A method and application and device for automatically identifying quality control liquid and samples

Abstract

The application relates to a method for automatically identifying a quality control liquid and a sample, comprising the following steps: applying an alternating voltage to an electrode of an electrochemical testing device to detect an impedance value of a sample to be measured; judging whether the sample to be measured is the quality control liquid or the sample according to the impedance value; and the quality control liquid containing a lithium salt. The application also relates to an application of the method and a biosensor device.

Description

Technical Field

[0001] This invention belongs to the field of in vitro diagnostic technology, and in particular relates to a method, application and device for automatic identification of quality control solutions and samples. Background Technology

[0002] Quantitatively determining the concentrations of important substances in human blood, such as blood glucose, blood ketones, blood lactate, cholesterol, uric acid, and triglycerides, is crucial for clinical diagnosis and health management. Currently, electrochemical testing systems are primarily used to measure the concentration of target analytes in blood. To ensure the reliability and accuracy of these systems, regular quality control testing is necessary to determine if they are functioning correctly. For example, common blood glucose testing systems include a blood glucose control solution. Operators must measure the control solution at regular intervals. If the measured value exceeds the control concentration range of the solution, it indicates a decrease in the reliability of the blood glucose testing system, rendering it unsuitable for clinical use.

[0003] A common quality control measurement mode for electrochemical testing systems involves the operator manually selecting the control solution measurement mode on the electrochemical testing instrument, installing the electrodes of the electrochemical testing device into the instrument, and adding the control solution to the electrodes. In this mode, the operator needs to manually switch between two measurement modes: control solution and actual sample (e.g., blood). If the operator performs actual sample measurements in control solution mode or vice versa, there is a risk of inaccurate test results, which may not guide the operator to make correct clinical judgments.

[0004] Therefore, this application provides a new measurement method for automatically distinguishing between quality control solutions and actual samples in an electrochemical testing system. This method is of great significance for simplifying quality control operation steps, avoiding operational errors in manual quality control mode, and improving the accuracy of measurement results. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention provides a method for automatic identification of quality control solutions and samples, comprising: applying an alternating voltage to the electrodes of an electrochemical testing device and detecting the impedance value of the sample to be tested; determining, based on the impedance value, whether the sample to be tested is a quality control solution or a sample; wherein the quality control solution contains lithium salt.

[0006] In some embodiments of the present invention, the mass concentration of lithium salt in the quality control solution is 1%-10%.

[0007] In some embodiments of the present invention, the mass concentration of lithium salt in the quality control solution is 1%-5%.

[0008] In some embodiments of the present invention, the mass concentration of lithium salt in the quality control solution is 1%-2%.

[0009] In some embodiments of the present invention, the lithium salt is selected from LiFL6, lithium perchlorate, or lithium tetrafluoroborate.

[0010] According to the present invention, the lithium salt is LiFL6.

[0011] In some embodiments of the present invention, the quality control solution also includes other conventional components well known in the art, such as the target analyte, thickener, and buffer.

[0012] In some embodiments of the present invention, the amplitude of the AC voltage is 0.1-0.42V and the frequency is 20000-40000Hz.

[0013] In some embodiments of the present invention, the amplitude of the AC voltage is 0.2-0.42V and the frequency is 30000-40000Hz.

[0014] According to the present invention, the amplitude of the AC voltage is, for example, 0.2V, 0.25V, 0.3V, 0.32V, 0.34V, 0.35V, 0.37V, 0.39V, 0.4V, 0.41V, or 0.42V, and the frequency is, for example, 30000Hz, 32000Hz, 35000Hz, 36000Hz, 38000Hz, or 40000Hz.

[0015] In some embodiments of the present invention, determining whether the sample to be tested is a quality control liquid or a sample based on the impedance value includes: comparing the impedance value with a preset impedance range to determine the impedance range to which the impedance value belongs, and determining whether the sample to be tested is a quality control liquid or a sample based on the impedance range to which the impedance value belongs.

[0016] In some embodiments of the present invention, the impedance range includes the quality control liquid impedance range and the sample impedance range.

