Gene amplification module

Abstract

According to one aspect of the present invention, there is provided a gene amplification module including: a thermal block in which a reaction vessel accommodating space is formed; a heating unit provided below the thermal block; a cooling unit provided below the heating unit; and a fluid supply unit provided opposite one side of the thermal block and supplying a cooling fluid to the thermal block, wherein the thermal block has a sidewall that forms a periphery of the thermal block, and the sidewall has one or more supply holes formed therein through which the cooling fluid is supplied.

Description

Technical Field

[0001] This application claims the benefit of priority based on Korean Patent Application No. 10-2019-0006143, filed on January 17, 2019, and all the contents disclosed in the document of the corresponding Korean patent application are incorporated herein by reference as part of this specification.

[0002] The present invention relates to a gene amplification module capable of rapidly heating and cooling a sample in a reaction vessel as compared with the prior art.

Background Art

[0003] In order to perform gene diagnosis in which various biological information in a sample can be obtained, a gene amplification module for nucleic acid amplification (polymerase chain reaction, or polymerase chain reaction) is essential. That is, at the time of gene diagnosis, after amplifying a specific gene in a sample collected by a gene amplification module to increase the quantity of genes in the sample, the desired biological information can be obtained by confirming the degree of amplification of the specific gene.

[0004] Such gene amplification is performed by repeated temperature adjustment. More specifically, the temperature of the sample is periodically increased and decreased at predetermined time intervals to amplify the genes of the sample.

[0005] However, according to the prior art, in a gene amplification module, the cycle of temperature increase and decrease is long, and there is a limit to speeding up gene amplification. In particular, according to the prior art, when periodically adjusting the temperature of a sample in a gene amplification module, there is a problem that the cooling rate is slower than the heating rate. This causes a problem that the time required to amplify the genes of the sample increases, and as a result, the time required for gene diagnosis increases.

Summary of the Invention

Problems to be Solved by the Invention

[0006] The problem that this invention aims to solve is to reduce the time required to diagnose genes by reducing the time required to amplify the genes in a sample. [Means for solving the problem]

[0007] According to one aspect of the present invention for achieving the above objective, a gene amplification module is provided, comprising: a heat block having a reaction vessel housing space for housing a reaction vessel containing the sample to be amplified; a heating unit provided below the heat block for heating the heat block by heat exchange through heat conduction; a cooling unit provided below the heating unit for cooling the heat block by heat exchange through heat conduction; and a fluid supply unit provided facing one side of the heat block for supplying a cooling fluid to the heat block, wherein the heat block has side walls forming the periphery of the heat block, and one or more supply holes for supplying the cooling fluid are formed in the side walls.

[0008] An empty space is formed inside the heat block, and this empty space can be connected to the supply hole.

[0009] The heat block has a total of m × n reaction vessel housing spaces formed in an m × n matrix (where m and n are mutually distinct natural numbers), and the supply holes can be formed between each of the reaction vessel housing spaces.

[0010] The fluid supply unit may include a first fluid supply unit provided so as to face the side wall of the heat block in which the supply hole is formed, and a second fluid supply unit provided so as to face the other side wall of the heat block in which the supply hole is formed.

[0011] The fluid supply unit can be provided in close contact with the side wall in which the supply hole is formed.

[0012] The aforementioned empty space may not be connected to the reaction vessel containment space and may be located separately from the reaction vessel containment space.

[0013] The empty space may include a first empty space connected to the supply hole and a second empty space formed by intersecting the first empty space.

[0014] Discharge holes connected to the second open space can be formed in the side wall of the heat block.

[0015] The discharge holes can be formed at both ends of the second open space.

[0016] The fluid supply unit may include a rotatable fan to supply the cooling fluid into the empty space of the heat block. [Effects of the Invention]

[0017] According to the present invention, by adding a method for cooling the sample compared to the conventional method, the cooling rate can be increased, thereby reducing the time required to amplify the genes in the sample and thus reducing the time required to diagnose the genes. [Brief explanation of the drawing]

[0018] [Figure 1] This is a perspective view illustrating an example of the structure of the heat block of the gene amplification module according to the present invention. [Figure 2] This is a horizontal cross-sectional view illustrating an example of the structure of the heat block of the gene amplification module according to the present invention. [Figure 3] This is a perspective view illustrating the coupling relationship between the heat block and the fluid supply unit in the gene amplification module according to the present invention. [Figure 4] This is a perspective view illustrating the structure of the gene amplification module according to the present invention. [Figure 5] This is a perspective view illustrating another example of the structure of the heat block of the gene amplification module according to the present invention. [Figure 6] It is a horizontal sectional view showing another example of the structure of the heat block of the gene amplification module according to the present invention.

