Nucleic acid amplification microfluidic diagnostic module capable of multi-temperature control and nucleic acid amplification microfluidic point-of-care testing device comprising same

Abstract

The present invention relates to a nucleic acid amplification microfluidic diagnostic module capable of multi-temperature control, and a nucleic acid amplification microfluidic point-of-care testing device comprising same. The nucleic acid amplification microfluidic diagnostic module capable of multi-temperature control, according to the present invention, comprises a frame having a flow path through which a sample introduced from the outside to the inside moves. The frame may comprise: an amplification unit arranged at a position corresponding to an amplification module which amplifies nucleic acids in the introduced sample; a diagnostic unit extending from the amplification unit, in which the nucleic acid-amplified sample moves along a membrane provided in the flow path and reacts with at least one biorecognition material to generate a detectable signal; and a control unit which opens and closes a space between the amplification unit and the diagnostic unit according to a set temperature and controls the movement of the sample moving from the amplification unit to the diagnostic unit.

Description

Nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control and nucleic acid amplification microfluidic point-of-care testing device including the same

[0001] The present invention relates to a nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control and a nucleic acid amplification microfluidic field inspection device including the same. More specifically, the invention relates to a nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control and a nucleic acid amplification microfluidic field inspection device including the same, which is used to rapidly and conveniently amplify nucleic acids from a sample in the field and inspect it using a microfluidic diagnostic method.

[0002] In modern fields of infectious disease diagnosis, food safety management, environmental monitoring, and emergency and disaster medical care, the importance of Point-of-Care Testing (POCT) technology, which enables results to be obtained immediately at the site—outside the laboratory—is rapidly increasing. Consequently, there is a growing demand for technologies that can achieve the accuracy level of molecular diagnostics while maintaining speed and convenience.

[0003] For example, conventional technologies include membrane-based microfluidic diagnostic technologies such as LFA (Lateral Flow Assay). These technologies allow for the simple reading of colorimetric signals resulting from the binding of antibodies, antigens, or target molecules while moving the sample naturally through capillary action. While they are suitable for point-of-care diagnosis as they can be used without power and are intuitive to use, they have the problem of being difficult to achieve sufficient sensitivity at low virus or bacterial concentrations or in the early stages of infection.

[0004] Accordingly, a method is utilized by applying membrane-based microfluidic diagnostic technology after selectively amplifying target nucleic acids in a sample using nucleic acid amplification technology such as PCR (Polymerase Chain Reaction) to secure very high sensitivity and specificity.

[0005] However, in the case of such nucleic acid amplification microfluidic diagnostic modules, the entire nucleic acid-amplified sample moves along the membrane and reacts with biometric materials to generate and detect only a single signal, so only mono-target analysis was possible, and there was a problem in that it was difficult to optimize for temperature-dependent reactions.

[0006] In other words, considering multi-target analysis or temperature-dependent reaction optimization, it was unavoidable to use complex equipment with a risk of contamination in a laboratory rather than on-site, making rapid and convenient on-site inspection virtually impossible.

[0007] The present invention is designed to solve the problems of the aforementioned prior art and aims to provide a nucleic acid amplification microfluidic diagnostic module capable of multi-temperature control and a nucleic acid amplification microfluidic field inspection device including the same, which is used to rapidly and conveniently amplify nucleic acids from samples in the field and inspect them using a microfluidic diagnostic method.

[0008] The problems of the present invention are not limited to those mentioned above, and other unmentioned problems will be clearly understood by those skilled in the art from the description below.

[0009] A nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control according to the present invention for achieving the aforementioned purpose and a nucleic acid amplification microfluidic field inspection device including the same may be configured to include a frame having a flow path formed therein for a sample introduced from the outside to the inside, wherein the frame comprises: an amplification unit corresponding to a position corresponding to an amplification module that amplifies the nucleic acid of the introduced sample; a diagnostic unit extending from the amplification unit, wherein the nucleic acid-amplified sample moves along a membrane provided in the flow path and reacts with at least one biometric material to generate a detectable signal; and a control unit that controls the movement of the sample moving from the amplification unit to the diagnostic unit by opening and closing the amplification unit and the diagnostic unit according to a set temperature.

[0010] At this time, the control unit may be configured to be a valve that opens when the set temperature is reached by heat applied from the outside, and to control the movement of the sample moving from the amplification unit to the diagnosis unit by adjusting the heat applied from the outside.

