JP3457968B2 - Method of regenerating biological treatment instrument - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for washing an analyzer, an instrument, etc., and more specifically, for reusing a sample nozzle, a reagent dispensing nozzle, a reaction container, etc. to a reusable state. The present invention relates to a method for cleaning a portion in contact with a sample or a reagent.

[0002]

2. Description of the Related Art In clinical tests, various body fluid components such as urine, serum and plasma are analyzed by using various analyzers. The measurement method used for the analysis is not limited to the usual biochemical measurement method, and the antigen-
It includes a wide variety of methods such as an immunological assay method using an antibody reaction, a method using a DNA probe, and a biochemical assay method using an enzyme activity. In such a measuring method, it is necessary that the instruments used are clean in order to obtain accurate measurement results. In particular, with the increase in sensitivity of analysis methods and the expansion of measurement range, especially sample dispensing nozzles,
In recent years, it has become more and more important to clean a portion such as a reaction container that contacts a sample.

Many proposals have been made for cleaning nozzles in the related art, but basically, many of them are intended to mechanically increase the cleaning efficiency with cleaning water (JP-A-62-24285).
8, JP-A-62-288574, Jikken-3-3357
2, Japanese Patent Publication No. 52-38754). However, merely increasing the cleaning effect mechanically has a limit and is not sufficient.

On the other hand, Japanese Patent Laid-Open No. 1-254871 proposes a cleaning method using a piezoelectric vibrator. But,
Although this method is thought to improve cleaning efficiency,
Since the substance adsorbed on the nozzle maintains adsorption equilibrium on the nozzle surface, it is not always effective depending on the strength of affinity between the adsorbed substance and the probe surface.

Therefore, a proposal has been made regarding a mechanism for disposing the sample nozzle (Japanese Patent Laid-Open No. 63-243762, Japanese Patent Laid-Open No. 1-184465, Japanese Utility Model Laid-Open No. 1-146162, Japanese Utility Model Laid-Open No. 1-141466, Japanese Patent Laid-Open No. 63-146466. -106567).

By being made disposable, problems such as contamination between samples due to poor cleaning of the sample nozzle and carryover can be reliably avoided. However, discarding the sample nozzle for each sample is not only costly but also undesirable from the viewpoint of environmental protection, which is increasing in recent years.

[0007]

Each of the above-mentioned conventional techniques has advantages and disadvantages, and it is difficult to satisfy all the requirements of non-disposable, non-carry-over and non-contamination. Under such circumstances, the direction of technological development related to the cleaning method is shifting to disposable as far as recent patent applications are concerned. This suggests how difficult it is to develop a perfect cleaning method.

As a measure for avoiding carry-over and contamination, it is common knowledge to wash or dispose of and dispose. Therefore, rather than performing excessive mechanical cleaning as in the past, it is rather non-cleaning in view of the conventional cleaning concept, and is non-disposable and practically reusable. Attempts to secure were considered insane and unrealizable. An object of the present invention is to dare to overcome this difficulty and provide an effective reproducing method that is unprecedented in the past.

The method of regenerating the biological treatment means according to the invention is such that the biologically active substance or the active substance is contained therein.
Sequential contact with multiple different materials
While performing a treatment to analyze the activity of the material
Applied sense means, before said processing means is in contact with the following different said material, where the said material in said processing means
Regardless of whether the contact area is sterilized or disinfected.
The activity is lost, and the treatment means after the activity is lost is used to contact the next different material. Hereinafter, the details of the present invention will be described.

Mainly when performing immunological measurement methods, the degree of perfection of washing is required in a portion in contact with a sample or a reagent such as a sample nozzle, a reagent dispensing nozzle and a reaction container in an analyzer. And a case where the biological activity is measured as in a DNA assay using a DNA probe or the like. All of these measuring methods are methods whose measuring range and sensitivity have been significantly improved in recent years.
Also, when observing cells or the like by histochemically staining or emitting light, since biological activities such as antigens, antibodies and enzymes are often used, the cells from different cells during processing such as sectioning can be used. There should be no contamination.

