Computer-implemented method for performing performance verification on thermal block circulator unit

Abstract

The invention proposes a computer-implemented method for verifying the performance of a thermal block circulator unit (110) for automated thermal processing of at least one sample. The thermal block circulator unit (110) includes at least one thermal block (118) configured to receive at least one sample vessel. The thermal block circulator unit (110) further comprises a plurality of hardware modules (120). The hardware module (120) comprises a plurality of heating and / or cooling elements and at least one temperature sensor (122). The method comprises: continuously performing functional tests on the hardware module, in which the order of tests is defined taking into account the following criteria: each continuous test is used to test the thermal energy of its preceding test and / or the state of the thermal block circulator unit (110) of its preceding test; and-balancing the energy consumption between steps in such a way that the difference between the input temperature before the continuous testing of the hardware module (120) and the output temperature after the continuous testing of the hardware module (120) is minimized.

Description

Technical Field

[0001] The present invention relates to a computer-implemented method for performance verification of a thermal block cycler unit, a laboratory system, a computer program, a computer-readable storage medium, and a non-transitory computer-readable medium. The method and apparatus may be used in the fields of biochemical analysis or research or clinical diagnosis or research. For example, the laboratory system may be used to automate thermal processing of samples. However, other applications are also possible. Background Art

[0002] Functional testing of hardware modules is a common practice in medical devices, which ensures the correct operation of the instrument and collects data for, for example, predictive maintenance. Such functional tests are known, for example, from WO 2022 / 101870 A1, US 2014 / 0122006 A1, US 5,602,756 A, EP 2 108942 A1, US 10,850,283 B2, US 2013 / 0157376 A1, KR 2375707 B1, EP 3253 492 A2, US 6,703,236 B2, AU 741806 B2 or US 2008 / 0212643 A1.

[0003] However, the performance of functional testing can have several disadvantages. For example, it reduces the effective time during which the module or instrument can be used by the end user, it consumes energy, it shortens the useful life of the module or instrument, and in many cases, it requires the end user to bring the instrument to the correct state to begin operation.

[0004] Issues to be resolved

[0005] It is therefore desirable to provide methods and devices that address the technical challenges mentioned above. In particular, a method, a computer program and a device are to be proposed that allow minimizing energy consumption and the time during which a thermal block cycler unit is unavailable to a user. Summary of the invention

[0006] The problem is solved by a computer-implemented method for performance verification of a thermal block cycler unit, a laboratory system, a computer program, a computer-readable storage medium and a non-transitory computer-readable medium having the features of the independent claims. In the dependent claims and throughout the description, advantageous embodiments are listed which can be realized individually or in any combination.

[0007] As used below, the terms "having", "comprising" or "including" or any grammatical variations thereof are used in a non-exclusive manner. Thus, these terms may refer to the absence of other features in the entity described in this context in addition to the features introduced by these terms, or the presence of one or more other features. As an example, the expressions "A has B", "A includes B" and "A contains B" may refer to the absence of other elements in A in addition to B (i.e., the presence of A solely and exclusively consisting of B); or to the presence of one or more other elements in entity A in addition to B (such as element C, element C and element D, or even other elements).

[0008] Further, it should be noted that the terms "at least one", "one or more" or similar expressions indicating that a feature or element may be present once or more than once are usually used only once when introducing the corresponding feature or element. In the following, in most cases, when referring to the corresponding feature or element, the expression "at least one" or "one or more" is not repeated even though the corresponding feature or element may be present only once or more than once.

[0009] Further, as used hereinafter, the terms "preferably", "more preferably", "particularly", "more particularly", "specifically", "more specifically" or similar terms are used in conjunction with optional features without limiting the possibilities of alternatives. Therefore, the features introduced by these terms are optional features and are not intended to limit the scope of the claims in any way. As the skilled person will recognize, the present invention may be carried out using alternative features. Similarly, the features introduced by "in one embodiment of the present invention" or similar expressions are intended to be optional features without any limitation on alternative embodiments of the present invention, without any limitation on the scope of the present invention, and without any limitation on the possibility of combining the features introduced in this manner with other optional or non-optional features of the present invention.

[0010] In a first aspect, a computer-implemented method for performance verification of a thermal block cycler unit for automating thermal processing of at least one sample is disclosed. The thermal block cycler unit includes at least one thermal block configured to receive at least one sample vessel. The thermal block cycler unit further includes a plurality of hardware modules, wherein the hardware modules include a plurality of heating and / or cooling elements and at least one temperature sensor.

[0011] As used herein, the term "computer-implemented" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited 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 include at least one processor configured to perform at least one of the method steps of the method according to the present invention. Preferably, each of the method steps is performed by a computer and / or computer network and / or cloud. The method may be performed completely automatically (e.g., without user interaction). As used herein, the term "automatically" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, a process performed entirely with the aid of at least one computer and / or computer network and / or cloud and / or machine (e.g., without manual action and / or interaction with a user).

[0012] The method can be used in the field of in vitro diagnosis. As used herein, the term "in vitro diagnosis" is a broad term and should be given its common and customary meaning for those of ordinary skill in the art, and should not be limited to a special or custom meaning. For example, in vitro diagnosis may include performing at least one test on a sample (e.g., a biological sample obtained from a human or animal body). The method may be performed by using a laboratory system, such as in a laboratory or other environment for conducting scientific or technical research, experiments and / or measurements. For example, a laboratory system may be part of a clinical laboratory, a medical laboratory, a forensic laboratory, or a blood bank.

[0013] As used herein, the term "sample" is a broad term and is given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or custom 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 is given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or custom 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 from any biological source, such as a physiological fluid, including blood, saliva, lens fluid, cerebrospinal fluid, sweat, urine, milk, ascites, mucus, synovial fluid, peritoneal fluid, amniotic fluid, tissue, cells, etc. For example, a biological sample may be or may include an aliquot of a substance (such as a biological compound). For example, a biological sample may be or may include at least one biological specimen, such as one or more of the following: blood; serum; plasma; urine; saliva. The biological sample may be a liquid sample. For example, a liquid sample may be or may include at least one pure liquid, such as a liquid substance and / or a solution containing one or more liquid substances, which contains a biological substance. A liquid sample may be or may include a liquid mixture, such as a suspension, emulsion and / or dispersion of a biological substance. A biological sample may be a solid sample, for example, at least one tissue sample. The sample may be pretreated before use, such as preparing plasma from blood, diluting a viscous liquid, lysing, etc.; the treatment method may involve filtering, distilling, concentrating, inactivating interfering components, and adding reagents. The sample may be used directly after being obtained from the source, or it may be pretreated to change the characteristics of the sample, such as after dilution with another solution or after mixing with a reagent, for example, so as to complete one or more diagnostic tests, such as clinical chemistry tests, immunoassays, coagulation tests, nucleic acid detection, etc. Therefore, the term "sample" as used herein is not only used to represent the original sample, but also may refer to a sample that has been processed (such as pipetting, diluting, mixing with a reagent, enriching, purifying, amplifying, etc.). As used herein, the term "analyte" may refer to a compound or composition to be detected or measured.

[0014] As used herein, the term "thermal block cycler unit" (also denoted as thermal cycler, PCR machine or DNA amplification instrument) is a broad term and should be given its ordinary and customary meaning to those of ordinary skill in the art, and should not be limited to a special or custom meaning. The term specifically may refer to, but is not limited to, a device configured to perform at least one cyclic temperature change (e.g., a plurality of predefined temperature cycles). A thermal block cycler may be configured to perform temperature cycling, for example, to perform a temperature sensitive reaction (e.g., an amplification reaction), such as to perform a polymerase chain reaction (PCR). For example, a thermal block cycler unit may be designed as described in EP 1 710 017 A1, which is incorporated herein by reference in its entirety. Thus, for example, a thermal block cycler unit may include a thermal block, at least one thermoelectric cooler, at least one vapor chamber mount, and a radiator.

