EP3784401A1 - Analyseur automatique et procédé de mesure optique pour obtenir des signaux de mesure de milieux liquides - Google Patents

Analyseur automatique et procédé de mesure optique pour obtenir des signaux de mesure de milieux liquides

Info

Publication number
EP3784401A1
EP3784401A1 EP19720760.8A EP19720760A EP3784401A1 EP 3784401 A1 EP3784401 A1 EP 3784401A1 EP 19720760 A EP19720760 A EP 19720760A EP 3784401 A1 EP3784401 A1 EP 3784401A1
Authority
EP
European Patent Office
Prior art keywords
cuvette
cuvettes
light
stationary
unit
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.)
Pending
Application number
EP19720760.8A
Other languages
German (de)
English (en)
Inventor
Herfried Huemer
Arnold Bartel
Patrick KRAUS-FÜREDER
Robert SCHOLZ-MAREICH
Wolfgang Sprengers
Michael Bergbaur
Reinhard MARIK
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.)
Meon Medical Solutions and Co KG GmbH
Original Assignee
Meon Medical Solutions and Co KG GmbH
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
Priority claimed from ATA50341/2018A external-priority patent/AT521189B1/de
Priority claimed from ATA50021/2019A external-priority patent/AT522107B1/de
Application filed by Meon Medical Solutions and Co KG GmbH filed Critical Meon Medical Solutions and Co KG GmbH
Publication of EP3784401A1 publication Critical patent/EP3784401A1/fr
Pending legal-status Critical Current

Links

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
    • B01L3/02—Burettes; Pipettes
    • B01L3/0289—Apparatus for withdrawing or distributing predetermined quantities of fluid
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/59—Transmissivity
    • 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
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/026—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having blocks or racks of reaction cells or cuvettes
    • 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
    • G01N35/1002—Reagent dispensers
    • 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
    • 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
    • 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
    • G01N2035/00346—Heating or cooling arrangements
    • G01N2035/00356—Holding samples at elevated temperature (incubation)
    • 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
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04—Details of the conveyor system
    • G01N2035/0401—Sample carriers, cuvettes or reaction vessels
    • G01N2035/0437—Cleaning cuvettes or reaction vessels
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/251—Colorimeters; Construction thereof
    • G01N21/253—Colorimeters; Construction thereof for batch operation, i.e. multisample apparatus
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/06—Illumination; Optics
    • G01N2201/063—Illuminating optical parts
    • G01N2201/0631—Homogeneising elements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/08—Optical fibres; light guides
    • G01N2201/0813—Arrangement of collimator tubes, glass or empty
    • 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

