Method for operating a pipetting apparatus, and such an apparatus

Abstract

The invention relates to a method for operating a pipetting apparatus using a control device and to such a pipetting apparatus. In order to keep the number of pipette tips to be used in a work process as low as possible, pipetting operations of a previously determined sequence of pipetting operations to be carried out are categorized, wherein each category is assigned a predefined pipette tip class, wherein each pipette tip class is assigned at least a service life and a storage location as features for the use of the pipette tips to be used in the pipetting operations. For the pipette tips assigned to the respective pipette tip classes, the service life and the storage location are in each case determined by a class-specific feature parameter. The pipette tips to be used are each assigned to a pipette tip class when the determined sequence of categorized pipetting operations is being carried out, wherein the control device controls the pipetting unit on the basis of the assignment of the pipetting operations to categories and the assignment of the pipette tips to a respective one of the pipette tip classes in the work process, wherein the pipetting unit takes into account the class-specific feature parameters when selecting and using the pipette tips.

Description

[0001] Method for operating a pipetting device and such a device

[0002] Field of invention

[0003] The invention relates to a method for operating a pipetting device, in particular for coordinating pipette tips in a workflow carried out by means of the device, in which a pipetting unit with a pipetting element performs pipetting operations for the treatment of samples in the workflow using a plurality of provided pipette tips, wherein the method is carried out using a control device. The invention also relates to such a pipetting device, in particular for the treatment of samples in blood culture analysis.

[0004] Devices for pipetting and methods for operating such devices using a control unit are known and are generally referred to as computer-controlled or automated liquid handling systems. Both the high reliability and the progressive simplification of such systems, for example through the use of analysis kits, have contributed to the establishment of the aforementioned devices and methods in various scientific or application-oriented fields, such as medicine, biology, pharmacy, and chemistry.

[0005] A computer-controlled workstation for handling liquids and a control method for this workstation are known, for example, from document EP 2 269 077 B1. The workstation disclosed therein comprises a work surface for placing liquid containers, a motorized pipetting robot with a pipette, and a control computer. The control computer is electrically connected to the pipetting robot and controls it in such a way that the pipette is positioned at specific locations relative to the work surface in order to aspirate and dispense volumes of liquid.

[0006] Such systems are typically designed for processing multiple samples. Pipetting operations are usually performed using a pipetting element or pipettes with interchangeable pipette tips. These tips are generally disposable, meaning they are discarded after a single use. Disposable pipette tips offer the advantage of preventing cross-contamination between samples. However, a disadvantage is that a new pipette tip is required for each step in a workflow, resulting in a high number of used and, consequently, disposed pipette tips.With an increasing number of samples to be processed, both the high number of pipette tips required and their disposal represent a significant and cumulative cost factor. Reducing the number of pipette tips needed is therefore of general interest, particularly with regard to conserving the environment and resources.

[0007] Document EP 1 772 192 B1 discloses a device for the biochemical processing of samples, designed to reduce the number of pipette tips required when processing multiple samples. The device comprises multiple reaction zones of various types, a pipette for dispensing a liquid (with a detachable pipette tip attached to the pipette), and pipette tip storage compartments, each capable of holding a pipette tip. Each pipette tip is intended to be used for all processing steps of a specific sample and discarded only after the complete processing of that sample. The described device provides several reaction zones for different processing steps, each reaction zone having a pipette tip storage compartment for used pipette tips.Pipette tip storage rooms allow for the temporary storage of pipette tips, enabling the use of different tips for processing samples in different reaction areas. For example, if two or more samples are processed alternately in different steps, the pipette tip already used for the first sample can be temporarily stored in the designated pipette tip storage room, while a new tip is attached to the pipette for processing the second sample. This new tip can then be used to process the second sample in a different step.

[0008] However, the approach described above is not applicable to systems where at least one process fluid is drawn from the same container to treat multiple samples. If the treatment of the multiple samples involves pipetting operations that require direct contact between the pipette tip and the sample, the process fluid would become contaminated with sample material from the samples if the same pipette tip were used for all pipetting operations intended for a specific sample. This contamination would then be transferred to the other samples being treated. The necessary consequence would be the time-consuming cleaning of the pipette tip between pipetting operations.Particularly in application-oriented fields such as medicine, where the high reliability of such automated systems in sample preparation, from the initial sample to the final analysis, can be advantageously utilized, the time factor can play a crucial role, for example, when it comes to sample preparation in sepsis diagnostics. Therefore, there is a need to further develop and optimize corresponding processes and devices.

[0009] The invention is therefore based on the objective of enriching the prior art and providing an improved method for operating a pipetting device or an improved pipetting device itself. In particular, the invention is based on the objective of demonstrating a method for operating a pipetting device and a pipetting device itself that make it possible to minimize the number of pipette tips used in a single workflow and, at the same time, the cleaning requirements for the pipette tips.

[0010] Description of the invention

[0011] The invention solves the underlying problem in a method for operating a pipetting device of the type mentioned above, with the features of the method according to claim 1. The invention also solves the underlying problem with a pipetting device according to claim 15. Advantageous embodiments of the invention are the subject of the dependent claims and are explained in more detail in the following description, in particular with reference to the figures.

[0012] The invention relates in a first aspect to a method for operating a pipetting device, in particular for coordinating pipette tips in a workflow carried out in the pipetting device, wherein a pipetting unit with a pipetting element performs pipetting operations for the treatment of samples in the workflow using a plurality of provided pipette tips, wherein the method is carried out using a control device, comprising at least the following steps:

[0013] - Determining a sequence of pipetting operations to be performed in the workflow by adapting a predefined sequence of pipetting operations to a predetermined number of samples to be processed; - Assigning the pipetting operations to be performed to categories, wherein each category is assigned a predefined pipette tip class, and wherein each pipette tip class is assigned at least one service life and a storage location as characteristics for the use of the pipette tips to be used in the pipetting operations, wherein the service life and the storage location for the pipette tips assigned to the respective pipette tip classes are each determined by a class-specific characteristic parameter;

[0014] - Executing the determined sequence of categorized pipetting operations, wherein the pipette tips to be used are each assigned to a pipette tip class, and wherein the control device controls the pipetting unit based on the assignment of the pipetting operations to categories and the assignment of the pipette tips to each of the pipette tip classes in the workflow, wherein the pipetting unit selects and uses the pipette tips taking into account the class-specific characteristic parameters.

[0015] Preferably, the method can be used in conjunction with a pipetting device in an analytical or medical laboratory. In particular, the method can be used in conjunction with a pipetting device used in sepsis diagnostics for preparing sample material for blood culture analysis. The method can be specifically designed to operate a pipetting device configured as a pipetting robot or liquid handling system, or which includes a pipetting robot or liquid handling system. The method is, in particular, a method for operating an automated pipetting device, meaning that the pipetting operations for sample processing are computer-controlled or automated.

[0016] According to the invention, the pipetting unit is controlled by the control unit. The control unit can comprise a computer unit and a positioning unit. The computer unit, in turn, can comprise at least one memory unit and a processor unit. The memory unit can comprise a data memory and a system memory. A data memory is configured to receive and store information in a retrievable manner. The processor unit can be configured to issue commands and / or provide feedback to a user. By means of the positioning unit, the position of the pipetting unit relative to a work surface of the device can be changed, for example, in a plane parallel to the work surface or by changing the distance of the pipetting unit from the work surface. The positioning unit can comprise a drive unit and a guide device.Alternatively, it is conceivable that the positioning unit includes a robot unit.

[0017] The pipetting unit comprises a pipetting element. The pipetting element can be designed for pipetting various fluid media. In particular, the pipetting element is configured to aspirate and / or dispense fluid volumes. Within the scope of the disclosure, the pipetting element of the pipetting unit is designed such that a pipette tip can be repositioned, and in particular replaced, onto the pipetting element. Pipette tips are devices with a shape essentially corresponding to a truncated cone, both ends of which are open. The end with the larger diameter is the end that is placed onto the pipetting element. In particular, the pipette tips can be commercially available pipette tips, especially single-use pipette tips.

[0018] The samples are primarily fluid samples. The samples may be liquids. The samples may be biological samples. The samples may be in suspension. The samples may contain cells. The cells may be of human, animal, or plant origin and / or include such cells. The cells may also be microbial cells and / or include microbial cells. Microbial cells may include bacterial cells or human-pathogenic infectious fungal cells, especially yeasts or molds. The samples may contain a mixture of cells of human, animal, or plant origin and microbial cells.The samples may be or include all types of samples examined in analytical, medical, clinical, or research laboratories, including but not limited to blood, serum, plasma, blood fractions, synovial fluid, urine, semen, saliva, feces, cerebrospinal fluid, gastric contents, vaginal secretions, tissue homogenates, bone marrow aspirates, bone homogenates, sputum, aspirates, swabs and swab washes, blood products (e.g., platelets, serum, plasma, leukocyte fractions, etc.), organ or tissue samples from donors, other body fluids, and the like. In particular, the samples disclosed may include blood samples or a blood culture.It should be noted at this point that the inventive method can also be transferred to other suitable automated or computer-controlled pipetting systems in which the treatment of fluid, pasty, gel-like or other pipettable samples is provided.

