EP3820615A1 - Procédé et dispositif pour le mélange et la thermostatisation de fluides - Google Patents

Procédé et dispositif pour le mélange et la thermostatisation de fluides

Info

Publication number
EP3820615A1
EP3820615A1 EP19742671.1A EP19742671A EP3820615A1 EP 3820615 A1 EP3820615 A1 EP 3820615A1 EP 19742671 A EP19742671 A EP 19742671A EP 3820615 A1 EP3820615 A1 EP 3820615A1
Authority
EP
European Patent Office
Prior art keywords
cuvette
temperature
cuvettes
liquid media
block
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
EP19742671.1A
Other languages
German (de)
English (en)
Inventor
Reinhard MARIK
Arnold Bartel
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
Application filed by Meon Medical Solutions and Co KG GmbH filed Critical Meon Medical Solutions and Co KG GmbH
Publication of EP3820615A1 publication Critical patent/EP3820615A1/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
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • B01L3/50255—Multi-well filtration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1822—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
    • B01L2400/0439—Moving fluids with specific forces or mechanical means specific forces vibrational forces ultrasonic vibrations, vibrating piezo elements

Definitions

  • the invention relates to a method and an apparatus for mixing and
  • cuvettes of a cuvette array that are lined up next to one another are introduced, the cuvettes of the cuvette array being form-fitting in receptacles one at a time
  • Block temperature thermostatted cuvette blocks are arranged.
  • a sample-reagent mixture in a cuvette for example by means of optical methods such as extinction, fluorescence, scattered light or luminescence measurement, homogenization of the sample-reagent mixture by circulation or stirring is absolutely necessary in a first step , while in a second step the sample-reagent mixture is brought to a target temperature stabilized at about 0.1 ° C.
  • a target temperature stabilized at about 0.1 ° C.
  • a temperature between 25 and 42 ° C, preferably between 36.5 and 37.5 ° C, which is constantly stabilized to about 0.1 ° C is desirable.
  • the kinetics of enzymatic and immunochemical detection reactions depend on the temperature, the kinetics generally increasing with an increase in temperature.
  • Biological sample components such as proteins (e.g. albumin, globulins and enzymes) are components of e.g. blood plasma and urine to be determined, but denature with increasing speed when temperatures> 40 ° C are exceeded, while enzymes and antibodies are essential
  • Pre-thermostatted block made of highly thermally conductive material or a circulated heat transfer medium can be thermostatted without using a separate control circuit for each cuvette, consisting of a temperature sensor, heating element and electronic control unit.
  • Thermostatization of liquid media in the sense of the invention includes both heating a sample reagent mixture and particle-containing media or mixtures (suspensions), including the stabilization of an achieved one
  • Liquor etc.
  • this includes both homogeneous liquid media and heterogeneous liquid-liquid
  • Reagents used can be in the form of suspended magnetic beads or, for example, colloidal latex particles in the mixture
  • a cuvette in the sense of the present invention denotes one side
  • a cuvette in the sense of the present invention has at least one for the
  • a temperature-controlled cuvette arrangement has become known.
  • a thermostattable cuvette block 55 is provided with a plurality of receiving shafts 56 into which cuvettes 57 can be inserted.
  • the cuvettes 57 which are tapered downwards and have lateral measuring windows 58, are positively inserted into a U-shaped, highly heat-conducting adapter 59, which makes 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 be optically measured in each case through a measuring channel 61 in the cuvette block 55.
  • the disadvantage here is that the temperature of the sample-reagent mixture only heats up slowly to the temperature of the cuvette block. This makes it difficult to achieve a high sample throughput in an analyzer because the
  • JP 2007-303964 A discloses - as shown in FIG. 1b of the present application - a device for thermostatting cuvettes 62, which are arranged in receptacles of a rotatable carousel 63.
  • the device has a piezoelectric substrate 64 fastened to the side wall of each cuvette 62, on which both an electrode structure of an interdigital transducer (IDT) as an ultrasound transducer 65 and a temperature sensor 66 for the non-invasive measurement of the temperature of the cuvette contents are integrated.
  • IDT interdigital transducer
  • a temperature control unit 68 of a control unit 69 connected via sliding contacts 67 forms, together with the driver unit 70 for the ultrasound transducer 65, a control circuit in order to thermostate a reaction mixture in the cuvette 62.
  • the sample-reagent mixture is heated directly to the target temperature by absorbing ultrasonic energy.
