WO2020058461A1 - Verfahren zur steuerung eines thermocyclers und thermocycler - Google Patents
Verfahren zur steuerung eines thermocyclers und thermocycler Download PDFInfo
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- WO2020058461A1 WO2020058461A1 PCT/EP2019/075286 EP2019075286W WO2020058461A1 WO 2020058461 A1 WO2020058461 A1 WO 2020058461A1 EP 2019075286 W EP2019075286 W EP 2019075286W WO 2020058461 A1 WO2020058461 A1 WO 2020058461A1
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- WIPO (PCT)
- Prior art keywords
- temperature
- thermal cycler
- temperature control
- plan
- temperature change
- Prior art date
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Classifications
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- 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
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
- B01L2200/143—Quality control, feedback systems
- B01L2200/147—Employing temperature sensors
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/02—Identification, exchange or storage of information
- B01L2300/024—Storing results with means integrated into the container
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/02—Identification, exchange or storage of information
- B01L2300/025—Displaying results or values with integrated means
- B01L2300/027—Digital display, e.g. LCD, LED
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/04—Closures and closing means
- B01L2300/041—Connecting closures to device or container
- B01L2300/043—Hinged closures
Definitions
- the invention relates to a method for determining a temperature change rate for controlling the temperature control device of a thermal cycler.
- the invention also relates to a thermal cycler, the control of which is set up to carry out such a method.
- a thermal cycler is a laboratory device that is able to set the temperature of at least one laboratory sample in succession to a predetermined temperature and to keep it at this temperature level for a predetermined duration.
- the sequence of this temperature control is cyclical. This means that a predetermined temperature cycle, that is to say a sequence of at least two temperature levels, typically three temperature levels, is carried out repeatedly. This procedure is usually used to carry out a polymerase chain reaction (PCR).
- PCR polymerase chain reaction
- the user When performing DNA duplication using a PCR, the user is dependent on the optimal result for the temperature being precisely and reproducibly tempered over the course of a temperature control schedule specified by the user.
- the temperature cycle of a thermal cycler is specified by the user by setting a temperature control plan, usually directly on an operating device of the device.
- a cycle with setting option is shown by way of example in FIG. 2a with reference to a screen display of an exemplary thermal cycler according to the invention.
- the user sets the level of each temperature level of a cycle and its holding time, as well as the total number of cycles to be completed.
- the control of the thermal cycler ensures that the temperature control plan is implemented as precisely as possible according to these specifications. In most cases, the user cannot determine exactly, the device control uses certain control parameters that are adapted to the hardware components used in the thermal cycler.
- Peltier elements which are used in the temperature control devices of the thermocyclers mostly as temperature control elements for temperature control of the sample block (thermoblocks) different performance values. The result of the tempering is also everyone
- Hardware and material parameters of the thermal cycler are determined, which have an influence on the heat transfer, i.e. the heat supply and heat dissipation, from the liquid laboratory samples to the Peltier element.
- the maximum temperature change rates or ramp rates are usually not reached or only for a short time.
- the knowledge of the maximum temperature change rate which is shown in the figure as the steepest straight line 2
- the time interval of the temperature change here referred to as At s cooi .
- the maximum differential 2 of the temperature curve in the area of the time interval is not equal to the difference quotient 1 in the time interval.
- the difference quotient in the time interval is subsequently also called effective temperature change rate or effective heating rate / effective cooling rate.
- the difference quotient, starting from a first point in time t1 (end of the point in time of the first temperature level) and a second point in time t2 (start of the point in time of the second temperature level) and a first temperature T1 (t1) and a second temperature T2 (t2), is defined as (T2 (t2) - T 1 (t1)) / (t2 - t1).
- the hardware-specific parameters are usually ignored by the user when carrying out a PCR. Instead, the temperatures are optimized (eg using a gradient) in order to obtain an optimal yield. When a PCR is migrated to another class of thermal cyclers, this yield usually decreases. This is not only due to the temperature deviating from the original device, but in particular also due to deviations in the dynamic behavior, ie on the ramp and during the transient response. Many users steer clear of that Repetition of attempts to switch to another device, as this does not produce the same result despite the same programming and application of the same temperature control plan.
- the object on which the invention is based relates to the reproduction of a temperature profile in a thermal cycler when a user-defined temperature control plan is used again, in particular in a situation in which the hardware-specific performance values have changed, as is the case, for example, when the thermal cycler is changed.
