WO2023038467A1 - Bloc thermique - Google Patents

Bloc thermique Download PDF

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Publication number
WO2023038467A1
WO2023038467A1 PCT/KR2022/013549 KR2022013549W WO2023038467A1 WO 2023038467 A1 WO2023038467 A1 WO 2023038467A1 KR 2022013549 W KR2022013549 W KR 2022013549W WO 2023038467 A1 WO2023038467 A1 WO 2023038467A1
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WO
WIPO (PCT)
Prior art keywords
block
stepped
thermal block
thermal
present
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Application number
PCT/KR2022/013549
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English (en)
Korean (ko)
Inventor
김진원
노진석
강동우
백승민
Original Assignee
주식회사 씨젠
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Application filed by 주식회사 씨젠 filed Critical 주식회사 씨젠
Priority to KR1020247011123A priority Critical patent/KR20240055060A/ko
Publication of WO2023038467A1 publication Critical patent/WO2023038467A1/fr

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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
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/686—Polymerase chain reaction [PCR]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0663—Stretching or orienting elongated molecules or particles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B01L2200/147—Employing temperature sensors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1894—Cooling means; Cryo cooling

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 8, 64 wells of 8 X 8, 96 wells of 8 X 12, or even larger. It is formed with 384 wells of 16 X 24.
  • an object of the present invention is to provide a heat block in which the temperature control of the central and outer parts of the heat block is uniform, and the temperature difference between the central part and the outer part is minimized.
  • 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.
  • an object of the present invention is to reduce the temperature deviation of each well by modifying the structure of the heat block to reduce the volume of the central portion having a large heat capacity.
  • an object of the present invention is to solve the problem that thermal conductivity is lowered by an air layer in using a metallic material as a thermal conductive material by using a phase change material (PCM) in contact with a thermal block as a thermal conductive material.
  • PCM phase change material
  • 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 formed on the upper surface. On the lower surface, a stepped surface with a barrier accommodating the phase change material is formed.
  • 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.
  • the thermal 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
  • thermal equilibrium can be secured for the heat block by using a phase change material as a thermal conductive material.
  • FIG. 1 is a perspective view of a thermal block of the present invention.
  • FIG. 2 is a cross-sectional view of a portion of a thermal block of the present invention.
  • FIG. 3 is a bottom view of the thermal block of the present invention.
  • FIG. 4 is a bottom view of a thermal block of the present invention.
  • FIG. 5 is a partial cross-sectional view of a thermal block of the present invention.
  • FIG. 6 is a bottom view of the thermal block of the present invention.
  • FIG. 7 is a bottom view of a thermal block of the present invention.
  • FIG. 8 is a perspective view of a thermal block of the present invention.
  • FIG. 9 is a plan view of a thermal block of the present invention.
  • FIG. 10 is a cross-sectional view of a thermal block of the present invention.
  • FIG. 11 is a side view of a thermal block of the present invention.
  • 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 improved the structure of the heat block to minimize the speed of temperature change at each well of the heat block and the difference in temperature change in the temperature holding section while reducing the heat capacity of the heat block. That is, the structure of the heat block is improved to lower the heat capacity of the central part of the heat block to minimize the temperature difference between the center and the outer part, thereby improving the performance degradation of reagents 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): 1482-5 (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.
  • stepped surface is one or more surfaces formed on the lower surface of the thermal block, and means a surface having a different height from the surrounding surface. That is, the lower surface of the heat block is flat, and the stepped surface is a surface formed to be stepped upward compared to the flat surrounding surface.
  • the stepped surface can be defined in terms of the following terms: depression and protrusion.
  • the term “depression” refers to a shape that is recessed upward from the flat lower surface of the heat block. That is, the term “depression” is a shape in which the lower surface of the heat block is engraved upward. The term “depression” may mean that a stepped surface is formed in a form in which the lower surface of the heat block is engraved.
  • protrusion refers to a shape protruding downward from the flat lower surface of the heat block. Therefore, a region that does not protrude from the lower surface is a stepped surface.
  • the term “barrier” is a structure having a height in the downward direction to distinguish a stepped surface from the surrounding surface on the lower surface of the heat block. In one embodiment of the present invention, the term “barrier” is a region excluding a stepped surface that is recessed and recessed. In another embodiment of the present invention, the term “barrier” is a protruding area to form a stepped surface.
