Composite material for thermal block of thermal cycler, and thermal block of low-specific-heat thermal cycler, manufactured using same.

Abstract

The present invention relates to a composite for a thermal block of a thermal cycler. The composite has both low specific heat characteristics and remarkably improved thermal conductivity, and thus, w

Description

Composite material for thermal block of thermal cycler and low specific heat capacity thermal cycler heat block manufactured using the same

[0001] The present invention relates to a composite material for a heat block of a thermal cycler, and more particularly, to a composite material for a heat block of a thermal cycler having excellent thermal conductivity and low specific heat, and a heat block of a thermal cycler having low specific heat manufactured using the same.

[0002] With recent industrial developments, the number of heat-dissipating and heat-generating electronic products has increased, and technologies for materials with superior thermoelectric properties are increasingly recognized as crucial. Their importance is growing in areas such as heat dissipation components for personal computers, LED heat sinks, and thermal block components for thermal cyclers. Thermal cyclers, in particular, are becoming increasingly important as basic diagnostic equipment for genetic diagnosis, and heat transfer material technology for high-speed diagnosis is attracting significant attention.

[0003] In the field of biotechnology, especially in the field of genetic diagnosis, the most important device is the PCR (Polymerase Chain Reaction) thermal cycler. The PCR reaction is a DNA replication technology called Polymerase Chain Reaction (PCR) developed by Mullis et al. in 1983. PCR is a method of continuously replicating template DNA using enzymes. The PCR step is divided into three steps: the denaturation step, which unwinds the double-stranded template DNA to be replicated into single strands; the annealing step, which binds a primer of several dozen bases to designate where the reaction will begin on the unwound single strand and help initiate the enzymatic reaction; and the extension step, which replicates DNA from the position where the primer is attached to create a complete double-helix DNA structure.

[0004] If the above three steps are performed, the amount of DNA theoretically increases by two times, and if this process is repeated n times, the amount of DNA theoretically increases by 2n times.

[0005] Typically, a PCR thermal cycler uses a temperature-controlled thermal block, and the thermal block is operated by periodically repeating temperature increases and decreases at regular time intervals to control the temperature.

[0006] A key component of a PCR (Polymerase Chain Reaction) thermal cycler is a thermal block with superior thermal properties. PCR involves repeated temperature rises and falls, requiring a thermal block with high thermal conductivity and low specific heat capacity. Conventional thermal blocks are typically made of aluminum, while high-speed PCR thermal cyclers utilize silver.

[0007] However, the aluminum used in these PCR thermal cyclers has poor specific heat capacity, making high-speed PCR reactions difficult. Furthermore, the use of silver poses economical challenges due to its high cost. Therefore, ongoing research is being conducted into various thermal conductive materials to address these issues.

[0008] To solve these problems, a heat block manufactured using a composite material in which tin powder with excellent specific heat properties and metal powder with excellent thermal conductivity are mixed has been provided.

[0009] However, in a PCR thermal cycler equipped with multiple unit heat blocks, the thermal conductivity characteristics of the unit heat blocks are poor, so there is a large difference in the temperature rise and fall rates between the unit heat blocks or in different regions within the unit heat blocks, which reduces the reliability of the PCR thermal cycler when an ultra-high-speed PCR reaction is performed.

[0010] Therefore, there is a need to develop a composite material that can provide a thermal block for a thermal cycler that has excellent specific heat properties and significantly improves thermal conductivity properties.

[0011] The purpose of the present invention is to provide a composite material for a heat block of a thermal cycler having both low specific heat characteristics and excellent thermal conductivity characteristics.

[0012] Another object of the present invention is to provide a heat block of a low specific heat capacity thermal cycler that has excellent thermal conductivity characteristics and can significantly reduce temperature change rate deviation when the temperature rises and falls.

[0013] Another object of the present invention is to provide a PCR thermal cycler that can ensure reliability even in ultra-high-speed PCR reactions, including the aforementioned thermal block.

[0014] According to one aspect of the present invention, a composite material for a thermal block of a thermal cycler is provided, which comprises a powder metal which is a first metal or an alloy containing the first metal; and

[0015] A metal nanowire having a core-shell structure in which a shell containing a third metal is positioned on a core containing a second metal.

[0016] In a composite material for a thermal block of a thermal cycler according to one embodiment of the present invention, the first metal may be tin, and the alloy may be at least one selected from the group consisting of tin-silver, tin-copper, tin-aluminum, tin-bismuth, tin-antimony, tin-copper-bismuth, tin-silver-bismuth, tin-copper-antimony, tin-silver-antimony, tin-copper-silver, tin-copper-silver-antimony, and tin-copper-silver-bismuth.

[0017] In a composite material for a thermal block of a thermal cycler according to one embodiment of the present invention, the second metal may be copper, and the third metal may be silver or gold.

[0018] In a composite material for a thermal block of a thermal cycler according to one embodiment of the present invention, the metal nanowire may be a silver-coated copper nanowire.

[0019] In a composite material for a thermal block of a thermal cycler according to one embodiment of the present invention, the metal nanowire has an Ag 3d of silver in an X-ray photoelectron spectroscopy spectrum. 5 / 2 Peak intensity (I1) of copper and Cu 2p of copper 3 / 2 The peak intensity (I2) may satisfy the following equation 1.

[0020] (Formula 1)

[0021] I2 / I1≤ 0.2

[0022] In a composite material for a thermal block of a thermal cycler according to one embodiment of the present invention, the diameter of the metal nanowire may be 100 to 500 nm, and the aspect ratio may be 5 to 100.

[0023] In a composite material for a thermal block of a thermal cycler according to one embodiment of the present invention, the particle size (D) of the powder metal p ): Diameter of metal nanowire (D) w ) of the ratio (D) p / D w ) can be 1:0.0001 to 0.01.