[0017] In some embodiments of the present invention, the method for determining the impedance range includes:

[0018] S1. The method for determining the sample impedance range includes: preparing multiple blood samples with a hematocrit of 5%-20% and multiple blood samples with a hematocrit of 70%-80%, measuring the impedance value of each sample, and determining the sample impedance range based on the measured impedance value;

[0019] S2. The method for determining the impedance range of the quality control solution includes: preparing multiple quality control solutions with a lithium salt mass concentration of 1%-10%, measuring the impedance value of each quality control solution, and determining the impedance range of the quality control solution based on the measured impedance value.

[0020] In some embodiments of the present invention, the average impedance value of multiple blood samples with a hematocrit of 5%-20% is used as the lower limit of the sample impedance range, and / or, the average impedance value of multiple blood samples with a hematocrit of 70%-80% is used as the upper limit of the sample impedance range; or, 80%-100% of the minimum impedance value of multiple blood samples is used as the lower limit of the sample impedance range, and / or, 100%-120% of the maximum impedance value of multiple blood samples is used as the upper limit of the sample impedance range.

[0021] In other embodiments of the present invention, 80%-100% of the average impedance value of multiple blood samples with a hematocrit of 5%-20% is used as the lower limit of the range, and / or 100%-120% of the average impedance value of multiple blood samples with a hematocrit of 70%-80% is used as the upper limit of the sample impedance range.

[0022] In some embodiments of the present invention, 80%-100% of the minimum impedance value of multiple control solutions is used as the lower limit of the impedance range of the control solutions, and / or 100%-120% of the maximum impedance value of multiple control solutions is used as the upper limit of the impedance range of the control solutions.

[0023] In some embodiments of the present invention, the sample impedance range does not overlap with the quality control liquid impedance range.

[0024] In some embodiments of the present invention, the method for automatic identification of quality control solution and sample specifically includes the following steps:

[0025] S1, apply an alternating current voltage to the electrodes of the electrochemical testing device to detect the impedance value of the sample to be tested; wherein, the amplitude of the alternating current voltage is 0.1-0.42V and the frequency is 20000-40000Hz; preferably, the amplitude of the alternating current voltage is 0.2-0.42V and the frequency is 30000-40000Hz.

[0026] S2, compare the impedance value measured in step S1 with a preset impedance range to determine the impedance range to which the impedance value belongs; wherein, the impedance range includes the quality control liquid impedance range and the sample impedance range;

[0027] S3, determine whether the sample to be tested is a quality control solution or a sample based on the impedance range to which the impedance value belongs. The determination method includes: if the impedance value is within the impedance range of the quality control solution, then the sample to be tested is determined to be a quality control solution; if the impedance value is within the impedance range of the sample, then the sample to be tested is determined to be a sample.

[0028] Preferably, the impedance range is determined before step S2; the method for determining the impedance range includes: preparing multiple blood samples with a hematocrit of 5%-20% and multiple blood samples with a hematocrit of 70%-80%, measuring the impedance value of each sample, and determining the sample impedance range based on the measured impedance values; preferably, the average impedance value of the multiple blood samples with a hematocrit of 5%-20% is used as the lower limit of the sample impedance range, and / or, the average impedance value of the multiple blood samples with a hematocrit of 70%-80% is used as the lower limit of the sample impedance range. The upper limit value; or, 80%-100% of the minimum impedance value of multiple blood samples as the lower limit value of the sample impedance interval, and / or, 100%-120% of the maximum impedance value of multiple blood samples as the upper limit value of the sample impedance interval; more preferably, 80%-100% of the average impedance value of multiple blood samples with a hematocrit of 5%-20% as the lower limit value of the interval, and / or, 100%-120% of the average impedance value of multiple blood samples with a hematocrit of 70%-80% as the upper limit value of the sample impedance interval;

[0029] Multiple control solutions with a lithium salt mass concentration of 1%-10% are prepared, and the impedance value of each control solution is measured. The impedance range of the control solution is determined based on the measured impedance value. Preferably, 80%-100% of the minimum impedance value of the multiple control solutions is taken as the lower limit of the impedance range of the control solution, and / or 100%-120% of the maximum impedance value of the multiple control solutions is taken as the upper limit of the impedance range of the control solution.

