WO1999004271A1

WO1999004271A1 - Nozzle washing device

Info

Publication number: WO1999004271A1
Application number: PCT/JP1998/003165
Authority: WO
Inventors: Toshimi Kawamura; Yuzaburo Nanba; Syuji Takahashi; Eiji Ishiwata
Original assignee: Sanko Junyaku Co., Ltd.; Eisai Co., Ltd.; Kanda Tsushin Kogyo Co., Ltd.
Priority date: 1997-07-18
Filing date: 1998-07-15
Publication date: 1999-01-28
Also published as: JPH1138016A

Abstract

A nozzle washing device capable of minimizing an opening area of a nozzle washing hole, being reduced in volume, minimizing an amount of a washing liquid used, and eliminating adhesion of crystallites to a reaction pipe which is caused by the washing liquid. Specifically, the device which washes nozzles for drawing liquid received in reaction vessels and nozzles for injecting liquid into the reaction vessels, and which comprises nozzle holding means provided above a location where the reaction vessels are installed and for holding the nozzles vertically movably so that the nozzles can enter the reaction vessels, a nozzle washing casing provided between the nozzle holding means and the location where the reaction vessels are installed, nozzle passages which are provided within the nozzle washing casing and through which the nozzles held by the nozzle holding means can pass vertically movably, and washing mechanisms disposed in the nozzle passages.

Description

Specification

Technical Field The present invention relates to an injection nozzle for injecting various liquids (reaction solution and washing liquid) into a reaction vessel (also referred to as a reaction tube) used in an automatic analyzer such as an automatic immunoassay apparatus, and an inlet for the liquid. TECHNICAL FIELD The present invention relates to a nozzle cleaning device capable of efficiently cleaning a suction nozzle that sucks a liquid from a reaction tube. Background art

Conventionally, as immunoassays utilizing an antigen-antibody reaction, a one-step method and a two-step method, a non-competitive San Germanti method and a competitive method are known.

A method for measuring the amount of antigen contained in a sample such as blood collected from a patient by a one-step non-competitive sandwich method will be described. For example, an antibody (solid phase antibody) bound to an insoluble simple substance (solid phase) such as a synthetic resin container inner wall or particles (particles) and an antibody (labeled) bound to a labeling substance such as a radioactive substance, a fluorescent substance, or an enzyme Antibody) is added to the reaction tube to which the sample to be measured is added in advance.

As a result, in the reaction tube, the antigen contained in the sample undergoes an antigen-antibody reaction (immune reaction) with the solid-phase antibody to form an antigen-antibody complex, and at the same time, the antigen-antibody complex is labeled with the labeled antibody. The complex also forms a complex in which the three components, solid-phase antibody and antigen-labeled antibody, are sandwiched. In this way, the label of the labeled antibody is bound to the solid phase using the antigen in the sample as an intermediate.

Next, extra labeled antibodies other than the label bound to the solid phase and not binding to the antigen added to the reaction tube or antibody components not involved in the immune reaction are washed out. The separation (B / F separation) operation is performed, and finally, the amount of the label, which is proportional to the amount of the antigen bound to the solid phase, is quantitatively measured by a physical or chemical method utilizing the properties of the label. Determine the antigen concentration in the sample.

On the other hand, in the two-step non-competitive sandwich method, only the solid phase antibody is first added in advance. This is a method in which the first reaction is performed by adding a sample to the reaction tube to which the sample is added, and then the labeled antibody is added to perform the second reaction to perform the measurement.

In addition to the non-competitive sandwich method, there is also a method called a competitive method in which an antigen (labeled antigen) previously labeled with a labeling substance and an antigen in a sample are competitively reacted with the solid phase antibody described above. Are known.

An automatic analyzer such as an automatic immunoassay is known as an apparatus for automatically performing the measurement in such an immunoassay. In this automatic analyzer, it is necessary to wash the inside of the reaction tube, especially in the B / F separation process, and a suction nozzle that sucks the reaction solution and the washing solution from the reaction vessel and an injection that injects the washing solution into the reaction vessel. Many nozzles are used. These nozzles must be cleaned each time they are used to prevent contamination of other solutions (contamination). Therefore, a nozzle cleaning device for cleaning the nozzle has been conventionally used.