[0024] In a composite material for a thermal block of a thermal cycler according to one embodiment of the present invention, the weight ratio of the powder metal:metal nanowire may be 1:0.001 to 0.1.

[0025] In another aspect, the present invention provides a heat block of a low specific heat capacity thermal cycler manufactured by sintering, casting, rolling or casting the composite material described above.

[0026] The present invention also provides a heat block of a low specific heat capacity thermal cycler comprising tin or a tin alloy; and silver-coated copper nanowires; according to another aspect.

[0027] In the heat block of the low specific heat thermal cycler according to one embodiment of the present invention, the weight ratio of the tin or tin alloy: silver-coated copper nanowire may be 1:0.001 to 0.1.

[0028] In the heat block of the low specific heat thermal cycler according to one embodiment of the present invention, the silver-coated copper nanowire has an Ag 3d of silver in the X-ray photoelectron spectroscopy spectrum. 5 / 2 Peak intensity (I1) of copper and Cu 2p of copper 3 / 2 The peak intensity (I2) may satisfy the following equation 1.

[0029] (Formula 1)

[0030] I2 / I1≤ 0.2

[0031] In a heat block of a low-temperature thermal cycler according to one embodiment of the present invention, the thermal conductivity of the heat block may be 70 to 100 W / (m K) at 21°C.

[0032] According to another aspect of the present invention, a PCR (Polymerase Chain Reaction) thermal cycler is provided, comprising: a heating element; a heat block having one end in contact with one surface of the heating element and an insertion hole at another end positioned opposite the one end; wherein the heat block is formed by sintering, casting, rolling or casting the above-described composite material.

[0033] In the provided PCR (Polymerase Chain Reaction) thermal cycler according to one embodiment of the present invention, the thermal block may satisfy the following equation 2.

[0034] (Formula 2)

[0035] H a - H b ≤ ± 0.5 ℃ / sec

[0036] H in Equation 2 a is the heating rate in the region of 0.1 to 0.3t, defined as region A based on one end in contact with one surface of the heating element, in a heat block with a height of t, and H b is the heating rate in the 0.7t to 1.0t region, which is defined as region B.

[0037] The composite material for the thermal block of the thermal cycler of the present invention comprises a powder metal which is a first metal or an alloy containing the first metal; and a metal nanowire having a core-shell structure in which a shell containing a third metal is positioned on a core containing a second metal; thereby having low specific heat characteristics and significantly improving thermal conductivity characteristics.

[0038] In addition, in the case of a heat block manufactured using the composite material described above, when a temperature rise and fall change occurs in the heat block, there is an advantage in that the temperature change rate deviation between multiple unit heat blocks and / or in different regions within a unit heat block can be significantly reduced.

[0039] Furthermore, the PCR thermal cycler including the aforementioned thermal block has the advantage of ensuring reliability even in ultra-high-speed PCR reactions.

[0040] FIG. 1 is a schematic diagram illustrating a sintering, casting, rolling or casting process for a low specific heat composite material including silver-coated copper nanowires on tin or tin alloy according to the present invention.

[0041] Figure 2 is a schematic diagram showing a three-dimensional drawing of a thermal block molded product of a thermal cycler manufactured by sintering, casting, rolling or casting a low-thermal-density composite material according to the present invention.

[0042] The following examples will further describe the composite material for the heat block of a thermal cycler according to the present invention and the heat block of a low-specific-heat thermal cycler including the same. However, the following examples are merely references for explaining the present invention in detail, and the present invention is not limited thereto, and may be implemented in various forms.

[0043] Additionally, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein is for the purpose of describing specific embodiments only and is not intended to be limiting of the present invention.

[0044] In addition, in the following description, descriptions of known effects and configurations that may unnecessarily obscure the gist of the present invention are omitted. In the following specification, units used without special mention are based on weight, and for example, units of % or ratio mean weight% or weight ratio.

[0045] Additionally, the singular forms used in the specification of the present invention may be intended to include the plural forms as well, unless the context specifically indicates otherwise.

[0046] Additionally, when a part in this specification is said to "include" a certain component, this does not mean that it excludes other components, but rather that it may include other components, unless specifically stated otherwise.

[0047] Additionally, the numerical ranges used herein may include lower and upper limits and all values ​​within that range, increments logically derived from the shape and width of the defined range, all doubly defined values, and all possible combinations of upper and lower limits of numerical ranges defined in different shapes. Unless otherwise specifically defined in the present specification, values ​​outside the numerical range that may arise due to experimental error or rounding of values ​​are also included in the defined numerical range.

[0048] A composite material for a thermal block of a thermal cycler according to one embodiment of the present invention comprises a powder metal which is a first metal or an alloy containing the first metal; and a metal nanowire having a core-shell structure in which a shell containing a third metal is positioned on a core containing a second metal.

[0049] Gene amplification technology using polymerase chain reaction (PCR) is widely used for research and development and diagnostic purposes in fields such as life sciences, genetic engineering, and medicine.

[0050] PCR is a reaction that uses enzymes to continuously replicate template genes through the denaturation (melting) step, annealing step, and extension step, and repeats the aforementioned steps to amplify the amount of genes.

[0051] At this time, the denaturation step is usually carried out at 95°C, and the annealing step and extension step are carried out at 75°C or lower. As described above, in order to amplify the gene by repeatedly performing each step, it is necessary to repeatedly raise and lower the temperature of the gene sample.

[0052] For gene amplification, a device that can control the temperature of the genetic sample is essential, and a thermal cycler is widely used as such a device.

[0053] Typically, PCR thermal cyclers utilize a temperature-controlled thermal block, which periodically adjusts its temperature by repeatedly increasing and decreasing it at regular intervals. This thermal block requires excellent thermal conductivity and low specific heat, and is typically made of aluminum. High-speed PCR thermal cyclers utilize silver.