[0019] Within the context of the disclosure, a workflow can be understood as one or more consecutive, identified sequences of pipetting operations to be performed. An identified sequence of pipetting operations, within the context of the disclosure, is understood as a defined sequence of differing pipetting operations. Pipetting operations, within the context of the disclosure, can include transferring and / or dispensing and / or mixing the media to be pipetted. Mixing, within the context of the disclosure, can be understood, for example, as multiple pipetting steps. Successive sequences of pipetting operations within a workflow can differ. It is also conceivable that a workflow comprises multiple, repeating, identical sequences of pipetting operations. In particular, it is conceivable that a workflow comprises both identical and differing sequences of pipetting operations.

[0020] A predefined sequence of pipetting operations, as defined in the disclosure, can be understood as a sequence of pipetting operations required for the treatment, in particular the preparation, of a single sample and can be stored in the memory unit. In particular, the stored sequence can be determined, specified, or programmed. The predefined sequence can (i) comprise the pipetting operations required for the complete treatment, in particular the preparation, of the sample material of a single sample, or (iii) comprise a subset of the pipetting operations required for the complete treatment, in particular the preparation, of the sample material of a single sample. The sequence of pipetting operations to be performed is determined by adapting the predefined sequence of pipetting operations to a predetermined number of samples to be treated.The number of samples can be limited by an individual embodiment of the device. The number of samples to be processed in the workflow can be detected or read out by a readout device or specified by a user. This adjustment can be automated using the computer unit. Within the scope of the disclosure, the determined sequence of pipetting operations can thus include at least the pipetting operations required for the complete processing, in particular preparation, of the sample material of a single sample. Typically, a determined sequence of pipetting operations can include the pipetting operations required for the complete processing, in particular preparation, of several samples.In certain embodiments, the determined sequence of pipetting operations to be performed within the scope of the disclosure may also comprise only a subset of the pipetting operations that would be necessary for the complete treatment, in particular preparation, of the sample material of a single sample or multiple samples. This means that pipetting operations may be required / must be performed for the complete treatment of a sample or multiple samples that do not belong to the determined sequence of pipetting operations. While the pipetting operations of the determined sequence may follow one another chronologically in the workflow, they do not necessarily have to follow each other immediately, provided that the treatment of the one or more samples includes further pipetting operations that do not belong to the determined sequence of pipetting operations.This means that one or more pipetting operations that do not belong to the determined sequence of pipetting operations can be interspersed with the pipetting operations of the determined sequence.

[0021] It should be noted here that a workflow, in addition to the identified sequence(s) of pipetting operations, can also include one or more steps that do not involve pipetting. It is also conceivable that, besides pipetting operations within a specific sequence, additional pipetting operations unrelated to the sequence may occur, such as transferring process fluids from the containers in which they are purchased into special containers, for example, those that can be opened automatically by the pipetting unit. In particular, these can also be pipetting operations that are not part of the sample processing.

[0022] For the purposes of this disclosure, a process fluid may be understood to be a medium, in particular a liquid, used in a workflow for the treatment of samples, selected from a group comprising or consisting of, but not limited to: (i) chemicals, (ii) reagents, (iii) buffers, for example a phosphate-buffered salt solution (PBS), (iv) solvents, for example deionized water, (v) nutrient solutions, for example a nutrient broth, (vi) washing liquids, for example isopropanol, or (vii) water.

[0023] According to the invention, pipetting operations are assigned to categories. Several pipetting operations in the determined sequence of pipetting operations to be performed can correspond to the same category. The assignment of pipetting operations to categories can be automated using the computer unit. Categorization can be understood as the systematic ordering of pipetting operations.

[0024] Different categories can be assigned within the framework of the disclosure, for example, task-related / activity-related, meaning that different categories can be based on different intended tasks / activities that a pipetting process fulfills.A task / activity, and thus a category, may be selected, for example, from a group comprising or consisting of, but not limited to: (i) adding a liquid, in particular a process liquid, to an infectious or sterile sample; (ii) decanting a supernatant from an infectious sample; (iii) decanting a supernatant from a sterile sample; (iv) mixing an infectious sample with an added liquid, in particular a process liquid; (v) mixing a sterile sample with an added liquid, in particular a process liquid; (vi) transferring an infectious sample; (vii) transferring a sterile sample; (viii) dividing an infectious sample; (ix) dividing a sterile sample. The above list is exemplary, in particular expandable and not limiting. Other categories are conceivable.In particular, it is conceivable that pipette tips of a specific pipette tip class, in addition to the pipetting operations of their corresponding category, are used for one or more further pipetting operations that do not belong to this category, especially because they do not belong to the determined sequence of pipetting operations to be performed and therefore do not belong to any category. Cross-activity categories are also conceivable.

[0025] Alternatively, different categories can be assigned based on properties within the disclosure, particularly with regard to the medium to be pipetted. Different categories can thus be based on a property of the medium to be pipetted. Property-based, within the context of the disclosure, can be understood to mean that the media to be pipetted in different categories differ, for example, in type, state, or volume. The above list is expandable and not limiting. Different types of media to be pipetted that can result in different categories can, for example, be (i) process fluids, (ii) infectious samples, or (iii) sterile samples. Different states of media to be pipetted that can result in different categories can, for example, be based on different viscosities, such as liquid, gel-like, or pasty.Different volumes of media to be pipetted, which may result in different categories, may, for example, be selected from a group comprising or consisting of: (i) <2.5 pL, (ii) <100 pL, (iii) <100 pL, (iv) <200 pL, (v) <1 mL, or any other volume (specified as capacity) between 0.1 pL and 10 mL. In particular, the pipette tips assigned to different categories based on different volumes may themselves have different capacity volumes or be selected according to their capacity.

[0026] According to the invention, each category is assigned a predefined pipette tip class.

[0027] The predefined pipette tip classes can be stored in the memory unit. Each predefined pipette tip class is assigned features for the use of the pipette tips to be used in the pipetting processes. According to the invention, the features storage location and service life are assigned to the predefined pipette tip classes. In certain embodiments of the method, the feature list can be supplemented by further features, in particular features that can be selected arbitrarily. The features determine the use of the pipette tips by means of a class-specific feature parameter. A (feature) parameter is to be understood within the scope of the disclosure as a variable that is assigned to the respective feature in a class-specific manner. In this context, "predefined" is to be interpreted such that the feature parameter of at least one feature, or one pipette tip class, can be stored in the memory unit.Within the scope of the disclosure, a pipette tip class can thus be understood as a grouping of a subset of related specific feature parameters from a totality of feature parameters, wherein the feature parameters assigned to a pipette tip class are adapted to the respective category to which the pipette tip class is assigned.

[0028] The invention is based on the understanding that a workflow for processing samples in a pipetting device can be made more cost-efficient and environmentally and resource-friendly by reducing the number of pipette tips used and, consequently, the number of pipette tips to be disposed of. Such a reduction can be achieved if pipette tips can be used for longer or more frequently than is typical for disposable pipette tips.To achieve this, according to the invention, the pipette tips to be used are each assigned to a pipette tip class, wherein the control device controls the pipetting unit based on the assignment of the pipetting operations to categories and the assignment of the pipette tips to one of the pipette tip classes in the workflow, wherein the pipetting unit selects and uses the pipette tips taking into account the class-specific feature parameters.

[0029] Certain pipetting operations, such as adding a substance, can be performed without contact with the samples being treated (free dispense), while other pipetting operations, such as mixing or transferring samples, particularly fluids, require direct sample contact. Accordingly, the characteristic parameters for the service life of the pipette tips assigned to the individual pipette tip classes can differ depending on the class. By assigning the pipette tips to pipette tip classes, which according to the invention are each assigned to a category of pipetting operations, a pipette tip can be used for several pipetting operations of the associated category over the specified (i.e., defined) service life, in which the pipette tip comes into contact with the same medium being pipetted.The repeated and correspondingly extended use of individual pipette tips made possible in this way, for example even over a multiple determined sequences of pipetting operations to be carried out in a workflow, enables a significant reduction in the number of pipette tips to be used and accordingly disposed of in the workflow, thereby saving costs and conserving resources in a beneficial way in the long term.

[0030] The pipette tips can be provided in a carrier unit, which is usually commercially available, from which they are removed for pipetting operations. According to the invention, each class of pipette tips is assigned a storage location as a feature for the use of the pipette tips to be used in the pipetting operations. Within the scope of the disclosure, the feature "storage location" is to be understood as a place where a pipette tip is temporarily stored after its first use and during its respective service life, in particular between the intended pipetting operations. A feature parameter is assigned to each class-specific feature "storage location." Within the scope of the disclosure, a class-specific feature parameter for a storage location can be a specific location from a plurality of predefined specific locations on a work surface provided for the pipetting operations.By defining the storage location for each pipette tip within a specific class, it can be located, for example, in the immediate vicinity of the pipetting operation to be performed. This minimizes the risk of contamination between pipette tips of different tip classes. In particular, the storage location defined for each class can be different from the carrier unit described above. This advantageously allows such pipette tips to be removed from the standard exchange cycles of that carrier unit.