As shown in FIG. 9, the conventional nozzle cleaning apparatus 110 performs cleaning of the nozzles using a cleaning case 112 having an independent installation position and structure separately from a nozzle group (not shown). The cleaning case 112 has a cleaning case body 116 having a recess 114 opened upward.

At the center of the cleaning case main body 116, a cleaning liquid outlet 118 is provided, which penetrates the bottom wall 120 downward and opens. Nozzle washing holes 1 2 2 and 1 2 2 are provided on the outside of the periphery of the outlet 1 1 8. The nozzle washing holes 1 2 2 and 1 2 2 are provided in the washing case main body 1 1 6. The cleaning liquid supply ports 124, 124 open through the bottom wall 120 of the cleaning liquid sideways.

To clean the tips of the nozzles N 1 and N 2, insert the tips of the nozzles N 1 and 2 into the nozzle cleaning holes 1 2 and 1 2 2, and from the nozzle cleaning holes 1 2 2 and 1 2 2 The cleaning liquid is continuously injected, and overflows from the bottom of the nozzle cleaning holes 122 and 122 toward the upper opening. With the continuous overflow of the cleaning liquid, the tips of the nozzles N 1 and N 2 are cleaned. The cleaning liquid overflowed from the nozzle cleaning holes 1 2 and 1 2 2 is discharged to the outside through the discharge port 1 18.

The nozzles Nl and N2 are moved to the installation position and the washing position of the reaction tube T by a nozzle moving means (not shown) which moves in the X direction and the Z direction, respectively. At the installation position, required operations such as suction of the reaction solution and the cleaning solution and injection of the cleaning solution are performed, and at the cleaning position, the tips of the nozzles N1 and N2 are washed as described above.

In the conventional nozzle cleaning device 110 shown in FIG. 9, the position where the reaction solution is sucked and the access for injecting and sucking the cleaning solution and the position of the cleaning case 112 are different. It was at a different position, and it was essential to move the nozzles Nl and N2 in two directions. Therefore, the volume of the conventional nozzle cleaning device 110 becomes large, and the cost increases accordingly.

The nozzles N 1 and N 2 are taken out of the nozzle washing holes 1 2 2 to suck and inject the reaction solution and the cleaning solution. It is repeated to be reinserted into 2 and washed. Therefore, if the opening area of the nozzle cleaning holes 122 is made small enough to allow the nozzles N1 and N2 to pass through, the nozzles N1 and N2 will be cleaned when the nozzles Nl and N2 are inserted. There was an inconvenience that it was broken along the edge of the hole 122. Further, in the conventional nozzle cleaning device 110, the amount of cleaning liquid used is large, which is uneconomical.

If the cleaning liquid contains a special component, for example, a surfactant, a phenomenon occurs in which the crystals adhere to the cleaning case 112 during drying, and the crystals cause the cleaning case 112 to lose power. s There was a problem that the cleaning ability was deteriorated with time due to the contamination.

SUMMARY OF THE INVENTION The present invention has been made in view of the above-described problems of the related art, and it is an object of the present invention to minimize the opening area of a nozzle cleaning hole, reduce the volume of an apparatus, and minimize the amount of a cleaning liquid to be used. It is another object of the present invention to provide a nozzle cleaning apparatus which enables the cleaning liquid and eliminates the adhesion of crystals to the nozzle and the nozzle cleaning case caused by the cleaning liquid. Disclosure of the invention

In order to solve the above problems, a nozzle cleaning device of the present invention is a device for cleaning a nozzle for sucking a liquid in a reaction container and a nozzle for injecting a liquid into the reaction container, and is provided above a position where the reaction container is installed. And a nozzle is advanced into the reaction vessel. A nozzle holding means for vertically holding the nozzle so that it can be inserted, a nozzle cleaning case provided between the nozzle holding means and the installation position of the reaction vessel, and a nozzle held by the nozzle holding means, It is characterized by having a nozzle passage provided in the nozzle cleaning case so as to be movably insertable, and a cleaning mechanism for cleaning a nozzle located in the nozzle passage.

The nozzle cleaning mechanism may be configured to include a unit that jets a cleaning liquid into the nozzle passage and a unit that suctions the jetted cleaning liquid.