  • the barrier is a structure distinct from a stepped surface, and may be in the shape of a continuous line with a predetermined thickness.
  • the barrier is a structure distinct from the stepped surface and may have a shape having a predetermined area.
  • FIG. 1 is a perspective view of a heat block according to the present invention
  • Figure 2 is a cross-sectional view of a part of a heat block according to the present invention
  • Figure 3 is a bottom view of a heat block according to the present invention
  • Figure 4 is a heat block according to the present invention 5 is a partial cross-sectional view of a heat block according to the present invention
  • Figure 6 is a bottom view of a heat block according to the present invention
  • Figure 7 is a bottom view of a heat block according to the present invention
  • Figure 8 is a heat block according to the present invention
  • FIG. 9 is a plan view of a heat block according to the present invention
  • FIG. 10 is a cross-sectional view of a heat block according to the present invention
  • FIG. 11 is a side view of a heat block according to the present invention.
  • the heat block 100 of the present invention is a heat block for performing a reaction of a plurality of received samples, and the top surface 110 and the bottom surface 120 are parallel to each other and have lengths and widths. , bottom surface), and a plurality of sample wells 111 open upwards are formed on the upper surface 110.
  • a barrier 122 and a stepped surface are formed on the lower surface 120 .
  • the barrier and the stepped surface formed on the lower surface 120 accommodate the phase change material and prevent it from being separated.
  • 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.
  • the longitudinal direction refers to the x-axis direction
  • the width direction refers to the y-output direction
  • the height direction refers to 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, 800 mm or less, 700 mm 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 accommodate a sample or be inserted into a reaction container 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, 8 or more, 12 or more, 16 or more, 24 or more, 32 or more. , 40 or more, 48 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 384 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 may be 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 micrometers or more, 20 micrometers or more, 30 microliters or more, or 40 microliters or more. can be formed to accommodate.
  • the sample well 111 has a thickness of 700 micrometers or less, 600 micrometers or less, 500 micrometers or less, 400 micrometers or less, 300 micrometers or less, 200 micrometers or less, or 100 micrometers. It may be formed to accommodate a reaction vessel including a container having a volume of less than or equal to 50 micrometers or less of the reaction solution.
  • the thermal block 100 includes a plurality of non-sample holes 112 .
  • the non-sample hole 112 is formed to open upward from the upper surface 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 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.
  • the lower surface 120 of the thermal block 100 is in thermal contact with, for example, a thermoelectric element such as a Peltier element to perform heat exchange with the thermal block 100. do.
  • 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 .
  • the stepped surface 121 may include a sensor groove 123 configured to accommodate a temperature sensor. That is, a sensor groove 123 in which at least one temperature sensor is located may be formed on the stepped surface 121 .
  • the shape of the sensor groove 123 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 sensor groove 123 is formed extending inwardly from the outside of the lower surface 121 and may be located on the stepped surface 121 .
  • the inner side of the sensor groove 123 may be located on the step surface 121 and the outer side of the sensor groove 123 may be located on the outer portion of the lower surface 121 .
  • the barrier 122 provided on the lower surface 121 and forming a step of the stepped surface 121 may be penetrated or cut through the sensor groove 123 .
  • the sensor groove 123 may be formed through the barrier 122 .
  • the barrier 122 may include a hole, and the sensor groove 123 may extend through the hole.
  • the sensor groove 123 may be formed by cutting the barrier 122 . That is, the barrier 122 may include a gap, and the sensor groove 123 may extend through the gap.
  • phase change material that mediates heat exchange between the heat block 100 and, for example, a thermoelectric element is applied to the stepped surface 121, and the sensor groove 123 is the stepped surface 121 ) It is formed so that the phase change material applied to the solid state does not leak through the sensor groove 123 even when it becomes a liquid or gel state.
  • a barrier 122 accommodating the phase change material and a stepped surface 121 are formed on the lower surface 120 of the thermal block 100 .
  • the barrier and the stepped surface prevent the phase change material from being separated.