In the above cases, it is effective only to completely wash out biologically active substances (eg, antigens, antibodies, enzymes, bacteria, viruses, DNA, RNA, etc.) present in samples and reagents. Not a wash. That is, since the purpose of cleaning is to regenerate the instrument in a reusable state, the active substance present in the sample or reagent attached to the instrument is not inactivated so as not to affect the analysis result. The purpose of cleaning can be effectively achieved only by deactivating.

Based on the above basic idea, the inventors examined the regeneration effect of the device by various inactivation treatments. In particular, we proceeded with studies on methods having protein denaturing or degrading effects.

Conventionally, protein denaturants or inactivators have been used as bactericides and disinfectants, among which are the following: acids or alkalis (eg mineral acids, caustic soda, barium hydroxide). , Benzoic acid, para-hydroxybenzoic acid, lactic acid, propionate), heavy metals (eg Hoei, Mercurochrome, Marthiolate, mercurials such as mercury phenylacetate, arsenicals such as salvalsan, copper sulphate, silver nitrate), Oxidizing agents (eg potassium permanganate, bromine, halogens such as iodine or fluorine), formalin, pigments (eg basic or acidic pigments) and the like.

However, a drug for sterilization or disinfection,
The conventional denaturation or inactivation of proteins using ultraviolet rays, heated steam, ultrasonic waves, etc. is to calm or weaken the harmful living ability of microorganisms such as infectious, parasitic, and proliferative. Since it is performed for the purpose of activating or killing, it is not necessarily the same as eliminating the activity of substances such as antigens, antibodies and enzymes. That is, in the case of sterilization or disinfection, the material containing the biologically active substance to be treated is preliminarily killed by the pretreatment of foreign substances or microorganisms as impurities other than the treatment target. In treating the physical activity, it must not be a treatment that inactivates it. In particular, the activity of antigens and antibodies, for example, the purification of various proteins with ethanol or acetone,
Sterilization of insoluble antigens using formalin and phenol,
It is important that the above-mentioned activity is used as it is after being subjected to the same treatment as sterilization and disinfection such as immunohistochemical staining after fixation of formalin.

[0015] Various protein denaturants and inactivators that have been conventionally used were also considered to be used by adding them to the washing solution. However, the residual effect thereof may affect the analysis results, or Problems such as chemical damage occurred. In addition, since the washing time with a general analyzer is as short as several seconds, it is necessary to increase the concentration of the denaturing agent or inactivating agent used in order to obtain a sufficient effect, which is not very practical. It was This was expected,
It is for this reason that it has not been put into practical use as an almost effective cleaning means, although it seems that many engineers have considered it.

Under such circumstances, we focused on the peroxide gas. In general, a peroxide gas such as ozone or hydrogen peroxide has a strong oxidizing action, and is unstable and easily inactive, so that it has a property that the remaining property is equal to zero. This property is important and advantageous in realizing the basic idea of the present invention in that it does not affect the analysis result. In particular, ozone can be electrically controlled in its generation amount and time, which is also an important property not found in other substances.

It is known that cysteine, methionine, cystine, tyrosine, and histidine are affected by the strong oxidative effect of ozone (M. Kuroda,
F. Sakiyama, K .; Narita, J .; Bio
chem. , 78, 641 (1975)). It has also been proposed to use ozone for sterilization and disinfection (Japanese Patent Laid-Open Nos. 63-236593 and 61-13858).
6, JP-A-61-263691). Furthermore, proposals have been made regarding endoscope disinfection devices using ozone water (Japanese Patent Laid-Open Nos. 3-111026 and 3-68331).

However, the time required for sterilization and disinfection varies greatly depending on the size, morphology, resistance, protein composition, etc. of microorganisms, and the action speed becomes slower as it becomes aseptic. It is processed within a range of 24 hours. Therefore, there has been no evidence that the effect of completing sterilization or disinfection can be expected by ozone treatment for a short time, for example, several seconds to about 1 minute, which can be used for cleaning the analyzer. In addition, antigen, antibody, enzyme or DNA
There is no literature showing that it is possible to eliminate such activities at a practical level. On the contrary, there is a report that protein denaturation requires several tens of minutes (water and wastewater P894 Vol. 30 No. 9 (1988)). Therefore, from the common sense from the description of these prior art documents, it seems impossible to realize the basic idea of the present invention.

