JP3035393B2 - Cleaning method using charge on solid surface - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sample nozzle, a diluted sample nozzle, a cup for preparing a diluent,
The present invention relates to a method for washing a portion, such as a reaction vessel, in contact with a sample or a reagent.

[0002]

2. Description of the Related Art In clinical examinations and the like, various body fluid components such as urine, serum, and plasma are analyzed by using various analyzers. Such analysis is not limited to a normal biochemical assay, but may be a variety of different assays such as an immunoassay using an antigen-antibody reaction, a assay using a DNA probe, or an electrophoresis assay. Has been adopted.

[0003] In recent years, these analytical methods have been significantly improved in sensitivity and the measurement range has been expanded. Along with that, especially like sample dispensing nozzles and reaction vessels,
The cleaning of the part in contact with the sample has become increasingly important.

Conventionally, a number of ideas have been devised for cleaning the nozzle, but many of them basically use a cleaning water or a detergent to mechanically increase the cleaning efficiency (Japanese Patent Laid-Open Publication No. H11-163873). No. 62-242858, JP-A No. 62-242
No. 288574, No. 3-23572, Tokiko 52
-38754). However, there is a limit to simply increasing the cleaning effect mechanically, and this cannot be said to be sufficient.

Further, Japanese Patent Application Laid-Open No. 1-248771 discloses that
A cleaning method using a piezoelectric vibrator has been proposed. However, in this case, although the cleaning efficiency is considered to be increased according to the method, since the substance adsorbed on the nozzle maintains the adsorption equilibrium with the nozzle surface, it is not necessarily required depending on the affinity between the adsorbed substance and the probe surface. Effective cleaning cannot be said to be achieved.

In view of this, there has been proposed a mechanism for disposing a portion in contact with a sample such as a sample nozzle or the like (Japanese Patent Laid-Open No. 63-243).
762, JP-A-1-184465, JP-A-1-14
No. 6162, Japanese Utility Model Laid-Open No. 1-1141466,
No. 106567)

[0007] By being disposable,
Problems such as contamination between samples or carry-over caused by poor cleaning of a sample nozzle or the like can be reliably avoided. However, in this case, each time one sample is measured, the sample nozzle and other parts are discarded, which increases the cost. Not only from the viewpoint of environmental protection, which is increasing in recent years, it is not preferable that the amount of waste increases.

[0008]

As described above, each of the conventional techniques has its advantages and disadvantages, and it is difficult to satisfy all the demands of non-disposable, non-carry-over and non-contamination by using any of the methods. It is.

[0009] On the other hand, looking at the transition of the proposed technology for the cleaning method, it has shifted to disposable.
This suggests how difficult a perfect cleaning method can meet the above requirements. The present invention has been made in view of such circumstances, and an object of the present invention is to provide an effective cleaning method that can meet the above-mentioned requirements.

[0010]

SUMMARY OF THE INVENTION In the cleaning of a portion in contact with a sample or a reagent, such as a sample nozzle, a diluted sample nozzle, a diluent cup, etc., of an analyzer, there is a strong demand for completeness of the cleaning method. This is mainly the case where an analytical method such as an immunological assay, which has recently been significantly improved in sensitivity and which can achieve an expanded measurement range, is used. In such an analytical method, a level of contamination that is not a problem in the conventional method becomes a problem, and it is necessary to wash to a very low level of contamination (1/1 to 1/5 million).

However, the prior art using water and detergents is inefficient, so that an attempt to achieve the above-mentioned degree of cleaning on an extension thereof would have to be accompanied by a significant increase in cost.

The present invention utilizes the phenomenon that particles of biological substances such as proteins, lipids, carbohydrates, and nucleic acids that cause contamination move under an electric field, and the particles existing in an equilibrium state with respect to the nozzle wall. To destroy the equilibrium state and effectively increase the cleaning effect.

On the basis of this basic idea, the situation of insufficient washing results from the particles (mainly proteins) being in adsorption equilibrium with the wall and not easily desorbing from the adsorbing wall. . Particles in such a state are generally in an equipotential state under a certain environment, and a cleaning effect cannot be obtained unless the equipotential state is broken by any method.

