JPH0783934A - Analytical instrument equipped with a thermostatic chamber with temperature compensation function - Google Patents

Abstract

(57) [Summary] [Purpose] To provide an analyzer equipped with a thermostatic chamber that maintains the temperature of an analyte accurately and accurately even when there are factors such as changes in air temperature and changes in the exothermic temperature of the device itself. [Composition] Each constant temperature bath temperature sensor incorporated in the constant temperature bath and a monitoring temperature sensor 1 are arranged in an internal space of a housing 10 surrounding the constant temperature bath, and the monitoring measurement temperature and the high monitoring measurement temperature with respect to each constant temperature bath temperature,
A thermostatic chamber in which a heater and a cooling device are controlled by an arithmetic and control circuit 103 for adding a value (hereinafter, compensation temperature) depending on the size of low to the thermostatic chamber temperature is provided in the analyzer. Further, a monitor sensor 1 for detecting the ambient temperature inside the housing 10 is provided, and the compensation temperature determined by a linear linear line is added to the monitor temperature by the arithmetic control circuit 103.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an analyzer, and more particularly to an analyzer equipped with a thermostat having a temperature compensating function that is hardly affected by the ambient temperature around the thermostat.

[0002]

2. Description of the Related Art In a conventional analyzer, a sample and a reagent are placed in a container in a thermostatic chamber covered with a housing, cooled to a constant temperature according to the characteristics of the sample and the reagent, and vice versa. It is used after being warmed. Then, the required amount of these samples and reagents is transferred to a reaction container by a pipetting mechanism, and the sample and the reagent react with each other in the reaction container to be changed into an analytical substance, which is measured by an analytical measurement unit. .

Generally, in a reaction between a sample and a reagent, it is necessary to maintain a constant temperature, particularly in a biological sample, to keep the reaction container and the analytical substance at 37 ° C., which is substantially equal to the body temperature, with good reproducibility of measurement results. Is required as a parameter to improve. As a constant temperature bath and a control device in such an analyzer, circulating water controlled to a target temperature is used as a heat medium as disclosed in the techniques described in JP-A-56-168553 and JP-A-63-182568. A device for accurately keeping the temperature of the analytical substance by immersing the reaction vessel in the heat medium water is known as
Many have been put to practical use.

However, since these devices use a liquid called water, these devices have a large scale by incorporating a pump for circulating water, a mechanism for maintaining the water quality and the amount of water, and routing pipes. Become. In addition, for example, in optical analysis, it is sometimes necessary to use the wavelength light absorbed by water as the measurement light.

In the analysis operation, the reaction container itself may be vibrated at a high speed for stirring the sample / reagent mixture. As described above, there are many analysis methods and devices which cannot utilize the means for soaking the water in the water as a heat medium to keep the heat.

[0006] As described above, as an apparatus in which water cannot be used as a heat medium, an apparatus using an air constant temperature bath is generally widely known. As an example of the analyzer equipped with the air constant temperature oven, US Pat. , 133,936 and the like.
As for the thermostatic chamber and its circuit using air, which is an example of a gas chromatograph,
As in the technique disclosed in Japanese Patent No. 3926, in the temperature control bridge circuit, the temperature sensing resistor for control detection inside the thermostat and the resistor for detection outside the thermostat have the same temperature coefficient, thereby changing the ambient temperature. A device that considers compensation can be given.

[0007]

In the recent analyzers, automation has progressed, and analytical substances are successively produced in a plurality of reaction vessels arranged side by side. However, in order to control these temperatures, a direct temperature sensor is used. The method of inserting the compound into the analytical substance is not used in consideration of the properties of the analytical substance. Therefore, as described above, an indirect temperature control method is used by controlling the temperature of the heat medium surrounding the reaction vessel such as water or air, or by controlling the constant temperature bath main body surrounding the reaction vessel. .