  • each cuvette 62 requires a glued-on piezoelectric substrate 64 with an 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 only record the temperature of the liquid indirectly via the heat conduction of the vessel wall of the cuvette 62, as a result of which, in particular when the liquid is heated quickly and required for a high sample throughput, the temperature increases in the Liquid cannot be measured with sufficient speed and accuracy to be able to rule out a permanent or temporary exceeding of the target temperature by a critical value for the sample components.
  • a measurement of the temperature in the liquid for example with the aid of a submersible probe, cannot be carried out without disadvantages, since this can lead to a carryover of sample material into other cuvettes.
  • EP 1 995 597 Al (OLYMPUS) describes a device for stirring
  • Liquids in cuvettes 71 are known, which - as shown in FIG. 1c of the present application - are arranged on a rotatable cuvette carousel 72, with a sound generator 73 on the side wall of each cuvette
  • the sound generator 73 is used only for mixing and stirring the
  • the resulting heat input is undesirable.
  • the heat input can be reduced by limiting the operating time
  • Ultrasonic generator can be minimized.
  • an individual Peltier element 76 for each cuvette 71 can be directly attached to the substrate of the adhesive by means of an actuator 75
  • the signal generator 77 for the sound generator 73 is controlled by a driver unit 78 of a control unit 74.
  • Cuvette carousels a predetermined ultrasound entry into the cuvette to achieve a predefinable target temperature of the cuvette contents.
  • a temperature measurement of the liquid can be carried out from above with a stationary infrared sensor but depending on the rotating position of the carousel, only on a specific one Cuvette, and cannot be performed on several cuvettes of the carousel at the same time.
  • known infrared sensors have the disadvantage that they only measure because of the measurement of long-wave infrared
  • JP 2007-010345 A describes an ultrasonic stirring device with which the content L of a cuvette 81 can be mixed.
  • a piezoceramic ultrasound generator (thickness transducer 83) is glued to the bottom 82 of the cuvette 81, the shape and the material of the cuvette bottom forming an acoustic lens 84 in order to collect the ultrasound energy at point F bundle just below the liquid surface.
  • the thickness transducer 83 made of lead zirconate titanate (“sounding body”) has a flat disk 85 with electrical contacts 86 that are flat on both sides, with a diameter that is larger than that of the cell bottom 82.
  • thermostatted water bath of a cuvette carousel are arranged.
  • a stirring station in the form of a
  • the individual cuvettes of the cuvette carousel must each be fed to the stirring station in a disadvantageous manner.
  • the object of the invention is to improve a method and a device for mixing and thermostatting liquid media which are introduced into rows of cuvettes of a cuvette array in such a way that the time from the introduction of the liquid media into the cuvette until it reaches a
  • the device has a cuvette block with form-fitting receptacles for the cuvettes which is regulated to a predeterminable block temperature, which block is equipped with a thermostat and is in thermal contact with the individual cuvettes in that at least one ultrasonic transducer is attached to each cuvette for introducing ultrasound energy into the cuvettes, and that the ultrasound transducer is designed as a piezoelectric oscillator and is connected to a control unit that controls the at least one ultrasound transducer as a function of parameter values of the liquid media.
  • the method according to the invention for mixing and thermostatting liquid media which are introduced for the determination of analytes in rows of cuvettes of a cuvette array, the cuvettes of the cuvette array being arranged positively in recordings of a cuvette block thermostatted to a block temperature, are characterized by the following steps: a) Heating the empty cuvettes to a predefinable target temperature of 25 to 42 ° C, preferably 36.5 to 37.5 ° C, by heat conduction from the thermostated cuvette block, whose block temperature TBL 0.1 to 1 ° C, preferably 0.1 to 0.5 ° C, is above the target temperature, b) adding one or more liquid media with a lower one
  • the liquid media in the cuvette having an initial temperature below the target temperature, c) heating the liquid media with the aid of the thermostatted one
  • Cuvette blocks in order to achieve the specified target temperature, d) in the heating phase by heat conduction according to point c), before reaching the target temperature, additional introduction of a predetermined amount of ultrasound energy with the aid of at least one (contacting) ultrasound transducer attached to each cuvette for increasing the heating rate, and e) simultaneous mixing of the liquid media with the aid of the in point d)
  • thermal energy from two different heat sources is thus supplied to the cuvette contents.