Definitions

  • the invention relates to an automatic analyzer for carrying out chemical, biochemical and / or immunochemical analyzes of liquid samples present in a sample store of the analyzer, with the aid of liquid reagents present in at least one reagent store of the analyzer, a method for automatic chemical, biochemical and / or immunochemical analysis of liquid samples, as well as an optical
  • Measuring method for obtaining measurement signals from liquid media Measuring method for obtaining measurement signals from liquid media.
  • a stationary detection unit such as a stationary photometer
  • a disc-shaped, rotatable holder with cuvettes for receiving the to be measured
  • optical measuring unit for obtaining measurement signals from liquid media different types of measurement are used:
  • the physical effect underlying the photometric measurement is the absorption of light of specific wavelengths by certain substances present in a liquid.
  • the molar concentration c can thus be calculated directly from the result of an extinction or transmission measurement. This type of measurement is used in chemical and enzymatic reactions to determine the
  • Substance concentration of certain in the sample blood plasma, urine, etc.
  • existing analytes are used.
  • light-absorbing substances dyes
  • the molar concentration of the analyte to be determined is concluded.
  • This type of measurement is used in homogeneous immunoassays, with certain analytes, such as enzymes, peptides or proteins, with
  • Antibodies be reacted. This results in larger structures that cause increased light scattering or turbidity of the sample.
  • the intensity of the continuous light beam attenuates as a result of increasing turbidity
  • the intensity of the scattered light beam increases with increasing haze at a detection angle of 90 °.
  • the turbidity measurement in the form of transmission measurement is called turbidimetry.
  • the relevant measuring device as a turbidimeter.
  • Measuring device as a nephelometer.
  • analyzer For a better understanding of the invention, a few essential technical terms used in the subject application are further defined: analyzer:
  • x-axis means the horizontal longitudinal axis, y-direction the horizontally extending latitude or longitude axis, and z- the vertical height axis of the analyzer (see, e.g., Figure 3).
  • a cuvette in the sense of the present invention denotes an all-round
  • a cuvette in the sense of the present invention has at least one window which is permeable to the applied optical measuring method and is arranged in a side wall of the cuvette or is entirely optically transparent.
  • stationary cuvette array :
  • Container for receiving reagents needed to perform the analysis.
  • Vessel or container which contains in the analyzer the analytical sample (the sample to be analyzed), from which for the analysis of individual analytes or parameters several times smaller sample quantities (aliquots) can be taken.
  • the analysis does not take place in the vessel of the analytical sample, but instead after addition of the reagents in the cuvette, which serves in this sense as a reaction vessel.
  • the analytical sample (usually called only a sample or a substance sample) is the material to be analyzed that is introduced into the analyzer.
  • This material is a liquid mixture and may, for example, be a body fluid such as e.g. Blood serum, blood plasma, urine and cerebrospinal fluid. Other mixtures are e.g.
  • the analytes or analytes are those substances contained in an analytical sample which are to be used to make statements with an analyzer via a chemical analysis with the aid of liquid reagents, i. which are determined quantitatively, indicating the concentration.
  • the analysis or test (also called immunoassay in immunochemical analyzes) are those which are carried out automatically with an analyzer
  • Fluid transfer between different vessels which includes one or more movable pipettors including all mobile and stationary components necessary for their function, including supplying fluidics (hose connections, pumps, valves, containers, etc.), sensors, control and power supply.
  • fluidics hose connections, pumps, valves, containers, etc.
  • sensors control and power supply.
  • the pipettor includes one
  • Suspension component with at least one pipetting module that can be moved in a y-direction that is essentially normal in the x-direction.
  • Pipetting module Denotes a device attached to the pipettor, movable in the y-direction device comprising a movable in the vertical z-direction holder for at least one cannula or hollow needle, together with their connection elements for fluidics.
  • Automaton component which is stationary in the analyzer and during the normal measurement operation is not moved along the linear cuvette array (moved).
  • optical elements for generating as parallel a beam path as possible. Basically, the light of a more or less punctiform source is transformed into a parallel bundle of rays.
  • Optical elements that align the light emanating from an LED substantially parallel for example, converging lenses, TIR lenses, parabolic mirrors, and aperture arrangements.
  • optical elements for filtering
  • optical components in particular interference filters, for frequency-dependent transmission of the transmitted light, i. color-dependent for visible light, to filter.
  • these components are constructed as dielectric layers on a thin carrier. After the wavelength-dependent
  • Transmittance depends on the angle of incidence of the light, it is advantageous if the light rays incident on the filter element as parallel as possible and are aligned parallel to the optical axis.
  • Bandsafe filters longpass filters, shortpass filters, bandpass filters and dichroic interference filters are used. Particularly preferred are bandpass filters because they have a high transmittance for a particular wavelength band while absorbing shorter or longer wavelengths.
  • Reagent dispenser the mixing device, optical measuring device and
  • the thermostating of the cuvettes can be integrated, for example, in the form of a temperature-controlled water bath in the turntable.
  • the sample containers are placed on a sample turntable that locates reagents on a reagent turntable.
  • the analyzer includes a sample disk on which a number of sample containers can be mounted for receiving a sample; a first reagent disc and a second reagent disc, on each of which a number of reagent containers for receiving a first reagent
  • Reagent or a second reagent can be arranged; and a
  • Reaction disc on which along the circumferential direction a number of cuvettes or reaction containers is arranged.
  • Sample dispensing apparatus provided which emits a sample sucked on the sample container in the reaction vessel. Furthermore, a first reagent dispensing device is provided between the reaction disc and the first reagent disc, which dispenses a reagent sucked up from the reagent container on the first reagent disc into the reaction container. Likewise, a second one is between the reaction disc and the second reagent disc
  • Reagent dispenser which emits a sucked from the reagent container on the second reagent disc reagent in the reaction vessel.
  • the sample delivery device and the two reagent delivery devices are stationarily arranged at defined points along the circumference of the reaction disc.
  • Reaction vessel sends, and a container cleaning mechanism for cleaning the reaction vessel provided in this order in the rotational direction of the reaction disc.
  • a stationary spectroscopic system In a position opposite to the light source, a stationary spectroscopic system is arranged such that the reaction disc is located therebetween. In the vicinity of the spectroscopic system, a signal processing circuit is provided which processes the signals from the spectroscopic system.
  • the signal processing circuit is connected to a computer.
  • Such analyzers are disadvantageous because all processes are predetermined by rigid clock cycles of the carousel and must run in predetermined time windows. Actions such as dispensing, mixing, measuring and washing can only take place if the respective cuvettes are located at the positions of the respective device components.
  • a sample (not anytime, but) can be dispensed into an empty cuvette only when the empty cuvette passes the position of the sample pipettor and stops the cuvette carousel at that position.
  • a reagent can only be dispensed into a cuvette containing the sample as the cuvette passes the position of the reagent pipettor and stops the cuvette carousel at that position. The same applies to the stirring of reaction mixtures from the sample and the reagents in the cuvettes with mechanical stirring and for the optical measurement at the position of the optical measuring device.
  • a particular cuvette can not be optically measured at any time or not repeatedly in small time intervals, since it is only necessary to wait until the cuvette in question at the position of the optical
  • Measuring unit is located or is passed on this "on the fly" during the measurement.
  • a cuvette can not be readily washed and provided for a new test disadvantageously.
  • a cuvette can not be washed and provided for a new test until the cuvette in question is in the position of the cuvette washing station and at a fixed time or a fixed period of time from the start of the test to the one corresponding to the cuvette
  • the cuvettes are arranged in an outer ring and the reagent vessels in two inner rings.
  • the axis of rotation of a stationary pipettor is positioned, which is surrounded by an annular washing vessel for the lowerable pipetting needle of the pipettor.
  • the sample vials of the analyzer are located on a separate turntable on the periphery of the stationary cuvette ring.
  • An optical measuring unit reaches the measuring cuvettes by means of a rotary movement about the central axis of the analyzer. The optical path leads through the liquid surface along the longitudinal axis of the individual
  • the pipetting needle reaches the sample vessels, the measuring cuvettes, the reagent vessels and the washing vessel by means of rotational movements of two
  • the disadvantage is that the disclosed configuration allows only an independently movable pipetting needle for sample and reagents, that the reagent storage is limited to the surface of the inner stationary rings and that the optical path passes through the surface of the reaction liquid.
  • a particular disadvantage is that the cuvettes can not be washed, but must be replaced after use sector by sector with the outer ring.
  • WO 99/046601 A1 shows a linear, movable cuvette array with stationary device components (dispensers for sample liquid and
  • Support frame or a transport bar 7 at predetermined intervals in a thermostatic chamber (water bath) 1 is arranged.
  • the transport bar with the reaction vessels 2 is linearly moved by means of a drive unit 8 in the direction of arrow 9. Further, in addition to the thermostatically controlled chamber 1 a
  • Measuring unit 4 a Bruvettenwasch exotic material
  • a first stirring mechanism 6a and a second stirring mechanism 6b for stirring the contents of the
  • Reaction vessels 2 are provided.
  • the stirring mechanism 6a or 6b can also be designed as an ultrasonic generator, which acts on the reaction vessels 2 via the water bath in the chamber 1.
  • the water in the thermostatically controlled chamber 1 is kept at a constant temperature at which the reactions take place and the optical measurement can be carried out.
  • a reaction vessel 2 stops at the
  • Sample pipetting unit 3a which discharges the sample into the reaction vessel 2.
  • the reagent injection unit 3b discharges the reagent used for the examination into the corresponding reaction vessel 2.
  • the first one is stirred
  • a disadvantage of this concept is that the transport bar 7 necessarily requires a lot of free space for the linear movement of the reaction vessels 2 to the left or right of the stationary device components 3a, 3b, 6a, 6b and 5.
  • the longitudinal axis of the analyzer inevitably increases by at least twice the length of the transport bar. 7
  • the cuvettes or reaction vessels 2 of the device according to WO 99/046601 A1 are thus moved past the stationary device components, analogously to the turntable variant described above.
  • the system is inflexible, there are essentially the disadvantages that have already been mentioned in point A).
  • the rotatable device which carries the light source in the form of an LED and the photodetector in the form of a photodiode can be arranged below the receptacle of the sample vessels, whereby it is always possible to access the sample vessels by means of a gripping arm.
  • the rotatable device may also include multiple LEDs of different wavelengths and multiple photodiodes to allow the samples to be measured at multiple wavelengths.
  • the photodiodes may be replaced by a CCD element.
  • EP 2 309 251 A1 is unsuitable, for example, for clinical chemical analyzers (cc analyzers) and directed to an analyzer for haemostatic measurements (for the determination of blood coagulation).
  • This arrangement may also be part of a multi-device system (e.g., PCR analyzer, refrigerator).
  • the sample vessels are not reused but optionally passed to other components of a system, e.g. disposed of by means of a gripping arm or after the determination of the coagulation parameters.
  • analyzers with such photometers always use cell-free Analysis samples, such as blood plasma or blood serum, which are also greatly diluted by the addition of reagents.
  • the vessels with the incoming samples are used directly for the optical measurement.
  • An analyzer of the subject invention will always use cell-free analysis samples, for example, body fluids such as blood plasma / blood serum, urine, and cerebrospinal fluid; Drinking water, sewage, wine, beer and
  • a typical analyzer for performing biochemical analyzes of liquid samples using microtiter plates is e.g. from EP 0 259 386 B1 (TECAN).
  • the analyzer comprises a primary rack for holding a plurality of sample vessels, a cross table positionable next to the primary rack in the x-y direction for receiving a microtiter plate, one arranged above the primary rack and the cross table, arbitrarily in an upper horizontal plane
  • Microtiter plates contain many mutually isolated wells in rows and columns (2D arrays). They are used for a wide variety of operations.
  • Pipetting is performed either manually or with high throughput screening (HTS) using pipetting robots.
  • HTS high throughput screening
  • a pipetting device which has a pipettor with a plurality of flat, juxtaposed frame elements, which together with their pipetting needles on a main frame body in a horizontal, normal to the main frame body x Direction are movable.
  • the pipetting device serves to transfer samples or reagents from a first row of vessels to an x-directional second row of vessels.
  • the pipetting needles are first adjusted in y-direction to the distance of the vessels of the first row to receive sample or reagent liquid and then - adapted to dispense the sample or reagent liquid - to the distance of the second row of vessels.
  • the analysis module has a microtiter plate heating plate located near the bottom of the wells of the microtiter plate to convect the contents of the wells by convection.
  • the extraction unit further comprises a mixing device controlled by an electromagnet to effect alternate reciprocation of the pipetting needle when this is in a lowered position in a well of the microtiter plate to mix the mixture of samples and reagents.
  • US Pat. No. 5,897,837 A discloses a pipetting apparatus suitable for sample pretreatment of an immunoassay analyzer having a first block of a pipettor movable horizontally in the x- and y-direction and equipped with two pipetting needles side by side is that can be lowered or raised independently. In this case, one of the two needles can be assigned to reagents that have other needle samples.
  • a second block which can be moved in the x-y direction and has a lowerable pipetting needle is also present.
  • a stationary needle washing station For the needle cleaning, a stationary needle washing station must be started up.
  • the two pipetting needles of the first movable block are disadvantageously only jointly movable. This has the disadvantage that the masses of the robot components of the pipettor can not be divided into the two horizontal axes x and y, so that the mass of the second pipetting unit must always be accelerated for approaching positions in the y direction.
  • the mass of the needle washing unit including needle washing vessel must always be mitbeuggt in both horizontal directions. Furthermore, it is not possible due to the common horizontal movement, both needles simultaneously for pipetting at different, not adjacent positions of a
  • Deflection mirror 30 is irradiated in the present in the reaction vessel 24 sample 31.
  • a light source a semiconductor laser can also be used.
  • a photodetector 32 of the photometer 27 is arranged on the opposite side of the reaction vessel 24. In and out of the reaction vessel 24 are in the measuring position 33 of the photometer 27 aperture 34 for the input and
  • US 2013/0301051 A1 (Pogosyan) describes a low-cost, portable photometer which has several LEDs with different wavelengths as light sources and a photodiode or a photomultiplier as detector.
  • the photometer can be used for the examination of chemical, biological or pharmaceutical samples, which can be found in a sample holder between the
  • Light sources and the detector are located.
  • the light from the light sources is directed onto a light-scattering surface and passes through a collimator lens and a slit diaphragm into the sample present in the sample holder.
  • the detector can be pivoted from a first position to a second position.
  • a collimator lens functions optimally if the scattering surface is chosen to be very small, more or less punctiform, which, however, reduces the luminous efficacy.
  • US 8,064,062 B2 discloses a photometer having a stationary LED array with a plurality of light sources and a stationary detector array with a plurality of photodiodes, wherein each light source is associated with a photodiode.
  • the cuvettes located on a turntable are arranged between the LED array and the detector array. In a rotational movement of the cuvettes, the optical beam paths are crossed and the samples in the cuvettes can be successively acted upon by the light of different wavelengths.