Embodiments for Carrying Out the Invention

[0019] Hereinafter, the structure of the gene amplification module according to the present invention will be described with reference to the drawings.

[0020] Gene amplification module FIG. 1 is a perspective view showing an example of the structure of the heat block of the gene amplification module according to the present invention, and FIG. 2 is a horizontal sectional view showing an example of the structure of the heat block of the gene amplification module according to the present invention. FIG. 3 is a perspective view showing the coupling relationship between the heat block and the fluid supply part in the gene amplification module according to the present invention.

[0021] As shown in FIG. 1, the gene amplification module according to the present invention can include a heat block 100.

[0022] The heat block 100 can be configured to accommodate a sample to be amplified. By being periodically heated and cooled by the heat transfer of the heat block 100, the gene of the sample accommodated in the heat block 100 can be amplified. For efficient heat transfer during the heating and cooling processes, the heat block 100 can be manufactured from a highly thermally conductive material such as gold, silver, copper, or an alloy. For example, the heat block 100 can be manufactured from aluminum.

[0023] For this purpose, as shown in FIG. 1, a reaction vessel accommodation space R for accommodating a reaction vessel (not shown) provided with a sample to be amplified can be formed in the heat block 100. FIG. 1 shows a case where a total of four reaction vessel accommodation spaces R are formed in a 2×2 matrix in the heat block 100. However, the number or arrangement structure of the reaction vessel accommodation spaces R is not limited to FIG. 1. On the other hand, the reaction vessel can be made of a plastic material.

[0024] Next, referring to Figure 1, the heat block 100 can have side walls 110 that form the periphery of the heat block 100. Figure 1 illustrates a case where four side walls are each formed as wavy curved surfaces. When the side walls of the heat block 100 are manufactured as wavy curved surfaces, the weight of the heat block 100 is minimized compared to the case where four flat surfaces are in contact with each other to form the side walls of the heat block. As a result, the heat capacity of the heat block 100 is reduced, and the heating and cooling rates of the heat block can be minimized. However, the shape of the side walls forming the periphery of the heat block 100 according to the present invention can have various shapes other than wavy. In other words, the shape of the side walls of the heat block 100 according to the present invention is not limited to wavy.

[0025] On the other hand, at least one hole can be formed in the side wall of the heat block 100. The hole formed in the heat block 100 may be configured for supplying and discharging a cooling fluid to cool the heated heat block 100. As illustrated in Figures 1 and 2, a supply hole SH for supplying the cooling fluid can be formed in a part of the side wall 110 of the heat block 100, and a discharge hole DH for discharging the cooling fluid to the outside can be formed in another part of the side wall 110 of the heat block 100. In this case, the cooling fluid may be a gas. For example, the cooling fluid may be air at room temperature.

[0026] Next, referring to Figure 2, an empty space V can be formed inside the heat block 100. The empty space V can be connected to the supply port SH and the discharge port DH. Thus, the empty space V can provide a path for the cooling fluid supplied to the heat block 100 to flow.

[0027] On the other hand, two supply holes SH can be formed, and in this case, the supply holes SH can be formed on opposite sides of the empty space V.

[0028] As illustrated in Figure 2, the empty space V formed in the heat block 100 can be formed so as not to be connected to the reaction vessel containment space R, but to be separated from the reaction vessel containment space R.

[0029] As described above, the reaction vessel containment space R can accommodate a reaction vessel containing the sample to be amplified. However, if the reaction vessel containment space R and the empty space V are connected to each other, the inner wall forming the reaction vessel containment space R will not be able to adequately enclose the reaction vessel. In this case, the sample will not be rapidly heated or cooled by the heat block 100, and the time required for amplification of the sample will increase. Therefore, according to the present invention, it is preferable that the reaction vessel containment space R is not connected to the empty space V so that the sample is rapidly heated or cooled by the heat block 100.

[0030] Furthermore, as illustrated in Figure 2, the empty space V formed inside the heat block 100 may include a first empty space V1 and a second empty space V2. Of these, both ends of the first empty space V1 can be connected to the supply holes SH. The second empty space V2 may be formed intersecting with the first empty space V1.

[0031] On the other hand, additional holes can be formed in the side walls of the heat block 100, in addition to the supply holes SH. That is, as shown in Figure 2, additional discharge holes DH can be formed in the side walls of the heat block 100. Figure 2 shows a case where one discharge hole DH is formed on each of the left and right side walls of the heat block 100, relative to Figure 2. The discharge holes DH can be connected to the second empty space V2. Multiple discharge holes DH can also be provided, for example, as shown in Figure 2, the discharge holes DH can be formed at both ends of the second empty space V2.

