Methods and laboratory systems for providing control samples for validating diagnostic tests

Abstract

The present disclosure relates to a method for providing control samples for validating diagnostic tests within a laboratory system. The laboratory system comprises a dispensing device, a storage device, a transport system, at least two analyzers and one control unit. A total number of control sample aliquots and an aliquot volume of each control sample aliquot is determined based on a validation schedule. A total control sample volume is provided and divided into the determined total number of control sample aliquots having the determined aliquot volume. The resulting control sample aliquots are transported to one or more of the at least two analyzers according to the validation schedule.

Description

Technical Field

[0001] The present disclosure is in the field of automated in vitro diagnostic laboratory testing. In this field, the present disclosure relates to a method, a laboratory system, a computer program product, and a computer-readable storage medium for providing a control sample for validating a diagnostic test within a laboratory system. Background Art

[0002] In an automated diagnostic laboratory environment, diagnostic tests are used to analyze a large number of test samples in a careful and efficient manner to produce accurate and reliable test results that provide critical information to physicians. Faulty diagnostic tests can lead to erroneous test results, or in the worst case, false negative or false positive test results, which can lead to incorrect interpretation of test results, inappropriate further testing, and the initiation of potentially dangerous treatments for patients. Typically, an automated diagnostic laboratory environment includes a laboratory system with multiple analyzers that are configured to perform the same diagnostic test on test samples according to a predefined laboratory workflow to improve throughput and / or turnaround time.

[0003] During a diagnostic test, an analyte-related signal or parameter is measured on an analyzer and then processed into a test result indicating the presence and / or concentration of the target analyte in the test sample. The quality, reliability, and comparability of the test results depend on the condition of the test reagents used during the diagnostic test and / or the analyzer operating status. Therefore, diagnostic tests need to be regularly validated according to a validation schedule during analyzer operation to monitor their performance and effectiveness. To validate a diagnostic test, a control sample with a known analyte and a known or determined analyte concentration is measured on the analyzer, and the resulting validation result is compared to a predefined allowable result range. Only if the validation result is within the predefined allowable result range can the test result of the diagnostic test be released for further diagnosis. If the validation result is outside the range, appropriate action is initiated to restore the analyzer to the required specifications. For laboratory systems consisting of multiple analyzers, the management and preparation of control samples can be very time-consuming for operators. Performing numerous manual steps to execute the validation schedule can introduce unnecessary errors, potentially leading to erroneous test results, delayed test results, or operational downtime. EP1747470, US6984527 and WO 2018017768 disclose automated solutions for providing control samples for validating diagnostic tests on an analyzer.

[0004] As the throughput and turnaround time of laboratory systems improve, the number of control samples that must be provided for verification and the demand for corresponding storage space are also growing. However, control samples and storage space are expensive and therefore must be used effectively. In addition, the availability and time of transporting control samples to the analyzer to verify the diagnostic test should not become a limiting factor in the laboratory workflow, so that test results can be provided on time and the test results of the required quality can be provided for further diagnosis. In addition, the verification results generated by different analyzers performing the same diagnostic test must be comparable to each other in order to reliably and consistently monitor the effectiveness of the diagnostic test within the laboratory system. Summary of the Invention

[0005] The present disclosure relates to a method, laboratory system, computer program product, and computer-readable storage medium for providing control samples for controlling diagnostic tests within a laboratory system in a simple, reliable, and cost-effective manner, thereby better meeting the needs of automated in vitro diagnostic laboratory testing.

[0006] The present disclosure relates to a method for providing a control sample for validating a diagnostic test within a laboratory system. The laboratory system comprises: an aliquoting device configured to generate a control sample aliquot from a total control sample volume; a storage device configured to store the control sample aliquot; a transport system configured to transport the control sample aliquot; at least two analyzers configured to perform the diagnostic test and validate the diagnostic test by measuring a control sample; and a control unit. The aliquoting device, the storage device, and the at least two analyzers are operably connected to the transport system. And the aliquoting device, the storage device, the transport system, and the at least two analyzers are communicatively connected to the control unit. The method comprises the following steps:

[0007] a) determining, by the control unit, a total number of control sample aliquots and an aliquot volume of each control sample aliquot based on a validation schedule, wherein each aliquot volume includes a dead volume and a volume including a determined number of control samples, each control sample having a volume required to validate the diagnostic test once

[0008] b) providing one or more containers containing said total control sample volume to said aliquoting device, wherein said total control sample volume is at least the sum of the aliquot volumes of said total number of control sample aliquots

[0009] c) generating said determined total number of control sample aliquots having said determined aliquot volumes by said aliquoting device

[0010] d) controlling the transport system by the control unit to transport at least one control sample aliquot to the storage device or one of the at least two analyzers according to the validation schedule to validate the diagnostic test by measuring a control sample of the at least one control sample aliquot.

[0011] As used herein, the term "control sample" refers to a sample of known volume, known analyte, and known or determined analyte concentration. Therefore, a control sample can be a measured control sample that has been analyzed by the manufacturer to make the analyte concentration known, or an unmeasured control sample, and the laboratory that purchases the control sample must determine its analyte concentration. The control sample includes the volume that needs to be verified once for the diagnostic test. When the test sample is analyzed by performing an analyte-specific diagnostic test on the analyzer, the analyte of the control sample corresponds to the target analyte. The analyzer measures the control sample in the same manner as the test sample to monitor whether the diagnostic test performed by the analyzer is effective and to produce accurate and reliable test results. The control sample can include one or more different analytes with known or determined concentrations and can be used to verify one or more different diagnostic tests.

[0012] As used herein, the term "validating a diagnostic test" refers to a process used to monitor the validity of a diagnostic test. During diagnostic test validation, a control sample containing an analyte corresponding to the target analyte of the diagnostic test is measured by an analyzer configured to perform the diagnostic test when analyzing a test sample. The measured analyte-related signal is processed into a validation result, and the validation result is compared to a predefined allowable result range. Only if the validation result is within the predefined allowable result range is the diagnostic test performed on the analyzer valid and produces an accurate and reliable test result that can be released for further diagnosis.

[0013] As used herein, the term "diagnostic test" refers to the analysis or study of a test sample to determine the presence and, if necessary, concentration of a target analyte. Thus, a diagnostic test defines the analyte or parameter that must be analyzed in a test sample. Based on the presence and / or concentration of the determined analyte, a qualitative or quantitative test result is generated, which can help make a diagnosis, plan a treatment or therapy, see if a treatment or therapy is working, or monitor a disease over time. A diagnostic test can be based on a specific analytical method that uses one or more specific techniques or processes for qualitatively and / or quantitatively detecting or measuring a signal or physical parameter associated with the analyte. The analytical method defines how and in what manner the analyte is detected in a test sample or control sample. If the signal or physical parameter associated with the analyte is directly detectable, the analytical method may include only a detection method. Alternatively, the analytical method may include a prior test reaction for generating a detectable signal associated with the analyte and a detection method for detecting the generated signal. The signal or physical parameter detected or measured associated with the analyte is then processed into a test result for the diagnostic test, which indicates the presence and / or concentration of the target analyte in the test sample.

[0014] As used herein, the term "test sample" refers to a patient specimen (e.g., serum, plasma, whole blood, urine, stool, sputum, cerebrospinal fluid, bone marrow, etc.) from which a diagnostic test can be used to determine the presence of an analyte and, if necessary, measure its concentration or parameter. Because the test samples are obtained from a single patient at a given time, the corresponding test sample properties are unique to each test sample.

[0015] As used herein, the term "aliquoting device" refers to a device comprising a pipetting device configured to divide the total control sample volume into control sample aliquots of determined aliquot volumes. The aliquoting device can divide the total control sample volume into control sample aliquots of equal or unequal aliquot volumes. The aliquoting device may include one or more holding positions configured to hold one or more containers comprising the total control sample volume and one or more holding positions configured to hold one or more control sample aliquot tubes. The pipetting device then transfers the control sample aliquots of determined aliquot volumes from the total control sample volume of the one or more containers to the one or more control sample aliquot tubes.

[0016] As used herein, the term "control sample aliquot" refers to a portion of the total control sample volume, wherein the volume (aliquot volume) determined is included in a test tube (control sample aliquot test tube). Each determined aliquot volume of each control sample aliquot includes a dead volume and the volume of a determined number of control samples, and each control sample has the volume required for verifying a diagnostic test once. Therefore, the volume of a control sample is needed to produce a verification result. For each verification of a diagnostic test, the control sample aliquot is transported to one or more of at least two analyzers, wherein one or more of the at least two analyzers aspirate a control sample of the control sample aliquot so as to subsequently measure a control sample by one or more of the at least two analyzers. As used herein, the term "dead volume" refers to the residual volume of the control sample in the control sample aliquot test tube after one or more analyzers in at least two analyzers aspirate a determined number of control samples. Therefore, dead volume cannot be used to produce a verification result or verify a diagnostic test. The dead volume ensures that one or more of the at least two analyzers can aspirate a defined amount of control sample without the inherent risk of partial air aspiration or damage to the control sample aliquot tube of the analyzer or the pipetting device due to physical contact between the control sample aliquot tube and the pipetting device.

[0017] In one embodiment, the control sample in the one or more containers is a liquid control sample. Thus, the pipetting device of the aliquoting device can transfer a control sample aliquot of a defined aliquot volume from the total control sample volume of the one or more containers directly into the one or more control sample aliquot tubes without further preliminary processing of the total control sample volume.

[0018] In another embodiment, the control sample in the one or more containers is a lyophilized control sample. In this case, the one or more containers comprising the total control sample volume include one or more containers comprising the lyophilized control sample and one or more containers comprising a liquid in which the control sample can be reconstituted. The aliquoting device is further configured to reconstitute the lyophilized control sample, and step b) of the method further comprises:

[0019] - Reconstitute the lyophilized control sample in one or more containers to the total control sample volume by an aliquoting device.

[0020] In an alternative embodiment, the laboratory system further comprises a reconstitution device configured to reconstitute the lyophilized control sample, and step b) of the method further comprises:

[0021] - reconstitute the lyophilized control sample in the one or more containers to the total control sample volume by the reconstitution device before providing the one or more containers comprising the total control sample volume to the aliquoting device.

[0022] The control sample is reconstituted by transferring the liquid from one or more containers containing the liquid in which the control sample can be reconstituted to one or more containers containing the lyophilized control sample using a pipetting device of an aliquoting device or a reconstitution device. In a specific embodiment, the one or more containers containing the liquid in which the control sample can be reconstituted can be composed of a device connected to a pure water supply. The reconstitution of the control sample can also include mixing, shaking and / or heating the one or more containers containing the mixture of the lyophilized control sample and the liquid using a mixing device, a shaking device and / or a heating device of the aliquoting device or the reconstitution device.

