WO2023075405A1 - Thermal block - Google Patents

Thermal block Download PDF

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Publication number
WO2023075405A1
WO2023075405A1 PCT/KR2022/016462 KR2022016462W WO2023075405A1 WO 2023075405 A1 WO2023075405 A1 WO 2023075405A1 KR 2022016462 W KR2022016462 W KR 2022016462W WO 2023075405 A1 WO2023075405 A1 WO 2023075405A1
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WO
WIPO (PCT)
Prior art keywords
sample
hole
holes
adjacent
wells
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PCT/KR2022/016462
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French (fr)
Korean (ko)
Inventor
김진원
노진석
강동우
백승민
Original Assignee
주식회사 씨젠
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Application filed by 주식회사 씨젠 filed Critical 주식회사 씨젠
Publication of WO2023075405A1 publication Critical patent/WO2023075405A1/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices

Definitions

  • the present invention relates to a thermal block for carrying out a plurality of reactions.
  • PCR polymerase chain reaction
  • Denaturation of DNA proceeds at about 95 degrees, and binding and extension of primers proceed at a temperature lower than 95 degrees, 55 to 75 degrees. Therefore, the nucleic acid amplification reaction of the sample is performed by repeating the process of raising and lowering the temperature of the reaction vessel or chambers in which the sample is accommodated.
  • a heat block having a plurality of sample wells into which a reaction container accommodating the samples is inserted is sometimes used. That is, the reaction container for accommodating the respective samples is inserted into the sample well of the heat block, and the heat block is heated or cooled using a Peltier element, thereby simultaneously performing the nucleic acid amplification reaction of each sample.
  • the sample wells of the column block are arranged in rows and columns on a plane, and the sample wells are 16 wells of 4 X 4, 32 wells of 4 X 6, 64 wells of 6 X 6, 96 wells of 6 X 12, or even larger. It is formed with 364 wells of 16 X 24.
  • a thermal block also referred to as a heating block, has a plurality of wells formed therein to accommodate a plurality of reaction vessels, and is made of metal for fast heat conduction.
  • metal has a high specific gravity and specific heat, so there is a problem in that a large amount of energy must be supplied or removed to control the temperature of the heat block.
  • the PCR reaction is a reaction in which a target nucleic acid sequence is amplified by repeating the steps of hybridizing a primer specific to a target nucleic acid sequence, extending it with a polymerase, and separating the extended strand.
  • the PCR reaction efficiently performs this series of steps by maintaining the reaction mixture at specified temperatures for a specified period of time. Therefore, it is very important to maintain the correct temperature at each step in the PCR reaction. This is because the reaction efficiency in each step may vary depending on the temperature.
  • the temperature deviation continuously occurring between wells causes the amplification reaction to proceed with different efficiency for each of a plurality of samples in which the amplification reaction has been performed in different wells. do.
  • nucleic acid amplification is repeated dozens of cycles, and since the nucleic acid strand generated in the previous cycle becomes the template for the next cycle, the difference in amplification efficiency occurring in each cycle can greatly affect the analysis result.
  • the PCR device in order to preserve the material in the high-temperature container during the PCR process and prevent the lid of the reaction container from being opened, the PCR device includes a hot lid that can press the top of the reaction container so that it does not open.
  • the hot lead is kept in close contact with the upper surface of the reaction vessel and pressurized the reaction vessel.
  • the pressure may be transmitted to the heat block through the reaction vessel to deform the heat block.
  • the durability of the heat block becomes weaker.
  • deformation or damage to the sample well of the heat block may occur.
  • the present invention provides a heat block that can prevent the problem of incorrectly mounting the reaction vessel while minimizing the heat energy required for temperature change of the heat block by removing unnecessary parts of the heat block. It has a purpose to provide.
  • an object of the present invention is to increase the efficiency of the nucleic acid amplification reaction and the performance of the device by minimizing the difference in temperature change rate and temperature holding period between samples by uniformly controlling the temperature of the heat block.
  • a plurality of non-sample holes are located in the unit area of the heat block and the form in which the non-sample holes are located in each unit area is the same, thereby maximizing the reduction of unnecessary mass in the heat block and reducing the temperature deviation between each sample well. It has a purpose to reduce.
  • the present invention is formed so that the thermal conductive effect of the non-sample holes located in the unit area for each of the four adjacent sample wells defining the unit area of the thermal block is the same to improve the thermal uniformity between the sample wells.
  • the present invention has an object to improve the overall durability of the heat block while reducing the unnecessary mass of the heat block.
  • a thermal block according to an embodiment of the present invention is a thermal block for performing a plurality of reactions, and includes upper and lower surfaces that are parallel to each other and have a length and width, and a plurality of sample wells open upwards are regularly arranged on the upper surface. It is formed in an array, and a plurality of non-sample holes open upwards are formed on the upper surface, and the plurality of non-sample holes are formed in (i) a first surface opening that is shorter than the diameter of the sample well in the longitudinal direction and equal to or longer than the diameter of the sample well in the width direction.
  • non-sample holes and (ii) second non-sample holes that are shorter in the width direction and equal to or longer in the length direction, wherein the first non-sample holes are located between adjacent sample wells in the longitudinal direction, and 2 non-sample holes are located between adjacent sample wells in the width direction.
  • the heat block of the present invention can increase the efficiency of the nucleic acid amplification reaction and the performance of the device by minimizing the difference in temperature change rate and temperature holding period between samples by uniformly controlling the temperature.
  • the heat block of the present invention changes the structure of the conventional heat block to secure the uniformity of the temperature rise and fall rate and temperature maintenance section using the heat block, thereby reducing the performance of reagents sensitive to temperature deviations. that can be prevented
  • the temperature difference between the central part and the outer part is minimized.
  • the temperature control of the central part and the outer part of the heat block can be made uniform.
  • FIG. 1 is a perspective view of a thermal block of the present invention.
  • FIG. 2 is a plan view of a thermal block of the present invention.
  • FIG. 3 is a view for explaining the arrangement of sample wells and non-sample holes formed in the thermal block of the present invention.
  • Figure 4 is a cross-sectional view of the thermal block of the present invention taken along A-A in Figure 2;
  • Figure 5 is a cross-sectional view of the thermal block of the present invention taken along line B-B in Figure 2;
  • FIG. 6 is a perspective view of a thermal block of the present invention.
  • FIG. 7 is a plan view of a thermal block of the present invention.
  • FIG. 8 is a cross-sectional view of a thermal block of the present invention.
  • FIG. 9 is a side view of a thermal block of the present invention.
  • first, second, A, B, (a), (b), (i), and (ii) may be used. These terms are only used to distinguish the component from other components, and the nature, sequence, or order of the corresponding component is not limited by the term.
  • the present inventors intensively tried to improve the structure of the heat block in order to increase the efficiency of the nucleic acid amplification reaction and the performance of the device.
  • the present inventors have improved the structure of the heat block so as to minimize the heat energy required for the temperature change of the heat block by removing unnecessary mass of the heat block, and prevent the reaction container from being erroneously mounted.
  • the present inventors improved the structure of the thermal block to minimize the temperature change rate at each well location of the thermal block and the temperature change difference in the temperature holding section. That is, the structure of the heat block is improved to lower the overall heat capacity of the heat block and minimize the temperature difference between the central part and the outer part of the heat block, thereby improving the performance degradation of the reagent sensitive to the temperature difference.
  • the term "thermal block” may be used as a reaction vessel in which a plurality of sample wells formed in the thermal block directly receive and react with samples, or formed to fit the plurality of sample wells formed in the thermal block. It can be used as a receptor for accommodating a reaction vessel.
  • the thermal block may be manufactured using a material having excellent thermal conductivity. It may be made of a metal or metal alloy (eg, iron, copper, aluminum, gold, silver or an alloy containing the same).
  • a thermal block may be machined from a single solid piece of metal or formed by connecting several pieces of metal.
  • the heat block of the present invention is a heat block for carrying out a plurality of reactions.
  • the reaction refers to a chemical, biochemical or biological transformation involving at least one chemical or biological substance (eg, solution, solvent, enzyme).
  • the reaction may preferably be initiated, stopped, accelerated or inhibited by a thermal change in the reaction system.
  • the reaction may be a reaction in which decomposition or binding of a biological or chemical substance proceeds as a result of a change in temperature, or an activity of an enzyme that produces or decomposes a biological or chemical substance is promoted or inhibited as a result of a change in temperature. .
  • the reaction may mean an amplification reaction.
  • the amplification reaction may be a reaction that increases the target analyte (eg, nucleic acid) itself, or may be a reaction that increases or decreases a signal generated depending on the presence of the target analyte.
  • a reaction that increases or decreases the signal generated depending on the presence of the target analyte may or may not be accompanied by an increase in the target analyte.
  • the target analyte is a nucleic acid molecule, and the reaction may be a polymerase chain reaction (PCR) or real-time PCR.
  • PCR polymerase chain reaction
  • PCR polymerase chain reaction
  • the change in constant conditions is an increase in the number of repetitions of the reaction, and the repeating unit of the reaction including the series of steps is set as one cycle.
  • Various nucleic acid amplification reactions can be performed using the heat block of the present invention.
  • PCR polymerase chain reaction
  • LCR ligase chain reaction
  • LCR ligase chain reaction
  • GLCR gap filling LCR
  • Q-beta replicase amplification Q-beta replicase amplification; Q-beta, see Cahill P, et al., Clin Chem., 37(9): 1462-5 (1991), US Pat. No.
  • the heat block of the present invention is usefully used in a polymerase chain reaction-based nucleic acid amplification reaction.
  • Various nucleic acid amplification methods based on polymerase chain reaction are known. For example, quantitative PCR, digital PCR, asymmetric PCR, reverse transcriptase PCR (RT-PCR), differential display PCR (DD-PCR), nested PCR, random priming PCR (AP-PCR), multiplex PCR, SNP genome typing PCR and the like.
  • FIG. 1 is a perspective view of a thermal block of the present invention
  • FIG. 2 is a plan view of the thermal block of the present invention
  • FIG. 3 is a view for explaining the arrangement of sample wells and non-sample holes formed in the thermal block of the present invention
  • Figure 5 is a cross-sectional view of the heat block of the present invention
  • Figure 6 is a perspective view of the heat block of the present invention
  • Figure 7 is a plan view of the heat block of the present invention
  • the heat block 100 of the present invention is a heat block for performing a plurality of reactions, and is parallel to each other and has a length and width of an upper surface (110, top surface) and a lower surface (120, bottom surface) Including, a plurality of sample wells 111 open upwards are regularly arranged on the upper surface 110, a plurality of non-sample holes 112 open upwards are formed on the upper surface 110, and a plurality of non-sample wells 112 open upwards are formed on the upper surface 110.
  • the sample holes 112 are formed shorter in the width direction and equal to or longer in the length direction than the first non-sample holes 112a in which the upper surface opening is shorter in the longitudinal direction than the diameter of the sample well 111 and equal to or longer in the width direction. It includes second non-sample holes 112b, the first non-sample holes 112a are located between adjacent sample wells 111 in the longitudinal direction, and the second non-sample holes 112b are located in the width direction It is located between adjacent sample wells 111 as .
  • the thermal block 100 of the present invention may have a hexahedral shape, particularly a rectangular parallelepiped shape, having a certain height (thickness).
  • the upper surface 110 and the lower surface 120 may have different lengths and widths, and side surfaces may have curves.
  • length, width, and height directions are shown as x, y, and z axis directions, respectively. Referring to FIGS. 1 and 7 , in the present specification, the length direction means the x-axis direction, the width direction means the y-axis direction, and the height direction means the z-axis direction.
  • the heat block 100 may have a thickness of 5 mm to 20 mm.
  • the thickness of the heat block 100 is 5 mm or less, it may be difficult for the sample well 111 formed in the heat block 100 to have a sufficient depth to accommodate the reaction vessel, and when the thickness is 20 mm or more, the thermal capacity of the heat block 100 This may become excessively large and the efficiency of heating or cooling may be low.
  • the length and width of the thermal block 100 may vary depending on the size and number of sample wells 111 formed on the upper surface 110 .
  • the length and width of the heat block 100 may be 10 mm or more, 20 mm or more, or 30 mm or more, respectively.
  • the length and width of the heat block 100 may be 1000 mm or less, 900 mm or less, 600 mm or less, 700 m or less, 600 mm or less, 500 mm or less, 400 mm or less, 300 mm or less, or 200 mm or less, respectively.
  • a plurality of sample wells 111 open upwards are formed on the upper surface 110 of the thermal block 100 of the present invention.
  • the sample well 111 may be formed to directly receive a sample or may be formed to insert a reaction container for accommodating the sample.
  • the sample well 111 is in thermal-conductively contact with the sample or reaction vessel accommodated in the sample well 111 .
  • the thermal block 100 of the present invention is formed to simultaneously perform a reaction for a plurality of samples.
  • the number of sample wells 111 formed in the heat block 100 is plural, and the heat block 100 has 4 or more, 6 or more, 6 or more, 12 or more, 16 or more, 24 or more, 32 or more. , 40 or more, 46 or more sample wells.
  • the thermal block 100 may include 96 or less, 192 or less, 288 or less, or 384 or less sample wells. According to one embodiment of the present invention, 4 or more and 364 or less sample wells 111 open upward may be formed on the upper surface 110 of the thermal block 100 .
  • the sample wells 111 of the thermal block 100 of the present invention are regularly arranged on the upper surface 110.
  • the regular arrangement means that directions and distances between adjacent sample wells among the plurality of sample wells 111 are determined according to a certain rule.
  • the arrangement of the plurality of sample wells 111 is determined according to the above rules.
  • the plurality of sample wells of the present invention may be arranged side by side in a plurality of rows parallel to the longitudinal direction (x direction) on the upper surface 110, and also in a plurality of columns parallel to the width direction (y direction). can be arranged Sample wells belonging to each row and each column may be arranged at regular intervals.
  • the regular array may be a rectangular array.
  • the rectangular arrangement means that a plurality of sample wells arranged side by side in a plurality of rows parallel to each other in the longitudinal direction are arranged side by side in a plurality of rows parallel to each other also in the width direction.
  • the regular arrangement may be a square arrangement.
  • the square arrangement is a special form of the rectangular arrangement, and means a form in which the number of sample wells belonging to each row and the number of sample wells belonging to each column are the same.
  • a plurality of sample wells 111 may be formed to accommodate reaction vessels.
  • the reaction vessel may be a reaction tube including one container, or may be a reaction strip or reaction plate including a plurality of containers.
  • the reaction strip refers to a reaction vessel in which a plurality of containers are arranged in a row at regular intervals
  • the reaction plate refers to a reaction vessel in which a plurality of containers are formed in two or more rows at regular intervals.
  • the container refers to a unit capable of accommodating a reactant (eg, a reaction solution or a reaction mixture).
  • the reaction vessel may be named a test tube, a PCR tube, a strip tube, or a multi well PCR plate depending on its use and shape.
  • the shape of the sample well 111 of the present invention may vary depending on the shape of the container of the reaction vessel used.
  • the sample well 111 of the present invention may be formed to accommodate a general conical tube for nucleic acid amplification.
  • the sample well 111 has a circular opening opened upward from the upper surface 110 and may be tapered to have a smaller diameter toward the lower side.
  • an embodiment in which the opening of the sample well 111 is circular is shown as an exemplary form.
  • the sample well 111 is a reaction vessel including a container having a volume capable of accommodating a reaction solution of 10 microliters or more, 20 microliters or more, 30 microliters or more, or 40 microliters or more. can be formed to accommodate.
  • the sample well 111 is 700 microliters or less, 600 microliters or less, 500 microliters or less, 400 microliters or less, 300 microliters or less, 200 microliters or less, 100 microliters or less. It may be formed to accommodate a reaction vessel including a container having a volume of less than or equal to 50 microliters or less of the reaction solution.
  • the areas of the upper surface 110 and the lower surface 120 of the thermal block 100 are different from each other.
  • the area of the lower surface 120 is larger than that of the upper surface 110 . Therefore, a side step may be formed on the side of the thermal block 100 where the lower surface 120 is wider than the upper surface 110 .
  • the upper surface 110 and the lower surface 120 of the thermal block 100 have the same area. Accordingly, the thermal block 100 has a rectangular parallelepiped shape as a whole.
  • the side of the heat block 100 is not stepped and may be formed in a vertically flat shape.
  • thermoelectric element such as a Peltier element is in thermal contact with the lower surface 120 of the thermal block 100 to perform heat exchange with the thermal block 100 .
  • the heat block 100 is heated as heat is supplied from the lower surface 120 or cooled as heat is absorbed from the lower surface 120, and thus the sample accommodated in the sample well 111 or the reaction inserted into the sample well 111 An amplification reaction of the sample accommodated in the vessel may be performed.
  • a temperature sensor may be mounted on the lower surface 120 of the thermal block 100 .
  • a sensor groove in which at least one temperature sensor is located may be formed on the stepped surface 121 .
  • the shape of the sensor groove may vary depending on the shape of the temperature sensor, and may be, for example, a shape into which a probe-type or button-type temperature probe can be mounted.
  • the thermal block 100 includes a plurality of non-sample holes 112 .
  • the non-sample hole 112 is formed to open upward from the top surface 110 of the thermal block 100 .
  • the non-sample hole 112 is separated from the sample well 111, and the reaction vessel is not accommodated in the non-sample hole 112.
  • the non-sample hole 112 is formed to reduce energy required to change the temperature of the sample well 111 by reducing the mass of the thermal block 100 .
  • the shape of the non-sample hole 112 is not particularly limited, but a container fitted to the sample well 111 is formed so as not to be inserted into the non-sample hole 112 .
  • the container having a shape suitable for the sample well 111 means a container having an outer surface in close contact with the inner wall of the sample well 111 when inserted into the sample well 111 . That is, since the non-sample hole 112 is formed so that a container of a shape suitable for the sample well 111 is not inserted, the reaction container to be inserted into the sample well 111 is prevented from being inserted into the non-sample hole 112 by mistake. can do.
  • the plurality of non-sample holes 112 include first non-sample holes 112a having an upper surface opening shorter than the diameter of the sample well 111 in the longitudinal direction and equal to or longer than the diameter of the sample well 111 in the width direction, and short in the width direction and lengthwise. It includes second non-sample holes 112b formed equal to or longer. That is, the plurality of non-sample holes 112 include first non-sample holes 112a having a length shorter than the diameter of the sample well 111 and second non-sample holes 112b having a narrow width.
  • FIG. 4 is a cross-sectional view taken along the line A-A of FIG.
  • a container of a shape suitable for the sample well 111 is inserted into the first non-sample hole 112a formed to have a length shorter than the diameter of the sample well 111 or the second non-sample hole 112b formed to have a narrow width. Therefore, the user is prevented from incorrectly inserting the reaction vessel to be inserted into the sample well 111 into the non-sample hole 112, thereby improving work efficiency and reducing the reaction vessel or heat block by the pressure provided by the hot lead. damage can be prevented.
  • the shape of the non-sample hole 112 is not particularly limited, and may be, for example, a circular shape, an elliptical shape, or a polygonal shape such as a square or a triangle.
  • the non-sample hole 112 is formed in the form of a hexagon that is stretched in the longitudinal or width direction, but a portion located between the sample wells 111 is compressed.
  • the area opened to the top surface 110 of the non-sample holes 112 may be different.
  • the non-sample holes 112 of the present invention are not required to have the same overall shape or size.
  • non-sample holes disposed at the outermost part of the upper surface 110 may have a different shape from non-sample holes disposed inside.
  • the non-sample holes disposed at the outermost periphery of the upper surface 110 have the same shape, but among them, the non-sample holes disposed along the longitudinal direction and the non-sample holes disposed along the width direction Non-sample holes may be positioned in different directions.
  • the non-sample holes disposed inside have the same shape, but among them, the non-sample holes disposed along the longitudinal direction and the non-sample holes disposed along the width direction may be located in different directions.
  • the non-sample holes 112 may be regularly arranged in the thermal block 100 .
  • the regular arrangement means that directions and distances between adjacent non-sample holes among the plurality of non-sample holes 112 are determined according to a certain rule.
  • the arrangement of the plurality of non-sample holes 112 is determined according to the above rules. For example, looking along the line A-A of FIG. 2 (A), the first non-sample hole 112a may be located between the sample wells 111 arranged along the length direction. That is, the sample wells 111 and the first non-sample holes 112a may be alternately arranged along the longitudinal direction.
  • the second non-sample hole 112b may be located between the sample wells 111 arranged along the width direction. That is, the sample well 111 and the second non-sample hole 112b may be alternately arranged along the width direction.
  • the non-sample holes 112 may be formed in the same pattern as the thermal block 100 . Being formed in the same pattern means that when a plurality of figures having the same shape and area are drawn by connecting the center points of four adjacent sample wells 111 among the plurality of sample wells 111 in the thermal block 100, the shape And it means that the shapes in which the non-sample holes 112 are located in a plurality of figures having the same area are the same.
  • the non-sample holes 112 have the same pattern formed by the non-sample holes 112 within the unit area 130 defined by connecting the center points of four adjacent sample wells 111 in the thermal block 100. is formed to Referring to (B) of FIG. 2, the four sample wells 111a to 111d adjacent to each other are a combination of the four sample wells closest to each other among the sample wells formed on the upper surface 110 of the thermal block 100.
  • the combination of the four sample wells closest to each other determines one sample well 111a and another sample well 111b closest to the one sample well 111a, and the determined two sample wells ( 111a and 111b) and may be determined by a method of additionally determining the closest two sample wells 111c and 111d that are not parallel to each other.
  • the fact that the two sample wells 111a and 111b are not aligned means that the additionally determined two sample wells 111c and 111d are not located on a straight line connecting the center points of the two sample wells 111a and 111b. it means.
  • the four sample wells 111a to 111d adjacent to each other may be a combination of four sample wells that are closest to each other and connect their center points to form a square.
  • the unit area 130 is an area defined to explain the pattern of the sample well 111 and the non-sample hole 112 of the thermal block 100 of the present invention.
  • the unit area 130 refers to an area formed by connecting the center points of the four adjacent sample wells 111a to 111d.
  • a portion excluding the space occupied by the sample wells in the unit area is defined as a mass region.
  • a space occupied by the four adjacent sample wells is not included in the mass area. Therefore, the mass area is an area where the reaction vessel is not located. Accordingly, as the mass of the mass region decreases, the amount of change in thermal energy required to change the reactants in the reaction vessel to a desired temperature decreases.
  • the mass region is a region in which no sample wells are formed among regions formed by connecting the center points of the four adjacent sample wells.
  • the mass area may be an area excluding an area occupied by the sample wells in a rectangular area formed by connecting the center points of the four adjacent sample wells 111a to 111d.
  • the non-sample hole 112 formed in the thermal block 100 may be formed in the mass area. By forming the non-sample hole 112, the mass of the mass region can be reduced, and accordingly, the amount of change in thermal energy required to change the reactants in the reaction vessel to a desired temperature is reduced.
  • the positions of the non-sample holes 112 in each of the plurality of unit areas 130 are identical to each other. This is the distribution (relative position) of the non-sample holes 112 and the size and shape of the non-sample holes 112 in each of the plurality of unit areas 130 defined by the four sample wells adjacent to each other in the thermal block 100. This means that the composition is identical to each other.
  • Dotted lines in (A) of FIG. 2 arbitrarily indicate some of the unit regions 130 that may be defined in the thermal block 100 of the present invention. As shown in (A) of FIG. 2, all unit regions 130 formed by four adjacent sample wells in the thermal block 100 of the present invention have non-sample holes 112 located therein. shapes are identical to each other.
  • the thermal block 100 of the present invention Since the plurality of sample wells 111 are regularly arranged in the thermal block 100 of the present invention, all unit regions 130 in the thermal block 100 have the same shape and area. Therefore, when the non-sample holes 112 form the same pattern within the unit area 130, since the thermal conductive effect of the non-sample holes 112 is the same for all sample wells 111, the heat block is rapidly heated. Alternatively, a temperature deviation between each sample well that may occur due to cooling may be minimized.
