EP4163011A1 - Temperaturregelung - Google Patents

Temperaturregelung Download PDF

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Publication number
EP4163011A1
EP4163011A1 EP22197262.3A EP22197262A EP4163011A1 EP 4163011 A1 EP4163011 A1 EP 4163011A1 EP 22197262 A EP22197262 A EP 22197262A EP 4163011 A1 EP4163011 A1 EP 4163011A1
Authority
EP
European Patent Office
Prior art keywords
shaped container
thermal chamber
circular disc
axis
temperature
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
EP22197262.3A
Other languages
English (en)
French (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/de
Pending legal-status Critical Current

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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.
  • 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.
  • Another embodiment of the invention relates to a system comprising a heating element for air that is connected to the inlet and outlet of the thermal chamber's housing.
  • 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 prcessing 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 rhe 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 movment 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 temeraure is controlled and maintained so that an optical read-out may be performed.
  • stepC 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 indented 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. 3 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.
  • Hot air is introduced into the thermal chamber 20, which is indicated by the arrowa at both sides of the thermal chamber 20, so that the circular disc-shaped container 20 and its content will be heated.
  • the arrow on the right part of the chamber indicates a location for optical measurements through a transparent window in the upper surface 21 of the thermal chamber 20 for instance.
  • FIG.2 shows the circular disc-shaped container 5 set still within the meaning that no rotation takes place.
  • the circular disc-shaped container 5 is lowered and thus pressed towards the Peltier element 25 tempered inner bottom surface 22 of the thermal chamber 20 for cooling it.
  • FIG. 3 shows a perspective view of 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.
  • Alternative approaches may encompass different technical means for heating or cooling of the gaseous media and the solid phase.
  • the consumable may have a different shape in comparison to the above-described disc shaped consumable.
  • Device and method of the present disclosure may be used for other assays than PCR.

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)
EP22197262.3A 2021-10-07 2022-09-22 Temperaturregelung Pending EP4163011A1 (de)

Applications Claiming Priority (1)

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

Publications (1)

Publication Number Publication Date
EP4163011A1 true EP4163011A1 (de) 2023-04-12

Family

ID=78085827

Family Applications (1)

Application Number Title Priority Date Filing Date
EP22197262.3A Pending EP4163011A1 (de) 2021-10-07 2022-09-22 Temperaturregelung

Country Status (1)

Country Link
EP (1) EP4163011A1 (de)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005118144A1 (en) * 2004-06-04 2005-12-15 Abacus Diagnostica Oy Temperature control of reaction vessel, system with reaction vessel, software product for system and use of system
WO2017139447A1 (en) * 2016-02-10 2017-08-17 Coyote Bioscience Usa Inc. Methods and systems for analyzing nucleic acids
US20180214877A1 (en) * 2016-09-12 2018-08-02 Delta Electronics Int'l (Singapore) Pte Ltd Nucleic acid analysis apparatus
US20210041379A1 (en) * 2018-03-12 2021-02-11 The Penn State Research Foundation Method and apparatus for temperature gradient microfluidics

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005118144A1 (en) * 2004-06-04 2005-12-15 Abacus Diagnostica Oy Temperature control of reaction vessel, system with reaction vessel, software product for system and use of system
WO2017139447A1 (en) * 2016-02-10 2017-08-17 Coyote Bioscience Usa Inc. Methods and systems for analyzing nucleic acids
US20180214877A1 (en) * 2016-09-12 2018-08-02 Delta Electronics Int'l (Singapore) Pte Ltd Nucleic acid analysis apparatus
US20210041379A1 (en) * 2018-03-12 2021-02-11 The Penn State Research Foundation Method and apparatus for temperature gradient microfluidics

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