[0031] According to the invention, each pipette tip class is assigned a service life as a feature for the use of the pipette tips to be used in pipetting operations. A feature parameter is assigned to the service life feature, specific to each class. Within the scope of the disclosure, the service life feature can be understood as a maximum number of possible pipetting operations or as a maximum period of use. In a preferred embodiment, the feature parameter for the service life considers a maximum number of possible pipetting operations and / or a maximum period of use as criteria. The feature parameter for the service life is determined by achieving at least one of the two criteria.In other words, maximum service life is reached as soon as one of the two criteria reaches its maximum value, even if the other criterion has not yet reached its maximum value. The maximum number of possible pipetting operations can be determined by any empirically ascertainable numerical value. In particular, the maximum number of possible pipetting operations can be limited to the number of pipetting operations for which each pipette tip of a specific pipette tip class is intended within a determined sequence of pipetting operations. This numerical value can be determined by the processing unit and, in particular, displayed visually by an output device on the instrument.In particular, the numerical value can alternatively be an estimated value indicating how many pipetting operations a new pipette tip can be used for before it becomes unusable, for example, due to the accumulation of dust particles in the pipette. The maximum usage period can be defined in any unit, such as hours, days, or weeks, and determined within that unit by any empirically determinable numerical value. Specifically, the maximum usage period can result implicitly from a change in a property of the respective pipette tips. In this case, the criterion for the maximum usage period can have a dynamically changing value. One property of the pipette tips could be, for example, their opacity, where increasing opacity can indicate chemical wear.Another characteristic of the pipette tip can be deformation, for example, from contact with surfaces, with increasing deformation indicating mechanical wear. Yet another characteristic of the pipette tip can be clogging. This list is exemplary and not exhaustive. The properties of a pipette tip described above can be detected, for example, using a sensor unit. In particular, it is conceivable that the maximum service life for the pipette tips of at least one pipette tip class could alternatively or additionally be implicitly determined by the sufficient availability and / or usability of the medium to be pipetted with the respective pipette tip, for example, a process fluid.Usability can be determined by a maximum number of days that the medium to be pipetted may be used after opening, i.e., after initial opening ("in-use stability"). The usability described above can, for example, be read via a barcode or identifier. Availability can then be considered "sufficient" if enough of the medium to be pipetted is available to perform a pending work step.

[0032] In another preferred embodiment, the feature parameters for the number of possible pipetting operations or the service life for at least one of the pipette tip classes are defined by input parameters. Alternatively, the feature parameters for the number of possible pipetting operations and the service life for at least one of the pipette tip classes are defined by input parameters. The feature parameters for the number of possible pipetting operations and / or the service life can be defined for all of the pipette tip classes by input parameters. The input parameters can take on any empirically validated numerical values, as explained above.

[0033] In another preferred embodiment, the input parameters are specified by a user of the pipetting device. This can be done, for example, using an operating device integrated into the device. This can include input parameters that determine the maximum number of possible pipetting operations or that define a specific (non-dynamically changing) maximum service life. Input parameters can be assigned to a specific pipette tip class. In particular, input parameters can be specified by the user on a class-specific basis, so that the characteristic value for the service life of the pipette tips of several pipette tip classes can be defined class-specifically via input parameters.In particular, it is conceivable that the input parameters, which define a specific (non-dynamically changing) maximum usage period and are linked to the usability of a medium to be pipetted after opening, are read in by a user, especially using a reading unit. Alternatively or simultaneously, it is conceivable that the input parameters are determined implicitly during the workflow. This can be done, for example, using a sensor unit as part of the device. This can concern the input parameters that define a specific, dynamically changing maximum usage period. The input parameters can be processed by the computer unit to be assigned to the corresponding pipette tip class and stored in the memory unit.

[0034] In a further preferred embodiment, each pipette tip class is assigned at least one additional feature for the use of the pipette tips to be used in the pipetting processes, selected from a group comprising or consisting of: (i) treatment of the pipette tip after use in a work step, (ii) disposal of the pipette tip after reaching a maximum service life; which determines the use of the pipette tips by a class-specific feature parameter. The foregoing list can be extended as desired and is not to be understood as limiting.

[0035] Post-use treatment, meaning treatment after at least one use of the pipette tip, can be useful to remove dried residues such as salts or sample material that may have accumulated on the tip during use. Post-use treatment might include, for example, cleaning, washing, or disinfecting the pipette tip. Washing can be done, for example, by immersing the pipette tip in a washing solution. A washing solution could be water, especially distilled or deionized water. Disinfection can be done, for example, by immersing the pipette tip in a disinfectant, such as alcohol.

[0036] Disposal of pipette tips after reaching their maximum service life can be determined by selecting from a range of options, including separate disposal and conventional disposal. One factor influencing pipette tip disposal might be whether the tips of a particular class come into contact with sterile (i.e., uncontaminated) media or with infectious (i.e., potentially contaminated) media. Contaminated pipette tips could, for example, be disposed of in a separate receiving facility, thereby reducing the proportion of pipette tips requiring special disposal. Conventional disposal can be understood as disposal without any special requirements or safety precautions.

[0037] In a preferred embodiment of the method, individual feature parameters for the characteristics of the individual pipette tip classes can be predefined and, in particular, stored in the memory unit and assigned to the individual pipette tip classes. Specifically, the feature parameters for the characteristics storage location, post-treatment, or disposal of the pipette tips can be predefined for the individual pipette tip classes and, in particular, stored in the memory unit and assigned to the individual pipette tip classes. Alternatively, it is conceivable that all feature parameters for the characteristics of the individual pipette tip classes can be defined by a user. Specifically, it is conceivable that the feature parameters for the characteristics storage location, post-treatment, or disposal of the pipette tips for the individual pipette tip classes can be defined by a user, for example, using an operating device.

[0038] In a further preferred embodiment, the feature parameters of at least one of the features assigned to the pipette tip classes differ for at least two of the pipette tip classes. In particular, the feature parameters of the feature that governs a service life for the pipette tips assigned to the respective pipette tip classes differ for at least two of the pipette tip classes. It is conceivable that the feature parameters of a further feature assigned to the pipette tip classes do not differ for at least two or all of the pipette tip classes. Preferably, the feature parameters of several or all of the features assigned to the pipette tip classes differ for at least two or all of the pipette tip classes. An embodiment of the invention is also conceivable in which at least one pipette tip class comprises at least two subclasses.The pipette tips assigned to such a pipette tip class can each be assigned to one of the subclasses. A characteristic parameter of at least one characteristic can differ for individual subclasses of a pipette tip class.

[0039] In another preferred embodiment, the pipette tips are assigned to one of the pipette tip classes successively. Specifically, the assignment of each pipette tip to a particular class occurs the first time it is used in the workflow. This assignment is determined primarily by the sequence of categorized pipetting operations for which the pipette tips are used. The assignment can be stored in the memory unit. Alternatively, it is conceivable that the assignment of a provided plurality of pipette tips to one of the pipette tip classes is performed in advance for all pipetting operations in the determined sequence and is specifically stored in the memory unit.It is also conceivable that the assignment of a pipette tip to one of the pipette tip classes does not occur upon its first use in the workflow, but only upon subsequent use. Specifically, a pipette tip can only be assigned to a pipette tip class when it is used for a pipetting operation within the identified sequence of pipetting operations—that is, for a pipetting operation that is assigned to a category. For example, a pipette tip might initially be used for one or more pipetting operations that do not belong to the identified sequence of pipetting operations and are therefore not assigned to any category.

[0040] In a further preferred embodiment, a number of process liquids to be used in the workflow is specified. The sequence of pipetting operations to be performed in the workflow is adapted to the number of process liquids to be used. For this purpose, a basic sequence of pipetting operations to be performed for the treatment of a single sample using a single process liquid can be stored in the memory unit, which can be adapted to the number of process liquids to be used in the workflow. The number of process liquids to be used in the workflow can be detected or read out by a readout device or specified by a user.

[0041] In a further preferred embodiment, the number of pipette tips assigned to a given pipette tip class in the sequence of pipetting operations is determined based on the predetermined number of samples to be processed for at least one pipette tip class. This can particularly apply to a pipette tip class that is assigned to a category of pipetting operations that involve sample contact and thus suggest a sample-specific assignment. Alternatively, the number of pipette tips assigned to a given pipette tip class in the sequence of pipetting operations can be determined based on the predetermined number of process liquids to be used for at least one, and in particular another, pipette tip class.This can particularly affect a pipette tip class that is assigned to a category of pipetting operations in which the pipette tip, while coming into contact with the process fluid, transfers it from the samples being treated to the samples being treated without contact or touching, thus enabling a process fluid-specific assignment. However, it is also conceivable that the same pipette tip is used across multiple process fluids.In particular, an embodiment of the invention is conceivable in which the number of pipette tips assigned to a first pipette tip class in the sequence of pipetting operations is determined by the predetermined number of samples to be treated, while the number of pipette tips assigned to a second pipette tip class in the sequence of pipetting operations is determined by the predetermined number of process liquids to be used. The terms "first" and "second" used above are not to be understood as a temporal sequence and are used merely to clarify that these are two different pipette tip classes. In particular, for at least the first pipette tip class, the number of pipette tips assigned to that class in the sequence of pipetting operations can correspond to the predetermined number of samples to be treated.Simultaneously, particularly for at least the second pipette tip class, the number of pipette tips assigned to that class in the sequence of pipetting operations can correspond to the specified number of process liquids to be used. This allows each pipette tip assigned to a particular class to be allocated to one of the specified samples or one of the process liquids to be used.

