JPH0378585B2 - - Google Patents

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to an automatic analyzer that performs biochemical analysis and immunological analysis, and particularly to an automatic analyzer that speeds up analysis processing time in this type of automatic analysis. The present invention also relates to improvements in automatic analyzers that can dramatically improve reliability in measurement accuracy.

[Prior art and its problems]

Conventionally, various types of automatic analyzers have been proposed, and the automatic analyzer shown in Japanese Patent Publication No. 59-24380 is known as a typical example.

This automatic analyzer is configured to hold the required number of reaction vessels in a row in a loop, and rotate the reaction vessels 360 degrees + 1 pitch (for 1 vessel). This method has the advantage of high reliability in measurement accuracy because it can provide cell blanks and sample blanks.

However, although the above-mentioned automatic analyzer has various advantages, the analysis processing time is long and
The problem was that it could only process 180 sample positions per hour.

In order to solve such problems,
Automatic analyzers such as the one seen in No. 59-51357 have been proposed, and now some are capable of automatically analyzing as many as 720 samples per hour.

However, although automatic analyzers such as those shown in Japanese Patent Application Laid-Open No. 59-51357 can speed up the analysis process, they have the problem of not being able to obtain cell blanks or sample blanks. Therefore, there was a problem in that the reliability of measurement accuracy was low.

[Means and actions for solving problems]

The present invention was devised in view of the current situation, and its purpose is to significantly improve the number of samples processed per unit time, and to improve the reliability of measurement accuracy by measuring cell blanks and sample blanks. The aim is to provide an automatic analyzer that can dramatically improve performance.

In order to achieve the above object, the present invention includes a sample container holder holding a required number of sample containers, a reaction container holder holding a required number of reaction containers, and a container corresponding to a measurement item in the reaction container. A reagent dispensing device for dispensing a reagent, an optical measuring device,
The technical premise is an automatic analyzer comprising a cleaning device for cleaning reaction vessels after optical measurement has been completed, and the reaction vessel holder is arranged coaxially to hold the required number of reaction vessels in a loop shape. One of the outer holder and the inner holder is drive-controlled so as to intermittently transport the reaction containers one by one toward the first reagent dispensing position, and The other of the outer holder and the inner holder is drive-controlled so as to scan and rotate the held reaction container to the optical measurement position, and the outer holder and the inner holder have opposing portions of the portions where the reaction container is held. are opened and communicated with each other so that the reaction vessels can pass therethrough, and the reaction vessels held in one of the holders are transferred to the other holder through the openings after dispensing the first reagent, and the reaction vessels are transferred to the other holder. The replaced reaction container is characterized in that it can be transferred to one of the holders through the opening after the cleaning operation is completed.

〔Example〕

Hereinafter, the present invention will be described in detail based on embodiments shown in the accompanying drawings.

1 to 4 show a first embodiment of the present invention, and as shown in FIG. 1, an automatic analyzer A according to this embodiment stores a sample (serum) to be measured. a plurality of sample containers 1,
A sample cassette 2 that holds 10 sample containers 1 each, a drive device (not shown) that transports the sample containers 1 to the sample suction position a, and a sample container 1 that has been transported to the sample suction position a.
a sampling pipette device 4 for aspirating a required amount of sample from inside and dispensing it into a corresponding reaction container 5 of an outer holder 10 (to be described later); Exchange devices 30, 40 for transferring each reaction container 5 of the holder 20 at a predetermined position, and double pipette devices 6, 6 for aspirating and dispensing a required amount of reagent corresponding to a measurement item into the reaction container 5 at a predetermined position. ', an optical measurement device 7 that optically measures the reaction between a sample and a reagent at a predetermined wavelength after a predetermined period of time has elapsed, and a cleaning device 8 that cleans the reaction vessel 5 after the optical measurement operation has been completed.

The sample container 1 is made of a material such as synthetic resin and has a cylindrical shape with a bottom.

The sample cassette 2, as shown in FIG.
The above-mentioned required number of ten sample containers 1 is held, and the sample containers 1 are intermittently transferred to the sample suction position a via the drive device.

