JPH0510914A - Biosensor bath - Google Patents

Abstract

(57) [Summary] (Corrected) [Purpose] A constant temperature bath that uses water as a heat medium to maintain a constant temperature
You need a magnetic stirrer, stirrer, etc.,
Since it occupies a large volume and is troublesome in terms of maintenance management,
It is easy to maintain and compact without using water as the heat medium. A biosensor thermostatic bath of the present invention is configured such that a biosensor is inserted into one opening 20 of a metal thermostatic bath block 19 and a heat exchanger 21 is inserted into the other opening 22 to perform heat exchange. Piping system of the sample liquid that passes through the biosensor from the vessel 21 and is discharged to the outside, the sheet-shaped heater 4a attached to the bottom of the constant temperature oven block 19, and the constant temperature oven block 19
It is provided with a heat insulating material that covers the heat insulating material and a resin case that wraps the heat insulating material, and it is not necessary to use water as the heat medium of the constant temperature bath, and the maintenance and management of the device becomes very easy. Also, since it does not use a magnetic stirrer,
The occupied volume is extremely small and can be made compact.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a thermostatic bath for a biosensor of an apparatus for analyzing the components of a sample liquid by an immobilization membrane in which an enzyme, a microorganism or the like is fixed on a porous membrane as a molecular identification element (receptor).

[0002]

2. Description of the Related Art A biosensor of this type is a molecular identification element (receptor) that recognizes a substance to be measured in a sample liquid, and is immobilized on a porous membrane by applying a biofunctional substance such as an enzyme or a microorganism. It is a sensor that analyzes the components of a sample liquid by combining a chemical film and an electrochemical detector using an electrode.

In this sensor, a sample solution is brought into contact with an immobilization film, a change caused by a biochemical reaction caused by the detection is detected as an output current of an electrode, the measured value is calculated, and a signal is processed by a control section to obtain the value. It is based on the principle that the measured value is measured, and because it has the characteristic of excellent measurement selectivity that the measurement target can be determined by a biofunctional substance, it can be used for medical treatment such as blood glucose level measurement in blood tests. It is used in fields such as fermentation for measuring the concentration of alcohol in food quality control, measurement in the food industry, and environmental measurement in water quality measurement in wastewater treatment.

Generally, the reactivity, growth rate, and activity of enzymes and microorganisms used in biosensors change depending on temperature. The activity is low at low temperatures, and increases at high temperatures. It is known that when the maximum temperature is reached and the temperature becomes higher, it is inactivated due to heat denaturation and the activity decreases, and it is desirable to use it at around the optimum temperature in terms of reactivity and stability of the reaction. ing. Since biosensors also apply these substances,
Naturally, the output characteristics of the biosensor fluctuate depending on temperature, so it is necessary to perform measurement under constant temperature conditions.
The apparatus is configured to be suitable for this, and the measurement is performed with the temperature kept constant.

For example, FIG. 6, FIG. 7, and FIG.
7 is a device configuration diagram described in Japanese Patent Publication No. 7641, FIG. 6 is a sectional view taken along the line DD of FIG. 7, FIG. 7 is a sectional view taken along the line CC of FIG. 6, and FIG. It is the perspective view which separated and showed the component member.

This device will be described with reference to FIGS. 6 to 8, a thermometer 1 is used to control a constant temperature water tank 2
The temperature of the water inside is detected and the heater 4 is operated by the temperature controller 3.
The temperature of this water is maintained at the desired constant temperature by controlling the on / off of the water. At this time, the water in the constant temperature water tank 2 is agitated by externally rotating the stirrer 5 with the magnetic stirrer 6, so that the heat exchange efficiency is increased.
The constant temperature water tank 2 is placed on the magnetic stirrer 6. A storage tank 7 is attached to the upper part of the constant temperature water tank 2, and a biosensor 11 in which a flow cell 9 equipped with an immobilization membrane 8 and an electrochemical detector (electrode) 10 are combined in the storage tank 7. It is provided and the signal line 12 of the biosensor 11 is drawn out. Sample solution 13
Is sent from the inflow port 15 of the pipe 14a to the inside of the apparatus by a liquid sending pump (not shown), is heated through a heat exchanger 16 provided inside the constant temperature water tank 2, and then is sent to the pipe 14b.
Through the piping 17a in the storage tank 7 and the piping 1 for the flow cell 9
7b, the components are analyzed by the biosensor 11 , and then discharged from the outlet 18 to the outside of the system.