  • a predetermined, non-conductive input of thermal energy is carried out by means of ultrasound. This means that the contents of the cuvette can be heated more quickly to a precisely specifiable target temperature (without exceeding the Target temperature) can be reached, whereby the cuvette contents are simultaneously mixed by the input of the ultrasonic energy.
  • the main entry of thermal energy is made by heat conduction and a relatively smaller entry by means
  • one or more liquid media are preferably added when the cuvette block has reached the target temperature
  • the amount of ultrasound energy introduced in point d) is determined as a function of parameter values of the liquid media added in point b), such as amount, heat capacity, viscosity, thermal conductivity and temperature.
  • the amount of ultrasound energy to be introduced can be determined in the factory in a test or calibration step, for example, by test measurements and / or calculations, with corresponding information in the form of
  • Storage data or optically readable codes is provided by the user.
  • the method according to the invention effectively prevents any local hotspots that occur during rapid heating, since the introduction of
  • Ultrasonic energy is regulated by control codes, which are stored, for example, in an analysis protocol and were determined as a function of parameter values of the liquid, in such a way that the liquid in the cuvette is heated and always circulated at the same time.
  • the temperature of the cuvette contents can never be higher than that of the cuvette block pre-thermostatted to a final temperature compatible with the sample. This can largely cause thermal damage to biological samples and reagents from hotspots or a short-term exceeding of the target temperature
  • the temperature control is technically particularly simple and reliable
  • TBL coherent, thermally conductive material
  • An asymptotic approach to the block temperature TBL is typical for the heating of the cuvette contents from a pre-thermostatted heat source, so that the heating takes place first quickly and then slowly. Since the block temperature TBL is never fully reached, a slightly lower temperature of TBL- X is accepted as the target temperature in block thermostatting, which is typically in the range of 0.1-1 ° C., preferably in the thermostatting of biological samples as part of an optical measurement of certain analytes from 0.1 - 0.5 ° C, is below the block temperature and must not change by more than 0.1 ° C during the measurement (s) (see Fig. 5a, 5b).
  • the ultrasound energy according to point d) can be in several directions.
  • Pulses are introduced into the liquid media in a pulsed manner.
  • Liquid) favorable signal form can be selected, starting from a
  • the amplitude of the fundamental frequency of the ultrasound transducer can be modulated by an impressed, in comparison, lower frequency, the amplitude being able to be varied between a full modulation (100%) of the signal and until the signal is switched off (0%).
  • An amplitude modulation with the amplitude ratio (100: 0) would correspond to a burst pattern. It can in both cases
  • Modulation waveforms such as sine, square, sawtooth or the like for
  • the fundamental frequency of the ultrasound transducer is preferably one
  • Modulation frequency of the amplitude from 1 to 100 Hz impressed.
  • the basic frequencies of suitable designs are between approximately 200 kHz and 10 MHz, preferably approximately 0.5 to 10 MHz. If glued-on interdigital transducers are used, the basic frequencies of suitable designs (depending on the size and dimension of the transducer and the substrate) are around 10 to 200 MHz, preferably around 50-150 MHz.
  • the ultrasonic transducers can also be pressed against the individual cuvettes using spring force.
  • Fig. 2b shows the device of FIG. 2a with the front part removed
  • FIG. 3a shows the device according to Fig. 2a in a sectional view along line III-III in Fig. 2a,
  • FIG. 3b is a sectional view of a cuvette and its surroundings along line IV-IV in Fig. 3a,
  • Fig. 3c a cuvette including ultrasonic transducer of the invention
  • FIG. 4 shows a block diagram for the electronic control of the device for mixing and thermostatting liquid media according to FIG. 2a
  • Fig. 5a is a temperature diagram showing a first
  • 5b is a temperature diagram to illustrate a second
  • Embodiment of a thermostatting and mixing process of a liquid Embodiment of a thermostatting and mixing process of a liquid.
  • Thermostating liquid media relate to examples of the prior art and have already been explained in detail in the introduction to the description above.
  • Thermostatization of liquid media serves to thermostatize the liquid media introduced into the cuvettes 201 of a cuvette array 200 which are arranged next to one another.
  • the example shown is a linear, stationary cuvette array 200.
  • the individual cuvettes 201 of the cuvette array 200 are in one
  • thermostattable cuvette block 820 with a high thermal capacity compared to the cuvettes, and made of a highly thermally conductive material, for example made of anodized aluminum, the walls of the funnel-shaped receptacles 823 in the region of the lower half of the cuvette being at least 10%, preferably at least 20%, of the walls touch the cuvettes 201 in a form-fitting manner to ensure optimal heat transfer.
