EP2186565A1 - Appareil de mesure et procédé de détermination de paramètres de fluide préparés par un système de laboratoire - Google Patents

Appareil de mesure et procédé de détermination de paramètres de fluide préparés par un système de laboratoire Download PDF

Info

Publication number
EP2186565A1
EP2186565A1 EP09175882A EP09175882A EP2186565A1 EP 2186565 A1 EP2186565 A1 EP 2186565A1 EP 09175882 A EP09175882 A EP 09175882A EP 09175882 A EP09175882 A EP 09175882A EP 2186565 A1 EP2186565 A1 EP 2186565A1
Authority
EP
European Patent Office
Prior art keywords
hybridization
measuring
measuring unit
sensor
standard 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Withdrawn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
EP09175882A
Other languages
German (de)
English (en)
Inventor
Wolfgang Streit
Gerald Probst
Juha Koota
Gyoergy Wenczel
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.)
Tecan Trading AG
Original Assignee
Tecan Trading AG
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 Tecan Trading AG filed Critical Tecan Trading AG
Publication of EP2186565A1 publication Critical patent/EP2186565A1/fr
Withdrawn legal-status Critical Current

Links

Images

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/028—Modular arrangements
    • 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
    • B01L2200/143—Quality control, feedback systems
    • B01L2200/146—Employing pressure sensors
    • 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
    • B01L2200/143—Quality control, feedback systems
    • B01L2200/147—Employing temperature sensors
    • 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
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/024—Storing results with means integrated into the container
    • 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
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/043—Hinged closures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0663—Whole sensors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0822—Slides
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0877—Flow chambers
    • 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
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation

Definitions

  • the invention relates to a measuring device with a measuring unit and a processing unit for determining fluid parameters provided by a laboratory system.
  • This measuring unit is integrally formed in this laboratory system.
  • the invention also relates, according to the preamble of independent claim 20, to a method for determining fluid parameters provided by a laboratory system. For carrying out this method, the measuring device quoted above is used.
  • Automated laboratory systems are known for performing a variety of processes, such as handling larger volumes of liquids (such as fermenters or automated pipetting machines) or smaller volumes of liquid (such as spotting / immobilizing biological samples on supports), nucleic acid amplifications (such as the polymerase chain reaction). PCR, or sequencing reactions) or else for carrying out hybridization reactions.
  • hybridization reactions are preferably carried out in gap-shaped, small spaces.
  • the sample to be hybridized is immobilized on a solid substrate surface.
  • These samples to be hybridized are then contacted with a suspension containing the desired binding partner, the pattern.
  • Hybridization reactions form the basis for various investigation techniques in molecular biology laboratories.
  • Immobilized samples may include, for example, amino acid-containing (eg, proteins, peptides) or nucleic acid-containing (eg, DNA, cDNA, RNA) samples.
  • Samples added to the immobilized samples can be any molecules or chemical compounds (eg, DNA, cDNA, and / or proteins or polypeptides) that hybridize or otherwise bind to the immobilized samples.
  • molecules or chemical compounds eg, DNA, cDNA, and / or proteins or polypeptides
  • Devices or systems for the automated implementation of such hybridization reactions are already available.
  • the DNA microarray technique has become established for hybridizing DNA. This is based on a hybridization reaction in which simultaneously or simultaneously thousands of genes are detected and / or analyzed.
  • This technique involves the immobilization of DNA samples from many genes on a substrate, e.g. on a glass slide for a light microscope.
  • the DNA samples are preferably stored in a defined array of sample spots or "spots", i. in a two-dimensional grid arrangement, applied to the substrate. Later, starting from a specific position within such an array, it is possible to deduce the origin of the corresponding DNA sample and thus its identity.
  • the technique further includes contacting the DNA sample array with RNA pattern suspensions to detect specific nucleotide sequences in the DNA samples.
  • RNA patterns may be labeled with a so-called "tag” or "label", i. be provided with a molecule which is e.g. emits a fluorescent light having a specific wavelength.
  • RNA samples hybridize or bind to immobilized DNA samples and together with them form hybrid DNA-RNA strands.
  • the differences in binding / hybridization of RNA patterns to the various DNA samples of an array can be determined by measuring the intensity and wavelength dependence of the fluorescence of each individual microarray element. Thus, it can then be found out whether and to what extent the degree of gene expression in the examined DNA samples varies. With the use of DNA microarrays comprehensive statements can thus be made about the expression of large quantities of genes and their expression patterns, although only small amounts of biological material must be used.
  • DNA microarrays have established themselves as successful tools.
  • the laboratory systems for carrying out hybridizations have been continually improved (cf., for example, US Pat US 6,238,910 or the document EP 1 260 265 B1 the applicant of the current patent application).
  • These documents disclose systems with devices for providing a hybridization space for the hybridization of nucleic acid samples, proteins or tissues on a microscope slide.
  • Such a known standard device forms a gap-shaped hybridization space with the slide. she is in FIG. 1 and is described in more detail in the following section.
  • thermocouple can be integrated in a cover part of this experimental unit.
  • the present invention thus provides a method and a measuring device for carrying out the method with which, in particular, fluid parameters that are provided by a laboratory system can be determined. This allows for an effective result analysis by processing the signals provided by the respective sensors, which are indirect information about instrument parameters of laboratory systems.
  • gases, liquids and gas / liquid mixtures are considered as fluids.
  • a measuring device 4 comprises a measuring unit 5 and a processing unit 6 (cf. Fig. 4 ).
  • the measuring unit 5 is designed so that it can be integrated into a laboratory system 1 in order to determine there the fluid parameters provided by the laboratory system 1.
  • laboratory systems 1 such systems should be understood here, which make it possible to run a variety of laboratory processes. It is preferred that the laboratory processes can be carried out automatically by means of these laboratory systems 1.
  • Exemplary laboratory systems 1 can be designed to handle larger or smaller volumes of liquid. These are known as fermenters or pipetting machines (larger volumes), or as systems for spotting / immobilizing eg biological samples on laboratory-typical carriers.
  • Other conceivable laboratory systems 1 are systems for carrying out PCR or sequencing reactions or, in a particularly preferred embodiment, systems for carrying out hybridization reactions.
  • hybridization systems 2 the present invention will be described in more detail, but its scope is not limited.
  • FIG. 1 shows a vertical longitudinal section through an already known from the prior art hybridization unit 3 of such a hybridization system 2.
  • the hybridization unit 3 comprises a standard device 33 and is from the document EP 1 260 265 B1 or from the document EP 1 614 466 A2 known. Both documents are patents or patent applications of the applicant of the current application.
  • This standard device 33 is designed as a lid movable relative to a slide 35.
  • a slide comprises 35 nucleic acid probes, proteins or tissue slices that are to be contacted (hybridized) with a pattern. They are immobilized on a surface 36 of the slide 35.
  • Typical slides 35 may be glass slides 35 suitable for light microscopy or at least have approximate dimensions to such glass slides, even if they are made of a different material (eg
  • plastic Also known are slides on glass or plastic base, on which, for example, a cellulose membrane is attached.
  • the standard device 33 can be inserted into a holder 26. This holder 26 is then - with inserted standard device 33 - moved via an axis 29 relative to the slide 35.
  • the standard device 33 defines with the slide 35 a gap-shaped hybridization space 34.
  • the slide 35 can be positioned on a frame 28.
  • the frame 28 can serve both for positioning slides 35 within a hybridization unit 3 and for transporting or storing the slides 35. It is itself positioned on a base plate 51 of the hybridization unit 3.
  • the standard device 33 comprises a sealing surface 50, which is preferably designed as an annular seal, for example as an O-ring. It seals the hybridization space 34 from the environment by applying a sealing surface 50 to a surface 36 of the slide 35.
  • the standard device 33 also includes lines 39 for feeding and discharging media into the hybridization space 34 or out of the hybridization space 34.
  • the standard device 33 further comprises a pattern supply line 41 adapted for supplying sample liquids into the hybridization space 34 and an agitation device 42 for moving liquids in the hybridization space 34.
  • a pattern supply line 41 adapted for supplying sample liquids into the hybridization space 34
  • an agitation device 42 for moving liquids in the hybridization space 34. Possible embodiments are described in detail in the above-mentioned documents EP 1 260 265 B1 and EP 1 614 466 A2 so that reference is made expressly to these documents for details.
  • This agitation device 42 comprises for moving liquids a pressure chamber 44 in which an agitation pressure is generated.
  • the pressure chamber 44 is separated by a membrane 43 from an agitation chamber 45.
  • the agitation chamber 45 is in turn connected via an agitation line 46 to the hybridization space 34.
  • a fluid is introduced into the pressure chamber 44 via a pressure line or discharged from it.
  • the membrane 43 bends through, reduced or enlarged accordingly the agitation chamber 45 and moves the liquid through the Agitations effet 46 in the hybridization space 34.
  • a variant of a standard device may include a second agitator 42 'with a pressure chamber 44', a membrane 43 ', an agitation chamber 45' and an agitation line 46 ', so that both devices can generate a pendulum motion of liquids in the hybridization space.
