JPH0468589B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to an automatic analyzer, and more particularly to an automatic analyzer capable of multi-purpose and multi-item measurements that can perform biochemical analysis with high precision and high speed.

[Prior Art] Various automatic analyzers of this type have been proposed in the past, and biochemical analyzes and the like are performed using simple and miniaturized devices.

For example, a sample table holding a required number of sample containers and dilution tubes, a rotatable reaction table on the outer circumference of the table, and a first reagent table and a second reagent table near the reaction table. a sampling pipette device for selectively dispensing a sample or a diluted sample into a reaction tube or a dilution tube, a first reagent pipette device and a second reagent pipette device for dispensing a first reagent and a second reagent into the reaction tubes respectively; A pipette device was placed near the reaction table, and colorimetric measurements were performed using an optical measuring device. In this way, biochemical analysis and the like can be performed using the automatic analyzer. (For example, see Japanese Patent Application Laid-Open No. 60-64255.) Automatic analyzers use a large number of samples, various types of reagents, and many reaction tubes, etc., and can handle a large number of measurement items. There are demands for speed, accuracy, simplicity of the device, etc.

[Problems to be Solved by the Invention] However, the above-mentioned conventional automatic analyzers disclosed in, for example, Japanese Patent Application Laid-Open No. 60-64255 cannot quickly carry out operations for sampling large quantities, dispensing reagents, and reaction operations. Moreover, there was a problem that it could not be done easily. In addition, there is a problem in that the structure of the optical measurement device becomes complicated, such as requiring a correction device for differences in light intensity between filters.

The present invention solves these conventional problems, and has the advantage of being able to quickly and easily perform sampling and reagent dispensing operations, reaction operations, and optical measurements for a large number of samples. The purpose of this invention is to provide an automatic analyzer with

[Means for Solving the Problems] In order to achieve the above object, the present invention holds a plurality of sample containers for general specimens on the outer periphery and has the same number of dilution tubes as the sample containers for general specimens on the intermediate periphery. A turret-shaped sample table that holds a sample container for an emergency specimen on its inner periphery, and a required number of reaction tubes arranged concentrically on the outer periphery of the sample table so as to be rotatable in forward and reverse directions are held. A reaction table, a first reagent table and a second reagent table placed on both sides of the reaction table, respectively, and a sample in the sample container are selected with a pipette nozzle into a reaction tube or a dilution tube. A holder which is disposed adjacent to the reaction table for dispensing and which holds the pipette nozzles at both ends thereof is movable vertically, rotationally and horizontally, so that when the pipette nozzle at one end is selectively dispensed, the pipette nozzle at the other end is movable. a sampling pipette device for alternately washing the pipette nozzles of the first reagent table; A holder disposed between the first reagent table and holding the pipette nozzle at both ends is made vertically and rotatably so that when the pipette nozzle at one end is dispensing, the pipette nozzle at the other end is alternately washed. a first reagent pipette device for dispensing a required amount of a second reagent and a third reagent in a reagent bottle placed on a second reagent table into a reaction tube using a pipette nozzle; A holder disposed between the table and holding the pipette nozzle at both ends can be moved up and down and rotated so that when the pipette nozzle at one end is dispensing, the pipette nozzle at the other end is alternately washed. This system is equipped with a second reagent pipette device and an optical measurement device disposed in the middle of the reaction table, first reagent table, and second reagent table for optically measuring the reaction solution in the reaction tube.