[0030] More preferably, the sample impedance range does not overlap with the quality control liquid impedance range.

[0031] In some embodiments of the present invention, the sample includes blood.

[0032] According to the present invention, the analytes in the sample are blood glucose, uric acid, lactic acid or cholesterol.

[0033] In some embodiments of the present invention, the quality control solution is a blood glucose quality control solution, a uric acid quality control solution, a lactic acid quality control solution, or a cholesterol quality control solution.

[0034] The second aspect of the present invention provides an application of the method described in the first aspect in the in vitro detection of human blood.

[0035] In some embodiments of the present invention, the application includes the use of detecting blood glucose, uric acid, lactic acid, or cholesterol in human blood in vitro.

[0036] A third aspect of the present invention provides a biosensor device for implementing the method of the first aspect or the application of the second aspect, characterized in that the biosensor device comprises:

[0037] The power module is used to apply AC voltage to the electrodes of the electrochemical testing device;

[0038] Impedance measurement module is used to measure the impedance value when an AC voltage is applied to the electrodes of an electrochemical testing device;

[0039] A storage module is used to store preset impedance ranges; the storage module includes an impedance range acquisition unit and an impedance range storage unit, the impedance range acquisition unit is used to acquire the impedance range of the quality control liquid and the impedance range of the sample, and store the impedance range in the impedance range storage unit; preferably, the impedance range of the quality control liquid and the impedance range of the sample do not overlap with each other in terms of impedance range;

[0040] The judgment module, coupled with the impedance measurement module and the storage module, is used to compare the measured impedance value with a preset impedance range, determine the impedance range to which the measured impedance value belongs, and determine whether the sample to be tested is a quality control liquid or a sample based on the impedance range to which the impedance value belongs.

[0041] The beneficial effects of this invention are:

[0042] The method for automatic identification of quality control solutions and samples provided by this invention can simplify quality control operation steps, avoid operational errors in manual quality control mode, and is of great significance for improving the accuracy of measurement results. Detailed Implementation

[0043] To make the present invention easier to understand, the present invention will be described in detail below with reference to embodiments. These embodiments are for illustrative purposes only and are not limited to the scope of application of the present invention.

[0044] Whole blood impedance is primarily related to hematocrit (HCT). Blood cells impede electrical current, and the number of red blood cells at different concentrations is directly proportional to their impediment. As hematocrit increases, the blood sample's impedance value increases. Generally, the normal HCT value for adult males is 40%-50%, for adult females it is 37%-48%, and for newborns it is 48%-68%. Therefore, to cover all blood sample conditions, multiple blood samples are prepared, and the hematocrit values ​​of these samples are adjusted to preset values, such as 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, and 80%. By applying sinusoidal AC voltages of different amplitudes and frequencies to the electrodes of the electrochemical testing device, the impedance values ​​of multiple blood samples with different hematocrit values ​​are obtained, and the applied sinusoidal AC voltage amplitude and frequency setting conditions with better accuracy are selected.

[0045] ① Set the applied sinusoidal AC voltage frequency to 40000Hz, and try applying sinusoidal AC voltage amplitudes of 0.1V, 0.2V, and 0.42V. Blood samples with different HCT values ​​were tested 20 times each, and the average impedance and CV (coefficient of variation) were recorded. The results are shown in Table 1.

[0046] Table 1. Blood sample impedance values ​​at different AC voltage amplitudes

[0047]

[0048]

[0049] As shown in Table 1, the test results showed the smallest relative deviation and the highest accuracy when the amplitude of the sinusoidal AC voltage was 0.42V.

[0050] ② Set the applied sinusoidal AC voltage amplitude to 0.42V, and try applying sinusoidal AC voltages at frequencies of 20000Hz, 30000Hz, and 40000Hz. Blood samples with different HCT values ​​were tested 20 times each, and the average impedance and CV were recorded. The results are shown in Table 2.

[0051] Table 2. Blood sample impedance values ​​at different AC voltage frequencies.

[0052]

[0053] As shown in Table 2, the test results at a sinusoidal AC voltage frequency of 40000 Hz have the smallest relative deviation and the highest accuracy.