  • the standard device 33 in addition to the agitator 42,42 'includes a completely separate from this printing device 47, with which a space pressure in the hybridization space 34 is generated.
  • This volume pressure is increased in relation to the surrounding atmospheric pressure and is superimposed by the agitation pressure in the hybridization space.
  • the room pressure serves to prevent or suppress the formation of air bubbles in the hybridization space 34.
  • FIG. 2 shows a vertical longitudinal section through an exemplary measuring unit 5 of an inventive measuring device 4 in a highly simplified and schematic representation.
  • An inventive measuring device 4 serves to determine fluid parameters provided by a laboratory system 1.
  • the measuring device 4 according to the invention is also suitable for carrying out a method according to the invention.
  • the measuring unit 5 of the measuring device 4 th integrated into a laboratory system 1.
  • the measuring device 4 is to be explained in more detail in connection with hybridization systems 2, but it is not limited to the use in such systems.
  • the measuring block 15 is designed such that it does not provide any space for carrying out a laboratory process or a reaction or can form part of such a space.
  • a reaction space 34 is referred to in the context of this invention, a space in which a biological or chemical process (reaction) can proceed.
  • reaction a biological or chemical process
  • the at least one sensor 17 is arranged on or in fluidic connection with cavities 16 of the measuring block 15. These cavities 16 serve to receive fluids 13 provided by the laboratory system 1 and the hybridization system 2. By virtue of this arrangement, the sensors 17 are capable of determining the physical and / or chemical parameters of the fluids contained in the cavities 16.
  • These cavities 16 may be formed as fluid lines and / or as fluid chambers, which are arranged substantially completely within the measuring block 15.
  • the arrangement of the orifices of fluid lines and fluid chambers in this connection plane 38 ' corresponds essentially to an arrangement of supply and / or discharge lines in a common connection plane 38 of a laboratory system 1.
  • the connection plate 37 of the hybridization system 2 in which its lines 39 'also open into a plane, the cavities 16 of the measuring unit 5 are tightly connected to the line system of the hybridization system 2 and thus functionally integrated into the hybridization system 2.
  • the measuring units 5 according to the invention can simply be used at the location of a standard device 33 in a hybridization system 2.
  • the at least one sensor 17 is arranged on or in fluidically active connection with the cavities 16 of the measuring block 15.
  • the at least one sensor 17 is preferably positioned either on or in the cavities 16 so that it is in direct contact with the fluid 13 to be measured, without influencing the parameters of the fluids 13 themselves.
  • the at least one sensor 17 is arranged in fluidic connection with the cavities 16 of the measuring block 15.
  • the sensor 17 is not necessarily in direct contact with the fluid 13 of the cavities 16, but it may for example be separated from the cavities 16 by a membrane or other layer.
  • the fluid parameters are then detected by the at least one sensor 17 via the fluidically active connection.
  • FIG. 2 for a sensor 17 designed as a pressure sensor 20 for gases. Fluid parameters, such as flow or fluid pressure, can then be detected by the sensor 17 via the fluidic connection.
  • a measuring device 4 when it is integrated in a laboratory system 1, the current parameters of fluids 13 provided by the laboratory system 1 are determined under at least approximately practical conditions within the measuring block 15: the parameters which are not measured are not measured of the measuring block 15 from external Devices, such as pressure pumps or heating / cooling systems, were generated on the fluid (target values).
  • the measuring device 4 thus provides substantially comparable cavities with similar volumes or flow resistances as a standard device 33 has. This determines those fluid parameters which prevail within the laboratory system at the destination (actual values).
  • the fluid parameters provided by external devices may differ more or less strongly from the parameters prevailing in the measuring block 15 after passage through various lines and valves.
  • Crucial for the factually reliable assessment of a reaction quality is the determination of the actual value. On the basis of this actual value, one can then make sound conclusions about the reaction process that has taken place in the laboratory system. On the other hand, for example, an experimenter, a service technician or the producer can use the actual value determination for calibrating and adjusting the external devices.
  • Parameters to be recorded are, for example, pressure, flow velocity, mass flow or volume flow, temperature, sound conductance or density, optical properties (eg coloration or turbidity), or else substance concentrations or pH values.
  • Prefers measured fluid parameters are the pressure, the volume flow (determined on the basis of the flow velocity or the flow) and the temperature of a fluid.
  • the measurement signal output by the at least one sensor 17 is processed by a processing unit 6 of the measuring device 4 into a desired size or response for evaluation.
  • the processing unit 6 comprises at least one microcontroller 11, which transmits the digital data received by the at least one sensor 17 to a computer 12 of the processing unit 6.
  • the processing unit 6 comprises data control systems 8, 9, 10, which process and forward the signals emitted by the sensor for the microcontroller 11.
  • data control systems 8, 9, 10 include analog / digital converters 10, serial or parallel data buses 8 and direct digital input / output connections 9. It is also conceivable to use other elements or methods known from the prior art in the processing unit 6 which are necessary for a controlled data forwarding and processing.
  • the at least one sensor is for determining a flow velocity of a fluid or for determining a Fluid pressure formed.
  • the at least one sensor 17 for determining a flow velocity of a fluid can be designed as a flow sensor 19 for liquids or gases.
  • the at least one sensor 17 for determining a fluid pressure may be designed as a pressure sensor 20 for liquids or gases.
  • sensors 17 used in this and the following embodiments are:
  • the measuring unit 5 comprises at least two sensors 17.
  • at least one pressure and a flow rate of fluids 13 provided by a laboratory system 1 are measured with the measuring unit 5.
  • Sensor is designed as a flow sensor 19 and the second sensor as a pressure sensor 20.
  • the two regions of the cavities 16, on which the sensors 19, 20 are arranged are separated from one another by means of valves. This is desirable in particular when, for example, a gas pressure sensor 20 used is impaired in its function during liquid contact.
  • a gas pressure sensor 20 used is impaired in its function during liquid contact.
  • Such an embodiment is exemplary in the Figures 4B and 4C shown.
  • Various variants of measuring concepts with a measuring unit 5 and a processing unit 6 are shown here.
  • a pressure sensor 20 designed as a high-pressure sensor (with a measuring range of up to 3.5 bar) is preferably used (for example the SenSpecial TM pressure sensor SCPB-BO / 3.5G50i2C32717R5 from SensDev LTD.).
  • the pressure to be measured of the drying fluid in a preferred embodiment is between 1.5 and 3.5 bar, in a particularly preferred embodiment between 2 and 3 bar and in a most preferred embodiment, between 2.5 and 2.9 bar above ambient atmospheric pressure.
  • the pressure to be determined by the low-pressure sensor which is composed in particular of chamber pressure and agitation pressure, is between 10 mbar and 1.5 bar above the ambient normal pressure.
  • a preferably used, designed as a low pressure sensor pressure sensor 20 is the SenSpecial TM pressure sensor SCPB-B0 / 1.5G50i2C32717R5 SensDev LTD.
  • This use of two separate sensors 20 for low pressure and high pressure of gases makes it possible, for example, to detect structural defects in a hybridization system 2 according to the invention. For example, if a membrane 43, 43 'of the agitator 42, 42' is defective, the pressure drop can be detected specifically by the low pressure sensor become. The error detection is thus sensor-specific.
  • the measuring unit 5 for determining a flow speed of a fluid 13 comprises at least two identically constructed sensors 19, 20, which are arranged at a distance from one another or in fluidic connection with a cavity 16.
