JP2723922B2 - Automatic analyzer with air oven - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an automatic analyzer, and more particularly, to an automatic analyzer having a function of keeping a row of reaction vessels at a constant temperature with air.

[Conventional technology]

In order to analyze and measure a biological sample such as blood, a reaction solution obtained by reacting the sample with a reagent is generally measured with a photometer. In particular, when a large number of analysis items are measured for each sample, a discrete automatic analyzer that generates a reaction solution in a reaction vessel also serving as a photometric cell for each analysis item is often used.

Biological samples need to be reacted at a constant temperature of around 37 ° C. For this purpose, in a conventional automatic analyzer, for example, as described in JP-A-56-168553, a method of using a constant temperature water bath as a constant temperature bath and immersing a row of reaction vessels in the constant temperature water is adopted.

[Problems to be solved by the invention]

When a constant temperature water bath is used as the constant temperature bath, a large space is required to circulate the constant temperature water between the constant temperature water supply unit for producing the constant temperature water and the bathtub, so that the entire analyzer is necessarily large. I had to take shape.

When trying to make the automatic analyzer a tabletop, it is advisable to employ an air thermostat instead of a thermostat bath. However, since air has a smaller heat capacity than water, arranging a heat block in an air oven alone takes a long time (for example, 30 minutes) to raise the temperature of the liquid collected in the reaction vessel to 37 ° C. Minutes), which results in a problem that the overall analysis time becomes longer.

An object of the present invention is to provide an automatic analyzer that can raise the temperature of a liquid collected in a reaction vessel to a predetermined temperature in a short time by using a small preliminary temperature raising device even when using an air thermostat, and thereafter can maintain the temperature at a constant temperature. Is to provide.

[Means for solving the problem]

The present invention relates to a reaction table for rotatingly transferring a row of reaction vessels in an annular path, a dispensing device for dispensing a liquid to the reaction vessels in the reaction vessel row, and a photometer for measuring the reaction vessels on the reaction table. In an automatic analyzer provided with an air thermostat that keeps a reaction vessel row at a predetermined temperature, a heat block disposed on an inner wall of the annular path is located between a liquid receiving position and a photometry position on the reaction vessel row. A pre-heating device arranged near the liquid receiving position, and the pre-heating device includes a pre-heating device for controlling a reaction in the pre-heating device from a direction substantially perpendicular to a traveling direction of the reaction vessel row. An air circulation path for circulating the constant temperature air blown to the liquid storage portion of the container is formed, an opening / closing lid for introducing outside air is provided on a wall of the air circulation path, and the liquid is transferred to the photometry position after exiting the preliminary temperature raising device. The reaction vessel is heated to a predetermined temperature by a heat block. Characterized by being configured to maintain the.

[Action]

In the present invention, a heat block is arranged on the inner wall of the annular room in which the row of reaction vessels is placed. By arranging a heat block around the reaction vessel row and surrounding it and heating the heat block with a sheet-like heater or the like, the entire vessel thermostat can be maintained at a constant temperature, for example, 37 ° C. When a new reagent solution is introduced into a specific reaction vessel at the liquid receiving position on the reaction vessel row, the temperature of this
If the temperature is in ° C, the temperature of the mixture of the sample and the reagent also decreases, so that the temperature is raised to 37 ° C in a short time. The preliminary heating device
It is arranged near the liquid receiving position so that the temperature of the received liquid can be raised quickly.

The preliminary heating device has a heater and a blower, and air whose temperature is controlled to a constant temperature (37 ° C.) is blown toward the reaction container that has received the liquid. As a result, heat is efficiently supplied to the reaction vessel, and the liquid in the reaction vessel is heated to a constant temperature in a relatively short time by heat conduction of the reaction vessel wall.

〔Example〕

Hereinafter, embodiments of the present invention will be described with reference to the drawings. Second
FIG. 1 shows an overall schematic configuration of an automatic analyzer according to one embodiment of the present invention.