[Function] The present invention has the following effects due to the above configuration. That is, the sampling pipette device is activated, and the pipette nozzle at one end aspirates the required amount of specimen from the sample container, and then dispenses it into the reaction tube, and at the same time, the pipette nozzle at the other end is cleaned internally and externally. . Subsequently, the above-described sampling operation corresponding to the measurement item of the specimen is repeated. On the other hand, for a certain measurement item, the sample is diluted at a predetermined ratio as a diluted sample, and after the sampling pipette device is activated and the required amount of diluted sample is aspirated from the dilution tube, it is dispensed into the reaction tube. be done.
The type of specimen depends on the urgency of the clinical test.
Samples are classified into general samples and emergency samples, and emergency samples are sampled with priority over general samples. Then,
When the first reagent bottle and second reagent bottle table corresponding to the measurement item arrive at the predetermined reagent suction position, the pipette nozzle at one end of the first reagent pipette device and the pipette nozzle at one end of the second reagent pipette device are activated, respectively. After each of the first reagent and the second reagent is measured by suction, they are injected into the reaction tube. At about the same time, the pipette nozzle at each other end is cleaned internally and externally. The reaction liquid dispensed into these reaction tubes is stirred by the movement of air bubbles generated by air introduction.
Manipulations are carried out to homogenize and accelerate the reaction. In the optical measurement device, the measurement light enters the light guide hole of the reaction table and passes through the reaction liquid in the reaction tube, is separated by a concave diffraction grating, is measured using a photodiode, and is measured by a microcomputer. Calculations are made. As mentioned above, a large number of sample containers and dilution tubes for general and emergency samples can be held, and operations for dispensing reagents and reaction operations can be performed quickly and easily according to a predetermined sequence. be able to.

[Example] Embodiments of the present invention will be described below with reference to the drawings.

1 and 2 show the structure of an embodiment of the present invention. In Figures 1 and 2, X indicates an automatic analyzer, 4 is a turret-shaped sample table, 6 is a reaction table placed on the outer circumferential side of the sample table 4, and 7 is a reaction table placed near the reaction table 6. 1 and 8 respectively indicate a reagent table and a second reagent table. Further, 9 indicates a sampling pipette device, 11 indicates a first reagent pipette device, and 13 indicates a second reagent pipette device, all of which are arranged adjacent to the reaction table 6. Reference numeral 14 denotes an optical measuring device disposed at an intermediate portion between the first reagent table 7 and the second reagent table 8. On the sample table 4, a plurality of sample containers 1 for general specimens are arranged on the outer periphery, then the same number of dilution tubes 2 are arranged on the middle periphery, and further sample containers 3 for emergency specimens are arranged concentrically on the inner periphery. A large number of each is maintained. In addition, sample container 1
and 3 contain a required amount of a specimen (serum, urine, etc.) collected from a living body to be measured, and dilution tubes 2 each contain a diluted specimen obtained by diluting the specimen at a predetermined ratio. The turret-shaped sample table 4, reaction table 6, first reagent table 7, and second reagent table 8 are each driven by a drive device 4.
1, 61, 71, and 81, it is controlled to freely rotate in forward and reverse directions according to a predetermined sequence.

When the sample table 4 is rotationally driven by the drive device 41 and a predetermined sample container 1 reaches a predetermined sample suction position a, the sample in the sample container 1 is passed through the pipette nozzle 105 at one end of the sampling pipette device 9. After the required amount has been aspirated, the corresponding reaction tube 5 is opened at the sample discharge position b.
It is dispensed within. When a sample in a predetermined sample container 3 is used, the sample table 4 is rotated and transferred to a predetermined sample suction position a' as shown in FIG. After the tool 104 moves and the pipette nozzle 105 at one end aspirates a required amount of the sample from the sample container 3, the sample is dispensed into the corresponding reaction tube 5 at the sample discharge position b shown in FIG.

Furthermore, sample container 1 or sample container 3
When storing a diluted sample obtained by diluting the sample in the pipette at a required ratio into the dilution tube 2, the holder 104 of the sampling pipette device is moved in the same manner as described above.
After the pipette nozzle 105 at one end aspirates the sample in the sample container 1 or sample container 3, the sample is injected into the dilution tube 2 as a diluted sample.

When the diluted sample is dispensed from the dilution tube 2 into the corresponding reaction tube 5, it is also dispensed via the pipette nozzle 105 at one end of the sampling pipette device 9 in accordance with the above operation.

