A thermostat tank cleaning solution, a preparation method and application thereof

Abstract

The present application belongs to the technical field of in vitro diagnosis and equipment maintenance, and particularly relates to a thermostat cleaning solution, a preparation method and application thereof. According to the weight percentage, the thermostat cleaning solution provided by the present application comprises 0.5-3% of organic acid, 1.5-5% of inorganic salt, 0.01-0.5% of non-ionic surfactant, 0.01-0.5% of metal chelating agent, 0.01-1% of bacteriostatic agent and the balance of water. The thermostat cleaning solution of the present application is added to the thermostat water bath system of a biochemical analyzer, which can effectively inhibit the formation of scale and reduce the pollution risk caused by the residue of the water bath liquid on the sample needle, reagent needle and outer wall of the reaction cup. The thermostat cleaning solution of the present application has stable performance, good compatibility with the equipment, can significantly prolong the maintenance cycle of the water bath system, improve the stability of the instrument operation and the reliability of the detection result, and reduce the maintenance cost.

Description

Technical Field

[0001] This invention belongs to the field of in vitro diagnostics and equipment maintenance technology, specifically relating to a constant temperature bath cleaning solution, its preparation method, and its application. Background Technology

[0002] Fully automated biochemical analyzers are core equipment in clinical testing. Their reaction systems typically require a constant temperature environment (usually 37°C) to ensure the accuracy of biochemical processes such as reactions. This constant temperature environment is usually provided by a built-in circulating water bath system. However, during long-term operation, the water bath system faces many problems: (1) Scaling problem: Calcium, magnesium and other metal ions in the water are prone to form scale such as carbonates and sulfates under heating conditions, which adhere to the heating rod, pipeline and outer wall of the reaction cup, seriously affecting the heat transfer efficiency, resulting in uneven or unstable temperature, and thus affecting the accuracy and precision of the test results; (2) Corrosion problem: The water bath liquid is in a warm and humid environment for a long time, and may be weakly alkaline due to the occasional infiltration of other cleaning liquids, which will cause corrosion to the metal inner wall of the water bath tank, the impeller of the circulating pump and other metal parts, shortening the equipment life, and the corrosion products may also pollute the system; (3) Microbial growth: The constant temperature water environment of 37℃ is a breeding ground for bacteria and algae. The formation of microbial film will block the pipeline, and its metabolic products may pollute the outer wall of the reaction cup, and even affect the detection system through aerosols; (4) Risk of cross-contamination: During the movement of sample needles and reagent needles, their outer walls may carry trace amounts of samples or reagents. When they pass through the surface of the water bath, these residues may dissolve into the water bath and circulate with it, posing a potential risk of indirect cross-contamination.

[0003] Currently, the main maintenance method involves periodically changing the water bath solution and manually cleaning the water tank, but this is time-consuming, labor-intensive, and downtime affects testing efficiency. A few high-end instruments use specialized water bath solutions, but these are expensive. Therefore, developing a high-efficiency, multifunctional, and economical constant temperature bath cleaning solution has significant practical value. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art, solve the problems of scaling, corrosion, microbial growth and potential cross-contamination in the water bath system of a fully automated biochemical analyzer, extend the system maintenance cycle, and ensure the stable operation of the instrument.

[0005] This invention provides a constant temperature bath cleaning solution, which, by weight percentage, comprises the following components: 0.5-3% organic acid, 1.5-5% inorganic salt, 0.01-0.5% nonionic surfactant, 0.01-0.5% metal chelating agent, 0.01-1% antibacterial agent, and the balance being water.

[0006] Preferably, the constant temperature bath cleaning solution comprises the following components: 1-2% organic acid, 1.6-4.6% inorganic salt, 0.05-0.2% nonionic surfactant, 0.05-0.2% metal chelating agent, 0.5-0.82% antibacterial agent, and the balance being water.

[0007] Preferably, the pH value of the cleaning solution in the constant temperature bath is 4.5~5.5.

[0008] Preferably, the organic acid includes one or more of citric acid, acetic acid, oxalic acid, and acetic acid.

[0009] Preferably, the inorganic salt includes one or more of sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium chloride, and sodium bicarbonate.

