JPS62133355A - Eia automatic analyzer - Google Patents

Abstract

PURPOSE:To make automatic analysis possible by rotating and transferring the reaction vessels with which a cleaning operation ends to a bead supplying position and rotating the vessels in the same direction after the supply of the beads then transferring the vessels from the cleaning end position to the position advanced by >=1 pitches in the direction opposite from the rotating direction. CONSTITUTION:A driving device 11 transfers the reaction vessels 4 in the bead supply ing position (k) again to the position (c) advanced by 60 vessels in a counter-clockwise direction by step rotations upon ending of the operations for supplying the beads, discarding the beads, discharging the reactive liquid and cleaning the beads. As a result, the respective vessels 4 are intermittently transferred by each one pitch in the clockwise direction which is the rotating direction opposite from the step rotating direction at every step rotation of a holder 5. More specifically, the vessels 4 are intermittently transferred from a sample dispensing position (b) to the 1st reagent dispensing position (d), reactive liquid discharging and bead cleaning position (e), 2nd reagent dispensing position (g), bead discarding position (j), bead supplying position (k), fluorescent detecting position (l), optical measuring position (n) and cleaning position. The vessels arrive at the cleaning end position (p), where the vessels are reused. The immunological analysis by the immunological measurement method (EIA) is thus automated.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to an EIA automatic analyzer that can fully automate immunoassay using an antigen-antibody reaction (hereinafter referred to as EIA). .

[Prior art]

In recent years, EIA has become popular as an immunoassay method that utilizes antigen-antibody reactions.
is now being carried out. In such EIA, antibody or antigen insolubilized carriers (hereinafter referred to as beads), which are formed by immobilizing antibodies or antigens on glass beads, glass chips, silicon disks, synthetic resin beads, etc., are used. , carcinoembryonic antigen, HBe antigen, HBe antibody, etc., are frequently used in kits for routine measurement.

Generally, in measurements using beads, an antibody reaction is carried out in a predetermined reaction container into which an immunoreaction measurement solution is injected, and then an antibody labeled with a predetermined enzyme (also referred to as a buffer; hereinafter referred to as the first reagent) is prepared. ) was further added to perform the second stage antigen-antibody reaction, and then the beads after the reaction were thoroughly washed to separate B/F, and then transferred to a separately prepared enzyme reaction container where the enzyme activity was determined. Measurement method (non-competitive sand inch method), ■Presence of antigen or antibody labeled with a specified enzyme during the reaction between the specimen and beads, and then thorough washing of the beads after the reaction and B/F separation. This is carried out by a method (competitive method) in which the enzyme is transferred to a separately prepared container for enzyme reaction and the enzyme activity is measured there.

[Problems with conventional technology]

However, in such conventional EIA analysis, it is necessary to manually supply beads to a reaction container, dispose of the beads, wash the beads after the sample and beads have reacted, and transfer the beads. Moreover, since these tasks must be performed at predetermined timings taking into account reaction time, these tasks are extremely complicated, and there are problems in that workers must be present at all times for analysis. was.

[Purpose of the invention]

The present invention was devised in view of the current situation, and its purpose is to completely automate the supply and disposal of beads and the cleaning of beads after reaction, thereby making it possible to completely automate the supply and disposal of beads and the cleaning of beads after reaction. The aim is to provide an EIA automatic analyzer at a low price, which allows analysis to be performed much easier than EIA analysis.

[Structure of the invention]

In order to achieve the above object, the present invention includes a reaction container holder that holds a required number of reaction containers in a loop shape, and a reaction container that is disposed at a predetermined position along the intermittent transfer direction of the reaction containers held by the holder. sample dispensing device, reagent dispensing device,
An EIA automatic analyzer comprising a bead disposal device, a bead supply device, an optical measurement device, a cleaning device, and a transfer device that transfers the reaction container held in the reaction container holder to the working position of each device. The reaction container holder is rotated stepwise to transfer the reaction container that has been cleaned by the cleaning device to the bead supply position, and the same reaction container to which beads have been supplied at the same position is again rotated in the same direction as the step rotation direction. The drive is controlled so as to move by step rotation from the cleaning end position to a position one or more pitches in the direction opposite to the step rotation direction.

〔Example〕

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

The EIA automatic analysis device A according to this example is as follows.