As a result of intensive studies under the above circumstances, the inventors have found that ozone water, water mixed with bubbles of air containing ozone, or air containing ozone is effective for cleaning the analyzer. We have confirmed that it can be used. In particular, cleaning with air containing ozone has been effective and has produced results unlike any other in the past. This result was quite unexpected and surprising. Therefore, the present invention has been completed by combining the above-mentioned advantage of being able to electrically control the generation amount and time of ozone and this surprising result, and it has become possible to provide an optimum cleaning method for an analyzer. It is a thing.

[0020] As device applying the method of the present invention, test
Treat body and / or reagents or mixtures thereof
Examples thereof include a dispensing nozzle, a syringe, a suction tube, various sample reagent containers, a reaction container, a measurement container, an agitator, a filter, a sensor, and the like. In the case of the analysis device, the cleaning-related parts such as the instrument exchange system and the drainage system can be extremely reduced or completely omitted.

The field in which the present invention can be applied is not limited to an analyzer, and can be used for cleaning instruments used manually such as surgical scalpels, microtomes, tweezers, test tubes, petri dishes, flasks, objective optical lenses, and pipettors. Needless to say, it can be used.

The method of the present invention can be applied to an apparatus using various analysis methods. In particular, it can be carried out for an apparatus using an immunological measurement, for example, an analyzer using a particle agglutination reaction such as erythrocyte, latex immunoassay, immunoturbidimetric method , radioimmunoassay, enzyme immunoassay, fluoroimmunoassay, chemiluminescence immunoassay. Further, it is considered that the ozone oxidizing action has a sufficient effect even on the sample using DNA, RNA, etc. or the sample using the DNA probe as a reagent.

The peroxide gas such as ozone may be handled under the conditions described in publicly known papers or handbooks, and if necessary, means for recovering ozone after use, decomposing or detoxifying it is provided. Is preferred.

Since the regeneration method of the present invention inactivates biological activities common to organisms such as antigen-antibody reaction and enzyme reaction, there is a great variation in effects depending on the type of microorganism such as sterilization and disinfection. Few. Further, since the cleaning time is extremely short, it can be flexibly applied to any analyzer.

[0025]

【Example】

<First Embodiment> This embodiment relates to cleaning using air containing ozone.

FIG. 1 shows an example of an apparatus for carrying out the first embodiment of the present invention. This device is configured to wash by flowing air containing ozone. Rather, it is an attempt to inactivate the components in the sample rather than washing.

In FIG. 1, 1 is a sample cup containing a sample, 2 is a nozzle for dispensing a sample into a predetermined reaction container, 3 is a container for cleaning the nozzle, 4 is a syringe, and 5 is an electromagnetic valve. , 6 is an ozone generator, 7 is an air pump, 8 is a connecting portion, and 9 is a plunger.

In the embodiment using this device, the sample in the sample cup 1 is moved to the nozzle 2 by the operation of the plunger 9.
After being sucked in and discharged into a predetermined reaction container, the nozzle 2 is washed in the container 3 with air containing ozone. The number of processes is extremely small, and air is sent to the ozone generator 6 by the air pump 7, and the air containing ozone is supplied to the nozzle 2 for an appropriate time.
It is only released from. At this time, the container 3 is not always necessary, but it is more effective because the air containing ozone easily comes into contact with the inner wall and the outer wall of the nozzle 2 in the container 3. Cleaning with gas also has the effect of draining water and preventing clogging. It is also possible that a liquid such as water is stored in the container 3 and the nozzle 2 is bubbled by air containing ozone in the water. However, this liquid is not always needed.

Further, after the air containing ozone is discharged from the nozzle 2 for an appropriate time, the ozone generator 6 is stopped,
Only the air can be sent to the nozzle 2 by the air pump 7. When the air containing ozone affects the analysis result, it is desirable to prevent the effect of ozone in this way. Measurement of cleaning effect (1)

25 μL of anti-HB _s antibody solution (L represents liter; the same applies hereinafter) was sucked and discharged, and then the nozzle 2 was washed with the configuration shown in FIG. Antibody titer of anti-HB _s antibody 2 ¹⁸ (anti-HB _s antibody assay reagent Serokuritto anti HB
_s [measured by Chemistry and Serum Therapy Research Institute]). The cleaning conditions are as follows.・ Amount of liquid in container 3; pure water 7 ml; amount of ozone generated by ozone generator 6; 50 mg / h ・ amount of air sent by air pump 7; 1.2 L / min ・ washing time; 5 sec. I bubbled at. Also,
As a control, cleaning was also performed under the condition that the ozone generation rate was 0 mg / h.

