JPS6244663A - Multi-item automatic analyzer - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Application of the Invention] The present invention relates to a multi-item automatic analyzer, and more particularly, to a multi-item automatic analyzer that rotates a row of reaction vessels across the optical path of a photometer.

The present invention relates to a multi-item automatic analyzer suitable for use in biochemical tests and immunological tests. [Background of the Invention] In a discrete one-line multi-item automatic analyzer, reagents for reacting multiple items are sequentially added to a series of reaction vessels on one reaction line according to each analysis item.

As an example of a one-line multi-item automatic analysis device, for example, the Japanese Patent Publication No. 59-22905 is known, but this device
Two reagent dispensing mechanisms are installed near the reaction line, and the first reagent dispensing mechanism adds the first reagent to the reaction container according to the analysis item, and the second reagent dispensing mechanism adds the first reagent to the reaction container according to the analysis item. A second reagent is added.

This conventional technology reduces the previous requirement of one pipetting device for each reagent to only two pipetting mechanisms, achieving a significant simplification of the mechanism and miniaturization of the analyzer. It was effective. However, recently there has been a demand for further downsizing of analyzers.

[Purpose of the invention]

SUMMARY OF THE INVENTION An object of the present invention is to provide a multi-item automatic analyzer that can be further downsized and easier to maintain and inspect.

[Summary of the invention]

In the present invention, when a row of reaction containers is in a transfer state, the row is rotated across the optical path of a photometer, and when the row of reaction containers is in a stopped state, a sample is dispensed into a reaction container at a sample addition position, and a reagent is dispensed. reaction vessel) at the addition position. Trial 11.
．． l,,iAka. A multinomial, automatic, folding device. □Awaru. In the present invention, the first
A rotatable holding means is provided which holds a row of reagents and also holds a row of a second reagent to be added after the first reagent, the first suction position on the first reagent row and the second reagent row. a single reagent pipetting mechanism movable between a second inlet position on the reagent column and a reagent dispensing position on the reaction vessel column, wherein a reaction vessel requiring a first reagent is positioned in the reagent dispensing position; When the reagent pipetting mechanism is located, the reagent pipetting mechanism is moved between the first suction position, where the first reagent corresponding to one analysis item is located, and the reagent discharge position, and
When a reaction container requiring a reagent is positioned at the reagent discharge position, the reagent pipetting mechanism is moved between the second suction position where a second reagent corresponding to the analysis item is positioned and the reagent discharge position. It is characterized by being configured to allow

[Embodiments of the invention]

In a preferred embodiment of the present invention, a turntable-type reaction table on which a predetermined number of translucent reaction cuvettes are mounted is rotated by one rotation and one container (one reaction cuvette). A so-called divided rotation is performed in which a plurality of stop periods (usually 2 to 3 times) are provided during the rotation. Control is performed so that the reaction cuvette to which the first reagent, second reagent, third reagent, etc. are to be added in that cycle is stopped at one reagent discharge position determined in each stop period. In synchronization with this, the reagent installation table, on which multiple reagents (usually up to the third reagent) are loaded at predetermined positions for each measurement item, is controlled so that the necessary reagents are stopped at the predetermined suction position. A single system reagent dispensing mechanism having a pipetting probe that rotates and moves between the suction position and the discharge position in synchronization with the pipetting probe is operated. In addition, the absorbance of all reaction cuvettes required during divided rotation of the reaction table for each cycle is measured at one cycle interval.

FIG. 2 shows an overall external view of an embodiment of an automatic analyzer based on the present invention. FIG. 1 shows a principle diagram of the main parts of the same embodiment. In this apparatus, a predetermined number (40 in this example) of translucent rectangular glass reaction vessels 6 are held on a rotary reaction table 5. A predetermined number (up to 48 in this example) of reagent containers 3 are arranged in two rows on a rotary reagent table 2.

Containers 1'1 containing a predetermined number of samples to be measured (40 in this example), standard samples (20 in this example), and control samples (10 in this example) are placed on a rotating sample table 10.
be done. A sample sampling mechanism 8 and a microsyringe mechanism 15 suck a predetermined amount of various sample liquids based on input information from a sample container at a fixed position on the sample table 10 and discharge the sample into a reaction container 6 at a fixed position on the reaction table 5. be.