[0010] Preferably, the metal chelating agent includes one or more of disodium ethylenediaminetetraacetate, ethylenediaminetetraacetic acid, and sodium hexametaphosphate.

[0011] Preferably, the nonionic surfactant includes one or more of Triton X-100, fatty alcohol polyoxyethylene ether, alkyl glycoside and polysorbate 20.

[0012] Preferably, the antibacterial agent includes one or more of sodium benzoate, sodium sorbate, ethanol, and Proclin 300.

[0013] The present invention provides a method for preparing the constant temperature bath cleaning solution described in the above technical solution, comprising the following steps: adding organic acid, inorganic salt, metal chelating agent, nonionic surfactant and antibacterial agent to water in sequence, mixing evenly and filtering to obtain the constant temperature bath cleaning solution.

[0014] This invention provides the application of the constant temperature bath cleaning solution described in the above technical solution or the constant temperature bath cleaning solution prepared by the above technical solution in the maintenance of a fully automated biochemical analyzer.

[0015] Beneficial effects: This invention provides a constant temperature bath cleaning solution, which, by weight percentage, comprises the following components: 0.5-3% organic acid, 1.5-5% inorganic salt, 0.01-0.5% nonionic surfactant, 0.01-0.5% metal chelating agent, 0.01-1% antibacterial agent, and the balance water. The constant temperature bath cleaning solution provided by this invention has the following functions: (1) Multifunctional integration: It simultaneously achieves four functions: scale inhibition, corrosion inhibition, antibacterial, and auxiliary cleaning. (2) Protecting equipment and extending service life: It effectively prevents scale buildup and metal corrosion, protects key components such as heating rods, circulating pumps, and temperature sensors, reduces equipment failure rate, and extends service life. (3) Improving detection reliability: It maintains a uniform and stable water bath temperature, reducing detection errors caused by temperature fluctuations. It inhibits the risk of microorganisms and cross-contamination, providing a cleaner background environment for detection results. (4) Reducing maintenance costs: It significantly extends the water bath solution replacement and water bath cleaning cycle, reducing the frequency of manual maintenance and downtime. Compared with imported special water bath solutions, the cost is significantly reduced. (5) Safety and environmental protection: The components contained are biodegradable and are friendly to the environment and operators. Detailed Implementation

[0016] This invention provides a constant temperature bath cleaning solution, which, by weight percentage, comprises the following components: 0.5-3% organic acid, 1.5-5% inorganic salt, 0.01-0.5% nonionic surfactant, 0.01-0.5% metal chelating agent, 0.01-1% antibacterial agent, and the balance being water.

[0017] In one embodiment, the concentration of organic acid in the constant temperature bath cleaning solution of the present invention is 1-2%. In another embodiment, the organic acid includes one or more of citric acid, acetic acid, oxalic acid, and acetic acid; in yet another embodiment, the organic acid is acetic acid, or citric acid, or acetic acid, or a mixture of citric acid and acetic acid. In one embodiment, the mass ratio of citric acid to acetic acid in the mixture of citric acid and acetic acid is 1:1. The present invention selects one or more of citric acid, acetic acid, oxalic acid, and acetic acid, which, compared to other types of organic acids, has the advantages of low corrosiveness to the metal parts of the constant temperature bath, safe use, and no generation of irritating acid mist.

[0018] In one embodiment, the concentration of inorganic salts in the constant temperature bath cleaning solution of the present invention is 1.6-4.6%; in another embodiment, the concentration of inorganic salts in the constant temperature bath cleaning solution of the present invention is 2-4.5%; in another embodiment, the concentration of inorganic salts in the constant temperature bath cleaning solution of the present invention is 2.5-4%; in yet another embodiment, the concentration of inorganic salts in the constant temperature bath cleaning solution of the present invention is 3-3.5%. In one embodiment, the inorganic salts of the present invention include one or more of sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium chloride, and sodium bicarbonate; in another embodiment, the inorganic salts of the present invention are disodium hydrogen phosphate, sodium chloride, or a mixture of disodium hydrogen phosphate and sodium chloride. In one embodiment, the mass ratio of disodium hydrogen phosphate to sodium chloride in the mixture of disodium hydrogen phosphate and sodium chloride of the present invention is 1.6:3. This invention selects one or more of sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium chloride, and sodium bicarbonate. Compared with other types of inorganic salts, it has the advantages of moderate buffering capacity and conductivity, assisting in stabilizing the pH of cleaning solution, not easily forming insoluble precipitates on pipeline surface, and good compatibility with organic acids and chelating agents.

