Quality control solution, kit and use thereof in combined detection of glucose and uric acid

Abstract

The present application relates to the technical field of biological detection, and in particular to a quality control liquid, a kit and the use thereof in the combined detection of glucose and uric acid. The quality control liquid comprises glucose, dissolved uric acid, a buffer and a stabilizer, wherein the pH of the buffer is 4.5-5.3, and the stabilizer comprises polyethylene glycol and propylene glycol. The quality control liquid provided by the present application does not interfere with each detection channel when used in the simultaneous detection of glucose and uric acid, and the detection results are accurate and reliable, and can truly reflect the specific recognition ability of a multi-parameter analyzer for each target, thereby providing a reliable benchmark for the system performance verification of the instrument and test paper.

Description

Technical Field

[0001] This invention relates to the field of biological detection technology, specifically to quality control solutions, reagent kits, and their use in the combined detection of glucose and uric acid. Background Technology

[0002] Blood glucose, uric acid, and blood ketone tests are routine medical examinations. Blood glucose testing involves measuring the concentration of glucose in a blood sample. It is primarily used for diabetes screening and diagnosis, daily monitoring of diabetic patients, assessment of metabolic status, pre- and post-operative evaluation, and management of gestational diabetes. Uric acid testing measures the amount of uric acid in blood or urine. Uric acid is the end product of purine metabolism and is mainly excreted through the kidneys. Uric acid testing is mainly used for gout diagnosis and monitoring, assessing kidney function, assessing the risk of kidney stones, evaluating metabolic syndrome, monitoring chemotherapy for tumors, and guiding diet and medication. Blood ketone testing quantitatively measures the concentration of ketone bodies in a blood sample. β-hydroxybutyrate accounts for 70-80% of blood ketones and is the primary indicator. Blood ketone testing is an important objective indicator for assessing the body's lipid metabolism status, especially valuable in the early identification of acute diabetic complications and the precise management of ketogenic diets. Compared to urine ketone testing, blood ketone testing reflects the true state of ketone body metabolism in the body more accurately and promptly.

[0003] The detection of blood glucose, uric acid, and blood ketones typically involves electrochemical detection methods, and these physiological indicators usually utilize quality control solutions. A quality control solution is a standard solution of known concentration or properties used to verify the accuracy and stability of a medical testing system. It contains a specific concentration of the analyte (such as glucose, uric acid, etc.) and possesses stable physicochemical properties.

[0004] Multi-index combined detection composite quality control solution refers to a single quality control solution containing multiple analytes for various detection items, used to verify the overall performance of a multi-index combined detection system in a single step. Multi-index combined detection composite quality control solution is an important tool for efficient quality control in modern laboratory medicine. It optimizes the traditional "single-item quality control" into "multi-item combined verification," making it particularly suitable for modern laboratories with high levels of automation and integrated detection items. It is a key quality control means to ensure the accuracy of multi-index combined detection reports.

[0005] However, the current composite quality control solution used for multi-index joint detection still has the following technical bottlenecks: (1) The quality control mode is limited and true synchronization has not been achieved. Specifically, the existing "multi-in-one" quality control solution only realizes the physical mixing of multiple components. When using it, it is still necessary to perform time-sharing detection of a single item in sequence. In essence, it is still a simple superposition of single-substance quality control. It cannot output the quality control values ​​of multiple items in the same detection cycle at the same time. It has not broken through the technical barrier of "one sample addition and simultaneous quality control of multiple indicators"; (2) When multiple analytes coexist in the same liquid phase system, they face the problem of conflicting stability conditions between components and easy mutual interference and degradation; (3) Significant cross-interference and doubtful detection accuracy. Specifically, the stable system of one substance in the quality control solution may interfere with the detection of other substances, so that the accuracy and specificity of the composite quality control solution in the detection of multiple targets cannot be guaranteed; (4) Harsh storage and transportation conditions and poor ease of use make it difficult to meet the convenience requirements of POCT scenarios for room temperature storage and transportation and ready-to-use; (5) Insufficient adaptability to application scenarios makes it difficult to meet diverse clinical needs.

[0006] Therefore, there is an urgent need to develop a quality control solution that can simultaneously detect multiple substances with a single sample addition, without interference, and is accurate and stable. Summary of the Invention

[0007] This invention aims to at least partially solve the technical problems in related technologies. Therefore, one objective of this invention is to provide a novel composite quality control solution and its application. The quality control solution provided by this invention ensures that the detection channels do not interfere with each other during simultaneous detection of glucose and uric acid, resulting in accurate and reliable detection results. It can truly reflect the specific identification capability of a multi-parameter analyzer for each target analyte, providing a reliable benchmark for the system performance verification of the instrument and test strips.

[0008] Therefore, in a first aspect, the present invention provides a quality control solution. According to a specific embodiment of the present invention, the quality control solution comprises: Glucose, dissolved uric acid, buffer solution, and stabilizer. The pH of the buffer solution is 4.5~5.3. The dissolved uric acid in the quality control solution is obtained by the following method: S1: Dissolve uric acid powder in an alkaline aqueous solution to obtain uric acid stock solution; S2: Mix the uric acid stock solution with the buffer solution so that the uric acid in the quality control solution exists in a dissolved uric acid form. The stabilizers include polyethylene glycol and propylene glycol.

[0009] This invention addresses the technical shortcomings of existing composite quality control solutions by providing a novel composite quality control solution and its applications. The inventors optimized the components and pH of the quality control solution, achieving simultaneous detection of two substances with a single sample addition, without interference, and with high precision and stability.

[0010] The optimized composite quality control solution provided by this invention has the following advantages: (1) Achieving true multi-index simultaneous quality control. Existing "all-in-one" quality control solutions only achieve simple physical mixing of multiple analytes. During use, different test strips for different items still need to be inserted sequentially for time-sharing detection, which is essentially a serial operation of single-substance quality control. Although users do not need to change the quality control solution bottle, they still need to operate repeatedly and wait for multiple detection cycles, and the cumbersome operation has not been fundamentally solved. This invention systematically optimizes the compatibility of each analyte in the electrochemical reaction system, precisely controls the pH of the buffer system in a slightly acidic range of 4.5~5.3, selects a combination of polyethylene glycol and propylene glycol as stabilizers, and uses molecular uric acid as the uric acid source. The three form a synergistic effect, achieving a technological breakthrough of one-time sample addition and simultaneous quality control of multiple indicators. Users only need to perform one sample addition operation, and the instrument can output two quality control results, blood glucose and uric acid, in the same detection cycle, without the need for multiple detections or waiting for multiple cycles. Technical effects achieved: This invention upgrades "one bottle of liquid, multiple tests" to "one sample addition, simultaneous verification", which greatly simplifies the quality control operation process, improves quality control efficiency, and more realistically simulates the simultaneous detection scenario of multi-index analyzers in actual use. (2) Overcoming the stability challenge of multiple coexisting components and ensuring long-term stability. In existing technologies, when multiple analytes coexist in the same liquid phase system, there are problems such as conflicting stability conditions between components and easy mutual interference and degradation. This invention constructs a synergistically stable system suitable for multiple parameters by systematically optimizing the pH range of the buffer system, using dissolved uric acid, and a special combination of stabilizers. Among them, the inventors discovered and verified through a large number of experiments that special acidic conditions (pH 4.5~5.3), a specific form of uric acid, and a special combination of stabilizers (polyethylene glycol and propylene glycol) are the key to solving the stable coexistence of uric acid and glucose. When the pH of the quality control solution is in the range of 4.5~5.3, the oxidative degradation of uric acid is effectively inhibited, while glucose and other components can still maintain good stability. On this basis, stabilizers that match this pH condition were further screened, forming a complete stable system. Long-term stable coexistence of blood glucose and uric acid in the same system was achieved, significantly extending the shelf life of the quality control solution and solving the technical problem of rapid degradation of the effective components of the quality control solution with multiple coexisting components. (3) Eliminating cross-interference between components and ensuring detection accuracy. In existing composite quality control solutions, the stabilization system of one substance may interfere with the detection of another item. For example, preservatives may inhibit enzyme activity, and stabilizers may affect electrochemical mediator reactions, resulting in the inability to guarantee the accuracy and specificity of the composite quality control solution in glucose and uric acid detection. This invention ensures that each component (buffer system, stabilizer, etc.) in the quality control solution is highly compatible with both blood glucose and uric acid detection systems and does not interfere with each other through strategies such as systematically screening and optimizing the pH range of the buffer system, using dissolved uric acid, and a special combination of stabilizers. Glucose and uric acid coexisting in the quality control solution react independently during detection, and their signals do not affect each other, thus accurately reflecting the actual concentration of each indicator.

[0011] A second aspect of the present invention provides the use of the aforementioned quality control solution in glucose detection systems, uric acid detection systems, and combined glucose and uric acid detection systems.

[0012] Existing quality control solutions are primarily designed for laboratories or specialized testing departments, lacking targeted optimization for different application scenarios. In hospital laboratories, simultaneous testing of multiple indicators is impossible, requiring medical staff to perform separate quality control procedures for blood glucose and uric acid, increasing workload and prolonging the quality control process, especially severely impacting efficiency in high-frequency testing scenarios. In pharmacies / community health points, the complexity of separate testing is extremely unfriendly to non-professionals, with two sample additions, two waiting periods, and two interpretations easily leading to errors or omissions, resulting in significant low quality control efficiency. In home testing, users need to perform two operations, record and compare the two results separately, which is cumbersome and error-prone. Furthermore, some products rely on refrigerated storage, further reducing user compliance. To address these issues, this invention, through systematic optimization of the formulation system, achieves a composite quality control solution that allows for "one-time sample addition, simultaneous detection of two substances without interference, and precise and stable testing," solving the three major technical challenges of existing technologies: cumbersome separate testing, instability of multiple components, and severe cross-interference. Meanwhile, this invention achieves a leap from "multi-stage operation" to "one-step solution" in terms of application scenarios, effectively adapting to the convenient quality control needs of multiple scenarios such as hospitals, pharmacies / community medical points, and home self-testing. It can meet the quality control requirements of glucose detection systems, uric acid detection systems, and combined glucose and uric acid detection systems in multiple scenarios, providing a truly efficient solution for the quality control of multi-parameter analyzers.