The single reagent pipetting mechanism 4 and the syringe mechanism 17 rotate based on input information, and their stopping positions are controlled at fixed positions on the reagent table 2 (not necessarily at fixed points, but on concentric circles drawn by the mechanism 4). In this example, there are two points: the inner circle and the outer circle, and if the number of reagents is increased, there are three points.
A predetermined amount of reagent based on the input information is aspirated from the reagent bottle (a quadruple circle reagent table may be used) and added to the reaction container at a fixed position on the reaction table.

There is a stirring mechanism 9 in the middle of the reaction line. In addition, a high-speed multi-wavelength photometer 13 that measures the absorbance of each reaction vessel 6 that crosses the optical axis when the reaction table 5 rotates at a predetermined wavelength (one wavelength or the difference between two wavelengths) based on input information. A cleaning nozzle mechanism 12 for cleaning the reaction vessel after the aJ period, a cleaning water supply and drainage pump mechanism 16, and a sampling syringe mechanism 1
5, LOG amplifier 18, A/D converter 19, computer 1 for control and data processing, printer 2 for output
1. CRT 20 for input/output display, keyboard 23 for input/output
, a floppy disk mechanism 22 for program and data memory, a circulating constant temperature water tank 14 for maintaining each reaction container on the reaction table at a constant temperature, an interface 24 for connecting the computer 1 and each mechanical system, a deionized water supply fi [ It is composed of a 25° drainage vacuum pump 26, etc.

Before starting measurements using this device, first
The pelleter moves the control sample, standard sample, and sample to be measured to the inner circle of the sample table 10 (
Items to be measured for each sample liquid (up to 24 items in this example), i.e. item selection information for each sample liquid. input. In addition, all reagents (up to 48 types in this example) necessary for measuring 24 items are set in the reagent table 2. Furthermore, the measurement conditions for each measurement item are input.

Examples of measurement conditions that can be input are shown in Table 19, Table 29, and Table 3.

As shown in Tables 1 to 3, the measurement conditions include the sample absorbance calculation conditions (ASSAY VODE in the table), the sample collection amount ((7) SAMPLE VOLUME in the table), and the 1st. Dispensing conditions for the second and third reagents (RI VOL, R2V
OL,, R3VOL,) measurement wavelength (WAVELENG)
THI, 2), concentration of standard solution (RGT, BLK, C0N
C, STD, C0NC), K factor (FACTO
R), type of control liquid used (CONTRO
L ID, NO, ), etc. are input from the keyboard 23.

Reagent dispensing conditions include, in addition to the dispensing amount of each reagent as shown in Tables 1 to 3, the position on the reagent table where each reagent is set (in this example, expressed as an integer from 1 to 48). ) must be entered. Depending on the measurement item, the one-liquid method using only the first reagent as shown in input example Table 1, the two-liquid method using the first and second reagents as shown in Table 2, and the first and second reagents as shown in Table 3. A three-liquid method using all of the third reagent is possible, with a 16-degree angle and a 4-degree angle. A two-liquid method (R2=O) using □0, □□3 vesicles is also possible. That is, the first reagent is used in all measurement orders, but the second
．． The amount of the third reagent to be dispensed is zero input as required, and in this case, the reagent dispensing mechanism described later does not perform a dispensing operation.

After completing the above preparations, the operator starts the equipment. When the apparatus starts, the reaction table 5 and sample table 10 rotate, and the sample liquid to be measured first (standard, control, or test sample) and the clean reaction container to be used first are placed in predetermined positions on each table. be positioned. In this state, the sample pipetting mechanism 8
and the amount adapted to the measurement item to be measured first of the sample by the microsyringe mechanism 15 (SAM in Tables 1 to 3).
PLE VOL, ) is collected into the reaction vessel.

Next, the reaction table 6 performs a predetermined rotation operation in the counterclockwise direction, which will be described later, but ultimately stops at a position rotated by 1 rotation + 1 pitch (for 1 reaction container) and shifts to the operation of the first cycle. . That is, each operating cycle (in this example, 1
The cycle is 20 seconds.

