JP4259666B2 - incubator - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an incubator for promoting a reaction such as proliferation by changing the temperature of a reaction sample such as DNA collected from blood, a specimen or the like.
[0002]
[Prior art]
A conventional incubator of this type is shown as an apparatus for synthesizing DNA or the like in, for example, Japanese Patent Laid-Open No. 6-277036 (C07H21 / 00). The synthesizer shown there is an automatic synthesizer for DNA or RNA by the phosphotriester method, a reaction block for holding a reaction sample, a heating block provided with a heater, and a thermo module based on the Peltier effect as a cooling device And a cooling block provided with the reaction block, and the reaction block is selectively brought into contact with the heating block and the cooling block by the transfer means based on the output of the temperature sensor.
[0003]
Here, the method for synthesizing DNA or the like by the phosphotriester method is a method for promoting DNA growth by repeating the four steps of masking, deprotection, drying, and condensation in this order. In the apparatus, a sample mixed with DNA and various reagents / solvents is placed in a reaction block, a heater is controlled based on the output of the temperature sensor, and the heating block is heated to + 42 ° C. While performing a process, it moved to a cooling block by the transfer means, and it comprised so that a deprotection process might be performed by cooling a cooling block to +20 degreeC by the cooling effect | action of a Peltier device.
[0004]
Another conventional synthesis apparatus is a Peltier element in which the outer periphery of a reactor is covered with a heat block as shown in, for example, Japanese Utility Model Publication No. 62-44979, and the heat block has a heating and cooling function by the Peltier effect. And a thermistor is embedded in the Peltier element.
[0005]
In this case, the synthesis method using the synthesizer is to put a sample mixed with DNA and various reagents / solvents into the reactor, and control the energization of the Peltier element by the thermistor to heat the heat block to + 42 ° C. The demasking process was performed by performing the three steps of masking, drying and condensation, and cooling the heat block to + 20 ° C. by changing the energization direction of the Peltier element.
[0006]
[Problems to be solved by the invention]
However, in the former configuration, since a heater is used as a heating means, there is a problem that power consumption by the heater increases and running cost increases. In the latter configuration, the surface of the Peltier element that contacts the heat conductive heat block is repeatedly expanded during heat dissipation and contracted during heat absorption, which causes cracks in the Peltier element due to thermal stress. was there.
[0007]
Furthermore, in the latter case, since the sample was heated and cooled by switching the energizing direction of the Peltier element, the temperature was changed from heating to cooling and from cooling to heating depending on the heat capacity of the heat block and the Peltier element itself. Is not performed quickly, and there is a problem that there is a limit in improving the efficiency of the proliferation reaction.
[0008]
Therefore, the present invention has been made to solve the conventional technical problems, and the temperature of the reaction sample can be changed quickly and accurately, and the operation efficiency and durability are improved. The purpose is to provide an incubator.
[0009]
[Means for Solving the Problems]
The incubator of the present invention selectively contacts a heating block and a cooling block with a heat conductive reaction block holding a reaction sample, a heat conductive heating block, a heat conductive cooling block, and a reaction block. A first Peltier element that heats the heating block with a heat radiating surface, a second Peltier element that cools the cooling block with a heat absorbing surface, and the heat absorption of the first Peltier element. A heat conductive connecting member that connects the surface and the heat dissipation surface of the second Peltier element, and a fan for promoting heat dissipation on the heat dissipation surface of the second Peltier element, When the cooling effect is insufficient, the fan is operated .
[0010]
According to the present invention, the heat conductive reaction block holding the reaction sample, the heat conductive heating block, the heat conductive cooling block, and the reaction block are selectively brought into contact with the heating block and the cooling block. In the incubator provided with a transfer means, a first Peltier element that heats the heating block with a heat dissipation surface, a second Peltier element that cools the cooling block with an endothermic surface, and an endothermic surface of the first Peltier element Since it has a heat conductive connecting member for connecting the heat dissipation surface of the second Peltier element and a fan for promoting heat dissipation on the heat dissipation surface of the second Peltier element, the temperature of the reaction material held in the reaction block Can be changed quickly and accurately, and the reaction work efficiency can be remarkably improved.
[0011]
The heating block is heated by the heat dissipation surface of the first Peltier element, the cooling block is cooled by the heat absorption surface of the second Peltier element, and the heat absorption surface of the first Peltier element and the heat dissipation surface of the second Peltier element Are connected by a heat conductive connecting member, the heat energy generated from the heat dissipation surface of the second Peltier element can be recovered at the heat absorption surface of the first Peltier element and used for heating the heating block. .