  • the stepped surface 121 constitutes a part of the lower surface 120, and the barrier 122 prevents the phase change material provided on the stepped surface 121 from being separated.
  • the barrier 122 is formed by a step between the stepped surface 121 and a peripheral area adjacent to the stepped surface 121 . Due to the step difference, the step surface 121 has a shape that is depressed upward compared to the adjacent peripheral area.
  • the stepped surface 121 may be provided by recessing the lower surface 120 of the thermal block 100 upward, and by a step formed as the lower surface 120 is recessed upward.
  • a barrier 122 is formed.
  • the barrier 122 may be formed by a protrusion protruding from the lower surface 120 of the thermal block 100, and the barrier 122 is formed by a step formed by the protrusion. do.
  • the barrier 122 may be formed by a protrusion protruding from the lower surface 120 .
  • the stepped surface 121 may be provided by forming a protrusion on the lower surface.
  • the stepped surface 121 is located inside the protruding part and may have a shape that is recessed upward compared to the protruding part. These protrusions may be located on the outermost side of the lower surface 120, or may be spaced apart from the outermost side of the lower surface 120 to the inside.
  • the outermost part means an edge.
  • the barrier 122 may be spaced apart from the edge of the lower surface 120 to the inside.
  • the stepped surface 121 may be provided in plural numbers. In such a case, the outer protrusion may be located on the outermost surface of the lower surface 120, or the outermost surface of the lower surface 120. It can be spaced inwardly from.
  • the step of the stepped surface 121 may be formed when the lower surface 120 is depressed, and the barrier 122 is formed by the step of the stepped surface 121 formed when the lower surface 120 is depressed. do. That is, the stepped surface 121 may have a shape that is recessed upward than the rest of the lower surface 120 of the stepped surface 121 .
  • the barrier 122 which is a protruding portion, is spaced apart from the outermost part of the lower surface 120 to the inside. At this time, the position where the barrier 122 is spaced from the outermost to the inside of the lower surface 120 may be implemented in various ways.
  • the barrier 122 may be spaced apart from the outermost circumference of the lower surface 120 to the inside by 0.5mm to 20mm.
  • the barrier 122 may be positioned in a form extending inwardly from the side of the thermal block 100.
  • the barrier 122 may be located outside the upper surface 110 on a line perpendicular to the outer surface of the sample well 111 located at the outermost part.
  • the barrier 122 may be located on the inside of the upper surface 110 on a line perpendicular to the outer surface of the outermost sample well 111 .
  • the barrier 122 may be positioned on a line perpendicular to the outer surface of the outermost sample well 110 on the top surface 110 .
  • the barrier 122 according to the present invention is formed to a predetermined height so as to have a height difference from the stepped surface 121 of the lower surface 120.
  • the barrier 122 may be formed to have a rectangular pillar shape lying down, and to have a square side cross section (eg, ' ⁇ ' shape).
  • the barrier 122 has a semi-cylindrical shape lying down and may be formed to have a semi-circular side section (eg, ' ⁇ ' shape).
  • the barrier 122 may be formed to have a triangular prism shape and a triangular cross section (eg, ' ⁇ ' shape).
  • Barriers which are protrusions of various shapes, may be formed on the lower surface of the present invention as described above, but it is preferable that the barrier 122 having a rectangular cross-section is formed.
  • the barrier 122 included in the thermal block 100 of the present invention may be made of various materials.
  • the barrier 122 is made of the same material as that of the heat block 100, and may be integrally formed with the heat block 100.
  • the barrier 122 is made of the same material as the heat block 100 and may be coupled to the heat block 100 as a separate material.
  • the barrier 122 is made of a material different from that of the heat block 100 and may be coupled to the heat block 100. At this time, the material of the barrier 122 may be made of various materials such as metal, alloy, rubber, silicon, and plastic.
  • the thermal block 100 of the present invention may include a phase change material on the stepped surface 121 .
  • the stepped surface 121 includes a phase change material. That is, the phase change material is provided in a space in which the stepped surface 121 is stepped upward with respect to the peripheral area.
  • a phase change material refers to a material whose physical state changes between a solid and a liquid according to physical factors such as external temperature.
  • the phase change material may include, but is not limited to, one or more materials selected from the group consisting of, for example, metals, ceramics, thermoplastic polymers, thermosetting polymers, conductive polymers, and water.
