Correcting calibration data used by a diagnostic analyzer based on reagent storage conditions

Abstract

Calibration data initially provided with reagents in a diagnostic analyzer used to measure analytes in biological samples may need to be corrected based on reagent storage conditions, including average storage temperature and storage time. The average reagent storage temperature can be determined by measuring the pH and / or pO2 of the correction fluid provided with the reagent. The average reagent storage temperature, along with the determined storage time of the reagent, can be used to determine whether calibration data correction is needed, and if so, to correct it. Numerous other aspects are also provided.

Description

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 610,040, filed December 14, 2023, pursuant to 35 § 119(e) of the United States Code. The entire contents of the patent application cited above are therefore expressly incorporated herein by reference. Technical Field

[0002] This disclosure relates to calibration data used to calibrate diagnostic analyzers for measuring analytes in biological samples. Background Technology

[0003] Diagnostic analyzers can use one or more analyte / sample-specific sensors and / or one or more test reagents, which are mixtures of chemicals added to biological samples (e.g., blood, urine, interstitial fluid, cerebrospinal fluid, and the like) or non-biological buffered aqueous solutions to perform a “sample” (analytical test procedure) to determine the amount of analyte that may be present in the sample. A “calibration reagent” is a solution of a chemical / substance added with a specific target value. This solution can be used by the diagnostic analyzer as a reference to check the validity of measurements made by the analyzer and, if necessary, to adjust for maintaining high analytical performance. Calibration reagents may be provided with data indicating, for example, the quantity, concentration, or ratio of reagent components. However, the storage conditions of the reagents before their use in the diagnostic analyzer may affect those quantities, concentrations, or ratios, and thus affect the accuracy of the associated data and subsequent sample calibration. This, in turn, may adversely affect the analytical performance of the sample.

[0004] Therefore, there is a need for improved devices and methods for calibrating diagnostic analyzer samples. Summary of the Invention

[0005] In some embodiments, a method is provided for calibrating a sample in a diagnostic analyzer used to measure analytes in biological samples. The diagnostic analyzer includes a computer processor, and the method includes receiving a kit in the diagnostic analyzer, wherein the kit includes a temperature correction fluid, calibration data, and a manufacturing date. The method also includes determining, via the computer processor, a storage time of the kit based on the manufacturing date; and measuring the pH or pO2 (partial pressure of oxygen) of the temperature correction fluid via one or more analyte sensors of the diagnostic analyzer. The method further includes determining, via the computer processor, an average storage temperature of the kit based on the measured pH or pO2 relative to a corresponding pH or pO2 value of the temperature correction fluid included in the calibration data; and correcting the calibration data via the computer processor in response to the determined average storage temperature and the determined storage time indicating that calibration data needs to be corrected. The method also includes calibrating the diagnostic analyzer sample via the corrected calibration data via the computer processor.

[0006] In some embodiments, a diagnostic analyzer is provided for measuring analytes in biological samples. The diagnostic analyzer includes a computer processor, an analyte sensor for measuring analytes in biological or quality control samples, one or more other analyte sensors for measuring pH or pO2, a clock for indicating the current date, and a reservoir for receiving a kit. The kit includes a temperature correction fluid, calibration data, and a manufacturing date. The computer processor is programmed to receive the calibration data and manufacturing date when receiving the kit in the reservoir. The computer processor is also programmed to determine the storage time of the kit based on the manufacturing date and the current date provided by the clock, and to measure the pH or pO2 of the temperature correction fluid via one or more other analyte sensors. The computer processor is also programmed to determine an average storage temperature based on the measured pH or pO2 relative to the corresponding pH or pO2 value of the temperature correction fluid included in the calibration data. The computer processor further operates to correct the calibration data in response to a determined average storage temperature and a determined storage time indicating that calibration data needs to be corrected, and uses the corrected calibration data to calibrate the sample for measuring the analyte using the corrected calibration data in response to the calibration data being corrected.

[0007] Other aspects, features, and advantages of this disclosure may become apparent from the following detailed description and illustration of several exemplary embodiments and implementations (including the best mode for carrying out the invention). This disclosure is also capable of other and different embodiments, and several details thereof may be modified according to various aspects without departing from the scope of the invention. For example, although one embodiment described herein is relative to calibrating a sample for measuring creatinine and / or creatine in a biological sample, this disclosure can be readily applied to calibrating samples for measuring other analytes (such as, for example, pCO2 and glucose) in a biological sample. The determination of the average storage temperature disclosed herein can be used to indicate that the kit has been exposed to temperatures outside a specific range. Advantageously, this can prevent the use of kits that may be damaged due to exposure to such temperatures. Furthermore, this can prevent the reporting of potentially incorrect patient test results due to calibration data no longer being valid. This disclosure is intended to cover all modifications, equivalents, and alternatives falling within the scope of the appended claims below. Attached Figure Description

[0008] The accompanying drawings described below are for illustrative purposes and are not necessarily drawn to scale. Therefore, the drawings and description are to be considered illustrative in nature and not restrictive. The drawings are not intended to limit the scope of the invention in any way.