[0012]
As a result, the efficiency (COP) is significantly improved compared to the case where a normal electric heater is used for heating the heating block, and the heating / cooling is performed by switching energization of a single Peltier element. As a result, the life of the Peltier element is extended and the durability is improved.
[0013]
In particular, when the cooling effect on the heat absorption surface of the second Peltier element is insufficient, the fan is operated, so that heat dissipation on the heat dissipation surface of the second Peltier element can be promoted. Thereby, even in a situation where the cooling effect on the heat absorption surface of the second Peltier element is insufficient, the fan is operated to perform air cooling, and the heat dissipation on the heat dissipation surface is promoted, thereby cooling the second Peltier element. Will be able to maintain.
[0014]
DETAILED DESCRIPTION OF THE INVENTION
Next, embodiments of the present invention will be described in detail with reference to the drawings. FIG. 1 is a front view of an incubator 1 of the present invention, and FIG. 2 is an electric circuit diagram of a control device 2 of the incubator 1.
[0015]
The incubator 1 of the example is referred to as a so-called PCR method in which this cycle is repeated a plurality of times, with a heat denaturation step of chromosomal DNA as a reaction sample, an annealing step with primers, and a strand extension step as one cycle. A device for realizing a DNA propagation method, a reaction block 3, a heating block 4 and a cooling block 5 formed of a heat conductive material such as aluminum, and a transfer device 6 as a transfer means for transferring the reaction block 3. (FIG. 2), a Peltier element 7 for heating the heating block 4, and a Peltier element 8 for cooling the cooling block 5.
[0016]
The Peltier element 7 is a semiconductor element having a heat absorbing / dissipating function based on the Peltier effect, and the lower surface (heat absorbing surface) of the Peltier element 7 contacts the heat conductive connecting member 13 in heat exchange and is connected to one end of the connecting member 13. It is attached. The upper surface (heat radiating surface) of the Peltier element 7 is attached to the heating block 4 in a heat conduction relationship, and a heating temperature sensor 12 made of a thermistor is embedded in the heating block 4.
[0017]
The Peltier element 8 is also a semiconductor element having a heat absorbing / dissipating function by the Peltier effect, and its lower surface (heat radiating surface) is attached to the other end of the connecting member 13 in heat exchange contact with the connecting member 13. Yes. A heat radiating fin 9 is attached to the lower surface of the other end portion of the connecting member 13, and a fan 14 that promotes heat radiation is provided opposite thereto. The cooling block 5 is attached to the upper surface (heat absorption surface) of the Peltier element 8 in a heat conductive relationship, and is arranged in parallel with the heating block 4 at a predetermined interval. A cooling temperature sensor 16 is embedded.
[0018]
The transfer device 6 includes a motor, a gear, and a support arm or a belt (not shown), and the reaction block 3 is attached to the support arm and the like. A plurality of holding holes 19 are formed on the upper surface of the reaction block 3 for holding and holding the tube 18 containing the above-described reaction sample. A reaction temperature sensor 21 comprising a thermistor is provided in the reaction block 3. Buried.
[0019]
The transfer device 6 transfers the reaction block 3 holding a plurality of such tubes 18 between the heating block 4 and the cooling block 5 and brings the lower surface of the reaction block 3 into contact with the upper surface of the heating block 4 or the cooling block 5. Is. At this time, the lower surface of the reaction block 3 and the upper surfaces of the heating block 4 and the cooling block 5 are all horizontal and smooth flat surfaces, whereby the reaction block 3 and the heating block 4 or the cooling block 5 have a wide area. So that heat transfer can be performed smoothly.
[0020]
In FIG. 2, the control device 2 is constituted by a general-purpose microcomputer 23 as control means, and the outputs of the reaction temperature sensor 21, the heating temperature sensor 12, and the cooling temperature sensor 16 are connected to the input of the microcomputer 23, The transfer device 6, the fan 14, the Peltier element 7 and the Peltier element 8 are connected to the output of the microcomputer 23.
[0021]
The operation of the incubator 1 of the present invention with the above configuration will be described. The set temperature (high temperature set temperature) of the reaction sample in the heat denaturation step is + 94 ° C., the set temperature (low temperature set temperature) in the annealing step and the extension step is + 37 ° C., and the microcomputer 23 sets the heat denaturation step to 3 for example. The annealing method and the elongation step are combined for 3 minutes, and this is repeated 30 times (3 hours) as one cycle to execute the PCR method.
