TWI495874B - Control solution for non-enzymatic electrochemical detection system and method of using the same - Google Patents

Description

Quality control liquid for non-enzyme type electrochemical detection system and use method thereof

The present invention relates to a quality control fluid and a method of using the same. In particular, it relates to a quality control liquid for a non-enzyme type electrochemical detection system having a long shelf life, high stability, accurate detection, and simple process, and a method for using the same.

The electrode test piece prepared by the electrochemical method can be divided into two types, an enzyme type electrode test piece and a non-enzyme type electrode test piece. Because many enzyme electrode test pieces have many disadvantages such as limited storage conditions, complicated process and cumbersome control conditions, the production cost is high and mass production cannot be achieved. Therefore, in recent years, research on electrochemical detection systems has mostly progressed toward non-enzymatic electrode test strips.

The detection of uric acid in blood or other body fluids is one of the tools used by the medical community to diagnose and monitor different conditions. There are a number of different ways to detect uric acid levels. Common methods of detection include chemical methods and enzyme methods. However, the chemical method has the disadvantages of being easily disturbed and having poor specificity, and the enzyme method is expensive to inspect and inconvenient to store and cannot be widely used at home. Thus, a non-enzymatic uric acid detection electrode test piece as disclosed in U.S. Patent No. 6,258,230 B1 has been developed.

In addition, the blood donation center for blood screening and blood donor safety protection must be controlled by the heme detection system, which has many detection methods, including chemical method, gas measurement method, specific gravity method and colorimetric method, among which The detection methods used were a ketone sulfate specific gravity method and a heme detector. The hemoglobin detector is also most commonly used by Hemocue manufactured by HemoCue Inc. Hemocue It is a detector that utilizes an optical principle, but requires a higher cost of optical components and consumables. Therefore, U.S. Patent No. 4,876,205 provides a hemoglobin electrochemical test strip.

In general, the main purpose of the quality control fluid is to confirm whether the function of the electrochemical detection system is normal, and when there is a doubtful result in the detection process, and if the detection system is confirmed to be abnormal, it can be based on the quality control liquid. The result of the test is used as a basis for judging whether the detection system is normal.

Generally, the commercially available hemoglobin detector uses the animal recombinant blood as a quality control liquid for the calibration detector. However, the quality control fluid containing the recombinant blood of the animal needs to be stored in a low temperature state, the storage condition is not easy to control and the effect period is not long, about 1 to 3 months, and is easily affected by temperature and improper use of the operation, so that the quality control liquid The quality is so contaminated that such hemoglobin detectors are significantly limited in their use based on the quality of the quality control fluid.

In view of the above factors, it is necessary to provide a quality control fluid suitable for non-enzyme type electrochemical detection systems with long storage period, high stability, accurate detection and simple process to meet the requirements of the detection system.

The main object of the present invention is to provide a quality control liquid for a non-enzymatic electrochemical detection system, which can be used for quality control of a hemoglobin, uric acid or other detection system for an analyte to be detected without using an enzyme.

The quality control liquid of the present invention comprises an alkali metal ferrocyanide salt and an aqueous medium, wherein the aqueous medium is used for dissolving the alkali metal salt of ferrocyanide.

Another object of the present invention is to provide a method for controlling a non-enzymatic electrochemical detection system comprising: (a) contacting a quality control liquid of the present invention with ferricyanide on the non-enzyme type electrochemical detection system (b) applying a fixed voltage to the test system; and (c) measuring the change in current and converting it to a detected reading of the system.

The invention relates to a quality control liquid for a non-enzyme type electrochemical detection system, which comprises an alkali metal salt of ferrocyanide and an aqueous medium capable of dissolving the alkali metal salt of the ferrocyanide.

In the present invention, the term "quality control" refers to confirming whether the function of the non-enzymatic electrochemical detection system is normal, and confirming whether the result data measured by the detection system for the sample to be tested is a reliable value.