[0054] In summary, when the applied sinusoidal AC voltage amplitude is set to 0.42V and the frequency to 40000Hz, the sinusoidal AC voltage has strong signal stability and can obtain a more accurate whole blood impedance range.

[0055] Example 1

[0056] This embodiment provides a method for automatic identification of quality control solution and sample. The quality control solution is blood glucose quality control solution, and the sample is blood. A blood glucose electrochemical testing system is used. The composition of the electrode enzyme membrane of the blood glucose electrochemical testing system is shown in Table 3. The composition of the blood glucose quality control solution is shown in Table 4.

[0057] Table 3 Electrode and enzyme membranes of the blood glucose electrochemical testing system

[0058]

[0059] Table 4 shows the components of the blood glucose control solution.

[0060]

[0061] ① Multiple blood samples with different glucose concentrations and hematocrits ranging from 5% to 80% were prepared. A sinusoidal AC voltage with an amplitude of 0.42V and a frequency of 40000HZ was applied to the electrodes of the blood glucose electrochemical testing system. The multiple blood samples were tested 20 times each, and the average impedance and CV of the blood samples were recorded. The results are shown in Table 5.

[0062] Table 5 Impedance values ​​of blood samples

[0063]

[0064]

[0065] ② Prepare multiple blood glucose control solutions with LiFL6 mass concentrations of 0%-10% and different glucose concentrations. Apply a sinusoidal AC voltage with an amplitude of 0.42V and a frequency of 40000HZ to the electrodes of the blood glucose electrochemical testing system. Test each blood glucose control solution 20 times and record the average impedance and CV of the blood glucose control solution. The results are shown in Table 6.

[0066] Table 6 Impedance values ​​of blood glucose control solution

[0067]

[0068] As shown in Table 6, when the glucose concentration is the same but the lithium salt concentration is different in the quality control solution, the measured impedance values ​​vary significantly (for example, when the glucose concentration is always low and the lithium salt concentration is 0-10%, the measured impedance values ​​range from 17.8 to 3.5 kΩ). Conversely, when the glucose concentration is different but the lithium salt concentration is the same, the measured impedance values ​​vary less (for example, when the lithium salt concentration is 1% and the glucose concentration is low, medium, or high, the measured impedance values ​​range from 8.3 to 8.5 kΩ). In other words, under suitable amplitude and frequency, the impedance value of the blood glucose quality control solution is mainly related to the lithium salt concentration in the solution.

[0069] As shown in Tables 5 and 6, when the lithium salt concentration in the blood glucose control solution is 1-10%, the obtained impedance value is significantly different from that of the blood sample. That is, when the control solution contains lithium salt with a mass concentration of ≥1%, and the impedance value is detected under appropriate voltage and frequency, it can be clearly distinguished from the impedance value of the blood sample.

[0070] For example, based on the test results in Table 5, the impedance range of the sample when the analyte is blood glucose can be determined to be (9.6, 50.2); based on the test results in Table 6, the impedance range of the blood glucose control solution when the lithium salt mass concentration is 1% can be determined to be (8.3, 8.5).

[0071] Example 2

[0072] This embodiment provides a method for automatic identification of quality control solution and sample. The quality control solution is uric acid quality control solution, and the sample is blood. A uric acid electrochemical testing system is used. The composition of the electrode enzyme membrane of the uric acid electrochemical testing system is shown in Table 7. The composition of the uric acid quality control solution is shown in Table 8.

[0073] Table 7 Electrode and enzyme membranes of the uric acid electrochemical testing system

[0074]

[0075] Table 8 shows the components of the uric acid quality control solution.

[0076]

[0077] ① Multiple blood samples with different uric acid concentrations and hematocrits ranging from 5% to 80% were prepared. A sinusoidal AC voltage with an amplitude of 0.42V and a frequency of 40000HZ was applied to the electrodes of the uric acid electrochemical testing system. The multiple blood samples were tested 20 times each, and the average impedance and CV of the blood samples were recorded. The results are shown in Table 9.

