JP3001994B2 - Automatic analyzer - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an automatic analysis technique, for example, an automatic analysis relating to a clinical test represented by an immunological automatic analysis for measuring an antigen or an antibody contained in a sample by utilizing an immunological reaction. It concerns the device.

[0002]

2. Description of the Related Art In an automatic analysis in a clinical test, for example, in an immunological analysis method, proteins such as globulin and enzymes contained in blood, body fluids, etc., hormones, bacteria and viruses have similar molecular structures. Since the amount is very small, it is difficult to identify and quantify it using ordinary analysis methods. Therefore, an immunological analysis method utilizing an antigen-antibody reaction is generally employed for the analysis of these substances. Such an immunological analysis method is described in, for example, JP-A-59-135366, JP-A-61-258171, and JP-A-62-50662, and a clinical laboratory magazine "Medical Technology" published in July 1989, Vol. .17, No. 8.

In this immunological analysis method, for example, RIA (radioimmunoassay), EIA (enzyme immunoassay), FIA
(Fluoroimmunoassay). Methods using these labeling substances include, for example, an immune complex (Bound) produced by causing an antigen-antibody reaction between an antibody (antigen) labeled with the labeling substance and an antigen (antibody) in a sample; An operation of separating a labeled antibody (antigen) remaining in a free state without being involved in an antibody reaction, that is, a heterogeneous method that requires so-called BF separation; It is classified into the homogeneous method that does not require it. Also,
Without using a labeling substance, using a particle carrier reagent in which an antibody or an antigen is immobilized, an antigen-antibody reaction is performed between this and a sample to form a suspension, and the turbidity is measured to determine the antigen or antigen in the sample. Nephelometry for quantifying antibodies is also known.

[0004]

However, in the conventional automatic analyzer, a series of analysis steps such as dispensing of a sample and injection of a reagent are performed while a reaction vessel is transported along a reaction line in a reaction section. Therefore, there is a problem that the reaction time is greatly restricted and the processing capacity cannot be increased, and a problem that the configuration around the reaction line is complicated. Also, in the conventional apparatus for transferring reaction vessels, the reaction vessel housing itself is the reaction section itself, and the reaction vessel cannot be taken in and out during analysis, and the dispensing of samples and reagents is performed by the dedicated dispensing section. And it was difficult to increase the degree of freedom of the reaction system.

The present invention has been made in view of such a conventional problem, and can improve the processing capability,
An object of the present invention is to provide an automatic analyzer capable of simplifying a configuration around a reaction line.

[0006]

To achieve the above object, an automatic analyzer according to the present invention comprises: a sample container storage section in which a plurality of sample containers can be set; a reaction container storage section in which a plurality of reaction vessels can be set; A reaction unit in which a reaction container set in a container storage unit can be set, and a sample container set in the sample container storage unit to a reaction container set in the reaction container storage unit or a reaction container set in the reaction unit. A dispensing unit for dispensing a sample and a reagent, and a transfer unit that stops the reaction container in the reaction container storage unit according to a reaction time, and transfers the reaction container between the reaction container storage unit and the reaction unit; Means for measuring a reaction solution containing the sample and the reagent contained in the reaction vessel at least in the reaction section. In a preferred embodiment of the present invention, in the above-described configuration, the reaction container housing section is kept at a constant temperature, and the transfer means transfers the reaction container between the reaction container housing section and the reaction section a plurality of times. .

[0007]

According to this automatic analyzer, the reaction vessel is stopped in the reaction vessel storage section by the transfer means according to the reaction time, and the reaction vessel can be transferred between the reaction section and the reaction vessel storage section. For an analysis item having a long reaction time, it is possible to transfer the analysis item to the reaction section after a sufficient reaction time has elapsed and perform photometry. Therefore, the degree of freedom of the reaction time can be increased, and analysis items having different reaction times or analysis items that can achieve high sensitivity by reacting for a long time can be dealt with by a single apparatus, and the processing capacity can be improved. Further, by making the temperature of the reaction container housing constant, the reaction container can be kept warm in the reaction container housing, so that the reaction time can be shortened and the processing capacity can be further improved.

