JPH03118475A - Chemical analysis method - Google Patents

Abstract

PURPOSE:To measure the sample characterized by quick reaction highly accurately by rotating a rotary table twice or more for one conveying measurement. CONSTITUTION:When a measurement starting signal is inputted from a control part 114, a sample 101, a first reaction reagent 104 and a diluent liquid 106 are added into a reaction container 101 at a position (a) through a sample distributing device 105 and a diluent-liquid distributing device 107. Thus the first distribution is performed. Then, the control part 114 rotates a rotary table 102 by one container. The first distribution is performed on the container 101 which is moved to the position (a). A second reaction reagent 108 is added into the container 101 which is moved to a position (b), and the second distribution is performed. Then, the control part 114 rotates the table 102 at least two or more rotations. The chemical change of the sample is measured by two or more times through optical detecting means 110 and 111. The conveying measurement such as this is performed. The distribution and the conveying measurement are alternately repeated by the same way, the measuring time interval can be shortened without the restriction on the distributing time and the measuring time interval can be adjusted by the rotating speed of the table.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to chemical analysis methods, and in particular, chemical reactions and antigen-antibody reactions in which reaction changes are large in the initial stage of the reaction and observation of the reaction progress in the early stage of the reaction is important. etc., relates to a chemical analysis method that can appropriately analyze a sample.

[Conventional technology]

As a conventional chemical analysis method, for example, JP-A-59-36
There is a chemical analysis method using a turntable and a stationary photometer as shown in Japanese Patent No. 227. In this chemical analysis method, a row of reaction vessels arranged on a turntable repeats a transport state and a stop state by rotating the turntable, and passes through a sample addition position and an optical path of a stationary photometer. After adding a sample to a specific container in the reaction container, move the reaction container row so that the specific container approaches the photometer optical path and travels the distance between the multiple containers, and then move the reaction container row to the sample addition position. In this method, a new reaction vessel is positioned, multiple pieces of measurement data based on a specific sample are obtained as the vessel is moved, and changes in the reaction are observed from these multiple pieces of measurement data.

In other words, the dispensing process (sample addition) and the transport measurement process (
Rotation with a turntable and measurement with a photometer) are repeated, and multiple reaction vessels can be measured between dispensing processes, making it possible to measure a large number of samples with a single stationary photometer. This is how it was done. By applying this chemical analysis method using a turntable and a stationary photometer, it is possible to observe a large number of samples at the same time, improving throughput, and lengthening the observation time for sample reactions. can do.

On the other hand, the concentration of a sample undergoing chemical analysis ranges over a wide range from low to high, and the reaction speed also varies from as fast as several tens of seconds to as slow as several hours. In general, there is a proportional relationship between the reaction speed and concentration of a sample. Therefore, when measuring an unknown sample, it is best to detect the approximate concentration in advance by some method, and then dilute it to an appropriate concentration before analysis. Common. However, when measuring a large number of samples with a wide concentration range in the medical testing field, it is difficult to detect the concentration of each sample and dilute it to an appropriate concentration before measuring. Measured in a region tailored to the concentration.

[Problem to be solved by the invention]

However, according to conventional chemical analysis methods, the dispensing process and transport measurement process are repeated, and although multiple samples are measured between the dispensing processes, Since only one measurement is performed in one transport measurement process, the measurement time interval (interval from one measurement to the next measurement) becomes "dispensing processing time + α", and in the case of a sample with a fast reaction rate, the reaction There was a problem in that photometric analysis of the progress could not be performed. That is, since the dispensing process generally requires several seconds (usually around 3 seconds), the conventional method is not suitable, for example, for analyzing samples with rapid reaction changes that require measurement data several times per second.

Furthermore, in the case of a sample whose reaction time (time from the start of the reaction to the end of the reaction) is around several tens of seconds, the number of measurements is reduced, resulting in a problem in that the measurement accuracy is reduced.

Furthermore, in conventional chemical analysis methods, all prepared samples are measured unconditionally.
Since the process is carried out continuously until the measurement is stopped, there are problems such as decreased work efficiency due to unnecessary measurements and wasteful consumption of samples.

A first object of the present invention is to provide a chemical analysis method that can measure a sample with a fast reaction rate and improve measurement accuracy.

A second object of the present invention is to provide a chemical analysis method that can avoid a decrease in work efficiency due to unnecessary measurements and wasteful consumption of samples.

[Means to solve the problem]

In order to achieve the first object, the present invention provides a chemical analysis method in which a rotary table is rotated at least twice or more per transport measurement process to obtain a plurality of measurement data.

In addition, in order to achieve the second objective, a chemical analysis method is provided in which the dilution ratio of the sample to be measured next is changed as necessary based on a plurality of measurement data obtained by carrying out the transport measurement process. It is something.

That is, the chemical analysis method of the present invention rotates the rotary table at least twice or more to obtain a plurality of measurement data in one transport measurement process, thereby shortening the sample measurement time interval and reducing the reaction rate. It enables fast sample measurement and improves measurement accuracy by obtaining a large amount of measurement data within a certain period of time.

By changing the dilution ratio of the next sample to be measured as necessary based on multiple measurement data obtained in one (or several) transfer measurement processes, it is possible to make it pointless to continue measurement. This makes it possible to catch cases early and avoid unnecessary measurements. In other words, by feeding back and controlling the analysis results at the initial stage of the reaction to the pretreatment of the sample before addition to the reaction vessel, work efficiency is improved and measurement throughput is improved. .

Furthermore, the present invention also provides that the same object can be achieved by making it possible to arbitrarily change the rotational speed of the rotary table, and by adjusting the measurement time interval by the optical detection means by changing the rotational speed. It is.

[Effect]

In the chemical analysis method of the present invention, a sample is dispensed into reaction vessels arranged on the rotary table while the rotary table is stopped. After that, the reaction container is transported by rotating the rotary table at least two times or more (for example, four times), and the chemical change in the sample is measured at least twice (four times in the case of four revolutions) through the optical detection means. A plurality of pieces of measurement data are obtained in one conveyance measurement process. Further, based on a plurality of pieces of measurement data obtained in one (or several) times of the transport measurement process, the dilution ratio of the next sample, etc. is changed as necessary. This makes it possible to catch cases where it is meaningless to continue measurement at an early stage and avoid unnecessary measurements. Generally, dispensing a sample into a reaction container takes a considerable amount of time (
For example, it takes 4 seconds or more). For this reason, in the conventional method of incorporating a dispensing process every rotation of the rotary table, shortening of the measurement time interval using optical detection means was restricted. By performing at least two rotations, the measurement time interval can be significantly shortened without being restricted by the dispensing processing time. Furthermore, by making it possible to arbitrarily change the rotational speed of the rotary table, it is possible to finely adjust the measurement time interval by the optical detection means according to the reaction rate of the sample.

〔Example〕

The chemical analysis method of the present invention will be explained in detail below.

FIG. 1 shows a first embodiment of a chemical analysis apparatus to which the chemical analysis method of the present invention is applied. A sample dispenser 105 dispenses a reagent 104 into the reaction container 101 stopped at a predetermined position a, and a diluent dispenser 107 dispenses a diluent 106 into the reaction container 101 stopped at a predetermined position a for dilution. and a reaction reagent dispenser 109 that dispenses the second reaction reagent 108 into the reaction container 101 stopped at a predetermined position 11b, and a predetermined dispensing process via the sample dispenser 105 and the reaction reagent dispenser 109. LED 110 for measuring chemical changes in the reaction vessel 101 in which the reaction was carried out. A photosensor 111 (optical detection means), a data processing unit 112 that inputs measurement data measured by the LEDIIO and the photosensor 111 and performs arithmetic processing, and a printer 113 that outputs the processing results of the data processing unit 112. ,
It is composed of a control section 114 that controls the dispensing process of each dispenser 105, 107, 109, the rotation of the rotary table 102, and the measurement control of the LED IIO and photosensor 111. Note that in the first embodiment, the rotary table 10
2 is configured to be detachable from the apparatus main body, and the reaction vessel 101
The rotating tape 102 can be removed to remove and dispose of the sample inside the reaction vessel 101 and to clean the reaction vessel 101, thereby simplifying the apparatus configuration. Note that a separate reagent dispenser may be used for each reagent, or the same dispenser may be used for both purposes as appropriate.

In the above configuration, before explaining the operation, we will explain about ■dispensing process, ■conveyance measurement process, and ■feedback process.
Explain in detail.

■Dispensing process In the dispensing process, the sample 103 is placed in the reaction vessel 101 while the rotary table 102 is stopped. First reaction reagent 104. Diluent 106. The process of dispensing the second reaction reagent 108 is also shown. Reaction container 101 as needed during dispensing process
It is also possible to perform a washing operation and use the reaction vessel repeatedly.