[0007]

However, as shown in FIG.
The conventional analyzer shown in FIG. 8 has the following problems especially with respect to the constant temperature water tank 2. That is, since the constant temperature water tank 2 uses water as a heat medium, it is necessary to always stir the water in order to keep the temperature constant. Therefore, the stirrer 5 and the magnetic stirrer 6 for stirring the water are required. Therefore, it is necessary to replace the stirrer 5 periodically because of the necessity of replenishing the water, and because the stirrer 5 is worn and the inside of the constant temperature water tank 2 is contaminated. In addition, the volume occupied by both the constant temperature water tank 2 and the magnetic stirrer 6 becomes large, which makes it difficult to maintain and manage the tank during long-term use.

The present invention has been made to solve the above problems, and an object thereof is to provide a thermostatic bath for biosensors which is compact, easy to maintain and obtains high measurement accuracy.

[0009]

In order to solve the above-mentioned problems, the thermosensor for a biosensor of the present invention is formed with two openings having an open upper surface and a pipe groove communicating with the two openings and passing through to a side wall. A thermostat block made of metal, a biosensor inserted into one opening of this thermostat block, a heat exchanger inserted into the other opening of the thermostat block, and a biosensor A piping system that discharges the sample liquid to the outside through the sensor, a heater that is attached to the bottom of the thermostatic bath block to set the thermostatic bath block to a predetermined temperature, a heat insulating material that covers the thermostatic water block, and a resin that wraps this heat insulating material. And a case.

[0010]

The biosensor thermostatic bath of the present invention is constructed as described above, and has the function of keeping the temperature condition of the biosensor constant by using the metal thermostatic bath block, and the sample liquid flowing into the flow cell of the biosensor. Since it is a constant temperature bath that has a heat exchange function to keep the temperature constant, it is possible to directly adjust the temperature of the sample liquid to a predetermined temperature, and it is not necessary to use water as the heat medium in the constant temperature bath, and this water is agitated. A stirrer and a magnetic stirrer are not required, and it is not necessary to replenish water or replace the stirrer regularly, and because the stirrer is not worn away, the inside of the device is very easy to maintain and manage. become. Further, the biosensor constant temperature bath of the present invention does not use a magnetic stirrer,
The occupied volume is extremely small compared to the conventional constant temperature water tank, and it can be made compact.

[0011]

EXAMPLES The present invention will be described below based on examples. For convenience of explanation, in the drawings shown below, the same reference numerals are used for the members common to FIGS. 6 to 8. FIG. 1 is a perspective view in which constituent members of essential parts are shown separately in order to explain the concept of the constant temperature oven of the present invention. In FIG. 1, the constant temperature bath block 19 has an opening 20 for inserting a biosensor on the upper surface thereof and a heat exchanger 2
It is a metal block in which an opening 22 for inserting 1 is formed. The opening 20 and the opening 22 are partially communicated with each other, and the pipe groove 23 reaching the end face of the constant temperature bath block 19 is for passing the pipe. The heat exchanger 21 is, for example, a collared A
l A coil-shaped stainless steel pipe 24 formed to have a sufficient length for heat exchange is fitted on the outer periphery of the main body 21a of the cylinder, and the stainless pipe 24 has a larger diameter so as not to easily come off from the main body 21a. 21b is fixed to one end, and the thermometer 1 is built in the upper part of the heat exchanger 21 . For example, a sheet-shaped heater 4a having a heating element embedded in silicon rubber is attached to the bottom surface of the constant temperature bath block 19, and the heater 4a and the thermometer 1 are connected to a temperature controller (not shown) to control at a predetermined temperature. can do.

When used outdoors, the heater 4
Instead of a, a functional element for heating / cooling by the Peltier effect can be attached. The Peltier effect is a phenomenon in which heat is generated or absorbed in addition to Joule heat when a current is applied to a contact between different types of conductors or semiconductors. By changing the direction of the current, heat generation and absorption are opposite. . Therefore, in the constant temperature bath of the present invention, the heater 4a
Instead of this, by using a functional element based on this Peltier effect and a temperature controller equipped with a power supply capable of reversing the direction of current, when the ambient temperature is higher than the set temperature, the functional element based on the Peltier effect is used. Acts as a cooler, and when the ambient temperature becomes lower than the set temperature, the direction of the electric current is reversed and acts as a heater, and in any case, the temperature of the constant temperature bath can be accurately kept constant. Therefore, in a place where the temperature greatly changes like the outdoors and the ambient temperature is higher than the set temperature depending on the season, a functional element based on the Peltier effect is used instead of the heater 4a, so that a stable and highly accurate sample can be obtained. It becomes possible to analyze the components of the liquid.