[0013] A third aspect of the present invention provides a reagent kit. According to a specific embodiment of the present invention, the reagent kit includes the quality control solution described in the first aspect.

[0014] The kit containing the aforementioned quality control solution provided by this invention solves the three major technical problems that have long existed in the prior art: "cumbersome multiple-stage testing, instability of multiple components, and serious cross-interference." It provides an efficient, accurate, and convenient solution for the quality control of multi-parameter analyzers.

[0015] A fourth aspect of the present invention provides a method for confirming whether an electrochemical detection system is operating normally. According to a specific embodiment of the present invention, the method includes: The quality control solution described in the first aspect is added to the sample application port of the test card or the sample application area of ​​the test strip. The electrochemical detection system outputs blood glucose and uric acid values. The blood glucose and uric acid values ​​are compared with the nominal target value range of the quality control solution. Based on the comparison results, it is determined whether the electrochemical detection system and the test card or test strip are in normal condition.

[0016] This invention also provides a method for confirming whether an electrochemical detection system is operating normally. Using this method, the quality control solution described in this invention is added to the sample application port of the detection card or the sample application area of ​​the test strip, and the output value of the detection system is confirmed to be within a predetermined range. This verifies whether the electrochemical sensor or signal processing circuit is normal, the validity of the test strip (whether the enzyme activity and electrode function are intact), and whether the operator's technique is correct.

[0017] Beneficial effects: This invention addresses the technical deficiencies of existing composite quality control solutions by systematically optimizing the formula, achieving the following technical breakthroughs: (1) Addressing the problem of "multiple detections and cumbersome operations" in existing technologies, this invention achieves true multi-index synchronous quality control. By optimizing the compatibility of each analyte in the electrochemical reaction system and combining it with a test strip that can simultaneously detect blood glucose and uric acid, this invention achieves the technical breakthrough of "same test strip, one sample addition, and synchronous detection." Users only need to perform one sample addition operation. The quality control solution flows through the uric acid reaction zone and the glucose reaction zone, and the instrument simultaneously collects the current signals of the two channels. Within the same detection cycle, it simultaneously outputs two quality control results: blood glucose and uric acid. The two readings are presented synchronously, truly achieving multi-index synchronous quality control; (2) The quality control solution provided by this invention uses special slightly acidic conditions (pH 4.5~5.3), a specific source of uric acid (molecular uric acid generated in situ through the "alkali dissolution and acid precipitation" method), and a specific combination of stabilizers (PEG4000 and 1,2-propanediol), solving the problem of long-term stable coexistence of multiple components. The quality control solution provided by this invention, verified by accelerated aging experiments, shows that the uric acid concentration deviation is far superior to that of the quality control solution in the prior art, solving the technical problem of rapid degradation of the effective components of multi-component quality control solution. Specifically, after accelerated aging at 65°C for 2 weeks, the absolute value of the relative deviation of uric acid concentration in the preferred scheme of this invention is controlled within 1.5% (low concentration) and within 1.5% (high concentration), while the quality control solution of sodium urate commonly used in the prior art has a deviation of up to -13.62% for high-concentration uric acid under the same conditions. The degradation rate is reduced from 10%~22% in the prior art to within 1.5%, achieving long-term stable coexistence of the two analytes; (3) In response to the problem of "cross-interference between components and doubt about the accuracy of detection" in the prior art, this invention eliminates cross-interference in the multi-component coexistence system. Through systematic screening and optimization, this invention ensures that each component in the quality control solution is highly compatible with the two detection systems of blood glucose and uric acid. The detection results of the dual-index composite quality control solution and the single-index quality control solution are highly consistent: the deviation of YSI / biochemical reference value is less than 0.1% (actual ≤0.08%), the absolute value of current output deviation is less than 0.6% (actual ≤0.53%), and all coefficients of variation (CV%) are within 3% (<5%), proving that the two analytes do not interfere with each other when they coexist, and the detection results are accurate and reliable. (4) In view of the problem of "insufficient adaptability to application scenarios and complex operation process" in the existing technology, the present invention realizes the leap from "multiple operations" to "one-step operation". The design of the existing quality control solution does not fully consider the operational convenience requirements of different application scenarios.This invention demonstrates significant advantages in various application scenarios through its technological breakthrough of "single sample addition, simultaneous detection, and simultaneous output of two results": in hospital laboratories, the quality control process time is reduced by about 50%, improving work efficiency; in pharmacies / community health points, the number of operation steps is reduced by about 50%, reducing the complexity and error risk for non-professionals; in home self-testing, the simplified operation improves user compliance and ensures the reliability of self-test results.

[0018] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description

[0019] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which: Figure 1 The diagram shows the breakdown structure of a test strip capable of simultaneously detecting blood glucose and uric acid according to an embodiment, wherein 1: first HCT (hematocrit) detection electrode; 2: second HCT detection electrode; 3: uric acid detection area; 4: counter electrode area; 5: glucose detection area; 6: full blood detection electrode. Detailed Implementation

[0020] The embodiments of the present invention are described in detail below. The embodiments described below are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention.

[0021] It should be noted that the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. Furthermore, in the description of this invention, unless otherwise stated, "a plurality of" means two or more.

[0022] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0023] To facilitate understanding of the invention, certain technical and scientific terms are specifically defined below. Unless otherwise expressly defined elsewhere in this document, all other technical and scientific terms used herein have the meanings commonly understood by one of ordinary skill in the art to which this invention pertains.

[0024] In this document, the terms “comprising” or “including” are open-ended expressions, meaning they include the contents specified in this invention but do not exclude other aspects.

[0025] In this document, the terms “optionally,” “optionally,” or “optionally” generally refer to an event or condition that may, but may not, occur, and the description includes both cases in which the event or condition occurs and cases in which the event or condition does not occur.

[0026] "Dissolved uric acid" refers to uric acid that is dissolved in blood, urine, or other body fluids and is uniformly dispersed in ionic or molecular form, as opposed to crystalline uric acid (solid uric acid that precipitates). In this document, dissolved uric acid specifically refers to molecular uric acid in the quality control solution, which exists stably in molecular form in the composite quality control solution of this invention.

[0027] According to a specific embodiment of the present invention, the present invention provides a quality control solution, the quality control solution comprising: Glucose, dissolved uric acid, buffer solution, and stabilizer. The pH of the buffer solution is 4.5~5.3. The dissolved uric acid in the quality control solution is obtained by the following method: S1: Dissolve uric acid powder in an alkaline aqueous solution to obtain uric acid stock solution; S2: Mix the uric acid stock solution with the buffer solution so that the uric acid in the quality control solution exists in a dissolved uric acid form. The stabilizers include polyethylene glycol and propylene glycol.

[0028] This invention, through systematic formulation optimization of the quality control solution, utilizes a slightly acidic pH condition (4.5~5.3), employs dissolved uric acid, and a specific combination of polyethylene glycol and propylene glycol as stabilizers to resolve the contradiction of stable coexistence between uric acid and glucose. It enables "single sample addition, simultaneous detection of two substances, no interference, and precise stability," solving four major technical problems that have long existed in existing technologies: "cumbersome multiple-stage detection, instability of multiple components, severe cross-interference, and insufficient adaptability to different scenarios." This provides an efficient, accurate, and convenient solution for quality control of multi-parameter analyzers.

[0029] The quality control solution provided by this invention, by using a specific combination of polyethylene glycol and propylene glycol as stabilizers, can further improve the stability of the analytes in the quality control solution, making the quality control results more accurate.

[0030] It should be noted that the quality control solution provided by this invention contains glucose and dissolved uric acid, enabling simultaneous quality control of blood glucose and uric acid. Theoretically, adding an appropriate concentration of β-carotene to the quality control solution... Sodium hydroxybutyrate can also achieve simultaneous quality control of blood glucose, uric acid, and blood ketones, or simultaneous quality control of blood glucose and blood ketones.

[0031] It should be noted that there are no particular limitations on the type of buffer solution contained in the quality control solution of this invention. For example, it can be one or more of HEPES (4-hydroxyethylpiperazine ethanesulfonic acid), MES (2-morpholinoethanesulfonic acid), Bis-Tris (bis(2-hydroxyethyl)iminoTris), or PEPES (piperazine-N,N'-bis(2-ethanesulfonic acid)). Any other type of buffer solution known in the art that can be used in quality control solutions is also covered within the scope of protection of the quality control solution of this invention. Preferably, the buffer solution is HEPES. HEPES, as a Good's buffer solution, has the characteristics of strong biological inertness, weak binding to metal ions, and excellent buffering capacity within the physiological pH range, making it particularly suitable for multi-parameter detection systems.

[0032] It should be noted that there are no particular restrictions on the alkaline aqueous solution used to dissolve uric acid powder. For example, it can be potassium hydroxide or sodium hydroxide aqueous solution, or other types of alkaline aqueous solution, all of which are covered within the scope of protection of this invention. However, these selectable alkaline aqueous solutions need to meet the requirement that they do not affect the components and stability of the quality control solution.

[0033] It should be noted that there are no particular limitations on the ratio of polyethylene glycol to propylene glycol in the stabilizer. According to a specific embodiment of the present invention, the weight ratio of polyethylene glycol to propylene glycol is (0.5~3):1. For example, the weight ratio of polyethylene glycol to propylene glycol can be 0.5:1, 1:1, 1.5:1, 2:1, 2.5:1, 3:1, etc.

[0034] The inventors discovered that when the weight ratio of polyethylene glycol to propylene glycol in the stabilizer is within this range, it can further improve the stability of enzymes in the detection paper strip and further improve the accuracy of quality control results. At the same time, the polyethylene glycol stabilizer can effectively protect the natural conformation of the analyte molecules through steric hindrance and hydrogen bonding, preventing them from agglomerating or degrading during storage.

[0035] According to a specific embodiment of the present invention, there is no particular limitation on the molecular weight of the polyethylene glycol. According to a preferred embodiment of the present invention, the molecular weight of the polyethylene glycol is 2000-6000. For example, the molecular weight of the polyethylene glycol is 2000, 3000, 4000, 5000, 6000, etc. More preferably, the molecular weight of the polyethylene glycol is 4000.