[0008]

FIG. 1 shows a first embodiment of the present invention. A rack 13 for holding a large number of sample containers 12 is detachably provided in the sample container storage section 11, and the rack 13 can be moved in the front-rear direction of the apparatus, that is, in the Y direction by a drive mechanism (not shown). A sample dispensing device 14 for dispensing a sample is provided above the sample container housing 11 so that its nozzle can be moved along a rail 15 in the X direction and the vertical direction perpendicular to the Y direction. At the same time, the nozzle cleaning device 16 can clean the nozzle. Such a moving mechanism of the rack 13 and the sample dispensing device 14 includes:
It is well known in the field of automatic analyzers, and its specific configuration will not be described in detail in this specification. Further, the sample container storage unit 11 includes a sample ID detection device,
A special sample ID detecting device such as a sample for calibration, a QC sample, or an emergency sample is provided, but these detecting devices are also known in the field of automatic analyzers and are not shown in the drawings.

Next to the sample container housing 11 is a reaction container housing.
21 is provided, and a rack 23 holding a large number of reaction vessels 22 is detachably accommodated in the reaction vessel accommodating section 21 so that the rack 23 can be moved in the Y direction by a drive mechanism (not shown). Reaction vessel held in rack 23
After holding and lifting the 22, there is provided a reaction vessel transfer device 24 for transferring the X-direction along the rail 15. In this embodiment, the reaction container housing section 21 is maintained at a constant temperature substantially equal to a reaction table to be described later or a predetermined temperature according to items by a constant temperature device (not shown).

In this embodiment, after a sample accommodated in a sample container 12 of a sample container accommodating section 11 is aspirated by a sample dispensing device 14, the nozzle thereof is moved in the X direction and the reaction container accommodating section 11 is moved.
Dispense into 21 reaction vessels 22. Thereafter, the reaction container 22 into which the sample has been dispensed is gripped by the reaction container transfer device 24, transported to the reaction table 31 constituting the reaction line, and stored in a predetermined place. In these configurations, the sample may be dispensed into the reaction container 22 after the reaction container 22 is stored in the reaction table 31. The nozzle of the sample dispensing device 14 is cleaned by the nozzle cleaning device 16 before or after dispensing the sample.

The reaction table 31 is configured so that the entire circumference thereof is thermostated by a thermostat (not shown), and is rotated according to a designated sequence. Above this reaction table 31,
The first and second B / F separation units 32 and 33, the substrate liquid dispensing device 34 and the photometric device 35 are arranged at a predetermined angle, and the first reagent storage unit 36 and the second reagent storage A part 37 is provided. In this embodiment, the first and second reagents are set. However, if necessary, a large number of reagents such as a third reagent and a fourth reagent can be set at predetermined positions. is there.

In the first reagent storage section 36, a large number of particle reagent containers 38 each having a first reagent immobilized with a predetermined antibody or antigen corresponding to an analysis item can be set. In 37, a large number of conjugate reagent containers 39 containing enzyme-labeled antibodies or antigens (conjugate reagents) corresponding to the analysis items can be set. The particle reagent container 38 and the conjugate reagent container 39 set in the first reagent storage portion 36 and the second reagent storage portion 37,
It can be moved in the Y direction by a drive mechanism (not shown).

A first reagent dispensing device 41 for dispensing the first reagent and a second reagent dispensing device 41 for dispensing the second reagent are provided above the first reagent storing portion 36 and the second reagent storing portion 37. A two-reagent dispenser 42 is provided and their nozzles are
The nozzles can be moved in the vertical and vertical directions, and the nozzles are washed by the corresponding nozzle washing devices 43 and 44 before or after the dispensing of the reagent.

The first B / F separation section 32 is used for immunologically reacting with a predetermined antibody or antigen immobilized on the surface of the carrier particles and for immobilizing the antigen or antibody in the sample with the immunological reaction. The second B / F separator 33 separates the antigen or the antibody in the unreacted sample from the antigen or the antibody, and immobilizes the second B / F separator 33 by immunologically reacting with the antigen or the antibody in the sample captured by the carrier particles. Separated conjugate reagent from conjugate reagent that has not undergone immunological reaction.

In FIG. 1, the photometric device 35 is provided with a mechanism for automatically adjusting the amount of light in accordance with the color or light emission of the test solution, so that it can cope with a wide range of color or light emission. May be.