[0054] However, aluminum has poor specific heat properties, which limits its use in high-speed PCR reactions, and the method of using silver is not economical, which limits its use.

[0055] To solve these problems, conventionally, a thermal block manufactured using a composite material in which tin powder and metal powder with excellent thermal conductivity are mixed has been provided. However, in a PCR thermal cycler equipped with a plurality of unit thermal blocks, the thermal conductivity characteristics of the unit thermal blocks are poor, so that a large deviation in the temperature rise and fall speeds occurs between the unit thermal blocks and / or in different regions within the unit thermal blocks, and when an ultra-high-speed PCR reaction is performed, there is a problem in that the reliability of the PCR thermal cycler is lowered.

[0056] On the other hand, the composite material for the thermal block of the thermal cycler according to one embodiment of the present invention has a low specific heat characteristic and significantly improves the thermal conductivity characteristic by including a powder metal and a core-shell structured metal nanowire, and is advantageous in terms of economic efficiency. Therefore, in the case of a thermal block manufactured using the composite material described above, when a temperature rises and falls in the thermal block, the temperature change rate deviation between a plurality of unit thermal blocks and / or in different regions within the unit thermal block can be significantly reduced while being economical. In addition, the PCR thermal cycler including the thermal block described above has the advantage of ensuring reliability even in ultra-high-speed PCR reactions.

[0057] Specifically, the powder metal and core-shell structured metal nanowires included in the composite material for the heat block of the thermal cycler can be compression-molded to manufacture the heat block of the thermal cycler, wherein the flexible metal nanowires are compressed at a high density together with the powder metal and at the same time form a network between the metal nanowires to provide a uniform thermal movement path within the heat block, thereby significantly improving the thermal conductivity characteristics and significantly reducing the deviation in the temperature rise and fall rates between unit heat blocks and / or in different regions within the unit heat block.

[0058] On the other hand, when manufacturing a heat block using a composite material in which tin powder and a metal powder with excellent thermal conductivity are mixed, as in the past, there is a limit to uniformly dispersing the metal powder with excellent thermal conductivity, and as a result, the thermal movement path within the block cannot but be formed randomly, so that there is a large difference in the temperature rise and fall rates between unit heat blocks and / or in different regions within the unit heat block.

[0059] In one embodiment, in the first metal or alloy including the first metal, which is a powder metal, the first metal may be tin, and the alloy may be at least one selected from the group consisting of tin-silver, tin-copper, tin-aluminum, tin-bismuth, tin-antimony, tin-copper-bismuth, tin-silver-bismuth, tin-copper-antimony, tin-silver-antimony, tin-copper-silver, tin-copper-silver-antimony, and tin-copper-silver-bismuth.

[0060] By using tin or an alloy containing the tin as a powder metal in a composite material for a heat block of a thermal cycler, a heat block manufactured using the composite material can be provided with low specific heat characteristics.

[0061] In one specific example, the average particle size of the powder metal may be 40 to 200 μm, specifically 70 to 140 μm, and more specifically 80 to 120 μm.

[0062] In one embodiment, the second metal included in the core of the core-shell structured metal nanowire included in the composite material may be a metal having superior thermal conductivity compared to the first metal, and as an advantageous example, the second metal may be copper considering both thermal conductivity characteristics and cost efficiency.

[0063] As a specific example, in a metal nanowire having a core-shell structure, the third metal included in the shell may be a metal having a thermal conductivity similar to or equal to that of the second metal and satisfying the following equation 1.

[0064] At this time, a level similar to or equal to the thermal conductivity of the second metal may mean a level of at least 70%, 80%, 90%, or 100% of the thermal conductivity of the second metal, and the upper limit is not limited.

[0065] (Formula 1)

[0066] 0.6 ≤ C1 / C3 ≤ 2

[0067] (In Equation 1, C1 is the specific heat of the first metal, and C3 is the specific heat of the third metal)

[0068] As a specific example, the ratio (C1 / C3) of the specific heat of the first metal (C1) to the specific heat of the third metal (C3) may be 0.6 or more, 0.7 or more, 0.8 or more, 0.9 or more, and may be substantially 2 or less.

[0069] In this way, since the third metal included in the shell of the metal nanowire has a thermal conductivity similar to or higher than the thermal conductivity of the second metal and satisfies Equation 1 below, it is included in a composite material for a heat block of a thermal cycler together with the powder metal that is the first metal or an alloy including the first metal, and a heat block manufactured using the composite material can have remarkably excellent thermal conductivity characteristics along with low specific heat characteristics.

[0070] As a specific example, the third metal may be silver or gold.

[0071] In one embodiment, the diameter of the core-shell structured metal nanowire may be 100 to 500 nm, specifically 150 to 500 nm, more specifically 200 to 500 nm, and the aspect ratio of the metal nanowire may be 5 to 100, preferably 8 to 60, more preferably 10 to 40.

[0072] Since the diameter and aspect ratio of the metal nanowires included in the composite material for the heat block of the thermal cycle satisfy the above-mentioned range, when manufacturing the heat block using the same, a stable and uniform thermal movement path can be provided within the heat block.

[0073] As an advantageous example, the metal nanowire may be a silver-coated copper nanowire.

[0074] Silver-coated copper nanowires possess excellent thermal conductivity along with low specific heat, making them advantageous for inclusion in composite materials for thermal cycler heat blocks, along with powdered metals such as first metals or alloys containing the first metals, to enhance the thermal properties of heat blocks manufactured using the composite materials. Furthermore, the significant improvement in thermal properties is not cost-effective, making them economically viable.