  • the automatic pipetting apparatus 10 has a first pipettor 20, which can be moved horizontally in the x and y directions, and which has two pipetting needles 11 and 12
  • a second, in x-y direction movable pipettor 21 with a lowerable pipette needle 13 is also present.
  • the first, horizontally movable pipettor 20 carries a needle washing unit 22, which is horizontally movable back and forth between the vertical lowering paths of the two pipetting needles 11, 12. In this case, one of the two needles can be cleaned alternately, while the other needle performs a pipetting process.
  • the two pipetting needles 11, 12 of the first pipettor 20 can only be moved together in the x and / or y direction.
  • Pipetting unit must always be mitbeuggt. So must the crowd the needle washing unit 22 together with needle washing vessel are always mitbeuggt in both horizontal directions.
  • Robot assembly for the life science sector has become known, which includes a plurality of robot modules 131. As shown in Fig. Id of the subject application, each of the couplable modules 131 is provided with a stationary X-axis arm 132 on which at least one Y-axis arm 133 is movably arranged in the X direction. On the Y-axis arm 133 is movable in the Y direction
  • the working module 134 can be designed as a pipetting module with a plurality of pipetting needles 135 or as a gripper module.
  • the samples to be pipetted 136 are arranged on a working deck 137, wherein in a work platform 137 with the X-axis arm 132 connecting column 139, a replaceable dispensing module 138 is arranged, which is connected via hose lines with the working module 134.
  • the Y-axis arm 133 may include two working-module docking devices 134 on opposite sides of the Y-axis arm 133. The coupling devices are then independently movable in the Y direction.
  • a plurality of modules 131 may be coupled such that their X-axis arms connect to each other, wherein the Y-axis arms can be moved to adjacent modules, but are not moved past each other.
  • a temperature-controlled cuvette arrangement has become known.
  • a thermostattable cuvette block 55 with a plurality of receiving wells 56 is provided, into which cuvettes 57 can be inserted.
  • the downwardly tapered, lateral measuring window 58 having cuvettes 57 are positively inserted into a U-shaped, good heat-conducting adapter 59, which establishes thermal contact with the cuvette block 55 via the walls 60 of the receiving shaft 56.
  • the sample-reagent mixture in each of the cuvettes 57 can each be optically measured by a measuring channel 61 in the cuvette block 55.
  • the disadvantage here is that the temperature of the sample-reagent mixture heats up only slowly to the temperature of the cuvette block. Thus, the achievement of a high sample throughput in an analyzer is difficult because the
  • Thermostatization in the analysis of a sample always counts among the processes with the highest time requirement.
  • JP 2007-303964 A discloses - as shown in Figure 2b of the subject application - a device for thermostating cuvettes 62, which are arranged in recordings of a rotatable carousel 63.
  • the device has a piezoelectric substrate 64 attached to the sidewall of each cuvette 62, on which is integrated both an electrode structure of an interdigital transducer (IDT) as the ultrasonic transducer 65 and a temperature sensor 66 for non-invasive measurement of the temperature of the cuvette contents.
  • IDT interdigital transducer
  • a connected via sliding contacts 67 temperature control unit 68 of a control unit 69 forms together with the driver unit 70 for the ultrasonic transducer 65, a control loop to thermostate a reaction mixture in the cuvette 62.
  • the sample-reagent mixture is heated by absorption of ultrasonic energy directly to the target temperature.
  • each cuvette 62 requires a glued piezoelectric substrate 64 with integrated temperature sensor 66, which must be brought into contact with an electronic control unit 68. Furthermore, the temperature measured on the substrate of the ultrasonic transducer 65 can be falsified by the self-heating of the ultrasonic transducer and thus does not correspond to the temperature of the sample reagent mixture in the cuvette 62.
  • the temperature sensor 66 is not in contact with the liquid, but can absorb the temperature of the liquid only indirectly via the heat conduction of the vessel wall of the cuvette 62, whereby in particular with a very rapid heating of the liquid, a temperature increase in the liquid not with sufficient speed and Accuracy can be measured to exclude a permanent or temporary overshoot of the target temperature by a critical value for the sample components can.
  • Liquids in cuvettes 71 are known, which - as shown in Fig. 2c of the subject application - are arranged on a rotatable carousel 72, wherein on the side wall of each cuvette a sound generator 73 (interdigital transducer (IDT)) glued to the irradiation of ultrasonic energy in the cuvette 71 is.
  • IDT interdigital transducer
  • the critical heat input caused by the operation of the sound generator 73 is determined by thermal characteristics of the thermal energy stored in a control unit 74
  • the heat input can be limited by limiting the
  • an own Peltier element 76 can be applied directly to the substrate of the glued sound generator 73 by means of an actuator 75 for each cuvette 71, during this process actively cooling the plant.
  • the signal generator 77 for the sound generator 73 is driven by a driver unit 78 of the control unit 74.
  • a temperature measurement of the liquid can be carried out from above with a stationary infrared sensor, but only at a particular cuvette of the carousel can be performed at its stoppage.
  • a thermostating with the above technical features has the disadvantage over a block thermostating in a constant temperature cuvette recording the disadvantage that the system with regard to exceeding the target temperature during heating and tempering can not be considered as inherently safe.
  • JP 2007-010345 A describes an ultrasonic stirring device with which the contents L of a cuvette 81 can be mixed.
  • a piezoceramic ultrasonic generator (thickness vibrator 83) is adhered to the bottom 82 of the cuvette 81, the shape and material of the cuvette bottom forming an acoustic lens 84, just below the ultrasonic energy at point F. to concentrate the liquid surface.
  • the thickness oscillator 83 made of lead zirconate titanate (“sounding body”) has a flat disk 85 with double-sided electrical contacting 86, with a diameter which is greater than that of the cuvette bottom 82.
  • the object of the invention is in automatic analyzers for carrying out chemical, biochemical and / or immunochemical analyzes of liquid samples, the above - especially in connection with the predetermined by rigid clock cycles and run in predetermined time windows processes limited sample throughput of known systems - mentioned disadvantages and to propose improvements that increase the sample throughput without significantly increasing the cost of the individual analysis or the analyzer, at least maintaining the quality of the analysis. Furthermore, an improved method for automatic chemical, biochemical and / or immunochemical analysis of liquid samples is to be proposed.
  • an analyzer with cuvettes for receiving the liquid samples and reagents, each having a side entrance window and at least one side exit window, wherein a plurality of cuvettes is arranged as at least one stationary, linear cuvette array in the analyzer, with movable and stationary
  • Machine components at least comprising:
  • Movement line in the x-direction movably executed pipettor which is equipped with at least one in y-direction - substantially normal to the x-direction - movable pipetting module, whose at least one
  • Hollow needle in the z-direction in the cuvettes and in individual vessels of the sample and / or reagent storage is designed to be lowered
  • a mixer unit for mixing the samples and reagents in the cuvettes
  • a stationary light supply unit which has at least one light distributor device which feeds the light of a plurality of LED light sources emitting spectrally different spectrally in the UV / VIS / NIR wavelength range into the entry windows of the individual cuvettes of the cuvette array, and
  • a needle washing unit for cleaning the at least one hollow needle for cleaning the at least one hollow needle
  • An evaluation and control unit wherein the light distribution device has a cavity whose inner surfaces are at least partially mirrored and / or designed to be diffusely reflective, and wherein each cuvette of the stationary cuvette array is assigned at least one fixed photodiode.
  • An essential advantage of the analyzer according to the invention with its special optical measuring unit is that the cuvettes are arranged as immovable, stationary cuvette array, each cuvette their individual Detectors (transmitted light detector and / or scattered light detector) of the optical
  • Measuring unit are assigned fixed and therefore the light emerging from the individual cuvettes - including any dark signals - each cuvette can be measured indefinitely. Thus, it is not necessary to measure in passing the detectors or to position a detector in sequential order in front of several cuvettes in stop-and-go operation. As a result, more accurate measurement results can be obtained, and measurement procedures can be made considerably more flexible.
  • the light supply unit has at least one stationary light distributor device which distributes the light of the individual LED light sources to the individual cuvettes of the cuvette array, the light distributor device having a cavity whose inner surfaces are at least partially mirrored and / or diffusely reflecting are.
  • the light distribution device for each LED light source an inlet opening to
  • the multiple LED light sources different
  • Wavelength stationary associated with a number of cuvettes.
  • the stationary cuvette array may be segmented, with each segment being a separate cuvette array
  • Light distribution device is assigned permanently. Overall, therefore, an optical measuring unit is realized which has no moving components.
  • the inner surface of the cuvettes facing the outlet openings is
  • Light distribution device designed diffuse reflective.
  • Reagents which are present in at least one reagent storage of the analyzer, for Determining at least one analyte concentration in the sample is characterized by the following steps:
  • Reagent fluid from a reagent vessel of the reagent storage in the cuvette of the stationary, linear cuvette array by means of a hollow needle of the first or the second pipetting module of the at least one movable along the cuvette array pipettor;
  • photometric measurement of the contents of the cuvette by means of an optical measuring unit arranged along the cuvette array with a stationary light supply unit and a stationary detection unit; and determination of at least one measured value;
  • At least two of the automatic components are independently movable in the x-direction: the pipettor (in the simplest case a single pipettor with a single pipetting module) and the cuvette washing unit.
  • the Mixing unit can be stationary or movable, the optical measuring unit and the Thermostatisierü are stationary. It should also be noted that two different moveable machine components accessing the cuvette openings can not simultaneously access one and the same cuvette. In practice, however, it is not necessary anyway that, for example, Pipettor and
  • Automate components in particular the cuvette washing unit on any cuvettes and the at least one pipettor (with at least one pipetting module) on any sample vessels, reagent vessels and cuvettes, the throughput increases significantly compared to a rotary-organized machine with the same number of cuvette.
  • the analyzer has two independently movable in the x-direction pipettors.
  • first pipettor can pipette samples into a first cuvette
  • second pipettor can simultaneously pipette reagents into an arbitrary second cuvette.
  • Pipetting module wherein each of the pipetting modules at least one
  • Hollow needle has.
  • the two pipetting modules of a pipettor can thus pass each other independently of one another in the y-direction, without having to
  • two different types of needles may also be used (e.g., for different pipetting volumes, with special coatings for different sample and reagent types, without the need for another pipettor or a needle exchange station).
  • Needle washing unit is arranged on Pipettor and run with this movable.
  • Pipetting modules can be independent of the Pipettor entrained needle washing unit, a division of the moving masses of the robotics components on the two horizontal axes is possible, so that only in the x direction
  • the measuring method according to the invention is furthermore distinguished by
  • That light is introduced into at least one light distributor device of the stationary light supply unit for the photometric measurement of the contents of the cuvettes - successively in succession - by a plurality of LED light sources emitting spectrally different wavelengths in the UV / VIS / NIR wavelength range, the light distributor device irradiating at least one segment of the light source
  • each cuvette their individual detectors are permanently assigned and that the light emerging from the individual cuvettes - including any
  • the measuring radiation emerging from the cuvettes is converted into an electrical measuring signal and displayed in a display unit after appropriate preparation.
  • the analyzer furthermore has a mixer unit, for example a hollow needle of a pipetting module which can be displaced in rotation or vibration and which is connected to the Mixing of the samples and reagents can be lowered into the respective cuvettes.
  • a mixer unit for example a hollow needle of a pipetting module which can be displaced in rotation or vibration and which is connected to the Mixing of the samples and reagents can be lowered into the respective cuvettes.
  • the analyzer has a cuvette washing unit, which according to the invention is designed as a movable automatic component which has access to a cuvette or a group of cuvettes, preferably to two to five cuvettes arranged side by side, at the same time in each washing position.
  • the cuvette washing unit can also have a stirring element which can be used for
  • Mixing of the samples and reagents can be lowered into the respective cuvettes.
  • Measuring temperature have a Thermostatisierussi comprising heating foils which contact individual cuvettes or groups of cuvettes thermally and can be acted upon with different temperature levels.
  • the individual cuvettes or groups of cuvettes may also be accommodated in a thermostatable cuvette block which also serves as a cuvette holder.
  • the cuvettes have in a near-ground region preferably plane-parallel to each other arranged inlet and outlet windows, which are permeable to the entrance and exit radiation or measuring radiation of the optical measuring unit.
  • 1a shows an automatic analyzer with linearly arranged, movable reaction vessels or cuvettes according to the prior art
  • 1b shows an automatic analyzer with cuvettes arranged in a circle on a turntable, together with the optical measuring unit according to the prior art
  • FIG. 3 shows an automatic analyzer according to the invention for carrying out chemical, biochemical and / or immunochemical analyzes of liquid samples with two pipettors on a linear, stationary cuvette array in a three-dimensional overall view
  • FIG. 4 is a sectional view of the analyzer according to line IV-IV in Fig. 5, 5 is a simplified plan view of the analyzer of FIG. 3,
  • FIG. 6a two independently movable pipettors of the automatic analyzer according to FIG. 3 in a three-dimensional view
  • 6b shows an embodiment variant of a pipetting device with a pipettor in a three-dimensional view
  • FIG. 7 a shows an optical measuring unit according to the invention of the analyzer according to FIG.
  • FIG. 7b shows the optical measuring unit according to FIG. 7a in a three-dimensional view, looking towards the detection unit, FIG.
  • FIG. 8a is a sectional view of the light providing unit of FIG. 7a along line II-II in Fig. 8b,
  • FIG. 8b is a sectional view of the light providing unit of FIG. 7a along line III-III in Fig. 8a,
  • Fig. 8c is a three-dimensional detail of a tube body of
  • FIG. 8d is an enlarged detail view of Fig. 8a
  • FIG. 8e shows a variant of the light supply unit in a sectional view according to FIG. 8a, FIG.
  • FIG. 8f shows the variant of the light supply unit according to FIG. 8e in one
  • FIG. 8g to 8i show three different detail variants of the beam guidance on the input and output side of a cuvette in a sectional representation according to FIG. 8f, FIG.
  • 10a shows a first diagram to illustrate a measuring sequence (modes 1, 2)
  • 10b shows a second diagram to illustrate a measurement procedure (mode 3),
  • FIG. 11 shows a movable cuvette washing unit of the automatic analyzer according to FIG. 3 in a three-dimensional view
  • FIG. 12 is a needle washing unit of the automatic analyzer of FIG. 3 in a three-dimensional, partially cutaway view
  • FIG. 13 shows a thermostating unit for the cuvettes of the automatic analyzer according to FIG. 3 in a three-dimensional, partially.
  • FIG. 14 shows fluidic elements of a hollow or a pipetting needle of a pipetting module according to FIG. 6a in a schematic illustration, FIG.
  • Fig. 15 fluid elements of a needle washing unit of FIG. 12 in a
  • FIG. 16 shows fluidic elements of a cuvette washing unit according to FIG. 11 in one.
  • Fig. 17a a device for mixing and thermostating liquid media of an automatic analyzer according to Figure 3 to 5 in a
  • FIG. 17b shows the device according to FIG. 17a in a sectional representation according to FIG.
  • Fig. 17c is a cuvette including ultrasonic transducer of the invention
  • 18 is a block diagram for the electronic control of the device for
  • Fig. 19a is a temperature diagram for showing a first
  • Fig. 19b is a temperature diagram illustrating a second
  • Embodiment of a Thermostatisier- and mixing process of a liquid Embodiment of a Thermostatisier- and mixing process of a liquid.
  • FIGS. 1 a and 1 b The automatic analyzers shown in FIGS. 1 a and 1 b, the pipetting devices shown in FIGS. 1 c and 1 d, and those shown in FIGS. 2 a to 2 d