  • the fact that the thermally conductive effect of the non-sample hole is the same for all the sample wells means that the thermally conductive change occurring in the sample well and the reactant in the reaction container is the same according to the temperature change of the heat block.
  • the amount of change in thermal energy generated by the reactant in the reaction vessel accommodated in each sample well is the same at every moment, and the reactant in each reaction vessel is in thermal equilibrium with the heat block to form a heat balance at the desired temperature. ), the time to reach the state is the same.
  • the non-sample hole 112 is formed to have the same thermal conductivity effect on each of the four adjacent sample wells 111a to 111d. Therefore, the thermal conductivity received from the surrounding non-sample holes 112 to each sample well 111 formed in the thermal block 100 becomes uniform, and thermal uniformity between each sample well is maintained. it helps to The fact that the non-sample holes 112 are formed to have the same thermal conductive effect on each of the four sample wells adjacent to each other means that, for example, the non-sample holes 112 define the unit area 130 in the four sample wells. (111a ⁇ 111d) may be formed identically or symmetrically with respect to each center point.
  • the thermal block 100 of the present invention can maintain thermal uniformity between each sample well 111 .
  • Non-sample holes not included in the unit area may be arranged in consideration of the arrangement of sample wells and non-sample holes in the entire column block.
  • one non-sample hole 112 may be formed over two or more adjacent unit areas 130. If the pattern formed by the non-sample holes 112 inside each unit area 130 is the same, one non-sample hole 112 may be formed across two or more adjacent unit areas 130 . In other words, one non-sample hole is not all formed in one unit area, but a part of one non-sample hole is located in each unit area, and a plurality of non-sample holes may be partially located in one unit area. .
  • Each of the four non-sample holes 112 may be partially located.
  • a part of one non-sample hole may be located in one unit area and the rest may be located in another unit area. That is, non-sample holes are located across the boundary of the unit area, and each part of the non-sample holes across the boundary is located within the same unit area.
  • the non-sample hole 112 may be formed across unit regions 130 adjacent to each other among the plurality of unit regions 130 . That is, the non-sample hole 112 may be formed over unit areas adjacent to each other in the length direction or width direction of the thermal block 100 . The non-sample hole formed over the unit area adjacent in the length direction may not be formed over the unit area adjacent in the width direction. Similarly, non-sample holes formed over unit areas adjacent in the width direction may not be formed over unit areas adjacent in the length direction.
  • the unit area 130 is a minimum rectangular area defined by connecting the center points of four adjacent sample wells in the column block 100, and the non-sample hole 112 is all the minimum rectangular areas. Patterns of non-sample holes in the region may be formed to be identical to each other.
  • the minimum square is formed by selecting four sample wells that can form a square by connecting their center points among the sample wells 111 formed on the upper surface 110 of the thermal block 100, and connecting their center points to form a square. It refers to a quadrangle with the smallest area and the smallest sum of the lengths of four sides among the quadrangles that can be formed when formed.
  • the first non-sample hole 112a intersects a first straight line defined by connecting the center points of adjacent sample wells 111 in the longitudinal direction. can do. That is, the first non-sample hole 112a is located on a straight line connecting the center points of the sample wells 111 adjacent in the longitudinal direction. In other words, the first non-sample hole 112a is located on a straight line connecting the center points of the left and right sample wells 111 with respect to FIG. 3(A). In addition, the first non-sample hole 112a does not contact or overlap with the sample wells 111 adjacent in the longitudinal direction.
  • the first straight line refers to a straight line defined by connecting the center points of the sample wells 111 arranged side by side in the longitudinal direction
  • the second straight line is defined by connecting the center points of the sample wells 111 arranged side by side in the width direction.
  • the first non-sample hole 112a has a shape symmetrical with respect to a first straight line, and is formed to provide the same thermal conductivity to adjacent sample wells 111 in the longitudinal direction.
  • the first non-sample hole 112a has a shape symmetrical with respect to a straight line connecting the center points of the sample wells disposed in the longitudinal direction. That is, the first non-sample hole 112a has a vertically symmetrical shape based on (A) of FIG. 3 .
  • the symmetry may be line symmetry based on the first straight line.
  • the symmetrical shape is a shape in which thermal conductive effects on adjacent sample wells in the longitudinal direction are the same.
  • the shape having the same thermal conductive effect means a shape formed such that thermal energy variations applied to sample wells adjacent in the longitudinal direction according to temperature changes of the heat block are not different from each other. That is, the shape of the first non-sample hole 112a is the shape of heat flow occurring between the first non-sample hole 112a and the sample well 111 on the left side with reference to FIG. 3(A). The movement of thermal energy generated between the first non-sample hole 112a and the right sample well 111 has the same shape. Accordingly, the thermal conductivity of the first non-sample hole 112a to adjacent sample wells in the longitudinal direction is the same. Meanwhile, the first non-sample hole 112a may have a symmetrical shape in the width direction as well.
  • the first straight line intersects the first non-sample hole 112a at two intersection points
  • (ii) is parallel to the first straight line, and the sample wells adjacent in the longitudinal direction
  • the common tangent line may intersect the first non-sample hole at two other intersection points.
  • a distance between the two intersection points defined by the common tangent line may be greater than or equal to a distance between the two intersection points defined by the first straight line.
  • the first non-sample hole 112a has a width of the sample wells 111 adjacent to each other in the longitudinal direction, rather than a length in the longitudinal direction located on a straight line to which the center points of the sample wells adjacent in the longitudinal direction are connected.
  • a length in the longitudinal direction positioned on a straight line to which one end of the direction is connected may be equal to or greater than a length in the longitudinal direction positioned on a straight line to which the other end in the width direction is connected.
  • the length in the longitudinal direction located on the straight line connecting the center points of the sample wells adjacent in the longitudinal direction of the first non-sample hole 112a refers to the first straight line connecting the center points of the sample wells adjacent in the longitudinal direction and the first non-sample hole 112a. This is the overlapping length of the non-sample hole 112a.
  • the common tangent line parallel to the first straight line as a common tangent line of sample wells adjacent in the longitudinal direction may be a straight line connecting one end of the sample wells 111 adjacent in the longitudinal direction in the width direction or a straight line connecting the other end.
  • a straight line connecting one end of the widthwise direction of the sample wells 111 adjacent in the longitudinal direction and a straight line connecting the other end of the sample well 111 are a straight line connecting the upper ends of the sample wells 111 on both sides based on FIG. 3 (A). and a straight line connecting the lower end.
  • the first non-sample hole 112a has a length overlapping with a straight line connecting the upper ends of the sample wells on both sides (hereinafter referred to as a first length) rather than a length overlapping with a straight line connecting the center points of the sample wells on both sides (hereinafter, a first length).
  • a second length) and a length overlapping a straight line connecting the lower end may be formed equal to or larger.
  • the first non-sample hole 112a may have a second length and a third length equal to the first length.
  • the first non-sample hole 112a may be a rounded rectangle having a constant length in the longitudinal direction.
  • the second length and the third length of the first non-sample hole 112a may be greater than the first length.
  • both sides of the first non-sample hole 112a in the longitudinal direction may be concave.
  • both sides of the first non-sample hole 112a in the longitudinal direction are concave, so that the first non-sample hole 112a and a sample adjacent to the first non-sample hole 112a in the longitudinal direction are formed.
  • the thickness of the mass region positioned between the wells 111 may be constant within a predetermined range. That is, a non-sample hole region is located between the non-sample hole and the sample well, and the thickness of the non-sample hole region of the mass region can be formed uniformly within a predetermined range.
  • 3(A) shows an embodiment in which the thickness of a non-sample hole region among the mass regions is constant within a predetermined range on both sides of the width direction based on a straight line connecting the center points of adjacent sample wells in the longitudinal direction.
  • the second non-sample hole 112b intersects a second straight line defined by connecting the center points of adjacent sample wells 111 in the width direction. can do. That is, the second non-sample hole 112b is located on a straight line connecting the center points of adjacent sample wells 111 in the width direction. In other words, the second non-sample hole 112b is located on a straight line connecting the center points of the vertically arranged sample wells 111 based on (B) of FIG. 3 . In addition, the second non-sample hole 112b does not contact or overlap with the sample wells 111 adjacent to each other in the width direction.
  • the second straight line refers to a straight line defined by connecting the center points of the sample wells 111 arranged side by side in the width direction.
  • the second non-sample hole 112b has a shape symmetrical with respect to the second straight line, and is formed to provide the same thermal conductivity to adjacent sample wells 111 in the width direction.
  • the second non-sample hole 112b has a shape symmetrical with respect to a straight line connecting the center points of the sample wells arranged in the width direction. That is, the second non-sample hole 112b has a left-right symmetrical shape based on FIG. 3(B).
  • the symmetry may be line symmetry based on the second straight line.
  • the symmetrical shape is a shape in which thermal conductive effects on adjacent sample wells in the width direction are the same.
  • the shape having the same thermal conductive effect refers to a shape formed such that the amount of change in thermal energy applied to the sample wells adjacent in the width direction according to the temperature change of the heat block is not different from each other. That is, the shape of the second non-sample hole 112b is the shape of the thermal energy movement occurring between the second non-sample hole 112b and the upper sample well 111 based on (B) of FIG. 3 and the second ratio The movement of thermal energy generated between the sample hole 112b and the lower sample well 111 has the same shape. Therefore, the thermal conductivity of the second non-sample hole 112b on adjacent sample wells in the width direction is the same. Meanwhile, the second non-sample hole 112b may have a symmetrical shape in the longitudinal direction as well.
  • the second straight line intersects the second non-sample hole at two intersections
  • (ii) is parallel to the second straight line
  • the common tangent of sample wells adjacent in the width direction is It may intersect the second non-sample hole at two other intersection points.
  • a distance between the two intersection points defined by the common tangent line may be greater than or equal to a distance between the two intersection points defined by the second straight line.
  • the second non-sample hole 112b is longer than the width of the sample wells 111 adjacent in the width direction located on a straight line to which the center points of the sample wells adjacent in the width direction are connected.
  • a width in the width direction positioned on a straight line connecting one end in the direction and a width in the width direction positioned on a straight line connecting the other end in the longitudinal direction may be equal to or larger than each other.
  • the width in the width direction located on a straight line connecting the center points of the sample wells adjacent in the width direction of the second non-sample hole 112b means the second straight line connecting the center points of the sample wells adjacent in the width direction and the second non-sample hole 112b. This is the overlapping width of the non-sample hole 112b.
  • a common tangent line parallel to the second straight line which is a common tangent line of sample wells adjacent in the width direction, means a straight line connecting one end of the sample wells 111 adjacent in the width direction in the longitudinal direction or a straight line connecting the other end.
  • a straight line connecting one end of the longitudinal direction of the sample wells 111 adjacent to each other in the width direction and a straight line connecting the other end of the sample well 111 are a straight line connecting the left ends of the sample wells 111 on both sides based on FIG. 3 (B). and a straight line connecting the right end.
  • the second non-sample hole 112b has a width (hereinafter, a first width) overlapping with a straight line connecting the center points of both sample wells and a straight line connecting the left ends of the sample wells on both sides (hereinafter referred to as a first width).
  • a second width) and a width overlapping a straight line connecting the right end may be formed equal to or larger.
  • the second non-sample hole 112b may have a second width and a third width equal to the first width.
  • the second non-sample hole 112b may be a rounded rectangle having a constant width in the width direction.
  • the second non-sample hole 112b may have a second width and a third width larger than the first width.
  • both sides of the second non-sample hole 112b in the width direction may be concave.
  • the second non-sample hole 112b is formed concave on both sides in the tactile direction, so that the sample adjacent to the second non-sample hole 112b and the second non-sample hole 112b in the width direction
  • the thickness of the mass region positioned between the wells 111 may be constant within a predetermined range. That is, a non-sample hole region is located between the non-sample hole and the sample well, and the thickness of the non-sample hole region of the mass region can be formed uniformly within a predetermined range.
  • 3(B) shows an embodiment in which the thickness of an area other than a non-sample hole among the mass areas is constant within a predetermined range on both sides of the length direction based on a straight line connecting the center points of adjacent sample wells in the width direction.
  • a straight line connecting the center points of two diagonally adjacent sample wells 111 among a plurality of sample wells 111 is a non-sample hole. It does not touch or intersect with (112).
  • a straight line connecting the center points of two adjacent sample wells 111 in a diagonal direction among four adjacent sample holes among the plurality of sample wells 111 does not touch or intersect the non-sample holes 112 .
  • the diagonal direction or the diagonal direction may be, for example, a direction of a line B-B in (A) of FIG. 2 or a direction orthogonal thereto.
  • the contact means contact between one non-sample hole and one straight line at one point, and the contact point is referred to as a tangent point.
  • Intersecting means that one straight line contacts one non-sample hole at two points, and the two contact points are called intersections. Accordingly, when a straight line connecting the center points of two diagonally adjacent sample holes and the non-sample holes do not touch or intersect, the four sample wells adjacent to each other are physically connected in the diagonal direction. Therefore, the heat block 100 of the present invention reduces the mass of the mass region to reduce the amount of change in thermal energy required to change the temperature of the reactant in the reaction vessel to the desired temperature, and at the same time has excellent durability compared to the conventional heat block. do.
  • the regular arrangement of the plurality of sample wells 111 is a rectangular arrangement, and a diagonal line formed by connecting the center points of adjacent sample wells 111a to 111d forming the unit area 130. does not contact or cross the non-sample hole 112 located in the unit area 130. That is, referring to (B) of FIG. 2, a plurality of sample wells 111 are arranged in a rectangular array, and the unit area 130 defined by four adjacent sample wells 111a to 111d has a rectangular shape.
  • FIG. 5 is a cross-sectional view taken along line B-B of FIG. 2 (A), and is a cross-sectional view in the diagonal direction. In the cross-sectional view along line B-B, the cross section of the sample well 111 is shown, but the cross section of the non-sample hole 112 is not shown. As shown in FIG. 5, a straight line connecting the sample wells 111 in the diagonal direction does not contact or intersect the non-sample hole 112, and the sample wells 111 are physically connected in the diagonal direction. Thus, the durability of the heat block 100 of the present invention is improved.
  • the first ratio is located on a straight line to which the center points of the sample wells 111 adjacent in the longitudinal direction are connected.
  • the second non-sample holes 112b located on a straight line connecting the sample holes 112a and the center points of the sample wells 111 adjacent in the width direction are two sample holes diagonally adjacent among the four adjacent sample holes.
  • the center points of the wells 111 are symmetrical with respect to a straight line connected thereto.
  • the symmetrical shape is a shape in which thermal conductive effects on adjacent sample wells in the diagonal direction are the same.
  • the shape having the same thermal conductive effect means a shape formed such that the amount of change in thermal energy applied to the sample wells adjacent in the diagonal direction according to the temperature change of the heat block is not different from each other. That is, the shape of the non-sample holes 112 is based on the heat energy movement occurring between the first and second non-sample holes 112a and 112b and the sample well 111 on one diagonal side of FIG. 3 (C). The shape and the shape of the transfer of thermal energy occurring between the first and second non-sample holes 112a and 112b and the sample well 111 on the other side have the same shape. Therefore, the thermal conductivity of the first and second non-sample holes 112a and 112b to the diagonally adjacent sample wells is the same.
  • a thermal block 600 including a through hole 610 for reducing the mass of the thermal block may be provided.
  • the heat block 600 of the present invention is a heat block for performing a reaction of a plurality of received samples, and includes an upper surface 110 and a lower surface 120 that are parallel to each other and have a length and width, and an upper surface 110 ) has a plurality of sample wells 111 open upwards, and may include a through hole 610 penetrating the thermal block.
  • the through hole 610 may be a through hole 610 penetrating the thermal block 100 between the upper surface 110 and the lower surface 120 .
  • the through hole 610 may include at least one through hole 610 .
  • the through hole 610 is formed to reduce the energy required to change the temperature of the sample well 111 by reducing the mass of the thermal block 100. Formed to reduce the mass of the central part.
  • a plurality of non-sample holes open upward are formed on the upper surface, and the upper surface opening of each non-sample hole is formed with a shorter length in the longitudinal direction or a narrower width in the width direction than the sample well, and among the plurality of sample wells In each of a plurality of unit regions defined by connecting the center points of four adjacent sample wells, ten blocks having the same shape in which non-sample holes are located may be provided.
  • a thermal block including at least one through hole penetrating the thermal block between the upper and lower surfaces may be provided.
  • a plurality of non-sample holes are formed on the upper surface, and a thermal block including at least one through hole penetrating the thermal block between the upper surface and the lower surface may be provided.
  • the through hole 610 is formed to pass through the mass area, which is an area other than the area occupied by the sample well 111, of the unit area 130. That is, the through hole 610, like the non-sample hole 112, reduces the mass of the mass region to reduce the amount of change in thermal energy required to change the reactant in the reaction vessel to a desired temperature.
  • the through hole 810 may be parallel to the upper surface 110 and the lower surface 120 .
  • the through hole 610 is formed parallel to the upper surface 110 and the lower surface 120 between the upper surface 110 and the lower surface 120 . That is, each through hole 610 is located at a certain height from the lower surface 120 .
  • the through hole 610 is formed parallel to the longitudinal direction and may be arranged in plurality in the width direction.
  • the through hole 610 is formed parallel to the width direction and may be arranged in plurality in the length direction.
  • the through hole 610 is formed to pass through the thermal block 100 in the longitudinal direction or the width direction, and the through hole 610 may be formed to pass through the center of the through surface.
  • the penetrating surface is a surface of a thermal block in which the through hole 610 is formed, and the center of the penetrating surface is the center of the penetrating surface in the longitudinal direction or width direction.
  • the center of the penetrating surface may include the center of the longitudinal or widthwise direction and the surrounding area. Therefore, the through hole 610 reduces the mass of the central portion, not the outer portion, of the thermal block 600 of the present invention, thereby reducing the difference in heat capacity between the central portion having a relatively large heat capacity and the outer portion having a relatively small heat capacity.
  • the temperature of the central part and the outer part can be maintained uniformly.
  • FIG. 7 (A) and (B) show an embodiment in which five through-holes are formed penetrating the thermal block 100 in the longitudinal direction and an embodiment in which five through-holes penetrating in the width direction are formed, respectively.
  • the central through hole (610a) passes through the middle of the longitudinal and width directions of the thermal block 100, and the remaining through holes (610b) pass through the central peripheral area and are arranged on both sides.
  • the heat block 100 may be formed with both a through hole penetrating the heat block in the longitudinal direction and a through hole penetrating the heat block in the width direction.
  • the plurality of through-holes are provided, and the plurality of through-holes may be arranged side by side between the upper surface and the lower surface. That is, the plurality of through holes 610a and 610b are arranged left and right and can penetrate the heat block 100 in the longitudinal direction and/or the width direction, and the plurality of through holes 610a and 610b are formed on the surface to be penetrated. can pass through the middle. Therefore, the through hole 610 penetrates the central portion of the thermal block 100, and as a result, the mass of the central portion of the thermal block 100 is reduced, thereby reducing the temperature deviation from the outer portion.
  • a plurality of through holes 610 are provided, and at least one of the plurality of through holes may be configured to pass through the center of the length or the center of the width.
  • the center of the length refers to the center of the heat block 100 in the longitudinal direction.
  • the longitudinal direction is shown in the x-axis direction in the drawing.
  • the middle of the longitudinal direction may include the center of the longitudinal direction of the thermal block 100 and the surrounding area.
  • the center of the width refers to the center of the thermal block 100 in the width direction.
  • the width direction is shown in the y-axis direction in the drawing.
  • the center in the width direction may include the center of the heat block 100 in the width direction and the surrounding area.
  • one to three through holes 610 may be formed.
  • one to five through holes 610 may be formed.
  • one to seven through holes 610 may be formed.
  • 1 to 9 through holes 610 may be formed.
  • the through hole 610 may be formed in an area other than both end areas of the thermal block 100 in the longitudinal direction and/or in the width direction. That is, the through hole 610 is formed to penetrate between the adjacent sample holes 111 and the sample holes 111, and between the sample holes 111 and the sample holes 111 located adjacently in the both end regions can be prevented from forming.
  • the present invention has through-holes 610 positioned side by side in the longitudinal direction in an area other than both end areas in the width direction of the heat block 600 A thermal block 600 is provided.
  • the present invention includes a thermal block 600 having through holes 610 located side by side in the width direction in an area other than both end areas in the longitudinal direction. to provide.
  • the through-holes 610 are not formed between the sample holes 111 in the first column and/or the first row from both ends in the longitudinal direction and/or the width direction and the sample holes 111 adjacent thereto. don't
  • the through hole 610 is formed in the area between the sample holes 111 in two columns and/or two rows from both ends in the longitudinal direction and/or the width direction and the sample holes 111 adjacent thereto. do not form
  • both through holes 610 shown in (A) and (B) of FIG. 6 may be formed. That is, a through hole formed in the longitudinal direction and a through hole formed in the width direction may be located together in one thermal block 100 . In this case, the thermal capacity of the central portion of the thermal block 100 may be more reduced than that of the outer portion.
  • the through-holes in the longitudinal direction and the through-holes in the width direction are orthogonal to each other and overlap at orthogonal positions.
  • the through hole 610 may be located between the plurality of sample wells 111 .
  • the through hole 610 is located between the plurality of sample wells 111 .
  • the through holes 610 are located between the gaps between each sample well 111 and the adjacent sample wells 111.
  • the through hole 610 is formed so as not to overlap with the plurality of sample wells 111 .
  • the through hole 610 does not cross the plurality of sample wells 111 . That is, the through hole 610 located between adjacent sample wells 111 is formed with a diameter that does not overlap with the sample wells 111 .
  • 8 (A) shows a cross-sectional view of an embodiment in which a through hole 610 penetrating the thermal block 100 in the longitudinal direction is formed, and (B) of FIG. 8 shows a cross-sectional view penetrating the thermal block 100 in the width direction. A cross-sectional view of an embodiment in which a through hole 610 is formed is shown. Therefore, the sample well 111 is not penetrated by the through hole 610, and the contact area with the reaction vessel inserted into the sample well 111 is not reduced by the through hole 610.
  • a plurality of through holes 610 may be provided and positioned at least two or more heights from the lower surface 120 . That is, the plurality of through holes 610 may be located at different positions in the vertical direction.
  • 9(A) shows an implementation example in which a plurality of through holes 610 penetrating the thermal block 100 in the width direction are located at two different heights
  • FIG. 9(B) shows a thermal block It shows an embodiment in which a plurality of through holes 610 passing through (100) in the longitudinal direction are located at two different heights.
  • the number of upper through holes among the plurality of through holes may be greater than or equal to the number of lower through holes.
  • the through hole located on the upper side means a through hole located closer to the upper surface 110 than the rest, and the through hole located on the lower side means a through hole located closer to the lower surface 120 than the rest.
  • the through holes located on the upper side are five through holes 610c located on the upper side, and the through holes 610 located on the lower side are three through holes 610d located on the lower side. .
  • the number of through-holes 610 located at the lower side among the plurality of through-holes 610 may be greater than or equal to the number of through-holes 610 located at the upper side.
  • implementing different numbers of through holes 610 formed on the upper and lower sides is to reduce the thermal capacity of the thermal block 100 itself and to reduce the difference in thermal capacity between the central portion and the rest of the outer portion.
  • the upper through hole 610 of the plurality of through holes 610 may be formed in the longitudinal direction, and the lower through hole 610 may be formed in the width direction.
  • the through hole 610 positioned at the upper side of the plurality of through holes 610 may be formed in the width direction, and the through hole 610 positioned at the lower side may be formed in the longitudinal direction.
  • the plurality of through holes 610 are orthogonal to reduce the thermal capacity of the thermal block 100 .