[0032] On the other hand, as illustrated in Figure 3, the gene amplification module according to the present invention may further include a fluid supply unit 400 that is positioned opposite one of the side walls of the heat block 100 and supplies cooling fluid to the heat block 100. The fluid supply unit 400 can face the side wall in which a supply hole SH (see Figure 2) is formed. Therefore, the fluid supply unit 400 can supply cooling fluid to the empty space V (see Figure 2) inside the heat block 100 through the supply hole.

[0033] Next, referring to Figure 3, the fluid supply unit 400 of the gene amplification module according to the present invention can be provided in multiple quantities. The number of fluid supply units 400 can be equal to the number of supply holes SH (see Figure 2). Figure 3 shows a first fluid supply unit 410 provided so as to face the side wall of the heat block 100 in which one of the two supply holes formed in the heat block 100 is formed, and a second fluid supply unit 420 provided so as to face the side wall of the heat block 100 in which the other of the two supply holes formed in the heat block 100 is formed.

[0034] On the other hand, the fluid supply unit 400 according to the present invention may include a rotatable fan so that cooling fluid is supplied into the empty space of the heat block 100.

[0035] As shown in Figure 3, the fluid supply unit 400 can be mounted in close contact with the side wall in which the supply hole SH (see Figure 2) is formed. Therefore, leakage of the cooling fluid from the fluid supply unit 400 to other parts other than the heat block 100 can be minimized.

[0036] On the other hand, as described above, the heat block 100 can have supply holes SH and discharge holes DH (see Figure 2), but the gene amplification module may further include a fluid discharge section (not shown) that is positioned opposite the discharge holes and discharges the cooling fluid inside the heat block 100 to the outside through the discharge holes.

[0037] Figure 4 is a perspective view illustrating the structure of the gene amplification module according to the present invention.

[0038] As described above, the gene amplification module 10 according to the present invention may include a heat block 100 and a fluid supply unit 400.

[0039] Furthermore, the gene amplification module 10 according to the present invention may include a heating unit 200 provided at the bottom of the heat block 100 for heating the heat block 100. The heating unit 200 can come into contact with the heat block 100. Therefore, the heating unit 200 can exchange heat with the heat block 100 by heat conduction. The heating unit 200 according to the present invention may be configured to heat the heat block 100 by a localized temperature increase due to the Peltier effect.

[0040] The Peltier effect refers to the phenomenon in which, when a voltage is applied to both sides of an object, thermal energy is transferred along with the electric current, resulting in a temperature difference between the two sides. The heating unit according to the present invention may be configured to heat a heat block by this Peltier effect.

[0041] Referring to Figure 4, the gene amplification module 10 according to the present invention may further include a cooling unit 300 provided below the heating unit 200 for cooling the heat block 100. The cooling unit 300 can be in contact with the heating unit 200. Therefore, the cooling unit 300 can cool the heat block 100 through heat exchange by heat conduction between the cooling unit 300 and the heating unit 200, and through heat exchange between the heating unit 200 and the heat block 100. In other words, the cooling unit 300 according to the present invention may be a heat sink with a lower temperature and significantly larger heat capacity compared to the heat block 100 and the heating unit 200.

[0042] The operation method of the gene amplification module 10 according to the present invention will be described below, based on the above-mentioned content and drawings.

[0043] After placing the reaction vessel containing the sample inside the reaction vessel housing space R of the heat block 100, the heating unit 200 is activated. As the temperature of the heating unit 200 rises, the temperature of the heat block 100 rises due to heat exchange by heat conduction between the heat block 100 and the heating unit 200, and consequently, the temperature of the sample inside the reaction vessel also rises.

[0044] When the sample temperature reaches a predetermined value, the operation of the heating unit 200 is interrupted. Consequently, the temperature of the heat block 100 decreases due to heat exchange by conduction between the cooling unit 300 and the heating unit 200, and heat exchange by conduction between the heating unit 200 and the heat block 100, and the temperature of the sample in the reaction vessel also decreases accordingly.

[0045] In particular, according to the present invention, as the cooling unit 300 is in operation, the cooling fluid is supplied by the fluid supply unit 400 through the supply holes SH of the heat block 100 into the empty space V of the heat block 100. As a result, the cooling fluid can further cool the heat block 100, allowing the heat block 100 and the sample to be cooled more quickly, and significantly reducing the overall time required for the sample amplification process.