The nozzle cleaning mechanism opens a cleaning liquid jet port and a cleaning liquid suction port so as to face the nozzle path, and jets a cleaning liquid from the cleaning liquid jet port into the nozzle path to clean the nozzle. It is preferable that the cleaning liquid is sucked and discharged from the cleaning liquid suction port.

By providing the cleaning liquid jet port at the lower part of the nozzle passage and providing the cleaning liquid suction port at the upper part of the nozzle path, the flow of the cleaning liquid is piled up from the bottom by gravity and flows. As long as the effect is large and the cleaning liquid is sucked from the cleaning liquid suction port by a suction pump or the like, there is no accident that the cleaning liquid drops from the lower opening.

If the installation distance between the cleaning liquid jet port and the cleaning liquid suction port is set to be longer than the length of the immersion portion of the nozzle when the nozzle enters the liquid in the reaction vessel, the nozzle is immersed in the liquid. There is an advantage that the cleaning liquid is surely cleaned over a wider portion than the contaminated portion by the cleaning liquid, so that there is no leakage of cleaning.

At the top of the nozzle passage, a nozzle holder having a nozzle through hole at the center is formed, and the diameter of the lower end of the nozzle insertion hole can be moved up and down in close contact with the nozzle. With this configuration, when the cleaning liquid is sucked from the cleaning liquid suction port, there is no leakage or dispersion of the suction power due to the nozzle insertion hole, and all the suction power can be effectively used for suctioning the cleaning liquid. BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a top view showing one embodiment of an automatic immunoassay apparatus including a nozzle cleaning apparatus according to the present invention. FIG. 2 is a front view of FIG.

FIG. 3 is a partial cross-sectional side view of the nozzle cleaning device of the present invention, showing a state where the nozzle is housed in a cleaning case.

FIG. 4 is a partial cross-sectional side view similar to FIG. 3, showing a state in which the nozzle is projected to the position of the reaction vessel.

FIG. 5 is an enlarged sectional view of a main part of the nozzle cleaning device of the present invention.

FIG. 6 is a perspective view showing the cleaning case.

FIG. 7 is a sectional view taken along line AA of FIG.

FIG. 8 is an explanatory cross-sectional view showing a state where the nozzle holder is mounted on the cleaning case of FIG. 7 and the nozzle is inserted into the nozzle passage.

FIG. 9 is a schematic sectional explanatory view showing a conventional nozzle cleaning device. BEST MODE FOR CARRYING OUT THE INVENTION

An embodiment of the present invention will be described below with reference to the accompanying drawings.

In FIG. 1, reference numeral 12 denotes an automatic analyzer according to the present invention, specifically, an automatic immunoassay device, which has a reaction tube 14 which rotates intermittently at a predetermined speed. At the periphery of the upper surface of the reaction tube evening plate 14, there is formed a reaction tube holding portion 18 having a plurality of reaction tube holders 16 arranged in two rows, an inner circumferential row and an outer circumferential row. I have. The number of the reaction tube holders 16 provided on the upper surface of the reaction tube 14 may be appropriately set according to the mode of the reaction, but in the example of FIG. The figure shows an example in which 0, a total of 60 reaction tube holders 14 are installed.

Reference numeral 20 denotes a reaction tube rack, which holds the reaction tubes in a large number of receiving portions 21 (the example of FIG. 1 shows a case where two reaction tube racks are installed). Reference numeral 22 denotes a reaction tube transfer means, which has a reaction tube holding portion 22 a at a lower portion, and transfers the reaction tube held in the receiving portion 21 of the reaction tube rack 20 to the reaction tube holder 16. The operation of transferring and transferring the reaction tubes held in one reaction tube holder 16 to another reaction tube holder 16 by skipping the desired number of reaction tube holders 16 is performed.

In this case, the reaction tubes held in the inner or outer rows of the reaction tube holders 16 can be transferred to the reaction tube holders 16 of the same circumference, or the reaction tubes of other circumferences can be transferred. It can also be transferred to 1-16. The reaction tube transfer means 22 has a reaction tube supply operation of supplying a reaction tube to the reaction tube holding unit 18, and a reaction tube disposal operation of taking out a measured reaction tube from the reaction tube holding unit 18 and discarding it. Perform

26 is a particle supply means for supplying particles to the reaction tube, and a particle nozzle 26a is provided below the particle supply means. Reference numeral 28 denotes a reagent dispensing means for dispensing a labeled reagent into the reaction tube, and a reagent nozzle 28a is provided below the reagent dispensing means. Reference numeral 30 denotes a nozzle cleaning device according to the present invention, which is used for B / F separation processing. 32 is a measuring reagent dispensing means for dispensing the measuring reagent into the reaction tube. Reference numeral 34 denotes a measuring means for measuring the amount of the label in the reaction solution after the reaction in the reaction tube.

