KR101113829B1 - Dual manifold and thermal cycling system comprising the same - Google Patents

Abstract

An object of the present invention is to provide a manifold in which the flow rate and temperature of each fluid discharged are equalized. It is also an object of the present invention to provide a manifold that takes up less space.

In order to achieve the above object, the present invention is:

At least one inlet pipe;

At least two discharge pipes;

An exterior defining a flow passage communicating with the inlet and outlet tubes; And

A double pipe manifold having an inner tube disposed to be spaced apart from the outer surface and defining the flow passage together with the outer surface.

Description

Dual manifold and thermal cycling system comprising the same

1 is a perspective view showing a conventional manifold;

2 is a perspective view showing a double tube manifold according to the present invention;

3 is a system diagram showing a thermocycler having a double tube manifold according to the present invention,

4 is an example of a temperature profile used in the enzymatic polymerization chain reaction.

Explanation of symbols on the main parts of the drawings

110: double pipe manifold, first manifold 111a, b, c: first, second, third inlet pipe

111c ': Inlet 112 of third inlet pipe: Appearance

113: inner tube 114: cap

115a, b, c, d, e, f: 1, 2, 3, 4, 5, 6 discharge pipe

115f ': outlet of the sixth discharge pipe

121, 122, 123, 124, 125, 126: 1st, 2, 3, 4, 5, 6 tank

121a, 122a, 123a, 124a, 125a, 126a: 1, 2, 3, 4, 5, 6 microtiter plates

130: second manifold 141, 142, 143: 1st, 2, 3 tank                 

141a, 142a, 143a: second valve 141b, 142b, 143b: cooling means

141c, 142c, 143c: heating means 141d, 142d, 143d: pump

141e, 142e, 143e: first valve C: center line of inner tube and outer tube

P: flow path R: radius of inner tube

G: gap between inner tube and outer tube

L: Distance between discharge pipe and inlet pipe closest to it

The present invention relates to a double tube manifold and a thermocycler having the same.

The conventional manifold shown in FIG. 1 includes a collection tube 12 for collecting fluid flowing through the first, second, and third inlet pipes 11a, 11b, and 11c. Distribution pipe 14 for branching the fluid discharged through the 5, 6 discharge pipes 15a, 15b, 15c, 15d, 15e, and 15f, and the fluid of the collection pipe 12 to move to the distribution pipe 14. Guide first and second connectors 13a, 13b are provided.

The basic function of the manifold is to branch the fluid introduced through the inlet duct. The pressure, flow rate and temperature of each branched fluid are preferably equal.

However, in the case of the conventional manifold shown in FIG. 1, the fluids flowing through the first, second, and third inlet pipes 11a, 11b, and 11c are collected in the collecting pipe 12 and the connecting pipes 13a and 13b. ), And the flow rate of each of the fluids discharged from the first, second, second, third, fourth, fifth, and sixth discharge pipes 15a, 15b, 15c, 15d, 15e, and 15f is not sufficiently mixed in the distribution pipe 14. And there is a problem that the temperature is not even. This non-uniform problem is between the first discharge pipe 15a and the sixth discharge pipe 15f and the other discharge pipes 15b, 15c, 15d, and 15e which are farthest from the connecting pipes 13a and 13b. It's even worse. The problem of inequality is even worse when the flow rate of the fluid flowing through the inlet tubes is high.

In addition, since the conventional manifold shown in FIG. 1 includes connecting pipes 13a and 13b connecting the collecting pipe 12 and the distribution pipe 14 at predetermined intervals to connect them, the space occupied by the manifold is limited. There is also a problem that it is large and therefore difficult to be installed in a narrow space.

An object of the present invention is to solve the above problems and to provide a manifold in which the flow rate and temperature of each of the discharged fluids are equalized.

It is also an object of the present invention to provide a manifold that takes up less space.