  • the phase change material of the present invention may be a matrix filled with metal and ceramic.
  • the phase change material of the present invention is a thermally conductive material, and its physical properties are changed into a soft thermally conductive material by heating. Therefore, it closely adheres to the micro-curves on the surface of the heat block, enabling efficient heat transfer.
  • the phase change material may be, for example, Laird Technologies, Inc.'s T-pcm 580S series.
  • one surface of the phase change material may contact the stepped surface.
  • the phase change material may be applied to the stepped surface.
  • One surface of the phase change material contacts the stepped surface and the other surface contacts an element for heating or cooling the thermal block 100 .
  • the other surface of the phase change material may contact a heating element and/or a cooling element.
  • the other surface of the phase change material may contact the thermoelectric element.
  • the other surface of the phase change material may contact a thermal conductor.
  • the thermal conductor prevents direct contact of the phase change material with a heating element, a cooling element, or a thermoelectric element and mediates heat exchange, and may be formed of a thin conductive foil.
  • heat exchange of the thermal block 100 is performed by a thermoelectric element.
  • the thermoelectric element may contact the phase change material applied to the stepped surface 121 to exchange heat with the thermal block 100 of the present invention.
  • the thermal conductivity of the phase change material is lower than the thermal conductivity of a metal forming the thermal block 100, for example, aluminum, but higher than the thermal conductivity of the air layer.
  • the stepped surface 121 is a part of the lower surface 120 and its area is smaller than that of the lower surface 120 . If the area of the stepped surface 121 is too small compared to the area of the lower surface 120, the efficiency of heat exchange by the thermoelectric element is lowered, so it is necessary to sufficiently secure the area of the stepped surface 121. Accordingly, the area of the stepped surface 121 compared to the area of the lower surface 120 may be 60% or more, 70% or more, 80% or more, or 90% or more.
  • the stepped surface 121 of the present invention includes the center of the lower surface 120. That is, the center of the lower surface 120 is located on the stepped surface 121 .
  • the center of the lower surface 120 means a point located at the center of the longitudinal direction and the center of the width direction of the lower surface 120 . Referring to FIG. 3 , the center of the lower surface 120 means a point at which axes A and B intersect. Therefore, the thermoelectric element performs heat exchange with the heat block 100 by heating or cooling the central part of the heat block 100, thereby controlling the temperature of the central part with a relatively large heat capacity and the outer part with a relatively small heat capacity. can be performed uniformly.
  • the stepped surface 121 is formed symmetrically with respect to the center of the longitudinal direction and the center of the width direction of the heat block 100 so that the temperature change of the heat block 100 of the present invention is uniform in the longitudinal direction or the width direction.
  • the stepped surface may be formed to be line symmetric with respect to the center line of the longitudinal direction and the center line of the width direction of the lower surface, respectively.
  • axis A which is the center of the lower surface in the longitudinal direction
  • axis B which is the center of the width direction
  • the stepped surface 121 is not biased to one side in the longitudinal direction or one side in the width direction.
  • the stepped surface 121 is symmetric about the axis A, which is the center of the lower surface 120 in the longitudinal direction, and also symmetric about the axis B, which is the center of the width direction. Therefore, when the thermoelectric element performs heat exchange with the thermal block 100 through the phase change material applied to the stepped surface 121, a temperature deviation in the longitudinal direction or the width direction does not occur.
  • a plurality of stepped surfaces 121 may be provided, and the plurality of stepped surfaces 121 are formed symmetrically with respect to the center of the longitudinal direction and the center of the width direction of the lower surface 120 .
  • the stepped surface 121 of the present invention may be formed flat.
  • the stepped surface 121 may have a constant depth and be formed parallel to the upper surface 110 .
  • the depth of the stepped surface 121 can be formed constant and the height of the protrusion can also be formed constant, and therefore the phase change material applied to the stepped surface 121 is formed with a constant thickness. It can be.
  • the thermoelectric element that heats or cools the heat block 100 in contact with the phase change material can perform heat exchange uniformly over the entire stepped surface 121.
  • the depth of the stepped surface 121 may be 0.1 mm to 2 mm.
