CN217016658U

CN217016658U - Nucleic acid analyzer

Info

Publication number: CN217016658U
Application number: CN202220092365.1U
Authority: CN
Inventors: 白晨
Original assignee: Shenzhen Gangzhu Medical Technology Co ltd
Current assignee: Shenzhen Chenghui Medical Technology Co ltd
Priority date: 2022-01-13
Filing date: 2022-01-13
Publication date: 2022-07-22
Anticipated expiration: 2032-01-13

Abstract

The present invention relates to a nucleic acid analysis device including: the centrifugal driving mechanism is used for driving the microfluidic chip to rotate and comprises a rotating shaft, and the rotating shaft is used for being connected with the microfluidic chip; the extraction temperature control mechanism comprises a top temperature control unit and a bottom temperature control unit which are positioned at two sides of the microfluidic chip; the amplification temperature control mechanism is positioned beside the extraction temperature control mechanism and comprises an upper temperature control module and a lower temperature control module, and the upper temperature control module and the lower temperature control module are used for sealing the amplification cavity and regulating the temperature of the amplification cavity when the amplification cavity carries out amplification reaction; and the detection mechanism forms an optical detection channel with the amplification cavity through the amplification temperature control module. The nucleic acid analysis device controls the temperature of different extraction temperature areas on the microfluidic chip and independently controls the temperature of the amplification cavity, so that the temperature influence among different areas of the microfluidic chip is reduced, and the detection process is convenient and quick.

Description

Nucleic acid analysis device

Technical Field

The present invention relates to the field of biomedical technology, and in particular, to a nucleic acid analyzer.

Background

Nucleic acid detection is one type of molecular diagnostics. It is widely used because of its high accuracy and timeliness of early diagnosis. The detection process can be divided into: sampling, extracting nucleic acid, amplifying, detecting and the like. The nucleic acid extraction process generally requires sequential steps of lysis, washing and elution to remove materials present in the sample that may affect the amplification step. Each step needs to add different reagents correspondingly and is carried out at a certain temperature, so that pure nucleic acid is obtained finally for subsequent amplification.

Nucleic acid amplification is generally performed by using Polymerase Chain Reaction (PCR) to amplify a nucleic acid sequence to be detected, and the purpose of amplification is to amplify a target nucleic acid, which is a trace and difficult to detect, to a large amount and then to easily detect the target nucleic acid. PCR amplification is generally carried out for 40 cycles, and one cycle can be divided into three steps of denaturation, annealing and extension, and theoretically, the number of target nucleic acid fragments is doubled after one cycle. Wherein, each step is realized by the temperature change of the PCR reaction system, namely, each step corresponds to one temperature. It is known that the key to the realization of PCR amplification lies in the rapid and accurate temperature control. In the PCR amplification reaction system, a target nucleic acid fragment is marked by utilizing a fluorescent group, and the fluorescence becomes stronger along with the amplification of the target nucleic acid fragment. The S-shaped amplification curve can be drawn by collecting fluorescence data in real time through the optical module so as to analyze and further complete detection.

Because the nucleic acid detection process has more steps, in the existing scheme for completing the whole nucleic acid detection, a PCR instrument and a nucleic acid extraction instrument are used, and auxiliary equipment such as a blending instrument, a centrifugal machine, a liquid transfer gun and the like is also needed, so that the sample circulation is complicated, the detection process is complex, and the cost is higher.

SUMMERY OF THE UTILITY MODEL

In view of this, it is necessary to provide a nucleic acid analyzer in order to solve the problem of redundancy of the conventional nucleic acid detecting apparatus.

A nucleic acid analysis device for analyzing a sample in a microfluidic chip, the microfluidic chip comprising an extraction region and an amplification chamber, the extraction region comprising a plurality of extraction temperature zones, comprising:

the centrifugal driving mechanism is used for driving the microfluidic chip to rotate and comprises a rotating shaft, and the rotating shaft is used for being connected with the microfluidic chip;

the extraction temperature control mechanism comprises a top temperature control unit and a bottom temperature control unit which are positioned at two sides of the microfluidic chip and are used for respectively controlling the air temperature of different extraction temperature areas on the microfluidic chip;

the amplification temperature control mechanism is positioned beside the extraction temperature control mechanism and comprises an upper temperature control module and a lower temperature control module, and the upper temperature control module and the lower temperature control module are used for sealing the amplification cavity and regulating the temperature of the amplification cavity when the amplification cavity carries out amplification reaction;

and the detection mechanism forms an optical detection channel with the amplification cavity through the amplification temperature control mechanism.

In one embodiment, the top temperature control unit comprises a top heat insulation cover and a top heating element, the top heating element is located in the top heat insulation cover, the bottom temperature control unit comprises a bottom heat insulation cover and a bottom heating element, the bottom heating element is located in the bottom heat insulation cover, and when the microfluidic chip is connected to the rotating shaft, the top heat insulation cover and the bottom heat insulation cover are both not in contact with the microfluidic chip.