- the task is to be solved to make it easier for the user to switch from one thermal cycler to another thermal cycler with different performance values.
- the thermal cycler is designed in particular in accordance with the definitions of the present invention.
- Applying the invention increases the probability of successfully reproducing a temperature profile.
- the dynamic behavior, including in particular the ramp rates and settling behavior, of an original thermal cycler is simulated or simulated without the user having to make great effort in the form of experiments and entering numerous parameters.
- the temperature change rates in particular the heating and cooling rates, which the temperature control device of the thermal cycler uses to reach the respective temperature level can be determined from the running time of a temperature control plan run through on a thermal cycler.
- the running time then includes the at least one holding time of the at least one temperature level of the temperature control plan and at least one time interval during which the setting of this at least one temperature level is carried out as a function of at least one temperature change rate.
- the running time T of the temperature control plan consisting of repetitions of the same temperature cycle results from the time intervals At s _heat heating and holding times Tsjieat at this higher temperature level and from the time intervals At s-CO oi cooling and holding times T sC ooi at this low temperature level:
- r H is the rate of temperature change (heating rate) to heat the temperature block by a temperature difference A s-he at
- r c is the rate of temperature change (cooling rate) to cool the temperature block by a temperature difference A sC ooi.
- heating rate, cooling rate and rate of temperature change respectively denote the effective heating rate, the effective cooling rate and the effective rate of temperature change, and not, for example, extreme values which are present for a short time when the temperature changes.
- the effective heating rate and the effective cooling rate are roughly constant. This can be easily determined for known thermal cyclers and saved as a table. This table can be stored in a data storage device in the thermal cycler or method according to the invention.
- the rates of temperature change are determined in particular on the assumption of a medium transient response (standard). This is exemplarily shown in Fig. 2d. This affects the input variables As jeat , As cool T s_ heat and Ts cooi (for all s). It can be roughly assumed that there is a constant period of time in each of the heating and cooling time intervals
- the settling time period is included, which takes into account the settling of the control loop to the respective level of the temperature level.
- the settling time period is to be set by the period between the presence of the constant temperature change rate and the presence of a Temperature level determined.
- the settling time period for certain commercial thermal cyclers can also be determined and saved in a table.
- a table can contain a pre-selection from a limited selection of typical control modes. The table can be stored in a data storage device in the thermal cycler or method according to the invention.
- the thermal cycler or method according to the invention can be set up so that the user changes the constant value of the settling time period as a variable, in particular by input via a user interface device of the thermal cycler and a data input in this way.
- the user can thus easily correct the result by changing the transient response if the yield is not correct in the method.
- a temperature control of the temperature control block of a thermal cycler that is optimized for the controlled settling is known in principle.
- the oscillation to the desired target temperature of a temperature level of the temperature cycle uses an overshoot of the temperature set in the temperature control block to a maximum temperature value which is above the setpoint to be set, followed by an undershoot to a temperature value below the setpoint, to then switch back to a lower temperature value above the setpoint, etc., until the setpoint is reached.
- the settling can then be characterized by the temperature difference between the maximum overshoot temperature (for cooling: the minimum undershoot temperature) and the duration of the overshoot until the target temperature is reached. With a rapid settling, this temperature difference and the duration are small.
- the user can be given a preselection from a limited number of transient modes for selection.
- Any such attack mode can by certain values of said temperature difference and duration each for heating and cooling, be characterized, ie in particular by two pairs of values: Modus_x (Temperaturdifferenz_x, Treasure_x) Hei z s, (Temperaturdifferenz_x, Treasure_x) Kühien ⁇
- Modus_x Temporaturdifferenz_x, Dauer_x
- Hei z s Temporaturdifferenz_x, Dauer_x
- kuien ⁇
- Such modes can one offers the user via list selection on the display, for example under the marking “Fast”, “Intermediate”, “Standard”, “Safe”, as is the case in the exemplary embodiment in FIG is provided.
- thermocontrol can also be carried out by additionally observing the effect of the temperature control on the temperature of the liquid sample which is contained in the vessel which is inserted in the thermal block of the thermal cycler, as is known, for example, from EP 1 452 608 B1.
- the method according to the invention and / or the thermal cycler according to the invention can be set up in such a way that a particular commercial thermal cycler TC X can be selected by the user, in particular via a user interface device of the thermal cycler, for example via a list selection that is displayed on a display or touchscreen of the user interface device and can be operated.
