Thermal cycler

Abstract

A thermal cycler according to the present disclosure includes a thermal block on which a reaction vessel configured to accommodate a sample is seated, a thermal block heating flexible printed circuit board (FPCB) configured to, above the thermal block, heat the thermal block, thermoelectric elements configured to, below the thermal block, exchange heat with the thermal block, and a heat sink thermally connected to the thermoelectric elements, wherein the thermal block FPCB includes resistance heating elements that configure heating channels, and a block temperature sensor, and the heating channels are provided to be independently controllable.

Description

THERMAL CYCLER

[0001] The present disclosure relates to a thermal cycler used for detecting a target analyte, and a target analyte detection device including the same.

[0002] As interest in health among modern individuals increases and life expectancy extends, the importance of accurate analysis of pathogens and in vitro nucleic acid-based molecular diagnosis, such as genetic analysis for patients, is rising, leading to an increased demand. Nucleic acid-based molecular diagnosis involves extracting nucleic acids from a sample and then confirming the presence or absence of a target nucleic acid among the extracted nucleic acids.

[0003] Polymerase chain reaction (PCR) is the most widely used nucleic acid amplification method, encompassing repeated cycles of denaturation of double-stranded deoxyribonucleic acid (DNA), annealing of oligonucleotide primers to the DNA templates, and extension of the primers by DNA polymerase.

[0004] A typical real-time PCR device includes a thermal cycler at a lower portion thereof in which a nucleic acid amplification reaction occurs, and an optics mechanism at an upper portion thereof to analyze or monitor the nucleic acid amplification reaction in real time.

[0005] Denaturation of DNA occurs at about 95 °C, and annealing and extension of a primer occur at a temperature lower than 95 °C, i.e., between 55 °C and 75 °C. Thus, a thermal cycler performs a nucleic acid amplification reaction on samples accommodated in reaction vessels included in a thermal block by repeatedly raising and lowering the temperatures of the reaction vessels. Here, heat provided to the thermal block is generated by a heat-generating element, and the heat generated by the heat-generating element is discharged outward through a heat sink.

[0006] One or more thermal cyclers in which a nucleic acid amplification reaction occurs are provided, and the optics mechanism measures fluorescence generated from the reaction vessel in which an amplification reaction is caused by each thermal cycler.

[0007] 1: An embodiment of the present disclosure provides a thermal cycler capable of achieving a temperature gradient precisely and rapidly, including a resistance heating element that heats a thermal block by complementing a thermoelectric element that exchanges heat with a thermal block, and a block temperature sensor that measures the temperature of the thermal block.

[0008] 2: An embodiment of the present disclosure provides a thermal cycler capable of achieving a temperature gradient precisely and rapidly by measuring the temperature of a heat sink exchanging heat with a thermoelectric element to complement a thermoelectric element exchanging heat with a thermal block, or by measuring the temperature of air around the heat sink.

[0009] In addition, an embodiment of the present disclosure provides a thermal cycler capable of measuring temperatures at a plurality of points of a heat sink that exchanges heat with a thermoelectric element, and utilizing the temperature of the heat sink for thermal control.

[0010] 3: An embodiment of the present disclosure provides a thermal cycler capable of uniformly transferring heat to reaction vessels positioned at the center and periphery of a thermal block.

[0011] In addition, an embodiment of the present disclosure provides a thermal cycler capable of minimizing or preventing condensation of a vaporized sample within a reaction vessel.

[0012] 1: In order to achieve the above objectives, an aspect of the present disclosure may provide a thermal cycler including: a thermal block on which a reaction vessel configured to accommodate a sample is seated; a thermal block heating flexible printed circuit board (FPCB) configured to, above the thermal block, heat the thermal block; thermoelectric elements configured to, below the thermal block, exchange heat with the thermal block; and a heat sink thermally connected to the thermoelectric elements, wherein the thermal block FPCB includes resistance heating elements that configure heating channels, and a block temperature sensor, and the heating channels are provided to be independently controllable.

[0013] Here, the thermal block may include a plurality of recesses in which a plurality of wells of the reaction vessel are respectively accommodated, the thermal block FPCB includes apertures corresponding to some or all of the recesses of the thermal block, and the recesses of the thermal block and the apertures of the thermal block FPCB are arranged in a plurality of rows and a plurality of columns.

[0014] In addition, the thermal block may further include a protrusion that protrudes from an upper surface of the thermal block, and forms the recesses, and the thermal block FPCB is attached to the upper surface of the thermal block while accommodating the protrusions in the apertures.

[0015] In addition, the thermal cycler may further include a duct to provide a flow passage for air passing through cooling fins of the heat sink; and a cooling fan to introduce and discharge air, wherein a row direction of the apertures of the thermal block FPCB is parallel to a flow direction of air passing through the duct.

[0016] Here, the resistance heating elements may be provided in the thermal block FPCB to heat a peripheral portion of the thermal block relatively more than a center of the thermal block in a column direction of the apertures.

[0017] In addition, the thermal block FPCB may further include an edge heating channel extending in the row direction along the peripheral portion of the thermal block.

[0018] Here, the apertures of the thermal block FPCB may include four or more apertures in the column direction, and the edge heating channel is provided in an area covering less than half of a distance from both edges to a center in the column direction.

[0019] Here, the block temperature sensor may be positioned further inward than the edge heating channel.

[0020] Here, the block temperature sensor may be positioned at a center between four apertures arranged adjacent to each other.

[0021] Here, the block temperature sensor may include a plurality of block temperature sensors, which are arranged at regular intervals in the row direction of the apertures, and are arranged at positions symmetrical to each other with respect to a center of the apertures in a column direction, respectively.

[0022] Here, the thermoelectric elements may include a plurality of thermoelectric elements, which are individually controlled independently of each other, and arranged side by side in the row direction of the apertures, and the block temperature sensor is configured to measure temperatures of zones of the thermal block respectively corresponding to the plurality of thermoelectric elements.

[0023] Here, the plurality of thermoelectric elements may be provided as a bar type to have lengths in the column direction greater than widths of the apertures in the row direction.

[0024] In addition, the thermal cycler may further include: a duct to provide a flow passage for air passing through cooling fins of the heat sink; and a cooling fan to introduce and discharge air, wherein the thermoelectric elements are arranged side by side in a flow direction of air passing through the duct.

[0025] Here, the thermoelectric elements may be provided as a bar type to have lengths greater than widths in a direction in which the thermoelectric elements are arranged, and the resistance heating elements are provided in the thermal block FPCB to heat a peripheral portion of the thermal block relatively more than a center of the thermal block in a lengthwise direction of the thermoelectric elements.

[0026] In addition, the thermal cycler may further include a first air temperature sensor configured to measure a temperature of air on an inlet side of the duct, and a second air temperature sensor configured to measure a temperature of air on an outlet side of the duct.

[0027] Here, the block temperature sensor may be provided as a resistance temperature detector (RTD) or a temperature sensor capable of linearly estimating a resistance value according to a temperature change.

[0028] In addition, the thermal cycler may further include an insulating member positioned above the thermal block FPCB and including apertures corresponding to recesses of the thermal block, respectively, wherein the block temperature sensor is surface-mounted on an upper surface of the thermal block FPCB.

[0029] In addition, the thermal cycler may further include a thermal circuit board provided around the thermal block or the heat sink, and connected to each of the thermal block FPCB and the thermoelectric elements.

[0030] Here, the thermal circuit board may form an opening to accommodate the heat sink therein, and is positioned lower than the thermoelectric elements, a connector of the thermal block FPCB is connected to an upper surface of the thermal circuit board, and connectors of the thermoelectric elements pass through the opening of the thermal circuit board to be connected to a lower surface of the thermal circuit board.

[0031] According to another embodiment of the present specification, there may be provided a thermal cycler including: a thermal block on which a reaction vessel having a plurality of wells capable of accommodating a sample is seated, wherein the thermal block includes recesses in which the plurality of wells are accommodated, respectively; a heat sink including cooling fins to dissipate heat from the thermal block; a duct to provide a flow passage for air passing through the cooling fins; a cooling fan to introduce and discharge air; a thermal block heating flexible printed circuit board (FPCB) that is provided above the thermal block, and includes apertures corresponding to the recesses of the thermal block, respectively, resistance heating elements configured to heat a peripheral portion of the thermal block relatively more than a center of the thermal block in a direction perpendicular to an air flow direction, and a block temperature sensor configured to measure a temperature of the thermal block; and a plurality of thermoelectric elements that are provided to, below the thermal block, exchange heat with the thermal block, and are individually controlled independently of each other, wherein the plurality of thermoelectric elements are arranged side by side in the air flow direction.

[0032] According to another embodiment of the present specification, there may be provided a thermal cycler including: a thermal block on which a reaction vessel configured to accommodate a sample is seated; thermoelectric elements configured to, below the thermal block, exchange heat with the thermal block; a heat sink thermally connected to the thermoelectric elements, and including a plurality of cooling fins; a duct to provide a flow passage for air passing through the plurality of cooling fins; and an air temperature sensor configured to measure a temperature of air around the plurality of cooling fins.

[0033] In addition, the thermal cycler may further include: a heat sink temperature sensor configured to measure a temperature of the heat sink; and a heat sink flexible printed circuit board (FPCB) attached to the heat sink, and on which the heat sink temperature sensor and the air temperature sensor are mounted.

[0034] According to another embodiment of the present specification, there may be provided a thermal cycler including: a thermal block on which a reaction vessel configured to accommodate a sample is seated; and a heat lid assembly to press and heat an upper portion of the reaction vessel, wherein the heat lid assembly includes: a thermally conductive layer that is able to come into contact with an upper surface of the reaction vessel; a heating layer provided above the thermally conductive layer, and including a central heating channel and a peripheral heating channel that are controllable independently of each other; and an insulating layer provided above the heating layer.

[0035] Here, the heating layer may be a heat lid flexible printed circuit board (FPCB) attached to an upper surface of the thermally conductive layer, and each of the central heating channel and the peripheral heating channel of the heat lid FPCB includes a resistance heating element and a temperature sensor.

[0036] 2: In order to achieve the above objectives, an aspect of the present disclosure may provide a thermal cycler including: a thermal block on which a reaction vessel configured to accommodate a sample is seated; thermoelectric elements configured to, below the thermal block, exchange heat with the thermal block; a heat sink thermally connected to the thermoelectric elements, and including a plurality of cooling fins; a duct to provide a flow passage for air passing through the plurality of cooling fins; and an air temperature sensor configured to measure a temperature of air around the plurality of cooling fins.

[0037] In addition, the thermal cycler may further include: a heat sink temperature sensor configured to measure a temperature of the heat sink; and a heat sink flexible printed circuit board (FPCB) attached to the heat sink, and on which the heat sink temperature sensor and the air temperature sensor are mounted.

[0038] Here, the heat sink FPCB may be provided on three or more surfaces around the cooling fins, the heat sink temperature sensor and the air temperature sensor may be respectively arranged on both sides in the lengthwise direction of the flow passage for air with respect to the center of the heat sink, and the heat sink temperature sensors may be respectively arranged on both sides in the widthwise direction of the flow passage for air with respect to the center of the heat sink.

[0039] Alternatively, the heat sink may include a body that supports the thermal block, cooling fins extending downward from the body, and a flange portion extending outward from the body, wherein the flange portion protrudes toward openings on both sides of the cooling fins, and the heat sink FPCB may be attached to a lower surface of the flange portion and may include a portion attached to the flange portion that protrudes toward openings on both sides of the cooling fins.

[0040] Here, the heat sink temperature sensor may include four temperature sensors positioned at portions corresponding to the corners of a quadrangle based on the center of the heat sink, and the air temperature sensors may be arranged on both sides of the air flow passage in the lengthwise direction, and may be arranged between the heat sink temperature sensors.

[0041] In addition, the heat sink temperature sensor may be connected to the lower surface of the heat sink FPCB, and the air temperature sensor may be connected to the heat sink FPCB via a conductive wire, and may be provided away from the cooling fins in the air flow direction.

[0042] In addition, the air temperature sensor may include a first air temperature sensor that measures the temperature of one side of the flow passage for air, and a second air temperature sensor that measures the temperature of the other side of the flow passage for air.

[0043] Here, the thermal cycler may further include cooling fans positioned on both sides of the flow passage for air, respectively, and the first air temperature sensor may measure the temperature of introduced air, and the second air temperature sensor may measure the temperature of air being discharged.

[0044] In addition, the heat sink temperature sensor may be provided as a resistance temperature detector (RTD) or a temperature sensor capable of linearly estimating a resistance value according to a temperature change.

[0045] Here, the air temperature sensor may be provided as a negative-temperature-coefficient (NTC) thermistor.

[0046] In addition, the thermal cycler may further include a thermal circuit board provided around the thermal block or the heat sink and connected to each of the thermoelectric elements.

[0047] Here, the thermal circuit board may form an opening for accommodating the heat sink therein, and the heat sink FPCB may be positioned below the thermal circuit board and may include an interface portion connected to the thermal circuit board.

[0048] Here, the heat sink may include a body that supports the thermal block, cooling fins extending downward from the body, and a flange portion extending outward from the body, wherein the flange portion may protrude toward openings on both sides of the cooling fins, the body may include a portion protruding upward from the flange portion, the thermal circuit board may be positioned above the flange portion, and the heat sink FPCB may be provided on three or more surfaces around the cooling fins and include the interface portion that is bent upward and passes through the flange portion to be connected to the lower surface of the thermal circuit board.

[0049] In addition, a plurality of thermoelectric elements, which are individually controlled independently of each other, may be arranged side by side in the direction of the flow passage for air.

[0050] Here, the thermoelectric elements may be provided as a bar type to have lengths greater than widths in the arrangement direction, and a single thermoelectric element may be provided in the lengthwise direction.

[0051] According to another embodiment of the present specification, there may be provided a thermal cycler including: a thermal block on which a reaction vessel having a plurality of wells capable of accommodating a sample is mounted, the thermal block including recesses for accommodating the wells, respectively; a plurality of thermoelectric elements that are provided to exchange heat with the thermal block, are individually controlled independently of each other, and are arranged side by side in an air flow direction; a heat sink thermally connected to the thermoelectric elements and including a plurality of cooling fins; a duct to provide a flow passage for air passing through the cooling fins; a heat sink temperature sensor configured to measure a temperature of the heat sink; and an air temperature sensor configured to measure a temperature of air passing through the duct, wherein the air temperature sensor includes a first air temperature sensor configured to measure a temperature of one side of the flow passage for air, and a second air temperature sensor configured to measure a temperature of the other side of the flow passage for air.

[0052] According to another embodiment of the present specification, there may be provided a thermal cycler including: a thermal block on which a reaction vessel configured to accommodate a sample is seated; a thermoelectric element configured to, below the thermal block, exchange heat with the thermal block; a heat sink thermally connected to the thermoelectric element and including a plurality of cooling fins; a duct to provide a flow passage for air passing through the cooling fins; and a heat sink temperature sensor configured to measure a temperature of the heat sink, wherein the heat sink includes flange portions protruding on both sides of the cooling fins in the air flow direction, and the heat sink temperature sensor is provided in each of the flange portions on both sides.

[0053] In addition, the thermal cycler may further include an air temperature sensor provided in the flange portion of the heat sink and configured to measure the temperature of air around the cooling fins.

[0054] Here, the thermal cycler may further include a heat sink FPCB attached to a lower portion of the flange portion of the heat sink and on which the heat sink temperature sensor and the air temperature sensor are mounted, the heat sink temperature sensor and the air temperature sensor are respectively arranged on both sides in the lengthwise direction of the flow passage for air based on the center of the heat sink, and the heat sink temperature sensors may be respectively arranged on both sides in the widthwise direction of the flow passage for air based on the center of the heat sink.

[0055] Here, the heat sink temperature sensor may include four temperature sensors positioned at portions corresponding to the corners of a quadrangle based on the center of the heat sink, and the air temperature sensors may be arranged between the heat sink temperature sensors.

[0056] 3: In order to achieve the above objectives, an aspect of the present disclosure may provide a thermal cycler including a thermal block on which a reaction vessel configured to accommodate a sample is seated, and a heat lid assembly to press and heat an upper portion of the reaction vessel, wherein the heat lid assembly includes a thermally conductive layer that is able to come into contact with an upper surface of the reaction vessel, a heating layer provided above the thermally conductive layer, and including a central heating channel and a peripheral heating channel that are controllable independently of each other, and an insulating layer provided above the heating layer.

[0057] Here, the heating layer may be a heat lid FPCB attached to the upper surface of the thermally conductive layer.

[0058] Here, each of the central heating channel and the peripheral heating channel of the heat lid FPCB may include a resistance heating element and a temperature sensor.

[0059] In addition, the peripheral heating channel may be heated at a temperature equal to or higher than that of the central heating channel.

[0060] In addition, the peripheral heating channel may be arranged to surround the central heating channel.

[0061] Here, the peripheral heating channel may include four peripheral heating channels that are positioned at four corners of the heating layer, and arranged in shapes symmetrical to each other.

[0062] Alternatively, the central heating channel may be provided in a quadrangular shape.

[0063] Alternatively, the peripheral heating channel may be provided to cover four zones defined by edges of the central heating channel, and a lateral center extension line and a longitudinal center extension line of the central heating channel.

[0064] Alternatively, the peripheral heating channel may be provided in a wider area than the central heating channel.

