JP2003226893A - Method for cleaning cell of biochemical analyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a cleaning liquid capable of cleaning combined stains which are caused by using a reagent containing synthetic latex and strongly adhere to a cell, or the like, of a biochemical analyzer. <P>SOLUTION: The cleaning liquid comprises (a) an organic solvent for cleaning and removing the stains, (b) a diluting organic solvent, and (c) a surfactant. The cleaning liquid is used in cleaning the cell, or the like, of the biochemical analyzer to which the combined stains caused by the synthetic latex adhere. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for cleaning a biochemical analyzer, and particularly to analysis of clinical test samples such as blood and urine, and analysis of many biological samples such as immunological tests in a continuous and diverse manner. The present invention relates to a cleaning solution for a cell or the like of a clinical biochemical automatic analyzer for performing the method and a cleaning method using the same.

[0002]

Biochemical analysis of blood, urine and the like, immunological tests are extremely important as means for obtaining basic data in clinical medical diagnosis and the like. These analyzes and tests require dozens of analysis / test items for each of a large number of samples, and it is necessary to obtain results in the shortest possible time. It is becoming more and more done by devices. Due to automation, the reporting of measurement results has become quicker and more labor-saving, and in the future, analytical reagents using a wide variety of reaction principles will appear.
Simultaneous measurement will be performed.

An outline of the procedure for using blood as a sample by such an automatic clinical biochemistry analyzer is as follows. The sample blood is first centrifuged and placed in the sample tray. The supernatant serum is pipetted out, transferred to a dilution cell contained in a dilution turntable, and diluted with physiological saline or the like. The diluted solution is sampled and injected into the reaction cell housed in the reaction cell holder of the rotary reactor. Reagents necessary for various analyzes and tests are added thereto and stirred to react. A measured value is obtained from the reacted sample in the reaction cell by optical measurement such as absorbance measurement. After the measurement is completed, the reaction cell is washed and dried. The automatic analyzer is a sample tray, a dilution turntable, a rotary reactor, and a reagent that accommodates a large number of cells or cups in which the specimen, the diluent, the reaction solution, and the reagent are stored, and operates in a rotary manner. Equipped with a turntable.

Since many optical measurements are performed in such automatic analysis, in order to obtain accurate measured values in these tests, cells, especially reaction cells in which optical measurements are performed, are always used in a clean state. I have to. Therefore,
Conventionally, the used reaction cell and the like have been washed with an alkaline aqueous detergent containing a surfactant.

However, the reagents used in the biochemical analysis are as many as several tens, similar to the analysis items, and among them, there are quite a few reagents containing synthetic latex such as polystyrene latex. The synthetic latex is composed of fine synthetic resin particles, and has a protective layer and a functional layer formed on the surface thereof, and has an antigen immobilized on the surface and is transparent. When this is added as a reagent to the sample, an antigen-antibody reaction occurs with the antibody contained in the sample, cross-linking / aggregation occurs between the synthetic resin particles, and the sample has a reduced light transmittance. The change in turbidity is measured by absorbance to grasp the concentration of the antibody in the sample. The analysis method using synthetic latex particles having such a principle has become extremely important in analysis of various hormones, bacteria, viruses, diabetes tests and the like. For example, hemoglobin A1c (glycated hemoglobin) (diabetes test reagent) contains a large amount of synthetic latex, and is used very frequently.

The reaction products of many reagents remain as stains on the inner wall of the reaction cell, etc. The stains after the test with the reagent containing the synthetic latex are contaminated with stains of the protein in the reagent, the protein in the sample and the lipid in the sample. It becomes stubbornly stuck as complex dirt.

Contamination caused by such a synthetic latex-containing reagent can be carried out by a conventional cleaning method, in addition to the cleaning with an alkaline cleaning agent containing a surfactant, and the combined use of physical means such as spraying cleaning water or ultrasonic cleaning. Is difficult to wash sufficiently, especially when it is often used for measurement using a reagent containing a large amount of synthetic latex such as hemoglobin A1c, it becomes unusable due to synthetic latex composite stain in an extremely short period of time. I had to replace it with a new reaction cell.