[0015] The thermal block circulator may include at least one thermal block. The thermal block may be a solid-state device configured to have good thermal conductivity. There are a variety of materials known to those skilled in the art with good thermal conductivity, and without being bound by theory, most materials with good electrical conductivity are also good thermal conductors. Thus, materials such as copper, aluminum, silver or graphite are suitable for thermal blocks. On the other hand, plastics and ceramics may also have sufficient thermal conductivity to be used as materials for thermal blocks.

[0016] The thermal block circulator unit may further include a heat sink configured for dissipating heat. Generally speaking, the heat sink is made of a thermally conductive material similar to the thermal blocks outlined above. Therefore, the heat sink is mostly made of metal, preferably aluminum or silver. Alternatively, if only good thermal conductivity is achieved, the heat sink may be formed from plastic and ceramic. In order to achieve maximum heat dissipation, the heat sink is arranged to provide a large surface area to volume ratio. This can be achieved by a fin assembly arranged on a base plate. The large surface area to volume ratio reduces the thermal transfer resistance between the heat sink and the surrounding air.

[0017] As used herein, the term "heat treatment" is a broad term and should be given its common and customary meaning for those of ordinary skill in the art, and should not be limited to a special or custom meaning. The term specifically may refer to, but is not limited to, at least one processing step of a sample, which includes at least one temperature change, such as heating and / or cooling. The temperature change may include alternating heating and cooling of the sample. Heat treatment may include raising and / or lowering the temperature. The temperature change may be performed continuously or discontinuously in discrete predefined steps.

[0018] 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 to be integral with the thermal block.

[0019] As used herein, the term "sample vessel" is a broad term and should be given its common and customary meaning for those of ordinary skill in the art, and should not be limited to a special or custom meaning. The term may specifically refer to, but is not limited to, a device configured to store and / or hold at least one sample. The sample vessel may be or may include one or more of the following items: at least one tubular container, at least one bracket, at least one puck, or at least one slide. For example, the sample vessel may include at least one porous plate. As used herein, the term "porous plate" is a broad term and should be given its common and customary meaning for those of ordinary skill in the art, and should not be limited to a special or custom meaning. The term may specifically refer to, but is not limited to, any plate-like device configured to store samples (e.g., small amounts of fluid) permanently or temporarily. In this regard, a small amount should be understood as a fluid amount in the range of nl to ml, such as 10nl to 100ml, preferably 0.1μl to 10ml, and even more preferably 0.1μl to 5ml. Basically, the design of the porous plate may depend on the corresponding application. The porous plate can be designed as a device for storing a single fluid sample or a plurality of fluid samples. Similarly, the geometry of the corresponding storage area of ​​the porous plate can depend on the corresponding application of the porous plate. The storage area can be designed as a hole, a channel, a recess, a groove, etc. For example, the porous plate can include a plurality of holes. As used herein, the term "porous plate" can refer to a flat plate with a plurality of "holes" used as a small test tube. Such a porous plate is also referred to as a microtiter plate. Microtiter plates have become standard tools in analytical research and clinical diagnostic test laboratories. The porous plate can generally have, for example, 6, 24, 96, 384 or 1536 sample holes arranged in a 2:3 rectangular matrix. The hole can be circular or square. The porous plate can be configured as a treatment plate. The treatment plate can be configured to undergo at least one sample treatment step. The sample treatment can include one or more of the sample specific steps such as aliquoting, heating, cooling, magnetic separation, mixing, washing, eluting, diluting, chemical reaction, cracking sample, capturing nucleic acid, releasing nucleic acid, extracting nucleic acid, etc. The sample vessel may be a plastic vessel. For example, the sample vessel may be designed to allow for optimal heat transfer.

[0020] As used herein, the term "sample block" is a broad term and should be given its ordinary and customary meaning to those of ordinary 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 block-like structural member that includes 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 the sample vessel is inserted into the sample block, the temperature of the sample block may be changed, for example, raised and / or lowered according to a predefined temperature cycle.

[0021] As used herein, the term "performance" is a broad term and should be given its ordinary and customary meaning to those of ordinary 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 measure that characterizes the thermal behavior of a thermal block circulator unit. Performance may be characterized as good or poor thermal performance. Good thermal performance may be associated with performance within the manufacturer's specifications. Poor thermal performance may be associated with performance that deviates from the manufacturer's specifications. Performance may be characterized relative 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), etc. The performance of a thermal block circulator unit may be affected by the performance of various elements of the thermal block circulator unit (such as hardware modules of the thermal block circulator unit).

[0022] As used herein, the term "performance verification" 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, but is not limited to, quality control of the performance of a thermal block cycler unit, such as at least one process for verifying good thermal performance of a thermal block cycler unit.

[0023] The method steps may be performed in a given order or may be performed in a different order. Further, there may be one or more additional method steps not listed. Further, one, more than one or even all method steps may be performed repeatedly.

[0024] The method comprises: performing functional tests on the hardware modules successively, wherein the order of the tests is defined taking into account the following criteria:

[0025] - each successive test is used to test the thermal energy of its previous test and / or the status of its previous test's thermal block circulator unit, and

[0026] - Balancing the energy consumption between the steps in such a way that the difference between the input temperature before the hardware module is tested successively and the output temperature after the hardware module is tested successively is minimized.

[0027] As used herein, the term "functional testing" is a broad term and should be given its ordinary and customary meaning to a person of ordinary skill in the art, and should not be limited to a special or custom meaning. The term may specifically refer to, but is not limited to, testing at least one basic function of a corresponding hardware module (such as whether the hardware module is working) and / or testing the corresponding hardware module for its corresponding specifications. As used herein, the term "continuously" performing functional testing is a broad term and should be given its ordinary and customary meaning to a person of ordinary skill in the art, and should not be limited to a special or custom meaning. The term may specifically refer to, but is not limited to, performing sequential functional testing of hardware modules (e.g., all hardware modules of a thermal block circulator unit). Functional testing may include testing corresponding hardware modules or groups of hardware modules (e.g., of the same type) individually.

[0028] Using the criteria listed above allows energy efficiency and speed. These two goals can be achieved by setting the order of the test steps so that each successive step benefits from the heat energy and / or thermal cycler state of its previous step. Therefore, the amount of energy input into the system can be minimized, thereby helping to reduce execution time. In addition, energy can be balanced between steps in such a way that the difference between the starting temperature of the test (the temperature before the test starts) and the end temperature of the test (the temperature after the test ends) is minimized. This allows reducing the time during which the thermal cycler cannot be used for the end user.

[0029] As used herein, the term "testing the thermal energy for its prior test" is a broad term and should be given its ordinary and customary meaning for those of ordinary skill in the art, and should not be limited to a special or custom meaning. The term specifically refers to, but is not limited to, using thermal energy as a starting point for testing and / or as a test condition during testing. As used herein, the term "state of a thermal block circulator unit" is a broad term and should be given its ordinary and customary meaning for those of ordinary skill in the art, and should not be limited to a special or custom meaning. The term specifically refers to, but is not limited to, any state of at least one hardware module of a thermal block circulator unit determined and / or set and / or reached during a previous test and / or by a previous test. The state can be the state of a hardware module tested during a prior test and / or the state of a hardware module tested so far during the method. For example, the state can be the thermal state of a thermal block circulator unit, such as at the end of a prior test. The thermal state can be used as a starting point for testing and / or as a test condition during testing. For example, the state can be a test result of a prior test, such as a pass or fail state, such as relative to at least one specified acceptance criterion. For example, if one or more previous steps fail, the next test step cannot be performed. For example, if a temperature sensor is detected to be inoperative and / or if the cooling system has a damaged pump, the thermal block will not be heated. As used herein, the term "testing the state of a thermal block circulator unit previously tested" is a broad term and should be given its ordinary and customary meaning to those of ordinary skill in the art, and should not be limited to a special or customized meaning. The term specifically may refer to, but is not limited to, considering the state of a thermal block circulator unit (e.g., test results) and / or as a setting for the next test. For example, the state can be used as a starting point for a test and / or as a test condition during a test.

[0030] As used herein, the term "energy consumption" is a broad term and should be given its ordinary and customary meaning to those of ordinary skill in the art and should not be limited to a special or customized meaning. The term specifically may refer to, but is not limited to, any energy applied to a thermal block cycler unit to perform a method for performance validation, such as electrical energy for heating and / or cooling.