The control unit 114 stops the rotary table 102 and transfers the sample to a specific reaction container 101 (at a predetermined position a) via the sample dispenser 105.
A predetermined amount of the sample 103 is dispensed into the reaction vessel 101) which has been stopped, and then the first reaction reagent 104 is added. At the same time, a preset amount of diluent 106 is dispensed via the diluent dispenser 107 to prepare the sample 103 and the first reaction reagent 1.
Dilute the mixture of 04. At this time, the sample dispenser 105
Since the dispensing by the diluent dispenser 107 and the dispensing by the diluent dispenser 107 are started at the same time, the first reaction reagent 104 is added to the sample 103 diluted with the diluent 106 in the reaction container 101. On the other hand, at a predetermined position, a second reaction reagent 108 is added to the reaction container 101 via a reaction reagent dispenser 109. By adding the second reaction reagent on the 10th day, the reaction conditions in the reaction container 101 (the presence of the sample 103, the first reaction reagent 104, and the second reaction reagent 108) are established, and the chemical reaction starts. be done.

In the first embodiment, the time from when the rotary table 102 stops until it starts rotating, that is, the dispensing processing time, is set to 3 seconds, and the dispensing work described above is performed within this time. .

■Transport measurement process The transport measurement process moves the reaction container 101 at a predetermined position a (or predetermined position b) to a predetermined position b (or predetermined position C), and moves the reaction container 101 to perform the next dispensing. A transport function that guides the reaction liquid (sample 103. first reaction reagent 104. second reaction reagent 10) to a predetermined position a (or predetermined position b)
The reaction container 101 containing the mixed liquid of No. 8) is passed through the optical path of the optical detection means (LED 110, photosensor 111) multiple times, and the chemical reaction is measured multiple times.

After the dispensing process is completed, the control unit 114 controls the rotary table 10.
2 to start transporting the reaction container 101, and measurement is performed by passing through the optical path of the optical detection means (LED 110, photosensor 111).

In this embodiment, the transport measurement processing time T is 4 seconds, the rotation of the rotary table 102 is 16+α rotations, and 16 measurements are performed on one reaction vessel 101 in one transport measurement processing. Therefore, the measurement time interval S is approximately 0.25 seconds (S=T/1
6). After carrying out 16 measurements at a measurement time interval of about 0.25 seconds, the control unit 114 stops the rotation so that the reaction container 101, which was at the predetermined position a at the start of rotation, comes to the predetermined position a, and ends the process. On the other hand, optical detection means (LED
Measurement data measured by the photo sensor 111) is subjected to arithmetic processing by the data processing unit 112 and outputted via the printer 113.

■Feedback processing The data processing unit 112 selects the measurement data of the reaction vessel 101 in which the first measurement was performed after the start of the reaction, from among the 16 pieces of measurement data obtained for each reaction vessel 101, in other words,
Reaction container 10 that was in a predetermined position at the start of the transport measurement process
1 measurement data is output to the control unit 114. Control unit 11
Step 4 determines whether subsequent measurements are valid or invalid based on the first 16 measurement data from the start of the reaction. Specifically, as shown in Figure 2, when 16 pieces of data from the first piece of data show approximate values and show the shape of the measured data curve A, it is determined that the reaction rate is slow. , subsequent measurements are valid. In addition, if the 16 data show the shape of measurement data curve C, after the reaction starts,
It is determined that the reaction is almost complete within 1 second (up to the fourth measurement), and subsequent measurements are invalidated. Furthermore, if the 16 pieces of data show the shape of the measurement data curve B, it is determined that the reaction will be completed within several transport measurement processing times. Based on the above-described determination, for example, if the subsequent measurement is valid, the control unit 114 continues to perform the next dispensing process,
If the subsequent measurements are invalid, the sample dispenser 105. Diluent dispenser 107. Then, the two-reaction reagent dispenser 109 is controlled to adjust the dilution ratio of the reaction solution to make correction (feedback) so that the reaction rate becomes slower.

In addition, if it is determined that the reaction will be completed within several times of conveyance measurement processing time, the data processing unit 112 and the printer 11
3, a message is output to notify the user to decide whether or not to continue the measurement.

The operation will be explained based on the configuration and each process described above.

First, as a preparation process for starting measurement, the sample 103 is placed in a predetermined container, and a dilution factor is set via an input means (not shown). The dilution factor determines the ratio between the amount of sample 103 to be dispensed and the amount of diluent 106 to be dispensed in the dispensing process.