In order to achieve the above object, the present invention is:

At least one inlet pipe;

At least two discharge pipes;

An exterior defining a flow passage communicating with the inlet and outlet tubes; And                     

A double pipe manifold having an inner tube disposed to be spaced apart from the outer surface and defining the flow passage together with the outer surface.

In addition, in order to achieve the above object, the present invention is:

At least two tanks;

At least one tank capable of containing fluid conveyed from said baths;

Cooling means capable of cooling the fluid in the tank;

Heating means capable of heating the fluid in the tank;

A pump for transferring the fluid in the tank to a water tank; And

And a first manifold having a structure of the double pipe manifold, for branching the fluid transferred from the tank to the water tanks.

The double pipe manifold may be further provided with a cap installed at an end of the outer surface to define the flow passage and support the inner pipe.

The inner tube is preferably disposed between the inlet of the inlet pipe and the outlet of the outlet pipe, the center line of the inner tube and the center line of the appearance is preferably matched, the interval between the inner tube and the appearance is 7% to the radius of the inner tube to It is preferably 10%.

The number of the discharge pipes is twice the number of the inlet pipes, and the distance from the closest inlet pipe of all the discharge pipes is preferably the same, and the inner pipe is preferably formed of a metal having high thermal conductivity.

The thermocycler may include at least two tanks and a second manifold for branching fluid from the baths to the tanks. The second manifold may include at least one inlet pipe through which fluid transferred from the tanks flows in, at least two outlet pipes through which fluid transferred to the tank is discharged, and a flow passage communicating with the inlet pipes and the discharge pipes. It has an external appearance to define.

It is preferable that a first valve is provided between the tank and the first manifold to transfer at least a portion of the fluid transferred from the tank to the tank, and between the second manifold and the tank to the tank. Preferably, a second valve is provided to adjust the amount of fluid to be conveyed.

Next, the double pipe manifold according to an embodiment of the present invention will be described in detail with reference to FIG. 2. The double pipe manifold according to the present invention has at least one inlet pipe (111a, 111b, 111c), at least two outlet pipes (115a, 115b, 115c, 115d, 115e, 115f), the flow in communication with the inlet and outlet pipes An exterior 112 defining the passage P and an inner tube 113 spaced apart from the exterior within the exterior define a flow passage P together with the exterior.

The number of the discharge pipes 115a, 115b, 115c, 115d, 115e, and 115f illustrated in this embodiment is six, which is three times the number of the inlet pipes 111a, 111b and 111c. In addition, the first inlet pipe (111a), the third discharge pipe (115a) and the fourth discharge pipe (115d) for the inlet pipe (the first discharge pipe (115a) and the second discharge pipe (115b) closest to all discharge pipes In the case of the 2nd inflow pipe 111b, the 5th discharge pipe 115e, and the 6th discharge pipe 115f, the distance L of the 3rd inflow pipe 111c) is the same.                     

In the double pipe manifold 110 having the above-described structure, the fluid (for example, water) introduced through one inlet pipe (for example, the first inlet pipe 111a) is mainly two adjacent outlet pipes (for example, water). For example, the first passage pipe (115a) and the second discharge pipe (115b)) is divided into a flow passage (P) of narrow slit (slit) shape is also defined by the fluid 112 and the inner tube (113). Since the pressure drops and the vortex flows through the through, the pressure, flow rate, and temperature of each of the fluids discharged through the discharge pipes 115a, 115b, 115c, 115d, 115e, and 115f are all equalized. Also, unlike the conventional manifold shown in FIG. 1, the double pipe manifold 110 has a narrow flow path P connecting the inflow pipes and the discharge pipes in one pipe (exterior 112). It is advantageous to be installed in a space.

In order to uniformize the temperature of the fluid in the flow passage P, the inner tube 113 is preferably formed of a metal having high thermal conductivity, for example, copper, aluminum, or the like. For the same purpose, the appearance 112 is also preferably formed of a metal with high thermal conductivity. However, when the exterior is formed of a metal having high thermal conductivity, the exterior surface may be formed of a material having a low thermal conductivity such as glass fiber or plastic, in order to prevent the heat energy of the fluid from being discharged to the outside air through the exterior. It is preferable to cover with material.