  • Analyzes of liquid samples For simplicity, only those components of the Analyzer 100 shown, which are essential for the subject invention, wherein analyzer components, such as pumps, valves, evaluation, control and drive units, not discussed.
  • the liquid samples are present in sample containers 921 in a sample storage 920 of the analyzer 100 and are analyzed with the aid of liquid reagents which are present in reagent containers 951 a, 951 b in two reagent storage units 950 a, 950 b of the analyzer 100.
  • the cuvettes 201 for receiving the liquid samples and reagents are arranged in the form of a stationary, linear cuvette array 200 in the analyzer 100 and remain in their original position during a large number of individual analyzes.
  • the cuvette array 200 is disposed between the first reagent storage 950a and the second reagent storage 950b in the illustrated example.
  • the automatic analyzer 100 according to FIGS. 3 to 5 is equipped with movable and stationary machine components, namely:
  • the hollow needles 307 of which are inserted into the cuvettes 201 in the z-direction are designed to be lowered into the sample containers 921 located in the sample storage 920 and into the reagent containers 951a, 951b located in the reagent storage units 950a, 950b and in a y-direction substantially perpendicular to the x-direction between the cuvettes 201 and
  • Sample bearing 920 and / or the two reagent bearings 950a, 950b are carried out movable;
  • a mixing unit (not shown) for mixing the samples and reagents in the cuvettes 201;
  • a cuvette washing unit 600 for cleaning the cuvettes 201 which can be moved along the line of movement defined by the cuvette array 200 in the x direction,
  • the pipettors 300a, 300b are fixed by means of movable receiving elements (not shown) to the parallel rails purple, 111b, furthermore, a corresponding rail 113 for receiving the optical measuring unit 500 and a rail 112 together with movable receptacle 601 for the
  • Cuvette washing unit 600 is provided.
  • the movable recordings of the pipettors 300a, 300b, and the receiving oil are driven, for example, by means of toothed belts and stepper motors, not shown here, at one end of the rails 112, 111a and 111b.
  • At least two-in the illustrated example several-of the automatic components are independent of one another along or parallel to that defined by the linear cuvette array 200
  • Movement line executed in the x-direction movable, and can each access different cuvettes 201 or groups of cuvettes 201 in arbitrary order.
  • the analyzer 100 has a sample storage 920, a first reagent storage 950 a and a second
  • the storage areas can be completely or partially cooled.
  • vessels 921 with analysis samples are introduced into the sample storage 920 manually or by means of robotics into predetermined positions. The for the individual analysis samples
  • reagent vessels 951a, 951b with reagents for analyzing different analytes are introduced into the two reagent stores 950a, 950b of the analyzer 100 in predetermined positions either manually or by robotics.
  • Vessels containing calibration fluids and reference samples can also be placed in the sample or reagent storage facilities.
  • the analyzer according to FIGS. 3 to 5 has two pipettors 300a, 300b which can be moved independently of one another in the x-direction, accessing individual cuvettes 201 of the cuvette array 200 completely independently of one another and in an arbitrary order, with the exception of the same cuvette can.
  • the two pipettors 300a, 300b according to FIG. 6a each have a vertical tower 303a, 303b, as well as an arm 304a oriented horizontally in the y-direction, 304b, so that a substantially L-shaped support structure (pipettor 300a) for the two pipetting modules 301al, 301a2 and T-shaped support structure (pipettor 300b) is formed for the two pipetting modules 301bl, 301b2, along the rail lilac and 111b, respectively Can be moved in the x-direction.
  • Each pipettor thus has two independently, parallel to each other in the y-direction movable
  • the pipetting modules 301al, 301a2 and 301bl, 301b2 are fastened to the left and right of the arm 304a and 304b, respectively, by means of a receptacle 305 movable in the y-direction and can thereby unhindered against one another
  • Each receptacle 305 has a downwardly projecting one
  • the individual pipetting modules 301al, 301a2 and 301bl, 301b2 each have a needle holder 308 with a region projecting in the direction of the cuvette array 200, which carries the hollow needle 307. This leaves even with an aligned on the cuvette 201 aligned or lowered hollow needle 307 of
  • Pipetting module 301b2 enough space for the L-shaped pipettor 300a to pass the T-shaped pipettor 300b can (see Fig. 4).
  • Pipetting modules 301bl, 301b2 access only the sample vessels 921 in the sample storage 920 and the reagent vessels 951b in the reagent storage 950b,
  • All pipetting modules 301al, 301a2 or 301bl, 301b2 can be moved to the level of the cuvette array 200 and lowered into the individual cuvettes 201.
  • a substantial increase in the sample throughput can be achieved by arranging the needle washing units 700al, 700a2 or 700bl, 700b2 on the pipettor 300a or 300b, respectively, and making it movable with it.
  • each pipetting module 301al, 301a2 each pipetting module 301al, 301a2
  • 301bl, 301b2 has its own needle washing unit 700al, 700a2, 700bl, 700b2, which can be arranged, for example, in each case on the vertical tower 303a or 303b of the pipettor 300a or 300b.
  • one of the hollow needles 307 of the pipetting modules 301al or 301bl in the associated needle washing unit 700al or 700bl can be washed, while the respective other hollow needle 307 dips into a cuvette 201 (see FIG. 6a).
  • a single pipettor 300 can have a base structure 340 which can be moved in the x-direction, on which two parallel aligned beams 341, 342 projecting horizontally in the y direction are attached, each of which can be moved independently past one another on the longitudinal sides facing one another Pipetting modules 3011, 3012 are arranged, wherein each pipetting module 3011, 3012 at least one, in the individual cuvettes 201 lowered hollow needle 307 has.
  • the x-directionally movable pipettor 300 has two pipetting modules 3011, 3012 on a horizontally projecting arm 304 along a y-direction which is substantially normal in the x-direction.
  • Two parallel aligned horizontal beams projecting in the y direction 341, 342 are fastened to a base structure 340 which can be moved in the x direction, on the mutually facing longitudinal sides of which the two independently movable pipetting modules 3011, 3012 are arranged, each of the pipetting modules 3011, 3012
  • Hollow needle 307 has.
  • the two pipetting modules 3011, 3012 are moved in the y direction via linear drives (for example, toothed belt drives) (not shown here).
  • the two bars 341, 342 of the pipettor 300 may be connected at the end face of the arm 304 by a connecting web 351 to a substantially rectangular frame structure 343 in order to stiffen the pipettor against deformations in the x direction.
  • the resulting frame structure can be made even more rigid if on the inside stiffening elements 349 are each provided at the intersection between the beam 341 or 342 and the connecting web 351 or the base structure 340 (not shown).
  • the pipettor 300 consisting of the structural features according to the invention can be manufactured in one or more parts.
  • the arm 304 is suspended via the - for example trapezoidally shaped - base structure 340 on a horizontal running rail 111, which allows a method of the pipettor 300 in a longitudinal direction defined as the x-direction of the working surface 114 of a sample and reagent deck 930.
  • the arm 304 is movable in the variant shown in Fig. 3b via a linear drive, such as a toothed belt drive (not shown), which is connected to a servo motor 347.
  • the running rail 111 is anchored to a solid, vertically oriented back plate 348, which serves as both counterweight in acceleration and in the
  • the back plate 348 may be made of aluminum and a mass of 20 kg
  • the machine frame (not shown in detail) below the working surface 114 has a mass of> 300 kg.
  • the pipettor 300 of the pipetting apparatus has one with the pipettor 300
  • movable needle washing unit 700 for washing the two hollow needles 307 of the two pipetting modules 3011 and 3012 on.
  • the needle washing unit 700 is in this case entrained on a suspended carrier structure 344 on the pipettor 300, wherein an actuator, for example in the form of a spindle drive acting in the x direction, changes the position of the spindle
  • Needle washing unit 700 on the support structure 344 allows, so that the
  • Hollow needles 307 of the two movable in the y-direction pipetting modules 3011 and 3012 with a single needle washing unit 700 can be washed. Furthermore, an exchange of the x-position of the needle washing unit 700 may also be provided by suspension on a horizontally pivotable arm of a rotary actuator (not shown).
  • the support structure 344 may, for example, be rigidly connected to the arm 304 or to the base structure 340.
  • a separate energy chain 312 may be provided for the tracking of Fluidiktechnischen and any electrical supply and signal lines of the needle washing unit 700 in the x direction. However, it is also possible to carry these lines in the unrollable energy chain 310 of the pipettor 300.
  • each of the two pipetting modules 3011 and 3012 may each have its own needle washing unit 700 fixed to one of the pipetting modules 3011 or 3012.
  • Needle washing unit 700 on the support structure 344 be exactly in the middle between the hollow needles to be washed 307 of the two pipetting 3011 and 3012 be arranged, wherein the opening of the needle washing unit 700 may be performed, for example, as a slot, so that at a low x-distance on the inside the bar 341.342 movable hollow needles 307 of
  • Opening the needle washing unit 700 can be lowered.
  • the hollow needles 307 of the two movable past each other pipetting 3011, 3012 at their passage a minimum distance in the x direction of only 2 to 16 mm, preferably 2 to 4 mm, to each other.
  • the pipettor 300 according to FIG. 6b can advantageously have on the outside of at least one of the beams 341, 342 a receptacle 305 which can be moved in the y-direction for fastening a working module (not shown).
  • Working module may include a gripper for the transfer or exchange of vessels (for example, cuvettes).
  • the movement of the working module may e.g. be coupled with the movement of a on the opposite side of the corresponding bar 341,342 traversing pipetting module 3011 or 3012 via a corresponding entrainment mechanism.
  • the working module can optionally be fixed to the receptacle 305 or moved along a lateral extension (not shown here) of one of the pipetting modules 3011 or 3012.
  • the supply lines of the gripper can then easily be carried along on one of the two energy chains 3111 or 3112 together with the supply lines of the adjacent pipetting module 3011 or 3012.
  • the gripper of the working module can be used for the transfer of cuvettes from a cuvette storage to an optical measuring unit 500 or to a cuvette disposal container (not shown).
  • Analyzer of Figures 3 to 5 is for obtaining measurement signals from liquid media stored in cascades 201 of a stationary (i.e.
  • Cuvette arrays 200 exiting measuring radiation and conversion of
  • the detection unit 550 is designed so that each cuvette 201 of the cuvette array 200 at least one photodiode 551 is assigned fixed and stationary.
  • the optical measuring unit 500 has at least one stationary one
  • Light distribution device 542 which distributes the light of the individual LED light sources 541 on the individual cuvettes 201 of the stationary cuvette array 200.
  • the light distribution device 542 has a cavity formed by walls, the inner surfaces 543, 544, 545 and the rear wall and the two
  • End surfaces at least partially mirrored and / or diffusely reflective
  • the light distribution device 542 has for each LED light source 541 in the bottom surface 545 an inlet opening 546 for feeding the light in the cavity and has for each cuvette 201 of the cuvette array 200 via an outlet opening 547 for feeding the light into the cuvette 201th
  • the inlet 546 of the LED light sources 541 opposite, inner surface 544 on the top surface of the
  • Light distribution device 542 wavy and reflective carried out, wherein the waves of the corrugated inner surface 544 preferably normal to the longitudinal extent of
  • Light Distributor 542 are aligned to optimally distribute the light entering from the individual LED light sources 541 in the longitudinal direction of the light distribution device 542 (see Fig. 8b).
  • Light distribution device 542 diffuse reflective performed (see Fig. 8a).
  • a material for coating the inner surface 543 in the field of view starting from the entrance window 202 of the cuvette 201 for example, barium sulfate is suitable.
  • At least individual LED light sources 541 of the light supply unit 540 for improving the spectral characteristic and for feeding the light into the light distribution device 542 have optical elements for collimation and a narrowband filter on the output side.
  • the LED light source 541 may include an LED 548 arranged in a TIR lens 549, a tube body 552 for eliminating non-parallel beam portions of the LED, and an entrance side into the light distribution device 542 a narrow-band filter, preferably a
  • the tube body 552 parallel to the longitudinal axis of the LED light source 541 extending, elongated passage openings 570 have, the walls 571 consist of a light-absorbing material or coated with such a material (see the detailed illustration of FIG. 8c). It thus reach - within a certain tolerance - only parallel aligned rays on the interference filter 553, as deviating rays are absorbed by the tube body 552.
  • Bottom surface 545 of the light distribution device 542 are arranged, is shown in the sectional views of FIG. 8e and 8f.
  • a converging lens 590 is arranged, which aligns the light emitted by an LED 548 in parallel for entry into the interference filter 553, the output side of the interference filter 553 a preferably aspherical dispersion lens 591 for fanning the in the
  • Light distribution device 542 radiation may be arranged.
  • the light beams are preferably fanned out to such an extent (see marginal rays Si, S 2 in FIG. 8 f) that the inner surfaces of the light distribution device 542 are illuminated as homogeneously as possible.
  • the surface 544 lying opposite the bottom surface 545 is particularly preferably illuminated as extensively as possible, while the lateral surface 543 is not exposed directly.
  • the light rays exit conically, whereby the surface 544 of the light distributor device directly opposite the LED light source 541 is exposed in a substantially circular manner (see FIG. 8f, second LED light source from the left, edge jets S 3 , S 4 ). , In order in all exit windows 547 as uniform a light amount of each LED light source 541 of
  • Light distribution device 542 to emerge, as homogeneous a possible illumination of the entire surface 544 by means of an aspherical scattering lens 591 is advantageous (see Fig. 8f, first LED light source from the left, marginal rays Si, S 2 ).
  • the LED light source 541 on the far right in the figure of FIG. 8f has no
  • photodiodes 551 of the detection unit 550 on the input side of the entrance window 202 and on the exit side of the exit window 203 of each cuvette 201 are channel-like passages 578 in the wall of the cell
  • Light distribution device 542 emerging inlet beam and unwanted radiation components U 2 serve the emerging from the cuvette 201 measuring radiation.
  • Cuvette receptacle 578 according to a variant shown in Fig. 8i as a channel 594 smooth surface, be designed with a smaller diameter in relation to the length of the bore and thereby hide the unwanted radiation components Ui, U 2 on the way to the photodiode 551.
  • the channel-like feedthrough 578 according to FIG. 8h can have an exemption 593 or a cavity in which the unwanted radiation components Ui, U 2 run dead.
  • the channel-like bushings 578 according to FIG. 8g can have a grooved or toothed structure 592, at which unwanted radiation components Ui, U 2 , which have too large an angle deviation from the beam axis, are blocked or absorbed. This variant can be cost effective in a single, above all
  • Grooved structure 592 can be realized by means of threaded holes.
  • the light guidance or light guidance in the optical measuring unit takes place in several steps to meet the requirements:
  • the spatially broadly emitted light of the LEDs 548 is collected by means of TIR lenses 549 or parabolic mirrors, parallelized and directed in the direction of the interior of the light distribution device 542.
  • the LED 548 also in the focal point of
  • optical bandpass filters such as interference filters 553, are provided to obtain a predetermined, narrowband, monochromatic light.
  • the interference filter 553 may be followed by a diverging lens 591 in order to emit those exiting from the interference filter 553
  • the substantially parallelepiped light distributor device 542 is configured in such a way that the outlet openings 547 have a diffuse one reflective surface 543 is arranged and with the exception of the inlet and outlet openings, the remaining inner surfaces have diffusely reflecting and / or reflecting surfaces.
  • the cover surface has a corrugated structure 544 (see FIG. 8b), while the remaining inner surfaces are preferably planar, so that light is scattered or reflected as effectively as possible over a spectral range of approximately 340 to 800 nm.
  • the outlet openings 547 are arranged, through which the light can pass directly to the entrance windows 202 of the cuvettes 201.
  • a lead-in 578 possibly with the interposition of a diaphragm between the light distributor device 542 and the cuvette 201, is used to direct a cell 201 into the interior of the cuvette 201
  • the measuring radiation is directed from the exit window 203 of the cuvette 201, if necessary with the interposition of an aperture, to the photodiode 551 of the detection unit 550.
  • the light distribution device 542 on the output side of in a wall, for example, the rear wall, the light distribution device 542 arranged through holes or pinholes 576 monitor or
  • Reference detectors 575 arranged with which fluctuations of the measuring radiation can be detected at any time.