[0065] Another aspect of the present disclosure may provide a thermal cycler including a thermal block on which a reaction vessel configured to accommodate a sample is seated; and a heat lid assembly configured to press and heat an upper portion of the reaction vessel, wherein the heat lid assembly includes a thermally conductive layer that may come into contact with an upper surface of the reaction vessel, a heat lid FPCB configured to, above the thermally conductive layer, heat the thermally conductive layer, and an insulating layer provided above the heat lid FPCB, wherein the heat lid FPCB includes resistance heating elements and a temperature sensor, and the resistance heating elements configure a plurality of heating channels that are provided to be controllable independently of each other.

[0066] Here, the heating channels of the heat lid FPCB may include a central heating channel and a peripheral heating channel.

[0067] Here, the peripheral heating channel may include four peripheral heating channels that are arranged at four corners of the heat lid FPCB, respectively, to surround the central heating channel.

[0068] Here, the temperature sensor may include a central temperature sensor positioned at the center of the central heating channel, and a peripheral temperature sensor positioned on an outside of the peripheral heating channel.

[0069] In addition, the thermally conductive layer and the heat lid FPCB may include apertures that open optical paths in upper portions of the reaction vessels, the apertures may be arranged in a plurality of rows and a plurality of columns, and the heat lid FPCB may heat the periphery of the thermally conductive layer relatively more than the center of thermally conductive layer in the row and column directions of the apertures.

[0070] Another aspect of the present disclosure may provide a thermal cycler including: a thermal block on which a reaction vessel configured to accommodate a sample is seated, and in which a plurality of recesses for accommodating wells of the reaction vessel are arranged in rows and columns; a thermal block FPCB configured to, above the thermal block, heat the thermal block; a heat lid assembly including a heat lid FPCB that is arranged to press an upper portion of the reaction vessel and heat the reaction vessel; and a control unit, wherein the control unit controls a temperature of the heat lid FPCB to be equal to or higher than a temperature of the thermal block FPCB.

[0071] Here, the thermal block FPCB may include resistance heating elements that configure a block heating channel, and the block temperature sensor configured to measure the temperature of the thermal block, the heat lid FPCB may include resistance heating elements that configure a heat lid heating channel, and the heat lid temperature sensor configured to measure the temperature of the reaction vessel, and the control unit may compare information of the block temperature sensor with information of the heat lid temperature sensor to control the thermal block FPCB and the heat lid FPCB.

[0072] Alternatively, the thermal block FPCB may include first apertures corresponding to some or all of the recesses of the thermal block, and the heat lid FPCB may include second apertures corresponding to some or all of the recesses of the thermal block, wherein the recesses, the first apertures, and the second apertures may be aligned in a vertical direction.

[0073] Here, the thermal cycler may further include: a heat sink that dissipates heat below the thermal block; and a duct to provide a flow passage for air passing through the cooling fins of the heat sink, wherein the row directions of the first apertures and the second apertures may be parallel to the flow direction of air passing through the duct, the thermal block FPCB may include resistance heating elements that configure a block heating channel, the resistance heating elements may be provided to heat the periphery of the thermal block relatively more than the center of the thermal block in the column direction of the first apertures, the heat lid FPCB may include resistance heating elements that configure a heat lid heating channel, and the resistance heating elements may be provided to heat a peripheral portion of the reaction vessel relatively more than a central portion of the reaction vessel in the row and column directions of the second apertures.

[0074] In addition, an operation, performed by the heat lid assembly, of pressing and heating the upper portion of the reaction vessel may include an operation in which the thermal block ascends.

[0075] In addition, the thermal cycler may further include: a heat sink to dissipate heat below the thermal block; and a duct to provide a flow passage for air passing through the cooling fins of the heat sink, wherein the air flow direction of the duct and the row direction of the recesses may be arranged parallel to each other, the thermal block FPCB may include resistance heating elements that configure a block heating channel, and the block temperature sensor, the resistance heating elements may be provided to heat the periphery of the thermal block relatively more than the center of the thermal block in the column direction of the recesses, the heat lid FPCB may include resistance heating elements that configure a heat lid heating channel, and the heat lid temperature sensor, and the resistance heating elements may be provided to heat the periphery of the reaction vessel relatively more than the center of the reaction vessel in the row and row directions of the recesses.

[0076] 1: According to an embodiment of the present disclosure, precise and uniform temperature control is possible by using resistance heating elements to eliminate temperature gradient imbalance according to the shape of thermoelectric elements. For example, even when the temperature of the thermoelectric element is relatively lower at both sides in the lengthwise direction than at the center, the temperature difference may be quickly reduced by using an edge heating channel of the resistance heating elements corresponding to both sides of the thermal block.

[0077] In addition, according to an embodiment of the present disclosure, a block temperature sensor may be mounted on a thermal block heating flexible printed circuit board (FPCB) positioned above the thermal block, to accurately and sensitively measure the temperature of the thermal block. In particular, in a case in which a plurality of thermoelectric elements are used, a block temperature sensor corresponding to each thermal zone corresponding to each thermoelectric element may be provided.

[0078] In addition, according to an embodiment of the present disclosure, because a block temperature sensor is mounted on a thermal block FPCB that is in thermal contact with an upper portion of a thermal block, there is no need to form a separate aperture in the thermal block to mount a temperature sensor, thereby facilitating manufacturing, and the temperature may be precisely measured at a position closest to the thermal block.

[0079] In addition, according to an embodiment of the present disclosure, a block temperature sensor, which is provided as a resistance temperature detector (RTD) or a temperature sensor capable of linearly estimating a resistance value according to a temperature change, is mounted on a thermal block FPCB, facilitating calibration and control of each temperature sensor. For example, a temperature linearity compensation function may be derived by calculating an error between a temperature of the thermal block measured by using an external temperature measuring device, and a temperature of the thermal block detected by the block temperature sensor, and the temperature compensation may be controlled by using the temperature linearity compensation function.

[0080] 2: According to an embodiment of the present disclosure, the temperature of each zone of a heat sink may be measured to complement thermoelectric elements and achieve precise and uniform temperature control.

[0081] In addition, according to an embodiment of the present disclosure, a temperature sensor may be mounted on a portion that protrudes around cooling fins, making it easy to mount and repair the temperature sensor in the heat sink.

[0082] In addition, according to an embodiment of the present disclosure, the temperature of air around the cooling fins may be measured to complement the thermoelectric elements and achieve precise and uniform temperature control.

[0083] In addition, according to an embodiment of the present disclosure, a heat sink temperature sensor, which is provided as an RTD or a temperature sensor capable of linearly estimating a resistance value according to a temperature change, is mounted on a heat sink circuit board, facilitating calibration and control of each temperature sensor. For example, a temperature linearity compensation function may be derived by calculating an error between a temperature of the thermal block measured by using an external temperature measuring device, and a temperature of the thermal block detected by the block temperature sensor, and the temperature compensation may be controlled by using the temperature linearity compensation function.

[0084] 3: According to an embodiment of the present disclosure, even when heat loss occurs around a heat lid, sufficient heat may be transferred to reaction vessels positioned around the thermal block.

[0085] In addition, according to an embodiment of the present disclosure, problems that may occur when the temperature of the heat lid is increased to prevent condensation in the reaction vessel positioned at the periphery of the thermal block, such as damage due to overheating of the heat lid or a phenomenon in which the reaction vessel at the center melts and sticks to the heat lid, may be prevented.

[0086] The effects of the present disclosure are not limited to the foregoing, and should be understood to include all effects that may be inferred from the detailed description of the present disclosure or the configuration described in claims.

[0087] FIG. 1 is a perspective view illustrating a thermal module for a thermal cycler according to an embodiment.

[0088] FIG. 2 is an exploded perspective view of the thermal module of FIG. 1.

[0089] FIG. 3 is a diagram illustrating the thermal module of FIG. 2 as viewed from below.

[0090] FIG. 4 is a detailed exploded perspective view of the thermal module of FIG. 2.

[0091] FIG. 5 is a diagram illustrating the thermal module of FIG. 4 as viewed from below.

[0092] FIG. 6 is a side view of a thermal module.

[0093] FIG. 7 is a cross-sectional view taken along line A-A of FIG. 6.

[0094] FIG. 8 is an exploded perspective view of a thermal unit according to an embodiment.

[0095] FIG. 9 is a diagram illustrating the thermal unit of FIG. 8 as viewed from below.

[0096] FIGS. 10 is a diagram illustrating a configuration of a control unit of a thermal cycler.

[0097] FIG. 11 is a perspective view illustrating a thermal block circuit board.

[0098] FIG. 12 is a plan view of a thermal block circuit board.

[0099] FIG. 13 is a cross-sectional view illustrating a state in which a thermal block circuit board is installed.

[0100] FIGS. 14 is a graph showing resistance change values according to the temperature of a resistance temperature detector (RTD) and a negative-temperature-coefficient (NTC) thermistor.

[0101] FIGS. 15A to 15F illustrate thermal block circuit boards according to various embodiments.

[0102] FIG. 16 is a side view of a thermal unit according to another embodiment.

[0103] FIG. 17 is a perspective view illustrating a thermal unit according to another embodiment, as viewed from below.

[0104] FIG. 18 is a perspective view illustrating a heat sink circuit board according to an embodiment.

[0105] FIG. 19 is a perspective view illustrating a state in which a heat sink circuit board is installed in a heat sink, according to an embodiment.

[0106] FIGS. 20A to 20D are plan views illustrating heat lid circuit boards according to various embodiments.

[0107] Hereinafter, the present disclosure will be described in detail with reference to embodiments and example drawings. The embodiments are for illustrative purposes only, and it should be apparent to those of skill in the art that the scope of the present disclosure is not limited to the embodiments.

[0108] In addition, in adding reference numerals to the components of each drawing, it should be noted that same reference numerals are assigned to same components as much as possible even though they are shown in different drawings. In addition, in describing the embodiments of the present disclosure, when it is determined that a detailed description of a related well-known configuration or function interferes with the understanding of the embodiments of the present disclosure, the detailed description thereof will be omitted.

[0109] In addition, in describing the components of the embodiments of the present disclosure, terms such as first, second, A, B, (a), (b), (i), (ii), etc. may be used. These terms are only for distinguishing the components from other components, and the nature or order of the components is not limited by the terms. When a component is described as being "connected," "coupled" or "fastened" to other component, the component may be directly connected or fastened to the other component, but it will be understood that another component may be "connected," "coupled" or "fastened" between the components.

[0110] An embodiment of the present specification may relate to a detection device for detecting a target analyte in a sample.

[0111] As used herein, the term "sample" may include a biological sample (e.g., cells, tissues, and fluids from a biological source) and a non-biological sample (e.g., food, water, and soil). Examples of the biological sample may include viruses, bacteria, tissues, cells, blood (e.g., whole blood, plasma, or serum), lymph, bone marrow fluid, saliva, sputum, swab, aspiration, milk, urine, feces, ocular fluid, semen, brain extract, spinal fluid, joint fluid, thymic fluid, bronchoalveolar lavage fluid, ascites, and amniotic fluid. In addition, the sample may include natural nucleic acid molecules isolated from a biological source, and synthetic nucleic acid molecules. According to an embodiment of the present disclosure, the sample may include an additional substance such as water, deionized water, saline solution, pH buffer, acid solution, or alkaline solution.

[0112] In the present specification, a sample may include a substance necessary for detecting a target analyte. For example, the sample may include an optical label. The optical label refers to a label that generates an optical signal depending on the presence of a target nucleic acid. The optical label may be a fluorescent label. The fluorescent label useful herein may include any molecule known in the art.

[0113] A target analyte refers to a substance that is the subject of analysis. The analysis may refer to obtaining information about, for example, the presence or absence, content, concentration, sequence, activity, or properties of the analyte in the sample. The analyte may include various substances (e.g., biological substances and non-biological substances such as compounds). In detail, the analyte may include a biological substance such as nucleic acid molecules (e.g., deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)), proteins, peptides, carbohydrates, lipids, amino acids, biological compounds, hormones, antibodies, antigens, metabolites, or cells. According to an embodiment of the present disclosure, the analyte may be a nucleic acid molecule.

[0114] Thus, a target analyte detection device according to an embodiment of the present specification may be a target nucleic acid detection device. The target nucleic acid detection device causes a nucleic acid reaction to occur in a sample, to detect a target nucleic acid.

[0115] The nucleic acid reaction refers to a series of physical and chemical reactions that generate a signal depending on the presence or amount of a nucleic acid of a specific sequence in the sample. The nucleic acid reaction may include the binding of a nucleic acid of a specific sequence in a sample to other nucleic acids or substances, and replication, cleavage, or decomposition of a nucleic acid of a specific sequence in the sample. The nucleic acid reaction may involve a nucleic acid amplification reaction. The nucleic acid amplification reaction may include amplification of a target nucleic acid. The nucleic acid amplification reaction may specifically amplify the target nucleic acid.

[0116] The nucleic acid reaction may be a signal-generation reaction that may generate a signal depending on the presence / absence or amount of a target nucleic acid in a sample. The signal-generation reaction may be a process of genetic analysis such as polymerase chain reaction (PCR), real-time PCR, or microarray.

[0117] A thermal cycler according to an embodiment of the present specification may be a nucleic acid detection device, and may detect a signal that is generated depending on the presence of a target nucleic acid. The nucleic acid detection device may involve nucleic acid amplification to amplify and detect a signal. Alternatively, the nucleic acid detection device may amplify and detect a signal without nucleic acid amplification. Preferably, the nucleic acid detection device detects a signal with nucleic acid amplification.

[0118] A thermal cycler according to an embodiment of the present specification may include a nucleic acid amplification device.

[0119] The nucleic acid amplification device refers to a device capable of performing a nucleic acid amplification reaction to amplify a nucleic acid having a specific nucleotide sequence. Examples of methods for amplifying the nucleic acid include PCR, ligase chain reaction (LCR), transcription-mediated amplification, nucleic acid sequence-based amplification (NASBA), rolling circle amplification (RCA), Q-beta replicase, etc.

[0120] A thermal cycler according to an embodiment of the present specification may be a device for performing a nucleic acid amplification reaction while causing a change in temperature. For example, the nucleic acid amplification device may perform a denaturing step, an annealing step, and an extension (or amplification) step, to amplify DNA having a specific base sequence.

[0121] In the denaturing step, a solution containing a reagent and a sample containing double-stranded DNA, which is a template nucleic acid, is heated to a specific temperature, for example, about 95 °C, to separate the double-stranded DNA into single-stranded DNA. In the annealing step, an oligonucleotide primer having a nucleotide sequence complementary to the nucleotide sequence of a nucleic acid to be amplified is provided, and the primer and the separated single-stranded DNA are cooled down to a specific temperature, for example 60 °C, to bind the primer to a specific nucleotide sequence of the single-stranded DNA so as to form a partial DNA-primer complex. In the extension step, the solution is maintained at a specific temperature, for example 72°C, after the annealing step, to form double-stranded DNA by DNA polymerase based on the primer of the partial DNA-primer complex.

[0122] The above-described three steps may be repeated, for example, 10 to 50 times, to exponentially amplify DNA having the specific nucleotide sequence. In some cases, the nucleic acid amplification device may perform the annealing step and the extension step simultaneously. In this case, the nucleic acid amplification device may complete one cycle by performing two steps including a denaturing step and an annealing / extension step.

[0123] In particular, a thermal cycler according to an embodiment of the present specification may be a device for performing a nucleic acid amplification reaction and a reaction that generates an optical signal depending on the presence of a nucleic acid, while causing a change in temperature, and detecting the generated optical signal.

[0124] A thermal cycler according to an embodiment of the present specification may include a thermal module, an optical module, and a main control unit. In addition, the optical module may include a light-emitting module and a detection module.

[0125] According to an embodiment, the light-emitting module supplies an appropriate optical stimulus to a sample accommodated in a sample holder, and the detection module detects an optical signal that is generated from the sample in response to the optical stimulus.

[0126] The optical signal may be luminescence, phosphorescence, chemiluminescence, fluorescence, polarized fluorescence, or another colored signal. The optical signal may be an optical signal generated in response to the optical stimulus applied to the sample.

[0127] The thermal module according to an embodiment may perform thermal cycling by applying heat to the sample holder and cooling the sample holder. For example, the thermal module may perform a nucleic acid amplification reaction of the sample while performing thermal cycling.

[0128] The sample holder has a sample accommodation portion formed therein to accommodate a sample. The sample holder is a component that directly accommodates a sample in the sample accommodation portion, or accommodates a reaction vessel containing the sample.

[0129] In the present specification, the expression "the sample holder may accommodate a sample" may be used to comprehensively indicate cases in which the sample holder accommodates the sample directly in the sample accommodation portion or accommodates the reaction vessel containing the sample.

[0130] The sample holder allows the sample to be placed at a predetermined position such that an optical stimulus from the light-emitting module reaches the sample, and an optical signal generated from the sample reaches the detection module.

[0131] The sample holder may receive heat supplied from a thermal element, and the heat may be transferred to a sample accommodated directly in the sample holder or to a sample accommodated in the reaction vessel.

[0132] The sample holder may have the shape of a block or a plate. The sample holder may include a recess for accommodating the reaction vessel, or may have a flat surface. Alternatively, the recess formed in the sample holder may be provided in the shape of a well, or may be a hole penetrating the sample holder.

[0133] In addition, the sample holder that accommodates the reaction vessel may have a structure that may guide the position of the reaction vessel or fix the reaction vessel.

[0134] A single sample holder may be provided to accommodate one or more reaction vessels. That the sample holder accommodates the reaction vessels may mean that the reaction vessels are placed in a plurality of recesses formed in the sample holder, or are placed at the assigned position on the sample holder.

