A diluent for blood cell analysis, its preparation method and uses

By adding inorganic salts, preservatives, and anti-precipitants to the diluent for blood cell analysis, the problems of instrument clogging and diluent stability were solved, achieving efficient cleaning and long-term stable detection results, and reducing maintenance costs.

CN122306527APending Publication Date: 2026-06-30JINHUA XINKE PHARMA TECH CO LTD

Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
JINHUA XINKE PHARMA TECH CO LTD
Filing Date
2026-03-31
Publication Date
2026-06-30

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Abstract

This invention relates to the field of hematology analysis technology, and in particular to a diluent for hematology analysis, its preparation method, and its uses. The diluent comprises the following components: 0.5-15 g / L of inorganic salt, 0.01-5.0 g / L of preservative, and 0.1-0.5 g / L of stabilizing agent; the solvent of the diluent is water; the diluent also includes an anti-precipitant, selected from one or more of salt-based and organic anti-precipitants; the salt-based anti-precipitant includes one or more of thiocyanate and nitrate, with a content of 2.0-5.0 mmol / L; the organic anti-precipitant includes one or more of trehalose, mannitol, and amino acid ionic liquids, with a content of 4.0-8.0 mmol / L. In this diluent, the components work synergistically to reduce the maintenance cost of the hematology analyzer, increase its service life, and improve detection efficiency.
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Description

Technical Field

[0001] This invention relates to the field of blood cell analysis technology, and in particular to a diluent for blood cell analysis, its preparation method, and its uses. Background Technology

[0002] Blood cell analyzers are among the most widely used instruments in hospital clinical laboratories. Blood cell testing is an indispensable part of biomedical research and plays a vital role in the diagnosis, treatment, and prevention of diseases. The accuracy of the values ​​provided by a blood cell analyzer is crucial for both doctors and patients.

[0003] Blood cell analyzers experience various malfunctions during routine use, with port clogging being the most common problem, especially in large hospitals handling high volumes of tests. This is because protein components in the samples bind to cationic surfactants in the lysing agent, causing protein denaturation and leaving residues or adsorbed in the tubing and test cells. Anti-clogging technology for blood cell analyzer diluents has evolved from simple physical rinsing and isotonic environment maintenance to a comprehensive solution integrating chemical cleaning, physical lubrication, biomorphic stability, and specificity. The complexity and precision of its formulation directly determine the instrument's analytical accuracy, reliability, and maintenance frequency. Since conventional blood cell analyzer diluents are insufficient for efficiently cleaning the test tubing, port clogging easily occurs when the daily test volume accumulates to a certain level. Resolving port clogging requires time spent cleaning the tubing and test cells with sodium hypochlorite solution, significantly impacting testing efficiency. Furthermore, frequent and prolonged use of sodium hypochlorite solution can negatively affect the test cells and tubing, shortening the instrument's lifespan and increasing operating costs.

[0004] Currently mentioned additives that can reduce the probability of instrument clogging include low-foaming surfactants or the addition of certain enzymes to remove residual plasma proteins, fibrin, cell debris, and other protein blockages in the tubing. Surfactant molecules easily adsorb onto the inner walls of instrument tubing and cuvettes. Even trace amounts of surfactant residue can be carried away by subsequent sample or reagent flows, contaminating the reaction system and potentially causing drift or abnormal results. Furthermore, "low-foaming" does not mean "foam-free." During high-speed mixing, stirring, or reagent aspiration, fine, persistent foam may still be generated. Since the instrument relies on capacitance or optical principles to detect the liquid surface, the foam layer can interfere with detection, leading to inaccurate sample volume or errors. If a mixture of foam and liquid is aspirated, the actual sample volume will be inaccurate, directly affecting the precision and accuracy of the test results. Methods using enzymes to remove specific substances that may clog pores or interfere with detection also have hidden risks. Enzymatic reactions produce a large number of degradation products. For instruments based on impedance methods, these particles of varying sizes may be mistaken for "cells" and counted, leading to falsely elevated platelet counts and inaccurate white blood cell counts (especially in lymphocyte and monocyte regions). For instruments based on optical methods (scattered light, fluorescence), the impact includes increased background turbidity, severely interfering with light signal acquisition and making white blood cell differential and reticulocyte analysis impossible. Furthermore, enzyme reactions require time, while blood cell analysis is typically completed quickly after dilution (within tens of seconds to minutes). If the enzyme continues to act during the detection process, it can lead to unstable results, with significant differences in the same sample detected at different times. Enzyme activity is also highly temperature-sensitive, increasing the demands on the instrument's temperature control system and potentially causing inconsistencies in results under different laboratory environments.

[0005] Furthermore, the diluent itself contains inorganic salts and other components, providing nutrients for microbial growth. After opening, conventional diluents can deteriorate over time due to the introduction of bacteria and fungi from the air, evaporation of moisture, or changes in pH and conductivity, leading to inaccurate test results. For smaller hospitals or local township health centers, the number of samples tested daily may not be particularly large. A typical 20L package of diluent may be used for six months to a year after opening, placing significant demands on the stability and antibacterial properties of the diluent.

[0006] Therefore, there is an urgent need to develop a new dispersant system and its matching diluent, so that in silicon carbide wafer polishing applications, it can maintain a high initial polishing rate, significantly improve cycle stability, and reduce polishing rate decay, thereby meeting the stringent requirements of semiconductor manufacturing for process window and cost control. Summary of the Invention

[0007] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide a diluent for blood cell analysis, its preparation method, and its uses. This addresses the problem in the prior art where the diluent for blood cell analysis cannot efficiently clean the detection tubing, easily causing instrument clogging.

[0008] To achieve the above and other related objectives, the present invention is obtained through the following technical solution.

[0009] The first aspect of this invention discloses a diluent for blood cell analysis, the diluent comprising the following components: 0.5-15 g / L of inorganic salt, 0.01-5.0 g / L of preservative, and 0.1-0.5 g / L of stabilizing agent; the solvent of the diluent is water; the diluent further comprises an anti-precipitant, the anti-precipitant being selected from one or more of salt-based anti-precipitants and organic anti-precipitants; the salt-based anti-precipitant comprising one or more of thiocyanate and nitrate, the content of the salt-based anti-precipitant being 2.0-5.0 mmol / L; the organic anti-precipitant comprising one or more of trehalose, mannitol, and amino acid ionic liquid, the content of the organic anti-precipitant being 4.0-8.0 mmol / L. In the diluent, the components work synergistically to reduce the adsorption of protein substances on the pipeline or to reduce the maintenance cost of the blood cell analyzer from the source by increasing the viscosity of the diluent, thereby increasing the service life of the instrument and improving the detection efficiency. Moreover, the diluent can maintain a stable pH and conductivity even after long-term storage after opening, and will not produce bacteria, thus extending the open-use time of the diluent.