[0075] For example, if the metal nanowire is a silver-coated copper nanowire, the metal nanowire has the Ag 3d of silver in the X-ray photoelectron spectroscopy spectrum. 5 / 2 Peak intensity (I1) of copper and Cu 2p of copper 3 / 2 The peak intensity (I2) may satisfy the following equation 2.

[0076] (Formula 2)

[0077] I2 / I1≤ 0.2

[0078] In the case of copper, when exposed to air, it is easily oxidized and its electrical and thermal properties may deteriorate due to the formation of copper oxide. However, as described above, since the metal nanowire, i.e., the silver-coated copper nanowire, satisfies the above equation 2, it has excellent oxidation stability and may be advantageous in maintaining the electrical and thermal properties of the silver-coated copper nanowire.

[0079] In a specific example, Ag 3d of silver in the X-ray photoelectron spectroscopy spectrum 5 / 2 Peak intensity (I1) of copper and Cu 2p of copper 3 / 2The ratio of peak intensities (I2) (I2 / I1) may be 0.2 or less, preferably 0.1 or less, more preferably 0.05 or less, even more preferably 0.03 or less, and may be 0.001 or more.

[0080] Ag 3d of silver in X-ray photoelectron spectroscopy spectrum 5 / 2 Peak intensity (I1) of copper and Cu 2p of copper 3 / 2 If the ratio (I2 / I1) of the peak intensities (I2) of silver in the core-shell structure is greater than 0.2, the copper exposed to the outside of the core-shell structure may be oxidized, which may reduce the oxidation stability of the metal nanowire, and thus the Ag 3d in the X-ray photoelectron spectroscopy spectrum may be reduced. 5 / 2 Peak intensity (I1) of copper and Cu 2p of copper 3 / 2 It is desirable that the ratio (I2 / I1) of the peak intensity (I2) satisfies the above-mentioned range.

[0081] In one specific example, the thickness of the silver coating, i.e., the cell, may be from 5 to 40 nm, specifically from 5 to 30 nm, more specifically from 5 to 20 nm, and even more specifically from 6 to 10 nm.

[0082] If the thickness of the shell is less than 5 nm, oxidation of copper contained in the core cannot be effectively suppressed, and if the thickness of the shell is more than 40 nm, the uniformity of the shell located on the core is poor, so there may be a possibility of copper oxide being generated, and it is not advantageous from an economic perspective, so it is recommended that the thickness of the shell satisfy the aforementioned range.

[0083] As an example of implementation, the average particle size (D) of the powder metal included in the composite material for the heat block of the thermal cycler p ): Diameter of metal nanowire (D) w ) of the ratio (D) p / D w ) can be 1:0.0001 to 0.01, specifically 1:0.0005 to 0.005.

[0084] When the ratio of the average particle size of the powder metal included in the composite material for the heat block of the thermal cycler to the diameter of the metal nanowire satisfies the above-mentioned range, the compactness of the heat block can be improved when manufacturing the heat block using the composite material.

[0085] At this time, the composite material for the heat block of the thermal cycler may contain 0.1 to 60 wt%, specifically 0.5 to 30 wt%, and more specifically 1 to 10 wt% of metal nanowires.

[0086] In one embodiment, the weight ratio of the powder metal:metal nanowire included in the composite material for the heat block of the thermal cycler may be 1:0.001 to 0.5, advantageously 1:0.001 to 0.1, more advantageously 1:0.005 to 0.1, and even more advantageously 1:0.01 to 0.05.

[0087] For example, a composite material for a heat block of a thermal cycler can be manufactured by physically mixing powdered metal and metal nanowires. However, if the weight ratio of powdered metal to metal nanowires is less than 0.001, the powdered metal and metal nanowires can be uniformly mixed, but there is a limit to the formation of a thermal movement path through the formation of a network of metal nanowires, so there is a limit to improving the thermal conductivity characteristics. In addition, if the weight ratio of powdered metal to metal nanowires exceeds 0.5, the mixing of powdered metal and metal nanowires may not occur uniformly, which may actually deteriorate the thermal conductivity characteristics. In addition, an unnecessarily large amount of metal nanowires may be included, which may lower economic efficiency. Therefore, it is preferable that the weight ratio of powdered metal to metal nanowires included in the composite material for a heat block of a thermal cycler satisfies the aforementioned range.

[0088] At this time, the composite material for the heat block of the thermal cycler can be manufactured using a high-speed rotating mixer that mixes powdered metal and metal nanowires that satisfy the aforementioned weight ratio. For example, the high-speed rotating mixer may have a rotation speed of 150 to 1000 rpm, specifically 300 to 800 rpm, and more specifically 400 to 600 rpm.

[0089] In addition, the mixing process using a high-speed rotating mixer for uniform mixing of powdered metal and metal nanowires can be performed one or more times, two or more times, or three or more times, and although the upper limit is not limited, it is of course possible to perform it less than 10 times in practice.

[0090] The present invention provides a heat block of a low specific heat thermal cycler manufactured by sintering, casting or casting a composite material for a heat block of the above-described thermal cycler.

[0091] In addition, the present invention provides a heat block of a low specific heat capacity thermal cycler comprising tin or a tin alloy; and silver-coated copper nanowires.

[0092] Here, the lead alloy is similar or identical to the alloy containing the first metal described above, and a detailed description thereof is omitted.

[0093] In one embodiment, the weight ratio of tin or tin alloy: silver coated copper nanowires may be 1:0.001 to 0.5, advantageously 1:0.001 to 0.1, more advantageously 1:0.005 to 0.1, and even more advantageously 1:0.01 to 0.05.

[0094] Since the heat block includes tin or tin alloy and silver-coated copper nanowires in the weight ratio described above, a network can be formed between the silver-coated copper nanowires to provide a uniform thermal movement path within the heat block, thereby significantly reducing the difference in temperature rise and fall rates between unit heat blocks and / or in different regions within the unit heat block.

