Computer implemented method for performance verification of thermal block cycler unit

Abstract

To minimize energy consumption and time in performance verification of a thermal block cycler unit.SOLUTION: A thermal block cycler unit 110 includes; at least one thermal block 118 configured to receive at least one sample container; and a plurality of hardware modules 120 which includes a plurality of heating and / or cooling elements and at least one temperature sensor 122. The order of the successive functional tests of the hardware modules is such that all successive tests are used to test the thermal energy of the preceding test and / or the state of the thermal block cycler unit 110 of the preceding test, taking into account a criterion that energy consumption is balanced between steps so that the difference between the input temperature before testing and the output temperature after testing is minimized.SELECTED DRAWING: Figure 3

Description

[Technical field]

[0001] The present invention relates to a computer-implemented method, a laboratory system, a computer program, a computer readable storage medium, and a non-transitory computer readable medium for performance verification of a thermal block cycler unit. The method and device can be used in the field of biochemical analysis or research, or clinical diagnostics or research. The laboratory system can be used, for example, for automated heat treatment of samples. However, other applications are also feasible. [Background technology]

[0002] Functional testing of hardware modules is a common practice in medical devices to ensure correct operation of the equipment and to collect dates for predictive maintenance, for example. Such functional testing is known, for example, from WO 2022 / 101870, US 2014 / 0122006, US 5,602,756, EP 2108942, US 10,850,283, US 2013 / 0157376, KR 2375707, EP 3253492, US 6,703,236, AU 741806 or US 2008 / 0212643.

[0003] However, running functional tests can have several drawbacks, such as reducing the effective time that an end user can use a module or device, consuming energy, reducing the lifespan of the module or device, and often requiring the end user to get the device in the right state to start running. Summary of the Invention [Problem to be solved by the invention]

[0004] It is therefore desirable to provide a method and device that addresses the aforementioned technical problems. In particular, a method, computer program and device should be proposed that allows minimizing energy consumption and the time during which the thermal block cycler unit is not in use for a user. [Means for solving the problem]

[0005] This problem is addressed by a computer implemented method, laboratory system, computer program, computer readable storage medium and non-transitory computer readable medium for performance verification of a thermal block cycler unit with the features of the independent claims. Advantageous embodiments, which may be realized alone or in any combination, are set out in the dependent claims as well as throughout the specification.

[0006] When used below, the terms "having", "comprises" or "including" or any grammatical variants thereof are used in a non-exclusive manner. These terms may therefore refer both to the situation where, apart from the features introduced by these terms, no further features are present in the entity described in this context, and to the situation where one or more further features are present. As an example, the expressions "A has B", "A comprises B" and "A includes B" may refer both to the situation where no other elements are present in A apart from B (i.e., the situation where A is exclusively composed of B), and to the situation where, apart from B, one or more further elements are present in the entity A, such as element C, elements C and D, or even further elements.

[0007] Furthermore, it should be noted that the terms "at least one" or "one or more" or similar expressions indicating that a feature or element may be present more than once are typically used only once when introducing each feature or element. In the following, in most cases, when referring to each feature or element, the expressions "at least one" or "one or more" will not be repeated, despite the fact that each feature or element may be present more than once.

[0008] Furthermore, when used hereinafter, the terms "preferably", "more preferably", "particularly", "more particularly", "particularly", "more particularly" or similar terms are used with optional features without limiting the possibility of substitution. Features introduced by these terms are therefore optional features and are not intended to limit the scope of the claims in any way. The invention may be implemented by using alternative features, as would be understood by a person skilled in the art. Similarly, features introduced by "in an embodiment of the invention" or similar expressions are intended to be optional features without any limitation with respect to alternative embodiments of the invention, without any limitation with respect to the scope of the invention, and without any limitation with respect to the possibility of combining the feature introduced in such a way with other optional or non-optional features of the invention.

[0009] In a first aspect, a computer-implemented method for performance verification of a thermal block cycler unit for automated thermal processing of at least one sample is disclosed. The thermal block cycler unit comprises at least one thermal block configured to receive at least one sample container. The thermal block cycler unit further comprises a plurality of hardware modules, the hardware modules comprising a plurality of heating and / or cooling elements and at least one temperature sensor.

[0010] As used herein, the term "computer-implemented" is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to a special or customized meaning. The term may specifically, but not limited to, refer to a method involving at least one computer and / or at least one computer network or cloud. The computer and / or computer network and / or cloud may comprise at least one processor configured to perform at least one of the method steps of the method according to the invention. Preferably, each of the method steps is performed by the computer and / or computer network and / or cloud. The method may be performed fully automatically, e.g., without user interaction. As used herein, the term "automatically" is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to a special or customized meaning. The term may specifically, but not limited to, refer to a process performed fully by at least one computer and / or computer network and / or cloud and / or machine, e.g., without manual action and / or user interaction.

[0011] The method may be used in the field of in vitro diagnostics. The term "in vitro diagnostics" as used herein is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to a special or customized meaning. For example, in vitro diagnostics may include performing at least one test on a sample, such as a biological sample obtained from a human or animal body. The method may be performed by using a laboratory system, such as a laboratory or other environment for performing scientific or technical research, experiments and / or measurements. For example, the laboratory system may be part of a clinical laboratory, a medical laboratory, a forensic laboratory, or a blood bank.

[0012] As used herein, the term "sample" is a broad term and should be given its ordinary and customary meaning to one of skill in the art and should not be limited to a special or customized meaning. The term may specifically refer to, but is not limited to, a material suspected of containing at least one analyte of interest. The sample may be a biological sample. As used herein, the term "biological sample" is a broad term and should be given its ordinary and customary meaning to one of skill in the art and should not be limited to a special or customized meaning. The term may specifically refer to, but is not limited to, at least one biological material that may potentially contain at least one analyte of interest. The sample may be derived from any biological source, such as physiological fluids including blood, saliva, eye lens fluid, cerebrospinal fluid, sweat, urine, milk, peritoneal fluid, mucus, synovial fluid, peritoneal fluid, amniotic fluid, tissue, cells, and the like. For example, a biological sample may be or may include an aliquot of a substance, such as a biological compound. For example, the biological sample may be or include at least one biological sample, such as one or more of blood, serum, plasma, urine, saliva. The biological sample may be a liquid sample. For example, the liquid sample may be or include at least one pure liquid containing biological material, such as a liquid substance and / or a solution containing one or more liquid substances. The liquid sample may be or include a liquid mixture, such as a suspension, emulsion, and / or dispersion of biological material. The biological sample may be an individual sample, such as at least one sample of tissue. The sample may be pre-treated before use, such as preparation of plasma from blood, dilution of viscous fluids, dissolution, etc. Methods of treatment may include filtration, distillation, concentration, inactivation of interfering components, and addition of reagents.A sample may be used directly as obtained from a source or after pretreatment to modify the characteristics of the sample, for example, after dilution with another solution or mixing with a reagent, for performing one or more diagnostic assays, such as clinical chemistry assays, immunoassays, coagulation assays, nucleic acid tests, etc. Thus, the term "sample" as used herein refers not only to the original sample, but also to a sample that has already been processed, such as pipetted, diluted, mixed with a reagent, concentrated, purified, amplified, etc. As used herein, the term "analyte" may refer to a compound or composition to be detected or measured.

[0013] As used herein, the term "thermal block cycler unit", also referred to as thermocycler, PCR machine or DNA amplifier, is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to a special or customized meaning. The term may specifically, but not exclusively, refer to an apparatus configured to perform at least one cyclical temperature change, e.g., a plurality of predetermined temperature cycles. The thermal block cycler may be configured to perform temperature cycles, e.g., for a temperature-sensitive reaction, e.g., an amplification reaction, such as polymerase chain reaction (PCR). For example, the thermal block cycler unit may be designed as described in European Patent Application No. 1710017, which is incorporated herein in its entirety by reference. Thus, for example, the thermal block cycler unit may comprise a thermal block, at least one thermoelectric cooler, at least one vapor chamber mount, and a heat sink.