[0009] Figure 1A schematic diagram of a diagnostic analyzer according to an embodiment provided herein is illustrated.

[0010] Figure 2A The figure illustrates the pH stability of a temperature-corrected fluid stored at 25°C relative to storage time, according to the embodiments provided herein.

[0011] Figure 2B The figure illustrates the pO2 stability of a temperature-corrected fluid stored at 25°C relative to storage time, according to an embodiment provided herein.

[0012] Figure 3 The illustration shows a graph of predicted creatine concentration relative to storage time in a calibration solution containing creatine but without creatine anhydride at the time of manufacture, according to the embodiments provided herein, at six average storage temperatures.

[0013] Figure 4 The illustration shows a graph of the predicted creatine concentration and the experimentally determined creatine concentration relative to storage time in a calibration solution containing creatine but without creatine anhydride at 25°C, according to the embodiments provided herein.

[0014] Figure 5 The illustration shows a graph of the predicted creatinine concentration and the experimentally determined creatinine concentration relative to storage time in a calibration solution containing creatine but without creatinine at the time of manufacture, according to the embodiments provided herein, at 25°C.

[0015] Figure 6 The illustration shows a flowchart of a method for calibrating a diagnostic analyzer sample for measuring analytes in biological samples, according to an embodiment provided herein. Detailed Implementation

[0016] Diagnostic analyzer sample operation is used to measure the amount of an analyte (e.g., creatinine, glucose, serum albumin, oxygen, pH, sodium, potassium, etc.) that may be present in a biological sample (e.g., whole blood, serum, plasma, urine, interstitial fluid, pleural fluid, cerebrospinal fluid, and the like). To perform accurate analyte measurements, the diagnostic analyzer sample can be calibrated using calibration reagents and associated calibration data, packaged together with one or more test reagents in a kit or reagent pack (hereinafter referred to as a "kit"). The kit is configured to be received in the diagnostic analyzer. The calibration reagent is a solution comprising chemicals / substances added to a matrix (i.e., all components of the solution except the analyte of interest) at a specific target value (e.g., level, quantity, ratio, or concentration) that provides a reference for the diagnostic analyzer. An analyte sensor (or similar measuring device) in contact with the calibration reagent generates an electrical signal that is measured (e.g., in mV or nA) and converted into the amount of the analyte. In some embodiments, two or more calibration reagents with known (different) concentrations can be used. The values ​​of the two or more electrical signals generated therefrom are used to create a calibration curve, against which sensor measurements can be made. Subsequently, when the analyte sensor measures an analyte in a quality control sample or biological sample, the resulting electrical signals can be compared with the reference values ​​of the calibration reagents (forming a calibration curve) to determine the amount of analyte that may be present in the quality control sample or biological sample.

[0017] Calibration data can be stored in an electronic device (e.g., a radio frequency identification (RFID) tag) provided using the kit. Alternatively, calibration data can be encoded in a barcode affixed to the kit. Calibration data may include, for example, one or more reference values ​​(e.g., levels, quantities, ratios, or concentrations) of one or more analytes to be measured and / or other chemicals / substances in one or more calibration reagents known at the time of manufacture. Upon receiving the kit in a diagnostic analyzer, the calibration reagents and calibration data can be used to calibrate the diagnostic analyzer.

[0018] However, storage conditions prior to use, such as, for example, the length of time from manufacturing to installation in the diagnostic analyzer and / or the average temperature of the kit while it is in storage, may cause changes in one or more of the known component values ​​in the calibration reagent. This can adversely affect the accuracy of calibration, and therefore adversely affect the measurement accuracy of the diagnostic analyzer.

[0019] According to one or more embodiments provided herein, a diagnostic analyzer can overcome the disadvantages described above caused by reagent storage conditions by determining whether known component values ​​in calibration data need to be corrected, and, if so, by correcting those values. According to the embodiments described herein, the determination of whether known component values ​​in calibration data need to be corrected can be achieved by providing a temperature correction fluid in the kit and including in the calibration data the pH and / or pO2 (oxygen partial pressure) values ​​initially measured in the temperature correction fluid at the time of manufacture. The pH and / or pO2 of the temperature correction fluid undergo predictable changes relative to its initial manufacturing values ​​in response to temperature changes over time. Also included in the calibration data is the manufacturing date of the kit (indicating or representing the manufacturing dates of the reagent and the temperature correction fluid). The change in the pH and / or pO2 values ​​in the temperature correction fluid from the time of manufacture to the time the kit is installed in the diagnostic analyzer is used to determine (estimate) the average storage temperature of the kit from the time of manufacture to the time of installation (also known as the bulk kinetic temperature). Then, the average storage temperature and storage time (measured from the manufacturing date to the kit installation date) are used to determine whether calibration data correction is needed, and if so, the calibration data are corrected based on a software model determined experimentally on how the average storage temperature and storage time affect the relevant reagent calibration data.