FIG. 2 is a biosensor used in the present invention.
It is a schematic cross section which shows the structure of the principal part of 11 . In FIG. 2, a flow cell 9 includes an electrochemical detector (electrode) 10,
The signal line 12, the oxygen permeable film 25, and the immobilization film 8 are fixed by O-rings 26a and 26b to form the biosensor 11 . Reference numeral 17a is a pipe for introducing the sample solution 13 into the flow cell 9, and 17b is a pipe for discharging the sample solution 13 out of the system.

3 and 4 are schematic cross-sectional views of the constant temperature oven of the present invention, which will be described below with reference to both figures. FIG. 3 is a schematic cross-sectional view of the thermostatic bath block 19 in which the biosensor 11 is inserted, as seen from the biosensor 11 side. Around the thermostatic bath block 19, a heat insulating material 27 not shown in FIG. The figure shows a state in which the thermostat block 19 is surrounded by a resin case 28 that contains the heat insulating material 27 as a whole. Biosensor 1 here
When 1 is set vertically to the bottom of the constant temperature bath block 19,
When the sample liquid 13 flows through the flow cell 9, since the sample liquid 13 contains air, the bubbles act so as to obstruct the flow of the sample liquid 13. In consideration of this point, in the present invention, in order to make the sample liquid 13 flow smoothly, the biosensor 11
The thermostat bath block 19 is preliminarily formed with an opening so that it has an inclination with respect to the direction perpendicular to the bottom surface of the thermostat bath block 19, and the biosensor 11 is attached at an inclination as shown in FIG. The inclination angle of the biosensor 11 does not have to be set precisely, but is preferably about 40 °. Then, in order to improve the heat conduction from the thermostatic bath block 19, the biosensor 11 is inserted in close contact with the flow cell 9 so that the contact area with the inner wall surface of the opening 20 of the thermostatic bath block 19 becomes as large as possible.

FIG. 4 is a schematic cross-sectional view of the thermosensor for biosensor of the present invention viewed from the direction perpendicular to FIG. 3, in which the sample solution 13 is introduced from the inlet 15 and passes through the stainless pipe 24 in the heat exchanger 21 . , Heat is exchanged to a predetermined temperature, and the biosensor 11 passes from the other pipe 14b to the pipe 17a.
After coming into contact with the immobilization membrane 8 of the flow cell 9 shown in FIG. 2, the gas is discharged from the outlet 18 through the pipe 17b to the outside of the system.

FIG. 5 is a characteristic diagram showing the results of measuring the temperature of each part of the biosensor constant temperature bath, where the vertical axis is temperature and the horizontal axis is elapsed time. In FIG. 5, T ₁ is the temperature of the inflowing sample liquid 13 at the inlet of the heat exchanger 21 , T ₂
Is the temperature of the sample solution 13 immediately after flowing out of the heat exchanger 21 , T
₃ indicates the temperature of the flow cell 9 and T ₄ indicates the temperature around the constant temperature bath block 19. As shown in FIG. 5, when the temperature T ₁ of the inflowing sample liquid 13 changes in the range of 13 ° C. to 36 ° C., the value of the temperature T ₂ of the sample liquid 13 immediately after flowing out of the heat exchanger 21 is 30.6. The temperature is accurately controlled within the range of + 0.7 ° C. and −0.5 ° C., which is a range in which the change in the output characteristics of the biosensor 11 can be ignored. Also,
As described above, when the temperature of the sample liquid 13 flowing in is higher than the set temperature, it is also found that the temperature can be controlled with high accuracy by cooling by using the functional element having the Peltier effect instead of the heater 4a. It was

[0017]

