JPH0385454A - Automatic analyser - Google Patents

Abstract

PURPOSE:To increase a treatment speed by allotting an analytical item to a reaction tube block one at a time and distributing different specimens in respective reaction tubes. CONSTITUTION:A plurality of holes 2 are arranged to a microplate 4 as reaction tubes in one row to be integrated and the microplate 4 is fitted in a base 6 to constitute a reaction tube block 1. An analytical item is allotted to each block one at a time and arranged to each groove of the rack of a reaction tube block supply apparatus 8 and specimens are arranged to a specimen chain 21. An item to be analyzed with respect to each of the specimens is inputted to a computer and, when an item to be distributed is selected, the supply appara tus 8 supplies the block of said item and the specimen chain 21 of a specimen distribution mechanism transfers a specimen cup and a specimen distributor 20 injects a specimen in the reaction tubes. A plurality of specimens to be subjected to the measurement of said item are distributed to the reaction tubes of different blocks and the block after the completion of distribution is sent to an analytical part. As mentioned above, by performing the distribution of a reagent in a block unit all at once, a treatment speed can be enhanced.

Description

[Detailed Description of the Invention] (Industrial Application Field) The present invention is applicable to biochemical analyzers and EIAC enzyme immunoassay devices)
This article relates to automatic analysis methods and devices suitable for such applications.

(Conventional technology) As an automatic analyzer known so far.

There are (1) single-multi method, (2) multi-line method, (3) batch processing method, or some modified version of these methods.

The single-multi method is equipped with a reaction line in which reaction tubes are arranged in a row, and by dividing each adjacent reaction tube into a different analysis item, it is possible to analyze multiple items even though there is only one reaction line. Measurements can be taken. With the single-multi method, multiple items can be measured by simply inserting the received samples into the analyzer one after the other, so random access is possible, and efficiency is high even when only a few items are measured for one sample. It has an advantage that does not go down. However, since the analytical items of adjacent reaction tubes are different, it is necessary to pay particular attention to contamination of reagents, and it is also necessary to sequentially move the reaction tubes one by one. Furthermore, since the analysis items are different for each reaction tube, processes such as reagent dispensing, washing, and reaction time must be changed for each adjacent reaction tube, which complicates the mechanism and reduces efficiency. For this reason, it is unsuitable for analytical devices that require high throughput.

The multi-line method has reaction lines equal to the number of analysis items, and each reaction line is occupied by each analysis item.

The multi-line method has the advantage of not having to worry about contamination between analysis items and of relatively high processing speed. However, when measuring only a small number of items for one sample, there is a disadvantage that the processing speed is extremely reduced because many reaction tubes are left unused.

In the batch processing method, all samples are processed one item at a time, and the batch processing method is suitable for high-speed processing and is efficient. However, random access cannot be performed, and even if you try to quickly find out the measurement results of all the items of the specimen of interest, you will only be able to know them after the measurements of all the specimens have been completed.

Therefore, the present inventors have proposed an automatic analysis method and device that can improve the drawbacks of the above-mentioned method, increase processing speed, and enable random access (Japanese Patent Application No. 129080), the proposed method combines multiple reaction tubes into a reaction tube block, assigns common analysis items to the multiple reaction tubes belonging to one reaction tube block, and analyzes each sample. One reaction tube block for each item for multiple analysis items to be measured.
Sequentially dispense the sample into individual reaction tubes.

To enable analysis of arbitrary different items in units of adjacent reaction tube blocks.

(Problem to be solved by the invention) A method for dispensing a sample with an automatic analyzer using a reaction tube block is to sequentially dispense the sample into the reaction tube blocks of the necessary measurement items for one sample. There is a sample priority method and an item priority method in which samples corresponding to the analysis items to be measured in one reaction tube block are sequentially dispensed. Operability (7)-
From point 11, it is desirable to use the sample priority method, but in that case, the sample dispensed earlier into the same reaction tube block and the sample dispensed after a considerable amount of time will coexist.

This time difference causes a large error. On the other hand, when dispensing samples using the item priority method, results for each sample cannot be obtained until all items have been measured for all samples, and the next sample must be added to the sample dispenser and lined up during analysis. I can't.

Therefore, an object of the present invention is to provide an automatic analyzer using an item-prioritizing method in units of one reaction tube block as an intermediate approach between the sample-prioritizing method and the item-prioritizing method.