[0135] The reaction vessel is used to accommodate a sample to be analyzed, and includes various types of containers, for example, a tube, a vial, a strip having a plurality of tubes connected thereto, a plate having a plurality of tubes connected thereto, a microcard, a chip, a cuvette, or a cartridge.

[0136] The reaction vessel may be made of plastic, ceramic, glass, or metal. In addition, the reaction vessel may be made of various materials as needed. The sample holder that directly accommodates a sample in the sample accommodation portion may be prepared with the shape and material of the reaction vessel described above. Hereinafter, the sample holder that accommodates a reaction vessel containing a sample will be described.

[0137] The sample holder may be made of a material having thermal conductivity. When the sample holder comes into contact with the reaction vessel, heat may be transferred to the sample by reaction vessel conduction. In some cases, heat is transferred from the reaction vessel to the sample by convection or radiation.

[0138] The sample holder may be made of iron, aluminum, gold, silver, nickel, copper, or an alloy including one or more thereof. In addition, the sample holder may be made of various materials as needed, and in some cases, may be made of plastic or ceramic.

[0139] The sample holder may include a thermal block or a heat block. The thermal block or heat block includes various sizes and shapes used in the same or similar technical fields.

[0140] The sample holder is formed to accommodate a plurality of samples, and controls the temperature of the plurality of samples to allow a reaction for detection, such as a nucleic acid amplification reaction, to occur.

[0141] For example, in a case in which the sample holder is a thermal block having a plurality of wells formed therein, the sample holder may be formed as one thermal block, and all wells of the thermal block may be formed not to be thermally independent of each other. In this case, the temperatures of all wells in which samples are accommodated in the sample holder are the same within the margin of error, and it is impossible to control the temperatures of the accommodated samples according to different protocols.

[0142] As another example, the sample holder may be configured to allow the temperatures of some of the samples accommodated in the sample holder to be controlled according to different protocols. To this end, the sample holder may include two or more thermally independent reaction zones. Each of the reaction zones may be thermally independent. No or only a reference amount of heat or less is transferred from one reaction zone to another reaction zone. For example, an insulating material or an air gap may be present between the reaction zones.

[0143] The temperature of each of the reaction zones may be independently controlled. A user may individually set, for each of the reaction zones, a reaction protocol including a temperature and a time, and each of the reaction zones may perform a reaction according to the independent protocol. Because reactions are performed in the respective reaction zones according to the independent protocols, time points of light detection in the reaction zones may be independent of each other.

[0144] In an embodiment, the sample holder may be partitioned into a plurality of sample areas. The sample areas are distinguished by excitation light irradiation areas of the light-emitting module.

[0145] That is, the light-emitting module according to an embodiment of the present specification may include a plurality of light source elements, and the sample holder may be partitioned into a plurality of sample areas. Each of the plurality of sample areas refers to an area on the sample holder where samples are positioned and optical signal detection reactions are performed by the same light source element. In other words, the sample area of the present disclosure refers to a group of reaction sites in which optical signal detection reactions are performed by the same light source element, among a plurality of reaction sites included in the sample holder. That is, the sample area is distinguished by an excitation light irradiation area of the light source element. Each sample area may have one or more wells or holes formed therein.

[0146] According to an embodiment, in a case in which the sample holder is a thermal block, an empty space may be formed between wells, to reduce the heat capacity. For example, the heat capacity may be reduced by forming grooves or holes between the wells of the thermal block. In addition, the edge effect may be reduced by designing the heat capacities of a central area and an edge area of the thermal block to be different from each other. The edge effect refers to the phenomenon in which the temperature rises more slowly at the edge area of the thermal block than at the central area of the thermal block when heated, and falls more quickly at the edge area of the thermal block than at the central area of the thermal block when cooled.

[0147] In an embodiment, the sample holder may have formed therein a plurality of wells or a plurality of holes in a regular arrangement. For example, the plurality of wells may be formed in a matrix configuration with columns and rows. The plurality of wells may be formed in various configurations, such as 16 wells in a 4 x 4 configuration, 24 wells in a 6 x 4 configuration, 32 wells in a 4 x 8 configuration, 60 wells in a 5 x 12 configuration, 90 wells in a 5 x 18 configuration, 96 wells in an 8 x 12 configuration, or 384 wells in a 16 x 24 configuration, but are not limited thereto, and the sample holder may mainly employ a 16-well configuration, a 32-well configuration, a 96-well configuration, or a 384-well configuration. The shape, size, etc. of the wells may be determined to suit the reaction vessel to be accommodated.

[0148] According to an embodiment, the sample holder may be partitioned into a plurality of thermal zones. The thermal zone refers to an area defined according to the arrangement of thermal elements or temperature sensors. The thermal zone may be a physically distinct area, but may also be a virtual area defined for convenient temperature control.

[0149] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the accompanying drawings such that those of skill in the art may easily practice the present disclosure.

[0150] FIGS. 1 to 7 illustrate a thermal module 10 for a thermal cycler according to an embodiment.

[0151] FIG. 1 is a perspective view illustrating the thermal module 10 for a thermal cycler according to an embodiment. In addition, FIG. 2 is an exploded perspective view of the thermal module 10 of FIG. 1, and FIG. 3 is a diagram illustrating the thermal module 10 of FIG. 2 as viewed from below. In addition, FIG. 4 is a detailed exploded perspective view of the thermal module 10 of FIG. 2, and FIG. 5 is a diagram illustrating the thermal module 10 of FIG. 4 as viewed from below. In addition, FIG. 6 is a side view of the thermal module 10, and FIG. 7 is a cross-sectional view taken along line A-A of FIG. 6.

[0152] Hereinafter, in FIG. 1, the x-axis direction includes a first direction or the same direction as the lengthwise direction of a thermal block 110, the y-axis direction includes a second direction or the same direction as the widthwise direction of the thermal block 110, and the z-axis direction includes a vertical direction.

[0153] Referring to FIGS. 1 to 7, a thermal cycler according to an embodiment of the present specification may include the thermal module 10 configured to perform thermal cycling by heating and cooling the thermal block 110.

[0154] The thermal module 10 may include a thermal unit 100, a control unit 300, and a cooling unit 200.

[0155] The thermal unit 100 may include the thermal block 110 on which a reaction vessel (e.g., a 96-well plate) for accommodating a sample is mounted, a thermal element in thermal contact with the thermal block 110, and a first heat sink 150 to dissipate heat from the thermal block 110.

[0156] In addition, the control unit 300 may include a control circuit board 310 configured to control the thermal element, and a second heat sink 320 to dissipate heat from the control circuit board 310.

[0157] In addition, the cooling unit 200 may include a cooling fan 220 to supply and / or discharge air to and / from the first heat sink 150 and the second heat sink 320, and a duct 210 to provide a flow passage for air.

[0158] According to an embodiment, the thermal module 10 may be provided as an integrated module in which the thermal unit 100, the control unit 300, and the cooling unit 200 are combined with each other. For example, the thermal module 10 may be sequentially connected to the thermal unit 100, the cooling unit 200, and the control unit 300 from top to bottom. In addition, the thermal module 10 may include an integrated cover or case.

[0159] The cooling unit 200 may cool the thermal unit 100 and the control unit 300 simultaneously. According to an embodiment, the first heat sink 150 of the thermal unit 100 may be positioned at an upper portion of the duct 210 of the cooling unit 200, and the second heat sink 320 of the control unit 300 may be positioned at a lower portion of the duct 210. In detail, first cooling fins 151 of the first heat sink 150 and second cooling fins 321 of the second heat sink 320, which are arranged close to each other, may be cooled by the flow of air passing through the duct 210.

[0160] In addition, the thermal module 10 may include a first cover, an intermediate frame, and a second cover. Hereinafter, the cover and frame are not limited in shape and structure by their names used herein. In some cases, the cover or frame may also be referred to as 'case', 'housing', etc.

[0161] The thermal module 10 according to an embodiment may include an upper cover 20, an intermediate frame 30, and a lower cover 40. The upper cover 20 may be coupled to an upper portion of the intermediate frame 30, and the lower cover 40 may be coupled to a lower portion of the intermediate frame 30.

[0162] The upper cover 20 may be provided to open all or part of the upper surface of the thermal block 110 and surround the side surface of the thermal block 110. In addition, the intermediate frame 30 may be coupled to a lower portion of the upper cover 20.

[0163] The upper cover 20 is opened in whole or in part at a place on which a reaction vessel is seated. According to an embodiment, the opening of the upper cover 20 may be provided as a through hole into which a well of the reaction vessel may be inserted. In addition, the through hole of the upper cover 20 may be at a position corresponding to a recess of the thermal block 110. For example, a well protruding downward from the reaction vessel may pass through the through hole of the upper cover 20 to be accommodated in the recess of the thermal block 110.

[0164] The intermediate frame 30 may have a first cooling fan installed on one side thereof, and a second cooling fan installed on the opposite side. In addition, the intermediate frame 30 may form a duct that forms a flow passage for air between the first cooling fan and the second cooling fan. In addition, the lower cover 40 may be coupled to a lower portion of the intermediate frame 30.

[0165] According to an embodiment, in the thermal module 10, the first cooling fan may be provided as an intake cooling fan 220 through which air is sucked in and introduced into the duct 210, and the second cooling fan may be provided as an exhaust cooling fan 220 through which air that has passed through the duct 210 is discharged.

[0166] The lower cover 40 may be provided to surround the bottom surface and the side surface of the control circuit board 310. In addition, the intermediate frame 30 may be coupled to an upper portion of the lower cover 40. In addition, a shock prevention structure or a shock prevention member may be adopted between the lower cover 40 and the control circuit board 310.

[0167] The thermal module 10 may be provided as an independent integrated module in which the upper cover 20, the intermediate frame 30, and the lower cover 40 are combined with each other to form a single housing. The thermal module 10 provided as an integrated module is easy to repair and replace, and its specifications may be changed reliably. For example, a manufacturer may prepare thermal modules 10 with various specifications, and when a customer wants to change the specifications, the customer may easily change the specifications by simply replacing the thermal module 10 in the thermal cycler. For example, the specifications of the thermal block 110 may include 6 wells, 12 wells, 24 wells, 48 wells, 96 wells, 192 wells, 384 wells, or the like. In addition, in a case in which the thermal block 110 is provided to allow a plurality of reaction vessels to be arranged thereon, the specifications of the thermal block 110 may include 96x1, 96x2, 96x3, or the like.

[0168] The thermal unit 100 will be described with reference to FIGS. 8 and 9.

[0169] FIG. 8 is an exploded perspective view of the thermal unit 100 according to an embodiment, and FIG. 9 is a diagram illustrating the thermal unit 100 of FIG. 8 as viewed from below.

[0170] The thermal unit 100 may include the thermal block 110, thermal elements, a thermal circuit board 140, and the first heat sink 150.

[0171] The thermal block 110 may be arranged under a reaction vessel to accommodate or support the reaction vessel, and may come into contact with the reaction vessel to apply heat to a sample or absorb heat from the sample.

[0172] The thermal block 110 may be made of a material with high thermal conductivity, for example, metal. According to an embodiment, the thermal block 110 may be made of aluminum (Al) or an alloy containing aluminum.

[0173] According to an embodiment, the reaction vessel is provided as a well plate in which a plurality of wells are arranged in rows and columns, and the thermal block 110 may have formed therein a plurality of recesses for accommodating the wells of the well plate, respectively. In addition, the interiors of the recesses of the thermal block 110 are coated (e.g., with Teflon) to prevent the wells of the well plate from sticking to the thermal block 110.

[0174] The thermal elements may include thermoelectric elements 130 and resistance heating elements (e.g., electrical resistance elements).

[0175] The thermoelectric elements 130 may be positioned below the thermal block 110. In detail, the thermoelectric elements 130 may be provided between the thermal block 110 and the first heat sink 150, and may transfer heat between the thermal block 110 and the first heat sink 150.

[0176] In addition, the resistance heating elements may be positioned above the thermal block 110. In detail, the resistance heating elements may be provided between the upper cover 20 and the thermal block 110.

[0177] The thermoelectric elements 130 include Peltier elements or thermoelectric coolers (TECs). The thermoelectric elements 130 may generate heat flux at a junction of heterogeneous materials by using the Peltier effect. The thermoelectric elements 130 may function as a heat pump by transferring heat to the thermal block 110 or dissipating heat from the thermal block 110. In addition, the thermoelectric elements 130 may be used for thermal cycling that involves repeating heating and cooling.

[0178] In addition, the thermal elements may include a plurality of thermoelectric elements 130 arranged adjacent to each other. For example, six bar-type thermoelectric elements 130 may be arranged side by side, and the thermal block 110 may be partitioned into at least six thermal zones. In addition, by independently controlling each of the thermoelectric elements 130, the temperature of the corresponding thermal zone may be individually controlled. For example, by independently controlling each of the thermoelectric elements 130, adjacent thermal zones may be controlled to have temperature gradients. Alternatively, by independently controlling each of the thermoelectric elements 130, temperature differences between the thermal zones may be reduced.

[0179] In addition, the thermoelectric elements 130 may be arranged in the air flow direction of the duct 210. By independently controlling each of the thermoelectric elements 130, the temperature of the thermal block 110, which varies in the air flow direction, may be uniformly controlled.

[0180] The resistance heating element refers to an element that generates heat by Joule heating. For example, the resistance heating element may be provided as a film heater or a flexible printed circuit board (FPCB). In addition, the resistance heating elements may be used to uniformly control the temperature of the thermal block 110. For example, heat may be generated by using the resistance heating element positioned in a thermal zone with a relatively low temperature among the plurality of thermal zones of the thermal block 110, to increase the temperature of the corresponding thermal zone.

[0181] As the thermal block exchanges heat with outside air, the temperature at the periphery of the thermal block may become lower than the temperature at the center of the thermal block. That is, heat loss to the outside air at the periphery of the thermal block leads to a decrease in the thermal uniformity. Thus, in order to ensure the thermal uniformity of the thermal block, it is necessary to supplement the temperature of the periphery of the thermal block. By using the resistance heating elements 121, additional heat may be provided to the periphery of the thermal block to improve the thermal uniformity.

[0182] In addition, a first heat transfer member 161 may be provided between the thermoelectric elements 130 and the thermal block 110, and a second heat transfer member 162 may be provided between the thermoelectric elements 130 and the first heat sink 150. The first and second heat transfer members 161 and 162 may be made of a material with high thermal conductivity, and may be provided as a tape, a pad, a film, or an adhesive. For example, the first and second heat transfer members 161 and 162 may each include acrylic foam, polyethylene terephthalate (PET), or a copper foil, and their materials may be selected by considering adhesion, heat resistance, conductivity, flame retardancy, etc.

[0183] The first heat transfer member 161 may be provided to have an area suitable for covering the thermal block 110, and the second heat transfer member 162 may be provided to have an area suitable for covering each of the thermoelectric elements 130. The first heat transfer member 161 may be provided to have a width suitable for covering the plurality of thermoelectric elements 130 to enable uniform heating of the thermal block 110. In addition, the second heat transfer member 162 may be provided to have a width suitable for covering each of the thermoelectric elements 130 to individually cool the thermal block 110. For example, in a case in which six thermoelectric elements 130 are provided, the first heat transfer member 161 may be provided as a single layer with one heat transfer member covering the width of the six thermoelectric elements 130, and the second heat transfer member 162 may be provided as a single layer with six heat transfer members arranged side by side, each of which covers the width of one thermoelectric element 130.

[0184] In addition, a third heat transfer member (not shown) may be provided between the resistance heating elements and the thermal block 110. The third heat transfer member may be made of a material with high thermal conductivity, and may be provided as a tape, a pad, a film, or an adhesive. For example, the third heat transfer member may include acrylic foam, PET, or a copper foil, and its material may be selected by considering adhesion, heat resistance, conductivity, flame retardancy, etc.

[0185] In addition, an insulating member may be provided between the resistance heating elements and the upper cover 20. The insulating member may be made of a material with low thermal conductivity to prevent upward loss of heat generated in the resistance heating elements 121. For example, the insulating member may include silicone, silicone sponge, or a sealant. Preferably, the insulating member may be an elastic insulating pad having a shape corresponding to the size and area of the thermal block 110.

[0186] The resistance heating elements may be positioned between the reaction vessel and the thermal block 110, and the upper cover 20 and the insulating member may be positioned between the reaction vessel and the resistance heating elements 121. Thus, it is possible to prevent heat of the resistance heating elements from being directly transferred to the reaction vessel. In addition, the third heat transfer member may be provided between the resistance heating elements and the thermal block 110 to increase the thermal efficiency of transferring the heat of the resistance heating elements to the thermal block 110.

[0187] In addition, the thermal elements may be electrically connected to the thermal circuit board 140. A connector of a thermal block circuit board on which the resistance heating elements are provided may be electrically connected to the thermal circuit board 140, and furthermore, may be detachably connected to the thermal circuit board 140. In addition, the thermoelectric elements 130 may be electrically connected to the thermal circuit board 140 through a metal wire.

[0188] The thermal circuit board 140 may be a thermal printed circuit board (PCB) positioned inside the upper cover 20 and having a first interface portion 141 provided on one side thereof. In addition, the first interface portion 141 of the thermal circuit board 140 may be exposed through one side surface of the upper cover 20 to be connected to an interface unit 400 to be described below. To this end, the upper cover 20 may form a first opening that exposes the first interface portion 141 of the thermal circuit board 140.

