JPH0150859B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a liquid sample analyzer, and more particularly to an analyzer that measures a reaction liquid by placing a sample and a reagent liquid into a plurality of reaction vessels and allowing them to react.

Automatic chemical analyzers used in clinical tests, etc.
It is common for a single device to quantitatively analyze multiple types of analysis items. Normally, two types of reagent solutions are used for one analysis item, so in order to analyze 12 items, 24
Seed reagent solution is required. However, the conventional reagent supply mechanism uses the same number of pump (syringe) mechanisms as the number of reagent types, and a pump mechanism is disposed between each reagent discharge nozzle and each reagent liquid tank. Therefore, a large number of pump mechanisms are installed in a multi-item analyzer, and the number of component parts is large, resulting in poor maintainability and an increase in the size of the analyzer. In addition, in conventional analyzers, reagent liquid was supplied via the pump mechanism, which resulted in a very large capacity in the reagent flow path system, and a large amount of reagent liquid was wasted when starting the analyzer. There was a problem that I had to do it.

In order to solve this problem, we have discovered that the reagent supply mechanism can be simplified and downsized by selectively supplying a large number of reagent solutions using one pump mechanism and a reagent flow path selection switching valve. The inventors found out. However, if a pump mechanism is simply shared, a plurality of reagents will be contaminated with each other, resulting in significant errors in the quantitative results of analysis items.

The present invention has been made in view of the above points, and
The purpose is to provide a liquid sample analyzer that can prevent contamination between reagents even when a reagent liquid delivery mechanism is shared for supplying multiple types of reagents.

The present invention is characterized by: a liquid feeder that performs a suction operation and a discharge operation of a liquid; a plurality of reagent evacuation channels into which reagent liquid can be introduced in conjunction with the suction operation of the reagent liquid container;
a plurality of connection selection means, each of which selectively communicates either a reagent introduction channel for introducing a reagent solution from a reagent container or a reagent solution discharge tube for discharging a reagent solution into a reaction container with a corresponding reagent evacuation channel; Each of the plurality of reagent evacuation channels is branched, and the suction side multi-channel switcher is connected to one of the branched channels of each of the plurality of reagent evacuation channels, and the plurality of reagent evacuation channels are connected to A discharge side multi-flow path switch to which the other of each branch path is connected, and a common flow path that connects the suction side multi-flow path switch and the discharge side multi-flow path switch to the same liquid feeder. and when one of the suction side multi-channel switching device and the discharge side multi-channel switching device communicates the common channel with any of the plurality of reagent evacuation channels,
The other is configured to block communication between the common channel and the plurality of reagent evacuation channels.

In a preferred embodiment of the present invention, a device exclusively for liquid suction and a device exclusively for liquid discharge each have a plurality of flow path switching valves, and the switching valve on the suction side and the switching valve on the discharge side are provided in the same pump mechanism. Flow path connected. Only a cleaning liquid such as distilled water is introduced into the pump mechanism. Due to the suction and discharge operations of the pump, cleaning liquid is sucked in through the suction side switching valve and discharged through the discharge side switching valve.

An embodiment of the present invention will be described below with reference to the drawings. The embodiment shown in FIG. 1 shows a multi-sample processing automatic analyzer that performs analysis of 12 items using one reaction table.
The sampling mechanism 17 has two sampling nozzles that move horizontally and vertically, and each nozzle sucks samples for two items from the sample cup on the sample table 7 and transfers them to the reaction container 3 on the reaction table 2. 4 during one cycle of operation.
It is configured so that samples for each item are distributed on the reaction table 2.