  • Each cuvette 201 may be assigned a pinhole plate 576 together with a reference detector 575. If each cuvette 201 a
  • Reference photodiode is assigned, these are preferably at the
  • Reference detectors 576 provide.
  • the stationary cuvette array 200 may
  • each segment 210 a separate light distribution device 540, is assigned fixed.
  • Each segment 210 is associated with a common, over the entire length of the segment extending light distribution device 542, which has more than 20 mounting positions for LED light sources 541 for up to 16 optical channels with light of different wavelengths (l ⁇ to l16).
  • the individual LEDs of the LED light sources 541 may preferably be arranged in the form of an LED array on a common printed circuit board 582, for example made of aluminum. Adjacent installation positions can be equipped with LED light sources of the same wavelength to increase the intensity.
  • the light distributor device 542 In the region of the front entrance window 202 of each cuvette 201 adjacent to the light distributor device 542, the light distributor device 542 has a circular opening, the so-called exit opening 547, through which the light generated by the LEDs is radiated through the entrance window 202 into the interior of the cuvette 201.
  • Feedthrough 578 in the cuvette receptacle 579, between the outlet opening 547 and the entrance window 202 into the cuvette 201 can also be seen in FIG. 8d
  • the optical feedthroughs 578 in the cuvette receptacle 579 can thus be funnel-shaped (FIG. 8 d) independently of one another on both sides of the inlet 202 and outlet windows 203 of the cuvette 201, as a smooth-surfaced channel 594 (FIG. 8i), with grooved or serrated structure 592 (FIG. 8g), or with cavity or clearance 593 (FIG. 8h) in the channel.
  • Cell receptacle 579 made of a light-absorbing material or are coated with such.
  • the light of each optical channel of the LED light sources 541 passes through the circular
  • the measurement of the intensity I of the light transmitted through the cuvettes 201 takes place by means of a stationary array of photodiodes 551 (at least one
  • Light distribution device 542 facing away exit window 203 of the cuvettes 201 are placed.
  • a solid aluminum block 583 for example with the aid of Peltier components tempered (cooling and heating possibility) attached to the circuit board 582 of the LED light sources 541.
  • the electronics shown schematically in FIG. 9 for the optical measuring unit 500 consists of a plurality of circuit units that are distributed over a plurality of printed circuit boards and are geometrically placed according to their function on the stationary cuvette array 200 (see arrow).
  • the printed circuit board of the transmitting unit 580 contains 16 parallel current sources 581 which are each assigned to a specific light source (LED 548) with a specific wavelength.
  • the current sources 581 may be controlled by an optical controller (584) in magnitude and in pulse length, so that a desired current pulse in length and magnitude for the
  • Light pulse can be adjusted.
  • the LED supply voltage can also be controlled individually for each LED channel.
  • the board of the transmitting unit 580 becomes for the purpose of thermostating with an aluminum block 583 including cooling ribs 577 (see Fig. 7a) screwed and by means of Peltier elements on an adjustable
  • the thermal drift of the current sources 581 can thereby be reduced to a minimum.
  • the power loss occurring in the current sources 581 is determined by the time
  • Current source 581 activated per unit of time, thus always only light with a certain predetermined wavelength is generated.
  • the actual light sources are realized on a separate, cooled aluminum circuit board 582 by means of 16 selected LEDs 548 having the desired 16 wavelengths.
  • the aluminum circuit board 582 is due to the better thermal
  • a constant temperature for example, + 37 ° C
  • the aluminum circuit board or board 582 with the LEDs is directly on the
  • Light distribution device 542 (see Fig. 7a) arranged to best possible
  • the light of the LEDs 548 is first aligned in parallel via TIR lenses 549 and tube body 552, then spectrally filtered via optical filters 553 and then evenly distributed in the interior of the light distribution device 542 so that the light on 16 adjacent outlet openings 547 to the 16th
  • Another circuit board 585 is equipped with up to 16 monitor or reference photodiodes 575 which detect the light generated by the LEDs 548 prior to passage of the respective cuvette.
  • monitor or reference photodiodes 575 only two global monitor or reference photodiodes 575 can be used. In this case, the light is not directly in front of each cuvette but in several suitable places of the
  • Light distribution device 542 measured. Due to the constant geometric conditions, the light in front of each cuvette can be converted using a geometry factor.
  • the printed circuit board 586 of the detector unit 550 On the output side of the cuvettes of the cuvette array 200 is the printed circuit board 586 of the detector unit 550.
  • This printed circuit board contains 16 photodiodes 551 for the transmitted light from the cuvettes 201.
  • the detector unit processes two analog values of the two associated photodiodes 551, 575 of each cell
  • nephelometry can be detected by each cuvette by a laterally arranged photodiode, a third analog value, the signal path, however, for reasons of clarity in Fig. 9 is not shown.
  • the two signal paths starting from the photodiodes 551, 575 are processed synchronously by two 16: 1 multiplexers 587, inverters, integrators and ADCs and converted into a digital measured value.
  • Multiplexers 587 allow the selection, for example, of 16 cuvette channels, and to switch sequentially in a configurable sequence.
  • each segment 210 is assigned a separate light distribution device 540 (see FIG. 7a / b)
  • additional circuit boards indicated by dashed lines are provided at the transmission unit 580, the circuit board for the LEDs 582, the circuit board for the monitor - respectively.
  • the central circuit board 584 for the optical measuring unit 500 is equipped with the optical controller.
  • the optical control unit is realized by a programmable logic (FPGA) as state machine and can at the same time operate the transmitting unit 580 and the detector unit 586.
  • FPGA programmable logic
  • the individual light measurements are broken down into light and dark measurements and can be parameterized differently line by line in a configuration memory.
  • the state machine processes these configuration lines in sequence, whereby lines can also be skipped.
  • the distinction for light and dark measurement is defined by a flag in the configuration line, as well as the desired cuvette channel and light source. Furthermore, in the configuration line, the desired delay settings, amperage and
  • Pulse length the selection of the reference photodiode, the LED supply voltage, the oversampling and averaging default and the
  • the detector unit 586 is driven synchronized to the transmitting unit 580 and can be set by global parameters with averaging or oversampling settings. Furthermore, the desired integration time is read out of the configuration line with which the light signal is to be integrated. Likewise, the delay time for the integrator and the integration slope can be selected here by means of global parameters, so that the settling times of the measurement signal and the integration speed can be switched over.
  • the analog measured value is thus selected from the corresponding photodiode 551 with transimpedance amplifier via the multiplexer 587 and measured by means of inverter and integrator and optional logarithmic amplifier and digitized with a high-resolution ADC measurements with or without oversampling.
  • three Analog measured values transmitted light, monitor or reference light, scattered light
  • three ADCs stored as raw measured values in the internal memory line by line. It is essential that the measurement of transmitted light and monitor or
  • the internal memory contains all raw data and is cyclically read by the evaluation processor by software and converted by a conversion algorithm into a final measured value.
  • the conversion takes into account the dark value and light value as well as the Io measurement and Ii measurement before and after mixing in of the reagents.
  • the temporal change of the measured values can also be detected by successive measurements. It is essential that the measurements are periodic and give a repeatable measurement cycle in accordance with the set period.
  • the calculated data are packaged per cuvette into defined data packets and transmitted to the main computer 588 by means of a local Ethernet interface. As a result of this data reduction, it is possible to process all cuvettes of the cuvette array 200 of the optical measuring unit 500 and to transfer them to the main computer 588.
  • Detection unit 500 to control or read.
  • the periodic drive signal of the individual LED light sources 541 is determined in terms of pulse and integration duration and the current level used for each combination of cuvette and wavelength for the measurement mode used and not changed during operation.
  • the control of 16 LED light sources 541 takes place via 16 separate current sources 581 and their environment hardware.
  • the exposure of each cuvette to each spectral channel of the LED light sources 581 and the integration times used are individually defined (16 x 16 combinations).
  • the individual LEDs emit (or in individual positions to increase the intensity also several LEDs) in the course of a measurement cycle in sequential
  • Sequence one light pulse which is repeatedly reflected in the interior of the light distribution device 542 on the inner walls and finally passes through the 16 outlet openings 547 to the 16 associated cuvettes 201 (see Fig. 8a).
  • Mode 1 Detection of the dynamic LED flash signal with constant
  • the measurement is done individually for each combination of cuvette and wavelength, whereby in modes 1 and 2 a light pulse is generated for each measurement point.
  • the spectral channels (l ⁇ ... l16) of the individual LED light sources 581 are activated and deactivated in a fixed sequence.
  • the resulting light flashes are detected and measured by the photodiode 551 selected by the multiplexer 587.
  • the sensors After passing through all the spectral channels, the sensors are moved from the cuvette position K1 to the
  • the measuring method according to modes 1 and 2 is thus characterized in that the spectral channels AI ... lh the individual LED light sources 581 in one
  • the LED light sources 541 are switched in a different order than in modes 1 and 2, respectively.
  • Each LED light source 541 or each spectral channel is in the cycle (indicated by the dotted line) only turned on once and then measured all 16 cuvettes in a row, with no dark measurement between these individual measurements.
  • the first cuvette Kl comes with a delay
  • each LED is turned on only once, measuring all 16 cuvettes at a time. If a dark measurement is required, a dark value is measured once, for example at the beginning or end of the cycle for the measurement of the 16 cuvettes.
  • Cuvette positions require 16 x 16 light measurements. Adding the 16 dark measurements (once per cycle) gives 272 individual measurements.
  • the measuring method according to mode 3 is thus characterized in that the spectral channel AI of the first LED light sources 581 is activated, wherein in a predetermined order the photodiodes 551 arranged in the cuvette positions Kl ... Km are detected, wherein after the passage of all
  • Mode 3 is faster overall than the 512 alternately running modes
  • a mixer unit is assigned to the entire cuvette array 200, preferably to individual groups of cuvettes 201.
  • the mixer unit may, for example, be realized by a pipetting or hollow needle displaceable in rotation or vibration, which can be lowered for mixing the samples and reagents into the respective cuvettes.
  • the mixer unit could also be realized by a stirring mechanism according to WO 99/046601 A1 cited above.
  • Stirring element which can be lowered for mixing the samples and reagents in the respective cuvettes.
  • the cuvette washing unit 600 shown in FIG. 11 is designed to be movable in the x-direction via a receptacle 601 along the rail 112 (see FIG. 4).
  • the head 602 of the unit 600 may be vertically aligned Rail section 603, which is guided in the receptacle 601, are moved in the z-direction up and down to introduce either the washing bodies 610 or the dry punches 620 in the cuvettes 201 of the cuvette array 200.
  • Adjustment element 604 which is guided in the head 602 and the example four
  • Dry stamp 620 and washing body 610 carries can be switched by a shift in the y-direction from the washing position to the drying position.
  • Individual fingers 605, which carry the washing bodies 610 and drying punches 620, can be swung up, as indicated by arrow 691, so that only one or a few cuvettes 201 are washed simultaneously.
  • Fig. 12 shows in an enlarged sectional view the construction of a needle washing unit indicated by the general reference numeral 700, which substantially identically identifies the needle washing units 700, 700al, 700a2, 700b, 700b2 shown at different positions in Figs. 3 to 5 and 6a and 6b and a pipetting module together with hollow needle 307 which is identified by the general reference numeral 301 and which corresponds to the pipetting modules 3011, 3012, 301al, 301a2, 301bl, 301b2 of substantially identical construction, shown at different positions in FIGS. 3 to 5 and 6a and 6b.
  • the general reference numeral 700 substantially identically identifies the needle washing units 700, 700al, 700a2, 700b, 700b2 shown at different positions in Figs. 3 to 5 and 6a and 6b and a pipetting module together with hollow needle 307 which is identified by the general reference numeral 301 and which corresponds to the pipetting modules 3011, 3012, 301al, 301a2, 301bl, 301b
  • Hollow needle 307 of the pipetting modules 301 is introduced through a receiving opening 711 in the housing 710 of a needle washing unit 700, wherein at the same time the lumen of the hollow needle 307 with a system liquid 712 and the outside of the needle with a lateral cleaning nozzles 713 from an annular chamber 715th
  • supplied flushing liquid 714 can be cleaned. For indoor and
  • External cleaning of the hollow needle 307 by repeated aspiration and expulsion of washing solution from the lower part of the needle washing unit 700 can be presented via a radial inlet 716 washing solution, which can then be emptied through a suction 717.
  • FIG. 13 shows an enlarged detail of the linear cuvette array 200 of the analyzer 100 with the partially cut-away housing 892 and a cuvette 201 arranged therein, which are used to set a predefinable
  • the cuvette 201 has laterally in a region near the ground, preferably arranged plane-parallel to one another
  • Measuring window in the example shown inlet and outlet windows 202, 203
  • the housing 892 has corresponding openings 895.
  • the individual pins 893, 894 snap into corresponding contact openings.
  • Locking elements 896 are formed, which engage in a carrier element for fastening the cuvette array 200.
  • FIG. 14 shows the fluidic circuit diagram of a pipetting module 301, the hollow needle 307 of which is connected via a pressure transfer channel 712 filled with a degassed liquid to a precision piston pump 325, preferably a positive displacement pump (dilutor) driven by a stepper motor.
  • the positive displacement pump has an additional fluid connection on the side, which is connected via a
  • Solenoid valve 326 is connected to a system liquid supply unit 320, which is supplied via a rinsing pump 321 from a storage vessel 322, e.g. degassed, deionized water promotes, which can be refilled via a solenoid valve 323, or under pressure can be set.
  • a system liquid supply unit 320 which is supplied via a rinsing pump 321 from a storage vessel 322, e.g. degassed, deionized water promotes, which can be refilled via a solenoid valve 323, or under pressure can be set.
  • the pressure transmission channel 712 in the vicinity of the pipetting module 301 has a further connection to a pressure sensor 324, which is connected to an evaluation and control unit, not shown here, for example for detecting obstruction of the hollow needle 307.
  • the pipetting module 301 For the transfer of a defined amount of liquid with the pipetting module 301, it is first moved horizontally to a first vessel, 5 pL of air (spacer) sucked into the tip of the hollow needle 307 and lowered the hollow needle 307 in the direction of the liquid surface of the first vessel. To a sufficient, but not too large immersion depth of the hollow needle 307 to
  • Fluid volume from a first vessel causes.
  • the hollow needle 301 is now moved together with the aspirated liquid, which is separated by a separating air bubble (spacer) from the system liquid to a second vessel, the process now runs in the opposite direction and the aspirated liquid via the tip of the hollow needle 307 in the second Vessel is discharged.
  • a needle washing unit 700 see FIG. 12
  • FIG. 15 shows the fluidic circuit diagram of a needle washing unit 700 according to FIG. 12 with hollow needle 307 of the pipetting module 301 lowered therein.
  • the housing 710 of the needle washing unit has a concentrically encircling upper part Ring chamber 715, which acts as a media supply for a plurality of internal, concentrically aligned cleaning nozzles 713, and each connected via solenoid valves to a supply unit 719 for a rinsing liquid (for example, deionized water), and a supply unit 727 for dry air.
  • a rinsing liquid for example, deionized water
  • An inlet 716 radially arranged in the middle of the height of the housing 710 of the needle washing unit 700 is likewise connected to a magnetic valve and serves exclusively for the supply of surfactant-containing washing solution from one
  • Wash solution each have a pump 720, 724, which promote a surfactant-containing washing solution or rinsing liquid from the respective storage containers 721, 725, each of which can be refilled via a solenoid valve 722, 726, or pressurizable.
  • the air supply unit 727 has an air pump 728 for providing compressed air and possibly a drying template (not
  • the suction opening 717 located at the bottom of the needle washing unit 700 is connected via a solenoid valve 718 to the submerged sewage collecting unit 729 which essentially consists of a collecting tank 730 which has a connection to a vacuum pump 731 in the gas space above the liquid Solenoid valve is connected to the sump 730.