[0014] The thermal block cycler may comprise at least one thermal block. The thermal block may be a solid device arranged to have good thermal conductivity. There are several materials known to those skilled in the art that have good thermal conductivity, and without being bound by theory, most materials that have good electrical conductivity are also good thermal conductors. Thus, materials such as copper, aluminum, silver or graphite are suitable for the thermal block. On the other hand, plastics and ceramics may also have sufficient thermal conductivity to be used as materials for the thermal block.

[0015] The thermal block cycler unit may further comprise a heat sink configured to dissipate heat. Typically, the heat sink is formed from a similar thermally conductive material as the thermal block outlined above. Thus, the heat sink is mostly made from metal, preferably aluminum or silver. Alternatively, the heat sink may be formed from plastics and ceramics, only if good thermal conductivity is achieved. To achieve maximum heat dissipation, the heat sink is arranged to provide a large surface-to-volume ratio. This may be achieved by an assembly of fins arranged on a base plate. A large surface-to-volume ratio reduces the heat transfer resistance between the heat sink and the surrounding air.

[0016] The term "thermal treatment" as used herein is a broad term and should be given its ordinary and customary meaning to one of skill in the art and should not be limited to a special or customized meaning. The term may specifically refer to at least one processing step on a sample that includes at least one temperature change, such as, but not limited to, heating and / or cooling. The temperature change may include alternating heating and cooling of the sample. The thermal treatment may include increasing and / or decreasing the temperature. The temperature change may be performed continuously or non-continuously in discrete predetermined steps.

[0017] The thermal block is configured to receive at least one sample vessel. The thermal block cycler, in particular the thermal block, may comprise at least one sample block configured to receive at least one sample vessel. The sample block may be designed integrally with the thermal block.

[0018] The term "sample vessel" as used herein is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to a special or customized meaning. The term may specifically refer to, but is not limited to, a device configured to store and / or contain at least one sample. The sample vessel may be or comprise one or more of at least one tubular vessel, at least one rack, at least one pack or at least one slide. For example, the sample vessel may comprise at least one multi-well plate. The term "multi-well plate" as used herein is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to a special or customized meaning. The term may specifically refer to, but is not limited to, any plate-like device configured to store samples, e.g., small volumes of fluids, either permanently or temporarily. Small volumes in this respect should be understood as volumes of fluids ranging from nl to ml, such as 10 nl to 100 ml, preferably 0.1 μl to 10 ml, even more preferably 0.1 μl to 5 ml. Basically, the design of a multiwell plate may depend on the respective application. A multiwell plate may be designed as a device for storing a single fluid sample or multiple fluid samples. Similarly, the geometric shape of each storage area of ​​a multiwell plate may depend on the respective application of the multiwell plate. The storage area may be designed as a well, a channel, a depression, a recess, etc. For example, a multiwell plate may comprise multiple wells. The term "multiwell plate" as used herein may refer to a flat plate with multiple "wells" used as small test tubes. Such multiwell plates are also known as microtiter plates. Microtiter plates have become a standard tool in analytical research and clinical testing laboratories. Multiwell plates may typically have 6, 24, 96,384 or 1536 sample wells arranged in a rectangular matrix, for example 2:3.The wells can be either round or square. The multi-well plate may be configured as a processing plate. The processing plate may be configured to undergo at least one sample processing step. The sample processing may include one or more of sample specific steps, aliquoting, heating, cooling, magnetic separation, mixing, washing, elution, dilution, chemical reaction, lysis of the sample, capture of nucleic acid, release of nucleic acid, extraction of nucleic acid, etc. The sample container may be a plastic container. For example, the sample container may be designed to allow optimal heat transfer.

[0019] The term "sample block" as used herein is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art and should not be limited to a special or customized meaning. The term may specifically, but not be limited to, refer to a block-shaped structural member comprising at least one chamber and / or recess configured to receive a sample vessel. The sample block may be configured to achieve rapid temperature changes and uniform temperature throughout the block. After inserting a sample vessel into the sample block, the temperature of the sample block may be altered, e.g., increased and / or decreased according to a predetermined temperature cycle.

[0020] As used herein, the term "performance" is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to a special or customized meaning. The term may specifically refer to, but is not limited to, an index that characterizes the thermal behavior of the thermal block cycler unit. Performance may be characterized as good or poor thermal performance. Good thermal performance may relate to performance within the manufacturer's specifications. Poor thermal performance may relate to performance that deviates from the manufacturer's specifications. Performance may be characterized with respect to at least one parameter, such as at least one parameter selected from the group consisting of heating rate, cooling rate, temperature distribution, thermal uniformity, thermal accuracy, thermal resolution, energy efficiency (heat loss), and the like. The performance of the thermal block cycler unit may be affected by the performance of individual elements of the thermal block cycler unit, such as the hardware modules of the thermal block cycler unit.

[0021] The term "performance verification" as used herein is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art and should not be limited to any special or customized meaning. The term may specifically refer to, but is not limited to, quality control of the performance of a thermal block cycler unit, such as at least one process to verify good thermal performance of the thermal block cycler unit.

[0022] The method steps may be performed in a given order or in a different order. Further, there may be one or more additional method steps not listed. Further, one, more than one, or even all of the method steps may be performed repeatedly.

[0023] The method includes sequential functional testing of the hardware modules, the sequence of testing being: - every successive test uses the thermal energy and / or thermal block cycler unit conditions of the preceding test for the test; and The energy consumption is balanced between the steps such that the difference between the input temperature before the continuous testing of the hardware modules and the output temperature after the continuous testing of the hardware modules is minimized; It is specified taking into consideration the following criteria.

[0024] The term "functional testing" as used herein is a broad term and should be given its ordinary and customary meaning to one skilled in the art and should not be limited to a special or customized meaning. The term may specifically refer to, but is not limited to, testing at least one basic function of each hardware module, such as whether the hardware module is working at all, and / or testing each hardware module against its respective specifications. The term "sequential" functional testing as used herein is a broad term and should be given its ordinary and customary meaning to one skilled in the art and should not be limited to a special or customized meaning. The term may specifically refer to, but is not limited to, sequentially functional testing of a hardware module, such as all hardware modules of a thermal block cycler unit. Functional testing may include individually testing each hardware module or groups of hardware modules, for example of the same type.

[0025] The use of the above criteria allows for energy efficiency and speed. These two objectives can be achieved by setting the sequence of test steps such that every successive step benefits from the thermal energy and / or thermocycler conditions of its preceding step. Thus, the amount of energy put into the system can be minimized, which contributes to a shorter run time. Also, the energy can be balanced between steps such that the difference between the start temperature (temperature before the start of the test) and the end temperature (temperature after the end of the test) is minimized. This can also reduce the time that the thermocycler is not used by the end user.

[0026] The term "use of thermal energy of a prior test for testing" as used herein is a broad term and should be given its ordinary and customary meaning to one skilled in the art and should not be limited to a special or customized meaning. The term may specifically, but not limited to, refer to using thermal energy as a starting point for testing and / or as a test condition during testing. The term "state of the thermal block cycler unit" as used herein is a broad term and should be given its ordinary and customary meaning to one skilled in the art and should not be limited to a special or customized meaning. The term may specifically, but not limited to, refer to any state of at least one hardware module of the thermal block cycler unit that has been determined and / or set and / or reached during and / or by a prior test. The state may be the state of a hardware module that has been tested during a prior test and / or the state of a hardware module that has been tested so far during execution of the method. For example, the state may be the thermal state of the thermal block cycler unit at, for example, the end of a prior test. The thermal state may be used as a starting point for testing and / or as a test condition during testing. For example, the state may be the test result of a preceding test, e.g., a pass or fail state with respect to at least one specified acceptance criterion. For example, if one or more previous steps fail, the next test step may not be performed. For example, if a temperature sensor is detected as not functioning and / or if a pump of the cooling system is faulty, the thermal block will not be heated. As used herein, the term "use to test the state of the thermal block cycler unit of its preceding test" is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to a special or customized meaning. The term may specifically refer to, but is not limited to, the state of the thermal block cycler unit, e.g., taking into account the test result and / or the setup for the next test. For example, the state may be used as a starting point for a test and / or as a test condition during the test.

