CN216738277U - Nucleic acid extraction element based on closed micro-fluidic chip - Google Patents

Nucleic acid extraction element based on closed micro-fluidic chip Download PDF

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Publication number
CN216738277U
CN216738277U CN202123014746.2U CN202123014746U CN216738277U CN 216738277 U CN216738277 U CN 216738277U CN 202123014746 U CN202123014746 U CN 202123014746U CN 216738277 U CN216738277 U CN 216738277U
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microfluidic chip
nucleic acid
fluorescence
closed microfluidic
acid extraction
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不公告发明人
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Shanghai Weiwei Micro Diagnostic Technology Co ltd
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Shanghai Weiwei Micro Diagnostic Technology Co ltd
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Abstract

The utility model relates to a nucleic acid extraction element based on closed micro-fluidic chip. When the closed micro-fluidic chip is used, a sample liquid is injected into the preset cavity at the head through the sample inlet, so that the sample liquid reacts with a stored reagent in the preset cavity, a magnetic bead carries a target object after reaction, the magnetic bead is adsorbed by the magnetic adsorbing piece, the micro-fluidic chip or the magnetic adsorbing piece is moved by the first moving mechanism, the magnetic bead carries the target object to move to the next preset cavity and finally enter the last preset cavity, and the target object is obtained in the last preset cavity; then, the gas power assembly acts to enable the target object to enter the sample detection chamber, and amplification and detection operations can be completed in the sample detection chamber. Therefore, the extraction operation of the target object is completed in the preset chamber in a closed state, the operation difficulty can be reduced, the sample can be prevented from being polluted, and the accuracy of the detection result can be improved.

Description

Nucleic acid extraction element based on closed micro-fluidic chip
Technical Field
The utility model relates to a micro-fluidic technology field especially relates to a nucleic acid extraction element based on closed micro-fluidic chip.
Background
Polymerase Chain Reaction (PCR) is a molecular biology technique developed at the end of the 20 s, and large-scale replication of specific nucleic acid fragments is achieved through denaturation, annealing and extension. Due to the high sensitivity and specificity of the PCR technology, the PCR technology is widely applied to the fields of molecular diagnosis to realize the aspects of diagnosis of infectious diseases, early screening of tumors, medication guidance, screening of congenital diseases and the like.
The application scenario of the traditional PCR technology needs to be carried out in a professional molecular laboratory, the whole process is strictly controlled, and an independent sample preparation room, a reagent preparation room, an analysis laboratory and the like need to be arranged. A user needs to use a large workstation or an extractor to extract nucleic acid of a sample, then the extracted nucleic acid fragment is transferred into a PCR tube, and then the PCR tube is loaded on a PCR instrument to carry out amplification analysis detection. Such operations not only require professional personnel and at a professional site, but also have the potential to contaminate the sample during the operation, thereby leading to erroneous test results.
SUMMERY OF THE UTILITY MODEL
Based on this, it is necessary to overcome the defects in the prior art, and provide a nucleic acid extraction device based on a closed microfluidic chip, which can reduce the operation difficulty, avoid polluting the sample, and is beneficial to improving the accuracy of the detection result.
The technical scheme is as follows: a nucleic acid extraction device based on a closed micro-fluidic chip comprises a magnetic bead and a plurality of preset chambers which are communicated with each other, wherein the magnetic bead is arranged in the preset chambers, and phase change valves for controlling the on-off are arranged at the communicated positions of the two preset chambers; the nucleic acid extraction device based on the closed microfluidic chip comprises: a first temperature control assembly having a heating mechanism for heating the phase change valve such that the phase change valve is opened to communicate the two pre-chambers; the magnetic attraction piece is positioned in a preset distance range with the closed microfluidic chip and is used for adsorbing the magnetic beads; and the first moving mechanism drives the closed microfluidic chip or the magnetic suction piece to move so that the magnetic beads move in the communicated preset chambers.
In one embodiment, the first temperature control assembly is provided with a temperature reduction mechanism for carrying out temperature reduction treatment on the phase change valve so that the phase change valve blocks the communication between the two preset chambers.
In one embodiment, the nucleic acid extraction device based on the closed microfluidic chip further comprises a first support plate for placing the closed microfluidic chip; the first moving mechanism drives the first supporting plate to move.
In one embodiment, the closed microfluidic chip-based nucleic acid extraction device further comprises a frame and a first guide assembly; the first guide assembly is arranged on the rack, and the first support plate is connected with the first guide assembly.
In one embodiment, two first pressing plates are arranged on the first supporting plate, and the two first pressing plates respectively press two opposite sides of the closed microfluidic chip correspondingly.
In one embodiment, a second pressing plate and a driving mechanism for driving the second pressing plate to move are arranged on the first supporting plate, and the second pressing plate can be pressed on the waterproof breathable film of the closed microfluidic chip and seals the waterproof breathable film under the driving of the driving mechanism.
In one embodiment, the closed microfluidic chip-based nucleic acid extraction device further comprises a second moving mechanism; the second moving mechanism is connected with the first temperature control assembly and the magnetic suction piece.
In one embodiment, the heating mechanism comprises a first heating plate, and the magnetic attraction piece is arranged adjacent to the first heating plate.
In one embodiment, the nucleic acid extraction device based on the closed microfluidic chip further comprises a mixing mechanism for mixing the liquid in the preset chamber.
In one embodiment, the blending mechanism comprises a first bracket, an ultrasonic transducer arranged on the first bracket, and a first guide wheel rotationally arranged on the first bracket; the first support is arranged on the rack or the ground through a second elastic part, the first support plate is provided with a hollow area capable of exposing at least one preset chamber, and the side part of the first support plate is provided with a first avoidance hole; the first moving mechanism drives the first supporting plate to move to the position above the blending mechanism, and when the bottom surface of the first supporting plate is abutted to the first guide wheel, a space is formed between the ultrasonic transducer and the closed microfluidic chip arranged on the first supporting plate; when the first guide wheel moves into the first avoidance hole, the ultrasonic transducer is in contact with one of the preset chambers.
In one embodiment, the number and the positions of the first avoidance holes correspond to all the preset chambers one by one.
In one embodiment, the blending mechanism further comprises a third guide assembly, and the first support is connected with the rack or the ground through the third guide assembly.
In one embodiment, the nucleic acid extraction device based on the closed microfluidic chip further comprises a second temperature control component, and the second temperature control component can heat the sample detection chamber of the closed microfluidic chip.
In one embodiment, the second temperature control assembly comprises a second heating plate and a third heating plate which are arranged at intervals, the temperature heated by the second heating plate is higher than that heated by the third heating plate, and the second heating plate and the third heating plate cyclically and alternately heat the sample detection chamber.
In one embodiment, the second temperature control assembly further comprises two semiconductor refrigeration pieces, a radiator and a heat radiation fan; one semiconductor refrigeration piece is arranged between the second heating plate and the radiator, the other semiconductor refrigeration piece is arranged between the third heating plate and the radiator, and the radiator is connected with the cooling fan.
In one embodiment, the second temperature control assembly is arranged on the rack or the ground through a third elastic member, the second temperature control assembly is provided with a second guide wheel, the side part of the first support plate is provided with a second avoidance hole, and the first moving mechanism can drive the first support plate to move above the second temperature control assembly; when the bottom surface of the first supporting plate is abutted against the second guide wheel, a space is arranged between the second heating plate and the closed microfluidic chip arranged on the first supporting plate; when the second guide wheel moves into the second avoidance hole, the second heating plate or the third heating plate is in contact with the sample detection chamber.
