EP2087362A1 - Dispositif fluidique et procédé pour faire fonctionner ce dispositif - Google Patents

Dispositif fluidique et procédé pour faire fonctionner ce dispositif

Info

Publication number
EP2087362A1
EP2087362A1 EP07819500A EP07819500A EP2087362A1 EP 2087362 A1 EP2087362 A1 EP 2087362A1 EP 07819500 A EP07819500 A EP 07819500A EP 07819500 A EP07819500 A EP 07819500A EP 2087362 A1 EP2087362 A1 EP 2087362A1
Authority
EP
European Patent Office
Prior art keywords
liquid
cleaning
metering
fluidikeinrichtung
metering device
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP07819500A
Other languages
German (de)
English (en)
Inventor
Erik HÖHNE
Nenad Gajovic-Eichelmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Original Assignee
Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV filed Critical Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Publication of EP2087362A1 publication Critical patent/EP2087362A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • 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
    • G01N35/1004—Cleaning sample transfer devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L13/00—Cleaning or rinsing apparatus
    • B01L13/02—Cleaning or rinsing apparatus for receptacle or instruments
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0289—Apparatus for withdrawing or distributing predetermined quantities of fluid
    • B01L3/0293—Apparatus for withdrawing or distributing predetermined quantities of fluid for liquids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/141—Preventing contamination, tampering
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/56—Labware specially adapted for transferring fluids
    • B01L3/563—Joints or fittings ; Separable fluid transfer means to transfer fluids between at least two containers, e.g. connectors
    • 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
    • G01N35/1004—Cleaning sample transfer devices
    • G01N2035/1006—Rinsing only the inside of the tip
    • 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
    • G01N2035/1027—General features of the devices
    • G01N2035/1048—General features of the devices using the transfer device for another function
    • G01N2035/1058—General features of the devices using the transfer device for another function for mixing
    • G01N2035/106—General features of the devices using the transfer device for another function for mixing by sucking and blowing
    • 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
    • G01N2035/1027—General features of the devices
    • G01N2035/1048—General features of the devices using the transfer device for another function
    • G01N2035/1062—General features of the devices using the transfer device for another function for testing the liquid while it is in the transfer device
    • 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
    • G01N35/1081—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices characterised by the means for relatively moving the transfer device and the containers in an horizontal plane
    • G01N35/109—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices characterised by the means for relatively moving the transfer device and the containers in an horizontal plane with two horizontal degrees of freedom
    • 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