[0036] According to a specific embodiment of the present invention, the content of the stabilizer is 10% to 40% based on the total weight of the quality control liquid. For example, the mass fraction of the stabilizer in the quality control liquid can be 10%, 15%, 20%, 25%, 30%, 35%, 40%, etc.

[0037] According to a specific embodiment of the present invention, the quality control solution further comprises inorganic salts.

[0038] According to a specific embodiment of the present invention, the inorganic salt is selected from one or more of sodium chloride, potassium chloride, calcium chloride, and magnesium sulfate. The addition of the inorganic salt can adjust the ionic strength and osmotic pressure of the quality control solution, enabling it to exhibit conductivity characteristics similar to real blood during electrochemical detection.

[0039] According to a preferred embodiment of the present invention, the inorganic salt includes sodium chloride and calcium chloride.

[0040] According to a further preferred embodiment of the present invention, the weight ratio of sodium chloride to calcium chloride is (10~100):1. For example, the weight ratio of sodium chloride to calcium chloride can be 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, 100:1, etc.

[0041] According to a specific embodiment of the present invention, the content of the inorganic salt is 0.1% to 5% based on the total weight of the quality control solution. For example, the mass fraction of the inorganic salt in the quality control solution can be 0.1%, 1%, 2%, 3%, 4%, 5%, etc.

[0042] According to a specific embodiment of the present invention, the concentration of the buffer solution is 0.01 mol / L to 2 mol / L. For example, the concentration of the buffer solution can be 0.01 mol / L, 0.05 mol / L, 0.1 mol / L, 0.2 mol / L, 0.5 mol / L, 1.0 mol / L, 1.2 mol / L, 1.4 mol / L, 1.6 mol / L, 1.8 mol / L, 2.0 mol / L, etc.

[0043] According to one specific embodiment of the present invention, the quality control solution further comprises blood-simulated dyes and / or preservatives.

[0044] In this article, "blood-simulating dyes" refers to specialized dyes or dye formulations used to simulate the optical, rheological, or chemical properties of blood. These dyes are widely used in medical teaching, medical device testing, imaging technology verification, and scientific research experiments. The addition of blood-simulating dyes makes the quality control solution closely resemble real blood in optical properties (such as absorbance and transmittance), thus making it suitable for biochemical detection platforms based on optical principles.

[0045] According to a specific embodiment of the present invention, the blood-simulating dye includes, but is not limited to, one or more of sulfonylrhodamine B, Congo Red, Mito Red, Acid Red, Fluorescent Red, Allura Red, Cresol Red, Amaranth Red, Chlorophenol Red, or sulfonylrhodamine 101.

[0046] The addition of the preservative can prevent bacterial growth in the quality control solution and extend its shelf life. According to a specific embodiment of the present invention, the preservative includes, but is not limited to, one or more of sodium azide, sodium benzoate, Proclin-150, Proclin-200, Proclin-300, or Proclin-5000.

[0047] According to a specific embodiment of the present invention, the quality control solution includes glucose, dissolved uric acid, buffer solution, stabilizer, blood-simulated dye, inorganic salt, preservative, etc.

[0048] According to a specific embodiment of the present invention, the quality control solution comprises the following components based on its total weight: 10%–40% stabilizer; 0.1% to 5% inorganic salts; 0.1% to 2% preservative; 0.1%–2% blood-simulated dye, and buffer solution, The concentration of the buffer solution is 0.01 mol / L to 2 mol / L.

[0049] It should be noted that there are no particular limitations on the working concentrations of glucose and dissolved uric acid in the quality control solution. Low-concentration or high-concentration glucose standard solutions or low-concentration or high-concentration dissolved uric acid solutions can be prepared according to actual needs. According to a specific embodiment of the present invention, the working concentration of glucose in the quality control solution is 10 mg / dL to 600 mg / dL; the working concentration of dissolved uric acid is 200 μmol / L to 1000 μmol / L.

[0050] For example, the working concentration of glucose in the quality control solution can be 10 mg / dL, 20 mg / dL, 30 mg / dL, 40 mg / dL, 50 mg / dL, 100 mg / dL, 150 mg / dL, 200 mg / dL, 250 mg / dL, 300 mg / dL, 350 mg / dL, 400 mg / dL, 450 mg / dL, 500 mg / dL, 550 mg / dL, 600 mg / dL, etc.; the working concentration of dissolved uric acid can be 200 μmol / L, 250 μmol / L, 300 μmol / L, 350 μmol / L, 400 μmol / L, 450 μmol / L, 500 μmol / L, 550 μmol / L, 600 μmol / L, 650 μmol / L, 700 μmol / L, 750 μmol / L, 800 μmol / L, etc. μmol / L, 850 μmol / L, 900 μmol / L, 950 μmol / L, 1000 μmol / L, etc.

[0051] In this article, "dL" is an abbreviation for deciliter, a unit of volume in the International System of Units (SI). 1 dL (deciliter) equals 100 mL and is a unit of volume unique to the field of medical testing, especially in the detection of indicators such as blood glucose and blood lipids, which is still in use today.

[0052] This invention provides a composite quality control solution comprising a buffer system, stabilizers, inorganic salts, preservatives, a mimic dye, and two analytes, glucose and uric acid, suitable for immunoassay, biochemical assay, and electrochemical assay. This invention also provides the application of the composite quality control solution in the simultaneous quality control of blood glucose and uric acid.

[0053] According to a specific embodiment of the present invention, the composite quality control solution of the present invention has the following components and content ranges: The composite quality control solution has a buffer concentration of 0.01 mol / L to 2 mol / L and a pH of 4.5 to 5.3; a stabilizer content of 10% to 40% (w / w); an inorganic salt content of 0.1% to 5% (w / w); a preservative content of 0.1% to 2% (w / w); and a blood-simulated dye content of 0.1% to 2% (w / w).

[0054] The quality control solution provided by this invention can be used in glucose detection systems, uric acid detection systems, and combined glucose and uric acid detection systems to perform quality control on whether these detection systems are operating normally.

[0055] According to a specific embodiment of the present invention, the present invention also provides a kit comprising the aforementioned quality control solution.

[0056] According to a specific embodiment of the present invention, the present invention also provides a method for confirming whether an electrochemical detection system is operating normally, the method comprising: The aforementioned quality control solution is added to the sample application port of the test card or the sample application area of ​​the test strip. The electrochemical detection system outputs blood glucose and uric acid values. The blood glucose and uric acid values ​​are compared with the nominal target value range of the quality control solution. Based on the comparison results, it is determined whether the electrochemical detection system and the test card or test strip are in normal condition.

[0057] It should be noted that the quality control solution provided by this invention can be added to any type of glucose and uric acid combined detection system and its matching test card or test strip to perform quality control on whether the detection system is operating normally, so as to ensure the accuracy and stability of the detection results of the medical detection system.

[0058] The quality control solution and integrated electrode structure provided by this invention are compatible and work together to achieve automatic sample identification and simultaneous detection of multiple indicators. No manual mode switching is required, avoiding quality control errors caused by misjudgment of sample type; two quality control results are output simultaneously on a single test strip, simplifying the hardware structure and intelligentizing the detection process, further improving operational convenience and result reliability.

[0059] According to a specific embodiment of the present invention, the application principle of the composite quality control solution on the electrochemical detection platform is as follows: See appendix Figure 1 As shown, when the composite quality control solution sample is introduced into the sample channel through the sample inlet, it first flows through a pair of hematocrit (HCT) detection electrodes set in the channel, namely the first HCT detection electrode 1 and the second HCT detection electrode 2. This pair of electrodes has dual functions: blood entry detection and sample type identification. On the one hand, the system continuously monitors the impedance change between the two electrodes. When the impedance value exceeds a preset threshold due to liquid filling, it automatically determines that a sample has entered the detection channel and immediately triggers preparation for subsequent detection procedures. On the other hand, by applying a high-frequency AC signal to the sample to detect its impedance characteristics, the system automatically identifies the sample type based on a preset impedance characteristic database. In the composite quality control solution described in this invention, by optimizing the types and ratios of inorganic salts, it possesses impedance characteristics significantly different from real blood, thus being automatically identified by the detection system as a "quality control solution" sample rather than a real blood sample. Based on this, the system automatically switches to the quality control detection mode, calling preset quality control parameters for detection and result interpretation.

[0060] After being identified by the HCT electrode, the sample continues to flow forward, passing sequentially through the uric acid detection zone 3 and the glucose detection zone 5. A full-blood detection electrode 6 is located at the end of the channel. The system applies an excitation voltage to the full-blood detection electrode 6. When the detected electrical signal (such as impedance or current) exceeds a preset threshold, it indicates that the sample has completely filled the entire detection channel and covered all reaction areas; at this point, the system determines that the sample injection is sufficient.

[0061] After the full-blood detection electrode 6 confirms that the sample injection is sufficient, the system simultaneously starts the electrochemical detection program of uric acid detection area 3 and glucose detection area 5. The two detection areas work in parallel without interfering with each other.

[0062] Within the uric acid detection zone 3, the system applies a preset excitation voltage to the sample, inducing an electrochemical oxidation-reduction reaction of uric acid on the electrode surface. Specifically, uric acid loses electrons on the electrode surface and is oxidized to allantoin; the resulting electrons are transferred to the electrode, forming a Faraday current signal proportional to the uric acid concentration. The current response value is acquired in real time by measuring the current between electrode zone 4 and uric acid detection zone 3, and the uric acid concentration detection result is output after conversion by a built-in algorithm.

[0063] Simultaneously, within glucose detection zone 5, the system applies another set of preset excitation voltages, triggering a specific enzymatic oxidation reaction of glucose on the enzyme electrode surface. Catalyzed by glucose oxidase or glucose dehydrogenase, glucose reacts with oxygen or electron mediators to generate gluconolactone and hydrogen peroxide (or a reduced mediator). The generated electrons are transferred to the electrode surface, forming a current signal proportional to the glucose concentration. The current response value is acquired in real-time by measuring the current between electrode zone 4 and glucose detection zone 5, and the glucose concentration detection result is output after conversion using a built-in algorithm.