  • the depth of the stepped surface 121 may be 0.2 mm.
  • the edge portion 124 for providing an empty space in the outer portion of the bottom surface 120 so that thermal equilibrium between the outer portion and the center of the thermal block having a difference in heat capacity can be quickly achieved. can be formed As shown in (A) of FIG. 2, the edge portion 124 has a protrusion protruding from the lower surface 120 to form a barrier 122 by being spaced apart from the outermost surface of the lower surface 120 and located on the inside. can be formed That is, when heating or cooling is performed on the lower surface of the heat block, it is possible to solve the problem that the outer portion of the heat block is heated faster and cooled faster than the central portion of the heat block. To this end, a space is formed on the outer part of the lower surface so that heating and cooling can be performed in the same or similar way as the central part.
  • the outer portion may be heated or cooled faster than the central portion.
  • heat conduction to the outer portion of the heat block 100 is slow, so that the thermal balance between the center and the outer portion is more It is done quickly, and the time for the central part and the outer part to rise to the target temperature may be the same or similar.
  • the stepped surface 121 of the present invention may be formed slanting. Referring to FIG. 4 , the depth of the stepped surface 121 of the present invention may be formed the deepest in the central portion of the lower surface 120 . Alternatively, the depth of the stepped surface 121 of the present invention may be formed to be the shallowest in the central portion of the lower surface 120. That is, the stepped surface 121 is not formed to have a constant depth, and the depth of some areas may be different from that of other areas.
  • the central portion may be the central point 411 of the lower surface 120 shown in (A) and (C) of FIG. 4 .
  • the central point 411 means a point located at the center of the lower surface 120 in the longitudinal and width directions.
  • the depth of the stepped surface 121 of the present invention may decrease or increase from the central point 411 to the outermost part. That is, the stepped surface 121 may be formed inclined as a whole.
  • the depth of the stepped surface 121 of the present invention may decrease or increase from the central point 411 to the outer region 431 .
  • the outer region 431 is an area adjacent to the outermost part, and may be defined as between boundaries spaced inwardly by a predetermined distance from the outermost part and the outermost part in the length direction and the width direction, respectively.
  • the outer region 431 may be formed flat. That is, the stepped surface 121 of the present invention may be inclined in an area other than the outer area 431 .
  • the central portion may be the central region 421 of the lower surface 120 shown in (B) and (D) of FIG. 4 .
  • the central region 421 includes a point located at the center of the lower surface 120 in the longitudinal and width directions, and means a region symmetrical with respect to the center in the longitudinal direction and the center in the width direction.
  • the depth of the stepped surface 121 of the present invention may decrease or increase from the central region 421 to the outermost portion.
  • the central region 421 may be formed flat. That is, the depth of the stepped surface 121 may be inclined in an area other than the central area 421 . Referring to (D) of FIG.
  • the depth of the stepped surface 121 of the present invention may decrease or increase from the central area 421 to the outer area 431 .
  • the central area 421 and the outer area 431 may be formed flat. That is, the stepped surface 121 may be inclined in an area other than the central area 421 and the outer area 431 .
  • the stepped surface 121 may have a constant slope in an inclined region. That is, the remaining inclined regions of the stepped surface 121 except for the flat region may be formed with a constant slope.
  • the stepped surface 121 may have a constant slope between the central point 411 and the outermost part, or may have a constant slope between the central point 411 and the outer region 431, Alternatively, it may have a constant slope between the central region 421 and the outermost portion, or may have a constant slope between the central region 421 and the outer region 431 .
  • FIG. 5 shows a somewhat exaggerated height of the protruding portion 122 for convenience of illustration and understanding.
  • the stepped surface 121 is formed flat. Accordingly, the stepped surface 121 may be formed parallel to the upper surface 110 .
  • the stepped surface 121 may be formed to be inclined. As shown in (B) and (D) of FIG. 5, the depth of the stepped surface 121 may be formed deepest in the central part of the lower surface 120, or shown in (C) and (E) of FIG. As described above, the depth of the stepped surface 121 may be formed to be the shallowest in the central portion of the lower surface 120 . As shown in (B) and (C) of FIG. 5, the stepped surface 121 may be formed with a constant slope, or as shown in (D) and (E) of FIG. 5, the stepped surface 121 ) may be formed as a convex or concave curved surface. 5 (B) to (E) show an embodiment in which the stepped surface 121 is formed inclined as a whole, but the central region and/or the outer region of the stepped surface 121 are formed flat and the remaining regions are formed inclined. It could be.