A non-enzymatic electrochemical detection system suitable for use in the present invention is any known non-enzymatic electrochemical detection system of the art, including, but not limited to, US Patent No. 6,258,230 B1, Republic of China No. 466344, and Chinese An electrode test piece for detecting heme and uric acid and a sensor thereof are disclosed in the invention patent application No. 092106502. The non-enzymatic electrochemical detection system suitable for use in the present invention generally comprises a non-enzymatic electrochemical test piece and an electrochemical sensor.

The quality control liquid of the present invention utilizes an electron carrier (such as ferricyanide (such as potassium ferricyanide)) on a non-enzyme type electrochemical test piece and a ferrocyanide ion of an alkali metal ferrocyanide salt. After the reaction, the electron mediator is reduced from the oxidized state to the reduced state, and then the electron media is promoted by applying an applied voltage. The principle that the medium is restored from the reverse state to the oxidized state and the redox reaction is generated. During the reaction, the change of the electronic signal is detected to measure the concentration of the ferrous cyanide alkali metal salt, and then the concentration value is determined to be Within a predetermined range of values, to determine whether the non-enzymatic electrochemical detection system is normal, it can be applied to the measurement of the sample to be tested.

Alkali cyanide alkali metal salts suitable for use in the present invention include, but are not limited to, potassium ferrocyanide, sodium ferrocyanide or lithium ferrocyanide. The aqueous medium suitable for use in the present invention is any medium which can be used to dissolve the ferrous metal cyanide alkali metal salt and provide electron transport, including but not limited to water or various buffers (such as phosphate buffer, citric acid buffer). Liquid or citrate buffer), preferably water.

The skilled person can formulate a quality control solution containing different concentrations of alkali metal ferrocyanide according to different non-enzyme type electrochemical detection systems, for example, according to the standard range of normal use of non-enzyme type electrochemical detection systems. In a specific embodiment of the invention, the higher the content of the ferrous cyanide alkali metal salt, the proportional increase in the detection reading of the non-enzymatic electrochemical detection system.

In general, the content of the ferrocyanide alkali metal salt in the quality control fluid is related to the type of sample to be tested. In a preferred embodiment of the present invention, when the non-enzymatic electrochemical detection system is used for detecting hemoglobin, the content of the ferrocyanide alkali metal salt in the quality control liquid is about 0.05 weight percent (w /v%) to about 0.5 w/v%, preferably about 0.16 w/v% to about 0.2 w/v%; when the non-enzymatic electrochemical detection system is used for detecting uric acid, in the quality control liquid The content of ferricyanide is from about 0.01 w/v% to about 0.05 w/v%, preferably from about 0.015 w/v% to about 0.03 w/v%.

The quality control fluid of the present invention may further comprise other components well known to those skilled in the art that do not adversely affect the quality control fluid of the present invention, such as xanthan gum, glycerol or Polyethylene glycols (PEG).

In addition, the present invention provides a method for controlling a non-enzymatic electrochemical detection system comprising: (a) contacting a quality control liquid of the present invention with ferricyanide on the non-enzymatic electrochemical measuring system; (b) Applying a fixed voltage to the test system; and (c) measuring the current change and obtaining a ferrocyanide alkali metal salt concentration value.

The method for controlling a non-enzymatic electrochemical detection system of the present invention further comprises comparing the measured result value with a predetermined range of values, and if the measured result value falls within the predetermined range of values, indicating the non- The function of the enzyme type electrochemical detection system is normal, and can be applied to the measurement of the sample to be tested; if the value of the measurement result is higher or lower than the predetermined range of values, it means that the function of the non-enzymatic electrochemical detection system is not Normal, not applicable to measurements of the sample under test. The skilled person can determine the range of values determined in advance based on the different types of non-enzymatic electrochemical detection systems and the types of samples to be tested.