[0010] The anti-precipitation agent, without damaging the blood sample, increases the viscosity of the diluent, improves the rheological properties of the fluid in the micropores, acts as a lubricant, reduces the chance of particles colliding and adsorbing with the pore walls, or enhances the stability of the cells themselves, preventing blood samples from remaining in the detection pool and pipes, thereby preventing instrument clogging.

[0011] The concentration of the anti-precipitant salt can be 2–2.5 mmol / L, 2.5–3 mmol / L, 3–3.5 mmol / L, 3.5–4 mmol / L, 4–4.5 mmol / L, or 4.5–5 mmol / L. If the concentration of the anti-precipitant salt is below 2.0 mmol / L, the concentration in the diluent will be too low to prevent protein aggregation. If the concentration is above 5.0 mmol / L, the osmotic pressure of the diluent may be too high, resulting in smaller cell volume after diluting the blood sample and affecting the accuracy of the test results. Within the range of 2.0–5.0 mmol / L, the higher the concentration of the anti-precipitant salt, the better the effect of preventing protein aggregation.

[0012] The concentration of the organic anti-precipitant can be 4–4.5 mmol / L, 4.5–5 mmol / L, 5–5.5 mmol / L, 5.5–6 mmol / L, 6–6.5 mmol / L, 6.5–7 mmol / L, 7–7.5 mmol / L, or 7.5–8 mmol / L. If the concentration of the organic anti-precipitant is below 4.0 mmol / L, the concentration in the diluent is too low to prevent protein aggregation. If the concentration is above 8.0 mmol / L, it will significantly increase the osmotic pressure of the solution, affecting the detection results. It will also increase the solution viscosity, increasing the flow resistance in the microfluidic channel or sample needle, making it more prone to stagnation and blockage in finer areas. Within the range of 4.0–8.0 mmol / L, the higher the concentration of the organic anti-precipitant, the better the effect of preventing protein aggregation.

[0013] The content of the stabilizer can be 0.1~0.2 g / L, 0.2~0.3 g / L, 0.3~0.4 g / L, or 0.4~0.5 g / L. If the content of the stabilizer is below 0.1 g / L, the concentration of the stabilizer in the diluent is too low to stabilize the diluent, resulting in high background and poor repeatability in the detection results. If the content of the stabilizer is above 0.5 g / L, it may lead to low sensitivity, slow reaction, increased risk of physical blockage, and matrix interference. Within the range of 0.1~0.5 g / L, the higher the concentration of the stabilizer, the better the effect on stabilizing pH and conductivity.

[0014] The content of the preservative can be 0.01~0.05 g / L, 0.05~0.1 g / L, 0.1~0.5 g / L, 0.5~1 g / L, 1~1.5 g / L, 1.5~2 g / L, 2~2.5 g / L, 2.5~3 g / L, 3~3.5 g / L, 3.5~4 g / L, 4~4.5 g / L, or 4.5~5 g / L. If the preservative content is below 0.01 g / L, the concentration of preservative in the diluent is too low to prevent bacterial growth and inhibit the spoilage of the diluent. If the preservative content is above 5 g / L, although it can effectively inhibit microbial growth, it will have a serious negative impact on reagent performance, detection accuracy, and operational safety. Within the range of 0.01~5 g / L, the higher the preservative concentration, the better the effect of preventing bacterial growth and inhibiting the spoilage of the diluent.

[0015] The inorganic salt content can be 0.5~1 g / L, 1~2 g / L, 2~3 g / L, 3~4 g / L, 4~5 g / L, 5~6 g / L, 6~7 g / L, 7~8 g / L, 8~9 g / L, 9~10 g / L, 10~11 g / L, 11~12 g / L, 12~13 g / L, 13~14 g / L, or 14~15 g / L. If the inorganic salt content is below 0.5 g / L, the concentration of inorganic salts in the diluent is too low to maintain osmotic pressure and preserve cell morphology. If the inorganic salt content is above 15 g / L, it will cause protein salting out and aggregation. Within the range of 0.5~15 g / L, the inorganic salt concentration is moderate, which can stabilize cell biological activity and reduce the risk of protein salting out.

[0016] Preferably, the amino acid ionic liquid is selected from one or more of the following: choline alanine salt ionic liquid, 1-ethyl-3-methylimidazolium glycine salt ionic liquid, tetraethylammonium glycine salt ionic liquid, and arginine-aspartic acid ionic liquid.

[0017] Preferably, the content of the inorganic salt is 2~10 g / L. The inorganic salt provides an isotonic environment for the blood sample, preventing cell rupture or shrinkage and maintaining the accuracy of the MCV value detected by cell analysis.

[0018] Preferably, the preservative content is 0.05~2.0 g / L. The preservative inhibits bacterial growth in the diluted solution, thus extending the shelf life and prolonging the shelf life after opening.

[0019] Preferably, the inorganic salt is selected from one or more of sodium chloride, potassium chloride, sodium sulfate, and potassium sulfate.

[0020] Preferably, the preservative is selected from one or more of diazoalkylurea, imidazoalkylurea, and pyrithioneurea.

[0021] Preferably, the stabilizing agent is selected from one or more of polyvinylpyrrolidone, propylene glycol, 2-methyl-2,4-pentanediol, and PEGylated phospholipids. The stabilizing agent maintains the uniformity and dispersion stability of the diluent by relying on the steric hindrance, film-forming properties, and thickening effect of its polymer chains, or by adjusting its polarity and water molecule binding capacity, maintaining the solubility, cell activity, and freeze-thaw stability of the components in the diluent, thereby improving the stability of the diluent and ensuring the accuracy of the detection results.

[0022] In this application, the weight-average molecular weight of the polyvinylpyrrolidone is 2500-10000. For example, it can be 2500-3000, 3000-4000, 4000-5000, 5000-6000, 6000-7000, 7000-8000, 8000-9000, or 9000-10000.

[0023] Preferably, the diluent further includes 0.5~10 g / L of buffer.

[0024] More preferably, the buffer is selected from one or more of borates, phosphates, organic sulfonates, organic carboxylates, and N-(2-acetamido)-2-aminoethanesulfonic acid. The buffer works synergistically with other components in the diluent to maintain a stable pH value in the diluent, thereby enhancing the stability of the detection results.

[0025] More preferably, the content of the buffer is 0.5~8 g / L. For example, it can be 0.5~1 g / L, 1~2 g / L, 2~3 g / L, 3~4 g / L, 4~5 g / L, 5~6 g / L, 6~7 g / L, or 7~8 g / L.

[0026] Preferably, the diluent further includes 0.1~25 g / L of a complexing agent.

[0027] The content of the complexing agent can be 0.1~5 g / L, 5~10 g / L, 10~15 g / L, 15~20 g / L, or 20~25 g / L.