As shown in No. 1121, a sample holder 3 holds a required number of sample containers 1 in a loop shape on the outer circumference side, and holds a required number of auxiliary containers 2 in a loop shape on the inner circumference side, which are used for example for emergency specimens. , a reaction container holder 5 which is rotatably arranged on the outer periphery of the holder 3 and holds a required number of reaction containers 4 in a loop shape, and a buffer or enzyme reaction solution arranged on the inner periphery of the holder 5. a reagent table 6 containing a specimen or an auxiliary container 2 in the sample container 1;
pipette device 8 for dispensing the required amount of the sample in the reaction container 4;
and a plurality of reagent bottles 9 placed on the reagent table 6.
A first reagent pipette device 10 dispenses the required amount of the first reagent (buffer) in the reaction container 4 into the reaction container 4, and an enzyme reaction solution (hereinafter referred to as “buffer”) in the plurality of reagent bottles 9b placed on the reagent table 6. , referred to as the second reagent) into the reaction vessel 4, and the state of the enzyme reaction by the labeled enzyme (peroxidase) bound to the surface of the beads 3 is analyzed by spectrophotometry at a wavelength of 492 nm. an optical measurement device 13B that performs absorption photometric analysis using measurement light of another predetermined wavelength, a drive device 14 that rotates the sample holder 3 intermittently at required timing, and a reagent table 6 that rotates the reagent table 6 in forward and reverse directions, respectively. a drive device 7 that controls rotation to transfer reagent bottles 9a and 9b corresponding to measurement items to predetermined first and second reagent suction positions; and a drive control 11 that controls rotation of the reaction container holder 5 at a required timing. , a bead supply device 1 that supplies beads B to the reaction container 4 after washing
5, a bead disposal device 16 that discards the beads in the reaction container 4 after the measurement has been completed, and a cleaning device 17A that drains only the reaction liquid in the reaction container and washes the inside of the reaction container and the beads B immediately before dispensing the second reagent. , a cleaning device 17B that cleans the inside of the reaction vessel after measurement, and a stirring device R.

The sample holder 3 is rotated clockwise in FIG. 1 via the drive device 14 to intermittently transport each sample container 1 one after another to the sample suction position a.

Each sample container 1 contains a required amount of a specimen (serum) to be measured. As a matter of course, the auxiliary container 2 is also intermittently transferred together with the sample container 1 as the sample container 1 is intermittently transferred. Further, as shown in FIGS. 1 and 2, this sample holder 3 is pivotally supported on a support base 18 that can slide linearly to the left, and this sliding operation constitutes a sample holder sliding device. This is done when the pipette device 8 aspirates the sample in the auxiliary container 2 by the actuator 11, and the amount of movement is as follows:
As shown in FIG. 2, the distance between the sample container 1 and the auxiliary container 2 is controlled to be approximately the same as the longitudinal distance l. Note that the sliding operation of the sample holder 3 is not limited to an actuator, and a known sliding mechanism such as a rack and pinion mechanism can be applied, for example.

When the predetermined sample container 1 or auxiliary container 2 is transferred to the predetermined sample suction position a in this way, the required amount of the sample in the sample container 1 or the auxiliary container 2 is aspirated via the pipette device 8, and then As will be described later, beads B are dispensed into corresponding reaction vessels 4 supplied with beads B by the bead supply device 15.

The pipetting device 8 has the same structure as a known pipetting device.
Although not shown, there is an arm with one end supported by a shaft, a pipette disposed at the other end of this arm, and a sample ring pump that is communicatively connected to this pipette and aspirates the required amount of sample and discharges it into the reaction container 4. , and a drive device that controls the rotation of the arm from the sample suction position a to the sample discharge position and further to the washing position at a predetermined timing around an axis, and controls the movement up and down at each position. This method of measuring a sample involves filling the suction system with water, separating the sample and water via air, then suctioning and weighing the sample, discharging only the sample, and then passing washing water through the pipette. Clean the inside of. During this cleaning, the pipette is of course set at the pipette cleaning position (not shown). In addition, this pipette is equipped with a suction amount confirmation device (not shown) having a known configuration for checking the suction amount of the sample, etc.
The system is configured to detect the absolute amount of a specimen, etc. each time sampling is performed, and automatically correct the sample amount. The reaction vessel holder 5 is rotationally controlled in the counterclockwise direction in FIG. 1 via the driving arrangement 1 as described above. A pulse motor is applied to the drive device 11, and the plate 11 currently held in the reaction container holder 5 is located at a position P that is one pitch before the sample dispensing position and where the cleaning operation by the cleaning device 17B has been completed. The reaction container 4 is rotated by a first step (ie, 85.5 degrees) and transferred from the same position p to the bead supply position k, which is 19 containers counterclockwise in FIG. 1 (ie, 85.5 degrees). Due to this first step rotation, the reaction vessel 4, which was at the position m in Fig. 1 after the absorption photometric analysis by the fluorescence detector 13A was completed, has also moved forward by 19 vessels in the counterclockwise direction in Fig. 1 from the same position m. The beads are transferred to the bead disposal position j arranged at the position j, and at the same position j, the used beads in the reaction container 4 are discarded by the bead disposal device 16, and at the same time, they are transferred to the position f immediately before the second reagent is dispensed. The reaction container 4 that was there is transferred to the reaction liquid discharge/bead cleaning position e, which is located 19 containers counterclockwise in FIG. 1 from the same position f, and is cleaned by the cleaning device 17A.