- the thermal cycler or the method then has the additional information that the runtime T specified by the user relates to the implementation of the temperature control plan on the thermal cycler of the TC X type.
- the method according to the invention and / or the thermal cycler according to the invention can access the tables in which the ratio r H / r c or the settling time is stored as a function of TC X , the calculation of the rates of temperature change can be made according to the selection made by the user TC X done automatically.
- the method is used to determine at least one temperature change rate for the control of the temperature control device of a thermal cycler, the control tempering a sample-receiving thermoblock of the thermal cycler for carrying out polymerase chain reactions in these samples according to a temperature control schedule, during which the temperature is changed by changing the temperature with a Temperature change rate is changed, comprising the steps:
- the temperature plan data preferably determine at least a first hold time and a first temperature of a first temperature level and at least a second hold time and a second temperature of a second temperature level of the temperature plan.
- a cycle of the temperature control plan also has three temperature levels, if it is a PCR, so that the temperature control plan data also determine a third holding time and a third temperature of the third temperature level.
- the first temperature is assumed to be higher than the second temperature, and according to the temperature control plan, switching between temperature levels is carried out by cooling from the first temperature with a first temperature change rate (cooling rate) and heating starting from the second temperature with a second temperature change rate (heating rate) becomes.
- the evaluation program preferably uses the temperature plan data and the runtime data to determine the at least one first temperature change rate, which is used as the cooling rate for setting the second temperature level, and at least one second temperature change rate is determined, which is used as the heating rate for setting the first temperature level.
- These at least one cooling rate and at least one heating rate are preferably provided for the control of the temperature control device of the thermal cycler.
- a cycle of the temperature control schedule in particular there is at least one time interval during which at least one constant rate of temperature change is used, and that also one Settling time period, which can be determined by the period between the presence of the constant rate of temperature change and the presence of a temperature level to be set, during which period a settling process is carried out by the control of the temperature control device of the thermal cycler, which is part of the temperature control of a thermal cycler, which The method comprises the step:
- the method preferably includes the step:
- the runtime can also include a latency interval, during which, at the beginning of a temperature control plan, a heatable cover, which covers the temperature control block of the thermal cycler containing the samples during the implementation of the polymerase chain reaction, is set to a target temperature, the runtime data also providing information about this latency interval include.
- the method according to the invention is preferably used to control the temperature control device of a thermal cycler, the method of controlling the temperature control device preferably containing a method for determining at least one temperature change rate from runtime data and temperature control plan data.
- the thermal cycler has the temperature control device for temperature control of a thermoblock holding the samples for carrying out Polymerase chain fractions in these samples in accordance with the temperature control plan mentioned in the method according to the invention, and has an electronic control device which is set up to control the temperature control device by means of control parameters.
- the method of controlling the temperature control device of a thermal cycler has the steps of the method for determining at least one temperature change rate from runtime data and temperature control plan data and the following steps:
- the method for controlling the temperature control device is, in particular, a method for controlling a first thermal cycler by simulating the temperature control behavior of a second thermal cycler, the method for controlling the temperature control device including the method for determining at least one temperature change rate from temperature control plan data and runtime data, which control the temperature control behavior of the second thermal cycler characterize.
- the first thermal cycler can be operated at a first maximum temperature change rate, which is a cooling rate or a heating rate
- the second thermal cycler can in particular be operated at a second maximum temperature change rate, which is a cooling rate or a heating rate, the first maximum temperature rate of change being greater or is equal to the second maximum rate of temperature change.
- the first thermal cycler preferably tempers faster than the second thermal cycler.
- thermocycler® X50 from Eppendorf AG, Hamburg, Germany.
- the Mastercycler® X50 heats at a maximum of 10 ° C / s and cools at a maximum of 5 ° C / s.
- the first thermal cycler has the temperature control device for temperature control of a thermoblock holding the samples for carrying out polymerase chain reactions in these samples in accordance with the temperature control plan defined in the method for determining at least one temperature change rate, and an electronic control device which is set up to control the temperature control device.
- the method for controlling the temperature control device has, in particular, the steps of the method for determining at least one temperature change rate from temperature control plan data and runtime data and the following steps:
- the at least one rate of temperature change is in particular smaller than the first maximum rate of temperature change.