  • a plurality of stepped surfaces 121 may be formed on the lower surface 120 of the thermal block 100 . Even when a plurality of stepped surfaces 121 are provided on the lower surface 120, similarly to the case where one stepped surface 121 is provided, the plurality of stepped surfaces 121 as a whole are located at the center and in the longitudinal direction of the thermal block 100. It is formed symmetrically about the center in the width direction.
  • the phase change material is applied to each of the plurality of stepped surfaces 121, and similarly, the heating element, cooling element, thermoelectric element, or thermal conductor contacts the phase change material applied to each of the plurality of stepped surfaces 121.
  • Each of the plurality of stepped surfaces 121 may be independently formed by being recessed in the lower surface 120 of the thermal block 100 or provided by a protrusion protruding from the lower surface 120 .
  • the barrier 122 is formed on the lower surface 120 by the depression or protrusion of the lower surface 120 forming each of the plurality of stepped surfaces 121 .
  • the plurality of stepped surfaces 121 may be two or more, three or more, four or more, or five or more.
  • the number of stepped surfaces 121 may be 9 or less, 8 or less, 7 or less, or 6 or less.
  • the plurality of stepped surfaces 121 may have the same area. According to one embodiment, as shown in (A) of FIG. 6 and (A) of FIG.
  • the plurality of stepped surfaces 121 may have the same length and width. Some of the plurality of stepped surfaces 121 may be formed with a different area than the rest. According to one embodiment, as shown in (B) of FIG. 6 , at least some of the plurality of stepped surfaces 121 may have a different length from the rest. According to one embodiment, as shown in (B) of FIG. 7 , at least some of the plurality of stepped surfaces 121 may have a different width than the rest.
  • a plurality of stepped surfaces 121 are provided, and the plurality of stepped surfaces 121 may be arranged in a longitudinal direction. That the plurality of stepped surfaces 121 are arranged along the longitudinal direction means that the plurality of stepped surfaces 121 are arranged in a plurality of rows parallel to the width direction. In the drawing, an embodiment in which three stepped surfaces 121 are arranged in single row or double row is shown. The plurality of stepped surfaces 121 arranged along the longitudinal direction are spaced apart from each other in the longitudinal direction, and the distance between the stepped surfaces in the longitudinal direction may be constant. According to one embodiment, as shown in (A) of FIG.
  • the plurality of stepped surfaces 121 arranged in the longitudinal direction may be formed to have the same length. That is, the size of the plurality of stepped surfaces 121 in the longitudinal direction may be the same.
  • the length of the plurality of stepped surfaces 121 arranged in the longitudinal direction may not be constant.
  • a stepped surface located on the inner side in the longitudinal direction may be formed to have a longer length than a stepped surface located on the outer side.
  • the stepped surface located on the inner side in the longitudinal direction may have a larger size in the longitudinal direction than the stepped surface located on the outer side.
  • the stepped surface located on the inner side in the longitudinal direction means a stepped surface located on the central side in the longitudinal direction among a plurality of stepped surfaces arranged in the longitudinal direction
  • the stepped surface located on the outer side in the longitudinal direction means a stepped surface located on the outer side in the longitudinal direction among a plurality of stepped surfaces arranged in the longitudinal direction. It means the stepped surface located at both ends in the longitudinal direction.
  • the stepped surface located on the inside in the longitudinal direction is the central stepped surface 121b
  • the stepped surface located on the outside in the longitudinal direction is the left and right stepped surfaces 121a. am. Due to the length difference, the area of the stepped surface located inside the longitudinal direction is larger than the area of the stepped surface located outside the longitudinal direction, and therefore, the thermoelectric element contacting the plurality of stepped surfaces heats the central portion of the heating block 100. By cooling or cooling, heat exchange with the heat block 100 is performed, and the temperature difference between the central portion and the outer portion is minimized.