[0028] More preferably, the complexing agent is selected from one or more of ethylenediaminetetraacetic acid (EDTA), citric acid, and ethylene glycol bis(2-aminoethyl ether)tetraacetic acid (EDTA). The complexing agent prevents blood samples from clotting in the diluent and is a functional additive capable of forming stable complexes with metal ions. Its core function is to precisely control the concentration of free metal ions in the reaction system. For example, ethylene glycol bis(2-aminoethyl ether)tetraacetic acid (EDTA) has the key advantage of being a complexing agent because it has high selectivity for calcium ions, while its affinity for magnesium ions is much lower than that of EDTA. It works synergistically with other components in the diluent to maintain a stable pH, maintain an isotonic environment for cells, and improve cell dispersion. Through chelation, the complexing agent can inhibit precipitation reactions and metal-catalyzed hydrolysis, assist the buffer system in maintaining long-term pH stability, regulate ion transmembrane flow and stabilize membrane structure, precisely maintain an isotonic environment, prevent cell damage due to osmotic stress, and reduce non-specific protein adhesion, resulting in highly uniform monodisperse cells in the diluent, providing a reliable guarantee for high-precision analysis and subsequent experiments.

[0029] Preferably, the pH value of the diluent is 6-8. For example, it can be 6-6.5, 6.5-6.8, 6.8-6.9, 6.9-7.0, 7.0-7.1, 7.1-7.2, 7.2-7.3, 7.3-7.4, 7.4-7.5, or 7.5-8.

[0030] The second aspect of the present invention discloses a method for preparing the diluent as described above, the method comprising the following steps: stirring and mixing the raw material components.

[0031] The third aspect of the present invention also discloses the use of the diluent described above in blood cell analysis.

[0032] Preferably, the application includes protecting blood cells and stabilizing the liquid system during the blood dilution phase, thereby reducing the probability of instrument clogging and ensuring the accuracy of test results.

[0033] The fourth aspect of this invention also discloses the use of an anti-precipitant in reducing the probability of clogging in instruments using diluents for blood cell analysis, wherein the anti-precipitant is selected from one or more of salt-based anti-precipitants and organic anti-precipitants; the salt-based anti-precipitant includes one or more of thiocyanate and nitrate; and the organic anti-precipitant includes one or more of trehalose, mannitol, and amino acid ionic liquids.

[0034] Preferably, the content of the salt anti-precipitant is 2.0~5.0 mmol / L, and the content of the organic anti-precipitant is 4.0~8.0 mmol / L.

[0035] Compared with the prior art, the present invention has the following beneficial effects:

[0036] 1) In the diluent described in this application, the anti-precipitation agent prevents pore blockage from the source by maintaining cell integrity and a stable liquid environment, shifting from "passive cleaning" to "active protection". It does not rely solely on using strong cleaning agents to remove blockages afterward, but creates an extremely friendly environment during the dilution stage to maximize the protection of blood cells and stabilize the liquid system, thereby fundamentally reducing the probability of pore blockage and ensuring the accuracy of test results.

[0037] 2) In the diluent described in this application, the stabilizing substance and preservative inhibit bacterial growth in the diluent, allowing the reagent to remain effective for a longer period after opening without affecting the test results, thus extending the shelf life of the diluent after opening.

[0038] 3) The diluent disclosed in this application reduces the maintenance cost of blood cell analyzers, increases the service life of instruments and improves detection efficiency through the synergistic effect of each component. Moreover, the diluent remains stable even after long-term storage after opening, which extends the open-use time of the diluent and enhances the stability of the detection results. Attached Figure Description

[0039] Figure 1 The graph shows a linear regression of the WBC (white blood cell) test results of the diluents described in Example 1 and Comparative Example 1 of this invention.

[0040] Figure 2 The graph shows the linear regression results of the RBC (red blood cell) test of the diluents described in Example 1 and Comparative Example 1 of this invention.

[0041] Figure 3 The graph shows the linear regression results of HGB (hemoglobin) tests for the diluents described in Example 1 and Comparative Example 1 of this invention.

[0042] Figure 4 The graph shows a linear regression of the MCV (mean corpuscular volume) test results of the diluents described in Example 1 and Comparative Example 1 of this invention.

[0043] Figure 5 The graph shows the linear regression results of the PLT (platelet-rich plasma) test of the diluents described in Example 1 and Comparative Example 1 of this invention.

[0044] Figure 6 The graph shows the linear regression results of the WBC (white blood cell) test of the diluents described in Example 2 and Comparative Example 1 of this invention.

[0045] Figure 7 The graph shows the linear regression results of the RBC (red blood cell) test of the diluents described in Example 2 and Comparative Example 1 of this invention.

[0046] Figure 8 The graph shows the linear regression results of the HGB (hemoglobin) test of the diluents described in Example 2 and Comparative Example 1 of this invention.

[0047] Figure 9 The graph shows the linear regression results of the MCV (mean corpuscular volume) test of the diluents described in Example 2 and Comparative Example 1 of this invention.

[0048] Figure 10 The graph shows the linear regression results of the PLT (platelet-rich plasma) test of the diluents described in Example 2 and Comparative Example 1 of this invention.

[0049] Figure 11 The graph shows the linear regression results of the WBC (white blood cell) test of the diluents described in Example 3 and Comparative Example 1 of this invention.

[0050] Figure 12 The graph shows the linear regression results of the RBC (red blood cell) test of the diluents described in Example 3 and Comparative Example 1 of this invention.

[0051] Figure 13 The graph shows the linear regression results of HGB (hemoglobin) tests for the diluents described in Example 3 and Comparative Example 1 of this invention.

[0052] Figure 14 The graph shown is a linear regression plot of the MCV (mean corpuscular volume) test results of the diluents described in Example 3 and Comparative Example 1 of this invention.

[0053] Figure 15 The graph shows the linear regression results of the PLT (platelet-rich plasma) test of the diluents described in Example 3 and Comparative Example 1 of this invention. Detailed Implementation

[0054] The following specific embodiments illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification.

[0055] Before further describing specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terminology used in the embodiments of the present invention is for describing specific embodiments and not for limiting the scope of protection of the present invention. Test methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the respective manufacturers.

[0056] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the present invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art. In addition to the specific methods, apparatus, and materials used in the embodiments, based on the knowledge of the prior art possessed by one of ordinary skill in the art and the description of this invention, any prior art methods, apparatus, and materials similar to or equivalent to those described, apparatus, and materials in the embodiments of this invention may be used to implement the present invention.