[0031] As used herein, the term "balance" is a broad term and should be given its ordinary and customary meaning to a person of ordinary 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, ensuring that there is a minimum overall temperature gradient, such as a minimum overall temperature gradient between an input temperature and an output temperature before and after a hardware module is tested continuously. Balancing may include: ensuring a minimum temperature gradient between an output temperature of a test of a hardware module and an input temperature of a continuous test or hardware module. The temperature characteristics of the method steps for performance verification may be as isothermal as possible. Balancing may include: determining (e.g., calculating) a plurality of potential test sequences for functional testing of a hardware module, and selecting a test sequence having an order of functional testing of the hardware module that meets the requirement.

[0032] Performance verification can be part of the automatic diagnostic workflow of the thermal block circulator unit. For example, performance verification can be part of the workflow for predictive maintenance. For example, performance verification can be part of the workflow for verifying the calibration of the thermal block circulator unit. Performance verification can be performed at the beginning of operation, such as during initial setup and / or each time the thermal block circulator unit is turned on. The method can be performed at regular time intervals and / or according to the needs of the user. Performance verification can be automatically and repeatedly performed at predefined times (e.g., every 10 runs, or once a day, or during each instrument startup). In the case of observing deviations in the performance of at least one hardware module (such as the absence of signals from temperature sensors, failures in electronic devices, etc.), performance verification can be automatically triggered and performed. For example, a performance test can be triggered to detect the root cause by detecting at least one deviation from any desired feature in terms of heating and / or cooling ramps. For example, a performance test can be triggered in the case of high or low heat sink temperatures during operation. Performance verification can be automatically triggered and / or performed by at least one control unit. In addition, performance verification can be performed according to user needs (e.g., via at least one user interface).

[0033] As used herein, the term "control unit" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, any device or system configured to perform a specified operation, preferably by using at least one data processing device, and more preferably by using at least one processor and / or at least one application-specific integrated circuit. Thus, as an example, at least one control unit may include at least one data processing device having software code stored thereon, the software code including a plurality of computer commands. The control unit may provide one or more hardware elements for performing one or more specified operations, and / or may provide one or more processors with software running thereon for performing one or more specified operations. The control unit may include one or more programmable devices, such as one or more computers, application-specific integrated circuits (ASICs), digital signal processors (DSPs), or field-programmable gate arrays (FPGAs). However, in addition or alternatively, the control unit may also be implemented in whole or in part by hardware. The thermal block circulator unit may include and / or be connected to at least one control unit.

[0034] As used herein, the term "processor" or "processing device" is a broad term and should be given its ordinary and customary meaning to a person of ordinary skill in the art, and should not be limited to a special or custom meaning. The term may specifically refer to, but is not limited to, any logic circuit system configured to perform the basic operations of a computer or system; and / or, in general, a device configured to perform calculations or logical operations. In particular, a processor may be configured to process basic instructions that drive a computer or system. As an example, a processor may include at least one arithmetic logic unit (ALU), at least one floating point unit (FPU) (such as a math coprocessor or a numerical coprocessor), a plurality of registers (specifically registers configured to provide operands to the ALU and store operation results) and memory (such as L1 and L2 cache memories). In particular, the processor may be a multi-core processor. In particular, the processor may be or may include a central processing unit (CPU). Additionally or alternatively, the processor may be or may include a microprocessor, so that, in particular, the elements of the processor may be contained in a single integrated circuit (IC) chip. Additionally or alternatively, the processor may be or may include 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 one or more chips, such as dedicated machine learning optimized chips, etc. The processor may be specifically configured (such as by software programming) to perform one or more evaluation operations.

[0035] The method may include: displaying the results of the performance verification via at least one communication interface and / or at least one user interface. Additionally or alternatively, the method may include: reporting the results of the performance verification to a laboratory information management system (LIMS) via the communication interface. The method may include at least one action depending on the results of the performance verification, such as one or more of the following: continuing operation, repeating at least one step of the performance verification, issuing a warning, issuing a message to a manufacturer or service provider, replacing a hardware module, requesting thermal calibration, calling service, controlling a coolant (in the case of liquid cooling), controlling an electrical connection to a heating module.

[0036] As used herein, the term "communication interface" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, an item or element that forms a boundary that is configured to transmit information. A communication interface may be configured to transmit information from a computing device (e.g., a computer), such as to send or output information to, for example, another device. Additionally or alternatively, a communication interface may be configured to transmit information to a computing device (e.g., to a computer), such as to receive information. A communication interface may specifically provide a means for transmitting or exchanging information. In particular, a communication interface may provide a data transmission connection, such as Bluetooth, NFC, inductive coupling, etc. As an example, a communication interface may be or may include at least one port, including 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. As used herein, the term "user interface" is a broad term and should be given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may refer to, but is not limited to, features of a laboratory instrument that is configured to interact with its environment, such as for purposes of exchanging information unidirectionally or bidirectionally, such as for exchanging one or more of data or commands. For example, a user interface may be configured to share information with a user and receive information from a user. A user interface may have features that interact visually with a user, such as a display, or have features that interact acoustically with a user. As an example, a user interface may include one or more of: a graphical user interface; a data interface, such as a wireless and / or wired data interface.

[0037] The hardware module includes a plurality of heating and / or cooling elements and at least one temperature sensor.

[0038] The hardware module may include at least one temperature sensor. As used herein, the term "sensor" is a broad term and should be given its common and customary meaning to a person of ordinary skill in the art, and should not be limited to a special or custom meaning. The term specifically may refer to, but is not limited to, any element or device configured to detect at least one condition or to measure at least one measurement variable. As used herein, the term "temperature sensor" is a broad term and should be given its common and customary meaning to a person of ordinary skill in the art, and should not be limited to a special or custom meaning. The term specifically may refer to, but is not limited to, a sensor configured to measure temperature (e.g., absolute value and / or temperature change). The thermal block circulator 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.

[0039] As used herein, the term "heating and / or cooling element" is a broad term and should be given its ordinary and customary meaning to those of ordinary skill in the art and should not be limited to a special or customized meaning. The term specifically may refer to, but is not limited to, a device configured to change (e.g., increase and / or decrease) its temperature and / or the temperature of the environment and / or the temperature of another device.

[0040] For example, the hardware module includes one or more of the following: at least one fan, at least one operating pump, at least one thermoelectric cooler, at least one vapor chamber mount.

[0041] The hardware module may include at least one fan. The fan may be configured to cool the thermal block circulator unit during operation. The fan may be configured to provide an air flow through the thermal block circulator unit. The air flow may be exhausted from the thermal block circulator unit at an opening of a housing of the thermal block circulator unit. The thermal block circulator unit may include a plurality of fans.

[0042] The hardware module may include at least one operational pump. The thermal block circulator unit may include at least one water cooling system with an operational pump and with solid-liquid and liquid-air heat exchangers.

[0043] The hardware module may include at least one thermoelectric cooler (TEC). A thermoelectric device is a solid-state heat pump made of semiconductor material, which includes a series of p-type and n-type semiconductor pairs or junctions sandwiched between ceramic plates. When electrons are transferred from low energy levels in p-type elements to higher energy levels in n-type elements, heat is absorbed by the electrons at the cold junction. At the hot junction, when electrons move from high energy n-type elements to low energy p-type elements, energy is discharged to, for example, a radiator. A DC power supply can provide energy to move electrons through the system. A typical TEC may contain up to 127 junctions and may pump up to 120W of heat. The amount of heat pumped may be proportional to the amount of current flowing through the TEC, and therefore tight temperature control is possible. By reversing the current, the TEC can be used as a heater or cooler, which can be used to control objects in a changing ambient environment or in different temperature cycles. The size range is 2mm to 62mm, and multiple TECs can be used to achieve greater cooling. Since a relatively large amount of heat is pumped over a small area, a TEC generally requires a radiator to dissipate the heat into the ambient environment. A well-known type of TEC is the Peltier element. A thermal block circulator unit can be driven by multiple thermoelectric coolers. For example, a thermal block circulator unit can be driven by six Peltier elements.