[0046] Figure 5 is a perspective view illustrating another example of the structure of the heat block of the gene amplification module according to the present invention, and Figure 6 is a horizontal cross-sectional view illustrating another example of the structure of the heat block of the gene amplification module according to the present invention.

[0047] As described above, the heat block according to the present invention can have a total of four reaction vessel containment spaces arranged in a 2x2 matrix. However, the heat block can have a different structure. For example, as shown in Figures 5 and 6, the heat block 100 of the gene amplification module according to the present invention can have a total of nine reaction vessel containment spaces R arranged in a 3x3 matrix. Alternatively, the heat block 100 can have a total of nine reaction vessel containment spaces R arranged in a 4x4 matrix. Generalizing this, the heat block 100 of the gene amplification module according to the present invention can have a total of n reaction vessel containment spaces R arranged in an nxn matrix. 2A space for housing individual reaction vessels can be formed.

[0048] Alternatively, the thermal block of the gene amplification module according to the present invention may have a total of m × n reaction vessel containment spaces arranged in an m × n matrix (where m and n are mutually distinct natural numbers). For example, the thermal block may have a total of six reaction vessel containment spaces arranged in a 2 × 3 matrix.

[0049] Next, referring to Figures 5 and 6, multiple supply holes SH and discharge holes DH can be formed on the side walls forming the periphery of the heat block 100. For example, as shown in Figure 6, if a total of nine reaction vessel housing spaces R are formed in a 3x3 matrix in the heat block 100, two supply holes SH can be formed on each of the two side walls formed on opposite sides of the first empty space V1 formed inside the heat block 100, resulting in a total of four supply holes SH being formed in the heat block 100. Similarly, as shown in Figure 6, if a total of nine reaction vessel housing spaces R are formed in a 3x3 matrix in the heat block 100, two different side walls formed on opposite sides of the second empty space V2 formed inside the heat block 100, resulting in a total of four discharge holes DH being formed in the heat block 100. Generalizing this, the heat block of the gene amplification module according to the present invention can have a total of n in an nxn matrix. 2 When a reaction vessel housing space is formed, n-1 supply holes are formed in each of the two side walls formed on opposite sides of the first empty space of the heat block, and a total of 2 × (n-1) supply holes can be formed in the heat block. Similarly, in the heat block of the gene amplification module according to the present invention, a total of n × n supply holes can be formed in an n × n matrix. 2 When a reaction vessel housing space is formed, n-1 discharge holes are formed in each of the two side walls formed on opposite sides of the second empty space of the heat block, so that a total of 2 × (n-1) discharge holes can be formed in the heat block.

[0050] On the other hand, as described above, the heat block of the gene amplification module according to the present invention can have a total of m × n reaction vessel housing spaces formed in an m × n matrix (where m and n are mutually distinct natural numbers). In this case, m-1 supply holes are formed on each of the two side walls opposite each other across the first empty space of the heat block, so that a total of 2 × (m-1) supply holes can be formed in the heat block. On the other hand, n-1 discharge holes are formed on each of the two side walls opposite each other across the second empty space of the heat block, so that a total of 2 × (n-1) discharge holes can be formed in the heat block.

[0051] When a total of m × n reaction vessel containment spaces are formed in an m × n matrix in the heat block, m-1 supply holes are formed on each of the two side walls opposite each other across the first empty space of the heat block, and n-1 discharge holes are formed on each of the two side walls opposite each other across the second empty space of the heat block, because the supply holes SH and discharge holes DH are formed between the reaction vessel containment spaces R, as illustrated in Figures 5 and 6.

[0052] Furthermore, as illustrated in Figures 5 and 6, the supply hole SH, formed on opposite sides of the first empty space V1, and the discharge hole DH, formed on opposite sides of the second empty space V2, can be connected to the first empty space V1 and the second empty space V2, respectively.

[0053] Example 1 A thermal block measuring 16 mm wide and 16 mm long was manufactured. Each of the four side walls of the thermal block was formed with a wavy curved surface, creating a total of four reaction vessel housing spaces arranged in a 2x2 matrix. Each reaction vessel housing space had a diameter of 4.5 mm. The thermal block was made of aluminum.

[0054] Each of the four side walls of the heat block had a hole with a diameter of 4.8 mm, creating a cross-shaped void inside the heat block. The voids connected each hole to the others.

[0055] A Peltier-type thermoelectric heating element was fitted tightly to the bottom of the heat block. The heating element, which heats the heat block using the Peltier effect, was a VT-127-1.4-1.15-71 model manufactured by TE Technology, Inc. of the United States.