Twelve types of _R1 reagent containers 18 and _R2 reagent containers 19 used for analysis are arranged in the cold storages 4 and 5, and each reagent is connected to the _R1 reagent nozzle via the reagent flow path switching valves 20 and 60. It is connected to the moving mechanism 21, the _R2 reagent nozzle moving mechanism 22, and the multiple flow path switching sections 32 and 62 through piping. Multiple flow path switching parts 32, 62
Metering syringes 23 and 24 as liquid feeders that perform suction and discharge operations of liquid are connected to the common flow path, and suction and discharge operations are performed in accordance with the switching operations of the multiple flow path switching units 32 and 62. Do this. The _R1 reagent nozzle moving mechanism 21 and the _R3 reagent nozzle moving mechanism 22 move back and forth with respect to the row of reaction vessels 3, and stop the plurality of nozzle rows so that the reagents necessary for analysis are added to the reaction vessels 3. Position is controlled. Therefore, analysis reagents corresponding to each of the four items are selectively added to the samples sent in sequence, and analysis is performed one after another.

As the reaction table 2 rotates, the reaction containers 3 to which reagents have been added at respective predetermined positions are sequentially positioned in the stirring mechanism 8, the optical path of the spectrometer 9, and the cleaning mechanism 10. The empty reaction container 3 that has been cleaned by the cleaning mechanism 10 is transferred to the sample receiving position and used again. The spectrometer 9 receives light from a white light source placed near the center of the reaction table 2, splits it into multiple wavelengths, and uses a photodetector to extract only light of a specific wavelength corresponding to the analysis item. , calculate the analysis item concentration.

FIG. 2 is an explanatory diagram of the operation of the reagent dispensing system for four items in the embodiment of FIG. 1. The multiple flow path switching section 32 has a suction side switching valve 29 and a discharge side switching valve 30, and these switching valves 29 and 30 are interlocked by a motor 31. Nozzles 11a to 11d having reagent discharge ports are connected to reaction vessels 3a to 3d that are stopped at reagent liquid receiving positions on the reaction table 2.
It is attached to a base 42, which will be described later, in a corresponding manner. The reagent evacuation tubes 26a to 26d are the nozzles 1 as reagent liquid discharge tubes that discharge the reagent liquid into the reaction container.
This is a connection flow path that connects each of 1a to 11d and the multiple flow path switching section 32. Reagent evacuation tubes 26a to 26
d indicates suction side flow passages 27a to 27d, each of which is attached to the suction side switching valve 29, and discharge side flow passages 28a to 28a, each of which is attached to the discharge side switching valve 30.
28d. Such a branch pipe has a unique function as described below.

In the middle of the reagent evacuation tubes 26a to 26d, flow path switching valves 20a to 20d are provided as individual connection selection means.
are installed, and these switching valves 20a to 20d
Reagent tubes 25a to 25 as reagent introduction channels
d is connected. Reagent tubes 25a-25
d is inserted into reagent bottles 18a to 18d containing reagent solutions corresponding to four types of analysis items.

Positions V1 to V4 of the suction side switching valve 29 are connected to the flow paths, respectively, but positions V5 to V8 are closed. The V9 position communicates with the drain passage 35. Positions V1 to V4 of the discharge side switching valve 30 are closed, and positions V5 to V8 are connected to the flow paths, respectively. The V9 position is occluded. Although the suction side switching valve 29 and the discharge side switching valve 30 are independent in terms of flow paths, they are constructed as an integral structure. A suction side slide valve 35 and a discharge side slide valve 36, which are rotatably disposed in each of the switching valves 29 and 30 in a liquid-tight manner, are coaxially attached and rotated by a motor 31.

The common flow path 40 connected to the suction side switching valve 29 and the common flow path 41 connected to the discharge side switching valve 30 are integrated into a single common flow path for the reagent volume metering syringe 23 that sucks and discharges washing water. will be communicated to.
The syringe 23 is connected to a distilled water tank 37 containing distilled water serving as a cleaning liquid via a solenoid valve 34 and a liquid feed pump 38 provided in a distilled water flow path 33. A piston 13 that can reciprocate within the syringe 23 is moved by a rack and pinion mechanism 14 that moves in conjunction with the operation of a pulse motor 15. The operation of the pulse motor 15, switching valves 29, 30, motor 31, solenoid valve 34, switching valves 20a to 20d, etc. is controlled at appropriate timing by a control device equipped with a microcomputer. Although FIG. 2 shows an example in which one syringe 23 supplies four types of reagent liquids, this embodiment apparatus is similar to that shown in FIGS. but
Used for dispensing 12 types of reagent solutions.