[0044] The hardware module may include at least one steam chamber mounting member. The heat block circulator unit may include multiple steam chamber mounting members. For example, the VCM may be designed as described in EP 1 710 017 A1 or WO 2013 / 075839, which are incorporated herein by reference in their entirety. The steam chamber mounting member may be configured to provide temperature uniformity on the heat block. The VCM may be configured to transfer and distribute heat. The steam chamber mounting member may have a plate-like structure at least in part. The VCM may include a lower shell and an upper shell. At least one airtight and liquid-tight intermediate space may be formed between the lower shell and the upper shell, in which a fluid working medium and a porous material are arranged. The porous material may contact the upper shell and / or the lower shell at least in a region, but does not completely fill the intermediate space, thereby forming at least one cavity-shaped steam gap. For example, ammonia, water, acetone or methanol are typically used as working media. The control unit may modify the thermal conductivity of the VCM, for example by adjusting the flow rate in the intermediate space.

[0045] For example, the method comprises: testing the temperature sensor. The test may comprise an electrical test. The electrical test may comprise: testing whether a temperature value is generated by the temperature sensor. The electrical test may comprise a basic functional test (e.g. irrelevant to the correctness of the measured temperature) of the temperature sensor or different temperature sensors being run. If a temperature value is generated (e.g. a signal from the temperature sensor is received by the control unit), the temperature sensor passes the test. Otherwise, the temperature sensor is faulty. In this case, an error may be issued and / or recorded by the control unit.

[0046] Additionally or alternatively, for example, the method comprises: testing the temperature sensor, wherein the test comprises: testing the response behavior of the temperature sensor. Such a test may also mean testing the heating capacity of the heat block. Testing the response behavior may comprise: increasing the temperature to a maximum temperature or decreasing the temperature to a minimum temperature for a predefined time range, reading the temperature value generated by the temperature sensor before and after changing the temperature, calculating the difference and comparing the difference with at least one predefined threshold for a minimum temperature change. The threshold for the minimum temperature change may be defined relative to the thermal design of the heat block under the assumption of a worst case scenario (i.e., worst ambient thermal conditions). If the threshold for the minimum temperature change is exceeded or at least reached, the temperature sensor passes the test. Otherwise, the temperature sensor is faulty. In this case, an error may be issued and / or recorded by the control unit.

[0047] Additionally or alternatively, the method comprises testing the fan. The test may comprise testing the fan speed. The testing of the fan speed may comprise setting the fan to maximum, monitoring the fan speed (e.g. by using a fan internal status signal), and comparing the fan speed to at least one predefined threshold for the maximum fan speed. The threshold may be defined as the desired fan speed according to a data sheet for the fan. If the threshold is exceeded and / or reached, the fan passes the test. Otherwise, the fan has an error. In this case, an error may be issued and / or recorded by the control unit.

[0048] Additionally or alternatively, the method comprises: testing the operating pump. The test may comprise: testing the pump speed. The test of the pump speed may comprise: setting the pump to maximum, monitoring the pump speed (e.g. by using its internal status signal), and comparing the pump speed with at least one predefined threshold value for the maximum pump speed. The threshold value may be defined as the expected pump speed according to the data sheet of the pump. If the threshold value is exceeded and / or reached, the pump passes the test. Otherwise, the pump has an error. In this case, an error may be issued and / or recorded by the control unit.

[0049] Additionally or alternatively, the method comprises testing a thermoelectric cooler (TEC). Testing the TEC may comprise testing a plurality of thermoelectric cooler pairs in succession. The test may comprise measuring the current and / or voltage during heating and cooling. The test may further comprise comparing the current and / or voltage measured during heating and during cooling with a predefined threshold. The threshold may be defined based on electrical parameters of the TEC under an assumed worst case scenario (e.g., worst ambient thermal conditions). If the threshold is exceeded and / or reached, the respective thermoelectric cooler pair passes the test. Otherwise it is faulty. In this case, an error may be issued and / or recorded by the control unit.

[0050] Additionally or alternatively, the method comprises: testing all thermoelectric coolers. The test may comprise: testing the power consumption during heating. The power consumption may be compared with a predefined threshold. The threshold may be defined according to electrical parameters of the TEC under an assumed worst case scenario (e.g. worst ambient thermal conditions). If the threshold is exceeded and / or reached, the thermoelectric cooler passes the test. Otherwise at least one of them is faulty. In this case, an error may be issued and / or logged by the control unit.

[0051] Additionally or alternatively, the method may include testing at least one vapor chamber mount (VCM). The test may include sequentially controlling a thermoelectric cooler and monitoring the heat distribution of the vapor chamber mount. The TEC may be spatially arranged between the solid-liquid heat exchanger and the VCM. The TEC may be sequentially controlled and the heat distribution in the VCM may be monitored. The heat distribution may be compared to a predefined threshold. The threshold may be defined as a maximum deviation from a desired temperature uniformity after a defined time. If the threshold is not exceeded and / or reached, the VCM passes the test. Otherwise, at least one of them is erroneous. In this case, an error may be issued and / or recorded by the control unit.

[0052] For example, the method includes the following test sequence:

[0053] i. Perform basic electrical tests on the temperature sensor;

[0054] ii. Test the fan;

[0055] iii. Test the pump;

[0056] iv. Testing multiple thermoelectric cooler pairs in succession;

[0057] v. Test the power consumption of all thermoelectric coolers;

[0058] vi. Test the temperature sensor ramp;

[0059] vii. Testing of steam room mountings,

[0060] viii. At least one shutdown action, the at least one shutdown action comprising one or more of: disabling all active elements, and reporting data.

[0061] This order of tests may allow the above criteria to be met. However, other orders may be possible. The method may include all of the steps i. to viii. listed above, or one or more tests may be skipped, for example if a steam chamber mount is not present in the thermal block circulator unit, the test of the steam chamber mount may be skipped. In addition, the steps may be performed in a given order or in a different order. In addition, one or more of the method steps may be performed in parallel and / or in a time-overlapping manner. In addition, one or more of the method steps may be repeated. In addition, there may be additional method steps that are not listed.

[0062] The tests to be performed and / or the order of the tests may depend on the hardware modules present in the thermal block cycler unit. The order of the tests and / or steps to be performed may be determined (eg, automatically).

[0063] 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, e.g. according to a test scheme (such as predefined by the manufacturer). Said testing of each hardware module may comprise determining at least one thermal signature for each test. The thermal signatures for 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 mentioned criteria.

[0064] The method may be performed fully automatically. For example, each of the steps may be performed by a control unit by controlling the operation of a corresponding hardware module. The control unit may be configured to receive the test results via a communication interface. The control unit may be configured to evaluate the test results and to issue an error and / or at least one other action.

[0065] The method may include testing the complete sequence of steps or aborting the sequence in the event of an error.

[0066] First, a basic electrical test of the temperature sensor may be performed. 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, for example, the temperature may be increased or decreased. Step iv. may include the following consecutive sub-steps: 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, where the temperature is increased. In step vi., a test of the temperature sensor ramp may be performed, and the temperature sensor heating ramp rate may be measured using the rising temperature of the previous step. This step may include: reversing the TEC for cooling and measuring the cooling ramp rate. The steam chamber installation may be tested so that the final temperature is similar to the starting temperature of the complete sequence. The shutdown action may include: disabling all active elements and / or reporting data.

[0067] In another aspect, a laboratory system comprises at least one instrument for performing a temperature-dependent reaction, the at least one instrument comprising: a thermal block cycler unit for automating thermal treatment of at least one sample, at least one control unit, and at least one communication interface. The laboratory system is configured to perform a method for performance verification according to the invention, such as described above or described in more detail below. For details, options and definitions, reference may be made to the method as described above.

[0068] As used herein, the term "instrument" is a broad term and should be given its ordinary and customary meaning to those of ordinary 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, any device configured to perform a sample processing step. For example, the instrument may be a clinical diagnostic analyzer.