[0011] In particular, the control unit may be configured to be a multi-stage temperature response valve that sets the set temperature to a plurality of values ​​and opens and closes in stages according to the temperature gradient, thereby controlling the sequential movement of a specific component of the sample corresponding to the temperature gradient from the amplification unit to the diagnosis unit by adjusting the heat applied from the outside.

[0012] At this time, the multi-stage temperature response valve may be a phase-change valve (PCV) composed of multiple waxes with different melting points.

[0013] Here, the phase change valve may be composed of a first wax valve that melts at a temperature of 53 to 58 degrees Celsius and a second wax valve that melts at a temperature of 65 degrees Celsius or higher, and the control unit may be configured to adjust the heat applied from the outside so that the second wax valve opens after the first wax valve opens.

[0014] Meanwhile, the control unit may be configured to have a separate buffer space between the amplification unit and the diagnostic unit so that communication is established from the amplification unit to the diagnostic unit through the buffer space, thereby allowing the sample to move steadily through the buffer space when the connection between the amplification unit and the diagnostic unit is opened.

[0015] At this time, the buffer space may be configured such that the path through which the sample flows into the amplification unit and the path through which the sample is discharged to the diagnosis unit do not coincide.

[0016] In addition, the buffer space may be configured such that the membrane provided in the diagnostic unit is extended so that the sample introduced from the amplification unit is discharged along the membrane to the diagnostic unit.

[0017] Meanwhile, the above frame may further include a pre-treatment unit capable of pre-treating the sample before the sample introduced from the outside into the inside moves to the amplification unit.

[0018] Meanwhile, a nucleic acid amplification microfluidic field inspection device according to the present invention for achieving the aforementioned purpose may be configured to include: a nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control as described above; an amplification module disposed at a position corresponding to the amplification part of the frame included in the diagnostic module to amplify the nucleic acid of the sample; and a reading module that reads the sample from a signal generated from the diagnostic part of the frame included in the diagnostic module.

[0019] According to the nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control and the nucleic acid amplification microfluidic field inspection device including the same, the movement of a sample moving from the amplification unit to the diagnostic unit can be controlled by component through a control unit that opens and closes the amplification unit and the diagnostic unit according to a set temperature.

[0020] As a result, the nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control according to the present invention and the nucleic acid amplification microfluidic field inspection device including the same enable multiple target analysis or temperature-dependent reaction optimization, thereby providing the effect of being able to inspect samples quickly and easily at the field.

[0021] The effects of the present invention are not limited to those mentioned above, and other unmentioned effects will be clearly understood by those skilled in the art from the description in the claims.

[0022] FIG. 1 is a perspective view illustrating an embodiment of a nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control according to the present invention.

[0023] FIGS. 2 to 5 are schematic diagrams illustrating the operating state of an embodiment shown in FIG. 1.

[0024] FIG. 6 is a graph illustrating the operation of a phase change valve included in one embodiment of a nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control according to the present invention.

[0025] FIG. 7 is a perspective view illustrating one embodiment of a nucleic acid amplification microfluidic field inspection device according to the present invention.

[0026] FIG. 8 is a cross-sectional view illustrating an embodiment shown in FIG. 7.

[0027] Various embodiments in which the objectives of the present invention can be specifically realized will be described below with reference to the attached drawings.

[0028] Prior to this, terms and words used in this specification and claims must be interpreted in a meaning and concept consistent with the technical spirit of the invention, based on the principle that the inventor can appropriately define the concept of the terms to best describe his invention.

[0029] Furthermore, the terms and words used in this specification and claims are used merely to describe specific embodiments and are not intended to limit the invention.

[0030] For example, a singular expression includes a plural expression unless the context clearly indicates otherwise. Furthermore, terms such as "include," "equip," or "have" are intended to specify the existence of the features, numbers, steps, actions, components, parts, or combinations thereof described in the specification, and should be understood as not precluding the existence or addition of one or more other features, numbers, steps, actions, components, parts, or combinations thereof.

[0031] Furthermore, when a part such as a layer, membrane, region, or plate is said to be "above" another part, this includes not only the case where it is "directly above" the other part, but also the case where there is another part in between. Conversely, when a part such as a layer, membrane, region, or plate is said to be "below" another part, this includes not only the case where it is "directly below" the other part, but also the case where there is another part in between.

[0032] In addition, terms including ordinal numbers, such as "first," "second," etc., used in this specification may be used to describe various components, but said components are not limited by said terms, and said terms are used solely for the purpose of distinguishing one component from another.