  • this cavity 16 is designed as a fluid line which corresponds in its dimension to a fluid line of a laboratory system 1, for example a standard device 33 of a hybridization system 2 described here.
  • This alternative embodiment is particularly preferred for the determination of a liquid flow.
  • the flow speed is measured on a measuring section. This measuring section is that section of the fluid line which lies between the two flow sensors 19.
  • the principle of such a flow measurement is that each of the two preferably identical sensors 19 provides a signal when a liquid front passes the sensor.
  • the amplitude of the signal is then not used, but the time t (the time signal) which the liquid needs to flow through the measuring section between the two identically constructed sensors 19 is determined.
  • the time t the time signal which the liquid needs to flow through the measuring section between the two identically constructed sensors 19 is determined.
  • FIG. 3 An exemplary measurement of the fluid flow in the measuring section between the two flow sensors 19 was carried out by means of a prototype of the measuring block 15 of the measuring unit 5 according to the invention (cf. Fig. 2 ) and is in FIG. 3 shown.
  • the abscissa is the time axis, which is divided into steps of 5'000 ms and 5 s, respectively.
  • the ordinate shows the intensity or the amplitude of the flow sensor signal in [mV].
  • the sensors 17 of identical construction for measuring a flow velocity of a fluid are designed as flow sensors 19.
  • a flow sensor 19 can emit an acoustic or electrically capacitive signal, while the sensors designed as light barriers 21 emit optical signals for further processing. The signals emitted by the sensors are then used by the processing unit 6 of the measuring device 4 to calculate a flow velocity of the fluid 13.
  • the measuring device 4 can determine "on site” the fluid parameters provided by the laboratory system 1 (actual values).
  • the measuring unit 5 of the measuring device 4 is inserted into a hybridization system 2.
  • a hybridization system 2 is to be understood as meaning a laboratory system 1 which is suitable for carrying out hybridization reactions.
  • such hybridization systems 2 provide at least one reaction space 34 in which the hybridization reaction can proceed. It further comprises vessels for storing fluids 13, conduits, pumps, valves, seals, devices for generating fluid parameters, and the like.
  • Such an exemplary hybridization system is the one mentioned above and from the documents EP 1 260 265 B1 or EP 1 614 466 A2 known from the prior art.
  • the measuring unit 5 is integrated into a hybridization unit 3 of this hybridization system 2.
  • FIG. 2 is simplified, such a hybridization system 2 is shown, in which a measuring unit 5 of a measuring device 4 according to the invention is integrated.
  • the hybridization system 2 comprises a hybridization unit 3 with a standard device, wherein the standard device 33 with a slide 35 defines the hybridization space 34.
  • a measuring unit 5 of the measuring device 4 according to the invention is inserted into the holder 26, so that the measuring unit 5 can be moved by means of the holder 26 with respect to the slide 35 or the base plate 51.
  • the measuring unit 5 is to be used in another laboratory system 1, it can also be used in another way in this system 1.
  • simple slip-on or sliding mechanisms may be used, as well as other mechanisms known in the art which are well known to those skilled in the art and therefore will not be discussed further here.
  • the measuring unit 5 of the measuring device 4 is corresponding FIG. 2 used in a hybridization system 2, no hybridization reactions are performed at this position, since the measuring unit 5 according to the embodiments described so far does not include or define a reaction space 34. If reactions are to be carried out parallel to the measurement, an arrangement of 2 or more hybridization units 3 is preferred, one of which is replaced by the measuring unit 5 (cf. Fig. 5A ). In this way, reactions can be carried out by means of the hybridization unit 3, and the parameters can be determined in parallel from the same fluids by means of the measuring instrument 4. This is made possible by the supply lines and leads 39 'of the hybridization system 2 via terminals of the measuring unit 5 with the cavities 16 of the measuring block 15 are connectable.
  • substantially all the cavities 16 of the measuring block 15 open in a common connection plane 38 'of the measuring unit 5.
  • connection plate 37 of the hybridization system 2 By means of the connection plate 37 of the hybridization system 2, a tight connection of the cavities 16 of the measuring unit 5 with the lines 39' of the hybridization system 2 is made possible.
  • temperature is also an important parameter.
  • the temperature of a hybridization reaction is determined by the temperature of the fluids 13 provided and also by the temperature of the slide 35. It is usually influenced by temperature regulators and heating elements 49.
  • temperature regulators correspond for example to the temperature control plate of the hybridization system 2 described here.
  • Such a temperature control plate can be tempered via one or more heating elements 49.
  • Peltier elements are preferred, but other heating elements well known to those skilled in the art are also usable in this connection.
  • the measuring unit 5 of the measuring device 4 comprises a niche 25, in which at least one temperature sensor 24 is arranged. If such a measuring unit 5 is integrated in the hybridization system 2, it is preferably designed to be movable by means of the holder 26 against a surface 31 of the hybridization system 2, from which a temperature is to be determined.
  • FIG. 2 shows such a measuring unit 5, in the example, two temperature sensors 24 are arranged in the niche 25.
  • Surfaces 31 of the hybridization system are, for example The surface 36 of a slide 35 or the surface 52 of the base 51 of the hybridization unit 3.
  • the temperature sensor 24 or the two temperature sensors 24 are arranged on a circuit board 22 in the niche 25 that during a movement of the measuring unit 5, the surface 31 is acted upon by a metal plate 23.
  • This metal plate 23 is preferably made of a metal with good thermal conductivity, such as aluminum or aluminum alloys and is in good thermal contact with the temperature sensors 24, which are connected via the circuit board 22 to the processing unit 6.
  • the metal plate 23 may for example be dimensioned so that it substantially corresponds to the surface of the niche 25 and thus does not protrude laterally beyond this.
  • the metal plate 23 is dimensioned to be partially disposable within the niche 25 (with respect to its height). Alternatively, however, it may also be larger than the niche 25 and protrude beyond it, but preferably it is not larger than the surface 31 which acts on it.
  • the at least one temperature sensor 24 of the measuring unit 5 is formed on a surface 31 of the hybridization system 2, of which a temperature is to be determined, resiliently acted upon.
  • at least one spring element 32 is mounted in the niche 25, but depending on the shape of sensor 24 and niche 25, a plurality of spring elements 32 may also be used. This arrangement is particularly advantageous when the temperature sensor or the temperature sensors 24 are to be brought as close as possible to the surface 31 of the hybridization system 2, but without this surface 31, for example. damaged by too much imprint.
  • the surface 31 of the hybridization system 2 be formed as a temperature control plate. If the surface 31 is contacted directly by the temperature sensor 24, ie by its metal plate 23, then the temperature of the metal plate 23 equalizes in a very short time that of the surface 31, so that the measurement can be done simply by touch contact and heat conduction. Thus, by means of the temperature sensor 24 of the measuring unit 5, the actual prevailing temperature of the surface 31 can be determined. If the measurement, however, by means of detection of heat radiation, the Sensor 24 does not necessarily contact the surface 31, but could be arranged at a defined distance from this (not shown). A measurement of the temperature at the surface 31 by convection would be conceivable; However, this variant is inferior to the detection of heat radiation and the measurement by means of touch contact and heat conduction.
  • a temperature sensor 24 is used which preferably has a large measuring range with the highest possible accuracy.
  • a temperature sensor 24 used in this particularly preferred variant is, for example, the temperature sensor TSic-306F from IST AG (Industriestr. 2, 9630 Wattwil, Switzerland).
  • IST AG Siemens AG
  • a temperature-linear voltage is generated, which is digitized by an analog-to-digital converter.