[0019] In one embodiment, the concentration of nonionic surfactant in the constant temperature bath cleaning solution of the present invention is 0.05~0.2%; in another embodiment, the concentration of nonionic surfactant in the constant temperature bath cleaning solution of the present invention is 0.1~0.15%. In one embodiment, the metal chelating agent of the present invention includes one or more of disodium ethylenediaminetetraacetate (EDTA), ethylenediaminetetraacetic acid (EDTA), and sodium hexametaphosphate; in another embodiment, the metal chelating agent of the present invention is disodium ethylenediaminetetraacetate, or EDTA, or a mixture of disodium ethylenediaminetetraacetate and EDTA. In one embodiment, the mass ratio of disodium ethylenediaminetetraacetate to EDTA in the mixture of disodium ethylenediaminetetraacetate and EDTA in the present invention is 1:1. This invention selects one or more of disodium ethylenediaminetetraacetate (EDTA), ethylenediaminetetraacetic acid, and sodium hexametaphosphate. Compared with other types of nonionic surfactants, it has the advantages of good solubilization, dispersion and scale removal ability at low concentrations, less foam, good compatibility with metal chelating agents and inorganic salts, no corrosion to constant temperature bath materials such as stainless steel and plastic, and no impact on subsequent detection background.

[0020] In one embodiment, the concentration of the metal chelating agent in the constant temperature bath cleaning solution of the present invention is 0.05~0.2%; in another embodiment, the concentration of the metal chelating agent in the constant temperature bath cleaning solution of the present invention is 0.08~0.15%; in yet another embodiment, the concentration of the metal chelating agent in the constant temperature bath cleaning solution of the present invention is 0.1%. In one embodiment, the nonionic surfactant of the present invention includes one or more of Triton X-100, fatty alcohol polyoxyethylene ether, alkyl glycoside, and polysorbate 20; in one embodiment, the nonionic surfactant of the present invention is fatty alcohol polyoxyethylene ether, or Triton X-100 (TX-100), or an alkyl glycoside, or a mixture of Triton X-100 and polysorbate 20. In one embodiment, the mass ratio of Triton X-100 to polysorbate 20 in the mixture of Triton X-100 and polysorbate 20 of the present invention is 0.1:0.05. This invention selects one or more of Triton X-100, fatty alcohol polyoxyethylene ether, alkyl glycoside, and polysorbate 20. Compared with other types of metal chelating agents, it has strong chelating ability, good thermal stability, and can effectively complex Ca at low concentrations. 2+ Mg 2+ Fe 2+ / Fe 3+ It has the advantages of being free from scale-causing metal ions, having good biodegradability, and being less corrosive to the metal and plastic parts of the constant temperature bath.

[0021] In one embodiment, the concentration of the antibacterial agent in the constant temperature bath cleaning solution of the present invention is 0.5-0.82%; in another embodiment, the concentration of the antibacterial agent in the constant temperature bath cleaning solution of the present invention is 0.6-0.8%. In one embodiment, the antibacterial agent of the present invention includes one or more of sodium benzoate, sodium sorbate, ethanol, and Proclin 300; in another embodiment, the antibacterial agent of the present invention is sodium benzoate, or Proclin 300, or a mixture of Proclin 300 and ethanol. In one embodiment, the mass ratio of Proclin 300 to ethanol in the mixture of Proclin 300 and ethanol of the present invention is 0.02:0.8. The present invention selects one or more of sodium benzoate, sodium sorbate, ethanol, and Proclin 300, which, compared with other types of antibacterial agents, has the advantages of broad-spectrum antibacterial activity, good stability in weakly acidic systems, minimal interference with subsequent biochemical detection, low biotoxicity, and compliance with laboratory safety and environmental protection requirements.

[0022] In one embodiment, the water described in this invention is deionized water.

