EP4163011B1 - Régulation de température - Google Patents

Régulation de température

Info

Publication number
EP4163011B1
EP4163011B1 EP22197262.3A EP22197262A EP4163011B1 EP 4163011 B1 EP4163011 B1 EP 4163011B1 EP 22197262 A EP22197262 A EP 22197262A EP 4163011 B1 EP4163011 B1 EP 4163011B1
Authority
EP
European Patent Office
Prior art keywords
thermal chamber
shaped container
circular disc
temperature
axis
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.)
Active
Application number
EP22197262.3A
Other languages
German (de)
English (en)
Other versions
EP4163011A1 (fr
Inventor
Hannes Kirzinger
Bernd Gröhbühl
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.)
Stratec SE
Original Assignee
Stratec SE
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 Stratec SE filed Critical Stratec SE
Publication of EP4163011A1 publication Critical patent/EP4163011A1/fr
Application granted granted Critical
Publication of EP4163011B1 publication Critical patent/EP4163011B1/fr
Active legal-status Critical Current
Anticipated expiration legal-status Critical

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
    • B01L3/50—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
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502753—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B01L7/525—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples with physical movement of samples between temperature zones
    • B01L7/5255—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples with physical movement of samples between temperature zones by moving sample containers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • 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
    • B01L2300/0803—Disc shape
    • 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
    • B01L2300/0803—Disc shape
    • B01L2300/0806—Standardised forms, e.g. compact disc [CD] format
    • 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
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1838—Means for temperature control using fluid heat transfer medium
    • B01L2300/1844—Means for temperature control using fluid heat transfer medium using fans