[0031] As described above, the operation to wash the suction of anti HB _s antibody solution was repeated three times in the same vessel 3. In addition to the cleaning effect of the nozzle 2 at that time, the container 3
The increase in inward contamination was also investigated. After washing the nozzle 2 under the above conditions, it was examined for anti-HB _s antibody remaining on the nozzle 2. The measurement operation is as follows.

First, 50 μL of a sample diluent of an anti-HB _s antibody measuring reagent (cellocrit anti-HB _s ) was sucked by the nozzle 2 after washing and discharged. Then, with respect to the effluent 25 [mu] L, the HB _s Ag sensitized blood cells 25 [mu] L of the Serokuritto anti HB _s was reacted with V-bottom microplate. The presence or absence of anti-HB _s antibody remaining in the nozzle 2 was examined by the presence or absence of aggregation of HB _s Ag sensitized blood cells at that time. The measurement results are as shown in Table 1 below. In addition, the judgment criteria in the table follow the written description of the above reagents. In other words, (−) in the table means that there is no contamination, and (±) means that there is some contamination but it hardly affects the measurement.

[0033]

[Table 1]

Inferred from the change in antibody titer shown in Table 1,
In air containing ozone only fed to the nozzle 2, 2 ^-18
The above decrease in antibody titer was confirmed. This result demonstrates the very high cleaning effect of the above method. Further, even though the container 3 contains only 7 ml of pure water, the conventional cleaning method cannot maintain the sufficient cleaning effect even if the cleaning is repeated in the same container 3. It is an effect. Measurement of cleaning effect (2)

The sample is treated with anti-H
The measurement was performed by changing the B _s antibody solution to the HB _s Ag solution. H
The titer of B _s Ag is 2 ¹⁷ (measured with HB _s antigen measuring reagent Cellodia HB _s [manufactured by Fujirebio]). For the measurement, HB _s antigen measurement reagent (Cerodia HB _s ) was used. The measurement results are as shown in Table 2 below.

[0036]

[Table 2]

As shown in Table 2, a very high cleaning effect is proved only by sending the air containing ozone into the nozzle 2, whereas, of course, in the case of only air, the nozzle is HB _s Ag remains in 2. Also,
It can be seen that the amount of HB _s Ag in the container 3 increases every time cleaning is performed, and as a result HB _s Ag remains in the nozzle 2.

The first embodiment can also be implemented by using the apparatus shown in FIG. 2, 10 is a water supply port, 11 is a drain port, 12 is a sample cup, 13 is a syringe, 14
Is a connecting part, 15 is a solenoid valve, 16 is a solenoid valve, 17 is an ozone generator, 18 is an air pump, 19 is a water tank, 20 is a water pump, 21 is a container for cleaning nozzles, 22
Is a plunger, and 23 is a nozzle.

The feature of the configuration of FIG. 2 is that, compared with the apparatus of FIG. 1, mechanical cleaning can be performed with the solution supplied from the water supply tank 19. The solution may be sent from the water supply port 10 to the container 21 for cleaning the nozzle, or only the drainage may be performed. The nozzle 23 sucks the sample in the sample cup 12, discharges it into a predetermined reaction container, and then cleans it in the container 21. However, it is preferable to wash once with the solution supplied from the water supply tank 19 and then wash with the air containing ozone as in the case of FIG. <Second Embodiment> This embodiment relates to a method for generating fine bubbles of air containing ozone in water for cleaning.

FIG. 3 shows an example of the apparatus used in this embodiment. In the figure, 24 is a sample nozzle, 2
5 is a sample cup, 26 is a washing container, 27 is a mill generator, 28 is a solenoid valve, 29 is an ozone generator, 30 is an air pump, 31 is a connecting portion, 32 is a solenoid valve, 33 is a syringe,
Denoted at 34 are plungers, respectively.