  • a plurality of stepped surfaces 121 may be provided, and the plurality of stepped surfaces may be arranged along the width direction. That the plurality of stepped surfaces 121 are arranged along the width direction means that the plurality of stepped surfaces 121 are arranged in a plurality of rows parallel to the longitudinal direction.
  • the plurality of stepped surfaces 121 arranged along the width direction are spaced apart from each other in the width direction, and intervals between the stepped surfaces in the width direction may be constant. According to one embodiment, as shown in (A) of FIG.
  • the plurality of stepped surfaces 121 arranged in the width direction may be formed to have the same width. That is, the size of the plurality of stepped surfaces 121 in the width direction may be the same.
  • the widths of the plurality of stepped surfaces 121 arranged in the width direction may not be constant.
  • a stepped surface located on the inner side in the width direction may be formed with a wider width than a stepped surface located on the outer side.
  • a stepped surface located on the inside in the width direction may have a larger size in the width direction than a stepped surface located on the outside.
  • the stepped surface located on the inner side in the width direction means a stepped surface located on the center side in the width direction among a plurality of stepped surfaces arranged in the width direction
  • the stepped surface located outside the width direction means a stepped surface located on the outer side in the width direction among a plurality of stepped surfaces arranged in the width direction. It means the stepped surface located at both ends in the width direction.
  • the stepped surface located on the inside in the width direction is the middle step surface 121d
  • the stepped surface located on the outside in the width direction is the upper and lower stepped surfaces 121c.
  • the area of the stepped surface located inside the width direction is larger than the area of the stepped surface located outside the width direction, and therefore, the thermoelectric element contacting the plurality of stepped surfaces heats the central portion of the heating block 100.
  • heat exchange with the heat block 100 is performed, and the temperature difference between the central portion and the outer portion is minimized.
  • the plurality of stepped surfaces 121 may be arranged in a plurality of rows and a plurality of columns on the lower surface 120 .
  • a plurality of stepped surfaces arranged in a double-column double row may be arranged at regular intervals in the longitudinal direction and the width direction, respectively.
  • a plurality of stepped surfaces arranged in a double-column double-row may have the same length and width, or may have different lengths and widths.
  • a thermal block 800 including a through hole 810 for reducing the mass of the thermal block may be provided.
  • the heat block 800 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 810 penetrating the thermal block.
  • the through hole 810 may be a through hole penetrating the thermal block 100 between the upper surface 110 and the lower surface 120 .
  • the through hole may include at least one through hole 810 .
  • the through hole 810 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 thermal block having a barrier accommodating a phase change material and a stepped surface formed on a lower surface 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 barrier and a stepped surface for accommodating the phase change material are formed on the lower surface, and a thermal block including at least one through hole penetrating the thermal block between the upper and lower surfaces may be provided.
  • the through hole 810 may be parallel to the upper surface 110 and the lower surface 120 .
  • the through hole 810 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 810 is located at a certain height from the lower surface 120 .
  • the through hole 810 is formed parallel to the longitudinal direction and may be arranged in plurality in the width direction.
  • the through hole 810 is formed parallel to the width direction and may be arranged in plurality in the length direction.
  • the through hole 810 is formed to pass through the thermal block 100 in the longitudinal direction or the width direction, and the through hole 810 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 810 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.
  • 9 shows an embodiment in which five through holes penetrating the thermal block 100 in the longitudinal direction and the width direction are formed, respectively, and each central through hole 810a is formed in the longitudinal direction and width of the thermal block 100.
  • the plurality of through-holes may be 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 810a and 810b are arranged left and right and may pass through the heat block 100 in the longitudinal direction and/or the width direction, and the plurality of through holes 810a and 810b are formed on the surface through which they pass through. can pass through the middle.
  • a plurality of through holes 810 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 middle of the width direction may include the middle of the heat block 100 in the width direction and the surrounding area.
  • one to three through holes 810 may be formed.
  • one to five through holes 810 may be formed.
  • one to seven through holes 810 may be formed.
  • one to nine through holes 810 may be formed.
  • the through hole 810 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 810 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 810 located side by side in the longitudinal direction in an area other than both end areas in the width direction of the heat block 800 A thermal block 800 is provided.