  • each orthogonal through hole 610 is divided into an upper side and a lower side, they do not overlap with each other. Therefore, the thermal capacity of the central portion of the thermal block 100 can be greatly reduced, and the thermal capacity of the outer portion can be reduced to a small extent.
  • sample well 112 non-sample hole
  • thermal block 610 through hole

Abstract

The present invention relates to a thermal block for performing a plurality of reactions, the thermal block including an upper surface and a lower surface that are parallel to each other and have a length and width, wherein a plurality of sample wells open upwards are regularly arranged on the upper surface, a plurality of non-sample holes open upwards are formed on the upper surface, the plurality of non-sample holes include: (i) first non-sample holes in which an upper surface opening is shorter in the longitudinal direction and equal to or longer in the width direction than the diameter of the sample wells; and (ii) second non-sample holes formed shorter in the width direction and equally or longer in the longitudinal direction, the first non-sample holes are located between sample wells adjacent in the longitudinal direction, and the second non-sample holes are located between sample wells adjacent in the width direction.

Description

열블록heat block
본 발명은 복수의 반응을 수행하기 위한 열블록에 관한 것이다.The present invention relates to a thermal block for carrying out a plurality of reactions.
중합효소 연쇄반응(Polymerase chain reaction: PCR)으로 공지된 가장 많이 사용되는 핵산 증폭 반응은 이중가닥 DNA의 변성, DNA 주형에로의 올리고뉴클레오타이드 프라이머의 결합 및 DNA 중합효소에 의한 프라이머 연장의 반복된 사이클 과정을 포함한다(Mullis 등, 미국 특허 제4,663,195호, 제4,663,202호 및 제4,600,159호; Saiki et al., (1965) Science 230, 1350-1354).The most used nucleic acid amplification reaction, known as the polymerase chain reaction (PCR), is a repeated cycle of denaturation of double-stranded DNA, binding of an oligonucleotide primer to a DNA template, and primer extension by DNA polymerase. (Mullis et al., US Pat. Nos. 4,663,195, 4,663,202 and 4,600,159; Saiki et al., (1965) Science 230, 1350-1354).
DNA의 변성은 약 95도에서 진행되고, 결합 및 프라이머의 연장은 95도보다 낮은 온도인 55도 내지 75도에서 진행된다. 따라서, 샘플이 수용되는 반응용기 또는 챔버들의 온도를 올렸다 내리는 과정을 반복하여 샘플의 핵산 증폭 반응을 수행한다.Denaturation of DNA proceeds at about 95 degrees, and binding and extension of primers proceed at a temperature lower than 95 degrees, 55 to 75 degrees. Therefore, the nucleic acid amplification reaction of the sample is performed by repeating the process of raising and lowering the temperature of the reaction vessel or chambers in which the sample is accommodated.
복수의 샘플에 대해 핵산 증폭 반응을 수행하기 위해, 샘플을 수용하는 반응용기가 삽입되는 복수의 샘플웰(well)이 형성된 열블록을 사용하는 경우가 있다. 즉, 열블록의 샘플웰에 각각 샘플을 수용하는 반응용기를 삽입하고, 예를 들어 펠티어 소자를 이용하여 열블록을 가열하거나 냉각함으로써 각 샘플의 핵산 증폭 반응을 동시에 수행한다. 일반적으로 열블록의 샘플웰은 평면 상에서 행, 열로 배열되며, 샘플웰은 4 X 4의 16웰, 4 X 6의 32웰, 6 X 6의 64웰, 6 X 12의 96웰, 더 크게는 16 X 24의 364웰로 형성된다.In order to perform a nucleic acid amplification reaction on a plurality of samples, a heat block having a plurality of sample wells into which a reaction container accommodating the samples is inserted is sometimes used. That is, the reaction container for accommodating the respective samples is inserted into the sample well of the heat block, and the heat block is heated or cooled using a Peltier element, thereby simultaneously performing the nucleic acid amplification reaction of each sample. In general, the sample wells of the column block are arranged in rows and columns on a plane, and the sample wells are 16 wells of 4 X 4, 32 wells of 4 X 6, 64 wells of 6 X 6, 96 wells of 6 X 12, or even larger. It is formed with 364 wells of 16 X 24.
히팅 블록으로도 명명되는 열블록(thermal block)은 복수의 반응용기를 수용할 수 있도록 복수의 웰(well)이 형성되어 있으며, 빠른 열전도를 위하여 금속으로 제작된다. 다만, 금속은 비중 및 비열이 높아 열블록의 온도를 조절하기 위해서 많은 양의 에너지를 공급하거나, 제거하여야 하는 문제가 있다.A thermal block, also referred to as a heating block, has a plurality of wells formed therein to accommodate a plurality of reaction vessels, and is made of metal for fast heat conduction. However, metal has a high specific gravity and specific heat, so there is a problem in that a large amount of energy must be supplied or removed to control the temperature of the heat block.
이러한 문제를 해결하기 위한 방법으로 열블록의 상면에 구멍을 형성하는 방법이 제시되었는데, 즉 열블록의 불필요한 부분을 제거하여 보다 빠르게 열블록의 온도를 변화시키고자 한 것이다. 하지만, 사용자가 반응용기를 샘플웰이 아니라 상면에 형성된 구멍에 위치시키는 경우가 빈번하게 발생하는 문제가 있었으며, 또한 열블록에 형성된 샘플웰과 질량 감소용 구멍의 패턴이 균일하지 않아 각 샘플웰에 수용되는 반응용기들 간에 온도 편차가 발생하는 새로운 문제도 발생하였다.As a method for solving this problem, a method of forming a hole on the upper surface of the heat block has been proposed, that is, to change the temperature of the heat block more rapidly by removing unnecessary parts of the heat block. However, there was a problem in that the user frequently placed the reaction container in the hole formed on the upper surface instead of the sample well, and the pattern of the sample well formed in the heat block and the hole for mass reduction was not uniform, so that each sample well A new problem also arises in that temperature deviations occur between accommodated reaction vessels.
또한, 열블록의 샘플웰에 복수의 반응용기가 삽입되어 동시에 핵산 증폭 반응이 수행됨에 따라 모든 샘플의 온도제어를 균일하게 수행하는 것이 중요하다. 그런데, 열블록의 중앙부와 나머지 외곽부를 비교하면 외곽부 대비 중앙부의 열용량이 크기 때문에, 열블록을 가열할 때에는 외곽부보다 중앙부의 온도가 늦게 상승하고 열블록을 냉각할 때에는 외곽부보다 중앙부의 온도가 늦게 하강하는 구조적인 한계가 있다. 이로 인해 중앙부의 샘플웰에 삽입된 반응용기와 외곽부의 샘플웰에 삽입된 반응용기의 온도제어를 균일하게 수행하기 어려우며, 중앙부의 온도변화에 의한 응답지연이 증가할수록 각 샘플들 간의 온도 유지 구간의 차이가 커져 핵산 증폭 반응을 수행하는 장치의 성능이 저하되는 문제가 있다. 특히, 이러한 문제는 열블록의 크기가 커질수록 더욱 증대된다.In addition, since a plurality of reaction vessels are inserted into the sample wells of the heat block and the nucleic acid amplification reaction is performed simultaneously, it is important to uniformly control the temperature of all samples. However, when comparing the central part of the heat block with the rest of the outer part, since the heat capacity of the central part is larger than that of the outer part, when heating the heat block, the temperature of the central part rises later than the outer part, and when cooling the heat block, the temperature of the central part is higher than that of the outer part. There is a structural limit to the slow descent. For this reason, it is difficult to uniformly control the temperature of the reaction vessel inserted into the sample well of the central part and the reaction vessel inserted into the sample well of the outer part. There is a problem in that the performance of the apparatus for performing the nucleic acid amplification reaction deteriorates due to the large difference. In particular, this problem further increases as the size of the thermal block increases.
PCR 반응은 타겟 핵산 서열에 특이적인 프라이머를 혼성화 시키고, 이를 중합효소에 의해 연장시킨 후, 연장가닥을 분리하는 단계를 반복하여 타겟 핵산 서열을 증폭시키는 반응이다. PCR 반응은 반응 혼합물을 지정한 각 온도들에서 정해진 시간 동안 유지하는 방법으로 이와 같은 일련의 단계를 효율적으로 수행하게 한다. 따라서, PCR 반응에서 각 단계별로 정확한 온도를 유지하는 것은 매우 중요한 일이다. 온도에 따라 각 단계에서의 반응 효율이 달라질 수 있기 때문이다. The PCR reaction is a reaction in which a target nucleic acid sequence is amplified by repeating the steps of hybridizing a primer specific to a target nucleic acid sequence, extending it with a polymerase, and separating the extended strand. The PCR reaction efficiently performs this series of steps by maintaining the reaction mixture at specified temperatures for a specified period of time. Therefore, it is very important to maintain the correct temperature at each step in the PCR reaction. This is because the reaction efficiency in each step may vary depending on the temperature.
특히 PCR 반응을 이용하여 복수의 샘플에 대하여 동일한 검사를 하는 경우, 웰간 지속적으로 발생하는 온도 편차는 서로 다른 웰에서 증폭반응이 진행된 복수의 샘플마다 상기 증폭반응이 서로 다른 효율로 진행되게 하는 원인이 된다. PCR 반응은 핵산의 증폭반응을 수십 사이클을 반복하며, 이전 사이클에서 생성된 핵산가닥이 다음 사이클의 template가 되므로, 이러한 매 사이클 발생하는 증폭효율의 차이가 분석 결과에 큰 영향을 미칠 수 있다.In particular, when the same test is performed on a plurality of samples using a PCR reaction, the temperature deviation continuously occurring between wells causes the amplification reaction to proceed with different efficiency for each of a plurality of samples in which the amplification reaction has been performed in different wells. do. In the PCR reaction, nucleic acid amplification is repeated dozens of cycles, and since the nucleic acid strand generated in the previous cycle becomes the template for the next cycle, the difference in amplification efficiency occurring in each cycle can greatly affect the analysis result.
한편, PCR 과정에서 고온의 용기내 물질을 보존하고, 반응용기의 뚜껑이 열리는 것을 방지하기 위하여, PCR기기는 반응용기의 상부를 열리지 않게 누를 수 있는 고온의 덮개(hot lid)를 포함한다. 상기 핫 리드는 반응용기의 상면에 밀착되고, 반응용기에 압력을 가한 상태로 유지된다. 상기 압력은 반응용기를 통하여 열블록에 전달되어 열블록을 변형시킬 수 있는데, 샘플웰들 간의 수평적 연결이 약할수록 이러한 열블록의 내구성이 약해진다. 특히 반응용기를 잘못 장착하고 핫리드를 덮는 경우 열블록의 샘플웰의 변형이나, 파손이 발생할 수 있다.On the other hand, in order to preserve the material in the high-temperature container during the PCR process and prevent the lid of the reaction container from being opened, the PCR device includes a hot lid that can press the top of the reaction container so that it does not open. The hot lead is kept in close contact with the upper surface of the reaction vessel and pressurized the reaction vessel. The pressure may be transmitted to the heat block through the reaction vessel to deform the heat block. As the horizontal connection between the sample wells becomes weaker, the durability of the heat block becomes weaker. In particular, when the reaction container is incorrectly mounted and the hot lead is covered, deformation or damage to the sample well of the heat block may occur.
따라서, 복수의 반응용기 간의 온도 편차, 특히, 중앙부와 외곽부 간의 온도편차를 최소화하면서 동시에 반응용기를 잘못 위치시키는 오류를 방지할 수 있고, 내구성이 우수한 새로운 열블록의 개발이 필요한 실정이다.Therefore, there is a need to develop a new heat block having excellent durability and minimizing the temperature deviation between the plurality of reaction vessels, in particular, the temperature difference between the central portion and the outer portion, and at the same time preventing an error in erroneously positioning the reaction vessel.
상술한 종래기술의 문제점을 극복하기 위해서, 본 발명은 열블록의 불필요한 부분을 제거하여 열블록의 온도변화에 필요한 열 에너지를 최소화하면서도, 반응용기가 잘못 장착되는 문제를 방지할 수 있는 열블록을 제공하기 위한 목적이 있다.In order to overcome the problems of the prior art described above, the present invention provides a heat block that can prevent the problem of incorrectly mounting the reaction vessel while minimizing the heat energy required for temperature change of the heat block by removing unnecessary parts of the heat block. It has a purpose to provide.
또한, 본 발명은 열블록의 온도제어를 균일하게 수행함으로써 샘플들 간의 온도 변화 속도 및 온도 유지 구간의 차이를 최소화하여 핵산 증폭 반응의 효율 및 장치의 성능을 증가시키기 위한 목적이 있다.In addition, an object of the present invention is to increase the efficiency of the nucleic acid amplification reaction and the performance of the device by minimizing the difference in temperature change rate and temperature holding period between samples by uniformly controlling the temperature of the heat block.
또한, 본 발명은 열블록의 단위 영역에 복수개의 비샘플홀이 위치되고 단위 영역 각각에 비샘플홀이 위치하는 형태가 동일하여 열블록 내의 불필요한 매스의 감소를 극대화하면서 각 샘플웰 간의 온도 편차를 감소시키기 위한 목적이 있다.In addition, in the present invention, a plurality of non-sample holes are located in the unit area of the heat block and the form in which the non-sample holes are located in each unit area is the same, thereby maximizing the reduction of unnecessary mass in the heat block and reducing the temperature deviation between each sample well. It has a purpose to reduce.
또한, 본 발명은 열블록의 단위 영역을 정의하는 서로 인접한 4개의 샘플웰 각각에 대한 단위 영역에 위치한 비샘플홀의 열전도적 영향이 동일하도록 형성되어 샘플웰 간의 열적 균일성(thermal uniformity)를 향상시키기 위한 목적이 있다.In addition, the present invention is formed so that the thermal conductive effect of the non-sample holes located in the unit area for each of the four adjacent sample wells defining the unit area of the thermal block is the same to improve the thermal uniformity between the sample wells. there is a purpose for
또한, 본 발명은 열블록의 불필요한 매스를 감소시키면서도 열블록의 전체적인 내구성을 향상시키기 위한 목적이 있다.In addition, the present invention has an object to improve the overall durability of the heat block while reducing the unnecessary mass of the heat block.
본 발명의 일 구현예에 따른 열블록은, 복수의 반응을 수행하기 위한 열블록으로서, 서로 평행하며 길이와 폭을 가지는 상면 및 하면을 포함하고, 상면에는 상측으로 열린 복수의 샘플웰이 규칙적으로 배열되게 형성되며, 상면에는 상측으로 열린 복수의 비샘플홀이 형성되며, 복수의 비샘플홀들은 (i) 상면 개구가 샘플웰의 지름보다 길이 방향으로 짧고 폭 방향으로 같거나 길게 형성되는 제1비샘플홀들과 (ii) 폭 방향으로 짧고 길이 방향으로 같거나 길게 형성되는 제2비샘플홀들을 포함하며, 상기 제1비샘플홀은 상기 길이방향으로 인접한 샘플웰들 사이에 위치하고, 상기 제2비샘플홀은 상기 폭 방향으로 인접한 샘플웰들 사이에 위치한다.A thermal block according to an embodiment of the present invention is a thermal block for performing a plurality of reactions, and includes upper and lower surfaces that are parallel to each other and have a length and width, and a plurality of sample wells open upwards are regularly arranged on the upper surface. It is formed in an array, and a plurality of non-sample holes open upwards are formed on the upper surface, and the plurality of non-sample holes are formed in (i) a first surface opening that is shorter than the diameter of the sample well in the longitudinal direction and equal to or longer than the diameter of the sample well in the width direction. non-sample holes and (ii) second non-sample holes that are shorter in the width direction and equal to or longer in the length direction, wherein the first non-sample holes are located between adjacent sample wells in the longitudinal direction, and 2 non-sample holes are located between adjacent sample wells in the width direction.
본 발명의 특징 및 이점을 요약하면 다음과 같다.The features and advantages of the present invention are summarized as follows.
(1) 본 발명의 열블록은, 열블록의 불필요한 매스를 제거함으로써 열블록의 온도변화에 필요한 열 에너지를 최소화하면서도, 반응용기가 잘못 장착되는 문제를 방지할 수 있다.(1) In the heat block of the present invention, by removing unnecessary mass of the heat block, heat energy required for temperature change of the heat block is minimized, and the problem of incorrectly mounting the reaction vessel can be prevented.
(2) 본 발명의 열블록은, 온도제어를 균일하게 수행함으로써 샘플들 간의 온도 변화 속도 및 온도 유지구간의 차이를 최소화하여 핵산 증폭 반응의 효율 및 장치의 성능을 증가시킬 수 있다.(2) The heat block of the present invention can increase the efficiency of the nucleic acid amplification reaction and the performance of the device by minimizing the difference in temperature change rate and temperature holding period between samples by uniformly controlling the temperature.
(3) 본 발명의 열블록은, 종래의 열블록의 구조를 변경하여 열블록을 이용한 온도 상승 및 하강 속도와 온도 유지 구간의 균일성을 확보함으로써, 온도 편차에 민감한 시약의 성능 저하가 발생하는 것을 방지할 수 있다.(3) The heat block of the present invention changes the structure of the conventional heat block to secure the uniformity of the temperature rise and fall rate and temperature maintenance section using the heat block, thereby reducing the performance of reagents sensitive to temperature deviations. that can be prevented
(4) 본 발명의 열블록은, 중앙부와 외곽부의 온도편차가 최소화되어. 열블록의 중앙부와 외곽부의 온도제어가 균일하게 이루어지게 할 수 있다.(4) In the heat block of the present invention, the temperature difference between the central part and the outer part is minimized. The temperature control of the central part and the outer part of the heat block can be made uniform.
도 1은 본 발명의 열블록의 사시도이다.1 is a perspective view of a thermal block of the present invention.
도 2는 본 발명의 열블록의 평면도이다.2 is a plan view of a thermal block of the present invention.
도 3은 본 발명의 열블록에 형성되는 샘플웰 및 비샘플홀의 배치를 설명하기 위한 도면이다.3 is a view for explaining the arrangement of sample wells and non-sample holes formed in the thermal block of the present invention.
도 4는 도 2의 A-A를 따른 본 발명의 열블록의 단면도이다.Figure 4 is a cross-sectional view of the thermal block of the present invention taken along A-A in Figure 2;
도 5는 도 2의 B-B를 따른 본 발명의 열블록의 단면도이다.Figure 5 is a cross-sectional view of the thermal block of the present invention taken along line B-B in Figure 2;
도 6은 본 발명의 열블록의 사시도이다.6 is a perspective view of a thermal block of the present invention.
도 7은 본 발명의 열블록의 평면도이다.7 is a plan view of a thermal block of the present invention.
도 8은 본 발명의 열블록의 단면도이다.8 is a cross-sectional view of a thermal block of the present invention.
도 9은 본 발명의 열블록의 측면도이다.9 is a side view of a thermal block of the present invention.
이하, 본 발명을 실시예와 예시적인 도면을 통해 상세하게 설명하고자 한다. 이들 실시 예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시 예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.Hereinafter, the present invention will be described in detail through examples and exemplary drawings. These examples are only for explaining the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
또한, 각 도면의 구성요소들에 참조부호를 부가함에 있어서, 동일한 구성요소들에 대해서는 비록 다른 도면상에 표시되더라도 가능한 한 동일한 부호를 가지도록 하고 있음에 유의해야 한다. 또한, 본 발명을 설명함에 있어, 관련된 공지 구성 또는 기능에 대한 구체적인 설명이 본 발명의 요지를 흐릴 수 있다고 판단되는 경우에는 그 상세한 설명을 생략한다. In addition, in adding reference numerals to components of each drawing, it should be noted that the same components have the same numerals as much as possible even if they are displayed on different drawings. In addition, in describing the present invention, if it is determined that a detailed description of a related known configuration or function may obscure the gist of the present invention, the detailed description will be omitted.
또한, 본 발명의 구성요소를 설명하는 데 있어서, 제1, 제2, A, B, (a), (b), (i), (ii) 등의 용어를 사용할 수 있다. 이러한 용어는 그 구성요소를 다른 구성요소와 구별하기 위한 것일 뿐, 그 용어에 의해 해당 구성요소의 본질이나 차례 또는 순서 등이 한정되지 않는다. 어떤 구성요소가 다른 구성요소에 “연결”, “결합” 또는 “접속”된다고 기재된 경우, 그 구성요소는 다른 구성요소에 직접적으로 연결되거나 또는 접속될 수 있지만, 각 구성요소 사이에 또 다른 구성요소가 “연결”, “결합” 또는 “접속”될 수 있는 것으로 이해될 수 있다.Also, in describing the components of the present invention, terms such as first, second, A, B, (a), (b), (i), and (ii) may be used. These terms are only used to distinguish the component from other components, and the nature, sequence, or order of the corresponding component is not limited by the term. When an element is described as being “connected”, “coupled” or “connected” to another element, that element is directly connected or connectable to the other element, but there is another element between each element. It can be understood that can be "connected", "coupled" or "connected".
본 발명자들은 핵산 증폭 반응의 효율 및 장치의 성능을 증가시키기 위하여 열블록의 구조를 개선하고자 예의 노력하였다. 그 결과, 본 발명자들은 열블록의 불필요한 매스를 제거함으로써 열블록의 온도변화에 필요한 열 에너지를 최소화하면서도, 반응용기가 잘못 장착되는 문제를 방지할 수 있도록 열블록의 구조를 개선하였다. 또한, 본 발명자들은 열 블록의 각 웰 마다의 위치에서 온도 변화의 속도 및 온도 유지 구간에서의 온도 변화 차이를 최소화할 수 있도록 열블록의 구조를 개선하였다. 즉, 열블록의 전체적인 열 용량을 낮추고 열블록의 중앙부와 외곽부 간의 온도 편차가 최소화되도록 열블록의 구조를 개선하여, 이를 통해 온도 편차에 민감한 시약의 성능 저하가 발생하는 것을 개선하였다.The present inventors intensively tried to improve the structure of the heat block in order to increase the efficiency of the nucleic acid amplification reaction and the performance of the device. As a result, the present inventors have improved the structure of the heat block so as to minimize the heat energy required for the temperature change of the heat block by removing unnecessary mass of the heat block, and prevent the reaction container from being erroneously mounted. In addition, the present inventors improved the structure of the thermal block to minimize the temperature change rate at each well location of the thermal block and the temperature change difference in the temperature holding section. That is, the structure of the heat block is improved to lower the overall heat capacity of the heat block and minimize the temperature difference between the central part and the outer part of the heat block, thereby improving the performance degradation of the reagent sensitive to the temperature difference.
본원에서 사용된 용어 “열블록(thermal block)”은 열블록에 형성된 복수의 샘플웰이 직접적으로 샘플을 수용하여 반응하는 반응용기로서 사용될 수 있으며, 또는 열블록에 형성된 복수의 샘플웰에 맞게 형성된 반응용기를 수용하는 수용체로 사용될 수 있다. 본 발명의 일 구현예에 따르면, 열블록은 열 전도도 등이 우수한 소재를 사용하여 제작될 수 있다. 금속 또는 금속 합금(예를 들어, 철, 구리, 알루미늄, 금, 은 또는 이를 포함하는 합금)으로 제작될 수 있다. 열블록은 하나의 단단한 금속 조각으로 가공되거나, 여러 개의 금속 조각을 연결하여 형성될 수 있다.As used herein, the term "thermal block" may be used as a reaction vessel in which a plurality of sample wells formed in the thermal block directly receive and react with samples, or formed to fit the plurality of sample wells formed in the thermal block. It can be used as a receptor for accommodating a reaction vessel. According to one embodiment of the present invention, the thermal block may be manufactured using a material having excellent thermal conductivity. It may be made of a metal or metal alloy (eg, iron, copper, aluminum, gold, silver or an alloy containing the same). A thermal block may be machined from a single solid piece of metal or formed by connecting several pieces of metal.