When these four steps of supplying beads, discarding beads, discharging reaction solution, and cleaning beads are completed, the drive device 11 moves the reaction container 4 located at the bead supply position k again counterclockwise in FIG. 1 by 60 containers ( In other words, it is transferred to the advanced position C by 270 degrees) by the second step rotation.

As a result, each reaction vessel 4 is placed in the first position of the reaction vessel holder 5.
And for each second step rotation, one pitch is intermittently transferred in the clockwise direction in FIG. Reaction liquid discharge/bead washing position e, second reagent dispensing position g, bead disposal position j, bead supply position k,
It is intermittently transferred to a fluorescence detection position, an optical measurement position n, and a cleaning position. Slightly above the bottom of each reaction vessel holding hole of this reaction vessel holder 5, a light guiding hole is provided which horizontally penetrates the reaction vessel holding hole. The reaction liquid in the rectangular cylindrical reaction vessel 4 receives fluorescent light and/or light guided through the light guide hole.
Alternatively, each optical characteristic is measured using measurement light.

The beads B transferred as described above and supplied through the bead supply neck 15, which will be described later in the bead supply position 1'&, are filled with iron, cobalt, nickel, etc. as shown in Fig. 3. As shown, it is made ferromagnetic to have both polarities.

These may be encapsulated in powder form and made ferromagnetic so as to have bipolar properties; however, they are usually in the form of small lumps (
It is preferable to use ferromagnetic material in the form of (a) from the viewpoint of manufacturing. As such small-sized ferromagnetic material, particles with a diameter of about 2 to 4 mm are suitable.

A carrier layer (b) made of a desired material is placed on the outer periphery of this ferromagnetic material.
Beads B are obtained by coating the surface with a desired antibody or antigen and immobilizing the desired antibody or antigen on the surface. Covering carrier layer (
The material for (b) may be the same as that used for beads as conventional antibody or antigen insolubilization carriers, for example,
Examples include glass and synthetic resin. However, other solids can be used as long as they can immobilize antibodies or antigens and are stable in aqueous media. Among these, it is preferable to use synthetic resins, such as polystyrene.

When using glass, coating methods include pouring molten glass into a predetermined mold, introducing the ferromagnetic material into the mold, and slowly cooling it, or coating the outer periphery of the ferromagnetic material with hydrous lower alcohol of lower alkoxysilane. A solution is applied and dried to form a gel-like film, and this process is repeated multiple times to form a hydroxide silane glass gel film of a predetermined thickness, and this is further heat-treated to convert it into an oxide glass film. Examples include methods. On the other hand, in the case of synthetic resin, methods include a method in which molten resin is poured into a mold and a ferromagnetic material is introduced and molded, and a method in which a resin layer is grown on the outer periphery of the ferromagnetic material by a solution coating method.

The shape of the beads B obtained in this way is a small sphere or a small piece. Usually, it is preferable to form it into a small spherical shape from the viewpoint of surface planting, and for example, the diameter thereof is suitably about 3 to 6 mm.

μ ′−ノ− ＾ くん−l
↓ 口 I ↓ The method itself can be carried out by a method known in the art. This immobilization can be broadly divided into those based on chemical bonding and those based on physical adsorption. A typical example of a method using chemical bonding is to introduce hydroxyl groups into the surface, especially the surface of a glass material, by acid or alkali treatment, and then react with a silane coupling agent such as γ-7minoprobyltriethoxysilane. Examples include a method of chemically bonding a desired antibody or antigen to a carrier using glutaraldehyde;
Examples of the physical adsorption method include a method in which beads B are immersed in a solution of the desired antibody or antigen and left for a long period of time. In either method, it is preferable to roughen the surface of the beads B, and in some cases, the beads B may have a shape with a large number of small protrusions formed during the formation of the carrier layer (B).