In one embodiment, the top temperature control unit further includes a top fan structure and a top flow guiding disc, the top fan structure is located in the top heat insulating cover, and the top fan structure is sleeved on the rotating shaft and located on one side of the top flow guiding disc; the bottom temperature control unit further comprises a bottom fan blade structure, a bottom flow guide disc and an idle shaft, wherein the bottom fan blade structure, the bottom flow guide disc and the idle shaft are located in the bottom heat insulation cover, the bottom fan blade structure is sleeved on the idle shaft and located on one side of the bottom flow guide disc, and the idle shaft is used for being connected with the rotating shaft to rotate synchronously along with the rotating shaft.

In one embodiment, the top deflector disc and the bottom deflector disc are both provided with a through air inlet and at least one air outlet.

In one embodiment, a through air inlet is formed in the central area of the top flow guide disc, and a through air outlet is formed in the edge position of the top flow guide disc; the central area of the bottom flow guide disc is provided with a through central air inlet, and the bottom flow guide disc is provided with an inner ring air outlet and an outer ring air outlet along the radial direction.

In one embodiment, the bottom deflector comprises a first air distribution plate and a second air distribution plate which are stacked, and the first air distribution plate and the second air distribution plate can rotate relatively to enable one of the inner ring air outlet and the outer ring air outlet to be communicated with the central air inlet.

In one embodiment, a containing groove is disposed on the upper temperature control module or the lower temperature control module, and the containing groove is used for containing the amplification cavity.

In one embodiment, the amplification temperature control mechanism further comprises a driving module, the movable module comprises an upper connecting rod, a lower connecting rod, a horizontal slider guide rail and a vertical slider guide rail, the horizontal slider guide rail and the vertical slider guide rail are vertically arranged, the vertical slider guide rail comprises an upper slider connected with the upper temperature control module and a lower slider connected with the lower temperature control module, one end of the upper connecting rod is hinged to the upper slider, the other end of the upper connecting rod is hinged to the slider on the horizontal slider guide rail, one end of the lower connecting rod is hinged to the lower slider, and the other end of the lower connecting rod is hinged to the slider on the horizontal slider guide rail.

In one embodiment, the driving module further includes a transmission shaft and a cam sleeved on the transmission shaft, the cam abuts against the upper temperature control module, and the upper temperature control module and the lower temperature control module can approach or separate from each other in the rotation process of the cam.

In one embodiment, the amplification temperature control mechanism further includes an elastic member, one end of the elastic member is connected to the upper temperature control module, the other end of the elastic member is connected to the lower temperature control module, when the upper temperature control module and the lower temperature control module are away from each other, the elastic member is in a deformed state, and when the upper temperature control module and the lower temperature control module are in contact with each other, the elastic member is in an original state.

On one hand, the nucleic acid analysis device adopts the microfluidic chip to integrate the extraction, amplification and analysis of nucleic acid into a whole, thereby reducing the equipment investment. On the other hand, the extraction temperature control mechanism controls the temperature of different extraction temperature areas on the micro-fluidic chip, so that the temperature influence among the extraction temperature areas can be reduced, and the amplification temperature control mechanism controls the temperature of an amplification cavity on the micro-fluidic chip independently, so that the temperature required by the amplification cavity can be controlled accurately and quickly. On the other hand, an optical detection channel can be formed between the detection mechanism and the amplification cavity, and the detection process is convenient and quick.

Drawings

FIG. 1 is a schematic structural view of a nucleic acid analysis apparatus according to an embodiment of the present invention.

Fig. 2 is a schematic structural diagram of a microfluidic chip according to an embodiment of the present invention.

FIG. 3 is a schematic structural diagram of a centrifugal temperature control device in the nucleic acid analysis apparatus according to an embodiment of the present invention.

Fig. 4 is a cross-sectional view of fig. 3.

FIG. 5 is a cross-sectional view of a top fan blade structure and a top deflector in a nucleic acid analysis device according to an embodiment of the present invention.

FIG. 6 is a schematic structural diagram of a bottom baffle in the nucleic acid analysis apparatus according to an embodiment of the present invention.

FIG. 7 is a schematic diagram of an amplification temperature control mechanism of a nucleic acid analysis apparatus according to an embodiment of the present invention.

FIG. 8 is a schematic diagram illustrating an embodiment of a nucleic acid analyzer with a support frame omitted from an amplification temperature control mechanism.

FIG. 9 is a schematic view of a nucleic acid analysis apparatus according to another embodiment of the present invention.

Detailed Description

The present invention may be embodied in many different forms than those specifically described herein and those skilled in the art will be able to make similar modifications without departing from the spirit and scope of the utility model and it is therefore not intended to be limited to the specific embodiments disclosed below.