In the cleaning using this apparatus, air is sent to the ozonizer 29 by the air pump 30 and the air containing ozone is passed through the millet generator 27 to the cleaning container 2
Vent to 6. The millet generator 27 may be in the form of a porous filter or may utilize an ultrasonic oscillator. The inside of the nozzle 24 can be cleaned by sucking and discharging the solution in the cleaning container 26 in which bubbles of air containing ozone are generated by the plunger 34. Cleaning effect measurement

After 25 μL of two kinds of anti-HB _s antibody solution was sucked and discharged, the nozzle 24 was washed using the apparatus shown in FIG. The antibody titers of the above-mentioned two kinds of anti-HB _s antibody solutions were 2 ¹⁵ and 2 ¹⁸ (anti-HB _s antibody measurement reagent serocrit anti-H, respectively).
B _s [measured by Chemistry and Serum Therapy Institute]). The washing conditions are as follows. -Solution in container 26 Pure water 10 ml-Ozone generation amount of ozone generator 29 50 mg / h-Air supply amount of air pump 30 1.2 L / min-Washing suction and discharge 5 sec. 2 times Ozone generation amount 0 mg / h as a control It was also washed under the conditions.

[0043] The operation to wash the above anti-HB _s antibody solution suction were repeated three times in the same vessel 26. At that time, together with the cleaning effect of the nozzle 24, an increase in contamination into the container 26 was also examined. After washing the nozzle 24 under the above conditions, it was examined for anti-HB _s antibody remaining on the nozzle 24. The measurement operation is as follows.

First, 50 μL of a sample diluent of an anti-HB _s antibody measuring reagent (cellocrit anti-HB _s ) was sucked by the nozzle 24 after washing and discharged. Then, 25 μL of this discharged liquid
On the other hand, 25 μL of the HB _s Ag-sensitized blood cells of the serocrit anti-HB _s were reacted in a V-bottom microplate. The presence or absence of anti-HB _s antibody remaining in the nozzle 24 was examined by the presence or absence of aggregation of HB _s Ag sensitized blood cells at that time. The measurement results are as shown in Tables 3 and 4 below.

[0045]

[Table 3]

[0046]

[Table 4]

As shown in Tables 3 and 4, when the ozone treatment was not carried out, the sample having the antibody titer of 2 ¹⁵ did not have carryover, but the sample having the antibody titer of 2 ¹⁸ had insufficient carry and had carryover. On the other hand, when ozone treatment was performed, there was no carryover at all for the antibody titers 2 ¹⁵ and 2 ¹⁸ and the excellent cleaning effect was exhibited. <Combination of the first and second embodiments>

FIG. 4 uses both the method of cleaning with the air containing ozone of the first embodiment and the method of cleaning with generating fine bubbles of the air containing ozone in the water of the second embodiment. 1 shows a device configured for the purpose.

In FIG. 4, 35 is a sample nozzle, 3
6 is a sample cup, 37 is a drain port, 38 is a washing container,
39 is a millet generator, 40 is a solenoid valve, 41 is a water inlet, 42
Is a connecting portion, 43 is an ozone generator, 44 is an air pump, 4
5 is a connecting portion, 46 is an electromagnetic valve, 47 is a water supply pump, 48 is an electromagnetic valve, 49 is an electromagnetic valve, 50 is a connecting portion, 51 is a syringe, 52 is a plunger, and 53 is a water supply tank. <Third Embodiment> This embodiment relates to a method of cleaning with a cleaning liquid in which ozone is dissolved.

FIG. 5 shows an example of an apparatus for carrying out the method of this embodiment. In the figure, 54 is a sample nozzle, 55 is a sample cup, 56 is a drainage port, 57 is a water supply port, 58 is a solenoid valve, 59 is a cleaning container, 60 is a connecting portion, 61 is a solenoid valve, 62 is a syringe, and 63 is 63. Plunger, 64 solenoid valve, 65 connecting part, 66 water supply pump,
67 is an ozone vent, 68 is a solenoid valve, 69 is an ozone generator, 70 is an air pump, and 71 is a water supply tank. This embodiment is less effective than the first and second embodiments, but can be used when it is mechanically difficult to ventilate a container such as a nozzle. Cleaning effect measurement

The aspirated anti HB _s antibody solution 25 [mu] L, it was drained and washed with nozzle 54 by using the apparatus shown in FIG. The antibody titer of the anti-HB _s antibody solution is 2 ¹⁸ (measured with anti-HB _s antibody measurement reagent serocrit anti-HB _s [manufactured by Chemistry and Serum Therapy Research Institute]). The washing conditions are as follows. -Liquid amount in container 59 pure water 1.5 ml-Water tank 71 capacity 10 ml-Ozone generation amount of ozone generator 69 50 mg / h-Air pump 70 air supply amount 1.2 L / min-Cleaning liquid drainage amount 200 μL Examples 1, 2 After cleaning in the same manner as above, the anti-H remaining in the nozzle 54
We examined the presence or absence of B _s antibody. The measurement operation is the same as in Examples 1 and 2.