[0022]
And the tube 18 which accommodated the said reaction sample is hold | maintained in the holding hole 19 of the reaction block 3, and operation | movement is started. In this initial state, since the microcomputer 23 separates the reaction block 3 from either the heating block 4 or the cooling block 5 by the transfer device 6, the temperature of the reaction block 3 is normal temperature. Then, the microcomputer 23 energizes the Peltier element 7 to heat the heating block 4. Then, based on the output of the heating temperature sensor 12, the temperature of the heating block 4 is maintained at + 120 ° C., which is a heating standby temperature higher than the high temperature set temperature.
[0023]
Next, the Peltier element 8 is energized, and after the temperature of the cooling block 5 is lowered to the cooling standby temperature of + 20 ° C., + 20 ° C. lower than the low temperature set temperature is maintained. And after predetermined time passes, the transfer apparatus 6 is controlled by the microcomputer 23, and the reaction block 3 is made to contact the heating block 4. FIG. As a result, the heat of the heating block 4 starts to be transmitted to the reaction block 3 and heating of the reaction sample in the tube 18 is started.
[0024]
At this time, since the reaction block 3 and the heating block 4 are thermally conductive and are in contact with each other over a wide area, heat transfer from the heating block 4 to the reaction block 3 is performed quickly. In addition, since the heating block 4 is maintained at a high temperature standby temperature (+ 120 ° C.) higher than the high temperature set temperature (+ 94 ° C.) in the standby state, the reaction block 3 is rapidly heated. The microcomputer 23 controls the energization of the Peltier element 7 based on the reaction temperature sensor 21 so that the temperature of the reaction block 3 is maintained at + 94 ° C. of the high temperature set temperature.
[0025]
Next, the microcomputer 23 continues to maintain the temperature of the cooling block 5 at + 20 ° C. of the cooling standby temperature by controlling the energization of the Peltier element 8 based on the cooling temperature sensor 16. Further, based on the integration of the timer, the reaction block 3 is maintained at the high temperature set temperature (+ 94 ° C.) until the time of the heat denaturation step of 3 minutes elapses after the reaction block 3 is brought into contact with the heating block 4. .
[0026]
When the heat denaturation time elapses, the microcomputer 23 ends the heat denaturation step, controls the transfer device 6 to separate the reaction block 3 from the heating block 4, and this time the reaction block 3 is brought into contact with the cooling block 5. . As a result, the heat of the reaction block 3 begins to be absorbed by the cooling block 5 and cooling of the reaction sample in the tube 18 is started.
[0027]
At this time, since the reaction block 3 and the cooling block 5 are thermally conductive and are in contact with each other over a wide area, heat transfer from the reaction block 3 to the cooling block 5 is performed quickly. Further, since the cooling block 5 is maintained at a low temperature standby temperature (+ 20 ° C.) lower than the low temperature set temperature (+ 37 ° C.) in the standby state, the reaction block 3 is rapidly cooled. The microcomputer 23 controls the energization of the Peltier element 8 based on the reaction temperature sensor 21 so that the temperature of the reaction block 3 is maintained at + 37 ° C. of the low temperature set temperature.
[0028]
Further, the microcomputer 23 controls the energization of the first Peltier element of the Peltier element 7 based on the heating temperature sensor 12 to maintain the temperature of the heating block 4 at + 120 ° C. of the heating standby temperature. On the other hand, the reaction block 3 is kept at the low temperature setting temperature (+ 37 ° C.) from the time when the reaction block 3 is brought into contact with the cooling block 5 until the time of the annealing / extension process for 3 minutes elapses.
[0029]
When the annealing / extension time has elapsed, the microcomputer 23 ends the annealing / extension process, and repeats the above processes, for example, 30 times. At this point, the number of DNA has grown to 100,000 times the initial number.
[0030]
When the proliferation reaction is completed, the microcomputer 23 brings the reaction block 3 into contact with the cooling block 5 and controls the energization of the Peltier element 8 based on the reaction temperature sensor 21, thereby increasing the temperature of the reaction block 3 to, for example, + 5 ° C. maintain. Thereby, the synthesized DNA is stored cold.