In the description of the present invention, the terms "vertical", "horizontal", "upper", "lower", "left", "right", "center", "longitudinal", "lateral", "length", and the like are used to indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, only for the convenience of description of the present invention and for simplicity of description. The first feature may be "on" or "under" the second feature such that the first and second features are in direct contact, or the first and second features are in indirect contact via an intermediate. The terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. In the description of the present invention, "a plurality" means at least two, e.g., two, three, etc., unless specifically limited otherwise.

In the present invention, the terms "mounted," "connected," "secured," and the like are to be construed broadly unless otherwise specifically indicated and limited. When an element is referred to as being "fixed" or "disposed" to another element, it can be directly on the other element or intervening elements may also be present. When an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may also be present.

Referring to fig. 1, fig. 1 is a schematic structural diagram of a nucleic acid analysis apparatus according to an embodiment of the present invention, and the nucleic acid analysis apparatus according to the embodiment of the present invention may be used in conjunction with a microfluidic chip 10 to implement molecular diagnosis, such as nucleic acid detection. The micro-fluidic chip 10 integrates nucleic acid extraction and PCR amplification functions, and before the PCR amplification function is performed, pretreatment such as cracking-cleaning and elution is required to be performed on a sample to realize nucleic acid extraction and purification. These pre-treatment sections need to be performed at different temperatures, and the temperatures required for the pre-treatment sections and the PCR amplification often differ. For this purpose, the nucleic acid analysis apparatus includes a centrifugal temperature control device 20, an amplification temperature control mechanism 300, and a detection mechanism 500, wherein the centrifugal temperature control device 20 is configured to provide a driving force for liquid flow to the microfluidic chip 10 and to control temperature during pre-processing. The amplification temperature control mechanism 300 is used for temperature control of PCR amplification. The detection mechanism 500 is used for detecting a product in the amplification chamber on the microfluidic chip 10 after the microfluidic chip 10 completes the PCR amplification.

Referring to fig. 2, in the present embodiment, the microfluidic chip 10 is a centrifugal microfluidic chip, and is in a disc shape, and is provided with an extraction area for performing a pre-treatment and a PCR amplification chamber, because the temperatures required in the steps of the extraction area are different, in the present embodiment, the parts of the microfluidic chip 10 located in the extraction area are named as a first extraction temperature area a, a second extraction temperature area B, and a third extraction temperature area C according to different functions to be implemented, and the first extraction temperature area, the second extraction temperature area, and the third extraction temperature area are concentric annular areas. The PCR amplification chamber is marked with P in the figure and is positioned at the edge of the microfluidic chip 10. The PCR amplification cavity protrudes from the surface of the microfluidic chip 10. The center of the microfluidic chip 10 is provided with a spline hole for connecting with the centrifugal temperature control device 20.

Referring to FIG. 3, FIG. 3 is a schematic structural view of a centrifugal temperature control device 20 in a nucleic acid analysis apparatus according to an embodiment of the present invention. The centrifugal temperature control device 20 includes a frame 21, and a bracket 23, an extraction temperature control mechanism 100, a centrifugal drive mechanism 900, and a lifting mechanism 200, which are located on the frame 21. The extraction temperature control mechanism 100 includes a top temperature control unit 110 and a bottom temperature control unit 130, which are vertically spaced. The top temperature control unit 110 is connected to the frame 21 and the bottom temperature control unit 130 is connected to the lift mechanism 200. The bracket 23 is used for pushing the microfluidic chip 10 to a set position, the lifting mechanism 200 is used for pushing the microfluidic chip 10 to be connected with the centrifugal driving mechanism 900, and the top temperature control unit 110 and the bottom temperature control unit 130 are respectively located at two sides of the microfluidic chip 10 and used for regulating and controlling the temperature of different areas of the microfluidic chip 10. When the microfluidic chip 10 is mounted on the centrifugal driving mechanism 900, the top temperature control unit 110 and the bottom temperature control unit 130 on both sides of the microfluidic chip 10 are not in contact with the microfluidic chip 10.

In this embodiment, the top temperature control unit 110 is used for controlling the air temperature above the first extraction temperature zone of the microfluidic chip 10, and the bottom temperature control unit 130 is used for controlling the air temperature above the second extraction temperature zone and the air temperature above the third extraction temperature zone of the microfluidic chip 10.

Referring to fig. 3, the centrifugal driving mechanism 900 includes a driving motor 920 and a rotating shaft 930, the driving motor 920 is located at the top end of the frame 21, a power output end of the driving motor 920 is connected to one end of the rotating shaft 930, and the other end of the rotating shaft 930 is used for being connected to the microfluidic chip 10. In one embodiment, the end of the rotating shaft 930 for connecting to the microfluidic chip 10 is provided with a chuck for connecting to a spline hole of the microfluidic chip 10 through the chuck.