When the control unit 114 inputs the measurement start signal from the input means, the control unit 114 inputs the measurement start signal through the sample dispenser 105 and the diluent dispenser 107.
An amount of sample 103. based on the dilution factor is placed in the reaction container 101 at a predetermined position a. First reaction reagent 104. And diluent 10
6 (first dispensing process). When the first dispensing process is completed, the control unit 114 controls the rotary table 102.
is rotated by one reaction container, the reaction container 101 at the predetermined position a is moved to a predetermined position, and the sample 103 is poured into the reaction container 101 newly moved to the predetermined position a in the same manner as in the first dispensing process. ．． The first reaction reagent 104 and the diluent 106 are added to the reaction container 101 in a predetermined position (the reaction container 101 to which the sample 103 etc. were added in the first dispensing process)
), the second reaction reagent 108 is added via the reaction reagent dispenser 109 (second dispensing process). Control unit 11
4, when the second dispensing process is completed, the rotary table 1
02 to perform the first conveyance measurement process. Similarly, the third dispensing process.

By repeating the dispensing process and the conveyance measurement process alternately like the second conveyance measurement process and the fourth dispensing process, 16 pieces are collected per reaction container 101 containing the reaction liquid in one conveyance measurement process. Obtain measurement data.

On the other hand, for each transport measurement process, the measurement data of the reaction container 101 that was in a predetermined position at the start of rotation (measurement data obtained in the first transport measurement process) is sent to the control unit 114, and feedback processing is performed. Correction of the dilution ratio, output of notification messages, etc. are performed.

In the first embodiment, it is possible to obtain a large amount of measurement data within the transportation measurement processing time T (4 seconds) with a short measurement time interval S (about 0.25 seconds). It is possible to analyze samples with rapid reaction changes that require measurement data of 1,000 yen, and achieve high measurement accuracy. Therefore,
It is possible to appropriately analyze samples such as chemical reactions and antigen-antibody reactions in which reaction changes are large in the early stage of the reaction and observation of the reaction progress in the early stage of the reaction is important.

In the first embodiment, the rotation table 102 rotates 16 times per unit time (transport measurement processing time T).
It is not particularly limited to this, for example, 4 rotations, 8 rotations,
It may be set to rotation, 20 rotations, etc. Further, the number of rotations may be changed as necessary via input means or the like.

Furthermore, although the dilution magnification was adjusted under the control of the control unit 114 and the feedback process was performed, it is also possible to change the number of rotations of the rotary table 102 together with the dilution magnification (the control unit 1
Instead of the control in step 14, a manual adjustment method may be used.

FIG. 3 shows a second embodiment of a chemical analysis apparatus to which the chemical analysis method of the present invention is applied, in which a first reaction reagent 302 is dispensed into a reaction container 101 via a reaction reagent dispenser 301 at a predetermined position d. Pour the sample dispenser 30 into the reaction vessel 101 at a predetermined position e.
3, a sample 304 and a diluent 305 are dispensed through a reaction reagent dispenser 306, and finally a second reaction reagent 307 is dispensed at a predetermined position r via a reaction reagent dispenser 306 to start a reaction.

In addition, 308 is a constant temperature bath for keeping the reaction conditions constant;
9 indicates a stirring probe that stirs the liquid dispensed at predetermined positions d, e, and f. Other configurations are the same as those of the first embodiment, so explanations and illustrations will be omitted. In the above configuration,
An example of feedback processing based on measurement data obtained through multiple conveyance measurement processing will be described.

Prior to measurement, the sample, reagent, and standard substance are set at predetermined positions, and the reaction container 101 is heated to
The sample is heated to ˚C and then measured using standard substances to create a calibration curve for each item.

In the second example, the stop process was 4 seconds, the conveyance measurement process was 11 seconds, and the measurement time interval was 2 seconds. Hereinafter, the measurement procedure will be explained in detail with reference to the timing chart of FIG.

The first reaction reagent 302 is dispensed into the reaction container 101 stopped at a predetermined position d via the reaction reagent dispenser 301, and simultaneously stirred for 2 seconds using the stirring probe 309. Thereafter, the first reaction reagent 30 was kept warm for 2 minutes in a constant temperature bath 308 and dispensed.
2 to 37°C.