Reference numeral 36 denotes a reagent table mechanism, which has a reagent table 37. The reagent table 37 is provided with mounting holes 37a and 37a, and the reagent holders 38 and 38 are detachable via the mounting holes 37a and 37a. It is attached to. In the reagent holders 38, 38, a particle bin 40 and a labeling reagent bin 42 are individually mounted.

An embodiment of the nozzle cleaning device 30 according to the present invention will now be described with reference to FIGS. 3 and 4, the nozzle cleaning device 30 has a base 50. A guide rail 52 is provided in the longitudinal direction of one side of the base 50.

A movable support 54 is attached to the guide rail 52 so as to be vertically movable. Reference numeral 56 denotes a timing belt connected to the movable column 54. The evening belt 56 is suspended on a pair of pulleys 58, 58 driven by a drive source (not shown). The movable support 54 is moved up and down by the rotation of the timing belt 56.

An arm member 60 serving as a nozzle holding means is provided at the upper end of the movable support 54 so as to extend to the side. The arm member 60 holds an injection nozzle N1 for injecting a liquid into the reaction vessel T and a suction nozzle N2 for aspirating the liquid in the reaction vessel T, with the distal end thereof facing downward. Reference numerals 62 and 62 denote mounting blocks embedded in the arm member 60 and into which the nozzles N1 and N2 are press-fitted.

The upper end of the injection nozzle N1 is connected to, for example, a cleaning liquid supply tank (not shown). Then, a required amount of liquid can be injected into the reaction tube T. The upper end of the suction nozzle Ν2 is connected to a liquid outlet (not shown), and the liquid such as the reaction solution or the cleaning liquid existing in the reaction vessel に is supplied to suction means such as a vacuum pump. It performs more suction and discharge from the liquid discharge port.

Reference numeral 64 denotes a cleaning case which is located below the arm member 60 and is provided to extend laterally from the base 50. In the cleaning case 64, the injection nozzle passage 66a for the injection nozzle Ν1 and the suction nozzle passage 66b for the suction nozzle N2 are vertically arranged corresponding to the injection and suction nozzles Ν1 and Ν2. Are formed.

Below the injection nozzle passage 66a and the suction nozzle passage 66b, a number of reaction vessels T held by the reaction tube holder 16 of the reaction tube turret 14 are intermittently rotated and positioned one after another. Can be The injection nozzle N1 only needs to enter the middle of the reaction vessel T to inject and discharge the liquid. On the other hand, since the suction nozzle N2 needs to suck all the liquid in the reaction vessel T, the suction nozzle N2 enters the bottom of the reaction vessel T and performs a suction operation as shown in FIG.

As shown in FIG. 8, nozzle holders 68, 68 are attached to the upper end portions of the injection nozzle passage 66a and the suction nozzle passage 66b. Nozzle through holes 70, 70 are formed in the center of the nozzle holders 68, 68. O-rings 72, 72 are fixed to lower ends of the nozzle insertion holes 70, 70, respectively. The O-rings 7 2, 7 2 are in close contact with the respective outer peripheral surfaces of the nozzles N 1, N 2, and the nozzles N 1, N 2 are vertically movable with respect to the O-rings 7 2, 7 2 in a close state. Abuts.

Since the lower ends of the nozzle holes 70 and 70 are completely sealed by the nozzles Nl and N2 and the rings 72 and 72, the cleaning liquid suction port 74b , 76b, there is no air leakage from the nozzle insertion holes 70, 70, so that all suction power can be effectively used for suction of the cleaning liquid.