Definitions

  • the invention relates to a device and a method for rapidly changing and controlling the temperature of diagnostic consumables and their contents in a diagnostic analyser system.
  • Automated analyser systems for use in clinical diagnostics and life sciences are produced by a number of companies.
  • STRATEC ® SE Birkenfeld, Germany
  • STRATEC designs and manufactures diagnostic instruments with functional modules that have to process a various number of different reaction container like consumables or vessels with an also various number of different handling and processing steps.
  • Such instruments are used for vitro diagnostics (IVD) comprising the crude extraction of nucleic acids and successive real-time polymerase chain reaction (PCR).
  • a consumable that has a disc shape is used in devices known from the prior art for solid phase heating and cooling.
  • a metal disc holder is heated with radiation of light and cooled with ambient air.
  • the temperature inhomogeneity of the disc holder during cooling and heating causes increased costs for spare parts and maintenance.
  • variations in the ambient air temperature are leading to variations in cooling speeds and thus influence the assay or instrument performance.
  • WO 2017/139447 A1 discloses a system for moving a sample holder between chambers with heating blocks and a cooling zone comprising a fan.
  • Peltier based thermocycler need a relatively massive heatsink for fast cooling. They further need a lot of space and energy to achieve homogenous heating and cooling. The edges of such devices are due to their increased surface related to a delayed reach of a temperature equilibrium so that systems using a solid phase for heat transfer are usually slower than systems which use a gaseous medium.
  • the present invention provides a system for performing biochemical assays with a fluid, comprising
  • system's upper surface of the thermal chamber's housing comprises an optically transparent element for optical measurements.
  • the cooling element can be a Peltier element.
  • the system may also comprise control electronics for the drive and the control electronics can be connected to the heating element.
  • the system may further comprise a housing for accepting the drive and the thermal chamber.
  • Another object of the invention relates to a method for thermal cycling of a fluidic sample, comprising the steps of
  • Another aspect of the invention relates to a method, wherein the third temperature is higher than the second temperature but lower than the first temperature.
  • the method may further comprise the step of the fluidic sample in the circular disc-shaped container being illuminated through an optically transparent part in the upper surface of the thermal chamber's housing and an optical measurement is performed.
  • the circular disc-shaped container provides more than one fluidic sample, wherein each fluidic sample is comprised in a separate compartment of the circular disc-shaped container
  • the core of the invention consists of a combination of different media to allow fast temperature shifts for objects that are moving in or on the surface of those media.
  • the present disclosure relates to a system and method for rapidly changing and controlling the temperature of a sample which is comprised in a container like a consumables for processing in a diagnostic analyzer system by altering the physical thermal contact by means of mechanical motion for tempering media with different states of aggregation. This allows fast temperature changes.
  • the system according to the present disclosure comprises a circular disc-shaped container as consumable which comprises at least one compartment for taking up a fluidic sample which has to be processed in a biochemical or diagnostic assay.
  • a fluid may be a liquid, gas, or solid which flows under shear stress or gravitation.
  • the circular disc-shaped container is placed into a further part of the system according to the present invention, a thermal chamber.
  • Said thermal chamber may also have a circular shape.
  • An axis spans through a bottom plate of the thermal chamber and the upper end of the axis is connected to the circular disc-shaped container.
  • the axis can be actuated in two different ways. It may rotate so that a container which is connected to the upper end of the axis is rotating around the axis and the axis and respectively a connected container may be lifted or lowered by a vertical movement of the axis.
  • the axis is connected to drives like a motor for performing said motions.
  • a gearing mechanism may be used for transferring a drive's movement to the axis.
  • Hot air is introduced into the thermal chamber through an inlet of the thermal chamber, wherein the inlet is connected to a source for heated air like a fan for instance.
  • the circular disc-shaped container is lifted and fast-spinning while the hot air is blown into the thermal chamber which can be designated as forced convection heating.
  • PCR polymerase chain reaction
  • the circular disc-shaped container or its compartments may be filled with fluidic reagents for real-time PCR, which can be rotated and moved in an up and downward direction (z-axis). This design allows free rotation for heating and signal measurement in a gaseous media (air).
  • FIG. 1 shows the repeating cycling steps A, B, and C.
  • step A the circular disc shaped container is lifted and the thermal chamber is filled with hot air while spinning the circular disc-shaped container.
  • step B is the circular disc-shaped container is lowered and pressed onto a heat sink for cooling.
  • step C the temperature is controlled and maintained so that an optical read-out may be performed.
  • step C the circular disc-shaped container is lifted again and Step A is repeated so that a cycling of the sequence of steps A, B and C is achieved.
  • step A in an assay for isolation DNA the disc-shaped container is heated up towards denaturation temperature and is lifted and spined freely inside the thermal chamber.
  • An increased temperature of the Peltier base located at the inner bottom surface of the thermal chamber is connected to a Peltier element.
  • heated air is introduced into the thermal chamber for raising the inner temperature of the thermal chamber and thus the temperature of the disc-shaped container's content. Circulating hot air is used for a forced convection heating of the disc-shaped container and to achieve an optimized homogeneity of the heating process.
  • step B the cold plate arranged at the inner bottom surface of the thermal chamber an connected to the Peltier element is cooled by the Peltier element down to the desired temperature, e.g. an annealing temperature appropriate for the respective DNA sequence intended for amplification.
  • the thermal chamber is opened and the heated air inside the thermal chamber is ventilated out of the thermal chamber and replaced with ambient air. Afterwards the chamber closes again.
  • the disc-shaped container stops spinning and is pressed onto the solid phase Peltier base at the inner bottom surface of the thermal chamber until it reaches a desired lower temperature level.
  • step C the temperature of the disc-shaped container and the thermal chamber is raised and adjusted to the desired elongation temperature for the PCR reaction.
  • the disc is lifted again and starts spinning again.
  • an optical measurement unit can illuminate and read-out every reaction compartment or cavity on the disc circumference when passing the unit.
  • FIG. 2 shows a perspective view onto a circular disc-shaped container 5 according to the present disclosure.
  • the container comprises a centrally arranged acceptance for the axis of the drive (both not shown).
  • FIG. 2 shows a schematic setup of a circular disc-shaped container 5 arranged within a thermal chamber 20.
  • the drives 30 for rotating and lifting the circular disc-shaped container 5 are arranged below the thermal chamber 20.
  • the left part of FIG. 2 shows the disc-shaped container 5 freely rotating on a centrally engaged axis 31 in the thermal chamber 20.
  • the arrow indicates the rotation. It is obvious for a skilled person that the circular disc-shaped container may rotate clockwise or counterclockwise.
  • FIG. 3 shows a perspective view of the ventilated thermal chamber 20 in a mechanical integration.
  • the design enables a fast heating and cooling, by taking advantage of low heat capacity of air to allow heating and a quick and homogeneous heat transfer to a steady state cooled bottom plate. Since many consecutive repeats of heat and cooling phases are necessary for this application is especially useful and timesaving.
  • This invention combines the positive aspects of fast heating with a gaseous medium and fast and homogeneous cooling on a solid phase block.
  • a steady state tempered cooling plate allows fast cycling with a reduced space and energy consumption in comparison to state of the art thermocyclers.
  • the solid phase Since the solid phase will not undergo repetitive temperature changes, it can use a high mass to allow an excellent temperature homogeneity, while accepting heat from the consumable quite fast. This will minimize or even prevent edge effects.

Landscapes

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

Claims (10)

  1. Un système pour réaliser des analyses biochimiques avec un fluide, comprenant
    - un récipient circulaire en forme de disque (5) avec au moins un compartiment destiné à recevoir le fluide à traiter dans le test biochimique, dans lequel le récipient circulaire en forme de disque (5) comporte un logement central pour un axe ;
    - une chambre thermique (20), comprenant un boîtier destiné à recevoir le récipient en forme de disque circulaire, dans lequel le boîtier comprend
    i. une surface supérieure plane (21) et une surface inférieure plane (22), et dans lequel une plaque froide (25) reliée à un élément de refroidissement est disposée au-dessus de la surface inférieure plane à l'intérieur du boîtier de la chambre thermique, et
    ii. une entrée et une sortie pour une alimentation en air ; et
    - un élément chauffant pour l'air qui est relié à l'entrée et à la sortie du boîtier de la chambre thermique de telle sorte que de l'air chauffé puisse être soufflé dans la chambre thermique afin d'élever la température à une première température dans la chambre thermique ;
    - un entraînement (30) comprenant l'axe (31) avec une extrémité supérieure pour sa connexion au récipient en forme de disque circulaire (5) en traversant une surface inférieure du boîtier de la chambre thermique, dans lequel l'axe est connecté à un moteur pour faire tourner l'axe, et dans lequel l'axe est en outre connecté à un moteur pour déplacer l'axe verticalement à l'intérieur de la chambre thermique.
  2. Le système selon la revendication 1, dans lequel la surface supérieure du boîtier de la chambre thermique comprend un élément optiquement transparent pour des mesures optiques.
  3. Le système selon l'une quelconque des revendications 1 à 2, dans lequel l'élément de refroidissement est un élément Peltier.
  4. Le système selon l'une quelconque des revendications 1 à 3, comprenant une électronique de commande pour l'entraînement.
  5. Le système selon la revendication 4, dans lequel l'électronique de commande est reliée à l'élément chauffant.
  6. Le système selon l'une quelconque des revendications 1 à 5, comprenant en outre un boîtier destiné à recevoir l'entraînement et la chambre thermique.
  7. Un procédé de cyclage thermique d'un échantillon fluide, comprenant les étapes consistant à
    - fournir l'échantillon fluide dans un récipient circulaire en forme de disque (5) comportant au moins un compartiment ;
    - Disposer le récipient circulaire en forme de disque sur un axe (31) relié à un entraînement (30) pour faire tourner, lever et abaisser l'axe qui traverse la surface inférieure (22) d'un boîtier d'une chambre thermique (20) renfermant le récipient circulaire en forme de disque ;
    - Fermer la chambre thermique ;
    - Soulever le récipient circulaire en forme de disque à l'aide de l'axe qui y est relié et le faire tourner dans la chambre thermique tandis que de l'air chauffé est soufflé dans la chambre thermique afin d'élever la température à une première température dans la chambre thermique ;
    - Arrêter la rotation du récipient en forme de disque circulaire lorsque la première température est atteinte et remplacer l'air chauffé dans la chambre thermique par de l'air ambiant ;
    - abaisser le récipient en forme de disque circulaire sur une plaque froide qui est disposée sur la surface inférieure interne du boîtier de la chambre thermique par un mouvement vers le bas de l'axe ;
    - Refroidir le récipient en forme de disque circulaire sur la plaque froide qui est thermiquement reliée à un élément de refroidissement à une deuxième température ;
    - Élever le récipient en forme de disque par un mouvement ascendant de l'axe relié au récipient circulaire en forme de disque ; et
    - élever la température dans la chambre thermique à une troisième température.
  8. Le procédé selon la revendication 7, dans lequel la troisième température est supérieure à la deuxième température mais inférieure à la première température.
  9. Le procédé selon la revendication 7 ou 8, dans lequel l'échantillon fluide dans le récipient en forme de disque circulaire est éclairé à travers une partie optiquement transparente dans la surface supérieure du boîtier de la chambre thermique et une mesure optique est effectuée.
  10. Le procédé selon l'une quelconque des revendications 7 à 9, dans lequel le récipient en forme de disque circulaire fournit plus d'un échantillon fluide, chaque échantillon fluide étant contenu dans un compartiment séparé du récipient en forme de disque circulaire.
EP22197262.3A 2021-10-07 2022-09-22 Régulation de température Active EP4163011B1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP21201394 2021-10-07

Publications (2)

Publication Number Publication Date
EP4163011A1 EP4163011A1 (fr) 2023-04-12
EP4163011B1 true EP4163011B1 (fr) 2026-01-28

Family

ID=78085827

Family Applications (1)

Application Number Title Priority Date Filing Date
EP22197262.3A Active EP4163011B1 (fr) 2021-10-07 2022-09-22 Régulation de température

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EP (1) EP4163011B1 (fr)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7754473B2 (en) * 2004-06-04 2010-07-13 Abacus Diagnostica Oy Temperature control of reaction vessel, system with reaction vessel, software product for system and use of system
CN109642198A (zh) * 2016-02-10 2019-04-16 卡尤迪生物科技（北京）有限公司 用于分析核酸的方法和系统
US10850281B2 (en) * 2016-09-12 2020-12-01 Delta Electronics Int'l (Singapore) Pte Ltd Nucleic acid analysis apparatus
WO2019178121A1 (fr) * 2018-03-12 2019-09-19 The Penn State Research Foundation Procédé et appareil pour la microfluidique a gradient de température

Also Published As

Publication number Publication date
EP4163011A1 (fr) 2023-04-12

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