In the configuration shown in FIG. 2, the cleaning operation within the channel system and the replacement operation of old and new reagents will be explained.

The nozzles 11a to 11d are the reagent nozzle moving mechanism 2.
1, the reagent is moved onto a waste liquid tank (not shown), and the reagent flow path switching valves 20a to 20d are switched to the solid line side. At this time, the suction side slide valve 35 and the discharge side slide valve 36 are each stopped at the V1 position.
Further, the solenoid valve 34 is in a closed state. Since the pump 38 constantly circulates distilled water and maintains the distilled water channel 33 under pressure, distilled water passes through the reagent metering syringe 23 by opening the electromagnetic valve 34 and passes through the suction side switching valve 29 and the discharge side. The side switching valve 30 is pressurized. Since the slide valves 35 and 36 are initially located at V1, the suction side flow path 2 communicating with the common flow path 40
7a, distilled water for cleaning is discharged into the waste liquid tank through the reagent evacuation pipe 26a and the nozzle 11a, thereby cleaning the inside of these channels.

Next, slide valves 35 and 36 are switched to the V2 position,
The suction side channel 27b, reagent evacuation tube 26b, and nozzle 11b are cleaned. Furthermore, the slide valves are switched to the V3 position and V4 position, and the nozzles 11c and 11d are
Clean the flow path system. Continuing, slide valve 35,
36 to the V5 position, the common flow path 40 side is closed, the common flow path 41 is communicated with the discharge side flow path 28a, and distilled water passes through the discharge side flow path 28a, the reagent evacuation pipe 26a, and the nozzle 11a, and is discharged as waste liquid. Discharged into a tank. Thereafter, the slide valves are sequentially positioned at V6 to V8 to clean the insides of the discharge-side channels 28b, 28c, and 28d.

Cold storage 4 along with reagent flow path switching valves 20a to 20d
Since the reagent liquids in the reagent bottles 18a to 18d housed inside are maintained at low temperatures, deterioration of the reagents is prevented. After cleaning the flow path system with cleaning water,
New reagents are introduced into the flow path system and reagent solutions are added to the required reaction vessels. After the old reagent is discharged by cleaning, a replacement operation for introducing a new reagent into the flow path is performed while each nozzle 11a to 11d is positioned above the waste liquid tank.

By replacing only the necessary portion of the distilled water filling the channel system with the reagent liquid, the reagent liquid to be dispensed is prevented from being diluted by water. First, close the solenoid valve 34, switch the reagent flow path switching valves 20a to 20d to the dashed line side, and
5, 36 at the V1 position, and remove the reagent evacuation tube 26a.
The common flow path 40 is communicated with the common flow path 40 . In this state, the pulse motor 15 is driven by a predetermined number of pulses to drive the syringe 2.
3, and a predetermined amount of reagent liquid is drawn from the reagent bottle 18a into the reagent evacuation tube 26a and the suction side flow path 27a.
Inhale inside. Next, the slide valves 35 and 36 are switched to the V2 position to cause the syringe 23 to perform a further suction operation, and a predetermined amount of reagent liquid is aspirated from the reagent bottle 18b into the reagent evacuation pipe 26b and the suction side flow path 27b. Subsequently, the slide valves 35 and 36 are sequentially switched to the V3 and V4 positions, and the reagent solution is aspirated into the corresponding channels by the suction operation of the syringe 23. Distilled water sucked in from each channel on the switching 29 side in each channel as a result of these reagent suction operations is held in the common channel 40 . That is, the common flow path 40 has a sufficient length to have a capacity that can accommodate all the liquid to be drawn. During the suction operation of the dummy reagent liquid into each channel, the piston 13 is lowered step by step by a predetermined stroke.