[0052]

[Table 5] As shown in Table 5, the method of this example is more effective than that without ozone treatment. <Fourth Embodiment>

The present invention can be used not only for cleaning the sample nozzle as shown in Examples 1, 2 and 3, but also for cleaning various solid surfaces such as reaction vessels. In this fourth embodiment,
This is an experimental confirmation of the effect when used for cleaning the reaction vessel.

FIG. 6 is a diagram for explaining the method of this embodiment. In the figure, 72 is a microplate,
73 is an ozone blowing nozzle, 74 is an ozone generator, 7
Denoted at 5 are air pumps, respectively. Human 1
1 gG of human was artificially adsorbed on the inner surface of the microplate, and the cleaning effect by ozone was examined.

(1) Human 1 gG 10 μg / ml serially diluted solution was prepared using 0.01 M PBS pH 7.4.
50 μl of this was dispensed into a module U-16 maxisorp (product name), which is a microplate manufactured by NUNC, and solid-phased overnight at 4 ° C. (2) The solution was washed 3 times with 250 μl of 0.01 M PBS pH 7.4, and the solution was shaken off.

(3) Similar to the structure shown in FIG. 6, ozone-containing air was blown into the inner surface of the microplate. The conditions are as follows. Amount of ozone generated: 50
mg / h, the amount of air blown in; 1.2 L / min, the blowing time; 5 sec, 60 sec. (4) The effect was examined from the reactivity of anti-human 1 gG sensitized particles (manufactured by Olympus Optical Co., Ltd.) with the inner surface of the microplate. The results are shown in Table 6, and it is proved from the results that the present invention is effective for cleaning a solid surface that is adsorbed on a microplate and is difficult to be mechanically cleaned.

[0057]

[Table 6]

In the cleaning method of this embodiment, not only is air blown in as shown in FIG. 6, but an aqueous solution in which bubbles of air containing ozone are mixed or an aqueous solution in which ozone is dissolved is used. It can also be implemented. These first
-According to the results shown in the fourth embodiment, the cleaning effect by ozone is effective within 1 minute, and the treatment for 5 seconds has already been put to practical use.
It was a level. In addition, when washing with washing water is also used
In this case, by using a significantly smaller amount of washing water than before,
The above cleaning effect could be achieved. Fifth Example This example relates to enzyme cleaning.

According to the following procedure, peroxidase was artificially adsorbed on the inner surface of the microplate with the structure shown in FIG. 6 similar to that of the fourth embodiment, and the cleaning effect by ozone was examined.

(1) A double dilution of peroxidase (500 ng / ml) was prepared using 0.01 M PBS pH 7.4. This was dispensed in 100 μl aliquots on a flat-bottom maxisorp (product name), which is a microplate manufactured by NUNC. The reaction was carried out at room temperature (RT) for 1 hour (h), and peroxidase was artificially adsorbed on the inner surface of the microplate. (2) It was washed 5 times with 200 μl of pure water, and the pure water was shaken off.

(3) Air containing ozone was blown into each well. The conditions are as follows. Ozone generation rate: 0 mg / h, 50 mg / h, amount of blown air: 1.2
L / min, blowing time: 10 sec.

(4) 0.2M phosphoric acid-citric acid buffer
r pH 4.5, H ₂ O ₂ 0.04%, o-phenylenediamine 0.5 mg / ml were added 100 μl each. R
T, 15 min. (5) 5NH ₂ SO ₄ was added at 50 μl / well, and OD49
Measured at 0 nm. The results are as shown in Table 7 below.