Referring to fig. 4, the top temperature control unit 110 includes a top heat insulating cover 111 and a top heating member 120. The top thermal shield 111 is fixed to the frame 21 on a side facing away from the driving motor 920. The top heat insulating cover 111 is hollow, the top heating element 120 is located in the top heat insulating cover 111, and the rotating shaft 930 is partially inserted into the top heat insulating cover 111. The top heating member 120 is used to generate heat and conduct the heat out to heat the air in the area covered by the heat insulating cover 111, so as to heat the corresponding area on the microfluidic chip 10 connected to the rotating shaft 930. The side of the top thermal shield 111 away from the top of the frame 21 has a small gap with the microfluidic chip 10.

In this embodiment, the top heating element 120 is a spiral-shaped annular resistance wire whose radial dimension is adapted to the first temperature range.

Referring to fig. 4, the top temperature control unit 110 further comprises a top air circulation assembly located within the top thermal shield 111, the top air circulation assembly comprising a top fan blade structure 113 and a top deflector 115. The top baffle plate 115 is connected to the inner wall of the top heat shield 111, and divides the inner space of the top heat shield 111 into an upper chamber and a lower chamber. The top heating element 120 and the top fan blade structure 113 are both located on the side of the top deflector 115 facing away from the microfluidic chip 10, i.e. both located in the upper chamber of the top thermal shield 111. The top heating element 120 surrounds the outside of the top fan blade structure 113. The top blade structure 113 is sleeved on the shaft 930 and can rotate synchronously under the rotation of the shaft 930.

For ease of viewing, fig. 5 shows a schematic cross-sectional view of top blade structure 113 and top diaphragm 115 in isolation. The top blade structure 113 includes a plurality of circumferentially disposed blades. The top deflector 115 is provided with an air inlet 112 and an air outlet 114, the air inlet 112 is formed in the central area of the top deflector 115, and the air outlet 114 is formed at the edge of the top deflector 115. The air outlets 114 are provided in a plurality and are uniformly distributed around the central axis of the top baffle 115. The upper chamber and the lower chamber inside the top thermal insulation cover 111 are communicated with the air outlet 114 through the air inlet 112. In this embodiment, the top heating element 120 is located at the air outlet 114 of the top deflector 115.

As shown in fig. 4 and fig. 5, when the top blade structure 113 is driven by the rotating shaft 930 to rotate, a negative pressure is generated in the central area of the top blade structure 113, so as to cause the air in the top thermal shield 111 to flow. Air flows into the intake 112 and out of the outtake 114 to create a flowing air stream, and so on. The air flow of the circulating air drives the air flow in the vicinity of the top heating element 120, whereby the temperature of the air inside the top heat insulating cover 111 can be made uniform. Because the air outlet 114 is located at the periphery of the air inlet 112, that is, the air inlet 112 is located in the area surrounded by the air outlet 114, a small gap exists between the top heat-insulating cover 111 and the microfluidic chip 10, so that an "air short circuit" is formed between the air outlet 114 and the air inlet 112, that is, flowing gas is constrained to flow trajectory between the air outlet 114 and the air inlet 112, and cannot diffuse, thereby ensuring that the gas flow circularly flows inside the top heat-insulating cover 111.

Referring to fig. 4, the bottom temperature control unit 130 includes a bottom heat insulating cover 131 and a bottom heating element 140. The bottom heat-insulating cover 131 is hollow, and the bottom heating element 140 is located in the bottom heat-insulating cover 131. There is a small gap in the vertical direction between the bottom thermal shield 131 and the microfluidic chip 10. The bottom heating member 140 is used for heating the air in the region covered by the bottom thermal insulation cover 131, so as to heat the corresponding region of the microfluidic chip 10.

The bottom heating element 140 is a helical, circular resistance wire.

Referring to fig. 4, similar to the top temperature control unit 110, the bottom temperature control unit 130 further comprises a bottom air circulation assembly within the bottom thermal shield 131, the bottom air circulation assembly comprising a bottom fan structure 133, a bottom deflector 135, and an idler shaft 230. The bottom blade structure 133 and the top blade structure 113 have similar structures and different sizes, and the central axes of the two structures are located on the same straight line. The bottom diaphragm 135 is similar in structure and function to the top diaphragm 115. The axis of the idle shaft 230 is aligned with the axis of the rotation shaft 930. The bottom fan blade structure 133 and the bottom heating element 140 are both located on a side of the bottom deflector 135 facing away from the microfluidic chip 10. The bottom heating member 140 surrounds the bottom blade structure 133, and the bottom blade structure 133 is sleeved on the idle shaft 230. When the microfluidic chip 10 is connected to the rotating shaft 930, the idle shaft 230 is also connected to the rotating shaft 930, so that only one driving motor 920 is needed to drive the idle shaft 230 and the rotating shaft 930 to rotate simultaneously, and further drive the bottom blade structure 133 and the top blade structure 113 to rotate. In one embodiment, the idler shaft 230 is also coupled to the spindle 930 via the chuck.