After the suction operation of the dummy reagent, the liquid sucked into the common flow path 40 is discharged to the outside of the system. While the solenoid valve 34 remains closed, the slide valves 35 and 36 are switched to the V9 position to communicate with the drain pipe 39. In this state, the pulse motor 15 is driven to move the piston 13 up the entire stroke. As a result, the liquid in the common flow path 40 is discharged to the outside through the drain pipe 39.

Next, the distilled water in each nozzle 11a to 11d is replaced with a reagent solution. With the solenoid valve 34 closed, the slide valves 35 and 36 are stopped at the V1 position, and the syringe 23
performs a suction operation of a predetermined stroke, and further sucks new reagent liquid into the reagent evacuation tube 26a. Subsequently, the slide valves 35 and 36 are sequentially stopped at positions V2, V3, and V4, and the syringe 23 is caused to perform a suction operation, thereby sucking the reagent into each of the reagent evacuation tubes 26b, 26c, and 26d. Next, the reagent flow path switching valve 20
Switch a to 20d to the solid line side, and slide valves 35, 3
6 is positioned sequentially from V5 to V8. When the slide valve stops at the V5 position, the syringe 23 is caused to perform the first discharge operation, and the common flow path 41 and the discharge side flow path 28a are
The liquid is pushed out through the nozzle 11a, and the reagent liquid is discharged into the waste liquid tank from the discharge port of the nozzle 11a. After filling the inside of the nozzle 11a with the reagent solution in this way, the slide valves 35 and 36 are sequentially switched, and the second to
The fourth discharge operation is performed, and each nozzle 11b to 11
Also fill the space d with the reagent solution. Even when the filling operation of reagent liquid into each nozzle is completed, the reagent evacuation tube 26a
Since the reagent solution remains in ~26d, when the reagent solution for dispensing is inhaled later, the new reagent solution will not come into contact with distilled water and will not be diluted.

This completes the reagent replacement operation. Such a reagent replacement operation is normally performed when the analyzer is started up and prior to the actual analysis operation.

Thereafter, the nozzles 11a to 11d are moved by the reagent nozzle moving mechanism 21 onto the row of reaction vessels 3 on the reaction table 2, and normal analysis operation is started. Once the sample has been dispensed into the rows of reaction vessels 3 in FIG. 1 and the reaction vessels have been transferred to the first reagent receiving position, the first reagent liquid from the _R1 reagent vessel 18 is added and the second When the second reagent solution is transferred to the reagent solution receiving position of R2, the second reagent solution from the _R2 reagent container 19 is added.

Referring to FIG. 2, the operation of adding a reagent to a reaction container will be explained. The reagent flow path switching valves 20a to 20d are switched to the dotted line side, the slide valves 36 and 36 are sequentially positioned at V1 to V4, and an inhalation operation is performed. A predetermined volume of reagent liquid is sucked into the reagent evacuation tube 26a by the suction operation at the V1 position. Similarly, reagent evacuation tube 26b~
A reagent solution is also sucked into 26d. Next, the reagent flow path switching valves 20a to 20d are switched to the solid line side, and the slide valves are sequentially positioned at V5 to V8, and at each position,
The syringe 23 is caused to perform a discharging operation for each predetermined stroke. A reagent solution corresponding to each analysis item is added from the discharge port of each nozzle 11a to 11d to the corresponding reaction container 3a to 3d, respectively.

After discharging the reagent, the slide valves 36, 36 are stopped at the V9 position, the solenoid valve 34 is opened, and distilled water is sent and discharged from the drain pipe 39 to clean the inside of the common flow path 40.
The above reagent addition operation and common channel cleaning operation are repeated every cycle to execute reagent dispensing corresponding to the analysis item. After adding reagents to all samples,
The inside of the channel system is cleaned. The operation of cleaning the reagent evacuation tubes 26a to 26d and the nozzles 11a to 11d with distilled water is the same as described above.