  • This sensor has a measuring range of 0 ° C to 100 ° C with an accuracy of +/- 0.1 ° C to 0.3 ° C.
  • it is also possible to use two or more temperature sensors 24 for determining the temperature wherein each of these temperature sensors 24 used has a different measuring range, each with high accuracy. A shortening of the measuring section facilitates the necessary offset calibration.
  • one or more sensors with specificity for a wide variety of fluid parameters can be used for the measuring device 4 according to the invention.
  • Particularly preferred embodiments and variants of sensors and their arrangement within the measuring device have already been discussed in this document and can also be the FIGS. 4A to 4C be removed.
  • These figures show different variants of measuring concepts of a measuring device 4 according to the invention.
  • These measuring concepts illustrate the networking of the sensors and the computer for evaluating the sensor signals by means of various data management systems 8, 9, 10 and at least one microcontroller 11.
  • the microcontroller 11 is part of the computer 12.
  • the sensor data are first transported via connections 7 to the data management systems 8,9,10 and processed so that they of the microcontroller 11 and the computer 12 are evaluated.
  • These data management systems 8, 9, 10 are preferably structurally encompassed by the computer 12, as in FIG. 4A shown. Alternatively, the data management systems 8, 9, 10 are combined separately into a structural unit, which is independent of the computer 12 ( Fig. 4C ), or that is encompassed by a second computer 12 ( Fig. 4B ).
  • the processing units 6 are similar to these three measurement concepts and comprise a serial / parallel data bus 8; a direct digital input / output line 9, an analog / digital (A / D) converter 10 and a microcontroller 11, which communicate with each other via connecting lines 7 or exchange data or signals.
  • FIGS. 4A, 4B and 4C each show a first pressure sensor 20, which is designed for measuring lower pressures (eg 10 mbar to 1500 mbar), which are provided by the fluid source A.
  • the pressure measuring signals are passed on via the A / D converter 10 to the microcontroller 11 for evaluation.
  • FIGS. 4A, 4B and 4C each show a second pressure sensor 20, which is designed for measuring higher pressures (eg 1.5 to 3.5 bar), which are provided by the fluid source B.
  • the pressure measurement signals are again passed via the A / D converter 10 to the microcontroller 11 for evaluation.
  • the three measuring concepts differ here in that this second pressure sensor 20 in the Figures 4B and 4C can be separated by a valve from the source B, which is in the FIG. 4A not the case.
  • the FIG. 4C shows a first flow sensor 19, which is designed exclusively for measuring the gas flow, which is provided by the fluid source B.
  • the gas flow measuring signals are transmitted via the serial / parallel data bus 8 to the microcontroller 11 for evaluation.
  • the FIG. 4C shows a second and third flow sensor 19, which are in direct fluid communication with each other and which are designed exclusively for measuring the liquid flow, which is provided by the fluid source C and leaves the measuring unit 5 via the liquid drain D.
  • the fluid flow measurement signals are also passed on the serial / parallel data bus 8 to the microcontroller 11 for evaluation on.
  • the show FIGS. 4A and 4B a second and third flow sensor 19, which are also in direct fluid communication with each other, which are, however, designed to measure a liquid flow and a gas flow, wherein the liquid flow from the fluid source C, the gas flow but from the source B is provided. In any case, these media leave the measuring unit 5 via the liquid drain D.
  • All three variants according to the FIGS. 4A, 4B and 4C comprise at least one temperature sensor 24 arranged independently of all these fluid flows and is connected via separate connection lines 7 with the direct digital input / output line 9 and the microcontroller 11 of the computer 12.
  • the measuring unit 5 of the measuring device 4 is integrated into a hybridization system 2 from the prior art.
  • a hybridization system 2 comprises at least one hybridization unit 3.
  • This hybridization unit 3 provides the reaction space 34 defined by at least one standard device 33 and one slide 35.
  • the principle is that the measuring device 4, when it is integrated into the hybridization system 2 via its measuring unit 5, determines "on-site" the actual values of the fluid parameters provided by the hybridization system.
  • the measuring unit 5 comprises substantially the same connections for the supply and discharge of fluids 13 provided by the hybridization system 2 as the standard device 33.
  • the measuring unit 5 is designed in its essential dimensions so that it can be used instead of Standard device 33 can be inserted into a hybridization unit 3. Even in the dimensions of the cavities 16, a measuring unit 5 largely corresponds to those dimensions of the cavities of a standard device 33.
  • the fluid parameters measured in the measuring unit can be mathematically corrected or adjusted so that they can be considered as measured under "real-time conditions" and with the ratios in a reaction space 34 of the standard device 33 can be compared. The measured in the measuring unit 5 fluid parameters are thus transferable to the fluid parameters of a hybridization reaction.
  • the measuring unit 5 of the measuring device 4 is designed so that it can be used in place of a first standard device 33 'in a hybridization system 2.
  • the standard device 33 of the hybridization unit is designed as this first standard device 33 '. It defines, in combination with a slide 35, a single hybridization space 34.
  • a first standard device 33 ' is shown in U.S. Pat FIG. 5A at position I in the holder 26 of the hybridization system shown used.
  • the measuring unit 5 is designed such that it can be inserted into the hybridization system 2 at the location of a further first standard device 33 '. Such a situation is in FIG. 5A at position II in the holder 26 of the hybridization system 2.
  • the measuring unit 5 does not include or define a reaction space 34.
  • the further positions III and IV are also occupied by a further first standard device 33 '.
  • up to three hybridization reactions can be carried out parallel to the determination of fluid parameters.
  • no slide 35 or a slide without immobilized samples is placed at position II.
  • the hybridization spaces 34 at the positions I, III and IV are indicated by the sealing surfaces 50.
  • the measuring unit 5 of the measuring device 4 can be used instead of a second standard device 33 "of a hybridization system 2.
  • the standard device 33 of a hybridization unit 3 of the hybridization system 2 is designed as this second standard device 33" , This defines, in combination with a slide 35, at least two hybridization spaces 34. These two hybridization spaces 34 are sealed from the environment by means of two sealing surfaces of the second standard device 33 "Such a second standard device 33" is in the document EP 1 614 466 A2 described and in FIG. 5B shown inserted in position I in the holder 26 of the hybridization system.
  • Such a second standard device 33 either comprises a common agitation device 42 for both hybridization spaces 34 as well as common connections for the individual lines 39.
  • this second standard device 33 preferably has individual connections Hybridization space, which lie in a common connection plane 38.
  • a measuring unit 5 of this variant is designed such that it can be inserted in the hybridization system 2 instead of a second standard device 33 " FIG. 5B shown at position II. In this case, the measuring unit 5 next to the measuring block 15 without reaction space 34 and at least a sensor 17 and a reaction block 40.
  • This reaction block 40 defines with the slide 35 at least one hybridization space 34, which is preferably delimited by a sealing surface 50 from the environment.
  • the reaction block 40 comprises substantially the same conduits 39 "as the second standard device 33" for a hybridization space 34 as well as substantially the same ports 38 "for the delivery and discharge of fluids 13 provided by the hybridization system 2 as the second standard device 33 ".
  • the arrangement of four hybridization units into a group according to the FIGS. 5A and 5B is preferred insofar as that the temperature control plate of the hybridization system 2 has such dimensions that a frame 28 of the size of a microplate with four mutually parallel slides 35 just fits on the temperature control plate. All hybridization spaces 34 of such a hybridization unit 3 thus have identical temperature conditions.
  • 33 replacement by measuring units 5. In this way, the fluid parameters can be determined and optionally adjusted on each of the positions I-IV.