[0056] A cooling unit was fitted in close contact with the lower part of the heating unit. The cooling unit was designed as a heat sink capable of absorbing heat. A fan was installed at the lower end of the heat sink to lower its temperature. The heat sink and fan were manufactured by Coolertech, a South Korean company, and are model number CTV-GF-04.

[0057] Of the four side walls of the thermal block, fluid supply units were fitted tightly to two opposite side walls. The fluid supply units are configured to supply cooling fluid to the empty spaces of the thermal block by operating a fan. The fan used in the fluid supply units is a product named HFD 0200605 SEM, B-type, manufactured by YeHAUS Corporation of China.

[0058] In Example 1, the heating unit was operated under a voltage and current of 14.8V and 5A to heat the heat block until its temperature reached 95 degrees Celsius. After that, the heating unit was stopped, and the fluid supply unit was operated under 11.1V, 0.28A, and 3.1W to cool the heat block to 60 degrees Celsius using the cooling fluid and a cooling unit installed at the lower end. In particular, during the cooling process, a blower fan installed at the lower end of the heat sink was operated to lower the temperature of the heat sink, creating a gradient between the heat block and the heat sink to cool the heat block. The heating and cooling processes were repeated.

[0059] Example 2 The procedure was the same as in Example 1, except that the fluid supply unit was operated under 7.4V, 0.21V, and 1.5W to cool the temperature of the heat block until it reached 60 degrees Celsius.

[0060] Comparative Example The procedure was the same as in Example 1, except that a fluid supply unit was not provided.

[0061] Experimental example The time taken to complete 30 heating and cooling cycles was measured for the examples and comparative examples.

[0062] In Example 1, it took 602 seconds to complete 30 heating and cooling cycles, while in Example 2, it took 674 seconds. In the comparative example, it took 840 seconds.

[0063] As can be confirmed from the experimental results, when cooling fluid is supplied to the empty space of the heat block in Examples 1 and 2, the time required for the heating and cooling processes is significantly reduced compared to when it is not supplied. For example, compared to the comparative example, in Example 1, the time required for the heating and cooling processes to be completed was reduced by approximately 30%.

[0064] Although the present invention has been described above with reference to limited embodiments and drawings, it goes without saying that the present invention is not limited thereto, and that various implementations are possible within the equivalent scope of the technical concept of the present invention and the claims described below by persons with ordinary skill in the art to which the present invention pertains. [Explanation of symbols]

[0065] 10 Gene amplification modules 100 Heat Blocks 200 Heating section 300 Cooling section 400 Fluid supply section SH supply hole

Claims

1. A gene amplification module for performing gene amplification that requires temperature control, A thermally conductive heat block having a reaction vessel housing space formed therein for housing a reaction vessel containing a sample to be amplified, A heating unit is provided at the lower part of the heat block and heats the heat block by heat exchange through heat conduction with the heat block, A cooling unit is provided below the heating unit and cools the heat block by heat exchange through heat conduction with the heating unit, It includes a fluid supply unit provided opposite the side of the heat block and for supplying a cooling fluid to the heat block, The heat block has side walls that form the periphery of the heat block. The side wall has one or more supply holes formed therein, through which the cooling fluid is supplied. An empty space is formed inside the aforementioned heat block. The aforementioned empty space is connected to the supply hole, The heat block has a total of m × n reaction vessel housing spaces formed in an m × n matrix (where m and n are mutually distinct natural numbers). The supply holes are each formed between the reaction vessel containment spaces, The aforementioned fluid supply unit is A first fluid supply unit is provided so as to face the side wall of the heat block in which the supply hole is formed, A second fluid supply unit is provided so as to face the other side wall of the heat block in which the supply hole is formed, A gene amplification module, including...

2. The gene amplification module according to claim 1, wherein the fluid supply unit is provided in close contact with the side wall in which the supply hole is formed.

3. The gene amplification module according to claim 1, wherein the empty space is not connected to the reaction vessel containment space and is located separately from the reaction vessel containment space.

4. The aforementioned vacant space is A first empty space connected to the supply hole, The gene amplification module according to claim 1, comprising a second empty space formed by intersecting the first empty space.

5. The gene amplification module according to claim 4, wherein an exhaust hole connected to the second empty space is formed in the side wall of the heat block.

6. The gene amplification module according to claim 5, wherein the discharge holes are formed at both ends of the second empty space.

7. The aforementioned fluid supply unit is The gene amplification module according to claim 1, comprising a fan that is rotatable so as to supply the cooling fluid into the empty space of the heat block.

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