[0042] In a further preferred embodiment, the pipette tips assigned to a particular pipette tip class are each assigned to one of the predefined samples. Alternatively, the pipette tips assigned to a particular pipette tip class are each assigned to one of the process liquids to be used. In particular, an embodiment of the invention is conceivable in which the pipette tips assigned to a first pipette tip class are each assigned to one of the predefined samples, while the pipette tips assigned to a second pipette tip class are each assigned to one of the process liquids to be used.

[0043] In a further preferred embodiment, the pipette tip assigned to one of the samples to be treated is used for all pipetting operations of the corresponding category relating to that sample. Alternatively, the pipette tip assigned to one of the process liquids to be used is used for all pipetting operations of the corresponding category relating to that process liquid. In particular, an embodiment of the invention is conceivable in which the pipette tip assigned to one of the samples to be treated is used for all pipetting operations of the corresponding category relating to that sample, and the pipette tip assigned to one of the process liquids to be used is used for all pipetting operations of the corresponding category relating to that process liquid.

[0044] In another preferred embodiment, before each pipetting operation, it is first determined whether a pipette tip has already been assigned to the respective operation. If a pipette tip is already assigned, the corresponding pipette tip is selected and used for that operation. If no pipette tip has yet been assigned, a new pipette tip is selected and used. In a further preferred embodiment, the assignment of a pipette tip to one of the pipette tip classes is maintained in the workflow until one of the criteria determining its service life is met.In other words, this means that the assignment of a pipette tip to one of the pipette tip classes in the workflow can be maintained in certain cases, for example, when the usage time is determined by the availability of a medium to be pipetted, even across a determined sequence of pipetting operations, i.e., across several successive determined sequences of pipetting operations.

[0045] In another preferred embodiment, a control file is generated based on the assignment of pipetting operations to categories, which the control device uses to control the pipetting unit in the workflow. Alternatively, the control file used by the control device to control the pipetting unit in the workflow can be generated based on the assignment of the pipette tips to be used to each of the pipette tip classes. In particular, the control file used by the control device to control the pipetting unit in the workflow can be generated based on the assignment of the pipetting operations to categories and the assignment of the pipette tips to be used to each of the pipette tip classes.

[0046] In a second aspect, the invention relates to a pipetting device, comprising at least a pipetting unit with a pipetting element onto which a pipette tip can be interchangeably placed, a work surface comprising a plurality of storage devices for pipette tips, and an electronic control device for controlling the pipetting unit in a workflow in which the pipetting unit performs pipetting operations for the treatment of samples using a plurality of provided pipette tips, wherein the electronic control device is designed and programmed to operate the pipetting device using the method described above.

[0047] The pipetting device can be used in an analytical or medical laboratory, particularly in the field of sepsis diagnostics. The pipetting device can be specifically designed and / or configured for handling samples during blood culture analysis.

[0048] The pipetting device, as defined in the invention, is an automated device, meaning that the pipetting operations for processing the samples are computer-controlled or automated. The pipetting device can be designed as a pipetting robot or liquid handling system, or it can include a pipetting robot or liquid handling system. The device can be configured such that a plurality of samples can be processed in a determined sequence of pipetting operations within a workflow performed by means of the device. Preferably, the device can be configured to allow the processing of up to eight samples in a determined sequence of pipetting operations within a workflow. It is also conceivable that the device can be configured to allow the processing of more than eight samples, e.g.,ten, twelve or sixteen samples, within a determined sequence of pipetting operations is made possible.

[0049] The control unit is designed to operate the pipetting device using the method described above. According to the invention, the control unit controls the pipetting unit. The control unit can comprise a computer unit and a positioning unit. The computer unit, in turn, can comprise at least one memory unit and a processor unit. The memory unit can comprise a data memory and a system memory. A data memory is configured to receive and store information for retrieval. The processor unit can be configured to issue commands and / or provide feedback to a user. In particular, the computer unit can be configured to determine the sequence of pipetting operations to be performed in the workflow.This can be achieved, for example, by adapting a basic sequence of pipetting operations, stored particularly in the memory unit, to the number of samples to be processed and / or the number of process fluids to be used. The positioning unit allows the position of the pipetting unit relative to a work surface of the device to be changed, for example, in a plane parallel to the work surface or by adjusting the distance between the pipetting unit and the work surface. The positioning unit can include a drive unit and a guide mechanism. Additionally or alternatively, it is conceivable that the positioning unit includes a robotic unit.

[0050] The pipetting unit comprises a pipetting element. Furthermore, the pipetting unit may include a pump system, which can be connected to the pipetting element via a tube, and is designed to enable the pipetting element to aspirate and / or dispense fluid volumes, e.g., liquid volumes, gel-like or pasty volumes. The pipetting unit may be configured such that reaction vessels, designed as so-called "flip tubes," can be opened and closed by the pipetting unit. For this purpose, the pipetting unit may include a rod unit which, by lowering it, exerts pressure on a section of the flip tube's cover to open or close the cover.

[0051] The pipetting element can be configured for transferring, dispensing, and / or mixing fluids. In particular, the pipetting element can be configured to draw in and / or dispense fluid volumes. For this purpose, the pipetting unit can include a line through which the pipetting element is connected to a pump system. The pipetting element can be configured for pipetting various media, especially liquids. Within the scope of the disclosure, the pipetting element of the pipetting unit is designed such that a pipette tip can be repositioned, in particular replaced, onto the pipetting element.

[0052] With regard to the interpretation of the terms samples, workflow, determined sequence of pipetting operations to be carried out, categories and pipette tip classes, reference is made to the explanations given in connection with the method according to the invention.

[0053] In a preferred embodiment, the pipetting device comprises an operating device. The operating device is configured and / or designed for a user to specify at least one input parameter. The input parameters allow the user to define the characteristic value for the service life of the pipette tips for at least one pipette tip class. The operating device can be configured so that input parameters can be assigned to a specific pipette tip class. In particular, the operating device can be configured so that input parameters can be specified class-specifically, allowing the characteristic value for the service life of the pipette tips of several pipette tip classes to be defined class-specifically. The operating device can have an input device and / or an output device. The input device can be configured for entering the input parameters.The input device can include a keyboard. The output device can be configured to visually display input or output information. The output device can include a display. Alternatively, the input device and the output device can be configured as a single, integrated unit, for example, a touchscreen display. The input parameters can be processed by the computer unit to be assigned to the corresponding pipette tip class and stored in the memory unit. In a further preferred embodiment, the pipetting device includes at least one sensor unit. The sensor unit is configured and / or designed to detect at least one property of pipette tips. Several sensor units for detecting properties of pipette tips can be provided.One property of a pipette tip that can be detected by the sensor unit could be, for example, an optical property, in particular the degree of opacity of the pipette tip, which may indicate chemical wear. Another property of a pipette tip that can be detected by the sensor unit, e.g., optically, could be, for example, the degree of deformation of the pipette tip, which may indicate mechanical wear. It is conceivable that at least one further sensor unit is provided for detecting the availability of at least one medium to be pipetted. Several further sensor units, each for detecting the availability of a specific medium to be pipetted, could be provided. Availability could be detected, for example, via an optical property, such as the fill level in a container supplying the medium.The sensor units can belong to a sensor system.

[0054] In a further preferred embodiment, the pipetting device includes a readout device. The readout device is configured and / or designed to detect a sample identifier. The sample identifier can be a sample name. In this way, the number of samples to be processed in the workflow can be predetermined. In particular, the sample identifier can be a barcode. Simultaneously, the readout device can be configured and / or designed to detect an identifier for process liquids. In this way, the number of process liquids to be used in the workflow can be predetermined.

[0055] In a further preferred embodiment, the pipetting device comprises a plurality of pipetting areas. Each pipetting area can provide one of the storage devices for storing pipette tips or a treatment device for post-treatment of pipette tips. In particular, a pipetting area can provide one of the storage devices for storing pipette tips and a treatment device for post-treatment of pipette tips. In particular, embodiments of the invention are conceivable in which there is one or more pipetting areas that provide one of the storage devices and a treatment device, while at least one pipetting area provides only one storage device or one treatment device.Within the scope of the disclosure, the storage facility provided by the pipetting area and the pipetting area itself, or the treatment facility provided by the pipetting area and the pipetting area itself, may constitute a single structural unit or separate structural units. In the case of separate structural units, the term "provided" is to be interpreted analogously as "assigned".

[0056] In a further preferred embodiment, the storage devices have a plurality of separate storage positions. Each storage position is designed to receive a single pipette tip. The storage positions are specifically configured such that each position can selectively hold either a pipette tip of a first type or a second type of pipette tip that differs from the first. Different types of pipette tips can, within the scope of this disclosure, be pipette tips with different capacities. The storage devices can each be designed as a holding device or a frame, in particular as a so-called "rack," which provides the separate storage positions.

[0057] In a further preferred embodiment, the treatment device comprises means for cleaning pipette tips. Alternatively, the treatment device comprises means for disinfecting pipette tips. The treatment devices can each be configured as a reservoir or a container for holding a liquid medium. Liquid media can be, for example, water, cleaning fluids, or disinfecting fluids. A reservoir can be configured as a recess in a working surface of the device. A reservoir can be cylindrical, rectangular, or of another shape. The reservoir can, for example, provide a holding volume of 100 mL to 1 L.