본 발명의 열블록은 복수의 반응을 수행하기 위한 열블록이다. 상기 반응은 적어도 하나의 화학적 또는 생물학적 물질(예를 들어, 용액, 용매, 효소)이 관여한 화학적, 생화학적 또는 생물학적 변환(transformation)을 말한다. 본 발명에서 상기 반응은 바람직하게는 반응계의 열적 변화에 의하여 개시, 중단, 촉진 또는 저해되는 반응일 수 있다. 예를 들어, 상기 반응은 온도 변화에 따라 생물학적 또는 화학적 물질의 분해 또는 결합이 진행되거나, 온도 변화에 따라 생물학적 또는 화학적 물질의 생산 또는 분해를 수행하는 효소의 활성이 촉진 또는 저해되는 반응일 수 있다.The heat block of the present invention is a heat block for carrying out a plurality of reactions. The reaction refers to a chemical, biochemical or biological transformation involving at least one chemical or biological substance (eg, solution, solvent, enzyme). In the present invention, the reaction may preferably be initiated, stopped, accelerated or inhibited by a thermal change in the reaction system. For example, the reaction may be a reaction in which decomposition or binding of a biological or chemical substance proceeds as a result of a change in temperature, or an activity of an enzyme that produces or decomposes a biological or chemical substance is promoted or inhibited as a result of a change in temperature. .
구체적으로 상기 반응은 증폭 반응을 의미할 수 있다. 상기 증폭 반응은 타겟 분석물질(예를 들어, 핵산) 자체를 증가시키는 반응일 수 있으며, 또는 상기 타겟 분석물질의 존재에 의존적으로 발생되는 신호를 증가 또는 감소시키는 반응일 수 있다. 상기 타겟 분석물질의 존재에 의존적으로 발생되는 신호를 증가 또는 감소시키는 반응은 타겟 분석물질의 증가가 동반되거나 또는 동반되지 않을 수 있다. 구체적으로 상기 타겟 분석물질은 핵산 분자이며, 상기 반응은 중합효소 연쇄반응(Polymerase Chain Reaction; PCR) 또는 실시간 PCR 일 수 있다.Specifically, the reaction may mean an amplification reaction. The amplification reaction may be a reaction that increases the target analyte (eg, nucleic acid) itself, or may be a reaction that increases or decreases a signal generated depending on the presence of the target analyte. A reaction that increases or decreases the signal generated depending on the presence of the target analyte may or may not be accompanied by an increase in the target analyte. Specifically, the target analyte is a nucleic acid molecule, and the reaction may be a polymerase chain reaction (PCR) or real-time PCR.
일반적으로 중합효소 연쇄반응(PCR)은 핵산의 변성단계(denaturation), 핵산과 프라이머의 결합 단계(hybridization 또는 annealing) 및 프라이머의 연장 단계(extension)를 포함하는 반응을 포함하는 사이클을 반복하여 수행된다. 이 경우 일정한 조건의 변화는 반응의 반복 횟수의 증가이며, 상기 일련의 단계를 포함하는 반응의 반복 단위가 하나의 사이클로 설정된다.In general, polymerase chain reaction (PCR) is performed by repeating cycles including reactions including denaturation of nucleic acids, binding of nucleic acids to primers (hybridization or annealing), and extension of primers. . In this case, the change in constant conditions is an increase in the number of repetitions of the reaction, and the repeating unit of the reaction including the series of steps is set as one cycle.
본 발명의 열블록을 이용하여 다양한 핵산 증폭 반응을 수행할 수 있다. 예를 들어, 중합효소 연쇄 반응(polymerase chain reaction; PCR), 리가아제 연쇄 반응(ligase chain reaction; LCR, 참조 Wiedmann M, 등, "Ligase chain reaction (LCR)- overview and applications." PCR Methods and Applications 1994 Feb;3(4):S51-64), 갭 필링 LCR(gap filling LCR; GLCR, 참조 WO 90/01069, 유럽 특허 제439162호 및 WO 93/00447), Q-베타 리플리카제 증폭(Q-beta replicase amplification; Q-beta, 참조 Cahill P, 등, Clin Chem., 37(9): 1462-5(1991), 미국 특허 제5556751호), 가닥 치환 증폭(strand displacement amplification; SDA, 참조 G T Walker 등, Nucleic Acids Res. 20(7):16911696(1992), 유럽 특허 제497272호), 핵산 서열-기반 증폭(nucleic acid sequence-based amplification; NASBA, 참조 Compton, J. Nature 350(6313):912(1991)), 전사 매개 증폭(Transcription-Mediated Amplification; TMA, 참조 Hofmann WP 등, J Clin Virol. 32(4):269-93(2005); 미국 특허 제5666779호) 또는 롤링 서클 증폭(Rolling Circle Amplification; RCA, 참조 Hutchison C.A. 등, Proc. Natl Acad. Sci. USA. 102:1733217336(2005))에 의해 실시된다.Various nucleic acid amplification reactions can be performed using the heat block of the present invention. For example, polymerase chain reaction (PCR), ligase chain reaction (LCR, see Wiedmann M, et al., "Ligase chain reaction (LCR)- overview and applications." PCR Methods and Applications 1994 Feb;3(4):S51-64), gap filling LCR (GLCR, see WO 90/01069, EP 439162 and WO 93/00447), Q-beta replicase amplification (Q -beta replicase amplification; Q-beta, see Cahill P, et al., Clin Chem., 37(9): 1462-5 (1991), US Pat. No. 5556751), strand displacement amplification (SDA, see G T Walker et al, Nucleic Acids Res. 912 (1991)), Transcription-Mediated Amplification (TMA, see Hofmann WP et al., J Clin Virol. 32(4):269-93 (2005); US Patent No. 5666779) or Rolling Circle Amplification Circle Amplification; RCA, see Hutchison C.A. et al., Proc. Natl Acad. Sci. USA. 102:1733217336 (2005)).
특히, 본 발명의 열블록은 polymerase chain reaction 기반의 핵산 증폭 반응에 유용하게 이용된다. polymerase chain reaction을 기반으로 하는 다양한 핵산 증폭 방법이 알려져 있다. 예를 들어, 정량 PCR (quantitative PCR), digital PCR, 비대칭 PCR (asymmetric PCR), 역전사 효소 PCR (RT-PCR), 분별 디스플레이 PCR (Differential Display PCR: DD-PCR), 중첩 (nested PCR) 임의적 프라이밍 PCR(AP-PCR), 멀티플렉스 PCR, SNP 지놈 타이핑 PCR 등을 포함한다.In particular, the heat block of the present invention is usefully used in a polymerase chain reaction-based nucleic acid amplification reaction. Various nucleic acid amplification methods based on polymerase chain reaction are known. For example, quantitative PCR, digital PCR, asymmetric PCR, reverse transcriptase PCR (RT-PCR), differential display PCR (DD-PCR), nested PCR, random priming PCR (AP-PCR), multiplex PCR, SNP genome typing PCR and the like.
도 1은 본 발명의 열블록의 사시도, 도 2는 본 발명의 열블록의 평면도, 도 3은 본 발명의 열블록에 형성되는 샘플웰 및 비샘플홀의 배치를 설명하기 위한 도면, 도 4는 본 발명의 열블록의 단면도, 도 5는 본 발명의 열블록의 단면도, 도 6은 본 발명의 열블록의 사시도, 도 7은 본 발명의 열블록의 평면도, 도 8은 본 발명의 열블록의 단면도, 도 9은 본 발명의 열블록의 측면도이다. 1 is a perspective view of a thermal block of the present invention, FIG. 2 is a plan view of the thermal block of the present invention, FIG. 3 is a view for explaining the arrangement of sample wells and non-sample holes formed in the thermal block of the present invention, FIG. A cross-sectional view of the heat block of the present invention, Figure 5 is a cross-sectional view of the heat block of the present invention, Figure 6 is a perspective view of the heat block of the present invention, Figure 7 is a plan view of the heat block of the present invention, Figure 8 is a cross-sectional view of the heat block of the present invention 9 is a side view of the thermal block of the present invention.
도 1을 참고하여 살펴보면, 본 발명의 열블록(100)은 복수의 반응을 수행하기 위한 열블록으로서, 서로 평행하며 길이와 폭을 가지는 상면(110, top surface) 및 하면(120, bottom surface)을 포함하고, 상면(110)에는 상측으로 열린 복수의 샘플웰(111)이 규칙적으로 배열되게 형성되며, 상면(110)에는 상측으로 열린 복수의 비샘플홀(112)이 형성되며, 복수의 비샘플홀(112)들은 상면 개구가 샘플웰(111)의 지름보다 길이 방향으로 짧고 폭 방향으로 같거나 길게 형성되는 제1비샘플홀(112a)들과 폭 방향으로 짧고 길이 방향으로 같거나 길게 형성되는 제2비샘플홀(112b)들을 포함하며, 제1비샘플홀(112a)은 상기 길이 방향으로 인접한 샘플웰(111)들 사이에 위치하고, 상기 제2비샘플홀(112b)은 상기 폭 방향으로 인접한 샘플웰(111)들 사이에 위치한다. 다시말해, 복수의 샘플웰(111)들 중 길이 방향으로 인접한 샘플웰(111)들의 사이에는 제1비샘플홀(112a)이 위치하고, 폭 방향으로 인접한 샘플웰(111)들 사이에는 제2비샘플홀(112b)이 위치한다. 본 발명의 열블록(100)은 일정한 높이(두께)를 갖는 육면체, 특히 직육면체 형상을 가질 수 있다. 상면(110)과 하면(120)의 길이와 폭은 다를 수 있으며, 측면은 굴곡을 가질 수 있다. 도면에는 이해의 편의를 위하여 길이, 폭, 및 높이 방향을 각각 x, y, z 축 방향으로 도시하였다. 도 1 및 도 7을 참고하여, 본 발명 명세서에서 길이 방향은 x 축 방향을 의미하며, 폭 방향은 y 축 방향을 의미하며, 높이 방향은 z 축 방향을 의미한다.Referring to FIG. 1, the heat block 100 of the present invention is a heat block for performing a plurality of reactions, and is parallel to each other and has a length and width of an upper surface (110, top surface) and a lower surface (120, bottom surface) Including, a plurality of sample wells 111 open upwards are regularly arranged on the upper surface 110, a plurality of non-sample holes 112 open upwards are formed on the upper surface 110, and a plurality of non-sample wells 112 open upwards are formed on the upper surface 110. The sample holes 112 are formed shorter in the width direction and equal to or longer in the length direction than the first non-sample holes 112a in which the upper surface opening is shorter in the longitudinal direction than the diameter of the sample well 111 and equal to or longer in the width direction. It includes second non-sample holes 112b, the first non-sample holes 112a are located between adjacent sample wells 111 in the longitudinal direction, and the second non-sample holes 112b are located in the width direction It is located between adjacent sample wells 111 as . In other words, among the plurality of sample wells 111, the first non-sample holes 112a are positioned between adjacent sample wells 111 in the longitudinal direction, and the second non-sample holes 112a are positioned between adjacent sample wells 111 in the width direction. A sample hole 112b is located. The thermal block 100 of the present invention may have a hexahedral shape, particularly a rectangular parallelepiped shape, having a certain height (thickness). The upper surface 110 and the lower surface 120 may have different lengths and widths, and side surfaces may have curves. In the drawings, for convenience of understanding, length, width, and height directions are shown as x, y, and z axis directions, respectively. Referring to FIGS. 1 and 7 , in the present specification, the length direction means the x-axis direction, the width direction means the y-axis direction, and the height direction means the z-axis direction.
본 발명의 일 구현예에 따르면, 열블록(100)의 두께는 5mm 내지 20mm일 수 있다. 열블록(100)의 두께가 5mm 이하인 경우, 열블록(100)에 형성되는 샘플웰(111)이 반응용기를 수용하기에 충분한 깊이를 가지기 어려울 수 있으며, 20mm 이상인 경우 열블록(100)의 열용량이 지나치게 커져 가열 또는 냉각의 효율이 낮을 수 있다.According to one embodiment of the present invention, the heat block 100 may have a thickness of 5 mm to 20 mm. When the thickness of the heat block 100 is 5 mm or less, it may be difficult for the sample well 111 formed in the heat block 100 to have a sufficient depth to accommodate the reaction vessel, and when the thickness is 20 mm or more, the thermal capacity of the heat block 100 This may become excessively large and the efficiency of heating or cooling may be low.
열블록(100)의 길이와 폭은 상면(110)에 형성되는 샘플웰(111)의 크기 및 수에 따라 달라질 수 있다. 열블록(100)의 길이와 폭은 각각 10mm 이상, 20mm 이상, 30mm 이상일 수 있다. 또한, 열블록(100)의 길이와 폭은 각각 1000mm 이하, 900mm 이하, 600mm 이하, 700m 이하, 600mm 이하, 500mm 이하, 400mm 이하, 300mm 이하, 또는 200mm 이하일 수 있다.The length and width of the thermal block 100 may vary depending on the size and number of sample wells 111 formed on the upper surface 110 . The length and width of the heat block 100 may be 10 mm or more, 20 mm or more, or 30 mm or more, respectively. In addition, the length and width of the heat block 100 may be 1000 mm or less, 900 mm or less, 600 mm or less, 700 m or less, 600 mm or less, 500 mm or less, 400 mm or less, 300 mm or less, or 200 mm or less, respectively.
도 1을 참고하여 살펴보면, 본 발명의 열블록(100)의 상면(110)에는 상측으로 열린 복수의 샘플웰(111)이 형성된다. 샘플웰(111)은 샘플을 직접적으로 수용하게 형성되거나, 샘플을 수용하는 반응용기가 삽입되게 형성될 수 있다. 샘플웰(111)은 샘플웰(111)에 수용된 샘플 또는 반응용기와 열전도적으로 접촉(thermal-conductively contact)한다.Referring to FIG. 1 , a plurality of sample wells 111 open upwards are formed on the upper surface 110 of the thermal block 100 of the present invention. The sample well 111 may be formed to directly receive a sample or may be formed to insert a reaction container for accommodating the sample. The sample well 111 is in thermal-conductively contact with the sample or reaction vessel accommodated in the sample well 111 .
본 발명의 열블록(100)은 복수의 샘플에 대한 반응을 동시에 수행할 수 있도록 형성된다. 열블록(100)에 형성되는 샘플웰(111)은 복수개로서, 열블록(100)은 4개 이상, 6개 이상, 6개 이상, 12개 이상, 16개 이상, 24개 이상, 32개 이상, 40개 이상, 46개 이상의 샘플웰을 포함할 수 있다. 또한, 열블록(100)은 96개 이하, 192개 이하, 288개 이하, 384개 이하의 샘플웰을 포함할 수 있다. 본 발명의 일 구현예에 의하면, 열블록(100)의 상면(110)에는 상측으로 열린 4개 이상 364개 이하의 샘플웰(111)이 형성될 수 있다.The thermal block 100 of the present invention is formed to simultaneously perform a reaction for a plurality of samples. The number of sample wells 111 formed in the heat block 100 is plural, and the heat block 100 has 4 or more, 6 or more, 6 or more, 12 or more, 16 or more, 24 or more, 32 or more. , 40 or more, 46 or more sample wells. In addition, the thermal block 100 may include 96 or less, 192 or less, 288 or less, or 384 or less sample wells. According to one embodiment of the present invention, 4 or more and 364 or less sample wells 111 open upward may be formed on the upper surface 110 of the thermal block 100 .
본 발명의 열블록(100)의 샘플웰(111)은 상면(110)에서 규칙적으로 배열된다. 상기 규칙적인 배열이란 복수의 샘플웰(111) 중 서로 인접한 샘플웰 간의 방향 및 거리가 일정한 규칙에 의하여 결정되는 것을 의미한다. 복수의 샘플웰(111)들의 배열은 상기 규칙에 의하여 결정된다. 예를 들어, 본 발명의 복수의 샘플웰은 상면(110)에서 길이 방향(x 방향)과 평행한 복수의 행으로 나란히 배열될 수 있으며, 또한 폭 방향(y 방향)과 평행한 복수의 열로 나란히 배열될 수 있다. 상기 각 행과 각 열에 속하는 샘플웰들은 일정한 간격으로 배열될 수 있다.The sample wells 111 of the thermal block 100 of the present invention are regularly arranged on the upper surface 110. The regular arrangement means that directions and distances between adjacent sample wells among the plurality of sample wells 111 are determined according to a certain rule. The arrangement of the plurality of sample wells 111 is determined according to the above rules. For example, the plurality of sample wells of the present invention may be arranged side by side in a plurality of rows parallel to the longitudinal direction (x direction) on the upper surface 110, and also in a plurality of columns parallel to the width direction (y direction). can be arranged Sample wells belonging to each row and each column may be arranged at regular intervals.
본 발명의 일 구현예에 의하면, 상기 규칙적인 배열은 직사각형 배열(rectangular array)일 수 있다. 상기 직사각형 배열은 상기 길이 방향으로 서로 평행한 복수의 행(column)으로 나란히 배열된 복수의 샘플웰들이 상기 폭 방향으로도 서로 평행한 복수의 열(row)로 나란히 배열되는 것을 의미한다. 또는, 본 발명의 일 구현예에 의하면, 상기 규칙적인 배열은 정사각형 배열일 수 있다. 상기 정사각형 배열은 상기 직사각형 배열의 특수한 형태로서, 상기 각 행에 속하는 샘플웰의 개수와 상기 각 열에 속하는 샘플웰의 개수가 동일한 형태를 의미한다.According to one embodiment of the present invention, the regular array may be a rectangular array. The rectangular arrangement means that a plurality of sample wells arranged side by side in a plurality of rows parallel to each other in the longitudinal direction are arranged side by side in a plurality of rows parallel to each other also in the width direction. Alternatively, according to one embodiment of the present invention, the regular arrangement may be a square arrangement. The square arrangement is a special form of the rectangular arrangement, and means a form in which the number of sample wells belonging to each row and the number of sample wells belonging to each column are the same.
본 발명의 일 구현예에 따르면, 복수의 샘플웰(111)은 반응용기를 수용하게 형성될 수 있다. 상기 반응용기는 하나의 컨테이너를 포함하는 반응튜브일 수 있으며, 복수의 컨테이너를 포함하는 반응스트립 또는 반응플레이트일 수 있다. 상기 반응스트립은 복수의 컨테이너가 일렬로 일정 간격을 가지게 형성된 반응용기를 말하며, 상기 반응플레이트는 복수의 컨테이너가 2열 이상으로 일정 간격을 가지게 형성된 반응용기를 말한다. 상기 컨테이너는 반응물(예를 들어, 반응용액 또는 반응혼합물)을 수용할 수 있는 단위체(unit)을 말한다. 상기 반응용기는 그 용도 및 형태에 따라 테스트 튜브, PCR 튜브, 스트립 튜브, multi well PCR 플레이트로 명명될 수 있다.According to one embodiment of the present invention, a plurality of sample wells 111 may be formed to accommodate reaction vessels. The reaction vessel may be a reaction tube including one container, or may be a reaction strip or reaction plate including a plurality of containers. The reaction strip refers to a reaction vessel in which a plurality of containers are arranged in a row at regular intervals, and the reaction plate refers to a reaction vessel in which a plurality of containers are formed in two or more rows at regular intervals. The container refers to a unit capable of accommodating a reactant (eg, a reaction solution or a reaction mixture). The reaction vessel may be named a test tube, a PCR tube, a strip tube, or a multi well PCR plate depending on its use and shape.
본 발명의 샘플웰(111)의 형태는 사용되는 반응용기의 컨테이너의 형상에 따라 달라질 수 있다. 예를 들어, 본 발명의 샘플웰(111)은 원뿔형의 일반적인 핵산 증폭용 튜브를 수용하도록 형성될 수 있다. 이 경우 샘플웰(111)은 상면(110)에서 상측으로 열린 개구가 원형이며, 하측으로 갈수록 직경이 작아지게 테이퍼질 수 있다. 도면들에는 예시적인 형태로서 샘플웰(111)의 개구가 원형인 일 구현예가 도시되어 있다.The shape of the sample well 111 of the present invention may vary depending on the shape of the container of the reaction vessel used. For example, the sample well 111 of the present invention may be formed to accommodate a general conical tube for nucleic acid amplification. In this case, the sample well 111 has a circular opening opened upward from the upper surface 110 and may be tapered to have a smaller diameter toward the lower side. In the drawings, an embodiment in which the opening of the sample well 111 is circular is shown as an exemplary form.
본 발명의 일 구현예에 따르면, 샘플웰(111)은 10 마이크로리터 이상, 20 마이크로리터 이상, 30 마이크로리터 이상, 40 마이크로리터 이상의 반응액을 수용할 수 있는 부피의 컨테이너를 포함하는 반응용기를 수용하게 형성될 수 있다. 또한, 본 발명의 일 구현예에 따르면, 샘플웰(111)은 700 마이크로리터 이하, 600 마이크로리터 이하, 500 마이크로리터 이하, 400 마이크로리터 이하, 300 마이크로리터 이하, 200 마이크로리터 이하, 100 마이크로리터 이하, 또는 50 마이크로리터 이하의 반응액을 수용할 수 있는 부피의 컨테이너를 포함하는 반응용기를 수용하게 형성될 수 있다.According to one embodiment of the present invention, the sample well 111 is a reaction vessel including a container having a volume capable of accommodating a reaction solution of 10 microliters or more, 20 microliters or more, 30 microliters or more, or 40 microliters or more. can be formed to accommodate. In addition, according to one embodiment of the present invention, the sample well 111 is 700 microliters or less, 600 microliters or less, 500 microliters or less, 400 microliters or less, 300 microliters or less, 200 microliters or less, 100 microliters or less. It may be formed to accommodate a reaction vessel including a container having a volume of less than or equal to 50 microliters or less of the reaction solution.
본 발명의 일 구현예에서, 열블록(100)의 상면(110)과 하면(120)의 면적은 서로 상이하다. 바람직하게는 상면(110)의 면적보다 하면(120)의 면적이 더 크다. 따라서, 열블록(100)의 측면에는 상면(110)보다 하면(120)이 넓은 측면 단차가 형성될 수 있다. In one embodiment of the present invention, the areas of the upper surface 110 and the lower surface 120 of the thermal block 100 are different from each other. Preferably, the area of the lower surface 120 is larger than that of the upper surface 110 . Therefore, a side step may be formed on the side of the thermal block 100 where the lower surface 120 is wider than the upper surface 110 .
본 발명의 다른 구현예에서, 열블록(100)의 상면(110)과 하면(120)의 면적은 서로 같다. 따라서, 열블록(100)은 전체적으로 직육면체의 형상이다. 열블록(100)의 측면은 단차지지 않으며, 수직으로 평평한 형태로 형성될 수 있다.In another embodiment of the present invention, the upper surface 110 and the lower surface 120 of the thermal block 100 have the same area. Accordingly, the thermal block 100 has a rectangular parallelepiped shape as a whole. The side of the heat block 100 is not stepped and may be formed in a vertically flat shape.
열블록(100)의 하면(120)에는 예를 들어 펠티어 소자와 같은 열전소자가 열적으로 접촉(thermally contact)하여 열블록(100)과의 열교환을 수행한다. 열블록(100)은 하면(120)으로부터 열이 공급됨에 따라 가열되거나 하면(120)에서 열이 흡수됨에 따라 냉각되며, 따라서 샘플웰(111)에 수용된 샘플 또는 샘플웰(111)에 삽입된 반응용기에 수용된 샘플의 증폭 반응이 수행될 수 있다. 열블록(100)의 하면(120)에는 온도센서가 장착될 수 있다. 본 발명의 일 구현예에 의하면, 단차면(121)에는 적어도 하나 이상의 온도센서가 위치하는 센서 홈이 형성될 수 있다. 센서 홈의 형상은 온도센서의 형태에 따라 달라질 수 있으며, 예를 들어 탐침형, 버튼형의 온도 프로브가 장착될 수 있는 형상일 수 있다.A thermoelectric element such as a Peltier element is in thermal contact with the lower surface 120 of the thermal block 100 to perform heat exchange with the thermal block 100 . The heat block 100 is heated as heat is supplied from the lower surface 120 or cooled as heat is absorbed from the lower surface 120, and thus the sample accommodated in the sample well 111 or the reaction inserted into the sample well 111 An amplification reaction of the sample accommodated in the vessel may be performed. A temperature sensor may be mounted on the lower surface 120 of the thermal block 100 . According to one embodiment of the present invention, a sensor groove in which at least one temperature sensor is located may be formed on the stepped surface 121 . The shape of the sensor groove may vary depending on the shape of the temperature sensor, and may be, for example, a shape into which a probe-type or button-type temperature probe can be mounted.