The reagent table 17 holds a reagent container 18 in a reagent cool box 19. The sample table 16 is fitted and mounted on the reagent table 17, but is outside the reagent cool box 19. In the sample table 16, sample containers 20 are arranged in two rows on the circumference, and are driven by the same drive shaft as the reagent table 17. On the other hand, the reaction disk mechanism includes a reaction table 65, a reaction thermostat 21, and a reaction vessel 22. Further, a cleaning mechanism 23 for sucking the reaction liquid in the reaction container 22 and discharging and cleaning the cleaning liquid is provided. The suction of the reaction liquid is performed by a peristaltic pump 24, and the discharge of the cleaning liquid is performed by a cleaning syringe 25.

The dispensing mechanism 15 for aspirating the reagent in the reagent container 18 and the sample in the sample container 20 and transferring it to the discharge position 60 on the row of reaction vessels and discharging the same is provided between the sample / reagent disk mechanism and the reaction disk mechanism. It is arranged. This suction / discharge operation is performed by a dispensing syringe 26, and is connected to a probe attached to the tip of the arm of the dispensing mechanism 15 by piping. In front of the dispensing mechanism 15, a probe washing tank 27 is arranged on the rotation path of the probe, and on the rotation path of the reaction vessel 22, a fluorometer 28 for measuring the fluorescence of the reaction solution is provided in a reaction thermostat. It is located in 21.

The first rotation is performed clockwise from the position 60 where the reagent is discharged by the dispensing mechanism 15 until the measurement is performed by the fluorometer 28.
The pre-heating device shown in the figure is installed,
Raise the temperature to 37 ° C. This preliminary heating device has a forced circulation preheating function, and the temperature is controlled by the preheating amplifier 30. The printer 10, the CTR 11, the operation panel 12, the floppy disk drive (FDD) 9, and the A / D converter 32 for processing the output signals of the fluorometer 28 are each an interface 33.
Is connected to and controlled by the CPU.

Next, the operation of the automatic analyzer in FIG. 2 will be described.
As a sample, a biological fluid containing a test antigen such as serum, plasma or urine is used. As the reagent, a commonly used reagent is used. Particularly, when a virus immune reaction or the like is analyzed, a reagent solution containing a solid phase coated with an antibody is used. First, a number of sample containers 20 are held on the sample table 16, and the reagent containers 18 are cooled and held at a predetermined temperature in a reagent cool box 19. A predetermined amount of sample is aspirated from the sample container 20 on the sample table 16 by the dispensing mechanism 15 with a probe,
It is transferred to and discharged from the reaction vessel 22 at the designated position 60 on the reaction table 65. After the ejection, the probe of the dispensing mechanism 15 is sufficiently washed in the probe washing tank 27 to prevent contamination due to carry-over of the sample solution. Next, the reaction table 65 is vibrated for several seconds by a vibration driving device to stir the reaction solution, and thereafter, the reaction vessel row is rotated and transferred.

By repeating this operation sequentially, the required number of samples are first transferred and dispensed into the reaction container 22. This step is shown at 55 in FIG. Next, the reagent is similarly dispensed from the reagent container 18.
The liquid is sucked at 15 and transferred and dispensed to the reaction container 22 on the discharge position 60. The dispensing cycle sequentially transfers and dispenses from the first reagent in the reagent series of the reagent container group. This step is shown at 56 in FIG. Thus, the designated rotation is performed on the reaction table 65, and the sample and the reagent are batch-dispensed into the reaction container 22.

The reaction vessel 22 is maintained at a predetermined temperature, for example, 37 ° C. by a reaction air thermostat. Regarding the reaction between the sample and the reagent, the reaction is stabilized particularly in a thermostated bath, and highly sensitive measurement can be performed with good reproducibility.

FIG. 3 shows a cross-sectional view of an air thermostat provided with a preliminary temperature raising device 29 in part. The air oven 21 has a ring-shaped room almost all around the row of reaction vessels. This annular air thermostat is formed near the outer periphery of the reaction table 65, and is disposed below it. A row of reaction vessels 22 is hung inside the air thermostat 21, and its annular path is shaped so as not to hinder the rotational movement of the row of reaction vessels. The entire air thermostat is maintained at 37 ° C. by a metal heat block 35 having a U-shaped cross section opened upward so as to surround both side portions and the bottom portion of the row of reaction vessels. A sheet heater is arranged on the outer periphery of the heat block 35 to supply heat.