The desired antibodies and antigens to be immobilized may be selected from those known in the art, and specific examples include anti-insulin antibodies, anti-AFP antibodies, anti-ferritin antibodies, CEA antibodies, anti-TSH antibodies, Examples include anti-HBe antibodies and corresponding antigens.

The reason why beads B are made of a bipolar ferromagnetic material is to stir the reaction solution without contact. In this stirring device R, as shown in FIG. 4, the base body r is disposed on the lower surface of the reaction vessel holder 5 with a slight distance therebetween. and,
The magnets Rs and RN are arranged alternately so that they are located directly below the bottom of the reaction container 4 held by the reaction container holder 5 when the reaction container 4 is at the stop position before and after the first and second step rotations. It is set up. Therefore, according to this stirring device R, when the beads B are immersed in the sample or reaction solution in the reaction container 4, each time the reaction container 4 passes over the magnets R5 and RN by step rotation. , beads B and permanent magnet R
5. Beads B are transferred in the sample/reaction liquid in the same container 4 by the suction φ/repulsion with RN, and the sample/reaction liquid is stirred by this transfer of beads B.

The drive device 7, which controls the forward and reverse rotation of the reagent table 6, transports the reagent bolts 9a and 9b containing reagents corresponding to the measurement items to the first reagent suction position d and the second reagent suction position g, as described above. do. The first and second reagent bottles 9a and 9b arranged on this table 6 are set at predetermined positions and memorized in the control device.
a reagent bottle 9a containing a reagent corresponding to the measurement item;
9b is transferred by each of the drive devices 7 described above.

In this way, the reagent bottles 9a, 9 corresponding to the measurement items are
When b arrives at a predetermined reagent suction position, the corresponding buffer or enzyme reaction solution is dispensed into the corresponding reaction container 4 for each required layer via the first and second reagent pipette devices 10.12, respectively.

The first and second reagent pipettes MIO and 12 are
- A gear 30a is carved on the side edge.

It is composed of a rack 30 having a pipette 34 and a pinion 31 that meshes with a gear 30a of this rack 30. By rotating the pinion 31, the rack 30 moves forward and backward in a linear direction. That is, when the pinion 31 rotates counterclockwise in FIG. 1 for a certain period of time, the rack 30 moves forward to the left in FIG. 1, reaches the reagent suction position, and stops directly above i. After this, the support 35 supporting the first and second reagent pipette devices 10.12 is lowered, whereby the pipette 34 is inserted into the reagent bottle 9 and the pipette 34 then dispenses the required amount of buffer or enzyme reaction solution. After suction and these operations are completed, the support stand 35 is raised, and the pinion 31 is then rotated several rotations clockwise in FIG. This allows rack 3
0 moves backward to the right in FIG. 1 and is set directly above the reagent discharge positions d and g. Thereafter, the support stand 35 is lowered again, the pipette 34 is inserted into the reaction container 4, and the required amount of the aspirated buffer or enzyme reaction solution is discharged. When the discharging operation of the buffer or enzyme reaction solution is completed in this way, the pinion 31 rotates clockwise in FIG. 1 again, and the rack 30
is returned to its original position. After returning to this original position, the pipette 34 is cleaned. Note that the reagent aspirated into each pipette 34 fills the suction system channel with water.
The reagent and water are separated by air, only the reagent is pushed out by a reagent pump during discharge, and the inside of the flow path is cleaned with water filled in the flow path. Konogin, Pipette 34
is set to the wash position. Although not shown, a heating device and a suction amount confirmation device are installed in the reagent suction channel, which detects the suction amount at the reagent suction position and automatically corrects the reagent amount. It is configured. Note that a known sampling pump is used as the reagent pump. In the figure, 33 is a guide roller of the rack 30.