74 a, 76 a and 74 b, 76 b are provided with cleaning liquid jets formed in the inner wall surfaces of the nozzle passages 66 a, 66 b so as to face the nozzle passages 66 a, 66 b. Outlet and cleaning solution suction port. The cleaning liquid jets 74 a and 76 a are connected to cleaning liquid supply ports 78 a and 80 a formed through the lower portion of the side wall of the cleaning case 64 via a liquid passage 82. I have. The cleaning liquid suction ports 74 b and 76 b are connected to the cleaning liquid discharge ports 78 b and 8 Ob formed through the upper portion of the side wall of the cleaning case 64 via a liquid passage 82. The cleaning liquid supplied from the cleaning liquid supply ports 78a and 80a is ejected from the cleaning liquid jet ports 74a and 76a into the nozzle paths 66a and 66b through the liquid passage 82, and the nozzles N1, N2 While washing, the liquid flows upward by the suction force of the cleaning liquid suction ports 74b and 76b, is sucked into the cleaning liquid suction ports 74b and 76b, and is discharged from the cleaning liquid discharge ports 78b and 80b through the liquid passage 82.

In the case of washing the reaction vessel, for example, performing B / F separation, the reaction vessel T containing the reaction solution reaches the washing position, absorbs the reaction solution in the reaction vessel T, discards the reaction solution, and injects the washing solution. Cleaning is performed according to the procedure of aspirating and discarding the cleaning liquid. Therefore, for example, in the case where the reaction tube holders 16 are arranged in the reaction tube turret 14 in two rows of the inner circumference and the outer circumference, the suction nozzle N1 and the injection nozzle N2 are arranged as shown in FIG. Then, a washing operation of suction-injection-suction-injection-inhalation can be performed. In this case, two washes can be performed.

A case where the nozzles Nl and N2 are cleaned by the above configuration will be described. As shown in FIG. 6, when the B / F separation is performed on the reaction vessels held by the reaction tube holders 16 in the inner and outer rows of the reaction tube holding unit 18, the nozzles in the inner and outer rows are used. Nl and N2 can be washed at the same time.

As shown by the arrow in FIG. 6, for example, when the reaction tube 14 is rotated clockwise, the reaction vessels T and た containing the reaction solution are suction nozzles at the far right end in FIG. When the nozzles 下方 2 and Ν2 reach below the nozzles Ν2 and Ν2, the suction nozzles Ν2 and Ν2 descend and enter the bottoms of the reaction vessels Τ and 吸引 (Fig. 4), and suck all the reaction solution. When the suction is completed, the suction nozzles Ν2 and Ν2 rise and are stored in the suction nozzle passage 66b in the cleaning case 64 (FIG. 3). At this time, as shown in FIG. 3, if the lower ends of the suction nozzles N 2 and N 2 are positioned above the installation position of the cleaning liquid ejection port 76 a, good cleaning can be performed. When the N2 is stored in the bow suction I nozzle passage 66b, the cleaning liquid is jetted from the cleaning liquid jet port 76a, and the jetted cleaning liquid is lifted upward against the gravity by the suction force from the cleaning liquid suction port 76b. To clean the suction nozzles N2 and N2 Then, the liquid is sucked from the cleaning liquid suction port 76b and discharged from the cleaning liquid discharge ports 78b and 8 Ob.

The empty reaction vessels Τ and T, which have sucked the reaction solution, then rotate below the second injection nozzles Nl and N1 from the right in FIG. The injection nozzles N 1 and N 1 descend to enter the middle of an empty reaction vessel T, Τ (there is no need to enter the bottom because it is only injection), and the cleaning liquid is supplied to the reaction vessels Τ and Τ. Inject into When the injection is completed, the injection nozzles Nl and N1 rise and are stored in the injection nozzle passage 66a in the cleaning case 64 (Fig. 3).

The injection nozzles N 1 and N 1 do not stain much because they only inject the cleaning liquid, but they also need to be cleaned in order to prevent contamination due to contamination or the like and increase measurement accuracy. Also in this case, if the lower ends of the injection nozzles Nl and N1 are located above the installation position of the cleaning liquid ejection port 74a, it is the same that good cleaning can be performed.

When the injection nozzles N 1 and N 1 are housed in the injection nozzle passage 66 a, the cleaning liquid is jetted from the cleaning liquid jet port 74 a, and the jetted cleaning liquid is gravity driven by the suction force from the cleaning liquid suction port 74 b. The cleaning liquid flows upward to wash the injection nozzles N1 and N1, and is sucked from the cleaning liquid suction port 74b and discharged from the cleaning liquid discharge ports 78b and 80b.