An example of the analyzing operation according to this embodiment will be described below. First, the sample container 12 in the sample container
Is dispensed by the sample dispensing device 14 into the reaction container 22 of the reaction container storage unit 21. Thereafter, the reaction container 22 into which the sample has been dispensed is transferred to the reaction table 31 by the reaction container transfer device 24, set at a predetermined place, and transferred along the reaction line.

Next, the reaction container 22 transferred to the reaction table 31 is moved from the particle reagent container 38 corresponding to the analysis item set in the first reagent storage unit 36 by the first reagent dispenser 41 to the particles. The antigen-antibody reaction is performed by dispensing the reagent. Thereafter, at the time when a predetermined reaction time has elapsed, the first B / F separation unit 32 performs the immunological reaction with the predetermined antibody or antigen immobilized on the surface of the carrier particles to fix the sample. Is separated from the antigen or antibody in the sample that has not undergone an immunological reaction.

The B / F by the first B / F separation unit 32
When the separation is completed, the conjugate reagent is dispensed into the reaction container 22 from the conjugate reagent container 39 corresponding to the analysis item set in the second reagent storage section 37 by the second reagent dispensing device 42, and the antigen is removed. -Perform the antibody reaction. Thereafter, when a predetermined reaction time has elapsed, the conjugate reagent immobilized by the second B / F separation unit 33 by immunologically reacting with the antigen or antibody in the sample captured by the carrier particles is used. Conjugate reagents that have not undergone an immunological reaction.

Next, the B / F by the second B / F separation unit 33
When the separation is completed, the substrate liquid is dispensed into the reaction container 22 by the substrate liquid dispenser 34 to cause a color development or a luminescence reaction. Thereafter, the reaction container 22 having the test solution in which the color-forming or luminescent reaction has occurred is sent to the photometric device 35, and the color-forming or luminescent amount is measured to quantify the designated measurement item.

The data measured by the photometric device 35 is supplied to a signal processing device (not shown) to obtain a measurement result, and the data is displayed on a display device, printed out, or externally. Supply it to the host computer via the output device.

Thus, a series of analysis operations for one analysis item is completed, and the used reaction vessel 22 is transferred to the reaction vessel transfer device.
The reaction container 31 is taken out of the reaction table 31 by 24, returned to the original position of the reaction container storage section 21, and the next reaction container 22 into which the sample has been dispensed is set on the reaction table 31 by the reaction container transfer device 24. The sequential analysis of the sample can be performed while sequentially repeating such operations.

In the above-described analysis operation, after the reaction vessel 22 is set on the reaction table 31, it is held in the reaction table 31 until the analysis is completed. Alternatively, when the set capacity of the reaction container 22 in the reaction table 31 is small, the reaction container 22 is temporarily returned to the reaction container storage unit 21 by the reaction container transfer device 24 during the reaction, and after a predetermined time has elapsed, the reaction table 31 is returned again.
To perform the subsequent analysis operation. In this way, even in the case of an analysis item having a long reaction time, and even when the set capacity of the reaction vessel 22 in the reaction table 31 is small, the processing capacity can be effectively improved, and the reaction time can be reduced to a small size and a long reaction time. It is possible to provide an automatic analyzer that can cope with the problem and effectively improve the processing capacity.

FIG. 2 shows a second embodiment of the present invention. In this example, latex particles are used as a particle carrier on which a predetermined antibody or antigen is immobilized, and analysis is performed by turbidimetry. Therefore, in this embodiment, the first and second B / F separation units 32 and 33, the substrate liquid dispensing device 34 and the photometric device in the first embodiment shown in FIG.
A photometric unit for measuring the turbidity of the test solution through the reaction vessel 22 held on the reaction table 31 is provided inside the apparatus without the 35. A large number of first reagent containers 62 containing a stabilizing solution corresponding to the analysis item are set in the first reagent storage unit 61, and a predetermined number of the second reagent storage units 63 corresponding to the analysis item are stored in the second reagent storage unit 63. A large number of second reagent containers 64 having latex particles on which antibodies or antigens are immobilized are set, and the first and second reagents contained in the first and second reagent containers 62 and 64 are set in the first and second reagent containers. , And the second reagent dispensing devices 65 and 66 are dispensed to the reaction vessels 22 of the reaction table 31, respectively.