(Means for solving the problem) In order to realize item priority for each reaction tube block, there is a procedure for automatically determining which reaction tube block to select for each item, and a procedure for automatically determining which reaction tube block to select, and a sample size that allows samples to be added during analysis. Note mechanism must be developed.

Therefore, the automatic analyzer of the present invention integrates a plurality of reaction tubes, and the integrated reaction tube supplies a reaction tube block for analyzing a common item and a reaction tube block for one selected analysis item. A sample dispensing mechanism that dispenses different samples into the reaction tube blocks supplied from the one reaction tube block supply device and a sample dispensing mechanism that dispenses the same sample multiple times for different analysis items; and an analysis section that analyzes common items in each reaction tube block while transferring the poured reaction tube blocks, and the selection of analysis items in the reaction tube block supplying device is performed in accordance with the sample storage section in the sample dispensing mechanism. To automatically select a group of items equal to the number of holes in a reaction tube block, counting from the first sample in a certain range of undispensed samples.

(Function) A plurality of reaction tubes are integrated and arranged in the reaction tube block, and one analysis item is assigned to each reaction tube block. Therefore, reagent dispensing, washing, etc. can be performed simultaneously for each reaction tube block, resulting in high efficiency and increased processing speed.

Since processing is performed in units of reaction tube blocks, it is possible to allocate different arbitrary items to each reaction tube block, resulting in so-called multi-item random access. In this way, the method of the present invention performs block-based random
It is a concept called access, which combines the advantages of both batch processing method and single/multiple method.

When an item for sample dispensing is selected, the reaction tube block for that item is supplied from the reaction tube block supply device, and multiple samples are dispensed into the reaction tube block by the sample dispensing mechanism. corresponds to one analysis item, and a plurality of samples to be measured for that item are dispensed into different reaction tubes of that reaction tube block. After the sample has been completely dispensed, the reaction tube block is sent to the analysis section, where processing such as reagent dispensing and measurement is performed on a reaction tube block basis.

Specimens can be added if they are outside the fixed range of specimens used to select items.

(Embodiment) FIG. 1 schematically shows an apparatus in which the present invention is applied to an apparatus for performing one-step E-work-A measurement.

This automatic analyzer is roughly composed of a reaction tube block supply section, a sample dispensing section, and an analysis section.

8 is a reaction tube block supply device;
1 reaction tube block l for supplying from the sample dispensing section to the analysis section
An example of this is shown in FIG.

A microplate 4 in which a plurality of holes 2, which are reaction tubes, are arranged in a row is fitted into a stand 6 to prevent it from falling over.In the example shown in FIG. 2, there are eight holes 2 corresponding to one reaction tube. Although they are integrated, the number of holes 2 is not limited to this number.An antibody common to each reaction tube block is immobilized on the inner wall of the multi-holes 2 belonging to reaction tube block 1, and the number of holes 2 is not limited to this. common analysis items are assigned.

As shown in FIG. 3, the reaction tube block supply device 8 includes a rack 10 provided within a frame 9.
0 is guided in the X direction by a guide 13 with respect to the frame 9,
A screw 15 driven by a stepping motor 14 is passed through. The rack 10 is provided with a groove 11 in the Y direction, one end of the groove 11 (the left end in the figure) is open, and the reaction tube blocks 1 having the same analysis items are arranged vertically in the multi-groove 11. A lever 12 for advancing the reaction tube block 1 is provided at the other end of the multi-groove 11. In the example shown in FIG. Six items from A to F can be analyzed.

On the wall surface of the frame 9 on which the open end surface of the rack 10 slides, there is an outlet 16 from which one reaction tube block can be taken out.
is opened. The open end surface of the rack 10 is the outlet 1
6 is moved in the X direction along the wall surface of the frame in which the stepping motor 14 is driven. By pushing forward the lever 12 of the groove 11 positioned at the outlet 16, the reaction tube block 1 accommodated in the groove 11 is pushed out from the reaction tube block supply device 8.

A sample dispensing position 17 is located on the path from the outlet 6 of the reaction tube block supply device 8 to the reaction line 8 of the analysis section, and a sample dispensing mechanism is provided there. Samples to be measured for the analysis items are sequentially dispensed.

Returning to FIG. 1, a sample chain 21 is provided to constitute a sample dispensing mechanism. The sample chain 21 is made of a snake chain and can transport the sample cup. The area 22a indicated by a black circle on the sample cup is an area where the sample cup is reciprocated and the sample is dispensed, and the sample in this reciprocating movement area 22a is dispensed multiple times from the same sample for different analysis items. be noted. Reference numeral 20 denotes a sample dispenser for dispensing the sample in the reciprocating region 22a into the reaction tube block 1 at the sample dispensing position 17. Of the sample chain 21.