  • the collected wastewater can be discharged via a solenoid valve 732 at the bottom of the collecting container 730 and fed to a further wastewater treatment.
  • Suction 717) is introduced through the inlet 716 in the housing 710 of the needle washing unit 700 a defined volume of surfactant-containing wash solution, whereby the chamber fills in the lower part with a defined level of wash solution.
  • the Hollow needle 307 of the pipetting module 301 is lowered so far that by immersion in the washing solution an external wetting of the needle, and through
  • the contaminated washing solution is aspirated and flushed the interior of the hollow needle 307 with system liquid (eg degassed, deionized water), while the outside of the hollow needle 307 is simultaneously rinsed with flushing liquid from the delivery unit 719 by the overhead, concentrically arranged cleaning nozzles 713, wherein the tip of the hollow needle 307 is moved from the bottom up to improve the cleaning effect.
  • system liquid eg degassed, deionized water
  • the hollow needle 307 After completion of the simultaneous inner and outer rinsing, the hollow needle 307 is moved again in the lower holding position, the media supply the
  • FIG. 16 shows the fluidic circuit diagram and the longitudinal section of a finger 605 of the cuvette washing station 600 hinged to the adjustment element 604
  • washing body 610 and a dry stamp 620 see also Fig. 9), the descriptions of the providing units 630 (rinsing liquid), 634
  • Supply units 719 (rinsing liquid), 723 (washing solution), 727 (air) and 729 (waste water) of the figure description to FIG. 13 can be seen, which are functionally identical, or identical in construction with the units shown in FIG. 13
  • Cuvette washing station 600 can be controlled by horizontal and vertical
  • Translational movements are successively lowered into the cuvette to be washed 201 of a linear cuvette array, wherein after lowering into the cuvette 201 each have a circumferential gap of less than 1 mm between the inside of the cuvette 201 and the washing body or blind die remains free to a controlled flow of Cleaning media along the inner
  • the washing body 610 has at its upper end an elastomeric seal 611 which prevents leakage of the cleaning media between the upper cuvette rim and the bottom of the finger 605 during the washing process.
  • elastomeric seal 611 which prevents leakage of the cleaning media between the upper cuvette rim and the bottom of the finger 605 during the washing process.
  • Around the shaft of the rising channel 612 running in the middle of the washing body 610 for sucking off the waste water and exhaust air is arranged with an annular, circulating media feed, which allows flushing of the cuvette inside from top to bottom (see arrows).
  • the washing body 610 can be supplied with surfactant-containing washing solution from the supply unit 634, flushing liquid (for example deionized water) from the supply unit 630, or compressed air from the supply unit 638 via corresponding solenoid valves, which are discharged via the pressurized waste water collecting unit 640 in which these are supplied via a solenoid valve to the under-pressurized sewage collecting unit 640.
  • surfactant-containing washing solution from the supply unit 634
  • flushing liquid for example deionized water
  • compressed air from the supply unit 638
  • solenoid valves which are discharged via the pressurized waste water collecting unit 640 in which these are supplied via a solenoid valve to the under-pressurized sewage collecting unit 640.
  • Wastewater collection unit 640 consists essentially of a collecting container 730, which in the gas space above the liquid via a connection to a
  • Vacuum pump 642 which is connected via a solenoid valve to the reservoir 641.
  • the collected wastewater can be discharged via a solenoid valve 643 at the bottom of the reservoir 641 and another
  • Wastewater treatment are supplied.
  • the dry punch 620 is made of a porous air-permeable material and internally has a non-bottomed longitudinal channel 621 which serves to supply and distribute the compressed air through the wall of the porous dry stamp 620 into the cuvette 201.
  • Dry punch 620 does not close at the bottom of the finger 605 with a seal, but in the lowered state slightly over and forms between the top of the cuvette 201 and finger bottom a circumferential air outlet gap (see horizontal arrows).
  • the dry punch 620 may be connected to the compressed air from the delivery unit 638 via a solenoid valve.
  • the washing body 610 is lowered into the cuvette 201 to be washed, and the
  • Reagents / sample mixture which is located in the cuvette 201 after analysis, aspirated via the central riser channel 612 and the
  • Waste water collection unit 640 supplied.
  • the washing body 610 is then lifted out of the washed but residual moisture cuvette 201, and the finger is moved in the y direction.
  • the drying punch 620 is now lowered in the z-direction into the cuvette 201 and with dry compressed air from the
  • the inner side of the cuvette is blown past, wherein the air required for this purpose emerges uniformly from the porous body of the dry stamp 620, sweeps from bottom to top on the inside of the cuvette 201, and on the shaft of the cuvette
  • Dry stamp 620 exits.
  • the automatic analyzer according to FIGS. 3 to 5 operates, for example, as follows:
  • Analytical sample P x from the known and previously entered information compiles the control unit of the analyzer all the data required for the analysis of the analyte A x (analysis protocol, positions of the vessels 921, 951a, 951b with the analytical sample and with the reagents required for the analysis, position a free cuvette 201 in the cuvette array 200, cuvette temperature, selection of the measurement procedure, the calibration data, the measurement and evaluation algorithms).
  • the temperature of the cuvette 201 intended for the analysis is assigned by means of the cuvette 201
  • Thermostatic 800 regulated to a predetermined temperature.
  • Sample Store 920 from a first sample vessel 921 recorded a predetermined amount of a first analysis sample and a predetermined amount thereof discharged into a free cuvette 201. Following the pipetting operation, the pipetting module 301bl is washed and provided in the first needle washing unit 700bl of the pipettor 300b.
  • Reagent storage 950 a from a first reagent vessel 951 a recorded a predetermined amount of a first reagent liquid and pipetted a predetermined amount into the cuvette 201. Thereafter, the two liquids are mixed in the cuvette by brief (a few seconds) switching on the mixing unit 400 associated with the cuvette. Following the pipetting operation, the hollow needle 307 of the pipetting module 301al is washed and provided in a first needle washing unit 700al of the L-shaped pipettor 300a. Phase 3
  • the second pipetting module 301b2 of the T-shaped pipettor 300b in the reagent storage 950b receives a predetermined amount of a second reagent liquid from a reagent vessel 951b and dispenses a predetermined amount into the cuvette 201. Thereafter, the contents of the cuvette by brief (a few seconds) switching on a, the cuvette 21 associated mixing unit is mixed. Following the
  • Phase 4 begins with photometric measurements on cuvette 201, usually after completion of phase 2.
  • the stationary, optical measuring unit 500 collects at the exit windows 203 of the cuvettes 201, the exiting measuring radiation and forms with the aid of
  • measuring points can be generated at defined time intervals.
  • time-dependent measured values are obtained at one or more wavelengths, and associated with previously known, the respective analysis
  • the measurement process - especially in kinetic measurements - can extend over very different periods of a few seconds to the two-digit minute range.
  • the cuvette 201 is released for washing with the cuvette washing unit 600.
  • the washing process by means of cuvette washing unit 600 takes place immediately after release of the cuvette, preferably together with a plurality of adjacent cuvettes 201 also released for washing and after "releasing" the movable one
  • Cuvette washing unit 600 After washing and drying, the cuvette 201 is provided for the next analysis.
  • the sample bearing 920 Prior to performing multiple analyzes, the sample bearing 920 is manually or automatically loaded with the samples Pi to P n .
  • the type and number of for Analyzes A i through A n to be performed each sample P x are input to the controller of the analyzer 100.
  • the reagents bearings 950a, 950b are charged or replenished with the reagents required for the analyzes to be performed.
  • phase 1 For each analysis P X A X to be performed, the phases 1 to 4 described above are run through, each beginning with phase 1.
  • phase 1 of the subsequent analyzes P x A x + i or P x + i A x can not be completed until the completion of phase 1 and out of Phase 2 of the ongoing analyzes, for as many subsequent analyzes as there are "free" cuvettes, that is, cuvettes not claimed by other analysis processes.
  • the concept according to the invention makes it possible, in contrast to the systems described at the outset, for a cuvette to be promptly washed and made available for a new test after the measurement has been completed, without adversely affecting the processes of the ongoing analysis processes.
  • the combined apparatus 810 for mixing and thermostating liquid media illustrated in FIGS. 17a to 17c serves to thermostate the liquid media introduced into the cuvettes 201 of a cuvette array 200 arranged next to one another.
  • the illustrated example is a linear, stationary cuvette array 200.
  • the individual cuvettes 201 of the cuvette array 200 are in one
  • thermostatable cuvette block 820 for example made of aluminum
  • the funnel-shaped receptacles 823 lie positively against the walls of the cuvettes 201 in order to ensure optimum heat transfer.
  • the cuvette block 820 consists of a base part 821 with the receptacles 823 and a front part 822 which can be opened by a lateral pushing movement.
  • Thermostatisier worn 830 arranged, which has a cooling and heating device, for example in the form of one or more Peltier elements 831 and cooling fins 832.
  • a cooling and heating device for example in the form of one or more Peltier elements 831 and cooling fins 832.
  • To control the temperature of the cuvette block 830 is in a receptacle between the base part 821 and the Peltier element 831 a
  • Temperature sensor 833 arranged.
  • attachment surfaces 824 can be seen, which are also used for attaching a cooling and heating device, For example, Peltier elements can be used.
  • the front part 822 has openings 825 corresponding to the measurement windows 202 of the cuvettes 202, in order to enable optical measurement of the liquid media in the cuvettes 201.
  • each cuvette 201 Attached to the bottom 204 of each cuvette 201 is an ultrasonic transducer 840, such as a thickness transducer, e.g. glued or injected in the manufacture of the cuvette with which ultrasonic energy can be introduced into the cuvette 201.
  • the introduced ultrasonic energy is used both for mixing the liquid media and for selective heating - in addition to the base load from the
  • the ultrasonic transducer 840 is designed as a piezoelectric thickness vibrator which - as shown in detail in Fig. 17c - essentially of a
  • the cuvette-side electrode 841 is through-contacted via lateral contact strips 844 to the lower electrode 843, where it forms crescent-shaped contact surfaces 845.
  • each cuvette 201 and its ultrasonic transducer 840 is one of
  • the cuvette 201 has a collar 205 at the filling opening 207 and stop strips 206 at opposite sides, with which the cuvette 201 is held in the cuvette block 820, against the pressure of the contact springs 848.
  • the spring contact plate 846 is inserted at the edge in a horizontally extending groove 826 of the cuvette block 820 and is supported on the decoder plate 850 which carries its downward force, the circuits of which are explained in more detail in FIG.
  • FIG. 18 shows a block diagram for the electronic control of the device for mixing and thermostating liquid media according to FIG. 17 a, which shows the functional blocks personal computer 588, controller board 860,
  • Decoder board 850 includes.
  • the controller board 860 has a FPGA (Field Programmable Gate Array) as the processor 861 and is used to control the decoder board 850 and the
  • the personal computer 588 may for example be connected via an Ethernet interface to the controller board 860 and transmits depending on to be performed mixing and Thermostatisierankgabe in one of Cuvettes 201 of the cuvette block 820 corresponding orders for the execution of firmware programs on the controller board 860, as well as serves for
  • cuvettes 201 including the associated ultrasonic transducers 840 are respectively arranged at the positions K1 to K16 or PI to P16, wherein for the thermostating in the example shown in the positions PE1 to PE4 or TI to T4 are each a Peltier element 831 together with associated
  • the temperature control circuit 865 thus has four temperature control circuits 866 each of Peltier element 831, temperature sensor 833 and PID (Proportional, Integral, Derivative) controller RI to R4 and is connected via an interface with the controller board 860 for data exchange (receiving parameters such as temperature Setpoints and return of measured temperatures of the temperature control circuit 865 to the controller board 860).
  • PID Proportional, Integral, Derivative
  • the decoder board 850 is also connected via an interface to the controller board 860 and receives from it control signals for selecting individual ultrasonic transducers 840 via those implemented on the decoder board 850
  • the oscillator circuit 852 receives control signals for adjusting the frequency, duty cycle, duty factor, or duty cycle, burst pattern ), Amplitude, phase and ON and OFF states of signal generation of the oscillator.
  • the oscillator circuit 852 comprises a voltage-controlled oscillator 853 (VCO) whose frequency signal is fed via a voltage controlled oscillator 853 (VCO)
  • Burst generator 854 can be modulated.
  • the amplitude of the modulated signal can be further adjusted via a controllable preamplifier 855 and a downstream amplifier output stage 856.
  • the end amplified signal is transformed up to the required operating voltage of the ultrasound transducers 840 via a transmitter, and one of the 16 piezoelectric ultrasonic transducers 840 on the cuvettes 201 on the cuvette block 820 is connected via the opto-switches 857 selected in each case by the decoder circuit 851 in S1 to S16 ,
  • FIG. 19a shows a first example of a thermostatization process according to the invention of a sample reagent mixture in a cuvette, which is arranged in a thermostatable cuvette block (see FIG. 17a).
  • the temperature profile a shows the heating of the sample reagent mixture only by the cuvette block thermostatted to the temperature TBL, wherein the target temperature at which the sample reagent mixture can be measured, is reached only at time t 2 .
  • the required target temperature is reached when ultrasonic boosts in the periods M and A to C are introduced, as shown in the temperature profile ß.
  • the thermostating of the cuvette block is carried out at a substantially constant electric power PBL.
  • TBL block temperature
  • the sample reagent mixture has after
  • a mixing period of 1 to 3 seconds is sufficient for the homogeneous mixing, wherein the temperature deviation DT M of, for example, a 2-second mixing pulse may be about 3 ° C.
  • Ultrasonic power PP determined by experiments on different sample reagent mixtures and stored in the device.
  • an optical signal of an analyte measurement from the sample reagent mixture can be continuously measured and the
  • Temperature deviation DT A + DT B + DTV + DT h corresponds, wherein after delivery of the last ultrasonic pulse below the temperature TBL- X lying temperature T BL-Y is reached. From this temperature, the temperature is introduced into the cuvette contents purely via heat conduction between the cuvette block 820 and the cuvette contents.
  • TBL- X for the analysis, which is lower than the temperature of the cuvette block by the value x, where x is typically at a fixed value of 0.1 - 0.5 ° C.
  • the acceptable temperature is fixed between 36.5 and 37.5 ° C.
  • the temperature stability during the period of a subsequent optical measurement should be about 0.1 ° C.
  • FIG. 19b shows a second example of a device according to the invention
  • Example 1 Preheat the cuvette block with empty cuvettes therein to a block temperature TBL (typically 37.0 to 37.5 ° C) and stabilize the block temperature to 0.1 ° K
  • Example 2 (as Example 1) filling an empty cuvette with a sample reagent mixture of temperature T 0 .
  • the sample reagent mixture after pipetting into the cuvette has a temperature of 10-15 ° C, because the pipetted reagents come from a 5 ° C cooled storage area.
  • Example 3 (as in Example 1) delivery of an ultrasound signal for a predefined cumulative time M, which introduces an amount of energy M x PP in the sample reagent mixture and causes a calculated temperature deviation DT M , which consists of variable, from the data of the analysis to be performed known properties of the sample reagent mixture such as heat capacity, viscosity, thermal conductivity and its volume and constant, stored in the device data is calculated.
  • Temperaturhub DTM for example, a 2-second stirring pulse may be about 3 ° K.
  • the mixing time M required to obtain a stable measurement signal, a washing or incubation process may be given
  • Ultrasonic power PP can be determined by tests on different sample reagent mixtures and stored in the device.
  • an optical signal from the sample reagent mixture can be continuously measured, and the mixing process can be stopped as soon as a stable signal is obtained, wherein the temperature deviation DTM is calculated here as mentioned from known thermal characteristics.
  • acceptable temperature is fixed between 36.5 and 37.5 ° C.
  • the temperature stability during the period of a subsequent optical measurement should be about 0.1 ° K.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Clinical Laboratory Science (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

