment plant. It can also be arranged at a point in a sewage network, e.g. in a discharge point or in the area of a discharge point into the sewage network.

The sampling device can have a plurality of sample containers, each of which can be individually fluidically connected to the sample line. For this purpose, the sampling device can have a sample distributor fluidically connected to the sample line, e.g. in the form of a movable distributor arm, the position of which can be adjusted by the control electronics in order to fluidically connect one of the sample containers to the sample line by means of the sample distributor. Alternatively, the sample distributor can also be implemented by means of a valve device and fluid lines which can be individually connected to the sample line via the valve device and which lead to the sample containers.

Optionally, in the fluid flow path running between the sampling point and the sample container, preferably upstream of the sample container, a filter device with a filter or a filter cascade can be arranged, which is designed to filter solids from the sample liquid but to let the analyte through.

The means for concentration and / or extraction can comprise a collecting matrix which can be brought into contact with the liquid sample and which binds the analyte selectively or essentially selectively. The collecting matrix can be designed, for example, to selectively bind or immobilize a certain class of biopolymers, e.g. certain proteins or RNA or DNA of certain species, such as, for example, RNA from viruses of a certain type, e.g. of a certain order, family or genus. If the analyte is an anthropogenic trace substance, the collecting matrix can be designed to selectively bind or immobilize a certain substance or a certain class of low molecular weight organic substances.

In one possible embodiment, the collecting matrix can be arranged in the at least one sample container or in a unit that can be flowed through in a fluidic connection with the sample container, in particular a fluid line or a through-flow cartridge. The through-flow unit can be arranged in the fluid flow path, in particular upstream of the sample container. It can also be arranged in an upper area of the sample container, e.g. as an insert close to or in an opening of the sample container. The permeable unit can be detachably connected to the fluid line and / or the sample container, so that it is possible to remove the permeable unit together with the collecting matrix and the analyte bound to it from the sampling device and from the sample container and to a laboratory for the further Transport analysis. Alternatively, the collecting matrix can be present loose or in a removable insert in the sample container. The collecting matrix with the analyte bound to it can be removed in this case by removing the insert or by emptying the sample container while retaining the collecting matrix.

In order to concentrate and / or extract more than one analyte, the collecting matrix can be designed to immobilize several different, but in particular structurally and / or chemically similar analytes, for example, as already mentioned, certain proteins or a certain class of biopolymers. In one by eluting the immobilized analytes from the Samples obtained from the collecting matrix can be qualitatively or quantitatively determined independently of one another, for example by means of qPCR-based methods.

In order to concentrate and / or extract more than one analyte, it is also possible to provide several different collecting matrices in the sample container or in a unit that can be flown through in fluidic connection with the sample container. For example, the sampling device can have a plurality of flow-through cartridges arranged in the fluid flow path or in the sample container, each of which contains different collection matrices which are each designed to immobilize at least one specific analyte. The sampling device can also have a plurality of sample containers which each contain different collection matrices in such a way that each collection matrix immobilizes a different analyte. Different liquid samples are used to determine different analytes.

The collecting matrix advantageously has a large surface. The surface can have a functionalization that serves to selectively bind the analyte, e.g. RNA, DNA or proteins. For this purpose, it can be coated with silica, glass or cross-linked polymers that are modified with suitable functional groups (e.g. negatively charged hydroxyl groups) for selective interaction with the analyte (e.g. positively charged viruses). It can also consist entirely of silica, glass, or cross-linked polymers modified to interact selectively with the analyte. It is also possible for the surface to be modified by antibodies that specifically interact with the analyte or similar catcher structures or catcher molecules or recognition elements based on affine interactions. Aptamers, peptide nucleic acids (PNA), molecularly imprinted polymers (MIP) can be used as capture structures or recognition elements.

The collecting matrix can, for example, have a large number of surface-functionalized particles (beads or microbeads), e.g. polymer or magnetic beads, a surface-functionalized substrate with a roughened or three-dimensionally structured surface, a functionalized fleece, e.g. a functionalized filter fleece, or a chromatographic separation column.

The automatic sampling device can be designed to automatically empty and clean the at least one sample container before or after manual or automatic removal of the collecting matrix with the bound analyte, so that the sample container is available for receiving a new liquid sample. The sampling device can further be set up to present a new collecting matrix for selective binding or immobilization of the at least one analyte in the sample container after the sample container has been emptied and cleaned and the collecting matrix loaded with the analyte has been removed. The sampling device can alternatively also be set up to automatically empty the sample container, to elute the analyte retained in the collecting matrix from the collecting matrix and to collect the eluate as a sample made available for further analysis or to output it as a sample to an automatic analysis device connected to the sampling device. In this embodiment, the collecting matrix can remain in the sample container. After removal of the eluate and an optional cleaning process, the sample container with the remaining collecting matrix is available again for receiving a new liquid sample and for concentrating and extracting the analyte in this liquid sample by means of the collecting matrix.

In an alternative embodiment, the means for concentration and / or extraction can comprise a centrifuge integrated into the device.

The control electronics can be set up to store an identification of the liquid sample for each liquid sample taken from the extraction point, and to store a time stamp, which indicates the point in time at which the liquid sample is taken from the extraction point, for the identification. The identification of the liquid sample can at the same time be an identification of the sample container into which the liquid sample is transported. The control electronics can be set up to store the identifier and the time stamp locally in a memory of the control electronics and / or to a device connected for communication with the control electronics, e.g. a portable operating device (e.g. smartphone, tablet), one with the control electronics for communication connected PC or server to communicate. The server can be a component of the sampling device, in particular a component of the control electronics or a computer remote from the sampling device, in particular a component of a cloud.

The automatic sampling device can furthermore have at least one interface for connecting the control electronics to at least one sensor which can be brought into contact with the sample liquid present at the sampling point and which is set up to receive measurement signals of at least one measured variable To generate sample liquid, for example temperature, pH value or conductivity, and to output it to the control electronics, wherein the control electronics are further set up to at least one measured value of the measured variable derived from the measurement signals and that at the time at which the liquid sample is taken from the sampling point , is recorded to store the identification of the liquid sample. Using the additionally recorded measured variable, a measured value of the analyte concentration in the sample liquid determined on the basis of the liquid sample can be calculated more precisely. The control electronics can be set up to store the measured values locally and / or to communicate with the above-mentioned device connected to the control electronics for communication.

Further measured variables that can be measured by means of one or more additional sensors that can be connected to the control electronics are turbidity, concentrations of dissolved gases, ion concentrations or concentrations of photometrically or spectrometrically detectable molecules or sum parameters such as SAK value (spectral absorption coefficient), COD (chemical oxygen demand) or TOC (total organically bound carbon).