[0033] First, with reference to FIGS. 1 to 6, an embodiment of a nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control according to the present invention will be described.

[0034] Here, FIG. 1 is a perspective view illustrating an embodiment of a nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control according to the present invention, FIG. 2 to 5 are schematic diagrams illustrating the operating state of an embodiment illustrated in FIG. 1, and FIG. 6 is a graph for explaining the operation of a phase change valve included in an embodiment of a nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control according to the present invention.

[0035] As illustrated in FIGS. 1 to 6, one embodiment of a nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control according to the present invention comprises a frame (100) having a flow path formed therein through which a sample introduced from the outside into the inside moves.

[0036] At this time, the frame (100) may be configured to include a preprocessing unit (120), an amplification unit (140), a diagnostic unit (160), and a control unit (180).

[0037] First, the pretreatment unit (120) is configured to pre-treat the sample (S) before the sample (S) introduced from the outside to the inside through the inlet hole (122) moves to the amplification unit (140) to be described later.

[0038] At this time, pretreatment refers to a preliminary step performed to efficiently extract and purify the target nucleic acid within the sample (S), and may include homogenization, lysis, and purification of the sample, but there are no restrictions on the method, and even if the pretreatment unit (120) is not present in one embodiment of the present invention, the scope of the present invention is not limited if the pretreatment unit is not present in the case where the pretreatment sample (S) that has undergone pretreatment is introduced.

[0039] Meanwhile, the amplification unit (140) is configured such that the pre-processed sample (S) introduced therein is amplified into nucleic acid, and corresponds to a position corresponding to the amplification module (20) that supplies heat for nucleic acid amplification.

[0040] Since heat is supplied by the amplification module (20), the amplification unit (140) may be insulated as needed so that the heat supplied by the amplification module (20) is not transferred directly or indirectly to other components.

[0041] At this time, the insulation treatment may be performed by placing a separate insulating member around the amplification unit (140), but it is also possible to construct the amplification unit (140) itself with an insulating material.

[0042] Meanwhile, the diagnostic unit (160) is formed as an extension from the amplification unit (140) and is configured such that a nucleic acid-amplified sample (S) moves along a membrane (162) provided in a flow path and reacts with at least one biometric material to generate a detectable signal.

[0043] This diagnostic unit (160) can be configured in various ways without limitation, provided that the sample (S) and the biorecognized plant material react to generate a signal that can be detected and read by the reading module (30) described later.

[0044] That is, the signal generated in the diagnostic unit (160) can be various, such as visible signals and electrical signals converted through antigen-antibody reactions, nucleic acid hybridization, enzyme reactions, etc.

[0045] For example, the diagnostic unit (160) may generate a visible signal in a colorimetric manner in which metal nanoparticles aggregate / fixation according to antigen-antibody binding to produce a color change, or may generate an electrical signal in an electrochemical manner in which charges move on the electrode or changes in current or potential are detected and converted into an electrical signal according to the sample concentration.

[0046] Meanwhile, the control unit (180) is configured to control the movement of a sample (S) moving from the amplification unit (140) to the diagnosis unit (160) by opening and closing the amplification unit (140) and the diagnosis unit (160) according to the set temperature.

[0047] As long as such a control unit (180) can open and close between the amplification unit (140) and the diagnostic unit (160) according to the set temperature, it may be configured in any structure or form, and it is obvious that the scope of the present invention is not limited by this.

[0048] However, to explain an embodiment of the present invention in more detail, for example, the control unit (180) may be configured as a valve that opens when it reaches a set temperature by heat applied from the outside, and the control unit (180) may control the movement of a sample (S) moving from the amplification unit (140) to the diagnosis unit (160) by adjusting the heat applied from the outside.

[0049] At this time, the valve can be configured as a multi-stage temperature response valve (182) that sets multiple temperatures and opens and closes in stages according to the temperature gradient. When the valve is configured in this way, the control unit (180) can control the heat applied from the outside to sequentially move a specific component of the sample (S) corresponding to the temperature gradient from the amplification unit (140) to the diagnosis unit (160).

[0050] That is, the control unit (180) controls the movement of the sample (S) containing the first component and the second component in such a way that when the multi-stage temperature response valve (182) is first opened at the first temperature, only the first component moves, and when it is second opened at the second temperature higher than the first temperature, the second component moves subsequently.