However, apart from the heat medium whose specific heat is large like water and whose temperature does not easily fluctuate due to a small amount of heat entering from the outside, in the constant temperature tank whose specific heat is small and air is used as the heat medium, There is a problem that it is difficult to keep the temperature of the analyte in the reaction vessel at the target value because of air inflow and outflow between the housing and the space inside the housing, and changes in temperature and the heat generated by the device itself. there were.

Moreover, in the analyzer, ± 0.2 to 0.3
Since the temperature of the substance to be analyzed is controlled by the error accuracy of [° C.], the temperature compensation method according to the technique described in Japanese Utility Model Laid-Open No. 64-3926 used in the gas chromatograph device is insufficient. . The present invention has been made in order to solve the above-mentioned problems of the prior art. Even if there is a factor such as a change in air temperature or a change in exothermic temperature of the device itself, the temperature of the analyte is kept constant with high accuracy. An object is to provide an analyzer equipped with a tank.

[00010]

Means for Solving the Problems The above-mentioned object is to provide a constant temperature bath temperature sensor incorporated in a constant temperature bath and a monitoring temperature sensor in an inner space of a housing surrounding the constant temperature bath, and the monitoring sensor for each constant temperature bath temperature. By installing a calculation control circuit for adding a temperature value (hereinafter referred to as a compensation temperature) depending on the magnitude of the difference in detected temperature to the constant temperature bath temperature, and controlling each constant temperature bath by the added temperature. Can be achieved. Further, the compensation temperature value is achieved by determining a linear linear line with respect to a temperature value depending on the magnitude of the difference between the temperature detected by the monitoring temperature sensor and the temperature detected by the monitoring temperature sensor with respect to each constant temperature bath control temperature.

More specifically, the structure of an analyzer equipped with a constant temperature bath having a temperature compensation function according to the present invention comprises a housing, an analysis measuring section mounted in the housing,
A plurality of reaction containers for containing an analytical substance, a reaction container transfer mechanism for holding the reaction container and transferring it to the analysis and measurement unit, and a constant temperature bath for maintaining the reaction container equipped with a temperature sensor at a specific temperature, A container containing a sample and a reagent for producing the analysis substance, a transfer mechanism for holding and transferring the container, a thermostatic chamber for maintaining the container at a specific temperature, which is equipped with a temperature sensor, and each of the above. In an analyzer equipped with a pipetting mechanism that dispenses a required amount of a sample or each reagent into the reaction container, a monitoring sensor that detects the internal space temperature of the housing, and the temperature of each of the constant temperature baths are adjusted to the respective constant temperature. An arithmetic circuit for adding a constant compensation temperature related to the difference between the bath temperature and the housing internal space temperature detected by the monitoring sensor, and the respective arithmetic values Wherein those having a control unit for controlling the constant temperature bath to the respective temperatures based. The arithmetic circuit is configured to add to each temperature of each of the constant temperature baths, a compensation temperature determined by a linear linear type with respect to each difference between the temperature of each of the constant temperature baths and the detected temperature of the housing internal space. It was done.

[0012]

The function of each of the above technical means is as follows.
According to the configuration of the present invention, in the temperature sensor for monitoring, when the housing internal space temperature T _H [° C.], a predetermined compensation temperature value based on the detected temperature T _H [° C.] is calculated with respect to the constant temperature bath temperature. Since the heater and the cooler are operated in accordance with the added value, it is possible to accurately keep the temperature of the analyte in the reaction container at T [° C.], for example.

For example, the internal space of the housing is _TH [° C]
Under the condition of
(However, the T ≧ T _H) when kept at, given the like inflow and outflow behavior of the air, the temperature of the thermostatic chamber surrounding the reaction vessel is raised to T + △ T [℃], The analyte can be kept warm at T [° C]. Conversely, by setting the temperature of the thermostat itself to T + ΔT [° C], the analytical substance can be kept at T [° C].

The ΔT [° C.] is the compensation temperature, and generally, the larger the difference between T [° C.] and T _H [° C.], the larger the compensation temperature ΔT needs to be. Where T [° C] is _TH [° C]
△ T for constant regardless of the [℃] a T _H [℃]
Approximate the linear first-order straight line to. This can be experimentally confirmed to have a favorable effect.