[0058] It is clear to those skilled in the art that the device features described above do not constitute an exhaustive list and may include further features, for example a sample feeding device for feeding and introducing sample material into the workflow or a centrifuge unit for centrifuging the samples to be treated.

[0059] Brief description of the illustrations: Exemplary embodiments of the invention are described in more detail below with reference to the accompanying figures. These show:

[0060] Fig. 1: a first schematic top view of a section of a device according to the invention for pipetting,

[0061] Fig. 2: a schematic side view of a section of the device according to the invention for pipetting from Fig. 1, and

[0062] Fig. 3: a schematic flowchart of a method according to the invention for operating the pipetting device according to Fig. 1, illustrated by means of an exemplary selected workflow.

[0063] Detailed description

[0064] While the invention has been presented and explained with reference to a number of embodiments, those skilled in the field will recognize that various changes in form and detail can be made to it without deviating from the scope of the technical teaching defined in the attached claims.

[0065] Figure 1 shows a first schematic top view of a section of a pipetting device 10 according to the invention. In the exemplary embodiment, the device 10 is designed and configured for the automated processing, in particular preparation, of samples in blood culture analysis. In particular, the device 10 in the exemplary embodiment is configured such that the preparation of up to eight samples is enabled within a specific sequence of pipetting operations.

[0066] The device 10 comprises a pipetting unit 12 (Fig. 2). The pipetting unit 12 includes a pipetting element 14 (Fig. 2) and a pumping system (not shown in the figure). The pipetting element 14 is designed such that a pipette tip can be repositioned and, in particular, replaced on the pipetting element 14. The pipetting element 14 is configured to aspirate and / or dispense volumes of liquid. For this purpose, in the exemplary embodiment, the pipetting element 14 is in fluid communication with the pumping system via a line of the pipetting unit 12 (not shown in the figure).

[0067] The device 10 further comprises an electronic control unit 16 (Fig. 2). The control unit 16 controls the pipetting unit 12. The control unit 16 comprises a computer unit 18 and a positioning unit 20 (Fig. 2). The computer unit 18, in turn, comprises a storage unit (not shown) and a processor unit (not shown). The positioning unit 20 comprises a drive unit 22 and a guide unit 24. In this embodiment, the drive unit 22 is designed as a spindle drive. In this embodiment, the guide unit 24 is designed as a rail system. The pipetting unit 12 can be changed in its position relative to a work surface 26 of the device 10 by means of the positioning unit 20.The positioning device 20 is designed to have three degrees of freedom, meaning that the pipetting unit 12 can be moved in a plane parallel to the work surface 26 and can also be lowered and raised again at any point on the work surface 26. In particular, the control unit 16 is designed and configured to execute a method for operating the device 10 for pipetting, as described with reference to Figure 3. For this purpose, the processor unit issues instructions, whereby the pipetting unit 12 is guided by the guide device 24 to specific positions on the work surface 26 in order to perform specific pipetting operations there using the pipetting element 14.

[0068] The device 10 further comprises the work surface 26. The work surface 26 comprises a plurality of pipetting areas 28. In the exemplary embodiment, the work surface 26 comprises three pipetting areas 28a, 28b, 28c, each indicated in the figure by a dashed line. Other embodiments are conceivable in which the pipetting areas overlap in certain regions. The pipetting areas 28a, 28b, 28c each represent an area on the work surface 26 in which pipetting operations of the same category are performed. In the exemplary embodiment, the pipetting areas 28a, 28b, 28c each provide a storage device 30 for storing pipette tips. In the exemplary embodiment, the pipetting areas 28a, 28b also provide a treatment device 32 for post-treatment of pipette tips.It is also conceivable to use embodiments in which pipetting areas that overlap in certain areas have a common storage or treatment device, or, for example, share another functional device or functional area of ​​the apparatus.

[0069] The pipetting area 28a comprises a storage device 30a for storing pipette tips and a treatment device 32a for post-treatment of pipette tips after use. In the exemplary embodiment, the pipetting area 28a is configured for performing pipetting operations of a first category. The storage device 28a is accordingly designed for storing pipette tips belonging to a first pipette tip class assigned to the first category of pipetting operations. Furthermore, in the exemplary embodiment, the pipetting area 28a comprises a rack. In the exemplary embodiment, the rack is specifically designed as a "kit rack" 34 and is configured to accommodate a kit unit (not shown in the figure).For the purposes of this disclosure, a kit unit is understood to be a unit, particularly a commercially available one, which provides at least one process fluid and optionally other consumables. The kit rack 34 provides corresponding receiving units 35a, b for receiving the individual elements of the kit unit, of which only one receiving unit 35a, b is indicated with a reference numeral in the figure for clarity. Furthermore, in this embodiment, the kit rack 34 provides the storage device 28a for storing pipette tips. For this purpose, the kit rack 34 has a plurality of separate storage positions 36, wherein the storage positions 36 are designed such that a pipette tip can be stored in each storage position 36.In the exemplary embodiment, the storage device 30a has three storage positions 36 for pipette tips, of which, for clarity, only one of the storage positions 36 is provided with a reference numeral. In the exemplary embodiment, the treatment device 32a comprises two reservoirs 38, each designed to hold a cleaning medium.

[0070] The pipetting area 28b comprises a storage device 30b for storing pipette tips and a treatment device 32b for post-treatment of pipette tips after use. In this embodiment, the pipetting area 28b is configured for performing pipetting operations of a second category. The storage device 30b is accordingly designed for storing pipette tips belonging to a second pipette tip class assigned to the second category of pipetting operations. Furthermore, in this embodiment, the pipetting area 28b comprises a rack. In this embodiment, the rack is specifically designed as a "reaction vessel rack" 40 and is configured to hold reaction vessels (not shown in the figure) in which samples can be prepared, in receiving units 41, of which only one receiving unit 41 is indicated with a reference numeral in the figure for clarity.The storage device 28b is arranged adjacent to the reaction vessel rack 40 on the work surface 26. In this embodiment, the storage device 30b is designed as a holding device and has a plurality of separate storage positions 42, the storage positions 42 being designed such that a pipette tip can be placed in each storage position 42. In this embodiment, the storage device 30b has eight storage positions 42 for pipette tips, of which, for clarity, only one of the storage positions 42 is labeled. In this embodiment, the treatment device 30b includes a reservoir 44, which is designed to hold a disinfectant medium.In the embodiment, the treatment device 32b is spatially arranged between the storage device 30b and the work surface 26, so that pipette tips temporarily stored in the storage positions 42 of the storage device 30b are immersed with their tips in the disinfection medium provided in the reservoir 44.

[0071] The pipetting area 28c includes a storage device 30c for storing pipette tips. In this embodiment, the pipetting area 28c is configured for performing pipetting operations of a third category. The storage device 30c is accordingly designed for storing pipette tips belonging to a third pipette tip class assigned to this third category of pipetting operations. Furthermore, in this embodiment, the pipetting area 28c includes a sample preparation area 46. In this embodiment, the sample preparation area 46 is specifically configured for preparing a MALDI sample (MALDI = matrix-assisted laser desorption and ionization), which is subsequently subjected to mass spectrometric analysis, for example, time-of-flight mass analysis.In this embodiment, the storage device 30c corresponds to the carrier unit for pipette tips, in which the pipette tips are stored and made available for the workflow. In other words, the pipette tips used for the pipetting operations of this category are returned after use to the carrier unit from which they were removed, in particular to the storage position 47 of the carrier unit from which they were removed. In this embodiment, the work surface 26 provides at least one holding device 48, which is configured to receive such a carrier unit with pipette tips.

[0072] The device 10 further comprises an operating device 50. The operating device 50 is designed and configured for a user to specify input parameters. For this purpose, the operating device 50 includes an input device for entering the parameters and an output device for visually displaying the parameters. In the exemplary embodiment, the input device and the output device are designed in a common structural unit as a touch-sensitive display (touchscreen).

[0073] The device 10 further comprises a sensor assembly. In the exemplary embodiment, the sensor assembly comprises a first (optical) sensor unit 52 for detecting properties of a pipette tip. Furthermore, in the exemplary embodiment, the sensor assembly comprises a second (optical) sensor unit 54 for detecting the availability of two media to be pipetted, here two process liquids, by detecting the fill level in the two containers supplying the respective process liquid. The second sensor unit 54 is arranged adjacent to the kit rack 34 of the pipetting area 28a.

[0074] The device 10 further comprises a reading device 56. The reading device 56 is designed to detect a sample identifier. In the exemplary embodiment, the reading device 56 is configured and designed to detect a barcode of a sample identifier or an identifier of a process fluid.

[0075] In this embodiment, the device 10 comprises a centrifuge unit 58 for centrifuging samples. In this embodiment, the centrifuge unit 58 is designed such that up to eight samples can be centrifuged simultaneously.

[0076] In the exemplary embodiment, the device 10 comprises a sample feeding device 60. The sample feeding device 60 is designed to feed sample material into a work process.

[0077] Figure 2 shows a schematic side view of a section of the device 10 for pipetting according to the invention from Figure 1. Reference is made to the description of Figure 1. For clarity, only the pipetting unit 12 with pipetting element 14, the control unit 16 comprising the computer unit 18 and the positioning unit 20 with the drive unit 22 and the guide unit 24, as well as the work surface 26, are shown in Figure 2.