In one embodiment, the closed microfluidic chip-based nucleic acid extraction device further comprises an optical detection module; the optical detection module is used for optically detecting nucleic acid in the sample detection chamber.
In one embodiment, the optical detection module comprises a fluorescence excitation component, a fiber optic detection component and a fluorescence reading component; the fluorescence excitation assembly is used for generating fluorescence and emitting the generated fluorescence to the optical fiber detection assembly, and the optical fiber detection assembly is used for guiding the fluorescence to the sample detection chamber and guiding light reflected by nucleic acid in the sample detection chamber to the fluorescence reading assembly.
In one embodiment, the fluorescence excitation component comprises a fluorescence emission end, a dichroic mirror and a fluorescence exit end; the fluorescence generated by the fluorescence emission end enters the dichroic mirror and is emitted outwards through the dichroic mirror and the fluorescence emission end in sequence;
the optical fiber detection assembly comprises a first transmission optical fiber, a detection optical fiber and a second transmission optical fiber; the two ends of the first transmission optical fiber are respectively connected with the fluorescence emitting end and the detection optical fiber, the two ends of the second transmission optical fiber are respectively connected with the detection optical fiber and the fluorescence receiving end of the fluorescence reading assembly, and the detection optical fiber faces the sample detection chamber;
the fluorescence reading assembly comprises a detection camera, an optical filter and a fluorescence receiving end which are sequentially arranged, fluorescence reflected by a sample of the sample detection chamber is transmitted to the fluorescence receiving end through the detection optical fiber, the fluorescence receiving end is used for transmitting the fluorescence to the optical filter, and the fluorescence is incident to the detection camera after being filtered by the optical filter.
In one embodiment, the optical fiber detection assembly further comprises a third moving mechanism and a buffer seat which are arranged on the rack; the third moving mechanism is connected with the buffer seat, the third moving mechanism is used for driving the buffer seat to move to the first supporting plate, and the detection optical fiber is arranged on the buffer seat.
In one embodiment, the fluorescence reading assembly further comprises a mounting base, a fourth moving mechanism arranged on the mounting base, and an array base movably arranged on the mounting base; the fourth moving mechanism is connected with the array seat and is used for driving the array seat to move; the number of the fluorescence emission ends is at least two, and the number of the optical filters is at least two and is in one-to-one correspondence with the fluorescence emission ends; all the optical filters are sequentially arranged on the array seat, and when the fourth moving mechanism drives the array seat to move, the optical filters on the array seat can be sequentially aligned with the fluorescence receiving end.
When the nucleic acid extraction device based on the closed micro-fluidic chip is used together with the closed micro-fluidic chip, a sample liquid is injected into the first preset chamber through the sample inlet, so that the sample liquid reacts with a stored reagent in the preset chamber, a target object after the reaction is carried by the magnetic bead, the magnetic bead is adsorbed by the magnetic adsorbing piece, the micro-fluidic chip or the magnetic adsorbing piece is moved by the first moving mechanism, the target object carried by the magnetic bead is moved to the next preset chamber and finally enters the last preset chamber, and the target object is obtained in the last preset chamber; then, the gas power assembly acts to enable the target object to enter the sample detection chamber, and amplification and detection operations can be completed in the sample detection chamber. Therefore, the extraction operation of the target object is completed in the preset chamber in a closed state, the operation difficulty can be reduced, the sample can be prevented from being polluted, and the accuracy of the detection result can be improved.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this application, are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification.
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly described below, and it is obvious that the drawings in the description are only some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained without creative efforts.
Fig. 1 is a schematic structural diagram of a closed microfluidic chip according to an embodiment of the present invention;
FIG. 2 is a schematic diagram of a nucleic acid extraction apparatus based on a closed microfluidic chip according to an embodiment of the present invention;
FIG. 3 is a schematic view of the rack of FIG. 2 with one side panel hidden;
FIG. 4 is a schematic view of the structure of FIG. 2 with some parts hidden;
fig. 5 is a schematic structural view of a magnetic attraction member and a first temperature control assembly according to an embodiment of the present invention;
fig. 6 is a schematic structural view of a closed microfluidic chip disposed on a first support plate according to an embodiment of the present invention;
fig. 7 is a schematic structural diagram of a fluorescence excitation assembly according to an embodiment of the present invention;
fig. 8 is a schematic structural diagram of an optical fiber detection assembly according to an embodiment of the present invention;
fig. 9 is a schematic structural diagram of a fluorescence reading assembly according to an embodiment of the present invention.
10. A closed microfluidic chip; 11. a chip body; 111. presetting a chamber; 112. a first communicating passage; 113. a wallboard; 114. a sample detection chamber; 115. a first chip body; 116. a second chip body; 12. a gas power assembly;
20. a first temperature control assembly; 21. a first heating plate; 22. a cooling plate; 30. a magnetic member; 41. a first moving mechanism; 42. a first support plate; 421. positioning a groove; 422. a first platen; 423. a fastener; 424. a second platen; 425. a drive mechanism; 4251. an eccentric block; 4252. a frame; 426. a first limit rod; 427. a first avoidance hole; 428. a second avoidance hole; 43. a first guide assembly; 50. a frame; 61. a second moving mechanism; 62. a second guide assembly; 621. a first guide post; 622. a first sliding plate; 63. a second support plate; 70. a blending mechanism; 71. a first bracket; 72. an ultrasonic transducer; 73. a first guide wheel; 74. a third guide assembly; 81. a second temperature control assembly; 811. a second heating plate; 812. a third heating plate; 813. a semiconductor refrigeration sheet; 814. a heat sink; 815. a heat radiation fan; 82. a second guide wheel; 83. a fourth guide assembly; 90. an optical detection module; 91. a fluorescence excitation assembly; 911. a fluorescent light emitting end; 912. a dichroic mirror; 913. a fluorescence exit end; 92. an optical fiber detection assembly; 921. detecting the optical fiber; 922. a third moving mechanism; 923. a buffer seat; 924. a fifth guide assembly; 925. a third support plate; 93. a fluorescence reading assembly; 931. detecting a camera; 932. an optical filter; 933. a fluorescent receiving end; 934. a mounting seat; 935. an array base; 936. and a fourth moving mechanism.
Detailed Description
In order to make the above objects, features and advantages of the present invention more comprehensible, embodiments of the present invention are described in detail below with reference to the accompanying drawings. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein, as those skilled in the art will be able to make similar modifications without departing from the spirit and scope of the present invention.
Referring to fig. 1, fig. 1 shows a schematic structural diagram of a closed microfluidic chip 10. The closed microfluidic chip 10 includes a chip body 11, magnetic beads (not shown), and a pneumatic assembly 12. At least two preset chambers 111 which are sequentially communicated are arranged on the chip body 11. All the adjacent pre-chambers 111 are communicated through the first communication passage 112. Specifically, wall plates 113 are disposed between all adjacent pre-chambers 111, all first communication channels 112 are disposed at the top portions of the wall plates 113, and all first communication channels 112 are provided with phase change valves (not shown). Further, the mouths of all the pre-chambers 111 (as shown in fig. 1, the mouths are located on the top surface of the chip body 11) are sealed in a closed state by using, for example, a sealing film (not shown) which is hidden in fig. 1, and a reaction reagent or a cleaning liquid is provided inside the pre-chambers 111.