In order to remove these organic synthetic latex composite stains, it is conceivable to use a strong organic solvent that dissolves the organic polymer, but if the solvent is too strong,
There is a possibility that the reaction cell itself made of a synthetic resin such as polyethylene or ABS may be damaged by dissolution or swelling.

Further, such an organic solvent having a strong dissolving power is often toxic to the human body and living organisms, or a deleterious substance or a dangerous substance. Therefore, the safety of the human body of the worker may be affected, and the discharge of the cleaning liquid may be in conflict with the emission regulations regarding environmental problems of each local government.

[0010]

DISCLOSURE OF THE INVENTION The present invention makes it possible to reuse a biochemical analyzer, particularly an automatic analyzer, by washing the cell after use such as an absorbance measuring cell in which synthetic latex particles or the like are strongly adsorbed, and reusing the cell. It is an object of the present invention to provide a cleaning agent and a cleaning method therefor. Furthermore, the present invention not only removes dirt but also does not damage the material of the cell, does not affect the safety of the human body of the cleaning operator, and discharges the cleaning liquid is an environmental problem. It is an object of the present invention to provide the above-mentioned cleaning liquid and cleaning method having high cleaning performance and high practicality, which also satisfy the conditions such as not causing the above-mentioned problems.

[0011]

Means for Solving the Problems In order to solve the above-mentioned problems, the present inventors have searched various cleaning agents and cleaning methods while taking into consideration the stains on cells of a biochemical analyzer and the actual conditions of cleaning. , "Staining and removing organic solvent" which has strong dissolving power to remove stubborn dirt such as synthetic latex mixed dirt, and "Diluting organic solvent" which has cleaning power but does not damage resin such as cells. And an organic solvent-based cleaning solution composed of a "surfactant" that works on lipids in complex stains to help cleaning the cleaning solvent, the cleaning of the biochemical analyzer cell that solved many of the above problems The present invention has been completed by finding out that an agent and a cleaning method can be obtained.

That is, the present invention is a cleaning liquid for a cell of a biochemical analyzer, which comprises (a) an organic solvent for washing and removing, (b) a diluting organic solvent, and (c) a surfactant. The mixing ratio is
The weight ratio of the components (a) and (b) is 10:90 to 70:
It is preferable that the content of the component (c) is 0.001 to 5% by weight based on the total amount of the components (a) and (b).

In the present invention, the (b) diluted organic solvent may contain water, and among the total amount of the (a) wash-removed organic solvent and (b) diluted organic solvent (including water). It may contain up to 25% by weight of water.

The pH of the cleaning liquid is preferably 5.0 to 9.0.

Further, a preferred washing-removing organic solvent is N,
N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, ethyl acetate, benzyl alcohol, dimethylsulfoxide, orange oil, limonene, and a preferred diluting organic solvent is 3-methoxy- 3-methyl-1-butanol, propylene glycol, isobutylene glycol, ethylene glycol monopropyl ether, ethylene glycol monomethyl ether, propylene glycol monomethyl ether, diethylene glycol monobutyl ether,
Preferred surfactants selected from the group consisting of ethanol, methanol and isopropyl alcohol, and preferred surfactants are fluorine-based surfactants, anionic surfactants, cationic surfactants, nonionic surfactants and amphoteric surfactants. Selected from the group.

Further, according to the present invention, the above-mentioned cleaning liquid is injected with the liquid contact part of the biochemical analyzer attached to the device body, or the cell is removed from the device body and immersed in the cleaning liquid bath. A method for cleaning a cell of a biochemical analyzer is provided.

[0017]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of a cell cleaning solution and a cleaning method of a biochemical analyzer of the present invention will be described in detail below.

(Washing liquid) (a) Wash-removing organic solvent: The wash-removing organic solvent serves as a main washing solvent for removing stubborn stains such as synthetic latex mixed stains, and satisfies the following conditions. is there. It must be an organic solvent with a strong dissolving power that can also dissolve synthetic latex mixed stains. As a poisonous substance, a deleterious substance, or a dangerous substance, it should not be subject to strict regulations. When it is discharged as a cleaning solution, it causes fish toxicity in rivers and seas,
Environmental pollution is not a major concern.