Definitions

  • the invention relates to a Fluidik leverage, which is adapted for handling liquid samples, in particular a Fluidik leverage the features of the preamble of claim 1, and a method for their operation.
  • Fluidics techniques have numerous applications, e.g. As in clinical diagnostics, food and environmental analysis and biotechnology research, operations such. Aspiration and dosing of liquids, mixing of various liquids, washing of solid phase reagents or serial dilution steps. In particular, there is an interest in automatic techniques, e.g. As automated immunoassays or automated clinical chemical assays.
  • Typical requirements for fluidic techniques, in particular in analytical instruments and in diagnostics, are the precision in all fluidic operations and the sample throughput with regard to the cleaning and possibly sterilization of the devices used, in particular the flow paths (fluidic paths).
  • Fluidic techniques known in the art are generally based on the combination of pumps, valves and fluid lines.
  • the pumps include z.
  • the use of valves generally means an increased risk of contamination.
  • This disadvantage is in complex fluid operations, eg. B. Operations with at least two liquids (eg system solution and Wash solution), particularly critical, as these typically require at least one valve that can switch between the different fluidic pathways.
  • Fully automatic devices, eg. B. for performing immunoanalytical tests have to handle several different operations and therefore often require more than one pump and more than one valve.
  • automatic gantry robots are known in practice, which contain a plurality of diluters in a three-dimensionally constructed rail system, wherein valves are provided for switching between different system liquids and samples are taken or delivered with a dispensing needle mounted on a robot arm.
  • Conventional portal robots are typically designed for a wide range of applications. However, they have the following disadvantages. In general, the fluidic paths are relatively long due to the geometrical dimensions of the robot (distance storage vessel to dispensing needle), without any requirement for the test to be carried out. However, long fluid pathways are difficult to clean. Furthermore, they cause a high consumption of system fluids. Furthermore, such robots are expensive and maintenance-intensive and therefore in particular unsuitable for use in specialized consumer equipment.
  • the conventional fluidic techniques generally have disadvantages in terms of cleaning, especially in fully automatic cleaning processes. Liquid-filled system liquid tanks and hose lines may become contaminated when exposed to prolonged use. B. due to stagnant liquid in the system.
  • US Pat. No. 4,422,151 describes a valve-free fluidic device with a system fluid tank and a pump, in which samples are addressed sequentially by a 3-axis robotic arm with a dispensing needle mounted.
  • the fluidic device has the disadvantage that only cleaning with system solution (eg water) is possible.
  • system solution eg water
  • the system solution tank which must always be filled with liquid (eg water)
  • liquid eg water
  • a particular disadvantage is that the system solution tank can not be sterilized during operation.
  • washing liquid can be aspirated without entering the diul wells or the system liquid tank.
  • the liquid must be released through the tip again, it must be approached to a waste position.
  • intensive washing processes repeat this step several times, which increases the processing time.
  • the invention has for its object to provide an improved Fluidik adopted and an improved method for operating a Fluidik thanks with which the disadvantages of the conventional fluidic techniques are overcome.
  • the invention is based on the general technical teaching of a fluidic device with a fluid line extending between a metering device for receiving or dispensing at least one system fluid in a metering working area and a fluid port for receiving a cleaning fluid in a cleaning work area, and to be provided with a pump device for actuating the metering device, wherein the pump device is arranged on the liquid line and adapted for uninterrupted fluid delivery in the liquid line with changing conveying direction.
  • a single, continuous liquid line is used according to the invention.
  • the liquid line forms a branch-free fluidic path between the fluid connection and the metering device.
  • system liquid here refers to any liquid which fulfills a system function and / or represents a sample.
  • the system liquid comprises z.
  • at least two different system fluids may be used alternately (e.g., dilution buffer for sample dilution and wash fluid for rinsing).
  • system liquid here also includes sample liquids such.
  • sample liquids such as solutions, dispersions or suspensions containing certain sample molecules, eg. As proteins, or biological samples, for. For example, cells, cell groups or cell components.
  • the invention is characterized in that it is possible to work with a system liquid, which if necessary exclusively comprises a sample liquid, or with a plurality of different system liquids. Only with one sample liquid, ie without an additional system liquid, can precise aspirating and dosing step processes of sample liquids be performed, mixtures of two or more sample liquids, as well as the mixing of a sample or mixture of samples by blowing in air. In addition, dilution and serial dilution operations can be performed with a system fluid, and solid, eg, solid phase reagents (especially powdered samples) can be dissolved in a defined volume.