The area 22b with a white circle on the sample cup represents a waiting sample, and the area 22b with a hatched area on the sample cup represents a waiting sample.
c represents a sample for which dispensing has been completed.

The analysis section is provided with a reaction line 18 for transporting the reaction tube block 1 into which the sample has been dispensed. The reaction line 18 has a width in the longitudinal direction of the reaction tube block 1,
A transfer mechanism shown in FIG. 4 is provided to transfer the reaction tube blocks 1 that have been completely supplied from the reaction tube block supply device 8 one step at a time to the right in FIG. The transfer mechanism comprises belts 24, 26 which hold the ends of the reaction tube blocks 1 on both sides of the reaction line 18. The belts 24, 26 of the block transfer mechanism are moved one step apart at intervals of, for example, 60 seconds, and the reaction tube block 1 is transferred to the right in the figure. A block pushing part 28 is provided on the left side of the reaction line 18 in order to push the reaction tube block 1 into which the sample has been dispensed and pushed out into the reaction line 18 to the transfer start point A.

In FIG. 1, a reagent dispensing section 30, a washing section 32, an enzyme reaction color forming liquid dispensing section 34, a colorimeter 36, and a residual liquid suction section 38 are arranged to the right along the reaction line 8, and one reaction line A bag 40 for discarding the reaction tube block after measurement is provided at the right end of the tube 18.

In the reagent dispensing section 30, as shown in FIG.

Reagent turntable 44 equipped with a plurality of reagent tanks 42
is provided to suck the reagent from the reagent tank 42,
A reagent dispenser is provided, which includes a nozzle 46 for dispensing into reaction tubes, and a guide 48 for guiding the nozzle 46 in the reaction tube arrangement direction of the reaction tube block 1. The nozzle 46 is a pump (
(not shown) can perform suction and discharge, and
Can move up and down. The reagent is in the reagent dispensing section 3.
Since the reagent is to be dispensed to all reaction tubes in the reaction tube block l located at position 0, the reagent is sucked from the reagent tank 42 by the nozzle 46 as shown in FIG.

Dispense sequentially while moving as indicated by the arrows.

The reagent turntable 44 rotates and transfers a predetermined reagent to a reagent dispensing position.

The cleaning section 32 is provided at a predetermined distance from the reagent dispensing section 30. - For example, the distance between the reagent dispensing section 30 and the washing section 32 is set at such a distance that 60 reaction tube blocks 1 are arranged so that washing is performed one hour after reagent dispensing. As shown in FIG.
The eight reaction tubes of the reaction tube block 1 are simultaneously washed about five times in 0 seconds. In the cleaning section 32, a cleaning nozzle 50 moves vertically on each reaction tube. When cleaning is performed, the cleaning nozzle 50 is inserted into each reaction tube. The cleaning nozzle has a double tube, and cleaning is performed by supplying cleaning liquid from the inner tube and discharging the cleaning liquid from the outer tube.

The enzyme reaction coloring liquid dispensing section 34 uses a nozzle mechanism similar to the reagent dispenser described above to dispense a coloring liquid such as a substrate into all the reaction tubes in the reaction tube block 1 below.

The colorimeter 36 is provided at a certain distance from the coloring liquid dispensing section 34. In this case, for example, the measurement is performed 20 minutes after the substrate is dispensed.

The distance between the coloring liquid dispensing section 34 and the colorimeter 36 is set at such a distance that 20 reaction tube blocks 1 are arranged.

As shown in FIG. 7, in the colorimeter 36, white light from a light source is irradiated onto each reaction tube of the reaction tube block 1 below through an optical fiber 52, and the light transmitted through the reaction tubes is filtered through a filter 54. Light is received by each photocell 56.

The residual liquid suction unit 38 is provided to remove residual liquid before discarding the used reaction tube block 1, and after the residual liquid has been sucked, the reaction tube block 1 falls into the bag 40. , discarded.

Next, the operation of this embodiment will be explained.

Reaction tube blocks 1 for each item are arranged in the multi-groove 11 of the rack 10 of the reaction tube block supply device 8.

Specimens are arranged on the specimen chain 21. At the same time, a table of items to be analyzed for each sample is entered into the computer that controls this automatic analyzer.