Examples of the organic solvent satisfying such conditions are as follows. N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, ethyl acetate, benzyl alcohol, dimethyl sulfoxide, orange oil, limonene, etc., and one or more of these organic solvents may be used. It can be used in combination. Among these organic solvents, N-methyl-2-pyrrolidone is most preferably used because it has the best effect of washing and removing synthetic latex mixed soil and has high safety.

(B) Diluted organic solvent: The washing removal solvent is
Although it is extremely effective for cleaning and removing the synthetic latex composite stains alone, there is a possibility that the resin of the reaction cell or the like may be dissolved or swelled and damaged. Therefore, in the cleaning liquid of the present invention, the cleaning removal solvent is diluted with an organic solvent that satisfies the following conditions. It must have sufficient dissolving power to wash organic stains. It must be water-soluble so that it can be diluted in the wash water. Do not damage or corrode the resin of the reaction cell. It has low toxicity, dangerous physical properties, and environmental pollution.

The following can be exemplified as the organic solvent satisfying such conditions. 3-methoxy-3-methyl-1-
Butanol, propylene glycol, isobutylene glycol, ethylene glycol monopropyl ether, ethylene glycol monomethyl ether, propylene glycol monomethyl ether, glycol ethylene organic solvent such as diethylene glycol monobutyl ether or an organic solvent consisting of ethanol, methanol, isopropyl alcohol, etc. One kind or a combination of two or more kinds can be used. Among them, 3-methoxy-3-methyl-1-butanol can be most preferably used as the one that most satisfies the above conditions.

The mixing ratio of (a) the cleaning-removing organic solvent and (b) the diluting organic solvent is such that the synthetic latex composite stain can be sufficiently removed and the resin such as cells is not damaged, and the safety and environmental pollution The ratio is selected such that The appropriate mixing ratio differs depending on the combination of the solvent for washing and removing and the solvent for diluting, and the difference in the properties of the target synthetic latex mixed stains (synthesis due to the difference in the test items (difference in reagents) that frequently occur. The type of latex resin, the type of stains of proteins and lipids that come from reagents and samples), and the materials such as the reaction cell, etc. will vary depending on the individual situation.

For cell materials having excellent organic solvent resistance such as polyethylene (PE) and polypropylene (PP), in the mixed system of the components (a) and (b), the component (a) is a synthetic latex washed. The removal performance requires 10% by weight or more, and since there is almost no damage to the resin, it may be used up to about 100% by weight. However, polyvinyl chloride (PVC), polystyrene (PS), polycarbonate (PC), polyvinyl alcohol (PVA) is used as another cell material or as a material for peripheral parts that are exposed to the cleaning liquid together with the cell, such as a holder for containing the cell. There are various resin materials. In order to eliminate the problem of damage to the resin even in such a wide range of resin materials, the upper limit of the mixing ratio of the component (a) must be suppressed to about 70% by weight. That is, the preferred mixing ratio that is almost universal is
The weight ratio of the components (a) and (b) is 10:90 to 70:
The range is 30.

By the way, in the mixed system of (a) the organic solvent for washing and removal and (b) the diluted organic solvent of the present invention, it is water-soluble (b).
The diluted organic solvent is 25% of the total amount of the components (a) and (b).
It may be replaced with water up to about wt%. However, in such a water-containing system, the component (a) must be mixed in the water-containing mixed solvent system in an amount of at least 60% by weight or more in order not to impair the washing and removing power of the synthetic latex.

(C) Surfactant In the present invention, the stain of protein or lipid coming from the reagent or sample, which is one of the causes of the stubborn adherence of the synthetic latex mixed stain, is emulsified and easily peeled from the cell wall surface. for,
Use a surfactant. Surfactant contributes to the improvement of the cleaning and removing effect especially when the synthetic latex stain is severe, the mixed stain is extremely hard to remove depending on the type of reagent, or when the synthetic latex mixed stain is left for a long time. You can