- the invention relates to a thermal cycler, in particular for carrying out polymerase chain fractions in laboratory samples, comprising:
- thermoblock for tempering a sample-receiving thermoblock according to a tempering plan, during which switching between tempera ture levels by changing the temperature at the thermoblock with a temperature change rate; an electronic control device which has a data processing device and which is set up to control the temperature control device in order to carry out the following steps:
- tempering plan data that determine the tempering plan and runtime data that determines the running time of the tempering plan, and using the at least one, previously determined, in particular according to the method for determining at least one temperature change speed from temperature plan data and runtime data, at least one temperature change speed Determining control parameters which contain at least one rate of temperature change and which determine a temperature control plan corresponding to the temperature control plan;
- the electronic control device of the thermal cycler is set up, in particular, to carry out the method for determining at least one temperature change rate from temperature control plan data and runtime data, the electronic control device being set up to execute an evaluation program by means of the data processing device of the electronic control device, and which is set up to carry out the following steps:
- the data processing device of the electronic control device preferably has an interface device via which a data connection to an external data processing device can be established, the method for determining at least one temperature change rate from temperature control plan data and runtime data being carried out in particular on this external data processing device in order to provide the at least one temperature change rate, wherein the data processing device of the electronic control device is set up to receive this at least one temperature change rate, in particular also the temperature control plan data and / or the runtime data, via the data connection.
- the thermal cycler preferably has a user interface device, the electronic control device being set up to record the temperature control plan data entered by a user via the user interface device and to record the runtime data entered by a user via the user interface device.
- the invention also relates to a program code which carries out the following steps when it is executed by means of a data processing device, in particular the data processing device of an electronic control device of a thermal cycler:
- the invention also surpasses the use of the method for determining at least one temperature change rate from temperature control plan data and runtime data for controlling the temperature control device of a first thermal cycler by simulating the temperature control behavior of a second thermal cycler. This simulation helps the user migrate from the older, less powerful second thermal cycler to the more powerful first thermal cycler.
- a thermal cycler is a device that is able to set the temperature of at least one sample in succession to a predetermined temperature and to keep it at this temperature level for a predetermined holding time.
- the sequence of this temperature control is cyclical. That is, a predetermined temperature cycle, that is a sequence of at least two temperature levels is carried out repeatedly. This method is used in particular to carry out a polymerase chain reaction (PCR).
- PCR polymerase chain reaction
- a thermal cycler in particular the treatment device of the thermal cycler, preferably has a thermal block.
- a thermoblock is a sample holder made of a heat-conducting material, usually a metal-containing material or a metal, especially aluminum or silver.
- the sample holder has a contacting side which is contacted by at least one heating / cooling device of the thermal cycler, in particular at least one Peltier element, preferably several, in particular six, Peltier elements.
- the thermal cycler in particular the treatment device of the thermal cycler, has a control device with at least one control circuit, to which the at least one heating / cooling device is assigned as an actuator and at least one temperature measuring device as a measuring element.
- the temperature of a temperature level is regulated by means of the control device.
- a heat sink of the thermal cycler is used to cool sections of the thermal cycler, in particular the cooling of the Peltier elements.
- the thermal cycler in particular the treatment device of the thermal cycler, can have further heating and / or cooling elements.
- the thermal cycler, in particular the treatment device of the thermal cycler preferably has one
- Timer device with which time parameters of the setting of the temperature cycle can be controlled.
- the device-controlled treatment of the at least one laboratory sample corresponds to a temperature cycle treatment to which the at least one sample is subjected.
- Possible parameters, in particular program parameters, in particular user parameters, which are used to influence a temperature cycle treatment in a temperature control plan define in particular the temperature of a temperature level, the holding time of a temperature level, the control of further heating and / or cooling elements, and / or the number of temperature levels or Cycles, and / or at least one Process parameter that influences or defines the process, in particular the sequence, of a temperature control program consisting of several steps.
- the thermal cycler has, in particular, an electronic control device.
- a control device generally has, in particular, a data processing device, in particular a computing unit (CPU) for processing data and / or a microprocessor, or is a data processing device.
- the control device or a computing unit of the control device of a thermal cycler is preferably also set up for program-based control of the temperature control of the thermoblock.
- a thermal cycler for the cyclical temperature control of laboratory samples, in particular for carrying out a PCR in these laboratory samples, is a device-controlled treatment, that is to say in particular an at least partially automated treatment.