[0023] As used herein, the term "storage device" refers to a box of various sizes that can store multiple control sample aliquots in a storage rack or a carrying system, and the storage rack or the carrying system can be transported in and out of the storage device through a door. As used herein, the term "carrying system" refers to a device suitable for receiving, maintaining, conveying and / or releasing control sample aliquots. Such carrying systems are well known in the art and can be designed as described in EP3093071 or as described in EP3070479. In one embodiment, the storage device includes a control sample aliquot processor, which is configured to locate or insert the control sample aliquots into a storage rack or a carrying system, for example, for transferring the control sample aliquots between a storage rack and a carrying system. In one embodiment, the storage device can have a temperature regulating unit to keep the ambient temperature of the control sample aliquots in the storage device within a defined temperature range (e.g., 22°C ± 1°C) or below room temperature, possibly below 18°C, possibly below 10°C, and possibly below 0°C. In certain embodiments, the storage device may include a temperature control unit to maintain the ambient temperature of the control sample aliquots in the storage device between 4°C and room temperature. In another embodiment, the storage device may include a hygrometer and an air humidifier to reduce evaporation from uncapped control sample aliquots. The storage device may include multiple shelves within its interior for storing a number of storage racks or carrier systems in predetermined storage locations. In addition to or in lieu of shelves, the storage device may also include divider trays or inserts for the storage racks or carrier systems. Furthermore, shelves or compartments of varying heights may be provided to optimize available space when storing control sample aliquots of varying heights. In certain embodiments, the storage device is a refrigerator operably connected to the transport system or a storage unit for one or more of the at least two analyzers. In another specific embodiment, the storage device is a freezer operably connected to the transport system. Alternatively, the storage device may be a dedicated covered area of ​​the transport system that defines or forms a housing for storing multiple control sample aliquots in the carrier system.

[0024] As used herein, term " conveying system " refers to be designed to the system that will be transported to or be distributed to the pre-analysis workstation, analyzer or post-analysis workstation that the container, control sample aliquot test tube, test sample test tube, test reagent container or test consumable container that comprise total control sample volume are connected.Conveying system can comprise conveying plane, can convey the carrying system that is loaded with the container, control sample aliquot test tube, test sample test tube, test reagent container or test consumable container that comprise total control sample volume on described conveying plane.Conveying system can comprise conveyor belt to move carrying system.Alternatively, conveying system can comprise a certain number of electromagnetic actuators, described electromagnetic actuator is fixedly arranged below the conveying plane and is suitable for generating magnetic field to move carrying system.Alternatively, conveying system can comprise stable conveying plane, and self-propelled carrying system can move on described conveying plane.Alternatively, conveying system can comprise one or more tracks, can convey carrying system on described one or more tracks.

[0025] The pre-analysis workstation can generally be used for preliminary processing of control samples or test samples. In one embodiment, the pre-analysis workstation is an aliquoting device. In another embodiment, the pre-analysis workstation is a reconstitution device.

[0026] As used herein, the term "analyzer" refers to a device configured to perform a diagnostic test to analyze a test sample or a portion of a test sample to generate a measurable analyte-related signal, based on which a test result can be generated, the test result indicating the presence or absence and, if necessary, the concentration of an analyte or parameter. Furthermore, the analyzer is configured to perform the diagnostic test on a control sample to generate a measurable analyte-related signal, based on which a validation result can be generated, the validation result indicating whether the diagnostic test performed on the analyzer produces a valid and reliable test result, which can be released for further diagnosis.

[0027] In one embodiment, each of at least two analysers is the analyser module of a modular analyser system in at least two separate modular analyser systems.At least two separate modular analyser systems are operably connected to a conveying system and are communicatively connected to a control unit.In one embodiment, a plurality of analyser modules configured to perform different diagnostic tests can be combined in a modular analyser system so that the diagnostic test of different analytical methods can be performed to the same modular analyser system.For example, a modular analyser system can include two or more analyser modules, which are selected from immunochemical analysers, clinical chemistry analysers, nucleic acid analysers, coagulation analysers, hematology analysers, urine analysers, blood gas analysers or a combination thereof, to carry out different analytical methods so as to provide a laboratory test product combination for testing different analytes or parameters to carry out comprehensive diagnosis.In another example, a plurality of analyser modules configured to perform the same diagnostic test can be combined in a modular analyser system so that the throughput and the turnaround time of the diagnostic test can be improved.In addition, due to the redundancy of the analyser modules configured to perform the same diagnostic test, such a modular system may be more fail-safe.

[0028] The post-analysis workstation can generally be used for post-processing of control samples or test samples, such as storage or disposal of control samples or test samples. In one embodiment, the post-analysis workstation is a storage device. In another embodiment, the post-analysis workstation is another storage device. In another embodiment, the post-analysis workstation is a disposal unit.

[0029] The pre-analysis workstation, analyzer and post-analysis workstation may also include, for example, at least one device selected from the following devices: a sorting device, the sorting device is used to sort the test sample tubes or control sample aliquot tubes; a cap removal device, the cap removal device is used to remove the caps or seals on the test sample tubes or control sample aliquot tubes; a cap assembly device, the cap assembly device is used to assemble the caps or seals on the test sample tubes or control sample aliquot tubes; a cap removal / assembly device, the cap removal / assembly device is used to remove / assemble the caps or seals on the test sample tubes or control sample aliquot tubes; a pipetting device, the pipetting device is used to pipette the test sample or control sample; an aliquoting device, the aliquoting device is used to aliquot the test sample or control sample; a centrifugation device, the centrifugation device is used to centrifuge the test sample or control sample; an analyzing device, the analyzing device is used to analyze the test sample or control sample; a heating device, the heating device a device for heating a test sample or a control sample; a cooling device for cooling a test sample or a control sample; a mixing device for mixing a test sample or a control sample; a separating device for isolating an analyte of a test sample or a control sample; a storage device for storing a test sample or a control sample; an archiving device for archiving a test sample or a control sample; a test sample container type or a control sample aliquot test tube type determining device for determining a test sample container type or a control sample aliquot test tube type; a sample quality determining device for determining a test sample quality or a control sample quality; a test tube identification device for identifying a test sample test tube or a control sample aliquot test tube; a liquid level detection device for detecting a liquid level in a test sample test tube or a control sample aliquot test tube. Such pre-analytical workstations, analyzers, post-analytical workstations, and devices are well known in the art.

[0030] As used herein, the term "control unit" encompasses any physical or virtual processing device including a processor configured to control a laboratory system in a manner that provides control samples to validate diagnostic tests within the laboratory system. The control unit can receive information from a management unit about control samples that must be delivered to one or more of at least two analyzers in the laboratory system according to a validation schedule. The processor of the control unit can control at least an aliquoting device, a reconstitution device, a storage device, another storage device, a delivery system, and at least two analyzers communicatively connected to the control unit. The processor of the control unit can, for example, be embodied as a programmable logic controller adapted to execute a computer-readable program stored on a computer-readable storage medium provided with instructions for causing the laboratory system as described herein to perform the steps of the method to provide control samples to validate diagnostic tests in the laboratory system, as described below. The control unit can also include a user interface for inputting information or an order of test samples or control samples that must be processed on the laboratory instruments. In addition, an operator can use the user interface to display and / or configure a validation schedule or information about one or more containers containing a total control sample volume that is provided to validate diagnostic tests within the laboratory system according to the validation schedule.

[0031] As used herein, the term "validation schedule" refers to a plan at which a diagnostic test must be validated on one of at least two analyzers to monitor whether the analyzer is still producing valid and reliable test results at the planned time points. Thus, the validation schedule defines which control sample aliquot is planned to be delivered to which analyzer at which time points. In one embodiment, the validation schedule comprises a defined time period and at least one time period. The validation schedule defines a number of validation time points for each of the at least two analyzers and each of the at least one time period at which control sample aliquots are planned to be delivered to one or more of the at least two analyzers to validate the diagnostic test by measuring a control sample of the control sample aliquots. In one embodiment, the validation schedule comprises more than one time period, and the time periods may have the same or different lengths.

[0032] In a specific embodiment, the time period is a portion of the control sample aliquot airborne stabilization time or the control sample airborne stabilization time. The number of time periods of the verification schedule and the length of each time period can be determined based on the defined time period of the verification schedule and the control sample airborne stabilization time. As used herein, the term "control sample aliquot airborne stabilization time" refers to the duration that the control sample of the control sample aliquot remains on or under one or more defined conditions or experiences a certain number of allowed control sample aliquot processing steps for verifying a diagnostic test. If this duration has passed, the control sample aliquot comprising the control sample should no longer be transported to one or more of the at least two analyzers to verify a diagnostic test by measuring the control sample.

[0033] In one embodiment, the control sample aliquot onboard stabilization time is the maximum duration that a control sample aliquot can be maintained under one or more defined conditions, or the duration that a certain number of allowed control sample aliquot processing steps can be performed. The control sample aliquot onboard stabilization time can be a predefined maximum duration. Alternatively, the control sample aliquot onboard stabilization time can depend on a validation time point, in that the duration that a control sample aliquot can be maintained under one or more defined conditions, or the duration that a certain number of allowed control sample aliquot processing steps can be performed, can depend on a predetermined validation time point.

[0034] In certain embodiments, the defined condition is a defined temperature or open state of a control sample aliquot. For example:

[0035] -If the control sample aliquot onboard stabilization time is such that the control sample aliquot can be maintained at room temperature for a maximum duration of 2 days, and 2 days have passed at room temperature, then the control sample aliquot containing the control sample should no longer be transported to one or more of the at least two analyzers to validate the diagnostic test by measuring the control sample.

[0036] -If the control sample aliquot onboard stabilization time is such that the control sample aliquot can be maintained at room temperature for a maximum duration of 30 minutes and the control sample aliquot can be maintained at 4°C for 23.5 hours, and after 30 minutes at room temperature or 23.5 hours at 4°C, the control sample aliquot containing the control sample should no longer be transported to one or more of the at least two analyzers to validate the diagnostic test by measuring the control sample.

[0037] -If the control sample aliquot onboard stabilization time is such that the control sample can be kept in an open state for a maximum duration of 1 hour, and 1 hour has elapsed, the control sample aliquot containing the control sample should no longer be transported to one or more of the at least two analyzers to validate the diagnostic test by measuring the control sample.

[0038] In another specific embodiment, the number of control sample aliquot processing steps allowed is the maximum number of temperature changes that the aliquot can undergo, or the maximum number of transfers to one or more of at least two analyzers, wherein one or more of the at least two analyzers aspirates at least one control sample of the control sample aliquot to subsequently measure at least one control sample. For example:

[0039] -If the control sample aliquot onboard stabilization time is the duration over which the control sample aliquot may experience up to five temperature changes (e.g., from 4°C to room temperature, from room temperature to 4°C, from 4°C to room temperature, from room temperature to 4°C, from 4°C to room temperature) and the control sample experiences five temperature changes, then the control sample aliquot containing the control sample should no longer be transported to one or more of at least two analyzers to validate the diagnostic test by measuring the control sample.

[0040] -If the control sample aliquot onboard stabilization time is the duration over which the control sample aliquot can be transported five times to one or more of the at least two analyzers, wherein at least one of the at least two analyzers draws one control sample from the control sample aliquot each time and five control samples have been drawn from the control sample aliquot, then the control sample aliquot containing the control sample should no longer be transported to one or more of the at least two analyzers to validate the diagnostic test by measuring the control sample.