[0095] In one embodiment, silver-coated copper nanowires exhibit Ag 3d in the X-ray photoelectron spectroscopy spectrum. 5 / 2 Peak intensity (I1) of copper and Cu 2p of copper 3 / 2 The peak intensity (I2) may satisfy the following equation 2.

[0096] (Formula 2)

[0097] I2 / I1≤ 0.2

[0098] Since the silver-coated copper nanowire satisfies the above equation 2, it has excellent oxidation stability, which may be advantageous in maintaining the original electrical and thermal properties of the silver-coated copper nanowire.

[0099] In a specific example, Ag 3d of silver in the X-ray photoelectron spectroscopy spectrum 5 / 2 Peak intensity (I1) of copper and Cu 2p of copper 3 / 2 The ratio of peak intensities (I2) (I2 / I1) may be 0.2 or less, preferably 0.1 or less, more preferably 0.05 or less, even more preferably 0.03 or less, and may be 0.001 or more.

[0100] Ag 3d of silver in X-ray photoelectron spectroscopy spectrum 5 / 2 Peak intensity (I1) of copper and Cu 2p of copper 3 / 2 If the ratio (I2 / I1) of the peak intensity (I2) of silver is greater than 0.2, the copper exposed to the outside of the silver-coated copper nanowire may be oxidized, which may reduce the oxidation stability of the silver-coated copper nanowire. Therefore, the Ag 3d of silver in the X-ray photoelectron spectroscopy spectrum 5 / 2Peak intensity (I1) of copper and Cu 2p of copper 3 / 2 It is desirable that the ratio (I2 / I1) of the peak intensity (I2) satisfies the above-mentioned range.

[0101] At this time, the silver-coated copper nanowire is similar or identical to the metal nanowire of the core-shell structure described above, and thus a detailed description of the diameter, aspect ratio, and thickness of the silver-coated copper nanowire is omitted.

[0102] In one embodiment, the thermal conductivity of the heat block of the low-temperature thermal cycler may be 70 to 150 W / (m K), specifically 70 to 100 W / (m K), and more specifically 70 to 80 W / (m K) at 21°C.

[0103] As a specific example, the heat block of the low-density thermal cycler has a density of 5 to 20 g / mL, specifically 5 to 10 g / mL, a heat capacity of 0.2 to 1 J / (g K), specifically 0.2 to 0.5 J / (g K), and a volumetric heat capacity of 1 to 2 J / (cm 3 K), specifically 1 to 1.8 J / (cm 3 It may have the properties of K.

[0104] In this way, the heat block of the low-temperature thermal cycler includes tin or a tin alloy and silver-coated copper nanowires satisfying the above formula 2, and has the above-mentioned properties, so that it has the advantage of significantly reducing the temperature change rate deviation between multiple unit heat blocks and / or in different regions within a unit heat block in the temperature rise and fall changes of the heat block.

[0105] In addition, the present invention provides a PCR (Polymerase Chain Reaction) thermal cycler comprising: a heating element; a heat block having one end in contact with one surface of the heating element and an insertion hole at another end positioned opposite the one end; wherein the heat block is formed by sintering, casting, rolling, or casting the above-described composite material.

[0106] A PCR thermal cycler according to one embodiment of the present invention includes a heat block formed using the above-described composite material capable of significantly improving heat transfer efficiency, thereby improving gene amplification reaction efficiency and ensuring reliability even in ultra-high-speed PCR reactions.

[0107] In one specific example, the heating element may be a heat source that can transfer heat to the heat block and perform a cooling function at the same time by having one end of the heat block contact one surface of the heating element.

[0108] As a specific example, the heating element may be a Peltier element, and the Peltier element generates heat and cools in the same element by switching the direction of current, and the lower surface of the Peltier element acts as a cooling element, and the upper surface that comes into contact with one end of the heat block generates heat.

[0109] At this time, a heat sink may be attached to the lower surface of the Peltier element to improve cooling efficiency.

[0110] In one embodiment, the heat block may include an insertion hole at one end positioned opposite to one end that contacts one surface of the heating element, and a reagent or sample container may be inserted into the heat block through the insertion hole so that the inner surface of the heat block and the outer surface of the container come into surface contact, thereby inducing a temperature change in the reagent or sample. In this case, the shape of the insertion hole may be the same as the shape of the outer surface of the reagent or sample container, and the present invention is not limited by the shape of the insertion hole.

[0111] In one embodiment, the heat block may satisfy Equation 3 below.

[0112] (Formula 3)

[0113] H a - H b ≤ ± 0.5 ℃ / sec

[0114] H in Equation 3 a is the heating rate in the region of 0.1 to 0.3t, defined as region A based on one end in contact with one surface of the heating element, in a heat block with a height of t, and H b is the heating rate in the 0.7t to 1.0t region, which is defined as region B.

[0115] At this time, the heating rate may be the ratio (ΔT / Δs) of the temperature change (ΔT) measured based on the initial temperature to the time change (Δs) calculated by measuring the temperature in each of Area A and Area B after 15 seconds when increasing the temperature to 95℃ using a heating element.

[0116] In one specific example, the difference in heating rates in areas A and B (H a - H b ) may be ± 0.5 ℃ / sec or less, ± 0.4 ℃ / sec or less, ± 0.3 ℃ / sec or less, ± 0.2 ℃ / sec or less, and the lower limit value is not limited, but may be substantially ± 0.01 ℃ / sec or more, and more substantially ± 0.05 ℃ / sec or more.

[0117] As the thermal block satisfies the above equation 3, the efficiency of the gene amplification reaction can be improved, and the reliability of the PCR thermal cycler can be secured even for ultra-high-speed PCR reactions.