In addition, the chip body 11 is further provided with a sample inlet and an exhaust port. The sample inlet and the exhaust port are both communicated with a first preset chamber 111. The sample liquid is injected into the first preset chamber 111 through the sample inlet, in the sample injection process, the gas in the first preset chamber 111 is discharged outwards through the gas outlet by the entering sample liquid, the chip body 11 is further provided with a sample detection chamber 114, and the sample detection chamber 114 is communicated with the last preset chamber 111. The magnetic beads are moved in all pre-chambers 111 by the magnetic means. The gas dynamic assembly 12 is in communication with the last pre-chamber 111, and the eluent including nucleic acid in the last pre-chamber 111 is pushed to the sample detection chamber by providing gas pressure. The gas powered assembly 12 may also be in communication with the sample detection chamber 114 to provide suction to transfer the nucleic acid containing eluate from the last pre-chamber 111 to the sample detection chamber 114.
Referring to fig. 2 to 5, an embodiment of the present invention provides a nucleic acid extraction device based on a closed microfluidic chip 10, the nucleic acid extraction device based on the closed microfluidic chip 10 includes: the first temperature control assembly 20, the magnetic member 30 and the first moving mechanism 41. The first temperature control assembly 20 has a heating mechanism for heating the phase change valve so that the phase change valve is opened to communicate the two preset chambers, that is, the first temperature control assembly 20 can heat the phase change valve of the closed microfluidic chip 10 so that the phase change valve is opened. The magnetic attraction piece 30 and the closed microfluidic chip 10 are located within a preset distance range and used for adsorbing magnetic beads, and when the phase change valve is in an open state, the magnetic attraction piece 30 can adsorb and drive the magnetic beads inside the closed microfluidic chip 10 to move in all the preset chambers 111. The magnetic attraction member 30 includes, but is not limited to, a permanent magnet and an electromagnet. The first moving mechanism 41 drives the closed microfluidic chip 10 or the magnetic attraction member 30 to move, so that the magnetic beads move in the pre-chamber 111.
When the nucleic acid extraction device based on the closed microfluidic chip 10 is used with the closed microfluidic chip 10, a sample liquid is injected into the first preset chamber 111 through the sample inlet, so that the sample liquid reacts with a stored reagent in the preset chamber 111, a target object after the reaction is carried by the magnetic bead, the magnetic bead is adsorbed by the magnetic adsorbing element, the microfluidic chip or the magnetic adsorbing element is moved by the first moving mechanism 41, the target object carried by the magnetic bead is moved to the next preset chamber 111 and finally enters the last preset chamber 111, and the target object to be detected is obtained in the last preset chamber 111; then, the gas dynamic assembly 12 is operated to make the target object to be detected enter the sample detection chamber 114, so that the amplification and detection operations can be completed in the sample detection chamber 114. Therefore, the extraction operation of the target object to be detected is completed in the preset chamber 111 in a closed state, so that the operation difficulty can be reduced, the sample can be prevented from being polluted, and the accuracy of the detection result can be improved.
In one embodiment, the first temperature control assembly 20 has a temperature reduction mechanism that reduces the temperature of the phase change valve such that the phase change valve blocks communication between the two pre-chambers. In this way, when the phase change valve is heated by the heating mechanism of the first temperature control assembly 20, the phase change valve is changed from a solid state to a liquid state, i.e. the phase change valve is opened, so that the magnetic attraction member 30 can drive the attracted magnetic beads to pass through the phase change valve in the liquid state and enter another adjacent pre-chamber 111. On the contrary, after the magnetic bead enters into another adjacent preset cavity 111, cool down through the cooling mechanism of first temperature control assembly 20, can reduce the temperature of phase change valve fast for the phase change valve is changed into solid-state by liquid state fast, and the phase change valve closes promptly, can better keep apart two preset cavities 111 each other when the phase change valve closes, avoids mutual influence, thereby can guarantee the extraction precision of nucleic acid. Of course, as an alternative, the phase change valve may be cooled in the environment by natural heat dissipation.
Referring to fig. 2 to 4, in one embodiment, the nucleic acid extraction device based on the enclosed microfluidic chip 10 further includes a first support plate 42 for placing the enclosed microfluidic chip 10. The closed microfluidic chip 10 is disposed on the first support plate 42, and the first moving mechanism 41 drives the first support plate 42 to move. Thus, when the first moving mechanism 41 drives the first supporting plate 42 to move, the closed microfluidic chip 10 is correspondingly driven to move.
Referring to fig. 3, 4 and 6, in one embodiment, the nucleic acid extracting apparatus based on the enclosed microfluidic chip 10 further includes a frame 50 and a first guiding assembly 43. The first guide assembly 43 is disposed on the frame 50, and the first support plate 42 is connected to the first guide assembly 43. In this way, when the first moving mechanism 41 drives the first supporting plate 42 to move, the first supporting plate 42 can move smoothly under the guiding action of the first guiding assembly 43.
Specifically, the first moving mechanism 41 is provided on the frame 50 or at another position, for example, and is not limited herein, as long as the first support plate 42 can be driven to move. In addition, the first moving mechanism 41 includes, but is not limited to, a screw motor, a belt motor, an air cylinder, and a hydraulic cylinder, and can be set according to actual requirements.
In addition, the first guiding assembly 43 includes, but is not limited to, a sliding guiding manner of a sliding rail and a sliding block, and a sliding guiding manner of a guiding rod and a guiding sleeve.
Referring to fig. 1 again, in general, the closed microfluidic chip 10 includes a first chip body 115 (shown in a left portion of fig. 1) and a second chip body 116 (shown in a right portion of fig. 1) connected to each other. All the pre-chambers 111 are sequentially disposed on the first chip body 115, the sample detection chambers 114 are disposed on the second chip body 116, and the thickness of the first chip body 115 is greater than that of the second chip body 116. In addition, the second chip body 116 is a transparent plate material in order to optically detect the sample detection chamber 114.
Referring to fig. 1 again, in one embodiment, the sample detection chamber 114 has a liquid inlet end and a gas outlet end, the liquid inlet end of the sample detection chamber 114 is communicated with the last preset chamber 111, and the gas outlet end of the sample detection chamber 114 is provided with a waterproof and breathable film, for example. And when the eluent containing the nucleic acid in the last preset chamber 111 needs to be transferred to the sample detection chamber 114, the gas power assembly 12 acts on the last preset chamber 111, so that the eluent in the last preset chamber 111 is pushed into the sample detection chamber 114, and the gas in the sample detection chamber 114 is discharged outwards through the waterproof breathable film.
Referring to fig. 6, in one embodiment, the first supporting plate 42 is provided with a positioning groove 421 corresponding to the closed microfluidic chip 10. Thus, when the closed microfluidic chip 10 is placed in the positioning groove 421 on the first support plate 42, the position is relatively fixed, and the stability is good.
Referring to fig. 6, in an embodiment, two first pressing plates 422 are further disposed on the first supporting plate 42, and the two first pressing plates 422 respectively press two opposite sides of the first chip body 115 of the enclosed microfluidic chip 10. Thus, after the closed microfluidic chip 10 is placed on the first support plate 42, the two first press plates 422 are used for correspondingly pressing the two opposite sides of the first chip body 115 of the closed microfluidic chip 10, so that the closed microfluidic chip 10 can be stably arranged on the first support plate 42, and the nucleic acid extraction and detection effects can be ensured. In addition, since the two first pressing plates 422 press the two opposite sides of the first chip body 115 and are not pressed on the remaining area of the first chip body 115, the magnetic bead transfer, the ultrasonic mixing and the phase change valve state adjustment of the pre-chamber 111 are not affected.