A cap 114 is covered by the end portion 112a of the exterior shown in FIG. 2, and the end portion 113a of the inner tube is supported by the cap by being fitted into a hole formed in the center of the cap, and the cap 114 and The end 112a of the exterior is sealed by welding, and the cap 114 and the end 113a of the inner tube are also welded.                     

However, limiting the flow passage P by blocking the end portion 112a of the exterior using the cap 114 is just an example, and for example, there may be no cap 114. When the cap 114 is not present, the end 112a of the outer tube is pressed against the end 113a of the inner tube while the inner tube 113 is disposed in the outer tube 112, and the end 112a of the outer tube 112 and the inner tube are separated. The end 113a may be welded to define the flow passage P.

As shown in FIG. 2, the center line C of the inner tube 113 is used to limit the flow passage P using the cap 114 or to limit the flow passage P without using the cap. ) And the center line C of the appearance 112 preferably coincide as shown in FIG. 2.

If the gap G between the inner tube 113 and the outer 112 is too small, the flow friction of the fluid flowing in the flow passage P becomes large, so that the energy consumed by the pump for pumping the fluid becomes excessive. Not desirable On the contrary, if the distance G between the inner tube 113 and the outer tube 112 is too large, the fluid in the flow passage P is not sufficiently vortexed, and thus, the inner tube 113 is similar to the case where the inner tube 113 is not provided. Will be difficult to achieve. In consideration of such matters, the interval G between the inner tube 113 and the outer tube 112 is preferably 7% to 10% of the radius R of the inner tube 113.

Since the fluid introduced through the inlet pipes (111a, 111b, 111c) is preferably subjected to a vortex state for a sufficient time before discharged to the discharge pipes (115a, 115b, 115c, 115d, 115e, 115f), the inner tube 113 ) Is preferably disposed between the inlet of the inlet pipe (for example, the inlet 111c 'of the third inlet pipe) and the outlet of the outlet pipe (for example, the outlet 115f' of the sixth discharge pipe). . The inner tube 113 is disposed between the inlet and the outlet, which means that the inlet and outlet tubes form an angle of 90 ° to 180 ° (preferably 180 °) when viewed in the direction of the central axis C of the inner pipe. . For the same reason, the imaginary line V1 extending vertically from the inlet of the inlet pipe to the center line C of the inner tube is a virtual line V2 extending vertically from the outlet of the outlet pipe to the centerline C of the inner tube. It is more preferred to be substantially parallel to.

3 and 4, a thermal cycling system including the double pipe manifold 110 will be described.

A thermocycler is a device for controlling the temperature of a target object by allowing a fluid (eg, water) to pass through a specific object (eg, water tanks 121, 122, 123, 124, 125, 126). to be. This thermocycler can be used for various purposes, and recently, it has also been used in polymerase chain reaction (PCR) for DNA amplification.

The enzyme polymerization chain reaction refers to a reaction in which a heat-resistant polymerase amplifies DNA exponentially without cloning a part of a specific DNA. 4 illustrates the temperature profile of a bath equipped with a microtiter plate (MTP) 121a, 122a, 123a, 124a, 125a, 126a containing DNA. As shown, one enzyme polymerization chain reaction includes an activation step (Sa), a plurality of amplification cycles (Sc), and a drying step (Sd). The activation step (Sa) is continued for about 15 minutes while the temperature of the water tank is about 95 ℃, the drying step (Sd) lasts about 2 to 4 minutes when the temperature of the water tank is room temperature. Each of the amplification cycles (Sc) which are serially repeated between the activation step and the drying step includes a denaturing step for maintaining the temperature of the water tank for about 5 seconds at about 95 ° C, and the temperature of the water tank at about 56 ° C. An annealing step for lasting about 15 seconds, and an extension step for lasting 15 seconds for about 15 ° C. However, this is only one example, and the temperature profile may vary depending on the type of DNA to be amplified, the degree of amplification desired, and the like.