A table (worksheet) of items to be analyzed is shown in FIG. 8, for example. In Table 0, in which items to be analyzed are entered for each sample number, the circles are the items to be analyzed for that sample. Such a table is expressed as - aij = 1 or 0 (i = 1.2...6). "1" is when the i-th item, j-th specimen is selected, and "0" is when the i-th item, j-th specimen is not selected. Here, the sum 5i (i, k) of the number of analysis requests for each item from sample number 1 to sample number 2 is defined.

As an example, considering 1 to 14, S□(1,14)=7 S, (1, 14) = 8 S, (1,14)=5 S4(1,14)=7 S, (1, 14) = 5 S, (1,14)=2 becomes.

When the analysis starts, k of 5i (i, k) is 8, 9, 10, etc. from the worksheet shown in Figure 8.・・・・・・
What is needed is something different. The maximum value of k is the width K (temporarily assumed to be 26) of the reciprocating movement region 22a of the sample chain 21 in FIG.
An item for which 5i (i, k) is 8 can be found. In this example, for item 2 = 14 and 5z(t, 14
)==s. Therefore, the reaction tube block number 2 of the reaction tube block supply device 8 is supplied, and the sample pipette 2
0 for a total of eight samples (in the example in Figure 8, samples 1, 2, 4,
5, 8, 9°10.14) in the reaction tube block.
When one dispensing into two holes is completed, the circle mark on the worksheet in Figure 8 is removed, so S and (1, 14) become O.

Next, since S (1, 16) = 8.54 (1, 16) = 8, the reaction tube blocks of item 11 and item 4 are selected and sent out from the reaction tube block supply device 8, respectively.
The sample is dispensed.

When proceeding as shown in 2, ni = 26 (specimen chain 21
1 item 1, 2, 3 when the maximum value K) that can be returned is reached
, 4, and 5 have completed dispensing twice, once, once, once, and once, respectively, but item 6 only has 5s(x, zs)=s. However, we make one promise here, k=
26, items that have not been dispensed at all up to that time will be dispensed even if S i (1°26) is less than 8, and the sample chain 21 will proceed as a whole. When k=26 is completed, the worksheet excludes those for which dispensing has been completed, so in the example of FIG. 8, the test moves to the test marked with a double circle. Therefore, by shifting the worksheet by 15 and considering sample numbers 15 and above, S 1 (15,
Proceed in the same way from number 15 to number 40 in the form k).

The reciprocating width of the reciprocating movement area 22a of the sample chain 21 can be set (variable).If K is set large, the waste of the 8-hole reaction tube block will be reduced, but if the sample number is early (small), There is a delay in obtaining the measurement results for all items. The criterion for selecting K may be determined by the average number of specimens in which the eight least frequently measured items (in the case of an 8-well reaction tube block) are present.

Regarding the addition of a sample during analysis, a new sample can be added unless it is in the reciprocating motion area 22a of the sample chain that is already reciprocating for dispensing. At this time, new parts are added to the worksheet table as shown in FIG. 8 at the same time, and measurements are performed continuously.

In this way, one reaction tube block 1 is selected, sent out from the reaction tube block supply device 8, subjected to sample dispensing, and sent out to one reaction line 18. It is pushed to the transfer start position A of 18. The reaction tube block 1 that has reached the transfer start position i1A is moved by one step 6 by the transfer mechanism.
Transferred in 0 seconds.

Reaction tube block 1 has reached point B where reagent dispensing section 30 is located
A reagent such as an enzyme-labeled antibody is dispensed. One hour after dispensing the reagent, the cleaning section 32 reaches a certain 0 point, and the cleaning section 32
The supply and drainage of washing water is repeated several times to remove the reaction liquid, and then at point D, the enzyme reaction coloring liquid is dispensed by the coloring liquid dispensing section 34. If a common enzyme is used for all items as the labeling enzyme system, the coloring liquid in the coloring liquid dispensing section 34 can be used for all items, and if different enzyme systems are used, each reaction tube What is necessary is to switch to a different coloring liquid for each block.

20 minutes after dispensing the coloring solution, the colorimeter 36 reaches point E,
The color produced by the enzymatic reaction is read by a colorimeter 36. After that, the residual liquid is sucked out and the reaction tube block 1 is moved to the bag 4.
Discarded to 0.

The reaction time for antigen-antibody reaction can be adjusted by the length from position B to C, and the time for color development reaction can be adjusted by the length from position E to position B. In the example, the processing speed is 480 tests/hour, and E
As an IA, it belongs to a category that can perform a large amount of processing.