  • system fluids can be continuously washed and decontaminated throughout the fluidic path, with the wastes collected in a separate waste container to eliminate system solution contamination and fluidic pathways.
  • continuous conveying takes place in one direction only to prevent sample carryover and deposits.
  • metering work area here refers to the spatial area in which the metering device can be moved for dispensing or receiving system fluid.
  • cleaning work area here refers to the spatial area in which the fluid connection can be moved. The dosing and cleaning work areas are partially overlapped.
  • the pump device fulfills a dual function.
  • the pump means may be operated to receive or dispense at least one system fluid with the metering device.
  • the pump device can be operated such that the cleaning fluid is taken up by the fluid connection into the fluid line and flushed by the metering device or that the entire fluid line is ventilated.
  • the two operating modes in particular between the metering mode with the operation of the metering device and the cleaning mode with the cleaning of the metering device can be switched exclusively by the adjustment of the conveying direction and delivery time (delivery volume) of the pump device.
  • a valve-free fluidic path is thus provided between the metering device and the fluid connection.
  • the fluidic device according to the invention is characterized by a simple and efficient, hygienic cleaning and possibly sterilization of the fluidic path and therefore simplifies automatic process sequences. Preferred applications therefore result in the analysis and processing of complex liquids in analytical-chemical instruments, eg. For the purpose of completely cleaning the fluid line of sample residues, continuous one-way purging is allowed, with the cleaning and system liquids being continuously conveyed to a waste position can.
  • the fluidic device which can be flushed continuously in one direction according to the invention, is superior to a conventional system with a change in direction of liquid transport, in which cleaning fluid is aspirated and re-dispensed through a dispensing needle or switched over between two fluidic paths with a 3/2-way valve got to.
  • the liquid line of the fluidic device according to the invention preferably has a constant cross-sectional area between the metering device and the fluid connection.
  • the fluidic device is preferably equipped with a cleaning device.
  • the cleaning device is set up to receive a cleaning liquid.
  • the cleaning liquid is provided in the cleaning operating region of the fluidic device, so that the fluidic device can have relatively small dimensions.
  • the fluid connection is detachably arranged on the cleaning device.
  • the fluid connection can be temporarily connected to the cleaning device, z. B. inserted into a cleaning liquid in the cleaning device, in particular submersible. It is preferably provided that the fluid connection is changed from a state coupled to the cleaning device, in which the fluid connection protrudes into the cleaning fluid and the cleaning fluid can be flushed through the fluid line, into a free state, in which the fluid connection forms an open end Liquid line forms.
  • the separability of the fluid connection of the cleaning device, in particular of the cleaning liquid in the cleaning device is an important feature of the invention that, as it significantly facilitates the decoupling of the dosing and cleaning modes of Fluidik contrary is
  • the fluidic device is provided with a manipulator device. equipped with which the metering device can be moved and positioned.
  • the position of the metering device in the metering operating range can be set.
  • the interaction of the manipulator and pump devices allows system fluids to be transported within the metering work area.
  • the manipulator device for positioning the metering device is set up in all three spatial directions. Particularly preferred is a linear translation z. B. along rails provided in the
  • the manipulator device has the geometry of a conventional gantry robot.
  • the z. B. has three independent translation paths or simplified two coupled translation paths and an independent translation path, the metering device can be advantageously positioned in all three spatial coordinates. This allows different types of Probengefä wear, z. For example, tubes, miniature reaction vessels (e.g., so-called Eppendorf tubes, PCR tubes), beakers, and bottles typically up to 20 cm in height are started up with the metering device.
  • miniature reaction vessels e.g., so-called Eppendorf tubes, PCR tubes
  • beakers typically up to 20 cm in height are started up with the metering device.
  • the manipulator device is additionally set up for adjusting the position of the fluid connection.
  • the fluid connection of the fluid line can be moved with the manipulator device within the cleaning work area to the cleaning device and connected to it.
  • the manipulator device thus fulfills a dual function during the positioning of the metering device and of the fluid connection.
  • the operation of the Manipu- lator can be simplified if the metering device and the fluid connection with the manipulator device are jointly movable.