도 2의 (A)를 참고하여 살펴보면, 열블록(100)은 복수의 비샘플홀(112)들을 포함한다. 비샘플홀(112)은 열블록(100)의 상면(110)에서 상측으로 개구되게 형성된다. 비샘플홀(112)은 샘플웰(111)로부터 구분되며, 비샘플홀(112)에는 반응용기가 수용되지 않는다. 비샘플홀(112)은 열블록(100)의 질량을 감소시켜 샘플웰(111)의 온도를 변화시키는데 필요한 에너지를 저감하기 위해 형성된다.Referring to (A) of FIG. 2 , the thermal block 100 includes a plurality of non-sample holes 112 . The non-sample hole 112 is formed to open upward from the top surface 110 of the thermal block 100 . The non-sample hole 112 is separated from the sample well 111, and the reaction vessel is not accommodated in the non-sample hole 112. The non-sample hole 112 is formed to reduce energy required to change the temperature of the sample well 111 by reducing the mass of the thermal block 100 .
비샘플홀(112)의 형태는 특별히 한정되지 아니하나, 샘플웰(111)에 맞는(fitted) 형태의 용기가 비샘플홀(112)에는 삽입되지 않도록 형성된다. 상기 샘플웰(111)에 맞는 형태의 용기란 샘플웰(111)에 삽입되었을 때 외면이 샘플웰(111)의 내벽에 밀착되는 형태의 용기를 의미한다. 즉, 비샘플홀(112)이 샘플웰(111)에 맞는 형태의 용기가 삽입되지 않도록 형성됨에 따라 샘플웰(111)에 삽입되어야 할 반응용기가 비샘플홀(112)에 잘못 삽입되는 것을 방지할 수 있다.The shape of the non-sample hole 112 is not particularly limited, but a container fitted to the sample well 111 is formed so as not to be inserted into the non-sample hole 112 . The container having a shape suitable for the sample well 111 means a container having an outer surface in close contact with the inner wall of the sample well 111 when inserted into the sample well 111 . That is, since the non-sample hole 112 is formed so that a container of a shape suitable for the sample well 111 is not inserted, the reaction container to be inserted into the sample well 111 is prevented from being inserted into the non-sample hole 112 by mistake. can do.
복수의 비샘플홀(112)들은 상면 개구가 샘플웰(111)의 지름보다 길이 방향으로 짧고 폭 방향으로 같거나 길게 형성되는 제1비샘플홀(112a)들과, 폭 방향으로 짧고 길이 방향으로 같거나 길게 형성되는 제2비샘플홀(112b)들을 포함한다. 즉, 복수의 비샘플홀(112)들은 샘플웰(111)의 지름보다 짧은 길이를 가지는 제1비샘플홀(112a)들과 좁은 폭을 가지는 제2비샘플홀(112b)들을 포함한다. 도 4는 도 2의 (A)의 A-A 선을 따른 단면도로서 길이 방향을 따라 교대로 배열되는 샘플웰(111)과 제1비샘플홀(112a)을 도시하며, 샘플웰(111)의 지름보다 길이 방향으로 짧은 길이로 형성된 제1비샘플홀(112a)로 샘플웰(111)에 맞는 형태의 용기가 삽입되는 것이 방지될 수 있다. 마찬가지로, 샘플웰(111)의 지름보다 폭 방향으로 좁은 폭으로 형성된 제2비샘플홀(112b)로 샘플웰(111)에 맞는 형태의 용기가 삽입되는 것이 방지될 수 있다. 따라서, 샘플웰(111)에 맞는 형태의 용기는 샘플웰(111)의 지름보다 짧은 길이를 가지게 형성된 제1비샘플홀(112a) 또는 좁은 폭을 가지게 형성된 제2비샘플홀(112b)에 삽입될 수 없으며, 이에 사용자가 샘플웰(111)에 삽입되어야 할 반응용기를 비샘플홀(112)에 잘못 삽입하는 것이 방지됨으로써 작업효율을 향상시키고 핫리드가 제공하는 압력에 의한 반응용기 내지는 열블록의 파손을 방지할 수 있다.The plurality of non-sample holes 112 include first non-sample holes 112a having an upper surface opening shorter than the diameter of the sample well 111 in the longitudinal direction and equal to or longer than the diameter of the sample well 111 in the width direction, and short in the width direction and lengthwise. It includes second non-sample holes 112b formed equal to or longer. That is, the plurality of non-sample holes 112 include first non-sample holes 112a having a length shorter than the diameter of the sample well 111 and second non-sample holes 112b having a narrow width. FIG. 4 is a cross-sectional view taken along the line A-A of FIG. 2 (A), showing sample wells 111 and first non-sample holes 112a alternately arranged along the length direction, and the diameter of the sample well 111 is larger than the sample well 111. Insertion of a container having a shape suitable for the sample well 111 into the first non-sample hole 112a formed with a short length in the longitudinal direction can be prevented. Similarly, it is possible to prevent a container having a shape suitable for the sample well 111 from being inserted into the second non-sample hole 112b formed to be narrower in the width direction than the diameter of the sample well 111 . Therefore, a container of a shape suitable for the sample well 111 is inserted into the first non-sample hole 112a formed to have a length shorter than the diameter of the sample well 111 or the second non-sample hole 112b formed to have a narrow width. Therefore, the user is prevented from incorrectly inserting the reaction vessel to be inserted into the sample well 111 into the non-sample hole 112, thereby improving work efficiency and reducing the reaction vessel or heat block by the pressure provided by the hot lead. damage can be prevented.
비샘플홀(112)의 형태는 특별히 제한되지 아니하며, 예를 들어 원형, 타원형, 또는 사각형, 삼각형과 같은 다각형일 수 있다. 본 발명의 일 구현예에 따르면, 비샘플홀(112)은 도면들에 도시된 바와 같이 길이 방향 또는 폭 방향으로 인장된 육각형의 형태이되 샘플웰(111)의 사이에 위치한 부위가 압축되게 형성될 수 있다. 본 발명의 일 구현예에 의하면, 비샘플홀(112)들의 상면(110)으로 개구되는 면적은 다를 수 있다. 본 발명의 비샘플홀(112)들은 전체적으로 동일한 모양이나 크기를 가질 것이 요구되지 않는다. 예를 들어, 복수의 비샘플홀(112) 중 상면(110)에서 가장 외곽에 배치되는 비샘플홀들은 그보다 내측에 배치되는 비샘플홀들과 다른 모양을 가질 수 있다. 본 발명의 일 구현예에 따르면, 상기 상면(110)에서 가장 외곽에 배치되는 비샘플홀들은 서로 동일한 모양을 가지되 그 중 상기 길이 방향을 따라 배치되는 비샘플홀과 상기 폭방향을 따라 배치되는 비샘플홀이 서로 다른 방향으로 위치할 수 있다. 마찬가지로, 상기 내측에 배치되는 비샘플홀들은 서로 동일한 모양을 가지되 그 중 상기 길이 방향을 따라 배치되는 비샘플홀과 상기 폭 방향을 따라 배치되는 비샘플홀이 서로 다른 방향으로 위치할 수 있다.The shape of the non-sample hole 112 is not particularly limited, and may be, for example, a circular shape, an elliptical shape, or a polygonal shape such as a square or a triangle. According to one embodiment of the present invention, as shown in the drawings, the non-sample hole 112 is formed in the form of a hexagon that is stretched in the longitudinal or width direction, but a portion located between the sample wells 111 is compressed. can According to one embodiment of the present invention, the area opened to the top surface 110 of the non-sample holes 112 may be different. The non-sample holes 112 of the present invention are not required to have the same overall shape or size. For example, among the plurality of non-sample holes 112 , non-sample holes disposed at the outermost part of the upper surface 110 may have a different shape from non-sample holes disposed inside. According to one embodiment of the present invention, the non-sample holes disposed at the outermost periphery of the upper surface 110 have the same shape, but among them, the non-sample holes disposed along the longitudinal direction and the non-sample holes disposed along the width direction Non-sample holes may be positioned in different directions. Similarly, the non-sample holes disposed inside have the same shape, but among them, the non-sample holes disposed along the longitudinal direction and the non-sample holes disposed along the width direction may be located in different directions.
비샘플홀(112)은 열블록(100)에 규칙적으로 배열될 수 있다. 상기 규칙적인 배열이란 복수의 비샘플홀(112) 중 서로 인접한 비샘플홀 간의 방향 및 거리가 일정한 규칙에 의하여 결정되는 것을 의미한다. 복수의 비샘플홀(112)들의 배열은 상기 규칙에 의하여 결정된다. 예를 들어, 도 2의 (A)의 A-A 선을 따라 살펴보면, 제1비샘플홀(112a)은 길이 방향을 따라 배열되는 샘플웰(111)들의 사이에 위치할 수 있다. 즉, 길이 방향을 따라 샘플웰(111)과 제1비샘플홀(112a)이 교대로 배열될 수 있다. 또한, 제2비샘플홀(112b)은 폭 방향을 따라 배열되는 샘플웰(111)들의 사이에 위치할 수 있다. 즉, 폭 방향을 따라 샘플웰(111)과 제2비샘플홀(112b)이 교대로 배열될 수 있다.The non-sample holes 112 may be regularly arranged in the thermal block 100 . The regular arrangement means that directions and distances between adjacent non-sample holes among the plurality of non-sample holes 112 are determined according to a certain rule. The arrangement of the plurality of non-sample holes 112 is determined according to the above rules. For example, looking along the line A-A of FIG. 2 (A), the first non-sample hole 112a may be located between the sample wells 111 arranged along the length direction. That is, the sample wells 111 and the first non-sample holes 112a may be alternately arranged along the longitudinal direction. In addition, the second non-sample hole 112b may be located between the sample wells 111 arranged along the width direction. That is, the sample well 111 and the second non-sample hole 112b may be alternately arranged along the width direction.
비샘플홀(112)은 열블록(100)에 동일한 패턴으로 형성될 수 있다. 상기 동일한 패턴으로 형성된다는 것은 열블록(100) 내에서 복수의 샘플웰(111) 중 서로 인접한 4개의 샘플웰(111)들의 중심점을 연결하여 형태 및 면적이 동일한 복수의 도형들을 그렸을 때, 상기 형태 및 면적이 동일한 복수의 도형들 내에서 비샘플홀(112)들이 위치하는 형태가 서로 동일한 것을 의미한다.The non-sample holes 112 may be formed in the same pattern as the thermal block 100 . Being formed in the same pattern means that when a plurality of figures having the same shape and area are drawn by connecting the center points of four adjacent sample wells 111 among the plurality of sample wells 111 in the thermal block 100, the shape And it means that the shapes in which the non-sample holes 112 are located in a plurality of figures having the same area are the same.
구체적으로, 비샘플홀(112)은 열블록(100) 내 인접한 4개의 샘플웰(111)의 중심점을 연결하여 정의되는 단위 영역(130) 내에서 비샘플홀(112)들이 형성하는 패턴이 동일하도록 형성된다. 도 2의 (B)를 참고하여 살펴보면, 상기 서로 인접한 4개의 샘플웰(111a~111d)은 열블록(100)의 상면(110)에 형성된 샘플웰들 중 서로 가장 가까이 있는 4개의 샘플웰들의 조합을 의미한다. 상기 서로 가장 가까이 있는 4개의 샘플웰들의 조합은 하나의 샘플웰(111a) 및 상기 하나의 샘플웰(111a)과 가장 가까이 있는 다른 하나의 샘플웰(111b)을 결정하고, 상기 결정된 두 샘플웰(111a, 111b)과 나란하지 않으며 가장 가까이 있는 2개의 샘플웰(111c, 111d)를 추가로 결정하는 방법으로 결정될 수 있다. 상기 두 샘플웰(111a, 111b)과 나란하지 않다는 것은 상기 추가로 결정되는 2개의 샘플웰(111c, 111d)이 상기 두 샘플웰(111a, 111b)의 중심점을 연결하는 직선 상에 위치하지 않는 것을 의미한다.Specifically, the non-sample holes 112 have the same pattern formed by the non-sample holes 112 within the unit area 130 defined by connecting the center points of four adjacent sample wells 111 in the thermal block 100. is formed to Referring to (B) of FIG. 2, the four sample wells 111a to 111d adjacent to each other are a combination of the four sample wells closest to each other among the sample wells formed on the upper surface 110 of the thermal block 100. means The combination of the four sample wells closest to each other determines one sample well 111a and another sample well 111b closest to the one sample well 111a, and the determined two sample wells ( 111a and 111b) and may be determined by a method of additionally determining the closest two sample wells 111c and 111d that are not parallel to each other. The fact that the two sample wells 111a and 111b are not aligned means that the additionally determined two sample wells 111c and 111d are not located on a straight line connecting the center points of the two sample wells 111a and 111b. it means.
본 발명의 일 구현예에 따르면, 상기 서로 인접한 4개의 샘플웰(111a~111d)은 서로 가장 가까이 있으며, 그 중심점들을 연결하여 사각형을 형성하는 4개의 샘플웰들의 조합일 수 있다.According to one embodiment of the present invention, the four sample wells 111a to 111d adjacent to each other may be a combination of four sample wells that are closest to each other and connect their center points to form a square.
상기 단위 영역(130)은 본 발명의 열블록(100)의 샘플웰(111)과 비샘플홀(112)의 패턴을 설명하기 위하여 정의한 영역이다. 단위 영역(130)은 상기 서로 인접한 4개의 샘플웰들(111a~111d)의 각 중심점을 연결하여 형성되는 영역을 말한다.The unit area 130 is an area defined to explain the pattern of the sample well 111 and the non-sample hole 112 of the thermal block 100 of the present invention. The unit area 130 refers to an area formed by connecting the center points of the four adjacent sample wells 111a to 111d.
상기 단위 영역에서 샘플웰들이 차지하는 공간을 제외한 부분을 매스 영역(mass region)이라 정의한다. 상기 서로 인접한 4개의 샘플웰들이 차지하는 공간은 매스 영역에 포함되지 않는다. 그러므로, 상기 매스 영역은 반응용기가 위치하지 않는 영역이다. 따라서, 상기 매스 영역의 매스가 작을수록, 반응용기 내 반응물을 목적하는 온도로 변화시키기 위해 필요한 열에너지의 변화량이 감소한다.A portion excluding the space occupied by the sample wells in the unit area is defined as a mass region. A space occupied by the four adjacent sample wells is not included in the mass area. Therefore, the mass area is an area where the reaction vessel is not located. Accordingly, as the mass of the mass region decreases, the amount of change in thermal energy required to change the reactants in the reaction vessel to a desired temperature decreases.
도 2의 (B)를 참고하여 살펴보면, 상기 매스 영역은 상기 서로 인접한 4개의 샘플웰의 중심점들을 연결하여 형성되는 영역 중 샘플웰들이 형성되지 않은 영역이다. 본 발명의 일 구현예에 따르면, 상기 매스 영역은 상기 서로 인접한 4개의 샘플웰(111a~111d)의 중심점들을 연결하여 형성되는 사각형 영역에서 샘플웰들이 차지하는 영역을 제외한 영역일 수 있다.Referring to (B) of FIG. 2 , the mass region is a region in which no sample wells are formed among regions formed by connecting the center points of the four adjacent sample wells. According to one embodiment of the present invention, the mass area may be an area excluding an area occupied by the sample wells in a rectangular area formed by connecting the center points of the four adjacent sample wells 111a to 111d.
열블록(100)에 형성되는 비샘플홀(112)은 상기 매스 영역에 형성될 수 있다. 비샘플홀(112)의 형성에 의해 상기 매스 영역의 매스를 감소시킬 수 있으며, 이에 따라 반응용기 내 반응물을 목적하는 온도로 변화시키기 위하여 필요한 열에너지 변화량이 감소한다.The non-sample hole 112 formed in the thermal block 100 may be formed in the mass area. By forming the non-sample hole 112, the mass of the mass region can be reduced, and accordingly, the amount of change in thermal energy required to change the reactants in the reaction vessel to a desired temperature is reduced.
복수의 단위 영역(130) 각각에서 비샘플홀(112)이 위치하는 형태는 서로 동일하다. 이는 열블록(100) 내 서로 인접한 4개의 샘플웰에 의하여 정의되는 복수의 단위 영역(130) 각각에서 비샘플홀(112)의 분포(상대적인 위치)와 비샘플홀(112)의 크기 및 모양의 구성이 서로 동일하다는 것을 의미한다. 도 2의 (A)의 점선은 본 발명의 열블록(100)에서 정의될 수 있는 단위 영역(130)들 중 일부를 임의로 표시한 것이다. 도 2의 (A)에 도시된 바와 같이, 본 발명의 열블록(100) 내 서로 인접한 4개의 샘플웰에 의하여 형성되는 모든 단위 영역(130)들은 그 내부에서 비샘플홀(112)이 위치하는 형태가 서로 동일하다.The positions of the non-sample holes 112 in each of the plurality of unit areas 130 are identical to each other. This is the distribution (relative position) of the non-sample holes 112 and the size and shape of the non-sample holes 112 in each of the plurality of unit areas 130 defined by the four sample wells adjacent to each other in the thermal block 100. This means that the composition is identical to each other. Dotted lines in (A) of FIG. 2 arbitrarily indicate some of the unit regions 130 that may be defined in the thermal block 100 of the present invention. As shown in (A) of FIG. 2, all unit regions 130 formed by four adjacent sample wells in the thermal block 100 of the present invention have non-sample holes 112 located therein. shapes are identical to each other.
본 발명의 열블록(100)에는 상기 복수의 샘플웰(111)이 규칙적으로 배열되어 있으므로 열블록(100) 내의 단위 영역(130)은 모두 동일한 형상과 면적을 가진다. 그러므로, 단위 영역(130) 내에서 비샘플홀(112)이 동일한 패턴을 형성하는 경우 모든 샘플웰(111)에 대하여 비샘플홀(112)이 미치는 열전도적 영향이 동일하므로, 열블록의 급속한 가열 또는 냉각에 따라 발생할 수 있는 각 샘플웰 간의 온도 편차를 최소화할 수 있다. 상기 모든 샘플웰에 대하여 비샘플홀이 미치는 열전도적 영향이 동일하다는 것은, 열블록의 온도 변화에 따라 샘플웰 및 반응용기 내 반응물에 발생하는 열전도적 변화가 동일하다는 것을 의미한다. 따라서, 각각의 샘플웰에 수용된 반응용기 내 반응물에 발생하는 열에너지 변화량은 매 순간 동일하며, 각 반응용기 내 반응물이 열블록과 열적 평형(thermal equilibrium)을 이루어 목적하는 온도에서의 열 균형(heat balance) 상태에 도달하는 시간은 모두 동일하다.Since the plurality of sample wells 111 are regularly arranged in the thermal block 100 of the present invention, all unit regions 130 in the thermal block 100 have the same shape and area. Therefore, when the non-sample holes 112 form the same pattern within the unit area 130, since the thermal conductive effect of the non-sample holes 112 is the same for all sample wells 111, the heat block is rapidly heated. Alternatively, a temperature deviation between each sample well that may occur due to cooling may be minimized. The fact that the thermally conductive effect of the non-sample hole is the same for all the sample wells means that the thermally conductive change occurring in the sample well and the reactant in the reaction container is the same according to the temperature change of the heat block. Therefore, the amount of change in thermal energy generated by the reactant in the reaction vessel accommodated in each sample well is the same at every moment, and the reactant in each reaction vessel is in thermal equilibrium with the heat block to form a heat balance at the desired temperature. ), the time to reach the state is the same.
본 발명의 일 구현예에 따르면, 비샘플홀(112)은 상기 서로 인접한 4개의 샘플웰(111a~111d) 각각에 대하여 열전도적으로 동일한 영향을 미치도록 형성된다. 따라서, 열블록(100) 내 형성되는 각 샘플웰(111)들이 주위의 비샘플홀(112)들로부터 받는 열전도적 영향이 균일하게 되어, 각 샘플웰들 간의 열적 균일성(thermal uniformity)이 유지되는데 도움이 된다. 상기 비샘플홀들이 서로 인접한 4개의 샘플웰 각각에 대하여 열전도적으로 동일한 영향을 미치도록 형성되는 것은, 예를 들어, 비샘플홀(112)들은 단위 영역(130)을 정의하는 상기 4개의 샘플웰(111a~111d) 각각의 중심점에 대하여 동일하거나 대칭적으로 형성되는 것일 수 있다.According to one embodiment of the present invention, the non-sample hole 112 is formed to have the same thermal conductivity effect on each of the four adjacent sample wells 111a to 111d. Therefore, the thermal conductivity received from the surrounding non-sample holes 112 to each sample well 111 formed in the thermal block 100 becomes uniform, and thermal uniformity between each sample well is maintained. it helps to The fact that the non-sample holes 112 are formed to have the same thermal conductive effect on each of the four sample wells adjacent to each other means that, for example, the non-sample holes 112 define the unit area 130 in the four sample wells. (111a ~ 111d) may be formed identically or symmetrically with respect to each center point.
이와 같이 비샘플홀(112)들이 상기 단위 영역(130)을 형성하는 4개의 샘플웰(111a~111d) 각각에 대하여 동일하거나 대칭적인 패턴으로 형성되는 경우, 비샘플홀 그룹이 각 샘플웰에 열적으로 미치는 영향이 동일하게 된다. 따라서, 본 발명의 열블록(100)은 각 샘플웰(111) 간의 열적 균일성을 유지할 수 있다.In this way, when the non-sample holes 112 are formed in the same or symmetrical pattern with respect to each of the four sample wells 111a to 111d forming the unit area 130, the non-sample hole group is thermally has the same effect as Therefore, the thermal block 100 of the present invention can maintain thermal uniformity between each sample well 111 .
열블록의 모든 비샘플홀(112)이 열블록에 정의될 수 있는 단위 영역(130)들 중 어느 하나에 포함되도록 단위 영역(130)을 설정하는 것이 일반적이지만, 본 발명의 일 구현예에 따르면 단위 영역의 설정에 따라 일부 비샘플홀은 단위 영역에 포함되지 않을 수 있다. 상기 단위 영역에 포함되지 않는 비샘플홀은 열블록 전체에서 샘플웰 및 비샘플홀의 배열을 고려하여 배치될 수 있다.Although it is common to set the unit area 130 so that all non-sample holes 112 of the ten blocks are included in any one of the unit areas 130 that can be defined in the ten blocks, according to one embodiment of the present invention Depending on the setting of the unit area, some non-sample holes may not be included in the unit area. Non-sample holes not included in the unit area may be arranged in consideration of the arrangement of sample wells and non-sample holes in the entire column block.