[0027] The term "energy consumption" as used herein is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art and should not be limited to a special or customized meaning. The term may specifically refer to any energy applied to a thermal block cycler unit to perform a method for commissioning, such as, but not limited to, electrical energy for heating and / or cooling.

[0028] The term "balancing" as used herein is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to a special or customized meaning. The term may specifically refer, but is not limited to, for example, ensuring that the overall temperature gradient between the input and output temperatures before and after successive testing of hardware modules is minimal. Balancing may include ensuring that the temperature gradient between the output temperature of a test of a hardware module and the input temperature of successive tests or hardware modules is minimal. The temperature profile over the method steps for performance verification may be as isothermal as possible. Balancing may include determining, for example calculating, a number of potential test sequences for functional testing of hardware modules and selecting a test sequence having an order of functional testing of hardware modules that meets this requirement.

[0029] The performance verification may be part of an automated diagnostic workflow of the thermal block cycler unit. For example, the performance verification may be part of a workflow for predictive maintenance. For example, the performance verification may be part of a workflow for verifying the calibration of the thermal block cycler unit. The performance verification may be performed at the start of operation, e.g. during initial setup and / or every time the thermal block cycler unit is turned on. The method may be performed at regular time intervals and / or at the request of a user. The performance verification may be automatically and repeatedly performed at predefined times, e.g. every 10 runs, or once a day, or every boot of the instrument. The performance verification may be automatically triggered and performed when a deviation in performance is observed for at least one hardware module, such as a lack of signal from a temperature sensor, malfunction of the electronics, etc. For example, the performance test may be triggered by detection of at least one deviation of the heating and / or cooling slopes from any expected profile in order to detect the root cause. For example, the performance test may be triggered in case of high or low heat sink temperature during the run. The performance verification may be automatically triggered and / or performed by at least one control unit. Additionally, the performance verification may be performed upon request of a user, for example via at least one user interface.

[0030] The term "control unit" as used herein is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to a special or customized meaning. The term may specifically refer to any device or system configured to perform specified operations, preferably, but not limited to, by using at least one data processing device, more preferably, by using at least one processor and / or at least one application specific integrated circuit. Thus, by way of example, at least one control unit may comprise at least one data processing device in which software code including several computer commands is stored. The control unit may provide one or more hardware elements for performing one or more of the specified operations and / or provide one or more processors with software to be executed to perform one or more of the specified operations. The control unit may comprise one or more computers, application specific integrated circuits (ASICs), digital signal processors (DSPs), or one or more programmable devices such as field programmable gate arrays (FPGAs). However, additionally or alternatively, the control unit may also be embodied fully or partially by hardware. The thermal block cycler unit may comprise and / or be connected to at least one control unit.

[0031] The term "processor" or "processing device" as used herein is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to a special or customized meaning. The term may specifically, but not limited to, refer to any logic circuitry configured to perform the basic operations of a computer or system, and / or may generally refer to a device configured to perform calculations or logical operations. In particular, a processor may be configured to process basic instructions that run a computer or system. By way of example, a processor may include at least one arithmetic logic unit (ALU), at least one floating point unit (FPU), such as a numeric coprocessor or numeric coprocessor, a number of registers, specifically registers configured to provide operands to the ALU and store the results of the operations, and memories, such as L1 and L2 cache memories. In particular, a processor may be a multi-core processor. In particular, a processor may be or include a central processing unit (CPU). Additionally or alternatively, the processor may be or include a microprocessor, and thus specifically, the elements of the processor may be included in a single integrated circuit (IC) chip. Additionally or alternatively, the processor may be or include one or more chips, such as one or more application specific integrated circuits (ASICs) and / or one or more field programmable gate arrays (FPGAs) and / or one or more tensor processing units (TPUs) and / or dedicated machine learning optimization chips. The processor may be specifically configured, such as by software programming, to perform one or more evaluation operations.

[0032] The method may include displaying a result of the commissioning via at least one communication interface and / or at least one user interface. Additionally or alternatively, the method may include reporting a result of the commissioning to a Laboratory Information Management System (LIMS) via the communication interface. The method may include at least one action depending on the result of the commissioning, such as one or more of continuing operation, repeating at least one step of the commissioning, issuing an alert, issuing information to a manufacturer or service provider, replacing a hardware module, requesting a thermal calibration, calling service, controlling a coolant (in the case of liquid cooling), or controlling an electrical connection to a heating module.

[0033] The term "communication interface" as used herein is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to a special or customized meaning. The term may specifically refer to, but is not limited to, an item or element forming a boundary configured to transfer information. The communication interface may be configured to transfer information from a computing device, e.g., a computer, e.g., to transmit or output information to another device. Additionally or alternatively, the communication interface may be configured to transfer information to a computing device, e.g., a computer, e.g., to receive information. The communication interface may specifically provide a means for transferring or exchanging information. In particular, the communication interface may provide a data transfer connection, e.g., Bluetooth, NFC, inductive coupling, and the like. By way of example, the communication interface may be or may comprise at least one port comprising one or more of a network or Internet port, a USB port, and a disk drive. The communication interface may be at least one web interface. The term "user interface" as used herein is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art and should not be limited to a special or customized meaning. The term may refer to features of laboratory equipment that are configured to interact with its environment, such as for the purpose of exchanging information unidirectionally or bidirectionally, such as for one or more exchanges of data or commands, but is not limited thereto. For example, a user interface may be configured to share information with a user and receive information by a user. A user interface may be a feature that visually interacts with a user, such as a display, or a feature that acoustically interacts with a user. A user interface may comprise one or more of a graphical user interface, a data interface, such as a wireless and / or wired data interface, by way of example.

[0034] The hardware module comprises a number of heating and / or cooling elements and at least one temperature sensor.

[0035] The hardware module may include at least one temperature sensor. The term "sensor" as used herein is a broad term and should be given its ordinary and customary meaning to one skilled in the art and should not be limited to a special or customized meaning. The term may refer specifically, but not limited to, any element or device configured to detect at least one condition or measure at least one measurement variable. The term "temperature sensor" as used herein is a broad term and should be given its ordinary and customary meaning to one skilled in the art and should not be limited to a special or customized meaning. The term may refer specifically, but not limited to, a sensor configured to measure temperature, e.g., absolute value and / or temperature change. The thermal block cycler unit may include multiple temperature sensors. At least one temperature sensor may be used for absolute temperature control. At least one other temperature sensor may be used to determine temperature uniformity.

[0036] The term "heating element and / or cooling element" as used herein is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art and should not be limited to any special or customized meaning. The term may specifically, but is not limited to, refer to a device configured to change, e.g., increase and / or decrease, its temperature and / or the temperature of an ambient temperature and / or a further device.

[0037] For example, the hardware module may include one or more of at least one fan, at least one actuated pump, at least one thermoelectric cooler, and at least one vapor chamber mount.

[0038] The hardware module may include at least one fan. The fan may be configured to cool the thermal block cycler unit during operation. The fan may be configured to provide airflow through the thermal block cycler unit. The airflow may be emitted from the thermal block cycler unit at an opening in a housing of the thermal block cycler unit. The thermal block cycler unit may include multiple fans.

[0039] The hardware module may include at least one actuation pump. The thermal block cycler unit may include at least one water cooling system with actuation pumps and solid-liquid and liquid-air heat exchangers.

[0040] The hardware module may include at least one thermoelectric cooler (TEC). A thermoelectric device is a solid-state heat pump formed from a semiconductor material that includes a series of p-type and n-type semiconductor pairs or junctions sandwiched between ceramic plates. Heat is absorbed by the electrons at the cold junction as they move from the low energy level of the p-type element to the high energy level of the n-type element. At the hot junction, energy is released, for example to a heat sink, as the electrons move from the high energy n-type element to the low energy p-type element. A DC power source may provide the energy to move the electrons through the system. A typical TEC may include up to 127 junctions and can deliver as much as 120 W of heat. The amount of heat delivered may be proportional to the amount of current flowing through the TEC, allowing for tight temperature control. By reversing the current, the TEC can function as a heater or cooler, which may be useful for controlling an object in a changing ambient environment or cycling at different temperatures. Sizes range from 2 to 62 mm, and multiple TECs can be used for greater degrees of cooling. Due to the relatively large amount of heat delivered over a small area, TECs generally require a heat sink to dissipate the heat to the surrounding environment. A well-known type of TEC is the Peltier element. The thermal block cycler unit may be driven by multiple thermoelectric coolers. For example, the thermal block cycler unit may be driven by six Peltier elements.