In this embodiment, first, after the reaction container 22 having received the sample dispensed in the reaction container storage section 21 is transferred to the reaction table 31 by the reaction container transfer device 24, the first reagent dispensing device 65 The first reagent (stabilizing solution) is dispensed and reacted, and the reaction solution is measured with a measuring light having a predetermined wavelength in a photometric unit. Next, the second reagent (latex particles) is dispensed by the second reagent dispensing device 66 to cause a reaction, and the reaction solution is similarly subjected to photometry in the photometry unit. The photometry after the dispensing of the first and second reagents is performed a plurality of times in the rate assay. Thereafter, the reaction container 22 is returned to the reaction container storage section 21 by the reaction container transfer device 24. In this way, a desired item can be analyzed by turbidimetry.

In the second embodiment, after the dispensing of the first reagent or the dispensing of the second reagent, the reaction vessel 22 is moved from the reaction table 31 by the reaction vessel transfer device 24 to the reaction vessel storage section.
By returning to 21 once, various applications are possible. For example, the second reagent is not limited to latex, and may be a mixture of latex having a predetermined antibody or antigen immobilized thereon and magnetic particles. In this case, a magnet 71 is provided at a portion of the reaction container storage section 21 facing the bottom surface of the reaction container 22 as shown in FIG. 3, and the reaction container 22 into which the second reagent has been dispensed is transferred from the reaction table 31 to the reaction container. The magnetic particles and the latex particles bonded to the magnetic particles via the antigen or antibody in the sample by the magnet 71 are completely sedimented to the bottom surface of the reaction container 22 with time by being transferred to the reaction container storage unit 21 by the device 24. After that, the reaction vessel is immediately transferred to the reaction table 31 by the reaction vessel transfer device 24.
By returning 22 and performing photometry, stable photometry data with high sensitivity can be obtained. In other words, the reaction container housing can be operated as a magnetic particle separation device using a magnetic particle reagent by setting a magnet, and stable high-sensitivity analysis is possible by time-consuming magnetic particle separation. .

[0026]

As described above, according to the present invention, the reaction vessel can be stopped in the reaction vessel storage section by the transfer means according to the reaction time, and the reaction vessel can be transferred between the reaction section and the reaction vessel storage section. As a result, an analysis item having a long reaction time can be transferred to the reaction section after a sufficient reaction time has elapsed, and photometry can be performed. Therefore, it is possible to improve the processing capacity and to perform a sufficient photometry after the reaction according to the reaction time even for an item having a long reaction time. In addition, by making the temperature of the reaction container storage unit constant and preliminarily heating the reaction container in the reaction container storage unit, the reaction time can be shortened and the processing capacity can be further improved.

[Brief description of the drawings]

FIG. 1 is a diagram showing a first embodiment of the present invention.

FIG. 2 is a diagram showing a second embodiment of the present invention.

FIG. 3 is a diagram for explaining a modification of the second embodiment.

[Explanation of symbols]

 11 Sample container storage unit 12 Sample container 14 Sample dispensing device 21 Reaction container storage unit 22 Reaction container 24 Reaction container transfer device 31 Reaction table 32,33 B / F separation unit 34 Substrate liquid dispensing device 35 Photometric device 36 First reagent Storage part 37 Second reagent storage part 38 Particle reagent container 39 Conjugate reagent container 41 First reagent dispenser 42 Second reagent dispenser 61 First reagent storage 62 First reagent container 63 Second reagent storage 64 2 reagent container 65 1st reagent dispensing device 66 2nd reagent dispensing device

────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-62-255870 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) G01N 35/00-35/10

Claims (2)

(57) [Claims] A sample container accommodating portion in which a plurality of sample containers can be set; a reaction container accommodating portion in which a plurality of reaction containers can be set; a reaction portion in which a reaction container set in the reaction container accommodating portion can be set; A dispensing unit for dispensing a sample and a reagent from a sample container set in the sample container storage unit to a reaction container set in the reaction container storage unit or a reaction container set in the reaction unit, A transfer means for stopping the reaction container in the reaction container storage part and transferring the reaction container between the reaction container storage part and the reaction part; and a transfer means provided in at least the reaction part and stored in the reaction container. Means for measuring a reaction solution containing a sample and a reagent. 2. The method according to claim 1, wherein the temperature of the reaction vessel storage section is kept constant, and the reaction vessel is transported a plurality of times between the reaction vessel storage section and the reaction section by the transfer means. Automatic analyzer.