How the temperature profile is determined may vary depending on various conditions, but the temperatures at each particular time of each of the baths 121a, 122a, 123a, 124a, 125a, 126a should all be substantially the same. Herein, the temperature of the baths being substantially the same means that the maximum temperature difference between the baths is within 0.2 ° C. However, even if this maximum temperature difference is within 0.2 ° C, it is not guaranteed that all DNA contained in the microtiter plates mounted in all the tanks are amplified equally, and some may be amplified poorly (undesirably). Therefore, the maximum temperature difference between the baths needs to be minimized.

The thermocycler according to an embodiment of the present invention shown in FIG. 3 includes first, second, third, fourth, fifth, sixth tanks 121, 122, 123, 124, 125, 126, first, second, 3 tanks 141, 142, 143, cooling means 141b, 142b, 143b, heating means 141c, 142c, 143c, pumps 141d, 142d, 143d, a first manifold that is a double pipe manifold ( 110, a second manifold 130, first valves 141e, 142e, and 143e, and second valves 141a, 142a, and 143a.                     

The first, second, third, fourth, fifth, sixth tanks 121, 122, 123, 124, 125, and 126 are first, second, third, fourth, fifth, and sixth microtiter plates containing DNA to be amplified. Each of (121a, 122a, 123a, 124a, 125a, 126a) has a structure to which it can be mounted.

The first, second, and third tanks 141, 142, and 143 may accommodate the fluid transferred from the tanks therein, and cooling means 141b capable of cooling the fluid in each of the tanks. 142b and 143b and heating means 141c, 142c and 143c capable of heating the fluid are provided. The fluid contained in each of the tanks is transferred to the tanks via the first manifold 110 by pumps 141d, 142d, and 143d.

The cooling means may be, for example, a cooling tube through which a refrigerant flows. The cooling tube corresponds to an evaporator among the basic components forming a refrigeration system such as a compressor, a condenser, a throttle and an evaporator. The heating means may be, for example, a high resistance heating wire that generates a lot of heat when current flows.

The first manifold 110 is a double pipe manifold as described above and branches the fluid that is transported from the tanks to the water tanks. The second manifold 130 for branching the fluid transferred from the water tanks to the tanks is relatively less likely to be a double pipe manifold compared to the first manifold, which is a flow of fluid from the second manifold 130. This is because the temperature need not be precisely controlled.

The second manifold 130 of the present embodiment has the same structure as the manifold shown in FIG. 2 except that the inner tube 113 is not provided. In detail, the second manifold 130 includes six inflow pipes through which fluid transferred from the tanks 121, 122, 123, 124, 125, and 126 flows, and the tanks 141, 142, and 143. And three discharge pipes through which the fluid to be discharged is discharged, and a flow passage communicating with the inlet pipes and the discharge pipes. However, the second manifold 130 may have a double tube structure, such as the first manifold 110 as necessary, in which case the second manifold 130 is spaced apart from the exterior in the exterior and together with the exterior. It is further provided with an inner tube defining a flow passage.

Between each of the tanks 141, 142, 143 and the first manifold 110 there are first valves 141e, 142e, 143e that can convey at least a portion of the fluid transferred from a particular tank to the tank. Is installed. Also, between each of the tanks 141, 142, and 143 and the second manifold 130, second valves 141a, 142a, and 143a for controlling the amount of fluid transferred from the second manifold to a specific tank. Is installed.