  • the measuring unit 5 is designed so that it is used in place of a third standard device 33 "'in the hybridization unit 3 of a hybridization system 2.
  • the standard device 33 as a third standard device 33 "'formed. This, in combination with a slide 35, defines at least three or more hybridization spaces 34.
  • Such a third standard device 33 "' is incorporated in the FIGS. 5C and 5D each shown on the position I / II. The individual reaction spaces are delimited by separate sealing surfaces 50 from the environment.
  • the third standard devices 33 '' shown here each comprise four hybridization spaces 34. As in FIGS FIGS.
  • a third standard device 33 "' is formed in its essential dimensions greater than a first or second standard device 33" (verg FIGS. 5A and 5B ). More specifically, a third standard device 33 "'substantially corresponds in dimension to two interconnected first or second standard devices 33', 33". This enlargement is preferred in order to take account of the increased number of connections required as well as supply and discharge lines of fluids 13 provided by the hybridization system 2 and their supply lines to or their derivatives from the four hybridization spaces 34. In this case, the third standard device 33 "'common connections for the supply and discharge of media, or for each of them defined hybridization space 34 may include a separate set of connections for the supply and discharge of fluids 13.
  • the measuring unit 5 is designed in such a way that it can be inserted into the hybridization system instead of the third standard device 33 " FIGS. 5C and 5D each shown at position III / IV in the holder 26 of the hybridization system 2.
  • this measuring unit 5 comprises a measuring block 15 without reaction space 34 and with at least one sensor 17 and a reaction block 40.
  • the reaction block 40 defines at least two or more hybridization spaces 34 with the slide 35.
  • the number of hybridization spaces 34 defined by the reaction block 40 is variable.
  • a measurement unit 5 is shown at position III / IV, whose reaction space defines three hybridization spaces 34.
  • FIG. 5D By contrast, a measuring unit 5 at position III / IV is shown, whose reaction block defines four hybridization spaces.
  • all hybridization spaces 34 of a reaction block 40 are preferably defined with a single slide 35.
  • the measuring device 4 is preferably used in a hybridization system 2, the at least one group of two hybridization units 3, each with a third standard The measuring unit 5 of the measuring device 4 is then inserted into the hybridization unit instead of a third standard device 33 "'.
  • the FIGS. 5C and 5D show such a group of two hybridization units 3, which are inserted into a holder 26 of the hybridization system 2.
  • the reaction block 40 of the measuring unit 5 for replacing the second or third standard device 33 ", 33"' comprises further elements of these standard devices 33 for carrying out hybridization reactions.
  • the reaction block 40 preferably comprises at least one pattern supply line 41 for feeding sample liquids into at least one hybridization space 34. More preferably, the reaction block 40 further comprises at least one agitation device 42, 42 'for generating an agitation pressure and for moving liquids 13 in a reaction space 34
  • This agitation device 42 of the reaction block 40 is substantially constructed like that of the standard device 33. Depending on the standard device 33 passing through the reaction block 40 of a measuring unit 5 is replaced, this may also include a number of agitators 42, which corresponds to the number of hybridization spaces 34.
  • the reaction block 40 particularly preferably comprises at least one pressure device 47 which is completely separate from the agitation device 42 for establishing a spatial pressure to be superimposed by the agitation pressure in at least one hybridization space 34.
  • Pattern supply line 41, agitation device 42 and pressure device 47 are already associated with FIG FIG. 1 discussed and from the documents EP 1 260 265 B1 or EP 1 614 466 A2 known. These devices should therefore not be carried out again at this point. It is important that the principle of the standard device is transferred to a reaction block 40 of the measuring device 4 according to the invention.
  • This chamber pressure serves to inhibit the formation of gas bubbles in the reaction space 34 and is generated by the pressure device 47 (see Source A in FIG Fig. 4 ).
  • An exemplary sensor used is the low-pressure sensor described above, with which the chamber pressure and also this preferably cyclically superimposed agitation pressure are determined.
  • Particularly preferred variants of the described embodiments include a temperature control plate which is formed as a bottom plate. Such a temperature plate is thus capable of surface contact recording of up to four slides 35 capable. This may be desirable to avoid temperature loss between the temperature control plate and slide 35.
  • the temperature control plate is formed as a cover plate (not shown), with which up to four slides 35 (compared to the Figures 1 and 2 ) inverted standard devices 33 or measuring units 5 can be lowered. Also, up to four slides 35 (as compared to the Figures 1 and 2 ) normally oriented standard devices 33 or measuring units 5 are raised (not shown).
  • both snapshots of the parameters prevailing in a laboratory system 1 can be determined, as well as the behavior of the parameters as a function of time.
  • sensor data are continuously tracked and possibly recorded over a certain period of time. From this data can then be read, for example, the pressure curve or the temperature profile for a desired period.
  • the advantage here is the determination of pressure gradients or temperature gradients.
  • the present invention also includes, in addition to a measuring device 4, a method for determining fluid parameters provided by a laboratory system 1.
  • a method for determining fluid parameters provided by a laboratory system 1 comprises the use of a measuring device 4 with a measuring unit 5 and a processing unit 6, which has already been discussed in detail above.
  • the measuring device 4 is installed in a hybridization system 2.
  • the method according to the invention as well as the measuring device 4 according to the invention can be used at different usage levels of a laboratory system 1. For example, it can be used directly in production for setting and checking the newly manufactured laboratory system 1 to defined and standardized factory settings.
  • the sensors 17 used are calibrated by means of calibration sensors (eg the sensors F-20 / CV-5k0-ABD-33-V and L23-ABD-33-K-70S from Bronkhorst, Nenzlingerweg 5, 4153 Reinach, Switzerland) are initially externally checked for their function.
  • calibration sensors eg the sensors F-20 / CV-5k0-ABD-33-V and L23-ABD-33-K-70S from Bronkhorst, Nenzlingerweg 5, 4153 Reinach, Switzerland
  • a check of the preset parameters can be performed before, for example, particularly costly experiments on the laboratory system 1 should be performed. For example, a slide costs about 1000 CHF, so if you use 4 to 40 slides per trial series, you can expect up to 40,000 CHF.
  • diagnostic laboratories eg clinics
  • misdiagnoses due to device deficiencies can be reduced by regularly checking the settings of the systems by means of a measuring device 4 according to the invention. In this way it is possible to identify and correct malfunctions or incorrect calibrations of the laboratory system 1 used in questionable or critical reaction results in a simple method. It is particularly advantageous to look at the possibility to limit the troubleshooting by means of the inventive measuring device 4 early in the error analysis in such questionable or critical reaction results.
  • an error can already reliably be assigned to the device in a first step (in the case of a lack of devices) or, in the case of a detectable device error, to the application.
  • This method is preferably used for calibrating and / or adjusting the laboratory system 1 by means of the signals received by the at least one sensor 17 of the measuring unit 5 and processed by the processing unit 6.
  • calibration should be understood to mean the acquisition of measured data and the comparison of these data with defined standards. Under Adjustment in this context is accordingly to understand the acquisition of data, comparing with standard and the adjustment.
EP09175882A 2008-11-13 2009-11-13 Appareil de mesure et procédé de détermination de paramètres de fluide préparés par un système de laboratoire Withdrawn EP2186565A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH01772/08A CH699853A1 (de) 2008-11-13 2008-11-13 Messgerät und Verfahren zum Bestimmen von durch ein Laborsystem bereitgestellten Fluidparametern.