In other words, at the start of each cycle (180 tests/hour), the reaction table advances counterclockwise one pitch at a time, stops, and displays the first sample solution (based on the item selection information, in the case of the same sample as in the previous cycle). (may change to the next sample) is collected in the reaction vessel on the left.

Furthermore, when the reaction table is rotated, the absorbance of all reaction vessels passing through the optical axis is measured. In other words, for each cycle, the absorbance of all 40 reaction vessels is measured at each wavelength based on the input information.

Furthermore, in order to achieve the present invention, it is necessary to devise the rotational operation of the reaction table in each of the above-mentioned cycles.

That is, while the reaction table advances counterclockwise one rotation and one pitch as described above, there are three stops at appropriate timings and appropriate positions, and the reagent pipetting machine n.
4 and syringe mechanism 17. By interlocking the stirring mechanism 9, the first and second filters necessary for each reaction vessel and therefore for each measurement item. Second
゜The third reagent must be added and mixed. Of course 3
One of the stopping times can be the same as the starting time of each cycle described above, that is, the time of sample collection.

In other words, if we focus on the single reaction vessel that should be used first, at the first stop of the first cycle (corresponding to the start of each cycle described above), the specific reaction vessel is at A in Figure 1. The sample amount corresponding to the first item of the above-mentioned first sample is dispensed into a specific reaction container. Second
At the first stop of the cycle, the specific reaction container moves counterclockwise by one pitch and stops at position [B, and at the same time, the first reagent corresponding to the measurement item is moved to the suction position of reagent table 2 (position C in the figure). In this state, the reagent pipetting mechanism 4 and the syringe mechanism 17 operate to maintain a certain amount of the first reagent (input value, RIV in Tables 1 to 3).
OL, ) is added into a specific reaction vessel. At the first stop of the third cycle, the liquid contained in the specific reaction container is agitated by the stirring mechanism 9. Approximately 3 minutes after the addition of the first reagent, that is, at the third stop of the 12th cycle, the specific reaction container stops again at the fixed position B, and at the same time, the second reagent of the first measurement item on the reagent table 2 stops at the fixed position C. controlled to do so. In this state, the above-mentioned reagent pipetting mechanism 4 and syringe mechanism 17 operate, and the required amount of the second reagent (input value,
R2VOL,) is added.

At the third stop of the 12th cycle, the reaction vessel is stirred.

After approximately 3 minutes, that is, at the second stop of the 22nd cycle, the specific reaction container is stopped at the fixed position B for the third time, and at the same time, the third reagent necessary for this reaction is stopped at the fixed position C on the reagent table 2, and the specific reaction container is stopped at the fixed position C on the reagent table 2. The required amount of the third reagent (input value,
R3VOL, ) is added. At the second stop of the 23rd cycle, the container is agitated.

In other words, for the first reaction vessel, the sample liquid is collected in the first cycle, the first reagent is collected in the second cycle 20 seconds later, the second reagent is collected in the 12th cycle 3 minutes and 35 seconds later, and the sample liquid is collected in the 1st cycle. At the 22nd cycle of minutes and 45 seconds, the third reagent is added and the predetermined reaction proceeds. For each cycle, the reaction vessel passes through the optical axis of the multiwavelength photometer, and the appropriate wavelength is detected according to the input information. The absorbance (or the absorbance difference between two wavelengths) is measured and stored.Finally, when the measurement is carried out up to the 32nd cycle (9 minutes and 40 seconds after the first reagent addition), the first At the time of stopping, the specific reaction container is stopped at the position D in Figure 1 under the cleaning mechanism and is cleaned.The washed container is stopped at the above-mentioned position A at the first stop of the 41st cycle, and is cleaned at the 41st cycle. A sample liquid corresponding to the measurement item (not necessarily the measurement item of sample No. 41) is collected.

In reality, the adjacent 2nd, 3rd, etc., 40th reaction vessels are processed clockwise with a delay of every cycle, so the total reaction time for one device is 9 minutes and 45 seconds, and the intervals are 20 seconds. It is a fully automatic device that can process any measurement item (180 tests/hour).