[0031]
Thus, according to the incubator 1 of the present invention, the temperature of the reaction material held in the reaction block 3 can be changed quickly and accurately by using the heating block 4 dedicated to heating and the cooling block 5 dedicated to cooling. As a result, the reaction work efficiency can be remarkably improved.
[0032]
At this time, the heating block 4 is heated by the heat dissipation surface of the Peltier element 7, and the cooling block 5 is cooled by the heat absorption surface of the Peltier element 8, and the heat absorption surface of the Peltier element 7 and the heat dissipation surface of the Peltier element 8 are heated. The conductive connection members 13 are connected. Therefore, the heat energy generated from the heat dissipation surface of the Peltier element 8 is transmitted through the connection member 13 and is recovered at the heat absorption surface of the Peltier element 7.
[0033]
That is, since the heat energy absorbed from the cooling block 5 can be reused for heating the heating block 4, the efficiency (COP) is remarkably improved as compared with the case where the heating block 4 is heated by a normal electric heater. In addition, the life of the Peltier element becomes longer and the durability is improved as compared with the case where heating and cooling are performed by switching the energization of a single Peltier element.
[0034]
In a situation where the cooling effect on the heat absorbing surface of the Peltier element 8 is insufficient, the microcomputer 23 operates the fan 14 to cool the other end of the connecting member 13 and promotes heat dissipation on the heat radiating surface. The cooling effect is maintained.
[0035]
【The invention's effect】
As described above in detail, according to the present invention, a heat conductive reaction block holding a reaction sample, a heat conductive heating block, a heat conductive cooling block, and a reaction block are selected as a heating block and a cooling block. In an incubator provided with a transfer means for bringing them into contact with each other, a first Peltier element that heats the heating block by a heat dissipation surface, a second Peltier element that cools the cooling block by the heat absorption surface, and a first Peltier element A heat conductive connecting member that connects the heat absorption surface of the element and the heat dissipation surface of the second Peltier element, and a fan for promoting heat dissipation on the heat dissipation surface of the second Peltier element, are held in the reaction block. Thus, the temperature of the reaction data can be changed quickly and accurately, and the reaction work efficiency can be remarkably improved.
[0036]
The heating block is heated by the heat dissipation surface of the first Peltier element, the cooling block is cooled by the heat absorption surface of the second Peltier element, and the heat absorption surface of the first Peltier element and the heat dissipation surface of the second Peltier element Are connected by a heat conductive connecting member, the heat energy generated from the heat dissipation surface of the second Peltier element can be recovered at the heat absorption surface of the first Peltier element and used for heating the heating block. .
[0037]
As a result, the efficiency is significantly improved as compared with the case where a normal electric heater is used for heating the heating block, and compared with the case where heating / cooling is performed by switching energization of a single Peltier element, The life of the Peltier element is also extended and the durability is improved.
[0038]
In particular, when the cooling effect on the heat absorption surface of the second Peltier element is insufficient, the fan is operated, so that heat dissipation on the heat dissipation surface of the second Peltier element can be promoted. Thereby, even in a situation where the cooling effect on the heat absorption surface of the second Peltier element is insufficient, the fan is operated to perform air cooling, and the heat dissipation on the heat dissipation surface is promoted, thereby cooling the second Peltier element. Will be able to maintain.
[Brief description of the drawings]
FIG. 1 is a front view of an incubator according to the present invention.
FIG. 2 is an electric circuit diagram of a control device for an incubator according to the present invention.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 Incubator 2 Control apparatus 3 Reaction block 4 Heating block 5 Cooling block 6 Transfer apparatus 7 Peltier element (1st Peltier element)
8 Peltier element (second Peltier element)
12 Heating temperature sensor 16 Cooling temperature sensor 21 Reaction temperature sensor 23 Microcomputer

Claims (1)

A heat conductive reaction block for holding a reaction sample, a heat conductive heating block, a heat conductive cooling block, and a transfer means for selectively bringing the reaction block into contact with the heating block and the cooling block In an incubator with
A first Peltier element that heats the heating block by a heat radiating surface; a second Peltier element that cools the cooling block by a heat absorbing surface; a heat absorbing surface of the first Peltier element; and a heat radiating surface of the second Peltier element. A heat conductive connecting member for connecting the heat sink and a fan for promoting heat dissipation on the heat dissipation surface of the second Peltier element,
The incubator , wherein the fan is operated when a cooling effect on the heat absorbing surface of the second Peltier element is insufficient .

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