Publications (1)

Publication Number Publication Date
EP2186565A1 true EP2186565A1 (fr) 2010-05-19

Family

ID=40688307

Family Applications (1)

Application Number Title Priority Date Filing Date
EP09175882A Withdrawn EP2186565A1 (fr) 2008-11-13 2009-11-13 Appareil de mesure et procédé de détermination de paramètres de fluide préparés par un système de laboratoire

Country Status (3)

Country Link
US (1) US20100167406A1 (fr)
EP (1) EP2186565A1 (fr)
CH (1) CH699853A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102011109332A1 (de) 2011-08-03 2013-02-07 Eppendorf Ag Laborvorrichtung und Verfahren zur Behandlung von Laborproben
CN114985022B (zh) * 2022-04-28 2023-07-21 机械工业仪器仪表综合技术经济研究所 一种具有多环境参数的环境综合测试系统
US11964271B2 (en) * 2022-07-27 2024-04-23 Pilot Gene Technology (hangzhou) Co., Ltd. Drop preparation device and drop preparation method

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5281516A (en) * 1988-08-02 1994-01-25 Gene Tec Corporation Temperature control apparatus and method
WO2000009650A1 (fr) * 1998-08-10 2000-02-24 Genomic Solutions, Inc. Dispositif a cycles thermique et fluidique pour l'hybridation d'acide nucleique
DE10018036A1 (de) 2000-02-11 2002-02-28 Ibfb Gmbh Privates Inst Fuer B Verfahren zur Ermittlung von Nukleinsäure-Hybridisierungsparametern und Testmembran
WO2002072264A1 (fr) * 2001-03-09 2002-09-19 Biomicro Systems, Inc. Procede et systeme d'interfaçage microfluidique avec des reseaux
WO2003106033A1 (fr) 2002-06-13 2003-12-24 Millenium Biologix Ag Chambre de reaction
EP1260265B1 (fr) 2001-05-25 2005-02-02 Tecan Trading AG Système avec un set de traitament pour l'hybridation d'échantillons d'acide nucléique, protéines et tissus
EP1614466A2 (fr) 2004-07-08 2006-01-11 Tecan Trading AG Dispositif et procédé pour la prévention de bulles d'air dans une chambre d'hybridation

Family Cites Families (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5273905A (en) * 1991-02-22 1993-12-28 Amoco Corporation Processing of slide mounted material
US5580523A (en) * 1994-04-01 1996-12-03 Bard; Allen J. Integrated chemical synthesizers
EP0695941B1 (fr) * 1994-06-08 2002-07-31 Affymetrix, Inc. Procédé et appareil d'emballage de puces
US6287850B1 (en) * 1995-06-07 2001-09-11 Affymetrix, Inc. Bioarray chip reaction apparatus and its manufacture
US5902551A (en) * 1995-01-13 1999-05-11 Semi-Gas Systems, Inc. Process gas docking station with point-of-use filter for receiving removable purifier cartridges
GB9506312D0 (en) * 1995-03-28 1995-05-17 Medical Res Council Improvements in or relating to sample processing
US20020022261A1 (en) * 1995-06-29 2002-02-21 Anderson Rolfe C. Miniaturized genetic analysis systems and methods
US5856174A (en) * 1995-06-29 1999-01-05 Affymetrix, Inc. Integrated nucleic acid diagnostic device
US6132580A (en) * 1995-09-28 2000-10-17 The Regents Of The University Of California Miniature reaction chamber and devices incorporating same
US6258534B1 (en) * 1998-03-02 2001-07-10 Bbi Bioseq, Inc. Pressure-controlled nucleic acid hybridization
US6001231A (en) * 1997-07-15 1999-12-14 Caliper Technologies Corp. Methods and systems for monitoring and controlling fluid flow rates in microfluidic systems
US6251601B1 (en) * 1999-02-02 2001-06-26 Vysis, Inc. Simultaneous measurement of gene expression and genomic abnormalities using nucleic acid microarrays
US6673620B1 (en) * 1999-04-20 2004-01-06 Cytologix Corporation Fluid exchange in a chamber on a microscope slide
US6268219B1 (en) * 1999-07-09 2001-07-31 Orchid Biosciences, Inc. Method and apparatus for distributing fluid in a microfluidic device
DE19954855C1 (de) * 1999-11-15 2001-04-05 Siemens Ag System zur automatisierten Behandlung von Fluiden, mit einanderreihbaren, austauschbaren Prozeßmodulen
US7435579B2 (en) * 2000-04-17 2008-10-14 Purdue Research Foundation Biosensor and related method
EP1384022A4 (fr) * 2001-04-06 2004-08-04 California Inst Of Techn Amplification d'acide nucleique au moyen de dispositifs microfluidiques
US20030062067A1 (en) * 2001-09-23 2003-04-03 Irm, Llc Closed cell washer
US7468161B2 (en) * 2002-04-15 2008-12-23 Ventana Medical Systems, Inc. Automated high volume slide processing system
US20040101444A1 (en) * 2002-07-15 2004-05-27 Xeotron Corporation Apparatus and method for fluid delivery to a hybridization station
US6878271B2 (en) * 2002-09-09 2005-04-12 Cytonome, Inc. Implementation of microfluidic components in a microfluidic system
ITTO20020808A1 (it) * 2002-09-17 2004-03-18 St Microelectronics Srl Dispositivo integrato di analisi del dna.
WO2004083824A1 (fr) * 2003-03-20 2004-09-30 Dakocytomation Denmark A/S Systeme pour etablir un couvercle d'echantillon sur un substrat
US7011793B2 (en) * 2003-05-15 2006-03-14 Kionix, Inc. Reconfigurable modular microfluidic system and method of fabrication
WO2005003395A1 (fr) * 2003-07-02 2005-01-13 Caliper Life Sciences, Inc. Procede pour amplifier et detecter des acides nucleiques dans des dispositifs microfluidiques dans des conditions de flux continu et non continu
EP2486981B1 (fr) * 2003-09-09 2016-01-06 BioGenex Laboratories Microchambre avec couvercle
US20060029948A1 (en) * 2003-09-19 2006-02-09 Gary Lim Sealing cover and dye compatibility selection
JP4286094B2 (ja) * 2003-09-24 2009-06-24 オリンパス株式会社 生体関連物質の反応装置
US7615370B2 (en) * 2004-07-08 2009-11-10 Tecan Trading Ag System having device for preventing air bubbles in a hybridization chamber and corresponding method
DE202004011272U1 (de) * 2004-07-17 2004-09-09 Tecan Trading Ag Vorrichtung zum Bereitstellen einer Hybridisierkammer und zum Beeinflussen von Luftblasen in derselben
GB2421202B (en) * 2004-12-15 2009-12-09 Syrris Ltd Modular microfluidic system
PL1883474T3 (pl) * 2005-05-25 2021-10-18 Boehringer Ingelheim Vetmedica Gmbh System do zintegrowanej i zautomatyzowanej analizy dna lub białka oraz sposób działania takiego systemu
JP4721414B2 (ja) * 2005-08-15 2011-07-13 キヤノン株式会社 反応カートリッジ、反応装置および反応カートリッジの溶液の移動方法
US20080038714A1 (en) * 2005-11-02 2008-02-14 Affymetrix, Inc. Instrument to Pneumatically Control Lab Cards and Method Thereof
JP4732135B2 (ja) * 2005-11-10 2011-07-27 キヤノン株式会社 反応装置
WO2007110825A2 (fr) * 2006-03-29 2007-10-04 Koninklijke Philips Electronics N.V. Systeme de traitement de fluide et de determination de volume
US20080109175A1 (en) * 2006-08-30 2008-05-08 Sensicore, Inc. Systems and methods for dynamic monitoring of fluid movement in a fluid distribution network using controlled concentration pulses of additives
JP4938596B2 (ja) * 2006-08-31 2012-05-23 京セラ株式会社 流路デバイス