The reaction vessels Τ and T into which the cleaning liquid has been injected then turn below the third suction nozzles N2 and N2 from the right in FIG. The suction nozzles N2 and N2 descend and enter the bottom of the reaction vessels T and T (Fig. 4), and suck all the cleaning liquid. When the suction is completed, it is stored in the suction nozzle passage 66b and washed as described above.

These empty reaction vessels Τ and T further pivot below the fourth injection nozzles N 1 and N 1 from the right in FIG. 6, and the washing liquid is injected again as described above. After the injection is completed, the injection nozzles N1 and N1 are similarly cleaned in the injection nozzle passage 66a. The reaction vessels T and た into which the cleaning liquid has been injected are the fifth from the right in FIG. The cleaning liquid in the reaction vessels Τ and Τ is sucked and discharged in the same manner as described above after reaching the rotation below the suction nozzles Ν2 and 回動 2. After suction is completed, suction nozzles Ν2 and Ν2 The cleaning is performed in the suction nozzle passage 66b.

As described above, the injection nozzle N1 and the suction nozzle N2 are washed in the injection nozzle passage 66a and the suction nozzle passage 66b immediately after performing the injection operation and the suction operation. Even if a special component, such as a surfactant, is contained, the crystals are not left for a period of time so as to dry and become crystals, so that the crystals do not adhere to the reaction tube at all.

In the example shown in Fig. 6, the washing in the B / F separation of the reaction vessel T is performed by suction (reaction solution), one injection (washing solution), one suction (washing solution), one injection (washing solution), and one suction ( Cleaning solution), the cleaning process was performed twice. When increasing the number of washings in the B / F separation, it goes without saying that the number of combinations of the injection nozzle N1 and the suction nozzle N2 may be increased. Industrial applicability

As described above, according to the nozzle cleaning device of the present invention, the opening area of the nozzle cleaning hole can be minimized, the volume of the device can be reduced, and the amount of the cleaning liquid to be used can be minimized. In addition, the present invention has an effect that it is possible to eliminate the adhesion of the crystal to the nozzle and the nozzle cleaning case due to the cleaning liquid.

Claims

The scope of the claims

1. A device that cleans the nozzle that sucks the liquid in the reaction container and the nozzle that injects the liquid into the reaction container, is provided so as to be located above the installation position of the reaction container, and the nozzle is located in the reaction container. Holding means for holding a nozzle movably up and down so as to be able to enter the nozzle, a nozzle cleaning case provided between the nozzle holding means and the installation position of the reaction vessel, and a nozzle held by the nozzle holding means A nozzle cleaning device, comprising: a nozzle passage provided in the nozzle cleaning case so that the nozzle can be inserted in a vertically movable manner; and a cleaning mechanism for cleaning a nozzle located in the nozzle passage.

2. The nozzle cleaning device according to claim 1, wherein the nozzle cleaning mechanism includes a unit that jets a cleaning liquid into the nozzle passage, and a unit that sucks the jetted cleaning liquid.

3. The nozzle cleaning mechanism opens the cleaning liquid ejection port and the cleaning liquid suction port so as to face the nozzle passage, and ejects the cleaning liquid from the cleaning liquid ejection port into the nozzle passage to clean the nozzle. 2. The nozzle cleaning apparatus according to claim 1, wherein the cleaning liquid in the nozzle passage is suctioned and discharged from a cleaning liquid suction port.

4. The nozzle cleaning device according to claim 3, wherein the cleaning liquid ejection port is provided at a lower portion of the nozzle passage, and the cleaning liquid suction port is provided at an upper portion of the nozzle passage.

Claim 5. The installation distance between the cleaning liquid jet port and the cleaning liquid suction port is larger than the length of the immersion part of the nozzle when the nozzle is inserted into the liquid in the reaction vessel. 4. The nozzle cleaning device according to 4.

6. At the top of the nozzle passage, attach a nozzle holder with a nozzle through hole at the center to penetrate the nozzle, and adjust the diameter of the lower end of the nozzle through hole so that the nozzle is in close contact. The nozzle cleaning device according to any one of claims 3 to 5, wherein the nozzle cleaning device is formed so as to be able to move up and down.