Of course, as an alternative, the number of the first pressing plates 422 may be one or other, and when there is one first pressing plate 422, the first pressing plate 422 may be pressed against one side of the first chip body 115. In addition, the first pressing plate 422 is not limited to be pressed against the side portion of the first chip body 115, and may be pressed against other portions of the first chip body 115 as long as the pressed portion on the first chip body 115 does not interfere with magnetic bead transfer, ultrasonic mixing, and phase change valve state adjustment.
The first pressing plate 422 is detachably mounted on the first supporting plate 42, for example, by fasteners 423, and the magnitude of the pressure applied to the first chip body 115 can be adjusted by adjusting the tightness of the fasteners 423. The fastening member 423 may be, for example, a screw, a bolt, or the like, which is not limited herein.
Referring to fig. 6, in one embodiment, a second pressing plate 424 is further disposed on the first supporting plate 42. The second pressing plate 424 presses the second chip body 116 of the closed microfluidic chip 10, and the pressing area of the second pressing plate 424 on the second chip body 116 can cover the waterproof and breathable film of the closed microfluidic chip 10 and can expose the sample detection chamber 114 of the closed microfluidic chip 10. Thus, when the closed microfluidic chip 10 is placed on the first support plate 42, the second pressing plate 424 presses the second chip body 116 of the closed microfluidic chip 10, so that the closed microfluidic chip 10 is stably disposed on the first support plate 42, thereby ensuring the extraction and detection effects of nucleic acids. In addition, since the pressing area of the second pressing plate 424 on the second chip body 116 covers the waterproof and breathable membrane of the closed microfluidic chip 10, that is, when the second pressing plate 424 is pressed on the second chip body 116, the second pressing plate 424 blocks the waterproof and breathable membrane, so that the contamination caused by the mutual flow of the liquid in the preset chamber 111 and the liquid in the sample detection chamber 114 can be avoided, and only when the second pressing plate 424 leaves the waterproof and breathable membrane, under the power action of the gas power assembly 12, the eluent in the preset chamber 111 can be transferred into the sample detection chamber 114. In addition, since the pressing area of the second pressing plate 424 on the second chip body 116 is exposed out of the sample detection chamber 114 of the closed microfluidic chip 10, that is, the second pressing plate 424 is pressed on the second chip body 116 without shielding the light path, it can be ensured that the optical detection analysis of the sample detection chamber 114 is normally performed.
Referring to fig. 6, in an embodiment, the nucleic acid extracting apparatus based on the enclosed microfluidic chip 10 further includes a driving mechanism 425, the driving mechanism 425 is configured to drive the second pressing plate 424 to move, and the second pressing plate 424 is capable of pressing on and sealing the waterproof gas-permeable membrane of the enclosed microfluidic chip 10 under the driving of the driving mechanism 425. Specifically, the driving mechanism 425 is provided on the first support plate 42. The driving mechanism 425 can drive the second pressing plate 424 to move up and down or horizontally so as to be away from and close to the closed microfluidic chip 10. Thus, when the driving mechanism 425 drives the second pressing plate 424 to be far away from the closed microfluidic chip 10, the waterproof breathable film is loosened from the second pressing plate 424, the sample detection chamber 114 is communicated with the external environment through the waterproof breathable film, and the eluent in the last preset chamber 111 can enter the sample detection chamber 114 under the power action of the gas power assembly 12; and when the eluent completely enters the sample detection chamber 114, the driving mechanism 425 resets, the second pressing plate 424 resets and presses the second chip body 116 of the closed microfluidic chip 10, and the second pressing plate 424 blocks the waterproof breathable film, so that the liquid in the preset chamber 111 and the liquid in the sample detection chamber 114 can be prevented from flowing mutually to cause pollution.
Alternatively, the specific design of the driving mechanism 425 is more, as long as it can drive the second pressing plate 424 to move up and down, and as an example, the driving mechanism 425 includes, for example, a motor (not shown) disposed on the first supporting plate 42, an eccentric block 4251 disposed on a rotating shaft of the motor, and a frame 4252 disposed on the second pressing plate 424. When the rotating shaft of the motor drives the eccentric block 4251 to rotate, the eccentric block can abut against the frame 4252 and drive the frame 4252 to move upwards, and the frame 4252 correspondingly drives the second pressing plate 424 to move upwards to be separated from the closed microfluidic chip 10. The eccentric mass 4251 can also rotate to a position separated from the frame 4252, and the second pressing plate 424 is reset and pressed on the enclosed microfluidic chip 10.
Referring to fig. 6, in one embodiment, the first support plate 42 is provided with a first limiting rod 426 and a first elastic member (not shown) disposed on the first limiting rod 426. The second pressing plate 424 is provided with a first movable hole and sleeved on the first limiting rod 426 through the first movable hole, and the head of the first limiting rod 426 abuts against the surface of the second pressing plate 424 far away from the first supporting plate 42 through the first elastic member. Thus, when the driving mechanism 425 drives the second pressing plate 424 to move away from the enclosed microfluidic chip 10, the second pressing plate 424 moves along the first limiting rod 426 and compresses the first elastic element; when the driving mechanism 425 is reset, the second pressing plate 424 can be reset and pressed on the second chip body 116 under the elastic force of the first elastic member. It should be noted that the number of the first limiting rods 426 is not limited to one, and may be two, three or more, and the number of the movable holes on the second pressing plate 424 is the same as the number of the first limiting rods 426.
Referring to fig. 3 to 5, in one embodiment, the nucleic acid extracting apparatus based on the closed microfluidic chip 10 further includes a second moving mechanism 61. The second moving mechanism 61 is connected with the first temperature control assembly 20 and the magnetic attraction piece 30. Therefore, when the first moving mechanism 41 moves the closed microfluidic chip 10 to the preset position, the first temperature control assembly 20 or the magnetic part 30 is moved up and down by the second moving mechanism 61, so that the magnetic part 30 can be moved to the position attached to the top surface of the preset chamber 111 to adsorb magnetic beads inside the preset chamber 111, and the first temperature control assembly 20 can be moved to the position of the phase change valve, thereby heating or cooling the phase change valve.
Referring to fig. 1 and 5, in one embodiment, the first temperature control assembly 20 includes a first heating plate 21. The magnetic attraction piece 30 is arranged adjacent to the first heating plate 21, and when the magnetic attraction piece 30 is attached to and contacted with the top surface of any one of the preset chambers 111, the first heating plate 21 is synchronously close to the phase change valve adjacent to the preset chamber 111. Therefore, when the second moving mechanism 61 drives the magnetic attraction member 30 to move, and the magnetic attraction member 30 is attached to and contacted with the top surface of one of the preset chambers 111, the magnetic attraction member 30 can attract the magnetic beads in the preset chamber 111 to the top surface of the preset chamber 111, and meanwhile, the phase change valve is changed from a solid state to a liquid state due to the fact that the first heating plate 21 is synchronously close to the phase change valve adjacent to the preset chamber 111, so that when the first moving mechanism 41 drives the closed microfluidic chip 10 to move, the magnetic beads can penetrate through the phase change valve to enter the other adjacent preset chamber 111, and the nucleic acid extraction efficiency can be improved.