[0015]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An analyzer equipped with a temperature-controlled thermostatic chamber according to an embodiment of the present invention will be described below with reference to FIGS.

[Embodiment 1] FIG. 1 is a schematic explanatory view including a partial block diagram of an analyzer equipped with a thermostat having a temperature compensation function according to an embodiment of the present invention, and FIG. A partial cross-sectional view of the constant temperature oven used in the analyzer with constant temperature oven, FIG.
FIG. 1 is a temperature control circuit diagram used in the analyzer with a constant temperature bath,
4 is a diagram showing signal output conditions of the temperature control circuit of FIG. 3, FIG. 5 is a diagram showing an example of control characteristics in the temperature control circuit of FIG. 3, and FIG. 6 is a diagram of the temperature control circuit of FIG. FIG. 7 is a diagram showing an example of another control characteristic, and FIG. 7 is a diagram showing an example of still another control characteristic in the temperature control circuit of FIG.

In FIGS. 1, 2 and 3, 1 is a monitor resistance temperature detector, 9 is a fixing member for the monitor resistance temperature detector, and 1
0 is a housing, 21 is a fastener for fixing the reaction container, 3
0 is a reaction container, 35 is an analytical measurement substance, 40 is a reaction container constant temperature bath, 41 is a reaction container constant temperature bath resistance thermometer, 43 is a heater, 45 is a heat insulating material, 50 is a sample / reagent disc, 51 is a sample A container, 52 is a reagent container, 60 is a sample / reagent container thermostat, 61 is a sample / reagent thermostat, 70 is a reagent thermostat, 71 is a reagent thermostat, and 72 is Reagent reservoir, 80 pipetting mechanism, 90 analysis and measurement unit,
Reference numeral 101 is a monitor temperature measuring circuit, 102 is a constant temperature bath temperature measuring circuit, 103 is an arithmetic control circuit, 104 is an output circuit, 11
0, 111, 112 are the measurement circuits 101, 10 described above.
2, 103 is a variable resistor on the bridge side.

As shown in FIG. 1, a reaction disk 20 rotatably moved by a drive unit (not shown) inside the housing 10 which also serves as a support and a cover for the components of the analysis stage. It is arranged. A reaction container 30 is arranged along the outer peripheral edge of the reaction disk 20. A sample / reagent disc 50, which is rotationally moved by a drive unit (not shown), is disposed on the right side inside the housing 10 in the drawing.
At 0, the sample container 51 and the reagent container 52 are fixed at respective designated positions.

The surroundings of the reaction vessel 30 will be described more prominently with reference to FIG. The reaction vessel 30 is fixed to the reaction disk 20 by a fastener 21 and has an inner circumference (see FIG. 2).
In the left side), a constant temperature bath 40 for a reaction vessel is provided, which is surrounded from the outer periphery and the bottom in three directions.
Is fixed to the housing 10 (the fixed portion is not shown).

The reaction chamber 40 is formed of a metal having a large coefficient of thermal conductivity such as aluminum, and a small hole is formed in a part of the reaction chamber 40 so that the temperature of the reaction chamber 40 can be measured and controlled. A reaction vessel thermostatic chamber temperature measuring resistor 41 is inserted into the small hole. Further, in order to measure the ambient temperature in the housing 10, the resistance temperature detector for monitor 1 is
It is fixed to the fixing member 9, and the thermostat 40 for the reaction vessel is used.
It is installed near. Constant temperature bath 40 for the reaction vessel
The heater 43 is wound around the outer circumference of the heater, and is covered with a heat insulating material 45 to thermally shield the outside, including the portion where the heater 43 is wound.

Again, as shown in FIG. 1, the sample / reagent constant temperature bath 6 so as to enclose the sample / reagent disk 50.
No. 0 is provided, and a sample / reagent thermostat RTD 61 (not shown) is mounted therein as in the thermostat 40 for reaction vessels, and a predetermined temperature, for example, 10
It is controlled to around 0 ° C. to prevent spoilage and deterioration of the sample / reagent in the container.