The sampling pipette device 4 has four arms 4b extending radially from a shaft 4a, and a pipette 4c is disposed at the other end of each arm 4b, and each pipette 4c further holds a sample. A sampling pump that aspirates the required amount of sample at the position a in Figure 1 and discharges it at the position b is connected in communication, and each pipette 4c moves from the sample suction position a to the sample dispensing position b and furthermore to the washing position c. The rotation is controlled at a predetermined timing around the shaft 4a until the end. This sample measurement method involves filling the suction system with water, separating the sample and water via air, and then suctioning and measuring the sample. Only the sample is then discharged. After this, washing water is passed from inside the system to each sample. Wash the inside of the pipette 4c. Note that this pipette 4c is equipped with a suction amount confirmation device (not shown) having a known configuration for checking the amount of sample, etc. sucked up, and detects the absolute amount of sample, etc. each time sampling is performed. , if the sample amount is insufficient, this is automatically corrected.

As shown in FIG. 2, the reaction vessel 5 is made of a material such as transparent synthetic resin and has a polygonal shape (in the illustrated embodiment,
It is formed into a substantially octagonal shape, and a magnetized metal holder 5a is fitted on its outer surface. A hole 5b through which the measurement light from the optical measuring device 7 passes is provided in the lower surface of the holder 5a.

Of course, the entire reaction vessel 5 may be made of metal or a magnetic adsorbent, but it is assumed that at least the portion through which the measurement light of the optical measuring device 7 passes is formed transparent.

The reaction vessels 5 thus formed are each held in a loop shape by the outer holder 10 and the inner holder 20, 49 each.

The outer holder 10 is formed into a ring shape, and has bottomed holding holes 11 at predetermined intervals into which the reaction vessels 5 are fitted and held.
50 have been established.

The outer holder 10 configured in this way is
It is intermittently transferred one pitch at a time clockwise in FIG. 1 via a drive device (not shown).

The holding hole 11 is formed to have substantially the same outer shape as each holder 5a, and the inner holder side thereof is
In particular, as shown in FIG. 3, the reaction vessels 5 are opened so as to be able to go in and out of the holding holes 21 of the inner holder 20, and the outer peripheral wall of each of the holding holes 11 has a known structure. Permanent magnets or electromagnets (not shown) are respectively provided. Further, on the outer circumferential wall side of the holding hole 11, a first reaction vessel 5 is placed.
The piston rod 3 of the exchange device 30 is pressed and transferred to the holding hole 21 of the inner holder 20 at the position shown in Figure f.
Holes 12 are opened for each of the holes 12 to appear.

The inner holder 20 is disposed inside the outer holder 10 and is formed in a ring shape with a smaller diameter than the outer holder 10. The inner holder 20 also has the same number of bottomed holding holes 21 as the outer holder 10, in which the reaction vessels 5 are fitted and held, at predetermined intervals.

The inner holder 20 is a driving device (not shown)
49 containers clockwise in Figure 1 through
The reaction container 5 held by the inner holder 20 is rotated in steps of 352.8 degrees, and as a result, the reaction container 5 held by the inner holder 20 is intermittently rotated by one pitch (one container) in the counterclockwise direction in FIG. be transported.

The holding hole 21 is formed to have approximately the same external shape as each reaction container 5, and the outer holder side thereof is
In particular, as shown in FIG. 3, each of the holding holes 21 has an opening so that the reaction vessel 5 can be taken in and out, and a permanent magnet or electromagnet (not shown) of a known structure is installed on the inner peripheral wall side of each of the holding holes 21. are arranged respectively. Further, on the inner circumferential wall side of the holding hole 21, there are holes 22 in which the piston rods 41 of the exchange device 40, which presses and transfers the reaction vessel 5 to the holding hole 11 of the outer holder 10 at the position shown in FIG. It has been established. Therefore, the holding hole 11 of the outer holder 10 and the holding hole 21 of the inner holder 20 are
The openings are formed so as to face each other.

In the illustrated embodiment, a case has been described in which a magnetic material is provided on the walls of each of the holding holes 11 and 21 of the outer holder 10 and inner holder 20, but it is also possible to make the entire outer holder 10 and inner holder 20 magnetic. Of course, it is also possible to adopt a structure in which the reaction container 5 is adsorbed and held.

The exchanging devices 30 and 40 are composed of actuators having a known configuration, particularly as shown in FIG.
1, the reaction vessel 5 held in the outer holder 10 is transferred to the inner holder 20 at the position shown in FIG.
The drive is controlled so that the reaction container 5 held in the inner holder 20 is transferred to the outer holder 10 at the position shown in FIG.