[0064] The uric acid and glucose tests described above are completed synchronously within the same testing cycle. The testing system uses multi-channel parallel acquisition technology to simultaneously output the results of both uric acid and glucose tests within the same time window. Based on this testing principle, the composite quality control solution described in this invention achieves the technical effect of "one-time sample addition, synchronous detection, and simultaneous output of two quality control results," providing an efficient and accurate solution for verifying the system performance of multi-parameter analyzers.

[0065] According to a specific embodiment of the present invention, the composite quality control solution of the present invention has wide application adaptability in the fields of clinical testing and point-of-care testing, and its specific application methods in different scenarios are as follows: Take one bottle of the composite quality control solution of this invention, shake thoroughly, and then open the cap. The operator (or user) uses a dropper to directly add an appropriate amount of the quality control solution to the sample application port of the multi-parameter analyzer's test card or the sample application area of ​​the test strip. The instrument automatically identifies the sample type (quality control solution) through its built-in HCT electrode, initiates the preset quality control detection program, and simultaneously completes the detection of both blood glucose and uric acid indicators within a detection cycle of approximately 5-15 seconds, outputting two quality control results (blood glucose value and uric acid value) at the same time. The operator reads the two results displayed simultaneously on the instrument's screen and compares them with the nominal target value range of the quality control solution to complete the quality control interpretation of both indicators in one go, thereby determining whether the instrument and test strip system are in normal working order.

[0066] The above application method is adaptable to various usage scenarios: In hospital laboratories and clinical departments, where operators face high-frequency and high-volume testing needs, this invention shortens the two independent operations and two testing cycles required by traditional multi-stage testing to one sample addition and one testing cycle, significantly improving quality control efficiency; In pharmacies and community health points, where operators typically lack professional testing backgrounds, the simplified operation process of this invention (one sample addition, one interpretation) effectively reduces operational complexity and learning costs, and reduces the risk of errors caused by cumbersome steps; In home self-testing scenarios, users only need to perform a single sample addition action to complete two quality control verifications, greatly lowering the usage threshold and improving quality control compliance.

[0067] Compared to the cumbersome process of existing technologies that require separate blood glucose and uric acid tests, waiting for two testing cycles, and interpreting the results twice, this invention achieves a technological breakthrough of "one sample addition, simultaneous testing, and simultaneous output of two results," reducing the operation steps by about 50% and shortening the quality control process time by about 50%. While improving the convenience of operation, it effectively ensures the accuracy and reliability of the quality control results.

[0068] The present invention will be explained below with reference to embodiments. Those skilled in the art will understand that the following embodiments are for illustrative purposes only and should not be considered as limiting the scope of the invention. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be obtained commercially.

[0069] Example 1: Preparation and Performance Testing of Composite Quality Control Solution 1. Preparation of composite quality control solution (1) Preparation of buffer system: HEPES was selected as the buffer agent, the concentration of the buffer system was adjusted to 2 mol / L, and the pH was precisely controlled at 5.0±0.1 with acid-base adjuster; (2) Adding stabilizers: Add PEG4000 and propylene glycol (mass ratio of 1:1) as stabilizers to the buffer system, with an addition amount of 20% (w / w), and stir until completely dissolved; (3) Add inorganic salts: Add a mixture of sodium chloride and calcium chloride (mass ratio of 50:1), the total addition amount is 5% (w / w), and stir evenly; (4) Add preservative: Add preservative (Proclin-300) at a rate of 0.5% (w / w) and mix thoroughly; (5) Add simulated dye: Add Allura Red as a blood simulated dye at a concentration of 0.2% (w / w) and stir until evenly dispersed; (6) Add the analytes: Add glucose stock solution and uric acid stock solution respectively, mix thoroughly, and prepare low-concentration level quality control solution and high-concentration level quality control solution respectively; the glucose concentration in the low-concentration level quality control solution is 40 mg / dL and the uric acid concentration is 250 μmol / L; the glucose concentration in the high-concentration level quality control solution is 250 mg / dL and the uric acid concentration is 750 μmol / L. (7) Dispensing and storage: After the prepared quality control solution is shaken well, dispense it into small bottles at a volume of 2±0.2ml and seal for storage.

[0070] The above-mentioned uric acid reservoir is prepared by the following method: A 0.6% uric acid stock solution was prepared by dissolving uric acid powder in a sodium hydroxide solution. Under these alkaline conditions, uric acid forms soluble urate. When this stock solution is further added to a buffer system at pH 5.0, the urate is reprotonated, converting into molecular uric acid, which then exists stably in molecular form in the final composite quality control solution.

[0071] 2. Performance testing of composite quality control fluid To verify the performance of the quality control solution of the present invention, two concentrations of blood glucose and uric acid composite quality control solution, one low and one high, were prepared according to the above formula, and systematic tests were conducted on repeatability, stability, and anti-interference ability.

[0072] (1) Repeatability and precision test The YSI 2300 STAT PLUS glucose analyzer was used as the reference method for blood glucose detection, and the fully automated biochemical analyzer was used as the reference method for uric acid detection. The blood glucose and uric acid concentrations of different groups of quality control solutions were measured. Simultaneously, the matching electrochemical detection platform was used to measure the blood glucose / uric acid dual-index test strips. Figure 1 The current response values ​​on the test strips were measured. Each concentration level and each group was tested five times. The mean, standard deviation (SD), and coefficient of variation (CV%) of the test results were calculated. The CV% was used to evaluate the repeatability of the system. The results are shown in Table 1 below.

[0073] Table 1. Results of repeatability precision test (n=5)

[0074] The above test results show that the biochemical measurement repeatability of the quality control solution of the present invention and its current measurement repeatability in test strip applications are both excellent, with repeatability coefficients of variation (CV%) of less than 5%. Specifically, the CV% for biochemical measurements is as low as 0.09%, and the CV% for current measurements is within 3%. This indicates that the quality control solution of the present invention has good repeatability.

[0075] (2) Stability test Two separate bottles of quality control solutions (low and high concentration levels) were sealed and stored at room temperature (RT) as a control group. Another bottle of each group was placed in a 65℃ incubator for accelerated aging for 2 weeks (equivalent to 2 years of sealed storage at room temperature). After accelerated aging, the control solutions were removed and equilibrated at room temperature for 30 minutes. The blood glucose, uric acid concentrations, and current response values ​​of the control and accelerated aging groups were measured using the aforementioned reference method and electrochemical platform. The absolute and relative deviations (%) of the accelerated aging group relative to the room temperature control group were calculated, and the long-term stability of the system was evaluated using the relative deviation. The results are shown in Table 2 below.

[0076] Table 2 Stability Test Results

[0077] Specifically, the test results show that the deviation of the control solution stored at 65℃ for 2 weeks compared to that stored at room temperature is very small, with glucose levels controlled within ±2%. Specifically, the deviation of the glucose current test value in the low-concentration control solution compared to the room-temperature control solution is approximately 1.3%, while the deviation in the high-concentration control solution is approximately 1.9%. Uric acid levels are controlled within ±4%. Specifically, the deviation of the uric acid current test value in the low-concentration control solution compared to the room-temperature control solution is approximately 2.5%, while the deviation in the high-concentration control solution is approximately 3.3%. Therefore, the control solutions provided in this protocol exhibit good stability in testing both glucose and uric acid.

[0078] (3) Uric acid and glucose interference test For each group of formulations, single-index blood glucose control solution containing only glucose, single-index uric acid control solution containing only uric acid, and dual-index composite control solution containing both glucose and uric acid were prepared using the above method to ensure that the theoretical concentrations of the corresponding analytes in the single and dual systems were completely consistent. Parallel tests were performed under the same detection conditions, and the reference method test results and current response results of the dual-index composite control solution and the single-index control solution were compared. The relative deviation (%) between the two was calculated to evaluate the degree of cross-interference when the two components coexist. The results are shown in Table 3 below.

[0079] Table 3 Results of Cross-Interference Resistance Test

[0080] The above data shows that the detection results of the dual-index composite quality control solution (glucose and uric acid coexisting) are highly consistent with those of the single-index quality control solution (containing only a single analyte): the deviation of YSI / biochemical reference value is less than 0.1%; the absolute value of current output deviation is less than 0.6%; and all coefficients of variation (CV%) are within 3%. In the composite quality control solution provided by this invention, when glucose and uric acid coexist in the same system, they do not interfere with each other's detection signals, and can truly reflect the actual concentration of each index, achieving true multi-index synchronous quality control, with no significant difference in detection accuracy compared to the single-index quality control solution.

[0081] Example 2: Effects of different pH buffer systems on the performance of composite quality control solution This embodiment is used to verify the effect of the pH value of the buffer system on the repeatability, stability and anti-interference performance of the composite quality control solution, and to determine the preferred pH range of the present invention.

[0082] 1. Preparation of quality control solution The basic formulation was fixed as follows: HEPES buffer, concentration 2 mol / L; PEG4000 and propylene glycol (mass ratio 1:1) as stabilizers, added at 20% (w / w); a mixture of sodium chloride and calcium chloride (mass ratio 50:1) as inorganic salts, added at 5% (w / w); Proclin-300 as a preservative, added at 0.5% (w / w); and Allura Red as a blood-simulating dye, added at 0.2% (w / w). The low-concentration control solution contained 40 mg / dL glucose and 250 μmol / L uric acid; the high-concentration control solution contained 250 mg / dL glucose and 750 μmol / L uric acid. For specific preparation methods, refer to Example 1.

[0083] Six parallel experiments were conducted by adjusting the pH of the buffer system solely with acid-base adjusters: Group 2-1: pH = 4.5 ± 0.1 Group 2-2: pH = 5.0 ± 0.1 Groups 2-3: pH = 5.3 ± 0.1 Groups 2-4: pH = 6.0 ± 0.1 Groups 2-5: pH = 7.0 ± 0.1 Groups 2-6: pH = 7.5 ± 0.1 After all groups are prepared, shake well and dispense into high-density polyethylene vials at a volume of 2±0.2mL. Seal and store in the dark.