Referring to fig. 1 and 5, in one embodiment, the first temperature control assembly 20 further includes a cooling plate 22. The cooling plate 22, the magnetic member 30 and the first heating plate 21 are sequentially disposed. Thus, for example, when the magnetic attraction element 30 drives the magnetic beads to move from the first preset chamber to the second preset chamber 111, the magnetic attraction element 30 contacts with the top surface of the second preset chamber 111, the cooling plate 22 is synchronously close to the phase change valve between the first preset chamber 111 and the second preset chamber 111, so as to reduce the temperature of the phase change valve, so that the phase change valve is changed from a liquid state to a solid state, that is, the phase change valve is closed, and the first preset chamber 111 is isolated from the second preset chamber 111.
Referring to fig. 3 to 5, in one embodiment, the nucleic acid extraction device based on the enclosed microfluidic chip 10 further includes a frame 50 and a second guide assembly 62. The second moving mechanism 61 is mounted on the frame 50 through a second supporting plate 63, and a driving end of the second moving mechanism 61 is connected to the first temperature control assembly 20 and the magnetic member 30 through a second guiding assembly 62. Thus, under the guiding action of the second guiding component 62, the movement of the first temperature control component 20 and the magnetic attraction component 30 is more stable, so that the extraction efficiency of nucleic acid can be ensured.
The second moving mechanism 61 is similar to the first moving mechanism 41, and has many design forms, which are not limited herein and may be provided according to actual requirements.
It should be noted that the second guiding assembly 62 is similar to the first guiding assembly 43, mainly plays a guiding role, and the specific structure is not limited, and can be set according to actual requirements. Specifically, in this embodiment, the second guiding assembly 62 includes at least one first guiding post 621 disposed on the second supporting plate 63, and a first sliding plate 622 slidably sleeved on the first guiding post 621. The first sliding plate 622 is provided with a sliding hole and is fitted over the first guide post 621 through the sliding hole. The driving end of the second moving mechanism 61 is connected to the first sliding plate 622 to drive the first sliding plate 622 to move. The first temperature control assembly 20 and the magnetic member 30 are mounted on the first sliding plate 622.
Referring to fig. 1 to 4, in one embodiment, the nucleic acid extraction device based on the closed microfluidic chip 10 further includes a mixing mechanism 70. The mixing mechanism 70 is used for mixing the liquid in the preset chamber 111 of the closed microfluidic chip 10. Therefore, in the processes of nucleic acid cracking, cleaning and elution, when the uniform mixing mechanism 70 contacts any one of the preset chambers 111 of the closed microfluidic chip 10, the liquids in the preset chambers 111 can be uniformly mixed according to actual needs, so that the extraction effect of nucleic acid can be ensured.
Specifically, the blending mechanism 70 includes, but is not limited to, an ultrasonic blending mechanism 70, an oscillating blending mechanism 70, and the like.
Referring to fig. 1, 3, 4 and 6, in one embodiment, the kneading mechanism 70 includes a first bracket 71, an ultrasonic transducer 72 disposed on the first bracket 71, and a first guide wheel 73 rotatably disposed on the first bracket 71. The first support 71 is disposed on the rack 50 or the ground through a second elastic member (not shown), the first support plate 42 is disposed with a hollow area (not shown) capable of exposing the at least one preset chamber 111, a first avoiding hole 427 is disposed at a side of the first support plate 42, and the first moving mechanism 41 can drive the first support plate 42 to move above the blending mechanism 70. When the bottom surface of the first support plate 42 is abutted against the first guide wheel 73, a space is arranged between the ultrasonic transducer 72 and the closed microfluidic chip 10 placed on the first support plate 42; when the first guide wheel 73 moves into the first avoidance hole 427, the ultrasonic transducer 72 comes into contact with one of the pre-chambers 111. In this way, when the first guide wheel 73 moves into the first avoidance hole 427 in the process that the first moving mechanism 41 drives the first support plate 42 to move above the blending mechanism 70, the ultrasonic transducer 72 contacts one of the preset chambers 111 and blends the liquid in the preset chamber 111; when the first guide wheel 73 does not move into the first avoidance hole 427, at this time, the first guide wheel 73 contacts with the bottom surface of the first support plate 42 and is pressed down by the gravity of the first support plate 42, so that the second elastic member is compressed, and a space is provided between the ultrasonic transducer 72 and the closed microfluidic chip 10 placed on the first support plate 42, that is, the ultrasonic transducer 72 does not contact with the preset chamber 111, so that the ultrasonic transducer 72 does not transmit ultrasonic energy to the closed microfluidic chip 10.
Referring to fig. 1, 3, 4 and 6, in one embodiment, the number and the positions of the first avoiding holes 427 are arranged in a one-to-one correspondence with all the pre-chambers 111 of the closed microfluidic chip 10. Therefore, when the first support plate 42 drives the closed microfluidic chip 10 to move above the blending mechanism 70 and the first guide wheel 73 enters one of the first avoidance holes 427, the preset chamber 111 corresponding to the first avoidance hole 427 is conveniently contacted with the ultrasonic transducer 72, and the ultrasonic transducer 72 can realize the blending action of the preset chamber 111. Therefore, the ultrasonic transducer 72 can be in contact with the bottom surfaces of all the pre-chambers 111, that is, all the pre-chambers 111 can be uniformly mixed by the ultrasonic transducer 72 according to actual requirements.
It is understood that, as an alternative, the number of the first avoiding holes 427 may be less than the number of the preset chambers 111 of the closed microfluidic chip 10, and is not limited herein.
Referring to fig. 1, 3, 4 and 6, in an embodiment, first guide wheels 73 are disposed on two opposite sides of the first bracket 71, first avoidance holes 427 are disposed on two opposite sides of the first support plate 42, and the two first guide wheels 73 of the first bracket 71 can synchronously and respectively enter the two first avoidance holes 427. Therefore, in the process that the first supporting plate 42 moves above the blending mechanism 70, when the two first guide wheels 73 do not move into the two first avoidance holes 427, the first supporting plate 42 is in contact with the two first guide wheels 73 synchronously, and the motion stability of the first supporting plate 42 is better.
Referring to fig. 3, 4 and 6, in one embodiment, the blending mechanism 70 further includes a third guide assembly 74. The first bracket 71 is connected to the frame 50 or the ground through a third guide assembly 74. Therefore, under the guiding action of the third guiding assembly 74, the lifting mode of the first bracket 71 is linear lifting, and the stability is good. It should be noted that the specific combination of the third guiding assembly 74 is similar to the first guiding assembly 43, and is not limited herein. Further, the third guide assemblies 74 may be provided in one, two, three, or other number. In addition, the second elastic member is, for example, a spring, which is sleeved outside the third guide assembly 74, and one end of the second elastic member is connected to the first bracket 71, and the other end is connected to the third guide assembly 74 or connected to the frame 50.
Referring to fig. 1, 3 and 4, in one embodiment, the nucleic acid extraction device based on the closed microfluidic chip 10 further includes a second temperature control element 81. The second temperature control assembly 81 is capable of heating the sample detection chamber 114 of the enclosed microfluidic chip 10. Therefore, after the eluent enters the sample detection chamber 114, the eluent in the sample detection chamber 114 is circularly heated at high temperature and low temperature by the second temperature control component 81, so that nucleic acid amplification can be realized.