In a preferred embodiment of the invention, the non-enzymatic electrochemical detection system can measure hemoglobin ranging from about 4 grams per deciliter to about 20 grams per deciliter, and the uric acid range is about 3 mg per deciliter. Up to about 20 mg / dl. In a specific embodiment of the present invention, the test result of the heme system obtained by using the quality control liquid is From about 12 grams per deciliter to about 14 grams per deciliter or from about 16 grams per deciliter to about 19 grams per deciliter; the uric acid system using the quality control fluid test results from about 5 mg/dl to about 7 mg. / liters or about 10 mg / dl to about 12 mg / dl.

The following examples are intended to illustrate the invention and are not intended to limit the scope of the invention. Modifications and variations that may be readily made by those skilled in the art are included within the scope of the disclosure of the present disclosure and the scope of the appended claims.

Example Example 1: Preparation of the quality control liquid of the present invention

Two kinds of quality control liquids with different concentrations of potassium ferrocyanide in the non-enzyme type electrochemical heme detection system and the non-enzyme type electrochemical uric acid detection system are separately prepared. In the hemoglobin detection system, the quality control liquid contains about 0.16% by weight of potassium ferrocyanide, and when the balance is water, the obtained electrical signal is converted to obtain a detection reading of about 13.2 g/dl. When the quality control fluid contained about 0.20% by weight of potassium ferrocyanide and the balance was water, the resulting electrical signal was converted to obtain a detection reading of about 18.2 grams per deciliter. In the uric acid detection system, when the quality control liquid contains about 0.03% by weight of potassium ferrocyanide, the obtained electric signal is converted to obtain a detection reading value of about 11 mg/dl, and when the quality control is controlled When the liquid contained about 0.015% by weight of potassium ferrocyanide, the resulting electrical signal was converted to obtain a detection reading of about 6.8 mg/dl.

As can be seen from Table 1, in LEVEL 1, the concentration of potassium ferrocyanide used in the heme detection system is about 11 times that of the user of the uric acid detection system, but the system test results differ by about 1900 times. This result clearly shows that the concentration of potassium ferrocyanide used in the control tube of the present invention is not specific and depends on the non-enzyme type electrochemical detection system of the analyte to be analyzed. In addition, in the phase In the detection system of the analyte, the higher the content of potassium ferrocyanide, the proportional increase in the detection reading of the detection system.

According to the above, the present invention uses a highly stable ferrocyanide alkali metal salt solution to replace the conventional use of animal recombinant blood for quality control of a non-enzymatic electrochemical detection system. The quality control liquid of the non-enzyme type electrochemical detection system of the invention has the advantages of long storage period, high stability, accurate detection and simple process, and is suitable for detecting whether a plurality of non-enzyme type electrochemical detection systems are operating normally.

While the invention has been described above by way of a preferred embodiment, it is not intended to limit the invention, and the invention may be modified and modified without departing from the spirit and scope of the invention. The scope of protection is subject to the definition of the scope of the patent application.

Claims (4)

A method for controlling a non-enzymatic electrochemical detection system, comprising: (a) contacting a quality control liquid with ferricyanide on the non-enzymatic electrochemical measuring system, wherein the quality control liquid is substantially the following Composition: a ferrocyanide alkali metal salt; and an aqueous medium for dissolving the alkali metal salt of ferrocyanide; wherein the non-enzymatic electrochemical detection system is used for measuring heme, the ferrocyanide The content of the alkali metal salt is 0.05% by weight (w/v%) to 0.5 w/v%; and when the non-enzymatic electrochemical detection system is used for measuring uric acid, the content of the alkali metal salt of ferrocyanide From 0.01 w/v% to 0.05 w/v%; (b) applying a fixed voltage to the test system; and (c) measuring the change in current and converting it to the detected reading of the system. The method of claim 1, wherein the ferrocyanide alkali metal salt is potassium ferrocyanide. The method of claim 1, wherein the aqueous medium is selected from the group consisting of water and a buffer. The method of any one of claims 1 to 3, further comprising comparing the concentration of the ferrous cyanide alkali metal salt with a predetermined range of values to confirm whether the function of the non-enzymatic electrochemical detection system is normal.