L'invention concerne un procédé et un dispositif pour mettre en œuvre des analyses chimiques, biochimiques et/ou immunochimiques d'échantillons liquides qui se trouvent dans un porte-échantillons (920) d'un analyseur automatique (100), à l'aide de réactifs liquides qui se trouvent dans au moins un porte-réactifs (950a, 950b) de l'analyseur (100). L'analyseur comprend des cuvettes (201) destinées à recevoir les échantillons et les réactifs liquides, une pluralité de cuvettes étant agencée dans l'analyseur sous la forme d'au moins une série de cuvettes (200) fixe linéaire. L'analyseur présente une unité de mesure optique (500) comprenant une unité de production de lumière (540) fixe qui présente au moins un dispositif diffuseur de lumière (542) qui injecte la lumière de plusieurs sources de lumière DEL (541), émettant dans des domaines spectraux différents UV/VIS/NIR, dans la fenêtre d'entrée (202) des cuvettes (201) individuelles de la série de cuvettes (200), l'unité de mesure optique (500) étant en outre équipée d'une unité de détection (550) fixe qui est associée aux fenêtres de sortie (203) des cuvettes (201) et qui présente plusieurs photodiodes (551).
EP19720760.8A 2018-04-23 2019-04-12 Analyseur automatique et procédé de mesure optique pour obtenir des signaux de mesure de milieux liquides Pending EP3784401A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
ATA50341/2018A AT521189B1 (de) 2018-04-23 2018-04-23 Automatischer analysator und optisches messverfahren zur gewinnung von messsignalen von flüssigen medien
AT506052018 2018-07-13
ATA50021/2019A AT522107B1 (de) 2019-01-11 2019-01-11 Pipettiervorrichtung
PCT/AT2019/060124 WO2019204841A1 (fr) 2018-04-23 2019-04-12 Analyseur automatique et procédé de mesure optique pour obtenir des signaux de mesure de milieux liquides