[0084] 2. Performance Test Results and Data Analysis (1) Repeatability and precision test results Table 4. Repeatability and precision test results of quality control solutions at different pH levels (CV%, n=5)

[0085] As shown in Table 4, when the pH of the buffer system is within the range of 4.5 to 5.3 as defined in this invention, the coefficient of variation (CV%) of all test items in the quality control solution is less than 5%, fully meeting the industry requirements for repeatability and precision of in vitro diagnostic quality control products. Group 2-2 (pH 5.0) exhibits the best performance, with a CV as low as 0.35% for blood glucose biochemistry, a CV as low as 0.28% for uric acid biochemistry, and CVs for electrochemical current response all controlled within 3.1%, demonstrating excellent intra-batch consistency. When the pH exceeds 5.3 and enters the near-neutral and alkaline range, the repeatability of the quality control solution deteriorates significantly: in the pH 6.0 group, the CV for uric acid biochemistry increases to 1.02%, and the CV for current response exceeds 4%; in the pH 7.0 group, the CV for uric acid biochemistry increases to 2.18%, and the CV for current response exceeds 5%; in the pH 7.5 group, the CVs for all uric acid-related tests exceed 5%, and the CV for current response approaches 10%, failing to meet the repeatability requirements of the quality control product. The results demonstrate that the slightly acidic environment of pH 4.5 to 5.3 specified in this invention can effectively ensure the consistency of uric acid and glucose detection in the system and avoid fluctuations in detection results caused by unstable analyte structures.

[0086] (2) Results of accelerated stability test Table 5. Accelerated stability test results of quality control solutions at different pH levels (65℃ / 2 weeks, deviation %) relative to the room temperature control group.

[0087] As shown in Table 5, under the pH range of 4.5-5.3 specified in this invention, after accelerated aging at 65℃ for 2 weeks, the relative deviations in blood glucose detection and uric acid detection were all controlled within ±1.1%, and the relative deviations were all controlled within ±1.8%, far below the ±10% acceptable stability limit for quality control products in the in vitro diagnostics industry, demonstrating the system's excellent long-term storage stability. When the pH value exceeded 5.3, the stability of the quality control solution experienced a sharp decline, with the degradation rate of uric acid being much higher than that of glucose: the uric acid detection deviation in the pH 6.0 group was close to -5%, and in the pH 7.0 group it exceeded -9%, exceeding the industry acceptable range; the highest deviation in the pH 7.5 group reached -21.18%, indicating severe oxidative degradation. This result directly verifies the core finding of this invention: uric acid is highly susceptible to oxidative degradation in neutral and alkaline environments, while the slightly acidic buffer system of pH 4.5-5.3 specified in this invention can effectively inhibit the degradation reaction of uric acid.

[0088] (3) Results of anti-cross interference test Table 6. Cross-interference test results of quality control solutions at different pH levels (dual index vs. single index, relative deviation %)

[0089] As shown in Table 6, under the pH range of 4.5–5.3 specified in this invention, the detection results of the dual-index composite control solution and the single-index control solution show minimal deviation: the concentration deviation of the reference method is less than 0.3%, and the electrochemical current response deviation is less than 0.6%, proving that there is no significant cross-interference when glucose and uric acid coexist in this system, and it can truly reflect the actual concentration of each analyte. When the pH value exceeds 5.3, the degree of cross-interference between the two components increases significantly: the current response deviation in the pH 6.0 group is close to 1.5%, the deviation in the pH 7.0 group exceeds 3%, and the deviation in the pH 7.5 group is close to 6.5%. The core reason is that the byproducts of uric acid degradation under neutral / alkaline conditions interfere with the enzymatic reaction and electrochemical response of glucose, while the oxidation products of glucose further accelerate the degradation of uric acid, forming a vicious cycle. The slightly acidic system of pH 4.5–5.3 specified in this invention can simultaneously inhibit the side reactions of the two analytes, eliminating cross-interference between components at its source.

[0090] The above results indicate that the pH value of the buffer system is the core parameter determining the performance of the composite quality control solution. When the pH is within the range of 4.5 to 5.3 defined in this invention, the repeatability, precision, long-term stability, and resistance to cross-interference of the composite quality control solution all reach optimal levels. When the pH exceeds 5.3 and enters the near-neutral and alkaline range, the performance of the quality control solution deteriorates significantly, especially the stability and detection consistency of the uric acid component decrease dramatically. This invention defines pH 4.5 to 5.3 as the optimal range for the buffer system, with pH 5.0 being more preferred. The optimized pH range of the buffer system in this invention is supported by sufficient experimental data and can effectively solve the technical problem of incompatibility between the stability conditions of uric acid and glucose in the prior art.

[0091] Example 3: Effect of different stabilizer types on the performance of composite quality control liquid This embodiment is used to verify the effects of different types of stabilizers on the repeatability, stability and anti-interference performance of the composite quality control liquid, and to screen the preferred stabilizer system of the present invention.

[0092] 1. Preparation of quality control solution The basic formulation was fixed as follows: HEPES buffer system, concentration 2 mol / L, pH=5.0±0.1; a mixture of sodium chloride and calcium chloride (mass ratio 50:1) as inorganic salts, with a total addition of 5% (w / w); Proclin-300 as preservative, with an addition of 0.5% (w / w); and Allura Red as a blood-simulating dye, with an addition of 0.2% (w / w). The low-concentration control solution contained 40 mg / dL glucose and 250 μmol / L uric acid; the high-concentration control solution contained 250 mg / dL glucose and 750 μmol / L uric acid. For specific preparation methods, refer to Example 1.

[0093] Only the type of stabilizer was changed, while the addition amount of all stabilizers was fixed at 20% (w / w), and the following four parallel experiments were set up. Among them, mannitol is a sugar alcohol stabilizer, and propylene glycol and glycerol are small molecule alcohol stabilizers. These are all types of stabilizers commonly used in in vitro diagnostic quality control products, and they are representative controls for PEG4000.

[0094] Group 3-1: PEG4000 + 1,2-propanediol (mixed in a 1:1 mass ratio) Group 3-2: PEG4000 + Glycerin (mixed in a 1:1 mass ratio) Group 3-3: Mannitol + PEG4000 (mixed in a 1:1 mass ratio) Groups 3-4: PEG4000 After all groups are prepared, shake well and dispense into high-density polyethylene vials at a volume of 2±0.2mL. Seal and store in the dark.

[0095] 2. Performance Test Results and Data Analysis (1) Repeatability and precision test results Table 7. Repeatability and precision test results of quality control solutions with different stabilizers (CV%, n=5)

[0096] As shown in Table 7, Group 3-1 (PEG4000 + 1,2-propanediol) exhibited the best repeatability and precision, with biochemical detection CVs as low as 0.36% and 0.29% for blood glucose and uric acid, respectively. The electrochemical current response CV was also controlled within 2.8%, significantly better than other groups. Group 3-4 (PEG4000 alone) performed slightly worse, but still met the industry requirement of CV ≤ 5% for quality control products. Group 3-2 (PEG4000 + glycerol) showed a slightly higher CV, possibly related to the high viscosity and hygroscopicity of glycerol. Group 3-3 (mannitol + PEG4000) showed relatively poor repeatability, with a uric acid current CV close to 4.2%, indicating that the stabilizing effect of mannitol combined with PEG4000 might be weakened due to differences in solubility or intermolecular competition. The core mechanism of this result is that PEG4000 and 1,2-propanediol form a synergistic stabilizing effect. PEG4000 forms a protective hydration film on the surface of analyte molecules through steric hindrance, while 1,2-propanediol, as a small molecule co-solvent, can further improve the homogeneity and fluidity of the system. The complementarity of the two can minimize intermolecular aggregation and non-specific adsorption. However, glycerol has too high viscosity and mannitol has relatively poor solubility, so neither can achieve the same synergistic protective effect.

[0097] (2) Results of accelerated stability test Table 8. Accelerated stability test results of quality control solutions with different stabilizers (65℃ / 2 weeks, deviation %) relative to the room temperature control group

[0098] As shown in Table 8, Group 3-1 (PEG4000 + 1,2-propanediol) exhibited the best accelerated stability. After two weeks of accelerated aging at 65℃, the deviations in blood glucose detection were all controlled within ±0.8%, and the deviations in uric acid detection were all controlled within ±1.5%, far below the acceptable limit of ±10%. Group 3-4 (PEG4000 alone) showed significantly deteriorated stability, with high-concentration uric acid deviations reaching -8.95%, close to the industry's acceptable upper limit. Groups 3-2 (PEG4000 + glycerol) and 3-3 (mannitol + PEG4000) also showed significant deterioration in stability, with high-concentration uric acid deviations reaching -12.68% and -14.25%, respectively, both exceeding the acceptable range of ±10% and failing to meet the requirement of a shelf life of more than two years. The results validated the synergistic stabilizing effect of PEG4000 and 1,2-propanediol: the combined use of the two can form a denser hydration layer around the analyte molecules, more effectively isolating dissolved oxygen and oxidative active sites in the system, and inhibiting the oxidative degradation reaction of the analyte; while PEG4000 alone or in combination with glycerol or mannitol cannot achieve the same long-term protective effect.

[0099] (3) Results of anti-cross interference test Table 9. Cross-interference test results of quality control solutions with different stabilizers (dual index vs. single index, relative deviation %)

[0100] As shown in Table 9, group 3-1 (PEG4000 + 1,2-propanediol) exhibits the best anti-cross-interference performance. The concentration deviation of the reference method for both dual-index and single-index detection results is less than 0.15%, and the current response deviation is less than 0.35%, proving that this stabilizer combination does not cause cross-interference between glucose and uric acid and has no effect on enzymatic reactions and electrochemical responses. 1,2-propanediol, as a small molecule co-solvent, improves the system homogeneity and does not interfere with electrochemical detection itself; PEG4000, as a neutral long-chain polymer, lacks charge and active functional groups, and does not undergo non-specific adsorption on the electrode surface, thus having no inhibitory effect on enzyme activity. The combination of these two components maintains the bioinertness of PEG4000 while further improving the dispersibility and flowability of the system, making it the optimal stabilizer combination for this dual-index composite quality control solution. Group 3-3 (mannitol + PEG4000) shows a relatively large cross-interference deviation, which may be related to the slight influence of mannitol on the electrode surface or enzyme activity.