[0118] In addition, the difference in cooling rates in areas A and B may be similar to or identical to the difference in heating rates in areas A and B described above. In this case, the cooling rate may be the ratio (ΔT / Δs) of the temperature change (ΔT) measured based on the initial temperature to the time change (Δs) calculated by measuring the temperature in areas A and B after 15 seconds when lowering from 95°C to 25°C using a heating element.

[0119] In one implementation example, the absolute value of the ramping rate of the PCR thermal cycler may be 3.0°C or greater.

[0120] Specifically, the rise and fall speeds of the PCR thermal cycler can be independently different.

[0121] For example, the ramp rate of a PCR thermal cycler may be 3.0°C or higher, specifically 3.5°C or higher, more specifically 3.8°C or higher, and the upper limit may be, but is not limited to, 10°C or lower, and substantially 8°C or lower.

[0122] Unlike the rising speed of the PCR thermal cycler described above, the falling speed of the PCR thermal cycler has a negative value. Although it has a negative value, the falling speed of the PCR thermal cycler can be 3.0°C or higher, specifically 3.05°C or higher, and more specifically 3.08°C or higher based on the absolute value, and the upper limit is not limited, but can be 8°C or lower, and practically 6°C or lower.

[0123] In addition, the PCR thermal cycler may include, in addition to the aforementioned heating element and heat block, conventional components known in the art, such as a control device, an optical system, a fluorescence detection device, and an analysis device.

[0124] Hereinafter, the composite material for the thermal block of the thermal cycler according to the present invention and the thermal block including the same will be described in more detail through examples. However, the following examples are merely a reference for explaining the present invention in detail, and the present invention is not limited thereto, and may be implemented in various forms.

[0125] Additionally, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein is merely for the purpose of describing specific embodiments and is not intended to be limiting of the present invention.

[0126]

[0127] (Manufacturing Example 1)

[0128] 1200 ml of water (ultrapure water) and 15.0 g of the copper nanowires manufactured by the above manufacturing example were added to a 5 L flask, and the mixture was stirred at 10,000 rpm using a homomixer (Homomixer, K-Corporation, Primix). To remove the oxide film on the copper nanowires, 22.5 g of ethylenediaminetetraacetic acid disodium salt (EDTA-2Na Dihydrate, Samjeon Pure Chemical Industry) dissolved in 150 ml of water (ultrapure water) was added, and the mixture was stirred at 10,000 rpm for 3 minutes. To this, 13.1 g of L-ascorbic acid (C6H8O6, Samjeon Pure Chemical Industry), a reducing agent, was dissolved in 150 ml of water (ultrapure water), added, and stirred again for 3 minutes.

[0129] To perform the first silver coating on the copper nanowires from which the oxide film was removed, 150 ml of water (ultra-pure water) and 1.67 g of silver nitrate (AgNO3, Juntec) were mixed to prepare a first silver nitrate solution, and the solution was added at a rate of 10 ml per minute using a peristaltic pump (Leadfluid, BT100L) for about 15 minutes to allow the reaction.

[0130] Afterwards, the sample with the first silver coating was washed with 2 L of water (ultra-pure water) and dried to obtain a first silver-coated copper nanowire sample.

[0131] Next, to perform the secondary silver coating, the sample on which the primary silver coating was completed and 1,200 ml of water (ultra-pure water) were placed in a 5 L flask and stirred at 10,000 rpm using a homomixer (Homomixer, K-Corporation, Primix). To stably remove copper ions, 22.5 g of ethylenediaminetetraacetic acid disodium salt (EDTA-2Na Dihydrate, Samjeon Pure Chemical Industry) was dissolved in 150 ml of water (ultra-pure water) and added, and stirred at 10,000 rpm for 3 minutes.

[0132] 21 g of potassium sodium tartrate tetrahydrate (KNaC4H4O6·4H2O), a reducing agent, was dissolved in 150 ml of water (ultra-pure water) and added, and stirred for another 3 minutes. To perform the secondary silver coating, 4.23 g of silver nitrate was added to 655 ml of water (ultra-pure water) to prepare a silver nitrate solution, and then 4.34 ml of ammonia water (NH4OH, Samchun Pure Chemicals) was added to prepare a second silver nitrate-ammonia complex solution. The prepared second silver-ammonia complex solution was added at a rate of 10 ml per minute and reacted for approximately 66 minutes.

[0133] After the reaction was completed, the separated metal nanowires were washed with 2 L of water (ultrapure water) using a filter paper and dried at room temperature for 24 hours to obtain copper nanowires thinly and uniformly coated with silver.

[0134] The length and thickness of the obtained silver-coated copper nanowires were analyzed, and the length was measured to be 2.1 to 6.3 μm and the thickness to be 191 to 450 nm.

[0135] Additionally, Ag 3d was obtained from the XPS spectrum obtained by X-ray photoelectron spectroscopy (XPS, Thermo VG Scientific, Sigma Probe) on the surface of silver-coated copper nanowires. 5 / 2Peak intensity (I1) and Cu 2p 3 / 2 As a result of comparing the peak intensity (I2), it was confirmed that I2 / I1 was 0.029.

[0136]

[0137] (Manufacturing Example 2)

[0138] The same procedure as Manufacturing Example 1 was followed, except that the first silver coating reaction was not performed, and instead, a silver nitrate solution was prepared by adding 655 ml of water (ultrapure water) to 12.2 g of silver nitrate to perform the second silver coating, and then 4.34 ml of ammonia water (NH4OH, Samchun Pure Chemicals) was added to form a silver coating layer on the copper nanowire using only the second silver-ammonia complex solution.

[0139] At this time, Ag 3d derived from XPS spectrum 5 / 2 Peak intensity (I1) and Cu 2p 3 / 2 As a result of comparing the peak intensity (I2), it was confirmed that I2 / I1 was 0.41.