[0069] The instrument further comprises at least one detection unit. In addition to the thermal block cycler unit, the instrument may also comprise at least one optical unit (eg configured for fluorescence excitation and detection of fluorescence).

[0070] This article further discloses and proposes a computer program, which includes computer executable instructions, which, when executed on a computer or computer network, are used to perform the method according to the present invention in one or more embodiments attached hereto. Specifically, the computer program can be stored on a computer readable data carrier and / or a computer readable storage medium.

[0071] As used herein, the terms "computer-readable data carrier" and "computer-readable storage medium" may specifically refer to a non-transitory data storage device, such as a hardware storage medium having computer-executable instructions stored thereon. A computer-readable data carrier or storage medium may specifically be or may include a storage medium such as a random access memory (RAM) and / or a read-only memory (ROM).

[0072] Thus, in particular, one, more than one or even all of the method steps as indicated above (eg sequence i. to viii.) may be performed by using a computer or a computer network, preferably by using a computer program.

[0073] This article further discloses and proposes a computer program product with program code means, so that when the program is executed on a computer or computer network, the method according to the present invention is performed in one or more embodiments attached hereto. Specifically, the program code means can be stored on a computer-readable data carrier and / or on a computer-readable storage medium.

[0074] The present invention further discloses and proposes a data carrier having a data structure stored thereon, which, after being loaded into a computer or a computer network, such as after being loaded into a working memory or a main memory of the computer or the computer network, can execute a method according to one or more embodiments disclosed herein.

[0075] Further disclosed and proposed herein is a non-transitory computer-readable medium comprising instructions, which, 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.

[0076] This article further discloses and proposes a computer program product having a program code tool stored on a machine-readable carrier so that when the program is executed on a computer or computer network, a method according to one or more embodiments disclosed herein is performed. As used herein, a computer program product refers to a program that is a tradable product. The product can generally exist in any format (such as in paper format) or on a computer-readable data carrier and / or on a computer-readable storage medium. Specifically, the computer program product can be distributed on a data network.

[0077] Further disclosed and proposed herein is a modulated data signal containing instructions readable by a computer system or a computer network for performing a method according to one or more embodiments disclosed herein.

[0078] With reference to the computer-implemented aspects of the present invention, one or more method steps or even all method steps of the method according to one or more embodiments disclosed herein may be performed using a computer or a computer network. Therefore, generally speaking, any method step including providing and / or manipulating data may be performed using a computer or a computer network. Generally speaking, these method steps may include any method step other than method steps that typically require manual operation (such as providing samples and / or performing certain aspects of actual measurement).

[0079] Specifically, this article further discloses the following:

[0080] - a computer or a computer network comprising at least one processor, wherein the processor is adapted to perform a method according to one of the embodiments described in this specification,

[0081] - a computer-loadable data structure adapted to carry out a method according to one of the embodiments described in this specification when the data structure is executed on a computer,

[0082] - a computer program, wherein the computer program is adapted to carry out a method according to one of the embodiments described in the present description when the program is executed on a computer,

[0083] - a computer program comprising program means for carrying out a method according to one of the embodiments described in the present description when the computer program is executed on a computer or on a computer network,

[0084] - a computer program comprising program means according to the preceding embodiment, wherein the program means is stored on a computer-readable storage medium,

[0085] a storage medium, on which a data structure is stored and on which the data structure is suitable, after being loaded into a main memory and / or a working memory of a computer or a computer network, for carrying out a method according to one of the embodiments described in the present description, and

[0086] A computer program product having program code means, wherein the program code means can be stored or are stored on a storage medium for carrying out the method according to one of the exemplary embodiments described in the present description if the program code means is executed on a computer or a computer network.

[0087] To summarize and without excluding other possible embodiments, the following embodiments may be envisaged:

[0088] Embodiment 1. A computer-implemented method for performance validation of a thermal block cycler unit for automated thermal processing of at least one sample, wherein the thermal block cycler unit comprises at least one thermal block configured to receive at least one sample vessel,

[0089] wherein the thermal block cycler unit further comprises a plurality of hardware modules, wherein the hardware modules comprise a plurality of heating and / or cooling elements and at least one temperature sensor, wherein the method comprises: continuously performing functional tests on the hardware modules, wherein

[0090] Consider the following criteria to define the order of testing:

[0091] - each successive test is used to test the thermal energy of its previous test and / or the status of its previous test's thermal block circulator unit, and

[0092] - Balancing the energy consumption between the steps in such a way that the difference between the input temperature before the hardware module is tested successively and the output temperature after the hardware module is tested successively is minimized.

[0093] Embodiment 2. The method according to the above embodiment, wherein the hardware module comprises the following items:

[0094] One or more of: at least one temperature sensor, at least one fan, at least one operating pump, at least one thermoelectric cooler, at least one steam chamber mount.

[0095] Embodiment 3. The method according to the above embodiment, wherein the method comprises:

[0096] The sensor is tested, wherein the test comprises an electrical test, wherein the electrical test comprises: testing whether a temperature value is generated by the temperature sensor.

[0097] Embodiment 4. A method according to any one of the two preceding embodiments, wherein the method comprises: testing the temperature sensor, wherein the test comprises: testing the response behavior of the temperature sensor, wherein the test of the response behavior comprises: increasing the temperature to a maximum temperature or decreasing the temperature to a minimum temperature for a predefined time range, reading the temperature value generated by the temperature sensor before and after changing the temperature, calculating the difference and comparing the difference with at least one predefined threshold for a minimum temperature change, wherein if the threshold is exceeded and / or reached, the temperature sensor passes the test.

[0098] Embodiment 5. A method according to any one of the three preceding embodiments, wherein the method comprises: testing the fan, wherein the test comprises: testing the fan speed, wherein the test of the fan speed comprises: setting the fan to a maximum, monitoring the fan speed, and comparing the fan speed with at least one predefined threshold for the maximum fan speed, wherein if the threshold is exceeded and / or reached, the fan passes the test.

[0099] Embodiment 6. A method according to any one of the four preceding embodiments, wherein the method comprises: testing the operating pump, wherein the test comprises: testing the pump speed, wherein the test of the pump speed comprises: setting the pump to a maximum, monitoring the pump speed, and comparing the pump speed with at least one predefined threshold for the maximum pump speed, wherein if the threshold is exceeded and / or reached, the pump passes the test.

[0100] Embodiment 7. A method according to any one of the five preceding embodiments, wherein the method comprises: testing the thermoelectric cooler, wherein the test comprises: continuously testing a plurality of thermoelectric cooler pairs, wherein the test comprises: measuring the current and / or voltage during heating and cooling, wherein the test further comprises: comparing the current and / or voltage measured during heating and during cooling with a predefined threshold, wherein if the threshold is exceeded and / or reached, the corresponding thermoelectric cooler pair passes the test.

[0101] Embodiment 8. A method according to any one of the six preceding embodiments, wherein the method comprises: testing all thermoelectric coolers, wherein the test comprises: testing the power consumption during heating, wherein the power consumption is compared with a predefined threshold, wherein if the threshold is exceeded and / or reached, the thermoelectric cooler passes the test.

[0102] Embodiment 9. A method according to any one of the preceding seven embodiments, wherein the method comprises: testing a vapor chamber mount, wherein the test comprises: sequentially controlling the thermoelectric cooler and monitoring the thermal distribution of the vapor chamber mount, wherein the thermal distribution is compared with a predefined threshold, wherein the predefined threshold is defined as a maximum deviation from a desired temperature uniformity after a defined time, wherein if the threshold is not exceeded and / or reached, the vapor chamber mount passes the test.

[0103] Embodiment 10. The method according to any one of the preceding eight embodiments, wherein the method comprises

[0104] The following test sequence:

[0105] i. Perform basic electrical tests on the temperature sensor;

[0106] ii. Test the fan;

[0107] iii. Test the pump;

[0108] iv. Testing multiple thermoelectric cooler pairs in succession;

[0109] v. Test the power consumption of all thermoelectric coolers;

[0110] vi. Test the temperature sensor ramp;

[0111] vii. Testing of steam room mountings,

[0112] viii. At least one shutdown action, the at least one shutdown action comprising one or more of: disabling all active elements, and reporting data.