- a partially automated treatment it is in particular possible for the treatment to be carried out in such a way that at least one user input is made after the start of the treatment and before the end of the treatment, with which the user can influence the ongoing treatment, in particular, for example, by using one User interface device of the thermal cycler answers automatic query, in particular confirms or denies an entry or makes other entries.
- the treatment it is possible in particular for the treatment to have a plurality of treatment steps, which are in particular carried out automatically one after the other in time, and to have at least one treatment step which requires user input, in particular via a user interface device.
- user inputs on a thermal cycler are here the input of temperature control data, the input of the runtime, and / or optionally the input or selection of a thermal cycler TC X assigned to the input runtime.
- the device-controlled treatment is preferably a program-controlled treatment, that is to say a treatment controlled by a program.
- a program-controlled treatment of a sample is understood to mean that the treatment process essentially takes place by processing a plurality or a plurality of program steps.
- the program-controlled treatment is preferably carried out using at least one program parameter, in particular at least one program parameter selected by the user.
- a parameter selected by a user is also referred to as a user parameter.
- Typical user parameters for a thermal cycler determine the temperature control plan, in particular the height and holding time of the temperature levels of a temperature control cycle, the total number of cycles, and in the context of the present invention also the runtime of the temperature control plan, which is known to the user from previous thermal cycler applications of the same temperature control plan.
- the program-controlled treatment is preferably carried out with the aid of a digital data processing device, which can in particular be part of the control device of the laboratory device.
- the data processing device can have at least one processor, i.e. have a CPU and / or have at least one microprocessor.
- the program-controlled treatment is preferably controlled and / or carried out in accordance with the specifications of a program, in particular a control program. In particular, in the case of a program-controlled treatment, at least after the program parameters required by the user have been recorded, essentially no user activity is required.
- a program parameter is understood to be a variable which can be set in a predetermined manner within a program or subroutine, valid for at least one execution (call) of the program or subroutine.
- the program parameter is determined, for example by the user, and controls the program or subroutine and effects data output as a function of this program parameter.
- the program parameter influences and / or controls and / or the data output by the program control the control of the device, in particular the control of the treatment by means of the at least one treatment device.
- numeric keypad Use a numeric keypad to enter a number that corresponds to the desired value or by the user increasing or decreasing a value continuously or in increments until it corresponds to the desired value and thus setting the value.
- Other forms of input e.g. voice control and / or gesture control are conceivable.
- a program is understood in particular to be a computer program.
- a program is a sequence of instructions, in particular consisting of declarations and instructions, in order to be able to process and / or solve a specific functionality, task or problem on a digital data processing system.
- a program is usually available as software that is used with a digital data processing system.
- the program can be present in particular as firmware, in the case of the present invention in particular as firmware of the control device of the laboratory device.
- the program is usually on a data carrier as an executable program file, often in the so-called machine code, which is loaded for execution in the memory of the computer of the digital data processing system.
- the program is processed and executed by the processor (s) of the computer as a sequence of machine, ie processor instructions.
- “Computer program” is also understood to mean, in particular, the source text of the program, from which the executable code can arise in the course of the control of the laboratory device.
- a control program is understood to be an executable computer program which preferably controls and / or carries out the desired treatment of the at least one sample, in particular as a function of at least one program parameter.
- This program parameter can be a program parameter influenced by the user and / or a set one.
- the treatment can in particular be controlled by the control device generating one or more control parameters as a function of the program parameters, by means of which the at least one treatment device is controlled.
- the laboratory device preferably has an operating system, which can be or can have a control program.
- the control program can in particular designate an operating system of the laboratory device or a component of the operating system.
- the operating system controls the treatment and other operating functions of the laboratory device.
- the control program can be determined by control parameters that can be derived from the control device from program parameters or user parameters.
- a single container can be an open container or a closable container.
- a cover element in particular a closure cap, can be provided.
- the lid element can be firmly connected to the container, e.g. as a hinged lid or hinged closure cap, or can be used as a separate component.
- the plurality of individual containers are preferably arranged in fixed positions relative to one another, in particular arranged according to the crossing points of a grid pattern. This simplifies the automated control of the positions and in particular the individual addressing of samples.
- a multiple relationship can be designed as a plate element in which the individual containers are connected in such a way that they form a plate-shaped arrangement.
- the individual containers can or can be designed as depressions in a plate be connected to one another via web elements.
- the plate element can have a frame element in which the individual containers are held.