When the bottom blade structure 133 rotates, the bottom deflector 135 and the bottom blade structure 133 cooperate with each other to form a circulating airflow in the bottom heat-insulating cover 131, so that heat generated by the bottom heating element 140 is uniformly distributed in the bottom heat-insulating cover 131.

When the bottom temperature control unit 130 needs to regulate at least two extraction temperature zones, for example, to control the temperature of the second extraction temperature zone and the third extraction temperature zone of the microfluidic chip 10, it is necessary that the air with the set temperature in the bottom temperature-insulating cover 131 can be used to heat the different extraction temperature zones in a targeted manner. In addition to the above-mentioned points of common usage, the bottom baffle 135 and the top baffle 115 are different in that, in the present embodiment, the bottom baffle 135 has a central air inlet, an inner ring air outlet and an outer ring air outlet, which are through, that is, a plurality of air outlets are radially formed compared to the top baffle 115. The central air inlet is disposed in the central region of the bottom deflector 135, and the inner annular air outlet is closer to the center of the bottom deflector 135 than the outer annular air outlet. The airflow inlet is normally open, and the inner ring air outlet and the outer ring air outlet can be selectively opened or closed. When the bottom fan blade structure 133 rotates, the inner ring air outlet and the outer ring air outlet are respectively controlled to open and close, so that two different airflow circulation paths are provided in the bottom temperature control unit 130.

Referring to fig. 6, in one embodiment, the bottom deflector 135 includes first and second

air distribution discs

137, 139 of the same size. The first air distribution plate 137 is provided with a first air inlet 132, a first inner ring air outlet 134 and a first outer ring air outlet 136 which are through. The first air inlet 132 is formed in a central region of the first air distribution plate 137, and the first inner ring air outlet 134 is closer to a central point of the first air distribution plate 137 than the first outer ring air outlet 136. The first inner ring air outlet 134 and the first outer ring air outlet 136 are arranged in a plurality of numbers and are uniformly arranged in the circumferential direction. The second air distribution plate 139 is provided with a second air inlet 142, a second inner ring air outlet 144 and a second outer ring air outlet 146 which are through. The second air inlet 142 is formed in a central region of the second air distribution plate 139, and the second inner ring air outlet 144 is closer to a central point of the second air distribution plate 139 than the second outer ring air outlet 146. The second inner ring air outlet 144 and the second outer ring air outlet 146 are both provided in a plurality of numbers and are uniformly arranged in the circumferential direction.

In this embodiment, a connection line between the first inner ring outlet 134 and a center point of the first air distribution plate 137 and a connection line between the first outer ring outlet 136 and a center point of the first air distribution plate 137 are not located on the same radial line. The connecting line of the second inner ring air outlet 144 and the center point of the second air distribution plate 139 and the connecting line of the second outer ring air outlet 146 and the second air distribution plate 139 are positioned on the same radial line.

The first air distributor plate 137 and the second air distributor plate 139 are stacked to form the bottom deflector 135. The first air inlet opening 132 and the second air inlet opening 142 collectively form a central air inlet opening of the bottom diaphragm 135. When the first air distribution plate 137 and the second air distribution plate 139 rotate relatively, the first inner ring air outlet 134 and the second inner ring air outlet 144 are communicated, meanwhile, no air flow passes through the first outer ring air outlet 136 and the second outer ring air outlet 146, and the communicated first inner ring air outlet 134 and the second inner ring air outlet 144 form an inner ring air outlet of the bottom deflector 135 together; or the first outer ring air outlet 136 is communicated with the second outer ring air outlet 146, and meanwhile, no air flow passes through the first inner ring air outlet 134 and the second inner ring air outlet 144, at this time, the first outer ring air outlet 136 and the second outer ring air outlet 146 which are communicated form an outer ring air outlet of the bottom flow guide disc 135 together. By relatively rotating the first air distribution plate 137 and the second air distribution plate 139 to a predetermined angle, the central air inlet of the bottom deflector 135 can be communicated with the inner ring air outlet or the outer ring air outlet, respectively.

In cooperation with different air outlets of the bottom flow guiding disc 135, the bottom temperature control unit 130 further includes a partition plate 138 located on the bottom flow guiding disc 135 and located on a side of the bottom flow guiding disc 135 facing the microfluidic chip 10. The spacer 138 has a small gap with the microfluidic chip 10. At least two partition plates 138 are respectively located between the central air inlet and the inner ring air outlet, between the inner ring air outlet and the outer ring air outlet, and between the outer ring air outlet and the side surface of the bottom deflector 135, so as to enclose different annular spaces to correspond to different extraction temperature zones on the microfluidic chip 10. The provision of different partition plates 138 avoids the influence of the air flow having a predetermined temperature on the adjacent extraction temperature zone.