[0078] Figure 3 shows a schematic flowchart of a method according to the invention for operating the pipetting device 10 from Figure 1, illustrated by means of an exemplary workflow. The method is particularly useful for coordinating pipette tips in the workflow for sample preparation during blood culture analysis, carried out using the device 10. In this workflow, the pipetting unit 12 with the pipetting element 14 performs pipetting operations for sample treatment using a plurality of provided pipette tips. The method is carried out using the control unit 16.

[0079] The illustrated embodiment serves only to illustrate the invention and is not limiting to it. A workflow comprising a different number of successive, determined sequences of pipetting operations, or other sequences of pipetting operations, is possible. The method according to the invention can, in particular, also be applied to the operation of other automated or computer-controlled pipetting devices or sample handling systems, which are used, for example, in a medical, biological, physical, pharmaceutical, or chemical laboratory.

[0080] To illustrate the idea according to the invention, the illustrated workflow comprises two successive determined sequences of pipetting operations (AP1, AP2) to be performed for the preparation of infectious samples in blood culture analysis, wherein in sequence AP1 and in sequence AP2 the sample material from three different infectious samples is prepared.

[0081] According to the invention, the respective sequence of pipetting operations to be performed in the workflow is determined by adapting a predefined (basic) sequence of pipetting operations to the number of samples to be processed. The pipetting operations from the respective determined sequence are assigned to categories, with each category being assigned a predefined pipette tip class, each of which is associated with characteristics for the use of the pipette tips to be used in the pipetting operations. In the exemplary embodiment, these characteristics determine a service life, a storage location, and a post-treatment for the pipette tips assigned to the respective pipette tip classes by means of a class-specific characteristic parameter.

[0082] When executing the determined sequences of categorized pipetting operations, the pipette tips to be used are each assigned to a pipette tip class. The control unit 16 controls the pipetting unit 12 based on the assignment of the pipetting operations to categories and the assignment of the pipette tips to one of the pipette tip classes in the workflow, whereby the pipetting unit 12 uses the pipette tips taking into account the class-specific characteristic parameters.

[0083] In this embodiment, the following (basic) sequence of pipetting operations to be performed for the preparation of a single sample during blood culture analysis is stored in the storage unit:

[0084] A1: Addition of process fluid A to the sample

[0085] TI A2: Mixing the sample with the process fluid A

[0086] A3: Addition of process fluid B to the sample

[0087] A4: Mixing the sample with process fluid B

[0088] A5: Centrifuging the sample

[0089] A6: Transferring the sample to a sample carrier

[0090] The preparation process, in its basic sequence, involves the use of two process liquids, A and B. In this embodiment, process liquid A and process liquid B are each reagents that do not evaporate completely. In this embodiment, the previously infectious samples to be prepared are sterile after completion of step A4.

[0091] Step S10 marks the beginning of the flowchart and thus the start of the process. In step S10, the first sequence of pipetting operations (AP1) to be performed in the workflow is determined. For this purpose, the (basic) sequence of pipetting operations stored in the memory unit is adapted to the number of samples to be processed in the first sequence, which in this example is three samples. The three samples to be processed are fed one after the other by a user to the readout device 56 for the acquisition of a readout code.

[0092] In the exemplary embodiment, for the sequence AP1, with the intended number of three samples (P1, P2, P3) to be processed in the first sequence, six additional work steps result compared to the stored (basic) sequence for the treatment of a single sample, since work steps A1 to A4 and A6 are each performed for the three samples PIPS (A1 PI.PS to A4PI.PS, and A6PI.PS), while work step A5, which is the only work step in the exemplary embodiment that does not include a pipetting process, can be performed for all three samples simultaneously.

[0093] In step S12, the pipetting operations of the determined first sequence to be performed are categorized. In this embodiment, the categorization is task-related, meaning that different categories are based on the different intended tasks that the pipetting operations fulfill (as specified in Table 1). Each category is assigned a predefined pipette tip class. In this embodiment, the predefined pipette tip classes are each assigned the characteristics (i) service life, (ii) storage location, and (iii) (post-)treatment, to which a class-specific characteristic parameter is assigned that determines the use for the pipette tips assigned to the respective pipette tip classes. An overview of the categorization and assignment of the pipetting operations (work steps) of the determined sequence, as well as the assigned characteristic parameters, is shown in Table 1.

[0094] Table 1: Overview of the categorization and assignment of the pipetting processes (work steps) of the determined sequence, as well as the assigned characteristic parameters.

[0095] As shown in Table 1, steps A1 PI-P3 and A3PI.PS in the exemplary embodiment correspond to a first category of pipetting operations, namely the addition of a process fluid to a sample to be processed. In this exemplary embodiment, the process fluid is added to the sample to be processed in a free-dispense manner, i.e., without coming into contact with the sample. Steps A2PI.PS and A4PI.PS in the exemplary embodiment correspond to a second category, namely the mixing of an infectious sample with the added process fluid, whereby the previously infectious samples become sterile after the addition and mixing with the second process fluid (B). Step A6PI.PS in the exemplary embodiment corresponds to a third category, namely the transfer of a sterile sample.

[0096] The following assignment of feature parameters is provided for in the embodiment (see Table 1): The following feature parameters are assigned to the first pipette tip class in the embodiment: usage period of one day or one hundred pipetting operations; after use in one work step, storage in the storage device 30a of the first pipetting area 28a; after use in one work step, cleaning in the treatment device 32a of the first pipetting area 28a. The following feature parameters are assigned to the second pipette tip class in the embodiment: usage period or...The number of pipetting operations for each pipette tip corresponds to the number of pipetting operations in the determined sequence for which the pipette tip is used in the sequence; after use in a work step, storage in the storage device 30b of the second pipetting area 28b; after use in a work step, disinfection in the treatment device 32b of the second pipetting area 28b. The third pipette tip class is assigned the following feature parameters in the exemplary embodiment: the usage period or number of pipetting operations corresponds to the number of pipetting operations in the determined sequence for which the pipette tip is used in the sequence; after use in a work step, storage in the storage device 30c of the third pipetting area 28c; no post-treatment.

[0097] In this embodiment, the feature parameters for the service life of the pipette tips are specified class-specifically for each of the three predefined pipette tip classes assigned to the three categories of pipetting operations. Meanwhile, the feature parameters assigned to each pipette tip class for storage location and post-treatment are stored class-specifically in the memory unit. The feature parameters for service life consider a maximum number of possible pipetting operations and a maximum usage period as criteria. A maximum service life is reached as soon as one of the two criteria reaches its maximum value, even if the other criterion has not yet reached its maximum value.

[0098] In step S14, the characteristic parameters for the service life are defined by input parameters, specifying a number of possible pipetting operations and / or a usage period for the respective pipette tip classes. These input parameters are successively entered as numerical values ​​by a user of the device for each pipette tip class using an operating device. In the case of the usage period, a unit for the numerical values ​​is selected first.

[0099] In step S16, an identifier for process fluids A and B is scanned using the readout device to determine their expiration date and in-use stability. This implicitly influences the service life of the pipette tips of the first pipette tip class. Furthermore, the availability of process fluids A and B, continuously monitored during the workflow by sensor unit 54, also implicitly influences the service life of the pipette tips of the first pipette tip class. This implicit influence is expressed in the fact that a maximum service life for the pipette tips assigned to the first pipette tip class is considered reached even if one of the process fluids A or B is no longer available and / or usable, regardless of the specific characteristic parameters of the criteria "number of possible pipetting operations" and "maximum usage period".

[0100] Step S18 comprises the first determined sequence of pipetting operations. The first sequence of categorized pipetting operations AP1 is executed, whereby the pipette tips to be used are each assigned to a pipette tip class. The assignment is made successively, each time a pipette tip is used for the first time. The control unit 16 controls the pipetting unit 12 based on the assignment of the pipetting operations to categories and the assignment of the pipette tips to one of the pipette tip classes, with the pipetting unit 12 using the pipette tips taking into account the class-specific characteristic parameters.

[0101] The computer unit 18 determines how many pipette tips are to be assigned to each pipette tip class. In this embodiment, the first pipette tip class, according to its corresponding category, corresponds to the process fluids used for sample preparation. Accordingly, the number of pipette tips assigned to the first pipette tip class corresponds to the number of process fluids used for sample preparation. In this embodiment, the second and third pipette tip classes, according to their respective categories, each correspond to the samples to be prepared. Therefore, the number of pipette tips assigned to the second and third pipette tip classes, respectively, corresponds to the number of samples processed in a work cycle.Based on the assignment of pipette tip classes to different categories, the processor unit can determine which pipette tip from which class should be used for each specific step. Table 2 provides an overview of the pipette tips used and their assignment to work steps.

[0102] In step A1 PI, process fluid A is added to the first infectious sample P1. For this purpose, the pipetting unit 12 takes a first pipette tip from the provided carrier unit containing pipette tips. Since this step corresponds to the first category, the control unit 16 assigns this pipette tip to the first pipette tip class. This pipette tip is then assigned to the first process fluid A. The pipetting unit 12 then executes step A1 PI.