- These connections of components can be integral connections, ie integral connections and / or connections produced by a common injection molding process, or can be force-fit (English "force-fit") and / or form-fit (English “form-fit”).
- the plate element can in particular be a microtiter plate.
- Multiple containers can have a plurality (from 2 to 10) of individual containers. They can also have a large number (greater than 10), typically 12, 16, 24, 32, 48, 64, 96, 384, 1536 individual containers.
- the multiple container can in particular be a microtiter plate.
- a microtiter plate can be designed according to one or more industry standards ⁇ ), in particular the industry standards ANSI / SBS 1-2004, ANSI / SBS 2-2004, ANSI / SBS 3-2004, ANSI / SBS 4-2004.
- the maximum sample volume that can be taken up by a sample ratio is typically between 0.01 ml and 100 ml, in particular 10-100 ml, 100-500 ml, 0.5-5 ml, 5-25 ml, 25 -50 ml, 50-100 ml, depending on the type of transport container or sample container selected.
- the sample container is preferably partially or completely made of plastic. It is preferably a consumable that is typically used only for one treatment or a small number of treatment steps of the sample. However, the sample container can also consist partially or completely of another material.
- Preferred embodiments of the thermal cycler according to the invention can be found in particular in the description of one of the methods according to the invention.
- Preferred configurations of the processes according to the invention can be found in particular in the description of the thermal cyclers according to the invention.
- Further preferred configurations of the method according to the invention and of the thermal cycler can be found in the description of the exemplary embodiments according to the figures.
- FIG. 1 a shows the perspective front view of a thermal cycler according to the invention in one exemplary embodiment.
- Fig. 1 b shows the rear perspective view of the thermal cycler of Fig. 1 a.
- FIGS. 2a to 2e each show screen contents that can be displayed on the screen of the thermal cycler of FIGS. 1a and 1b.
- 2e shows a screen input mask in which the user, after entering the temperature control plan, can enter the runtime of the temperature control plan known to him, from which the thermal cycler independently calculates the rates of temperature change.
- 3a shows an example of a temperature control plan defined by the user, which is defined in the thermal cycler and method according to the invention in particular by temperature control data.
- FIG. 3b schematically shows a temperature control plan which is calculated by the thermal cycler and method according to the invention from the runtime and the temperature plan data of FIG. 3a.
- Fig. 3c schematically shows the temperature profile when changing between two temperature levels with the identification of the effective cooling rate as the difference quotient and the maximum cooling rate as the maximum differential.
- 4 schematically shows the sequence of an exemplary method according to the invention for determining at least one temperature change speed from temperature control plan data and runtime data
- FIG. 5 schematically shows the sequence of an exemplary method according to the invention for controlling a thermal cycler using the steps of the method for determining at least one temperature change rate from temperature plan data and runtime data from FIG. 3.
- the thermal cycler 100 is characterized by a lid handle 1 for closing and opening the heated lid, the heated lid 2, the heated lid 3 located in the heated lid to prevent condensation on the inside of the sample container with a heating plate 3 that can be heated to about 105 ° C., the aluminum thermoblock 4 with here 384 recordings for holding PCR tubes, in particular a 384 microtiter plate, which is contacted on its underside (not visible) here with six Peltier elements, which form the temperature control elements of the temperature control device of the thermal cycler for heating and cooling the thermoblock, and those on the underside ( are not visible) are contacted by a heat sink in order to dissipate the waste heat from the heat pumps to the environment, a mains connection socket with mains switch 5, a connection socket for Ethernet 6, a connection socket for data exchange with another thermal cycler 7, a flap 8 for covering a USB Connection, one as a user interface telle liked serving touchscreen 9,
- the thermal cycler 100 has a control device with a program-controlled microprocessor (not shown), which is set up to carry out the steps of the method 200 and 300 according to the invention in that the control program of the thermal cycler 100 is programmed to be able to carry out these steps.
- FIG. 3a shows a typical temperature control plan that may have been defined by a user on the touchscreen 9 (see, for example, FIG. 2a). It includes the desired (here: three) temperature levels 95 ° C, 65 ° C, 72 ° C and their folding times At1, At2, At3 of a cycle that is to be repeated successively 30 times ("x30").
- the temperature control plan has the time intervals At sC ooi, At s _heati and At sh eat2.