[0057] In this application, addressing the technical problem that existing hematology analyzer diluents cannot efficiently clean detection tubing, easily causing instrument clogging, the applicant provides a hematology analyzer diluent, its preparation method, and its uses. The diluent described in this application fundamentally reduces the maintenance costs of hematology analyzers, increases instrument lifespan, and improves detection efficiency. Furthermore, the diluent remains stable even after long-term storage after opening, extending its usability and enhancing the stability of test results.

[0058] Specifically, this embodiment of the invention provides a specific diluent, its preparation method, and its uses. The diluent comprises the following components: 0.5–15 g / L of an inorganic salt, 0.01–5.0 g / L of a preservative, and 0.1–0.5 g / L of a stabilizing substance. The solvent of the diluent is water. The diluent also includes an anti-precipitant, selected from one or more salt-based and organic anti-precipitants. The salt-based anti-precipitant includes one or more of thiocyanate and nitrate, with a concentration of 2.0–5.0 mmol / L. The organic anti-precipitant includes one or more of trehalose, mannitol, and amino acid ionic liquids, with a concentration of 4.0–8.0 mmol / L.

[0059] The content of each raw material component in this application can be adjusted according to actual polishing and production needs.

[0060] This invention provides a specific method for preparing a diluent, the method comprising the following steps: stirring and mixing the raw material components.

[0061] Example 1

[0062] This embodiment provides a specific method for preparing a diluent, the method comprising the following steps:

[0063] Under room temperature conditions, the raw materials were weighed according to the following amounts: 5.2 g / L sodium chloride, 7.0 g / L sodium sulfate, 5.3 g / L sodium dihydrogen phosphate, 0.5 g / L 3-morpholinopropanesulfonic acid, 2.0 g / L ethylenediaminetetraacetic acid, 0.5 g / L imidazolidinyl urea, 0.2 g / L polyvinylpyrrolidone with a weight average molecular weight of 8000, and 4 mmol / L sodium thiocyanate. The raw materials were dissolved in deionized water, stirred thoroughly, dissolved, and diluted to a final volume to obtain the diluted solution. The pH value of the diluted solution was measured to be 7.0 using a pH meter.

[0064] Example 2

[0065] This embodiment provides a specific method for preparing a diluent, the method comprising the following steps:

[0066] Under room temperature conditions, the raw materials were weighed according to the following amounts: 7.2 g / L sodium chloride, 5.0 g / L sodium sulfate, 5.3 g / L sodium dihydrogen phosphate, 0.5 g / L 3-morpholinopropanesulfonic acid, 2.0 g / L ethylenediaminetetraacetic acid, 0.5 g / L imidazolidinyl urea, 0.2 g / L polyvinylpyrrolidone with a weight average molecular weight of 8000, and 5 mmol / L arginine-aspartic acid ionic liquid. The raw materials were dissolved in deionized water, stirred thoroughly, dissolved, and diluted to a final volume to obtain the diluted solution. The pH value of the diluted solution was measured to be 6.9 using a pH meter.

[0067] Example 3

[0068] This embodiment provides a specific method for preparing a diluent, the method comprising the following steps:

[0069] Under room temperature conditions, the raw materials were weighed according to the following amounts: 5.2 g / L sodium chloride, 7.0 g / L sodium sulfate, 5.3 g / L sodium dihydrogen phosphate, 0.5 g / L 3-morpholinopropanesulfonic acid, 2.0 g / L ethylenediaminetetraacetic acid, 0.5 g / L imidazolidinyl urea, 0.2 g / L polyvinylpyrrolidone with a weight average molecular weight of 8000, and 6 mmol / L trehalose. The solutions were dissolved in deionized water, stirred thoroughly, dissolved, and brought to a final volume to obtain the diluted solution. The pH of the diluted solution was measured to be 7.1 using a pH meter.

[0070] Example 4

[0071] This embodiment provides a specific method for preparing a diluent, the method comprising the following steps:

[0072] Under room temperature conditions, the raw materials were weighed according to the following amounts: 5.2 g / L sodium chloride, 7.0 g / L sodium sulfate, 5.3 g / L sodium dihydrogen phosphate, 0.5 g / L 3-morpholinopropanesulfonic acid, 2.0 g / L ethylenediaminetetraacetic acid, 0.5 g / L imidazolidinyl urea, 0.2 g / L polyvinylpyrrolidone with a weight average molecular weight of 8000, and 4.5 mmol / L trehalose. The solutions were dissolved in deionized water, stirred thoroughly, dissolved, and brought to a final volume to obtain the diluted solution. The pH of the diluted solution was measured to be 7.2 using a pH meter.

[0073] Comparative Example 1

[0074] In this comparative example, a specific diluent is provided: the original diluent for Mindray BC5380 hematology analysis.

[0075] Comparative Example 2

[0076] This comparative example provides a specific method for preparing a diluent, the method comprising the following steps:

[0077] Under room temperature conditions, the raw materials were weighed according to the following amounts: 5.2 g / L sodium chloride, 7.0 g / L sodium sulfate, 5.3 g / L sodium dihydrogen phosphate, 0.5 g / L 3-morpholinopropanesulfonic acid, 2.0 g / L ethylenediaminetetraacetic acid, 0.5 g / L imidazolidinyl urea, and 0.2 g / L polyvinylpyrrolidone with a weight average molecular weight of 8000. The solutions were dissolved in deionized water, stirred thoroughly, dissolved, and brought to a final volume to obtain the diluted solution. The pH of the diluted solution was measured to be 7.1 using a pH meter.

[0078] The test results of the anti-clogging test of the diluent are shown in Table 1. The test results show that the absence of anti-precipitant in the diluent increases the number of times the instrument will alarm for clogging, and the probability of instrument clogging increases, indicating that the anti-precipitant cannot play a role in preventing precipitation.

[0079] Comparative Example 3

[0080] In this comparative example, a specific method for preparing the diluent is provided. The difference between this method and Example 3 is that the 4.5 mmol / L trehalose is replaced with 9 mmol / L trehalose.

[0081] The test results of the anti-clogging test of the diluent are shown in Table 1. The test results show that an excessive amount of anti-precipitant in the diluent will increase the number of times the instrument will alarm for clogging, and the probability of instrument clogging will increase. This indicates that an excessive amount of anti-precipitant cannot play a role in preventing precipitation.

[0082] Comparative Example 4

[0083] In this comparative example, a specific method for preparing the diluent is provided. The difference between this method and Example 3 is that the 4.5 mmol / L trehalose is replaced with 3 mmol / L trehalose.

[0084] The test results of the anti-clogging test of the diluent are shown in Table 1. The test results show that too little anti-precipitant in the diluent will increase the number of times the instrument will alarm for clogging, and the probability of instrument clogging will increase, indicating that too little anti-precipitant will not play a role in preventing precipitation.

[0085] Comparative Example 5

[0086] In this comparative example, a specific method for preparing the diluent is provided. The difference between this method and Example 3 is that the 4.5 mmol / L trehalose is replaced with 4.5 mmol / L glucose.