[0023] In one embodiment, the pH value of the constant temperature bath cleaning solution of the present invention is 4.5~5.5; in another embodiment, the pH value of the constant temperature bath cleaning solution of the present invention is 5.0. The present invention limits the pH value of the constant temperature bath cleaning solution to be weakly acidic, which is compatible with the plastic, stainless steel and other materials commonly used in biochemical analyzers, and is safe and environmentally friendly.

[0024] The present invention provides a method for preparing the constant temperature bath cleaning solution described in the above technical solution, comprising the following steps: adding organic acid, inorganic salt, metal chelating agent, nonionic surfactant and antibacterial agent to water in sequence, mixing evenly and filtering to obtain the constant temperature bath cleaning solution.

[0025] In one implementation method, under normal temperature and pressure conditions, the present invention involves sequentially adding organic acid, inorganic salt, metal chelating agent, nonionic surfactant, and antibacterial agent to water, followed by adding water to determine the weight, mixing thoroughly, and then filtering. This invention limits the order of addition, which has advantages such as preventing premature precipitation or micelle aggregation between components, ensuring that the metal chelating agent and organic acid form a stable microenvironment in the solution before introducing the surfactant, improving the solubility of each component and the uniformity of the system, and reducing scale precipitation or stratification caused by excessively high local concentrations, thereby enhancing the long-term storage stability and performance of the cleaning solution.

[0026] This invention provides the application of the constant temperature bath cleaning solution described in the above technical solution or the constant temperature bath cleaning solution prepared by the above technical solution in the maintenance of a fully automated biochemical analyzer.

[0027] In one embodiment, the operating temperature of the constant temperature bath cleaning solution of the present invention is 26.8~37.2℃; in another embodiment, the operating temperature of the constant temperature bath cleaning solution of the present invention is 37℃. In one embodiment, the constant temperature bath of the present invention is made of stainless steel.

[0028] To further illustrate the present invention, the following detailed description, in conjunction with embodiments, provides a constant temperature bath cleaning solution, its preparation method, and its application, but these descriptions should not be construed as limiting the scope of protection of the present invention.

[0029] Example 1 A constant temperature bath cleaning solution, by weight percentage, consists of the following components: 2% acetic acid, 1.6% disodium hydrogen phosphate, 0.05% disodium ethylenediaminetetraacetate, 0.05% fatty alcohol polyoxyethylene ether, 0.5% Proclin 300, and the balance water, pH=5.50.

[0030] The specific preparation method is as follows: Under normal temperature and pressure conditions, acetic acid, disodium hydrogen phosphate, disodium ethylenediaminetetraacetate, fatty alcohol polyoxyethylene ether, and Proclin 300 are added to water in sequence, weighed, and slowly stirred until evenly mixed. The mixture is then filtered to obtain the constant temperature bath cleaning solution.

[0031] Example 2 A constant temperature bath cleaning solution, by weight percentage, consists of the following components: 1.5% citric acid, 1.6% disodium hydrogen phosphate, 0.2% ethylenediaminetetraacetic acid, 0.2% TX-100, 1% sodium benzoate, and the balance water, pH=5.00.

[0032] The specific preparation method is as follows: Under normal temperature and pressure conditions, citric acid, disodium hydrogen phosphate, ethylenediaminetetraacetic acid, TX-100 and sodium benzoate are added to water in sequence, weighed, and slowly stirred until evenly mixed. After filtration, the constant temperature bath cleaning solution is obtained.

[0033] Example 3 A constant temperature bath cleaning solution, by weight percentage, consists of the following components: 1% acetic acid, 3% sodium chloride, 0.2% ethylenediaminetetraacetic acid, 0.2% alkyl glycoside, 0.1% sodium benzoate, and the balance being water, pH=4.50.

[0034] The specific preparation method is as follows: Under normal temperature and pressure conditions, acetic acid, sodium chloride, ethylenediaminetetraacetic acid, alkyl glycoside, and sodium benzoate are added to water in sequence, weighed, and slowly stirred until evenly mixed. After filtration, the constant temperature bath cleaning solution is obtained.

[0035] Examples 4-9 Similar to the constant temperature bath cleaning solution in Example 1, the specific differences are shown in Table 1 below.