[0041] The hardware module may include at least one vapor chamber mount. The thermal block cycler unit may include multiple vapor chamber mounts. For example, the VCM may be designed as described in European Patent Application No. 1710017 or International Publication No. WO 2013 / 075839, the entirety of which is incorporated herein by reference. The vapor chamber mount may be configured to provide temperature uniformity across the thermal block. The VCM may be configured to transport and distribute heat. The vapor chamber mount may have an at least partially plate-like structure. The VCM may include a lower shell and an upper shell. At least one gas-tight and liquid-tight intermediate space may be formed between the lower shell and the upper shell, in which the fluid working medium and the porous material are disposed. The porous material may contact the upper shell and / or the lower shell at least in some areas, but does not completely fill the intermediate space, forming at least one cavity-like vapor gap. For example, ammonia, water, acetone, or methanol are typically used as the working medium. The control unit can vary the thermal conductivity of the VCM, for example by adjusting the flow rate in the intermediate space.

[0042] For example, the method includes testing a temperature sensor. The test may include an electrical test. The electrical test may include testing whether a temperature value is generated by the temperature sensor. The electrical test may include a basic functional test whether the temperature sensor or a different temperature sensor is working at all, for example independent of the accuracy of the measured temperature. If a temperature value is generated, for example if a signal from the temperature sensor is received by the control unit, the temperature sensor has passed the test. If not, the temperature sensor is in error. In this case an error may be issued and / or signaled by the control unit.

[0043] Additionally or alternatively, for example, the method includes testing the temperature sensor, whereby testing includes testing the response behavior of the temperature sensor. Such a test may also mean testing the heating capacity of the thermal block. Testing the response behavior may include increasing the temperature to a maximum temperature or decreasing the temperature to a minimum temperature over a predefined time range, reading temperature values ​​generated by the temperature sensor before and after changing the temperature, calculating the difference and comparing the difference with at least one predefined threshold value for a minimum temperature change. The threshold value for a minimum temperature change may be defined with respect to the thermal design of the heating block, assuming a worst case scenario, i.e. worst case ambient thermal conditions. If the threshold value for a minimum temperature change is exceeded and / or at least reached, the temperature sensor has passed the test. If not, the temperature sensor is in error. In this case, an error may be issued and / or signaled by the control unit.

[0044] Additionally or alternatively, the method includes testing the fan. Testing may include testing the fan speed. Testing the fan speed may include setting the fan to maximum, monitoring the fan speed, for example by using a fan internal status signal, and comparing the fan speed to at least one predefined threshold at maximum fan speed. The threshold may be defined as an expected fan speed according to the fan's data sheet. If the threshold is exceeded and / or reached, the fan has passed the test. If not, the fan is in error. In this case, an error may be issued and / or signaled by the control unit.

[0045] Additionally or alternatively, the method includes testing the operational pump. Testing may include testing the pump speed. Testing the pump speed may include setting the pump to maximum, monitoring the pump speed, for example by using its internal status signal, and comparing the pump speed to at least one predefined threshold at the maximum pump speed. The threshold may be defined as an expected pump speed according to the pump's data sheet. If the threshold is exceeded and / or reached, the pump has passed the test. If not, the pump is in error. In this case, an error may be issued and / or signaled by the control unit.

[0046] Additionally or alternatively, the method includes testing a thermoelectric cooler (TEC). Testing the TEC may include testing multiple thermoelectric cooler pairs consecutively. Testing may include measuring current and / or voltage during heating and cooling. Testing may further include comparing the measured current and / or voltage during heating and cooling to a predefined threshold. The threshold may be defined according to electrical parameters of the TEC assuming a worst case scenario, e.g., worst case ambient temperature conditions. If the threshold is exceeded and / or reached, the respective thermoelectric cooler pair has passed the test. If not, the respective thermoelectric cooler pair is in error. In this case, an error may be issued and / or signaled by the control unit.

[0047] Additionally or alternatively, the method includes testing all thermoelectric coolers. Testing may include testing power consumption during heating. The power consumption may be compared to a predefined threshold. The threshold may be defined according to electrical parameters of the TEC, assuming a worst case scenario, e.g. worst case ambient temperature conditions. If the threshold is exceeded and / or reached, the thermoelectric cooler passes the test. If not, at least one of the thermoelectric coolers is in error. In this case, an error may be issued and / or signaled by the control unit.

[0048] Additionally or alternatively, the method may include testing at least one vapor chamber mount (VCM). Testing may include sequentially controlling a thermoelectric cooler and monitoring a thermal distribution of the vapor chamber mount. A TEC may be spatially disposed between the solid-liquid heat exchanger and the VCM. The TEC may be sequentially controlled and the thermal distribution in the VCM may be monitored. The thermal distribution may be compared to a predefined threshold. The threshold may be defined as a maximum deviation from an expected temperature uniformity after a predefined time. If the threshold is not exceeded and / or reached, the VCM has passed the test. Otherwise, at least one of the VCMs is in error. In this case, an error may be issued and / or signaled by the control unit.

[0049] For example, the method may include the following series of tests: i. Basic electrical testing of temperature sensors; ii. Fan testing; iii. Pump testing; iv. Sequential testing of multiple thermoelectric cooler pairs; v. Testing the power consumption of all thermoelectric coolers; vi. Temperature sensor gradient testing; vii. Vapor chamber mount testing; viii. At least one termination action, including one or more of disabling all active elements and reporting the data; Includes.

[0050] This order of tests may make it possible to meet the aforementioned criteria. However, other orders may be envisaged. The method may include all steps i-viii listed above, or one or more tests may be skipped, for example, the test of the vapor chamber mount may be skipped if no vapor chamber mount is present in the thermal block cycler unit. Furthermore, the steps may be performed in a given order or in a different order. Furthermore, one or more of the method steps may be performed in parallel and / or in a time-overlapping manner. Furthermore, one or more of the method steps may be performed repeatedly. Furthermore, there may be additional method steps not listed.

[0051] The tests and / or order of tests to be performed may depend on the hardware modules present in the thermal block cycler unit. The order of tests and / or steps to be performed may be determined, for example, automatically.

[0052] For example, during or upon initialization of the thermal block cycler unit, e.g. automatically, a test of each hardware module of the thermal block cycler unit may be performed according to a test protocol, e.g. as predefined by the manufacturer. Said testing of each hardware module may comprise determining at least one thermal profile for each test. The thermal profiles of the tests may be analyzed and the tests to be performed and / or the order of the tests of the method may be defined taking into account the aforementioned criteria.

[0053] The method may be performed fully automatically. For example, each step may be performed by a control unit by controlling the operation of the respective hardware modules. The control unit may be configured to receive the test results via the communication interface. The control unit may be configured to evaluate the test results and issue an error and / or at least one other action.

[0054] The method may include testing the complete order of steps or aborting the sequence if an error occurs.

[0055] A basic electrical test of the temperature sensor may be performed first. In step i, no energy may be input or output. This step may be performed quickly. In step ii, the temperature may be reduced. In step iii, the temperature is reduced. Steps iv. and v. may be temperature neutral, e.g., the temperature may be increased and decreased. Step iv. may include successive substeps of testing the first TEC pair, testing the second TEC pair, and testing the third TEC pair. In step v., the power consumption of all TECs may be tested and the temperature is increased. In step vi., a test of the temperature sensor gradient may be performed, and the temperature sensor heating rate of change may be measured using the increasing temperature of the previous step. This step may include reversing the TEC to cool and measuring the cooling rate of change. A test of the vapor chamber mount may be performed such that the end temperature is similar to the start temperature of the complete sequence. Termination actions may include disabling all active elements and / or reporting the data.