[0020] More specifically, in some embodiments, upon receiving the kit in the diagnostic analyzer and / or just before use, the diagnostic analyzer can determine the storage time of the kit and measure the pH and / or pO2 in the temperature correction fluid. The difference between the measured pH and / or pO2, based on the known pH and / or pO2 values ​​of the temperature correction fluid relative to the manufacturing time indicated in the calibration data, can be input along with the storage time into a first software model to determine (e.g., estimate / predict) the average storage temperature at which the kit is stored. Although measuring only one of pH or pO2 can be used to determine the average storage temperature, measuring both pH and pO2 can increase the confidence of the determined average storage temperature. Furthermore, it would be advantageous to use pH and / or pO2 to correct calibration data for pCO2 and glucose, in addition to creatinine.

[0021] Based on the determined average storage temperature and storage time of the kit, the current level / ratio / percentage of reagent components in the calibration reagent (or other solutions included in the kit) can be mathematically and / or experimentally determined via a second software model and compared with their originally assigned values ​​included in the calibration data provided using the kit. A difference exceeding, for example, 0.1-1%, 1-2%, 3-5%, 6-8%, or 9-10% between the originally provided and mathematically and / or experimentally determined reagent component values ​​may indicate the need for calibration data correction. The original calibration data can then be updated (i.e., replaced) using the new reagent component values ​​determined mathematically and / or experimentally, and stored in the non-volatile memory of the kit's electronics (e.g., RFID tags) and / or the diagnostic analyzer.

[0022] The sample can then be calibrated (or recalibrated) using the corrected or updated calibration data. This calibration procedure can be repeated periodically while the kit remains installed in the diagnostic analyzer to maintain accurate analyte measurements. If a temperature sensor is available in the diagnostic analyzer, it can provide temperature input while the kit is installed.

[0023] Advantages of the apparatus and method for calibrating analyte sensors according to the embodiments described herein include maintaining high analyte measurement accuracy by correcting calibration data that may be adversely affected by reagent storage conditions. Other advantages include indicating that reagent kits have been stored outside their specified range (e.g., 2°C–25°C), extending the shelf life and service life of reagents used by diagnostic analyzers, and / or extending the temperature range in which reagents can be transported and stored.

[0024] According to one or more embodiments, it will be combined below Figure 1-6 A more detailed explanation of how to operate a diagnostic analyzer to correct calibration data based on reagent storage conditions.

[0025] Figure 1 The illustration depicts a diagnostic analyzer 100, operating according to one or more embodiments, for measuring one or more analytes that may be present in a biological sample. The diagnostic analyzer 100 may include a controller 102, a sensor array 104, and a reagent reservoir 106. The diagnostic analyzer 100 may include other components (not shown). In some embodiments, the diagnostic analyzer 100 may be coupled to an automated track 108 for receiving and returning a sample container 110 carried by a sample carrier 112. In some embodiments, the diagnostic analyzer 100 may include a waste container for disposing of the sample container 110 after testing. Each sample container 110 may contain a biological sample to be tested at the diagnostic analyzer 100 for the presence and quantity of one or more analytes (e.g., creatinine and / or creatine).

[0026] Controller 102 may include a computer processor 102P, non-transitory memory 102M, and a clock 102C. Clock 102C may operate to indicate the current date and time of day and may be any suitable system or real-time clock. Non-transitory memory 102M may include programming instructions 102PI (e.g., software models, programs, algorithms, and the like) executable by computer processor 102P. Programming instructions 102PI may be additionally or alternatively stored in another non-transitory computer-readable medium. Non-transitory memory 102M may also include data / information accessible by computer processor 102P. Although non-transitory memory 102M is shown as being internal to controller 102, all or part of non-transitory memory 102M may be external to and / or remote from controller 102.

[0027] The controller 102 may include a user interface (not shown), which may include a display that enables the user to access various control and status display screens, and to input commands and / or data related to the operation of the diagnostic analyzer 100 into the controller 102. The controller 102 may alternatively or additionally include other processing devices / circuits (including microprocessors, A / D converters, amplifiers, filters, etc.), other storage devices, transceivers, interfaces, device drivers, and / or other electronic devices.

[0028] The controller 102 can communicate with the system controller (not shown) of an automated diagnostic analysis system (also not shown), which may include multiple automated or semi-automated diagnostic analyzers of the same and / or different types, as well as one or more input / output modules, centrifuges, quality inspection modules, cap removers, suction / dispensing modules, heaters, storage and / or refrigeration modules and / or other components.

[0029] In some embodiments, controller 102 may communicate with other computers, other system controllers, or other devices, such as automated diagnostic analysis systems, laboratory information systems, medical facilities, etc. This communication may occur directly via wired and / or wireless connections or via a network, for transmitting analytical measurement results and / or for receiving information related to biological samples, including one or more of, for example, patient information, the time and date the sample was acquired, medical facility information, tracking and routing information, and / or any other information related to the biological sample to be analyzed. The network may be, for example, a local area network (LAN), a wide area network (WAN), or other suitable communication network, including wired and wireless networks. In some embodiments, controller 102 may be part of an automated diagnostic analysis system, laboratory information system, medical facility, etc.