[0140]

[0141] (Example 1)

[0142] Tin powder (average particle size 100 μm) and silver-coated copper nanowires manufactured in Manufacturing Example 1 were mixed at a weight ratio of 99.5:0.5, and approximately 130 g of the mixture was placed in a high-speed fluidized mixer (HSFM-10-S, Isin Machinery) and mixed twice at 500 rpm for 10 minutes.

[0143] About 130 g of the mixture (composite material) mixed above was placed between upper and lower funnels in a mold (inner center diameter 40.0 mm) made of graphite, and the mold containing the mixture was mounted between presses of a vertical press structure in a high-temperature press device (D1P-20J; Daeheung Scientific), and then pressurized with a hydraulic cylinder and melt-molded at 260°C.

[0144] A processing process for manufacturing a molded product (heat block) using a composite material including tin powder and silver-coated copper nanowires is schematically illustrated in Fig. 1.

[0145] Specimens containing the above-mentioned formed tin- and silver-coated copper nanowires were subjected to non-destructive testing using an ultrasonic flaw detector (SISTSCAN 500, Kyungdo Yanghaeng Co., Ltd.). As a result, it was confirmed that the specimens containing the formed tin- and silver-coated copper nanowires were melt-formed without pores or defects.

[0146] In the above molding, the molding was performed under the condition of a melting temperature of 260°C and a holding time of 30 minutes. The sintered molded product was analyzed using a thermal diffusivity measuring device (Xenon Flash Instrument LFA 447; NETZSCH), and the thermal analysis results are summarized in Table 1 below.

[0147]

[0148] (Examples 2 to 6)

[0149] The same procedure as in Example 1 was followed, except that the mixing ratio of tin powder: silver-coated copper nanowires was changed to 99:1 (Example 2), 98.5:1.5 (Example 3), 98:2 (Example 4), 97.5:2.5 (Example 5), and 97:3 (Example 6). The thermal analysis results of each sintered molded product are summarized in Table 1 below, and a non-destructive test was performed on the molded specimen of Example 3. The non-destructive test results of Example 3 confirmed that the molded specimen including tin and silver-coated copper nanowires was melt-molded without pores or defects, similar to the results of Example 1.

[0150]

[0151] (Example 7)

[0152] The same procedure as Example 3 was followed, except that the silver-coated copper nanowires manufactured in Manufacturing Example 2 were used. The thermal analysis results of the sintered molded product are summarized in Table 1 below.

[0153]

[0154] (Example 8)

[0155] The same procedure as Example 3 was followed, except that the tin powder and silver-coated copper nanowires were mixed using a mortar and pestle instead of a high-speed fluidized bed mixer. The thermal analysis results of the sintered molded product are summarized in Table 1 below.

[0156] The results of non-destructive testing of specimens formed using a mixture of tin powder and silver-coated copper nanowires mixed using a mortar and pestle showed that, unlike the results of Examples 1 and 3, the specimens containing the formed tin and silver-coated copper nanowires had pores or defects exceeding the standard.

[0157]

[0158] (Comparative Example 1)

[0159] The same procedure as Example 1 was followed, except that tin powder was used alone. The thermal analysis results of the sintered molded product are summarized in Table 1 below.

[0160]

[0161] (Comparative Example 2)

[0162] The same procedure as Example 3 was followed, except that tin powder and silver powder were mixed and used, and the thermal analysis results of the sintered molded product are summarized in Table 1 below.

[0163]

[0164] Referring to Table 1, it was observed that the thermal conductivity characteristics of Example 3 were the best, and it was found that the specimens manufactured using a composite material mixed with tin powder and silver-coated copper nanowires had improved thermal conductivity characteristics compared to the specimens manufactured using only tin powder (Comparative Example 1) and the composite material mixed with tin powder and silver powder (Comparative Example 2).

[0165] In addition, when comparing the thermal conductivity characteristics of Examples 3 and 7, it was confirmed that the surface characteristics of the silver-coated copper nanowires included in the composite material affect the thermal conductivity characteristics.

[0166] Specifically, Ag 3d derived from XPS spectra 5 / 2 Peak intensity (I1) and Cu 2p 3 / 2 Based on the ratio (I2 / I1) of the peak intensity (I2) of the silver coating layer located on the copper nanowires, it can be seen that the thermal conductivity characteristics of the molded article using the composite material of Example 3 including silver-coated copper nanowires in which the silver coating layer is uniformly and densely formed on the copper nanowires is relatively superior to the thermal conductivity characteristics of the molded article using the composite material of Example 7 including silver-coated copper nanowires in which a portion of the copper is exposed because the silver is not uniformly coated.

[0167]

[0168] (Experimental example) Confirmation of heat transfer characteristics

[0169] In order to confirm the heat transfer characteristics of the manufactured specimens, the molded products of Examples 1, 3, 7 and Comparative Examples 1 and 2 were attached to the Peltier element to confirm the heat transfer characteristics.

[0170] At this time, voltage was applied to the Peltier element to raise the temperature of the molded product to 95℃, and the temperatures of the 0.2t section (area A) and the 0.8t section (area B) at the total height t of the molded product based on the contact surface of the molded product in contact with the Peltier element were measured simultaneously, and the measurements were made before and 15 seconds after the voltage was applied, respectively. The temperature change amount for 15 seconds in each area was used as the heating rate to compare the heat transfer characteristics of each molded product, and the results are summarized in Table 2 below.

[0171]

[0172] Referring to Table 2, in the cases of Examples 1, 3, and 7, it was observed that there was almost no difference in heating rate between the area near the bonding surface of the molded article attached to the Peltier element (Area A) and the area relatively spaced from the bonding surface (Area B), whereas in the cases of Comparative Examples 1 and 2, it was observed that the heating rate difference in each area was large, at 0.6°C or more.