The automatic sampling device can optionally comprise means for adjusting a pH value in the liquid sample. These means can include, for example, a pump controllable by means of the control electronics, possibly additional liquid lines and one or more reagents, e.g. one or more buffer solutions, one or more acids and / or one or more alkalis, which are transported into the sample container by means of the pump via the liquid lines can be used to adjust the pH of the liquid sample contained therein. Optionally, a pH sensor can be arranged in the sample container, which is connected to the control electronics in order to output measured pH values to it. The control electronics can use these pH measured values to regulate the pH value in the liquid sample. Alternatively, the control electronics can be connected via the interface mentioned in the previous paragraph to a pH sensor immersed in the sample liquid at the sampling point, and one or more of the reagents based on the pH measurement value recorded by this pH sensor at the time the liquid sample is taken add to the liquid sample in the sample container to adjust the pH. This is advantageous in systems in which the analyte is concentrated by selective adsorption on a collecting matrix, the adsorption preferably taking place in a certain pH range through electrostatic interactions.

In a further refinement, the sampling device can have a temperature sensor which is set up to detect measured values representing the temperature of a liquid sample contained in the at least one sample container and to output them to the control electronics. The control electronics can also be set up to store at least one of the measured values or a measured value profile for the identification of the liquid sample. The control electronics can be set up to store the measured values locally and / or to communicate with the above-mentioned device connected to the control electronics for communication. In this way, a temperature or a temperature profile to which the liquid sample with the analyte is exposed until the collecting matrix or a sample provided by concentration and extraction of the analyte from the liquid sample is removed from the sample container or from the sampling device for the purpose of further analysis , are taken into account when determining and / or interpreting the analysis result. For example, the temperature profile can be used to determine the analyte concentration in the sample liquid at the time the sample is taken.

On the one hand, the temperature of the sample liquid can influence the rate of degradation processes of the analyte or analytes. On the other hand, it can simultaneously influence the binding kinetics of the analyte (s) to the collecting matrix. It is therefore advantageous to record the temperature or the temperature profile to which the liquid sample and / or the collecting matrix is exposed after the liquid sample has been removed from the extraction point and to make it available for consideration in the qualitative and / or quantitative determination of the at least one analyte.

In a further embodiment, the automatic sampling device can comprise a temperature control device which is designed to control the temperature of the at least one sample container and the liquid sample contained therein, in particular to cool them. Optionally, the temperature control device can be designed to set a specific temperature in the area of the at least one sample container.

In a further embodiment, the sampling device can have a GPS receiver which is set up to output location data (GPS data) to the control electronics, the control electronics being set up to store the location data. The control electronics can be set up to store the location data locally and / or to communicate to the above-mentioned device connected to the control electronics for communication.

To communicate data to another device, the control electronics can have a communication interface. The other device can, for example, be the already mentioned control device or a server that is set up to store the data, for example in a central and / or decentralized database, and software, for example a web or cloud application, for display or to make available for data analysis. The software can be executed on the operating device, the server or on a further device, for example a further server or a PC, or in a cloud, of which the server can be a component. This enables the linking of liquid sample and / or sampling point-specific data, such as identifications, time stamps, temperature data, weather data, location data (e.g. GPS data of the sampling point), or measured values of the sample liquid, with those that can also be read into the control unit or the software, results of the qualitative and / or quantitative determination of the at least one analyte determined in the laboratory, hereinafter also referred to as analysis results for short, in the samples provided by the sampling point. In addition, the data, measured values and analysis results determined in this way from samples taken at various sampling points can be combined in a web or cloud application and compared with one another and / or with data from other sources.

• - eine automatische Probennahmevorrichtung zur Entnahme von Flüssigkeitsproben der Probenflüssigkeit an einer Probenentnahmestelle, z.B. eines Gewässers oder Behälters, insbesondere eines Rohrs in einem Wasserversorgungs- oder Abwassernetzwerks oder eines Zulaufs oder eines Beckens einer Kläranlage, nach einer der voranstehend beschriebenen Ausgestaltungen;
• - ein zur qualitativen oder quantitativen Bestimmung des mindestens einen Analyten eingerichtetes Analysegerät; und
• - eine Übergabeeinrichtung, die dazu ausgestaltet ist, eine Probe des mittels der Probennahmevorrichtung aufkonzentrierten oder extrahierten mindestens einen Analyten bereitzustellen.

The invention also comprises a measuring system for the qualitative or quantitative determination of at least one analyte, in particular a biopolymer, in a sample liquid, in particular water or wastewater, comprising:

• - An automatic sampling device for taking liquid samples of the sample liquid at a sampling point, for example a body of water or a container, in particular a pipe in a water supply or sewage network or an inlet or a basin of a sewage treatment plant, according to one of the configurations described above;
• an analysis device set up for the qualitative or quantitative determination of the at least one analyte; and
• a transfer device which is designed to provide a sample of the at least one analyte concentrated or extracted by means of the sampling device.

If the sampling device comprises, for example, a collecting matrix with functionalized magnetic beads to which the at least one analyte binds selectively, the transfer device can comprise a magnet which is set up to attract the magnetic beads after contact with the sample liquid and to transfer them into a further vessel. In this way, the collecting matrix with the analyte bound to it can be separated from the other components of the liquid sample. If, as mentioned above, the collecting matrix is contained in an insert of the sample container or in a removable cartridge, the transfer device can be designed to automatically remove the cartridge or the insert. The collecting matrix with the bound analyte can be provided, for example, as a sample of the analyte concentrated or extracted by means of the sampling device for further analysis by means of the analysis device.

The transfer device can furthermore comprise means for eluting the analyte from the collecting matrix, here for example from the magnetic beads. In this case, the eluate can be provided as a sample of the analyte concentrated or extracted by means of the sampling device. In an advantageous embodiment, the transfer device is further designed to transfer the prepared sample to the analysis device.

The measuring system can further comprise control electronics which are set up to control the transfer device for the automated transfer of a sample of the concentrated or extracted analyte to the analysis device. For example, the control electronics can control pumps, valves and moving parts, such as the magnet mentioned above, to move the collecting matrix from an original position in the sample vessel or in a flow-through unit in the fluid flow path of the sampling device into the analysis device or into a further container belonging to the transfer device to transfer and to elute the analyte from the collection matrix. The control electronics can be the above-mentioned control electronics of the automatic sampling device or a component of the control electronics of the automatic sampling device.