[0030] The controller 102, via a computer processor 102P that executes programming instructions 102PI and optionally accesses data stored in non-temporary memory 102M, can be considered a dedicated machine particularly suitable for controlling the overall operation of the diagnostic analyzer 100, thus becoming an automated or semi-automated diagnostic analyzer 100. Specifically, via the computer processor 102P executing program instructions 102PI, the controller 102 operates to automatically calibrate the sensors of the diagnostic analyzer 100, among other things, as described in more detail below.

[0031] Sensor array 104 may include a plurality of sensors that operate to measure one or more analytes and / or other quantities via electrical signals. In some embodiments, sensor array 104 may include sensors for measuring creatinine and / or creatine, sensors for measuring pH, and / or sensors for measuring pO2. Other types of sensors may be additionally or alternatively included. In some embodiments, sensor array 104 may be an alternative unit or cartridge (similar to kit 114) receivable in a sensor array reservoir (not shown) in diagnostic analyzer 100. In these embodiments, the sensor array cartridge may include its own electronics (e.g., a radio frequency identification (RFID) tag) for storing calibrated sensor calibration data.

[0032] Reagent reservoir 106 is configured to receive reagent kit 114 therein. Reagent kit 114 may include electronic device 114D, which operates to store data therein. Specifically, electronic device 114D may have calibration data (e.g., reagent values) stored therein. In some embodiments, electronic device 114D may be or include, for example, a radio frequency identification (RFID) tag. Electronic device 114D may be or include other types of data storage circuitry and / or devices. In other embodiments, sensor calibration data may be encoded in a barcode (not shown), which is affixed to reagent kit 114. When reagent kit 114 is received in reagent reservoir 106, the barcode may be read by a barcode reader (not shown) of diagnostic analyzer 100. When reagent kit 114 is received in reagent reservoir 106, computer processor 102P may communicate wirelessly with reagent kit 114 (and more particularly, with electronic device 114D). Alternatively, the reagent reservoir 106 may have electrical / electronic connectors / contacts for communicatively coupling the computer processor 102P to the electronics 114D of the reagent 114 via corresponding electrical / electronic connectors / contacts.

[0033] In some embodiments, the diagnostic analyzer 100 can be configured and operated to measure creatinine and / or creatine in a biological sample. For this purpose, the diagnostic analyzer 100 can use three enzymes (e.g., creatinine oxidase, creatine enzyme, and sarcosine oxidase) to convert the creatinine analyte into a quantifiable electrical signal. In the electrode design of the creatinine sensor, the active electrode operates to consume creatinine containing all three enzymes, while the inactive electrode operates to consume creatine containing only two of these enzymes (creatine enzyme and sarcosine oxidase).

[0034] The kit 114 of an embodiment of the diagnostic analyzer 100, configured and operated for measuring creatinine and / or creatine, may include three calibration solutions: a first calibration solution containing a first reagent of creatinine and creatine in a first ratio; a second calibration solution containing creatine and no creatinine at the time of manufacture; and a third calibration solution containing neither creatinine nor creatine (i.e., no analyte zero point). When these three calibration solutions are used together, the effect of creatine can be effectively calibrated, enabling the measurement system to be selective for creatinine to determine the amount of creatinine present in quality control samples or biological samples.

[0035] However, it should be noted that creatinine and creatine in solution are known to reversibly interconvert at a creatinine to creatine ratio (interconversion) based on the pH and temperature of the solution in which they are dissolved. This interconversion of creatinine and creatine may render the quantification of creatine in a second calibration solution, determined at manufacturing time and provided in the kit's calibration data, unreliable. Accurate values ​​of creatinine and creatine are required to calibrate a creatinine sensor with adequate analytical performance. Without calibration, such interconversion may reduce the shelf life of such calibration reagents and / or may limit the temperature range in which such reagents can be stored.

[0036] According to the embodiments described herein, the first calibration solution may contain a stable ratio of creatinine to creatine, and the second calibration solution may contain an unstable ratio of creatinine to creatine that may result in interconversion of creatinine and creatine based on the pH and temperature of the second calibration solution (or vice versa). That is, at a fixed temperature, creatine and creatinine will interconvert until equilibrium is reached. As the solution gets closer to equilibrium, the rate of interconversion will slow down. During manufacturing, the levels (e.g., amounts, ratios, concentrations, etc.) of creatinine and creatine in each of the first and second calibration solutions are encoded in the electronics 114D of the kit 114.

[0037] According to the embodiments described herein, by determining the average storage temperature and storage time of kit 114, possible changes in the levels of creatinine and creatine in an unstable second calibration solution during sensor calibration can be estimated / predicted. Note that, according to the embodiments described herein, the creatine and / or creatinine sensors, and the calibration solutions associated with creatine and creatinine, are independent of the estimation of the average storage temperature of the kit. Direct measurement of the levels of creatinine and / or creatine in the calibration solution is not used to estimate the average storage temperature of the kit. Using pH and / or pO2 sensors and pH and / or pO2 measurements from a temperature correction fluid allows the creatinine sensor and the calibration solution being calibrated to be independent.