[0189] In addition, the first interface portion 141 of the thermal circuit board 140 may be positioned on one side surface of the upper cover 20 facing a second direction (the y-axis direction in FIG. 1) that is perpendicular to the first direction (the x-axis direction in FIG. 1) that is the flow direction of air passing through the duct 210.

[0190] In addition, the thermal circuit board 140 may be configured to have a space formed therein. The internal space of the thermal circuit board 140 may be formed to accommodate therein the thermal block 110 when viewed from above, and the thermal block 110 and / or the thermal elements may be accommodated in the internal space. Alternatively, the thermal circuit board 140 may be provided along the periphery of the thermal block 110 when viewed from above, and may be configured in a '□' or 'ㄷ' shape.

[0191] In addition, the thermal elements may be electrically connected to a power module of the main control unit or the control unit 300 to generate heat by using power provided from the power module.

[0192] The first heat sink 150 may be positioned below the thermal block 110. The first heat sink 150 is a passive heat exchanger and efficiently dissipates heat from the thermal block 110.

[0193] The heat sink may be formed of metal, ceramic, or plastic. The heat sink may include a plurality of cooling fins or heat dissipation fins to increase the heat dissipation area. The cooling fins formed on the heat sink may be arranged in various directions depending on the implementation. The shape of the heat sink and the length, arrangement, and thickness of the cooling fins may be variously determined.

[0194] The first heat sink 150 may include a body supporting the thermal block 110, and a plurality of first cooling fins 151 extending downward from the body. For example, the first cooling fins 151 may be provided as straight fins and may be arranged in one direction below the body of the first heat sink 150. For example, the plurality of first cooling fins 151 may extend in the air flow direction of the duct 210, and may be arranged adjacent to each other in a direction perpendicular to the air flow direction of the duct 210. Air flowing through a space between adjacent first cooling fins 151 may exchange heat with the first cooling fins 151.

[0195] The cooling unit 200 and the control unit 300 will be described with reference to FIGS. 4 and 5.

[0196] The control unit 300 may include the control circuit board 310 and the second heat sink 320.

[0197] The control circuit board 310 may be a control PCB positioned inside the lower cover 40 and having a second interface portion 311 provided on one side thereof. In addition, the second interface portion 311 of the control circuit board 310 may be exposed through one side surface of the lower cover 40 to be connected to the interface unit 400 to be described below. To this end, the lower cover 40 may form a second opening that exposes the second interface portion 311 of the control circuit board 310.

[0198] In addition, the second interface portion 311 of the control circuit board 310 may be positioned on one side surface of the lower cover 40 facing the second direction that is perpendicular to the first direction that is the flow direction of air passing through the duct 210.

[0199] In addition, the first interface portion 141 of the thermal circuit board 140 and the second interface portion 311 of the control circuit board 310 may be arranged to face the same direction. That is, the first interface portion 141 and the second interface portion 311 may be exposed through one side surface of the integrated module formed by combining the upper cover 20, the intermediate frame 30, and the lower cover 40, in the second direction, and the interface unit 400 may be coupled to the one side surface of the integrated module.

[0200] In addition, the second heat sink 320 may be positioned on the control circuit board 310. The second heat sink 320 is a passive heat exchanger and efficiently dissipates heat from the control circuit board 310.

[0201] The second heat sink 320 may include a plurality of second cooling fins 321 extending upward. For example, the second cooling fins 321 may be provided as straight fins and may be arranged in one direction on the body of the second heat sink 320. For example, the plurality of second cooling fins 321 may extend in the air flow direction of the duct 210, and may be arranged adjacent to each other in a direction perpendicular to the air flow direction of the duct 210. Air flowing through a space between adjacent second cooling fins 321 may exchange heat with the second cooling fins 321.

[0202] The first cooling fins 151 of the first heat sink 150 may be provided spaced apart from the second cooling fins 321 of the second heat sink 320, in the vertical direction. Thus, the cooling efficiency may be improved as air flows through spaces between the first cooling fins 151 and the second cooling fins 321.

[0203] The first cooling fins 151 of the first heat sink 150 and the second cooling fins 321 of the second heat sink 320 may be arranged alternately with each other in the second direction that is perpendicular to the first direction that is the flow direction of air passing through the duct 210. Thus, the cooling efficiency may be improved by minimizing interference between the flow of air passing between the first cooling fins 151 and the flow of air passing between the second cooling fins 321, and increasing the flow rates of air.

[0204] In addition, although not illustrated in the drawings, a duct separation partition (not shown) may be provided between the first cooling fins 151 and the second cooling fins 321. The duct separation partition may be provided in a plate shape extending in the air flow direction of the duct 210, and the upper surface of the duct separation partition may be provided adjacent to the first cooling fins 151, and the lower surface of the duct separation partition may be provided adjacent to the second cooling fins 321. The duct separation partition may separate an air flow cooling the first heat sink 150 from an air flow cooling the second heat sink 320, such that thermal cycling enables more fine-tuned and predictable temperature gradients.

[0205] In addition, the duct separation partition may be thermally connected to and supported by the second heat sink 320. Heat from the duct separation partition may be circulated to the second heat sink 320.

[0206] The cooling unit 200 may include the cooling fan 220 and the duct 210.

[0207] The cooling fan 220 provides outside air to cool the first heat sink 150 and the second heat sink 320.　Various types of known cooling fans 220 may be used for the cooling fan 220. For example, axial fans, centrifugal fans, and cross-flow fans may be used.

[0208] The cooling fan 220 may include an inlet cooling fan or a first cooling fan 220 positioned on the inlet side of the duct 210, and an outlet cooling fan or a second cooling fan 220 positioned on the outlet side of the duct 210. According to an embodiment, the first cooling fan 220 and the second cooling fan 220 may be provided in the x-axis direction or the first direction. However, the arrangement direction of the first cooling fan 220 and the second cooling fan 220 may vary depending on the shape of the duct 210.

[0209] The duct 210 may include two side surfaces defining a flow passage for air. The first heat sink 150 and the second heat sink 320 may be positioned at an upper portion and a lower portion of the duct 210, respectively. A side surface of the duct 210 may be configured to connect the first cooling fan 220 to the second cooling fan 220, an inlet of the duct 210 adjacent to the first cooling fan 220 may include a gradient surface that expands an air flow area, and an outlet of the duct 210 adjacent to the second cooling fan 220 may include a gradient surface that reduces the air flow area.

[0210] In addition, although not illustrated in the drawings, a skirt may be provided between the inlet of the duct 210 and the heat sink to reduce the formation of vortexes in air. For example, the skirt may be made of a shape-deformable material, and may have a shape that guides an air flow passage toward the cooling fins.

[0211] In addition, the thermal module 10 may further include a heat lid (not shown) positioned above the reaction vessel. The heat lid may be understood as a functional component of the thermal module 10, but is not included in the integrated module partitioned with a housing. The heat lid may be positioned above the reaction vessel and may be electrically connected to the control module.

[0212] The heat lid may provide heat to the upper surface of the reaction vessel. As a reaction proceeds in the reaction vessel, the sample may evaporate, and the evaporated sample may condense on the lower surface of the cover. The heat lid may prevent or reduce condensation of the evaporated sample by applying heat to the upper surface of the reaction vessel. In the following description, the cover of the reaction vessel includes a cap and a sealing film.

[0213] In addition, the heat lid may provide pressure to the upper surface of the reaction vessel. As a reaction proceeds in the reaction vessel, the internal pressure of the reaction vessel may increase. The increase in the internal pressure may compromise the seal of the reaction vessel. The heat lid may prevent rupture of the cover by providing pressure to the upper surface of the reaction vessel, and promote the reaction by increasing the internal pressure of the reaction vessel. For example, the heat lid may come into contact with the covers of the reaction vessels, and press the covers of the reaction vessels to provide pressure to the reaction vessels.

[0214] In addition, the heat lid may maintain a high temperature. For example, the heat lid may include a heat plate (not shown) that maintains a temperature of 105 °C. In addition, the heat lid may simultaneously provide heat and pressure to the upper surface of the reaction vessel.

[0215] The heat lid includes a plurality of apertures. The apertures of the heat lid are formed at positions corresponding to the wells of the thermal block 110. Excitation light and emitted light may pass through the apertures of the heat lid.

[0216] In addition, the thermal module 10 may further include a temperature sensor.

[0217] The temperature sensor may further include a block temperature sensor configured to measure the temperature of the thermal block 110, a heat sink temperature sensor configured to measure the temperature of the heat sink, an air temperature sensor configured to measure the temperature of air in the duct 210, and a heat lid temperature sensor configured to measure the temperature of the heat lid.

[0218] The block temperature sensor may include a plurality of block temperature sensors corresponding to the plurality of thermal zones of the thermal block 110. Each thermal zone of the thermal block 110 may be provided with one or more block temperature sensors. For example, in a case in which the thermal block 110 is partitioned into a plurality of thermal zones in the lengthwise direction (the x-axis direction in FIG. 1), a plurality of block temperature sensors may be provided in each of the thermal zones of the thermal block 110 in the widthwise direction (the y-axis direction in FIG. 1) that is perpendicular to the lengthwise direction.

[0219] The thermal zones of the thermal block 110 may be defined by physically partitioning the thermal block 110. Alternatively, the thermal zones of the thermal block 110 may be defined by virtually partitioning the thermal block 110 in terms of heat transfer. For example, in a case in which the number of thermoelectric elements 130 arranged in the lengthwise direction of the thermal block 110 is a, the thermal block 110 may include a x n thermal zones (n is a positive integer).

[0220] According to an embodiment, the thermoelectric element 130 may include six thermoelectric elements 130 arranged in one direction of the thermal block 110. Here, the one direction in which the thermoelectric elements 130 are arranged may be the air flow direction of the duct 210. The thermoelectric elements 130 are arranged adjacent to each other, and each of the thermoelectric elements 130 extends in a direction perpendicular to one direction of the thermal block 110 to cover the width of the thermal block 110.

[0221] The thermal block 110 may be partitioned into six thermal zones in the direction of arrangement of the thermoelectric elements 130. In addition, the thermal block 110 may be partitioned into a plurality of thermal zones depending on the arrangement of the block temperature sensors. For example, in a case in which six thermoelectric elements 130 are arranged in the air flow direction of the duct 210 and two block temperature sensors are arranged in each of the thermoelectric elements 130 in the lengthwise direction, such that a total of twelve block temperature sensors are arranged, the thermal block 110 may be partitioned into at least six and at most twelve thermal zones.

[0222] The heat sink temperature sensor may measure the temperature of the heat sink, and may be provided as a resistance temperature detector (RTD). A plurality of heat sink temperature sensors may be provided. For example, four heat sink temperature sensors may be provided for front, rear, left, and right portions of the heat sink, respectively.

[0223] The heat sink temperature sensor may be mounted on a heat sink circuit board 170 (see FIG. 8). The heat sink circuit board may be electrically connected to a thermal element connection circuit board to be described below. For example, a heat sink FPCB may be connected to a thermal element connection PCB.

[0224] The air temperature sensor may measure the temperatures of an inlet end and an outlet end of the duct 210, and may be provided as a thermally variable resistor (e.g., a negative-temperature-coefficient (NTC) thermistor). The air temperature sensor may be connected to the heat sink circuit board 170 via a wire. According to an embodiment, the air temperature sensor may include a first air temperature sensor configured to measure the temperature of air on the inlet side of the duct 210, and a second air temperature sensor configured to measure the temperature of air on the outlet side of the duct 210.

[0225] The heat lid temperature sensor may measure the temperature of the heat lid, and may be provided as an RTD. A plurality of heat lid temperature sensors may be provided. For example, five heat lid temperature sensors may be provided for one central area and four corner areas of the thermal block 110, respectively.

[0226] The heat lid temperature sensor may be provided on a heat lid circuit board. The heat lid circuit board may be a heat lid FPCB. In addition, the heat lid circuit board may be electrically connected to an interface circuit board via a heat lid connection circuit board. The heat lid connection circuit board may be a heat lid connection FPCB, and the interface circuit board may be an interface PCB. In addition, the heat lid temperature sensor may be an RTD that is surface-mounted on the heat lid FPCB.

[0227] Referring to FIG. 7, the thermal module 10 may further include the interface unit 400 that is detachably coupled to the integrated module formed by combining the upper cover 20, the intermediate frame 30, and the lower cover 40.

[0228] The interface unit 400 includes an interface circuit board 410 that electrically connects the control circuit board 310 to the thermal circuit board 140. In detail, the interface circuit board 410 may extend in a vertical direction (the z-axis direction in FIG. 1) to connect the first interface portion 141 of the thermal circuit board 140, which is positioned at a relatively high level, to the second interface portion 311 of the control circuit board 310, which is positioned at a relatively low level, and may include a connector 401 connected to the first interface portion 141 of the thermal circuit board 140, and a connector 402 connected to the second interface portion 311 of the control circuit board 310.

[0229] In addition, the interface circuit board 410 may further include a connector 404 electrically connected to a main control board of the thermal cycler. The connector 404 connecting the interface circuit board 410 to the main control board may include a power port and a communication port.

[0230] In addition, the interface unit 400 may be detachably coupled to the integrated module formed by combining the thermal unit 100, the cooling unit 200, and the control unit 300. In detail, the interface unit 400 may be detachably coupled to the first interface portion 141 and the second interface portion 311. To this end, the connection between the first interface portion 141 and the second interface portion 311, and the interface unit 400 may form a board-to-board connector, and may include a pin through hole or a magnetic structure for alignment.

[0231] According to an embodiment, the intermediate frame 30 of the thermal module 10 may come into thermal contact with the first heat sink 150 to function as a heat sink of the thermal block 110.

[0232] Referring to FIGS. 2, 6, and 7, the first heat sink 150 may include a body 152 that supports the thermal block 110, the first cooling fins 151 that extend downward from the body 152, and a flange portion 153 that protrudes and extends outward from the body 152. The flange portion 153 may be configured to protrude further outward than the thermal block 110 when viewed from above, and to protrude further outward than the first cooling fins 151 when viewed from below.

[0233] The intermediate frame 30 may include a body that forms a space that accommodates therein the body 152 of the first heat sink 150, an upper coupling portion that is coupled to the upper cover 20 at an upper portion of the body, and a lower coupling portion that is coupled to the lower cover 40 at a lower portion of the body. Here, the body of the intermediate frame 30 may be configured such that the outer side surface is positioned to be more inward than the outer side surfaces of the upper cover 20 and the lower cover 40. That is, the body of the intermediate frame 30 may be positioned more inward in the second direction (or the y-axis direction) than the upper cover 20 when viewed from above.

[0234] The flange portion 153 of the first heat sink 150 may be supported on the body of the intermediate frame 30. In addition, a heat transfer member 32 may be provided at a portion where the first heat sink 150 and the intermediate frame 30 come into thermal contact with each other. For example, the heat transfer member 32 may be provided between the upper surface of the body of the intermediate frame 30 and the flange portion 153 of the first heat sink 150.

[0235] The heat transfer member 32 may extend along the body of the intermediate frame 30. For example, the heat transfer member 32 may extend in the first direction (the x-axis direction in FIG. 1), which is the air flow direction of the duct 210. In addition, a pair of heat transfer members 32 may be provided on both sides of the duct 210, respectively.

[0236] The intermediate frame 30 may further include external cooling fins 31 protruding outward from the body. A plurality of external cooling fins 31 may be arranged side by side in the first direction, which is the air flow direction of the duct 210. In addition, the external cooling fins 31 may extend in the second direction (the y-axis direction in FIG. 1) that is perpendicular to the first direction. In addition, the external cooling fins 31 may be provided to extend in the second direction from one side surface of the body, but not to protrude further outward in the second direction than the side surface of the upper cover 20.

[0237] The intermediate frame 30 may include upper external cooling fins 31 and lower external cooling fins 31, which are arranged apart from each other in the vertical direction. The cooling efficiency may be increased by allowing air to flow through spaces between the upper external cooling fins 31 and the lower external cooling fins 31. In addition, the external cooling fins 31 may be provided away from the upper cover 20 or the upper coupling portion of the intermediate frame 30, and the cooling efficiency may be increased by allowing air to flow through a space provided above the external cooling fins 31. In addition, the external cooling fins 31 may be provided away from the lower cover 40 or the lower coupling portion of the intermediate frame 30, and the cooling efficiency may be increased by allowing air to flow through a space provided below the external cooling fins 31.

[0238] The control unit of the thermal cycler according to an embodiment may be provided as a modular component. For example, the thermal cycler may include a distributed control module. The control module of the thermal cycler may include an optical control module configured to control the optical module, a thermal control module configured to control the thermal module 10, a drive control module configured to control a drive unit, and an integrated control module configured to comprehensively control the optical control module, the thermal control module, and the drive control module.

[0239] As such, many advantages arise as the control modules are distributed in the respective modules that perform independent functions, and the integrated control module that integrates the distributed control modules is provided.

[0240] For example, by using control modules distributed from an integrated control module, replacement or repair may be easier in a case in which some modules have problems or require upgrades. In the related art, when replacing or repairing a thermal module, it is necessary to disassemble a thermal cycler device and then separate an integrated control board along with the thermal module. At this time, there is the hassle of having to disassemble and reassemble numerous interface portions connected to the integrated control board, and there are also frequent cases in which the entire integrated control board needs to be replaced.

[0241] However, in a case in which control modules distributed from an integrated control module are used, replacement and repair may be performed simply by separating only the thermal module and its control modules without the need to separate the integrated control module. In addition, reinstallation may be easily performed because only the connectors of the thermal control module and the integrated control module need to be reconnected.