[0087] The test results of the anti-clogging test of the diluent are shown in Table 1. The test results show that adding other organic substances to the diluent as anti-precipitation agents will increase the number of times the instrument will alarm for clogging, and the probability of instrument clogging will increase, indicating that other organic substances cannot play a role in preventing precipitation.

[0088] Comparative Example 6

[0089] In this comparative example, a specific method for preparing the diluent is provided. The difference between this method and Example 1 is that the 4 mmol / L sodium thiocyanate is replaced with 4 mmol / L potassium acetate.

[0090] The test results of the anti-clogging test of the diluent are shown in Table 1. The test results show that adding other salts to the diluent as anti-precipitation agents increases the number of times the instrument will alarm for clogging, and the probability of instrument clogging increases, indicating that other salts cannot play a role in preventing precipitation.

[0091] Application Example 1

[0092] The diluents prepared in Examples 1-4 were placed in the corresponding positions of the Mindray BC5380 hematology analyzer and compared with the diluents described in Comparative Examples 1-6 to conduct a verification anti-clogging test.

[0093] Before each control experiment, the instruments were cleaned to ensure they were in optimal testing condition. During the measurement process, without cleaning the instruments, 1000 samples were measured in each group, with five replicates. It should be noted that the 1000 samples were venous blood samples, and the diluents used in Examples 1-4 and Comparative Examples 1-6 within the same group were identical, as were the instruments.

[0094] The statistical instrument triggered a blockage alarm. The lower the probability of the blockage alarm, the better the anti-blockage effect. The test results are shown in Table 1.

[0095] Table 1 Statistical Table of Anti-Clogging Hole Test Results

[0096]

[0097]

[0098] Test Results Data Explanation: In the instrument testing of the diluents in Examples 1-4, although occasional clogging occurred, the probability of clogging was significantly lower than that of the diluents in Comparative Examples 1-6. This indicates that the diluent described in this application reduces the probability of clogging, thereby fundamentally reducing the maintenance cost of the hematology analyzer, increasing the instrument's lifespan, and improving detection efficiency. The clogging probability mentioned in this application refers to the average number of clogging events after multiple experiments.

[0099] Application Example 2

[0100] The diluents prepared in Examples 1-4 and the diluents described in Comparative Examples 1 and 2 were placed in a constant temperature room at approximately 37°C. 0.5% (v / v) of *E. coli* was added to each of the different diluent formulations. After a period of time, the solutions of Comparative Examples 1 and 2 began to grow bacteria after about 3 months, becoming noticeably turbid and exhibiting a decrease in pH. The number of particles in the solutions was measured using a GWF-8JA particle detector, and the results are shown in Table 2. The number of large particles increased significantly. However, the diluents prepared in Examples 1-4 did not show any turbidity after being opened and stored for one year, and the pH of the solution remained stable at approximately 7.03.

[0101] Table 2. Detection of particle count in solution

[0102]

[0103] Application Example 3

[0104] The blood cell analyzer diluent prepared in Example 1 was placed on the corresponding position of the Mindray BC5380 blood cell analyzer for verification. Twenty venous blood samples were taken for whole blood mode measurement. The results were compared with the original diluent for the Mindray BC5380 blood cell analyzer described in Comparative Example 1 for WBC (white blood cells), RBC (red blood cells), HGB (hemoglobin), MCV (mean corpuscular volume), and PLT (platelets). The test results are shown in Tables 3-7.

[0105] Table 3. Results of WBC (White Blood Cell) Measurement

[0106] Whole blood specimen number Example 1: Determination of WBC (×10^9 / L) using dilution solution WBC (×10^9 / L) was determined using the dilution solution of Comparative Example 1. relative deviation Specimen 1 6.27 6.20 1.13% Specimen 2 9.15 9.14 0.11% Specimen 3 8.46 8.48 -0.24% Specimen 4 8.58 8.39 2.26% Specimen 5 5.66 5.73 -1.22% Specimen 6 7.29 7.31 -0.27% Specimen 7 5.62 5.59 0.54% Specimen 8 4.01 4.02 -0.25% Specimen 9 8.22 8.38 -1.91% Specimen 10 6.81 6.84 -0.44% Specimen 11 8.19 8.27 -0.97% Specimen 12 5.25 5.33 -1.50% Specimen 13 6.11 5.98 2.17% Specimen 14 6.71 6.59 1.82% Specimen 15 7.56 7.37 2.58% Specimen 16 4.34 4.39 -1.14% Specimen 17 8.60 8.65 -0.58% Specimen 18 4.55 4.43 2.71% Specimen 19 7.18 7.31 -1.78% Specimen 20 5.56 5.66 -1.77%

[0107] Table 4. Results of RBC (Red Blood Cell) Measurement

[0108] Whole blood specimen number Example 1: Determination of RBC (×10^12 / L) with dilution solution RBC (×10^12 / L) was determined using the dilution of Comparative Example 1. relative deviation Specimen 1 3.97 3.93 1.02% Specimen 2 3.55 3.57 -0.56% Specimen 3 4.53 4.52 0.22% Specimen 4 4.98 5.02 -0.80% Specimen 5 4.74 4.76 -0.42% Specimen 6 4.71 4.72 -0.21% Specimen 7 4.98 5.02 -0.80% Specimen 8 4.32 4.39 -1.59% Specimen 9 4.84 4.81 0.62% Specimen 10 4.95 4.88 1.43% Specimen 11 5.67 5.63 0.71% Specimen 12 3.59 3.66 -1.91% Specimen 13 4.47 4.45 0.45% Specimen 14 4.00 3.98 0.50% Specimen 15 5.46 5.50 -0.73% Specimen 16 3.23 3.23 0.00% Specimen 17 5.26 5.35 -1.68% Specimen 18 4.94 4.95 -0.20% Specimen 19 4.82 4.71 2.34% Specimen 20 5.20 5.13 1.36%

[0109] Table 5 HGB (hemoglobin) measurement results

[0110] Whole blood specimen number Example 1: Determination of HGB (g / L) using dilution solution HGB (g / L) was determined using the dilution solution of Comparative Example 1. relative deviation Specimen 1 122 122 0.00% Specimen 2 118 119 -0.84% Specimen 3 152 153 -0.65% Specimen 4 150 151 -0.66% Specimen 5 146 147 -0.68% Specimen 6 148 149 -0.67% Specimen 7 158 159 -0.63% Specimen 8 140 142 -1.41% Specimen 9 142 142 0.00% Specimen 10 152 151 0.66% Specimen 11 143 143 0.00% Specimen 12 119 119 0.00% Specimen 13 149 149 0.00% Specimen 14 141 142 -0.70% Specimen 15 168 169 -0.59% Specimen 16 100 99 1.01% Specimen 17 165 166 -0.60% Specimen 18 165 168 -1.79% Specimen 19 165 166 -0.60% Specimen 20 166 166 0.00%