Double pipette devices 6 and 6' for dispensing reagents corresponding to measurement items are arranged on the left and right sides of the sample suction position a formed along the transfer path of the reaction container 5.
After aspirating the reagent in the reagent bottle 60 at the first reagent suction position e, the reagent is dispensed into the reaction container 5 held by the outer holder 10 at the first reagent dispensing position d, and the double pipetting device 6' After aspirating the reagent in the reagent bottle device 60' at the second reagent suction position h, the reagent is sucked into the inner holder 2 at the second reagent dispensing position g.
It is dispensed into the reaction vessel 5 which is maintained at zero. In this way, the reason why the second reagent is added after the reaction container 5 is transferred and held in the inner holder 20 is to measure the sample blank when the reaction with the first reagent is completed. The necessary correction of the measured value is made according to the value.

A first reagent bottle and a second reagent bottle corresponding to the measurement item are set in the reagent bottle devices 60 and 60', respectively. Thirty first reagent bottles and thirty second reagent bottles are set radially on the reagent tables 62 and 62', and the first reagent is always kept cool at 8°C to 10°C by the first reagent cooler 61. In addition, the second reagent is always stored at
It is kept cold between ℃ and 10℃.

The reagent bottle devices 60, 60' are controlled to rotate in forward and reverse directions based on commands from the control unit 74, and transport the reagent bottles corresponding to the measurement items to the reagent suction positions e or h at high speed. Note that each of the first and second reagent bottles to be set is set at a predetermined position and memorized in the control device.

Next, the double pipette device 6 has fixed arms 6b that rotate around a shaft 6a, and a pipette 6c is disposed at the other end of each arm 6b. The pipette 6c is connected to a reagent pump that aspirates the required amount at position e, warms it to 37°C, and then discharges it at position d in FIG.
The rotation from the reagent dispensing position d to the cleaning position m is controlled at a predetermined timing around the shaft 6a, and two pipettes having the same configuration are arranged to form one double pipette device 6. It is configured. This is to speed up reagent dispensing, and each pipette 6c is driven and controlled alternately.

In addition, the double pipette device 6' has two stirrers 9.
The double pipetting device 6 has the same structure as the double pipetting device 6 described above, except that it is arranged on two arms 6b' and performing the stirring operation at the position i in Fig. 1. The same reference numerals as used will be given, and detailed explanation thereof will be omitted here.

The stirring body 9 is driven integrally with each arm 6b',
The part immersed in the reaction solution during each stirring operation is attached to each arm 6.
It is automatically disconnected in conjunction with the driving operation of b′. For stirring by the stirring body 9, a bubble stirring method is adopted, and the bubbles are sent from a stirring pump (not shown).

The method for measuring the reagent described above is to fill the suction system with distilled water, separate the reagent and distilled water through air, and then measure the reagent by suction. Only the reagent is then discharged. The inside of each pipette 6c, 6c' is washed through washing water, and the outside is washed with distilled water.

In addition, the pipettes 6c and 6c' are equipped with a suction amount confirmation device (not shown) having a known configuration for checking the amount of reagent sucked up. is detected, and if the amount of reagent is insufficient, this is automatically corrected.

As shown in FIG. 1, the optical measuring device 7 forming a detection part or an observation point is used to colorimetrically measure the reaction state of the reaction container 5 held in the inner holder 20 at a predetermined position, and uses a well-known diffraction method. Similar to the structure of the grating type optical measuring device, there is a light source 70, an optical system 71 that collects the measurement light irradiated from the light source 70, a light dispersion element 72, and a light dispersion element 72, and the measurement light is transmitted to the reaction vessel 5.
and a light-receiving element 73 that receives the amount of light after passing through it for each predetermined wavelength, and 49 reaction vessels 5 are measured in one rotation operation of the inner holder 20. The reaction vessel 5 is optically measured 49 times at regular intervals to obtain the reaction time course.

As shown in FIG. 4, the amount of light of the wavelength corresponding to the measurement item received by the light-receiving element 73 is converted into a voltage, and the control section 74 processes the analysis value.
A storage unit 75 that stores measurement results, and an operation unit/display 76 that performs all operations of the automatic analyzer A.
and a printer 77, and the result is printed out by the printer 77. The control unit 74 controls each operation of the automatic analyzer A, calculates measurement signals, and makes judgments thereof.

In FIG. 4, reference numeral 78 is a stabilized power source, 79 is a power source, and 80 is the first and second reagent cooler 61, 61'.
A cold storage control section 81 indicates a constant temperature control section that heats and maintains the reaction liquid in the reaction container 5 held in the outer holder 10 and the inner holder 20 at a biological temperature.