Examples of usable surfactants include the following. Perfluoroalkylamine oxide, perfluoroalkylethylene oxide adduct,
Fluorine-based surfactants such as perfluoroalkylcarboxylates, perfluoroalkylphosphates, perfluoroalkylbetaines, and perfluorotrimethylammonium salts; alkyl sulfates, polyoxyethylene alkyl ether sulfates, alkyl sulfones Anionic surfactants such as acid salts, alkyldiphenyl ether sulfonates, acylglutamates, metaxylene sulfonates, paratoluene sulfonates, alkylthio fatty acid salts; monoalkyl ammonium chloride, dialkyl ammonium chloride, dialkyl EO addition ammonium Cationic surfactants such as chloride, alkyldimethylbenzylammonium chloride, tetraalkylammonium chloride; polyoxyalkylene alkyl ether, alkyl poly Nonionic surfactants such as rucoside, polyoxyethylene alkyl ether, polyoxyethylene glyceryl alkyl ether, alkylaminoxide, polyoxyethylene block polymer, polyoxypropylene diglyceryl ether, and siloxaneoxyethylene copolymer; alkyl betaine, imidazo Examples include amphoteric surfactants such as lithium betaine. The above surfactants may be used alone or in combination of two or more.

Among the above-mentioned surfactants, those having a small amount of strong penetrating power include a fluorine-based surfactant, a silicic acid-based nonionic surfactant such as a siloxaneoxyethylene copolymer, and an anionic surfactant. Certain alkylthio fatty acid salts, silicon-containing carboxylic acid salts and the like are preferable, and fluorochemical surfactants are particularly preferable.

The amount of the (c) surfactant added to the cleaning liquid of the present invention is 0.001 to 5% by weight (as solid content) based on the total amount of the (a) wash-removed organic solvent and (b) diluted organic solvent. %
Is preferred. The surfactant is usually available in the form of a powder or an aqueous solution. However, even in the form of an aqueous solution, since the added amount in the cleaning liquid of the present invention is not large, the diluted organic solvent may contain water. Similarly, its water content has little effect on the organic solvent-like cleaning properties of the inventive cleaning solutions.

The cleaning liquid of the present invention basically comprises (a) an organic solvent for cleaning and removal, (b) a diluting organic solvent, and (c) a surfactant. In addition, if necessary, a preservative, an alkalizing agent, Components such as acidifying agents can be added.

However, even when other components are added as necessary, the resulting pH of the cleaning liquid of the present invention is 5.0 to 9.% from the viewpoint of safety and from the viewpoint of regulation of discharge of cleaning wastewater. It is preferably maintained in the neutral range of 0.

(Washing Method) The method for washing the cells of the biochemical analyzer with the above-mentioned washing solution of the present invention is not particularly limited, and the cells may be injected in the state of being attached to the main body of the device, Alternatively, the cell or the like may be removed from the main body of the device and immersed in a bath of the cleaning liquid.

Washing with the cell mounted on the main body of the device is performed in the following procedure. The reaction cell after the measurement of the absorbance is poured into the inside of the washing water from a nozzle or the like, washed, and then dried. Then, after pouring the organic solvent-based cleaning liquid of the present invention into the reaction cell and allowing it to stand for a predetermined time, discharging the cleaning liquid and repeating the operation of cleaning again with a new organic solvent-based cleaning liquid, and then performing drying. The cleaning is completed by.

In order to wash a large number of cells such as an automatic analyzer, if the holder for accommodating the plurality of cells is easily disassembled, the plurality of cells are taken out from each holder. It is convenient to immerse it in a bath of cleaning solution. In that case, as a device structure, if one holder does not contain all the cells but is divided into a plurality of holders, the dipping operation is easy and the cleaning bath is not so large, which is preferable.

The temperature of the cleaning liquid or its bath may be room temperature or about 40 ° C. Further, it is sufficient that the cleaning solution or its bath is immersed for about 30 seconds to 10 minutes. The cleaning solution or the cells taken out of the bath,
Rinse with distilled water about 10 times, drain water, and dry naturally.

The cleaning liquid of the present invention is to be cleaned.
The reaction cell to which the synthetic latex composite stain adheres is the main one, but in addition, a stirring blade for stirring the reaction solution.
Those that are contaminated with synthetic latex stains such as a stirring rod can be washed, and the dilution cell to which the protein and lipid stains from the sample are adhered may be washed. Since the whole cell holder is immersed and cleaned, the cleaning solution must not damage the synthetic resin from this point as well.