[0103] In steps A1 P2 and A1 P3, process fluid A is added to the second infectious sample P2 and the third infectious sample P3, respectively. These steps also correspond to the first category of pipetting operations. Since the first pipette tip has already been assigned to process fluid A, and its maximum service life has not yet been reached, the pipetting unit 12 reuses the first pipette tip, assigned to the first pipette tip class, for the two steps A1 P2 and A1 P3. The pipetting unit 12 performs the steps A1 P2 and A1 P3. After use in step A1 P3, the pipetting unit 12 transfers the pipette tip to the treatment unit 32a and then to a first storage position in the storage unit 30a of the first pipetting area 28a for temporary storage.

[0104] In step A2PI, the first sample P1 is mixed with the added process fluid A. Since this step corresponds to a new, namely the second, category, the pipetting unit 12 takes a new, second pipette tip from the provided carrier unit containing pipette tips. According to the category, the control unit 16 assigns this pipette tip to the second pipette tip class. This pipette tip is then assigned to the first sample P1. The pipetting unit 12 performs step A2PI. After use in step A2PI, the pipetting unit 12 places the pipette tip in a first storage position 42 in the storage device 30b of the second pipetting area 28b for temporary storage. The treatment device 32b is located below the storage device 30b, into which the pipette tip is immersed as a post-treatment during temporary storage and is thereby disinfected.

[0105] In steps A2P2 and A2P3, the second sample P2 is mixed with the added process liquid A, and the third sample P3 is mixed with the added process liquid A, respectively. Since these steps also belong to the second category, but involve the additional samples P2 and P3, and the second pipette tip is already assigned to the first sample P1, the pipetting unit 12 takes two new pipette tips—a third and fourth, respectively—from the provided pipette tip carrier. Because these steps also belong to the second category, the control unit 16 assigns these pipette tips to the second pipette tip class. Furthermore, the third pipette tip is assigned to the second sample P2, and the fourth pipette tip to sample P3. The pipetting unit 12 then performs steps A2P2 and A2P3.After use in the respective work step, the pipetting unit 12 transfers the pipette tips to a second or third storage position 42 in the storage device 30b of the second pipetting area 28b for temporary storage. During this temporary storage, the pipette tips are disinfected by immersion in the disinfectant solution of the treatment unit 32b.

[0106] In step A3PI, process fluid B is added to the first sample P1. This step again belongs to the first category. However, since this involves another process fluid B and the first pipette tip is already specifically assigned to the first process fluid A, the pipetting unit 12 takes a new, fifth pipette tip from the provided carrier unit containing pipette tips. Because this step corresponds to the first category, the control unit 16 also assigns this pipette tip to the first pipette tip class.

[0107] In steps A3P2 and A3P3, process fluid B is added to the second infectious sample P2 and the third infectious sample P3, respectively. These steps also correspond to the first category of pipetting operations. Since the fifth pipette tip was previously assigned to process fluid B, and its maximum service life has not yet been reached, the pipetting unit 12 again uses the fifth pipette tip, which belongs to the first pipette tip class, for the two steps A3P2 and A3P3. The pipetting unit 12 performs the two steps A3P2 and A3P3. After use in step A3P3, the pipetting unit transfers the pipette tip to the treatment unit 32a and then to a second storage position 42 in the storage unit 30a of the first pipetting area 28a for temporary storage.

[0108] In step A4PI, the first sample P1 is mixed with the added process fluid B. This step also corresponds to the second category. Since the second pipette tip is already sample-specifically assigned to the first sample P1, the pipetting unit again uses the second pipette tip, which belongs to the second pipette tip class. Pipetting unit 12 performs step A4PI. Because no further step in the determined first sequence is planned in which this pipette tip would be used, a maximum service life for this pipette tip has been reached, so after use, the pipette tip is transferred to a disposal container (not shown) for separate disposal.

[0109] In step A4P2 or A4P3, the second sample P2 is mixed with the added

[0110] Process fluid B, or the mixing of the third sample P3 with the added process fluid B, also corresponds to the second category. Since the third pipette tip is already assigned to the second sample P2, pipetting unit 12 uses the third pipette tip, assigned to the second pipette tip class, again for A4P2. Since the fourth pipette tip is already assigned to the second sample P3, pipetting unit 12 uses the fourth pipette tip, assigned to the second pipette tip class, again for A4P3. Pipetting unit 12 performs steps A4P2 and A4P3.Since no further work steps are planned in the identified initial sequence in which these pipette tips would be used, a maximum service life for these pipette tips has been reached, so that after use the pipette tips are transferred to a disposal container (not shown) for separate disposal.

[0111] It should be noted that the sequence of individual work steps can be modified to a certain extent when preparing multiple samples. For example, work steps A1 and A2 or A3 and A4 can each be completed consecutively for a single sample, instead of, as described in the exemplary embodiment, performing each individual work step for all samples to be processed before proceeding to the next step.

[0112] In step A5, the samples are centrifuged. Since the centrifuge unit 58 in this embodiment is designed to allow multiple samples to be centrifuged simultaneously, this step can be performed for all samples at the same time.

[0113] In step A6PI, the first, now sterile, sample P1 is transferred to a sample carrier for sample preparation. Since this step corresponds to the third category, the pipetting unit 12 retrieves a new, sixth pipette tip from the provided carrier unit containing pipette tips. This sixth pipette tip is assigned to the third pipette tip class and allocated to the first sample P1. The pipetting unit 12 then performs step A6PI. After use in step A6PI, the pipetting unit 12 places the pipette tip in a storage position 47 in the storage device 30c of the third pipetting area 28c. Because the storage device 30c corresponds to the carrier unit from which the pipette tips were removed, the pipette tip can be returned to the storage position in the carrier unit from which it was taken.The pipette tip remains in the carrier unit and is disposed of with it during the standard exchange cycle once all pipette tips provided in the carrier unit have been assigned to a specific pipette tip class. In steps A6P2 and A6P3, the second, now sterile sample P2 and the third, now sterile sample P3, respectively, are transferred to a sample carrier for sample preparation. These steps also correspond to the third category. However, since this involves the additional sample P2 and P3, and the sixth pipette tip is sample-specifically assigned to the first sample P1, the pipetting unit 12 removes two new pipette tips—a seventh and an eighth—from the provided carrier unit containing pipette tips.Since this operation corresponds to the third category, the control unit 16 also assigns these pipette tips to the third pipette tip class, with the seventh pipette tip being assigned to the second sample P2 and the eighth pipette tip to the third sample P3. The pipetting unit 12 performs operations A6P2 and A6P3. After use in operations A6P2 and A6P3, respectively, the pipetting unit 12 places the pipette tips in storage position 47 in storage device 30c of the third pipetting area 28c from which the pipette tip was taken. The pipette tips also remain in the carrier unit until the standard change cycle.

[0114] With the completion of work step A6P3, the execution of the pipetting operations of the first determined sequence of pipetting operations to be performed AP1 has been completely completed.

[0115] In step S20, the second sequence of pipetting operations to be performed in the workflow (AP2) is determined. For this purpose, the (basic) sequence of pipetting operations, described in relation to step S10 and stored in the memory unit, which is to be executed for the preparation of a single sample, is adapted to the number of three samples to be processed in the second sequence. This is done, as described in relation to step S10, by capturing a readout code of the respective sample using the readout device 56.

[0116] For the AP2 sequence, in the exemplary embodiment with a planned number of six samples (P4 - P9), twenty-five additional work steps result compared to the stored (basic) sequence for the treatment of a single sample, since work steps A1-A4 and A6 are each performed for six samples (AWre to A4P4-P9, and A6p4-pg), while work step A5, which is the only work step in the exemplary embodiment that does not include a pipetting process, can be performed for all samples simultaneously.

[0117] In step S22, the pipetting operations of the determined second sequence to be performed are categorized, as explained with reference to step S12, with each category being assigned a predefined pipette tip class. In step S24, the feature parameters for the number of possible pipetting operations and the service life for the respective pipette tip classes are defined by input parameters, as explained with reference to step S14. The input parameters are successively entered by the user of the device as numerical values ​​for the respective pipette tip classes using the operating device 50, with the exception of those for the first pipette tip class. This is because, in the exemplary embodiment, the maximum service life for the pipette tips assigned to this pipette tip class, which was already defined in connection with the first sequence of pipetting operations, has not yet been reached.

[0118] With regard to the feature parameters that are assigned to the pipette tip classes in the exemplary embodiment, reference is made to the explanations for the first sequence AP1.

[0119] Step S26 would correspond to capturing an identifier for the process fluids A and B. However, capturing this identifier is omitted in the exemplary embodiment in connection with the second determined sequence of pipetting operations to be carried out, since the process fluids A and B used in connection with the first determined sequence of pipetting operations are still available and usable.

[0120] Step S28 comprises the second determined sequence of pipetting operations (AP2). The second sequence of categorized pipetting operations AP2 is executed, with the pipette tips to be used being assigned to a pipette tip class. The control unit 16 controls the pipetting unit 12 based on the assignment of the pipetting operations to categories and the assignment of the pipette tips to one of the pipette tip classes, with the pipette unit 12 using the pipette tips taking into account the class-specific characteristic parameters. As explained in connection with step S18, the computer unit 18 determines how many pipette tips are to be assigned to the respective pipette tip classes.