[0041] In one embodiment, the validation time point for each of the at least two analyzers is determined by a predefined time interval, a predefined time, a predefined number of days, a predefined number of times a diagnostic test is performed, and / or a predefined event. For example:

[0042] - One control sample aliquot is planned to be delivered every 12 hours or 24 hours to one of at least two analyzers to validate the diagnostic test by measuring one control sample of the control sample aliquot.

[0043] - One control sample aliquot is scheduled to be delivered to one of at least two analyzers every Monday and Wednesday at 4 pm to validate the diagnostic test by measuring one control sample of the control sample aliquot.

[0044] After 30 diagnostic tests have been performed on the test samples, a control sample aliquot is scheduled to be delivered to one of at least two analyzers to validate the diagnostic test by measuring a control sample from the control sample aliquot. Because the exact duration required to perform a certain number of diagnostic tests on the test samples varies and depends on the incoming test order and / or the workload of the laboratory system, the validation time point can be defined by prediction based on past operational information. For example, if 30 diagnostic tests have been performed every Monday between 8:00 AM and 11:00 AM over the past five months, then 30 diagnostic tests can be expected to be performed between 8:00 AM and 11:00 AM next Monday.

[0045] In one embodiment, the predefined events are maintenance activities and / or calibration measurements. For example:

[0046] - Every day at 8 am, a certain maintenance activity is planned to be performed, and after the maintenance activity, a control sample aliquot is planned to be transported to one of the at least two analyzers to validate the diagnostic test by measuring a control sample of the control sample aliquot.

[0047] - Calibration measurements are performed every day for 8 hours to calibrate, gradually change or adjust the analytical method and after the calibration measurements, one control sample aliquot is planned to be delivered to one of at least two analyzers to validate the diagnostic test by measuring one control sample of the control sample aliquot.

[0048] - Every Monday at 8:00 a.m., a certain maintenance activity and subsequent calibration measurement is planned to be performed, and after the maintenance activity and subsequent calibration measurement, a control sample aliquot is planned to be delivered to one of at least two analyzers to validate the diagnostic test by measuring a control sample of the control sample aliquot.

[0049] In one embodiment, in step a), the total number of control sample aliquots is determined based on the number of the at least one time period and the number of control sample aliquots for each time period. The aliquot volume of the control sample aliquots for one of the at least one time period is determined based on the number of validation time points for one of the at least one time period. Thus, in step a), the setup of the laboratory system and the given or predetermined validation requirements are used to determine the minimum possible number of control sample aliquots for each control sample aliquot with the maximum possible aliquot volume. This has the advantage of minimizing the sum of all dead volumes and associated costs.

[0050] In another embodiment, the number of control sample aliquots for each time period is further determined by the maximum number of at least two analyzers, for which at least one identical validation time point is defined for each time period. And the aliquot volume of the control sample aliquot for one of at least one time period is further determined by the maximum number of at least two analyzers, for which at least one identical validation time point is defined for one of at least one time period. For example:

[0051] If N analyzers (where N is a positive integer) have at least one identical validation time point in a time period, then the number of control sample aliquots for that time period is multiplied by N.

[0052] If a first set of N+X analyzers (where N and X are positive integers) have at least one first identical validation time point in a time period, and a second set of N analyzers have at least one second identical validation time point in a time period, then the number of control sample aliquots for that time period is multiplied by N+X.

[0053] As used herein, the term "same validation time point" refers to a first validation time point defined for a first analyzer and a second validation time point defined for a second analyzer when the duration between the first validation time point defined for the first analyzer and the second validation time point defined for the second analyzer is too short to transport the control sample aliquot from the first analyzer to the second analyzer or from the second analyzer to the first analyzer.

[0054] In a specific embodiment, the determined number of control samples required for the certain number of validation time points in one of the at least one time period is distributed among the determined number of control sample aliquots in the at least one time period such that the difference in aliquot volume of each control sample aliquot in the at least one time period is equal to or less than one volume of the control sample. Thus, the number of control samples is distributed as evenly as possible among the number of control sample aliquots in order to produce control sample aliquots with the smallest possible difference in sample aliquot volume. This has the advantage that the resulting aliquots have comparable or similar physical and / or chemical properties, which may be important for comparable handling or processing of the control samples, thereby leading to comparable validation results.

[0055] In one embodiment, the validation schedule includes a defined time period and at least one validation cycle. The validation schedule defines a time sequence and a plurality of validation time points for a validation cycle at which control sample aliquots are scheduled to be delivered to one or more of the at least two analyzers to validate the diagnostic test by measuring a control sample. The validation cycle is repeated a certain number of times (e.g., X times, where X is an integer) during the defined time period of the validation schedule.

[0056] In a specific embodiment, in the step a) of the method, the total number of control sample aliquots is determined based on the defined time period of the validation schedule, the validation time point of each validation cycle, and the control sample aliquot stabilization time. And the aliquot volume of each control sample aliquot is determined based on the validation time point of each validation cycle and the control sample aliquot stabilization time. The control sample aliquot stabilization time equals a validation cycle or is a multiple thereof. Therefore, by increasing the defined time period or reducing the control sample aliquot stabilization time, the quantity of control sample aliquots increases. And by increasing all validation time points of the validation cycle, the aliquot volume of each control sample increases. Therefore, in step a), the setting of the laboratory system and given or predetermined validation requirements are used to determine that each control sample aliquot has the minimum possible quantity of the control sample aliquot of maximum possible aliquot volume. This has the advantage of reducing the sum of all dead volumes and associated costs to a minimum.

[0057] In another specific embodiment, in step a) of the method, the total number of control sample aliquots and the aliquot volume of each control sample aliquot are further determined by the maximum number of at least two analyzers, and for this purpose, at least one identical validation time point is defined for each validation cycle. Thus, by increasing the maximum number of analyzers, the number of control sample aliquots is increased and the aliquot volume of each control sample aliquot is reduced, and for this purpose, at least one identical validation time point is defined for each validation cycle.

[0058] In a more specific embodiment, the total control sample volume includes the volume of a first number of control sample aliquots having a first aliquot volume. The first number of control sample aliquots and the first aliquot volume are calculated as follows:

[0059] First number of control sample aliquots =

[0060] ROUNDDOWN(((C*D)-(B*((ROUNDUP((C*D) / B;0))-1)))*((A-(A-((ROU NDDOWN(A / D;0))*D))) / D);0)

[0061] First aliquot volume =

[0062] ((ROUNDUP((C*D) / B;0))*E)+F

[0063] A: Define the time period for the verification schedule (in days)

[0064] B: Maximum number of analyzers for which at least one identical validation time point per validation cycle is defined

[0065] C: Verification time point of each verification cycle

[0066] D: Control sample aliquot onboard stabilization time (in days)

[0067] E: Volume of one control sample required to validate a diagnostic test once

[0068] F: Dead volume of each control sample aliquot

[0069] In another specific embodiment, the total control sample volume also includes the volume of a second number of control sample aliquots having a second aliquot volume. The second number of control sample aliquots and the second aliquot volume are calculated as follows:

[0070] Second number of control sample aliquots =

[0071] ROUNDDOWN(((B*(ROUNDUP((C*D) / B; 0)))-(C*D))*((A-(A-((ROUND DOWN(A / D; 0)))*D))) / D); 0)

[0072] Second aliquot volume =

[0073] (((ROUNDUP((C*D) / B;0))-1)*E)+F

[0074] A: Define the time period for the verification schedule (in days)

[0075] B: Maximum number of analyzers for which at least one identical validation time point per validation cycle is defined

[0076] C: Verification time point of each verification cycle

[0077] D: Control sample aliquot onboard stabilization time (in days)

[0078] E: Volume of one control sample required to validate a diagnostic test once

[0079] F: Dead volume of each control sample aliquot

[0080] In another more specific embodiment, the total control sample volume also includes the volume of a third number of control sample aliquots having a third aliquot volume and the volume of a fourth number of control sample aliquots having a fourth aliquot volume. The third number of control sample aliquots, the third aliquot volume, the fourth number of control sample aliquots, and the fourth aliquot volume are calculated as follows:

[0081] The third number of control sample aliquots =

[0082] ROUNDDOWN(((C*(A-((ROUNDDOWN(A / D; 0)))*D)))-(B*((ROUNDUP ((C*(A-((ROUNDDOWN(A / D;0))*D))) / B;0))-1)))*((A-((ROUNDDOWN(A / D;0)))*D)) / ((IF(A-((ROUNDDOWN(A / D;0)))*D)=0;1;

[0083] A-((ROUNDDOWN(A / D;0))*D)))));0)

[0084] Third aliquot volume =

[0085] ((ROUNDUP((C*(A-((ROUNDDOWN(A / D; 0)))*D))) / B; 0))*E)+F

[0086] Fourth number of control sample aliquots =

[0087] ROUNDDOWN(((B*(ROUNDUP((C*(A-((ROUNDDOWN(A / D; 0)))*D))) / B; 0)))-(C*(A-((ROUNDDOWN(A / D; 0)))*D))))*((A-((ROUNDDOWN(A / D; 0)))* D)) / ((IF(A-((ROUNDDOWN(A / D; 0)))*D)=0;1;

[0088] A-((ROUNDDOWN(A / D;0))*D)))));0)

[0089] Volume of the fourth aliquot =

[0090] ((((ROUNDUP((C*(A-((ROUNDDOWN(A / D; 0)))*D))) / B; 0))-1))*E)+F

[0091] A: Define the time period for the verification schedule (in days)

[0092] B: Maximum number of analyzers for which at least one identical validation time point per validation cycle is defined

[0093] C: Verification time point of each verification cycle

[0094] D: Control sample aliquot onboard stabilization time (in days)

[0095] E: Volume of one control sample required to validate a diagnostic test once

[0096] F: Dead volume of each control sample aliquot

[0097] In one embodiment, the method further comprises the following steps before step a) of the method:

[0098] - Display of the verification schedule by the control unit on the user interface of the control unit

[0099] - confirmation or rejection by the operator using the user interface of the displayed verification schedule as the verification schedule of step a) of the method

[0100] - If the displayed verification schedule is rejected, configuring the displayed verification schedule by the operator using the user interface and confirming by the operator using the user interface to use the configured verification schedule as the verification schedule of step a) of the method.

[0101] In one embodiment, the displayed validation schedule includes a defined time period for each of the at least two analyzers and each of the predefined number of time periods, a predefined number of time periods of predetermined length, and predefined validation time points. Alternatively, the displayed schedule is a configurable validation schedule template.

[0102] In one embodiment, configuring a displayed verification schedule includes at least one of the following steps:

[0103] -Specify the diagnostic test for which the validation schedule will be configured

[0104] - Designation of control samples used to validate diagnostic tests (e.g., control sample onboard stabilization time)

[0105] - Define the time period for the verification schedule

[0106] - specifying a validation time point for each of the at least two analyzers according to validation requirements (e.g., a predefined time interval, a predefined time, a predefined number of days, a predefined number of times to perform a diagnostic test, and / or a predefined event)

[0107] -Specify the number of time periods

[0108] -Specify the length of each time period

[0109] For example, an operator can configure a validation schedule with a time period of 3 days for five analyzers using a control sample with an onboard stabilization time of 16 hours for the control sample. Based on the defined time period and the given onboard stabilization time of the control sample, the resulting validation schedule includes four time periods of 16 hours and one time period of 8 hours. Based on the validation requirements of the five analyzers, the validation time points for each time period can be determined. Finally, based on the number of time periods and the validation time points for the five analyzers within each time period, the total number of control sample aliquots and the aliquot volume of each control sample aliquot can be determined, and the operator can provide one or more containers containing the total control sample volume. Therefore, by defining the time period of the validation schedule, the operator can advantageously configure the validation schedule according to his work schedule and / or workload.