FIG. 9 shows another embodiment.

Compared to the embodiment shown in FIG. 1, the sample dispensing mechanism is different.

In the sample dispensing mechanism shown in FIG. 9, a turntable 60 is used to separate the parts that reciprocate and dispense multiple times from the same sample. A waiting specimen and its holder 62 are first set in the waiting specimen storage area 61.

Among the samples in the standby sample storage area 61, the turntable 6
The number of specimens required to reciprocate at 0 is automatically placed on the turntable 60. While rotating the turntable 60 back and forth, the sample is dispensed into the reaction tube block 1 for each item, and the sample that has been dispensed for all items is automatically removed to the dispensing finished sample storage area 63, and the sample is transferred to the turntable 60. Then, a new sample is replenished from the standby sample storage area 61 in the space vacated by the removal of the completed sample.

In the embodiment shown in FIG. 9 as well, the data of the specimens placed in the standby specimen storage area 61 are entered into a worksheet as shown in FIG.

The data on the worksheet regarding the sample that has been placed on the turntable 60 and has been dispensed is removed. A new sample can be freely added to the standby sample storage area 61, and the data of that sample is added to the worksheet.

(Effect of the invention) In the present invention, a plurality of reaction tubes are integrated into a reaction tube block, and one analysis item is assigned to each reaction tube block. Since different samples can be dispensed and different arbitrary items can be handled in units of one reaction tube block, ease of use equivalent to random access can be achieved, and patch processing elements have been incorporated, making reagent dispensing and measurement easy. It is possible to construct an automatic analyzer with high processing speed in block units. For example, eight reaction tubes can be integrated and processed.
Analyzes can be performed using a hole microplate in substantially the same manner as random access.

Since a microplate with holes arranged in a row can be used as the reaction tube block, the apparatus can be made smaller than the bead method or tube method even though the processing speed is high. Therefore.

It is particularly advantageous for EIA.

Even if only a small number of items are selected for one sample, the processing speed does not decrease.In this respect, there is no drawback to the multi-line method, which uses a dedicated line for each item.

This eliminates the difference in dispensing time between multiple samples in the same reaction tube block, which was a problem when applying the sample priority dispensing method to reaction tube blocks.

Continuous analysis is possible if the reaction tube block is automatically removed. That is, samples can be added one after another without stopping the analysis.

Therefore, the analysis should be started before all the samples have been collected.
Since it is possible to prepare a worksheet for the next sample and add samples in parallel during analysis, analysis efficiency is greatly improved.

[Brief explanation of drawings]

Fig. 1 is a schematic plan view showing one embodiment, Fig. 2 is a perspective view showing an example of a reaction tube block, Fig. 3 is a perspective view showing a reaction tube block supply device, and Fig. 4 is a block transfer in the analysis section. A plan view showing the mechanism, FIG. 5 is a schematic sectional view showing the reagent dispensing section in the same example, FIG. 6 is a schematic sectional view showing the washing section in the same example, and FIG. 7 is a colorimetric diagram in the same example. FIG. 8 is a diagram showing a worksheet in one embodiment, and FIG. 9 is a schematic plan view showing another embodiment. 1...Reaction tube block, 8...Reaction tube supply device. 10... Lever 18... Reaction line, 20... Sample dispenser, 21... Sample chain, 22a... Chain Reciprocating motion area, 24, 26... Transfer mechanism, 28...
・Block pushing part, 30...Reagent dispensing part, 32
. . . Washing section, 34 . . . Coloring liquid dispensing section. 36... Colorimeter, 38... Residual liquid suction section, 40... Block disposal section bag, 60...
··Turntable.

Claims (1)

[Claims] (1) A reaction tube block that integrates multiple reaction tubes so that the integrated reaction tube analyzes a common item, and a reaction tube block supply device that supplies the reaction tube block of the selected analysis item. , while dispensing different samples into the reaction tube block supplied from the reaction tube block supply device,
A sample dispensing mechanism for dispensing the same sample multiple times for different analysis items, and an analysis section for analyzing a common item in each reaction tube block while transporting the reaction tube block into which the sample has been dispensed, The selection of analysis items in the tube block supply device is based on the selection of the items that are collected in the number of holes in the reaction tube block first, counting from the first sample of undispensed samples in a certain range of the sample storage section in the sample dispensing mechanism. Automatic analyzer that is automatically selected.