[0121] The steps in AP2 are essentially the same as those in AP1, with the difference that, as explained above, pipette tips have already been assigned to process fluids A and B. To avoid repetition, the sequence of steps identified for the second procedure will therefore not be described in detail.

[0122] To clarify the inventive idea, it should be noted that the pipette tips assigned to the first process liquid A and the second process liquid B in sequence AP1 are also used in sequence AP2 for the corresponding steps in which process liquid A or process liquid B is added to a sample, according to the method according to the invention. This is because the predetermined characteristic parameters for the service life of these pipette tips have not yet reached their maximum value, and the availability and usability of the process liquids are still ensured. When performing the pipetting operations of the second determined sequence of pipetting operations, three new pipette tips are assigned to each of the second and third pipette tip classes, one pipette tip per specific sample.

[0123] In this embodiment, a specific maximum number of pipetting operations, and thus a maximum service life for the pipette tips assigned to the first pipette tip class, has not yet been reached at the end of the second determined sequence. Accordingly, these pipette tips could be reused in further determined sequences. In this embodiment, the workflow ends at the end of the second determined sequence of pipetting operations.

[0124] An overview of the allocation and consumption of the pipette tips in AP1 is shown in Table 2 for the exemplary embodiment.

[0125] As can be deduced from Table 2, in the embodiment based on the inventive idea, a total of 8 pipette tips are used in work cycle AP1 (column 5), whereas without the application of the inventive idea, with single use of each pipette tip, a total of 15 disposable pipette tips would be used (column 6). For the subsequent second work cycle AP2, based on the inventive idea, a total of 12 new pipette tips are added, since six new sample-specific pipette tips are used in A2 (which can also be used in A4) and six new sample-specific pipette tips are used in A6 (pipette tips No. 1 and No. 2, which belong to the first pipette tip class).Five pipette tips can be reused, as their maximum service life has not yet been reached. Without applying the inventive idea in AP2, 31 new disposable pipette tips would be required. The savings in pipette tips increase with the number of samples processed per work cycle or with the number of work cycles performed, particularly because individual pipette tips (in this embodiment, the pipette tips of the first pipette tip class) can be used across multiple determined sequences. Table 2: Overview of the allocation and consumption of pipette tips in AP1.

[0126] Assigning different storage locations advantageously allows pipette tips that have come into contact with infectious samples or have been exposed to other contamination to be stored separately from those that have only come into contact with sterile samples after pipetting operations have been completed. This not only minimizes the risk of contamination between pipette tips but also reduces the risk of a user accidentally coming into contact with contaminated pipette tips.

[0127] The invention is described above with reference to various particular embodiments. It is understood, however, that various aspects or details of the described embodiments can be modified without altering the scope of the invention. Furthermore, the features and measures disclosed in connection with different embodiments can be combined as desired, provided this appears practical to a person skilled in the art. Moreover, the above description serves only to illustrate the invention and not to limit the scope of protection, which is defined exclusively by the accompanying claims, taking into account any equivalent inventions.

[0128] Reference sign

[0129] 10 Pipetting device

[0130] 12 pipetting units

[0131] 14 Pipetting element

[0132] 16 Control unit

[0133] 18 computer units

[0134] 20 Positioning device

[0135] 22 Drive unit

[0136] 24 Guide system

[0137] 26 work surface

[0138] 28a Pipetting area

[0139] 28b Pipetting area

[0140] 28c Pipetting area

[0141] 30a Filing system

[0142] 30b Filing system

[0143] 30c filing system

[0144] 32a Treatment facility

[0145] 32b Treatment facility

[0146] 34 Kit-Rack

[0147] 35a, b Recording units

[0148] 36 storage positions

[0149] 38 Reservoir

[0150] 40 reaction vessel rack

[0151] 41 recording units

[0152] 42 storage positions

[0153] 44 Reservoir

[0154] 46 Sample preparation area

[0155] 47 Storage position

[0156] 48 Holding device

[0157] 50 Control unit

[0158] 52 sensor units

[0159] 54 sensor unit

[0160] 56 Reading device

[0161] 58 centrifuge units

[0162] 60 Sample feeding device

Claims

1. Patent claims 1. A method for operating a pipetting device, in particular for coordinating pipette tips in a workflow carried out by means of the device, wherein a pipetting unit with a pipetting element performs pipetting operations for the treatment of samples in the workflow using a plurality of provided pipette tips, wherein the method is carried out using a control device, comprising at least the following steps: - Determining a sequence of pipetting operations to be performed in the workflow by adapting a predefined sequence of pipetting operations to a given number of samples to be processed; - Assigning the pipetting operations to be performed to categories, wherein each category is assigned a predefined pipette tip class, and wherein each pipette tip class is assigned at least one usage duration and a storage location as characteristics for the use of the pipette tips to be used in the pipetting operations, wherein the usage duration and the storage location for the pipette tips assigned to the respective pipette tip classes are each determined by a class-specific characteristic parameter; - Executing the determined sequence of categorized pipetting operations, wherein the pipette tips to be used are each assigned to a pipette tip class, and wherein the control device controls the pipetting unit based on the assignment of the pipetting operations to categories and the assignment of the pipette tips to each of the pipette tip classes in the workflow, wherein the pipetting unit selects and uses the pipette tips taking into account the class-specific characteristic parameters.

2. Method according to claim 1, characterized in that the feature parameter for the service life takes into account as criteria a maximum number of possible pipetting operations and / or a maximum period of use, wherein the feature parameter for the service life is determined by achieving at least one of the criteria.

3. Method according to claim 2, characterized in that the feature parameters for the number of possible pipetting operations and / or the period of use for at least one of the pipette tip classes are determined by input parameters.

4. Method according to claim 3, characterized in that the input parameters are specified by a user of the pipetting device or are implicitly determined during the workflow.

5. Method according to one of the preceding claims, characterized in that each pipette tip class is assigned at least one further feature which determines the use of the pipette tips by a class-specific feature parameter, selected from a group comprising or consisting of: (i) treatment of the pipette tip after use in a work step, (ii) disposal of the pipette tip after reaching a maximum service life.

6. Method according to one of the preceding claims, characterized in that the feature parameters of at least one of the features assigned to the pipette tip classes differ for at least two of the pipette tip classes.

7. Method according to one of the preceding claims, characterized in that the assignment of the pipette tips to one of the pipette tip classes is successive and in particular takes place each time a pipette tip is used for the first time in the workflow, wherein the assignment in particular results in each case from the successive categorized pipetting operations for which the pipette tips are used.

8. Method according to one of the preceding claims, characterized in that a number of process liquids to be used in the workflow is specified, wherein the sequence of pipetting operations to be performed in the workflow is adapted to the number of process liquids to be used.

9. Method according to one of the preceding claims, characterized in that, based on the predetermined number of samples to be treated or of process liquids to be used for at least one pipette tip class, it is determined how many pipette tips of the pipette tip class are assigned in the sequence of pipetting operations to be performed.

10. Method according to claim 9, characterized in that the pipette tips assigned to the pipette tip class are each assigned to one of the specified samples or to one of the process liquids to be used.

11. Method according to claim 10, characterized in that the pipette tip assigned to one of the samples to be treated and / or the process liquids to be used is used for all pipetting operations of the associated category relating to that sample or process liquid.

12. Method according to claim 11, characterized in that before each pipetting operation, it is first determined whether a pipette tip is already assigned to the respective pipetting operation, and the corresponding pipette tip is used if a pipette tip is already assigned to the respective pipetting operation, or a new pipette tip is selected and used if no pipette tip is yet assigned to the respective pipetting operation.

13. Method according to one of the preceding claims, characterized in that the assignment of a pipette tip to one of the pipette tip classes is maintained in the workflow until one of the criteria determining the service life is reached.

14. Method according to one of the preceding claims, characterized in that, based on the assignment of the pipetting operations to categories and / or the pipette tips to be used to one of the pipette tip classes, a control file is generated, using which the control device controls the pipetting unit in the workflow.

15. Device for pipetting, in particular for the treatment of samples in blood culture analysis, comprising at least: a pipetting unit with a pipetting element onto which a pipette tip can be interchangeably placed, a work surface comprising a plurality of storage devices for pipette tips, and an electronic control device for controlling the pipetting unit in a workflow in which the pipetting unit performs pipetting operations for the treatment of samples using a plurality of provided pipette tips, wherein the electronic control device is configured and programmed to operate the device for pipetting using a method according to one of claims 1 to 14.

16. Device according to claim 15, characterized by an operating device for specifying at least one input parameter by a user.

17. Device according to claim 15 or 16, characterized by at least one sensor unit for detecting at least one property of a pipette tip.

18. Device according to claims 15 to 17, characterized by a reading device for detecting a sample identifier.

19. Device according to one of claims 15 to 18, characterized by a plurality of pipetting areas, wherein each pipetting area provides one of the storage devices for storing pipette tips and / or a treatment device for post-treatment of pipette tips.

20. Device according to claim 19, characterized in that the storage devices each have a plurality of storage positions that are separated from one another, wherein the storage positions are in particular designed such that a pipette tip of a first type, or of a second type of pipette tip that differs from the first, can be stored in each storage position.

21. Device according to claim 19 or 20, characterized in that the treatment device comprises means for cleaning or disinfecting pipette tips.

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