The analysis device can be set up to carry out the qualitative or quantitative determination of the analyte in a partially or fully automated manner. The analysis by means of the analysis device can be carried out, for example, using an affinity-based, in particular antibody-based, immunological assay or using a real-time qPCR-based method. In a further possible embodiment, the analysis device can be set up to carry out the qualitative or quantitative determination of the analyte by means of a spectroscopic method, e.g. by means of Raman spectroscopy, in particular also by means of Surface Enhanced Raman Spectroscopy (SERS) or Tip Enhanced Raman Spectroscopy (TERS), by means of mass spectrometry, or by means of hyperspectral imaging.

The analysis device can have a computing unit which is set up to determine a qualitative or quantitative analysis result, e.g. an analyte concentration in the original liquid sample, and which is further set up to control the analysis device for the automated determination of the analyte. The computing unit can be set up to store analysis results of the qualitative and / or quantitative determinations in the samples provided by the transfer device, in particular each linked to an identification of the liquid sample from which a sample provided by the transfer device was obtained. The computing unit of the analysis device can also have a communication interface for communicating data to another device. The other device can be, for example, the control electronics of the sampling device, the control device already mentioned above or the server mentioned above, which is set up to store data provided by the analysis device, for example in a central and / or decentralized database, and a To provide software, e.g. a web or cloud application, for display or data analysis. The software can be executed on the control device, the server or on another device, e.g. another server or a PC, or in a cloud, of which the server can be a component. As already mentioned, the software can link the analysis results made available by the analysis device with data of the associated liquid samples that were recorded by the sampling device and carry out a more extensive data analysis with the linked data.

• - Entnehmen eines vorgebbaren Volumens der Probenflüssigkeit als Flüssigkeitsprobe aus der Entnahmestelle mittels einer automatischen Probennahmevorrichtung, insbesondere der Probennahmevorrichtung nach einer der voranstehend beschriebenen Ausgestaltungen, aus der an einer Probenentnahmestelle, beispielsweise in einem Behälter oder einem Gewässer, insbesondere in einem Rohr in einem Wasserversorgungs- oder Abwassernetzwerk, an einer Einleitungsstelle zu einem Abwassernetzwerk oder in einem Zulauf oder einem Becken einer Kläranlage, vorliegenden Probenflüssigkeit;
• - Transportieren des Volumens der Probenflüssigkeit als Flüssigkeitsprobe in einen Probenbehälter; und
• - In-Kontakt-bringen der Flüssigkeitsprobe mit einer Sammelmatrix, die den Analyten immobilisiert, insbesondere im Wesentlichen selektiv bindet.

The invention also comprises a method for the automated provision of a sample for a qualitative and / or quantitative determination of at least one analyte, in particular a biopolymer, in a sample liquid, in particular water or waste water. The process consists of the following steps:

• - Removal of a predeterminable volume of the sample liquid as a liquid sample from the sampling point by means of an automatic sampling device, in particular the sampling device according to one of the configurations described above, from the at a sampling point, for example in a container or a body of water, in particular in a pipe in a water supply or Wastewater network, at an inlet point to a wastewater network or in an inlet or a basin of a sewage treatment plant, sample liquid present;
• - Transporting the volume of the sample liquid as a liquid sample into a sample container; and
• Bringing the liquid sample into contact with a collecting matrix which immobilizes the analyte, in particular binds it essentially selectively.

In an alternative embodiment, instead of bringing the liquid sample into contact with the collecting matrix, the method can also include extracting or concentrating the analyte by means of centrifugation or by means of a precipitation reaction.

As already described above in connection with the sampling device, the collecting matrix can be placed in the sample container or can be arranged in a flow-through unit fluidically connected to the sample container, in particular a fluid line or a flow-through filter cartridge. The collecting matrix can be configured as explained above in connection with the sampling device.

The method can further comprise removing the collecting matrix with the analyte from the device and / or eluting the analyte from the collecting matrix to form a solution of the analyte as a sample for the subsequent qualitative or quantitative determination. The subsequent qualitative or quantitative determination of the analyte can be carried out by means of an affinity-based, in particular antibody-based, immunological assay, by means of a real-time qPCR-based method or by means of a spectroscopic method. The result of this determination is referred to above and below as the analysis result for short. The analysis result can represent the concentration of the analyte in the sample provided and / or the concentration of the analyte in the original liquid sample.

The method can further include storing an identification of the liquid sample and a time stamp representing the point in time at which the liquid sample was removed from the removal point in an electronic control system of the automatic sampling device. The identification of the liquid sample and the associated time stamp can be stored by the control electronics and / or by a device that can be connected to the control electronics for communication, e.g. a, in particular portable, operating device, or a server and a software, e.g. a web or cloud application, which links the stored data with other data and, if necessary, carries out further data analyzes.

In addition, the method can record at least one measured value of at least one measured variable of the sample liquid, for example the temperature, the pH value or the conductivity, at the time the liquid sample is taken from the extraction point by means of an additional sensor and store the measured value in the control electronics to identify the Include liquid sample. Further measured variables that can be measured by means of one or more additional sensors that can be connected to the control electronics are turbidity, concentrations of dissolved gases, ion concentrations or concentrations of photometrically or spectrometrically detectable molecules or sum parameters such as SAK value (spectral absorption coefficient), COD (chemical oxygen demand) or TOC (total organically bound carbon). The at least one additionally determined measured value, in particular several additionally determined measured values of one or more different of these parameters, can be stored linked to the identification of the liquid sample. They can be taken into account when determining or evaluating the analysis result determined on the basis of the sample provided. For example, the at least one additional measured value can be included in a calculation model for determining the concentration of the analyte in the original liquid sample from a qPCR measurement result or from a measurement value of an immunological assay or from spectrometric measurement data.

A pH value measured in the sample liquid can also be used to automatically set a pH value in the liquid sample that is advantageous for binding to the collecting matrix by means of the control electronics. For this purpose, the sampling device can have storage containers with reagents that influence the pH value of the liquid sample, liquid lines, one or more pumps and, if necessary, one or more valves that are actuated by the control electronics to adjust the pH value of the liquid sample.

The method can further comprise the detection of a temperature or a temperature profile to which the liquid sample is exposed from the time it is removed. The temperature or the temperature profile can be stored by the control electronics and linked to the stored identification of the liquid sample. The temperature profile to which the liquid sample was exposed can be included in an evaluation and / or determination of the analysis result. For example, the stored temperature or the stored temperature profile can be included in a calculation model for determining the concentration of the analyte in the original liquid sample from a qPCR measurement result, from a measurement value from an immunological assay or from a spectroscopic measurement.

The method can further include the acquisition of location data that represent the location of the sampling point, for example by manual input or by a GPS receiver, and the storage of the location data in the control electronics.