[0110] In one embodiment, the method further comprises the following steps after step a) and before step b) of the method:

[0111] - calculating, by the control unit, a total control sample volume based on the determined total number of control sample aliquots and the aliquot volume of each control sample aliquot

[0112] - displaying, by the control unit, on a user interface of the control unit, the total control sample volume and instructions for providing one or more containers containing the total control sample volume

[0113] In one embodiment, the laboratory system further comprises a loading station, and providing one or more containers comprising the total control sample volume comprises the following steps:

[0114] - One or more containers containing the total control sample volume are loaded onto the loading station by the operator.

[0115] In one embodiment, the loading station may consist of an aliquoting device.

[0116] In an alternative embodiment, the loading station can be separate from the aliquoting device or the reconstitution device, operably connected to the transport system, and communicatively connected to the control unit. After loading one or more containers containing the total control sample volume into the loading station, the control unit controls the transport system to transport the one or more containers containing the total control sample volume from the loading station to the aliquoting device or the reconstitution device.

[0117] In another embodiment, the method further comprises the steps of:

[0118] e) controlling the transport system by the control unit to transport at least one control sample aliquot between the storage device and the at least two analyzers according to the validation schedule to validate the diagnostic test by measuring a control sample of the at least one control sample aliquot.

[0119] In a specific embodiment, step e) of the method further comprises:

[0120] - When the duration between step c) and the first verification time point or the duration between two subsequent verification time points exceeds a defined time threshold, controlling the transport system by the control unit to transfer at least one control sample aliquot to the storage device.

[0121] Thus, by measuring one control sample of the control sample aliquot, the control sample aliquot is always available for validation of the diagnostic test, while the control sample aliquot can be kept in the laboratory system for a longer period of time by providing optimal control sample storage conditions (e.g., storage at 4°C and / or optimal humidity.) Thus, the risk of erroneous test results, delayed test results, or operational downtime, as well as the number of control sample aliquots required and the corresponding dead volume, can be reduced.

[0122] If the total number of control sample aliquots produced includes at least one control sample aliquot and an additional control sample aliquot, and if, according to the validation schedule, the at least one control sample aliquot is planned to be delivered to one of the at least two analyzers just after step c) (for example, because the operator provides one or more containers containing the total control sample volume just before the validation schedule begins), the at least one control sample aliquot is delivered to one of the at least two analyzers and the additional control sample aliquot is delivered to the storage device.

[0123] If the total number of control sample aliquots generated includes at least one control sample aliquot and additional control sample aliquots, and if, according to the validation schedule, it is not planned to transport the at least one control sample aliquot to one of the at least two analyzers just after step c) (for example, because the operator provides one or more containers containing the total control sample volume at some time before the validation schedule begins), then the at least one control sample aliquot and the additional control sample aliquot are transported to the storage device when the validation schedule begins, and then the at least one control sample aliquot is transported to one of the at least two analyzers. Thus, the operator can provide one or more containers containing the total control sample volume not only for the next validation schedule but also for future validation schedules. This may be advantageous if the next validation schedule or future validation schedules begin at a time when the operator is unable to provide one or more containers containing the total control sample volume. Thus, the walk-away time of the laboratory system can be improved.

[0124] In another embodiment, the method further comprises the following steps after step e) of the method:

[0125] - controlling the transport system by the control unit to transport at least one further control sample aliquot from the storage device to one of the at least two analyzers to validate the diagnostic test by measuring a control sample of the at least one further control sample aliquot

[0126] - the transport system is controlled by the control unit to transport at least one further control sample aliquot between the storage device and the at least two analyzers according to the validation time to validate the diagnostic test by meter measuring a control sample of the at least one further aliquot.

[0127] The risk of erroneous test results, delayed test results, or operational downtime can be further reduced because additional control sample aliquots stored in the storage device can be transported from the storage device so that they can be used once a control sample aliquot is needed to validate a diagnostic test by measuring a control sample of the control sample aliquot.

[0128] In one embodiment, the laboratory system includes another storage device. The other storage device is operably connected to the transport system and is communicatively connected to the control unit. The storage device is configured for temporary storage of a control sample aliquot, and the other storage device is configured for long-term storage of a control sample aliquot. Step d) of the method further includes:

[0129] - The transport system is controlled by the control unit to transport the at least one control sample aliquot to the storage device for temporary storage or to one of the at least two analyzers for validating the diagnostic test by measuring one control sample of the at least one control sample aliquot according to the validation schedule and to transport the additional control sample aliquot to the other storage device for long-term storage, and to transport the at least one control sample aliquot and the additional control sample aliquot to the other storage device for long-term storage before transporting the at least one control sample aliquot to the storage device for temporary storage or to one of the at least two analyzers for validating the diagnostic test by measuring one control sample of the at least one control sample aliquot according to the validation schedule.

[0130] As used herein, the term "another storage device" refers to a box of various sizes configured for long-term storage of a plurality of control sample aliquots in a storage rack or a carrying system that can be transported into and out of the storage device through a door. The another storage device includes a temperature control unit to maintain the ambient temperature of the control sample aliquots in the another storage device below 0°C and possibly below -20°C. As used herein, the term "long-term storage" refers to a duration equal to or longer than the time period or the onboard stabilization time of the control sample aliquots, for example, the control sample aliquots in the another storage device can be stored at -20°C and therefore maintained on the laboratory system for a longer period than the onboard stabilization time of the control sample aliquots. Since the control sample aliquots can be stored for a longer period of time in the laboratory system, more control sample aliquots can be produced within a longer defined time period, and therefore, the operator must provide one or more containers containing the total control sample volume less frequently, thereby improving the fully automated operation time. If the laboratory system includes a storage device and another storage device, the storage device includes a temperature control unit to maintain the ambient temperature of the control sample aliquots within the storage device between 4°C and room temperature. As used herein, the term "temporary storage" refers to a duration shorter than the time period or onboard stabilization time of the control sample aliquots. For example, the control sample aliquots within the storage device can be maintained at 4°C for a time period and, therefore, can be quickly used for validation because no thawing time is required. In one embodiment, the other storage device includes a control sample aliquot handler configured to position or insert the control sample aliquots into a storage rack or a carrier system, for example, for transferring the control sample aliquots between a storage rack and a carrier system. The storage device may include multiple racks within the storage device for storing a certain number of storage racks or carrier systems in predetermined storage locations. In addition to or in lieu of the racks, the storage device may also include divider trays or inserts for the racks or carrier systems. Furthermore, racks or compartments of varying heights may be provided to optimize available space when storing control sample aliquots of varying heights. In certain embodiments, the long-term storage device is a freezer operably connected to the delivery system.

[0131] If the total number of control sample aliquots produced includes at least one control sample aliquot and an additional control sample aliquot, and if, according to the validation schedule, at least one control sample aliquot is planned to be transported to a storage device for temporary storage or to one of the at least two analyzers just after step c), then at least one control sample aliquot is transported to a storage device for temporary storage or to one of the at least two analyzers and the additional control sample aliquot is transported to another storage device for long-term storage.

[0132] If the total number of control sample aliquots produced includes at least one control sample aliquot and an additional control sample aliquot, and if, according to the validation schedule, it is not planned to transport the at least one control sample aliquot to a storage device for temporary storage or to one of the at least two analyzers just after step c), then when the validation schedule begins, the at least one control sample aliquot and the additional control sample aliquot are transported to another storage device for long-term storage, and then the at least one control sample aliquot is transported to the storage device for temporary storage or to one of the at least two analyzers. Thus, the operator can provide one or more containers containing the total control sample volume not only for the next validation schedule but also for future validation schedules. This may be advantageous if the next validation schedule or future validation schedules begin at a time when the operator is unable to provide one or more containers containing the total control sample volume. Thus, the fully automated operation time of the laboratory system can be improved.

[0133] In another embodiment, the method further comprises the steps of:

[0134] f) controlling the transport system by the control unit to transport at least one further control sample aliquot from the further storage device to a storage device for temporary storage or to one of the at least two analyzers to validate the diagnostic test by measuring a control sample of the at least one further control sample aliquot

[0135] g) controlling the transport system by the control unit to transport at least one further control sample aliquot between a storage device for temporary storage and the at least two analyzers according to the validation schedule to validate the diagnostic test by measuring a control sample of the at least one further aliquot.

[0136] The risk of erroneous test results, delayed test results, or operational downtime can be further reduced because additional control sample aliquots stored in another storage device can be transported from the other storage device so that they can be used once a control sample aliquot is needed to validate a diagnostic test by measuring a control sample of the control sample aliquot.

[0137] In one embodiment, each generated control sample aliquot includes a unique control sample aliquot identifier associated with at least one control sample aliquot onboard stabilization time. The laboratory system further includes a disposal unit operably connected to the transport system. The storage device, at least two analyzers, and the transport system have defined temperatures, and the storage device and at least two analyzers include a reader configured to read the unique control sample aliquot identifier. The method further includes the following steps:

[0138] h) reading the unique control sample aliquot identifier by the reading device each time a control sample aliquot arrives at or leaves one or more of the storage device and the at least two analyzers.

[0139] i) generating a timestamp by a reader when reading said unique control sample aliquot identifier

[0140] j) calculating, by the control unit based on the generated timestamps, a duration for which the control sample aliquot is maintained at one or more defined temperatures, a duration for which the control sample aliquot undergoes a certain number of temperature changes, or a duration for which the control sample aliquot is transported a certain number of times to one or more of the at least two analyzers.

[0141] k) comparing, by the control unit, the calculated duration with the control sample aliquot onboard stabilization time

[0142] 1) If the calculated time period exceeds the control sample aliquot onboard stabilization time, controlling the transport system by the control unit to transport the control sample aliquot to the processing unit.

[0143] As used herein, the term "unique control sample aliquot identification" refers to an identifier for identifying each control sample aliquot in different ways. A unique control sample aliquot identification is associated with at least one control sample aliquot onboard stabilization time. A unique control sample aliquot identification can be associated with other control sample attributes or information such as manufacturing information (e.g., batch information) or component information (e.g., one or more analytes, one or more concentrations, additives, etc.). A unique control sample aliquot identification can be a label attached to a control sample aliquot test tube. For example, a unique control sample aliquot identification can be a bar code or a radio frequency identification tag (RFID tag) attached to a control sample aliquot test tube. A unique control sample aliquot identification and associated control sample aliquot onboard stabilization time and other control sample attributes can be stored in a database that is communicatively connected to a control unit. Alternatively, a unique control sample aliquot identification and associated control sample aliquot onboard stabilization time and other control sample attributes can be stored on an RFID tag.

[0144] As used herein, the term "reading device" refers to a device configured to read a unique control sample aliquot identification. For example, the reading device can be a barcode reader, an RFID reader, or a camera. Alternatively, the reading device can be an RFID reader / writer that also includes write capability.

[0145] As used herein, the term "disposal unit" refers to a device configured to dispose of a control sample aliquot whose onboard stabilization time has expired and, therefore, is no longer viable for confirming a diagnostic test. In one embodiment, the disposal unit is spatially separated from the storage device or the at least two analyzers. In another embodiment, the disposal unit may consist of one or more of the storage device or the at least two analyzers.

[0146] In one embodiment, the laboratory system comprises a further storage device, wherein the further storage device has a defined temperature, wherein the further storage device comprises a further reading device, wherein the further reading device is configured to read the unique control sample aliquot identification, wherein step h) of the method further comprises:

[0147] - reading said unique control sample aliquot identification by said further reading device each time a control sample aliquot arrives at or leaves said further storage device,

[0148] The step i) of the method further comprises:

[0149] - generating a timestamp by said further reading device upon reading said unique control sample aliquot identification.

[0150] In one embodiment, the laboratory system further comprises: a seal removal device configured to remove the seal on the control sample aliquot tube; and a seal fitting device for fitting the seal on the control sample aliquot tube; or a seal removal / fitting device configured to remove / fit the seal on the control sample aliquot tube, wherein the seal removal device and the seal fitting device or the seal removal / fitting device further comprises another reading device for reading the unique control sample aliquot identification, wherein step h) of the method further comprises:

[0151] - reading the unique control sample aliquot identification by another reading device each time the control sample aliquot tube is closed and opened by the closure removal device and the closure assembly device or by the closure removal / assembly device,

[0152] The step i) of the method further comprises:

[0153] - generating a timestamp by said further reading device upon reading said unique control sample aliquot identification,

[0154] The step j) of the method further comprises:

[0155] - Calculating, by the control unit, the duration that the control sample aliquot remains in the one or more open states.

[0156] In one embodiment, each of the one or more containers comprises a unique container identifier, wherein the unique container identifier is associated with at least the control sample onboard stabilization time, wherein step c) of the method further comprises:

[0157] - allocating, by the control unit, a control sample onboard stabilization time associated with the unique container identification to each unique control sample aliquot identification of each generated control sample aliquot.

[0158] The present disclosure also relates to a laboratory system for providing a control sample for validating a diagnostic test within a laboratory system. The laboratory system comprises: an aliquoting device configured to generate a control sample aliquot from a total control sample volume; a storage device configured to store the control sample aliquot; a transport system configured to transport the control sample aliquot; at least two analyzers configured to perform the diagnostic test and validate the diagnostic test by measuring a control sample; and a control unit. The aliquoting device, the storage device, and the at least two analyzers are operably connected to the transport system. The aliquoting device, the storage device, the transport system, and the at least two analyzers are communicatively connected to the control unit. And the laboratory system is configured to perform steps a) to e) of the method to provide a control sample for validating a diagnostic test within the laboratory system described herein.

[0159] In one embodiment of the laboratory system, the laboratory system further comprises a reconstitution device configured to reconstitute the lyophilized control sample to a total control sample volume before providing the one or more containers to the aliquoting device.

[0160] In one embodiment, the laboratory system includes another storage device. The other storage device is operably connected to the transport system and is communicatively connected to the control unit. The storage device is configured for temporary storage of a control sample aliquot, and the other storage device is configured for long-term storage of a control sample aliquot. The laboratory system is configured to perform steps a) to g) of the method to provide a control sample for validation of a diagnostic test within the laboratory system described herein.

[0161] In another embodiment, the laboratory system further comprises a handling unit operably connected to the transport system. The storage device, at least two analyzers, and the transport system have defined temperatures, and the storage device and at least two analyzers comprise a reader configured to read a unique control sample aliquot identifier. The laboratory system is configured to perform steps a) to e) and steps h) to l) of the method to provide a control sample for validating a diagnostic test within the laboratory system described herein.

[0162] In one embodiment of the laboratory system, the laboratory system comprises another storage device. The another storage device has a defined temperature and comprises another reading device configured to read a unique control sample aliquot identification. The laboratory system is configured to perform steps a) to l) and further perform during step h) of the method:

[0163] - reading said unique control sample aliquot identification by said further reading device each time a control sample aliquot arrives at or leaves said further storage device.

[0164] And the laboratory system is configured to further perform during step i) of the method:

[0165] - generating a timestamp by said further reading device upon reading said unique control sample aliquot identification.

[0166] In one embodiment of the laboratory system, the laboratory system further comprises a seal removal device configured to remove the seal on the aliquot and a seal fitting device for fitting the seal on the aliquot, or a seal removal / fitting device configured to remove / fit the seal on the aliquot. The seal removal device and the seal fitting device or the seal removal / fitting device comprise another reading device for reading the unique control sample aliquot identification. The laboratory system is configured to perform steps a) to l) and further perform during step h) of the method:

[0167] - Each time a control sample aliquot is closed or opened by the closure removal device and the closure fitting device or by the closure removal / fitting device, the unique control sample aliquot identification is read by another reading device.

[0168] And the laboratory system is configured to further perform during step i) of the method:

[0169] - generating a timestamp by said further reading device upon reading said unique control sample aliquot identification.

[0170] And the laboratory system is configured to further perform during step i) of the method:

[0171] - Calculating, by the control unit, the duration that the control sample aliquot remains in the one or more open states.

[0172] The present disclosure also relates to a computer program comprising instructions to cause the laboratory system described herein to perform the steps of the method to provide a control sample for validating a diagnostic test within the laboratory system as described herein.

[0173] The present disclosure also relates to a computer-readable storage medium having stored thereon a computer program comprising instructions for causing the laboratory system described herein to perform the steps of the method to provide a control sample for validating a diagnostic test within the laboratory system as described herein.

[0174] Other and further objects, features and advantages will appear from the following description of exemplary embodiments and the accompanying drawings, which serve to explain the principles in more detail. BRIEF DESCRIPTION OF THE DRAWINGS

[0175] Figure 1 Depicted is a schematic diagram of a laboratory system for providing control samples to validate a diagnostic test within the laboratory system.

[0176] Figure 2 A through 2D illustrate flow charts of methods for providing control samples to validate diagnostic tests within a laboratory system.

[0177] Figure 3 A and 3B depict examples of a process for a validation schedule, control sample aliquots, and aliquot volumes during each time period of the validation schedule.

[0178] Figure 4A and 4B Another example of a process depicting a validation schedule, control sample aliquots, and aliquot volumes during each time period of the validation schedule.

[0179] Figure 5 Another example of a verification timeline is depicted.

[0180] Figure 6A and 6B Other examples of verification schedules are shown. DETAILED DESCRIPTION

[0181] exist Figure 1 , a schematic diagram of a laboratory system (38) for providing a control sample (36) to validate a diagnostic test within the laboratory system (38) is shown. The laboratory system (38) includes an aliquoting device (40) configured to produce a control sample aliquot (42) from a total control sample volume (44) included in one or more containers (62). The laboratory system (38) also includes a storage device (46) configured to store the control sample aliquot (42). Figure 1As shown in , the carrying system (47) can receive, hold, transport and / or release a control sample aliquot (42). The laboratory system (38) also includes at least two analyzers (50, 52), which are configured to perform a diagnostic test and verify the diagnostic test by measuring a control sample (36). In the illustrated embodiment, each of the at least two analyzers (50, 52) is an analyzer module of a modular analyzer system in two separate modular analyzer systems (51, 53), wherein each modular analyzer system includes 4 analyzer modules. The laboratory system (38) also includes a conveying system (48), which is configured to transport the carrying system (47) loaded with the control sample aliquot (42) to an aliquoting device (40) operably connected to the conveying system (48), a storage device (46) and at least two analyzers (50, 52). The laboratory system (38) also includes a control unit (54), which is as shown in FIG. Figure 1 The control unit (54) is communicatively connected to the aliquoting device (40), the storage device (46), and the at least two analyzers (50, 52) as indicated by the dashed lines in FIG. The control unit (54) includes a user interface (80) for displaying and / or configuring a verification schedule (58) or information about the number of containers (62) and the total control sample volume (44), the user interface being provided to verify the test diagnostic within the laboratory system (38) according to the verification schedule (58). The control unit (54) also includes a computer-readable storage medium (78) having a computer program stored thereon, the computer program including instructions for causing the laboratory system (38) to perform the following steps: Figure 2 and steps ( 12 , 14 , 16 , 18 , 20 , 22 , 24 , 26 , 28 , 30 , 32 , 34 ) of method ( 10 ) described in more detail in FIG. 6 .

[0182] In the embodiment shown, the laboratory system (38) includes a further storage device (70) configured for long-term storage of the control sample aliquots (42), and a disposal unit (74) for disposing of control sample aliquots whose onboard stabilization time (68) has expired and which are therefore no longer usable for validating the diagnostic test. If the laboratory system (38) includes a storage device (46) and a further storage device (70), the storage device is configured for temporary storage of the control sample aliquots. Figure 1As further shown, the storage device (46), the further storage device (70), and the at least two analyzers (50, 52) include a reading device (76) configured to read a unique control sample aliquot identifier (72) of the control sample aliquot (42) and generate a timestamp each time the control sample aliquot (42) arrives at or leaves the storage device (46), the further storage device (70), and the at least two analyzers (50, 52).

[0183] Figure 2 A to Figure 2 D depicts a flow chart of a method (10) for providing a control sample (36) to validate a diagnostic test within a laboratory system (38). Figure 1 As shown in FIG, the laboratory system (38) includes an aliquoting device (40), a storage device (46), a transport system (48), at least two analyzers (50, 52) and a control unit (54). Figure 2 A shows a first embodiment of the method (10), wherein in step a) (12) of the method (10), the control unit (54) determines the total number of control sample aliquots (42) and the aliquot volume (56) of each control sample aliquot (42) based on a validation schedule (58), as follows Figure 3 6 . Then, in step b)(14) of the method (10), one or more containers (62) containing a total control sample volume (44) are provided to the aliquoting device (40). The total control sample volume (44) is at least the sum of the aliquot volumes (56) of the total number of control sample aliquots (42). Subsequently, in step c)(16) of the method (10), the aliquoting device (40) produces a determined total number of control sample aliquots (42) having the determined aliquot volumes (56). In step d)(18) of the method (10), the control unit (54) controls the transport system (48) to transport at least one control sample aliquot (42) to the storage device (46) or one of the at least two analyzers (50, 52) according to the validation schedule (58) to validate the diagnostic test by measuring a control sample (36) of the at least one control sample aliquot (42).

[0184] In such Figure 2In a second embodiment of the method (10) shown in B, after step d)(18) of the method (10) of the first embodiment, in step e)(20) of the method (10), the control unit (54) controls the transport system (48) to transport at least one control sample aliquot (42) between the storage device (46) and the at least two analyzers (50, 52) according to the validation schedule (58) to validate the diagnostic test by measuring a control sample (36) of the at least one control sample aliquot (42).