[0036]

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples without departing from the gist thereof. In the following, the mixing ratio or% is based on weight.

Test Example 1 Fully automatic biochemical automatic analyzer BioMajesty JCA-BM 9030
(Manufactured by JEOL Ltd.), using hemoglobin A1c
Reaction cell (made of PE) that became unusable due to adsorption of synthetic latex particles used for fractionation measurement on the inner wall of the cell
Is (a) an organic solvent for washing removal, (b) a diluting organic solvent (or a part or all of which is replaced with water), and (c)
It was immersed in a cleaning liquid composed of a mixed system of surfactants. Here, N-methyl-2-pyrrolidone is used as the (a) organic solvent for washing and removal, and 3-methoxy-3 is used as the (b) diluted organic solvent.
-Methyl-1-butanol, (c) As the surfactant, perfluoroalkylamine oxide (added as a 30% aqueous solution; shown as pure content in Tables 1 to 3 below) was used.

(Washability of Latex Residue) The following test was carried out as a test of removability of latex residue. Immersion cleaning was carried out by adding the above-mentioned cleaning liquid of various mixing ratios to the reaction cell having latex particles adsorbed thereon, maintaining the liquid temperature at 37 ± 2 ° C., and leaving it for 10 minutes. After that, the cleaning liquid was discharged, rinsed with distilled water 10 times, drained and naturally dried indoors. After drying the cell,
The presence or absence of a latex residue was confirmed by visual inspection using a pes. The test results were evaluated in the following four stages. ◎ ・ ・ ・ No latex residue at all ○ ・ ・ ・ Latex residue remains slightly △ ・ ・ ・ Latex residue remains × ・ ・ ・ Latex residue hardly falls

Test Example 2 (Effect on Resin) With respect to the formulation Nos. 1 to 64 of the cleaning liquid, the effects on the following resins were examined. The above-mentioned various synthetic resin pieces were immersed in the cleaning liquids of formulation Nos. 1 to 64, and the state of the resin surface after 24 hours at a liquid temperature of 37 ± 2 ° C. was examined. The test results were evaluated in the following three stages. ◎ ・ ・ ・ No abnormalities on the resin surface ○ ・ ・ ・ Slight changes in the resin surface △ ・ ・ ・ Swelling, shrinking, or softening of the resin surface

(Test result)

[Table 1]

[0041]

[Table 2]

[0042]

[Table 3]

With respect to the removal of latex stains in the non-aqueous cleaning liquids of Formulation Nos. 1 to 8 in Table 1 in which the mixing ratio of (a) the cleaning removal organic solvent and (b) the diluted organic solvent was investigated.
(a) N-methyl-2-pyrrolidone and (b) 3-methoxy.
The compounding ratio of 3-methyl / 1-butanol is 60: 40-1.
The best cleaning property was obtained at 00:00, and regarding the influence on the synthetic resin, some resin showed changes such as swelling, shrinkage, and softening state on the resin surface at 80:20 to 100: 0. That is, the range in which the good cleaning removal property of latex dirt and the absence of influence on the resin are compatible with each other is the component (a):
The component (b) had a narrow range of 60:40 to 70:30. However, when a resin such as PE or PP is used as the cell material, almost no damage is observed in the resin even if the components (a) :( b) are 100: 0.

The cleaning liquids of formulation Nos. 9 to 16 and the cleaning liquids of formulation Nos. 17 to 24 in Table 1 were (a) an organic solvent for cleaning removal.
In addition to (b) diluted organic solvent, 0.003% and 0.006% of (c) surfactant are added, respectively.
When 0.003% was added, the cleaning and removing properties of the synthetic latex stain were better than those when the component (c) was not added, and both good cleaning and removing properties of the latex stain and no effect on the resin were achieved. The range is 40:60 for component (a): component (b).
It was about 70:30. Similar results were obtained when 0.006% was added. That is, the range in which the cleaning property and the resin non-damage property are compatible is widened by the effect of the surfactant (c).