[0051] A multi-stage temperature response valve (182) of this type can be any configuration or form as long as it is a valve that opens and closes in stages according to the temperature gradient by setting multiple temperatures. However, considering that an embodiment of the present invention is used in the field, it is advantageous for it to be structurally simple and lightweight when applied to the present invention.

[0052] For example, the multi-stage temperature response valve (182) can be composed of a phase-change valve (PCV) composed of a plurality of waxes with different melting points, more specifically, it can be composed of a first wax valve that melts at a temperature of 53 to 58 degrees Celsius and a second wax valve that melts at a temperature of 65 degrees Celsius or higher.

[0053] In this way, when the multi-stage temperature response valve (182) is configured as a phase change valve composed of multiple waxes, the control unit (180) controls the movement of the sample (S) by adjusting the heat applied from the outside so that the second wax valve opens after the first wax valve opens.

[0054] At this time, by appropriately mixing the first wax valve and the second wax valve, the time during which the first wax valve is open at a specific opening temperature can be controlled, and this can control the time during which a specific component of the sample (S) moves when the first wax valve is opened.

[0055] That is, as shown in FIG. 6, when the first wax valve and the second wax valve are mixed in a ratio of 1:3, the second wax valve opens after 2 minutes and 16 seconds have passed since the first wax valve opened, and when the first wax valve and the second wax valve are mixed in a ratio of 1:10, the second wax valve opens after 4 minutes and 26 seconds have passed since the first wax valve opened.

[0056] For reference, the first wax valve used to derive the graph in Fig. 6 is paraffin wax corresponding to catalog number 327204 manufactured by Sigma-Aldrich, and the second wax valve is paraffin wax corresponding to catalog number 411663 manufactured by Sigma-Aldrich. Since this can be adjusted in various ways depending on which wax valve is used, it is natural that the scope of rights is not limited by this.

[0057] Meanwhile, even if the control unit (180) is configured to open and close the amplification unit (140) and the diagnosis unit (160) in stages according to the set temperature using a multi-stage temperature response valve (182), the amount of a specific sample (S) that moves along the membrane (162) through the multi-stage temperature response valve (182) may not be constant, and this may hinder accurate diagnosis.

[0058] Accordingly, in order to buffer a specific sample (S) that is moved through a multi-stage temperature response valve (182) so that it can move consistently along the membrane (162), the control unit (180) may have a separate buffer space (184) between the amplification unit (140) and the diagnosis unit (160).

[0059] That is, by making the amplification unit (140) connected to the diagnosis unit (160) through the buffer space (184), when the connection between the amplification unit (140) and the diagnosis unit (160) is opened by the control unit (180), the sample (S) moves steadily through the buffer space (184).

[0060] At this time, in order to further enhance the buffering effect of the buffer space (184), it is advantageous that the path through which the sample (S) flows in from the amplification unit (140) and the path through which the sample (S) is discharged to the diagnosis unit (160) do not coincide with each other.

[0061] This is because when the path through which the sample (S) flows into the amplification unit (140) and the path through which the sample (S) is discharged to the diagnosis unit (160) coincide, the sample (S) moving from the amplification unit (140) to the diagnosis unit (160) occurs immediately upon opening the multi-stage temperature response valve (182), thereby reducing the buffering effect in the buffer space (184).

[0062] Additionally, the buffer space (184) prevents the first wax valve and the second wax valve constituting the multi-stage temperature response valve (182) from moving directly to the membrane (162), thereby allowing the sample (S) to move naturally to the diagnostic unit (160).

[0063] However, if the sample (S) is not discharged smoothly to the diagnostic unit (160) due to this buffer space (184), that is, if the buffer space (184) hinders the movement of the sample (S), it would be better not to have the buffer space (184). Therefore, to solve this problem, the membrane (162) provided in the diagnostic unit (160) can be formed to extend into the buffer space (184).

[0064] One embodiment of the nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control according to the present invention, which can be configured as described above, can be operated as follows.

[0065] First, as shown in FIG. 2, when a sample (S) is introduced into the pretreatment unit (120) through the inlet hole (122), pretreatment such as homogenization of the sample, cell lysis, and nucleic acid purification is performed to efficiently extract and purify the target nucleic acid within the sample (S).

[0066] The sample (S) pre-processed in this manner is moved to the amplification unit (140) as shown in FIG. 3, and nucleic acid is amplified through heat supplied by the amplification module (20).

[0067] However, if the first wax valve constituting the multi-stage temperature response valve (182) does not reach the melting point, the sample (S) cannot move and remains in the amplification section (140).

