JPH046468A - Method for accurately dispensing very small amount of specimen - Google Patents

Abstract

PURPOSE:To eliminate the effect of water pressure on the solenoid valve on the side of a syringe by connecting two solenoid valves for connecting and disconnecting a flow path to the syringe and a pump in series to attain to relax flow pressure and closing the solenoid valves to temporarily stop the pump at the time of the suction of a very small amount of a specimen and releasing the water pressure remaining between the solenoid valves during the stop of the pump by opening the solenoid valve on the side of the pump. CONSTITUTION:A pump 30 is stopped simultaneously with the falling of a dispenser mechanism 5 and, at the same time, a solenoid valve 28 is opened. By this mechanism, the water pressure remaining between solenoid valves 27, 28 is released and the closing operation of the solenoid valve 27 is stably held during the operation of a dispenser syringe 23 to make it possible to enhance the weighing accuracy of a specimen. The residual pressure slightly becomes negative pressure by the head of the pump 30 with a distilled water tank 29 but acts on the solenoid valve 27 in a good direction for the action in the direction supporting closing operation to enhance accuracy.

Description

[Detailed Description of the Invention] [Field of Industrial Application] The present invention relates to a dispensing method that improves the accuracy of dispensing samples and reagents in automatic analyzers. In particular, the present invention relates to a dispensing method that improves the accuracy of dispensing samples and reagents in automatic analyzers, and in particular, stops pump operation when aspirating a small amount of sample and switches the solenoid valve to open/close. prevention of inhibition.

The present invention also relates to a dispensing method that improves dispensing accuracy by minimizing the amount of water droplets that adhere to the dispensing probe in a cleaning tank.

[Conventional technology]

Regarding the dispensing method in the conventional automatic analyzer, there is no particular specification regarding the method of washing the dispensing probe with washing water or the operation of the pump that sucks up distilled water from the distilled water tank. Furthermore, most table-top automatic analyzers have a distilled water tank installed on the same table as the apparatus, and most floor-standing automatic analyzers have the tank placed on the floor.

[Problem to be solved by the invention]

In the above-mentioned conventional technology, there are few methods for sucking up water from a distilled water tank using a self-contained pump, and therefore, the pump itself is often of the priming type, such as a magnet pump. Since this magnetic pump does not have self-sufficient power, it cannot draw water from a floor-standing distilled water tank to a desktop-mounted automatic analyzer, and its usage conditions are limited. This device incorporates a small diaphragm pump into a tabletop device, making it possible to self-supply from a floor-standing tank. However, with diaphragm pumps, water flows intermittently due to the operation of the diaphragm, and this pressure fluctuation occurs in synchronization with the frequency of the pump power supply, which adversely affects the operation of the solenoid valves connected to the same flow path system and reduces the dispensing accuracy of samples and reagents. I made it worse. The present invention aims to improve the method of temporarily stopping the diaphragm pump when aspirating a minute sample. Another object of the present invention is to improve a probe cleaning method that minimizes the amount of water droplets that adhere when cleaning a probe contaminated by reagent suction with distilled water.

[Means to solve the problem]

To achieve the above objective, two solenoid valves for interrupting the flow path are connected in series between the syringe and the pump to reduce the flow pressure so as not to transmit the vibration pressure of the flowing water from the diaphragm pump to the syringe used to weigh the sample/reagent. Furthermore, when the solenoid valve is closed and a minute sample is aspirated, the pump is temporarily stopped and the water pressure remaining between the two solenoid valves is released by opening the pump side solenoid valve, thereby reducing the effect of water pressure on the syringe side solenoid valve. This eliminates the need for accurate dispensing.

Furthermore, in order to perform micro-dispensing of samples with high precision, a cleaning tank is used to remove the large amount of water adhering to the probe, which is generated by cleaning the dispensing probe from the membrane-coated reagent container required for immunoassays. This is an improvement to the dispensing method that prevents the sample from diluting during the next operation by reliably removing the probe pull-up using a two-step motion, something that could not be removed with the conventional cleaning operation of pulling the probe up from within in one operation. .

[Effect]

Residual pressure between two solenoid valves, which are installed to prevent water flow pressure fluctuations caused by the operation of the diaphragm pump from affecting the syringe, slightly affects the operation of the solenoid valve on the syringe side and adversely affects the weighing of minute samples. Since the diaphragm pump is stopped when aspirating samples and reagents, accurate weighing is possible.

In addition, water droplets that adhere to the dispensing probe in the cleaning tank flow down to the tip of the probe over time, so by lifting the probe from the cleaning water at that timing, the amount of water droplets that adhere to the probe can be minimized.

〔Example〕

A specific example of the automatic analyzer of the present invention will be explained step by step starting from FIG.

FIG. 1 shows the external configuration of an automatic analyzer to which the present invention is applied. All the main units and wiring of this device are built into the base 1, and an intermediate cover 2. Frame 3 is assembled, and side covers are installed.4. Side cover R (not shown) 5 and back cover (not shown) 6
are assembled to form the exterior. A waste liquid bottle (not shown) for storing waste liquid is located at the front left end of the base 1.
A waste liquid box 8 for putting in and taking out 7 and a floppy disk 9 are installed at the front right end. A unit used as an interface with this device is attached to the right inclined surface of the frame 3.

That is, the printer 10. CRTII, keyboard 1
2. Barcode readers 13 (not shown) are arranged at easy-to-operate positions. An upper cover 14 is attached to a large area on the left side of the device operation section so as to be openable and closable, and has a transparent portion that allows the internal state to be observed. When the upper cover 14 is opened, there is a dispensing mechanism 15 visible from the upper surface of the intermediate cover 2. A sample table 16 and a reagent table 17 which is inside the intermediate cover 2 and cannot be seen from the top surface are located directly below the sample table 16, and on the left side there is a reaction table 18 (not shown) for reacting the sample and reagent. ) is installed. A cleaning mechanism 2o is attached to the left side of the inclined surface 19 that is visible when the upper cover 14 is opened and that sucks the reaction liquid of the sample and reagent and separates it from the solid phase present in the reaction liquid.

A peristaltic pump 21 that is connected to the washing mechanism 20 and sucks the reaction liquid is installed on the left side of the washing mechanism 20, and a washing syringe pump 22 (not shown) that supplies a washing liquid for washing the solid phase and the dispensing mechanism 15 A dispensing syringe pump 23 (not shown) for weighing samples and reagents is installed inside the side cover L4. Further, inside the site cover R5 is a board unit 24 incorporating a microcomputer. A compressor unit 25 (not shown) is built into the inside of the back cover 6, and a reagent cooler is installed to keep the reagent containers 35 arranged on the reagent table 17 cooled to a temperature at which the reagents do not deteriorate. 26
(not shown) so that cold water can be circulated. The reagent may be cooled by a Peltier method or any other method.

Next, FIG. 2 and subsequent figures will be explained.

FIG. 2 shows a flow path system diagram that is involved in the weighing accuracy of samples and reagents. 15 in the figure is a dispensing mechanism that can move up and down and rotate, and a dispensing probe 15 is attached to one side of the dispensing arm 151.
2 are connected. The tube connected to the dispensing probe 52 is connected to the dispensing syringe pump 23, and furthermore, a solenoid valve (A) 27 and a solenoid valve (B) 28 are connected in series on its extension. The flow path between the solenoid valve (B) 28 and the floor-mounted distilled water tank 29 includes a diaphragm pump 30 that sucks up distilled water up to the tabletop, and a diaphragm pump 30 that removes air bubbles generated in the distilled water tank 29 and from the diaphragm pump 30. Air trap to capture31. A pressure gauge 32 is connected to the outlet of the pump 30 and measures the outflow force of the pump 30. The air bubbles captured in the air trap 31 flow out together with the cleaning water that cleans the outer periphery of the dispensing probe 152, and are returned to the distilled water tank 29 through the solenoid valve (C) 33 or to the aforementioned cleaning tank 34. It flows out. This flow path switching is performed by the solenoid valve (C) 33. The water used to clean the inside and outside of the dispensing probe 152 is stored in the drain tank 35.

The dispensing probe 152 that has been cleaned in the cleaning tank 34 is moved to the sample container 161 set on the sample table 16, and after aspirating a small amount of the sample therein by the operation of the aforementioned dispensing syringe 27, it is placed on the reaction table 18. Set reaction container 18
1 and discharge the aspirated sample into it. This operation is also performed for transferring reagents in reagent containers (not shown). The dispensing probe 152 moves through the respective tanks and containers in the order indicated by the arrows and performs dispensing operations. Next, the operation will be explained with reference to FIG.

FIG. 3 shows an operation time chart of each unit explained in FIG. 2. In the present invention, two operations not found in conventional automatic analyzers will be described in detail.

One is a solenoid valve (A) 27. Solenoid valve (B)28. solenoid valve(
C) The relationship between the operation of the pump 33 and the operation of the diaphragm pump 30.

That is, at the same time as the dispensing mechanism 15 descends, the pump 30 is stopped and the solenoid valve (B) 28 is opened at the same time.

This operation causes the solenoid valve (A) 27. The water pressure remaining between the solenoid valves (B) 28 is released, and the closing operation of the solenoid valves (A) 27 is kept stable throughout the period when the dispensing syringe 23 is operating, and the accuracy of weighing the sample is considerably improved. was completed. Conventional time chart and solenoid valve (A)27. Solenoid valve (B) 28
The relationship between the residual pressure fluctuation 36 and the pump discharge pressure fluctuation 37 is shown in FIG. 4, and a similar relationship according to the present invention is shown in FIG.

That is, in FIG. 5, the residual pressure 38 becomes slightly negative pressure due to the head difference between the pump 3o and the distilled water tank 29, but the solenoid valve (A) 27
Since it acts in a direction that helps the closing operation, it acts in a positive direction and improves the dispensing accuracy.

Another method for improving dispensing accuracy will be explained in detail with reference to FIGS. 3 and 7. Conventional reagent containers (not shown) allow reagents to be aspirated easily by removing the cap, but the capacity size is also small due to the use of small amounts of reagents, and reagents used in automatic immunoanalyzers in particular are used for antigen-antibody reactions. Since it is an expensive item, it is packaged in small quantities and is covered with a film made of rubber or the like to prevent evaporation. When the reagent is aspirated, the dispensing probe 152 breaks through this membrane, but after the dispensing probe 152 is removed, the membrane is sealed again to prevent evaporation of the reagent. However, since the dispensing probe 152 cannot be attached to detect the liquid level, the length from the bottom of the reagent container to the membrane surface is contaminated by the reagent. Therefore, to clean the outer periphery of the dispensing probe 152, it is necessary to spray cleaning water over the contaminated length and clean it with running water. The cleaning state is shown in FIG. Conventionally, the dispensing probe 162 was pulled up above the cleaning tank 34 in a single motion after cleaning, but because the cleaning length was long, the water that adhered to the outer wall of the dispensing probe 162 became large water droplets as shown in the figure and attached to the tip. However, the sample or reagent may be diluted in the next operation. In fact, we have seriously considered improving this point, but the method of slowly pulling it up from the cleaning tank 34 results in a loss of time, so once it has been pulled up halfway in the cleaning tank 34, it stops and the water drops come down. We used a two-stage motion method that started when the time was right and pulled it upwards. This relationship is shown in FIG.

This two-stage operation eliminates water droplets from adhering to the dispensing probe 162, and significantly improves sample/reagent dispensing accuracy.

〔Effect of the invention〕

According to the present invention, when the dispensing syringe 23 is operated, the pump 3
Stop the solenoid valve (B) 28 and open the solenoid valve (A).
By releasing the residual pressure between the tubes 27 and 27, and by making the operation of pulling up the dispensing probe 162 from the cleaning tank 34 into a two-step motion, it was possible to commercialize a highly sensitive automatic immunoanalyzer. The results are shown in FIGS. 8 and 9 as examples of dispensing reproducibility.

[Brief explanation of the drawing]

FIG. 1 is an external view of the entire automatic immunoanalyzer according to an embodiment of the present invention, and FIG. 2 is a flow path diagram of the sample/reagent weighing system of the device.
Figure 3 is an operation time chart of the flow path diagram, Figures 4 and 5 are relationship diagrams between solenoid valve operation and residual pressure, Figures 6 and 7 are state diagrams of water droplets attached to the dispensing probe, FIG. 8 and FIG. 9 are diagrams showing examples of dispensing reproducibility. 1...Base, 2...Intermediate cover, 3...Frame, 4...Sight cover, 5...Side cover R76
... Back cover, 7. Waste liquid bolt, 8. Waste liquid box, 9. Floppy disk, 10. Printer.
11...CI? , T, 12...Keyboard, 13
...Barcode reader. Ward 1

Claims (1)

[Claims] 1. A dispensing mechanism that weighs and transfers samples and reagents, a sample table that sets samples, a reagent table that sets reagents, a reaction table that sets reaction containers, and a reaction liquid in the reaction containers. This is an automatic analyzer equipped with a photometer for measuring concentration and an operating section.The distilled water tank used for analysis is installed in a low position, for example on the floor, and the analyzer is installed in a high position, for example on a tabletop. In automatic analyzers that have a pump that sucks water up to the analyzer located higher than the water tank, a self-contained small diaphragm pump that does not require priming is used to automatically draw water from the distilled water tank and flow inside the analyzer. When dispensing a sample or reagent using the above-mentioned dispensing mechanism, the solenoid valve on the pump side of the two solenoid valves in the flow path of the weighing system is operated by pump operation. A method for accurately dispensing a minute amount of sample, characterized in that the residual pressure between the solenoid valves is released by opening the solenoid valve when the solenoid valve is temporarily stopped. 2. In the method of efficiently cleaning the dispensing probe after aspirating the sample/reagent and discharging it into the reaction vessel, when the dispensing probe is dirty due to sample/reagent suction and extends to a long dimension, e.g. 30 mm, For cleaning longer dimensions e.g. 35m
In this case, if unexpected water droplets (water film) adhere to the outer circumference of the dispensing probe when the dispensing probe is pulled up in the single-stage motion after cleaning, and the dispensing probe descends over time, the dispensing probe in the two-stage motion The first stage is a lifting operation, and the tip of the dispensing probe is raised to the point where the cleaning water is applied.
A method for dispensing a trace amount of sample with high precision, characterized in that the water droplet of the dispensing probe is removed by performing a second pull-up at the timing when the water droplet descends (approximately 1.5 seconds later). .