[0111] Table 6 Results of MCV (Mean Red Cell Volume) Measurement

[0112] Whole blood specimen number Example 1: Determination of MCV (fL) using dilution buffer MCV (fL) was determined using the dilution solution of Comparative Example 1. relative deviation Specimen 1 91.7 91.2 0.55% Specimen 2 103.7 103.5 0.19% Specimen 3 99.6 98.9 0.71% Specimen 4 91.2 90.5 0.77% Specimen 5 95.1 94.8 0.32% Specimen 6 95 94.6 0.42% Specimen 7 95.1 94.7 0.42% Specimen 8 98.4 97.5 0.92% Specimen 9 90.3 89.5 0.89% Specimen 10 93.4 92.9 0.54% Specimen 11 79.7 79.4 0.38% Specimen 12 101.0 100.6 0.40% Specimen 13 103.2 102.8 0.39% Specimen 14 104.6 104.2 0.38% Specimen 15 93.5 92.9 0.65% Specimen 16 97.0 97.1 -0.10% Specimen 17 93.7 93.5 0.21% Specimen 18 95.4 93.1 2.47% Specimen 19 96.3 94.6 1.80% Specimen 20 89.1 87.7 1.60%

[0113] Table 7. PLT (platelet) assay results

[0114] Whole blood specimen number Example 1: Determination of PLT (×10^9 / L) with dilution solution PLT (×10^9 / L) was determined using the dilution solution of Comparative Example 1. relative deviation Specimen 1 223 222 0.45% Specimen 2 336 346 -2.89% Specimen 3 302 301 0.33% Specimen 4 368 368 0.00% Specimen 5 363 357 1.68% Specimen 6 202 203 -0.49% Specimen 7 269 274 -1.82% Specimen 8 280 273 2.56% Specimen 9 334 335 -0.30% Specimen 10 263 265 -0.75% Specimen 11 257 257 0.00% Specimen 12 293 299 -2.01% Specimen 13 328 330 -0.61% Specimen 14 210 217 -3.23% Specimen 15 319 322 -0.93% Specimen 16 124 122 1.64% Specimen 17 243 235 3.40% Specimen 18 259 263 -1.52% Specimen 19 231 230 0.43% Specimen 20 206 209 -1.44%

[0115] Using the test results of the diluent described in Comparative Example 1 as the x-axis and the test results of the diluent described in Example 1 of this invention as the y-axis, a linear regression was performed using Origin software. The results are shown in the appendix. Figures 1-5 As shown, the linear regression coefficients Rc of WBC, RBC, HGB, MCV, and PLT were obtained from the test data. 2 All are greater than 0.99.

[0116] Test results data: The diluent of Example 1 has the same and good performance as the original diluent for BC5380 blood cell analysis described in Comparative Example 1. The diluent of the present invention can still complete the determination on the fully automated analyzer after the addition of sodium thiocyanate, and the results are accurate.

[0117] Application Example 4

[0118] After the blood cell analyzer prepared in Example 2 was placed in the diluent for 5 months, it was placed in the corresponding position of the Mindray BC5380 blood cell analyzer for verification. Twenty venous blood samples were taken for whole blood mode measurement. The results were compared with those of the original diluent for the Mindray BC5380 blood cell analyzer described in Comparative Example 1 for WBC (white blood cells), RBC (red blood cells), HGB (hemoglobin), MCV (mean corpuscular volume), and PLT (platelets). The test results are shown in Tables 8-12.

[0119] Table 8. Results of WBC (White Blood Cell) Measurement

[0120] Whole blood specimen number Example 2: Determination of WBC (×10^9 / L) using dilution solution WBC (×10^9 / L) was determined using the dilution solution of Comparative Example 1. relative deviation Specimen 1 7.86 7.79 0.90% Specimen 2 8.56 8.39 2.03% Specimen 3 5.75 5.86 -1.88% Specimen 4 6.85 6.80 0.74% Specimen 5 7.86 7.87 -0.13% Specimen 6 7.89 7.99 -1.25% Specimen 7 6.33 6.20 2.10% Specimen 8 5.12 5.14 -0.39% Specimen 9 9.79 9.72 0.72% Specimen 10 9.84 9.65 1.97% Specimen 11 41.78 41.87 -0.21% Specimen 12 25.82 25.78 0.16% Specimen 13 11.17 10.94 2.10% Specimen 14 2.69 2.68 0.37% Specimen 15 5.95 6.06 -1.82% Specimen 16 5.83 5.73 1.75% Specimen 17 8.43 8.69 -2.99% Specimen 18 4.36 4.49 -2.90% Specimen 19 6.53 6.60 -1.06% Specimen 20 4.07 4.19 -2.86%

[0121] Table 9. RBC (Red Blood Cell) Measurement Results

[0122] Whole blood specimen number Example 2: Determination of RBC (×10^12 / L) using dilution solution RBC (×10^12 / L) was determined using the dilution of Comparative Example 1. relative deviation Specimen 1 3.83 3.79 1.06% Specimen 2 3.13 3.08 1.62% Specimen 3 4.35 4.27 1.87% Specimen 4 5.02 5.02 0.00% Specimen 5 4.58 4.57 0.22% Specimen 6 5.22 5.26 -0.76% Specimen 7 4.25 4.25 0.00% Specimen 8 4.98 4.96 0.40% Specimen 9 4.97 5.00 -0.60% Specimen 10 4.59 4.52 1.55% Specimen 11 2.42 2.42 0.00% Specimen 12 4.56 4.57 -0.22% Specimen 13 4.29 4.30 -0.23% Specimen 14 3.05 3.06 -0.33% Specimen 15 4.36 4.39 -0.68% Specimen 16 4.77 4.86 -1.85% Specimen 17 5.98 5.97 0.17% Specimen 18 4.80 4.72 1.69% Specimen 19 4.95 4.97 -0.40% Specimen 20 4.52 4.54 -0.44%

[0123] Table 10 HGB (hemoglobin) measurement results

[0124] Whole blood specimen number Example 2: Determination of HGB (g / L) using dilution solution HGB (g / L) was determined using the dilution solution of Comparative Example 1. relative deviation Specimen 1 125 125 0.00% Specimen 2 104 104 0.00% Specimen 3 125 123 1.63% Specimen 4 159 160 -0.62% Specimen 5 154 154 0.00% Specimen 6 165 166 -0.60% Specimen 7 141 141 0.00% Specimen 8 158 157 0.64% Specimen 9 160 162 -1.23% Specimen 10 89 89 0.00% Specimen 11 77 77 0.00% Specimen 12 121 121 0.00% Specimen 13 137 137 0.00% Specimen 14 110 109 0.92% Specimen 15 129 132 -2.27% Specimen 16 161 162 -0.62% Specimen 17 187 187 0.00% Specimen 18 155 157 -1.27% Specimen 19 161 161 0.00% Specimen 20 148 148 0.00%