Therefore, in the present invention, after the particles are brought into the (10) or (1) charged state by using the electrophoresis technique, the adsorbed wall is opposed to the charged particles. Is generated, and the particles are desorbed from the adsorption wall by utilizing the electric repulsion. As a result, it is possible to perform a level of cleaning (1 / 500,000 to 1 / 2,000,000 in an experiment), which is considered to be the limit in the cleaning method, using a small amount of detergent and water. In order to perform the cleaning effect more powerfully and efficiently, it is sufficient to take a large potential difference between the particles and the adsorbed wall.

Further, since some of the adsorbed particles are not uniformly charged even under the same environment, it is necessary to take measures against these. In such a case, the pH of the solution flowing as the washing water is changed at an appropriate time interval (every few seconds in an experiment), and the charge polarity of the particles causing the carry-over is changed. Can be washed out.

In the present invention, in order to make the charged state of the particles, generally, dilute hydrochloric acid is mixed into ion-exchanged water or the like on the acidic side, and sodium hydroxide or the like is mixed into the ion-exchanged water on the alkaline side, and this is used as a washing liquid. On the other hand, a stainless steel material is used for the probe and the cleaning tank, which are the adsorption walls of the particles, to effectively function as electrodes. It is needless to say that the application of the present invention is not limited to the analysis apparatus, and the present invention can be applied to cleaning manually used instruments and the like.

The analyzer or analytical instrument to which the present invention is applied includes immunological measurement, for example, particle agglutination of red blood cells and the like, latex inom assay, immunoturbidimetry, radio inom assay, enzyme inom assay, It may be used for analysis employing an analytical method such as a chemical luminescence inom assay. Further, it is considered that the washing method of the present invention shows a sufficient effect also on an apparatus or an instrument used for analysis using an analysis method using DNA, RNA or the like as a sample or an analysis method using a DNA probe as a reagent. .

[0018]

FIG. 1 is a view for explaining a method of cleaning a sample nozzle portion by utilizing an electric repulsion as one embodiment of the present invention. In FIG. 1, reference numeral 1 denotes a microsyringe for sampling and discharging a predetermined amount of a serum or plasma sample. Reference numeral 2 denotes a three-way valve provided in the flow path for switching the flow path between the micro syringe 1 and the washing water 4. Tank 3
The washing water 4 in the inside is ion exchange water,
It is supplied to the three-way valve 2 and the two-way valve 7 through the aspirator 6. The pH value is adjusted to about 2 to 3 with dilute hydrochloric acid or the like. p
The H-adjusted washing water 4 is supplied to a three-way valve 2 by a water supply pump 5.
And the two-way valve 7. Further, according to a sequence program (not shown), the cleaning water 4 is supplied from the three-way valve 2 and the two-way valve 7 to the sample nozzle 14 and the cleaning tank 10. The aspirator 6 is connected to the pH determination solutions 12 and 13 via the three-way valve 9, and by controlling the three-way valve 9 according to a sequence program, one of the pH determination solutions is selected and used. Branch pipe 2
According to 1, the flow path of the washing water 4 is the flow path toward the valves 2 and 7,
It is divided into a flow path returning to the original tank 3. Therefore,
When both the valves 2 and 7 are closed, the washing water 4 is returned to the original tank 3, so that the load on the water supply pump 5 is reduced to prevent a failure.

The sample nozzle 14 moves from the position of the washing tank 10 to the position of sucking the sample 23 and the position of the reaction vessel 15 and returns to the original position. Reference numeral 22 denotes a sample rack for storing sample tubes, and 23 denotes a sample. The sample 23 sucked into the sample nozzle 14 is
5 is discharged to the well 24 above.

The reagent is dispensed into the well 24 by a pressure divider and a reagent nozzle (not shown), and the reagent is stirred and reacted. After the reaction, photometric determination is made. Reference numeral 16 denotes an illumination unit of the photometric system. Reference numeral 17 denotes an image (reaction pattern) reading unit.