[0113] Embodiment 11. The method according to any one of the preceding embodiments, wherein the method comprises:

[0114] The results of the performance verification are displayed by at least one communication interface and / or at least one user interface.

[0115] Embodiment 12. The method according to the preceding embodiment, wherein the method comprises:

[0116] The communication interface reports the results of the performance verification to the LIMS system.

[0117] Embodiment 13. A method according to any one of the preceding embodiments, wherein the method is carried out in a regular

[0118] time intervals and / or based on user needs.

[0119] Embodiment 14. The method according to any one of the preceding embodiments, wherein the thermal block circulator unit

[0120] The element comprises and / or is connected to at least one control unit.

[0121] Embodiment 15. A laboratory system, the laboratory system comprising a

[0122] The laboratory system is configured to perform the method for performance verification according to any one of Examples 1 to 14.

[0123] Embodiment 16. The laboratory system according to the preceding embodiment, wherein the instrument further comprises

[0124] At least one detection unit.

[0125] Embodiment 17. A computer program comprising instructions, when the program is executed according to a method involving a laboratory system

[0126] When executed by a laboratory system according to any of the preceding embodiments of the system, the instructions cause the laboratory system to perform a method according to any of the preceding embodiments involving methods.

[0127] Embodiment 18. A computer-readable storage medium comprising instructions, when the instructions are generated according to the

[0128] When executed by a laboratory system according to any of the preceding embodiments of the laboratory system, the instructions cause the laboratory system to perform a method according to any of the preceding embodiments relating to methods.

[0129] Embodiment 19. A non-transitory computer readable medium comprising instructions, the instructions when executed by one or

[0130] When executed by the plurality of processors, the plurality of processors cause one or more processors to perform the method according to any one of the aforementioned embodiments involving methods. BRIEF DESCRIPTION OF THE DRAWINGS

[0131] Other optional features and embodiments will be disclosed in more detail in the subsequent description of embodiments, preferably in conjunction with the dependent claims. Wherein, as will be appreciated by those skilled in the art, each optional feature can be implemented in a separate manner and in any arbitrarily feasible combination. The scope of the present invention is not limited by the preferred embodiments. Embodiments are schematically depicted in the accompanying drawings. Wherein, the same reference numerals in these drawings refer to the same or functionally equivalent elements.

[0132] In the attached picture:

[0133] Figure 1 An exemplary flow chart illustrating an embodiment of a computer-implemented method for performance validation of a thermal block cycler unit;

[0134] Figure 2 The experimental data are shown, in particular, according to Figure 1 The temperature characteristics of five runs of the method used for performance verification, and

[0135] Figure 3 An embodiment of a laboratory system is shown. DETAILED DESCRIPTION

[0136] Figure 1An exemplary flow chart of an 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 is shown. The thermal block cycler unit 110 may be a component of a laboratory system 112, such as Figure 3 The laboratory system 112 further includes at least one control unit 114 and at least one communication interface 116 .

[0137] The method can be used in the field of in vitro diagnosis. For example, the laboratory system can be part of a clinical laboratory, a medical laboratory, a forensic laboratory or a blood bank. The sample can be a biological sample. The sample can be from any biological source, such as a physiological fluid, including blood, saliva, eye lens fluid, cerebrospinal fluid, sweat, urine, milk, ascites, mucus, synovial fluid, peritoneal fluid, amniotic fluid, tissue, cells, etc. For example, a biological sample can be or can include an aliquot of a substance (such as a biological compound). For example, a biological sample can be or can include at least one biological specimen, such as one or more of the following items: blood; serum; plasma; urine; saliva. The biological sample can be a liquid sample. For example, a liquid sample can be or can include at least one pure liquid, such as a liquid substance and / or a solution comprising one or more liquid substances, which comprises a biological substance. A liquid sample can be or can include a liquid mixture, such as a suspension, an emulsion and / or a dispersion of a biological substance. The biological sample can be a solid sample, for example, at least one tissue sample. The sample may be pre-treated before use, such as preparing plasma from blood, diluting viscous liquids, lysing, etc.; the treatment method may involve filtration, distillation, concentration, inactivation of interfering components, and addition of reagents. The sample can be used directly after being obtained from the source, or it can be pre-treated to change the characteristics of the sample, such as after dilution with another solution or after mixing with a reagent, for example, to perform one or more diagnostic tests, such as clinical chemistry tests, immunoassays, coagulation tests, nucleic acid detection, etc.

[0138] The heat block cycler unit 110 includes at least one heat block 118. The heat block 118 can be configured to perform temperature cycling, for example, to perform temperature-sensitive reactions (e.g., amplification reactions), such as to perform polymerase chain reactions (PCR). The heat block 118 is configured to receive at least one sample vessel. The heat block 118 may include at least one sample block configured to receive at least one sample vessel. The sample vessel may be or may include one or more of the following items: at least one tubular container, at least one bracket, at least one puck, or at least one slide. For example, the sample vessel may include at least one multi-well plate. The multi-well plate may typically have, for example, 6, 24, 96, 384, or 1536 sample wells arranged in a 2:3 rectangular matrix. The wells may be circular or square. The sample block may be configured to achieve rapid temperature changes and uniform temperature throughout the block. After the sample vessel is inserted into the sample block, the temperature of the sample block may be changed, for example, raised and / or lowered according to a predefined temperature cycle.

[0139] The thermal block cycler unit 110 further includes a plurality of hardware modules 120. For example, the thermal block cycler unit 110 further includes at least one temperature sensor 122. The thermal block cycler unit 110 may include a plurality 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.

[0140] In addition, the hardware module 120 includes a plurality of heating and / or cooling elements. For example, the hardware module includes one or more of the following: at least one fan 124 , at least one operating pump 126 , at least one thermoelectric cooler 128 , at least one vapor chamber mount 130 .

[0141] The fan 124 can be configured to cool the thermal block circulator unit 110 during operation. The fan 124 can be configured to provide air flow through the thermal block circulator unit 110. The air flow can be exhausted from the thermal block circulator unit 110 at an opening in the housing of the thermal block circulator unit 110. The thermal block circulator unit 110 can include a plurality of fans 124.

[0142] The thermal block circulator unit 110 may include at least one water cooling system with an operating pump 126 and with solid-liquid and liquid-air heat exchangers.

[0143] The thermal block circulator unit 110 may be driven by a plurality of thermoelectric coolers 128 (eg, six Peltier elements).

[0144] The vapor chamber mount 130 can be configured to provide temperature uniformity across the thermal block 118. The thermal block circulator unit 110 can include a plurality of vapor chamber mounts 130.

[0145] The proposed method allows for performance verification of the thermal block cycler unit 110. The method may be performed fully automatically (eg without user interaction).

[0146] Performance may be a measure 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 be associated with performance within the manufacturer's specifications. Poor thermal performance may be associated with performance that deviates from the manufacturer's specifications. Performance may be characterized relative 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), etc. The performance of the thermal block cycler unit 110 may be affected by the performance of various 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 for verifying good thermal performance of the thermal block cycler unit 110.

[0147] The method steps may be performed in a given order or may be performed in a different order. Further, there may be one or more additional method steps not listed. Further, one, more than one or even all method steps may be performed repeatedly.

[0148] The method includes: continuously performing functional tests on the hardware module 120, wherein the order of the tests is defined taking into account the following criteria:

[0149] - each successive test is used to test the thermal energy of its previous test and / or the status of its previous test's thermal block circulator unit, and

[0150] - Balancing the energy consumption between the steps in such a way that the difference between the input temperature before the hardware module is tested successively and the output temperature after the hardware module is tested successively is minimized.

[0151] Functional testing may include testing at least one basic function of the corresponding hardware module 120 (such as whether the hardware module is working) and / or testing the corresponding hardware module 120 against its corresponding specifications. Functional testing may include testing the corresponding hardware module (e.g., of the same type) or a group of hardware modules individually.