Next, a plurality of first reagent bottles 10 and a plurality of second reagent bottles 12 used for the reaction are placed on the first reagent table 7 and the second reagent table 8, respectively, and the reaction tubes into which the first sample has been dispensed are placed. 5 comes to the first reagent discharge position f, the first reagent table 7
is rotated, and the first reagent bottle 1 according to the measurement item is
0 to the first reagent suction position d, and the first reagent pipette device 1 is transferred from the inside of the first reagent bottle 10.
A required amount of the first reagent is sucked into the pipette nozzle 39 through the pipette 1, and the first reagent pipette is transferred to the first reagent discharge position f, where the required amount is dispensed into the reaction tube 5.
Furthermore, when two pitches of reagent are sent by the reaction table 6, air is sent by a stirring pump (not shown) to the stirring nozzle 41 arranged in parallel adjacent to the first reagent pipette nozzle 39, and the reaction liquid in the reaction tube 5 is stirred. be done. Furthermore, the reaction tube 5 is transferred with the required pitch, and when it reaches the second reagent discharge position g, the second reagent table 8 rotates and transfers the reagent bottle 12 corresponding to the measurement item to the second reagent suction position e, and A required amount of the second reagent is sucked into the pipette nozzle 40 from within the second reagent bottle 12 via the second reagent pipette device 13, and the second reagent pipette is transferred to the second reagent discharge position g to dispense the required amount into the reaction tube 5. be done. Continuing,
When two pitches of the reaction table 6 are fed, air is sent by a stirring pump (not shown) to the stirring nozzle 42 arranged in parallel with the second reagent pipette, and the reaction liquid in the reaction tube 5 is stirred. The stirring positions of the reaction solution using the first reagent and the second reagent on the reaction table 6 are indicated by h and i, respectively.

The above stirring of the reaction solution is carried out sufficiently by the introduction of air to generate bubbles and their movement, and is carried out in order to homogenize and accelerate the reaction, and the reaction tube 5 itself is The odor can be stirred on the reaction table 6 without being transferred to the outside.

The optical measurement device 14 uses a multiwavelength photometer, and as shown in FIGS. A mirror 143 reflects the measuring light that enters and passes through the reaction liquid in the reaction tube 5.
The concave diffraction grating 14 passes through the slit 144.
5, and a plurality of light-receiving elements 146, the current change of each wavelength is passed through an amplifier/AD converter, and the concentration is calculated by a microcomputer.

In the optical measurement, each time the reaction table 6 rotates one pitch less than one rotation, the absorbance at the measurement wavelength of each item of all the reaction tubes is measured. Therefore, the absorbance can be measured at each step up to the first nozzle position J of the reaction tube cleaning device 19 after stirring the second reagent, and the time course of the reaction can be obtained. can be measured. When this colorimetric measurement is completed, the reaction tube 5 reaches the first reaction tube cleaning position J, is cleaned by the reaction tube cleaning device 19, and is used again.

As mentioned above, since the optical measuring device 14 does not use a large number of filters that convert into different wavelengths, not only can the device and operation for setting the optical path be omitted, but also the difference in the light amount of each filter can be measured electrically. Since it is also possible to omit a circuit that performs correction, measurements can be made quickly and the structure can be simplified.

FIG. 3 is a detailed explanatory diagram of the sampling pipette device 9. The sampling pipette device 9 is
A holder 104 that holds the pipette nozzle 105 at both ends, and a vertical drive device 10 for the holder 104.
1. Rotary drive device 102 and telescopic drive device 10
3, the pipette nozzle 10
5 are arranged at symmetrical positions with respect to the rotation axis 106 at both ends of the holder 104, and sample containers 1,
3 and the diluted sample from the dilution tube 2 to the reaction tube 5, these samples are sucked and weighed by the sampling pump 21 shown in FIG. 1, and the vertical drive device 101,
Transfer is performed using the rotational drive device 102 and the telescopic drive device 103, and when the injection into the reaction tube 5 is completed, the flow path is changed by the solenoid valve 107, and the pipette nozzle 105 at the other end is used to transfer the water extruded from the sampling pump 21. Cleaning is performed depending on the remaining amount. Thus, the sampling rate in the sampling operation can be significantly increased.

FIG. 4 is a detailed explanatory diagram of the first reagent pipetting device 11 and the second reagent pipetting device 13, and the same reference numerals will be used to explain parts having common configurations.