The method can also include the transfer of the identification of the liquid sample and other data stored in the control electronics linked to the identification, e.g. a time stamp associated with the identification, measurement values associated with the identification, location information associated with the identification and / or data specific to the sampling point, to an operating device or an analysis device serving to analyze the provided sample, in particular to a laboratory device, or to a server connected to the analysis device and / or the control electronics for wireless or wired communication, which the data received from the control electronics and / or the analysis device and its memory can be accessed by software, for example a web or cloud application, in order to display the data and / or to carry out a further analysis of the data. The software can be executed on the operator panel, the server or another device.

• - Bereitstellen einer Probe mittels des voranstehend beschriebenen Verfahrens in einer seiner ebenfalls voranstehend beschriebenen speziellen Verfahrensausgestaltungen; und
• - qualitative oder quantitative Bestimmung des Analyten mittels eines Analyseverfahrens, insbesondere mittels eines affinitätsbasierten, insbesondere antikörperbasierten, Assays, mittels eines Echtzeit-qPCR-basierten Verfahrens oder mittels eines spektroskopischen Verfahrens.

The invention also comprises a method for the qualitative or quantitative determination of at least one analyte, in particular a biopolymer in a sample liquid, in particular water or wastewater, comprising:

• - Provision of a sample by means of the method described above in one of its special method embodiments also described above; and
• - Qualitative or quantitative determination of the analyte by means of an analysis method, in particular by means of an affinity-based, in particular antibody-based, assay, by means of a real-time qPCR-based method or by means of a spectroscopic method.

The method can be carried out with the measuring system described above.

The analysis process can be fully or partially automated on the sample provided be carried out by means of at least one analysis device which comprises a computing unit which is set up to determine a qualitative or quantitative analysis result, for example an analyte concentration in the original liquid sample.

The analysis device can be an online analysis device which is arranged directly at the sampling point. Alternatively, the sample provided can be brought to a laboratory and analyzed there in a partially or fully automated manner using at least one laboratory analyzer. The sample provided by the method described above, which is obtained by concentrating the analyte by means of a collecting matrix or alternatively also by another method, e.g. centrifugation, is less expensive to transport than a sample container containing the complete liquid sample. Because of the correspondingly smaller volume, cooling is also easier to achieve during transport.

As already described above, the method can include determining a concentration of the analyte in the original liquid sample with the additional inclusion of at least one measured value recorded at the sampling point, e.g. the temperature, the pH value or the conductivity, or one or more further measured variables , the measured value being made available by the control electronics of the sampling device. The concentration of the analyte in the original liquid sample also corresponds to the concentration of the analyte in the sample liquid that was present at the sampling point at the time the sample was taken.

The time of sampling can be represented by a time stamp, which is recorded by the control electronics of the sampling device and stored in the control electronics linked to the identification of the liquid sample and / or from the control electronics to another device, e.g. the analysis device, to an operating device or a Server, can be issued for storage associated with the identification of the liquid sample. The sampling point can be represented by location information, for example GPS data, which is recorded by the control electronics and stored by them and / or linked for storage with the identification of the liquid sample to another device, e.g. the analyzer, to the control unit and / or a server, which can be issued with the identification of the liquid sample for storage.

The control electronics of the sampling device can transmit the measured values to be included in the determination of the concentration of the analyte in the liquid sample together with the identification of the liquid sample to the analysis device for storage. Alternatively, the values, together with the identification of the liquid sample, can be read from the control electronics into an operating device for storage and output from the operating device to the analysis device and stored there. In a further variant, the values, together with the identification of the liquid sample, can be output by the control electronics to a server, which saves the values and makes them available to software, e.g. a web or cloud application. The analysis device or the computing unit of the analysis device can output the analysis results of the sample, e.g. a determined concentration of the analyte in the liquid sample, to the control electronics of the sampling device or to the control unit or the server or another server, the control electronics, the control unit, the server or the other server stores the analysis results linked to the identification of the liquid sample. The software can access the control unit, the server or the other server in order to read out the stored analysis results and the associated identification and use them for further data analysis.

The quantitative determination of the analyte, e.g. the determination of an analyte concentration in the original liquid sample including the at least one further measured value, can be carried out in one embodiment of the method by the computing unit of the analysis device using the data made available by means of the operating device or the software. In a further embodiment of the method, the quantitative determination of the analyte can be carried out by the software using an analysis result determined from the sample by the computing unit of the analysis device and output to the server and, if necessary, measured values recorded by the control electronics of the sampling device and output to the server.

The analyte concentration in the original liquid sample can be calculated using one or more measured values using a calculation model. The calculation model can, for example, take into account the influence of the temperature on the binding behavior of the analyte to a collecting matrix for the concentration and / or extraction of the analyte in the liquid sample and the influence of the temperature on the degradation process. In this model, measured temperature values or measured values of the temperature profile to which the liquid sample was exposed before the analysis can be entered by the sampling device.

The software can be run on the operator panel, the server, another server or distributed in a cloud.

The additional measured values recorded by the control electronics and associated with the liquid sample can not only be used to determine a concentration of the analyte. They can be used as an alternative or in addition to evaluating the analysis result, or to create or adapt chemometric or epidemiological models. They can also be used for statistical purposes.

The method can further comprise the communication of the analysis result and possibly additional data from the control electronics and / or the analysis device to the software mentioned, e.g. a web or cloud application, for further analysis. In addition to the additional measured values already mentioned and the time stamp assigned to the liquid sample, the additional data can be an identification of the sampling point, e.g. GPS data or other location data that identify the sampling point.

The software, in particular in the form of a cloud application, can access data from a large number of sampling devices at a large number of sampling points. For example, the data, in particular identifications of liquid samples, linked with associated time stamps, location information and measured values, can be stored in a central database or in a cloud on several computers, which the software can access. The analysis results that are obtained by means of the qualitative or quantitative determinations of the analyte carried out by the liquid samples collected by the sampling devices can also be stored in the database in association with the identifications of the associated liquid samples. The software can use the data for comprehensive data analysis. It can, for example, monitor a temporal course of the analysis results and thus provide an early warning system that detects an increase in the concentration of the analyte at a sampling point or in an area comprising several sampling points and generates a warning based on this.

The software can also use the data to analyze a temporal and / or spatial development of the analyte concentration in an extensive area, e.g. in a water or sewage network of a larger region or an extensive body of water. It can also provide a visualization in the form of a map of the analyte concentration. Trends, i.e. developments over time, can also be displayed on the map.

The software can make the results of the data analysis, in particular the mentioned displays of information from an early warning system or graphic representations of maps, available to other computers (end devices), in particular in a browser-based application on the end devices.