A reagent reservoir 72, a reagent reservoir constant temperature bath 70, and the reagent reservoir constant temperature bath RTD 71 are also installed in the center of the housing 10, and the temperature is controlled independently of the other constant temperature baths. The reagent in the reagent reservoir 72 is kept at a predetermined temperature.

The samples and reagents in the sample container 51, the reagent container 52 and the reagent reservoir 72 are stored in the constant temperature baths 40, 60 and 7 respectively.
By the vertical rotation movement of the pipetting mechanism 80 provided in the approximate center of the area surrounded by 0, the pipette mechanism 80 transfers and injects it from the tip of the nozzle 81 of the pipetting mechanism 80.

The respective samples and reagents transferred and injected into the reaction container 30 are mixed in the reaction container 30 to form an analytical substance 35, which is surrounded by the constant temperature layer 40 for the reaction container. It is gradually rotated and transferred while being heated to a predetermined temperature, and the data is measured by an analysis and measurement section 90 which is arranged below the reaction disk 20 and is constituted by a photometer or the like.

With reference to FIG. 3, the temperature control operation of the reaction vessel constant temperature bath will be described in detail. In FIG. 3, the monitor temperature measuring resistor 1 is connected to the monitor temperature measuring circuit 101, and the reaction vessel thermostatic chamber temperature measuring resistor 41 is connected to the thermostatic chamber temperature measuring circuit 102.

The temperature measuring circuit for monitor 101 and the temperature measuring circuit for constant temperature chamber 102 respectively include a bridge circuit including the temperature measuring resistor for monitoring 1 and the reaction vessel constant temperature chamber temperature measuring resistor 41 and a bridge output thereof. The differential amplifiers 120 and 121 for amplifying are provided. These outputs are transmitted to the arithmetic and control circuit 103.

The arithmetic control circuit 103 divides the output of the differential amplifier 120 by a resistor 112, and the divided output and the output of the differential amplifier 121 are operational amplifiers 123.
Is input to and amplified. Further, the arithmetic control circuit 103 is connected to the output circuit 104, and the output circuit 1
04 is connected to the heater 43 and is connected to the heater 43.
It has an output terminal TP for passing a current therethrough.

FIG. 3 shows a reaction vessel thermostatic chamber temperature measuring resistor 41.
Is shown inserted into the temperature measuring circuit for constant temperature chamber 102, the sample / reagent constant temperature chamber temperature measuring resistor 6
1. The reagent thermostat RTD 71 is also inserted into the thermostat temperature measuring circuit of the same configuration, and the arithmetic control circuit 10
3, connected to the output circuit 104. The cooling device (not shown) for the sample / reagent constant temperature bath 60 and the heater (not shown) for the reagent reservoir constant temperature bath 70 are controlled respectively, but the monitor temperature measuring circuit 101 is used. Are used in common to simplify the arithmetic control circuit 103.

Here, the temperature control characteristics of the biological sample automatic analyzer of the present embodiment will be examined. The heat insulation specifications required for the analytical substance 35 in the reaction container 30 are as follows.
The standard body temperature is 37 ° C ± 0.2 ° C, which is severe. In addition, as described above, in a thermostatic chamber using air as a heat medium, due to factors such as the influence of temperature changes, the heat generation of the power supply and drive motor in the device, or the influence of air flow in the device, It is technically extremely difficult to maintain the temperature within the control specifications.

Considering the temperature control for the configuration shown in FIG. 2, when the ambient temperature in the housing 10, that is, the detected temperature of the resistance temperature detector for monitoring 1 is lower than a predetermined temperature, for example, 37 ° C., the analytical substance 35 is discharged. In order to keep heating at T = 37 [° C.], the temperature of the reaction vessel thermostatic chamber 40 is T = 37.
It must be higher than [° C].