[0101] The combination of PEG4000 and 1,2-propanediol (1:1) provides the best synergistic stabilizing effect for both glucose and uric acid analytes in the composite quality control solution. It simultaneously improves the system's repeatability, precision, long-term storage stability, and resistance to cross-interference, significantly outperforming the PEG4000+glycerol combination, mannitol+PEG4000 combination, and PEG4000 alone. Particularly in terms of accelerated stability, after aging at 65℃ for 2 weeks, the deviation of high-concentration uric acid in groups 3-2 to 3-4 exceeded the industry acceptable limit of ±10%, while group 3-1 remained within ±1.5%, fully demonstrating the excellent long-term protective effect of the preferred stabilizer combination of this invention. The selection of PEG4000+1,2-propanediol as the preferred stabilizer combination in this invention is supported by sufficient experimental data.

[0102] Example 4: Effect of different ratios of PEG4000 to 1,2-propanediol on the performance of the composite quality control solution This embodiment is used to verify the effect of different mass ratios of PEG4000 and 1,2-propanediol on the repeatability, stability and anti-cross-interference performance of the composite quality control solution, and to determine the preferred ratio range of the present invention.

[0103] 1. Preparation of quality control solution The basic formulation was fixed as follows: a HEPES buffer system, concentration 2 mol / L, pH=5.0±0.1; a mixture of sodium chloride and calcium chloride as inorganic salts, in a ratio of 50:1, with a total addition of 5% (w / w); Proclin-300 as a preservative, added at 0.5% (w / w); and Allura Red as a blood-simulating dye, added at 0.2% (w / w). The low-concentration control solution contained 40 mg / dL glucose and 250 μmol / L uric acid; the high-concentration control solution contained 250 mg / dL glucose and 750 μmol / L uric acid. For specific preparation methods, refer to Example 1.

[0104] With the total stabilizer addition fixed at 20% (w / w), and only the mass ratio of PEG4000 to 1,2-propanediol varied, the following 5 parallel experiments were set up: Group 4-1: PEG4000 : 1,2-Propanediol = 0.3 : 1 Group 4-2: PEG4000 : 1,2-Propanediol = 0.5 : 1 Group 4-3: PEG4000 : 1,2-Propanediol = 1 : 1 Group 4-4: PEG4000 : 1,2-Propanediol = 3 : 1 Groups 4-5: PEG4000 : 1,2-Propanediol = 4 : 1 After all groups are prepared, shake well and dispense into high-density polyethylene vials at a volume of 2 ± 0.2 mL. Seal and store in the dark.

[0105] 2. Performance Test Results and Data Analysis (1) Repeatability and precision test results Table 10. Repeatability and precision test results (CV%, n=5) of quality control solutions with different PEG4000:1,2-propanediol ratios.

[0106] As shown in Table 10, when the ratio of PEG4000 to 1,2-propanediol is within the range of 0.5:1 to 3:1 as defined in this invention, the CV% of all test items in the quality control solution is less than 5%, fully meeting industry requirements. Group 4-3 (1:1) performs better than Groups 4-2 and 4-4, with a low CV for blood glucose biochemistry (0.36%), a low CV for uric acid biochemistry (0.29%), and current response CVs all controlled within 2.8%. When the ratio exceeds the lower limit (0.3:1), the PEG4000 content is severely insufficient, the steric hindrance protection effect is lost, repeatability deteriorates significantly, and the CV for uric acid current reaches as high as 7.32%. When the ratio exceeds the upper limit (4:1), the 1,2-propanediol content is too low, the system homogeneity is poor, and the excessive PEG4000 leads to excessive viscosity, also significantly deteriorating repeatability. The results demonstrate that the ratio of PEG4000 to 1,2-propanediol needs to be within the range of 0.5:1 to 3:1 as defined in this invention, with 1:1 being the preferred ratio.

[0107] (2) Results of accelerated stability test Table 11 Accelerated stability test results of quality control solutions with different PEG4000:1,2-propanediol ratios (65℃ / 2 weeks, deviation %) relative to the room temperature control group

[0108] As shown in Table 11, group 4-3 (1:1) exhibits superior accelerated stability. After two weeks of accelerated aging at 65℃, the blood glucose deviation was controlled within ±0.8%, and the uric acid deviation within ±1.5%. When the ratio is within the range of 0.5:1 to 3:1 defined in this invention, the uric acid deviation is controlled within ±3.0%, meeting industry requirements. When the ratio exceeds the lower limit (0.3:1), due to insufficient protection from PEG4000, uric acid undergoes severe oxidative degradation, resulting in a high-concentration uric acid deviation of -18.65%, far exceeding the acceptable limit of ±10%. When the ratio exceeds the upper limit (4:1), due to insufficient 1,2-propanediol, the system's antioxidant capacity is weakened, leading to a high-concentration uric acid deviation of -14.32%, also exceeding the acceptable range. These results demonstrate that the 0.5:1 to 3:1 ratio range defined in this invention can ensure the long-term storage stability of the quality control solution.

[0109] (3) Results of anti-cross interference test Table 12. Cross-interference test results of quality control solutions with different PEG4000:1,2-propanediol ratios (dual index vs. single index, relative deviation %)

[0110] As shown in Table 12, within the ratio range of 0.5:1 to 3:1 defined in this invention, the deviations between the dual-index and single-index detection results are small, with the reference method concentration deviation being less than 0.3% and the current response deviation being less than 0.7%. When the ratio exceeds the range, the degradation byproducts of the analyte increase due to system instability, and the cross-interference deviation increases significantly.

[0111] The mass ratio of PEG4000 to 1,2-propanediol is a key parameter affecting the performance of the composite quality control solution. When the ratio is within the range of 0.5:1 to 3:1 as defined in this invention, the repeatability, precision, long-term storage stability, and resistance to cross-interference of the quality control solution all meet industry requirements; 1:1 is a more preferred ratio, where all performance indicators reach optimal levels. When the ratio exceeds this range, the performance of the quality control solution deteriorates significantly and fails to meet the quality requirements of the quality control products. This invention limits the ratio of PEG4000 to 1,2-propanediol to 0.5:1 to 3:1, preferably 1:1, and is supported by sufficient experimental data.

[0112] Example 5: Effect of different stabilizer dosages on the performance of composite quality control liquid This embodiment is used to verify the effect of different stabilizer addition amounts on the repeatability, stability and anti-cross-interference performance of the composite quality control liquid, and to determine the preferred stabilizer addition range of the present invention.

[0113] 1. Preparation of quality control solution The basic formulation was fixed as follows: a HEPES buffer system, concentration 2 mol / L, pH=5.0±0.1; a mixture of sodium chloride and calcium chloride as inorganic salts, in a ratio of 50:1, with a total addition of 5% (w / w); Proclin-300 as a preservative, added at 0.5% (w / w); and Allura Red as a blood-simulating dye, added at 0.2% (w / w). The low-concentration control solution contained 40 mg / dL glucose and 250 μmol / L uric acid; the high-concentration control solution contained 250 mg / dL glucose and 750 μmol / L uric acid. For specific preparation methods, refer to Example 1.

[0114] The stabilizer used was the preferred combination selected from Examples 3 and 4 (PEG4000 + 1,2-propanediol, 1:1 mixture). Only the total amount of stabilizer added was varied, and the following 6 parallel experiments were conducted: Group 5-1: Stabilizer addition amount 5% (w / w) Group 5-2: Stabilizer addition 10% (w / w) Group 5-3: Stabilizer addition 20% (w / w) Group 5-4: Stabilizer addition 30% (w / w) Group 5-5: Stabilizer addition 40% (w / w) Groups 5-6: Stabilizer addition 50% (w / w) After all groups are prepared, shake well and dispense into high-density polyethylene vials at a volume of 2 ± 0.2 mL. Seal and store in the dark.

[0115] 2. Performance Test Results and Data Analysis (1) Repeatability and precision test results Table 13 Repeatability and precision test results of quality control solutions with different stabilizer addition amounts (CV%, n=5)

[0116] As shown in Table 13, when the stabilizer dosage is within the range of 10% to 40% as defined in this invention, the CV% of all test items in the quality control solution is less than 5%, fully meeting industry requirements. Group 5-3 (20% dosage) exhibits superior performance, with a blood glucose biochemistry CV as low as 0.36%, a uric acid biochemistry CV as low as 0.29%, and current response CVs all controlled within 2.8%. When the dosage is too low (5%), the stabilizer provides insufficient protection for the analytes, resulting in significantly deteriorated repeatability; the uric acid current CV reaches as high as 7.32%, exceeding the industry acceptable upper limit. When the dosage is too high (50%), the system viscosity is too high, affecting solution homogeneity and dispensing consistency, and repeatability also deteriorates significantly; the uric acid current CV approaches 6%. These results demonstrate that the stabilizer dosage needs to be within a moderate range. Too low a dosage fails to form an effective protective layer, while too high a dosage affects the physical properties of the system. The 10% to 40% range defined in this invention is the optimal dosage range, with 20% being a more preferred dosage.

[0117] (2) Results of accelerated stability test Table 14 Accelerated stability test results of quality control solutions with different stabilizer addition amounts (65℃ / 2 weeks, deviation %) relative to the room temperature control group

[0118] As shown in Table 14, group 5-3 (20% addition) exhibits superior accelerated stability. After two weeks of accelerated aging at 65℃, the blood glucose deviation was controlled within ±0.8%, and the uric acid deviation within ±1.5%. When the addition amount is within the range of 10% to 40% as defined in this invention, the uric acid deviation is controlled within ±3.2%, meeting industry requirements. When the addition amount is too low (5%), stability deteriorates significantly, with a high-concentration uric acid deviation reaching -15.35%, far exceeding the acceptable limit of ±10%. When the addition amount is too high (50%), stability decreases, with a high-concentration uric acid deviation reaching -7.68%, which, although still within the acceptable range, is significantly worse than the preferred range. These results indicate that a stabilizer addition amount of at least 10% is required to form an effective protective hydration layer, with 20% being the preferred balance point. The stability requirements can be met within the range of 10% to 40% as defined in this invention.