[0125] Table 11 Results of MCV (Mean Red Cell Volume) Measurement

[0126] Whole blood specimen number Example 2: Determination of MCV (fL) using dilution buffer MCV (fL) was determined using the dilution solution of Comparative Example 1. relative deviation Specimen 1 90.9 90.8 0.11% Specimen 2 93.8 94.2 -0.42% Specimen 3 83.5 83.5 0.00% Specimen 4 86.9 86.7 0.23% Specimen 5 97.2 97.7 -0.51% Specimen 6 90.5 90.8 -0.33% Specimen 7 93.2 93.9 -0.75% Specimen 8 89.0 89.8 -0.89% Specimen 9 92.0 93.3 -1.39% Specimen 10 58.7 60.0 -2.17% Specimen 11 90.7 91.9 -1.31% Specimen 12 82.9 84.2 -1.54% Specimen 13 92.4 92.9 -0.54% Specimen 14 100.8 101.8 -0.98% Specimen 15 86.0 85.7 0.35% Specimen 16 95.0 94.1 0.96% Specimen 17 86.8 86.0 0.93% Specimen 18 92.4 92.3 0.11% Specimen 19 89.3 88.7 0.68% Specimen 20 91.4 90.7 0.77%

[0127] Table 12 PLT (platelet) assay results

[0128] Whole blood specimen number Example 2: Determination of PLT (×10^9 / L) using dilution solution PLT (×10^9 / L) was determined using the dilution solution of Comparative Example 1. relative deviation Specimen 1 117 112 4.46% Specimen 2 496 504 -1.59% Specimen 3 224 221 1.36% Specimen 4 294 305 -3.61% Specimen 5 291 291 0.00% Specimen 6 272 276 -1.45% Specimen 7 284 271 4.80% Specimen 8 288 286 0.70% Specimen 9 229 234 -2.14% Specimen 10 322 327 -1.53% Specimen 11 28 28 0.00% Specimen 12 71 68 4.41% Specimen 13 778 760 2.37% Specimen 14 115 117 -1.71% Specimen 15 363 365 -0.55% Specimen 16 166 160 3.75% Specimen 17 302 295 2.37% Specimen 18 202 201 0.50% Specimen 19 216 220 -1.82% Specimen 20 178 178 0.00%

[0129] Using the test results of the diluent described in Comparative Example 1 as the x-axis and the test results of the diluent described in Example 2 of this invention as the y-axis, a linear regression was performed using Origin software. The results are shown in the appendix. Figures 6-10 As shown, the linear regression coefficients Rc of WBC, RBC, HGB, MCV, and PLT were obtained from the test data. 2 All are greater than 0.99.

[0130] Test results data: The diluent of Example 2 has the same and good performance as the original diluent for BC5380 blood cell analysis described in Comparative Example 1. After adding arginine-aspartic acid ionic liquid, the diluent of the present invention can still complete the measurement on the fully automated analyzer after being stored for 5 months, and the results are accurate, indicating that the diluent of the present invention has good stability.

[0131] Application Example 5

[0132] The blood cell analyzer diluent prepared in Example 3 was placed on the corresponding position of the Mindray BC5380 blood cell analyzer for verification. Twenty venous blood samples were taken for whole blood mode measurement. The results were compared with the original diluent for the Mindray BC5380 blood cell analyzer described in Comparative Example 1 for WBC (white blood cells), RBC (red blood cells), HGB (hemoglobin), MCV (mean corpuscular volume), and PLT (platelets). The test results are shown in Tables 13-17.

[0133] Table 13 WBC (white blood cell) assay results

[0134] Whole blood specimen number Example 3: Determination of WBC (×10^9 / L) using dilution solution WBC (×10^9 / L) was determined using the dilution solution of Comparative Example 1. relative deviation Specimen 1 10.34 10.52 1.74% Specimen 2 7.42 7.44 0.27% Specimen 3 8.25 8.44 2.30% Specimen 4 9.56 9.52 -0.42% Specimen 5 5.63 5.76 2.31% Specimen 6 5.97 6.11 2.35% Specimen 7 6.37 6.37 0.00% Specimen 8 12.69 12.69 0.00% Specimen 9 4.45 4.46 0.22% Specimen 10 5.92 6.03 1.86% Specimen 11 8.74 8.88 1.60% Specimen 12 6.00 6.06 1.00% Specimen 13 5.15 5.06 -1.75% Specimen 14 6.81 6.92 1.62% Specimen 15 5.73 5.86 2.27% Specimen 16 7.29 7.13 -2.19% Specimen 17 6.14 6.22 1.30% Specimen 18 7.00 6.97 -0.43% Specimen 19 4.16 4.08 -1.92% Specimen 20 5.06 5.06 0.00%

[0135] Table 14 RBC (Red Blood Cell) Measurement Results

[0136] Whole blood specimen number Example 3: Determination of RBC (×10^12 / L) using dilution solution RBC (×10^12 / L) was determined using the dilution of Comparative Example 1. relative deviation Specimen 1 5.18 5.19 0.19% Specimen 2 4.83 4.74 -1.86% Specimen 3 4.33 4.34 0.23% Specimen 4 4.98 4.96 -0.40% Specimen 5 4.33 4.31 -0.46% Specimen 6 5.25 5.24 -0.19% Specimen 7 4.98 4.9 -1.61% Specimen 8 4.76 4.79 0.63% Specimen 9 4.11 4.11 0.00% Specimen 10 4.23 4.26 0.71% Specimen 11 4.79 4.82 0.63% Specimen 12 5.19 5.12 -1.35% Specimen 13 4.49 4.53 0.89% Specimen 14 5.01 5.01 0.00% Specimen 15 5.23 5.26 0.57% Specimen 16 4.86 4.88 0.41% Specimen 17 4.87 4.81 -1.23% Specimen 18 4.37 4.39 0.46% Specimen 19 4.43 4.40 -0.68% Specimen 20 4.02 4.02 0.00%

[0137] Table 15 HGB (hemoglobin) measurement results

[0138] Whole blood specimen number Example 3: Determination of HGB (g / L) using dilution solution HGB (g / L) was determined using the dilution solution of Comparative Example 1. relative deviation Specimen 1 164 165 0.61% Specimen 2 137 136 -0.73% Specimen 3 113 114 0.88% Specimen 4 151 150 -0.66% Specimen 5 143 144 0.70% Specimen 6 163 164 0.61% Specimen 7 148 147 -0.68% Specimen 8 145 146 0.69% Specimen 9 127 128 0.79% Specimen 10 142 143 0.70% Specimen 11 154 155 0.65% Specimen 12 153 152 -0.65% Specimen 13 105 105 0.00% Specimen 14 158 158 0.00% Specimen 15 161 161 0.00% Specimen 16 155 155 0.00% Specimen 17 142 142 0.00% Specimen 18 117 118 0.85% Specimen 19 139 141 1.44% Specimen 20 132 132 0.00%