[0056] In a further embodiment, the laboratory system comprises at least one instrument for performing temperature-dependent reactions, comprising a thermal block cycler unit for automated heat treatment of at least one sample, at least one control unit and at least one communication interface. The laboratory system is configured to perform the method for performance verification according to the invention as described above or in more detail below. For details, options and definitions, reference may be made to the aforementioned method.

[0057] The term "instrument" as used herein is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art and should not be limited to a special or customized meaning. The term may refer to any device configured to perform a sample processing step, particularly, but not limited to, an instrument. For example, an instrument may be a clinical diagnostic analyzer.

[0058] The instrument further comprises at least one detection unit. In addition to the thermal block cycler unit, the instrument may comprise at least one optical unit configured for example for fluorescence excitation and detection of fluorescence.

[0059] Further disclosed and proposed herein is a computer program comprising computer executable instructions which, when executed on a computer or a computer network, performs the method according to the invention in one or more of the embodiments contained herein. In particular, the computer program may be stored on a computer readable data carrier and / or on a computer readable storage medium.

[0060] As used herein, the terms "computer-readable data carrier" and "computer-readable storage medium" may specifically refer to non-transitory data storage means such as hardware storage media having computer-executable instructions stored thereon. A computer-readable data carrier or storage medium may specifically be or include a storage medium such as a random access memory (RAM) and / or a read-only memory (ROM).

[0061] Thus, in particular, for example one, two or more, or even all, of the method steps of sequences i to iii may be carried out using a computer or a computer network, preferably using a computer program, as described above.

[0062] Further disclosed and proposed herein is a computer program product, which comprises program code means for executing the method according to the invention in one or more of the embodiments contained herein when the program is executed on a computer or a computer network. In particular, the program code means may be stored on a computer readable data carrier and / or a computer readable storage medium.

[0063] Further disclosed and proposed herein is a data carrier storing a data structure which, after being loaded into a computer or computer network, such as a working memory or main memory of a computer or computer network, is capable of performing the methods according to one or more of the embodiments disclosed herein.

[0064] Further disclosed and proposed herein is a non-transitory computer-readable medium comprising instructions that, when executed by one or more processors, cause the one or more processors to perform a method according to one or more of the embodiments disclosed herein.

[0065] Further disclosed and proposed herein is a computer program product having program code means stored on a machine-readable carrier for performing the method according to one or more of the embodiments disclosed herein when the program is executed on a computer or a computer network. As used herein, a computer program product refers to a program as a tradeable product. The product can generally be present in any format, such as a paper format, or on a computer-readable data carrier and / or a computer-readable storage medium. In particular, the computer program product may be distributed over a data network.

[0066] Finally, a modulated data signal containing instructions readable by a computer system or computer network for carrying out a method according to one or more of the embodiments disclosed herein is disclosed and proposed herein.

[0067] With respect to computer-implemented aspects of the present invention, one or more or all of the method steps of the method according to one or more of the embodiments disclosed herein may be performed by using a computer or a computer network. Thus, in general, any of the method steps involving providing and / or manipulating data may be performed by using a computer or a computer network. In general, these method steps may include any method steps, except for those method steps that typically require manual labor, such as providing a sample and / or certain aspects of performing the actual measurement. Specifically, in this specification, a computer or computer network comprising at least one processor, the processor being configured to execute a method according to one of the embodiments described herein, - a computer-loadable data structure configured, when executed on a computer, to carry out a method according to one of the embodiments described herein; a computer program configured, when it is run on a computer, to carry out a method according to one of the embodiments described herein, a computer program comprising program means for carrying out a method according to one of the embodiments described herein when said computer program is run on a computer or on a computer network, a computer program comprising program means according to the preceding embodiment, the program means being stored on a computer readable storage medium; a storage medium storing a data structure, the data structure being configured to execute a method according to one of the embodiments described herein after being loaded into a main memory and / or a working memory of a computer or a computer network, and A computer program product comprising program code means storable or stored on a storage medium, the program code means performing the method according to one of the embodiments described herein when executed on a computer or a computer network. is further disclosed.

[0068] In summary, without excluding further embodiments, the following embodiments can be envisaged:

[0069] Embodiment 1. A computer-implemented method for performance verification of a thermal block cycler unit for automated thermal processing of at least one sample, the thermal block cycler unit comprising at least one thermal block configured to receive at least one sample container; the thermal block cycler unit further comprises a plurality of hardware modules, the hardware modules comprising a plurality of heating and / or cooling elements and at least one temperature sensor; The method includes sequential functional testing of the hardware modules, the sequence of testing being: - every successive test uses the thermal energy and / or thermal block cycler unit conditions of the preceding test for the test; and Energy consumption is balanced between steps such that the difference between the input temperature before sequentially testing the hardware modules and the output temperature after sequentially testing the hardware modules is minimized. A method that is prescribed taking into consideration the following criteria.

[0070] Embodiment 2. The method according to the preceding embodiment, wherein the hardware module comprises one or more of at least one temperature sensor, at least one fan, at least one actuated pump, at least one thermoelectric cooler, and at least one vapor chamber mount.

[0071] Embodiment 3. The method according to the preceding embodiment, wherein the method includes testing a temperature sensor, wherein the testing includes an electrical test, wherein the electrical test includes testing whether a temperature value is generated by the temperature sensor.

[0072] Embodiment 4. A method according to any one of the two preceding embodiments, the method including testing a temperature sensor, the testing including testing a response behavior of the temperature sensor, the testing including increasing the temperature to a maximum temperature or decreasing the temperature to a minimum temperature over a predetermined time range, reading temperature values ​​generated by the temperature sensor before and after changing the temperature, calculating the difference and comparing the difference to at least one predetermined threshold at a minimum temperature change, where the temperature sensor has passed the test if the threshold is exceeded and / or reached.

[0073] Embodiment 5. A method according to any one of the three preceding embodiments, the method including testing the fan, wherein testing includes testing a fan speed, wherein testing the fan speed includes setting the fan to maximum, monitoring the fan speed, and comparing the fan speed to at least one predetermined threshold at maximum fan speed, wherein the fan passes the test if the threshold is exceeded and / or reached.

[0074] Embodiment 6. The method of any one of the four preceding embodiments, wherein the method includes testing the operational pump, wherein testing includes testing a pump speed, wherein testing the pump speed includes setting the pump to maximum, monitoring the pump speed, and comparing the pump speed to at least one predetermined threshold at the maximum pump speed, wherein the pump has passed the test if the threshold is exceeded and / or reached.

[0075] Embodiment 7. The method of any one of the five preceding embodiments, wherein the method includes testing thermoelectric coolers, wherein testing the thermoelectric coolers includes sequentially testing a plurality of thermoelectric cooler pairs, wherein testing the thermoelectric coolers includes measuring current and / or voltage during heating and cooling, wherein testing the thermoelectric coolers further includes comparing the measured current and / or voltage during heating and cooling to a predetermined threshold, wherein the respective thermoelectric cooler pair has passed the test if the threshold is exceeded and / or reached.

[0076] Embodiment 8. The method of any one of the six preceding embodiments, wherein the method includes testing all thermoelectric coolers, wherein the testing includes testing power consumption during heating, and the power consumption is compared to a predetermined threshold, and if the threshold is exceeded and / or reached, the thermoelectric cooler passes the test.

[0077] Embodiment 9. A method according to any one of the seven preceding embodiments, the method including testing a vapor chamber mount, the testing including sequentially controlling a thermoelectric cooler and monitoring a thermal distribution of the vapor chamber mount, the thermal distribution being compared to a predetermined threshold defined as a maximum deviation from an expected temperature uniformity after a predetermined time, and the vapor chamber mount passing the test if the threshold is exceeded and / or reached.