[0038] The average storage temperature can be determined based on the measurement and change of pH and / or pO2 in the temperature correction fluid also provided using kit 114. The temperature correction fluid is preferably a solution separated from the first and second creatinine / creatine calibration solutions and the third creatinine / creatine-free calibration solution, or a calibration solution otherwise independent of the analyte being calibrated. The temperature correction fluid experiences the same temperature over the same time period as the calibration reagents, as they are contained within the same kit. Based on the change in pH and / or pO2 in the temperature correction fluid, the average storage temperature can be determined and then applied to the first and second calibration solutions, which are calibrators for creatinine. Electronic device 114D can encode the values ​​of pH and pO2 measured in the temperature correction fluid also provided using kit 114. The temperature correction fluid is designed to have predictable changes in pH and pO2 over time and temperature.

[0039] In some embodiments, the calibration reagent and temperature correction fluid are buffered aqueous solutions with target values, which may include sodium, potassium, ionized calcium, chloride, ionized magnesium, glucose, lactate, and urea, quantified using a gas mixture comprising oxygen and carbon dioxide. To achieve and maintain the target values ​​for oxygen and carbon dioxide, the reagents are filled in a flexible laminated bag, which is heat-sealed with zero headspace. The flexible laminated bag containing the calibration reagent and temperature correction fluid with zero headspace is then added to the kit. The flexible laminated bag may then include access points (attached fittings) for connection to the kit, and then to a diagnostic analyzer. The kit is a consumable that supports the diagnostic analyzer. The kit may also include a sensor, or the sensor may be a separate consumable, such as a sensor cartridge. The temperature correction fluid may be used for purposes other than shelf-life calibration, such as, for example, as a quality control solution.

[0040] Subsequent comparisons of the pH and / or pO2 measured in the temperature-corrected fluid at the manufacturing time with the corresponding values ​​of pH and / or pO2 measured in the temperature-corrected fluid at the sensor calibration time (e.g., the time when the kit is installed in the diagnostic analyzer or periodically thereafter) can be used to mathematically and / or experimentally determine the average storage temperature (also known as the bulk kinetic temperature) of the kit 114 via a software model. Figure 2A The figure illustrates the decrease in pH in a temperature-corrected fluid maintained at 25°C for a period of time (e.g., 32 weeks), where line 202 represents actual pH data and line 204 represents modeled pH data. Figure 2B The figure illustrates the decrease in pO2 in a temperature-corrected fluid maintained at 25°C for a period of time (e.g., 32 weeks), where line 206 represents the actual pO2 data and line 208 represents the modeled pO2 data.

[0041] If using both pH and pO2, use a weighted average (if they are consistent within, for example, 10%). Confirm successful shelf-life calibration through further evaluation via quality control reagents. If the quality control evaluation determines the results are outside acceptable limits, recalibrating the sensor and repeating the shelf-life calibration process would be appropriate. Further failure to meet acceptable limits may indicate a quality problem with the overall system.

[0042] In addition to determining the average storage temperature, the manufacturing date provided in electronic device 114D and the time when kit 114 was installed in diagnostic analyzer 100 can be determined by clock 102C. Figure 1 The current date provided is used by computer processor 102P to calculate the storage time of kit 114.

[0043] Average storage temperature and storage time can be used as input to a mathematically and / or experimentally determined software model to estimate / predict and, if necessary, correct for the unstable creatinine and creatine levels in the second calibration solution described above. The software model can be executed by a computer processor 102P, can be stored in non-transitory memory 102M, and can be a programming instruction set 102PI (…). Figure 1 Part of ).

[0044] The software model can be based on the following equation: in: [A] is the molar concentration of creatinine at a given time, expressed in nM. [A]0 is the initial molar concentration of creatinine in nM; k1 is the sky -1 (day) -1The kinetic constant for the conversion of creatine to creatine, expressed in units of 1 / 2 kilohydrate. k2 is the sky -1 The kinetic constant for the conversion of creatine to creatine, expressed in units of creatine; and t is a unit of time called days.

[0045] Note that k1 and k2 are affected by the average storage temperature and were determined through modeling experiments.

[0046] Figure 3 Figure 300 illustrates a second calibration solution (containing creatine but without creatinine at manufacturing time), and shows the estimated / predicted output of a software model of creatine concentration (in mM) over a 300-day storage period at six average storage temperatures according to one or more embodiments. Creatine concentration curve 304 represents the estimated / predicted creatine concentration at an average storage temperature of 4°C. Creatine concentration curve 320 represents the estimated / predicted creatine concentration at an average storage temperature of 20°C. Creatine concentration curve 325 represents the estimated / predicted creatine concentration at an average storage temperature of 25°C. Creatine concentration curve 330 represents the estimated / predicted creatine concentration at an average storage temperature of 30°C. Creatine concentration curve 332 represents the estimated / predicted creatine concentration at an average storage temperature of 32°C. And creatine concentration curve 337 represents the estimated / predicted creatine concentration at an average storage temperature of 37°C. Figure 4 Figure 400 illustrates a second calibration solution (containing creatine but without creatinine at manufacturing time) and shows a comparison of the estimated / predicted creatine concentration and the experimentally determined creatine concentration at 25°C relative to a 100-day storage time, according to one or more embodiments. As shown, the estimated / predicted creatine concentration closely tracks the experimentally determined creatine concentration, thus establishing the effectiveness of the software model.