  • the fluid connection and the metering device are mechanically coupled.
  • the ends of the liquid line are generally attached to a common carrier, which is movable with the manipulator device.
  • the dosing device and the fluid connection are arranged offset on the carrier in the vertical direction.
  • the vertical distance is selected so that the fluid connection is located above the sample vessel or adjacent sample vessels when the metering device is actuated in the metering working area, in particular when dispensing or picking up a system fluid on a sample vessel.
  • the vertical distance may be selected as a function of the specifically realized geometry of the sample vessel in the dosing work area and is typically at least 1 cm, preferably at least 2 cm, such. B. 4 cm.
  • a variant of the invention in which the metering device and the fluid connection both through hollow conduits, z.
  • hollow needles are formed, which are vertically aligned attached to the carrier and open at the bottom.
  • the opening of the metering device which is set up to receive or discharge the system liquid, protrudes downwards in the vertical direction relative to the opening of the fluid connection, which is set up to receive the cleaning liquid.
  • the cleaning device comprises a storage vessel for receiving the cleaning liquid and a washing vessel, is set up for external cleaning of the metering device, the functionality of the cleaning device is advantageously improved.
  • the storage and washing vessels are arranged side by side in the cleaning work area.
  • the provided on the storage and washing vessels openings for receiving the fluid connection and the metering device have a predetermined distance accordingly.
  • the fluid connection and the metering device are fastened to the support of the manipulator device at a horizontal distance which is equal to the horizontal distance of the receptacles of the storage and washing vessels.
  • the fluid connection and the metering device can thus be transferred into the cleaning mode with a single movement of the carrier, in which the fluid connection to the storage vessel of the cleaning fluid and the metering device to the washing vessel are connected.
  • the washing vessel comprises an overflow vessel having a closed bottom and an overflow opening. The overflow vessel is adapted to receive the cleaning fluid, with which the metering device is rinsed, and to allow it to flow to the overflow opening via the outside of the metering device.
  • the storage vessel of the cleaning device is an open-topped container, which is arranged in the cleaning working area of the fluidic device.
  • the storage vessel is in the cleaning work area z. B. placed on a base block of Fluidik Surprise.
  • the container has on its upper side an opening through which the fluid connection can be inserted and submerged in a cleaning liquid in the container.
  • the storage vessel is exchangeable, preferably a disposable container is used.
  • the metering working area of the fluidic device is set up to receive a plurality of sample vessels.
  • the dosing work area has a holder for the sample containers, such. B. on a support platform. Two or more (eg, 10, 50, 100, 400, or even over 1000) sample cups are provided.
  • the sample vessels comprise individual compartments or compartment arrays, such. B. a 384 microtiter plate.
  • At least one system liquid reservoir is arranged in the dosing work area, further advantages for an effective handling of liquids for different fluidic operations can result.
  • the metering device is not connected to a permanently installed system fluid tank via the fluid line, but is set up to receive system fluids by movement to the system fluid reservoir and actuation of the pump device.
  • an open-topped container is preferably provided, which in the metering work area z. B. is placed on the base block of Fluidik Surprise.
  • the container has on its upper side an opening through which the metering device can be inserted and submerged in a system liquid in the container.
  • the container is like the storage vessel preferably arranged interchangeable, it is z. B. uses a disposable container.
  • a permanently installed system liquid tank is avoided, which would represent a risk of contamination of the system liquid.
  • system fluid reservoir is not necessarily provided.
  • an additional system liquid is not required in addition to the sample liquids.
  • the fluid conduit of the fluidic device according to the invention can in principle be made in any shape and with any material that is selected as a function of the specific application.
  • the liquid line consists of a flexible material, at least in some areas.
  • the pump device of the fluid line can thus be arranged in a stationary manner, while the fluid connection and the metering device can be positioned freely in the metering and cleaning work areas, in particular using the manipulator device.
  • the liquid line is formed in the respective sections by a flexible hose.
  • the entire fluid line consists of see the metering device and the fluid connection from the flexible hose or two pieces of tubing with the pump means, since in this case advantages for the simplification of the structure of Fluidik announced, the availability of inert tubing materials and the effectiveness of the pump device result.