[0078] Embodiment 10. The method of any one of the eight preceding embodiments, wherein the method comprises the following series of tests: i. Basic electrical testing of temperature sensors; ii. Fan testing; iii. Pump testing; iv. Sequential testing of multiple thermoelectric cooler pairs; v. Testing the power consumption of all thermoelectric coolers; vi. Temperature sensor gradient testing; vii. Vapor chamber mount testing; viii. At least one termination action, including one or more of disabling all active elements and reporting the data; A method comprising:

[0079] Embodiment 11. A method according to any one of the preceding embodiments, the method including displaying results of the performance verification via at least one communication interface and / or at least one user interface.

[0080] Embodiment 12. The method of any preceding embodiment, wherein the method includes reporting results of the performance verification to a LIMS system via a communications interface.

[0081] Embodiment 13. A method according to any one of the preceding embodiments, wherein the method is performed at regular time intervals and / or upon request by a user.

[0082] Embodiment 14. A method according to any one of the preceding embodiments, wherein the thermal block cycler unit comprises at least one control unit and / or is connected to at least one control unit.

[0083] Embodiment 15. A laboratory system comprising at least one instrument for performing a temperature-dependent reaction, comprising a thermal block cycler unit for automatic thermal treatment of at least one sample, at least one control unit and at least one communication interface, the laboratory system being configured to perform a method for performance verification according to any one of embodiments 1 to 14.

[0084] Embodiment 16. A laboratory system according to any preceding embodiment, wherein the instrument further comprises at least one detection unit.

[0085] Embodiment 17. A computer program comprising instructions which, when executed by a laboratory system according to any one of the preceding embodiments referring to a laboratory system, cause the laboratory system to perform a method according to any one of the preceding embodiments referring to a method.

[0086] Embodiment 18. A computer-readable storage medium comprising instructions that, when executed by a laboratory system according to any one of the preceding embodiments referring to the laboratory system, cause the laboratory system to perform a method according to any one of the preceding embodiments referring to the method.

[0087] Embodiment 19. A non-transitory computer-readable medium comprising instructions that, when executed by one or more processors, cause the one or more processors to perform a method as described in any one of the preceding embodiments referring to a method. [Brief description of the drawings]

[0088] Further optional features and embodiments are disclosed in more detail in the following description of the embodiments, preferably in conjunction with the dependent claims, in which each optional feature may be realized in an independent manner as well as in any possible combination, as understood by a person skilled in the art. The scope of the present invention is not limited by the preferred embodiments. The embodiments are illustrated diagrammatically in the figures, in which identical reference numbers refer to identical or functionally equivalent elements.

[0089] In the figure, [Figure 1-1] 1 shows an exemplary flow chart of one embodiment of a computer-implemented method for performance verification of a thermal block cycler unit. [Figure 1-2] 1 shows an exemplary flow chart of one embodiment of a computer-implemented method for performance verification of a thermal block cycler unit. [Diagram 2]2 shows experimental data, particularly the temperature profiles, of five runs implementing the method for performance validation according to FIG. 1. [Diagram 3] 1 illustrates an embodiment of a laboratory system. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0090] 1 shows an exemplary flow chart of one embodiment of a computer-implemented method for performance verification of a thermal block cycler unit 110 for automated thermal processing of at least one sample. The thermal block cycler unit 110 may be an element of a laboratory system 112, as shown for example in FIG. 3. The laboratory system 112 further comprises at least one control unit 114 and at least one communication interface 116.

[0091] The method may be used in the field of in vitro diagnostics. For example, the laboratory system may be part of a clinical laboratory, a medical laboratory, a forensic laboratory, or a blood bank. The sample may be a biological sample. The sample may be derived from any biological source, such as physiological fluids including blood, saliva, eye lens fluid, cerebrospinal fluid, sweat, urine, milk, peritoneal fluid, mucus, synovial fluid, peritoneal fluid, amniotic fluid, tissues, cells, and the like. For example, the biological sample may be an aliquot of a substance, such as a biological compound, or may include an aliquot of a substance, such as a biological compound. For example, the biological sample may be or may include at least one biological sample, such as one or more of blood, serum, plasma, urine, saliva. The biological sample may be a liquid sample. For example, the liquid sample may be or may include at least one pure liquid containing a biological substance, such as a liquid substance and / or a solution containing one or more liquid substances. The liquid sample may be or may include a liquid mixture, such as a suspension, emulsion, and / or dispersion of a biological substance. The biological sample may be an individual sample, such as at least one sample of tissue. The sample may be pre-treated before use, such as preparation of plasma from blood, dilution of viscous fluids, dissolution, etc. Methods of treatment may include filtration, distillation, concentration, inactivation of interfering components, and addition of reagents. The sample may be used directly as obtained from the source or after pre-treatment to modify the characteristics of the sample, for example after dilution with another solution or after mixing with a reagent, for example, to perform one or more diagnostic assays, such as clinical chemistry assays, immunoassays, coagulation assays, nucleic acid tests, etc.

[0092] The thermal block cycler unit 110 comprises at least one thermal block 118. The thermal block 118 may be configured to perform temperature cycles, for example for temperature sensitive reactions, for example amplification reactions, such as polymerase chain reaction (PCR). The thermal block 118 is configured to receive at least one sample vessel. The thermal block 118 may comprise at least one sample block configured to receive at least one sample vessel. The sample vessel may be or comprise one or more of at least one tubular vessel, at least one rack, at least one puck, or at least one slide. For example, the sample vessel may comprise at least one multiwell plate. A multiwell plate may typically have 6, 24, 96,384 or 1536 sample wells arranged, for example, in a 2:3 rectangular matrix. The wells may be either circular or square. The sample block may be configured to achieve rapid temperature changes and uniform temperature throughout the block. After inserting a sample vessel into the sample block, the temperature of the sample block may be changed, for example raised and / or lowered according to a predetermined temperature cycle.

[0093] The thermal block cycler unit 110 further comprises a number of hardware modules 120. For example, the thermal block cycler unit 110 further comprises at least one temperature sensor 122. The thermal block cycler unit 110 may comprise a number of temperature sensors 122. At least one temperature sensor 122 may be used for absolute temperature control. At least one other temperature sensor 122 may be used to determine temperature uniformity.

[0094] Additionally, the hardware module 120 may include a number of heating and / or cooling elements, such as one or more of at least one fan 124, at least one actuated pump 126, at least one thermoelectric cooler 128, and at least one vapor chamber mount 130.

[0095] The fan 124 may be configured to cool the thermal block cycler unit 110 during operation. The fan 124 may be configured to provide airflow through the thermal block cycler unit 110. The airflow may be expelled from the thermal block cycler unit 110 at an opening in a housing of the thermal block cycler unit 110. The thermal block cycler unit 110 may include multiple fans 124.

[0096] The thermal block cycler unit 110 may include at least one water cooling system with a working pump 126 and solid-liquid and liquid-air heat exchangers.

[0097] The thermal block cycler unit 110 may be powered by multiple thermoelectric coolers 128, for example six Peltier elements.

[0098] The vapor chamber mounts 130 may be configured to provide temperature uniformity across the thermal block 118. The thermal block cycler unit 110 may include multiple vapor chamber mounts 130.

[0099] The proposed method allows for performance verification of the thermal block cycler unit 110. The method can be performed fully automatically, e.g. without user interaction.

[0100] Performance may be an index that characterizes the thermal behavior of the thermal block cycler unit 110. Performance may be characterized as good or poor thermal performance. Good thermal performance may relate to performance within the manufacturer's specifications. Poor thermal performance may relate to performance that deviates from the manufacturer's specifications. Performance may be characterized with respect to at least one parameter, such as at least one parameter selected from the group consisting of heating rate, cooling rate, temperature distribution, thermal uniformity, thermal accuracy, thermal resolution, energy efficiency (heat loss), and the like. The performance of the thermal block cycler unit 110 may be affected by the performance of individual elements of the thermal block cycler unit 110, such as the hardware modules 120 of the thermal block cycler unit 110. Performance verification may include quality control of the performance of the thermal block cycler unit 110, such as at least one process to verify good thermal performance of the thermal block cycler unit 110.