The reaction vessel 22 held on the reaction table 65 is maintained at 37 ° C. while containing the reaction solution. Heat block 35
The outer periphery of the sheet heater 36 attached to the outer peripheral surface of the
Covered with 37, a cover is provided on it. The reaction table 65 is a washer 40 mounted on a shaft 39 supported by a drive base 38.
The pulley 41 attached to the other end of the shaft 39 and the pulley 43 attached to the pulse motor 42 are connected by a timing belt 44, and the rotational force of the pulse motor 42 is transmitted to the reaction table 65. The rotation angle position is controlled by a detection plate 45 and a photo interrupter 46 formed integrally with the reaction table 65.

FIG. 1 shows a preliminary heating device having a forced preheating function.
29 specific configurations are shown. The preliminary temperature raising device 29 is partially cut open at the upper portion and is open, and the vicinity of the opening 49 is a passage for the rows of the reaction vessels 22. Accordingly, the reaction container which has received the liquid at the liquid receiving position 60 shown in FIG. 2 will soon be sent to the opening 49 to be forcibly heated.
Except for the opening 49, the whole is surrounded by a case 48, and the outside thereof is covered with a heat insulating material 47.

Inside the case 48, a small case 50 is arranged,
The space between the inner wall of the case 48 and the outer wall of the small case 50 forms an air circulation path. An outside air introduction hole 70 communicating with the outside air is opened in the small case 50, and the introduced outside air is used for controlling the temperature of the air oven. By opening a cover member 53 attached to the small case 50 by a predetermined angle by a drive mechanism (not shown), outside air flows into the circulation path of the pre-heating device 29, and when the temperature reaches the lower limit of the temperature control range, the cover member is closed. 53 is closed. A self-controllable heater 51 such as a ceramic heater, a temperature detecting thermistor 52, and a hot air circulating fan 54 are arranged in the circulation path, and controls the circulated air to a constant temperature of 37 ° C. At the same time, air at 37 ° C. is blown toward the reaction vessel 22.

A reagent solution containing an antibody-coated solid phase as a reagent is placed on a reagent table, a sample solution containing an antigen such as a virus is placed in the reaction vessel 22, and then a reagent solution containing the antibody-coated solid phase is added, Using a driving device including a pulse motor 42, a pulley 43, a timing belt 44, a pulley 41 and a drive shaft 39 shown in FIG.
Vibration is achieved by controlling the drive signal of the above. The antigen and the solid phase contact each other and the variable portion of the antibody binds to the antigen. After a lapse of a predetermined time, the solid phase is washed by the washing mechanism 23, and the unreacted liquid, which is a noise source for high-sensitivity measurement, is discharged by the nozzle of the washing mechanism 23, and further washed by another nozzle by the operation of the washing syringe 25. Discharge the water and wash again. This state is shown as step 57 in FIG.

After washing the solid phase, a substrate solution, which is an enzyme reaction solution, is added. Immediately, a pre-warming device 29 blows air controlled at 37 ° C. into the reaction vessel 22 into which the substrate has been dispensed, and the temperature rises within 5 minutes. To 37 ° C. This state is shown in step 58 of FIG. After a lapse of 5 minutes from the substrate reaction, the reaction state is measured by a fluorometer 28 to analyze the concentration of the test component in the sample. This state is shown as step 59 in FIG. Reagent dispensing process 56 of the time chart in FIG.
Are programmed so that the number of steps can be increased or decreased according to the number of reagents required for the reaction.

The automatic analyzer of this embodiment can be used as a diagnostic device for acquired immunodeficiency syndrome (AIDS) by high-sensitivity immunoassay, and detects an antigen concentration of 10 ⁻⁶ to 10 ⁻¹³ Mol / in a sample,
High sensitivity measurement is possible. In biochemical analysis apparatus of a conventional compared to has failed obtained was measured only up to a concentration 10 ^-6 Mol / degree may be measured in about ¹⁰⁶ times more sensitive. For that purpose, it is an important condition how quickly the reaction solution can be heated to a predetermined temperature to increase the temperature.