[0173] In addition, when the current direction of the Peltier element was switched to change the temperature from 95℃ to 25℃ in the same manner as the heating rate described above, the cooling rate was calculated and compared, and it was confirmed that almost similar results were obtained.

[0174] It can be seen that the molded article manufactured using a composite material mixed with tin powder and silver-coated copper nanowires has almost no difference in heating and cooling rates between the area directly in contact with the heat source and the area relatively distant from the heat source, and from this, it can be seen that the heat transfer efficiency of the molded article is significantly excellent, and it can be seen that the molded article can be applied as a heat block of a PCR thermal cycler to improve the efficiency of gene amplification reaction and at the same time ensure reliability even in ultra-high-speed PCR reaction.

[0175] Additionally, a PCR heat block having the shape shown in Figure 5 was manufactured by casting at 260°C using the composite material of Example 3. The manufactured PCR heat block was mounted on a real-time PCR device (ExiCycler; Bioneer) to measure its thermal characteristics.

[0176] At this time, since the PCR reaction temperature is 95 ℃, the temperature was increased from 25 ℃ to 95 ℃ and decreased from 95 ℃ to 25 ℃, and the rising and falling speeds of the PCR cycler were measured three times each compared to those of the conventional aluminum PCR heat block, and the analysis results are summarized in Table 3 below.

[0177]

[0178]

[0179] As can be seen in Table 3 above, the PCR thermal cycler using a PCR thermal block manufactured using a composite material mixed with tin powder and silver-coated copper nanowires showed an average rising speed of 28.2% and an average falling speed of 32.3%, which were superior to those using an aluminum PCR thermal block.

[0180] Although the present invention has been described through specific matters and limited examples as described above, these are provided only to help a more general understanding of the present invention, and the present invention is not limited to the above examples, and those skilled in the art to which the present invention pertains can make various modifications and variations based on this description.

[0181] Therefore, the idea of ​​the present invention should not be limited to the described embodiments, and all things that are equivalent or equivalent to the following claims as well as the claims are considered to fall within the scope of the idea of ​​the present invention.

Claims

1. Powder metal which is a first metal or an alloy containing the first metal; and A composite material for a thermal block of a thermal cycler, comprising a core-shell structured metal nanowire in which a shell containing a third metal is positioned on a core containing a second metal.

2. In paragraph 1, A composite material for a heat block of a thermal cycler, wherein the first metal is tin, and the alloy is at least one selected from the group consisting of tin-silver, tin-copper, tin-aluminum, tin-bismuth, tin-antimony, tin-copper-bismuth, tin-silver-bismuth, tin-copper-antimony, tin-silver-antimony, tin-copper-silver, tin-copper-silver-antimony, and tin-copper-silver-bismuth.

3. In paragraph 1, A composite material for a heat block of a thermal cycler, wherein the second metal is copper and the third metal is silver or gold.

4. In paragraph 3, The above metal nanowire is a composite material for a thermal block of a thermal cycler, which is a silver-coated copper nanowire.

5. In paragraph 4, The above metal nanowires have peak intensities of Ag 3d5 / 2 of silver (I1) and Cu 2p of copper in the X-ray photoelectron spectroscopy spectrum. 3 / 2 A composite material for a heat block of a thermal cycler, the peak intensity (I2) of which satisfies the following equation 1. (Formula 1) I2 / I1≤ 0.2 6. In paragraph 1, A composite material for a thermal block of a thermal cycler, wherein the above metal nanowire has a diameter of 100 to 500 nm and an aspect ratio of 5 to 100.

7. In paragraph 1, The particle size (D) of the above powder metal p ): Diameter of metal nanowire (D) w ) of the ratio (D) p / D w ) is a composite material for a thermal block of a thermal cycler with a ratio of 1:0.0001 to 0.

01.

8. In paragraph 1, A composite material for a thermal block of a thermal cycler, wherein the weight ratio of the powder metal:metal nanowire is 1:0.001 to 0.

1.

9. A heat block of a low specific heat capacity thermal cycler manufactured by sintering, casting, rolling or casting a composite material according to any one of clauses 1 to 8.

10. Tin or tin alloy; and A heat block of a low specific heat capacity thermal cycler comprising silver-coated copper nanowires.

11. In paragraph 10, A heat block of a low specific heat capacity thermal cycler having a weight ratio of the above tin or tin alloy: silver coated copper nanowire of 1:0.001 to 0.

1.

12. In paragraph 10, The above silver-coated copper nanowires have Ag 3d in the X-ray photoelectron spectroscopy spectrum. 5 / 2 Peak intensity (I1) of copper and Cu 2p of copper 3 / 2 A thermal block of a thermal cycler, the peak intensity (I2) of which satisfies the following equation 1. (Formula 1) I2 / I1≤ 0.2 13. In paragraph 10, A heat block of a low specific heat thermal cycler having a thermal conductivity of 70 to 100 W / (m K) at 21°C.

14. Heating element; A heat block having one end in contact with one surface of the heating element and including an insertion hole at another end positioned opposite to the one end; A PCR (Polymerase Chain Reaction) thermal cycler, wherein the above-mentioned thermal block is formed by sintering, casting, rolling or casting a composite material according to any one of claims 1 to 8.

15. In paragraph 14, A PCR thermal cycler, wherein the above thermal block satisfies the following equation 2. (Formula 2) H a - H b ≤ ± 0.5 ℃ / sec (H in Equation 2 a is the heating rate in the region of 0.1 to 0.3t, defined as region A based on one end in contact with one surface of the heating element, in a heat block with a height of t, and H b is the heating rate in the 0.7t to 1.0t region defined as region B)

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