[0242] FIGS. 10 is a diagram illustrating a configuration of a control unit of a thermal cycler.

[0243] Referring to FIG. 10, the control unit of the thermal cycler may include an integrated control module, an optical control module, and a thermal control module. In addition, although not illustrated in FIG. 10, a drive control module configured to control a mechanical operation of the thermal cycler may be further included.

[0244] The thermal control module may include the control circuit board 310 (see FIG. 7), a driver circuit board, the interface circuit board 410 (see FIG. 7), a thermal element connection circuit board 140 (see FIG. 7), a thermal block circuit board 120 (see FIG. 7), the heat sink circuit board 170 (see FIG. 7), a heat lid connection circuit board, and a heat lid circuit board.

[0245] The control circuit board and the driver circuit board may be provided as separate boards and then connected to each other, or may be included in a single board. In addition, in some cases, the term 'control circuit board' may be used to encompass a driver circuit board.

[0246] The control circuit board may be a control PCB. The control PCB may control and process all functions of the thermal module. For example, the control PCB may control thermal cycling, temperature gradients, and the temperature of the heat lid, detect and process a current, and detect and process a temperature. In addition, the control PCB may process data while communicating with the integrated control module, and perform synchronization while communicating with the optical control module. For example, the control PCB may include an Ethernet unit for communicating with the integrated control module.

[0247] In addition, the control PCB may include a microcontroller unit (MCU) and peripheral circuits. The control PCB may configure a TEC control circuit, a heat lid control circuit, and a cooling fan control circuit. In addition, the control PCB may be provided in a modular form to correspond one-to-one with the thermal module. Thus, the control PCB may be maintained in a state optimized for the thermal module, and may be replaced or repaired when the thermal module is replaced or repaired.

[0248] The driver circuit board may be a driver PCB. The driver PCB may drive the thermal module, drive a TEC for temperature gradient, drive the heat lid, detect a current, and be connected to the control PCB and an interface PCB.

[0249] In addition, the driver PCB may include a thermal module drive circuit, a thermal block FPCB drive circuit, a heat lid FPCB drive circuit, and a heating section separation circuit for controlling the temperature of each zone. In addition, the driver PCB may include a circuit capable of controlling a cooling fan.

[0250] The interface circuit board may be an interface PCB. The interface PCB may be connected to the driver PCB, the thermal element connection PCB, and the heat lid connection FPCB. In addition, the interface PCB may be connected to the optical control module and the integrated control module.

[0251] In addition, the interface PCB may configure a connection circuit that connects the driver PCB to the thermal element connection PCB. In addition, the interface PCB may configure a high-current connection circuit to supply power to the TEC, the thermal block FPCB, and the heat lid FPCB. In addition, the interface PCB may configure a circuit that is connected to the integrated control module and the optical module.

[0252] The thermal element connection circuit board, the thermal block circuit board, and the heat sink circuit board may constitute a thermal circuit board. The thermal element connection circuit board, the thermal block circuit board, and the heat sink circuit board may be provided as separate boards and then connected to each other, or may be included in a single board. In addition, the term 'thermal circuit board' may be used to encompass one or more of the thermal element connection circuit board, the thermal block circuit board, and the heat sink circuit board.

[0253] The thermal element connection circuit board may be a thermal element connection PCB (thermal element / temperature sensor connection PCB). The thermal element connection PCB may be connected to the TEC (Peltier), the thermal block FPCB, and the heat sink FPCB. In addition, the thermal element connection PCB may include a receiver configured to convert a temperature detection signal (analog) of a temperature sensor (thermistor) into a digital signal.

[0254] In addition, the thermal element connection PCB may configure a TEC connection circuit, a connector, a high-precision temperature detection circuit (e.g., an RTD), and a high-resolution temperature signal circuit (analog-to-digital conversion).

[0255] The thermal block circuit board may be a thermal block FPCB. The thermal block FPCB may generate heat in the thermal block and perform high-precision temperature detection. The thermal block FPCB may perform Joule heating through thermal resistance pattern design, may be equipped with an RTD, and may separate heating sections for temperature gradient control.

[0256] The thermal block FPCB may employ a film heater, a flexible heater, a Kapton heater, a polyimide (PI) heater, or the like.

[0257] In addition, the thermal block circuit board may be attached to the upper surface of the thermal block. In addition, a thermally conductive layer may be provided between the thermal block circuit board and the thermal block to increase thermal conductivity.

[0258] In addition, the thermal block circuit board may include apertures corresponding to the recesses of the thermal block. Thus, when the reaction vessel is mounted on the thermal block, the wells of the reaction vessel may penetrate the apertures formed in the thermal block circuit board.

[0259] In addition, the thermal block circuit board may include heating channels corresponding to the thermal zones of the thermal block. In addition, the thermal block circuit board may independently control each heating channel.

[0260] In the present specification, the term 'channel' may refer to an independent unit that transfers electronic information or electric energy. For example, a heating channel refers to a unit that may independently control a temperature, and a sensing channel refers to a unit that may independently detect a temperature.

[0261] According to an embodiment, the thermal block circuit board may include heating channels corresponding to the thermal zones of the thermal block. For example, in a case in which the thermal block is partitioned into six thermal zones, the thermal block circuit board may include six heating channels. In addition, each heating channel of the thermal block circuit board may include two block temperature sensors (thermistors), and the thermal block circuit board may configure a total of 12 block temperature sensors.

[0262] The block temperature sensor may be positioned adjacent to an edge of the thermal block. For example, the thermal block circuit board may configure two block temperature sensors for each heating channel, which measure the temperature at two opposite edges of the thermal block.

[0263] The heat sink circuit board may be a heat sink FPCB. The heat sink FPCB may detect the temperature of the heat sink to enhance the thermal efficiency and cooling efficiency of thermal cycling. In addition, the heat sink FPCB may configure a high-precision temperature detection circuit (e.g., an RTD).

[0264] In addition, the heat sink circuit board may be attached to the lower surface of the heat sink. In addition, a thermally conductive layer may be provided between the heat sink circuit board and the heat sink to increase thermal conductivity. In addition, the heat sink circuit board may be provided along the periphery of the first cooling fins 151 when viewed from below, and may be configured in a 'ㅁ' or 'ㄷ' shape.

[0265] In addition, the heat sink circuit board may include four sensing channels, each of which may be configured with a heat sink temperature sensor (thermistor) 171. For example, the heat sink circuit board may include four corner sensing channels to sense the temperature of the respective corners of the heat sink.

[0266] The heat lid circuit board and the heat lid connection circuit board may be provided as separate boards and then connected to each other, or may be included in a single board. In addition, in some cases, the term 'heat lid circuit board' may be used to encompass the heat lid circuit board and the heat lid connection circuit board.

[0267] The heat lid connection circuit board may be a heat lid connection FPCB. The heat lid connection FPCB may be connected to the heat lid FPCB and connected to the interface PCB. In addition, the heat lid connection FPCB may convert a temperature detection signal (analog) of the heat lid temperature sensor into a digital signal. In addition, the heat lid connection FPCB may configure a high-precision temperature detection circuit (e.g., an RTD) and a high-resolution temperature signal circuit (analog-to-digital conversion).

[0268] The heat lid circuit board may be a heat lid FPCB. The heat lid FPCB may be expected to reduce reagent evaporation by heating the heat lid. In addition, the heat lid FPCB may perform high-precision temperature detection. The heat lid FPCB may perform Joule heating through thermal resistance pattern design, and may be equipped with an RTD. In addition, the heat lid FPCB may separate heating sections for overheating control.

[0269] In addition, the heat lid circuit board may be provided at a position spaced upward from the upper surface of the thermal block. In addition, the heat lid circuit board may move relative to the thermal block to be closer or further away from the thermal block.

[0270] In addition, the heat lid circuit board may include apertures corresponding to the recesses of the thermal block. Thus, a passage may be configured through which excitation light is emitted toward the reaction vessel or through which light is emitted from the reaction vessel.

[0271] In addition, the heat lid circuit board may include heating channels corresponding to a central area and edge areas of the thermal block. For example, the heat lid circuit board may include five heating channels, including one center heating channel and four corner heating channels. In addition, the heat lid circuit board may independently control each heating channel.

[0272] In addition, each heating channel of the heat lid circuit board is configured with a heat lid temperature sensor (thermistor), and the heat lid circuit board may include a total of five heat lid temperature sensors. In the heat lid circuit board, the heating channels and the sensing channels may be set in the same manner.

[0273] Next, the thermal block FPCB 120 will be described with reference to FIG. 11 and the subsequent drawings.

[0274] FIG. 11 is a perspective view illustrating a thermal block FPCB, and FIG. 12 is a plan view of a thermal block FPCB. In addition, FIG. 13 is a cross-sectional view illustrating a state in which a thermal block FPCB is installed.

[0275] The thermal block 110 may include a plurality of recesses in which a plurality of wells of a reaction vessel are respectively accommodated. For example, the thermal block may include 96 recesses to accommodate 96 wells of a 96-well plate, respectively. In addition, the thermal block FPCB 120 provided on the upper surface of the thermal block 110 may include 96 apertures 123 corresponding to the recesses of the thermal block 110, respectively. The recesses of the thermal block 110 may be provided inside the apertures 123 of the thermal block FPCB 120.

[0276] In addition, the apertures 123 of the thermal block FPCB 120, the recesses of the thermal block 110, and the wells of the reaction vessel may be centered on the same point. For example, the apertures 123 of the thermal block FPCB 120, the recesses of the thermal block 110, and the wells of the reaction vessel may form concentric circles, and the radii of the circles may increase in the order of the wells of the reaction vessel, the recesses of the thermal block 110, and the apertures 123 of the thermal block FPCB 120.

[0277] In addition, the wells of the reaction vessel, the recesses of the thermal block 110, and the apertures 123 of the thermal block FPCB 120 may each be arranged in a matrix form in a plurality of rows and a plurality of columns. For example, in a case in which the reaction vessel is a 96-well plate, the matrix may be arranged with 8 rows and 12 columns.

[0278] The thermal block FPCB 120 may be attached to the upper surface of the thermal block 110. The thermal block FPCB 120 may be attached to the upper surface of the thermal block 110 by using a heat transfer material (e.g., a film, a pad, a tape, or an adhesive). Here, the upper surface of the thermal block 110 refers to a plane facing upward and does not mean the highest surface. In addition, the upper surface of the thermal block 110 to which the thermal block FPCB 120 is attached may be a flat surface other than recess areas.

[0279] The thermal block 110 may be in a form in which a portion of the area other than the recesses is recessed to reduce the mass or heat capacity. Here, the recessed portion may form a recessed surface that is on the same plane, and the thermal block FPCB 120 may be attached to the recessed surface. Alternatively, the thermal block 110 may have a raised protrusion forming a recess on the upper surface. The protrusion may include a portion of the shape of a cylinder or cone forming a recess having a circular cross-section. Here, the surfaces around the protrusion may form the same plane, and the thermal block FPCB 120 may be attached to the plane around the protrusion.

[0280] The thermal block FPCB 120 may be provided in a size suitable for covering all of the recesses of the thermal block 110. In an embodiment, the thermal block FPCB 120 may be provided as one FPCB around all recesses. Alternatively, the thermal block FPCB 120 may be provided in a size suitable for covering some of the recesses of the thermal block 110. In an embodiment, the thermal block FPCB 120 is provided as two or more FPCBs spaced apart from each other, and may not be provided around some recesses. Alternatively, the thermal block FPCB 120 may be provided as one FPCB in a size suitable for covering some of the recesses of the thermal block 110. In an embodiment, the thermal block FPCB 120 may include FPCBs that are positioned apart from each other, and a connection FPCB that connects the FPCBs to each other, and may not be provided around some recesses. For example, the thermal block FPCB 120 may include FPCBs provided at two opposite edges of the thermal block 110 facing away from each other in the column direction, and a connection FPCB connecting the FPCBs to each other in the column direction.

[0281] A connector 124 may be connected to one side of the thermal block FPCB 120. The connector 124 may have flexibility and may be connected to the thermal circuit board 140 provided at a height different from that of the thermal block FPCB 120. For example, the thermal circuit board 140 is positioned lower than the thermal block FPCB 120, and the connector 124 of the thermal block FPCB 120 may be bent downward to be connected to the upper surface of the thermal circuit board 140.

[0282] A plurality of thermoelectric elements 130 that are individually controlled independently of each other may be arranged side by side in one direction. For example, the thermoelectric elements 130 may be provided in a bar type with a length greater than a width, and may be arranged side by side in the widthwise direction. For example, six bar-type thermoelectric elements 130 may be arranged side by side in the widthwise direction.

[0283] The thermoelectric elements 130 may be attached to the lower surface of the thermal block 110. For example, the thermoelectric elements 130 may be attached to the lower surface of the thermal block 110 by using the first heat transfer member 161 (see FIG. 8). The thermoelectric elements 130 may be attached to the upper surface of the heat sink 150. For example, the thermoelectric elements 130 may be attached to the upper surface of the heat sink 150 by using the second heat transfer member 162 (see FIG. 8). The first and second heat transfer members 161 and 162 may be thermal pads.

[0284] The thermal pads 161 and 162 may be made of thin materials with excellent heat transfer properties. For example, the thermal pads may have a thickness of about 0.5 mm and a heat transfer rate of about 15 W / mK. In addition, products, which do not tear or wrinkle and thus provide ease of handling, may be used as the thermal pads. In addition, reusable products may be used as the thermal pads, for facilitating maintenance.

[0285] The first heat transfer member 161 may be provided as a single sheet having a shape corresponding to the thermal block 110. The upper surface of the first heat transfer member 161 may be attached to the lower surface of the thermal block 110, and a plurality of thermoelectric elements 130 may all be attached to the lower surface of the first heat transfer member 161. The first heat transfer member 161 may improve thermal uniformity by allowing heat transfer at a boundary between adjacent thermoelectric elements 130.

[0286] The second heat transfer member 162 may be provided as a plurality of sheets having a shape corresponding to a single thermoelectric element 130. The upper surface of the second heat transfer member 162 may be attached to the lower surface of the thermoelectric element 130, and the lower surface of the second heat transfer member 162 may be attached to the upper surface of the heat sink 150. The second heat transfer member 162 allows the thermoelectric elements 130 adjacent to each other to independently exchange heat with the heat sink 150. The second heat transfer members 162 adjacent to each other may be provided apart from each other.

[0287] The thermoelectric elements 130 may be arranged in the air flow direction, that is, in the extension direction of the duct 210. Hereinafter, the air flow direction is referred to as a longitudinal direction, and a direction perpendicular to the air flow direction is referred to as a lateral direction. In addition, compared to the directions of the matrix in which the wells of the reaction vessel are arranged, the longitudinal direction may correspond to the row direction, and the lateral direction may correspond to the column direction. Unless otherwise specified, directions are set based only on the horizontal direction, without considering the vertical direction.

[0288] The thermal block 110 may be partitioned into a plurality of thermal zones of which temperatures may be independently controlled. Each thermal zone may be a physically distinct area, or may be a virtual area that is distinct only in terms of control. For example, the thermal block 110 may provide thermal zones corresponding to the thermoelectric elements 130. Alternatively, the thermal block 110 may provide various thermal zones depending on the relative arrangement of the thermoelectric elements 130 and the heating channels of the thermal block FPCB 120.

[0289] In an embodiment, the thermal block 110 may provide a plurality of thermal zones corresponding to the thermoelectric elements 130, respectively. For example, in a case in which six thermoelectric elements 130 are arranged in the longitudinal direction and each thermal zone corresponds to one thermoelectric element 130, the thermal block 110 may also be partitioned into six thermal zones in the longitudinal direction.

[0290] In another embodiment, the thermal block 110 may provide thermal zones corresponding to a plurality of thermoelectric elements 130. For example, in a case in which six thermoelectric elements 130 are arranged in the longitudinal direction and each thermal zone corresponds to two thermoelectric elements 130, the thermal block 110 may be partitioned into three thermal zones in the longitudinal direction.

[0291] In another embodiment, the thermal block 110 may provide thermal zones corresponding to portions of one thermoelectric element 130. For example, in a case in which six thermoelectric elements 130 are arranged in the longitudinal direction and each thermoelectric element 130 corresponds to three thermal zones in the lateral direction, the thermal block 110 may be partitioned into a total of 18 thermal zones in six columns in the longitudinal direction and three rows in the lateral direction. Here, some of the thermal zones arranged in the lateral direction in one thermoelectric element 130 may correspond to the heating channels of the thermal block FPCB 120. The control unit independently controls the heating channels of the thermal block FPCB 120 to relatively control the temperatures of the thermal zones arranged in the lateral direction.

[0292] In addition to the embodiments described above, various thermal zones may be provided depending on the number and arrangement of thermoelectric elements 130 and the number and arrangement of heating channels of the thermal block FPCB 120.

[0293] The thermal block 110 may be controlled to ensure uniform temperature over the entire area. Here, 'uniform temperature' means that the temperature is maintained within a certain range. The control unit may measure the temperature of each thermal zone and control the thermoelectric elements 130 and / or the resistance heating elements corresponding to a thermal zone with a relatively low temperature to increase the temperature. Alternatively, by controlling the thermoelectric elements 130 corresponding to a thermal zone with a relatively high temperature, the temperature may be lowered.