A more detailed description will be given with reference to FIG.
FIG. 4 shows the relationship between the control temperature of the reaction vessel thermostatic layer 40 and the output of the signal output terminal TP. As described above, when the ambient temperature in the housing 10 is lower than the predetermined temperature, the analytical substance 35 is obtained. ON-O of the heater 43 with the temperature T ₁ [° C.] higher than 37 [° C.] as the critical temperature.
It is necessary to operate the FF.

Then, the larger the temperature difference between the ambient temperature in the housing 10 and the maintaining temperature of the analyte 35, 37 [° C.], the higher T ₁ should be set. The difference between the ambient temperature in the housing 10 and the maintenance temperature of the analytical substance 35 is defined as a compensation temperature value. In this embodiment, the compensation temperature value is a linear primary with respect to the temperature detected by the monitor resistance temperature detector 1. Determine as a straight line. FIG. 5 shows the temperature detected by the monitor sensor on the horizontal axis and the control temperature on the vertical axis, showing an example of the relationship with the compensation temperature value.

When it is necessary to keep the temperature of not only the reaction container 30 but also the sample and the reagent with high accuracy, the temperature control of the sample / reagent thermostat 60 and the reagent reservoir thermostat 70 can be similarly performed. . However, when keeping the temperature of the reagent in the reagent storage tank 72, the reaction disk 2
Since the structure is not 0, a heat-shielding structure is relatively easy to take, and the compensation value linear gradient may be small in some cases. Figure 6
Shows the temperature detected by the monitor sensor on the horizontal axis and the control temperature on the vertical axis, showing an example of the relationship with the compensation temperature value.

In FIG. 3, the temperature measuring circuit for monitor 10 is used.
If the voltage output of 1 is X and the voltage output of the temperature measuring circuit 102 for constant temperature bath is Y, the output from the arithmetic control circuit 103 is
AX + Y (0 ≦ A ≦ 1).

As a specific example, the measuring circuits 101 and 10
The output variable resistors 110 and 111 of the bridge circuit of 2 are adjusted so that the reaction vessel constant temperature chamber temperature measuring resistance 41 is 37.5 [° C.].
Is detected, the differential voltage of the temperature measuring circuit 102 for constant temperature bath is 0, and when the resistance temperature detector 1 for monitoring of the temperature measuring circuit 101 for monitoring detects 37 [° C.], the differential voltage is 0. To do so. Further, the output circuit 104 is configured to realize thermal feedback so that the output from the arithmetic control circuit 103 becomes zero. The control temperature of the reaction vessel constant temperature bath 40 becomes many straight lines passing through the points of the coordinates (37 ° C., 37.5 ° C.) shown in FIG. 7.

The slope of the straight line is determined by the magnitude of A, that is, the magnitude of the voltage dividing variable resistor 112 of the output of the monitoring temperature measuring circuit 101 of the arithmetic control circuit 103. If it is desired to keep the analytical substance 35 at 37 [° C.] regardless of the monitor temperature, the difference between the control temperature indicated by the straight line and 37 [° C.] is the compensation temperature value for each detected temperature of the monitor sensor 1. Become.

The compensation temperature value can be easily obtained experimentally from the relationship between the temperature detected by the monitor sensor and the temperature of the analytical substance 35. The variable resistors 110, 111, 112 are adjusted so as to take the compensation temperature value. The analytical substance 35, which is surrounded by the controlled constant temperature bath 40 for a reaction container and kept warm by adding such a compensation temperature value, even if the temperature around the monitor detection changes due to a change in temperature or heat generated by the device itself. It is possible to accurately maintain, for example, 37 ° C. According to the data of the air constant temperature bath according to this embodiment,
Even if the outside air temperature of the device changes from 16 ° C. to 30 ° C., the analytical substance 35 can be kept at 37 ° C. ± 0.15.

[Embodiment 2] FIG. 8 is a sectional view including a partial control block diagram of an analyzer equipped with a temperature-controlled thermostatic chamber according to another embodiment of the present invention. As shown in FIG. 8, the case where the constant temperature bath for the reaction vessel is heated by the heated air blown by the fan will be described.