Referring to fig. 1, 3 and 4, in one embodiment, the second temperature control assembly 81 includes a second heating plate 811 and a third heating plate 812 spaced apart from each other. The second heating plate 811 is heated at a higher temperature than the third heating plate 812, and the second heating plate 811 and the third heating plate 812 heat the sample detection chamber 114 alternately and cyclically. Thus, the second heating plate 811 and the third heating plate 812 form a dual-temperature-zone heating, which reduces the time required for changing the temperature of the heat source, improves the heating and cooling rates of the liquid, and shortens the amplification detection time.
Referring to fig. 1, 3 and 4, in one embodiment, the second temperature control assembly 81 further includes two semiconductor cooling fins 813, a heat sink 814 and a heat dissipation fan 815. One semiconductor refrigerating sheet 813 is arranged between the second heating plate 811 and the heat sink 814, and the other semiconductor refrigerating sheet 813 is arranged between the third heating plate 812 and the heat sink 814. The heat sink 814 is connected to a heat dissipation fan 815.
Of course, the second heating plate 811 and the third heating plate 812 may also be heated by other methods, for example, heat conduction by heating wires, which is not limited herein, and may be set according to actual requirements.
Referring to fig. 1, 3 and 4, in one embodiment, the second temperature control assembly 81 is disposed on the frame 50 or the ground through a third elastic member (not shown), the second temperature control assembly 81 is provided with a second guide wheel 82, the side of the first support plate 42 is provided with a second avoiding hole 428, and the first moving mechanism 41 can drive the first support plate 42 to move above the second temperature control assembly 81. When the bottom surface of the first supporting plate 42 is abutted against the second guide wheel 82, a space is arranged between the second heating plate 811 and the third heating plate 812 and the closed microfluidic chip 10 placed on the first supporting plate 42; when the second guide wheel 82 moves into the second escape hole 428, the second heating plate 811 or the third heating plate 812 contacts the sample detection chamber 114. In this way, during the process that the first moving mechanism 41 drives the first supporting plate 42 to move above the second temperature control assembly 81, when the second guide wheel 82 moves into the second avoiding hole 428, the second heating plate 811 or the third heating plate 812 contacts with the sample detection chamber 114 and heats and amplifies the nucleic acid in the sample detection chamber 114; when the second guide wheel 82 does not move into the second avoiding hole 428, the second guide wheel 82 contacts with the bottom surface of the first supporting plate 42 and is pressed down by the gravity of the first supporting plate 42, so that the third elastic member is compressed, and a space is provided between the second heating plate 811 and the third heating plate 812 and the closed microfluidic chip 10 placed on the first supporting plate 42, that is, the second heating plate 811 and the third heating plate 812 do not contact with the sample detection chamber 114, so that the second temperature control assembly 81 does not transfer heat to the sample detection chamber 114.
Similarly, the second temperature control assembly 81 is disposed on the frame 50 through the fourth guide assembly 83, and the movement of the second temperature control assembly 81 is more stable under the guiding action of the fourth guide assembly 83.
Referring to fig. 6, in one embodiment, there are at least two second escape holes 428, and all the second escape holes 428 are sequentially disposed along the side of the first support plate 42. Specifically, in the process that the first supporting plate 42 drives the closed microfluidic chip 10 to move above the second temperature control assembly 81, and when the second guide wheels 82 sequentially enter the second avoidance holes 428, the second heating plate 811 and the third heating plate 812 sequentially contact the sample detection chamber 114, so that the sample detection chamber 114 is sequentially heated.
Referring to fig. 1, 3 and 4, in addition, when the pre-chamber 111 needs to be heated by the second temperature control assembly 81, that is, the number of the second avoiding holes 428 formed in the first support plate 42 is more than two, and the second avoiding holes 428 corresponding to the pre-chamber 111 are formed, when the second guide wheel 82 enters the second avoiding holes 428 corresponding to the pre-chamber 111, the heating plate of the second temperature control assembly 81 can contact the pre-chamber 111, so that heat can be transferred to the pre-chamber 111.
Referring to fig. 3, 7 to 9, in one embodiment, the nucleic acid extraction device based on the closed microfluidic chip 10 further includes an optical detection module 90. The optical detection module 90 is used to optically detect nucleic acids within the sample detection chamber 114.
Referring to fig. 3, 7 to 9, in one embodiment, the optical detection module 90 includes a fluorescence excitation component 91, a fiber optic detection component 92 and a fluorescence reading component 93. The fluorescence excitation assembly 91 is configured to generate fluorescence and emit the generated fluorescence to the fiber optic detection assembly 92, and the fiber optic detection assembly 92 is configured to introduce the fluorescence to the nucleic acids in the sample detection chamber 114 and to introduce light reflected from the nucleic acids in the sample detection chamber 114 to the fluorescence reading assembly 93.
Referring to fig. 7 to 9, in one embodiment, the fluorescence excitation assembly 91 includes a fluorescence emitting end 911, a dichroic mirror 912 and a fluorescence emitting end 913. The fluorescence generated by the fluorescence emitting end 911 enters the dichroic mirror 912, and is emitted outward through the dichroic mirror 912 and the fluorescence emitting end 913 in sequence.
Referring to fig. 7-9, in one embodiment, the optical fiber detection assembly 92 includes a first transmission optical fiber (not shown), a detection optical fiber 921 and a second transmission optical fiber (not shown). The two ends of the first transmission optical fiber are respectively connected with the fluorescence emitting end 913 and the detection optical fiber 921, the two ends of the second transmission optical fiber are respectively connected with the detection optical fiber 921 and the fluorescence receiving end 933 of the fluorescence reading assembly 93, and the detection optical fiber 921 faces to the sample detection chamber 114.
Referring to fig. 7 to 9, in an embodiment, the fluorescence reading assembly 93 includes a detection camera 931, a filter 932 and a fluorescence receiving end 933, which are sequentially disposed. Fluorescence reflected by the sample in the sample detection chamber 114 is transmitted to the fluorescence receiving end 933 through the detection optical fiber 921, and the fluorescence receiving end 933 is used for transmitting the fluorescence to the optical filter 932, and is filtered by the optical filter 932 and then enters the detection camera 931.
Referring to fig. 7 to fig. 9, in one embodiment, the optical fiber detecting assembly 92 further includes a third moving mechanism 922 and a buffer base 923 disposed on the rack 50. The third moving mechanism 922 is connected to the buffer base 923, and the third moving mechanism 922 is used for driving the buffer base 923 to move to the first support plate 42, and the detection optical fiber 921 is disposed on the buffer base 923. So, when first backup pad 42 drives closed micro-fluidic chip 10 and moves under optical fiber detection subassembly 92, move through third moving mechanism 922 drive buffer seat 923, buffer seat 923 moves to target in place and plays the cushioning effect through contacting first backup pad 42, detection optic fibre 921 is to sample detection chamber 114 on the closed micro-fluidic chip 10, just can realize incidenting the nucleic acid sample surface in sample detection chamber 114 with fluorescence, and the fluorescence of receiving to be reflected back by the nucleic acid sample surface.
It should be noted that, in this embodiment, the second pressing plate 424 is disposed on the first supporting plate 42, and the buffering seat 923 moves downward to abut against the second pressing plate 424 and then is positioned, that is, the buffering seat 923 indirectly contacts the first supporting plate 42.