[0036] Table 1 Comparison of the composition of the cleaning solution for the constant temperature bath in Examples 1 and 4-9

[0037] Comparative Example 1 A constant temperature bath cleaning solution similar to that of Example 1, the only difference being that acetic acid is not added.

[0038] Comparative Example 2 A constant temperature bath cleaning solution similar to that of Example 1, the only difference being that disodium hydrogen phosphate is not added.

[0039] Comparative Example 3 A constant temperature bath cleaning solution similar to that of Example 1, the only difference being that disodium ethylenediaminetetraacetate is not added.

[0040] Comparative Example 4 A constant temperature bath cleaning solution similar to that of Example 1, the only difference being that fatty alcohol polyoxyethylene ether is not added.

[0041] Comparative Example 5 A constant temperature bath cleaning solution similar to that of Example 1, the only difference being that Proclin300 is not added.

[0042] Comparative Example 6 A constant temperature bath cleaning solution similar to that of Example 1, the only difference being that tartaric acid is used instead of acetic acid.

[0043] Comparative Example 7 A constant temperature bath cleaning solution similar to that of Example 1, the only difference being that ethylene glycol diethyl ether diaminetetraacetic acid (EGTA) is used instead of disodium ethylenediaminetetraacetate (EDTA).

[0044] Comparative Example 8 A constant temperature bath cleaning solution similar to that of Example 1, the only difference being that sodium dehydroacetate is used instead of Proclin 300.

[0045] Test Example 1 Performance testing 1. Samples to be tested: The constant temperature bath cleaning solutions of Examples 1-9 and Comparative Examples 1-8.

[0046] 2. Optical stability experiment The samples to be tested were loaded into the Toshiba TBA2000-FR fully automated biochemical analyzer. For each type of constant temperature bath cleaning solution loaded, the reaction tank water was changed on the analyzer and the test cup blank was recorded. The absorbance values ​​of the cup blank at 340nm, 450nm, 604nm and 700nm were recorded 10 times in a row. The results are shown in Table 2.

[0047] Table 2 Comparison of Blank Absorbance of Cleaning Fluid Cups in Constant Temperature Bath

[0048] As can be seen from Table 2, the coefficients of variation (CV) of the blank absorbance of cup 7 at wavelengths of 340nm, 450nm, 604nm and 700nm in Examples 1 to 9, and the coefficients of variation (CV) of the blank absorbance of cup 7 at wavelength of 340nm in Comparative Examples 5 and 8 are <3%, while the CV values ​​of Comparative Examples 2 to 9 are significantly higher, with some CV values ​​exceeding 10%, and the blank absorbance values ​​of Comparative Examples 1 to 8 are more unstable.

[0049] 3. Precision Experiment In the TBA2000-FR fully automated biochemical analyzer, the reaction tank water was changed on the analyzer for each type of constant temperature bath cleaning solution loaded. The test item was β2-microglobulin (BMG), and the test results are shown in Tables 3 and 4.

[0050] Table 3. Precision test results of the cleaning solution in the constant temperature baths of Examples 1-9

[0051] Table 4. Precision test results of the cleaning solution in the constant temperature baths of Comparative Examples 1-9

[0052] As can be seen from Tables 3 and 4, the coefficient of variation of the constant temperature bath cleaning solution test samples of Examples 1 to 9 of the present invention is <2%, which meets the requirement that the CV of general diagnostic reagents is less than 5%, while the anti-contamination ability of Comparative Examples 1 to 8 is poor.

[0053] 4. Cleaning ability test On the biochemical analyzer, the constant temperature bath cleaning solutions of Example 1, Comparative Example 5 and Comparative Example 8 were used for 7 consecutive working days. After the instrument was turned on for self-test each day, the test cups were blank, and the absorbance values ​​at 340nm of reaction cups No. 7, No. 16 and No. 200 were recorded. The waste liquid was then replaced with a transparent waste liquid container to observe the waste liquid condition. The results are shown in Table 5.