  • the cuvette block 820 consists of a base part 821 with the receptacles 823 and a removable front part 822, the cuvette block 820 with the front part 822 removed being shown in FIG. 2b.
  • Thermostat device 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.
  • Temperature sensor 833 arranged.
  • connection surfaces 824 can be seen, which can also be used for attaching a cooling and heating device, for example Peltier elements. Furthermore, 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.
  • An ultrasonic transducer 840 for example a thickness transducer, is attached to the bottom 204 of each cuvette 201, e.g. glued or injected during the manufacture of the cuvette, with which ultrasonic energy can be introduced into the cuvette 201.
  • the ultrasonic energy introduced is used both for mixing the liquid media and for targeted heating - in addition to the base load from the
  • the ultrasound transducer 840 is designed as a piezoelectric thickness transducer which, as shown in detail in FIG. 3c, essentially consists of one
  • Contact electrodes 841 and 843 exist.
  • the electrode 841 on the side of the cuvette is plated through via lateral contact strips 844 to the lower electrode 843 and forms crescent-shaped contact surfaces 845 there.
  • Spring contact board 846 supported contact block 847 is provided, which has four contact springs 848, two of which contact the crescent-shaped contact surfaces 845 and two the lower contact electrode 843 of the ultrasonic transducer 840.
  • the cuvette 201 has a collar 205 on the filling opening 207 and stop strips 206 on opposite sides, with which the cuvette 201 is held in the cuvette block 820 against the pressure of the contact springs 848.
  • the edge of the spring contact board 846 is inserted in a horizontal groove 826 of the cuvette block 820 and is supported on the decoder board 850 which carries downwards and whose circuits are explained in more detail in FIG. 4.
  • FIG. 4 shows a block diagram for the electronic control of the device for mixing and thermostatting liquid media according to FIG. 2a, which comprises the functional blocks personal computer 588, controller board 860, decoder board 850, cuvette block 820, and a temperature control circuit 870.
  • the controller board 860 has an FPGA (Field Programmable Gate Array) as the processor 861 and serves to control the decoder board 850 and the
  • the personal computer 588 can, for example, be connected to the controller board 860 via an Ethernet interface and, depending on the mixing and thermostatting task to be carried out, transmits corresponding orders in one of the cuvettes 201 of the cuvette block 820 for executing firmware programs on the controller board 860 and serves for
  • cuvettes 201 with the associated ultrasound transducers 840 are arranged at the positions K1 to K16 and PI to P16, with a Peltier element in each case for the thermostatting in the example shown in the positions PE1 to PE4 or TI to T4 831 including assigned
  • the temperature control circuit 865 thus has four temperature control circuits 866 each made of a Peltier element 831, a temperature sensor 833 and a PID (proportional, Integral, derivative) controller RI to R4 and is connected via an interface to controller board 860 for data exchange (receiving parameters such as temperature setpoints and returning measured temperatures of temperature control circuit 865 to controller board 860).
  • PID proportional, Integral, derivative
  • the decoder board 850 is also connected to the controller board 860 via an interface and receives control signals from it for the selection of individual ultrasonic transducers 840 via the one implemented on the decoder board 850
  • the oscillator circuit 852 receives control signals for adapting the frequency, duty cycle (duty ratio, duty factor, or duty cycle), burst pattern (burst pattern), amplitude, phase and ON and OFF states of the signal generation of the oscillator.
  • the oscillator circuit 852 comprises a voltage-controlled oscillator (VCO) 853, the frequency signal of which via a
  • Burst generator 854 can be modulated.
  • the amplitude of the modulated signal can also be adjusted via a controllable preamplifier 855 and a downstream amplifier output stage 856.
  • the final amplified signal is transformed up to the required operating voltage of the ultrasonic 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 to the cuvettes 201 via the optoswitches from S1 to S16 selected by the decoder circuit 851.
  • FIGS. 2a, 2b shows a first example of a thermostatting process according to the invention of a sample-reagent mixture in a cuvette which is arranged in a thermostattable cuvette block (see FIGS. 2a, 2b).
  • the temperature profile a shows the heating of the sample-reagent mixture only by the cuvette block thermostatted to the temperature TBL, the target temperature (corresponds to a temperature TBL- X slightly below the temperature TBL) at which the sample-reagent mixture can be measured only for the first time Time t 2 is reached.