*본 발명의 일 구현예에 의하면, 하나의 비샘플홀(112)은 인접한 2 이상의 단위 영역(130)에 걸쳐 형성될 수 있다. 각 단위 영역(130) 별로 내부에서 비샘플홀(112)이 형성하는 패턴이 동일하다면, 하나의 비샘플홀(112)은 인접한 2 이상의 단위 영역(130)에 걸쳐 형성될 수 있다. 다시 말해, 하나의 비샘플홀이 전부 하나의 단위 영역 내에 형성되는 것이 아니라 단위 영역 각각에는 하나의 비샘플홀의 일부가 위치하며, 하나의 단위 영역에는 복수의 비샘플홀이 일부씩 위치할 수 있다. * According to one embodiment of the present invention, one non-sample hole 112 may be formed over two or more adjacent unit areas 130. If the pattern formed by the non-sample holes 112 inside each unit area 130 is the same, one non-sample hole 112 may be formed across two or more adjacent unit areas 130 . In other words, one non-sample hole is not all formed in one unit area, but a part of one non-sample hole is located in each unit area, and a plurality of non-sample holes may be partially located in one unit area. .
도 2의 (B)를 참고하여 살펴보면, 본 발명의 일 구현예에 의하면, 복수의 샘플웰(111) 중 서로 인접한 4개의 샘플웰(111a~111d) 중심점을 연결하는 복수의 단위 영역(130) 각각에는 4개의 비샘플홀(112)이 일부씩 위치할 수 있다. 다시 말해, 하나의 비샘플홀의 일부는 어느 하나의 단위 영역 내에 위치하고, 나머지는 다른 단위 영역 내에 위치할 수 있다. 즉, 단위 영역의 경계에 걸쳐 비샘플홀이 위치하고, 상기 경계에 걸친 비샘플홀들 각각의 일부가 동일한 단위 영역 내에 위치한다.Referring to (B) of FIG. 2 , according to one embodiment of the present invention, a plurality of unit regions 130 connecting the center points of four adjacent sample wells 111a to 111d among the plurality of sample wells 111 Each of the four non-sample holes 112 may be partially located. In other words, a part of one non-sample hole may be located in one unit area and the rest may be located in another unit area. That is, non-sample holes are located across the boundary of the unit area, and each part of the non-sample holes across the boundary is located within the same unit area.
본 발명의 일 구현예에 의하면, 비샘플홀(112)은 복수의 단위 영역(130) 중 서로 인접한 단위 영역(130)에 걸쳐 형성될 수 있다. 즉, 비샘플홀(112)은 열블록(100)의 길이 방향 또는 폭 방향으로 인접한 단위 영역들에 걸쳐 형성될 수 있다. 상기 길이 방향으로 인접한 단위 영역에 걸쳐 형성되는 비샘플홀은 상기 폭 방향으로 인접한 단위 영역에 걸쳐 형성되지 않을 수 있다. 마찬가지로, 상기 폭 방향으로 인접한 단위 영역에 걸쳐 형성되는 비샘플홀은 상기 길이 방향으로 인접한 단위 영역에 걸쳐 형성되지 않을 수 있다. 이와 같이 비샘플홀이 상기 길이 방향으로 인접한 단위 영역에만 걸쳐 형성되거나 상기 폭 방향으로 인접한 단위 영역에만 걸쳐 형성되는 경우, 샘플웰들을 연결하는 영역이 대각선 방향으로는 비샘플홀들에 의해 단절되지 아니하여 열블록의 내구성에 도움이 된다.According to one embodiment of the present invention, the non-sample hole 112 may be formed across unit regions 130 adjacent to each other among the plurality of unit regions 130 . That is, the non-sample hole 112 may be formed over unit areas adjacent to each other in the length direction or width direction of the thermal block 100 . The non-sample hole formed over the unit area adjacent in the length direction may not be formed over the unit area adjacent in the width direction. Similarly, non-sample holes formed over unit areas adjacent in the width direction may not be formed over unit areas adjacent in the length direction. In this way, when the non-sample holes are formed over only unit areas adjacent in the longitudinal direction or only over unit areas adjacent in the width direction, the area connecting the sample wells is not cut off by the non-sample holes in the diagonal direction. This helps the durability of the heat block.
본 발명의 일 구현예에 따르면, 단위 영역(130)은 열블록(100) 내 서로 인접한 4개의 샘플웰의 중심점들을 연결하여 정의되는 최소 사각형 영역이며, 비샘플홀(112)은 모든 상기 최소 사각형 영역 내의 비샘플홀의 패턴이 서로 동일하도록 형성될 수 있다. 상기 최소 사각형은 열블록(100)의 상면(110)에 형성된 샘플웰(111)들 중 중심점을 서로 연결하여 사각형을 형성할 수 있는 4개의 샘플웰을 선택하고, 이들의 중심점을 연결하여 사각형을 형성하였을 때 형성될 수 있는 사각형 중 그 면적이 최소이며 4개 변의 길이의 합이 최소인 사각형을 말한다.According to one embodiment of the present invention, the unit area 130 is a minimum rectangular area defined by connecting the center points of four adjacent sample wells in the column block 100, and the non-sample hole 112 is all the minimum rectangular areas. Patterns of non-sample holes in the region may be formed to be identical to each other. The minimum square is formed by selecting four sample wells that can form a square by connecting their center points among the sample wells 111 formed on the upper surface 110 of the thermal block 100, and connecting their center points to form a square. It refers to a quadrangle with the smallest area and the smallest sum of the lengths of four sides among the quadrangles that can be formed when formed.
도 3의 (A)를 참고하여 살펴보면, 본 발명의 일 구현예에 따르면, 제1비샘플홀(112a)은 길이 방향으로 인접한 샘플웰(111)들의 중심점을 연결하여 정의되는 제1직선과 교차할 수 있다. 즉, 제1비샘플홀(112a)은 길이 방향으로 인접한 샘플웰(111)들의 중심점이 연결되는 직선 상에 위치한다. 다시 말해, 제1비샘플홀(112a)은 도 3의 (A)를 기준으로 좌우로 배치되는 샘플웰(111)들의 중심점을 연결한 직선 상에 위치한다. 또한, 제1비샘플홀(112a)은 길이 방향으로 인접한 샘플웰(111)들과 접하거나 중첩되지 않는다. 따라서, 제1비샘플홀(112a)과 길이 방향으로 인접한 샘플웰(111)의 사이에는, 상기 매스 영역 중 비샘플홀이 아닌 영역이 위치한다. 본 명세서에서 제1직선은 길이 방향으로 나란히 배열된 샘플웰(111)들의 중심점을 연결하여 정의되는 직선을 말하며, 제2직선은 폭 방향으로 나란히 배열된 샘플웰(111)들의 중심점을 연결하여 정의되는 직선을 말한다.Referring to FIG. 3 (A), according to one embodiment of the present invention, the first non-sample hole 112a intersects a first straight line defined by connecting the center points of adjacent sample wells 111 in the longitudinal direction. can do. That is, the first non-sample hole 112a is located on a straight line connecting the center points of the sample wells 111 adjacent in the longitudinal direction. In other words, the first non-sample hole 112a is located on a straight line connecting the center points of the left and right sample wells 111 with respect to FIG. 3(A). In addition, the first non-sample hole 112a does not contact or overlap with the sample wells 111 adjacent in the longitudinal direction. Therefore, between the first non-sample hole 112a and the sample well 111 adjacent in the longitudinal direction, a non-sample hole region among the mass areas is located. In this specification, the first straight line refers to a straight line defined by connecting the center points of the sample wells 111 arranged side by side in the longitudinal direction, and the second straight line is defined by connecting the center points of the sample wells 111 arranged side by side in the width direction. Says a straight line
본 발명의 일 구현예에 의하면, 제1비샘플홀(112a)은 제1직선을 기준으로 대칭되는 형상이며, 길이 방향으로 인접한 샘플웰(111)들에 대하여 동일한 열전도적 영향을 제공하도록 형성될 수 있다. 제1비샘플홀(112a)은 상기 길이 방향으로 배치되는 샘플웰들의 중심점을 연결한 직선을 기준으로 대칭되는 형상이다. 즉, 제1비샘플홀(112a)은 도 3의 (A)를 기준으로 상하 대칭 형상이다. 상기 대칭은 제1직선을 기준으로 하는 선대칭일 수 있다. 상기 대칭 형상은 상기 길이 방향으로 인접한 샘플웰들에 대한 열전도적 영향이 동일한 형상이다. 상기 열전도적 영향이 동일한 형상은, 열블록의 온도 변화에 따라 상기 길이 방향으로 인접한 샘플웰들에 미치는 열에너지 변화량이 서로 상이하지 않도록 형성되는 형상을 의미한다. 즉, 제1비샘플홀(112a)의 형상은 도 3의 (A)를 기준으로 제1비샘플홀(112a) 및 좌측의 샘플웰(111) 사이에서 발생하는 열에너지 이동(heat flow)의 형태와 제1비샘플홀(112a) 및 우측의 샘플웰(111) 사이에서 발생하는 열에너지의 이동의 형태가 동일한 형상이다. 따라서, 제1비샘플홀(112a)이 길이 방향으로 인접한 샘플웰들에 미치는 열전도적 특성은 동일하다. 한편, 제1비샘플홀(112a)은 폭 방향으로도 대칭되는 형상일 수 있다.According to one embodiment of the present invention, the first non-sample hole 112a has a shape symmetrical with respect to a first straight line, and is formed to provide the same thermal conductivity to adjacent sample wells 111 in the longitudinal direction. can The first non-sample hole 112a has a shape symmetrical with respect to a straight line connecting the center points of the sample wells disposed in the longitudinal direction. That is, the first non-sample hole 112a has a vertically symmetrical shape based on (A) of FIG. 3 . The symmetry may be line symmetry based on the first straight line. The symmetrical shape is a shape in which thermal conductive effects on adjacent sample wells in the longitudinal direction are the same. The shape having the same thermal conductive effect means a shape formed such that thermal energy variations applied to sample wells adjacent in the longitudinal direction according to temperature changes of the heat block are not different from each other. That is, the shape of the first non-sample hole 112a is the shape of heat flow occurring between the first non-sample hole 112a and the sample well 111 on the left side with reference to FIG. 3(A). The movement of thermal energy generated between the first non-sample hole 112a and the right sample well 111 has the same shape. Accordingly, the thermal conductivity of the first non-sample hole 112a to adjacent sample wells in the longitudinal direction is the same. Meanwhile, the first non-sample hole 112a may have a symmetrical shape in the width direction as well.
본 발명의 일 구현예에 의하면, (i) 제1직선은 제1비샘플홀(112a)과 두 교차점에서 교차하고, (ii) 상기 제1직선과 평행하며, 상기 길이 방향으로 인접한 샘플웰들의 공통 접선은 상기 제1비샘플홀과 다른 두 교차점에서 교차할 수 있다. 이때, 상기 제1직선에 의해 정의된 상기 두 교차점 사이의 거리에 비해 상기 공통 접선에 의해 정의된 상기 두 교차점 사이의 거리가 크거나 같을 수 있다. 다시 말해, 제1비샘플홀(112a)은 상기 길이 방향으로 인접한 샘플웰들의 중심점이 연결되는 직선 상에 위치하는 길이 방향의 길이(length)보다, 상기 길이 방향으로 인접한 샘플웰(111)들의 폭 방향 일측 끝이 연결되는 직선 상에 위치하는 길이 방향의 길이와 폭 방향 타측 끝이 연결되는 직선 상에 위치하는 길이 방향의 길이가 같거나 더 클 수 있다. 제1비샘플홀(112a)의 상기 길이 방향으로 인접한 샘플웰들의 중심점이 연결되는 직선 상에 위치하는 길이 방향의 길이란, 상기 길이 방향으로 인접한 샘플웰들의 중심점이 연결되는 제1직선과 제1비샘플홀(112a)의 중첩되는 길이이다. 상기 길이 방향으로 인접한 샘플웰들의 공통 접선으로서 상기 제1직선과 평행한 공통 접선은 길이 방향으로 인접한 샘플웰(111)들의 폭 방향 일측 끝이 연결되는 직선 또는 타측 끝이 연결되는 직선일 수 있다.According to one embodiment of the present invention, (i) the first straight line intersects the first non-sample hole 112a at two intersection points, (ii) is parallel to the first straight line, and the sample wells adjacent in the longitudinal direction The common tangent line may intersect the first non-sample hole at two other intersection points. In this case, a distance between the two intersection points defined by the common tangent line may be greater than or equal to a distance between the two intersection points defined by the first straight line. In other words, the first non-sample hole 112a has a width of the sample wells 111 adjacent to each other in the longitudinal direction, rather than a length in the longitudinal direction located on a straight line to which the center points of the sample wells adjacent in the longitudinal direction are connected. A length in the longitudinal direction positioned on a straight line to which one end of the direction is connected may be equal to or greater than a length in the longitudinal direction positioned on a straight line to which the other end in the width direction is connected. The length in the longitudinal direction located on the straight line connecting the center points of the sample wells adjacent in the longitudinal direction of the first non-sample hole 112a refers to the first straight line connecting the center points of the sample wells adjacent in the longitudinal direction and the first non-sample hole 112a. This is the overlapping length of the non-sample hole 112a. The common tangent line parallel to the first straight line as a common tangent line of sample wells adjacent in the longitudinal direction may be a straight line connecting one end of the sample wells 111 adjacent in the longitudinal direction in the width direction or a straight line connecting the other end.
상기 길이 방향으로 인접한 샘플웰(111)들의 폭 방향 일측 끝이 연결되는 직선 및 타측 끝이 연결되는 직선이란, 도 3의 (A)를 기준으로 양측 샘플웰(111)의 상측 끝이 연결되는 직선 및 하측 끝이 연결되는 직선이다. 다시 말해, 제1비샘플홀(112a)은 양측 샘플웰의 중심점이 연결되는 직선과 중첩되는 길이(이하, 제1길이)보다, 상기 양측 샘플웰의 상측 끝이 연결되는 직선과 중첩되는 길이(이하, 제2길이) 및 하측 끝이 연결되는 직선과 중첩되는 길이(이하, 제3길이)가 같거나 더 크게 형성될 수 있다.A straight line connecting one end of the widthwise direction of the sample wells 111 adjacent in the longitudinal direction and a straight line connecting the other end of the sample well 111 are a straight line connecting the upper ends of the sample wells 111 on both sides based on FIG. 3 (A). and a straight line connecting the lower end. In other words, the first non-sample hole 112a has a length overlapping with a straight line connecting the upper ends of the sample wells on both sides (hereinafter referred to as a first length) rather than a length overlapping with a straight line connecting the center points of the sample wells on both sides (hereinafter, a first length). Hereinafter, a second length) and a length overlapping a straight line connecting the lower end (hereinafter, a third length) may be formed equal to or larger.
본 발명의 일 구현예에 의하면, 제1비샘플홀(112a)은 제2길이와 제3길이가 제1길이와 같을 수 있다. 예를 들어, 제1비샘플홀(112a)은 길이 방향으로 일정한 길이를 가지는 둥근 모서리의 사각형 형태(rounded rectangle)일 수 있다. 또는, 본 발명의 일 구현예에 의하면, 제1비샘플홀(112a)은 제2길이와 제3길이가 제1길이보다 클 수 있다. 예를 들어, 제1비샘플홀(112a)은 길이 방향 양측이 오목하게 형성될 수 있다. 본 발명의 일 구현예에 의하면, 제1비샘플홀(112a)은 길이 방향 양측이 오목하게 형성되어, 제1비샘플홀(112a) 및 제1비샘플홀(112a)과 길이 방향으로 인접한 샘플웰(111) 사이에 위치하는 매스 영역의 두께가 소정 범위 내에서 일정할 수 있다. 즉, 비샘플홀과 샘플웰의 사이에는 매스 영역 중 비샘플홀이 아닌 영역이 위치하는데, 상기 매스 영역 중 비샘플홀이 아닌 영역의 두께를 소정 범위 내에서 일정하게 형성할 수 있다. 도 3의 (A)에는 길이 방향으로 인접한 샘플웰들의 중심점이 연결되는 직선을 기준으로 폭 방향 양측 소정 범위 내에서 상기 매스 영역 중 비샘플홀이 아닌 영역의 두께가 일정한 구현예가 도시되어 있다.According to one embodiment of the present invention, the first non-sample hole 112a may have a second length and a third length equal to the first length. For example, the first non-sample hole 112a may be a rounded rectangle having a constant length in the longitudinal direction. Alternatively, according to one embodiment of the present invention, the second length and the third length of the first non-sample hole 112a may be greater than the first length. For example, both sides of the first non-sample hole 112a in the longitudinal direction may be concave. According to one embodiment of the present invention, both sides of the first non-sample hole 112a in the longitudinal direction are concave, so that the first non-sample hole 112a and a sample adjacent to the first non-sample hole 112a in the longitudinal direction are formed. The thickness of the mass region positioned between the wells 111 may be constant within a predetermined range. That is, a non-sample hole region is located between the non-sample hole and the sample well, and the thickness of the non-sample hole region of the mass region can be formed uniformly within a predetermined range. 3(A) shows an embodiment in which the thickness of a non-sample hole region among the mass regions is constant within a predetermined range on both sides of the width direction based on a straight line connecting the center points of adjacent sample wells in the longitudinal direction.
도 3의 (B)를 참고하여 살펴보면, 본 발명의 일 구현예에 따르면, 제2비샘플홀(112b)은 폭 방향으로 인접한 샘플웰(111)들의 중심점을 연결하여 정의되는 제2직선과 교차할 수 있다. 즉, 제2비샘플홀(112b)은 폭 방향으로 인접한 샘플웰(111)들의 중심점이 연결되는 직선 상에 위치한다. 다시 말해, 제2비샘플홀(112b)은 도 3의 (B)를 기준으로 상하로 배치되는 샘플웰(111)들의 중심점을 연결한 직선 상에 위치한다. 또한, 제2비샘플홀(112b)을 폭 방향으로 인접한 샘플웰(111)들과 접하거나 중첩되지 않는다. 따라서, 제2비샘플홀(112b)과 폭 방향으로 인접한 샘플웰(111)의 사이에는, 상기 매스 영역 중 비샘플홀(112)이 아닌 영역이 위치한다. 상기 제2직선은 폭 방향으로 나란히 배열된 샘플웰(111)들의 중심점을 연결하여 정의되는 직선을 말한다.Referring to FIG. 3 (B), according to one embodiment of the present invention, the second non-sample hole 112b intersects a second straight line defined by connecting the center points of adjacent sample wells 111 in the width direction. can do. That is, the second non-sample hole 112b is located on a straight line connecting the center points of adjacent sample wells 111 in the width direction. In other words, the second non-sample hole 112b is located on a straight line connecting the center points of the vertically arranged sample wells 111 based on (B) of FIG. 3 . In addition, the second non-sample hole 112b does not contact or overlap with the sample wells 111 adjacent to each other in the width direction. Accordingly, an area other than the non-sample hole 112 is located between the second non-sample hole 112b and the sample well 111 adjacent in the width direction. The second straight line refers to a straight line defined by connecting the center points of the sample wells 111 arranged side by side in the width direction.
본 발명의 일 구현예에 의하면, 제2비샘플홀(112b)은 제2직선을 기준으로 대칭되는 형상이며, 폭 방향으로 인접한 샘플웰(111)들에 대하여 동일한 열전도적 영향을 제공하도록 형성될 수 있다. 제2비샘플홀(112b)은 상기 폭 방향으로 배치되는 샘플웰들의 중심점을 연결한 직선을 기준으로 대칭되는 형상이다. 즉, 제2비샘플홀(112b)은 도 3의 (B)를 기준으로 좌우 대칭 형상이다. 상기 대칭은 제2직선을 기준으로 하는 선대칭일 수 있다. 상기 대칭 형상은 상기 폭 방향으로 인접한 샘플웰들에 대한 열전도적 영향이 동일한 형상이다. 상기 열전도적 영향이 동일한 형상은, 열블록의 온도 변화에 따라 상기 폭 방향으로 인접한 샘플웰들에 미치는 열에너지 변화량이 서로 상이하지 않도록 형성되는 형상을 의미한다. 즉, 제2비샘플홀(112b)의 형상은 도 3의 (B)를 기준으로 제2비샘플홀(112b) 및 상측의 샘플웰(111) 사이에서 발생하는 열에너지 이동의 형태와 제2비샘플홀(112b) 및 하측의 샘플웰(111) 사이에서 발생하는 열에너지의 이동의 형태가 동일한 형상이다. 따라서, 제2비샘플홀(112b)이 폭 방향으로 인접한 샘플웰들에 미치는 열전도적 특성은 동일하다. 한편, 제2비샘플홀(112b)은 길이 방향으로도 대칭되는 형상일 수 있다.According to one embodiment of the present invention, the second non-sample hole 112b has a shape symmetrical with respect to the second straight line, and is formed to provide the same thermal conductivity to adjacent sample wells 111 in the width direction. can The second non-sample hole 112b has a shape symmetrical with respect to a straight line connecting the center points of the sample wells arranged in the width direction. That is, the second non-sample hole 112b has a left-right symmetrical shape based on FIG. 3(B). The symmetry may be line symmetry based on the second straight line. The symmetrical shape is a shape in which thermal conductive effects on adjacent sample wells in the width direction are the same. The shape having the same thermal conductive effect refers to a shape formed such that the amount of change in thermal energy applied to the sample wells adjacent in the width direction according to the temperature change of the heat block is not different from each other. That is, the shape of the second non-sample hole 112b is the shape of the thermal energy movement occurring between the second non-sample hole 112b and the upper sample well 111 based on (B) of FIG. 3 and the second ratio The movement of thermal energy generated between the sample hole 112b and the lower sample well 111 has the same shape. Therefore, the thermal conductivity of the second non-sample hole 112b on adjacent sample wells in the width direction is the same. Meanwhile, the second non-sample hole 112b may have a symmetrical shape in the longitudinal direction as well.
본 발명의 일 구현예에 의하면, (i) 제2직선은 제2비샘플홀과 두 교차점에서 교차하고, (ii) 상기 제2직선과 평행하며, 상기 넓이 방향으로 인접한 샘플웰들의 공통 접선은 상기 제2비샘플홀과 다른 두 교차점에서 교차할 수 있다. 이때, 상기 제2직선에 의해 정의된 상기 두 교차점 사이의 거리에 비해 상기 공통 접선에 의해 정의된 상기 두 교차점 사이의 거리가 크거나 같을 수 있다. 다시 말해, 제2비샘플홀(112b)은 상기 폭 방향으로 인접한 샘플웰들의 중심점이 연결되는 직선 상에 위치하는 폭 방향의 너비 (width)보다, 상기 폭 방향으로 인접한 샘플웰(111)들의 길이 방향 일측 끝이 연결되는 직선 상에 위치하는 폭 방향의 너비와 길이 방향 타측 끝이 연결되는 직선 상에 위치하는 폭 방향의 너비가 같거나 더 클 수 있다. 제2비샘플홀(112b)의 상기 폭 방향으로 인접한 샘플웰들의 중심점이 연결되는 직선 상에 위치하는 폭 방향의 너비란, 상기 폭 방향으로 인접한 샘플웰들의 중심점이 연결되는 제2직선과 제2비샘플홀(112b)의 중첩되는 너비이다. 상기 폭 방향으로 인접한 샘플웰들의 공통 접선으로서 상기 제2직선과 평행한 공통 접선은 폭 방향으로 인접한 샘플웰(111)들의 길이 방향 일측 끝이 연결되는 직선 또는 타측 끝이 연결되는 직선을 의미한다.According to one embodiment of the present invention, (i) the second straight line intersects the second non-sample hole at two intersections, (ii) is parallel to the second straight line, and the common tangent of sample wells adjacent in the width direction is It may intersect the second non-sample hole at two other intersection points. In this case, a distance between the two intersection points defined by the common tangent line may be greater than or equal to a distance between the two intersection points defined by the second straight line. In other words, the second non-sample hole 112b is longer than the width of the sample wells 111 adjacent in the width direction located on a straight line to which the center points of the sample wells adjacent in the width direction are connected. A width in the width direction positioned on a straight line connecting one end in the direction and a width in the width direction positioned on a straight line connecting the other end in the longitudinal direction may be equal to or larger than each other. The width in the width direction located on a straight line connecting the center points of the sample wells adjacent in the width direction of the second non-sample hole 112b means the second straight line connecting the center points of the sample wells adjacent in the width direction and the second non-sample hole 112b. This is the overlapping width of the non-sample hole 112b. A common tangent line parallel to the second straight line, which is a common tangent line of sample wells adjacent in the width direction, means a straight line connecting one end of the sample wells 111 adjacent in the width direction in the longitudinal direction or a straight line connecting the other end.