[0152] Using the standards listed above allows energy efficiency and speed. These two goals can be achieved by setting the order of the test steps so that each successive step benefits from the heat energy and / or the state of the thermal cycler of the previous step. Therefore, the amount of energy input into the system can be minimized, thereby helping to reduce the execution time. In addition, energy can be balanced between steps in such a way that the difference between the starting temperature of the thermal cycler (the temperature before the test starts) and the end temperature of the thermal cycler (the temperature after the test ends) is minimized. This allows reducing the time during which the thermal cycler cannot be used for the end user.

[0153] Performance verification can be part of an automatic diagnostic workflow of the thermal block cycler unit 110. For example, performance verification can be part of a workflow for predictive maintenance. For example, performance verification can be part of a workflow for verifying the calibration of the thermal block cycler unit 110. Performance verification can be performed at the beginning of operation, such as during initial setup and / or each time the thermal block cycler unit 110 is turned on. The method can be performed at regular time intervals and / or according to user needs. Performance verification can be automatically and repeatedly performed at predefined times (e.g., every 10 runs, or once a day, or during each instrument startup). In the case of observing deviations in the performance of at least one hardware module 120 (such as the absence of a signal from a temperature sensor, a failure in the electronics, etc.), performance verification can be automatically triggered and performed. For example, a performance test can be triggered to detect the root cause by detecting at least one deviation from any desired feature in terms of heating and / or cooling ramps. For example, a performance test can be triggered in the case of high or low heat sink temperatures during operation. Performance verification can be automatically triggered and / or performed by at least one control unit. In addition, performance verification can be performed according to user needs (e.g., via at least one user interface).

[0154] Figure 1 A flow chart is shown in which the method includes the following exemplary test sequence:

[0155] i. (132) performing basic electrical testing on the temperature sensor 122;

[0156] ii. (134) testing the fan 124;

[0157] iii. (136) testing the pump 126;

[0158] iv. (138) continuously testing a plurality of thermoelectric coolers 128;

[0159] v. (140) testing the power consumption of all thermoelectric coolers 128;

[0160] vi. (142) testing the temperature sensor 122 ramp;

[0161] vii. (144) Testing the steam chamber mounting 130,

[0162] viii. (146) At least one shutdown action, the at least one shutdown action comprising one or more of: disabling all active elements, and reporting data.

[0163] This order of testing may allow the above criteria to be met. However, other orders may be possible.

[0164] The method may be performed fully automatically. For example, each of the steps may be performed by the control unit 114 by controlling the operation of the corresponding hardware module 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 to issue an error and / or at least one other action.

[0165] The method may include testing the complete sequence of steps or aborting the sequence in the event of an error.

[0166] Figure 1 The flowchart in is depicted in a tabular form, wherein the method steps are shown in the left column, the sub-steps included in the method steps are shown in the middle column, and the optional actions after the corresponding method steps are depicted in the right column, such as issuing an error code or switching the corresponding hardware module 120 being tested to perform subsequent testing of another hardware module 120.

[0167] exist Figure 1 In an embodiment, a basic electrical test 132 of the temperature sensor 122 may first be performed. The basic electrical test 132 may include a basic functional test of the temperature sensor 122 or different temperature sensors 122 (e.g., not related to the correctness of the measured temperature). If a temperature value is generated (e.g., a signal from the temperature sensor 122 is received by the control unit 114), the temperature sensor 122 passes the test. Otherwise, the temperature sensor 122 is faulty. In this case, an error may be issued and / or recorded by the control unit 114. For example, if Figure 1 As shown, the basic electrical test 132 may include sub-steps of reading all temperature sensors 122 ("Read All Sensors (Ambient Temperature)") and defining whether all temperature sensors 122 are valid ("Define Sensor Valid"). In step i., no energy can be input or output. This step can be performed quickly.

[0168] In step ii.134, the fan 124 is tested and the temperature may be reduced. Test 134 may include testing the fan speed. Testing the fan speed may include setting the fan to maximum ("Set fan to 100% on"), monitoring the fan speed ("Enable / Monitor TIM_ISR (Fan TACHO PIN)") (for example, by using the fan internal status signal), and comparing the fan speed with at least one predefined threshold for the maximum fan speed. The threshold may be defined as the desired fan speed according to the fan's data sheet. If the threshold is exceeded and / or reached, the fan passes the test. Otherwise, the fan is faulty. In this case, an error may be issued by the control unit 114 ("Fan_Error") and / or recorded. After this test 134, the fan 124 is turned off ("Set fan to 0% off").

[0169] In step iii.136, the pump 126 is tested. The temperature can be reduced in this step. For example, the liquid flow in the cooling circuit can cause energy transfer, so the temperature of the heating block can be reduced by increasing the temperature of the radiator (liquid-air heat exchanger). Test 136 may include: testing the pump speed. The test of the pump speed may include: setting the pump to the maximum ("set the pump to open 100%), monitoring the pump speed ("enable / monitor TIM_ISR (pump TACHO PIN)") (for example, by using its internal status signal), and comparing the pump speed with at least one predefined threshold for the maximum pump speed. The threshold can be defined as the expected pump speed according to the data sheet of the pump. If the threshold is exceeded and / or reached, the pump 126 passes the test. Otherwise, the pump 126 is wrong. In this case, an error ("pump_error") can be issued and / or recorded by the control unit 114. After this test 136, the pump 126 is turned off ("set the pump to close 0%).

[0170] Step iv.138 may include testing a plurality of thermoelectric cooler pairs 128 in succession, such as testing a first TEC pair (TEC1), testing a second TEC pair (TEC2), and testing a third TEC pair (TEC3). For each TEC pair, the test 138 may include measuring the current I and / or the voltage U during heating and cooling. For example, first, the heating is set to 100% ("Set Heating to 100%) and the current I and / or the voltage U are measured ("Measure U and I"). Next, the cooling is set to 100% ("Set Cooling to 100%) and the current I and / or the voltage U are measured ("Measure U and I"). Subsequently, the TEC pair being tested is turned off ("Set_TEC_Off(0%)"). For each TEC pair, the test 138 may further include comparing the current and / or voltage measured during heating UTTECi_heating (representing the corresponding TEC) and during cooling UTTECi_cooling (representing the corresponding TEC) to a predefined threshold ("threshold"). Figure 1 , the following deviations are calculated:

[0171] TEC deviation = (UTTECi heating + UTTECiTECj heating + UTTECj cooling)

[0172] Where i and j represent the respective TECs in the TEC pair. A threshold value may be defined based on the electrical parameters of the TECs under an assumed worst case scenario (e.g., worst ambient thermal conditions). If the threshold value is exceeded and / or reached, the respective thermoelectric cooler pair passes the test. Otherwise it is faulty. In this case an error ("TECi_error", representing the respective TEC) may be issued and / or recorded by the control unit 114.

[0173] Steps iv.138 and v.140 may be temperature neutral, for example increasing or decreasing the temperature.

[0174] In step v.140, the power consumption of all TECs 128 may be tested ("Test for short circuit"), wherein the temperature is increased. Test 140 may include: Testing the power consumption during heating. The power consumption may be compared to a predefined threshold. The threshold may be defined based on electrical parameters of the TECs under an assumed worst case scenario (e.g. worst ambient thermal conditions). If the threshold is exceeded and / or reached, the thermoelectric coolers 128 pass the test. Otherwise at least one of them is faulty. In this case, an error ("Overcurrent_Error") may be issued and / or logged by the control unit 114.

[0175] In step vi.142, a test of the ramp of the temperature sensor 122 may be performed and the ramp rate of heating the temperature sensor 122 may be measured using the rising temperature of the previous step. This step 142 may include reversing the TEC 128 to cool and measuring the cooling ramp rate. Figure 1 As shown, the test 142 for the response behavior may include: increasing the temperature to a maximum temperature ("Set_Heat 100% 1.5s") or decreasing the temperature to a minimum temperature for a predefined time range (e.g., for 1.5s), reading the temperature values ​​generated by the temperature sensor 122i before and after changing the temperature ("Read All Sensors (Hot Temperature)"), and calculating the differential temperature increment (i), for example, by:

[0176] TemperatureDelta(i)=(BlockController.SensorTemperature[i].Temperature-ShutdownTemperature[i]), and the difference TemperatureDelta(i) is compared with at least one predefined threshold value ("Threshold") for a minimum temperature change. The threshold value for a minimum temperature change may be defined relative to a thermal design of the heating block assuming a worst-case use case scenario (i.e., worst-case ambient thermal conditions). If the threshold value for a minimum temperature change is exceeded or at least reached, the temperature sensor 122i passes the test. Otherwise, the temperature sensor 122i is faulty. In this case an error ("Sensor_Error") may be issued and / or logged by the control unit 114.