The cleaning device 17A is located between the first reagent dispensing position d and the second reagent dispensing position Hg, and is 19 counterclockwise in FIG. 1 from a position if one pitch before the second reagent dispensing position g. It is arranged at a position e where the container has advanced and is used to wash the inside of the reaction container 4 and the beads B in the same volume ri 4 transferred to the same position e at the time of the first step rotation. Figures 5 and 6
As shown in the figure, a pair of water injection pipes 41 inject washing water 44 into the reaction container 4 at high speed, and a pair of water injection pipes 41 that inject washing water 44 into the reaction container 4 and suck and discharge the washing water 44 injected into the container 4 together with the sample-reaction liquid to the outside of the container 4. A pair of drain pipes 42, a pair of water injection pipes 41 and a drain pipe 42
a support body 40 which is arranged and held diagonally, and a lifting device 4 that guides the support body 40 up and down at a predetermined timing to insert or remove the six tubes 41 and 42 into the reaction vessel 4.
3, a pump 45 that pumps washing water, and a pump 47 that sucks the pre-purified water, etc. in the reaction vessel 4 at high speed and pumps the pre-purified water, etc. to the drain section 46. When inserted into the reaction vessel 4, the water injection pipe 41 is formed to a length that allows it to be set at a position slightly apart from the bottom of the reaction vessel 4, and the water injection pipe 41 is shorter than the drain pipe 42, and is preferably set at a position slightly apart from the bottom of the reaction vessel 4. It is formed in a length that is located at the top.

Therefore, the inside of the reaction container 4 and the beads B are agitated and washed by the pre-purified water 44 sprayed at high speed from the water injection pipe 41, and the surface of the beads B is rolled in the container 4 by the water pressure of the sprayed washing water. This washing water is then suctioned at high speed from the drain pipe 42 and drained to the drain section 46 together with the specimen and reaction liquid.

The bead disposal device 16 is connected to the first reagent dispensing position g from the second reagent dispensing position g.
Beads placed at position j after being transferred for 15 containers in the yJ direction, and for which optical measurement by the fluorescence detector 13A in the reaction container 4, which was transferred to the same position j by the first step rotation, have been completed. After suctioning B with a vacuum pump (not shown), it is configured to be disposed of at a predetermined bead disposal position.

The bead supply device 15 is disposed at a position K, which is the position where the washing is completed and is 19 containers ahead from a position P, which is one pitch in the counterclockwise direction in FIG. 1 from the sample dispensing position. The configuration of this bead supply device 15 is shown in FIG.
To explain based on figure g, 3 types are used for different EIA analyzes such as globulin, RA, and macroglobulin.
Three containers T each containing a required number of beads of the same type B I + B2 * B3.

U, V, and a pipe-shaped conductor 51a that successively guides each bead BI + B 2 * B3 from these bead containers T, U, and V to a selector 50 to be described later.
, 51b, 51c, and each of these conductors 51a, 51b, 5
It is comprised of a selector 50 that selects beads corresponding to the measurement item from among the beads supplied by 1c and supplies them to the reaction vessel 4.

Each of the bead containers T, U, and V is formed into a substantially funnel shape, and the inner diameter of the lower end portion and the inner diameter of each conductor 51a, 51b, and 51c connected to these, respectively, are the same as that of each bead container T, U.
, V are formed to have a slightly larger diameter than the outer diameter of each of the beads B, , B2, and B3 to be accommodated in the beads.

The selector 50 includes a cylindrical inner cylinder body 52 and a cylindrical inner cylinder body 52.
and an outer cylindrical body 53 that is fitted in the inner cylindrical body 53 so as to be rotatable and movable forward and backward. A drive control device 57 is operatively connected to move the body 52 straight forward and backward by a predetermined distance.

A shallow groove 54 is formed along the circumferential direction on the outer circumferential surface of the inner cylinder 52, and one bead receiving hole 55 is formed roughly at the bottom of the groove 54. This bead #accommodating hole 55 has a size that can accommodate any of the beads B l * B 2 * B 3 and a depth that can accommodate only - beads, and when beads are accommodated in the accommodation hole 55, Even if the inner cylindrical body 52 rotates within the outer cylindrical body 53, it will not fall out of the bead accommodation hole 55 and will not interfere with the rotation.

The outer cylindrical body 53 is formed into a pipe shape, and its inner diameter is slightly larger than the outer diameter of the inner cylindrical body 52. The outer cylindrical body 53 is provided with conductors 51a.

Each bead BI transferred by 51b and 51c
* Guide B2 + B3 to the bead accommodation hole 55 of the inner cylinder 52 fitted to the outer cylinder 53, and guide the conductor 51
Three through holes 55 to which a, 51b, and 51c are connected for communication.
a, 55b, 55c.