  • the pump device preferably comprises a positive displacement pump, which acts on the fluid line from the outside.
  • parts of the pumping device are separated from the cleaning system or sample liquids by the wall of the liquid line so that contamination of the pumping device is avoided.
  • a diaphragm pump or a peristaltic pump provided, which have advantages in terms of easy cleaning, low risk of contamination and large, continuously to be pumped volumes.
  • Another advantage is the high precision in all fluidic operations, especially when used in analyzers. During aspirations, dosing, washing and incubation, the variance in volume or flow rate of system or cleaning fluids can be minimized.
  • the field of application of the fluidic device can advantageously be extended.
  • the sensor device is provided for measuring at least one property of liquids in the liquid line, in particular in the metering device or an adjacent part of the liquid line.
  • the sensor device is set up to detect system fluids.
  • a particularly simple construction results when the sensor device is introduced into the liquid keits Arthur is integrated, ie forms part of the liquid line.
  • an optical sensor possibly in combination with a lighting device in the liquid line may be provided.
  • the invention is based on the general technical teaching, in a method for operating a fluidic device, in particular the fluidic device according to the invention, a transport of at least one system liquid in a metering operating range with a metering device which has a first end of a fluid line and is provided with a pump device, and a recording of a cleaning liquid in the liquid line by a fluid connection, which forms a second end of the liquid line to provide, during transport (delivery or recording) of the at least one system liquid or for receiving the cleaning liquid, the conveying direction Pump means which is arranged between the first and second ends of the liquid line is changed.
  • the metering device For transporting the at least one system liquid, the metering device is moved sequentially to at least one sample vessel in the metering working area and the pump device is actuated with repeatedly changed conveying direction such that the at least one system liquid is taken up by the metering device (sucked in) or at least one sample vessel is delivered.
  • the pump device is actuated with repeatedly changed conveying direction such that the at least one system liquid is taken up by the metering device (sucked in) or at least one sample vessel is delivered.
  • Dosiermodus all typical operations of liquid handling, such.
  • dosing conveying with predetermined, z. B. constant flow rate, dilution, in particular serial dilution, washing and / or mixing of the at least one system liquid in the at least one sample vessel provided.
  • a cleaning fluid is preferably taken up by a cleaning device through the fluid connection into the fluid line and flushed by the metering device and / or the fluid line is vented through the fluid connection.
  • the cleaning mode has the advantage that the fluid line and in particular the metering device is free of system fluids in idle mode.
  • the different modes of operation d. H. the dosing mode, in which the samples are sucked in and output by the metering device, and the cleaning mode in which cleaning solution is continuously sucked through the fluid connection and is discharged again by the metering device in the washing position, represent an essential feature of the method according to the invention.
  • the switching between these modes occurs without the use of a valve, with the advantageous consequence of a particularly easy and thorough cleaning of all fluidic pathways of the system and the avoidance of contamination risks.
  • the inventors have found that surprisingly with a single liquid line complex liquids such. As milk, handle very well, and that the Fluidik adopted can be completely flushed with a minimum use of cleaning solution.
  • the low consumption of cleaning solutions is an aspect which has particular significance in on-site devices or in dealing with explosive (toxic) liquids because of the associated disposal costs.
  • the fluidic device according to the invention can be stored for a long time without use, without contamination occurring, for example cyanobacteria or algae growth, dust Entry etc .. When commissioning after a break in operation no special cleaning protocols had to be used.
  • the use of the fluidics device according to the invention or the associated operating method, in particular in analytical-chemical analyzes, in liquid treatments of biological samples, in clinical diagnostics, in environmental analysis, in food chemistry and / or in the performance of immunoassays represents a further subject of the invention.
  • Preferred applications are in the analytical chemical study of pathogens, eg. B. Botulismuserregern (Clostriudium botulinum), Pesterregern (Y- ersinia pestis), and bacterial varieties that have developed resistance to antibiotics (Streptococcus aureus strains, MRSA etc). This listing of possible applications is without limitation of completeness.
  • the Fluidik sensible can be used as a so-called liquid handling robot z. B. be used as a single device for sample preparation or for sample processing.
  • the invention has the following further advantages. Since the used in clinical, food chemical and environmental analysis for analysis complex fluids such. As blood, milk, slurries, food samples have a high content of solids, the easy cleaning is an important advantage of Fluidik adopted. The Fluidik adopted works with high precision, d. H. while maintaining given volumes and volume flows and an exact timing of the fluidic operations (timing).
  • the device according to the invention thus has the potential of conventional technical solutions when used in fully automatic or partially automated analyzers of clinical and veterinary diagnostics, environmental analysis, Food chemistry and biotechnology, particularly in low-cost, on-site analyzers designed to perform complex analytical-chemical processes in the field.
  • the fluidic device is a fluid-handling system which is particularly simple in construction and which is particularly easy to clean and which can process two or more system fluids and up to several hundred sample fluids. It advantageously combines a continuously conveying pump with a single fluidic path consisting of two hollow needles of the fluid connection or the metering device and at least one hose connection, a 3-axis robot and disposable vessels for the supply of all liquids (system fluids and samples). Due to the constructive realization and the switching between two different operating modes (dosing mode or cleaning mode), the use of permanently installed system solution tanks can be dispensed with and no liquid remains in the system during idle operation.
  • the fluidic device is particularly suitable for liquid handling in low-cost on-site analyzers for carrying out complex analytic-chemical analyzes, in particular for carrying out immunoassays.
  • Figure 1 a schematic perspective view of a first
  • FIG. 2 shows an illustration of the combination according to the invention of a fluid line with a pump device
  • FIG. 3 shows a schematic perspective view of a further embodiment of the fluidic device according to the invention.
  • FIG. 1 illustrates a first embodiment of the fluidic device 100 according to the invention with the fluid line 10, the metering work area 20, the pump device 30, the cleaning device 40, the manipulator device 50 and the cleaning work area 60.
  • the components 10 to 30 and 60 are also enlarged in FIG Figure 2 shown.
  • a multiplicity of sample vessels 21, which contain samples for the treatment or processing with the fluidic device, and a system liquid reservoir 22 are arranged in the dosing working area 20, a multiplicity of sample vessels 21, which contain samples for the treatment or processing with the fluidic device, and a system liquid reservoir 22 are arranged.
  • the sample containers 21 are set up for storage and handling of the liquid samples and z. B. on a support (so-called tray).
  • the fluidic device 100 has a base block 110, on which the manipulator device 50 is mounted and in which Liquid waste container (not shown) is included.
  • a Fluidik Skewed, a Fluidik, a Controller, a control panel and possibly for automated detection of sample vessels and their posi- tions a camera device, which are known per se and not shown in the figures.
  • the liquid line 10 extends between a first end 11 with the metering device 12 and a second end 13 with the fluid connection 14.
  • the liquid line 10 consists of a first piece of tubing extending from the first end 11 to the pump means 30 and a second piece of tubing, the extends between the pumping device 30 and the second end 13.
  • an integral continuous tube may be provided which is integrated into the pump device 30.
  • the pieces of hose or the continuous hose consists z. B. silicone with an outer diameter of 3.2 mm and an inner diameter of 1.6 mm.
  • the metering device 12 is generally provided for receiving or dispensing liquids and comprises a hollow conduit, in particular a hollow needle and a metering reservoir, which is formed by the interior of the end of the liquid conduit 10.
  • the inner diameter of the hollow needle is preferably equal to the inner diameter of the liquid line.
  • the hollow needle is, for example, a steel cannula with a length of approx. 50 mm, an outer diameter of 2 mm and an inner diameter of 1.6 mm.
  • the fluid connection 14 is preferably also formed by a hollow needle, the z. B. as the hollow needle of the metering device is executed.
  • the pump device 30 comprises a peristaltic pump 31, which is attached to the manipulator device 50.
  • peer ristaltikpumpe 31 is z. B. the program-controlled, provided with a stepper motor pump type SR25-S300 (manufacturer: Rietschle Thomas AG) provided.
  • the manipulator device 50 comprises a three-axis gantry robot.
  • the manipulator device 50 comprises a bridge fixedly fixed to the base block 110 bridge 52, on which the carrier 51 of the metering device 12 and the fluid connection 14 with two linear translational drives in the orthogonal y- and z-
  • the carrier 51 consists of a carrier plate 54 and two laterally protruding needle holders 55.
  • the needle holders 55 each have a receptacle for the hollow needles of the metering device 12 and the fluid connection 14.
  • the receptacles of the needle holder 55 have in the horizontal direction (y-
  • Hollow needles of the metering device 12 and the fluid connection 14 include, have a mutual vertical displacement Z 0 ( Figure 2).
  • the vertical displacement Zo is chosen such that, in the case of all movements of interest, the hollow needle of the metering device 12 in the metering working region 20 enters