The first reagent pipetting device 11 and the second reagent pipetting device 13 include a holder 205 and a holder 20 that hold the pipette nozzles 39 and 40 at both ends, respectively.
5 vertical drive device 201 and rotation drive device 20
2, and the pipette nozzles 39 and 40 are disposed at opposite ends of the holder 205 at symmetrical positions with respect to the rotating shaft 205, and furthermore, the stirring nozzles 41 and 42 are provided as described above. It is as follows. When transferring the first reagent and second reagent from the first reagent bottle 10 and second reagent bottle 12 corresponding to the measurement item to the reaction tube 5, these reagents are transferred to the first reagent pump shown in FIG. 22. The second reagent pump 23 is used to aspirate and measure the reagent, and the above-mentioned vertical drive device 201 and rotation drive device 202 are used to transfer the reagent. When the injection into the reaction tube 5 is completed, the flow path is changed by the solenoid valve 203. However, the pipette nozzles 39 and 40 at the other end are cleaned by the remaining amount of water pushed out by the first reagent pump 22 and the second reagent pump 23. Thus, the reagent dispensing speed in the reagent dispensing operation can be significantly increased. Note that the first and second reagents are measured by filling microsyringes (not shown) in the first reagent pump 22 and second reagent pump 23 with water, and separating the reagent and water through air. Perform suction measurement in this state. Further, although not shown, the pipette nozzles 39 and 40 are equipped with liquid level sensors, and the vertical strokes are changed to prevent the outside of the pipette nozzles 39 and 40 from getting wet with the reagent more than necessary.

As mentioned above, the sampling pipette device 9, the first reagent pipette device 11, and the second reagent pipette device 13 are each provided with pipette nozzles at both ends, and the pipette nozzle at one end is used to aspirate and dispense a measured amount. Since the pipette nozzle at the other end is cleaned at approximately the same time, operations for sampling and reagent dispensing can be significantly speeded up.

When performing biochemical analysis using the automatic analyzer X, it is also possible to use the second reagent table 8 for the first reagent and the third reagent. In this case, the reaction table 6 repeats the operation of rotating the required steps after dispensing the sample, dispensing the first reagent in the second reagent table 8 at the second reagent discharge position g, and returning to the original position +1 again. Similarly, the third reagent can be dispensed by rotating the reaction table 6 in forward and reverse directions.

Next, the case where electrolyte analysis is performed using automatic analyzer X will be described. An electrolyte sampling pot is provided near the reaction table 6 and at a position C along the moving path of the sampling pipette device 9.

Electrolyte analysis can be performed in parallel with biochemical analysis, and the sample to be dispensed into the reaction tube 5 is automatically measured by the electrode measuring device 18 by discharging it to the electrolyte sampling pot position C, and the data is sent to the microcomputer 34. It will be sent and printed along with the biochemical analysis results.

In addition, a case will be described in which blood drug concentration is measured using the automatic analyzer X. reaction table 6
A fluorescence analyzer 15 is provided near the.
The operation at this time is almost the same as that for biochemical analysis, but since fluorescence measurement cannot be performed while the reaction table 6 is rotating, the fluorescence measurement is performed after the rotation is stopped. Therefore, although it is not possible to display the reaction time course, it is possible to perform highly sensitive measurements.

The fluorescence analyzer 15 is mainly used for precise measurement of drug concentration in blood. Light from a light source passes through an interference filter for excitation light (for example, 485 nm) and is applied to the reaction tube 5. Fluorescence in proportion to the drug concentration is emitted through an interference filter ( For example, 525 nm) is passed through the light receiving element, converted into digital data by an amplifier/AD converter, and then the concentration is calculated by a microcomputer.

In FIG. 1, reference numeral 19 indicates a reaction tube cleaning device, which is disposed near the reaction table 6 between the sampling pipette device 9 and the bead cleaning/discarding device 17, and is used to clean the reaction tube 6 after the measurement operation. When the placed reaction tube 5 reaches the cleaning position J, the cleaning pump device 24 discharges the cleaning liquid into the reaction tube 5 and suctions it to clean it, and discharges the waste liquid out of the system. The cleaning operation is performed in 8 stages, with alkaline detergent in the 2nd stage and 4 stages in the cleaning process.
Acidic detergent is injected into one stage, and pure water is injected into the other lines to ensure thorough cleaning.