A guide hole 56 is provided through the wall of the outer cylindrical body 53 for sorting and transferring the beads B accommodated in the bead accommodation hole 55 to the reaction vessel 4. These three through holes 55a.

55b and 55c are outer cylindrical bodies 53 that face the grooves 54 when the inner cylindrical body 52 is stopped at a predetermined bead selection position.
These are the surface portions that are opened along the circumferential direction of the outer cylinder 53 at predetermined intervals. On the other hand, the guide hole 56 extends from the opening portion of the through holes 55a, 55b, and 55c to the outer cylindrical body 53.
When the hole axis of the bead storage hole 55 and the hole axis of the guide hole 56 match at a bead transfer position spaced a predetermined distance along the axial direction of the beads, the beads naturally fall and are transferred to the reaction container 4. It is located in a convenient location.

Incidentally, the through holes 55a, 55b, 55c and the guide hole 56 are of course opened to have a diameter that allows the corresponding beads to pass through smoothly. A tubular conduit may also be used for communication between the two. Therefore, this bead supply device 1
5, when selecting beads B corresponding to the measurement item and supplying them to the reaction container 4, three bead containers T are selected.
, U, V accommodated in each bead B l , B2 +
B3 is a conductor 51a.

The selector 5 is guided in series by 51b and 51c.
0 and is set in a standby state. When selecting and supplying beads B, for example, to the reaction container 4 from this state, first, the drive control device 57 is rotated to align the hole axes of the bead accommodation hole 55 and the through hole 55a. Then, the beads B fall under their own weight and are accommodated in the bead accommodation hole 55. At this time, it is assumed that the beads B1 accommodated in the bead accommodation hole 55 are accommodated in a state in which they do not protrude outward from the outer peripheral surface of the inner cylinder body 52. When the beads B are accommodated in the bead accommodation hole 55 in this way, the drive control device 57 presses (or suctions) the inner cylinder 52, moves the inner cylinder 52 straight, stops, and then moves the inner cylinder 52. It is rotated so that the hole axes of the bead accommodation hole 55 and the guide hole 56 match. Then, the beads B accommodated in the bead accommodation hole 56 fall under their own weight and are transferred from the guide hole 56 to the reaction container 4 . beads B
2 or B3 can also be selected arbitrarily according to the measurement item using the same procedure as above, and information on the type of beads to be accommodated in the reaction vessel 4 can be input into the control device in advance to control the drive control device. By controlling the configuration, beads corresponding to measurement items can be sequentially supplied to a plurality of reaction vessels 4.

The fluorescence detector 13A is located in the reaction vessel 4, which has been moved to a position three vessels ahead in the clockwise direction in FIG. 1 from the bead supply position k.
It is constructed and arranged so that the state of the enzymatic reaction caused by the labeled enzyme bound to the surface of the beads 3 inside is analyzed spectrophotometrically at a wavelength of 492 nm.

The optical device 13B forming a detection section or observation point is for colorimetrically measuring the reaction liquid in the reaction container 4, which has been transferred to a position n, which is four containers ahead of the fluorescence detection position in the clockwise direction in FIG. A light source 20, a reflecting mirror 21 that reflects the measurement light emitted from the light source 20 to the diffraction grating 22 after passing through the reaction container 4, and the measurement light reflected by the diffraction grating 22 and separated into predetermined wavelengths. A required number of light receiving elements 23 that receive light at each predetermined wavelength, and data that converts the amount of light received by the light receiving elements 23 into voltage, and selects only the analysis values corresponding to the measurement item from among the voltage-converted analysis values. Processing section 2
4 and 1 display section 25. This optical device 13B is arranged so that the reaction container 4 crosses the optical path S when the reaction container holder 5 is in a rotating state, and the reaction liquid in the reaction container 4 that crosses the optical path S is The absorbance is measured and displayed on the printer 25. This optical path is connected to a part immediately before the washing position (in the illustrated embodiment, the reaction vessel 4 is located at an angle of 54° in the direction of the meter from the sample dispensing position).
(passing approximately through the center of).

The cleaning device 17 is configured to perform 7-stage cleaning, with cleaning water flowing in the first or second stage, water cleaning in the other cleaning lines, and water being stored in one of the -wood lines.
Since the details of the configuration are the same as those of known cleaning devices except that the blank value of the reaction container 4 itself is configured, the explanation thereof will be omitted here.