[0185] Figure 2C shows a third embodiment of the method (10) when the laboratory system (38) includes a storage device (46) and a further storage device (70). Steps a) to c) (12, 14, 16) of the third embodiment of the method (10) are the same as steps a) to c) (12, 14, 16) described above for the first embodiment. However, in step d)(18) of the method (10), if, according to the validation schedule (58), at least one control sample aliquot (42) is scheduled to be transported to a storage device (46) for temporary storage or to one of the at least two analyzers (50, 52) just after step c)(16) of the method (10), the control unit (54) controls the transport system (48) to transport at least one control sample aliquot (42) to the storage device (46) for temporary storage or to one of the at least two analyzers (50, 52) to validate the diagnostic test by measuring one control sample (36) of the at least one control sample aliquot (42), and to transport another control sample aliquot (42) to another storage device (70) for long-term storage. If, according to the validation schedule (58), it is not planned to transfer the at least one control sample aliquot (42) to a storage device (46) for temporary storage or to one of the at least two analyzers (50, 52) immediately after step c) (16), the at least one control sample aliquot (42) and the additional control sample aliquot (42) are transferred to another storage device (70) for long-term storage when the validation schedule (58) begins, and then the at least one control sample aliquot (42) is transferred to the storage device (46) for temporary storage or to one of the at least two analyzers (50, 52). After at least one control sample aliquot (42) has been transported to a storage device (46) for temporary storage or to one of at least two analyzers (50, 52), in step e)(20) of the method (10), the control unit (54) controls the transport system (48) to transport at least one control sample aliquot (42) between the storage device (46) and the at least two analyzers (50, 52) according to the validation schedule (58) to validate the diagnostic test by measuring a control sample (36) of the at least one control sample aliquot (42).For the next time period (64) of the validation schedule (58), or if no control sample (36) remains in at least one control sample aliquot (42), or if the control sample aliquot onboard stabilization time (68) has elapsed, the control unit (54) controls the transport system (48) in step f)(22) of the method (10) to transport at least one further control sample aliquot (42) from the further storage device (70) to a storage device (46) for temporary storage or to one of the at least two analyzers (50, 52) to validate the diagnostic test by measuring one control sample (36) of the at least one further control sample aliquot (42). After step f)(22) of the method (10), the control unit (54) controls the transport system (48) in step g)(24) of the method (10) to transport the at least one further control sample aliquot (42) between the storage device (46) for temporary storage and the at least two analyzers (50, 52) according to the validation schedule (58) to validate the diagnostic test by measuring a control sample (36) of the at least one further aliquot (42).

[0186] exist Figure 2In D, a fourth embodiment of the method (10) is shown, if each generated control sample aliquot (42) includes a unique control sample aliquot identification (72) associated with at least one control sample aliquot onboard stabilization time (68), the unique control sample aliquot identification can be used to track and control the disposal of at least one control sample aliquot (42) on the laboratory system (38). Therefore, the laboratory system (38) also includes a disposal unit (74), which is operably connected to the conveying system (48). The storage device (46), the at least two analyzers (50, 52) and the conveying system (48) have defined temperatures. In addition, the storage device (46) and the at least two analyzers (50, 52) include a reading device (76), which is configured to read the unique control sample aliquot identification (72). Steps a) to e)(12, 14, 16, 18) of the fourth embodiment of method (10) are the same as steps a) to e)(12, 14, 16, 18) described above for the second embodiment. In step h)(26) of method (10), each time a control sample aliquot (42) arrives at or leaves the storage device (46) and one or more of the at least two analyzers (50, 52), the storage device (46) and the reading device (76) of one or more of the at least two analyzers (50, 52) read the unique control sample aliquot identifier (72). Then, in step i)(28) of method (10), the storage device (46) and the reading device (76) of one or more of the at least two analyzers (50, 52) generate a timestamp when the unique control sample aliquot identifier (72) is read. Based on the generated timestamps, the control unit (54) calculates in step j)(30) the duration of maintaining the control sample aliquot (42) at one or more defined temperatures, the duration of undergoing a certain number of temperature changes of the control sample aliquot (42), or the duration of transporting the control sample aliquot (42) to one or more of the at least two analyzers (50, 52) a certain number of times. Subsequently, the control unit (54) compares the calculated duration with the control sample aliquot onboard stabilization time (68) in step k)(32) of the method (32). Finally, in step l)(34) of the method (10), if the calculated time period exceeds the control sample aliquot onboard stabilization time (68), the control unit (54) controls the transport system (48) to transport the control sample aliquot (42) to the disposal unit (74).

[0187] Figure 3A depicts an example of a validation schedule (58). The validation schedule (58) shown includes five time periods (64) for a defined time period (63) lasting three days: from time period 1 to time period 5. The time periods (64) shown are of different lengths. The length of the control sample aliquot onboard stabilization time (68) for time periods 1 to time period 4 is 16 hours. The length of the last time period 5 is 8 hours, which is only half of the control sample aliquot onboard stabilization time (68). In the example shown, the validation schedule (58) defines a certain number of validation time points (66) for each of the five analyzers (50, 52, 82, 84, 86) (analyzer A to analyzer E) and the five time periods (64), at which validation time points, the control sample aliquot (42, CSA) is planned to be delivered to one or more of the five analyzers (50, 52, 82, 84, 86) to validate the diagnostic test by measuring a control sample (36, CS) of the control sample aliquot (42, CSA). As Figure 3As shown in FIG. 1 , at the first verification time point (00:00) of the first time period 1, the first control sample aliquot CSA 1 is scheduled to be delivered to analyzer A (50), and at the second verification time point (04:00) of the first time period 1, the first control sample aliquot CSA 1 is scheduled to be delivered to analyzer B (52), and so on. As further shown, control sample aliquots CSA 2 to CSA 5 are stored in the storage device (46) during the first time period 1 because they are scheduled to be delivered to one or more of the five analyzers (50, 52, 82, 84, 86) only after the first time period 1. Control sample aliquot CSA 2 is scheduled to be delivered to analyzer B (52) at the first verification time point (00:00) of the second time period 2. Since the second verification time point of time period 2 is 00:00 the next day, control sample aliquot CSA 2 is returned from analyzer B (52) to the storage device (46) and then delivered to analyzer A (50) at the second verification time point of time period 2. Therefore, when the duration between two subsequent verification time points exceeds the defined time threshold, the control unit (54) controls the transport system (48) to transport the control sample aliquot CSA 2 to the storage device (46). According to the verification time point (66) of the third time period 3 of the verification schedule (58), the control sample aliquot CSA 3 is transported to one or more of the five analyzers (50, 52, 82, 84, 86) or to the storage device (46), according to the verification time point (66) of the fourth time period 4 of the verification schedule (58), the control sample aliquot CSA 4 is transported to one or more of the five analyzers (50, 52, 82, 84, 86) or to the storage device (46), and then according to the verification time point (66) of the fifth time period 5 of the verification schedule (58), the control sample aliquot CSA 5 is transported to one or more of the five analyzers (50, 52, 82, 84, 86) or to the storage device (46).

[0188] Figure 3 B shows the progression of control sample aliquots (42, CSA) and aliquot volumes (56) during each time period (62) of the validation schedule (58), as described above in Figure 3 As shown in A. In the example shown, the total number of control sample aliquots (42, CSA) used to validate the diagnostic test according to the validation schedule (58) is determined based on the number of time periods (64). And the aliquot volume (56) of the control sample aliquot (42, CSA) for one of the time periods (64) is determined based on the number of validation time points (66) in one of the time periods (64). Therefore, in order to validate the diagnostic test according to the validation schedule (58), the total number of control sample aliquots (42, CSA) used to validate the diagnostic test according to the validation schedule (58) is determined based on the number of validation time points (66) in one of the time periods (64). Figure 3The validation schedule (58) shown in Figure A requires five control sample aliquots (42, CSA) to validate the diagnostic test: control sample aliquot CSA 1 to control sample aliquot CSA 5. For time periods 1 and 4, four validation time points are defined, and the aliquot volume of control sample aliquot CSA 1 and the aliquot volume of control sample aliquot CSA 4 include the dead volume (60, DV) and the volume of four control samples (36, CS), each of which has the volume required to validate the diagnostic test once. For time periods 2 and 3, three validation time points are defined, and the aliquot volume of control sample aliquot CSA 2 and the aliquot volume of control sample aliquot CSA 3 include the dead volume (60, DV) and the volume of three control samples (36, CS), each of which has the volume required to validate the diagnostic test once. For the last time period 5, only one validation time point is defined, the aliquot volume of the control sample aliquot CSA 5 includes the dead volume (60, DV) and the volume of one control sample (36, CS) having the volume required for validating the diagnostic test once. Figure 3 As further shown in FIG. 4B , after each validation time point in a time period, the aliquot volume (56) of the corresponding delivered control sample aliquot (42, CSA) includes one less control sample (36, CS) because one control sample (36, CS) is aspirated by one of the five analyzers (50, 52, 82, 84, 86) for subsequent measurement of the control sample (36, CS). For example, the aliquot volume of control sample CSA 1 includes a dead volume (60, DV) and a volume including four control samples (36, CS), each having a volume required to validate the diagnostic test once before it is delivered to analyzer A (50) at the first validation time point (00:00) in time period 1. After the first validation time point (00:00) in time period 1, the aliquot volume of control sample CSA 1 includes a dead volume (60, DV) and a volume including three control samples (36, CS), each having a volume required to validate the diagnostic test once.

[0189] Figure 3 A and 3B also show that a container (62) containing a total control sample volume (44) is provided to the aliquoting device (40) before the first validation time point (00:00) of the first time period 1. The total control sample volume (44) is at least the sum of the aliquot volumes (56) of the five control sample aliquots CSA 1 to CSA 5, as indicated by the thick border.

[0190] Figure 4AAnother example of a validation schedule (58) is depicted. Only the first two time periods (64) of the validation schedule (58) are shown: Time Period 1 and Time Period 2. In the example shown, the validation schedule (58) defines a number of validation time points (66) for each of the five analyzers A through E (50, 52, 82, 84, 86) and the two illustrated time periods (64) at which a control sample aliquot (42, CSA) is scheduled to be delivered to one or more of the five analyzers (50, 52, 82, 84, 86) to validate the diagnostic test by measuring a control sample (36, CS) of the control sample aliquot (42, CSA). Figure 4AAs shown in FIG, for both analyzers A and B (50, 52), the same first verification time point (00:00) is defined in time period 1. Therefore, for time period 1 of the verification schedule (58), two control sample aliquots (42, CSA) are determined: control sample aliquots CSA 1 and CSA 2. Therefore, at the first verification time point (00:00) of the first time period 1, control sample aliquot CSA 1 is scheduled to be delivered to analyzer A (50) and control sample aliquot CSA 2 is scheduled to be delivered to analyzer B (52). Then, at the second verification time point (04:00) of the first time period 1, the first control sample aliquot CSA 1 is delivered to analyzer C (82). Since the third verification time point of time period 1 is 12:00, control sample aliquot CSA 2 is returned from analyzer B (52) to the storage device (46) and then delivered to analyzer D (84) at the third verification time point of time period 1. Control sample aliquots CSA 3, CSA 4, and CSA 5 are stored in the storage device (46) during the first time period 1 because they are scheduled to be delivered to one or more of the five analyzers (50, 52, 82, 84, 86) only during the second time period 2. In time period 2 of the validation schedule (58), the same first validation time point (16:00) is defined for the three analyzers A, B, and E (50, 52, 86), and the same second validation time (00:00) is defined for the two analyzers C and D (82, 84). Therefore, for time period 2 of the validation schedule (58), three control sample aliquots (42, CSA) are determined: control sample aliquot CSA 3 to control sample aliquot 5. Therefore, at the first verification time point (16:00) of the second time period 2, control sample aliquot CSA 3 is scheduled to be delivered to analyzer A (50), control sample aliquot CSA 4 is scheduled to be delivered to analyzer B (52), and control sample aliquot CSA 5 is scheduled to be delivered to analyzer E (86). Since the second verification time point of time period 2 is 00:00 on the next day, control sample aliquot CSA 3 and control sample aliquot CSA 4 are transported from analyzer A (50) and analyzer B (52) back to the storage device (46) and then delivered to analyzer C (82) and analyzer D (84) at the second verification time point (00:00) of time period 2.