[0139] Table 16 Results of MCV (Mean Red Cell Volume) Measurement

[0140] Whole blood specimen number Example 3: Determination of MCV (fL) using dilution solution MCV (fL) was determined using the dilution solution of Comparative Example 1. relative deviation Specimen 1 93.9 93.4 -0.53% Specimen 2 87.6 87.5 -0.11% Specimen 3 82.2 82.6 0.49% Specimen 4 90.5 91.2 0.77% Specimen 5 98.2 98.2 0.00% Specimen 6 92.9 93.0 0.11% Specimen 7 89.8 89.9 0.11% Specimen 8 93.2 93.6 0.43% Specimen 9 94.0 94.4 0.43% Specimen 10 99.6 99.8 0.20% Specimen 11 96.6 96.6 0.00% Specimen 12 90.2 90.2 0.00% Specimen 13 76.6 76.8 0.26% Specimen 14 92.7 93.1 0.43% Specimen 15 94.4 95.1 0.74% Specimen 16 93.6 93.9 0.32% Specimen 17 88.5 88.9 0.45% Specimen 18 86.1 86.3 0.23% Specimen 19 88.1 88.8 0.79% Specimen 20 91.5 91.9 0.44%

[0141] Table 17 PLT (platelet) assay results

[0142] Whole blood specimen number Example 3: Determination of PLT (×10^9 / L) with dilution solution PLT (×10^9 / L) was determined using the dilution solution of Comparative Example 1. relative deviation Specimen 1 223 221 0.90% Specimen 2 253 258 -1.94% Specimen 3 391 391 0.00% Specimen 4 320 329 -2.74% Specimen 5 174 171 1.75% Specimen 6 182 177 2.82% Specimen 7 196 204 -3.92% Specimen 8 256 261 -1.92% Specimen 9 195 205 -4.88% Specimen 10 150 157 -4.46% Specimen 11 255 252 1.19% Specimen 12 244 247 -1.21% Specimen 13 252 255 -1.18% Specimen 14 184 175 5.14% Specimen 15 206 206 0.00% Specimen 16 225 226 -0.44% Specimen 17 265 264 0.38% Specimen 18 214 217 -1.38% Specimen 19 274 267 2.62% Specimen 20 199 195 2.05%

[0143] Using the test results of the diluent described in Comparative Example 1 as the x-axis and the test results of the diluent described in Example 3 of this invention as the y-axis, a linear regression was performed using Origin software. The results are shown in the appendix. Figures 11-15 As shown, the linear regression coefficients Rc of WBC, RBC, HGB, MCV, and PLT were obtained from the test data. 2 All are greater than 0.99.

[0144] Test results data: The diluent of Example 3 has the same and good performance as the original diluent for BC5380 blood cell analysis described in Comparative Example 1. The diluent of the present invention can still complete the measurement on the fully automated analyzer after the addition of trehalose, and the results are accurate.

[0145] It should be noted that in Application Examples 3 to 5, the 20 venous blood samples are all different.

[0146] In summary, the blood cell analysis diluent provided by this invention provides accurate detection results when used in blood cell analysis, meets the requirements of the Mindray BC5380 blood cell analyzer, reduces the probability of clogging, and extends the shelf life of the diluent after opening.

[0147] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. A diluent for blood cell analysis, characterized in that, The diluent comprises the following components: 0.5–15 g / L of inorganic salt, 0.01–5.0 g / L of preservative, and 0.1–0.5 g / L of stabilizing agent; the solvent of the diluent is water; the diluent further comprises an anti-precipitant, which is selected from one or more of salt-based anti-precipitants and organic anti-precipitants; the salt-based anti-precipitant comprises one or more of thiocyanate and nitrate, and the content of the salt-based anti-precipitant is 2.0–5.0 mmol / L; the organic anti-precipitant comprises one or more of trehalose, mannitol, and amino acid ionic liquid, and the content of the organic anti-precipitant is 4.0–8.0 mmol / L.

2. The diluent according to claim 1, characterized in that, The content of the inorganic salt is 2~10 g / L; And / or, the content of the preservative is 0.05~2.0 g / L; And / or, the inorganic salt is selected from one or more of sodium chloride, potassium chloride, sodium sulfate, and potassium sulfate; And / or, the preservative is selected from one or more of diazoalkylurea, imidazoalkylurea, and pyrithioneurea; And / or, the stabilizing substance is selected from one or more of polyvinylpyrrolidone, propylene glycol, 2-methyl-2,4-pentanediol, and PEGylated phospholipids; And / or, the amino acid ionic liquid is selected from one or more of the following: choline alanine salt ionic liquid, 1-ethyl-3-methylimidazolium glycinate salt ionic liquid, tetraethylammonium glycinate salt ionic liquid, and arginine-aspartic acid ionic liquid.

3. The diluent according to claim 1, characterized in that, The diluent also includes a buffer of 0.5~10 g / L; And / or, the diluent further includes 0.1 to 25 g / L of a complexing agent.

4. The diluent according to claim 3, characterized in that, The buffer is selected from one or more of borates, phosphates, organic sulfonates, organic carboxylates, and N-(2-acetamido)-2-aminoethanesulfonic acid; And / or, the complexing agent is selected from one or more of ethylenediaminetetraacetic acid, citric acid, and ethylene glycol bis(2-aminoethyl ether)tetraacetic acid.

5. The diluent according to claim 3, characterized in that, The content of the buffer is 0.5~8 g / L.

6. The diluent according to claim 1, characterized in that, The pH value of the diluted solution is 6-8.

7. A method for preparing the diluent as described in any one of claims 1 to 6, characterized in that, The preparation method includes the following steps: stirring and mixing the raw material components.

8. The use of the diluent as described in any one of claims 1 to 6 in blood cell analysis.

9. The use of an anti-precipitant in reducing the probability of clogging in instruments using diluents for blood cell analysis, wherein the anti-precipitant is selected from one or more of salt-based anti-precipitants and organic anti-precipitants; wherein the salt-based anti-precipitant includes one or more of thiocyanate and nitrate; and wherein the organic anti-precipitant includes one or more of trehalose, mannitol, and amino acid ionic liquids.

10. The use according to claim 9, characterized in that, The content of the salt anti-precipitant is 2.0~5.0 mmol / L, and the content of the organic anti-precipitant is 4.0~8.0 mmol / L.