The cleaning liquids of formulation Nos. 25 to 32, the cleaning liquids of formulation Nos. 33 to 40, and the cleaning liquids of formulation Nos. 41 to 48 in Table 2 were (c) a surfactant of 0.03% and 0.3, respectively.
%, 3% was added, but both the cleaning and removability of latex dirt and the resin non-damage are 0.0% of the above-mentioned component (c).
The result is similar to the case of adding 03%. In the latex residue cleaning test, when the cell was pulled up in the middle of the test and observed, it was observed that as the concentration of the surfactant (c) increased, the latex stains tended to be removed in a short time.

In the water-containing cleaning liquid of Table 3 in which the mixing ratio of (a) the cleaning-removed organic solvent and (b) the diluted organic solvent and water was investigated, the composition Nos. 49 to 63, that is, (a) N-methyl. -Pyrrolidone at 60 to 80% did not show any effect on the resin material, but the formulation Nos. 64 and 65, that is,
When (a) N-methyl-2-pyrrolidone was 90%, changes such as swelling, shrinkage, and softening appeared on the surface of the resin material which was easily affected.

Regarding the latex detergency, No. 50 and No. 6 were used as long as the resin was not affected.
3, namely (a) N-methyl-2-pyrrolidone and (b) 3
The mixing ratio of -methoxy-3-methyl-1-butanol and water was the best at 60:30:10 and 80:10:10, respectively.

Compared to the non-aqueous cleaning liquid, the water-containing cleaning liquid has less influence on the resin if the water content increases even if the ratio of (a) N-methyl-2-pyrrolidone increases, but the latex cleaning is performed. Regarding the sex, it decreased in proportion to the weight% of water, and when the water content was 30% or more, the dirt of latex was hardly removed. That is, the water content of the water-containing cleaning solution is preferably 25% or less.

[0049]

EFFECTS OF THE INVENTION By using the cleaning liquid of the present invention in an automatic biochemical analyzer, it is possible to efficiently and surely clean the plastic reaction cell due to the adsorption of latex particles, which cannot be regenerated in the past. It has little effect on resin materials such as reaction cells. In addition to improving the accuracy and precision of measured values, it is also excellent in handling safety, and it becomes possible to conserve resources and consider the environment.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Susumu Saito             3-1-2 Musashino, Akishima-shi, Tokyo JEOL             Within the corporation F term (reference) 2G058 AA09 FB02 FB12 FB14                 4H003 AA02 AB01 AC01 AD01 AE01                       DA12 DA13 DA16 DB01 ED28                       ED29 ED31 ED32

Claims (5)

[Claims] 1. A cleaning liquid for a cell of a biochemical analyzer comprising (a) an organic solvent for cleaning and removal, (b) a diluting organic solvent, and (c) a surfactant. 2. The weight ratio of the component (a) and the component (b) is 1
0:90 to 70:30, wherein the component (c) is the component (a)
The cleaning liquid according to claim 1, which is 0.001 to 5% by weight based on the total amount of the component and the component (b). 3. The pH is 5.0 to 9.0.
The cleaning liquid according to any one of claims 1 to 3. 4. (a) The organic solvent which is removed by washing consists of N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, ethyl acetate, benzyl alcohol, dimethyl sulfoxide, orange oil and limonene. At least one selected from the group: (b1)
Diluted organic solvent is 3-methoxy-3-methyl-1-butanol, propylene glycol, isobutylene glycol,
At least one selected from the group consisting of ethylene glycol monopropyl ether, ethylene glycol monomethyl ether, propylene glycol monomethyl ether, diethylene glycol monobutyl ether, ethanol, methanol, and isopropyl alcohol,
4. The surfactant (c) is at least one selected from the group consisting of a fluorine-based surfactant, an anionic surfactant, a cationic surfactant, a nonionic surfactant and an amphoteric surfactant. The cleaning liquid according to any one of 1. 5. The cleaning liquid according to any one of claims 1 to 4 is injected in a state in which a cell of a biochemical analyzer is attached to a device body, or the cell or the like is removed from the device body in the cleaning liquid bath. A method for cleaning a cell of a biochemical analyzer, which is performed by immersing in a cell.