Furthermore, the case of performing enzyme immunoassay (EIA) using bead solid phase using automatic analyzer X will be described. In FIG. 1, reference numeral 16 indicates a bead table, and 17 indicates a bead washing/discarding device, which are arranged on both sides of the fluorescence analyzer 15 in the vicinity of the reaction table 6. FIG. 7 is a detailed explanatory diagram of the bead solid-phase EIA measuring device.
In Figures 1 and 7, bead table 1
6 is used when performing bead solid-phase EIA, and bead table 16 corresponds to the measurement items.
It holds a plurality of bead stockers 25 in which EIA beads 404 are stored, and the bead table 16 is rotated by a rotary drive device 403, and the bead stocker 25 corresponding to the measurement item is rotationally transferred to the bead drop position k. do. The bead stocker 25 is equipped with a lever 405 for dropping beads 404 one by one, and an electromagnetic solenoid 406 can drop beads 404 one by one into the reaction tube 5 according to the measurement item.
The bead washing/discarding device 17 is used when performing bead solid-phase EIA, and is composed of a vertical drive device (not shown), a rotation drive device, a bead washing nozzle, and a bead suction nozzle. Wash the beads and discard the beads after measurement.

Figures 5 and 6 show an optical measuring device used for bead solid-phase EIA measurements.

Furthermore, the operation in bead solid-phase EIA measurement will be explained.

The reaction tube 5 into which the beads have been inserted is rotated and transferred to the sample dispensing position b by the rotation of the reaction table 6, and then transferred to the sampling pipette device 9.
The sample is dispensed. After the required time has elapsed, the first reagent is dispensed using the first reagent pipette device 11 and stirred through two steps. After the required time has elapsed, the reaction tube 5 is transferred to the bead cleaning/disposal device 17.
The bead is then transferred to the washing/discarding position of the reaction tube, and the washing liquid is discharged and sucked into the reaction tube to wash the beads. Next, reaction tube 5
is rotated to the second reagent discharge position, and the second reagent is dispensed by the second reagent pipette device 13. After the required time has elapsed, the reaction tube 5 is washed again in the bead washing/disposal device 7. Next, the third reagent on the second reagent table 8 is dispensed in the same manner, and after the required time has elapsed, it is measured by the optical measuring device 14. Reaction tube 5 after measurement
The used beads are suctioned and discarded by the waste nozzle of the bead cleaning/discarding device 17, and the used reaction tube 5 is further cleaned by the reaction tube cleaning device 19 and used again.

FIGS. 5 and 6 show an optical measuring device 14 used for bead solid-phase EIA measurements. The optical measurement device 14 is attached with an optical path selection device 308, and is capable of measurement for both normal biochemical analysis and bead solid-phase EIA. The optical path selection device 308 is
Luminous flux correction lens 306 and four total reflection mirrors 30
7 and a vertical drive device 309, which is located at the bottom for normal measurements, and the light from the light source lamp 141 passes through the condensing lens 142, passes through the reaction tube 5 containing the liquid to be measured, and is converted into a multi-wavelength luminous intensity. This is done using a total of Y. Vertical drive device 30 for bead solid-phase EIA measurement
9, the optical path selection device 308 is positioned above so that the light beam passes above the beads 404, and optical measurements are performed while avoiding the beads. The optical path selection device 308 has the advantage that it can perform measurements with a small amount of reaction liquid in normal measurements, and can also perform measurements for bead solid-phase EIA using the same multi-wavelength photometer.

The aforementioned operations are then performed using the control device according to the predetermined sequence described in the embodiment.

In FIG. 1, the control device of automatic analyzer X is as follows:
It is composed of a power supply section 32, a microcomputer 33, an operation panel 34, and a personal computer 42 for data processing. Further, the personal computer 42 has a CPU
and keyboard 35 and CRT display device 3
6, a magnetic disk storage device 37, and a printer 38 for printing measurement results. The magnetic disk storage device 37 stores required data such as measurement request items for clinical tests.