Here, the role of branch roads will be explained. As the number of times the reagent solution is inhaled increases, each reagent flows backward through the channel due to a diffusion phenomenon. Therefore, if only one switching valve is used to select the flow path during suction and discharge operations without forming a branch path, the diffused reagent will reach the switching valve and reach the switching valve sliding surface. The reagents will be mixed with each other and discharged from the flow path system of other reagents during a long analysis operation. As a result, the measurement results for each analysis item will show abnormal values. Generally, it is said that an appropriate contamination rate between reagents is less than 1/1,000,000, and sufficient consideration must be given to this. In the above-mentioned embodiment, the suction side flow path 27a~
27d and discharge side flow paths 28a to 28d, the suction side flow paths 27a to 27d are used exclusively for suction, and the common flow path 40 that can evacuate contaminated liquid is cleaned in each cycle. Side switching valve 30
Contaminated liquid is not mixed into the flow path system.

FIG. 3 is a diagram showing the channel system for supplying reagents to each reagent liquid receiving position in the embodiment shown in FIG.
It has a function to add three times the number of reagents as shown in the figure for four items. Three series of four reagents each are connected to the suction side switching valve 29 and the discharge side switching valve 30, and these 12 reagent systems perform suction and discharge operations in response to movement of the nozzle moving mechanism 21.
Inhalation and ejection of these 12 types of reagents are performed by one syringe mechanism 23. The reagent nozzle moving mechanism 21 moves back and forth in synchronization with the switching operation of the multiple flow path switching valve 32 so as to selectively position the three rows of nozzle groups on the reaction container row.

FIG. 4 is a timing chart of each part of the embodiment device of FIG. 1. A is a sampling mechanism 17;
B is the reaction table 2, C is the reagent flow path switching valve 20,
60 and D are the operation timings of the multiple flow path switching units 32 and 62, E the reagent metering syringes 23 and 24, F the electromagnetic valve 34, and G the reagent nozzle moving mechanisms 21 and 22, respectively. The operation of the sampling mechanism 17 shown in A has each operation time of descent a, sample suction b, rise c, rotational movement e, and sample discharge f, and g in B is the stop time of the reaction table 2. During the operation of C, h indicates the state where the reagent flow path switching valve 20 is switched to the nozzle side, i indicates the state where it is switched to the reagent bottle side, and j and k in D
1 shows the switching operation and stopped state of the multiple flow path switching valves 23 and 24, respectively. Further, at timing E, l indicates a discharge operation and m indicates an inhalation operation. n in F indicates the opening time of the solenoid valve 34, and G
The symbol r in the figure represents the movement timing of the reagent nozzle movement mechanisms 21 and 22.

In FIG. 4, when the reaction table 2 is in a stopped state g, the reagent flow path switching valves 20 and 60 are located on the nozzle side. Multiple flow path switching unit 3 at timing D
The switching operation j of 2 and 62 and the discharging operation l of the syringes 23 and 24 at timing E are synchronized during the stop time g of the reaction table.

FIG. 5 is an explanatory diagram of the vicinity of the reagent nozzle moving mechanisms 21 and 22 of the embodiment shown in FIG. The three rows of nozzle groups 11 are attached to the base 42 and are moved between the rows of reaction vessels 3 and the waste liquid tank 12. The base 42 is fixed to a holder 43, and a rack 44 and a position detection plate 45 are attached to the holder 43.
The rotation of the pulse motor 48 is transmitted through the pinion gear 46, and reciprocating motion is performed using the shaft 47 as a guide. Sensors 49 and 50 are arranged before and after the holder 43, and detect the position at which the nozzle 11 should stop based on a command from a computer, and then stop the nozzle 11.