In the case of the thermocycler according to the embodiment of the present invention described above, the first, second, second, third, fourth, fifth, sixth tanks 121, 122, 123, 124, 125, and 126 of the first and second baths 121, 122, 123, 124, 125, and 126 according to the temperature profile shown in FIG. As a result of controlling the temperature, the maximum temperature difference between the baths at the same time was 0.324 ° C. In contrast, when the conventional manifold 10 shown in FIG. 1 is installed in place of the double tube manifold 110 shown in FIG. 3, the maximum temperature difference between the baths at the same time point is 1.724 ° C. As such, the maximum temperature difference at the same time between the water tanks of the thermocycler according to the present invention is only 18.8% of 1.724 ° C. which is the maximum temperature difference at the same time between the water tanks of the conventional thermocycler. DNAs contained in MTP: Microtiter Plates 121a, 122a, 123a, 124a, 125a, 126a are all well amplified.                     

In the above-described embodiment, the first valves 141e, 142e and 143e and the second valves 141a, 142a and 143a are installed as necessary and are not necessary. In the absence of the first valves and the second valves, the flow rate of the fluid may be controlled by the pumps 141d, 142d, and 143d. In addition, a valve for adjusting the flow amount of the fluid may be provided at a position other than the positions of the first valve and the second valve shown in FIG. 3.

The thermocycler of the embodiment described above has six tanks and three tanks, but the invention is not so limited. That is, the technical idea of the present invention may be applied to a thermocycler having at least two tanks and at least one tank. In this case, the first manifold 110 has one inlet tube and two outlet tubes. In this case, since there is only one tank, there may be no second manifold 130. If there is no second manifold, the fluid passing through the tanks is transferred to the tank via or without the second valve.

According to the present invention, there is provided a double tube manifold and a thermocycler having the same, in which the flow rate and temperature of each of the fluid discharged are equalized.

The present invention also provides a double tube manifold that takes up less space.

Although the present invention has been described with reference to the embodiments shown in the drawings, this is merely exemplary, and it will be understood by those skilled in the art that various modifications and equivalent other embodiments are possible. Therefore, the true technical protection scope of the present invention will be defined by the technical spirit of the appended claims.

Claims (10)

At least one inlet pipe; At least two discharge pipes; An exterior defining a flow passage communicating with the inlet and outlet tubes; And And an inner tube disposed to be spaced apart from the exterior in the exterior and defining the flow passage together with the exterior. The inner pipe is a double pipe manifold, characterized in that disposed between the inlet of the inlet pipe and the outlet of the discharge pipe. The method of claim 1, A double pipe manifold is provided at an end of the outer surface, the cap defining a flow passage and supporting the inner pipe. delete The method of claim 1, A double pipe manifold, characterized in that the center line of the inner tube and the center line of the appearance coincide. The method of claim 4, wherein The gap between the inner tube and the outer tube is characterized in that the double tube manifold of 7% to 10% of the radius of the inner tube. The method of claim 1, The number of outlet pipes is twice the number of inlet pipes, Double pipe manifold, characterized in that the distance of the closest inlet pipe of all outlet pipes is the same. The method of claim 1, Double tube manifold, characterized in that the inner tube is formed of a metal. At least two tanks; At least two tanks capable of containing the fluid conveyed from the tanks; Cooling means capable of cooling the fluid in the tank; Heating means capable of heating the fluid in the tank; A pump for transferring the fluid in the tank to a water tank; At least one inlet pipe into which the fluid conveyed from the tank flows in, at least two outlet pipes from which the fluid conveyed to the tank is discharged, an appearance defining a flow passage communicating with the inlet pipe and the discharge pipes, and the appearance A first manifold disposed within the exterior and having an inner tube defining a flow passage together with the exterior, the first manifold for branching fluid transferred from the tank to the tanks; And At least one inlet pipe into which fluid transferred from the tanks is introduced, at least two outlet pipes from which fluid to be transferred to the tank is discharged, and an exterior defining a flow passage communicating with the inlet pipe and the discharge pipes And a second manifold for branching the fluid transferred from the tanks to the tanks. delete The method of claim 8, Between the tank and the first manifold is provided a first valve capable of conveying at least a portion of the fluid transferred from the tank to the tank, And a second valve disposed between the second manifold and the tank to adjust an amount of fluid transferred from the second manifold to the tank.

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