It should be noted that the third moving mechanism 922 is similar to the first moving mechanism 41, and the specific structure is not limited as long as the driving buffer base 923 can move. In addition, the third moving mechanism 922 is installed in the rack 50 through the third support plate 925, and a fifth guide assembly 924 is arranged on the third support plate 925, and the fifth guide assembly 924 is connected with the buffer base 923, so that when the third moving mechanism 922 drives the buffer base 923 to move, the fifth guide assembly 924 guides, and the buffer base 923 moves more stably.
In one embodiment, fluorescence reading assembly 93 further includes a mount 934, a fourth movement mechanism disposed on mount 934, and an array mount 935 movably disposed on mount 934. The fourth moving mechanism is connected to the array base 935 and is configured to drive the array base 935 to move. At least two fluorescent emission terminals 911 are provided, and at least two optical filters 932 are provided in one-to-one correspondence with the fluorescent emission terminals 911. All the filters 932 are sequentially disposed on the array base 935, and when the fourth moving mechanism drives the array base 935 to move, the filters 932 on the array base 935 can be sequentially aligned with the fluorescence receiving end 933. Thus, the fluorescence emitting terminals 911 are sequentially turned on, and when the fluorescence emitting terminals 911 are turned on, the array base 935 is driven to move by the fourth moving mechanism, so that the optical filter 932 corresponding to the fluorescence emitting terminals 911 moves to the position aligned with the fluorescence receiving terminal 933, and thus, switching detection of multiple optical paths can be realized in a short time, detection time is reduced on the premise of ensuring accuracy, and detection speed is increased.
In one embodiment, a method for extracting nucleic acid based on the closed microfluidic chip 10, which uses the nucleic acid extraction device based on the closed microfluidic chip 10 of any of the above embodiments, includes the following steps:
step S10, when the magnetic attraction piece is used in cooperation with the closed microfluidic chip 10, the magnetic attraction piece adsorbs magnetic beads carrying a target object, and the first temperature control assembly 20 heats the phase change valve of the closed microfluidic chip 10 to enable the phase change valve to be opened;
step S20, the microfluidic chip or the magnetic element is moved by the first moving mechanism 41, so that the magnetic beads carrying the target object move from one of the pre-chambers 111 to the next pre-chamber 111 through the phase change valve in the open state.
In the nucleic acid extraction method based on the closed microfluidic chip 10, the extraction operation of the target object is completed in the closed preset chamber 111, so that the operation difficulty can be reduced, the sample can be prevented from being polluted, and the accuracy of the detection result can be improved.
In one embodiment, the nucleic acid extraction method based on the closed microfluidic chip 10 further comprises the steps of:
in step S30, when the magnetic beads carrying the target object move from one of the preset chambers 111 to the next preset chamber 111 through the phase change valve in the open state, the phase change valve in the open state is cooled by the first temperature control assembly 20, so that the phase change valve is closed from the liquid state to the solid state.
Step S40, after the phase change valve is closed, the magnetic attraction member is driven to move away from the closed microfluidic chip 10, and the closed microfluidic chip 10 or the uniform mixing mechanism 70 is moved, so that the uniform mixing mechanism 70 contacts the preset chamber 111 containing the magnetic beads, and the liquid in the preset chamber 111 is uniformly mixed by the uniform mixing mechanism 70.
Step S50, the above steps S10 to S40 are repeated until the magnetic beads carry the target substance into the last preset chamber 111.
Step S60, under the power action of the gas dynamic assembly 12, pushing the eluent in the last preset chamber 111 into the sample detection chamber 114;
step S70, moving the closed microfluidic chip 10 or the second temperature control component 81 so that the second temperature control component 81 contacts the sample detection chamber 114; the second temperature control assembly 81 provides two different preset temperatures to alternately operate at the two different preset temperatures and transfer heat to the sample detection chamber 114.
These two kinds of different temperature of predetermineeing are high temperature and low temperature respectively, and specific size can set up according to actual conditions, predetermine temperature cycle through second temperature control component 81 with two kinds of differences and contact sample detection chamber 114 in turn, can realize carrying out the amplification with the nucleic acid in sample detection chamber 114.
Step S80, after the second temperature control assembly 81 heats the sample detection chamber 114 for a preset time, the closed microfluidic chip 10 or the optical detection module 90 is moved, so that the optical detection module 90 can align with the sample detection chamber 114, and optically detect the nucleic acid in the sample detection chamber 114.
All possible combinations of the technical features in the above embodiments may not be described for the sake of brevity, but should be considered as being 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 represent some embodiments of the present invention, and the description thereof is specific and detailed, but not to be construed as limiting the scope of the present invention. It should be noted that, for those skilled in the art, without departing from the spirit of the present invention, several variations and modifications can be made, which are within the scope of the present invention. Therefore, the protection scope of the present invention should be subject to the appended claims.
In the description of the present invention, it is to be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential", and the like, indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for convenience of description and simplicity of description, and do not indicate or imply that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore, should not be construed as limiting the present invention.
Furthermore, 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. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. 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, unless otherwise expressly stated or limited, the terms "mounted," "connected," and "fixed" are to be construed broadly and may, for example, be fixedly connected, detachably connected, or integrally formed; can be mechanically or electrically connected; they may be directly connected or indirectly connected through intervening media, or they may be connected internally or in any other suitable relationship, unless expressly stated otherwise. The specific meaning of the above terms in the present invention can be understood according to specific situations by those skilled in the art.
In the present application, unless expressly stated or limited otherwise, the first feature may be directly on or directly under the second feature or indirectly via intermediate members. Also, a first feature "on," "over," and "above" a second feature may be directly or diagonally above the second feature, or may simply indicate that the first feature is at a higher level than the second feature. A first feature being "under," "below," and "beneath" a second feature may be directly under or obliquely under the first feature, or may simply mean that the first feature is at a lesser elevation than the second feature.
It will be understood that when an element is referred to as being "secured to" or "disposed on" 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. The terms "vertical," "horizontal," "upper," "lower," "left," "right," and the like as used herein are for illustrative purposes only and do not denote a unique embodiment.

Claims (21)

1. A nucleic acid extraction device based on a closed microfluidic chip is characterized in that the closed microfluidic chip comprises magnetic beads and a plurality of preset chambers which are communicated, the magnetic beads are arranged in the preset chambers, and phase change valves for controlling on-off are arranged at the communicated positions of the two preset chambers; the nucleic acid extraction device based on the closed microfluidic chip comprises:
a first temperature control assembly having a heating mechanism for heating the phase change valve such that the phase change valve is opened to communicate the two pre-chambers;
the magnetic attraction piece is positioned in a preset distance range with the closed microfluidic chip and is used for adsorbing the magnetic beads;
and the first moving mechanism drives the closed microfluidic chip or the magnetic suction piece to move so that the magnetic beads move in the communicated preset chambers.
2. The closed microfluidic chip-based nucleic acid extraction device according to claim 1, wherein the first temperature control assembly has a temperature reduction mechanism for performing temperature reduction treatment on the phase change valve so that the phase change valve blocks the communication between the two pre-chambers.
3. The closed microfluidic chip-based nucleic acid extraction device according to claim 1, further comprising a first support plate for placing the closed microfluidic chip; the first moving mechanism drives the first supporting plate to move.