The above devices and methods are suitable, for example, for monitoring water or sewage networks, areas in sewage treatment plants and discharge points in sewage networks for the occurrence or trends in the concentration of pathogens, e.g. viruses or bacteria, or parts of pathogens, e.g. DNA, RNA or Shell components, in the water. This can be used for modeling, forecasting and analyzing epidemics, especially as an early warning system. Such a pathogen can be, for example, the Sars-CoV-2 virus.

• 1 eine automatische Probennahmevorrichtung;
• 2a ein Detail der automatischen Probennahmevorrichtung in einer ersten Ausgestaltung;
• 2b ein Detail der automatischen Probennahmevorrichtung in einer zweiten Ausgestaltung;
• 3 ein Messsystem zur qualitativen oder quantitativen Bestimmung eines Analyten in einer Abwasserprobe in einer ersten Ausgestaltung; und
• 4 ein Messystem zur qualitativen oder quantitativen Bestimmung eines Analyten in einer Abwasserprobe in einer zweiten Ausgestaltung.

The invention is explained in more detail below with reference to the exemplary embodiments shown in the figures. Show it:

• 1 an automatic sampling device;
• 2a a detail of the automatic sampling device in a first embodiment;
• 2 B a detail of the automatic sampling device in a second embodiment;
• 3 a measuring system for the qualitative or quantitative determination of an analyte in a wastewater sample in a first embodiment; and
• 4th a measuring system for the qualitative or quantitative determination of an analyte in a waste water sample in a second embodiment.

In 1 is an automatic sampling device 1 shown. It is designed as a cabinet unit that is divided into an upper dosing space and a lower sample space. The dosing room has a dosing room door 2 lockable, the sample compartment with a sample compartment door 3 . The sample space is optionally cooled. There is a pump in the dosing room 4th arranged, which is designed in the present example as a hose pump. Other configurations, for example as a vacuum pump, are possible. The pump 4th works with a sample line 5 together, which in the present example is designed as a hose line.

The rehearsal line 5 is at its first end (in 1 not seen) with a Sampling point 12th ( 2a , 2 B) fluidly connectable, from which liquid samples can be taken from a sample liquid for analysis. The sampling point can be an open body of water or a channel. In this case, the fluidic connection is made by immersing the first end of the sample line 5 manufacturable. The sampling point 12th can also be a closed container, for example a pipe, through which the sample liquid flows. In this case, the fluidic connection can be established by means of a sampling valve.

The second end of the sample line 5 is with a sample distributor designed here as a rotary arm 6th fluidically connected. There are two bottle baskets in the dosing room 7th , in which several sample containers 8th , here in the form of plastic or glass bottles, are included. The sample distributor can by means of a distributor mechanism, here a rotating mechanism, over the sample container 8th moved away to the sample line 5 each with one of the sample containers 8th to connect fluidically. The tip of the rotating arm is located above the opening of a sample container 8th a fluid flow path is formed leading from the sampling site 12th via the sample line 5 and the sample distributor 6th into the sample container 8th runs. To direct the liquid along the fluid flow path is in the present example above the sample container 8th a distribution plate 9 arranged. However, this is only available as an option.

At the first end of the sample line 5 For example, a filter or a filter cascade can be arranged which, by means of size filtration, retain at least some of the solids contained in the sample liquid. The filter or filters can also be at another point in the fluid flow path between the first end of the sample line 5 and the sample container 8th be arranged.

The sampling device 1 further comprises control electronics 10 that is set up to do the pump 4th and the sample distributor 6th for transporting a predeterminable volume of the sample liquid from the extraction point into a sample container 8th to control. In the dosing room door 2 is a window 11th arranged through a display of the control electronics 10 visible and the control electronics 10 can be operated by means of input keys and a turn-push switch even when the dosing room door is closed.

The control electronics 10 has a processor and memory in which operating and evaluation programs are stored, which control electronics 10 for controlling the sampling device 1 for sampling and for collecting and storing data in connection with sampling. The sampling device 1 can optionally have a cooling device which serves to cool the sample space. A temperature of the sample space can be determined by means of the control electronics 10 be adjustable.

The control electronics 10 can in particular be set up to one in a sample container 8th the transported sample to save a label, as well as a time stamp assigned to the label, which marks the time of the sampling. The control electronics 10 can assign further information to the identification and save it, e.g. further measurement data, with the control electronics 10 connected sensors, such as temperature measurement data, pH measurement data, conductivity measurement data, turbidity measurement data, measurement value curves of these parameters and location data, for example the location of the sampling point at which the sampling device 1 is arranged.

The control electronics 10 also has one or more communication interfaces via which it can communicate with further data processing devices, for example with an analysis device that is used to analyze the data from the sampling device 1 provided samples is used, or with a portable control unit, via which an operator receives data from the control electronics 10 can read out or to the control electronics 10 can spend. The control electronics 10 can also be set up to transmit data to a server that stores the data and makes it available to software, for example a web or cloud application. These data can include the identifications and associated data of collected liquid samples, as well as location data identifying the sampling point. The software can access this data for further evaluation and analysis. Conversely, the software can use the control electronics server 10 Data or information for future sampling or for display on a user interface of the control electronics 10 provide.

The control electronics 10 can have one or more of the following types of communication interfaces: communication interfaces according to a standard of the process industry, eg 4 ... 20 mA, Profibus, HART, Modbus, or other, especially proprietary communication standards; but also communication interfaces for communication according to an Ethernet standard or a Bluetooth standard.

The sampling device 1 also has means for concentrating and / or extracting an analyte comprising a biopolymer taken from one of the sampling points. The analyte can be, for example, a virus or a virus component or a bacterium or a bacterial component. Among components of viruses and bacteria are understood here in particular to mean parts of their shells, in particular proteins, and polynucleotides such as RNA or RNA fragments, DNA or DNA fragments. Examples of means for concentrating and / or extracting such an analyte are given below with reference to FIG 2a and 2 B described.

In 2a and 2 B Figure 3 is a schematic of the fluid flow path between the sampling point 12th (here an indicated channel) and a sample container 8th shown (for the sake of clarity, the sample distributor is omitted from this illustration). A flow meter is located in the fluid flow path 13th , which is used to set the predeterminable sample volume. Via the sample line 5 can by means of the pump 4th the predeterminable volume of the sample liquid in the sample container 8th be transported.

In the in 2a The example shown is in the sample container 8th a collecting matrix in the form of a large number of magnetic or polymer beads 14th submitted whose surfaces are modified in such a way that the analyte in the sample liquid binds essentially selectively to the surfaces. If the analyte is, for example, virus RNA of a certain type of virus, essentially RNA of such viruses binds to the beads, but not - or at least to a much lesser extent - other RNA or DNA in the sample liquid. Such beads are known in the prior art for the enrichment and / or extraction of biomolecules, in particular biopolymers. Their surfaces can be modified by structuring or functionalization with antibodies or other capture structures in order to provide the desired selectivity.