[0119] (3) Results of anti-cross interference test Table 15. Cross-interference test results of quality control solutions with different stabilizer addition amounts (dual index vs. single index, relative deviation %)

[0120] As shown in Table 15, when the stabilizer dosage is within the range of 10% to 40% as defined in this invention, the deviations between the dual-index and single-index detection results are small, with the reference method concentration deviation less than 0.4% and the current response deviation less than 0.8%. The deviation is even smaller in the 20% dosage group, demonstrating that the stabilizer has relatively lower interference with the detection system at this dosage. When the dosage is too low (5%), the degradation byproducts due to insufficient analyte protection increase, significantly raising the cross-interference deviation, with the current response deviation approaching 3%. When the dosage is too high (50%), excessive stabilizer may cause slight non-specific adsorption on the electrode surface, leading to a deviation increasing to 1.35%. The 10% to 40% dosage range defined in this invention can minimize interference with the detection system while ensuring sufficient protection.

[0121] Comprehensive data shows that the amount of stabilizer added is a key parameter affecting the performance of the composite quality control solution. When the amount added is within the range of 10% to 40% as defined in this invention, the repeatability, precision, long-term storage stability, and resistance to cross-interference of the quality control solution all meet industry requirements; 20% is the preferred amount, with all performance indicators reaching optimal levels. Too low an amount (<10%) results in insufficient protective effect and significant deterioration in repeatability and stability; too high an amount (>40%) leads to diminishing marginal benefits and may affect the physical properties of the system, with both repeatability and resistance to interference decreasing. This invention limits the stabilizer addition to 10% to 40%, preferably 20%, supported by sufficient experimental data.

[0122] Example 6: Effects of different uric acid sources on the performance of composite quality control solution This embodiment is used to verify the influence of different uric acid sources on the repeatability, stability and anti-interference performance of the composite quality control solution, and to determine the preferred uric acid component form under the acidic system of the present invention.

[0123] 1. Preparation of quality control solution The basic formulation was fixed as follows: a HEPES buffer system, concentration 2 mol / L, pH=5.0±0.1; a mixture of sodium chloride and calcium chloride as inorganic salts, in a ratio of 50:1, with a total addition of 5% (w / w); Proclin-300 as a preservative, added at 0.5% (w / w); and Allura Red as a blood-simulating dye, added at 0.2% (w / w). The low-concentration control solution contained 40 mg / dL glucose and 250 μmol / L uric acid; the high-concentration control solution contained 250 mg / dL glucose and 750 μmol / L uric acid. For specific preparation methods, refer to Example 1.

[0124] To maintain a completely consistent effective molar concentration of uric acid in the system, and to change only the source form of uric acid, two parallel experiments were set up as follows: Group 6-1: A uric acid stock solution was prepared by dissolving uric acid powder in an alkaline aqueous solution (0.1M sodium hydroxide solution). Under these alkaline conditions, uric acid forms soluble urate. When this stock solution is further added to a buffer system with a pH of 4.5–5.3, the urate is reprotonated, converting into molecular uric acid, which then exists stably in the final composite quality control solution in molecular form.

[0125] Group 6-2: Sodium urate (using sodium urate salt as the active ingredient, representing a commonly used source of uric acid in current technology). It is prepared by directly dissolving sodium urate powder in purified water, ensuring consistency with the effective molar concentration of uric acid in Group 6-1.

[0126] After all groups are prepared, shake well and dispense into high-density polyethylene vials at a volume of 2±0.2mL. Seal and store in the dark.

[0127] 2. Performance Test Results and Data Analysis (1) Repeatability and precision test results Table 16. Repeatability precision test results of quality control solutions from different uric acid sources (CV%, n=5)

[0128] As shown in Table 16, there was no significant difference in the CV of blood glucose-related tests between the two groups. The CV of blood glucose biochemistry was less than 0.4%, and the CV of blood glucose current was less than 2.8%, both of which were at an excellent level. However, there was a highly significant difference in the repeatability of uric acid-related tests: the CV of uric acid biochemistry test in group 6-1 (uric acid reservoir) was as low as 0.29%, and the CV of current response was 2.78%, which fully met the industry quality control requirement of CV ≤ 5%. However, the CV of uric acid biochemistry test in group 6-2 (sodium urate) rose to 1.85%, and the CV of current response was as high as 6.85%, which exceeded the industry's acceptable upper limit and could not meet the requirements of high-precision quality control. The core mechanism of this result is as follows: In the slightly acidic system of pH 5.0 of this invention, the uric acid generated by the "alkali dissolution and acid precipitation" method exists mainly in an electrically neutral molecular state, which is consistent with the main form of uric acid in human blood. The redox reaction on the electrode surface has good uniformity, so the repeatability of the detection results is excellent. However, when sodium urate is added directly to the slightly acidic system, it will undergo a non-uniform protonation process, and some areas will be supersaturated to form local precipitation, which will lead to a decrease in the uniformity of the effective concentration of uric acid in the system, thereby causing fluctuations in the detection results and deterioration of repeatability.

[0129] (2) Results of accelerated stability test Table 17. Accelerated stability test results of control solutions from different uric acid sources (65℃ / 2 weeks, deviation %) relative to the room temperature control group

[0130] As shown in Table 17, there was no significant difference in the accelerated stability deviation of blood glucose between the two groups, with the deviation controlled within ±0.9%, far below the industry's acceptable limit of ±10%, indicating excellent performance. However, there was a highly significant difference in the stability of uric acid: the uric acid detection deviation of group 6-1 (uric acid reservoir) was controlled within ±1.5%, demonstrating excellent long-term storage stability; while the deviation of low-concentration uric acid in group 6-2 (sodium urate) rose to +7.85%, and the deviation of high-concentration uric acid exceeded -13.62%, exceeding the industry's acceptable limit of ±10%, and failing to meet the requirement of a shelf life of more than 2 years. The core mechanism of this result is that the molecular uric acid generated in situ from disodium urate can form a stable hydrogen bond encapsulation network with the long-chain molecules of PEG4000, effectively "encapsulating" it, isolating dissolved oxygen and oxidation sites in the system, and significantly improving its antioxidant capacity. In contrast, the protonation process of directly added sodium urate is uncontrolled in the acidic system, resulting in uric acid particles with many surface defects and no stabilizer protection. When exposed to the system, they are prone to oxidative degradation. At the same time, the sodium ions generated by dissociation will accelerate the oxidation side reaction of uric acid, further exacerbating the decrease in concentration.

[0131] (3) Results of anti-cross interference test Table 18 Results of anti-cross-interference test of quality control solutions from different uric acid sources (dual index vs. single index, relative deviation %)

[0132] As shown in Table 18, there was no significant difference in the deviation of blood glucose-related tests between the two groups. The deviation of blood glucose reference values ​​was less than 0.15%, and the deviation of blood glucose current response was less than 0.4%, both at extremely low levels. However, the anti-interference performance of uric acid-related tests showed a highly significant difference: the deviation of dual-index and single-index detection in group 6-1 (uric acid reservoir) was less than 0.35%, with no significant cross-interference; while in group 6-2 (sodium urate), the deviation of uric acid reference values ​​rose to -2.35%, and the deviation of current response exceeded -3.85%, indicating significant detection deviation. The core reason for this result is that the sodium ions generated by the dissociation of sodium urate in a slightly acidic system change the ionic strength of the system, affecting the double-layer structure and electron transfer efficiency of the electrode surface, thus interfering with the electrochemical response of uric acid; at the same time, the byproducts generated by the degradation of sodium urate further affect the stability of the detection system, leading to significant deviations in the detection results between the dual-index system and the single-index system. Previous studies have shown that increased sodium ion concentration alters the double-layer capacitance and zero-charge potential at the electrode / solution interface, thereby affecting the baseline stability and signal response intensity of electrochemical detection. In contrast, molecular-state uric acid does not alter the ionic environment of the system, exhibiting better compatibility with the detection system and eliminating the risk of cross-interference.

[0133] In the slightly acidic system of pH 4.5–5.3 of this invention, using a uric acid reservoir (0.6% uric acid dissolved in 0.1M NaOH, generating molecular uric acid in situ via an "alkali dissolution and acid precipitation" method) as the uric acid source, its performance is significantly superior to that of sodium urate commonly used in existing technologies. It simultaneously achieves excellent repeatability and precision (uric acid biochemical CV ≤ 0.29%, current CV ≤ 2.78%), long-term storage stability (65℃ / 2 weeks deviation ≤ ±1.5%), and resistance to cross-interference (deviation ≤ ±0.35%). It should be noted that the preferred uric acid reservoir in this invention is based on a slightly acidic pH range of 4.5–5.3. Under this specific pH condition, molecular uric acid is necessarily preferred. While sodium urate can also exist stably if the system pH > 6.5, one of the core innovations of this invention is precisely controlling the pH within the slightly acidic range to inhibit uric acid degradation. The present invention selects uric acid storage solution as the preferred source of uric acid, which has sufficient experimental data and mechanism support, and can effectively solve the technical problems of poor stability and insufficient detection consistency of existing sodium urate components in acidic systems.

[0134] Example 7: Effects of different inorganic salt compositions and ratios on the performance of composite quality control solutions This embodiment is used to verify the effects of different inorganic salt compositions and the mass ratio of sodium chloride to calcium chloride on the repeatability, stability and anti-cross-interference performance of the composite quality control solution, and to determine the preferred inorganic salt system and preferred ratio range of the present invention.

[0135] 1. Preparation of quality control solution The basic formulation was fixed as follows: HEPES buffer system, concentration 2 mol / L, pH=5.0±0.1; PEG4000 and 1,2-propanediol as stabilizers, with a weight ratio of 1:1, total addition 20% (w / w); Proclin-300 as preservative, addition 0.5% (w / w); Allura Red as blood-simulating dye, addition 0.2% (w / w). The low-concentration control solution contained 40 mg / dL glucose and 250 μmol / L uric acid; the high-concentration control solution contained 250 mg / dL glucose and 750 μmol / L uric acid. For specific preparation methods, refer to Example 1.