It should be noted that, if the second extraction temperature region of the microfluidic chip 10 is subjected to the corresponding pre-treatment, the temperature is not affected any more, that is, even if the temperature of the second extraction temperature region is increased again during the heating process of the third extraction temperature region, the final nucleic acid extraction result is not affected.

Referring to fig. 3, the lifting mechanism 200 includes a lifting motor 250, a lift pin 260, and an idler plate 210. The bottom temperature control unit 130 is located above the idle plate 210, and the top rod 260 is located below the idle plate 210. A slide rail structure is arranged between the left side and the right side of the idle disk 210 and the frame 21, the top rod 260 can push the idle disk 210 to move in the vertical direction relative to the frame 21 under the driving of the lifting motor 250, and the idle shaft 230 in the bottom temperature control unit 130 can push the microfluidic chip 10 in the bracket 23 to be connected with the rotating shaft 930.

Referring to fig. 4, the lifting mechanism 200 further includes an idle shaft support 220 and an elastic assembly 240, wherein the elastic assembly 240 includes a sheath 241 and an elastic element 243, and the elastic element 243 is located in the sheath 241. One end of the jacket 241 is connected with the top rod 260, and the other end is slidably sleeved on the idle shaft support 220. The idle shaft support 220 has one end abutting against the elastic member 243 located in the jacket 241 and the other end embedded in the center of the idle disk 210 to be rotatably fitted with the idle shaft 230. The elastic member 243 may buffer the sleeve 241 and the idle shaft support 220 when they are relatively moved.

After the bracket 23 sends the microfluidic chip 10 to a set position, the lifting motor 250 drives the sleeve 241 connected to the top rod 260 to move upward, the idle shaft support 220 moves upward under the support of the elastic element 243 in the sleeve 241, and further pushes the idle disk 210 to move upward, and the bottom temperature control unit 130 moves upward along with the idle disk 210. The idle shaft 230 is engaged with the microfluidic chip 10 during the upward movement, and pushes the microfluidic chip 10 to be disengaged from the bracket 23 until the microfluidic chip 10 is engaged with the rotating shaft 930. At this time, the rotation shaft 930, the microfluidic chip 10, and the idle shaft 230 are sequentially connected together. When the driving motor 920 drives the rotating shaft 930 to rotate, the microfluidic chip 10 and the idle shaft 230 also rotate synchronously, and then the top blade structure 113 sleeved on the rotating shaft 930 and the bottom blade structure 133 sleeved on the idle shaft 230 also rotate synchronously. With such an arrangement, a liquid flow driving force can be provided for the liquid in the microfluidic chip 10 by only driving the motor 920 in one step, and the ambient temperatures in the top temperature control unit 110 and the bottom temperature control unit 130 can be adjusted.

Referring to fig. 7, the amplification temperature control mechanism 300 includes a support frame 350, and a driving module 370, an upper temperature control module 310 and a lower temperature control module 330 disposed on the support frame 350, wherein the driving module 370 is configured to enable the upper temperature control module 310 and the lower temperature control module 330 to move toward each other to be clamped at two sides of the PCR amplification chamber of the microfluidic chip 10 or move away from the PCR amplification chamber in a reverse manner. The upper temperature control module 310 comprises a first heat radiator 311, a first semiconductor chilling plate 312 and a first heat conductor 313 which are sequentially connected in a stacked manner, and the lower temperature control module 330 comprises a second heat radiator 331, a second semiconductor chilling plate 332 and a second heat conductor 333 which are sequentially connected in a stacked manner. The first thermal conductor 313 is provided with a receiving groove (not shown in the figure) for receiving a PCR amplification chamber protruding from the surface of the microfluidic chip. When the temperature of the PCR amplification cavity is controlled, the first thermal conductor 313 and the second thermal conductor 333 are enclosed at two sides of the PCR amplification cavity, and the PCR amplification cavity is located in the accommodating groove, so that the PCR amplification cavity is completely wrapped, rapid temperature adjustment is achieved in a targeted manner, and the reaction time is saved. It can be understood that when the PCR amplification chamber protrudes from the other side surface of the microfluidic chip 10, the accommodating groove is disposed on the second thermal conductor 333.

The first and

second heat sinks

311 and 331 may include heat sinks and fans, and the first and

second heat conductors

313 and 333 may be made of metal.

For ease of viewing, the support 350 of the amplification temperature control mechanism 300 is omitted from FIG. 8. The drive module 370 includes a horizontal slider rail 320, a vertical slider rail 340, an upper link 375, and a lower link 376. The vertical slider rail 340 includes a vertical rail 341, an upper slider 342 and a lower slider 343 slidably coupled to the vertical rail 341. The vertical guide rail 341 is fixed on the supporting frame 350, the upper temperature control module 310 is connected with the upper slider 342, and the lower temperature control module 330 is connected with the lower slider 343. The horizontal slider rail 320 includes a cross rail 321, and a front slider 322 slidably coupled to the cross rail 321. The transverse guide rail 321 is fixed on the support frame 350, and the length direction thereof is perpendicular to the length direction of the vertical guide rail 341. One end of the upper link 375 is hinged to the upper slider 342, the other end is hinged to the front slider 322, one end of the lower link 376 is hinged to the lower slider 343, and the other end is hinged to the front slider 322. When the front slider 322 slides along the transverse rail 321, the upper connecting rod 375 is driven to drive the upper slider 342 to slide along the vertical rail 341, and the lower connecting rod 376 is driven to drive the lower slider 343 to slide along the vertical rail 341, so that the upper temperature control module 310 and the lower temperature control module 330 approach to each other or separate from each other.

The required travel of the upper and lower

temperature control modules

310, 330 can be accommodated by varying the length of the upper and

lower links

375, 376.

In order to stabilize the movement of the upper and lower

thermal control modules

310 and 330, the vertical slider rails 340 are arranged in two symmetrical sets, and the upper and

lower links

375 and 376 are also arranged in two symmetrical sets, and accordingly, a rear slider 323 is slidably disposed on the lateral rail 321 to be hinged to the other set of upper and

lower links

375 and 376.

Referring to fig. 8, in the present embodiment, the amplification temperature control mechanism 300 further includes a cam mechanism and an elastic member 360, the cam mechanism includes a transmission shaft 371 and a cam 373 sleeved on the transmission shaft 371, and the cam 373 abuts against the upper slide 342. One end of the elastic member 360 is connected to the upper temperature control module 310, and the other end is connected to the lower temperature control module 330. When the temperature increasing control mechanism 300 is not in operation, the elastic member 360 is in an undeformed state.

When the cam 373 rotates synchronously with the transmission shaft 371, the upper slider 342 slides along the vertical slider guide 340, and at the same time, the upper slider 342 drives the front slider 322 to slide along the transverse guide 321 through the upper link 375, and the lower link 376 connected with the front slider 322 also drives the lower slider 343 to slide along the vertical slider guide 340. In a series of linkage processes, the upper temperature control module 310 and the lower temperature control module 330 gradually move away from or close to each other; the elastic member 360 is also stretched as the upper temperature control module 310 and the lower temperature control module 330 are separated, and gradually restores its shape as the upper temperature control module 310 and the lower temperature control module 330 approach each other.

The elastic member 360 is disposed between the upper temperature control module 310 and the lower temperature control module 330, so as to ensure that the cam 373 is always attached to the upper slider 342. In other embodiments, a roller may be disposed between the cam 373 and the upper slider 342, and the roller may rotate relative to the upper slider 342 to reduce friction between the cam 371 and the upper slider 342.

Referring to fig. 9, the detecting mechanism 500 includes an optical fiber type fluorescence detector, the optical fiber type fluorescence detector includes a fixed disk 510 and a rotating disk 530, which are stacked, the fixed disk 510 is provided with an excitation light fiber 511 and an emission light fiber 512, and the rotating disk 530 is provided with an excitation light source module 531 and a fluorescence detecting module 532. One end of the excitation light fiber 511 is coupled to the excitation light source module 531, and the other end is connected to the first thermal conductor 313 in the amplification temperature control mechanism 300. One end of the emission optical fiber 512 is coupled to the fluorescence detection module 532, and the other end is connected to the first thermal conductor 313 in the amplification temperature control mechanism 300. The excitation light source module 531 is used for emitting excitation light, the excitation light is projected to the PCR amplification chamber through the excitation light fiber 511, the fluorescence is generated after the fluorescence in the PCR amplification chamber is excited, and the generated fluorescence is transmitted to the fluorescence detection module 532 through the emission light fiber 512 for processing to obtain a detection result.

In the present embodiment, the excitation-light source modules 531 and the fluorescence detection modules 532 are provided in three groups and arranged uniformly in the circumferential direction of the rotating disk 530. Different groups of excitation light source modules 531 and fluorescence detection modules 532 can form different optical detection channels with the excitation light fiber 511 and the emission light fiber 512 by rotating the rotating disk 530, so as to improve the detection efficiency.

According to the nucleic acid analysis device, in the nucleic acid extraction process, the extraction temperatures of different extraction areas of the microfluidic chip 10 are respectively controlled, and the temperature influence between adjacent extraction areas is reduced. The top fan blade structure 113 and the bottom fan blade structure 133 are synchronously rotated with the rotating shaft 930, and the air temperature above the extraction area of the microfluidic chip 10 can be adjusted by using one driving motor 920. Further, the top blade structure 113 drives air to form a dynamic airflow during rotation, and the airflow circulates only inside the top heat insulating cover 111, and similarly, the airflow formed during rotation of the bottom blade structure 133 also circulates only inside the bottom heat insulating cover 131, so that the temperatures of the air above the adjacent extraction regions do not affect each other while the temperatures in the top heat insulating cover 111 and the bottom heat insulating cover 131 are kept balanced. When the PCR amplification cavity carries out amplification reaction, the PCR amplification cavity is completely wrapped by the amplification temperature control mechanism, and the reaction temperature of the PCR amplification cavity can be quickly adjusted due to the large heating area and the short temperature transmission path of the PCR amplification cavity. The detection mechanism 500 is provided with a plurality of groups of optical detection channels, and all detection results can be obtained by rotating the rotating disc 530. Meanwhile, the corresponding groups of excitation light source modules 531 and fluorescence detection modules 532 can be arranged on the rotating disk 530 as required, so that the expansion is convenient. According to the nucleic acid analysis device, the whole nucleic acid detection process can be automatically controlled to be completed after the micro-fluidic chip 10 is placed in the bracket 23, and convenience and rapidness are achieved.

All possible combinations of the technical features of the above embodiments may not be described for the sake of brevity, but should be considered as within the scope of the present disclosure as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the utility model. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent should be subject to the appended claims.

Claims

1. A nucleic acid analysis device for analyzing a sample in a microfluidic chip, wherein the microfluidic chip comprises an extraction area and an amplification chamber, the extraction area comprises a plurality of extraction temperature zones, and the nucleic acid analysis device is characterized by comprising:

2. The nucleic acid analysis device of claim 1, wherein the top temperature control unit comprises a top temperature-insulating cover and a top heating element, the top heating element is located in the top temperature-insulating cover, the bottom temperature control unit comprises a bottom temperature-insulating cover and a bottom heating element, the bottom heating element is located in the bottom temperature-insulating cover, and when the microfluidic chip is connected to the rotating shaft, the top temperature-insulating cover and the bottom temperature-insulating cover are both not in contact with the microfluidic chip.

3. The apparatus according to claim 2, wherein the top temperature control unit further comprises a top fan structure and a top deflector located in the top thermal shield, the top fan structure being sleeved on the shaft and located on one side of the top deflector; the bottom temperature control unit further comprises a bottom fan blade structure, a bottom flow guide disc and an idle shaft, wherein the bottom fan blade structure, the bottom flow guide disc and the idle shaft are located in the bottom heat insulation cover, the bottom fan blade structure is sleeved on the idle shaft and located on one side of the bottom flow guide disc, and the idle shaft is used for being connected with the rotating shaft to rotate synchronously along with the rotating shaft.

4. The nucleic acid analysis device of claim 3, wherein the top baffle and the bottom baffle are each provided with an air inlet and at least one air outlet therethrough.

5. The nucleic acid analysis device of claim 3, wherein the top diversion plate has a through air inlet at a central region thereof and a through air outlet at an edge thereof; the central area of the bottom flow guide disc is provided with a through central air inlet, and the bottom flow guide disc is provided with an inner ring air outlet and an outer ring air outlet along the radial direction.

6. The nucleic acid analysis device of claim 5, wherein the bottom baffle comprises a first air distribution plate and a second air distribution plate stacked together, and the first air distribution plate and the second air distribution plate are relatively rotatable to communicate one of the inner ring air outlet and the outer ring air outlet with the central air inlet.

7. The apparatus according to claim 1, wherein a receiving chamber is provided on the upper temperature control module or the lower temperature control module, and the receiving chamber is configured to receive the amplification chamber.

8. The nucleic acid analysis device of claim 1, wherein the amplification temperature control mechanism further comprises a driving module, the driving module comprises an upper connecting rod, a lower connecting rod, and a vertically arranged horizontal slider rail and a vertical slider rail, the vertical slider rail comprises an upper slider connected to the upper temperature control module, and a lower slider connected to the lower temperature control module, one end of the upper connecting rod is hinged to the upper slider, the other end of the upper connecting rod is hinged to a slider on the horizontal slider rail, one end of the lower connecting rod is hinged to the lower slider, and the other end of the lower connecting rod is hinged to a slider on the horizontal slider rail.

9. The apparatus according to claim 8, wherein the driving module further comprises a transmission shaft and a cam sleeved on the transmission shaft, the cam abuts against the upper temperature control module, and the upper temperature control module and the lower temperature control module can move toward or away from each other during rotation of the cam.

10. The apparatus of claim 9, wherein the amplification temperature control mechanism further comprises an elastic member, one end of the elastic member is connected to the upper temperature control module, the other end of the elastic member is connected to the lower temperature control module, the elastic member is in a deformed state when the upper temperature control module and the lower temperature control module are away from each other, and the elastic member is in an original state when the upper temperature control module and the lower temperature control module are in contact with each other.