[0078] Table 9 Impedance values ​​of blood samples

[0079]

[0080] ② Multiple uric acid control solutions with LiFL6 mass concentrations ranging from 0% to 10% were prepared. A sinusoidal AC voltage with an amplitude of 0.42V and a frequency of 40000HZ was applied to the electrodes of the uric acid electrochemical testing system. Each uric acid control solution was tested 20 times. The average impedance and CV of the uric acid control solutions were recorded. The results are shown in Table 10.

[0081] Table 10. Impedance values ​​of uric acid quality control solution

[0082]

[0083] As shown in Table 10, in the quality control solution, when the uric acid concentration is the same but the lithium salt concentration is different, the measured impedance values ​​vary significantly (for example, when the uric acid concentration is always low and the lithium salt concentration is 0-10%, the measured impedance values ​​range from 18.2 to 3.7 kΩ). Conversely, when the uric acid concentration is different but the lithium salt concentration is the same, the measured impedance values ​​vary less (for example, when the lithium salt concentration is 1% and the uric acid concentration is low, medium, or high, the measured impedance values ​​range from 8.6 to 8.8 kΩ). That is, under suitable amplitude and frequency, the impedance value of the uric acid quality control solution is mainly related to the lithium salt concentration in the quality control solution.

[0084] As shown in Tables 9 and 10, when the lithium salt mass concentration of the uric acid quality control solution is 1-10%, the obtained impedance value is significantly different from that of the blood sample. That is, when the quality control solution contains lithium salt with a mass concentration of ≥1%, and the impedance value is detected under appropriate voltage and frequency, it can be clearly distinguished from the impedance value of the blood sample.

[0085] For example, based on the test results in Table 9, the impedance range of the sample when the analyte is uric acid can be determined to be (9.1, 36.9); based on the test results in Table 10, the impedance range of the uric acid quality control solution when the lithium salt mass concentration is 1% can be determined to be (8.6, 8.8).

[0086] Example 3

[0087] This embodiment provides a method for automatic identification of quality control solution and sample. The quality control solution is lactic acid quality control solution, and the sample is blood. A lactic acid electrochemical testing system is used. The composition of the electrode enzyme membrane of the lactic acid electrochemical testing system is shown in Table 11. The composition of the lactic acid quality control solution is shown in Table 12.

[0088] Table 11 Electrode and enzyme membranes of the lactate electrochemical testing system

[0089]

[0090]

[0091] Table 12 shows the components of the lactic acid quality control solution.

[0092]

[0093] ① Multiple blood samples with different lactate concentrations and hematocrits ranging from 5% to 80% were prepared. A sinusoidal AC voltage with an amplitude of 0.42V and a frequency of 40000HZ was applied to the electrodes of the lactate electrochemical testing system. The multiple blood samples were tested 20 times each, and the average impedance and CV of the blood samples were recorded. The results are shown in Table 13.

[0094] Table 13 Impedance values ​​of blood samples

[0095]

[0096] ② Multiple lactic acid control solutions with LiFL6 mass concentrations ranging from 0% to 10% were prepared. A sinusoidal AC voltage with an amplitude of 0.42V and a frequency of 40000HZ was applied to the electrodes of the lactic acid electrochemical testing system. Each lactic acid control solution was tested 20 times, and the average impedance and CV of the lactic acid control solution were recorded. The results are shown in Table 14.

[0097] Table 14 Impedance values ​​of lactic acid quality control solution

[0098]

[0099] As shown in Table 14, in the quality control solution, when the lactic acid concentration is the same but the lithium salt concentration is different, the measured impedance values ​​vary significantly (for example, when the lactic acid concentration is always low and the lithium salt concentration is 0-10%, the measured impedance values ​​range from 18.4 to 3.5 kΩ). Conversely, when the lactic acid concentration is different but the lithium salt concentration is the same, the measured impedance values ​​vary less (for example, when the lithium salt concentration is 1% and the lactic acid concentration is low, medium, or high, the measured impedance values ​​range from 8.3 to 8.5 kΩ). That is, under suitable amplitude and frequency, the impedance value of the lactic acid quality control solution is mainly related to the lithium salt concentration in the solution.