FIG. 6 is a diagram showing the structure of the switching valves 29 and 30 of the multiple flow path switching section of the embodiment shown in FIG. The aforementioned suction side switching valve and discharge side switching valve are integrally formed on the valve seat 51, and slide valves 35 and 36 made of resin, ceramic, etc. are arranged on the left and right sides of the valve seat 51 by being joined and fixed to valve holders 52 and 53. be. Slip valve 35, 36
is pressed against the valve seat 51 by push springs 54, 54', and has a structure in which the switching sliding surface can be sealed. Slip valves 35 and 36 located on both sides are connected to pin 5.
5 and 55', and is configured to slide and rotate at the same time as the motor 31 rotates. Further, a flow path position detection plate 58 is attached to the rotating shaft 56, and a detector 59 counts the position of each flow path to control and drive the position at which the flow path should be stopped.
The above-mentioned suction side flow path 27 and discharge side flow path 28 are connected to the valve seat 51 by piping, respectively, thereby forming a multiple flow path switching valve.

According to the embodiments of the invention described above, compressed air,
Even in a large device for processing multiple items and multiple samples in which a large number of reagents are dispensed and added using a motor or the like, the reagent addition mechanism can be configured with a small number of syringes, and therefore a small device can be realized. In addition, the reagent supply system is divided into a suction-only flow path and a discharge-only flow path, making it completely independent.
Since a flow path is formed, it is possible to prevent contamination between reagents when dispensing a large number of reagents with one syringe. When replacing a new reagent in each reagent flow path, there is no need to introduce the reagent into the pump mechanism or multiple flow path switching valve, and it is only necessary to introduce the reagent into the connecting flow path, which reduces the volume of the reagent flow path system. can be made much smaller than before, reducing waste of reagents. Incidentally, the amount of reagent used when replacing new and old reagents can be reduced to 1/5 to 1/8 compared to the conventional method, which greatly contributes to lowering the running cost of the analyzer. Furthermore, the reliability of the device is improved due to the significant reduction in the number of reagent syringes, and maintenance is also facilitated.

As explained above, according to the present invention, by providing an inhalation-only path and an ejection-only path, even if a reagent liquid feeding mechanism is shared for supplying multiple types of reagents,
Since contamination between reagents can be prevented, measurement errors in analysis items can be reduced.

[Brief explanation of drawings]

FIG. 1 is a diagram showing a schematic configuration of an embodiment of the present invention, FIG. 2 is a diagram for explaining a reagent dispensing method in the embodiment of FIG. 1, and FIG. A diagram showing the flow path system for supplying reagents, FIG. 4 is a timing chart of each part in the embodiment device of FIG. 1, FIG. 5 is an explanatory diagram of the vicinity of the reagent nozzle moving mechanism, and FIG. It is a sectional view showing the structure of a valve. 3... Reaction container, 11... Nozzle, 18, 19
... Reagent bottle, 20, 60 ... Reagent flow path switching valve,
23, 24...Syringe, 26...Reagent evacuation tube,
27...Suction side flow path, 28...Discharge side flow path, 29
...Suction side switching valve, 30...Discharge side switching valve, 3
2, 62...Multiple flow path switching unit, 35, 36...Slip valve, 40, 41...Common flow path.

Claims (1)

[Claims] 1. In a liquid sample analyzer that reacts a sample and a reagent solution in the reaction containers of a reaction container row, measures the reaction solution, and analyzes the analysis items of the sample, , a plurality of reagent evacuation channels into which a reagent solution can be introduced in accordance with the suction operation of the liquid feeder, a reagent introduction channel each introducing a reagent solution from a reagent container, and a reagent solution discharging the reagent solution into the reaction container. a plurality of connection selection means for selectively communicating one of the discharge pipes with a corresponding reagent evacuation channel; each of the plurality of reagent evacuation channels is branched; each of the plurality of reagent evacuation channels is branched; a suction side multi-flow path switch to which one of the branch paths is connected; a discharge side multi-flow path switch to which the other branch of each of the plurality of reagent evacuation channels is connected; a common flow path connecting a path switching device and the discharge side multi-flow path switching device to the liquid feeder, one of the suction side multi-flow path switching device and the discharge side multi-flow path switching device; is configured such that when the common channel communicates with any of the plurality of reagent evacuation channels, the other one blocks communication between the common channel and the plurality of reagent evacuation channels. Liquid sample analyzer.