With reference to FIGS. 3 and 1, the air flow in the forced circulation preheating function will be described in some detail. The air blown in the direction of the arrow by the fan 54 is blown to the heater 51. The temperature of the warm air heated through the heater 51 is detected by a thermistor 52, and its signal is processed by a control circuit so as to constantly control the temperature to a predetermined temperature of 37 ° C., and is fed back as a heater voltage. On the other hand, the warm air that has flowed out of the heater 51 is blown to the reaction vessel 22, and the temperature of the reaction solution inside is raised to 37 ° C. in a short time. The temperature circulates further and is sucked again by the fan 54. At this time, when the warm air is excessively heated, the thermistor 52
The outside air introduction lid 53 is opened in response to the detection signal of, and the cooled outside air is sucked to operate the temperature.

FIG. 5 shows the temperature state of the liquid in the reaction vessel according to the present embodiment. When the temperature of the outside air is 15 ° C, the reaction vessel in which the buffer solution (35 ° C) and the substrate solution (about 20 ° C) were dispensed at the liquid receiving position 65 on the reaction table 65 was transferred to the preliminary temperature raising device and raised. The case where it heated is shown. The change in the temperature of the contained liquid is as shown in the figure from the initial temperature position in FIG. 5, and the photometry can be performed by the fluorimeter after 5 minutes. When the outside air temperature is 15 ° C. to 32 ° C., the liquid temperature in the reaction vessel falls within the range between the solid line and the broken line in FIG.

According to the embodiment described above, it is possible to raise the temperature to 37 ° C. in a short time in spite of being an air thermostat, and it is possible to improve the disadvantages of the conventional water bath. In other words, there is no need to worry about contamination caused by bacteria generated in the water flow path experienced in conventional water thermostats and the hassle of maintenance, and there is no need to worry about spillage of water when replacing the reaction vessel. Can be provided.

〔The invention's effect〕

ADVANTAGE OF THE INVENTION According to this invention, it can implement | achieve efficiently raising the temperature of the reaction container which received the liquid near the predetermined temperature suitable for reaction in the small space which does not hinder the photometry of the reaction container.

[Brief description of the drawings]

FIG. 1 is a diagram for explaining a schematic configuration of a preliminary temperature raising device in the embodiment of FIG. 2, FIG. 2 is a schematic configuration diagram showing an entire automatic analyzer of one embodiment of the present invention, and FIG. Is an explanatory view showing the arrangement of a reaction table and an air thermostat in the embodiment of FIG. 2, FIG. 4 is a view showing a time chart of an analysis step,
FIG. 5 is a diagram showing a change state of the liquid temperature in the reaction vessel. 21 …… Air bath, 22… Reaction vessel, 28… Fluorometer, 29… Preliminary heating device, 35… Heat block, 36…
… Seat heater, 48 …… Case, 49 …… Opening, 50 ……
Small case, 51: heater, 54: fan, 65: reaction table, 70: outside air inlet.

Claims (1)

(57) [Claims] 1. A reaction table for rotatingly transferring a row of reaction vessels in an annular path, a dispensing device for dispensing a liquid to the reaction vessels in the row of reaction vessels, and a photometer for measuring the reaction vessels on the reaction table. In an automatic analyzer equipped with an apparatus and an air thermostat that keeps the reaction vessel row at a predetermined temperature, a heat block disposed on the inner wall of the annular path, and a liquid receiving position and a photometry position on the reaction vessel row. And a pre-heating device disposed between the liquid receiving position and the pre-heating device in a direction substantially perpendicular to the direction of travel of the reaction vessel row. An air circulation path for circulating the constant temperature air blown to the liquid storage portion of the reaction vessel in the apparatus is formed, an opening / closing lid for introducing outside air is provided on a wall of the air circulation path, and the photometry is performed after exiting the preliminary temperature raising device. The reaction vessel transferred to the position Automatic analyzer having an air thermostatic chamber, characterized by being configured to maintain a predetermined temperature by the over heat block.