  • the vertical distance Zo is selected by selecting a suitably sized plate 54 of the carrier 51.
  • a height adjustment may be provided by a displacement of the hollow needles in the receptacles of the needle holder 55 in the vertical direction.
  • the cleaning device 40 comprises the storage vessel 41 and the washing vessel 42, which are arranged in a cleaning work area 60 next to the metering work area 20 on the base block 110.
  • the storage and washing vessels 41 are located on the base block 110 next to the bridge 52 such that the hollow needles of the metering device 12 and the fluid port 14 by a movement of the carrier 51 in the y and z directions respectively in the storage vessel 41 and the Washing vessel 42 can be introduced.
  • the storage and washing vessels are arranged with a vertical working distance Zi, which is equal to the vertical distance Zo of the hollow needles of the metering device 12 and the fluid connection 14.
  • the washing vessel 42 is designed for passive cleaning by inner and outer rinsing of the dosing device 12.
  • the essential advantage of the invention is achieved that the metering device 12 and the fluidic connection 14 in the metering work area functionally decoupled and functionally coupled in the cleaning workspace 60. Contrary to the intuitive assumption that it is not possible to completely decouple the functions of the two mechanically coupled hollow needles or the dosing mode from the cleaning mode, it has been found that this can be achieved by the shown arrangement of the storage and washing vessels and the sample vessels.
  • a reservoir 41 and system liquid reservoir 22 are preferably disposable articles such.
  • the sample containers 21 are arranged so that they lie completely in the dosing working area 20.
  • the system fluid reservoir 22 is mounted so that it is at least partially disposed in the metering work area 20.
  • the storage vessel 41 is mounted so that it is at least partially disposed in the cleaning work area of the fluid port 14, and the distance of the fluid port 14 and the metering device 12 is selected so that the metering device 12 is immersed in the washing vessel 42 (overflow) when the Fluid connection 14 immersed in the cleaning liquid in the storage vessel 41.
  • the fluid port 14 is disposed at a fixed offset in the x and z directions so that it can never penetrate the metering work area 20 when the metering device 12 is moved in the metering work area 20.
  • the fluid connection 14 Depending on the depth (z height) of the sample vessels processed by the metering device 12, it is sufficient to mount the fluid connection 14 correspondingly higher and to correspondingly increase the mounting height of the cleaning fluid storage vessel 41.
  • the waste liquid container 111 is arranged so that the liquid wastes entering the passive washing station flow by gravity into the waste liquid container 111, ie it is below the liquid levels the storage vessels and the sample vessels and below the dosing work area and the cleaning work area.
  • FIG. 3 shows a modified embodiment of the fluidic device 100 with the fluid line 10, the metering work area 20, the pump device 30, the cleaning device 40, the manipulation device 50, the cleaning work area 60 and a sensor device 70.
  • the fluid line 10 is at a vertical distance the end, d. H. the metering device 12 and the fluid connection 14 on the carrier 51 of the manipulator device 50 is attached.
  • the pump device 30 is arranged in the liquid line 10.
  • a stationary metering operating region is provided in the fluidic device 100 according to FIG. 3, a stationary metering operating region is provided.
  • the manipulator device 50 is equipped with three linear drives (eg, stepper motors) for moving the carrier 51 in all three spatial directions.
  • the sensor device 70 is integrated in the liquid line 10 in the region of the metering device 12.
  • the sensor device 70 comprises z. B. a fluorescence measuring cell, z. B. with fiber optic sensors.
  • Figure 3 further illustrates the waste liquid container 111 which is connected to the washing vessel 42 of the cleaning device.
  • the cleaning liquid which is purged by the liquid line 10 during cleaning, flows from the overflow opening of the washing vessel 42 into the waste liquid container 111.
  • Example 1 Robot for handling liquid samples
  • Example 2 Immunosensor with flow cell and integrated sample handling robot
  • the Fluidik adopted for handling liquid samples of Example 1 is by integration of a sensor device 70th ( Figure 3) in the fluid path to an immunoassay analyzer with fully automated processing of clinical samples, food samples or environmental samples upgraded.
  • the sensor device comprises a through-sensor, in particular an immunosensor 70, such.
  • the Fluidik worn is z.
  • the milk samples are introduced into the fluidics device in a first group of sample containers (snap-cap bottles, eg from the manufacturer Fisher Scientific) in a sample carrier.
  • 12 further sample vessels for example manufactured by Eppendorf AG
  • doped with lyophilized antibody-fluorophore conjugates are also introduced into the fluidic device.
  • the fully automatic processing of the samples is carried out by the following sequence of fluidic operations:
  • control of the sequence of operations and the analysis of the measurement results are performed by an external computer or an embedded controller.