[0068] Afterwards, when the heat applied to the amplification module (20) is conducted or heat is applied separately and the first wax valve melts, the first wax valve opens, and as shown in FIG. 4, only the first component (s1) of the sample (S) moves into the buffer space (184).

[0069] And when a certain amount of the first component (s1) of the sample (S) is received in the buffer space (184), it moves along the membrane (162) at a constant rate and reacts with the biometric material in the diagnostic unit (160) to generate a detectable visible signal (R).

[0070] At this time, as illustrated in FIG. 5, when the heat applied to the amplification module (20) is continuously conducted or additional heat is separately applied so that the second wax valve constituting the multi-stage temperature response valve (182) melts, the second wax valve opens, and the second component (s2) of the sample (S) also moves sequentially to the buffer space (184).

[0071] Subsequently, although not separately described, the second component (s2) of the sample (S) may also move along the aforementioned membrane (162) to react with a biometric material in the diagnostic unit (160) to generate another detectable signal, or the second component (s2) of the sample (S) may move along a new membrane (162) through a different path to react with a biometric material in the diagnostic unit (160) to generate another detectable signal.

[0072] The present invention may be configured as a nucleic acid amplification microfluidic diagnostic device, including one embodiment of a nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control according to the present invention as described above, and this will be described in detail below with reference to FIGS. 7 and 8.

[0073] Here, FIG. 7 is a perspective view illustrating an embodiment of a nucleic acid amplification microfluidic field inspection device according to the present invention, and FIG. 8 is a cross-sectional view illustrating an embodiment illustrated in FIG. 7.

[0074] As illustrated in FIGS. 7 and 8, one embodiment of the nucleic acid amplification microfluidic field inspection device according to the present invention may be configured to include an amplification module (20) and a reading module (30) together with a diagnostic module (10) as described above.

[0075] At this time, the amplification module (20) is positioned at a location corresponding to the amplification section (140) of the frame (100) and configured to amplify the sample (S) into nucleic acid, and any structure or shape is acceptable as long as it can amplify the sample (S) into nucleic acid.

[0076] That is, the amplification module (20) is configured to amplify the nucleic acid of a sample (S), such as a polymerase chain reaction (PCR) device. Any structure or form is acceptable as long as it is configured to supply heat to perform nucleic acid amplification, which involves replicating or increasing nucleic acid molecules such as DNA or RNA in large quantities through an artificial biochemical reaction. However, for an embodiment of the nucleic acid amplification microfluidic field inspection device according to the present invention to be used in the field, it is advantageous to have a small weight or volume.

[0077] Meanwhile, the reading module (30) is configured to read the sample (S) from a signal generated in the diagnostic unit (160) of the frame (100), and it may have any structure or form as long as it can read the sample from a signal generated when the sample (S) reacts with a biometric material in the diagnostic unit (160).

[0078] That is, the reading module (30) is configured to read all of the various signals generated when a sample (S) reacts with a biorecognition material on the membrane (162), such as visible signals and electrical signals converted through antigen-antibody reactions, nucleic acid hybridization, enzyme reactions, etc., and can be configured in various ways depending on the type of signal.

[0079] For example, in the case where a visible signal is generated in a colorimetric manner in which metal nanoparticles aggregate / fixation according to antigen-antibody binding to cause a color change, it may be an LFA (Lateral Flow Assay) platform and an image acquisition device associated with said platform; and in the case where an electrical signal is generated in an electrochemical manner in which charge moves on an electrode or changes in current or potential are detected and converted into an electrical signal according to sample concentration, it may be a microelectrode-based LoC (Lab-on-a-Chip) platform and an electrical measurement device associated with said platform.

[0080] Meanwhile, one embodiment of the nucleic acid amplification microfluidic field inspection device according to the present invention may further expand its functions by including other components in addition to the diagnostic module (10), amplification module (20), and reading module (30), and it is obvious that the scope of the present invention is not limited even if such other components are included.

[0081] For example, one embodiment of the nucleic acid amplification microfluidic field inspection device according to the present invention may further include a case module (40) and a power module (50).

[0082] At this time, the case module (40) is configured to serve as a housing that encloses the aforementioned diagnostic module (10), amplification module (20), and reading module (30), and can be configured in a form that is portable in the field and sufficiently durable.

[0083] Additionally, the power module (50) is configured to supply power to the amplifier module (20), and can be configured in a form that allows power to be shared between equipment in the field, such as a portable terminal that enables power sharing recently.