The selective binding of the analyte to the collecting matrix can be optimized by setting a suitable pH value in the liquid sample. To adjust the pH, the sampling device can have one or more additional liquid containers 15th with one or more reagents, for example an acid, a base and / or a buffer solution, and another pump 16 include, by means of which the reagent or reagents can be added to the liquid sample. In the present example, it is the other pump 16 a peristaltic pump connected to a liquid line 17th cooperates to get a reagent from the liquid container 15th into the sample container 8th to transport. The pump 16 can from the control electronics 10 the sampling device 1 can be controlled in order to dose an amount of the reagent or reagents required to achieve a desired pH value. For this purpose, a pH sensor can be provided in the sample container, which sends the measured pH values to the control electronics 10 outputs so that it can control the addition of the reagent or reagents based on the pH measured values. Alternatively, the control electronics 10 also with one at the sampling point 12th be connected to the pH sensor immersed there in the sample liquid and pH measured values of this sensor for controlling the addition of the reagent or reagents to the liquid sample in the sample container 8th use.

The beads 14th with the analyte bound or immobilized on it, manually or by means of a (partially) automated transfer device (in 2a not shown) from the sample container 8th removed and transported to a laboratory for further analysis. This has the advantage that it does not require large-volume sample containers 8th , just the beads 14th transported and may have to be cooled during transport. To remove magnetic beads, a magnet, in particular a switchable electromagnet, can be used which, for example, can be moved in an automated manner to remove the magnetic beads and from the control electronics 10 can be controlled. In the event that the beads 14th are not magnetic, another way to remove the beads may be 14th from the sample container 8th consist of the sample container 8th automated to empty and the beads 14th hold back in a filter. The beads 14th can also be used in an insert in the sample container 8th be held and by removing the insert from the sample container 8th removed. If a transfer device is present, this can also comprise means for eluting the analyte from the beads, so that the sample provided for transport to the laboratory or for transfer to an analysis device for further qualitative or quantitative analysis is formed from the eluate.

In 2 B Another embodiment of the means for concentrating and / or extracting the analyte is shown. Here these means include one in the upper area of the sample container 8th arranged, removable cartridge 17th , in which an analyte-affine collection matrix is contained. This can be, for example, a functionalized fleece, a chromatography column. or a bed of surface-functionalized polymer beads. The beads or the fleece can be functionalized in a manner analogous to that in the example of FIG 2a used magnetic or polymer beads. While the sample liquid is on its way into the sample container when the sample is taken 8th through the cartridge 17th flows, the analyte in the cartridge is essentially selectively bound to the collecting matrix or, in the case of a chromatography column, separated chromatographically from further sample components and retained in the collecting matrix.

The cartridge 17th can also be used outside the sample container 8th be arranged at a different position in the fluid flow path. The cartridge 17th can be automated or manual from the sample container or from the fluid flow path in the sampling device 1 removed and transported to a laboratory for further analysis. The cartridge is removed 17th automated by means of a transfer device, this can, as in the example described above, additionally comprise means for eluting the analyte from the beads, so that the sample provided for transport to the laboratory or for transfer to an analysis device for further qualitative or quantitative analysis is formed from the eluate will.

Further examples of means for concentrating and / or extracting the analyte are conceivable, for example a centrifugation device in the sampling device 1 can be integrated.

In 3 is a measuring system 100 for the qualitative or quantitative determination of the analyte contained in the sample liquid by means of the sampling point 12th taken liquid samples shown schematically.

The measuring system 100 includes the 1 , 2a , 2 B sampling device already described 1 with the control electronics 10 . The rehearsal line 10 the sampling device 1 is fluidic with the sampling point 12th connected, which in the present example is an open basin, for example a basin or an inlet of a sewage treatment plant. In the one at the sampling point 12th If the sample liquid is present, an additional sensor is immersed 18th one that is on a faucet 19th is attached, and via a cable with the control electronics 10 the sampling device 1 connected for bidirectional communication. The additional sensor 18th can have a conductivity sensor, a pH sensor, a turbidity sensor, a temperature sensor, a photometric or spectrometric probe for determining a concentration of one or more substances, in particular a nitrate or SAC probe, or an ion-selective electrode. The additional sensor 18th sends measured values to the control electronics 10 the sampling device 1 the end. As related to 1 Mentioned above is the control electronics 10 set up for this purpose, an identification of a liquid sample taken, as well as a time stamp identifying the point in time when the sample was taken, and further data, in particular measurement data from the additional sensor 18th , to be linked with the identification and to be saved. Of course, the sampling device 1 also several with the control electronics 10 connected additional sensors 18th have, the measured values of which can be recorded and stored.

The measuring system 100 also has an in one of the sampling point 12th analyzer located in a remote laboratory 20th which comprises a liquid handling system for sample preparation and preparation as well as an analysis unit for the subsequent automated execution of an immunological assay or a real-time qPCR-based or spectroscopic analysis of the sample, as well as a computing unit. The one from the sampling device 1 liquid sample taken by concentration and / or extraction of the analyte obtained sample for further analysis is sent to the analysis device 20th transferred and analyzed from the sample in an automated or partially automated manner using this method known per se in the prior art. The computing unit is used, among other things, to calculate a quantitative analysis result, for example a concentration of the analyte in that of the sampling device 1 made available sample or in the original liquid sample, and possibly also for controlling by means of the analysis device 20th automated liquid handling and analysis procedures.

The analyzer 20th can, as in 3 indicated by a double arrow, with the sampling device 1 connected for communication, e.g. via a LAN connection (intranet or internet). The sampling device can use this connection 1 the identification of liquid samples and associated information such as sensor data, time stamp, location information to the computing unit of the analysis device 20th transfer. The computing unit of the analyzer 20th Conversely, analysis results can be sent to the sampling device together with the identification of the associated liquid samples 1 transfer. The computing unit of the analyzer 20th can be used by the sampling device to determine and / or evaluate the analysis results of the individual samples 1 refer to any additional information received. For example, when determining a quantitative analysis result, the influence of further measured variables of the sample liquid, for example the pH value or the conductivity of the sample liquid at the time of sampling, can be taken into account. The merging of the analysis equipment 20th determined analysis results and from the sampling device 1 The additional information provided is based on the identification of the samples.