[0191] Figure 4B The process of the required control sample aliquots (42, CSA) and aliquot volumes (56) during each of the indicated time periods (64) of the validation schedule (58) is shown, as described above in Figure 4AAs shown in . Based on the number of time periods (64) and the maximum number of five analyzers (50, 52, 82, 84, 86), a total number of control sample aliquots (42) for validating a diagnostic test according to a validation schedule (58) is determined, for which at least one identical validation time point (66) is defined for each time period (64). And based on the number of validation time points (66) for one of the time periods (64) and the maximum number of five analyzers (50, 52, 82, 84, 86), an aliquot volume (56) of a control sample aliquot (42, CSA) for one of the time periods (64) is determined, for which at least one identical validation time point (66) is defined for one of at least one time period (64). In the example shown, in order to validate the diagnostic test according to Figure 4A The validation schedule (58) shown in FIG. validates a diagnostic test, and two control sample aliquots (42, CSA) are determined for a first time period 1: control sample aliquot CSA 1 and control sample aliquot CSA 2, and three control sample aliquots (42, CSA) are determined for a second time period 2: control sample aliquot CSA 3 to control sample aliquot CSA 5. For time period 1, four validation time points are defined for five analyzers A through E (50, 52, 82, 84, 86), and two control sample aliquots are determined. The aliquot volume of control sample aliquot CSA 1 and the aliquot volume of control sample aliquot CSA 2 include a dead volume (60, DV) and a volume of two control samples (36, CS), each having a volume required for validating the diagnostic test once. For time period 2, five validation time points are defined for the five analyzers A through E (50, 52, 82, 84, 86), and three control sample aliquots are determined. The five control samples (36, CS) required for the five validation time points (66) are now distributed among the three control sample aliquots (42, CSA) such that the difference in aliquot volume (56) of control sample aliquots CSA 3, CSA 4, and CSA 5 is equal to or less than one volume of the control sample (36, CS). Thus, the aliquot volume (56) of control sample aliquot CSA 3 and the aliquot volume (56) of control sample aliquot CSA 4 include the dead volume (60, DV) and the volume of two control samples (36, CS), each of which has the volume required for validating the diagnostic test once. And the aliquot volume of control sample aliquot CSA 5 includes the dead volume (60, DV) and the volume of one control sample (36, CS), each of which has the volume required for validating the diagnostic test once. Figure 4BAs further shown, after each validation time point in a time period, the aliquot volume (56) of the corresponding delivered control sample aliquot (42, CSA) includes one less control sample (36, CS) because one control sample (36, CS) is aspirated by one of the five analyzers (50, 52, 82, 84, 86) for subsequent measurement of the control sample (36, CS).

[0192] Figure 5 Another example of a validation schedule (58) is depicted. The validation schedule (58) shown includes three validation cycles (65) of length 1 day: validation cycle 1 to validation cycle 3 (defined time periods (63) lasting three days). The validation schedule (58) defines a time sequence and a number of validation time points (66) for one validation cycle at which a control sample aliquot (42, CSA) is scheduled to be delivered to one or more of the five analyzers A to E (50, 52, 82, 84, 86) to validate the diagnostic test by measuring a control sample (36, CS) of the control sample aliquot (42, CSA). The validation cycle is then repeated three times during the defined time period (63) of the validation schedule (58). Figure 5As shown in FIG, during the first validation cycle 1 and the second validation cycle 2, the first control sample aliquot CSA1 is delivered to analyzer A (50) at each first validation time point (00:00), delivered to analyzer B (52) at each second validation time point (04:00), delivered to analyzer C (82) at each third validation time point (08:00), delivered to analyzer D (84) at each fourth validation time point (12:00), and delivered to analyzer E (86) at each fifth validation time point (16:00) of a validation cycle (65). Since the first validation time point (00:00) of the second validation cycle 2 is 8 hours after the fifth validation time point (16:00) of the first validation cycle 1, the control sample aliquot CSA1 is returned to the storage device (46) and then delivered to analyzer A (50) at the first validation time point of validation cycle 2. Thus, for the first validation cycle 1 and the second validation cycle 2, the same control sample aliquot CSA 1 is determined because the control sample aliquot stabilization time (68) is 2 days, which is twice the length of one validation cycle (65). During the first two validation cycles, the second control sample aliquot CSA 2 is stored in the storage device (46) because it is planned to be delivered to one or more of the five analyzers (50, 52, 82, 84, 86) only for the third validation cycle 3 after the first two validation cycles 1 and 2. In the example shown, the total number of control sample aliquots (42, CSA) is determined based on the defined time period (63), the validation time points of each validation cycle (66), and the control sample aliquot stabilization time (68). And the aliquot volume (56) of each control sample aliquot (42, CSA) is determined based on the number of validation time points (66) of each validation cycle (65) and the control sample aliquot stabilization time (68). Thus, to validate the diagnostic test according to the validation schedule (58) shown, two control sample aliquots (42, CSA) are required: control sample aliquot CSA 1 and control sample aliquot CSA 2. For validation cycles 1 and 2, ten validation time points (66) are defined, with the aliquot volume of control sample aliquot CSA 1 including the dead volume (60, DV) and the volume of ten control samples (36, CS), each of which has the volume required for validating the diagnostic test once (not shown). For validation cycle 3, five validation time points (66) are defined, with the aliquot volume of control sample aliquot CSA 2 including the dead volume (60, DV) and the volume of five control samples (36, CS), each of which has the volume required for validating the diagnostic test once (not shown).

[0193] Figure 6A and 6BOther examples of verification schedules (58, 59) are shown. Figure 6A , only the last three time periods (64) of the validation schedule (58) are shown: time period 6 to time period 8. The validation schedule (58) defines a plurality of validation time points (66) for each of the five analyzers A to E (50, 52, 82, 84, 86) and the three shown time periods 6 to 8, at which a control sample aliquot (42, CSA) is scheduled to be delivered to one or more of the five analyzers A to E (50, 52, 82, 84, 86) to validate the diagnostic test by measuring a control sample (35, CS) of the control sample aliquot (42, CSA). Figure 6A As shown in FIG, at the first verification time point (08:00) of time period 6, the control sample aliquot CSA 8 is transported to analyzer C (82) and then transported back to the storage device (46), and then further transported to analyzer B (52) at the second verification time point of time period 1. The laboratory system (38) includes another storage device (70) in addition to the storage device (46). In this laboratory system setting, the storage device (46) is configured to temporarily store the control sample aliquot (42, CSA). For example, the control sample aliquot (42, CSA) in the storage device (46) is kept at 4° C. and can therefore be quickly used for verification because no thawing time is required. The other storage device (70) is configured to store the control sample aliquot (42, CSA) for a long time. For example, the control sample aliquot (42, CSA) in the other storage device (70) can be stored at -20° C., so that the holding time in the laboratory system (38) can be longer than the onboard stabilization time of the control sample aliquot. For example, before the end of time period 6 of the validation schedule (58), the control sample aliquot CSA 9 is stored in another storage device (70) of the laboratory system (38), and for the first validation time point (00:00) of time period 7, the control sample aliquot CSA 9 is transported to analyzer A (50). After the control sample aliquot CSA 9 is first transported out of the another storage device (70), it is then transported back to the storage device (46) for temporary storage and then further transported to analyzer C (82) at the second validation time point (08:00) of time period 7. Thus, for each time period, another control sample aliquot (42, CSA) can be retrieved from the another storage device (70) and then transported between one or more of the five analyzers A to E (50, 52, 82, 84, 86) and the storage device (46) during one time period. Figure 6A The lower portion of the diagram indicates the progression of control sample aliquots (42, CSA) and aliquot volumes (56) during each time period (62) of the validation schedule (58).

[0194] During the operation of the analyzer, unexpected or unplanned events may occur, for which verification and validation results are required. For example, for analyzer D (84), the results need to be validated, and the control sample (36, CS) needs to be accidentally delivered to analyzer D (84) between the first validation time point (08:00) and the second validation time point (16:00) of time period 6, as shown in FIG. Figure 6A Although no verification time point was initially defined for analyzer D (84) between the first verification time point (08:00) and the second verification time point (16:00) of time period 6 in the verification schedule (58), no immediate operator intervention is required. In order to generate a verification result for analyzer D (84) after the unexpected event occurs, the control unit (54) defines a new verification time point (12:00) between the first verification time point (08:00) and the second verification time point (16:00) of time period 6. Then, as Figure 6A Indicated by the arrow in Figure 6B As further described in the specification, a control sample aliquot (42, CSA) or a series of control sample aliquots (42, CSA) that are to be delivered to one or more of the five analyzers (50, 52, 82, 84, 86) at a subsequent validation time point (66) are now delivered to one or more of the five analyzers (50, 52, 82, 84, 86) at least one validation time point in advance as originally defined in the validation time (58).

[0195] Figure 6B It is shown that after an unexpected or unplanned event occurs and the control unit (54) defines a new verification time point (12:00) between the first verification time point (08:00) and the second verification time point (16:00) of time period 6, Figure 6A Based on the updated version of the validation schedule (58), the control sample aliquot CSA 8 is now delivered to the analyzer D (84) at the new defined validation time point (12:00) instead of Figure 6A, as originally defined by the validation schedule (58), is delivered to the storage device (46). Subsequently, the control sample aliquot CSA 8 is delivered to the analyzer B (52) at the originally defined second validation time point (16:00) of time period 6. Then, another control sample aliquot CSA 9 is delivered from another storage device (70) to the analyzer E (86) at the originally defined third validation time point (20:00) of time period 6, and then to the analyzer A (50) at the first validation time point (00:00) of time period 7. Finally, another control sample aliquot CSA 11 is delivered from another storage device (70) to the analyzer C (82) at the second validation time point (08:00) of time period 7. Since the control sample aliquot CSA 11 is no longer available at the first validation time point (16:00) of time period 8 of the original validation schedule (58), as shown in FIG. Figure 6A ), so that the verification time point (16:00) of the original time period 8 is now defined as the first verification time point (16:00) of the first time period 1 of the next verification schedule (59). Therefore, one or more new containers (62) containing the total control sample volume (44) of the next verification schedule (59) must be provided before the end of the originally defined time period (63) of the original verification schedule (58). Therefore, for example, when an unexpected event or an unplanned event occurs, an alarm is displayed on the user interface (80) of the control unit (54), indicating that one or more new containers (62) containing the total control sample volume (44) of the next verification schedule (59) must be provided before the end of the originally defined time period (63). In addition, information about the one or more new containers (62) and the total control sample volume (44) of the next verification schedule (59) is displayed on the user interface (80) of the control unit (54). In the example shown in FIG. Figure 6B In the example shown in , the operator must provide one or more new containers (62) containing the total control sample volume (44) of the next validation schedule (59) before the first validation time point (16:00) of the first time period 1 of the next validation schedule (59). Therefore, the operator has sufficient time (24 hours after the occurrence of the unexpected event) to provide one or more new containers (62) containing the total control sample volume (44) and does not need to provide a control sample immediately when the unexpected or unplanned event occurs. Since the control sample (36, CS) of the control sample aliquot (42, CSA) determined for the subsequent validation time point can be used to validate the diagnostic test after the unexpected event, the risk of delayed test results or operational downtime can be further reduced. Figure 6BThe lower portion of FIG. 5 shows the progression of control sample aliquots (CSA, 42) and aliquot volumes (56) during each time period (62) of an updated version of a validation schedule (58) and a next validation schedule (59).