The temperature control device 31 is used to keep the reaction temperature of the reaction tube 5 constant, and the first and second reagent tables 7 and 8 are kept at about 10°C by cold air to prevent deterioration of the reagents. The temperature is controlled.

It goes without saying that the embodiments of the invention of this application are not limited to the above-mentioned embodiments.

[Effects of the Invention] As is clear from the above embodiments, the present invention can be applied to automatic analysis using a large number of samples, a large number of types of reagents, a large number of reaction tubes, etc., and corresponding to a large number of measurement items. It has the advantage of being quick, accurate, and simple to use. Then, the main parts used for analysis operations based on a predetermined sequence are placed close to each other,
Moreover, since the operations are linked together, samples and reagents can be transferred over short distances in a short time, making the device more compact than conventional automatic analyzers. At the same time, speed and analytical ability can be significantly improved.

Furthermore, the present invention can be used not only for biochemical analysis but also for electrolyte analysis, blood drug concentration measurement, fluorescence analysis, and enzyme immunoassay (EIA) using bead solid phase, so that the same configuration can be used. The above-mentioned automatic analysis has great effects, such as being able to perform sample analysis continuously at high precision and at high speed.

[Brief explanation of drawings]

FIG. 1 is a plan view of an automatic analyzer according to an embodiment of the present invention, FIG. 2 is a sectional view of the same device in FIG. 1, and FIG. 3 is a schematic illustration of a sampling pipette device of the same device. Figure 4 is a schematic illustration of the first and second reagent pipette devices of the same device, Figures 5 and 6 are illustrations of the optical measurement device of the same device, and Figure 7 is an illustration of the bead table of the same device. be. X... Automatic analyzer, 1... Sample container for general specimens, 2... Dilution tube, 3... Sample container for emergency specimens,
4... Sample table, 5... Reaction tube, 6... Reaction table, 7... First reagent table, 8... Second reagent table, 9... Sampling pipette device, 10...
First reagent bottle, 11...first reagent pipette device,
12...Second reagent bottle, 13...Second reagent pipetting device, 14...Optical measurement device.

Claims (1)

[Claims] 1. A turret-shaped sample that holds a plurality of sample containers for general specimens on the outer periphery, holds the same number of dilution tubes as the sample containers for general specimens on the middle periphery, and holds sample containers for emergency specimens on the inner periphery. A table, a reaction table holding a required number of reaction tubes arranged concentrically on the outer periphery of the sample table so as to be able to rotate forward and backward; A first reagent table and a second reagent table are arranged adjacent to the reaction table for selectively dispensing the sample in the sample container into a reaction tube or a dilution tube with a pipette nozzle, and the pipette nozzle is connected to both ends of the reaction table. A sampling pipette device in which a holder held in a section is vertically, rotatably and horizontally movable so that when a pipette nozzle at one end is selectively dispensing, the pipette nozzle at the other end is alternately washed; and a first reagent. A pipette nozzle is disposed between the reaction table and the first reagent table and holds the pipette nozzle at both ends in order to dispense a required amount of a first reagent in a reagent bolt placed on the table into a reaction tube using a pipette nozzle. A first reagent pipetting device in which the holder can be moved up and down and rotated so that when the pipette nozzle at one end is dispensing, the pipette nozzle at the other end is alternately washed; and a reagent placed on a second reagent table. A holder is disposed between the reaction table and the second reagent table and holds the pipette nozzle at both ends in order to dispense the required amount of the second reagent and third reagent in the bottle into the reaction tube using the pipette nozzle. A second reagent pipette device that can be moved up and down and rotatably so that when the pipette nozzle at one end is dispensing, the pipette nozzle at the other end is alternately washed; and a reaction table for optically measuring the reaction liquid in the reaction tube. An automatic analyzer characterized in that it is equipped with an optical measurement device disposed in an intermediate portion consisting of a first reagent table and a second reagent table.