[0294] In an embodiment, when a temperature difference occurs between thermal zones arranged in the longitudinal direction, the thermoelectric elements 130 may be individually controlled to uniformly control the temperature of the thermal block 110 in the longitudinal direction. For example, when the temperature of a thermal zone positioned at a peripheral portion in the longitudinal direction is lower than the temperature of a thermal zone positioned at a central portion, the temperatures may be uniformly controlled by relatively increasing the heating output of the thermoelectric elements 130 positioned at the peripheral portion in the longitudinal direction or relatively increasing the cooling output of the thermoelectric elements 130 positioned at the central portion in the longitudinal direction.

[0295] In addition, in a case in which a plurality of thermoelectric elements 130 are arranged in the lateral direction of the thermal block 110, the thermoelectric elements 130 may be individually controlled to uniformly control the temperature of the thermal block 110 in the lateral direction. However, in a case in which a single thermoelectric element 130 is provided in the lateral direction of the thermal block 110, there is a problem in that it is difficult to uniformize the temperature by using the thermoelectric elements 130 in the lateral direction of the thermal block 110.

[0296] There are several reasons why a temperature difference occurs in the lateral direction of the thermal block 110, but one of them is the edge effect in which heat loss is relatively greater at the periphery than at the center. For this reason, even when the thermal block 110 is heated by using the thermoelectric elements 130, the temperature of the periphery rises relatively slowly.

[0297] Another reason why a temperature difference occurs in the lateral direction of the thermal block 110 is efficiency gradients of the thermoelectric elements 130. The heat exchange efficiency of the thermoelectric elements 130 is highest at the center, and decreases toward the periphery. Because the width of the thermoelectric elements 130 is short in the longitudinal direction of the thermal block 110, the difference in heat exchange efficiency is not large, and because the thermoelectric elements 130 are arranged continuously in the longitudinal direction, the efficiency gradient in the longitudinal direction of the thermal block 110 is substantially linear. However, because the relative length of the thermoelectric elements 130 in the lateral direction of the thermal block 110 is long, an efficiency gradient occurs. Thus, when heating the thermal block 110 by using the thermoelectric elements 130, the heat exchange efficiency of the thermoelectric elements 130 is lower at the periphery than at the center in the lateral direction, and thus, the temperature at the periphery of the thermal block 110 in the lateral direction becomes lower than at the center.

[0298] The thermal module 10 according to an embodiment may include the thermal block FPCB 120 capable of partially heating the thermal block 110. The thermal module 10 may reduce the ramp rate by reducing the time required to make the temperature of the thermal block 110 uniform.

[0299] The thermal block FPCB 120 may include the resistance heating elements configured to heat the thermal block 110, and block temperature sensors 122 configured to detect the temperature of the thermal block 110.

[0300] The resistance heating element refers to an element that generates heat by Joule heating. For example, the resistance heating element may be an internal conductive heating element provided in an external insulator, and may form a pattern. In addition, the block temperature sensors 122 may be provided as RTDs or temperature sensors capable of linearly estimating a resistance value according to a temperature change.

[0301] FIGS. 14 is a graph showing resistance change values according to the temperature of an RTD and an NTC thermistor.

[0302] Both RTDs and NTC thermistors (hereinafter, referred to as NTCs) utilize the characteristics of resistance changing according to a temperature change. RTDs utilize the characteristic that resistance increases as temperature increases, and NTCs utilize the characteristic that resistance decreases as temperature increases.

[0303] RTDs utilize the characteristic of a metallic material where the resistance changes depending on the temperature, and may monitor the resistance to estimate the temperature in reverse. RTDs using metal materials may measure temperature with excellent precision over a significantly wide temperature range, offering advantages in terms of stability and repeatability. RTDs are mainly made of platinum, nickel, copper, tungsten, or the like.

[0304] RTDs exhibit linearity in resistance values in response to temperature changes. Here, linearity means that the values are not perfectly linear, but may be interpreted linearly by using various interpolation methods.

[0305] NTCs are also referred to as NTC thermistors. In addition, NTCs are typically made of ceramic metal oxide semiconductor materials, and the resistance-temperature characteristics vary depending on the type of materials used.

[0306] In general, resistance values of NTCs are not proportional to temperature changes, but show a curve. Thus, to measure a temperature by using an NTC, a data sheet using a simulation tool may be required.

[0307] In addition, when using a number of temperature sensors, RTDs have the advantage of facilitating calibration between sensors compared to NTCs. RTDs allow for easier calibration between multiple temperature sensors using linear interpolation from tests at fewer temperature points, while NTCs may exhibit different temperature-resistance characteristics between sensors, potentially requiring tests at more temperature points.

[0308] The thermal module 10 according to an embodiment has a plurality of thermoelectric elements 130 arranged in the longitudinal direction, and includes one or more block temperature sensors 122 corresponding to the thermoelectric elements 130, respectively. Here, the block temperature sensors 122 need to be mutually calibrated to reflect not only the deviation between the thermoelectric elements 130, but also the deviation between devices. The thermal module 10 has advantages in accuracy and convenience of calibration as it uses RTDs as the block temperature sensors 122.

[0309] The block temperature sensors 122 may be surface-mounted on the thermal block FPCB 120. The durability and stability of the block temperature sensor 122 may be improved by attaching, on the thermal block 110, the thermal block FPCB 120 having the block temperature sensors 122 surface-mounted thereon. Thus, there is no need to drill mounting holes on the thermal block 110 to mount the block temperature sensors 122. In detail, a lead wire of the block temperature sensor 122 may be soldered and connected to a soldering pad of the thermal block FPCB 120 in a state in which the bottom surface of the block temperature sensor 122 is fixed to the upper surface of the thermal block FPCB 120.

[0310] The thermal block FPCB 120 may include a double-layer structure. For example, the thermal block FPCB 120 may include, from the top, a top solder mask, a top layer, a core, a bottom layer, and a bottom solder mask. Here, the top layer and the bottom layer constitute a conductor layer made of metal such as copper. In addition, the solder mask and the core are made of insulating materials such as polyimide. The resistance heating elements and the block temperature sensors 122 are respectively connected to the top layer and the bottom layer to prevent mutual interference. For example, the resistance heating elements may be connected to the top layer, and the block temperature sensors 122 may be connected to the bottom layer.

[0311] In addition, the thermal block FPCB 120 may include a through hole penetrating the core. For example, the resistance heating elements are provided in the top layer, and the block temperature sensors 122 are attached on the top solder mask, but the lead wire of the block temperature sensors 122 may be connected to the bottom layer through the through hole. The thermal block FPCB 120 is not limited to the form described above, and may be provided with various circuit designs.

[0312] The resistance heating elements may include a plurality of heating channels that may be controlled independently of each other. The heating channel may be expressed as an area in which the resistance heating element is provided. In addition, in some cases, the resistance heating element and the heating channel may be used interchangeably, and may be assigned a common reference numeral.

[0313] In addition, in the thermal block FPCB 120, the resistance heating elements may be provided to heat the periphery of the thermal block relatively more than the center in the column direction. For example, the resistance heating elements may include edge heating channels configured to provide heat to the periphery of the thermal block 110 in the column direction, and extending in the row direction. In addition, the edge heating channels may be provided symmetrically on two opposite sides in the column direction.

[0314] The block temperature sensors 122 may be provided separately from each other so as not to overlap the resistance heating elements in a plane direction. That is, the block temperature sensors 122 may be mounted at points in the thermal block FPCB 120 at which the resistance heating elements are not provided. Because the block temperature sensors 122 are separated from the resistance heating elements in the plane direction, the temperature of the thermal block 110 may be measured more accurately. This is because, when the block temperature sensors 122 are positioned close to the resistance heating elements 121, it is difficult to measure the exact temperature of the thermal block 110 as heat generated from the resistance heating elements is directly transferred.

[0315] The block temperature sensors 122 may measure the temperatures of the thermal zones corresponding to the thermoelectric elements 130. According to an embodiment, two block temperature sensors 122 may be provided at mutually symmetrical positions in the lengthwise direction (the lateral direction or the column direction) of the thermoelectric element 130. In addition, the average of values measured by the two block temperature sensors 122 may be determined as the temperature of the thermal zones. According to another embodiment, one block temperature sensor 122 may be provided at the center in the lengthwise direction of the thermoelectric elements 130, and two block temperature sensors 122 may be provided at mutually symmetrical positions. In addition, the block temperature sensors 122 may measure the temperature of the center the thermal zones, and the temperatures of two opposite sides of the thermal zones, respectively.

[0316] The block temperature sensors 122 may be provided at two positions symmetrical with the center in the column direction. For example in a case in which the number of apertures 123 of the thermal block FPCB 120 in the column direction is 8, one block temperature sensor 122 is positioned at each of peripheral positions between the second and third apertures and between the sixth and seventh apertures, and thus, a total of two block temperature sensors 122 may be provided. In addition, a plurality of block temperature sensors 122 may be provided in the row direction and may be arranged at equal intervals. For example, in a case in which the number of apertures 123 in the thermal block FPCB 120 in the row direction is 12, one block temperature sensor 122 is positioned at each of peripheral positions between the first and second apertures, between the third and fourth apertures, between the fifth and sixth apertures, between the seventh and eighth apertures, between the ninth and tenth apertures, and between the eleventh and twelfth apertures, and thus, a total of six block temperature sensors 122 may be provided. That is, in a case in which the thermal block FPCB 120 is provided with 96 apertures 123, a total of 12 block temperature sensors 122 may be provided.

[0317] In addition, one block temperature sensor 122 may be positioned at the center of four adjacent apertures 123. Thus, the distances from the block temperature sensor 122 to the centers of the adjacent apertures 123 may be equal to each other. In detail, in a case in which the centers of four apertures 123 are arranged in a quadrangular shape, the block temperature sensor 122 may be provided at the intersection of two diagonals connecting the centers of the four apertures 123.

[0318] FIGS. 15A to 15F illustrate thermal block FPCBs according to various embodiments. Hereinafter, the inner and outer sides in the column direction are based on the center in the column direction, and the inner and outer sides in the row direction are based on the center in the row direction.

[0319] Referring to FIG. 15A, a thermal block FPCB 120-1 includes four edge heating channels 121-1 positioned at peripheral portions on both sides of the thermal block 110 in the column direction, and arranged on both sides with respect to the center in the row direction. The edge heating channels 121-1 may be provided to heat peripheral areas on both sides other than the center in the column direction of the thermal block 110, and to heat all areas in the row direction.

[0320] The thermal block FPCB 120-1 may independently control the four edge heating channels 121-1 on both sides in the column direction and both sides in the row direction according to values measured by the block temperature sensors 122. Each edge heating channel 121-1 may be positioned on an outer side in the column direction and may extend in the row direction.

[0321] The edge heating channels 121-1 may be provided in areas covering less than half of the distance from both edges to the center in the column direction, respectively. For example, in a case in which the number of apertures 123 of the thermal block FPCB 120-1 in the column direction is 8, the edge heating channel 121-1 may be provided in an area covering 1.5 apertures from the first aperture in the column direction.

[0322] The thermal block FPCB 120-1 may increase the temperature of both edges of the thermal block 110 in the column direction by flowing a current to the resistance heating elements of the edge heating channels 121-1. The thermal block FPCB 120-1 may independently control two edge heating channels 121-1 on both sides in the column direction by referring to values measured by the thermal block temperature sensors 122 in the column direction. For example, when the values measured by the block temperature sensors positioned above in the drawing is lower than the values measured by the block temperature sensors positioned below, the thermal block FPCB 120-1 may increase the current of the edge heating channels positioned above more than that of the edge heating channels positioned below, or may operate only the edge heating channels positioned above.

[0323] In addition, the two edge heating channels 121-1 arranged side by side in the column direction may be independently controlled by referring to values measured by the heat sink temperature sensors 171 to be described below.

[0324] The edge heating channels 121-1 may be provided in areas covering half of the distance from both edges to the center in the row direction, respectively. For example, in a case in which the number of apertures 123 of the thermal block FPCB 120-1 in the row direction is 12, the edge heating channel 121-1 may be provided in an area covering 6 apertures from the first aperture in the row direction.

[0325] The thermal block FPCB 120-1 may independently control two edge heating channels 121-1 on both sides in the row direction by referring to values measured by the thermal block temperature sensors 122 in the row direction. For example, in a case in which the average of values measured by three block temperature sensors positioned on the left side in the drawing is lower than the average of values measured by three block temperature sensors positioned on the right side, the thermal block FPCB 120-1 may increase the current of the edge heating channels positioned on the left side more than that of the edge heating channels positioned on the right side, or may operate only the edge heating channels positioned on the left side.

[0326] In addition, two edge heating channels 121-1 arranged side by side in the row direction may be independently controlled by referring to values measured by the heat sink temperature sensors 171 and air temperature sensors 172 to be described below. In particular, the edge heating channels 121-1 may be individually controlled by utilizing the difference in values measured by the air temperature sensors 172 positioned on both sides in the row direction.

[0327] In addition, the edge heating channels 121-1 may be provided not to overlap the block temperature sensors 122. The block temperature sensor 122 may be positioned between the second and third apertures in the column direction, and may also be positioned between adjacent apertures in the row direction. In this case, the edge heating channel 121-1 is provided to cover an area from an edge in the column direction to the center of the second aperture, so as not to overlap the block temperature sensors 122.

[0328] Referring to FIG. 15B, a thermal block FPCB 120-2 includes two edge heating channels 121-2 positioned at peripheral positions on both sides of the thermal block 110 in the column direction, respectively.

[0329] The edge heating channels 121-2 may extend to cover all apertures 123 in the row direction. For example, in a case in which the number of apertures 123 of the thermal block FPCB 120-2 in the row direction is 12, the edge heating channel 121-2 may be provided in an area covering 12 apertures from the first aperture in the row direction.

[0330] The thermal block FPCB 120-2 may independently control two edge heating channels 121-2 on both sides in the column direction according to values measured by the block temperature sensors 122.

[0331] Referring to FIG. 15C, a thermal block FPCB 120-3 includes edge heating channels 121-1 positioned at peripheral portions on both sides of the thermal block 110 in the column direction, and arranged on both sides with respect to the center in the row direction, and a central heating channel 121-3 covering an area between the edge heating channels 121-1. The central heating channel 121-3 may extend in the row direction. The central heating channel 121-3 may heat a central area between the block temperature sensors 122 on both sides in the column direction, and the edge heating channels 121-1 may heat outer areas of the block temperature sensors 122 on both sides in the column direction.

[0332] The edge heating channels 121-1 may be provided in areas covering half of the distance from both edges to the center in the row direction, respectively. For example, in a case in which the number of apertures 123 of the thermal block FPCB 120-3 in the row direction is 12, the edge heating channel 121-1 may be provided in an area covering 6 apertures from the first aperture in the row direction.

[0333] The thermal block FPCB 120-3 may independently control the central heating channel 121-3 and the four edge heating channels 121-1 by referring to values measured by the block temperature sensors 122.

[0334] Referring to FIG. 15D, a thermal block FPCB 120-4 includes two edge heating channels 121-2 positioned at peripheral positions on both sides of the thermal block 110 in the column direction, respectively, and the central heating channel 121-3 covering an area between the edge heating channels 121-2. The central heating channel 121-3 may extend in the row direction. The central heating channel 121-3 may heat a central area between the block temperature sensors 122 on both sides in the column direction, and the edge heating channels 121-2 may heat outer areas of the block temperature sensors 122 on both sides in the column direction.

[0335] The edge heating channels 121-2 may extend to cover all apertures 123 in the row direction. For example, in a case in which the number of apertures 123 of the thermal block FPCB 120-4 in the row direction is 12, the edge heating channel 121-2 may be provided in an area covering 12 apertures from the first aperture in the row direction.

[0336] The thermal block FPCB 120-4 may independently control the central heating channel 121-3 and the two edge heating channels 121-2 by referring to values measured by the block temperature sensors 122.

[0337] Referring to FIG. 15E, a thermal block FPCB 120-5 includes edge heating channels 121-1 positioned at peripheral portions on both sides of the thermal block 110 in the column direction, and arranged on both sides with respect to the center in the row direction, and central heating channels 121-4 covering an area between the edge heating channels 121-1 in the column direction, and arranged on both sides with respect to the center in the row direction. The central heating channels 121-4 may heat a central area between the block temperature sensors 122 on both sides in the column direction, and the edge heating channels 121-1 may heat outer areas of the block temperature sensors 122 on both sides in the column direction.

[0338] The thermal block FPCB 120-5 may independently control the two central heating channels 121-4 and the four edge heating channels 121-1 by referring to values measured by the block temperature sensors 122.

[0339] Referring to FIG. 15F, three block temperature sensors 122 may be provided in the column direction. For example, in a case in which the number of apertures 123 of a thermal block FPCB 120-6 in the column direction is 8, one block temperature sensor 122 is positioned at each of peripheral positions between the second and third apertures, between the fourth and sixth apertures, and between the sixth and seventh apertures, and thus, a total of three block temperature sensors 122 may be provided.

[0340] Among the three block temperature sensors 122 arranged in the column direction, the block temperature sensor at the center indicates the temperature of a central portion of the thermal block 110, and the block temperature sensors positioned on both sides indicate the temperatures of peripheral portions of the thermal block 110. There is an advantage in that more accurate temperature data may be obtained by comparing a value measured by the block temperature sensor positioned at the center in the column direction with values measured by the block temperature sensors positioned on both sides.

[0341] Next, a heat sink circuit board will be described.

[0342] FIG. 16 is a side view of a thermal unit according to another embodiment, and FIG. 17 is a perspective view illustrating a thermal unit according to another embodiment, as viewed from below.