[0100] As shown in Tables 13 and 14, when the lithium salt mass concentration of the lactic acid control solution is 1-10%, the obtained impedance value is significantly different from that of the blood sample. That is, when the control solution contains lithium salt with a mass concentration of ≥1%, and the impedance value is detected under appropriate voltage and frequency, it can be clearly distinguished from the impedance value of the blood sample.

[0101] For example, based on the test results in Table 13, the impedance range of the sample when the analyte is lactic acid can be determined to be (9.6, 46.9); based on the test results in Table 14, the impedance range of the lactic acid quality control solution when the lithium salt mass concentration is 1% can be determined to be (8.3, 8.5).

[0102] Example 4

[0103] This embodiment provides a method for automatic identification of quality control solution and sample. The quality control solution is cholesterol quality control solution, and the sample is blood. A cholesterol electrochemical testing system is used. The composition of the electrode enzyme membrane of the cholesterol electrochemical testing system is shown in Table 15. The composition of the cholesterol quality control solution is shown in Table 16.

[0104] Table 15 Electrode enzyme membranes of cholesterol electrochemical testing system

[0105]

[0106]

[0107] Table 16 Cholesterol Control Solution contains the following components:

[0108]

[0109] ① Multiple blood samples with different cholesterol concentrations and hematocrits ranging from 5% to 80% were prepared. A sinusoidal AC voltage with an amplitude of 0.42V and a frequency of 40000HZ was applied to the electrodes of the cholesterol electrochemical testing system. The multiple blood samples were tested 20 times each, and the average impedance and CV of the blood samples were recorded. The results are shown in Table 17.

[0110] Table 17 Impedance values ​​of blood samples

[0111]

[0112] ② Multiple cholesterol control solutions with LiFL6 mass concentrations ranging from 0% to 10% were prepared. A sinusoidal AC voltage with an amplitude of 0.42V and a frequency of 40000HZ was applied to the electrodes of the cholesterol electrochemical testing system. Each cholesterol control solution was tested 20 times, and the average impedance and CV of the cholesterol control solutions were recorded. The results are shown in Table 18.

[0113] Table 18 Cholesterol Control Solution Impedance Values

[0114]

[0115] As shown in Table 18, when the cholesterol concentration in the quality control solution is the same but the lithium salt concentration is different, the measured impedance values ​​vary considerably (for example, when all cholesterol concentrations are low and the lithium salt concentrations are 0-10%, the measured impedance values ​​range from 19.1 to 3.9 kΩ). Conversely, when the cholesterol concentration is different but the lithium salt concentration is the same, the measured impedance values ​​vary less (for example, when the lithium salt concentration is 1% and the cholesterol concentrations are low, medium, and high, the measured impedance values ​​range from 8.9 to 9.2 kΩ). In other words, under suitable amplitude and frequency, the impedance value of the cholesterol quality control solution is mainly related to the lithium salt concentration in the solution.

[0116] As shown in Tables 17 and 18, when the lithium salt mass concentration of the cholesterol control solution is 1-10%, the obtained impedance value is significantly different from that of the blood sample. That is, when the control solution contains lithium salt with a mass concentration of ≥1%, and the impedance value is detected under appropriate voltage and frequency, it can be clearly distinguished from the impedance value of the blood sample.

[0117] For example, based on the test results in Table 17, the impedance range of the sample when the analyte is cholesterol can be determined to be (10.2, 48.5); based on the test results in Table 18, the impedance range of the cholesterol quality control solution when the lithium salt mass concentration is 1% can be determined to be (8.9, 9.2).

[0118] In addition, to verify the effects of other lithium salts, the applicant replaced LiFL6 in Examples 1-4 with lithium perchlorate or lithium tetrafluoroborate and conducted tests accordingly. The results were similar to those of LiFL6.

[0119] Comparative Example 1

[0120] This comparative example provides a method for automatic identification of the quality control solution and the sample. The quality control solution is a blood glucose quality control solution, and the sample is blood. A blood glucose electrochemical testing system is used. The composition of the electrode enzyme membrane of the blood glucose electrochemical testing system is the same as that in Example 1. The composition of the blood glucose quality control solution is shown in Table 19.