  • the required target temperature is reached much earlier, at time ti, when ultrasound boosts are introduced in the time periods M and A to C, as is shown in the temperature curve ⁇ .
  • the cuvette block is thermostatted at an essentially constant electrical power PBL.
  • Block temperature TBL is 0.1 to 1 ° C above the target temperature and stabilization of the block temperature with an accuracy of 0.1 ° C.
  • the sample-reagent mixture is after Pipette into the cuvette at an initial temperature of 10-15 ° C if the pipetted reagents come from a storage area cooled to 5 ° C and heat up to 10-15 ° C in the pipettor and in the supply lines.
  • Delivery of an ultrasound signal for a predefined cumulative mixing period M which in the case of an ultrasound signal with the average electrical power PP introduces an amount of energy M x PP into the sample-reagent mixture and results in a calculated temperature rise DT M , which is based on variable data from the analysis to be carried out known properties of the sample-reagent mixture such as heat capacity, viscosity, thermal conductivity and its volume and constant, stored in the device
  • Reagents require stirring processes from 1 to 3, depending on the stirring task
  • the temperature rise DTM of a 2-second stirring pulse for example, depending on the intensity, being around 3 ° C.
  • Ultrasonic power PP is determined by tests on various sample-reagent mixtures and stored in the device.
  • an optical signal from an analyte measurement can be continuously measured from the sample-reagent mixture and the
  • thermal characteristics is calculated. ) Hold a pause> 0.5 s, for example to cool down the
  • TBL- X Reaching a target temperature TBL- X which is below the temperature of the cuvette block by the value x, where x is for example at a fixed value of 0.1-1 ° C, preferably 0.1-0.5 ° C.
  • the target temperature is fixed and in the example shown is between 36.5 and 37.5 ° C.
  • the temperature constancy during the subsequent optical measurement of an analyte concentration should be around 0.1 ° C.
  • Target temperature of 36.5 to 37.5 ° C thanks to the thermostatted cuvette block, whose block temperature TBL is 0.1 to 1 ° C above the target temperature and stabilization of the block temperature with an accuracy of 0.1 ° C.
  • Example 2 (as in Example 1) fill an empty cuvette with a sample reagent mixture which has an initial temperature To.
  • the sample-reagent mixture has one after pipetting into the cuvette
  • Reagents require stirring processes from 1 to 3, depending on the stirring task
  • the temperature rise DT M of a 2-second stirring pulse for example, depending on the intensity, being approximately 3 ° C.
  • the mixing time M required to obtain a stable measurement signal, a washing or incubation process can be given
  • Ultrasonic power PP is determined by tests on various sample-reagent mixtures and stored in the device.
  • an optical signal from the sample-reagent mixture can be measured continuously, for example a signal that correlates with an analyte concentration, and the mixing process can be stopped as soon as a stable signal is obtained, the temperature drop DT M - as mentioned - is calculated from known thermal characteristics.
  • Adherence to a pause> 0.5 s for example for cooling the cuvette bottom and, if necessary, a glue point to the ultrasonic transducer.
  • the temperature T ßL -y is calculated from the expected temperature rise and, depending on the operating scenario , is subject to an inaccuracy of one or more ° C, which is why T B Ly is set below the desired target temperature TBL-X. From this temperature, the temperature is entered into the cuvette content purely via heat conduction between the cuvette block and the cuvette content.
  • the target temperature is fixed and in the example shown is between 36.5 and 37.5 ° C.
  • the temperature constancy during the period of one subsequent optical measurement of an analyte concentration should be around 0.1 ° C.
  • mixing of two or more liquids individually introduced into one of the cuvettes 201 can in some cases not take place with sufficient mixing quality or mixing speed if the mixing is carried out exclusively via the introduced ultrasound energy from an external source
  • Ultrasonic transducers such as that attached to the cuvette 201
  • Ultrasonic transducer 840 Ultrasonic transducer 840.
  • the reagent liquids to be mixed that are introduced into one of the cuvettes 201 can have a high viscosity and / or a large viscosity
  • Buffer solutions that are placed in a cuvette for mixing.
  • the liquids can be introduced, for example, using a known x-y-z laboratory robot with an automatic pipettor.
  • steps 1) and 2) can be repeated several times.
  • the ultrasound mixing can be started by applying ultrasound before or during step 1) and 2) and can be carried out continuously or discontinuously, but in any case after a sequence of steps 1) and 2).
  • Reagent in aqueous solution in the cuvette 201 Reaspiration of 50 pl_ of the liquid volume already pipetted into the cuvette and re-release of the reaspired liquid volume into the cuvette 201