[0343] Referring to FIGS. 16 and 17, a thermal unit 100-1 according to another embodiment includes the thermal block 110 and the heat sink 150 positioned below the thermoelectric elements 130.

[0344] The heat sink 150 may include the body 152 (see FIG. 7) that supports the thermal block 110, the cooling fins 151 that extend downward from the body 152, and the flange portion 153 that protrudes and extends outward from the body 152.

[0345] The body 152 includes a shape protruding upward from the flange portion 153. The upper surface of the body 152 may be in thermal contact with the thermoelectric elements 130 (see FIG. 7). In addition, the second heat transfer member 162 (see FIG. 8) is provided between the body 152 and the thermoelectric elements 130 to increase the heat transfer rate. The height at which the body 152 protrudes above the flange portion 153 may be related to the heat capacity of the heat sink 150, and may be set to an optimal height for reducing the ramp rate.

[0346] The thermal circuit board 140 may be provided to surround the periphery of the body 152. The thermal circuit board 140 may be configured to have a space formed therein, and the body 152 may be accommodated in the space. An insulator may be arranged between the thermal circuit board 140 and the body 152, or may be positioned apart from the thermal circuit board 140 and the body 152.

[0347] According to an embodiment, the thermal circuit board 140 may be fixed to the heat sink 150 via a heat sink guide 142. The heat sink guide 142 may be made of an insulating material to block heat transfer between the heat sink 150 and the thermal circuit board 140. The heat sink guide 142 may be provided to surround the body 152, and one side of the heat sink guide 142 may be fixed to the heat sink 150.

[0348] The thermal circuit board 140 may be positioned above the flange portion 153. When viewed from above, the internal space of the thermal circuit board 140 may be positioned further inward than the flange portion 153. According to an embodiment, the heat sink guide 142 may be fixed to an upper portion of the flange portion 153, and the thermal circuit board 140 may be fixed to an upper portion of the heat sink guide 142.

[0349] According to an embodiment, the heat sink guide 142 may be arranged between the thermal circuit board 140 and the heat sink 150. The heat sink guide 142 may be arranged between the thermal circuit board 140 and the body 152 in the horizontal direction, and the heat sink guide 142 may be arranged between the thermal circuit board 140 and the flange portion 153 in the vertical direction.

[0350] The flange portion 153 may be configured to protrude further outward than the thermal block 110 when viewed from above, and to protrude further outward than the cooling fins 151 when viewed from below. The thermal circuit board 140 may be fixed above the flange portion 153 via the heat sink guide 142, and the heat sink circuit board 170 may be fixed below the flange portion 153.

[0351] FIG. 18 is a perspective view illustrating a heat sink circuit board according to an embodiment, and FIG. 19 is a perspective view illustrating a state in which a heat sink circuit board is installed in a heat sink, according to an embodiment.

[0352] Referring to FIGS. 18 and 19, the heat sink 150 may be equipped with the heat sink temperature sensors 171 and the air temperature sensors 172.

[0353] The heat sink temperature sensors 171 may measure the temperature of the heat sink 150. A plurality of heat sink temperature sensor 171 may be provided at positions symmetrical to each other with respect to the center of the cooling fins 151 or a straight line passing through the center of the cooling fins 151, when viewed from below. According to an embodiment, four heat sink temperature sensors 171 may be provided to measure the temperatures of four position of the heat sink 150. For example, the heat sink temperature sensors 171 may be positioned at four corners of a quadrangle centered on the center of the cooling fins 151. The quadrangle may be a rectangle with the air flow direction in the longitudinal direction, or a rhombus with the air flow direction in the diagonal direction.

[0354] The control unit may determine the temperature of the heat sink 150 by calculating the average of values measured by the four heat sink temperature sensors 171. Alternatively, when values measured by any one heat sink temperature sensor 171 differs by a reference range or greater from the average of values measured by the other three heat sink temperature sensors 171, the average of the values measured by the other three heat sink temperature sensors 171 may be determined as the temperature of the heat sink 150, excluding the value measured by the corresponding heat sink temperature sensor 171.

[0355] The control unit may preheat the heat sink 150 by operating the thermoelectric elements 130 until the temperature of the heat sink 150 measured by using the heat sink temperature sensors 171 reaches a starting temperature (e.g., 35 °C).

[0356] The control unit may predict a temperature gradient of the heat sink 150 through the distribution of temperatures of the heat sink 150 measured by using the four heat sink temperature sensors 171. For example, the control unit may predict the temperature gradient of the heat sink 150 assuming that the distribution of temperatures of the heat sink 150 is linear. Alternatively, the control unit may store information about a temperature gradient of the heat sink 150 that is actually measured during a calibration process of a device, and use the information and temperatures measured by the heat sink temperature sensors 171 to predict the temperature gradient of the heat sink 150.

[0357] According to an embodiment, the heat sink temperature sensors 171 may be provided on both sides in the longitudinal direction, which is the air flow direction, respectively. For example, a first heat sink temperature sensor may measure the temperature of the heat sink 150 on the inlet side where air is introduced, and a second heat sink temperature sensor may measure the temperature of the heat sink 150 on the outlet side where air is discharged.

[0358] According to an embodiment, the heat sink temperature sensors 171 may be provided on both sides in the lateral direction that is perpendicular to the air flow direction, respectively. For example, a first heat sink temperature sensor may measure the temperature of the heat sink 150 on the left side in the air flow direction, and a second heat sink temperature sensor may measure the temperature of the heat sink 150 on the right side in the air flow direction.

[0359] According to an embodiment, the heat sink temperature sensors 171 may be provided on both sides in the longitudinal direction, which is the air flow direction, and on both sides in the lateral direction, which is perpendicular to the longitudinal direction, respectively. For example, first and second heat sink temperature sensors may measure the temperatures of the heat sink 150 on the left and right sides of the inlet side where air is introduced, respectively, and third and fourth heat sink temperature sensors may measure the temperatures of the heat sink 150 on the left and right sides of the outlet side where air is discharged, respectively.

[0360] The control unit may use, for thermal control, temperatures for respective zones measured by the heat sink temperature sensors 171, and the temperature gradient of the heat sink 150. In detail, according to temperatures of respective zones of the heat sink 150 that are measured by the heat sink temperature sensors 171, and temperature gradients of the zones, the control unit may operate the heating elements and 130 corresponding to the respective zones to supplement heating and / or cooling of the thermal block 110.

[0361] Hereinafter, control performed in a case in which the heating elements and 130 is operating normally but the temperatures of the respective zones of the heat sink 150 vary depending on the shape of the heat sink 150 and external conditions will be described. On the contrary, when the heating elements and 130 are determined as not operating normally, an error code may be displayed and the device may wait for repair.

[0362] According to an embodiment, in an operation of heating the thermal block 110, the heating elements and 130 corresponding to a portion of the heat sink 150 where the temperature is relatively low may be operated to supplement the heating. For example, in an operation of heating the thermal block 110, the output of the thermoelectric elements 130 corresponding to a portion of the heat sink 150 where the temperature in the longitudinal direction is relatively low may be increased to uniformly heat the thermal block 110 in the longitudinal direction. Alternatively, in the operation of heating the thermal block 110, the output of the resistance heating element corresponding to a portion of the heat sink 150 where the temperature in the lateral direction is relatively low may be increased to uniformly heat the thermal block 110 in the lateral direction.

[0363] According to an embodiment, in an operation of cooling the thermal block 110, the heating elements and 130 corresponding to a portion of the heat sink 150 where the temperature is different from those of other portions may be operated to supplement uniform cooling. For example, in an operation of cooling the thermal block 110, the output of the thermoelectric elements 130 corresponding to a portion of the heat sink 150 where the temperature in the longitudinal direction is relatively high may be increased to uniformly cool the thermal block 110 in the longitudinal direction. Alternatively, in the operation of cooling the thermal block 110, the output of the resistance heating element corresponding to a portion of the heat sink 150 where the temperature in the lateral direction is relatively low may be increased to uniformly cool the thermal block 110 in the lateral direction.

[0364] The air temperature sensors 172 may measure the temperature of air around the cooling fins 151. For example, two air temperature sensors 172 may be provided, wherein a first air temperature sensor measures the temperature of air that has not been introduced into the cooling fins 151, and a second air temperature sensor measures the temperature of air being discharged after passing through the cooling fins 151.

[0365] The air temperature sensors 172 may be positioned at the center of the cooling fins 151 in the vertical direction and the horizontal direction, when viewed from the side. For example, the air temperature sensors 172 may be positioned in a middle region between the upper ends and the lower ends of the cooling fins 151 in the vertical direction, and in the middle of the cooling fins 151 on both sides in the horizontal direction. Here, the middle generally refers to a point or area that is at the same distance from the left and right, and the middle region may be defined as a larger area that includes the middle. Alternatively, the air temperature sensors 172 may be positioned in the middle of the cooling fan 220 (see FIG. 4) and thus in the middle of the air flow cross-section.

[0366] The air temperature sensors 172 may be connected via a conductive wire. In an embodiment, the air temperature sensors 172 may be mounted hanging downward and connected to the heat sink circuit board 170 that is attached to the heat sink 150, via wires.

[0367] The control unit may use, for thermal control, temperatures of air on both sides of the heat sink 150 that are measured by the air temperature sensors 172.

[0368] According to an embodiment, the control unit may measure temperatures around the cooling fins 151 by using the air temperature sensors 172, before starting thermal control. At this time, the temperatures of air measured by the air temperature sensors 172 are equal to the temperature sensor of outside air. The control unit may control the output of the thermoelectric elements 130 and the cooling fan 220 depending on whether the temperature of the outside air is higher or lower than a set range.

[0369] According to an embodiment, the control unit may measure temperatures around the cooling fins 151 by using the air temperature sensors 172, while performing thermal control. The control unit may control the output of the thermoelectric elements 130 and the cooling fan 220 by using the magnitudes and relative difference between an inlet-side temperature and an outlet-side temperature of the cooling fins 151. For example, in the operation of cooling the thermal block 110, when the outlet-side temperature of the cooling fins 151 is greater than a reference range, or the difference between the outlet-side temperature and the inlet-side temperature is greater than a reference range, the control unit may increase the output of the thermoelectric elements 130 or the cooling fan 220.

[0370] The control unit may use, for thermal control, the difference between the temperature of the heat sink 150 that is measured by the heat sink temperature sensors 171 and the temperature of the outside air that is measured by the air temperature sensors 172.

[0371] According to an embodiment, in the operation of heating the thermal block 110, when the temperature of the outside air is higher than the temperature of the heat sink 150, the control unit may increase the output of the cooling fan 220. Alternatively, in the operation of cooling the thermal block 110, when the temperature of the outside air is higher than the temperature of the heat sink 150, the control unit may decrease the output of the cooling fan 220.

[0372] According to an embodiment, in the operation of heating the thermal block 110, when the temperature of the outside air is lower than the temperature of the heat sink 150, the control unit may decrease the output of the cooling fan 220. Alternatively, in the operation of cooling the thermal block 110, when the temperature of the outside air is lower than the temperature of the heat sink 150, the control unit may increase the output of the cooling fan 220.

[0373] The heat sink circuit board 170 may be attached to the heat sink 150, and the heat sink temperature sensors 171 and the air temperature sensors 172 may be mounted on the heat sink circuit board 170. In addition, the heat sink circuit board 170 may be connected to the thermal circuit board 140. The heat sink circuit board 170 may be provided as a PCB or an FPCB. The heat sink circuit board 170 provided as a PCB may have a flexible connector connected to one side thereof, and the flexible connector may be connected to the thermal circuit board 140 positioned at a different height. Alternatively, one side of the heat sink circuit board 170 provided as an FPCB may be bent to be connected to the thermal circuit board 140 positioned at a different height.

[0374] The heat sink circuit board 170 may be directly or indirectly connected to the heat sink 150. According to an embodiment, the heat sink circuit board 170 may be fixed to the lower surface of the flange portion 153 that protrudes outward from an upper portion of the cooling fins 151. In addition, the heat sink circuit board 170 may be attached to the heat sink 150 by using an insulating tape or an insulating adhesive.

[0375] The heat sink temperature sensors 171 may be RTDs or NTCs mounted on the heat sink circuit board 170, and the air temperature sensors 172 may be NTCs connected to the heat sink circuit board 170 via a metal wire. The air temperature sensors 172 may extend downward in the direction of gravity from the heat sink circuit board 170 with a metal wire, to measure the temperature of air. For example, the height of the air temperature sensors 172 may correspond to a central position of the cooling fan 220 (see FIG. 1) that sucks in or discharges air.

[0376] The heat sink circuit board 170 may be formed in a "ㄷ" shape. For example, the flange portion 153 may protrude from four sides of the cooling fins 151, and the heat sink circuit board 170 may be attached to the bottom of three of the four surfaces of the flange portion 153.

[0377] The heat sink circuit board 170 may include a front portion positioned at the front of the heat sink 150 in the longitudinal direction, a rear portion positioned at the rear of the heat sink 150 in the longitudinal direction, a side portion connecting the front portion to the rear portion, and an interface portion connected to the thermal circuit board 140.

[0378] Two heat sink temperature sensors 171 and one air temperature sensor 172 may be mounted on each of the front portion and the rear portion of the heat sink circuit board 170. The air temperature sensors 172 may be positioned at the center of the heat sink 150 in the lateral direction, and the heat sink temperature sensors 172 may be positioned symmetrically at a certain distance to the left and right from the center of the heat sink 150 in the lateral direction.

[0379] The interface portion may connect the heat sink circuit board 170 positioned lower than the thermal circuit board 140, to the thermal circuit board 140. For example, the interface portion is bent upward at an outer edge of the heat sink circuit board 170, extends to the lower surface of the thermal circuit board 140, and then is bent outward to extend in a plane direction along the lower surface of the thermal circuit board 140. In addition, the interface portion may be electrically connected to a connector provided on the lower surface of the thermal circuit board 140.

[0380] FIGS. 20A to 20D are plan views illustrating heat lid circuit boards according to various embodiments.

[0381] The thermal cycler includes a heat lid assembly. Hereinafter, the heat lid assembly may be referred to as a heat lid.

[0382] The heat lid assembly includes a thermally conductive layer that may come into contact with the upper surface of the reaction vessel, a heating layer provided above the thermally conductive layer to provide heat, and an insulating layer provided above the heating layer and made of an insulating material.

[0383] The relative distance between the heat lid and the thermal block in the vertical direction may vary. For example, when mounting or detaching the reaction vessel on or from the thermal block, the heat lid and the thermal block move away from each other, and after the reaction vessel is seated on the thermal block, the heat lid and the thermal block move closer to each other such that the thermally conductive layer of the heat lid may come into contact with the upper surface of the reaction vessel. In addition, even after the heat lid comes into contact with the upper surface of the reaction vessel, a force may be applied in the direction toward the reaction vessel, thereby providing pressure to the reaction vessel.

[0384] According to an embodiment, the thermal cycler may be provided such that the thermal block moves up and down in a state in which the heat lid is fixed. As the thermal block moves down and thus the gap between the thermal block and the heat lid increases, the reaction vessel may be seated on the thermal block. In addition, after the reaction vessel is seated on the thermal block, the thermal block moves up and comes into contact with the thermally conductive layer of the heat lid, such that heat from the heat lid may be transferred to the reaction vessel. Furthermore, pressure may be provided to the reaction vessel as a force is applied in the direction in which the thermal block moves up. In addition, after a reaction in the reaction vessel is terminated, the thermal block moves down, widening the gap between the thermal block and the heat lid and allowing the reaction vessel to be detached in the corresponding space.

[0385] The thermally conductive layer may be made of a material with high thermal conductivity, for example, metal. Preferably, the thermally conductive layer may be made of aluminum or an alloy containing aluminum.

[0386] The thermally conductive layer may include apertures that may transmit excitation light transmitted to the reaction vessel, or light emitted from the reaction vessel. The apertures of the thermally conductive layer may correspond to the recesses of the thermal block. In addition, the heating layer may include apertures corresponding to the apertures of the thermally conductive layer, and the apertures of the heating layer may be provided in the same shape as the apertures of the thermally conductive layer or in a shape suitable for receiving the apertures of the thermally conductive layer therein.

[0387] The heating layer may be provided as a heat lid FPCB, and may be attached to the upper surface of the thermally conductive layer. The heat lid FPCB may employ a film heater, a flexible heater, a Kapton heater, a polyimide (PI) heater, or the like.

[0388] The heat lid FPCB may include a resistance heating element configured to heat the thermally conductive layer, and a heat lid temperature sensor configured to detect the temperature of the thermally conductive layer.

[0389] The resistance heating element refers to an element that generates heat by Joule heating. For example, the resistance heating element may be an internal conductive heating element provided in an external insulator, and may form a pattern. In addition, the heat lid temperature sensor may be provided as an RTD or a temperature sensor capable of linearly estimating a resistance value according to a temperature change.

[0390] The heat lid FPCB may include the features of the thermal block FPCB described above, and redundant descriptions will be omitted.

[0391] The heat lid FPCB may include a central heating channel and a peripheral heating channel that are independently controllable. The central heating channel and the peripheral heating channel may each include a resistance heating element and a temperature sensor. The heat lid FPCB may include zones classified as central portions and peripheral portions, and may measure the temperature of each zone and independently heat each zone.