[0054] Table 5. Absorbance values ​​of the 340nm cup blank

[0055] As shown in Table 5, the blank absorbance of the three reaction cups treated with the constant temperature bath cleaning solution in Example 1 decreased, indicating that it has a certain cleaning ability. In addition, there was no obvious scale in the waste liquid tank of Example 1, while there were obvious flocculent substances floating in the waste liquid of Comparative Examples 5 and 8, and there was a little scale residue on the wall of the waste liquid tank. This indicates that the sterilization ability of Comparative Examples 5 and 8 is insufficient and cannot inhibit the formation of scale.

[0056] 5. Stability test Examples 1-9 were left at room temperature for 12 months, and the pH was tested at 24-26℃. The pH values ​​were 5.55, 5.02, 4.56, 5.52, 5.49, 5.46, 5.58, 5.50, and 5.48, respectively, showing no significant change compared to when they were first prepared. Visually, the color of the cleaning solution in the constant temperature bath did not change, no precipitate formed, and no crystals formed.

[0057] Examples 1-3 were selected and loaded into the Toshiba TBA2000-FR fully automated biochemical analyzer. For each sample, a constant temperature bath cleaning solution was loaded, and the reaction tank water was changed on the analyzer. The test items were blood glucose (HK-GLU) and glucose-6-phosphate dehydrogenase (G6PD). The test results are shown in Table 6.

[0058] Table 6. Results of reagent precision test after 12 months

[0059] As can be seen from Table 6, the constant temperature bath cleaning solution obtained by the present invention has no significant impact on sample detection, and the constant temperature bath cleaning solution can be placed at room temperature for at least 12 samples.

[0060] As can be seen from the above, the constant temperature bath cleaning solution provided by the present invention can simultaneously solve the problems of scaling, corrosion, microbial growth and potential cross-contamination in the water bath system of a fully automated biochemical analyzer, extend the system maintenance cycle and ensure stable operation of the instrument.

[0061] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A constant temperature bath cleaning solution, characterized in that, The constant temperature bath cleaning solution comprises the following components by weight percentage: 0.5-3% organic acid, 1.5-5% inorganic salt, 0.01-0.5% nonionic surfactant, 0.01-0.5% metal chelating agent, 0.01-1% antibacterial agent, and the balance being water.

2. The constant temperature bath cleaning solution according to claim 1, characterized in that, The constant temperature bath cleaning solution comprises the following components: 1-2% organic acid, 1.6-4.6% inorganic salt, 0.05-0.2% nonionic surfactant, 0.05-0.2% metal chelating agent, 0.5-0.82% antibacterial agent, and the balance being water.

3. The constant temperature bath cleaning solution according to claim 1 or 2, characterized in that, The pH value of the cleaning solution in the constant temperature bath is 4.5~5.

5.

4. The constant temperature bath cleaning solution according to claim 1 or 2, characterized in that, The organic acids include one or more of citric acid, acetic acid, oxalic acid, and acetic acid.

5. The constant temperature bath cleaning solution according to claim 1 or 2, characterized in that, The inorganic salts include one or more of sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium chloride, and sodium bicarbonate.

6. The constant temperature bath cleaning solution according to claim 1 or 2, characterized in that, The metal chelating agent includes one or more of disodium ethylenediaminetetraacetate, ethylenediaminetetraacetic acid, and sodium hexametaphosphate.

7. The constant temperature bath cleaning solution according to claim 1 or 2, characterized in that, The nonionic surfactant includes one or more of Triton X-100, fatty alcohol polyoxyethylene ether, alkyl glycoside and polysorbate 20.

8. The constant temperature bath cleaning solution according to claim 1 or 2, characterized in that, The antibacterial agent includes one or more of sodium benzoate, sodium sorbate, ethanol, and Proclin 300.

9. The method for preparing the constant temperature bath cleaning solution according to any one of claims 1 to 8, characterized in that, The process includes the following steps: adding organic acid, inorganic salt, metal chelating agent, nonionic surfactant, and antibacterial agent to water in sequence, mixing them evenly, and then filtering to obtain the constant temperature bath cleaning solution.

10. The application of the constant temperature bath cleaning solution according to any one of claims 1 to 8 or the constant temperature bath cleaning solution obtained by the preparation method of claim 9 in the maintenance of a fully automated biochemical analyzer.

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