[0101] The method steps may be performed in a given order or in a different order. Further, there may be one or more additional method steps not listed. Further, one, more than one, or even all of the method steps may be performed repeatedly.

[0102] The method includes sequential functional testing of the hardware modules 120, the testing sequence being: - every successive test uses the thermal energy and / or thermal block cycler unit conditions of the preceding test for the test; and Energy consumption is balanced between steps such that the difference between the input temperature before sequentially testing the hardware modules and the output temperature after sequentially testing the hardware modules is minimized. A method that is prescribed taking into consideration the following criteria.

[0103] Functional testing may include testing at least one basic functionality of each hardware module 120, such as whether the hardware module is functioning at all, and / or testing each hardware module 120 against its respective specifications. Functional testing may also include testing each hardware module or groups of hardware modules individually, for example of the same type.

[0104] The use of the above criteria allows for energy efficiency and speed. These two objectives can be achieved by setting the sequence of test steps such that every successive step benefits from the thermal energy and / or thermocycler conditions of its preceding step. Thus, the amount of energy put into the system can be minimized, which contributes to a shorter run time. Furthermore, the energy can be balanced between steps such that the difference between the start temperature of the thermocycler (temperature before the start of the test) and the end temperature of the thermocycler (temperature after the end of the test) is minimized. This also reduces the time that the thermocycler is not used by the end user.

[0105] The performance verification may be part of an automated diagnostic workflow of the thermal block cycler unit 110. For example, the performance verification may be part of a workflow for predictive maintenance. For example, the performance verification may be part of a workflow for verifying the calibration of the thermal block cycler unit 110. The performance verification may be performed at the start of operation, e.g. during initial setup and / or every time the thermal block cycler unit 110 is turned on. The method may be performed at regular time intervals and / or at the request of the user. The performance verification may be automatically repeated at predefined times, e.g. every 10 runs, or once a day, or every boot of the instrument. The performance verification may be automatically triggered and performed when a deviation in performance is observed for at least one hardware module 120, such as a lack of signal from a temperature sensor, malfunction of the electronics, etc. For example, the performance test may be triggered by detection of at least one deviation of the heating and / or cooling slopes from any expected profile in order to detect the root cause. For example, the performance test may be triggered in case of high or low heat sink temperature during the run. The commissioning may be triggered and / or performed automatically by the at least one control unit. Additionally, the commissioning may be performed upon request of a user, for example via at least one user interface.

[0106] FIG. 1 illustrates a typical series of tests according to the present method: i. (132) Basic electrical testing of temperature sensor 122; ii.(134) Testing of Fan 124; iii. (136) Testing of pump 126; iv. (138) Multiple thermoelectric coolers vs. 128 consecutive tests; v.(140) Testing the power consumption of all thermoelectric coolers 128; vi.(142) Temperature sensor 122 gradient test; vii.(144) Testing of the vapor chamber mount 130; viii. (146) At least one termination action, including one or more of disabling all active elements and reporting data; 1 shows a flowchart including the steps of:

[0107] This order of testing may make it possible to meet the aforementioned criteria, however, other orders are also conceivable.

[0108] The method may be performed fully automatically. For example, each step may be performed by the control unit 114 by controlling the operation of the respective hardware modules 120. The control unit 114 may be configured to receive the test results via the communication interface 116. The control unit 114 may be configured to evaluate the test results and issue an error and / or at least one other action.

[0109] The method may include testing the complete order of steps or aborting the sequence if an error occurs.

[0110] The flowchart in FIG. 1 is shown in tabular form, with the method steps shown in the left column, the sub-steps included by the method steps shown in the middle column, and the optional actions after each method step, such as issuing an error code or switching the respective hardware module 120 under test for subsequent testing of a further hardware module 120, shown in the right column.

[0111] In the embodiment of FIG. 1, a basic electrical test 132 of the temperature sensor 122 may be performed first. The basic electrical test 132 may include a basic functional test whether the temperature sensor 122 or the different temperature sensors 122 are working anyway, for example independently of the accuracy of the measured temperature. If a temperature value is produced, for example if a signal from the temperature sensor 122 is received by the control unit 114, the temperature sensor 122 has passed the test. If not, the temperature sensor 122 is in error. In this case an error may be issued and / or signaled by the control unit 114. For example, as shown in FIG. 1, this basic electrical test 132 may include the sub-steps of reading all temperature sensors 122 ("Read All Sensors (TempAmb)") and defining whether all temperature sensors 122 are valid ("Define Sensors Valid"). In step i, no energy may be input or output. This step can be performed quickly.

[0112] In step ii.134, the fan 124 may be tested and the temperature reduced. The test 134 may include testing the fan speed. Testing the fan speed may include setting the fan to maximum ("SET FAN 100% ON"), monitoring the fan speed, for example by using a fan internal status signal ("TIM_ISR ENABLE / MONITOR (FAN TACHO PIN)"), and comparing the fan speed to at least one predefined threshold at maximum fan speed. The threshold may be defined as an expected fan speed according to the fan's data sheet. If the threshold is exceeded and / or reached, the fan has passed the test. If not, the fan is in error. In this case, an error may be issued ("FAN_err") and / or signaled by the control unit 114. After this test 134, the fan 124 is turned off ("SET FAN 0% OFF").

[0113] Step iii.136 comprises a test pump 126. In this step the temperature may be reduced. For example, the flow of liquid in the cooling circuit may cause energy transfer and thus the temperature of the heating block may be reduced if the temperature of the heat sink (liquid-air heat exchanger) increases. Test 136 may include testing the pump speed. Testing the pump speed may include setting the pump to maximum ("SET PUMP 100% ON"), monitoring the pump speed, for example by using its internal status signal ("TIM_ISR ENABLE / MONITOR (PUMP TACHO PIN)"), and comparing the pump speed to at least one predefined threshold at the maximum pump speed. The threshold may be defined as the expected pump speed according to the pump's data sheet. If the threshold is exceeded and / or reached, the pump 126 has passed the test. If not, the pump 126 is in error. In this case an error ("PUMP_err") may be issued and / or signaled by the control unit 114. After this test 136, the pump 126 is switched off ("Set Pump 0% OFF").

[0114] Step iv.138 may include sequentially testing multiple thermoelectric cooler pairs 128, for example a first TEC pair (TEC1), a second TEC pair (TEC2), and a third TEC pair (TEC3). For each TEC pair, testing 138 may include measuring the current I and / or voltage U during heating and cooling. For example, first, heating is set to 100% ("set heating 100%) and the current I and / or voltage U are measured ("measure U and I"). Next, cooling is set to 100% ("set cooling 100%) and the current I and / or voltage U are measured ("measure U and I"). Subsequently, the TEC pair under test is switched off ("set_TEC_off(0%)"). Test 138 may further include comparing, for each TEC pair, the measured current and / or voltage during heating UTTECi_heat (with an indication of the respective TEC) and the measured current and / or voltage during cooling UTTECi_cool (with an indication of the respective TEC) to a predefined threshold value ("Threshold"). For example, in FIG. 1, the following deviations are calculated:

number

[0115] where i and j indicate the respective TECs of the TEC pairs. The thresholds may be defined according to the electrical parameters of the TECs, assuming a worst case scenario, e.g., worst case ambient temperature conditions. If the thresholds are exceeded and / or reached, the respective thermoelectric cooler pairs pass the test. If not, the respective thermoelectric cooler pairs are in error. In this case, an error ("TECi_err", with an indication of the respective TEC) may be issued and / or signaled by the control unit 114.

[0116] Steps iv.138 and v.140 may be temperature neutral, for example the temperature may be increased and decreased.

[0117] In step v.140, the power consumption of all TECs 128 may be tested ("Test Short") and the temperature is increased. Testing 140 may include testing the power consumption during heating. The power consumption may be compared to a predefined threshold. The threshold may be defined according to the electrical parameters of the TECs, assuming a worst case scenario, e.g., worst case ambient temperature conditions. If the threshold is exceeded and / or reached, the thermoelectric coolers 128 will have passed the test. If not, at least one of the thermoelectric coolers is in error. In this case, an error ("Overcurrent_err") may be issued and / or signaled by the control unit 114.