In FIG. 8, the same reference numerals as those in FIG. 1 are the same parts, so detailed description thereof will be omitted and only new reference numerals will be described. 41a is a temperature measuring body for blowing air temperature, 44 is a blower fan, and 102a is a blowing air temperature measuring circuit. The temperature compensating value is added to the temperature detected by the temperature sensor 41a for blowing air temperature to control the constant temperature bath 40 for the reaction vessel. The present invention is not limited to the above embodiments, and various modes are conceivable.

[0040]

As described above in detail, according to the present invention,
The ambient temperature around the constant temperature bath is detected by the monitoring sensor, and the compensation temperature determined by a linear linear line to the ambient temperature is added and controlled by the arithmetic control circuit. Even if there is, it is possible to provide an analyzer equipped with a constant temperature bath that keeps the temperature of the analysis substance accurate and constant.

[Brief description of drawings]

FIG. 1 is a schematic explanatory view including a partial block diagram of an analyzer equipped with a temperature-controlled thermostat according to an embodiment of the present invention.

FIG. 2 is a partial cross-sectional view of a constant temperature oven used in the analyzer with constant temperature oven of FIG.

FIG. 3 is a temperature control circuit diagram used in the analyzer with a constant temperature bath of FIG.

FIG. 4 is a diagram showing a signal output condition of the temperature control circuit of FIG.

5 is a diagram showing an example of control characteristics in the temperature control circuit of FIG.

6 is a diagram showing an example of another control characteristic in the temperature control circuit of FIG.

FIG. 7 is a diagram showing an example of still another control characteristic in the temperature control circuit of FIG.

FIG. 8 is a control block diagram including a partial cross-sectional view of an analyzer equipped with a temperature-controlled thermostatic chamber according to another embodiment of the present invention.

[Explanation of symbols]

 1 RTD for monitor 10 Housing 30 Reaction vessel 35 Analytical measurement substance 40 Constant temperature bath for reaction vessel 41 RTD for control of constant temperature bath 41a RTD for blowing air 43 Heater 44 Blower fan 101 Temperature for monitor Measuring circuit 102 Constant temperature bath temperature measuring circuit 102a Spraying air temperature measuring circuit 103 Arithmetic control circuit 104 Output circuit 111 Variable resistor 110 Variable resistor 112 Variable resistor

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Pan Hashimoto, 1040 Imo, Katsuta, Ibaraki, Hitachi Science Systems Co., Ltd. 72) Inventor Kahei Shiraishi, 1040, Moe, Katsuta, Ibaraki, Hitachi Science Systems Co., Ltd.

Claims (2)

[Claims] 1. A housing, an analysis / measurement unit mounted in the housing, a plurality of reaction containers for containing an analyte, and a reaction container transfer mechanism for holding the reaction container and transferring it to the analysis / measurement unit. A constant temperature bath for maintaining the reaction container at a specific temperature equipped with a temperature sensor, a container containing a sample and a reagent for producing the analyte, a transfer mechanism for holding and transferring the container, and a temperature In an analyzer equipped with a thermostatic chamber for maintaining the container equipped with a sensor at a specific temperature, and a pipetting mechanism for dispensing a required amount of each sample or each reagent into the reaction container, the internal space temperature of the housing A monitoring sensor for detecting the temperature of each of the constant temperature baths, and the temperature of the constant temperature bath and the internal space temperature of the housing detected by the monitoring sensor. A constant temperature with temperature compensation function, comprising: an arithmetic circuit for adding a constant compensation temperature related to the difference; and a control unit for controlling each of the constant temperature baths to a predetermined temperature based on each of the calculated values. An analyzer equipped with a tank. 2. The arithmetic circuit provides, to each temperature of each of the constant temperature baths, a compensation temperature determined in a linear linear form with respect to each difference between the temperature of each constant temperature bath and the detected temperature of the housing internal space. An analyzer comprising a thermostatic chamber with a temperature compensation function according to claim 1, wherein the temperature is added.