[0047] Figure 5 Figure 500, also representing a second calibration solution (containing creatine and without creatinine at manufacturing time), illustrates a comparison of estimated / predicted creatinine concentrations and experimentally determined creatinine concentrations at 25°C relative to an 80-day storage time, according to one or more embodiments. As shown, creatinine increases over time (because creatine in the solution decreases over time - see...). Figure 4 As shown, the estimated / predicted creatinine concentration closely tracks the experimentally determined creatinine concentration, thus reinforcing the effectiveness of the software model.

[0048] Figure 6The illustration depicts a method 600 for calibrating a diagnostic analyzer sample for measuring analytes in biological samples, according to one or more embodiments, wherein the diagnostic analyzer includes a computer processor. At process block 602, method 600 may include receiving a kit in the diagnostic analyzer, the kit including temperature correction fluid, calibration data, and a manufacturing date. For example, refer to... Figure 1 The kit 114 can be received in the diagnostic analyzer 100 at the kit reservoir 106. The kit 114 may include an electronic device 114D in which calibration data, such as, for example, the pH and pO2 values ​​of the temperature-corrected fluid included with the kit, can be stored. The electronic device 114D may also store the manufacturing date of the kit 114.

[0049] At process block 604, method 600 may include determining the storage time of the reagent kit based on the manufacturing date via a computer processor. For example, when reagent kit 114 is installed in diagnostic analyzer 100, computer processor 102P may receive the manufacturing date from electronic device 114D and the installation date of reagent kit 114 from clock 102C. Computer processor 102P may then determine the number of days (storage time) between the manufacturing date and the installation date.

[0050] At process block 606, method 600 may include measuring the pH and / or pO2 of a temperature-corrected fluid included in the kit via one or more analyte sensors of a diagnostic analyzer.

[0051] At process block 608, method 600 may include determining the average storage temperature of the kit via a computer processor, based on measured pH and / or pO2 values ​​relative to corresponding pH and / or pO2 values ​​included in calibration data. For example, a first software model executing on computer processor 102P may determine the average storage temperature of the kit based on changes in measured pH and / or pO2 values ​​and a determined storage time. The first software model may be stored in non-transitory memory 102M.

[0052] Method 600 may include, at process block 610, correcting calibration data via a computer processor in response to a determined average storage temperature and a determined storage time indicating that calibration data correction is required. For example, the determined average storage temperature and determined storage time may be input to a second software model executed on computer processor 102P. The second software model, which may be stored in non-transitory memory 102M, determines how the average storage temperature and storage time affect the reagent calibration data, and if the reagent calibration data has changed by more than a predetermined amount or percentage, computer processor 102P may correct the reagent calibration data.

[0053] Furthermore, method 600 may be included at process block 612 to calibrate the analyte sensor using corrected calibration data.

[0054] While this disclosure allows for various modifications and alternatives, specific methods and apparatus embodiments have been shown by way of example in the accompanying drawings and described in detail herein. However, it should be understood that the specific methods and apparatus disclosed herein are not intended to limit this disclosure or the following claims.

[0055] Individuals with male or female gender identity are included in the term, independent of the use of grammatical terms.

[0056] Illustrative Examples The following is a non-limiting list of illustrative embodiments of this disclosure: Example 1: A method for calibrating a sample in a diagnostic analyzer used to measure analytes in biological samples, the diagnostic analyzer including a computer processor, the method comprising: The diagnostic analyzer receives a kit, which includes a temperature correction fluid, calibration data, and a manufacturing date. The storage time of the reagent kit is determined based on the manufacturing date via the computer processor; The pH or pO2 of the temperature-corrected fluid is measured via one or more analyte sensors of the diagnostic analyzer. The average storage temperature of the kit is determined via the computer processor based on a measured pH or pO2 relative to the corresponding pH or pO2 value of the temperature correction fluid included in the calibration data. In response to an indication that the calibration data needs to be corrected based on a determined average storage temperature and a determined storage time, the calibration data is corrected via the computer processor; and The diagnostic analyzer sample is calibrated using corrected calibration data via the computer processor.

[0057] Example 2: The method described in Example 1, wherein: The measurements also include measuring the pH and pO2 of the temperature-corrected fluid via one or more analyte sensors of the diagnostic analyzer; and Determining the average storage temperature via the computer processor also includes determining the average storage temperature of the kit based on measured pH and pO2 relative to the corresponding pH and pO2 values ​​of the temperature-corrected fluid included in the calibration data via the computer processor.

[0058] Example 3: The method according to any one of the foregoing example embodiments, wherein determining the average storage temperature of the kit via the computer processor includes determining the difference between the measured pH or pO2 and the corresponding pH or pO2 value of the temperature correction fluid included in the calibration data, and providing the difference to a software model operated for determining the average storage temperature, the software model being executed by the computer processor.