Next, to explain the operation of the EIA automatic analyzer A according to this embodiment, first the start switch (not shown)
When turned on, the reaction vessel 4 at the washing end position p is transferred to the bead supply position by the first step rotation in the counterclockwise direction of Ei%1 by the reaction vessel holder drive device a l l, and the bead supply position is Beads B corresponding to the measurement items are selected via the device 15 and supplied into the container 4.The container 4 into which the beads B are then supplied is moved counterclockwise in FIG. 881 by the reaction container holder driving device 11. The beads are transferred from the bead supply position k to the sample dispensing position by the second step rotation. When the reaction container 4 is transferred to the sample dispensing position in this way, the pipette of the pipette device 8 simultaneously moves the required amount of sample from the sample container l of the sample container group 3 at the sample suction position fia. After suction, the sample is rotated until it reaches the one reaction container position, and the required amount of specimen is dispensed into the reaction container 4 located at the sample dispensing position. In addition, if urgent specimen testing is required,
When the emergency sample serum is stored in the auxiliary container 2, it is detected that the auxiliary container 2 has arrived at the sample suction position, and the cutter 19 is automatically pressed to move the support base 1.
8 in a straight line, and the auxiliary container 2 is controlled to be located directly below the pipette of the pipette device 8. After that, the pipette aspirates the sample in the same container 2, and then moves it to the reaction container 4 in the same manner as described above. Dispense the sample into This auxiliary container 2
When it is no longer necessary to aspirate the sample in the tube, the cutter 19 is controlled to return to its original position so that the sample container 1 is directly below the pipette. Of course, this auxiliary container 2 may be used not for emergency specimens but for general specimens, or may be used to aspirate the specimen in the auxiliary container 2 after aspirating the specimens from all sample containers 1. good.

Next, the reaction container holder 5 moves the reaction container 4 into which the sample has been dispensed by the first and second step rotations toward the first reagent dispensing position d in the clockwise direction in FIG. The zero reaction container 4 to be transferred is at the first reagent dispensing position f! When reaching Ld, the rotation of the reagent table 6 is controlled in synchronization with this,
A first reagent bottle 9a containing a buffer is set at the reagent suction position, and a required amount of buffer is aspirated from inside the bottle 9a via the first reagent pipette device 10 by the pipette 34, and is aspirated into this pipette. The required amount of buffer is dispensed into the reaction vessel 4 which has arrived at the first reagent dispensing position d. Next, the reaction vessel 4 in which the buffer has been dispensed is intermittently transferred one pitch at a time in the clockwise direction in FIG. The reaction vessel 4 that has arrived at the position Mf in front of the pitch is moved to the cleaning position fe by the first step rotation of the reaction vessel holder driving device 11.
At the same position e, the reaction liquid in the reaction container 4 is suctioned and discharged by the cleaning device 17A, and
After the inside of the reaction container 4 and the surface of the beads B are washed with the washing water 44, the second
It is transferred to the second reagent dispensing position g by the step rotation.

In synchronization with this, the reagent table 6 is rotationally controlled, and the reagent bottle 9b containing the second reagent, which is an enzyme reaction solution corresponding to the measurement item, is transferred to the second reagent suction position i, and the second reagent pipette device 12, a required amount of the second reagent is aspirated.

This second reagent is dispensed into the reaction vessel 4.Next, the reaction vessel 4 into which this second reagent is dispensed is further rotated one pitch intermittently by the first and second step rotations of the reaction vessel holder 5. The state of the enzyme reaction by peroxidase bound to the surface of the beads 3 in the reaction container 4 is detected by the fluorescence detector 13A at wavelength 4.
Spectrophotometric analysis is performed at 92 nm. Thereafter, the reaction container 4 reaches a position m one pitch before the other optical measurement position n by the first and second step rotations, and when it reaches the same position m, the reaction container 4 moves to the first step. The beads are transferred to the bead disposal position j by the rotating operation, and the same container 4 is discarded at the same position j.
The beads B inside are suctioned and discarded by the bead discarding device 16. The reaction container 4 in which the beads B have been discarded in this manner is intermittently transferred to another optical measurement position n by the second step rotation.