[0196] In the foregoing description, many specific details have been described to provide a comprehensive understanding of the present disclosure. However, it will be apparent to one of ordinary skill in the art that these specific details need not be employed to practice the present teachings. In other cases, well-known materials or methods have not been described in detail to avoid obscuring the present disclosure.

[0197] In particular, modifications and variations of the disclosed embodiments are certainly possible in light of the above description. It is therefore to be understood that within the scope of the appended claims, the present invention may be practiced otherwise than as specifically designed in the foregoing embodiments.

[0198] References throughout the foregoing specification to "one embodiment," "an embodiment," "an example," or "example" indicate that a particular feature, structure, or characteristic described in connection with the embodiment or example is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment," "in an embodiment," "an example," or "example" in various places throughout the specification are not necessarily all referring to the same embodiment or example.

[0199] Furthermore, the particular features, structures or characteristics may be combined in any suitable combinations and / or subcombinations in one or more embodiments or examples.

Claims

1. A method (10) for providing a control sample (36) for use in validating a diagnostic test within a laboratory system (38), wherein the laboratory system (38) comprises: an aliquoting device (40) configured to generate a control sample aliquot (42) from a total control sample volume (44); a storage device (46) configured to store a control sample aliquot (42); a delivery system (48) configured to deliver the control sample aliquot (42); at least two analyzers (50, 52) configured to perform the diagnostic test and validate the diagnostic test by measuring a control sample (36); and a control unit (54), wherein the aliquoting device (40), the storage device (46), and the at least two analyzers (50, 52) are operably connected to the delivery system (48), wherein the aliquoting device (40), the storage device (46), the delivery system (48), and the at least two analyzers (50, 52) are communicatively connected to the control unit (54), wherein the method comprises the following steps (12, 14, 16, 18): a) determining, by the control unit (54), a total number of control sample aliquots (42) and an aliquot volume (56) of each control sample aliquot (42) based on a validation schedule (58), wherein each aliquot volume (56) comprises a dead volume (60) and a volume comprising a determined number of control samples (36), each control sample having a volume required to validate the diagnostic test once, wherein the validation schedule (58) comprises a defined time period (63) and at least one time period (64), wherein the validation schedule (58) defines a number of validation time points (66) for each of the at least two analyzers (50, 52) and for each of the at least one time period (64), at which time points the control sample aliquots (42) are scheduled to be delivered to one or more of the at least two analyzers (50, 52) for validating the diagnostic test by measuring one control sample (36) of the control sample aliquots (42); b) providing one or more containers (62) containing the total control sample volume (44) to the aliquoting device (40), wherein the total control sample volume (44) is at least the sum of the aliquot volumes (56) of the total number of control sample aliquots (42) c) generating a determined total number of control sample aliquots (42) having a determined aliquot volume (56) by said aliquoting device (40) d) controlling the transport system (48) by the control unit (54) to transport at least one control sample aliquot (42) to the storage device (46) or one of the at least two analyzers (50, 52) according to the validation schedule (58) to validate the diagnostic test by measuring a control sample (36) of the at least one control sample aliquot (42).

2. The method of claim 1, wherein the time period (64) is a control sample onboard stabilization time (68) or a portion of the control sample onboard stabilization time.

3. The method according to claim 1, wherein in step a)(12), the total number of the control sample aliquots (42) is determined based on the number of the at least one time period (64) and the number of control sample aliquots (42) for each time period (64), wherein the aliquot volume (56) of the control sample aliquots (42) for one of the at least one time period (64) is determined based on the number of verification time points (66) for one of the at least one time period (64).

4. The method according to claim 3, wherein the number of control sample aliquots (42) for each time period (64) is further determined by the maximum number of the at least two analyzers (50, 52), for which at least one identical verification time point (66) is defined for each time period (64), and wherein the aliquot volume (56) of the control sample aliquot (42) for one of the at least one time period (64) is further determined by the maximum number of the at least two analyzers (50, 52), for which at least one identical verification time point (66) is defined for the one of the at least one time period (64).

5. A method according to claim 4, wherein the determined number of control samples (36) required for the certain number of verification time points (66) of one of the at least one time periods (64) are allocated to the determined number of control sample aliquots (42) of the one of the at least one time periods (64), so that the difference in the aliquot volumes (56) of each control sample aliquot (42) of the one of the at least one time periods (64) is equal to or less than one volume of the control sample (36).

6. The method according to claim 1, further comprising the following steps (20): e) controlling the transport system (48) by the control unit (54) to transport the at least one control sample aliquot (42) between the storage device (46) and the at least two analyzers (50, 52) according to the validation schedule (58) to validate the diagnostic test by measuring a control sample (36) of the at least one control sample aliquot (42).

7. The method according to any one of claims 1 to 6, wherein the laboratory system comprises a further storage device (70), wherein the further storage device (70) is operatively connected to the transport system (48) and communicatively connected to the control unit (54), wherein the storage device (46) is configured for temporary storage of a control sample aliquot (42), and the further storage device (70) is configured for long-term storage of a control sample aliquot (42), wherein step d) (18) of the method further comprises: - the transport system (48) is controlled by the control unit (54) to transport the at least one control sample aliquot (42) to the storage device (46) for temporary storage or to one of the at least two analyzers (50, 52) for validation of the diagnostic test by measuring one control sample (36) of the at least one control sample aliquot (42) and to transport the further control sample aliquot (42) to the further storage device (70) for long-term storage according to the validation schedule (58), and to transport the at least one control sample aliquot (42) and the further control sample aliquot (42) to the further storage device (70) for long-term storage before transporting the at least one control sample aliquot (42) to the storage device (46) for temporary storage or to one of the at least two analyzers (50, 52) for validation of the diagnostic test by measuring one control sample (36) of the at least one control sample aliquot (42) according to the validation schedule (58).

8. The method according to claim 7, wherein the method further comprises the following steps (22, 24): f) controlling the transport system (48) by the control unit (54) to transport at least one further control sample aliquot (42) from the further storage device (70) to the storage device (46) for temporary storage or to one of the at least two analyzers (50, 52) in accordance with the validation schedule (58) to validate the diagnostic test by measuring a control sample (36) of the at least one further control sample aliquot (42) g) controlling the transport system (48) by the control unit (54) to transport the at least one further control sample aliquot (42) between the storage device (46) for temporary storage and the at least two analyzers (50, 52) according to the validation schedule (58) to validate the diagnostic test by measuring a control sample (36) of the at least one further control sample aliquot (42).

9. The method according to any one of claims 1 to 6, wherein each generated control sample aliquot (42) comprises a unique control sample aliquot identification (72) associated with at least one control sample aliquot onboard stabilization time (68), wherein the laboratory system (38) further comprises a handling unit (74) operably connected to the transport system (48), wherein the storage device (46), the at least two analyzers (50, 52) and the transport system (48) have a defined temperature, wherein the storage device (46) and the at least two analyzers (50, 52) comprise a reading device (76) configured to read the unique control sample aliquot identification (72), wherein the method further comprises the following steps (26, 28, 30, 32, 34): h) reading the unique control sample aliquot identifier (72) by the reader (76) each time a control sample aliquot (42) arrives at or leaves the storage device (46) and one or more of the at least two analyzers (50, 52) i) generating a timestamp by a reader (76) when reading the unique control sample aliquot identifier (72) j) calculating, by the control unit (54), based on the generated timestamp, a duration for which the control sample aliquot (42) is kept at one or more defined temperatures, a duration for which the control sample aliquot (42) undergoes a certain number of temperature changes, or a duration for which the control sample aliquot (42) is delivered a certain number of times to one or more of the at least two analyzers (50, 52) k) comparing said calculated duration with said control unit (54) said control sample aliquot onboard stabilization time (68) 1) If the calculated time period exceeds the control sample aliquot onboard stabilization time (68), the control unit (54) controls the transport system (48) to transport the control sample aliquot (42) to the disposal unit (74).

10. A laboratory system (38) for providing a control sample (36) for validating a diagnostic test within the laboratory system (38), the laboratory system comprising: an aliquoting device (40) configured to generate a control sample aliquot (42) from a total control sample volume (44); a storage device (46) configured to store a control sample aliquot (42); a transport system (48) configured to transport the control sample aliquot (42); at least two analyzers (50, 52) configured to perform the diagnostic test and verify the diagnostic test by measuring a control sample (36); and a control unit (54), wherein the aliquoting device (40), the storage device (46) and the at least two analyzers (50, 52) are operably connected to the transport system (48), wherein the aliquoting device (40), the storage device (46), the transport system (48) and the at least two analyzers (50, 52) are communicatively connected to the control unit (54), wherein the laboratory system (38) is configured to perform the steps (12, 14, 16, 18, 20) of the method (10) according to any one of claims 1 to 6.

11. A laboratory system (38) according to claim 10, wherein the laboratory system (38) includes another storage device (70), wherein the another storage device (70) is operably connected to the transport system (48) and communicatively connected to the control unit (54), wherein the storage device (46) is configured for temporary storage of control sample aliquots (42), and the another storage device (70) is configured for long-term storage of control sample aliquots (42), wherein the laboratory system (38) is configured to perform the steps (12, 14, 16, 18, 20, 22, 24) of the method (10) according to any one of claims 1 to 8.

12. The laboratory system (38) of claim 10, wherein the laboratory system (38) further comprises a handling unit (74) operably connected to the transport system (48), wherein the storage device (46), the at least two analyzers (50, 52) and the transport system (48) have a defined temperature, wherein the storage device (46) and the at least two analyzers (50, 52) comprise a reading device (76) configured to read a unique control sample aliquot identification (72), wherein the laboratory system (38) is configured to perform the steps (12, 14, 16, 18, 20, 26, 28, 30, 32, 34) of the method (10) of claim 9.

13. A computer program product comprising instructions for causing a laboratory system (38) according to any one of claims 10 to 12 to perform the steps (12, 14, 16, 18, 20, 26, 28, 30, 32, 34) of the method (10) according to any one of claims 1 to 6 and claim 9.

14. A computer-readable storage medium (78) having stored thereon the computer program product of claim 13.

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