  • the present invention provides a thermal block 800 having through holes 810 positioned side by side in the width direction in an area other than both end areas in the longitudinal direction. to provide.
  • the through hole 810 is not formed between the sample hole 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 hole 111 adjacent thereto. don't
  • the through hole 810 is formed in the region 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 810 shown in (A) and (B) of FIG. 8 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 810 may be located between the plurality of sample wells 111 .
  • the through hole 810 is located between the plurality of sample wells 111 .
  • the through holes 810 are located between the gaps between each sample well 111 and the adjacent sample wells 111.
  • the through hole 810 is formed so as not to overlap with the plurality of sample wells 111 .
  • the through hole 810 does not cross the plurality of sample wells 111 . That is, the through hole 810 located between adjacent sample wells 111 is formed with a diameter that does not overlap with the sample wells 111 .
  • 10 (A) shows a cross-sectional view of an embodiment in which a through hole 810 penetrating the thermal block 100 in the longitudinal direction is formed
  • FIG. 10 (B) is a cross-sectional view penetrating the thermal block 100 in the width direction. A cross-sectional view of an embodiment in which the through hole 810 is formed is shown. Therefore, the sample well 111 is not penetrated by the through hole 810, and the contact area with the reaction vessel inserted into the sample well 111 is not reduced by the through hole 810.
  • a plurality of through holes 810 may be provided and positioned at at least two or more heights from the lower surface 120 . That is, the plurality of through holes 810 may be located at different positions in the vertical direction.
  • 11(A) shows an embodiment in which a plurality of through holes 810 penetrating the thermal block 100 in the longitudinal direction are located at two different heights
  • FIG. 11(B) shows a thermal block It shows an embodiment in which a plurality of through holes 810 passing through (100) in the width 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 upper through holes are five upper through holes 810c, and the lower through holes 810 are three lower through holes 810d. .
  • the number of through-holes 810 located at the lower side among the plurality of through-holes 810 may be greater than or equal to the number of through-holes 810 located at the upper side.
  • implementing different numbers of through holes 810 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 810 of the plurality of through holes 810 may be formed in the longitudinal direction, and the lower through hole 810 may be formed in the width direction.
  • the through hole 810 positioned at the upper side of the plurality of through holes 810 may be formed in the width direction, and the through hole 810 positioned at the lower side may be formed in the longitudinal direction.
  • the plurality of through holes 810 are orthogonal to reduce the thermal capacity of the thermal block 100 .
  • each orthogonal through hole 810 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
  • barrier 123 sensor home
  • edge portion 411 central point

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Abstract

La présente invention concerne un bloc thermique pour réaliser une pluralité de réactions, comprenant une surface supérieure et une surface inférieure, qui sont parallèles et ont une longueur et une largeur, ayant une pluralité de puits d'échantillon formés sur la surface supérieure et ouverts vers le haut, et ayant, au niveau de la surface inférieure, une surface étagée et une barrière pour recevoir un matériau à changement de phase.
PCT/KR2022/013549 2021-09-13 2022-09-08 Bloc thermique WO2023038467A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
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
US20140008042A1 (en) * 2011-03-23 2014-01-09 Biocision, Llc Phase change thermal-sink apparatus
US20160279638A1 (en) * 2015-03-27 2016-09-29 Rechargeable Battery Corporation Self-heating device for warming of biological samples
KR101847998B1 (ko) * 2017-10-25 2018-04-11 주식회사 에프엠에스코리아 온도 조절 기능이 있는 항균 코팅 랙
KR101879500B1 (ko) * 2016-08-01 2018-07-19 한국기계연구원 회수형 미세유체소자

Patent Citations (5)

* Cited by examiner, † Cited by third party
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
US20140008042A1 (en) * 2011-03-23 2014-01-09 Biocision, Llc Phase change thermal-sink apparatus
US20160279638A1 (en) * 2015-03-27 2016-09-29 Rechargeable Battery Corporation Self-heating device for warming of biological samples
KR101879500B1 (ko) * 2016-08-01 2018-07-19 한국기계연구원 회수형 미세유체소자
KR101847998B1 (ko) * 2017-10-25 2018-04-11 주식회사 에프엠에스코리아 온도 조절 기능이 있는 항균 코팅 랙

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