[0121] Table 19 lists the components of blood glucose control solution.

[0122]

[0123] Multiple blood glucose control solutions with NaCl concentrations ranging from 0% to 10% were prepared. A sinusoidal AC voltage with an amplitude of 0.42V and a frequency of 40000HZ was applied to the electrodes of the blood glucose electrochemical testing system. Each blood glucose control solution was tested 20 times, and the average impedance and CV of the blood glucose control solution were recorded. The results are shown in Table 20.

[0124] Table 20 Impedance values ​​of blood glucose control solution

[0125]

[0126] As shown in Table 20, when the blood glucose control solution does not contain lithium salts but contains NaCl, the impedance value of the control solution decreases with increasing NaCl concentration, assuming the same glucose concentration. However, the impedance value of the blood glucose control solution containing 1-10% NaCl is relatively large, and the difference between it and the impedance value of the blood sample is small, or even overlapping, making it difficult to distinguish between the control solution and the sample (for example, in Table 20, the impedance value of the blood glucose control solution containing 1-10% NaCl ranges from 10.3 to 16.6 KΩ; in Table 5 of Example 1, the impedance value of the blood sample ranges from 9.6 to 50.2 KΩ, i.e., the impedance values ​​of the two overlap).

[0127] Furthermore, compared to Table 6 in Example 1, the CV value of the impedance value in this comparative example is larger, that is, the repeatability of the blood glucose control solution containing 1%-10% NaCl is worse than that of the blood glucose control solution containing 1%-10% lithium salt.

[0128] Test Example 1

[0129] Multiple blood glucose control solutions containing different concentrations of LiFL6 and NaCl were prepared, with blood glucose concentrations of 60 mg / dL, 120 mg / dL, and 250 mg / dL, respectively. The prepared blood glucose control solutions were incubated at room temperature and 65°C for 10 days, and the blood glucose concentrations in the control solutions were measured. The results are shown in Tables 21 and 22.

[0130] Table 21 Blood glucose control solutions containing LiFL6

[0131]

[0132] Table 22 Blood glucose control solutions containing NaCl

[0133]

[0134]

[0135] As shown in Tables 21 and 22, the blood glucose control solution containing different concentrations of LiFL6 has better stability than the blood glucose control solution containing different concentrations of NaCl.

[0136] It should be noted that the embodiments described above are only for explaining the present invention and do not constitute any limitation on the present invention. The present invention has been described with reference to typical embodiments, but it should be understood that the words used therein are descriptive and explanatory terms, not limiting terms. Modifications can be made to the present invention within the scope of the claims, and revisions can be made to the present invention without departing from the scope and spirit of the present invention. Although the present invention described herein relates to specific methods, materials, and embodiments, it does not mean that the present invention is limited to the specific examples disclosed herein; on the contrary, the present invention can be extended to all other methods and applications with the same function.

Claims

1. A method for automatic identification of quality control solutions and samples, characterized in that, include: An alternating voltage is applied to the electrodes of the electrochemical testing device to detect the impedance value of the sample to be tested; The impedance value indicates whether the sample to be tested is a quality control solution or a sample; the quality control solution contains lithium salt. The mass concentration of lithium salt in the quality control solution is 1%-10%; The lithium salt is selected from at least one of LiFL6, lithium perchlorate, or lithium tetrafluoroborate. The amplitude of the AC voltage is 0.42V and the frequency is 40000Hz.

2. The method according to claim 1, characterized in that, The mass concentration of lithium salt in the quality control solution is 1%-5%.

3. The method according to claim 1, characterized in that, The mass concentration of lithium salt in the quality control solution is 1%-2%.

4. The method according to claim 1, characterized in that, Determining whether the sample to be tested is a quality control solution or a sample based on the impedance value includes: comparing the impedance value with a preset impedance range, determining the impedance range to which the impedance value belongs, and determining whether the sample to be tested is a quality control solution or a sample based on the impedance range to which the impedance value belongs.