[0059] Example 4: The method according to any one of the foregoing example embodiments further includes experimentally determining the pH change of the temperature correction fluid over a temperature and time period before determining the average storage temperature via the computer processor.

[0060] Example 5: The method according to any one of the foregoing example embodiments further includes experimentally determining the change of pO2 of the temperature correction fluid over a temperature and time period before determining the average storage temperature via the computer processor.

[0061] Example 6: The method according to any one of the foregoing example embodiments, wherein the kit includes an electronic device for storing the calibration data and the manufacturing date, and the method further includes receiving the calibration data and the manufacturing date stored in the electronic device via the computer processor in response to receiving the kit in the diagnostic analyzer.

[0062] Example 7: The method according to any one of the foregoing example embodiments, wherein the electronic device includes a radio frequency identification (RFID) tag.

[0063] Exemplary Example 8: The method according to any one of the foregoing exemplary embodiments, wherein determining the storage time of the reagent kit via the computer processor includes: The manufacturing date is received from the kit via the computer processor; and The computer processor determines the difference in days between the manufacturing date and the date the kit was received in the diagnostic analyzer, as indicated by the clock of the diagnostic analyzer.

[0064] Example Example 9: The method according to any one of the foregoing example examples, wherein the kit comprises a multianalyte reagent.

[0065] Example 10: The method according to any one of the foregoing example embodiments, wherein: The calibration data includes the levels of creatinine and creatine in each of the two calibration reagents included in the kit, based on the manufacturing date. The determined average storage temperature and the determined storage time were used to determine the current levels of creatinine and creatine in the two calibration reagents; and If the determined current levels of creatinine and creatine differ from the levels of creatinine and creatine based on the manufacturing date, the computer processor stores the determined current levels of creatinine and creatine in the calibration data of the kit.

[0066] Example 11: The method according to any one of the foregoing example embodiments, wherein the diagnostic analyzer includes an analyte sensor that is operated to measure the amount of creatinine or creatine present in the biological sample.

[0067] Example 12: The method according to any one of the foregoing example embodiments, wherein the biological sample includes whole blood, serum, plasma, urine, interstitial fluid, pleural fluid, or cerebrospinal fluid.

[0068] Example 13: A diagnostic analyzer for measuring analytes in biological samples, comprising: Computer processor; An analyte sensor, which operates to measure analytes in the biological sample or quality control sample; Operate a reservoir for receiving a reagent kit, the reagent kit including temperature correction fluid, calibration data, and manufacturing date; One or more other analyte sensors, operated for measuring pH or pO2; and A clock, used to indicate the current date; where: The computer processor is operated via programmed instructions for: When the kit is received in the reservoir, the calibration data and the manufacturing date are received; The storage time of the reagent kit is determined based on the manufacturing date and the current date provided by the clock; The pH or pO2 of the temperature-corrected fluid is measured via one or more other analyte sensors; The average storage temperature is determined based on the measured pH or pO2 relative to the corresponding pH or pO2 value of the temperature correction fluid included in the calibration data. In response to an indication that the calibration data needs to be corrected based on a determined average storage temperature and a determined storage time, the calibration data is corrected; and In response to the calibration data being corrected, the corrected calibration data is used to calibrate the sample of the diagnostic analyzer used to measure the analyte.

[0069] Example 14: The diagnostic analyzer according to Example 13, wherein the computer processor is further operated via programming instructions for: The pH and pO2 of the temperature-corrected fluid are measured via one or more other analyte sensors; and The average storage temperature is determined based on the measured pH and pO2 values ​​relative to the corresponding pH and pO2 values ​​of the temperature-corrected fluid included in the calibration data.

[0070] Example 15: The diagnostic analyzer according to Example 13 or 14 further includes the reagent kit received in the reservoir.

[0071] Example 16: A diagnostic analyzer according to any one of Example Examples 13-15, wherein the temperature correction fluid includes predictable changes in pH over a temperature and time period.

[0072] Example 17: A diagnostic analyzer according to any one of Example Examples 13-16, wherein the temperature correction fluid includes predictable changes in pO2 over a temperature and time period.

[0073] Example 18: A diagnostic analyzer according to any one of Example Examples 13-17, wherein the kit further comprises one or more test reagents and one or more calibration reagents.

[0074] Example Example 19: A diagnostic analyzer according to any one of Example Examples 13-18, wherein the calibration data and the manufacturing date are stored in an electronic device included with the kit, or encoded in a barcode included with the kit.

[0075] Example 20: A diagnostic analyzer according to any one of Example Examples 13-19, wherein the computer processor is further operated via programming instructions to store calibrated calibration data in the electronic device.

Claims

1. A method for calibrating a sample in a diagnostic analyzer used to measure analytes in biological samples, the diagnostic analyzer including a computer processor, the method comprising: The diagnostic analyzer receives a kit, which includes a temperature correction fluid, calibration data, and a manufacturing date. The storage time of the reagent kit is determined based on the manufacturing date via the computer processor; The pH or pO2 of the temperature-corrected fluid is measured via one or more analyte sensors of the diagnostic analyzer. The average storage temperature of the kit is determined via the computer processor based on a measured pH or pO2 relative to the corresponding pH or pO2 value of the temperature correction fluid included in the calibration data. In response to an indication that the calibration data needs to be corrected based on a determined average storage temperature and a determined storage time, the calibration data is corrected via the computer processor; and The diagnostic analyzer sample is calibrated using corrected calibration data via the computer processor.