상기 폭 방향으로 인접한 샘플웰(111)들의 길이 방향 일측 끝이 연결되는 직선 및 타측 끝이 연결되는 직선이란, 도 3의 (B)를 기준으로 양측 샘플웰(111)의 좌측 끝이 연결되는 직선 및 우측 끝이 연결되는 직선이다. 다시 말해, 제2비샘플홀(112b)은 양측 샘플웰의 중심점이 연결되는 직선과 중첩되는 너비(이하, 제1너비)보다, 상기 양측 샘플웰의 좌측 끝이 연결되는 직선과 중첩되는 너비(이하, 제2너비) 및 우측 끝이 연결되는 직선과 중첩되는 너비(이하, 제3너비)가 같거나 더 크게 형성될 수 있다.A straight line connecting one end of the longitudinal direction of the sample wells 111 adjacent to each other in the width direction and a straight line connecting the other end of the sample well 111 are a straight line connecting the left ends of the sample wells 111 on both sides based on FIG. 3 (B). and a straight line connecting the right end. In other words, the second non-sample hole 112b has a width (hereinafter, a first width) overlapping with a straight line connecting the center points of both sample wells and a straight line connecting the left ends of the sample wells on both sides (hereinafter referred to as a first width). Hereinafter, a second width) and a width overlapping a straight line connecting the right end (hereinafter, a third width) may be formed equal to or larger.
본 발명의 일 구현예에 의하면, 제2비샘플홀(112b)은 제2너비와 제3너비가 제1너비와 같을 수 있다. 예를 들어, 제2비샘플홀(112b)은 폭 방향으로 일정한 너비를 가지는 둥근 모서리의 사각형 형태(rounded rectangle)일 수 있다. 또는, 본 발명의 일 구현예에 의하면, 제2비샘플홀(112b)은 제2너비와 제3너비가 제1너비보다 클 수 있다. 예를 들어, 제2비샘플홀(112b)은 폭 방향 양측이 오목하게 형성될 수 있다. 본 발명의 일 구현예에 의하면, 제2비샘플홀(112b)은 촉 방향 양측이 오목하게 형성되어, 제2비샘플홀(112b) 및 제2비샘플홀(112b)과 폭 방향으로 인접한 샘플웰(111) 사이에 위치하는 매스 영역의 두께가 소정 범위 내에서 일정할 수 있다. 즉, 비샘플홀과 샘플웰의 사이에는 매스 영역 중 비샘플홀이 아닌 영역이 위치하는데, 상기 매스 영역 중 비샘플홀이 아닌 영역의 두께를 소정 범위 내에서 일정하게 형성할 수 있다. 도 3의 (B)에는 폭 방향으로 인접한 샘플웰들의 중심점이 연결되는 직선을 기준으로 길이 방향 양측 소정 범위 내에서 상기 매스 영역 중 비샘플홀이 아닌 영역의 두께가 일정한 구현예가 도시되어 있다.According to one embodiment of the present invention, the second non-sample hole 112b may have a second width and a third width equal to the first width. For example, the second non-sample hole 112b may be a rounded rectangle having a constant width in the width direction. Alternatively, according to one embodiment of the present invention, the second non-sample hole 112b may have a second width and a third width larger than the first width. For example, both sides of the second non-sample hole 112b in the width direction may be concave. According to one embodiment of the present invention, the second non-sample hole 112b is formed concave on both sides in the tactile direction, so that the sample adjacent to the second non-sample hole 112b and the second non-sample hole 112b in the width direction The thickness of the mass region positioned between the wells 111 may be constant within a predetermined range. That is, a non-sample hole region is located between the non-sample hole and the sample well, and the thickness of the non-sample hole region of the mass region can be formed uniformly within a predetermined range. 3(B) shows an embodiment in which the thickness of an area other than a non-sample hole among the mass areas is constant within a predetermined range on both sides of the length direction based on a straight line connecting the center points of adjacent sample wells in the width direction.
도 3의 (C)를 참고하여 살펴보면, 본 발명의 일 구현예에 따르면, 복수의 샘플웰(111)들 중 대각선 방향으로 인접한 두 개의 샘플웰(111)들의 중심점이 연결되는 직선은 비샘플홀(112)들과 접하거나 교차하지 않는다. 구체적으로, 복수의 샘플웰(111)들 중 인접한 4개의 샘플홀 중 대각선 방향으로 인접한 두 개의 샘플웰(111)들의 중심점이 연결되는 직선은 비샘플홀(112)들과 접하거나 교차하지 않는다. 상기 대각선 방향 또는 대각 방향은 예를 들어 도 2의 (A)에서 B-B 선의 방향 또는 이와 직교하는 방향일 수 있다. 상기 접한다는 것은 하나의 비샘플홀과 하나의 직선이 하나의 지점에서 접촉하는 것을 의미하며, 상기 접촉하는 하나의 지점을 접점(tangent point)이라 한다. 상기 교차한다는 것은 하나의 직선이 하나의 비샘플홀과 2개의 지점에서 접촉하는 것을 의미하며, 상기 접촉하는 2개의 지점을 교차점(intersection)이라 한다. 따라서, 대각선 방향으로 인접한 두 개의 샘플홀들의 중심점을 연결한 직선과 상기 비샘플홀들이 접하거나 교차하지 않는 경우, 서로 인접한 4개의 샘플웰은 대각 방향으로 물리적으로 연결되어 있게 된다. 따라서, 본 발명의 열블록(100)은 상기 매스 영역의 매스를 감소시켜 반응용기 내 반응물의 온도를 목적하는 온도로 변화시키는데 필요한 열에너지 변화량을 감소시키는 동시에, 기존의 열블록에 비하여 내구성이 우수하게 된다.Referring to FIG. 3 (C), according to one embodiment of the present invention, a straight line connecting the center points of two diagonally adjacent sample wells 111 among a plurality of sample wells 111 is a non-sample hole. It does not touch or intersect with (112). Specifically, a straight line connecting the center points of two adjacent sample wells 111 in a diagonal direction among four adjacent sample holes among the plurality of sample wells 111 does not touch or intersect the non-sample holes 112 . The diagonal direction or the diagonal direction may be, for example, a direction of a line B-B in (A) of FIG. 2 or a direction orthogonal thereto. The contact means contact between one non-sample hole and one straight line at one point, and the contact point is referred to as a tangent point. Intersecting means that one straight line contacts one non-sample hole at two points, and the two contact points are called intersections. Accordingly, when a straight line connecting the center points of two diagonally adjacent sample holes and the non-sample holes do not touch or intersect, the four sample wells adjacent to each other are physically connected in the diagonal direction. Therefore, the heat block 100 of the present invention reduces the mass of the mass region to reduce the amount of change in thermal energy required to change the temperature of the reactant in the reaction vessel to the desired temperature, and at the same time has excellent durability compared to the conventional heat block. do.
본 발명의 일 구현예에 따르면, 복수의 샘플웰(111)의 규칙적인 배열은 직사각형 배열이며, 단위 영역(130)을 형성하는 서로 인접한 샘플웰(111a~111d)의 중심점을 연결하여 형성되는 대각선은 단위 영역(130)에 위치한 비샘플홀(112)에 접하거나 교차하지 않는다. 즉, 도 2의 (B)를 참고하여 살펴보면, 복수의 샘플웰(111)이 직사각형 배열로 배열되며 서로 인접한 4개의 샘플웰(111a~111d)이 정의하는 단위 영역(130)은 사각형의 형태로 형성되며, 서로 인접한 4개의 샘플웰(111a~111d)을 연결하는 직선 중 상기 길이 방향 또는 폭 방향과 나란하여 인접한 단위 영역(130)의 경계를 형성하는 직선을 제외한 대각방향의 직선은 비샘플홀(112)에 접하거나 교차하지 않는다. 도 5는 도 2의 (A)의 B-B 선을 따른 단면도로서, 상기 대각선의 방향으로의 단면도를 도시한다. B-B 선을 따른 단면도에는 샘플웰(111)의 단면은 나타나지만, 비샘플홀(112)의 단면은 나타나지 않는다. 도 5에 도시된 바와 같이, 상기 대각선 방향으로 샘플웰(111)들을 연결하는 직선은 비샘플홀(112)과 접하거나 교차하지 않으며, 샘플웰(111)들은 대각방향으로 물리적으로 연결된다. 따라서, 본 발명의 열블록(100)의 내구성이 향상된다.According to one embodiment of the present invention, the regular arrangement of the plurality of sample wells 111 is a rectangular arrangement, and a diagonal line formed by connecting the center points of adjacent sample wells 111a to 111d forming the unit area 130. does not contact or cross the non-sample hole 112 located in the unit area 130. That is, referring to (B) of FIG. 2, a plurality of sample wells 111 are arranged in a rectangular array, and the unit area 130 defined by four adjacent sample wells 111a to 111d has a rectangular shape. Of the straight lines connecting the four sample wells 111a to 111d adjacent to each other, straight lines in the diagonal direction excluding the straight line forming the boundary of the adjacent unit area 130 in parallel with the longitudinal or width direction are non-sample holes. It does not touch or intersect (112). FIG. 5 is a cross-sectional view taken along line B-B of FIG. 2 (A), and is a cross-sectional view in the diagonal direction. In the cross-sectional view along line B-B, the cross section of the sample well 111 is shown, but the cross section of the non-sample hole 112 is not shown. As shown in FIG. 5, a straight line connecting the sample wells 111 in the diagonal direction does not contact or intersect the non-sample hole 112, and the sample wells 111 are physically connected in the diagonal direction. Thus, the durability of the heat block 100 of the present invention is improved.
본 발명의 일 구현예에 따르면, 상기 복수의 샘플웰(111)들 중 인접한 4개의 샘플홀들에 있어서, 길이 방향으로 인접한 샘플웰(111)들의 중심점이 연결되는 직선 상에 위치하는 제1비샘플홀(112a)들과 폭 방향으로 인접한 샘플웰(111)들의 중심점이 연결되는 직선 상에 위치하는 제2비샘플홀(112b)들은, 상기 인접한 4개의 샘플홀 중 대각선 방향으로 인접한 두 개의 샘플웰(111)들의 중심점이 연결되는 직선을 기준으로 대칭되는 형상이다. 상기 대칭 형상은 상기 대각선 방향으로 인접한 샘플웰들에 대한 열전도적 영향이 동일한 형상이다. 상기 열전도적 영향이 동일한 형상은, 열블록의 온도 변화에 따라 상기 대각선 방향으로 인접한 샘플웰들에 미치는 열에너지 변화량이 서로 상이하지 않도록 형성되는 형상을 의미한다. 즉, 비샘플홀(112)들의 형상은 도 3의 (C)를 기준으로 대각선 일측의 제1, 제2 비샘플홀(112a, 112b) 및 샘플웰(111) 사이에서 발생하는 열 에너지 이동의 형태와 타측의 제1, 제2 비샘플홀(112a, 112b) 및 샘플웰(111) 사이에서 발생하는 열 에너지 이동의 형태가 동일한 형상이다. 따라서, 제 1,2 비샘플홀(112a, 112b)이 대각선 방향으로 인접한 샘플웰들에 미치는 열전도적 특성은 동일하다.According to one embodiment of the present invention, in four adjacent sample holes among the plurality of sample wells 111, the first ratio is located on a straight line to which the center points of the sample wells 111 adjacent in the longitudinal direction are connected. The second non-sample holes 112b located on a straight line connecting the sample holes 112a and the center points of the sample wells 111 adjacent in the width direction are two sample holes diagonally adjacent among the four adjacent sample holes. The center points of the wells 111 are symmetrical with respect to a straight line connected thereto. The symmetrical shape is a shape in which thermal conductive effects on adjacent sample wells in the diagonal direction are the same. The shape having the same thermal conductive effect means a shape formed such that the amount of change in thermal energy applied to the sample wells adjacent in the diagonal direction according to the temperature change of the heat block is not different from each other. That is, the shape of the non-sample holes 112 is based on the heat energy movement occurring between the first and second non-sample holes 112a and 112b and the sample well 111 on one diagonal side of FIG. 3 (C). The shape and the shape of the transfer of thermal energy occurring between the first and second non-sample holes 112a and 112b and the sample well 111 on the other side have the same shape. Therefore, the thermal conductivity of the first and second non-sample holes 112a and 112b to the diagonally adjacent sample wells is the same.
한편, 도 6을 참고하여 살펴보면, 본 발명에 따르면 열블록의 질량을 감소시키기 위한 관통홀(610)을 포함하는 열블록(600)이 제공될 수 있다. 즉, 본 발명의 열블록(600)은 복수로 수용되는 샘플의 반응을 수행하기 위한 열블록으로서, 서로 평행하며 길이와 폭을 가지는 상면(110) 및 하면(120)을 포함하고, 상면(110)에는 상측으로 열린 복수의 샘플웰(111)이 형성되어 있으며, 상기 열블록을 관통하는 관통홀(610)을 포함할 수 있다. 또한 일 구현예에서 상기 관통홀(610)은 상면(110)과 하면(120) 사이에서 열블록(100)을 관통하는 관통홀(610)일 수 있다. 또한 상기 관통홀(610)은 적어도 한 개 이상의 관통홀(610)을 포함할 수 있다. 관통홀(610)은 비샘플홀(112)과 마찬가지로 열블록(100)의 질량을 감소시켜 샘플웰(111)의 온도를 변화시키는데 필요한 에너지를 저감하기 위해 형성되는데, 특히 열블록(100)의 중앙부의 질량을 감소시키기 위해 형성된다. 요컨대, 본 발명에 따르면 상면에 상측으로 열린 복수의 비샘플홀이 형성되며, 각 비샘플홀의 상면 개구는 샘플웰보다 길이 방향으로 짧은 길이 또는 폭 방향으로 좁은 폭으로 형성되며, 복수의 샘플웰 중 서로 인접한 4개의 샘플웰의 중심점을 연결하여 정의되는 복수의 단위 영역 각각에서 비샘플홀이 위치하는 형태가 서로 동일한 열블록이 제공될 수 있다. 또한, 본 발명에 따르면 상면과 하면 사이에서 열블록을 관통하는 적어도 한 개 이상의 관통홀을 포함하는 열블록이 제공될 수 있다. 또한, 본 발명에 따르면, 상면에는 복수의 비샘플홀이 형성되고, 상면과 하면 사이에서 열블록을 관통하는 적어도 한 개 이상의 관통홀을 포함하는 열블록이 제공될 수 있다.Meanwhile, referring to FIG. 6 , according to the present invention, a thermal block 600 including a through hole 610 for reducing the mass of the thermal block may be provided. That is, the heat block 600 of the present invention is a heat block for performing a reaction of a plurality of received samples, and includes an upper surface 110 and a lower surface 120 that are parallel to each other and have a length and width, and an upper surface 110 ) has a plurality of sample wells 111 open upwards, and may include a through hole 610 penetrating the thermal block. Also, in one embodiment, the through hole 610 may be a through hole 610 penetrating the thermal block 100 between the upper surface 110 and the lower surface 120 . Also, the through hole 610 may include at least one through hole 610 . Like the non-sample hole 112, the through hole 610 is formed to reduce the energy required to change the temperature of the sample well 111 by reducing the mass of the thermal block 100. Formed to reduce the mass of the central part. In short, according to the present invention, a plurality of non-sample holes open upward are formed on the upper surface, and the upper surface opening of each non-sample hole is formed with a shorter length in the longitudinal direction or a narrower width in the width direction than the sample well, and among the plurality of sample wells In each of a plurality of unit regions defined by connecting the center points of four adjacent sample wells, ten blocks having the same shape in which non-sample holes are located may be provided. In addition, according to the present invention, a thermal block including at least one through hole penetrating the thermal block between the upper and lower surfaces may be provided. In addition, according to the present invention, a plurality of non-sample holes are formed on the upper surface, and a thermal block including at least one through hole penetrating the thermal block between the upper surface and the lower surface may be provided.
관통홀(610)은 단위 영역(130) 중 샘플웰(111)이 차지하는 영역을 제외한 영역인 매스 영역을 관통하게 형성된다. 즉, 관통홀(610)은 비샘플홀(112)과 마찬가지로 매스 영역의 매스를 감소시켜 반응용기 내 반응물을 목적하는 온도로 변화시키기 위해 필요한 열에너지의 변화량을 감소시킨다.The through hole 610 is formed to pass through the mass area, which is an area other than the area occupied by the sample well 111, of the unit area 130. That is, the through hole 610, like the non-sample hole 112, reduces the mass of the mass region to reduce the amount of change in thermal energy required to change the reactant in the reaction vessel to a desired temperature.
일 구현예에 따르면, 관통홀(810)은 상기 상면(110) 및 하면(120)과 평행할 수 있다. 관통홀(610)은 상면(110) 및 하면(120)의 사이에서 상면(110) 및 하면(120)과 평행하게 형성된다. 즉, 관통홀(610) 각각은 하면(120)으로부터 일정한 높이에 위치한다. 도 6의 (A)에 도시된 바와 같이 관통홀(610)은 길이 방향과 평행하게 형성되며, 폭 방향으로 복수개 배열될 수 있다. 또는, 도 6의 (B)에 도시된 바와 같이 관통홀(610)은 폭 방향과 평행하게 형성되며, 길이 방향으로 복수개 배열될 수 있다.According to one embodiment, the through hole 810 may be parallel to the upper surface 110 and the lower surface 120 . The through hole 610 is formed parallel to the upper surface 110 and the lower surface 120 between the upper surface 110 and the lower surface 120 . That is, each through hole 610 is located at a certain height from the lower surface 120 . As shown in (A) of FIG. 6 , the through hole 610 is formed parallel to the longitudinal direction and may be arranged in plurality in the width direction. Alternatively, as shown in (B) of FIG. 6 , the through hole 610 is formed parallel to the width direction and may be arranged in plurality in the length direction.
관통홀(610)은 열블록(100)을 길이 방향 또는 폭 방향으로 관통하게 형성되는데, 관통홀(610)은 관통되는 면의 가운데를 관통하게 형성될 수 있다. 상기 관통되는 면은 관통홀(610)이 형성되는 열블록의 면이며, 상기 관통되는 면의 가운데는 상기 관통되는 면의 길이 방향 또는 폭 방향의 가운데이다. 상기 관통되는 면의 가운데는 길이 방향 또는 폭 방향의 정가운데 및 그 주위 영역까지 포함할 수 있다. 따라서, 관통홀(610)에 의하여 본 발명의 열블록(600)의 외곽부가 아닌 중앙부의 매스가 감소되며, 그로 인해 상대적으로 열용량이 큰 중앙부와 상대적으로 열용량이 작은 외곽부 간의 열용량 차이를 감소시켜 상기 중앙부와 외곽부의 온도를 균일하게 유지할 수 있게 된다.The through hole 610 is formed to pass through the thermal block 100 in the longitudinal direction or the width direction, and the through hole 610 may be formed to pass through the center of the through surface. The penetrating surface is a surface of a thermal block in which the through hole 610 is formed, and the center of the penetrating surface is the center of the penetrating surface in the longitudinal direction or width direction. The center of the penetrating surface may include the center of the longitudinal or widthwise direction and the surrounding area. Therefore, the through hole 610 reduces the mass of the central portion, not the outer portion, of the thermal block 600 of the present invention, thereby reducing the difference in heat capacity between the central portion having a relatively large heat capacity and the outer portion having a relatively small heat capacity. The temperature of the central part and the outer part can be maintained uniformly.
도 7의 (A)와 (B)에는 각각 열블록(100)을 길이 방향향으로 관통하는 관통홀이 5개 형성되는 구현예 및 폭 방향으로 관통하는 관통홀이 5개 형성되는 구현예가 도시되어 있는데, 각각 중앙의 관통홀(610a)이 열블록(100)의 길이 방향 및 폭 방향 정가운데를 관통하고 나머지 관통홀(610b)은 상기 정가운데의 주위영역을 관통하며 양측으로 배열된다. 또는, 열블록(100)에는 열블록을 길이 방향으로 관통하는 관통홀 및 폭 방향으로 관통하는 관통홀이 모두 형성될 수도 있다. 따라서, 본 발명의 일 구현예에 의하면, 상기 관통홀은 복수개로 구비되며, 상기 복수의 관통홀은 상기 상면과 상기 하면 사이에서 나란히 배열될 수 있다. 즉, 복수개의 관통홀(610a, 610b)이 좌우로 배열되며 열블록(100)을 길이 방향 및/또는 폭 방향으로 관통할 수 있으며, 상기 복수개의 관통홀(610a, 610b)은 관통되는 면의 가운데를 관통할 수 있다. 따라서, 관통홀(610)은 열블록(100)의 중앙부를 관통하게 되며, 그로 인해 열블록(100)의 중앙부의 질량이 감소하여 외곽부와의 온도편차가 감소하게 되는 것이다. 본 발명의 일 구현예에서, 관통홀(610)은 복수개로 구비되며, 상기 복수의 관통홀 중 적어도 하나는 상기 길이의 중심 또는 상기 폭의 중심을 통과하도록 구성될 수 있다. 상기 길이의 중심은 열블록(100)의 길이 방향의 가운데를 말한다. 상기 길이 방향은 도면에서 x축 방향으로 도시되어 있다. 상기 길이 방향의 가운데는 열블록(100)의 길이 방향의 정가운데 및 그 주위 영역까지 포함할 수 있다. 상기 폭의 중심은 열블록(100)의 폭 방향의 가운데를 말한다. 상기 폭 방향은 도면에서 y축 방향으로 도시되어 있다. 상기 폭 방향의 가운데는 열블록(100)의 폭 방향의 정가운데 및 그 주위 영역까지 포함할 수 있다.7 (A) and (B) show an embodiment in which five through-holes are formed penetrating the thermal block 100 in the longitudinal direction and an embodiment in which five through-holes penetrating in the width direction are formed, respectively. There is, respectively, the central through hole (610a) passes through the middle of the longitudinal and width directions of the thermal block 100, and the remaining through holes (610b) pass through the central peripheral area and are arranged on both sides. Alternatively, the heat block 100 may be formed with both a through hole penetrating the heat block in the longitudinal direction and a through hole penetrating the heat block in the width direction. Therefore, according to one embodiment of the present invention, the plurality of through-holes are provided, and the plurality of through-holes may be arranged side by side between the upper surface and the lower surface. That is, the plurality of through holes 610a and 610b are arranged left and right and can penetrate the heat block 100 in the longitudinal direction and/or the width direction, and the plurality of through holes 610a and 610b are formed on the surface to be penetrated. can pass through the middle. Therefore, the through hole 610 penetrates the central portion of the thermal block 100, and as a result, the mass of the central portion of the thermal block 100 is reduced, thereby reducing the temperature deviation from the outer portion. In one embodiment of the present invention, a plurality of through holes 610 are provided, and at least one of the plurality of through holes may be configured to pass through the center of the length or the center of the width. The center of the length refers to the center of the heat block 100 in the longitudinal direction. The longitudinal direction is shown in the x-axis direction in the drawing. The middle of the longitudinal direction may include the center of the longitudinal direction of the thermal block 100 and the surrounding area. The center of the width refers to the center of the thermal block 100 in the width direction. The width direction is shown in the y-axis direction in the drawing. The center in the width direction may include the center of the heat block 100 in the width direction and the surrounding area.
본 발명의 일 구현예에서, 관통홀(610)은 1개 내지 3개로 형성될 수 있다. In one embodiment of the present invention, one to three through holes 610 may be formed.