4. The closed microfluidic chip-based nucleic acid extraction device according to claim 3, further comprising a frame and a first guide assembly; the first guide assembly is arranged on the rack, and the first supporting plate is connected with the first guide assembly.
5. The closed microfluidic chip-based nucleic acid extraction device according to claim 3, wherein the first support plate is provided with two first pressing plates, and the two first pressing plates respectively press two opposite sides of the closed microfluidic chip.
6. The nucleic acid extraction device based on the closed microfluidic chip according to claim 3, wherein a second pressing plate and a driving mechanism for driving the second pressing plate to move are arranged on the first support plate, and the second pressing plate can be pressed on the waterproof breathable film of the closed microfluidic chip and can seal the waterproof breathable film under the driving of the driving mechanism.
7. The closed microfluidic chip-based nucleic acid extraction device according to claim 3, further comprising a second moving mechanism; the second moving mechanism is connected with the first temperature control assembly and the magnetic suction piece.
8. The closed microfluidic chip-based nucleic acid extraction device according to claim 7, wherein the heating mechanism comprises a first heating plate, and the magnetic attraction member is disposed adjacent to the first heating plate.
9. The closed microfluidic chip-based nucleic acid extraction device according to claim 3, further comprising a mixing mechanism for mixing the liquid in the preset chamber.
10. The closed microfluidic chip-based nucleic acid extraction device according to claim 9, wherein the mixing mechanism comprises a first support, an ultrasonic transducer disposed on the first support, and a first guide wheel rotatably disposed on the first support; the first support is arranged on the machine frame or the ground through a second elastic part, the first support plate is provided with a hollowed-out area capable of exposing at least one preset chamber, and the side part of the first support plate is provided with a first avoidance hole; the first moving mechanism drives the first supporting plate to move to the position above the blending mechanism, and when the bottom surface of the first supporting plate is abutted to the first guide wheel, a space is formed between the ultrasonic transducer and the closed microfluidic chip arranged on the first supporting plate; when the first guide wheel moves into the first avoidance hole, the ultrasonic transducer is in contact with one of the preset chambers.
11. The closed microfluidic chip-based nucleic acid extraction device according to claim 10, wherein the number and positions of the first avoidance holes correspond to all the preset chambers one to one.
12. The closed microfluidic chip-based nucleic acid extraction device according to claim 11, wherein the mixing mechanism further comprises a third guide assembly, and the first support is connected to the rack or the ground through the third guide assembly.
13. The closed microfluidic chip-based nucleic acid extraction device according to claim 3, further comprising a second temperature control component capable of heating the sample detection chamber of the closed microfluidic chip.
14. The closed microfluidic chip-based nucleic acid extraction device according to claim 13, wherein the second temperature control assembly comprises a second heating plate and a third heating plate which are arranged at intervals, the second heating plate is heated to a higher temperature than the third heating plate, and the second heating plate and the third heating plate cyclically and alternately heat the sample detection chamber.
15. The closed microfluidic chip-based nucleic acid extraction device according to claim 14, wherein the second temperature control assembly further comprises two semiconductor cooling fins, a heat sink and a heat dissipation fan; one semiconductor refrigeration piece is arranged between the second heating plate and the radiator, the other semiconductor refrigeration piece is arranged between the third heating plate and the radiator, and the radiator is connected with the cooling fan.
16. The closed microfluidic chip-based nucleic acid extraction device according to claim 14, wherein the second temperature control assembly is disposed on the rack or the ground through a third elastic member, the second temperature control assembly is provided with a second guide wheel, the side of the first support plate is provided with a second avoiding hole, and the first moving mechanism can drive the first support plate to move above the second temperature control assembly; when the bottom surface of the first supporting plate is abutted against the second guide wheel, a space is arranged between the second heating plate and the closed microfluidic chip arranged on the first supporting plate; when the second guide wheel moves into the second avoidance hole, the second heating plate or the third heating plate is in contact with the sample detection chamber.
17. The closed microfluidic chip-based nucleic acid extraction device according to claim 3, further comprising an optical detection module; the optical detection module is used for optically detecting nucleic acid in the sample detection chamber.
18. The closed microfluidic chip-based nucleic acid extraction device according to claim 17, wherein the optical detection module comprises a fluorescence excitation component, an optical fiber detection component and a fluorescence reading component; the fluorescence excitation component is used for generating fluorescence and emitting the generated fluorescence to the optical fiber detection component, and the optical fiber detection component is used for guiding the fluorescence to the sample detection chamber and guiding light reflected by nucleic acid in the sample detection chamber to the fluorescence reading component.
19. The closed microfluidic chip-based nucleic acid extraction device according to claim 18, wherein the fluorescence excitation component comprises a fluorescence emission end, a dichroic mirror and a fluorescence exit end; the fluorescence generated by the fluorescence emission end enters the dichroic mirror and is emitted outwards through the dichroic mirror and the fluorescence emission end in sequence;
the optical fiber detection assembly comprises a first transmission optical fiber, a detection optical fiber and a second transmission optical fiber; the two ends of the first transmission optical fiber are respectively connected with the fluorescence emitting end and the detection optical fiber, the two ends of the second transmission optical fiber are respectively connected with the detection optical fiber and the fluorescence receiving end of the fluorescence reading assembly, and the detection optical fiber faces the sample detection chamber;
the fluorescence reading assembly comprises a detection camera, an optical filter and a fluorescence receiving end which are sequentially arranged, fluorescence reflected by a sample of the sample detection chamber is transmitted to the fluorescence receiving end through the detection optical fiber, the fluorescence receiving end is used for transmitting the fluorescence to the optical filter, and the fluorescence is incident to the detection camera after being filtered by the optical filter.
20. The closed microfluidic chip-based nucleic acid extraction device according to claim 19, wherein the optical fiber detection assembly further comprises a third moving mechanism and a buffer seat arranged on the rack; the third moving mechanism is connected with the buffer seat, the third moving mechanism is used for driving the buffer seat to move to the first supporting plate, and the detection optical fiber is arranged on the buffer seat.
21. The closed microfluidic chip-based nucleic acid extraction device according to claim 19, wherein the fluorescence reading assembly further comprises a mounting base, a fourth moving mechanism disposed on the mounting base, and an array base movably disposed on the mounting base; the fourth moving mechanism is connected with the array seat and is used for driving the array seat to move; the number of the fluorescence emission ends is at least two, and the number of the optical filters is at least two and is in one-to-one correspondence with the fluorescence emission ends; all the optical filters are sequentially arranged on the array seat, and when the fourth moving mechanism drives the array seat to move, the optical filters on the array seat can be sequentially aligned with the fluorescence receiving end.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107502544A (en) * 2017-09-20 2017-12-22 北京丰特云基科技发展有限公司 A kind of micro-fluidic chip detecting and controlling system
WO2023040476A1 (en) * 2021-09-17 2023-03-23 上海微创惟微诊断技术有限公司 Microfluidic chip and in vitro diagnostic analysis apparatus

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107502544A (en) * 2017-09-20 2017-12-22 北京丰特云基科技发展有限公司 A kind of micro-fluidic chip detecting and controlling system
CN107502544B (en) * 2017-09-20 2023-12-15 杭州梓晶生物有限公司 Micro-fluidic chip detection control system
WO2023040476A1 (en) * 2021-09-17 2023-03-23 上海微创惟微诊断技术有限公司 Microfluidic chip and in vitro diagnostic analysis apparatus

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