As mentioned above, in this example, the stop process is 4 seconds, the transport measurement process is 11 seconds, and the process is carried out in 15 seconds as a unit operation. During the heat retention period, the sample is transported from the predetermined position d to the predetermined position e, which is eight reaction vessels apart. Next, the sample 304 and diluent 305 are dispensed into the reaction vessel 101 stopped at a predetermined position e via the sample dispenser 303, and simultaneously stirred for 2 seconds using the stirring probe 309. Thereafter, the first reaction reagent 30 was similarly kept warm for 2 minutes in a constant temperature bath 308 and mixed.
2. Sample 304. And the diluent 305 is heated to 37°C. When the reaction container 101 reaches the predetermined position f, the second reaction reagent 307 is dispensed via the reaction reagent dispenser 306 to start the reaction. Rotate and take measurements. In this example, it is determined whether it is meaningful to continue the measurement in the first 60 seconds from the start of the reaction. In other words, a plurality of measurement data obtained in the first four transport measurement processes after the start of the reaction (here, 20 measurement data because five measurement data can be obtained in one transport measurement process). Based on this, it is determined whether there is any point in continuing the measurement. If it is meaningful, the measurement of the corresponding reaction solution is continued, and the transport measurement process is performed several times within 8 minutes from the start of the measurement. If it is meaningless, the measurement is stopped, and, for example, feedback processing is performed in the same manner as in the first embodiment, and the measurement is performed again.

In the first and second embodiments described above, the sample in the reaction vessel after measurement is removed and disposed of by replacing the rotary table 102. It may also be configured to be executed in parallel with the processing. Furthermore, a configuration may be adopted in which the rotation speed of the rotary table 102 can be changed arbitrarily. As a mechanism for making it possible to arbitrarily change the rotational speed of the rotary table 102, for example, a means is adopted in which a program that can arbitrarily change the rotational speed is connected to a pulse motor and the pulse motor is operated arbitrarily.

〔Effect of the invention〕

As explained above, in the chemical analysis method of the present invention, the rotary table is rotated at least twice in the transport measurement process, and a plurality of measurement data are obtained by performing the transport measurement process once. A sample with a fast reaction rate can be measured, and measurement accuracy can be improved. In addition, the dilution ratio of the next sample is changed as necessary based on multiple pieces of measurement data obtained in one transport measurement process, which reduces work efficiency due to unnecessary measurements. Wasted sample consumption can be avoided. Furthermore, by making it possible to arbitrarily change the rotational speed of the rotary table, it is possible to finely adjust the measurement time interval by the optical detection means according to the reaction rate of the sample.

[Brief explanation of drawings]

FIG. 1 is an explanatory diagram showing a first embodiment of a chemical analysis apparatus to which the chemical analysis method of the present invention is applied, FIG. 2 is an explanatory diagram showing a method for determining feedback processing in the control section, and FIG. FIG. 4 is an explanatory diagram showing a second embodiment of the chemical analysis apparatus to which the chemical analysis method is applied, and FIG. 4 is a timing chart illustrating the measurement procedure. Explanation of symbols 101 --- Reaction container 102 --- One rotation table 103 --- Sample 104 --- First reaction reagent 105 --- One sample dispenser 106-・-Diluent 107----Diluent dispenser 108-----Second reaction reagent 109-----Reaction reagent dispenser 110---L E D 110111---
---Photo sensor 111---Data processing section 113--Printer 114--Control section 301--Reaction reagent dispenser 302--Reaction reagent 303 ----Sample dispenser 304-----One sample 305--One diluent 305306----Reaction reagent dispenser 30630
7-------Reaction reagent 307

Claims (3)

[Claims] (1) A dispensing process in which a sample is dispensed into the reaction vessels arranged on the rotary table while the rotary table is stopped, and an optical detection method is performed while the rotary table is rotated to transport the reaction vessels. By repeating the dispensing process and the conveyance measurement process, a plurality of measurement data corresponding to the number of rotations of the rotary table is obtained, and these multiple measurements are performed. A chemical analysis method for analyzing chemical changes in a sample based on data, characterized in that the rotation table is rotated at least twice or more for each transfer measurement process to obtain a plurality of measurement data. chemical analysis method. (2) The chemical analysis method according to claim 1, wherein the dilution ratio of the sample to be measured next is changed as necessary based on a plurality of measurement data obtained by carrying out the transport measurement process. (3) A dispensing process in which samples are dispensed into the reaction vessels arranged on the rotary table while the rotary table is stopped, and an optical detection means is carried out while the rotary table is rotated to transport the reaction vessels. By repeating the dispensing process and the conveyance measurement process, a plurality of measurement data corresponding to the number of rotations of the rotary table is obtained, and these multiple measurements are performed. In a chemical analysis method for analyzing chemical changes in a sample based on data, the rotation speed of the rotary table can be changed arbitrarily, and the measurement time interval by the optical detection means is adjusted by changing the rotation speed. A chemical analysis method characterized by: