JPH03297377A - Automatic reactor - Google Patents

Abstract

PURPOSE:To provide the title reactor so designed that a thermostatic chamber is divided into two parts, and the current of a heating medium through the channel for each of the resulting thermostatic chambers is controlled using valves, thereby heating and cooling a reaction vessel vertically both from above and below leading to rapid temperature change within the reaction vessel, thus providing the thermostatic chamber with uniform temperature. CONSTITUTION:Heat transfer plates 30, 31 are provided for heating and cooling a reaction vessel 15 vertically both from above and below, and a higher- temperature chamber 28 and lower-temperature chamber 29 are kept at constant temperatures through controllers 32, 33, respectively. During heating, only valves 25, 22, 23, 20, 21, 24 are opened, pumps 16, 17 are driven, and a high-temperature heating medium is injected into the plates 30, 31. During cooling, only valves 27, 22, 23, 20, 21, 26 are opened, and a low-temperature heating medium is injected into the plates 30, 31. To maintain the system at a constant temperature, only valves 18 and 19, and either of the heating media is circulated using the pumps 16 and 17.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention enables the sample to be prepared by cyclically changing the temperature and reaction time to repeatedly proceed and stop the reaction between the sample and the enzyme filled in the reaction container. This invention relates to an improvement in an automatic reaction device for amplifying the amount of , and in particular, to an improvement in a thermostatic chamber installed in an automatic reaction device.

[Summary of the invention]

The present invention divides a constant temperature bath installed in an automatic reaction device into two parts, forms a wave path for flowing a heat medium in each part of the constant temperature bath, and connects a cooling unit that cools the heat medium and a cooling unit that heats the heat medium. The heating unit, constant temperature bath, cooling unit, and heating unit are each piped with insulated tubes, and each has a valve to control the flow of the heat medium.By heating and cooling from both the top and bottom of the reaction vessel, the reaction vessel is heated and cooled. The temperature of the sample and enzyme packed in the chamber is changed rapidly (at least 1° C./sec).

[Conventional technology]

Traditionally, reactions have been used for DNA cloning and amplification to amplify the amount of sample by cyclically changing the temperature and reaction time to repeatedly proceed and stop the reaction between the sample filled in a reaction container and an enzyme. ing. The structure of a constant temperature bath of an automatic reaction apparatus that automatically carries out the above reaction will be explained with reference to FIG. In FIG. 2, 51 is a reaction container filled with samples and enzymes, and this reaction container is housed in a plurality of recesses 52a formed in the aluminum block 52. A sheet-shaped heater 53 is disposed in close contact with the bottom surface of the aluminum block 52, and the outer surface including the aluminum block 52 is covered with a heat insulating material 54. Further, a flow path 52b for cooling liquid is formed in the aluminum block 52, and the flow path 52b is connected to the refrigerator (
(not shown).

When heating the reaction container 51, a current is passed through the sheet-like heater 53 to heat the aluminum block 52 from below. Cooling is carried out by circulating the cooling liquid inside the aluminum block 52 by the boiler of the refrigerator, and by heating and cooling the aluminum block 52 in this way, the aluminum block 52 is housed in the plurality of four parts 52a formed in the aluminum block 52. The reaction vessel 51 containing the liquid is heated and cooled.

[Invention tries to solve! II! ! ! However, in the structure of the constant temperature bath of the conventional automatic reaction device, the flow path 52 for the cooling liquid is
b, the size of the aluminum block 52 increases and its heat capacity also increases. On the other hand, since there is a limit to the amount of heat generated by the heating sheet heater 53, there is a time lag in which the temperature of the liquid in the reaction container does not start to change until after the aluminum block 52 has undergone a certain temperature change. Ta. Also, due to the structure, the cooling liquid remains inside the aluminum block, and when heating is performed, the cooling liquid is heated at the same time in the area around the flow path 52b compared to other parts, so an unnecessary amount of heat is taken and the area is heated. It takes time. Therefore, as a result, there is a drawback that temperature unevenness occurs in the aluminum block.

Therefore, the purpose of the present invention is to solve these conventional drawbacks by dividing the thermostatic chamber installed in the automatic reaction device into two parts and creating a wave path for flowing a heat medium into each part of the thermostatic chamber. By controlling the flow of heat medium with a valve, the reaction vessel is heated and cooled from both the top and bottom directions, and the temperature inside the reaction vessel can be changed rapidly (at least 1°C/sec), and the temperature is uniform. It was designed to obtain

c! ! ! ! Means for Solving A] In order to solve the above problems, the present invention divides a constant temperature bath installed in an automatic reaction device into two, and flows a plurality of branched heat carriers into each part of the constant temperature bath. In addition, the cooling unit that cools the heat medium, the heating unit that heats the heat medium, and the constant temperature chamber are each piped with heat-resistant tubes, and the flow of the heat medium is controlled by valves to control the flow of the constant temperature chamber. By flowing a heat medium in every corner, the reaction vessel is heated and cooled from both the top and bottom directions, and the thermostatic chamber is made of a good thermal conductive material only in the part facing the reaction vessel, and a heat insulating material in the other parts. By composing with two parts, the heat capacity is reduced.
The temperature of the sample and enzyme packed in the reaction vessel was increased rapidly (1
'C/see or higher) and uniformly changed.

[Effect]

If a thermostat installed in the automatic reaction device configured as described above is used, the control valve is operated to the position where the heat medium flows through the heating unit during heating, and the control valve is operated to the position where the heat medium flows through the cooling unit during cooling. The thermostatic bath is rapidly cooled by flowing water. Furthermore, by branching the flow paths in the thermostatic oven into a plurality of branches, the heat medium flows to every corner of the thermostatic oven, thereby making it possible to maintain a uniform temperature inside the thermostatic oven. Furthermore, when maintaining a constant temperature bath at a constant temperature, a heat medium can be circulated through the insulated system to maintain a constant temperature state without temperature unevenness.

〔Example〕

Embodiments of the present invention will be described below based on the drawings.

In FIGS. 1, 3, and 4, 1 is a reaction container filled with samples and enzymes. The thermostatic oven consists of a lid 2 and a main body 3, the lid 2 is composed of a good heat conduction plate 4 and a heat insulating plate 51, the main body 3 is composed of a good heat conduction block 6 and a heat insulating block 7, and the face where the cover 2 and the main body 3 face each other is is exposed with good thermal conductivity material, and other surfaces are covered with heat insulating material.

The lid 2 and the main body 3 are stacked, and the good heat conduction block 6 is formed with a plurality of recesses 6a for accommodating the reaction vessels 1. The surfaces of the good heat conduction plate 4 and the good heat conduction block 6 that are in contact with the heat insulation plate 5 and the heat insulation block 7 are provided with storage portions 6a.
The same number of grooves 4a and 6b as the rows are formed parallel to the rows of storage portions 6a. Further, the heat insulating plate 5 and the insulating block 7 have horizontal holes 5a and 7a formed on two opposing sides, respectively.
A groove 4a and a horizontal hole 5a at positions opposite to the grooves 4a and 6b,
Holes 5b and 7b are formed to connect the groove 6b and the horizontal hole 7a. The horizontal holes 5a and 7a have internal threads 5C and 7 in the center, respectively.
0 is formed, and pipe joints 8 and 9 are screwed together. The pipe joint 8 connects the outside of the control valve 10a and the insulation tube 1)
The inner side of the control valve 10a is also connected to the outer sides of the heating unit 12 and the cooling unit 13 through the heat insulating tube 1). Pipe fitting 9 is insulated tube 1
) is connected to the inside side of the heat medium flow pump 14. The control valve 1 is located on the outside side of the heat medium flow pump 14.
The inner side of the heating unit 2 and the cooling unit 3 are connected to the outside of the control valve 10b.

When rapidly heating the reaction vessel 1, the control valve 10b
is switched to the heating side, the heat medium flow pump 14 starts operating, the heat medium flows into the heating unit 12, and is heated while circulating in the heating unit 12,
It flows into the constant temperature bath via the control valve 10a. At this time, the control valve 10a is switched depending on which of the lid 2 and the main body 3 is to be heated first. The heat medium flows into the side holes 5a, 7a via the pipe joint 8, is branched at the connection holes 5b, 7b, and flows into the grooves 4a, 6b. At this time, the inflowing heat medium discharges the heat medium staying in the grooves 4a, 6b, so that only the heated heat medium exists in the grooves 4a, 6b. While flowing through the grooves 4a and 5b, the heat medium transfers heat to the good heat conduction plate 4 and the good heat conduction block 6, and the heat is transmitted to the reaction vessel 1. During cooling, the heat medium is similarly cooled while flowing through the cooling unit 13, and while the cooled heat medium flows between the good heat conduction plate 4 and the good heat conduction block 6, the heat transfer medium is cooled while flowing through the good heat conduction plate 4 and the good heat conduction block 6. Heat is removed from the heat conduction block 6 to cool the reaction container 1.

When heating and cooling, if the upper side of the reaction vessel 1 is lower in temperature than the lower side, the evaporated liquid will condense on the upper side of the reaction vessel 1, causing a problem that the reaction will not proceed sufficiently. The control valve 10a is controlled so that the temperature is slightly higher than that of the main body 3. Usually, aluminum or steel is used as a good heat conductor, Teflon or polyester resin with good heat resistance is used as a heat insulator, and the entire structure is covered with felt or the like. In addition, in this embodiment, the inlet and outlet of the heat medium are covered with a lid 2.
There are one groove each on the main body 3 and four grooves 6b, but this varies depending on the number of reaction vessels 1 that can be accommodated at one time. When the number of containers stored in reaction container 1 becomes 50 or 100,
If the constant temperature chamber becomes large and the heat medium has only one inlet and outlet, there is a risk of temperature unevenness. Ensure that the medium flows uniformly into the thermostatic chamber.

Further, FIG. 5 is an example that embodies FIG. 4.

The high temperature tank 28 and the low temperature tank 29 are always maintained at a constant temperature by controllers 32 and 33. During heating, only the valves 25, 22, 23, 20, 21, 24 are opened and the pumps 16, 17 are driven so that the high temperature heat medium is transferred to the upper heat conducting plate 30. Lower heat conduction plate 3
Pass through step 1 and heat. During cooling, valves 2722, 2
3. Open only 20.26 and the low-temperature heat medium flows through the upper heat conduction plate 30. It passes through the lower heat conduction plate 31 and is cooled.

In addition, in order to maintain a constant temperature, the heat medium is stirred by opening only the valves 18 and 19 and circulating the liquid with the pumps 16 and 17, and the upper heat conduction plate 30 and the lower heat conduction plate 31 are heated at a constant temperature without unevenness. temperature.

〔Effect of the invention〕

As described above, according to the present invention, the temperature can be changed rapidly by reducing the heat capacity of the constant temperature bath of the automatic reaction device, and by forming the flow path of the heat medium into a shape that branches into multiple parts. , the heating medium flows to every corner of the thermostatic oven, making it possible to maintain a uniform temperature inside the thermostatic oven. Therefore, the temperature of the sample and enzyme filled in the reaction vessel can be adjusted rapidly (1°C/sec).
It is possible to provide an automatic reaction device that can uniformly change the above).

[Brief explanation of drawings]

FIG. 1 is a front sectional view of the embodiment of the present invention, FIG. 2 is a sectional view of the conventional example, and FIG. 3 is a plan view of the thermostatic chamber main body of the embodiment of the present invention.
4 and 5 are piping diagrams of an embodiment of the present invention. 1...Reaction vessel 3...Main body 4...Good heat conduction plate 5...Insulation plate 6...Good heat conduction block 7...Insulation block 8.9...Pipe joint 1) ...Insulation tube 12...Heating unit 13...Cooling unit 2...Lid 10...Control valve 14, 15, 6 28, 0 31, 32, 33... Pump for heat medium flow... Reaction vessel 17...Pump 18-25...Valve...High temperature tank
29...Low temperature chamber...Upper heat transfer plate...Lower heat transfer plate...High temperature chamber controller...Low temperature chamber controller or higher

Claims (6)

[Claims] (1) In an automatic reaction device that changes temperature according to a preset program to proceed and stop the reaction between a sample and an enzyme filled in each of a plurality of reaction containers, the reaction container is heated and cooled from both the top and bottom directions. An automatic reaction device characterized by having a constant temperature bath. (2) A cooling unit for cooling the heat medium, a heating unit for heating the heat medium, and a tube for forming a flow path for the heat medium to flow in the constant temperature bath, and connecting each of the constant temperature bath, the cooling unit, and the heating unit using tubes. 2. The automatic reaction device according to item 1, which is equipped with piping and has a valve, and controls the temperature within the thermostatic chamber by controlling the flow of a heat medium. (3) In the control system for the heat medium, the temperature in the thermostatic chamber is controlled by switching the flow path for heating through the heating unit, the flow path for cooling through the cooling unit, and the heat medium to a circulating and insulated flow path. The automatic reaction device according to item 1, characterized in that the automatic reaction device is controlled. (4) The constant temperature bath consists of two parts: a part that heats and cools from the top surface of the reaction vessel and a part that heats and cools from the back of the reaction vessel, and the amount of heat medium flowing into the two parts of the constant temperature bath can be controlled independently. 2. The automatic reaction apparatus according to item 1, characterized in that the automatic reaction apparatus has a structure in which the temperature can be independently controlled by controlling the temperature. (5) The flow path formed in the constant temperature chamber has at least one entrance and exit in each of the upper and lower parts of the constant temperature chamber, and the flow path is structured to branch into multiple lines within the constant temperature chamber. The automatic reaction device according to item 1. (6) The automatic reaction apparatus according to item 1, wherein only the part of the thermostatic chamber facing the reaction vessel is made of a material with good thermal conductivity, and the other parts are made of a heat-insulating material.