2. The method according to claim 1, wherein: The measurements also include measuring the pH and pO2 of the temperature-corrected fluid via one or more analyte sensors of the diagnostic analyzer; and Determining the average storage temperature via the computer processor also includes determining the average storage temperature of the kit based on measured pH and pO2 relative to the corresponding pH and pO2 values ​​of the temperature-corrected fluid included in the calibration data via the computer processor.

3. The method of claim 1, wherein determining the average storage temperature of the kit via the computer processor comprises determining the difference between the measured pH or pO2 and the corresponding pH or pO2 value of the temperature correction fluid included in the calibration data, and providing the difference to a software model operated for determining the average storage temperature, the software model being executed by the computer processor.

4. The method of claim 1, further comprising, experimentally determining the pH change of the temperature correction fluid over a temperature and time period before determining the average storage temperature via the computer processor.

5. The method of claim 1, further comprising, before determining the average storage temperature via the computer processor, experimentally determining the change in pO2 of the temperature correction fluid over a temperature and time period.

6. The method of claim 1, wherein the kit includes an electronic device for storing the calibration data and the manufacturing date, and the method further includes receiving the calibration data and the manufacturing date stored in the electronic device via the computer processor in response to receiving the kit in the diagnostic analyzer.

7. The method of claim 6, wherein the electronic device comprises a radio frequency identification (RFID) tag.

8. The method of claim 1, wherein determining the storage time of the kit via the computer processor comprises: The manufacturing date is received from the kit via the computer processor; as well as The computer processor determines the difference in days between the manufacturing date and the date the kit was received in the diagnostic analyzer, as indicated by the clock of the diagnostic analyzer.

9. The method of claim 1, wherein the kit comprises a multianalyte reagent.

10. The method according to claim 1, wherein: The calibration data includes the levels of creatinine and creatine in each of the two calibration reagents included in the kit, based on the manufacturing date. The determined average storage temperature and the determined storage time were used to determine the current levels of creatinine and creatine in the two calibration reagents; as well as If the determined current levels of creatinine and creatine differ from the levels of creatinine and creatine based on the manufacturing date, the computer processor stores the determined current levels of creatinine and creatine in the calibration data of the kit.

11. The method of claim 10, wherein the diagnostic analyzer includes an analyte sensor operable to measure the amount of creatinine or creatine present in the biological sample.

12. The method of claim 1, wherein the biological sample comprises whole blood, serum, plasma, urine, interstitial fluid, pleural fluid, or cerebrospinal fluid.

13. A diagnostic analyzer for measuring analytes in biological samples, comprising: Computer processor; An analyte sensor, which operates to measure analytes in the biological sample or quality control sample; Operate a reservoir for receiving a reagent kit, the reagent kit including temperature correction fluid, calibration data, and manufacturing date; One or more other analyte sensors, operated for measuring pH or pO2; as well as A clock, used to indicate the current date; where: The computer processor is operated via programmed instructions for: When the kit is received in the reservoir, the calibration data and the manufacturing date are received; The storage time of the reagent kit is determined based on the manufacturing date and the current date provided by the clock; The pH or pO2 of the temperature-corrected fluid is measured via one or more other analyte sensors; The average storage temperature is determined based on the measured pH or pO2 relative to the corresponding pH or pO2 value of the temperature correction fluid included in the calibration data. In response to an indication that the calibration data needs to be corrected based on a determined average storage temperature and a determined storage time, the calibration data is corrected; and In response to the calibration data being corrected, the corrected calibration data is used to calibrate the sample of the diagnostic analyzer used to measure the analyte.

14. The diagnostic analyzer of claim 13, wherein the computer processor is further operated via programmed instructions for: The pH and pO2 of the temperature-corrected fluid are measured via one or more other analyte sensors; and The average storage temperature is determined based on the measured pH and pO2 values ​​relative to the corresponding pH and pO2 values ​​of the temperature-corrected fluid included in the calibration data.

15. The diagnostic analyzer of claim 13, further comprising the reagent kit received in the reservoir.

16. The diagnostic analyzer of claim 15, wherein the temperature-correcting fluid includes predictable changes in pH over a temperature and time period.

17. The diagnostic analyzer of claim 15, wherein the temperature correction fluid includes predictable changes in pO2 over a temperature and time period.

18. The diagnostic analyzer of claim 15, wherein the kit further comprises one or more test reagents and one or more calibration reagents.

19. The diagnostic analyzer of claim 15, wherein the calibration data and the manufacturing date are stored in an electronic device included with the kit, or encoded in a barcode included with the kit.

20. The diagnostic analyzer of claim 19, wherein the computer processor is further operated via programming instructions to store calibrated calibration data in the electronic device.

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