In addition, in the reagent dispensing conditions (Tables 1 to 3) input for each measurement item described above, the second reagent (R2) and the third reagent (
When the input value of R3) is O, the second or third reagent is not added to the reaction vessels corresponding to these items, and the one-liquid method (R1≠O, R2=O.

R3=O), two-liquid method (R1≠0.R2≠0.R3=O)
become.

Furthermore, the second reagent is not added and the third reagent is added (
R1≠O, R2=O, R3≠0) A two-liquid method with different addition times is possible.

For a more detailed understanding, the principle of operation centered on the reaction table 5 is shown in FIG. In other words, as mentioned above, FIG. 3 shows the n+
The operation of the fourth cycle is explained. (A-1) in the figure shows the state at the first stop of the n+1 cycle. At this time, the sample liquid S n”i corresponding to the n+1th measurement item from the mth sample liquid on the sample table (usually the relationship m<n is because multiple items are arbitrarily measured for one sample liquid) is pipetted and collected into the reaction container (n+1) at the preparative collection position.At the same time, the corresponding first reagent R1 is added to the reaction container (n) on the left from which the sample Sn was collected in the previous cycle. and the first cycle in the previous cycle.
Reagent R1. The container (n-1) to which -I has been added is stirred. In addition, reaction vessels that have been used for more than 30 cycles, i.e., vessels in which the prescribed reaction and measurement for 30 cycles (9 minutes and 40 seconds) have been completed (n 30) to (n-3)
As mentioned above, the four reaction vessels in 3) are under the cleaning mechanism and are being cleaned in preparation for next use.In other words, the function of the cleaning mechanism (12.16 in Figure 1) is that of the four adjacent vessels. After the remaining liquid in the reaction vessel is suctioned and discharged, the used reaction vessel is cleaned by repeatedly filling and discharging an appropriate amount of deionized water.

This f51 stop time is 4 seconds, and during this time, the above-mentioned sample liquid collection, addition of the first reagent, stirring, and washing of the used container are performed simultaneously and in parallel.

When the first stop time is over, the reaction table then rotates half a turn counterclockwise in 6 seconds (while measuring the absorbance of the 20 reaction vessels passing through the optical axis at the appropriate wavelength) to the Stop for 2 seconds in the second stop state shown in -2). At this second stop of 2 seconds, the first reagent has already been added 20 cycles ago, the second reagent has been added as needed (R2≠0) 10 cycles ago, and a reaction vessel (n
-20), a third reagent is added as necessary (R3≠0). At the same time, the reaction vessel (n-21) to which the third reagent was added in the previous cycle is stirred.

When the second stop time ends, the reaction table rotates 1/4 counterclockwise in 3 seconds while measuring the 10 reaction vessels passing through the optical axis at an appropriate wavelength according to the analysis item, as shown in Figure 1. It is stopped for 2 seconds in the third stop state shown in A-3). During the 2 seconds at this third stop, the first cycle has already started 10 cycles ago.
A reaction vessel (n-1
0), a second reagent is added as necessary (R2≠0).

At the same time, the reaction vessel (n
-11) is stirred.

When this third stop period is completed, the reaction table rotates 1/4 counterclockwise in 3 seconds while measuring the remaining 1 reaction container at the wavelength suitable for each analysis item, and completes this n + 1st cycle. complete the entire process.

) ,=oas"t[Io (B-")'"s
ah, *o+<kuru, i.e. the first of the n+2th cycle
At the time of stop (4 seconds), the sample solution corresponding to the n+2th measurement item is collected into the reaction container (n+2), and the first one is added to the reaction container (n+1) from which the sample was collected in the previous cycle.
Reagents are added, reaction vessel (n) is stirred, and reaction vessels (n-29) to (n-32) are washed. (C-
1) and (D-1) are also the n+3th cycle and n+4th cycle
The state at the first stop of the cycle is displayed. In other words, by continuously repeating these operations, it is possible to perform arbitrary measurements of up to 20 items for each sample liquid at a processing speed of 180 tests/hour.
A highly versatile automatic analysis device that has never been available before, such as a liquid method or a three-liquid method, will be constructed.