[0063]

[Table 7]

As shown in Table 7, it can be seen that the activity of peroxidase was lowered because the coloring was stopped by the ozone treatment. However, the activity is not as marked as the activity of the antibody and antigen in the previous examples.
However, it has been shown that it can be sufficiently used for washing the enzyme. The enzyme to which the present invention can be applied is not limited to peroxidase, and is considered to be effective for immunoassays such as alkaline phosphatase, glucose oxidase, luciferase, BD-galactosidase and the like, and for residual labeling enzyme used in DNA assay.

[0065]

As described above in detail, the method for regenerating an appliance according to the present invention ensures a practical cleaning method that realizes non-disposable non-carry-over or non-contamination. Moreover, this is a mild process of bringing a fluid containing ozone into contact with the device, and has an advantage that it has almost no effect on the next use of the device. Further, since a sufficient cleaning effect can be obtained in a short time, it is suitable for an automated device such as an analyzer. In addition, the method for regenerating the biological treatment means according to the present invention, the biologically active substance or a plurality of different materials containing the active substance are sequentially contacted with each other at a predetermined contact site so that the activity of the material is maintained. It can be applied to a processing means for performing processing for analysis. In particular, it is possible to cause the predetermined contact site of the treatment means with the material to lose its activity irrespective of the presence or absence of a sterilizing or disinfecting action before the treatment means comes into contact with the next different material. Is. Thereby, it is possible to contact the next different material using the treatment means after loss of activity.

[Brief description of drawings]

FIG. 1 is an explanatory diagram showing an example of a first embodiment of the present invention.

FIG. 2 is an explanatory diagram showing another example of the first embodiment of the present invention.

FIG. 3 is an explanatory diagram showing another example of the second embodiment of the present invention.

FIG. 4 is an explanatory view showing a method of combining the first embodiment and the second embodiment of the present invention.

FIG. 5 is an explanatory diagram showing another example of the third embodiment of the present invention.

FIG. 6 is an explanatory view showing fourth and fifth embodiments of the present invention.

[Explanation of symbols]

1, 12, 25 ... Sample cup, 2, 23, 24 ... Sample nozzle, 3 ... Nozzle, 4, 33 ... Syringe, 5,
15, 16, 32 ... Solenoid valve, 6, 29 ... Ozone generator,
7, 30 ... Air pump, 8, 14, 31 ... Connection part, 9,
22, 34 ... Plunger, 10 ... Water supply port, 11 ... Drainage port, 13 ... Syringe, 17 is an ozone generator, 18 ... Air pump, 19 ... Water supply tank, 20 ... Water supply pump 21,
26 ... Nozzle cleaning container, 27 ... Millet generator, 28 ... Electromagnetic valve, 29 ... Ozone generator.

   ─────────────────────────────────────────────────── ─── Continued front page       (56) References Japanese Patent Laid-Open No. 3-131697 (JP, A)                 Japanese Patent Laid-Open No. 2-80049 (JP, A)                 Actual development Sho 56-168147 (JP, U)

Claims (6)

(57) [Claims] 1. A device for treating an active substance while contacting it with a biologically active substance or a material containing the active substance is regenerated to a reusable state after use without avoiding carryover or contamination. A method of regenerating a device for: contacting the device with a fluid comprising ozone, wherein at least a portion of the active substance present on the surface of the device remains on the surface of the device. A method for regenerating a biological treatment instrument, characterized in that the property of the active substance affecting the treatment is lost by 2. The method for regenerating a biological treatment instrument according to claim 1, wherein the fluid containing ozone is a gas containing ozone. 3. The contact time between the active substance and the gas containing ozone is about 1 minute or less.
The method for regenerating the biological treatment instrument according to 1. 4. The method for regenerating a biological treatment instrument according to claim 1, wherein the biological activity is a specific binding reaction with an analytical reagent. 5. The active substance is an antigen, an antibody, an enzyme, or DN.
The method for regenerating a biological treatment instrument according to any one of claims 1 to 3, which is selected from the group consisting of A, RNA, a receptor, and complement. 6. The dispensing device for treating at least one of a sample and a reagent or a mixture thereof, a dispensing nozzle, a syringe, a suction tube, a sample container, a reagent container,
Characterized by being selected from the group consisting of a reaction container, a measuring container, a stirrer, a filter, and a sensor,
A method for regenerating the biological treatment instrument according to claim 1.