The optical measurement by this optical device 13 is carried out using the reaction container holder 5.
Each time the holder 5 is rotated stepwise in the counterclockwise direction in FIG. 1, the number of reaction vessels 4, one less than the total number of reaction vessels held in the holder 5, crosses the optical path S. The optical device 13 and the data processing unit 24 may print out data based on the reaction liquid in the reaction vessels that crossed the optical path S, or may print out data based only on the necessary number of reaction vessels. 0, the absorbance of the reaction liquid in the reaction container 4 located between the second reagent dispensing position ag and the optical measurement position n is measured when the reaction container holder 5 is in a stopped state. Therefore, the reaction container located at the second reagent dispensing position g.

Colorimetric measurements are performed multiple times (35 times in the illustrated example) until arriving at the optical measurement position n, and reaction time course data can be obtained based on these data, or by combining these data. It is also possible to obtain desired data. After the predetermined colorimetric measurement work has been completed, the reaction vessel 4 is transferred to a cleaning device, and after being subjected to a predetermined cleaning by the cleaning device 17, it reaches the cleaning end position p and is provided for reuse.

The operation control of each of these devices and the arithmetic processing of measurement data are controlled by a microcomputer.

Of course, each time the reaction container 4 containing the beads B rotates through the first and second steps, the beads B are transferred within the container 4 by the magnetic force of the stirring device R, and the reaction solution is stirred. .

In the above embodiment, the cleaning end position p is set to the position one pitch before the sample dispensing position, but the present invention is not limited to this, and the sample is moved from the position where cleaning is completed in the cleaning device 17. Any position up to the dispensing position ab may be set as the washing end position, and in this case, the first step rotation angle of the reaction vessel holder 5 is also present between the washing end position and the bead supply position. It is set in accordance with the number of reaction vessels, and the arrangement positions of other devices are changed accordingly, and the second step rotation angle can also be changed and applied in accordance with the above change.

〔Effect of the invention〕

Since this invention is configured as explained above, EIA analysis, which was conventionally considered to be complicated due to a lot of manual work, can be performed easily.
Since it can be performed automatically, work efficiency can be greatly improved, and homogeneous measurement results can be obtained, improving the reliability of this type of EIA analysis. Moreover, the entire device can be compact and compact. Because it can be easily configured, it can be provided at a low cost with fewer failures.Furthermore, it is possible to measure multiple items, and by repeating the rotation operation, it is possible to obtain a time course for the same reaction solution, allowing for highly accurate analysis. data can be obtained.

[Brief explanation of drawings]

The drawings show an EIA automatic analysis device according to an embodiment of the present invention, in which FIG. 1 is an explanatory diagram schematically showing the overall configuration of the device, and FIG. 2 is a cross section taken along line rx-n in FIG. 1. Figure, 3rd
The figure is a partially cutaway perspective view of the beads, Figure 4 is a partially cutaway perspective view showing the arrangement and configuration of the reaction vessel and stirring device, and Figure 5 is the cleaning of the reaction vessel and beads. An explanatory diagram schematically showing the configuration of the device, FIG. 6 is a cross-sectional explanatory diagram showing the cleaning state by the device, FIG. 7 is an explanatory diagram schematically showing the configuration of the bead supply device, and FIG. 8 is the bead supply device. FIG. [Explanation of symbols] A... EIA automatic analyzer B... Beads R... Stirring device l... Sample container 4... Reaction container 5... Reaction container holder 6... Reagent table 9a , 9b... Reagent bottle 10... II reagent pipette device 11... Reaction container holder drive device 12... Second reagent pipette device 13A... Fluorescence detector 13B... Optical measuring device 15 ... Bead supply device 16 ... Bead disposal device 17 ... Washing device b ... Sample dispensing position k ... Bead supply position p ... Washing end position

Claims (1)

[Claims] A reaction vessel holder that holds a required number of reaction vessels in a loop shape, a sample dispensing device, a reagent dispensing device, and a bead disposal device arranged at predetermined positions along the intermittent transfer direction of the reaction vessels held in the holder. An EIA automatic analyzer comprising a bead supply device, an optical measurement device, a cleaning device, and a transfer device for transferring a reaction container held in the reaction container holder to a working position of each device. The container holder transports the reaction container that has been cleaned by the cleaning device stepwise to the bead supply position, and then rotates the same reaction container supplied with beads at the same position again stepwise in the same direction as the step rotation direction. An automatic EIA analyzer characterized in that the EIA automatic analyzer is configured to be driven so as to be transferred from the cleaning end position to a position one pitch or more in a direction opposite to the step rotation direction.