The measuring system 100 can optionally use a mobile control unit 21 include, which is designed as a smartphone or tablet PC in the present example. In this example, the operator panel can 21 for bidirectional communication with both the sampling device 1 as well as with the analyzer 20th be set up. It can therefore be used for Transfer of data from one unit to the other can be used. It can also be used to read a visible on a sample container 8th or readable in an NFC or RFID chip on the sample container 8th Affixed marking to be used when transferring the concentrated samples from the sampling device 1 to the analyzer 20th to avoid confusion in the laboratory. The methods and means for unambiguously identifying sample containers used to identify and manage collected samples in sample containers during transport between a sampling point and a laboratory are well known to the person skilled in the art and can also be used here. It is therefore not discussed in detail here.

The control unit 21 , the analyzer 20th and the control electronics 10 the sampling device 1 are configured in the present example for communication with a server, which in the present example is part of a cloud 22nd is. The server can also be a local computer, ie a computer located at the sampling point or in the laboratory, or a single central computer that connects to the computer unit of the analysis device via the intranet or Internet 20th , the control unit 21 and / or the control electronics 10 can communicate.

The server can collect and save data, measured values and analysis results linked to the identification of the associated sample and use them for data analysis. The storage can take place in a central database or in the cloud. On the server, a computer that can be connected to the server, e.g. another server, a PC or the operating device, or in the cloud 22nd software can be executed that accesses the stored data and carries out further data analyzes and / or can display data and results of the data analyzes. This software can be a web or cloud application, for example.

The software or the cloud 22nd can be connected to a large number of sampling points and laboratory analysis devices and thus determine and analyze a large number of data from spatially distributed sampling points. Such a cloud application can, for example, record and evaluate quantitative or qualitative analysis results for certain analytes, such as viruses or other microorganisms, in particular pathogens, in a body of water, a water or sewage network or in a large number of different private and / or municipal sewage treatment plants. It can monitor changes in the concentration of the analyte over time, e.g. virus concentration at the individual sampling points or in a larger region comprising several sampling points, and thus serve as an early warning system for the outbreak of a disease or epidemic in the monitored region. If the cloud application has data from samples that were obtained and analyzed at a large number of sampling points, it can provide a map of the concentrations of the analytes at the various sampling points.

The cloud application 22nd can be set up to compare the analysis results and other data determined for the individual sampling points with data from other sources. If the analyte is, for example, a virus or a component of the virus, e.g. virus RNA, and the sampling points considered are channels or containers in sewage networks or sewage treatment plants, the analysis results obtained in this way, the concentration of the virus or the virus RNA in regional wastewater can be compared with data from regional health authorities in order to predict outbreaks of a disease caused by the virus at an early stage, to increase the number of locally performed tests on patients or to identify discrepancies between tests on patients and analysis results in wastewater.

In 4th is a further embodiment of a measuring system 101 shown, that of the qualitative or quantitative determination of the analyte contained in the sample liquid by means of the sampling point 12th taken liquid samples is used. Like the measuring system 100 , which is already based on 3 also includes the measurement system 101 the sampling device already described 1 with the additional sensor 18th and the control electronics 10 which is set up to control the sampling and to record and store identifications of liquid samples and associated additional data, e.g. time and location data as well as additional measured values.

The measuring system also includes 101 an analyzer 20th that of the qualitative or quantitative determination of the analyte in from the sampling device 1 provided samples is used.

Unlike in the example of 3 has the measuring system described here 101 a transfer device that can be operated completely automatically 23 which is configured to have one in a sample container 8th the sampling device 1 contained, the analyte essentially selectively binding collecting matrix from the sample container 8th to be removed automatically. In the present example, the collecting matrix is formed from a large number of surface-modified magnetic beads that are placed in the sample container 8th are presented in such a way that analyte present in the liquid sample forms on the magnetic beads. As described above, means for adjusting the pH value in the liquid sample can also be provided. The transfer device 23 points to the removal of the collecting matrix from the sample container 8th one or more movable and / or switchable magnets 24 with which the magnetic beads are attracted and removed from the sample container 8th can be removed. The magnetic beads are in the transfer device 23 rinsed with solvent and the analyte eluted from the collection matrix. The liquid sample obtained in this way is transferred from the delivery device 23 via a fluid line 25th into the analyzer 20th convicted. The transfer unit can be controlled by means of a local control unit or by means of the control electronics 10 of the sampling device 1 be performed.

The analyzer 20th can be done in the same way as above using 3 described analysis device for the automated implementation of a further sample preparation and for the subsequent implementation of an analysis, for example an immunological assay, a real-time qPCR-based analysis or a spectroscopic analysis of the sample. The analyzer 20th includes a computing unit 26th and an analysis cartridge 27 , in which the liquid analysis is controlled by means of the computing unit 26th he follows. The arithmetic unit 26th is for communication via cable 28 or wirelessly with the control unit 10 connected to read identifications and associated data of the samples to be analyzed and / or analysis results to the control electronics 10 return.

The control electronics 10 and / or the computing unit 26th can with a server, which in this example is part of a cloud 22nd is to communicate. Data exchange and analysis as well as further evaluations of the data and analysis results made available by means of a cloud application that accesses the data stored in the server can be carried out in a completely analogous manner as before using 3 described

The sampling device described here 1 and the measuring systems 100 and 101 can be used for process-compatible, systematic removal of liquid samples, in particular from water supply networks, sewage networks and sewage treatment plants, with subsequent analysis for the qualitative or quantitative determination of analytes comprising biopolymers, such as viruses, bacteria or DNA or RNA. The data can be made available systematically, in regular measurement cycles and with little personnel and time expenditure, and advantageously from a web or cloud application that can be accessed by a large number of end devices and that links the sample data with other data from other sources can be further analyzed or made available for further analyzes by authorities or scientific research institutions. On the one hand, this enables comprehensive studies on the course of epidemics; on the other hand, a reliable early warning system can be made available in the event of an increased occurrence of pathogens in the supply or wastewater.

Claims (26)

Automatic sampling device (1) for taking liquid samples from a sample liquid present at a sampling point (12) of a body of water or a container, in particular water or waste water, for the qualitative or quantitative determination of at least one analyte contained in the sample liquid, in particular a biopolymer, comprising: a with the sampling point (12) fluidly connectable sample line (5); a pumping device (4); at least one sample container (8) which can be fluidically connected to the sample line (5); and control electronics (10) which are set up to fluidically connect the sample line (5) to the at least one sample container (8), so that a flow from the sampling point (12) through the sample line (5) into the sample container (8 ) extending fluid flow path is formed, and wherein the control electronics (10) are further set up to transport a predeterminable volume of the sample liquid as a liquid sample along the fluid flow path into the sample container (8) by means of the pump device (5), characterized in that the sampling device ( 1) has means (14, 17) for concentrating and / or extracting the analyte present in the liquid sample. Automatic sampling device according to Claim 1 wherein the means for concentration and / or extraction comprise a collecting matrix which can be brought into contact with the liquid sample and which essentially selectively binds the analyte. Automatic sampling device according to Claim 2 , wherein the collecting matrix is arranged in the at least one sample container or in a unit that can be flowed through in a fluidically connected to the sample container, in particular a fluid line or a through-flow cartridge. Automatic sampling device according to Claim 2 or 3 , wherein the collecting matrix has a plurality of, in particular surface-functionalized, particles, in particular magnetic or polymer beads, a surface-functionalized substrate with a roughened or structured or porous surface, a functionalized fleece or a chromatographic separation column. Automatic sampling device according to Claim 4 , wherein the particles and / or the surface are functionalized for selective interaction with the analyte, in particular with antibodies or other capture molecules, for example aptamers or molecularly imprinted polymers. Automatic sampling device according to Claim 1 , wherein the means for concentration and / or extraction comprise a centrifuge integrated into the device. Automatic sampling device according to one of the Claims 1 until 6th , wherein the control electronics are set up to store an identification of the liquid sample for each liquid sample taken from the extraction point and to store a time stamp for the identification indicating the point in time at which the liquid sample is removed from the extraction point. Automatic sampling device according to Claim 7 , further comprising at least one interface for connecting the control electronics to at least one sensor which can be brought into contact with the sample liquid present at the sampling point and which is set up to transmit measurement signals of at least one measured variable of the sample liquid, for example temperature, pH value or conductivity, to generate and output to the control electronics, the control electronics being further set up to store at least one measured value of the measured variable derived from the measurement signals, which is recorded at the time at which the liquid sample is taken from the extraction point, for the identification of the liquid sample. Automatic sampling device according to Claim 7 or 8th , further comprising a temperature sensor, which is set up to detect a temperature of a liquid sample contained in the at least one sample container representing measured values and to output them to the control electronics, and wherein the control electronics are further set up to at least one of the measured values or a measured value curve for the To save the identification of the liquid sample. Automatic sampling device according to one of the Claims 7 until 9 , further comprising a GPS receiver which is set up to output location data to the control electronics, the control electronics being set up to store the location data for the identification of the liquid sample. Automatic sampling device according to one of the Claims 1 until 10 , the control electronics having a communication interface for outputting data, in particular identifications of liquid samples, additional information stored for the identifications, measured values, location data and time stamps to a, in particular portable, operating device or a server, the server being set up to transmit the data and to provide software, in particular a web or cloud application. Measuring system for the qualitative or quantitative determination of at least one analyte, in particular a biopolymer, in a sample liquid, in particular water or wastewater, comprising: an automatic sampling device for taking liquid samples of the sample liquid at a sampling point according to one of the Claims 1 until 11th ; an analysis device set up for the qualitative or quantitative determination of the at least one analyte; and a transfer device which is configured to provide a sample of the at least one analyte concentrated or extracted by means of the sampling device. Measuring system according to Claim 12 , wherein the transfer device is configured to automatically transfer the sample of the concentrated or extracted analyte to the analysis device. Measuring system according to Claim 12 or 13th , further comprising control electronics which are set up to control the transfer device for the automated transfer of a sample of the concentrated or extracted analyte to the analysis device. Measuring system according to one of the Claims 12 until 14th , wherein the analysis device is set up to carry out the qualitative or quantitative determination of the analyte partially or completely automatically, for example using an affinity-based, in particular antibody-based, assay, using a real-time qPCR-based method or using a spectroscopic method. A method for the automated provision of a sample for a qualitative and / or quantitative determination of at least one analyte, in particular a biopolymer, in a sample liquid, in particular water or wastewater, comprising: - Removal of a predeterminable volume of the sample liquid as a liquid sample from the removal point by means of an automatic Sampling device, in particular the sampling device according to one of the Claims 1 until 11th , from the sample liquid present at a sampling point, for example in a container or a body of water; - Transporting the volume of the sample liquid as a liquid sample into a sample container; and bringing the liquid sample into contact with a collecting matrix which immobilizes the analyte, in particular binds it essentially selectively. Procedure according to Claim 16 , wherein the collecting matrix is presented in the sample container or is arranged in a unit through which a flow can flow and which is fluidically connected to the sample container, in particular a fluid line or a filter cartridge which can be flowed through. Method according to one of the Claims 16 or 17th , further comprising: removing the collecting matrix with the analyte from the device and / or eluting the analyte from the collecting matrix to form a solution of the analyte as a sample for the subsequent qualitative and / or quantitative determination. Method according to one of the Claims 16 until 18th , further comprising the storage of an identification of the liquid sample and a time stamp representing the point in time at which the liquid sample was removed from the removal point in an electronic control system of the automatic sampling device. Procedure according to Claim 19 , further comprising the acquisition of at least one measured value of at least one measured variable of the sample liquid, for example the temperature, the pH value or the conductivity, at the time the liquid sample is removed from the extraction point by means of an additional sensor and storage of the measured value in the control electronics to identify the liquid sample . Method according to one of the Claims 19 or 20th , further comprising the detection of a temperature or a temperature profile to which the liquid sample is exposed from the point in time of its removal, and storage of measured values representing the temperature or the temperature profile in the control electronics to identify the liquid sample. Method according to one of the Claims 19 until 21 , further comprising the transfer of the identification of the liquid sample, the associated time stamp and other associated data and / or measured values to an operating device, to an analysis device used for analyzing the provided sample or to a server connected to the analysis device and / or the control electronics for communication, the stores the data and / or measured values received from the control electronics and / or the analysis device and accesses its memory by software, e.g. a web or cloud application, in order to display the data and / or a more detailed analysis of the data and / or measured values perform. A method for the qualitative or quantitative determination of at least one analyte, in particular a biopolymer, in a sample liquid, in particular water or wastewater, comprising: providing the sample by means of the method according to one of the Claims 16 until 22nd ; and - qualitative or quantitative determination of the analyte by means of an analysis method, in particular by means of an immunological assay or a real-time qPCR-based method. Procedure according to Claim 23 , further comprising: determining a concentration of the analyte in the original liquid sample with additional inclusion of at least one measured value recorded at the extraction point, in particular the temperature or the pH value or the conductivity, the at least one measured value being made available by control electronics of the sampling device . Procedure according to Claim 23 or 24 , further comprehensive communication of determined analysis results and, if necessary, additional data to software, in particular a web or cloud application. Procedure according to Claim 25 , wherein the software generates and displays a graphic representation of a spatial distribution and / or a development over time of the concentration of the analyte at a multiplicity of sampling points.

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