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

L'invention concerne un dispositif (810) et un procédé pour le mélange et la thermostatisation de fluides, qui sont introduits pour la détermination d'analytes dans des cuvettes (201) d'un réseau de cuvettes (200) alignées les unes par rapport aux autres, le dispositif (810) comprenant un bloc de cuvettes (820) réglé à une température de bloc pouvant être prédéfinie, comprenant des logements (823) à forme complémentaire pour les cuvettes (201). Selon l'invention, le bloc de cuvettes (820) est équipé d'un dispositif de thermostatisation (830) et est en contact thermique avec les cuvettes (201) individuelles, au moins un transducteur d'ultrasons (840) étant fixé sur chaque cuvette (201) pour l'introduction d'énergie ultrasonique dans la cuvette (201). Le transducteur d'ultrasons (840) est réalisé sous la forme d'un vibrateur piézoélectrique et est en connexion avec une unité de commande (860), qui commande l'au moins un transducteur d'ultrasons (840) en fonction de valeurs de paramètres des milieux liquides.
EP19742671.1A 2018-07-13 2019-07-11 Procédé et dispositif pour le mélange et la thermostatisation de fluides Pending EP3820615A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AT506052018 2018-07-13
PCT/AT2019/060231 WO2020010380A1 (fr) 2018-07-13 2019-07-11 Procédé et dispositif pour le mélange et la thermostatisation de fluides

Publications (1)

Publication Number Publication Date
EP3820615A1 true EP3820615A1 (fr) 2021-05-19

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EP19742671.1A Pending EP3820615A1 (fr) 2018-07-13 2019-07-11 Procédé et dispositif pour le mélange et la thermostatisation de fluides

Country Status (3)

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US (1) US20210268507A1 (fr)
EP (1) EP3820615A1 (fr)
WO (1) WO2020010380A1 (fr)

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DE60138934D1 (de) 2000-02-25 2009-07-23 Hitachi Ltd Mischvorrichtung für Analysenautomat
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
EP1995597A1 (fr) 2006-03-15 2008-11-26 Olympus Corporation Dispositif d'agitation et analyseur
JP2007248252A (ja) * 2006-03-15 2007-09-27 Olympus Corp 攪拌装置及び分析装置
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
JP2009210483A (ja) * 2008-03-05 2009-09-17 Olympus Corp 自動分析装置と液体試料の温度管理方法
JP2009270941A (ja) 2008-05-08 2009-11-19 Hitachi High-Technologies Corp 自動分析装置

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