[0177] Testing 144 of 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 arranged between the solid-liquid heat exchanger and the VCM 130. The TECs 128 may be sequentially controlled ("Set TECs 1-2, 5-6 to off for 1.5 s") and the thermal distribution in the VCM 130 may be monitored ("Read all sensors (hot temperatures)"). The thermal distribution may be compared to predefined thresholds. For example, an average of the ambient and hot temperatures of all valid temperature sensors may be calculated ("Calculate average of ambient and hot temperatures for all valid temperature sensors"). If the number of valid temperature sensors 122 is ≤ 2, an error ("VCM_ERR") may be issued and / or logged by the control unit 114. Otherwise, a deviation from a desired temperature uniformity after a defined time may be calculated, for example by:

[0178] Temperature Deviation (i) = Hot Temperature [i] - Temperature Environment [i] + Ambient Temperature Average - Temperature Average The threshold value may be defined as the maximum deviation from the desired temperature uniformity after a defined time (e.g., such as ±1.5°C). If the threshold value is not exceeded and / or reached, the VCM passes the test. Otherwise, at least one of them is in error. In this case an error ("VCM_Error") may be issued and / or recorded by the control unit 114. The test of the steam chamber installation may be performed so that the final temperature is similar to the starting temperature of the complete sequence.

[0179] Finally, at least one shutdown action may be performed, such as one or more of: disabling all active elements, and reporting data.

[0180] Figure 2 The experimental data are shown, in particular, according to Figure 1 Temperature profiles of five runs of the method used for performance verification. The graph shows that the above criteria are met.

[0181] Reference numerals list

[0182] 110 Thermal Block Circulator Unit

[0183] 112 Laboratory Systems

[0184] 114 Control Unit

[0185] 116 Communication Interface

[0186] 118 Heat Block

[0187] 120 Hardware Modules

[0188] 122 Temperature sensor

[0189] 124 Fan

[0190] 126 Pump

[0191] 128 Thermoelectric Cooler

[0192] 130 Steam Chamber Mounting

[0193] 132 Basic Electrical Tests

[0194] 134 Testing the fan

[0195] 136 Testing the pump

[0196] 138 Testing Multiple Thermoelectric Cooler Pairs

[0197] 140 Testing the power consumption

[0198] 142 Test the temperature sensor

[0199] 144 Testing of steam chamber mountings

[0200] 146 Close Action

Claims

1. A computer-implemented method for performance verification of a thermal block cycler unit (110) for automated thermal processing of at least one sample, wherein the thermal block cycler unit (110) comprises at least one thermal block (118) configured to receive at least one sample vessel, wherein the thermal block circulator unit (110) further comprises a plurality of hardware modules (120), wherein the hardware modules (120) comprise a plurality of heating and / or cooling elements and at least one temperature sensor (122), The method comprises: The hardware modules are functionally tested sequentially, wherein the order of the tests is defined taking into account the following criteria: - each successive test is used to test the thermal energy of its previous test and / or the status of the thermal block circulator unit (110) of its previous test, and - balancing energy consumption between steps in such a way as to minimize the difference between the input temperature before the hardware module (120) is tested successively and the output temperature after the hardware module (120) is tested successively.

2. A method according to the preceding claim, wherein the hardware module (120) comprises one or more of the following: at least one temperature sensor (122), at least one fan (124), at least one operating pump (126), at least one thermoelectric cooler (128), at least one steam chamber mount (130).

3. The method according to the preceding claim, wherein the method comprises: The temperature sensor (122) is tested, wherein the test includes an electrical test, wherein the electrical test includes testing whether a temperature value is generated by the temperature sensor (122).

4. The method according to any one of the two preceding claims, wherein the method comprises: The temperature sensor (122) is tested, wherein the test includes: testing the response behavior of the temperature sensor (122), wherein the test of the response behavior includes: increasing the temperature to a maximum temperature or decreasing the temperature to a minimum temperature for a predefined time range, reading the temperature values ​​generated by the temperature sensor (122) before and after changing the temperature, calculating a difference, and comparing the difference with at least one predefined threshold for a minimum temperature change, wherein if the threshold is exceeded and / or reached, the temperature sensor (122) passes the test.

5. The method according to any one of the three preceding claims, wherein the method comprises: The fan (124) is tested, wherein the test includes: testing fan speed, wherein the testing of the fan speed includes: setting the fan to maximum, monitoring the fan speed, and comparing the fan speed to at least one predefined threshold for maximum fan speed, wherein if the threshold is exceeded and / or reached, the fan (124) passes the test.

6. The method according to any one of the preceding four claims, wherein the method comprises: The operating pump (126) is tested, wherein the test includes: testing the pump speed, wherein the testing of the pump speed includes: setting the pump to maximum, monitoring the pump speed, and comparing the pump speed to at least one predefined threshold for the maximum pump speed, wherein if the threshold is exceeded and / or reached, the pump (126) passes the test.

7. The method according to any one of the five preceding claims, wherein the method comprises: The thermoelectric cooler (128) is tested, wherein the test includes: testing a plurality of thermoelectric cooler pairs (128) in succession, wherein the test includes: measuring current and / or voltage during heating and cooling, wherein the test further includes: comparing the current and / or voltage measured during heating and during cooling with predefined thresholds, wherein if the thresholds are exceeded and / or reached, the respective thermoelectric cooler (128) pair passes the test.

8. The method according to any one of the six preceding claims, wherein the method comprises: All thermoelectric coolers (128) are tested, wherein the test includes testing power consumption during heating, wherein the power consumption is compared to a predefined threshold, wherein if the threshold is exceeded and / or reached, the thermoelectric cooler (128) passes the test.

9. The method according to any one of the preceding seven claims, wherein the method comprises: At least one vapor chamber mount (130) is tested, wherein the test comprises sequentially controlling the thermoelectric cooler (128) and monitoring a thermal profile of the vapor chamber mount (130), wherein the thermal profile is compared to a predefined threshold, the predefined threshold being defined as a maximum deviation from a desired temperature uniformity after a defined time, wherein if the threshold is not exceeded and / or reached, the vapor chamber mount (130) passes the test.

10. The method according to any one of the preceding eight claims, wherein the method comprises the following test sequence: i. (132) performing basic electrical testing on the temperature sensor (122); ii. (134) testing the fan (124); iii. (136) testing the pump (126); iv. (138) continuously testing multiple thermoelectric cooler pairs (128); v. (140) testing the power consumption of all thermoelectric coolers (128); vi. (142) testing the temperature sensor (122) ramp; vii. (144) testing the steam chamber mounting (130), viii. (146) At least one shutdown action, the at least one shutdown action comprising one or more of: disabling all active elements, and reporting data.

11. The method according to any one of the preceding claims, wherein the method comprises: The result of the performance verification is displayed via at least one communication interface (116) and / or at least one user interface, and / or wherein the method comprises: reporting the result 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, the at least one instrument 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), wherein the laboratory system (112) is configured to perform a method for performance verification according to any one of claims 1 to 11.

13. A computer program comprising instructions which, when executed by a laboratory system (112) according to any of the preceding claims relating to laboratory systems, cause the laboratory system to perform a method according to any of the preceding claims relating to methods.

14. A computer-readable storage medium comprising instructions which, when executed by a laboratory system (112) according to any of the preceding claims relating to laboratory systems, cause the laboratory system to perform a method according to any of the preceding claims relating to methods.

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 a method according to any of the preceding claims relating to a method.

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