[0136] With the total amount of inorganic salts fixed at 5% (w / w), and only the mass ratio of sodium chloride to calcium chloride varied, the following 7 parallel experiments were set up: Group 7-1: NaCl Group 7-2: NaCl : CaCl2 = 200 : 1 Group 7-3: NaCl : CaCl2 = 100 : 1 Group 7-4: NaCl : CaCl2 = 50 : 1 Group 7-5: NaCl : CaCl2 = 10 : 1 Group 7-6: NaCl : CaCl2 = 5 : 1 Group 7-7: CaCl2 After all groups are prepared, shake well and dispense into high-density polyethylene vials at a volume of 2±0.2 mL. Seal and store in the dark.

[0137] 2. Performance Test Results and Data Analysis (1) Repeatability and precision test results Table 19 Repeatability and precision test results of quality control solutions with different inorganic salt ratios (CV%, n=5)

[0138] As shown in Table 19, when the ratio of NaCl to CaCl2 is within the range of 100:1 to 10:1 as defined in this invention (groups 7-3 to 7-5), the CV% of all test items in the quality control solution is less than 5%, fully meeting industry requirements. Among them, group 7-4 (50:1) performs relatively better, with a blood glucose biochemistry CV as low as 0.36%, a uric acid biochemistry CV as low as 0.29%, and the current response CV controlled within 2.8%. When the ratio exceeds this range (groups 7-1, 7-2, 7-6, 7-7), repeatability deteriorates significantly: when sodium chloride is used alone (group 7-1) or the ratio is too high (groups 7-2, 7-6), the calcium chloride content is too low or too high, both leading to a uric acid current CV exceeding 5%; calcium chloride alone (group 7-7) has the worst repeatability, with a uric acid current CV as high as 10.85%, failing to meet the basic requirements of the quality control product. The core mechanism behind this result is that sodium chloride primarily maintains the ionic strength and osmotic pressure of the system, providing a suitable ionic environment for enzymatic reactions; trace amounts of calcium chloride, containing calcium ions, act as cofactors for glucose oxidase and uricase oxidase, activating enzyme activity and improving detection sensitivity and consistency. When used in combination, sodium chloride provides the basic ionic environment, while calcium chloride provides enzyme activation, synergistically enhancing detection repeatability. When the ratio deviates from the optimal range, insufficient calcium ions lead to inadequate activation, while excessive calcium ions disrupt ionic balance, both resulting in decreased repeatability.

[0139] (2) Results of accelerated stability test Table 20 Accelerated stability test results of quality control solutions with different inorganic salt ratios (65℃ / 2 weeks, deviation %) relative to the room temperature control group

[0140] As shown in Table 20, group 7-4 (50:1) exhibits superior accelerated stability. After two weeks of accelerated aging at 65℃, the blood glucose deviation is controlled within ±0.8%, and the uric acid deviation is controlled within ±1.5%, far below the industry acceptable limit of ±10%. When the ratio is within the range of 100:1 to 10:1 as defined in this invention (groups 7-3 to 7-5), the uric acid deviation is controlled within ±3.0%, meeting industry requirements. When the ratio exceeds the range, stability deteriorates significantly: with sodium chloride alone (group 7-1) or with excessively high ratios (groups 7-6 and 7-7), the high-concentration uric acid deviation reaches -12.35%, -14.32%, and -18.62%, respectively, all exceeding the acceptable limit of ±10%; at a ratio of 200:1 (group 7-2), the high-concentration uric acid deviation is -8.95%, close to the upper limit. These results indicate that the combined use of sodium chloride and calcium chloride can improve long-term storage stability by maintaining the ion balance of the system and through the stabilizing effect of calcium ions on enzymes. Conversely, when sodium chloride is used alone, the lack of calcium ion stabilization leads to accelerated analyte degradation. When calcium chloride is used alone, the osmotic pressure imbalance and the potential for high-concentration calcium ions to catalyze oxidation reactions result in severe analyte degradation. The 100:1 to 10:1 ratio range specified in this invention ensures the long-term storage stability of the quality control solution.

[0141] (3) Results of anti-cross interference test Table 21 Results of cross-interference test for quality control solutions with different inorganic salt ratios (dual index vs. single index, relative deviation %)

[0142] As shown in Table 21, within the 100:1 to 10:1 ratio range specified in this invention (groups 7-3 to 7-5), the deviations between the dual-index and single-index detection results are relatively small, with the reference method concentration deviation less than 0.3% and the current response deviation less than 0.6%. Group 7-4 (50:1) shows a relatively smaller deviation, demonstrating that the inorganic salt composition has a relatively lower interference effect on the detection system at this ratio. When the ratio exceeds the range, the cross-interference deviation increases significantly due to enzyme activity changes caused by ion imbalance or electrode response interference: the current response deviations of groups 7-1 and 7-2 are close to 1.9%, the current response deviation of group 7-6 exceeds 3.2%, and the current response deviation of group 7-7 exceeds 3.5%, all exceeding the acceptable range. The core reason is that when calcium ions are insufficient, the activities of the two enzymes are insufficient and inconsistent, leading to increased detection deviation when the dual indicators coexist; when calcium ions are excessive, the high concentration of calcium ions severely interferes with the electron transfer efficiency on the electrode surface and simultaneously inhibits the reaction kinetics of the two enzymes to varying degrees, resulting in a significant increase in cross-interference.

[0143] The inorganic salt composition and the mass ratio of sodium chloride to calcium chloride are key parameters affecting the performance of the composite quality control solution. When the ratio is within the range of 100:1 to 10:1 as defined in this invention, the repeatability, precision, long-term storage stability, and resistance to cross-interference of the quality control solution all meet industry requirements; among them, 50:1 is the preferred ratio, with all performance indicators reaching optimal levels. When the ratio exceeds this range (including the use of sodium chloride alone or calcium chloride alone), the performance of the quality control solution deteriorates significantly, and some indicators fail to meet the quality requirements of the quality control product. This invention limits the ratio of NaCl to CaCl2 to 100:1 to 10:1, preferably 50:1, and has sufficient experimental data to support this.

[0144] Based on the experimental results of Examples 1-7, it can be seen that the present invention precisely controls the pH of the buffer system within a slightly acidic range of 4.5-5.3 (preferably 5.0), selects PEG4000 and 1,2-propanediol (preferably a mass ratio of 1:1) as a synergistic stabilizer combination (addition amount 10%-40%, preferably 20%), uses sodium chloride and calcium chloride (preferably a mass ratio of 50:1) as an optimized inorganic salt system (ratio 100:1-10:1), and introduces molecular uric acid as a source of uric acid through the "alkali dissolution and acid precipitation" method. The key parameters form a multi-dimensional synergistic effect. The slightly acidic pH provides a stable environment for the existence of molecular uric acid and glucose. The synergistic combination of PEG4000 and 1,2-propanediol forms a dense protective hydration layer around the analyte molecules to isolate oxidative attack. The combination of sodium chloride and calcium chloride maintains ion balance while activating enzyme activity to improve detection sensitivity. The uric acid reservoir itself avoids ionic strength interference caused by the introduction of sodium ions. The four dimensions work synergistically from the four levels of environment, protection, activation and source, and none of them can be omitted. This synergistic system enables the composite quality control solution to simultaneously possess excellent repeatability and precision (CV <3%), long-term storage stability (absolute deviation <2% at 65℃ / 2 weeks), and resistance to cross-interference (absolute deviation <0.6%). It achieves stable coexistence, simultaneous detection, and non-interference of glucose and uric acid analytes within the same system, effectively solving the four core technical challenges that have long existed in existing multi-parameter quality control solutions: cumbersome operation of multiple detections, poor stability of multiple components, severe cross-interference, and insufficient adaptability to different scenarios. It provides an efficient, accurate, and convenient quality control solution for blood glucose / uric acid dual-parameter detection systems.

[0145] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," "some implementations," or "some examples," etc., refer to specific features, structures, materials, or characteristics described in connection with that embodiment or example, which are included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0146] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.

Claims

1. A quality control solution for the joint detection of glucose and uric acid, characterized in that, The formula for the quality control solution is as follows: Glucose, dissolved uric acid, buffer solution, stabilizer, inorganic salts, preservatives, blood-simulated dyes, The buffer solution has a pH of 4.5 to 5.3, and the dissolved uric acid in the quality control solution is obtained by the following method: S1: Dissolve uric acid powder in an alkaline aqueous solution to obtain uric acid stock solution; S2: Mix the uric acid stock solution with the buffer solution so that the uric acid in the quality control solution exists in a dissolved uric acid form. The stabilizer comprises polyethylene glycol and propylene glycol, wherein the weight ratio of polyethylene glycol to propylene glycol is (0.5~3):1, and the polyethylene glycol is PEG4000. The inorganic salt includes sodium chloride and calcium chloride, wherein the weight ratio of sodium chloride to calcium chloride is (10~100):1; Based on the total weight of the quality control solution, the content of the stabilizer is 10%–40%, the content of the inorganic salt is 0.1%–5%, the content of the preservative is 0.1%–2%, and the content of the blood-simulated dye is 0.1%–2%. The buffer solution is HEPES buffer, the preservative is Proclin-300, and the blood-simulating dye is Allura Red.

2. The quality control solution of claim 1, wherein, The concentration of the buffer solution is 0.01 mol / L to 2 mol / L.

3. The quality control solution of claim 1, wherein, The working concentration of glucose in the quality control solution is 10 mg / dL to 600 mg / dL; The working concentration of the dissolved uric acid is 200 μmol / L to 1000 μmol / L.

4. Use of the quality control solution according to any one of claims 1 to 3 in a glucose detection system, a uric acid detection system, and a combined glucose and uric acid detection system.

5. A reagent kit, characterized in that, The quality control solution includes any one of claims 1 to 3.

6. A method for confirming whether an electrochemical detection system is operating normally, characterized in that, include: The quality control solution for the combined detection of glucose and uric acid, as described in any one of claims 1 to 3, is added to the sample application port of the test card or the sample application area of ​​the test strip. The electrochemical detection system outputs blood glucose and uric acid values. The blood glucose and uric acid values ​​are compared with the nominal target value range of the quality control solution. Based on the comparison results, it is determined whether the electrochemical detection system and the test card or test strip are in normal condition.

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