[0084] In particular, if the power module (50) is configured as a portable terminal capable of power sharing, it would be advantageous in that it can display to the user the test results read from various signals generated when a sample (S) reacts with a biometric material on the membrane (162) in conjunction with the reading module (30).

[0085] As described above, preferred embodiments according to the present invention have been examined. It is obvious to those skilled in the art that, in addition to the embodiments described above, the present invention may be embodied in other specific forms without departing from its spirit or scope. Therefore, the embodiments described above should be regarded as illustrative rather than restrictive, and accordingly, the present invention is not limited to the description above but may be modified within the scope of the appended claims and their equivalents.

[0086]

[0087] *[Explanation of symbols]

[0088] 1: Nucleic acid amplification microfluidic field inspection device according to the present invention

[0089]

[0090] 10: Nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control according to the present invention

[0091] 20: Amplification Module

[0092] 30: Reading module

[0093] 40: Case Module

[0094] 50: Power module

[0095]

[0096] 100: Frame

[0097] 120: Preprocessing section

[0098] 122: Inlet hole

[0099] 140: Amplification section

[0100] 160: Diagnostic Department

[0101] 162: Membrane

[0102] 180: Control unit

[0103] 182: Multistage temperature response valve

[0104] 184: Buffer space

[0105]

[0106] S: Sample

[0107] s1: First component of the sample

[0108] s2: Second component of the sample

[0109] R: Visible signal generated by the reaction of a sample with a biometric substance

Claims

1. A frame having a channel formed therein through which a sample introduced from the outside into the inside moves, The above frame is, An amplification unit corresponding to a position corresponding to an amplification module that amplifies nucleic acids from the above-mentioned sample; A diagnostic unit extending from the amplification unit, wherein the nucleic acid-amplified sample moves along a membrane provided in the fluid path and reacts with at least one biometric material to generate a detectable signal; and A nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control, characterized by including a control unit that controls the movement of the sample moving from the amplification unit to the diagnostic unit by opening and closing the amplification unit and the diagnostic unit according to a set temperature.

2. In Paragraph 1, The above control unit is, It consists of a valve that opens when the set temperature is reached by heat applied from the outside, A nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control, characterized by controlling the movement of the sample moving from the amplification unit to the diagnostic unit by adjusting the heat applied from the outside.

3. In Paragraph 2, The above control unit is, It is configured as a multi-stage temperature response valve that sets the above-mentioned temperature to multiple values ​​and opens and closes in stages according to the temperature gradient, A nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control, characterized by controlling the movement of a specific component of the sample corresponding to the temperature gradient from the amplification unit to the diagnostic unit by adjusting the heat applied from the outside.

4. In Paragraph 3, The above-mentioned multi-stage temperature response valve is, A nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control, characterized by being a phase-change valve (PCV) composed of multiple waxes with different melting points.

5. In Paragraph 4, The above phase change valve is, It is composed of a first wax valve that melts at a temperature of 53 to 58 degrees Celsius and a second wax valve that melts at a temperature of 65 degrees Celsius or higher, and The above control unit is, A nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control, characterized by adjusting externally applied heat so that the second wax valve opens after the first wax valve is opened.

6. In Paragraph 1, The above control unit is, A separate buffer space is provided between the amplification unit and the diagnostic unit, A nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control, characterized by allowing communication from the amplification unit through the buffer space to the diagnostic unit, thereby allowing the sample to move steadily through the buffer space when the connection between the amplification unit and the diagnostic unit is open.

7. In Paragraph 6, The above buffer space is, A nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control, characterized in that the path through which the sample is introduced from the amplification unit and the path through which the sample is discharged to the diagnostic unit are provided to be non-coordinate.

8. In Paragraph 6, The above buffer space is, A nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control, characterized in that the membrane provided in the diagnostic unit is extended so that the sample introduced from the amplification unit is discharged to the diagnostic unit along the membrane.

9. In Paragraph 1, The above frame is, A nucleic acid amplification microfluidic diagnostic module capable of multiple temperature control, characterized by further including a pre-treatment unit capable of pre-treating the sample before the sample introduced from the outside into the inside moves to the amplification unit.

10. A diagnostic module of any one of paragraphs 1 through 9; An amplification module disposed at a position corresponding to the amplification part of the frame included in the diagnostic module above, for amplifying the sample into nucleic acids; and A nucleic acid amplification microfluidic point-of-care testing device comprising: a reading module that reads the sample from a signal generated in the diagnostic unit of the frame included in the diagnostic module.

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