[0392] The peripheral heating channel may be heated at a temperature equal to or higher than that of the central heating channel. The thermally conductive layer of the heat lid has a relatively small heat capacity compared to the thermal block, and thus supplies heat quickly, but also losses a large amount of heat. When the central portion and the peripheral portions of the heat lid are heated at the same temperature, the temperature of the peripheral portions becomes lower than that of the central portion over time. When sufficient heat is not transferred to an upper portion of the reaction vessel positioned around the thermal block, condensation may occur within the reaction vessel, which may result in distortion or loss of an optical signal. When the temperature of the entire heat lid is set high to solve the problem of temperature decrease due to loss of heat around the heat lid, the center of the heat lid may be overheated, causing problems such as the reaction vessel melting and sticking to the thermally conductive layer, or damage to the heat lid FPCB.

[0393] According to an embodiment, the heat lid FPCB may independently control the central heating channel and the peripheral heating channel to set the temperature of the peripheral heating channel to be higher than the temperature of the central heating channel. Thus, it is possible to prevent the central portion of the heat lid from overheating while transferring sufficient heat to the reaction vessel positioned around the thermal block.

[0394] In addition, the heat lid FPCB may complement the thermal block FPCB to achieve thermal uniformity of the thermal block. Because the thermal block has a large heat capacity, it is difficult to change the temperature of the thermal block quickly. On the contrary, the thermally conductive layer of the heat lid has a relatively small heat capacity, and thus, it is possible to increase the temperature of the thermally conductive layer quickly. Thus, when the temperature of a peripheral portion of the thermal block is lower than that at the central portion, insufficient heat of the reaction vessel may be supplemented through the peripheral heating channel of the heat lid FPCB.

[0395] The central heating channel and the peripheral heating channel of the heat lid FPCB may be divided into one or more heating channels. In addition, each peripheral heating channel may include a resistance heating element and a temperature sensor.

[0396] The resistance heating element may be arranged to surround an aperture of the heating layer. The resistance heating element may include a heating wire pattern, and the heating wire pattern may be arranged to surround the aperture of the heating layer.

[0397] The thermal cycler according to an embodiment of the present specification may uniformly transfer heat to reaction vessels arranged in rows and columns in recesses of the thermal block, by using the thermal block FPCB and the heat lid FPCB.

[0398] The thermal block FPCB includes first apertures corresponding to some or all of the recesses of the thermal block, and the heat lid FPCB includes second apertures corresponding to some or all of the recesses of the thermal block, wherein the recesses, the first apertures, and the second apertures are aligned in a vertical direction. A reaction vessel is accommodated in the first aperture and the recess, excitation light from the optical module is received in the reaction vessel through the second aperture, and light emitted from a sample is emitted toward the detection module through the second aperture.

[0399] The thermoelectric elements are arranged below the thermal block in the row direction, and one thermoelectric element covers the recesses of the thermal block in the column direction. In addition, the heat sink and the duct are arranged below the thermoelectric elements, and the duct, which provides a flow passage for air passing through the cooling fins of the heat sink, allows air to flow in the row direction of the thermal block.

[0400] The thermal block FPCB includes the resistance heating elements that constitutes a block heating channel, and the resistance heating elements are provided such that peripheral portions of the thermal block may be heated relatively more than a central portion in the column direction of the first apertures. In addition, the heat lid FPCB includes the resistance heating elements that constitute a heat lid heating channel, and the resistance heating elements are provided such that peripheral reaction vessels may be heated relatively more than a central reaction vessel in the row direction and the column direction of the second apertures.

[0401] The thermal block does not have a large temperature difference in the row direction as heat is transferred by the flow of air passing through the duct that extends in the row direction. However, in the column direction, heat loss occurs at the peripheral portions, and thus, the temperatures of the peripheral portions become lower than that of the central portion. The resistance heating elements of the thermal block FPCB may configure edge heating channels positioned on two opposite outer edges of the thermal block in the column direction, to increase the temperatures of the peripheral portions more than that of the central portion. Thus, the loss of heat around the thermal block in the column direction may be complemented, such that the temperature may be uniform in the column direction.

[0402] In addition, since heat loss occurs in the heat lid in both the column direction and the row direction, the temperatures of upper, lower, left, and right peripheral portions become lower than that of the central portion. The resistance heating elements of the heat lid FPCB may compensate for heat loss by configuring the peripheral heating channels surrounding an edge of the heat lid.

[0403] In FIGS. 20A to 20D, the dotted lines are virtual lines indicating areas where the resistance heating elements are provided, and the actual resistance heating elements are provided around the apertures. In addition, although the boundary between the central heating channel and the peripheral heating channels is expressed as a straight line in the drawings, the central heating channel and the peripheral heating channels may include shapes that intersect each other in a straight line direction within a range where they do not overlap each other.

[0404] The temperature sensors may be positioned not to overlap the resistance heating elements. The temperature sensor of the central heating channel may be positioned between four apertures positioned at the center of the heating layer. The temperature sensor of the peripheral heating channel may be positioned on an outer side of the aperture positioned at a corner of the heating layer, and may be positioned on an outer side of the resistance heating element.

[0405] The peripheral heating channels may be arranged to surround the central heating channel. The peripheral heating channels may be positioned at four sides surrounding the central heating channel. The heat lid FPCB according to an embodiment may include one central heating channel and four peripheral heating channels that are symmetrical to each other. For example, four peripheral heating channels may be positioned at four corners of the heating layer, and arranged in shapes symmetrical to each other.

[0406] Referring to FIG. 20A, the heat lid FPCB according to an embodiment may include a central heating channel having a quadrangular shape. Hereinafter, the shape of a heating channel refers to the approximate shape of an area where the heating channel is provided, and the shape of the actual heating channel may be freely configured.

[0407] In addition, peripheral heating channels may be provided to cover four zones defined by the outer edges of the central heating channel, and a virtual lateral center extension line and a virtual longitudinal center extension line of the central heating channel.

[0408] In a case in which the reaction vessel is a multi-well plate provided with wells in a plurality of rows and a plurality of columns, the heat lid FPCB according to an embodiment includes a plurality of apertures corresponding to the wells of the reaction vessel. The central heating channel may be provided in a rectangular shape that covers the apertures in at least half of the total rows and at least two-thirds of the total columns.

[0409] In a case in which the reaction vessel is a 96-well plate provided with wells in 8 rows and 12 columns, the heat lid FPCB according to an embodiment includes 96 apertures corresponding to the wells of the reaction vessel. The central heating channel may be provided in a rectangular shape that covers the apertures in four rows and eight columns in the center. In addition, four peripheral heating channels may be provided that are distinguished from each other by dividing the 96-well plate into four parts in the lateral direction and the longitudinal direction with respect to the center of the 96-well plate. For example, the peripheral heating channel may be provided to include two inner apertures in the row direction, and two inner apertures in the column direction.

[0410] According to an embodiment, in the heat lid FPCB, the peripheral heating channels may be provided in wider areas than the central heating channel. In a case in which the peripheral heating channel includes a plurality of peripheral heating channels, the sum of the areas of the plurality of peripheral heating channels is greater than the area of the central heating channel.

[0411] Referring to FIG. 20B, the heat lid FPCB according to another embodiment may be provided such that the boundary between the central heating channel and the peripheral heating channels passes through the apertures. The apertures positioned on the boundary between the central heating channel and the peripheral heating channels may have its inner side heated by the central heating channel and its outer side heated by the peripheral heating channels. By setting the boundary between the central heating channel and the peripheral heating channels in this manner, the temperature difference between the apertures in contact with the boundary may be reduced. For example, the peripheral heating channel may be provided to include 1.5 inner apertures in the row direction, and 1.5 inner apertures in the column direction.

[0412] Referring to FIG. 20C, the heat lid FPCB according to another embodiment may include a central heating channel having a circular or elliptical shape. In addition, peripheral heating channels may be provided to cover four zones defined by the outer edges of the central heating channel, and a virtual lateral center extension line and a virtual longitudinal center extension line of the central heating channel. For example, the peripheral heating channel may be provided to include two or more inner apertures in the row direction, and two or more inner apertures the column direction, and may be provided to include three or more inner apertures in a diagonal direction, or such that the boundary passes through the boundary of the third aperture.

[0413] In addition, the heat lid FPCB according to another embodiment may be arranged such that the boundary between the central heating channel and the peripheral heating channels passes through some apertures.

[0414] Referring to FIG. 20D, the heat lid FPCB according to another embodiment may include central heating channels in two or more stages. The central heating channels may include a first central heating channel provided in a smaller quadrangular shape, and a second central heating channel provided in a larger quadrangular shape that includes the first central heating channel. For example, the first central heating channel may be provided to include two apertures in the column direction and four apertures in the row direction, and the second central heating channel may be provided to include eight or more apertures in the column direction and four or more apertures in the row direction.

[0415] In addition, peripheral heating channels may be provided to cover four zones defined by the outer edges of the second central heating channel, and a virtual lateral center extension line and a virtual longitudinal center extension line of the second central heating channel.

[0416] In addition, the boundary between the second central heating channel and the peripheral heating channels may be provided to pass through some apertures.

[0417] The above description merely explains the idea of the present disclosure and the present disclosure may be changed and modified in various ways without departing from the scope of the present disclosure by those of skill in the art. Accordingly, the embodiments described herein are provided not to limit, but to merely explain the idea of the present disclosure, and the idea of the present disclosure is not limited by the embodiments. The scope of the present disclosure should be construed by the following claims, and all technical ideas within the equivalent scope should be construed as being included in the scope of the present disclosure.

[0418] [EXPLANATION OF REFERENCE NUMERALS DESIGNATING THE MAJOR ELEMENTS OF THE DRAWINGS]

[0419] 10: Thermal module, 20: Upper cover,

[0420] 30: Intermediate frame, 31: External cooling fin,

[0421] 32: Heat transfer member, 40: Lower cover,

[0422] 100: Thermal unit, 110: Thermal block,

[0423] 120: Thermal block flexible printed circuit board (FPCB),

[0424] 121-1 to 121-4: Resistance heating element,

[0425] 122: Block temperature sensor, 123: Aperture, 124: Connector,

[0426] 130: Thermoelectric element,

[0427] 140: Thermal circuit board, 141: First interface portion,

[0428] 150: First heat sink, 151: First cooling fin,

[0429] 152: Body, 153: Flange portion,

[0430] 161: First heat transfer member, 162: Second heat transfer member,

[0431] 170: Heat sink FPCB,

[0432] 171: Heat sink temperature sensor, 172: Air temperature sensor,

[0433] 180: Heat lid FPCB, 181: Resistance heating element,

[0434] 182: Block temperature sensor, 183: Aperture, 184: Connector,

[0435] 200: Cooling unit, 210: Duct, 220: Cooling fan,

[0436] 300: Control unit, 310: Control circuit board,

[0437] 311: Second interface portion, 320: Second heat sink,

[0438] 321: Second cooling fin,

[0439] 400: Interface unit, 410: Connection circuit board.

Claims

1.A thermal cycler comprising:a thermal block on which a reaction vessel configured to accommodate a sample is seated;a thermal block heating flexible printed circuit board (FPCB) configured to, above the thermal block, heat the thermal block;thermoelectric elements configured to, below the thermal block, exchange heat with the thermal block; anda heat sink thermally connected to the thermoelectric elements,wherein the thermal block FPCB comprises resistance heating elements that configure heating channels, and a block temperature sensor, andthe heating channels are provided to be independently controllable.2.The thermal cycler of claim 1, wherein the thermal block comprises a plurality of recesses in which a plurality of wells of the reaction vessel are respectively accommodated,the thermal block FPCB comprises apertures corresponding to some or all of the recesses of the thermal block, andthe recesses of the thermal block and the apertures of the thermal block FPCB are arranged in a plurality of rows and a plurality of columns.3.The thermal cycler of claim 2, wherein the thermal block further comprises a protrusion that protrudes from an upper surface of the thermal block, and forms the recesses, andthe thermal block FPCB is attached to the upper surface of the thermal block while accommodating the protrusions in the apertures.4.The thermal cycler of claim 2, further comprising:a duct to provide a flow passage for air passing through cooling fins of the heat sink; anda cooling fan to introduce and discharge air,wherein a row direction of the apertures of the thermal block FPCB is parallel to a flow direction of air passing through the duct.5.The thermal cycler of claim 4, wherein the resistance heating elements are provided in the thermal block FPCB to heat a peripheral portion of the thermal block relatively more than a center of the thermal block in a column direction of the apertures.6.The thermal cycler of claim 5, wherein the thermal block FPCB further comprises an edge heating channel extending in the row direction along the peripheral portion of the thermal block.7.The thermal cycler of claim 6, wherein the apertures of the thermal block FPCB comprise four or more apertures in the column direction, andthe edge heating channel is provided in an area covering less than half of a distance from both edges to a center in the column direction.8.The thermal cycler of claim 6, wherein the block temperature sensor is positioned further inward than the edge heating channel.9.The thermal cycler of claim 2, wherein the block temperature sensor is positioned at a center between four apertures arranged adjacent to each other.10.The thermal cycler of claim 4, wherein the block temperature sensor comprises a plurality of block temperature sensors, which are arranged at regular intervals in the row direction of the apertures, and are arranged at positions symmetrical to each other with respect to a center of the apertures in a column direction, respectively.11.The thermal cycler of claim 4, wherein the thermoelectric elements comprise a plurality of thermoelectric elements, which are individually controlled independently of each other, and arranged side by side in the row direction of the apertures, andthe block temperature sensor is configured to measure temperatures of zones of the thermal block respectively corresponding to the plurality of thermoelectric elements.12.The thermal cycler of claim 11, wherein the plurality of thermoelectric elements are provided as a bar type to have lengths in the column direction greater than widths of the apertures in the row direction.13.The thermal cycler of claim 1, further comprising:a duct to provide a flow passage for air passing through cooling fins of the heat sink; anda cooling fan to introduce and discharge air,wherein the thermoelectric elements are arranged side by side in a flow direction of air passing through the duct.14.The thermal cycler of claim 13, wherein the thermoelectric elements are provided as a bar type to have lengths greater than widths in a direction in which the thermoelectric elements are arranged, andthe resistance heating elements are provided in the thermal block FPCB to heat a peripheral portion of the thermal block relatively more than a center of the thermal block in a lengthwise direction of the thermoelectric elements.15.The thermal cycler of claim 14, further comprising a first air temperature sensor configured to measure a temperature of air on an inlet side of the duct, and a second air temperature sensor configured to measure a temperature of air on an outlet side of the duct.16.The thermal cycler of claim 1, wherein the block temperature sensor is provided as a resistance temperature detector (RTD) or a temperature sensor capable of linearly estimating a resistance value according to a temperature change.17.The thermal cycler of claim 16, further comprising an insulating member positioned above the thermal block FPCB and comprising apertures corresponding to recesses of the thermal block, respectively,wherein the block temperature sensor is surface-mounted on an upper surface of the thermal block FPCB.18.The thermal cycler of claim 1, further comprising a thermal circuit board provided around the thermal block or the heat sink, and connected to each of the thermal block FPCB and the thermoelectric elements.19.The thermal cycler of claim 18, wherein the thermal circuit board forms an opening to accommodate the heat sink therein, and is positioned lower than the thermoelectric elements,a connector of the thermal block FPCB is connected to an upper surface of the thermal circuit board, andconnectors of the thermoelectric elements pass through the opening of the thermal circuit board to be connected to a lower surface of the thermal circuit board.20.A thermal cycler comprising:a thermal block on which a reaction vessel having a plurality of wells capable of accommodating a sample is seated, wherein the thermal block comprises recesses in which the plurality of wells are accommodated, respectively;a heat sink comprising cooling fins to dissipate heat from the thermal block;a duct to provide a flow passage for air passing through the cooling fins;a cooling fan to introduce and discharge air;a thermal block heating flexible printed circuit board (FPCB) that is provided above the thermal block, and comprises apertures corresponding to the recesses of the thermal block, respectively, resistance heating elements configured to heat a peripheral portion of the thermal block relatively more than a center of the thermal block in a direction perpendicular to an air flow direction, and a block temperature sensor configured to measure a temperature of the thermal block; anda plurality of thermoelectric elements that are provided to, below the thermal block, exchange heat with the thermal block, and are individually controlled independently of each other,wherein the plurality of thermoelectric elements are arranged side by side in the air flow direction.21.A thermal cycler comprising:a thermal block on which a reaction vessel configured to accommodate a sample is seated;thermoelectric elements configured to, below the thermal block, exchange heat with the thermal block;a heat sink thermally connected to the thermoelectric elements, and comprising a plurality of cooling fins;a duct to provide a flow passage for air passing through the plurality of cooling fins; andan air temperature sensor configured to measure a temperature of air around the plurality of cooling fins.22.The thermal cycler of claim 21, further comprising:a heat sink temperature sensor configured to measure a temperature of the heat sink; anda heat sink flexible printed circuit board (FPCB) attached to the heat sink, and on which the heat sink temperature sensor and the air temperature sensor are mounted.23.A thermal cycler comprising:a thermal block on which a reaction vessel configured to accommodate a sample is seated; anda heat lid assembly to press and heat an upper portion of the reaction vessel,wherein the heat lid assembly comprises:a thermally conductive layer that is able to come into contact with an upper surface of the reaction vessel;a heating layer provided above the thermally conductive layer, and comprising a central heating channel and a peripheral heating channel that are controllable independently of each other; andan insulating layer provided above the heating layer.24.The thermal cycler of claim 23, wherein the heating layer is a heat lid flexible printed circuit board (FPCB) attached to an upper surface of the thermally conductive layer, andeach of the central heating channel and the peripheral heating channel of the heat lid FPCB comprises a resistance heating element and a temperature sensor.

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