In addition, the inside and outside of the nozzle of the reagent pipetting mechanism 4 are 1
It has a function of preventing contamination between each reagent by washing the inside and outside of the washing tank 3o provided in the center of the reagent table 2 with deionized water every time the inhalation and ejection of one reagent is completed. Further, the nozzle of the sample pipetting mechanism 4 and the stirring rod of the stirring mechanism 9 are also washed with water in the same manner.

-Total protein (as an example) according to the measurement conditions shown in Tables 1 to
TP) one-component method, glutamate, oxaloacetate,
Two-component method for transaminase (GOT), bilirubin (
The three-liquid method of BIL) was actually measured using this device. TP is a one-liquid endpoint method based on the Biuret reaction, GOT is a two-liquid rate assay method based on ultraviolet (NADH) absorption, and BIL is a three-liquid endpoint method based on the Diendrassic-Fregtuon method. The sample was pooled serum from normal people. Table 4 shows the reproducibility results obtained by random measurement of 30 samples each, and shows that the apparatus of this embodiment has sufficient accuracy compared to conventional continuous measurement type models.

In addition, in the above embodiment, a maximum of three liquid method is possible, but the number of reagents that can be placed on the reagent table is increased, and the stopping time during one cycle of the reaction table is increased four times (for example, the stopping time is stopped every 1/4 rotation. By setting this and appropriately controlling the reagent dispensing mechanism, the rotation and stop position of the reagent table, and the stirring mechanism, three types of one-liquid methods, three types of two-liquid methods with different addition times, and two
An automatic analyzer capable of various three-liquid methods and four-liquid methods can be achieved. Of course, it is also possible to use reagents in the 5-liquid method or the 6-liquid method, but there are few actual requirements.

The automatic analyzer according to the embodiment described above is very simple, the main parts of which are a single reagent pipetting mechanism, a single reagent mounting table, a single reaction table, a single sample pipetting mechanism and a sample table. Although it is a simple device, it can flexibly accommodate measurement systems ranging from one-liquid method to multi-liquid method (usually up to three or four-liquid methods), as well as two-liquid to four-liquid methods with different addition times. It has unprecedented versatility.

On the other hand, having a single reagent dispensing system, which influences the reliability of the entire device, not only significantly increases the reliability of the device, but also significantly reduces the cost of the device.

〔Effect of the invention〕

According to the present invention, multi-item analysis using two or more methods can be performed simply by using a single reagent pipetting mechanism.
The analyzer can be made smaller and the number of parts is reduced, making maintenance and inspection easier.

[Brief explanation of drawings]

Fig. 1 is a functional explanatory diagram of one embodiment of the present invention, and Fig. 2 is a functional explanatory diagram of an embodiment of the present invention.
FIG. 3, which is an overall external view of the embodiment shown in the figure, is a diagram for explaining the operation of the reaction table. 2... Reagent table, 3... Reagent container, 4... Reagent pipetting mechanism, 5... Reaction table, 6...
・Reaction container, 10...Sample table, 13...
Photometer, 20...CRT, 23...keyboard.

Claims (1)

[Claims] 1. When the row of reaction containers is in the transfer state, it is rotated across the optical path of the photometer, and when the row of reaction containers is in the stopped state, the sample is dispensed into the reaction container at the sample addition position and the reagent is added. In a multi-item automatic analyzer that adds reagents to a reaction container at a certain position, a row of a first reagent to be added first to the sample is held, and a row of a second reagent to be added after the first reagent is held. A rotatable holding means is provided which holds a rotatable holding means, and is moved between a first suction position on the first reagent row, a second suction position on the second reagent row, and a reagent discharge position on the reaction container row. A single reagent pipetting mechanism is provided, and when a reaction container requiring a first reagent is positioned at the reagent discharge position, the reagent pipetting mechanism is provided with a single reagent pipetting mechanism that positions the first reagent corresponding to the analysis item.
When the reaction container requiring the second reagent is positioned at the reagent discharge position by moving between the suction position and the reagent discharge position, the reagent pipetting mechanism is moved to position the second reagent according to the analysis item. A multi-item automatic analyzer, characterized in that it is configured to move between the second suction position and the reagent discharge position.