- the average temperature measured by temperature sensors of the temperature control device on the temperature block is cooled from 95 ° C to 65 ° C, for example with the cooling rate 1, 0 ° C / sec, which is the maximum cooling rate of a previously used, older thermal cycler TCx corresponds to that which had required the runtime now entered by the user for execution.
- the temperature is increased from 65 ° C to 72 ° C in the time interval Ats heati , for example with a heating rate of 2.0 ° C / sec, which corresponds to the maximum heating rate of the older thermocycler TCx used earlier, which is carried out by the user had now entered entered runtime.
- the temperature is increased from 72 ° C to 95 ° C, for example with a heating rate of 2.0 ° C / sec, so that the cycle can start again.
- the thermal cycler according to the invention has a larger maximum heating and cooling rate, namely 10 ° C./sec and 5 ° C./sec, so that it can easily carry out the calculated heating and cooling rates of the older devices.
- a settling time according to a standard settling control is also included in the time interval.
- the thermal cycler according to the invention simulates the temperature control behavior of the older device, so that the user can easily reproduce his previously performed reaction protocols. In this way, the migration from an older device to the thermal cycler according to the invention is facilitated.
- FIG. 4 shows the exemplary method 200 according to the invention for determining at least one temperature change rate for controlling the temperature control device of a thermal cycler by calculating at least one Velocity of temperature change from the known running time of a known temperature control plan.
- the method 200 here comprises the following steps:
- FIG. 5 shows the exemplary method 300 according to the invention for controlling the temperature control device of a thermal cycler, wherein the thermal cycler has the temperature control device for temperature control of a thermoblock receiving the samples for carrying out polymerase chain reactions in these samples according to the temperature control plan defined in the method according to one of claims 1 to 5, and has an electronic control device which is set up to control the temperature control device by means of control parameters.
- the method 300 here comprises the following steps:
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Control Of Temperature (AREA)
- Devices For Use In Laboratory Experiments (AREA)
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US17/278,007 US20210370305A1 (en) | 2018-09-21 | 2019-09-20 | Method for controlling a thermal cycler, and thermal cycler |
AU2019343307A AU2019343307A1 (en) | 2018-09-21 | 2019-09-20 | Method for controlling a thermal cycler, and thermal cycler |
CN201980060990.9A CN112867567B (zh) | 2018-09-21 | 2019-09-20 | 用于控制热循环仪的方法和热循环仪 |
EP19774080.6A EP3852929A1 (de) | 2018-09-21 | 2019-09-20 | Verfahren zur steuerung eines thermocyclers und thermocycler |
CA3112630A CA3112630A1 (en) | 2018-09-21 | 2019-09-20 | Method for controlling a thermal cycler, and thermal cycler |
JP2021514511A JP2022501180A (ja) | 2018-09-21 | 2019-09-20 | サーマルサイクラーを制御する方法、及びサーマルサイクラー |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP18195975.0A EP3626344A1 (de) | 2018-09-21 | 2018-09-21 | Verfahren zur steuerung eines thermocyclers und thermocycler |
EP18195975.0 | 2018-09-21 |
Publications (1)
Publication Number | Publication Date |
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WO2020058461A1 true WO2020058461A1 (de) | 2020-03-26 |
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ID=63678498
Family Applications (1)
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PCT/EP2019/075286 WO2020058461A1 (de) | 2018-09-21 | 2019-09-20 | Verfahren zur steuerung eines thermocyclers und thermocycler |
Country Status (7)
Country | Link |
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US (1) | US20210370305A1 (de) |
EP (2) | EP3626344A1 (de) |