Each of the sample nozzle 14 and the electrode 11 installed in the cleaning tank 10 is connected to the DC generator 8. The sample nozzle 14 and the electrode 11 make an open loop electrically through the cleaning water 4. Due to the potential difference between the sample nozzle 14 and the electrode 11, the particles adsorbed on the tube wall of the sample nozzle 14 move into the washing water 4 by an electric repulsion. The particles that have moved into the washing water 4 are discharged together with the washing water 4 to which a constant amount is supplied. The particles separated from the tube wall are discharged to the outside of the apparatus by the constantly supplied cleaning water 4 without adhering to the electrode 11 that is electrically opposed.

On the other hand, for particles charged to the opposite polarity, the three-way valve 9 is switched to switch the pH-determining liquids 12 and 1 to one another.
3 is selected and used, the particles are separated from the tube wall by changing the charge polarity of the particles and performing the above operation again, and discharged out of the apparatus by the washing water 4. FIG. 2 is a view for explaining a method of cleaning the diluted sample preparation cup section 19 as another embodiment of the present invention.

The washing water 4 is sucked by a required amount by a water supply pump 5 and supplied to the discharge side of the suction / discharge double nozzle 20. The branch pipe 25 adjusts the supplied flow rate appropriately.
The suction / discharge double nozzle 20 is connected to the DC generator 8 and the diluted sample preparation cup unit 19. Therefore, the diluted sample preparation cup section 19 and the suction / discharge double nozzle 20 form an electric open loop via the cleaning water 4. Due to the potential difference between the diluted sample preparation cup section 19 and the suction / discharge double nozzle 20, particles adsorbed on the wall surface of the cup 19 become:
It moves into the washing water 4 by the electric repulsion. The particles that have moved into the washing water 4 are discharged together with the washing water 4 to which a constant amount is supplied. Due to the washing water 4 constantly supplied, particles separated from the tube wall are discharged out of the apparatus without adhering to the electrically opposed suction / discharge double nozzle 20. On the other hand, particles charged with the opposite polarity can also be washed by changing the charging polarity of the particles by using the pH determining solutions 12 and 13 by selecting the flow path of the three-way valve 9 and performing the above operation again. .

[0024]

As described above in detail, the cleaning method of the present invention utilizing the electric repulsion is particularly effective for antigens, antibodies, DNs, and the like.
This is effective for cleaning a sample nozzle, a diluting liquid preparation cup, a reaction vessel, and the like of an analyzer for treating charged particles such as A as a sample or a reagent.

[Brief description of the drawings]

FIG. 1 is an explanatory diagram showing one embodiment of the present invention.

FIG. 2 is an explanatory view showing another embodiment of the present invention.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Micro syringe, 2, 9 ... Three-way valve, 3 ... Wash water tank, 4 ... Wash water, 5 ... Water supply pump, 6 ... Aspirator, 7 ... Two-way valve, 8 ... Power supply, 10 ... Wash tank, 11 ... Electrode , 12, 13: pH determination solution, 14: sample nozzle, 15: reaction vessel, 16: photometric illumination unit, 17: reaction pattern reading unit, 19: diluted sample preparation cup unit, 2
0: double nozzle, 21: branch pipe, 22: sample rack, 23: sample, 24: well.

──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Ichi Sakuma 2-43-2 Hatagaya, Shibuya-ku, Tokyo Inside Olympus Optical Co., Ltd. (56) References JP-A-63-168558 (JP, A) (58) ) Field surveyed (Int.Cl. ⁷ , DB name) G01N 35/00-35/10 G01N 1/00 101

Claims (4)

(57) [Claims] 1. A washing method for removing an organism, a biological component such as an antigen, an antibody, an enzyme, or a DNA, from a surface of a solid object to which the component is attached by using electric repulsion. Giving a charge to the living body-related component, giving a potential of the opposite polarity to the charge on the surface of the object, and reversing the polarity of the charge given to the living body-related component at least once. How to wash. 2. In order to give a charge to the biologically relevant component, a physiological saline solution or a buffer solution having a predetermined pH value is brought into contact with the surface of the object, and the pH value is changed by changing the pH value. The cleaning method according to claim 1, wherein the polarity is reversed. 3. The cleaning method according to claim 1, wherein the surface of the object is formed of a conductive member. 4. The cleaning method according to claim 1, wherein the object is a part of an analyzer or an instrument that comes into contact with the biological component.