[0118] In step vi.142, a test of the temperature sensor 122 slope may be performed, and the increasing temperature of the previous step may be used to measure the heating rate of the temperature sensor 122. This step 142 may include reversing the TEC 128 to cool and measuring the cooling rate of change. As shown in FIG. 1, testing the response behavior 142 may involve increasing the temperature to a maximum temperature ("Set_Heating 100% 1.5s") or decreasing the temperature to a minimum temperature over a predetermined time range, for example for 1.5 seconds, reading the temperature values ​​generated by the temperature sensor 122i before and after the temperature change ("(TempHot)") and calculating the difference TempDelta(i), for example by:

number

[0119] Testing 144 the vapor chamber mount 130 may include sequentially controlling the thermoelectric coolers 128 and monitoring the thermal distribution of the vapor chamber mount 130. The TECs 128 may be spatially disposed between the solid-liquid heat exchanger and the VCM 130. The TECs 128 may be sequentially controlled ("Set TECs 1-2, 5-6 OFF for 1.5 seconds") and the thermal distribution in the VCM 130 may be monitored ("(TempHot)"). The thermal distribution may be compared to a predefined threshold. For example, an average of the ambient and hot temperatures of all valid temperature sensors may be calculated ("Calculate average values ​​TempAmb and TempHot for all valid temperature sensors"). If the number of valid temperature sensors 122 is ≦2, an error ("VCM_err") may be issued and / or signaled by the control unit 114. Otherwise, the deviation from the expected temperature uniformity after a predefined time may be calculated, for example, by:

number

[0120] The threshold may be defined as the maximum deviation from expected temperature uniformity after a given time, for example ±1.5° C. If the threshold is not exceeded and / or reached, the VCMs have passed the test. If not, at least one of the VCMs is in error. In this case, an error ("VCM_err") may be issued and / or signaled by control unit 114. The test of the vapor chamber mounts may be performed such that the end temperature is similar to the start temperature of the complete sequence.

[0121] Finally, at least one termination action may be taken, such as, for example, one or more of disabling all active elements and reporting the data.

[0122] Figure 2 shows experimental data, in particular the temperature profiles of five runs implementing the method for performance validation according to Figure 1. This figure shows that the aforementioned criteria are met. [Explanation of symbols]

[0123] 110 Thermal Block Cycler Unit 112 Laboratory Systems 114 Control Unit 116 Communication Interface 118 Thermal Block 120 Hardware Modules 122 Temperature Sensor 124 Fan 126 Pump 128 Thermoelectric cooler 130 Vapor chamber mount 132 Basic Electrical Tests 134 Fan Test 136 Pump Testing 138 Testing Multiple Thermoelectric Cooler Pairs 140 Power Consumption Test 142 Temperature Sensor Testing 144 Vapor Chamber Mount Testing 146 Termination Measures

Claims

1. 1. A computer-implemented method for performance verification of a thermal block cycler unit (110) for automated thermal processing of at least one sample, the thermal block cycler unit (110) comprising at least one thermal block (118) configured to receive at least one sample vessel; the thermal block cycler unit (110) further comprises a plurality of hardware modules (120), the hardware modules (120) comprising a plurality of heating and / or cooling elements and at least one temperature sensor (122); The method includes sequential functional testing of the hardware modules, the testing sequence comprising: - every successive test uses the thermal energy of the previous test and / or the state of the thermal block cycler unit (110) of the previous test for the test; and - the energy consumption is balanced between the steps so that the difference between the input temperature before the continuous testing of the hardware modules (120) and the output temperature after the continuous testing of the hardware modules (120) is minimized; A computer-implemented method is defined taking into consideration the following criteria:

2. 2. The method of claim 1, wherein the hardware module (120) comprises one or more of at least one temperature sensor (122), at least one fan (124), at least one actuated pump (126), at least one thermoelectric cooler (128), and at least one vapor chamber mount (130).

3. 3. The method of claim 1 or 2, wherein the method includes testing the temperature sensor (122), the testing including an electrical test, the electrical test including testing whether a temperature value is generated by the temperature sensor (122).

4. 4. The method of claim 2 or 3, wherein the method includes testing the temperature sensor (122), the testing including testing a response behavior of the temperature sensor (122), the testing including increasing the temperature to a maximum temperature or decreasing the temperature to a minimum temperature over a predetermined time range, reading temperature values ​​generated by the temperature sensor (122) before and after changing the temperature, calculating a difference, and comparing the difference to at least one predetermined threshold value of a minimum temperature change, whereby the temperature sensor (122) has passed the test if the threshold value is exceeded and / or reached.

5. 5. The method of claim 2, further comprising: testing the fan, the testing comprising testing a fan speed, the testing comprising setting the fan to a maximum, monitoring the fan speed, and comparing the fan speed to at least one predefined threshold at a maximum fan speed, the fan passing the test if the threshold is exceeded and / or reached.

6. 6. The method of claim 2, further comprising: testing the operational pump (126), the testing including testing a pump speed, the testing including setting the pump to a maximum, monitoring the pump speed, and comparing the pump speed to at least one predetermined threshold at a maximum pump speed, the pump (126) passing the test if the threshold is exceeded and / or reached.

7. 7. The method of claim 2, wherein the method includes testing the thermoelectric coolers (128), the testing including sequentially testing a plurality of thermoelectric cooler pairs (128), the sequentially testing the thermoelectric coolers (128) including measuring current and / or voltage during heating and cooling, the sequentially testing the thermoelectric coolers (128) further including comparing the measured current and / or voltage during heating and cooling to a predetermined threshold, the respective thermoelectric cooler (128) pair passing the test if the threshold is exceeded and / or reached.

8. 8. The method of claim 2, wherein the method includes testing all thermoelectric coolers (128), the testing including testing power consumption during heating, the power consumption being compared to a predetermined threshold, and the thermoelectric cooler (128) passing the test if it exceeds and / or reaches the threshold.

9. 9. The method according to claim 2, further comprising testing at least one vapor chamber mount, the testing including sequentially controlling the thermoelectric cooler and monitoring a thermal distribution of the vapor chamber mount, the thermal distribution being compared to a predetermined threshold defined as a maximum deviation from an expected temperature uniformity after a predetermined time, the vapor chamber mount passing the test if the threshold is exceeded and / or reached.

10. The method comprises the following series of tests: i. (132) Basic electrical testing of temperature sensor (122); ii. (134) Testing of the fan (124); iii. (136) Testing the pump (126); iv. (138) sequential testing of a plurality of thermoelectric cooler pairs (128); v. (140) Testing the power consumption of all thermoelectric coolers (128); vi. (142) Temperature sensor (122) gradient test; vii. (144) Testing of the vapor chamber mount (130); viii. (146) At least one termination action, including one or more of disabling all active elements and reporting data. The method of any one of claims 2 to 9, comprising:

11. 11. The method of claim 1, wherein the method includes displaying results of the performance verification via at least one communication interface (116) and / or at least one user interface, and / or the method includes reporting the results of the performance verification to a LIMS system via the communication interface (116).

12. A laboratory system (112) comprising at least one instrument for performing a temperature-dependent reaction comprising a thermal block cycler unit (110) for automated thermal treatment of at least one sample, at least one control unit (114) and at least one communication interface (116), the laboratory system (112) being configured to perform a method for performance verification according to any one of claims 1 to 11.

13. 13. A computer program comprising instructions that when executed by a laboratory system (112) according to any one of claims 1 to 12 referring to a laboratory system, cause the laboratory system to carry out the method according to any one of claims 1 to 12 referring to the method.

14. 14. A computer readable storage medium comprising instructions that, when executed by a laboratory system (112) according to any one of claims 1 to 13, cause the laboratory system to perform the method according to any one of claims 1 to 13, wherein the instructions refer to a laboratory system.

15. A non-transitory computer readable medium comprising instructions which, when executed by one or more processors, cause the one or more processors to perform the method of any one of claims 1 to 14 reciting a method.

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