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5281516A (en) * 1988-08-02 1994-01-25 Gene Tec Corporation Temperature control apparatus and method
WO2000009650A1 (fr) * 1998-08-10 2000-02-24 Genomic Solutions, Inc. Dispositif a cycles thermique et fluidique pour l'hybridation d'acide nucleique
US6238910B1 (en) 1998-08-10 2001-05-29 Genomic Solutions, Inc. Thermal and fluid cycling device for nucleic acid hybridization
DE10018036A1 (de) 2000-02-11 2002-02-28 Ibfb Gmbh Privates Inst Fuer B Verfahren zur Ermittlung von Nukleinsäure-Hybridisierungsparametern und Testmembran
WO2002072264A1 (fr) * 2001-03-09 2002-09-19 Biomicro Systems, Inc. Procede et systeme d'interfaçage microfluidique avec des reseaux
EP1260265B1 (fr) 2001-05-25 2005-02-02 Tecan Trading AG Système avec un set de traitament pour l'hybridation d'échantillons d'acide nucléique, protéines et tissus
WO2003106033A1 (fr) 2002-06-13 2003-12-24 Millenium Biologix Ag Chambre de reaction
EP1614466A2 (fr) 2004-07-08 2006-01-11 Tecan Trading AG Dispositif et procédé pour la prévention de bulles d'air dans une chambre d'hybridation

Also Published As

Publication number Publication date
US20100167406A1 (en) 2010-07-01
CH699853A1 (de) 2010-05-14

Similar Documents

Publication Publication Date Title
EP1192007B1 (fr) Dispositif matrice a microcircuit integre destine a l'amplification et a la caracterisation d'acides nucleiques
DE60208313T2 (de) Mikroelektronischer Detektor auf einem Chip
EP2809803B1 (fr) Pcr numérique multiplexée
AT505306B1 (de) Vorrichtung zur überwachung von wasser auf mikrobielle keime
DE112006000374B4 (de) Verfahren zum Bilden eines biologischen Sensors
WO2007121887A2 (fr) Système d'analyses de procédés à prélèvement stérile de matériaux sensibles mécaniquement, à partir d'un bioréacteur
EP1436086B1 (fr) Dispositif destine a maintenir un support de bibliotheque de substances
EP1260265A1 (fr) Appareil pour la préparation d'une chambre d'hybridation, set de traitament et système pour l'hybridation d'échantillons d'acide nucléique, protéines et tissus
WO2005098438A1 (fr) Jeu ordonne d'echantillons pour analyse, muni d'electrodes chauffantes et procedes pour analyses chimiques et biochimiques
EP1614466A2 (fr) Dispositif et procédé pour la prévention de bulles d'air dans une chambre d'hybridation
EP1710562A2 (fr) Système microfluidique et un procédé pour l'utilise
EP1880766A1 (fr) Système d'analyse basé sur un matériel poreux pour la détection de cellules individuelles
DE10143517A1 (de) Verfahren und Vorrichtung zur Analyse eines fluiden Mediums
DE10233212B4 (de) Messvorrichtung mit einer Biochip-Anordnung und Verwendung der Vorrichtung für ein Hochdurchsatzanalyseverfahren
EP2186565A1 (fr) Appareil de mesure et procédé de détermination de paramètres de fluide préparés par un système de laboratoire
EP0995098B1 (fr) Procede et dispositif pour prelever en serie des echantillons
DE10036174B4 (de) Verfahren und Vorrichtung zum Analysieren von chemischen oder biologischen Proben
EP1286771B1 (fr) Chambre de microhybridation
DE102013217959A1 (de) Mikrofluidikanalyse-Bauelement und Herstellungsverfahren
DE102005059536A1 (de) Verfahren und Biochip zur Untersuchung einer biologischen Probe
DE60029363T2 (de) Fluoreszenzverfahren zum Messen von Enzymaktivität unter Verwendung von Polyionen
DE112018007861T5 (de) Biochemische Kassette und biochemische Analysevorrichtung
DE102009010639B4 (de) Verfahren und Anordnung zur Inhibierung einer chemischen Reaktion von Substanzen in einer Flüssigkeit vor einer Messung
AT413214B (de) Messanordnung und verfahren zur detektion einer dna-sequenz
EP1706505A2 (fr) Procede pour valider et/ou calibrer un systeme pour l'execution d'experiences d'hybridation, jeu ordonne de micro-echantillons et necessaire correspondants

Legal Events

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

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR

RTI1 Title (correction)

Free format text: MEASUREMENT UNIT AND METHOD FOR DETERMINING FLUID PARAMETERS IN A LABORATORY SYSTEM

17P Request for examination filed

Effective date: 20101118

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

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

18D Application deemed to be withdrawn

Effective date: 20120601