본 발명의 다른 구현예에서, 관통홀(610)은 1개 내지 5개로 형성될 수 있다.In another embodiment of the present invention, one to five through holes 610 may be formed.
본 발명의 또 다른 구현예에서, 관통홀(610)은 1개 내지 7개로 형성될 수 있다. In another embodiment of the present invention, one to seven through holes 610 may be formed.
본 발명의 또 다른 구현예에서, 관통홀(610)은 1개 내지 9개로 형성될 수 있다.In another embodiment of the present invention, 1 to 9 through holes 610 may be formed.
관통홀(610)은 열블록(100)의 길이 방향 및/또는 폭방향 양쪽 단부 영역을 제외한 영역에 형성될 수 있다. 즉, 관통홀(610)은 인접한 샘플홀(111)과 샘플홀(111)의 사이를 관통하도록 형성되는데, 상기 양쪽 단부 영역에서 인접하게 위치한 샘플홀(111)과 샘플홀(111)의 사이에는 형성되지 않도록 할 수 있다. 도 6의 (A)를 참조하면, 본 발명의 일 구현예에 따르면, 본 발명은 열블록(600)의 폭 방향 양쪽 단부 영역을 제외한 영역에 길이 방향으로 나란히 위치하는 관통홀(610)을 가지는 열블록(600)을 제공한다. 도 6의 (B)를 참조하면, 본 발명의 일 구현예에 따르면, 본 발명은 길이 방향 양쪽 단부 영역을 제외한 영역에 폭 방향으로 나란히 위치하는 관통홀(610)을 가지는 열블록(600)을 제공한다.The through hole 610 may be formed in an area other than both end areas of the thermal block 100 in the longitudinal direction and/or in the width direction. That is, the through hole 610 is formed to penetrate between the adjacent sample holes 111 and the sample holes 111, and between the sample holes 111 and the sample holes 111 located adjacently in the both end regions can be prevented from forming. Referring to (A) of FIG. 6, according to one embodiment of the present invention, the present invention has through-holes 610 positioned side by side in the longitudinal direction in an area other than both end areas in the width direction of the heat block 600 A thermal block 600 is provided. Referring to (B) of FIG. 6 , according to one embodiment of the present invention, the present invention includes a thermal block 600 having through holes 610 located side by side in the width direction in an area other than both end areas in the longitudinal direction. to provide.
본 발명의 일 구현예에서, 관통홀(610)은 길이 방향 및/또는 폭 방향의 양쪽 끝단으로부터 1열 및/또는 1행의 샘플홀(111)과 그에 인접한 샘플홀(111) 사이에는 형성되지 않는다.In one embodiment of the present invention, the through-holes 610 are not formed between the sample holes 111 in the first column and/or the first row from both ends in the longitudinal direction and/or the width direction and the sample holes 111 adjacent thereto. don't
본 발명의 다른 구현예에서, 관통홀(610)은 길이 방향 및/또는 폭 방향의 양쪽 끝단으로부터 2열 및/또는 2행의 샘플홀(111)과 그에 인접한 샘플홀(111) 사이의 영역에는 형성하지 않는다.In another embodiment of the present invention, the through hole 610 is formed in the area between the sample holes 111 in two columns and/or two rows from both ends in the longitudinal direction and/or the width direction and the sample holes 111 adjacent thereto. do not form
본 발명의 일 구현예에서, 도 6의 (A)와 (B)에 도시된 관통홀(610)이 모두 형성될 수 있다. 즉, 하나의 열블록(100)에는 길이 방향으로 형성된 관통홀과 폭 방향으로 형성된 관통홀이 함께 위치할 수 있다. 이 경우, 열블록(100)의 중앙부의 열용량은 외곽부의 열용량보다 더 감소될 수 있다. 길이 방향의 관통홀과 폭 방향의 관통홀은 서로 직교하며, 직교되는 위치에서 중첩된다.In one embodiment of the present invention, both through holes 610 shown in (A) and (B) of FIG. 6 may be formed. That is, a through hole formed in the longitudinal direction and a through hole formed in the width direction may be located together in one thermal block 100 . In this case, the thermal capacity of the central portion of the thermal block 100 may be more reduced than that of the outer portion. The through-holes in the longitudinal direction and the through-holes in the width direction are orthogonal to each other and overlap at orthogonal positions.
본 발명의 일 구현예에 따르면, 관통홀(610)은 복수의 샘플웰(111)의 사이에 위치할 수 있다. 도 7을 참고하여 살펴보면, 관통홀(610)은 복수의 샘플웰(111)의 사이에 위치한다. 복수의 샘플웰(111)이 상면(110)에서 열과 행을 이루며 규칙적으로 배열되는 경우, 관통홀(610)은 각 샘플웰(111)이 인접한 샘플웰(111)과 이루는 간격 사이에 위치한다.According to one embodiment of the present invention, the through hole 610 may be located between the plurality of sample wells 111 . Referring to FIG. 7 , the through hole 610 is located between the plurality of sample wells 111 . When the plurality of sample wells 111 are regularly arranged in rows and columns on the upper surface 110, the through holes 610 are located between the gaps between each sample well 111 and the adjacent sample wells 111.
또한, 도 8을 참고하여 살펴보면, 관통홀(610)은 복수의 샘플웰(111)과 중첩되지 않게 형성된다. 일 구현예에 따르면, 관통홀(610)은 복수의 샘플웰(111)과 교차하지 않는다. 즉, 인접한 샘플웰(111) 사이에 위치한 관통홀(610)은 샘플웰(111)과 중첩되지 않는 직경으로 형성된다. 도 8의 (A)는 열블록(100)을 길이 방향으로 관통하는 관통홀(610)이 형성된 구현예의 단면도를 도시하고, 도 8의 (B)는 열블록(100)을 폭 방향으로 관통하는 관통홀(610)이 형성된 구현예의 단면도를 도시한다. 따라서, 샘플웰(111)은 관통홀(610)에 의해 관통되지 않으며, 샘플웰(111)에 삽입된 반응용기와의 접촉하는 면적이 관통홀(610)에 의해 감소되지 않는다.Also, referring to FIG. 8 , the through hole 610 is formed so as not to overlap with the plurality of sample wells 111 . According to one embodiment, the through hole 610 does not cross the plurality of sample wells 111 . That is, the through hole 610 located between adjacent sample wells 111 is formed with a diameter that does not overlap with the sample wells 111 . 8 (A) shows a cross-sectional view of an embodiment in which a through hole 610 penetrating the thermal block 100 in the longitudinal direction is formed, and (B) of FIG. 8 shows a cross-sectional view penetrating the thermal block 100 in the width direction. A cross-sectional view of an embodiment in which a through hole 610 is formed is shown. Therefore, the sample well 111 is not penetrated by the through hole 610, and the contact area with the reaction vessel inserted into the sample well 111 is not reduced by the through hole 610.
도 9를 참고하여 살펴보면, 관통홀(610)은 복수개 구비되어 하면(120)으로부터 적어도 두 개 이상의 높이에 위치할 수 있다. 즉, 복수개의 관통홀(610)은 상하방향으로 서로 다른 위치에 위치할 수 있다. 도 9의 (A)는 열블록(100)을 폭 방향으로 관통하는 복수의 관통홀(610)이 2개의 서로 다른 높이에 위치하는 구현예를 도시하고 있으며, 도 9의 (B)는 열블록(100)을 길이 방향으로 관통하는 복수의 관통홀(610)이 2개의 서로 다른 높이에 위치하는 구현예를 도시하고 있다. 복수의 관통홀(610)을 서로 다른 높이에 형성함으로써 열블록(100)의 중앙부를 관통하는 관통홀(610)의 개수를 증가시킬 수 있으며, 따라서 중앙부의 질량을 더욱 감소시켜 외곽부와의 온도편차를 저감할 수 있다.Referring to FIG. 9 , a plurality of through holes 610 may be provided and positioned at least two or more heights from the lower surface 120 . That is, the plurality of through holes 610 may be located at different positions in the vertical direction. 9(A) shows an implementation example in which a plurality of through holes 610 penetrating the thermal block 100 in the width direction are located at two different heights, and FIG. 9(B) shows a thermal block It shows an embodiment in which a plurality of through holes 610 passing through (100) in the longitudinal direction are located at two different heights. By forming a plurality of through-holes 610 at different heights, it is possible to increase the number of through-holes 610 penetrating the central portion of the thermal block 100, and thus further reduce the mass of the central portion so as to increase the temperature with the outer portion. deviation can be reduced.
본 발명의 일 구현예에 의하면, 복수의 관통홀 중 상측에 위치한 관통홀의 개수는 하측에 위치한 관통홀의 개수 이상일 수 있다. 상기 상측에 위치한 관통홀이란 나머지보다 상면(110)에 인접한 관통홀을 의미하며, 상기 하측에 위치한 관통홀이란 나머지보다 하면(120)에 인접한 관통홀을 의미한다. 도 9에 도시된 구현예에 있어서, 상기 상측에 위치한 관통홀은 상측에 위치한 5개의 관통홀(610c)이고, 상기 하측에 위치한 관통홀(610)은 하측에 위치한 3 개의 관통홀(610d)이다. According to one embodiment of the present invention, the number of upper through holes among the plurality of through holes may be greater than or equal to the number of lower through holes. The through hole located on the upper side means a through hole located closer to the upper surface 110 than the rest, and the through hole located on the lower side means a through hole located closer to the lower surface 120 than the rest. In the embodiment shown in FIG. 9 , the through holes located on the upper side are five through holes 610c located on the upper side, and the through holes 610 located on the lower side are three through holes 610d located on the lower side. .
본 발명의 다른 구현예에 의하면, 복수의 관통홀(610) 중 하측에 위치한 관통홀(610)의 개수는 상측에 위치한 관통홀(610)의 개수 이상일 수 있다.According to another embodiment of the present invention, the number of through-holes 610 located at the lower side among the plurality of through-holes 610 may be greater than or equal to the number of through-holes 610 located at the upper side.
상기 기재된 바와 같이, 상측과 하측에 형성되는 관통홀(610)의 개수를 상이하게 구현하는 것은 열블록(100) 자체의 열용량을 줄이고, 중앙부와 나머지 외곽부 간의 열용량의 차이를 줄이기 위함이다. As described above, implementing different numbers of through holes 610 formed on the upper and lower sides is to reduce the thermal capacity of the thermal block 100 itself and to reduce the difference in thermal capacity between the central portion and the rest of the outer portion.
본 발명의 일 구현예에서, 복수의 관통홀(610) 중 상측에 위치하는 관통홀(610)은 길이 방향으로 형성되고, 하측에 위치하는 관통홀(610)은 폭 방향으로 형성될 수 있다.In one embodiment of the present invention, the upper through hole 610 of the plurality of through holes 610 may be formed in the longitudinal direction, and the lower through hole 610 may be formed in the width direction.
본 발명의 다른 구현예에서, 복수의 관통홀(610) 중 상측에 위치하는 관통홀(610)은 폭 방향으로 형성되고, 하측에 위치하는 관통홀(610)은 길이 방향으로 형성될 수 있다.In another embodiment of the present invention, the through hole 610 positioned at the upper side of the plurality of through holes 610 may be formed in the width direction, and the through hole 610 positioned at the lower side may be formed in the longitudinal direction.
상기의 두 가지 구현예에 의하면 복수의 관통홀(610)이 직교되어 열블록(100)의 열용량을 줄일 수 있다. 다만, 직교되는 각각의 관통홀(610)은 상측과 하측으로 나뉘어 위치하기 때문에 서로 중첩되지 않는다. 따라서, 열블록(100)의 중앙부의 열용량은 크게 줄이고, 외곽부의 열용량은 적게 줄일 수 있다.According to the above two embodiments, the plurality of through holes 610 are orthogonal to reduce the thermal capacity of the thermal block 100 . However, since each orthogonal through hole 610 is divided into an upper side and a lower side, they do not overlap with each other. Therefore, the thermal capacity of the central portion of the thermal block 100 can be greatly reduced, and the thermal capacity of the outer portion can be reduced to a small extent.
이상의 설명은 본 발명의 기술 사상을 예시적으로 설명한 것에 불과한 것으로서, 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자라면 본 발명의 본질적인 품질에서 벗어나지 않는 범위에서 다양한 수정 및 변형이 가능할 것이다. 따라서, 본 발명에 개시된 실시예들은 본 발명의 기술 사상을 한정하기 위한 것이 아니라 설명하기 위한 것이고, 이러한 실시예에 의하여 본 발명의 기술 사상의 범위가 한정되는 것은 아니다. 본 발명의 보호 범위는 아래의 청구범위에 의하여 해석되어야 하며, 그와 균등한 범위 내에 있는 모든 기술사상은 본 발명의 권리범위에 포함되는 것으로 해석되어야 할 것이다.The above description is merely an example of the technical idea of the present invention, and various modifications and variations can be made to those skilled in the art without departing from the essential qualities of the present invention. Therefore, the embodiments disclosed in the present invention are not intended to limit the technical idea of the present invention, but to explain, and the scope of the technical idea of the present invention is not limited by these embodiments. The protection scope of the present invention should be construed according to the claims below, and all technical ideas within the scope equivalent thereto should be construed as being included in the scope of the present invention.
본 출원은 2021년 10월 29일에 제출된 대한민국 특허출원 제10-2021-0146648호에 대하여 우선권을 주장하며, 상기 특허출원의 개시 사항은 본 명세서에 참조로서 삽입된다.This application claims priority to Korean Patent Application No. 10-2021-0146648 filed on October 29, 2021, the disclosure of which is incorporated herein by reference.
[부호의 설명][Description of code]
100: 열블록 110: 상면100: heat block 110: top
111: 샘플웰 112: 비샘플홀111: sample well 112: non-sample hole
112a: 제1비샘플홀 112b: 제2비샘플홀112a: first non-sample hole 112b: second non-sample hole
120: 하면 130: 단위 영역120: lower surface 130: unit area
600: 열블록 610: 관통홀600: thermal block 610: through hole

Claims (19)

  1. 복수의 반응을 수행하기 위한 열블록으로서,As a heat block for carrying out a plurality of reactions,
    서로 평행하며 길이와 폭을 가지는 상면 및 하면을 포함하고,Including an upper surface and a lower surface that are parallel to each other and have a length and width,
    상기 상면에는 상측으로 열린 복수의 샘플웰이 규칙적으로 배열되게 형성되며,A plurality of sample wells open upward are regularly arranged on the upper surface,
    상기 상면에는 상측으로 열린 복수의 비샘플홀이 형성되며,A plurality of non-sample holes open upward are formed on the upper surface,
    상기 복수의 비샘플홀들은 (i) 상면 개구가 상기 샘플웰의 지름보다 상기 길이 방향으로 짧고 상기 폭 방향으로 같거나 길게 형성되는 제1비샘플홀들과 (ii) 상기 폭 방향으로 짧고 상기 길이 방향으로 같거나 길게 형성되는 제2비샘플홀들을 포함하며,The plurality of non-sample holes include (i) first non-sample holes having an upper surface opening shorter than the diameter of the sample well in the longitudinal direction and equal to or longer than the diameter of the sample well in the width direction; and (ii) short in the width direction and having the length Including second non-sample holes formed equal to or longer in the direction,
    상기 제1비샘플홀은 상기 길이방향으로 인접한 샘플웰들 사이에 위치하고,The first non-sample hole is located between adjacent sample wells in the longitudinal direction;
    상기 제2비샘플홀은 상기 폭 방향으로 인접한 샘플웰들 사이에 위치하는 열블록.The second non-sample hole is located between adjacent sample wells in the width direction.
  2. 제1항에 있어서,According to claim 1,
    상기 제1비샘플홀은 상기 길이 방향으로 인접한 샘플웰들의 중심점을 연결하여 정의되는 제1직선과 교차하며, 상기 제1비샘플홀은 상기 길이 방향으로 인접한 샘플웰들과 접하거나 교차하지 않는 것을 특징으로 하는 열블록.The first non-sample hole intersects a first straight line defined by connecting the center points of adjacent sample wells in the longitudinal direction, and the first non-sample hole does not contact or intersect the sample wells adjacent in the longitudinal direction. Characteristic heat block.
  3. 제2항에 있어서,According to claim 2,
    상기 제1비샘플홀은 상기 제1직선을 기준으로 대칭되는 형상이며, 상기 길이 방향으로 인접한 샘플웰들에 대하여 동일한 열전도적 영향을 제공하도록 형성되는 것을 특징으로 하는 열블록.The first non-sample hole has a shape symmetrical with respect to the first straight line, and is formed to provide the same thermal conductive effect to sample wells adjacent in the longitudinal direction.
  4. 제2항에 있어서,According to claim 2,
    상기 제1직선은 제1비샘플홀과 두 교차점에서 교차하고, The first straight line intersects the first non-sample hole at two intersection points,
    상기 제1직선과 평행하며, 상기 길이 방향으로 인접한 샘플웰들의 공통 접선은 상기 제1비샘플홀과 다른 두 교차점에서 교차하며,A common tangent of sample wells parallel to the first straight line and adjacent in the longitudinal direction intersects the first non-sample hole at two other intersection points;
    상기 제1직선에 의해 정의된 상기 두 교차점 사이의 거리에 비해 상기 공통 접선에 의해 정의된 상기 두 교차점 사이의 거리가 크거나 같은 것을 특징으로 하는 열블록.Thermal block, characterized in that the distance between the two intersection points defined by the common tangent line is greater than or equal to the distance between the two intersection points defined by the first straight line.
  5. 제1항에 있어서,According to claim 1,
    상기 제2비샘플홀은 상기 폭 방향으로 인접한 샘플웰들의 중심점을 연결하여 정의되는 제2직선과 교차하며, 상기 제2비샘플홀들은 상기 폭 방향으로 인접한 샘플웰들과 접하거나 교차하지 않는 것을 특징으로 하는 열블록.The second non-sample holes intersect with a second straight line defined by connecting center points of adjacent sample wells in the width direction, and the second non-sample holes do not contact or intersect the sample wells adjacent in the width direction. Characteristic heat block.
  6. 제5항에 있어서,According to claim 5,
    상기 제2비샘플홀은 상기 제2직선을 기준으로 대칭되는 형상이며, 상기 폭 방향으로 인접한 샘플웰들에 대하여 동일한 열전도적 영향을 제공하도록 형성되는 것을 특징으로 하는 열블록.The second non-sample hole has a shape symmetrical with respect to the second straight line, and is formed to provide the same thermal conductive effect to sample wells adjacent in the width direction.
  7. 제5항에 있어서,According to claim 5,
    상기 제2직선은 제2비샘플홀과 두 교차점에서 교차하고, The second straight line intersects the second non-sample hole at two intersections,
    상기 제2직선과 평행하며, 상기 넓이 방향으로 인접한 샘플웰들의 공통 접선은 상기 제2비샘플홀과 다른 두 교차점에서 교차하며,A common tangent of sample wells parallel to the second straight line and adjacent in the width direction intersects the second non-sample hole at two other intersection points;
    상기 제2직선에 의해 정의된 상기 두 교차점 사이의 거리에 비해 상기 공통 접선에 의해 정의된 상기 두 교차점 사이의 거리가 크거나 같은 것을 특징으로 하는 열블록.Thermal block, characterized in that the distance between the two intersection points defined by the common tangent line is greater than or equal to the distance between the two intersection points defined by the second straight line.
  8. 제1항에 있어서,According to claim 1,
    상기 복수의 샘플웰들 중 대각선 방향으로 인접한 두 개의 샘플홀들의 중심점을 연결한 직선은 상기 비샘플홀들과 접하거나 교차하지 않는 것을 특징으로 하는 열블록.Heat block, characterized in that a straight line connecting the center points of two diagonally adjacent sample holes among the plurality of sample wells does not touch or intersect the non-sample holes.
  9. 제1항에 있어서,According to claim 1,
    상기 샘플웰은 반응용기를 수용하도록 형성되는 것을 특징으로 하는 열블록.The sample well is a thermal block, characterized in that formed to accommodate the reaction vessel.
  10. 제1항에 있어서,According to claim 1,
    상기 복수의 샘플웰의 규칙적인 배열은 직사각형 배열인 것을 특징으로 하는 열블록.Thermal block, characterized in that the regular arrangement of the plurality of sample wells is a rectangular arrangement.
  11. 제1항에 있어서,According to claim 1,
    상기 상면과 하면의 사이에서 상기 열블록을 관통하는 관통홀을 포함하는 것을 특징으로 하는 열블록.Thermal block, characterized in that it comprises a through hole penetrating the thermal block between the upper and lower surfaces.
  12. 제11항에 있어서,According to claim 11,
    상기 관통홀은 상기 상면 및 하면과 평행한 것을 특징으로 하는 열블록.Thermal block, characterized in that the through hole is parallel to the upper and lower surfaces.
  13. 제11항에 있어서,According to claim 11,
    상기 관통홀은 상기 길이 방향과 평행한 것을 특징으로 하는 열블록.Thermal block, characterized in that the through hole is parallel to the longitudinal direction.
  14. 제11항에 있어서,According to claim 11,
    상기 관통홀은 상기 폭 방향과 평행한 것을 특징으로 하는 열블록.Thermal block, characterized in that the through hole is parallel to the width direction.
  15. 제11항에 있어서, According to claim 11,
    상기 관통홀은 복수개로 구비되며, 상기 복수의 관통홀 중 적어도 하나는 상기 길이의 중심 또는 상기 폭의 중심을 통과하도록 구성되는 것을 특징으로 하는 열블록.Thermal block, characterized in that the through-holes are provided in plurality, and at least one of the plurality of through-holes is configured to pass through the center of the length or the center of the width.
  16. 제11항에 있어서,According to claim 11,
    상기 관통홀은 상기 복수의 샘플웰들 사이에 위치한 것을 특징으로 하는 열블록.Thermal block, characterized in that the through hole is located between the plurality of sample wells.
  17. 제16항에 있어서,According to claim 16,
    상기 관통홀은 상기 복수의 샘플웰들과 교차하지 않는 것을 특징으로 하는 열블록.Thermal block, characterized in that the through hole does not intersect with the plurality of sample wells.
  18. 제11항에 있어서, 상기 관통홀은 복수개로 구비되며, 상기 복수개의 관통홀은 상기 상면과 상기 하면 사이에서 나란히 배열되는 것을 특징으로 하는 열블록.The heat block according to claim 11, wherein the plurality of through holes are provided, and the plurality of through holes are arranged side by side between the upper surface and the lower surface.
  19. 제11항에 있어서, 상기 관통홀은 복수개로 구비되며, 상기 복수개의 관통홀은 상기 하면으로부터 적어도 두 개 이상의 높이에 위치하는 것을 특징으로 하는 열블록.The heat block according to claim 11, wherein a plurality of through holes are provided, and the plurality of through holes are located at least two or more heights from the lower surface.
PCT/KR2022/016462 2021-10-29 2022-10-26 Thermal block WO2023075405A1 (en)

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JP2019047832A (en) * 2010-12-08 2019-03-28 ライフ テクノロジーズ コーポレーション Control systems and methods for biological applications
KR20210014739A (en) * 2018-06-28 2021-02-09 주식회사 씨젠 Thermal block
WO2021179442A1 (en) * 2020-03-10 2021-09-16 杭州博日科技有限公司 Thermal cycling device and pcr instrument

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Publication number Priority date Publication date Assignee Title
US20080003650A1 (en) * 2006-06-29 2008-01-03 Bio-Rad Laboratories, Inc., Mj Research Division Low-mass sample block with rapid response to temperature change
JP2013504181A (en) * 2009-09-01 2013-02-04 ライフ テクノロジーズ コーポレーション Thermal block assembly and equipment that provides low thermal non-uniformity for rapid thermal cycling
JP2019047832A (en) * 2010-12-08 2019-03-28 ライフ テクノロジーズ コーポレーション Control systems and methods for biological applications
KR20210014739A (en) * 2018-06-28 2021-02-09 주식회사 씨젠 Thermal block
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