Publications (1)

Publication Number Publication Date
EP3784401A1 true EP3784401A1 (fr) 2021-03-03

Family

ID=66349207

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19720760.8A Pending EP3784401A1 (fr) 2018-04-23 2019-04-12 Analyseur automatique et procédé de mesure optique pour obtenir des signaux de mesure de milieux liquides

Country Status (5)

Country Link
US (1) US20210197188A1 (fr)
EP (1) EP3784401A1 (fr)
JP (1) JP7327818B2 (fr)
CN (1) CN112041076B (fr)
WO (1) WO2019204841A1 (fr)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020090582A1 (fr) * 2018-10-29 2020-05-07 京セラ株式会社 Dispositif de mesure
JP2022086706A (ja) * 2020-11-30 2022-06-09 シスメックス株式会社 検出方法および検出装置
CN113030068A (zh) * 2021-02-01 2021-06-25 苏州易莱生物技术有限公司 电化学发光的检测设备
CN116848416A (zh) * 2021-03-16 2023-10-03 株式会社日立高新技术 自动分析装置
WO2024008326A1 (fr) * 2022-07-08 2024-01-11 Ayna Analytics Gmbh Technique de fabrication d'un dispositif de support d'échantillon réfléchissant pour spectrophotométrie nir et raman
CN115356180B (zh) * 2022-10-24 2023-01-03 莱阳市检验检测中心 一种食品安全检测仪
CN117030645B (zh) * 2023-10-09 2024-01-26 中国计量科学研究院 单通道移液器精度现场检测的光学系统及检测方法

Family Cites Families (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE754912A (fr) 1970-08-14 1971-01-18 Automation Chimique Et Nucleai Analyseur automatique
US4299796A (en) * 1977-04-22 1981-11-10 Vitatron Scientific B.V. Apparatus for performing tests and measurements on liquid samples
DE2726498A1 (de) 1977-06-11 1978-12-14 Hellma Gmbh U Co Kg Glastechni Temperierbare kuevettenanordnung
JPH0619351B2 (ja) * 1985-07-23 1994-03-16 和光純薬工業株式会社 ラテツクス凝集反応測定装置
CH669851A5 (fr) 1986-03-06 1989-04-14 Tecan Ag
FR2637377B1 (fr) 1988-10-03 1992-12-11 Biosema Analyseur automatique d'echantillons par colorimetrie notamment pour analyses sanguines
JP2834200B2 (ja) * 1989-08-02 1998-12-09 株式会社日立製作所 液体試料の分析装置および分析方法
PT644426E (pt) * 1993-09-17 2004-08-31 Hoffmann La Roche Aparelho de analises com um dispositivo para a suspensao de particulas e processo para a realizacao da suspensao
US5578270A (en) * 1995-03-24 1996-11-26 Becton Dickinson And Company System for nucleic acid based diagnostic assay
JPH0968536A (ja) * 1995-08-31 1997-03-11 Toa Medical Electronics Co Ltd 自動分析装置
US5897837A (en) 1997-02-06 1999-04-27 Toa Medical Electronics Co., Ltd. Dispensing device and Immunoassay apparatus using the same
JP3578084B2 (ja) 1998-03-13 2004-10-20 株式会社日立製作所 自動分析装置と分析方法
FR2801108B1 (fr) 1999-11-16 2002-03-01 Maxmat S A Analyseur chimique ou biochimique a regulation de la temperature reactionnelle
JP3781708B2 (ja) * 2002-09-26 2006-05-31 アロカ株式会社 分注装置
DE102004057450B4 (de) 2004-11-24 2013-07-25 Cybio Ag Automatisches Pipetier- und Analysegerät
JP2007010345A (ja) 2005-06-28 2007-01-18 Olympus Corp 攪拌装置、攪拌方法及び攪拌装置を備えた分析装置
DE102005049920A1 (de) 2005-10-17 2007-04-19 Manz Automation Ag Roboteranordnung
WO2007108238A1 (fr) 2006-03-15 2007-09-27 Olympus Corporation Dispositif d'agitation et analyseur
JP2007303964A (ja) 2006-05-11 2007-11-22 Olympus Corp 表面弾性波素子、攪拌装置及び分析装置
WO2008052526A1 (fr) * 2006-10-30 2008-05-08 Von Ardenne Anlagentechnik Gmbh Émetteur de lumière, récepteur de lumière et module de mesure pour la mesure de propriétés optiques de substrats transparents
JP2008281392A (ja) 2007-05-09 2008-11-20 Olympus Corp 測光装置及び自動分析装置
JP2010133924A (ja) * 2008-10-28 2010-06-17 Sysmex Corp 液体吸引機構および試料分析装置
DE112009002702B4 (de) 2008-11-17 2013-09-05 Hitachi High-Technologies Corporation Automatischer Analysator
WO2010073604A1 (fr) * 2008-12-24 2010-07-01 株式会社日立ハイテクノロジーズ Photomètre et système d'analyse fourni avec le photomètre
JP5517467B2 (ja) 2009-02-20 2014-06-11 株式会社日立ハイテクノロジーズ 自動分析装置
JP2010217050A (ja) * 2009-03-17 2010-09-30 Beckman Coulter Inc 自動分析装置とその液体試料の温度上昇抑制方法
DE102009043524A1 (de) 2009-09-30 2011-03-31 Siemens Healthcare Diagnostics Products Gmbh Vorrichtung für die photometrische Untersuchung von Proben
EP2322939A1 (fr) * 2009-11-16 2011-05-18 BIT Analytical Instruments GmbH Système d'analyse et procédé d'analyse
WO2011159982A2 (fr) 2010-06-18 2011-12-22 Andrew Pogosyan Photomètre à longueurs d'onde multiples à source de lumière dispersée
EP2410342B1 (fr) 2010-06-29 2020-02-19 F.Hoffmann-La Roche Ag Dispositif de pipetage avec pointes de pipette mobiles indépendamment
ES2719846T3 (es) * 2011-07-22 2019-07-16 Roche Diagnostics Hematology Inc Sistemas y métodos de preparación de muestras de fluidos
US10215687B2 (en) * 2012-11-19 2019-02-26 The General Hospital Corporation Method and system for integrated mutliplexed photometry module
US8912007B2 (en) * 2013-01-22 2014-12-16 Tecan Trading Ag Optical measuring apparatus and method for the analysis of samples contained in liquid drops
WO2014144759A1 (fr) 2013-03-15 2014-09-18 Abbott Laboratories Analyseur de diagnostic à piste linéaire
ES2778677T3 (es) * 2015-12-17 2020-08-11 Hoffmann La Roche Calibración y/o detección de errores en un dispositivo de medición óptica para muestras biológicas

Also Published As

Publication number Publication date
WO2019204841A1 (fr) 2019-10-31
JP7327818B2 (ja) 2023-08-16
JP2021522483A (ja) 2021-08-30
US20210197188A1 (en) 2021-07-01
CN112041076B (zh) 2023-04-18
CN112041076A (zh) 2020-12-04

Similar Documents

Publication Publication Date Title
WO2019204841A1 (fr) Analyseur automatique et procédé de mesure optique pour obtenir des signaux de mesure de milieux liquides
EP3651905A1 (fr) Analyseur automatique et procédé de mise en uvre d'analyses chimiques, biochimiques et/ou immunochimiques
US11635443B2 (en) Automatic analyzer and method for carrying out chemical, biochemical, and/or immunochemical analyses
EP2309251B1 (fr) Appareil et procédé pour l'examen photométrique d'échantillons et dispositif d'analyse comprenant un tel appareil
DE3234563C2 (de) Optischer, automatischer Analyse- und Meßapparat
DE69723076T2 (de) Nephelometer und turbidimeter kombination
DE60132142T2 (de) Analysevorrichtung und -verfahren mit Probenqualitätsmessung
EP0259386B1 (fr) Analyseur photometrique
DE112006002136B4 (de) Ein System zum optischen Analysieren einer Substanz
WO2003067228A1 (fr) Procede pour l'analyse de liquides et dispositif correspondant
EP2502082B1 (fr) Système d'analyse et procédé d'analyse
DE102005048807B3 (de) Vorrichtung für die qualitative und/oder quantitative Bestimmung von IR-aktiven Inhaltsstoffen in Flüssigkeiten sowie ein Verfahren zur qualitativen und/oder quantitativen Bestimmung von IR-aktiven Inhaltsstoffen in Flüssigkeiten
WO2020010379A1 (fr) Procédé et dispositif pour l'exécution de dosages immunologiques hétérogènes
AT521189B1 (de) Automatischer analysator und optisches messverfahren zur gewinnung von messsignalen von flüssigen medien
AT520151B1 (de) Analysator und verfahren zur durchführung von chemischen, biochemischen und/oder immunchemischen analysen
DE10214781B4 (de) FT-IR-Meßvorrichtung, insbesondere für die Spektrometrie wässriger Systeme
EP3784400A1 (fr) Unité de mesure optique et procédé de mesure optique pour obtenir des signaux de mesure de milieux liquides
WO2020010380A1 (fr) Procédé et dispositif pour le mélange et la thermostatisation de fluides
WO2021213635A1 (fr) Dispositif de pipetage et procédé de traitement d'un échantillon de fluide
EP3136106A1 (fr) Analyse photometrique d'un echantillon de liquide

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: UNKNOWN

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

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

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

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

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

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

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20201021

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL 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 RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)
RAP3 Party data changed (applicant data changed or rights of an application transferred)

Owner name: MEON MEDICAL SOLUTIONS GMBH & CO KG

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

Free format text: STATUS: EXAMINATION IS IN PROGRESS

17Q First examination report despatched

Effective date: 20231222