5. The method according to claim 4, characterized in that, The impedance range includes the quality control solution impedance range and the sample impedance range; The method for determining the impedance range includes: (1). The method for determining the sample impedance range includes: preparing multiple blood samples with a hematocrit of 5%-20% and multiple blood samples with a hematocrit of 70%-80%, measuring the impedance value of each sample, and determining the sample impedance range based on the measured impedance value; (2). The method for determining the impedance range of the quality control solution includes: preparing multiple quality control solutions with a mass concentration of lithium salt of 1%-10%, measuring the impedance value of each quality control solution, and determining the impedance range of the quality control solution based on the measured impedance value; The sample impedance range does not overlap with the quality control liquid impedance range.

6. The method according to claim 5, characterized in that, The lower limit of the range is 80%-100% of the average impedance value of multiple blood samples with hematocrit of 5%-20%, and / or the upper limit of the range is 100%-120% of the average impedance value of multiple blood samples with hematocrit of 70%-80%. Use 80%-100% of the minimum impedance value of multiple control solutions as the lower limit of the control solution impedance range, and / or use 100%-120% of the maximum impedance value of multiple control solutions as the upper limit of the control solution impedance range.

7. The method according to claim 1, wherein the method for automatic identification of quality control solution and sample specifically includes the following steps: S1, apply an AC voltage to the electrodes of the electrochemical testing device to detect the impedance value of the sample to be tested; wherein the amplitude of the AC voltage is 0.42V and the frequency is 40000Hz; S2, compare the impedance value measured in step S1 with a preset impedance range to determine the impedance range to which the impedance value belongs; wherein, the impedance range includes the quality control liquid impedance range and the sample impedance range; S3, determine whether the sample to be tested is a quality control solution or a sample based on the impedance range to which the impedance value belongs. The determination method includes: if the impedance value is within the impedance range of the quality control solution, then the sample to be tested is determined to be a quality control solution; if the impedance value is within the impedance range of the sample, then the sample to be tested is determined to be a sample. Before step S2, the impedance range is determined. The method for determining the impedance range includes: preparing multiple blood samples with a hematocrit of 5%-20% and multiple blood samples with a hematocrit of 70%-80%, measuring the impedance value of each sample, and determining the sample impedance range based on the measured impedance value. The lower limit of the range is 80%-100% of the average impedance value of multiple blood samples with hematocrit of 5%-20%, and / or the upper limit of the range is 100%-120% of the average impedance value of multiple blood samples with hematocrit of 70%-80%. Prepare multiple quality control solutions with a lithium salt mass concentration of 1%-10%, measure the impedance value of each quality control solution, and determine the impedance range of the quality control solution based on the measured impedance values; take 80%-100% of the minimum impedance value of the multiple quality control solutions as the lower limit of the quality control solution impedance range, and / or take 100%-120% of the maximum impedance value of the multiple quality control solutions as the upper limit of the quality control solution impedance range. The sample impedance range does not overlap with the quality control liquid impedance range.

8. The method according to claim 1, characterized in that, The sample includes blood; the analyte in the sample is blood glucose, uric acid, lactic acid, or cholesterol; and / or, the quality control solution is blood glucose control solution, uric acid control solution, lactic acid control solution, or cholesterol control solution.

9. The application of the method as described in any one of claims 1-8 in the in vitro detection of blood glucose, uric acid, lactic acid or cholesterol in human blood.

10. A biosensor device for implementing the method of any one of claims 1-8 or the application of claim 9, characterized in that, The biosensor device includes: The power module is used to apply AC voltage to the electrodes of the electrochemical testing device; Impedance measurement module is used to measure the impedance value when an AC voltage is applied to the electrodes of an electrochemical testing device; A storage module is used to store preset impedance ranges; the storage module includes an impedance range acquisition unit and an impedance range storage unit, the impedance range acquisition unit is used to acquire the impedance range of the quality control liquid and the impedance range of the sample, and store the impedance range in the impedance range storage unit; the impedance range of the quality control liquid and the impedance range of the sample do not overlap with each other in terms of impedance range; The judgment module, coupled with the impedance measurement module and the storage module, is used to compare the measured impedance value with a preset impedance range, determine the impedance range to which the measured impedance value belongs, and determine whether the sample to be tested is a quality control liquid or a sample based on the impedance range to which the impedance value belongs.

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