The cleaning device 8 is configured to perform the cleaning operation in 11 steps from the position j to the position k of the inner holder 20, and at the position j, the reaction liquid is sucked and removed.
Disposal work is carried out, the second stage is the injection and disposal of cleaning water, the third stage is the injection of cleaning fluid, the fourth stage is to leave the injected cleaning fluid, the fifth stage is the disposal of the cleaning fluid, and the sixth to eighth stages. The washing water is sucked and disposed of in the 9th stage, the washing water is injected in the 9th stage, and the washing water is sucked and disposed of in the 10th and 11th stages. As the inner holder 20 rotates, the water blank of the reaction vessel 5 into which the washing water is injected in the ninth stage is measured and used as a cell blank value to correct the measured value.

Incidentally, the disposal of the reaction liquid and the injection and disposal of the cleaning liquid and cleaning water are performed by a cleaning pipe of a cleaning drive section (not shown), and the cleaning liquid and cleaning water are sent from the reaction vessel cleaning pump.

Next, the operation of the automatic analyzer A according to this embodiment will be explained.

When you turn on the start switch (not shown),
Sample container 1 held in sample cassette 2
is transferred to the sample suction position a, and after the required amount of serum specimen in the sample container 1 is aspirated via the sampling pipette device 4 at the sample suction position a, the sample is transferred to the outer holder 10 at the sample dispensing position b.
The serum sample is dispensed into the reaction container 5 held in the chamber.

The reaction container 5 into which the serum sample has been dispensed in this way is intermittently transferred one pitch at a time to the first reagent dispensing position d, and at the same position d, the first reagent corresponding to the measurement item is dispensed via the double pipette device 6. The required amount is dispensed.

After this, the reaction container 5 into which the first reagent was dispensed
is intermittently transferred to position f while being held in the outer holder 10, and at the same position f, the reaction vessel 5 is transferred to the inner holder 20 via the exchange device 30.
can be transferred to.

The reaction vessels 5 transferred to the inner holder 20 in this manner are intermittently transferred one pitch at a time in the direction (counterclockwise in FIG. 1) opposite to the direction of rotation of the inner holder 20 (clockwise in FIG. 1). , at position g in Figure 1, the required amount of the second reagent corresponding to the measurement item is dispensed via the double pipette device 6', and at position i, one pitch upstream, bubble stirring is performed by the stirrer 9. The reaction state of the reaction liquid in the reaction container 5 is measured colorimetrically by the optical measuring device 7. Incidentally, as described above, the reaction container 5 is used after the reaction container 5 is transferred from the outer holder 10 to the inner holder 20 until the second reagent is dispensed.
, the sample blank is measured by the optical measuring device 7.

After the measurement by the optical measuring device 7 has been completed, the reaction container 5 is then transferred to the cleaning device 8 and its interior is cleaned, and the reaction container 5 that has been cleaned is
At position 1 in FIG. 1, the sample is transferred from the inner holder 20 to the outer holder 10 by the exchange device 40, and then intermittently transferred to the sample dispensing position b.

FIG. 5 shows an automatic analyzer A according to a second embodiment of the present invention, and in this embodiment,
The basic structure and operation are the same as in the first embodiment, except that the cleaning device 8 is disposed on the outer holder side and the drive control of the inner holder 20 is changed. The reference numerals are given and detailed explanations thereof are omitted here.

That is, the automatic analyzer A according to this example
In this case, the cleaning device 8 is disposed on the outer holder side, and the reaction vessel 5 containing the cleaning water in the ninth stage is placed as shown in FIG.
The cell blank is transferred to the outer holder 10 via the exchange device 130 at the position shown in FIG. It has added functionality.

Therefore, the inner holder 20 according to this embodiment
First, as the first rotation, the empty reaction vessel 5 at the l position is rotated clockwise in FIG. 5 by 64.8 degrees. At this n position, the reaction container 5 containing the washing water is transferred from the outer holder 10 to the inner holder 20 via the exchange device 130.

Next, as a second rotation, the reaction container 5 at the n position is rotated in steps of 712.8 degrees counterclockwise in FIG. 5 and transferred to the q position. This is to transfer the reaction vessel 5 whose cell blank measurement has been completed from the inner holder 20 to the outer holder 10 using the exchange device 140 at the same position q.

After this, the inner holder 20 is rotated for the third and final time from the q position clockwise in FIG.
The holding hole 21, which has been rotated in steps of 280.8 degrees (39 containers) and becomes empty at position q, is transferred to the reaction container exchange device f. In this third step rotation, the holding hole 21 at the q position may be rotated counterclockwise in FIG. 5 by 79.2 degrees (11 containers) for transfer.