JP (1) | JP2022501180A (de) |
CN (1) | CN112867567B (de) |
AU (1) | AU2019343307A1 (de) |
CA (1) | CA3112630A1 (de) |
WO (1) | WO2020058461A1 (de) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2024078737A (ja) * | 2022-11-30 | 2024-06-11 | 株式会社島津製作所 | 分析装置 |
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EP0488769A2 (de) | 1990-11-29 | 1992-06-03 | The Perkin-Elmer Corporation | Thermisches Kreisprozessgerät zur automatischen Ausführung der Polymerase-Kettenreaktion bei feiner Temperaturregelung |
US20020072112A1 (en) * | 1990-11-29 | 2002-06-13 | John Girdner Atwood | Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control |
EP2153901A1 (de) * | 2008-08-01 | 2010-02-17 | Eppendorf Ag | Temperierungsvorrichtung mit Testmöglichkeit und Verfahren zum Testen einer Temperierungsvorrichtung |
EP2338599A1 (de) * | 2009-12-23 | 2011-06-29 | Eppendorf Ag | Laborgerät mit einer Anordnung zum Temperieren von Proben und Verfahren zum Temperieren von Proben |
EP2907575A1 (de) * | 2014-02-14 | 2015-08-19 | Eppendorf Ag | Laborgerät mit Benutzereingabefunktion und Verfahren zur Benutzereingabe bei einem Laborgerät |
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US7188001B2 (en) * | 1998-03-23 | 2007-03-06 | Cepheid | System and method for temperature control |
US7939312B2 (en) * | 2006-08-30 | 2011-05-10 | Dxna Llc | Rapid thermocycler with movable cooling assembly |
US8871470B2 (en) * | 2007-03-21 | 2014-10-28 | Applied Biosystems, Llc | Adaptive thermal block temperature control method and system |
JP6078346B2 (ja) * | 2013-01-07 | 2017-02-08 | 株式会社日立ハイテクノロジーズ | 核酸増幅装置、温度制御方法、及び温度制御装置 |
JP2014147296A (ja) * | 2013-01-31 | 2014-08-21 | Hitachi High-Technologies Corp | 核酸検査装置 |
US9168533B2 (en) * | 2013-07-17 | 2015-10-27 | CrackerBio, Inc. | Thermal cycler device |
WO2015176253A1 (en) * | 2014-05-21 | 2015-11-26 | Coyote Bioscience Co., Ltd. | Systems and methods for low power thermal cycling |
JP2016144431A (ja) * | 2015-02-09 | 2016-08-12 | ソニー株式会社 | 核酸増幅用サーマルサイクラー、核酸分析装置、核酸増幅反応における温度変化率の制御システム、核酸増幅反応における温度変化率の制御方法、核酸分析方法及び核酸増幅反応における温度制御プログラム |
-
2018
- 2018-09-21 EP EP18195975.0A patent/EP3626344A1/de not_active Withdrawn
-
2019
- 2019-09-20 WO PCT/EP2019/075286 patent/WO2020058461A1/de unknown
- 2019-09-20 JP JP2021514511A patent/JP2022501180A/ja active Pending
- 2019-09-20 CN CN201980060990.9A patent/CN112867567B/zh active Active
- 2019-09-20 US US17/278,007 patent/US20210370305A1/en active Pending
- 2019-09-20 CA CA3112630A patent/CA3112630A1/en active Pending
- 2019-09-20 EP EP19774080.6A patent/EP3852929A1/de active Pending
- 2019-09-20 AU AU2019343307A patent/AU2019343307A1/en not_active Abandoned
Patent Citations (6)
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EP0488769A2 (de) | 1990-11-29 | 1992-06-03 | The Perkin-Elmer Corporation | Thermisches Kreisprozessgerät zur automatischen Ausführung der Polymerase-Kettenreaktion bei feiner Temperaturregelung |
US20020072112A1 (en) * | 1990-11-29 | 2002-06-13 | John Girdner Atwood | Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control |
EP1452608A1 (de) | 1990-11-29 | 2004-09-01 | Applera Corporation | Automatisierte Polymerasekettenreaktion |
EP2153901A1 (de) * | 2008-08-01 | 2010-02-17 | Eppendorf Ag | Temperierungsvorrichtung mit Testmöglichkeit und Verfahren zum Testen einer Temperierungsvorrichtung |
EP2338599A1 (de) * | 2009-12-23 | 2011-06-29 | Eppendorf Ag | Laborgerät mit einer Anordnung zum Temperieren von Proben und Verfahren zum Temperieren von Proben |
EP2907575A1 (de) * | 2014-02-14 | 2015-08-19 | Eppendorf Ag | Laborgerät mit Benutzereingabefunktion und Verfahren zur Benutzereingabe bei einem Laborgerät |
Also Published As
Publication number | Publication date |
---|---|
EP3852929A1 (de) | 2021-07-28 |
JP2022501180A (ja) | 2022-01-06 |
EP3626344A1 (de) | 2020-03-25 |
CN112867567B (zh) | 2023-11-07 |
CN112867567A (zh) | 2021-05-28 |
CA3112630A1 (en) | 2020-03-26 |
US20210370305A1 (en) | 2021-12-02 |
AU2019343307A1 (en) | 2021-05-06 |
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