Abstract

L'invention concerne un dispositif fluidique (100) qui comprend une conduite de liquide (10) dont la première extrémité (11) forme un dispositif de dosage (12), conçu pour prélever ou distribuer un liquide de système dans une zone de travail de dosage (20), et dont la seconde extrémité (13) présente un raccord fluidique (14), conçu pour prélever un liquide de nettoyage, ainsi qu'un dispositif de pompage (30) destiné à actionner le dispositif de dosage (12). L'invention se caractérise en ce que le dispositif de pompage (30) est disposé sur la conduite de liquide (10) entre la première et la seconde extrémité (11, 13) de celle-ci et en ce qu'il est conçu pour acheminer un liquide dans la conduite de liquide (10) dans un sens ou dans l'autre. L'invention concerne en outre un procédé pour faire fonctionner ce dispositif fluidique.
EP07819500A 2006-11-10 2007-10-31 Dispositif fluidique et procédé pour faire fonctionner ce dispositif Withdrawn EP2087362A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102006053096A DE102006053096A1 (de) 2006-11-10 2006-11-10 Fluidikeinrichtung und Verfahren zu deren Betrieb
PCT/EP2007/009468 WO2008055613A1 (fr) 2006-11-10 2007-10-31 Dispositif fluidique et procédé pour faire fonctionner ce dispositif

Publications (1)

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EP2087362A1 true EP2087362A1 (fr) 2009-08-12

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DE (1) DE102006053096A1 (fr)
WO (1) WO2008055613A1 (fr)

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DE202008016770U1 (de) * 2008-12-19 2010-05-27 Schröder Maschinenbau KG Vorrichtung zur Injektion von Flüssigkeit in Lebensmittelprodukte
DE102010037084A1 (de) * 2010-08-20 2012-02-23 LCTech GmbH Probenaufbereitungssystem sowie ein Verfahren zur Bearbeitung einer Probe
ES2526268B1 (es) 2013-06-03 2015-10-20 Manuel BORREGO CASTRO Procedimiento de limpieza de vasos de disolución y posterior dosificación de medio de disolución y equipo modular móvil de limpieza y dosificación para su puesta en práctica

Citations (1)

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FR2530814A1 (fr) * 1982-07-21 1984-01-27 Astec Procede de dilutions steriles

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FR2222306B1 (fr) 1973-03-22 1977-02-04 Nal Transfusion Sanguine Centr
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DE3831068A1 (de) * 1988-09-13 1990-03-22 Sihi Gmbh & Co Kg Verfahren zur reinigung einer stoffbuchslosen, rotierend arbeitenden foerdereinrichtung fuer fluide
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CA2132270A1 (fr) * 1993-10-28 1995-04-29 Erich Lerch Systeme de pipetage automatise dote d'un dispositif de rincage
SE503669C2 (sv) 1994-09-14 1996-07-29 Cma Microdialysis Holding Ab Förfarande för analys samt anordning för genomförande av förfarandet
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TW590795B (en) * 2002-04-17 2004-06-11 Rohm & Haas An automated system and process for the preparation of a high viscosity fluid formulation

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FR2530814A1 (fr) * 1982-07-21 1984-01-27 Astec Procede de dilutions steriles

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WO2008055613A1 (fr) 2008-05-15

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