EFFECTS OF THE INVENTION Since the thermostatic bath for biosensors has conventionally used water as a heat medium, it has various disadvantages for keeping the temperature constant. As described above, the biosensor and the heat exchanger are respectively inserted into the two openings of the metal thermostatic bath block, and the temperature is raised by using the sheet-like heater at the bottom of the block, so that a constant temperature can be obtained. Therefore, it is possible to dispense with water as a heat medium, so not only a stirrer for stirring water and a magnetic stirrer are not required, but also water replenishment, contamination of the constant temperature water tank due to wear of the stirrer, stirring There is no need for conventional maintenance work such as regular replacement of children. Further, since the magnetic stirrer is not used, the occupied volume is reduced by about 80%, so it is very small and compact and maintenance is easy. In addition to these, according to the present invention, it is possible to control the temperature of the sample liquid with high accuracy, and it is possible to obtain highly accurate measured values. Further, when the temperature of the sample liquid is higher than the set temperature, the same effect can be brought about by cooling by using the functional element having the Peltier effect instead of the heater.

[Brief description of drawings]

FIG. 1 is a perspective view in which main components of a constant temperature oven of the present invention are shown separately.

FIG. 2 is a schematic cross-sectional view showing a main configuration of a biosensor used in the present invention.

FIG. 3 is a schematic cross-sectional view of the thermostatic bath block used in the present invention viewed from the biosensor side.

FIG. 4 is a schematic cross-sectional view of a constant temperature oven block used in the present invention as seen from a direction perpendicular to FIG.

FIG. 5 is a temperature characteristic diagram of each part related to the constant temperature bath of the present invention.

FIG. 6 is a D- of FIG. 7 showing a schematic cross-sectional view of a conventional constant temperature water tank.
D line cross section

FIG. 7 is a C- of FIG. 6 showing a schematic sectional view of a conventional constant temperature water tank.
C line cross section

FIG. 8 is a perspective view in which main constituent members of a conventional constant temperature water tank are shown separately.

[Explanation of symbols]

1 Thermometer 2 Constant Temperature Water Tank 3 Temperature Controller 4 Heater 4a Heater 5 Stirrer 6 Magnetic Stirrer 7 Storage Tank 8 Immobilization Membrane 9 Flow Cell 10 Electrochemical Detector (Electrode) 11 Biosensor 12 Signal Line 13 Sample Liquid 14a Piping 14b Piping 15 Inlet 16 Heat exchanger 17a Piping 17b Piping 18 Outlet 19 Thermostat block 20 Opening 21 Heat exchanger 21a Main body 21b Lid 22 Opening 23 Piping groove 24 Stainless steel pipe 25 Oxygen permeable membrane 26a O-ring 26b O-ring 27 Insulation 28 case

Claims (6)

[Claims] 1. A flow cell equipped with an immobilization membrane in which a biofunctional substance is immobilized on a porous membrane, and an electrochemical detector (electrode).
A thermosensor for a biosensor of an apparatus for analyzing the components of a sample solution adjusted to a predetermined temperature by using a thermosensor and a temperature controller by a biosensor in which a. A metal thermostatic bath block in which two openings having an open upper surface and a piping groove communicating with these openings and passing through the side wall are formed, b. A biosensor inserted into one opening of the thermostat block, c. A heat exchanger inserted into the other opening of the constant temperature bath block, d. A piping system that introduces a sample solution, passes through the biosensor from the heat exchanger, and discharges the sample solution to the outside, e. Heating means attached to the bottom of the thermostat bath block to set the thermostat bath block to a predetermined temperature, f. A thermostat for a biosensor, comprising: a heat insulating material that covers the thermostatic bath block; and a resin case that wraps the heat insulating material. 2. The constant temperature bath for a biosensor according to claim 1, wherein the biosensor has an inclination with respect to a direction perpendicular to the bottom surface of the constant temperature bath block. 3. The thermosensor for biosensor according to claim 1 or 2, wherein the biosensor is inserted in close contact with an inner surface of one opening of the thermostat block. 4. The biosensor thermostat according to claim 1, wherein the heat exchanger has a coil-shaped stainless steel, one end of which is connected to a pipe through which the sample solution flows, and the other end of which is connected to the biosensor pipe. A thermosensor bath for biosensors, characterized in that a pipe is fitted into a cylindrical body. 5. The biosensor thermostat according to claim 1, wherein a sheet heater is used as the heating means. 6. The thermosensor for biosensor according to claim 1, wherein a Peltier element is used as a heating means.