These three step rotations are considered as one cycle, and the reaction vessel 5 held in the inner holder 20
will be transferred.

As described above, in this embodiment, the optical measurement is performed by rotating the inner holder 20 approximately twice, so that the optical measurement value during steady rotation of the inner holder 20 can be stably measured, as shown in FIG. Therefore, the reliability of measurement accuracy can be further improved.

In each of the above embodiments, the outer holder 10 is transferred intermittently, the inner holder 20 is rotated in steps, and the sample and the first reagent are dispensed into the reaction container 5 held in the outer holder 10.
Although the explanation has been given by taking as an example a case in which optical measurement is performed by dispensing the second reagent into the reaction container 5 of the inner holder 20, the present invention is not limited to this. The holder 20 is intermittently transferred, the outer holder 10 is rotated in steps, and the sample and the first reagent are dispensed into the reaction container 5 held in the inner holder 20.
It is also possible to perform optical measurement by dispensing the second reagent into the reaction container 5 of the outer holder 10.

Further, in each of the above embodiments, the case where one reaction container 5 is replaced with the outer holder 10 or the inner holder 20 has been explained as an example, but the present invention is not limited to this, and for example, two containers can be replaced at the same time. By configuring it to do so, it becomes possible to perform twice as many processes per unit time. Of course, in this case, the number of reaction vessels and devices such as sampling pipette devices and double pipette devices are also required to be doubled.

〔Effect of the invention〕

As explained above, the present invention holds a reaction container in an outer holder and an inner holder, drives and controls one of these holders so that the reaction container is intermittently transferred toward the first reagent dispensing position, and controls the drive of the other. driving and controlling the holder to scan and rotate the reaction container to the optical measurement position;
Moreover, the reaction container held in one of the holders is transferred to the other holder after dispensing the first reagent, and the reaction container transferred to the other holder is transferred to the one holder after the cleaning operation is completed. Since it is configured so that the sample can be transferred to another holder, the number of samples processed per unit time can be greatly increased.Furthermore, since the cell blank and sample blank of the reaction container held in one holder can be measured, the automatic analyzer can This has excellent effects such as dramatically improving the reliability of measurement accuracy.

[Brief explanation of drawings]

FIG. 1 is an explanatory diagram schematically showing the overall configuration of an automatic analyzer according to a first embodiment of the present invention, FIG. 2 is an exploded perspective view of a reaction vessel and a holder, and FIG. 3 is an exploded perspective view of an outer holder and an outer holder. A partially cutaway plan view showing the details of the structure of the inner holder, FIG. 4 is a block diagram showing the driving principle of the automatic analyzer, and FIG. 5 schematically shows the main parts of the automatic analyzer according to the second embodiment of the present invention. FIG. 6 is a graph diagram showing how to obtain optical measurement values using the automatic analyzer. Explanation of the code, A... Automatic analyzer, a... Sample suction position, b... Sample dispensing position, f, l
... Reaction container exchange position, 1 ... Sample container, 5
...Reaction vessel, 6,6'...Double pipette device,
7... Optical measuring device, 8... Cleaning device, 10...
Outer holder, 11... retaining hole of outer holder, 20... inner holder, 21... retaining hole of inner holder, 30, 40... exchange device.

Claims (1)

[Claims] 1. A sample container holder that holds the required number of sample containers, a reaction container holder that holds the required number of reaction containers, a reagent dispensing device that dispenses a reagent corresponding to the measurement item into the reaction container, and an optical measurement device. and,
and a cleaning device for cleaning a reaction vessel after optical measurement, wherein the reaction vessel holder is a coaxially arranged outer holder that holds a required number of reaction vessels in a loop shape. and an inner holder, and one of the outer holder and the inner holder holds one reaction vessel.
The drive is controlled so that the containers are intermittently transferred toward the first reagent dispensing position, and the other of the outer holder and the inner holder is configured to scan and rotate the reaction containers held therein and transfer them to the optical measurement position. The drive is controlled, and opposing portions of the outer holder and the inner holder where the reaction vessels are held are opened and communicated with each other so that the reaction vessels can pass through, and the reaction vessels held by one of the holders are , after dispensing the first reagent, the reaction container is transferred to the other holder through the opening, and the reaction container transferred to the other holder is transferred to the one holder through the opening after the cleaning operation is completed. An automatic analyzer characterized in that: