CN111187718B - Nucleic acid extraction device and nucleic acid detection system - Google Patents

Nucleic acid extraction device and nucleic acid detection system Download PDF

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CN111187718B
CN111187718B CN202010108593.9A CN202010108593A CN111187718B CN 111187718 B CN111187718 B CN 111187718B CN 202010108593 A CN202010108593 A CN 202010108593A CN 111187718 B CN111187718 B CN 111187718B
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nucleic acid
driving
sleeve
drive
acid extraction
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CN111187718A (en
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张东旭
黄玉麟
张剑滨
高润鑫
徐佳素
张师音
翁祖星
宋浏伟
葛胜祥
张军
夏宁邵
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Xiamen Innodx Biotechnology Co ltd
Xiamen University
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Xiamen Innodx Biotechnology Co ltd
Xiamen University
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1003Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813Hybridisation assays
    • C12Q1/6834Enzymatic or biochemical coupling of nucleic acids to a solid phase
    • C12Q1/6837Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips

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Abstract

The invention discloses a nucleic acid extraction device and a nucleic acid detection system, and relates to the field of microbiology equipment. The nucleic acid extraction device comprises a flow channel switching module, the flow channel switching module comprises a driving part, a driving shaft and a driving sleeve, and the driving shaft is in driving connection with the driving part; the drive sleeve is configured to switch between a drive connected position and a disconnected position. When the driving sleeve is positioned at the driving connection position, the driving shaft is in driving connection with the driving sleeve; when the drive sleeve is in the disengaged position, the drive shaft is drivingly disconnected from the drive sleeve. The technical scheme simply realizes the switching of the flow channels and the switching of the sealing state of the corresponding chip.

Description

Nucleic acid extraction device and nucleic acid detection system
Technical Field
The invention relates to the field of in-vitro diagnosis equipment, in particular to a nucleic acid extraction device and a nucleic acid detection system.
Background
The nucleic acid detection technology is a technology for directly detecting genetic materials of a living body, such as DNA and RNA. The nucleic acid detection technology has extremely high specificity and sensitivity, short window period and multiple detection capability. However, the nucleic acid detection process is very complex, the steps are many, and the requirements on detection environment, laboratory conditions and personnel skill level are very high. Therefore, the development trend of nucleic acid detection is immediate detection and random detection. In the field of in vitro diagnosis, such small-sized, portable, fast and simple, and instant-to-place detection means are called Point-of-care Test (POCT), which are also called bedside detection, field detection, and the like.
Disclosure of Invention
The invention provides a nucleic acid extraction device and a nucleic acid detection system.
The embodiment of the invention provides a nucleic acid extraction device, which comprises:
the flow channel switching module comprises a driving part, a driving shaft and a driving sleeve; the driving shaft is in driving connection with the driving part; the drive sleeve is configured to switch between a drive connection position and a disconnection position; wherein, when the driving sleeve is in a driving connection position, the driving shaft is in driving connection with the driving sleeve; when the drive sleeve is in the disengaged position, the drive shaft is drivingly disconnected from the drive sleeve.
In some embodiments, the drive sleeve is configured to be movable relative to the drive shaft in its own axial direction to switch between a drive connection position and a disconnection position.
In some embodiments, the flow channel switching module further comprises:
a first bracket having a mounting hole to which the driving shaft is mounted; and
the elastic piece is clamped between the first bracket and the driving sleeve;
wherein, the drive sleeve is arranged on the outer side of the drive shaft in a sleeved mode and is connected with the drive shaft in a sliding mode.
In some embodiments, the flow channel switching module further comprises:
the shaft sleeve is arranged outside the driving shaft and is positioned inside the mounting hole; the elastic piece is clamped between the shaft sleeve and the driving sleeve.
In some embodiments, the driving sleeve is provided with a key slot running through the driving sleeve itself in the axial direction, and the driving shaft is provided with a key; the key slot cooperates with the key.
In some embodiments, the end of the drive shaft is provided with a protrusion, and the protrusion is configured to retain the drive sleeve.
In some embodiments, the driving part includes:
a first motor; and
and the transmission assembly is used for driving and connecting the driving shaft with the first motor.
In some embodiments, the flow channel switching module further comprises:
the limiting clamping ring is arranged on the first bracket and is rotatably connected with the driving shaft; the limit snap ring is configured to limit movement of the drive shaft relative to the mounting hole along an axial direction of the drive shaft.
In some embodiments, the flow channel switching module further comprises:
an angle measurement assembly mounted to the drive shaft and configured to detect a rotation angle of the drive shaft.
In some embodiments, the nucleic acid extraction device further comprises:
a base plate to which the runner switching module is slidably mounted.
In some embodiments, the nucleic acid extraction device further comprises:
a pallet slidably mounted to the base plate; the runner switching module is carried by the support plate.
In some embodiments, the nucleic acid extraction device further comprises:
the first trigger assembly comprises a first photoelectric switch and a first baffle plate; the first photoelectric switch is fixed on the bottom plate, and the first blocking piece is fixed on the supporting plate; the first trigger assembly is configured to control an amount of displacement of the pallet relative to the base plate.
In some embodiments, the nucleic acid extraction device further comprises:
the second trigger assembly comprises a second photoelectric switch and a second baffle plate; the second photoelectric switch is fixed on the bottom plate, and the second baffle is fixed on the supporting plate; the second trigger assembly is configured to determine whether the drive shaft is in a drive position.
In some embodiments, the nucleic acid extraction device further comprises:
the third trigger assembly comprises a third photoelectric switch and a third baffle plate; the third photoelectric switch is fixed on the supporting plate, and the third baffle is fixed on the ultrasonic module of the nucleic acid extraction device; the third trigger assembly is configured to determine whether the ultrasound module is in a home position.
In some embodiments, the nucleic acid extraction device further comprises:
an ultrasound module comprising an ultrasound transducer and a second support; the ultrasonic transducer is movably mounted to the second support.
In some embodiments, the ultrasound module further comprises:
a third mount slidably mounted to the second mount, the ultrasonic transducer being slidably mounted to the third mount; and
the force measuring assembly is arranged at the end part of the third bracket far away from the ultrasonic transducer;
wherein the ultrasonic transducer is configured to be slidably movable relative to the third bracket into a position against the load cell assembly.
In some embodiments, the nucleic acid extraction device further comprises:
the liquid flow driving module comprises a fourth bracket, a power source and an adsorption part; the adsorption piece is arranged on the fourth bracket; one end of the adsorption piece is in driving connection with the power source, and the other end of the adsorption piece is open.
In some embodiments, the nucleic acid extraction device further comprises:
the magnetic module comprises a magnet and a driving part, and the driving part is in driving connection with the magnet so that the magnet can be switched between a working position and an original position.
The embodiment of the invention also provides a nucleic acid detection system, which comprises:
the chip comprises a chip body and a rotary valve arranged on the chip body; the rotary valve comprises a valve seat, a sealing element, a rotor and a valve cover; the valve seat is fixedly connected with the chip body, the valve cover is rotatably connected with the valve seat, the rotor is rotatably clamped between the valve seat and the valve cover, and the sealing element is positioned between the valve seat and the rotor; a plurality of flow channels are arranged in the chip body; and
according to the nucleic acid extraction device provided by any technical scheme of the invention, the driving shaft is in driving connection with the rotor, and the driving sleeve is in driving connection with the valve cover;
wherein the rotary valve is configured to switch a communication state between the two flow passages by rotation of the rotor, and the rotary valve is configured to rotate the valve cover in the pre-tightening position to the seal engagement position by rotation of the valve cover.
In some embodiments, the valve seat is configured to be annular, and the edge of the valve seat is provided with a first clamping groove and a second clamping groove which are communicated, wherein the second clamping groove is positioned on one side of the first clamping groove facing the chip body; the inner wall of the valve cover is provided with a buckle; when the valve cover is in a pre-tightening position, the buckle is matched with the first clamping groove; when the valve cover is in a sealing matching position, the buckle is matched with the second clamping groove.
In some embodiments, the first and second clamping grooves are provided in a plurality of sets at intervals along a circumference of the valve seat.
In some embodiments, the free end of the drive shaft is provided with a first retaining post, and the rotor is provided with a first retaining hole, the first retaining post cooperating with the first retaining hole.
In some embodiments, the free end of the driving sleeve is provided with a second retaining post, and the valve cover is provided with a second retaining hole, and the second retaining post is matched with the second retaining hole.
In some embodiments, the free end of the drive shaft is provided with a first retaining post, the rotor is provided with a first retaining hole, the free end of the drive sleeve is provided with a second retaining post, and the valve cover is provided with a second retaining hole;
wherein, the following two cooperation states can be selectively selected and exist: the first clamping column is matched with the first clamping hole, and the second clamping column is matched with the second clamping hole.
In some embodiments, when the driving shaft is in driving connection with the rotor of the chip, the other end of the adsorbing member of the liquid flow driving module of the nucleic acid extracting apparatus is in sealing connection with the suction port of the chip.
The nucleic acid extraction device provided by the technical scheme is provided with the driving shaft and the driving sleeve, and the driving shaft and the driving sleeve both adopt the power of the driving part to drive other parts to be driven. The drive shaft and the drive sleeve are switchable between two states, a drive connection and a non-drive connection. By adopting the flow channel switching module, the valve position of the chip can be switched, and the sealing state of the valve cover of the rotary valve can be changed, so that the chip is in a lower sealing state in a non-use state and is in a higher sealing state in use, the probability of abrasion and damage of relevant parts of the chip caused by excessive sealing is reduced, and the service lives of the chip and the rotary valve are prolonged. In addition, the nucleic acid extraction device provided by the above technical scheme requires a small number of power units, and the whole structure of the nucleic acid extraction device is more compact.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this application, illustrate embodiment(s) of the invention and together with the description serve to explain the invention without limiting the invention. In the drawings:
FIG. 1 is a first schematic view of a nucleic acid isolation apparatus according to an embodiment of the present invention;
FIG. 2 is a schematic diagram of a second usage state of the nucleic acid isolation apparatus according to the embodiment of the present invention;
FIG. 3 is a third schematic view of the nucleic acid isolation apparatus according to the present invention;
FIG. 4 is a schematic perspective view of a flow channel switching module of a nucleic acid extraction apparatus according to an embodiment of the present invention;
FIG. 5 is a schematic perspective sectional view of a flow channel switching module of a nucleic acid extraction device according to an embodiment of the present invention;
FIG. 6 is a partial perspective view of a magnetic module of the nucleic acid extraction device according to the present invention;
FIG. 7 is a partial perspective view of a liquid flow driving module of a nucleic acid isolation apparatus according to an embodiment of the present invention;
FIG. 8 is a partial perspective view of a nucleic acid isolation apparatus provided in an embodiment of the present invention at the drive shaft;
FIG. 9 is a partial perspective view of a driving sheath of a nucleic acid isolation apparatus according to an embodiment of the present invention;
FIG. 10 is a schematic perspective view of a chip of a nucleic acid isolation apparatus according to an embodiment of the present invention;
FIG. 11 is a schematic perspective view of a chip body of a chip of a nucleic acid isolation apparatus according to an embodiment of the present invention;
FIG. 12 is an exploded view of a rotary valve of a chip of a nucleic acid isolation apparatus according to an embodiment of the present invention;
FIG. 13 is a schematic view of a partial disassembly at a rotary valve of a chip of the nucleic acid isolation apparatus according to the embodiment of the present invention;
FIG. 14 is a schematic perspective view showing a valve cover of a rotary valve of a chip of the nucleic acid isolation apparatus according to the embodiment of the present invention;
FIG. 15 is another schematic perspective view of a valve cover of a rotary valve of a chip of the nucleic acid isolation apparatus according to the present invention;
FIG. 16 is a partial perspective view of the nucleic acid extracting apparatus according to the embodiment of the present invention at an ultrasonic module;
FIG. 17 is a schematic diagram showing the cooperation of a first trigger assembly of the nucleic acid isolation apparatus according to the embodiment of the present invention;
FIG. 18 is a schematic diagram showing the cooperation of a second trigger assembly of the nucleic acid isolation apparatus according to the embodiment of the present invention;
FIG. 19 is a schematic diagram showing the cooperation of a third trigger assembly of the nucleic acid isolation apparatus according to the embodiment of the present invention;
FIG. 20 is a schematic view of the structure of a nucleic acid isolation apparatus according to an embodiment of the present invention at the position of a support plate;
fig. 21 is a schematic view of the screw structure in fig. 20.
Detailed Description
The technical solution provided by the present invention will be explained in more detail with reference to fig. 1 to 21.
Before describing the nucleic acid extraction device provided by the embodiment of the present invention, a specific structure of the microfluidic chip (referred to as the chip 80 for short) is described. The nucleic acid extraction device is used for completing the nucleic acid extraction operation of the sample inside the chip 80. The chip 80 is mounted on the base plate 42 by the chip holder 20. The chip 80 can be lifted and lowered by the chip holder 20. Once positioned, the position of the chip 80 relative to the base plate 42 is fixed during the nucleic acid extraction process.
Referring to fig. 1, 10 to 13, the chip 80 includes a chip body 81 and a rotary valve 82. The chip body 81 is provided with a plurality of flow channels and a plurality of cavities therein. The chambers include a reservoir chamber 803, a reaction chamber 87, an amplification chamber 802, and a waste chamber 89. Specifically, a reservoir 803 is disposed on top of the chip 80, and the reservoir 803 includes a plurality of independent sub-chambers, each for storing one of a fluid and a reagent. These subchambers are each in communication with the rotary valve 82 via separate flow passages. An amplification cavity 802 and a reaction cavity 87 which are mutually independent are also arranged on two sides below the chip body 81. The waste liquid chamber 89 is located below the reaction chamber 87 and at the bottom of the chip body 81.
The rotary valve 82 is used to change the communication state between the chambers. Specifically, the rotary valve 82 is used to control two of the reservoir chamber 803, the reaction chamber 87, and the waste liquid chamber 89 to be in a conducting state. Specifically, any one of the sub-chambers can be controlled to be communicated with the reaction chamber 87; the conduction between the amplification chamber 802 and the reaction chamber 87 can be controlled; the reaction chamber 87 can be controlled to communicate with the waste liquid chamber 89.
Referring to fig. 10-13, the rotary valve 82 includes a valve seat 83, a rotor 85, and a valve cover 86. The valve seat 83 is fixedly connected with the chip body 81, the valve cover 86 is rotatably connected with the valve seat 83, and the rotor 85 is rotatably clamped between the valve seat 83 and the valve cover 86. When the rotor 85 of the rotary valve 82 rotates, the valve position of the rotary valve 82 changes, and different flow channels inside the chip 80 are communicated.
Further, a sealing member 84 is disposed between the valve seat 83 and the rotor 85, and the sealing member 84 is, for example, a sealing gasket. The seal 84 is of a relatively soft material that deforms upon compression to provide a seal and prevent the rotary valve 82 from leaking fluid during operation.
Referring to fig. 10-13, in some embodiments, the valve cover 86 of the rotary valve 82 has two connection locations with the valve seat 83: a pre-load position and a sealing engagement position. The pre-tightening position is an initial delivery position. In the preloaded position, the seal 84 is not crushed, thereby reducing or even avoiding the possibility of failure due to the seal 84 being crushed for an extended period of time. In the seal engaged position, the seal 84 is compressed, which provides a better seal for the rotary valve 82 and prevents fluid leakage during use. Based on the above, the rotary valve 82 is configured such that the rotation of the valve cover 86 causes the valve cover 86 in the pre-tightening position to rotate to the sealing engagement position. Rotation of the valve cover 86 from the pre-load position to the sealing engagement position is unidirectional. After the valve cover 86 is rotated from the pre-tightening position to the sealing engagement position, on the one hand, the valve seat 83 is structurally designed so that the valve cover 86 cannot be rotated reversely, and a specific implementation manner of the valve seat 83 will be described later; on the other hand, the chip 80 is a consumable that requires substantially no secondary use and the seal 84 has been crushed and deformed so that the valve cover 86 is no longer screwed back from the seal engagement position to the pre-tensioned position. As will be described later, the valve cover 86 is driven to rotate from the pre-tightening position to the sealing engagement position by the driving sleeve 413 of the flow passage switching module 41.
As above, the switching of the valve position of the chip 80 is realized by the rotation of the rotor 85. As will be described later, the rotor 85 is driven to rotate by the driving shaft 412 of the flow path switching module 41, so that the valve position of the rotary valve 82 is switched.
When the chip is shipped, the reagent is stored in the liquid storage cavity 803 of the chip 80 in advance; before the detection is started, a sample is put into the liquid storage chamber 803 of the chip 80. In the nucleic acid extraction operation, samples and reagents, for example, 1 sample and 9 reagents, are stored in the liquid storage chamber 803 of the chip 80. The nucleic acid extraction process comprises two steps: sample lysis operation and nucleic acid purification operation. Both operations are performed in reaction chamber 87.
Lysis of a sample means that the peripheral structures (e.g.cell membranes) of the sample are destroyed by some external effect, releasing the nucleic acids. In some embodiments of the invention, sample lysis is achieved using a combination of ultrasound and chemical lysis reagents.
After cleavage, the nucleic acid is often combined with other components that inhibit subsequent nucleic acid detection processes (e.g., amplification, digestion, hybridization, etc.), such as proteins, polysaccharides, lipid macromolecules, salts, etc. Therefore, nucleic acid purification is required, and nucleic acid is separated from other impurities by washing and elution reactions, thereby finally obtaining high-purity nucleic acid.
The following describes a specific implementation manner of the nucleic acid extraction apparatus provided in the embodiment of the present invention.
Referring to fig. 1 to 5, the embodiment of the invention provides a nucleic acid extraction device, which includes a flow channel switching module 41. The flow channel switching module 41 includes a driving part 411, a driving shaft 412, and a driving sleeve 413. The driving shaft 412 is in driving connection with the driving part 411; the drive sleeve 413 is configured to switch between a drive connection position and a disconnection position. Wherein, when the driving sleeve 413 is at the driving connection position, the driving shaft 412 is in driving connection with the driving sleeve 413. When the drive sleeve 413 is in the disengaged position, the drive shaft 412 is drivingly disconnected from the drive sleeve 413.
The driving part 411 may use various power sources to realize the rotation of the driving shaft 412. The driving sleeve 413 is not driven separately. The driving sleeve 413 has two connection states at the driving shaft 412: in the first state, the driving sleeve 413 is drivingly connected to the driving shaft 412, and in this case, the driving shaft 412 rotates to drive the driving sleeve 413 to rotate synchronously. The rotation of the driving sleeve 413 drives the rotation of the component to be driven which is connected with the driving sleeve 413 in a driving way. In some embodiments, the component to be driven in driving connection with the drive sleeve 413 is referred to above as the valve cap 86.
In the nucleic acid extraction operation, the rotary valve 82 is operated as follows: first, the driving portion 411 rotates the driving shaft 412, and the driving shaft 412 is in driving connection with the driving sleeve 413 in the initial state, so that the driving sleeve 413 is synchronously rotated. The driving sleeve 413 is in driving connection with the valve cover 86 of the rotary valve 82, for example, by matching with a shaft hole. Therefore, the bonnet 86 of the rotary valve 82 is screwed by the drive sleeve 413 from the pre-tightened position to the sealing engagement position.
When the bonnet 86 of the rotary valve 82 is in a sealed engagement position, it is subsequently no longer necessary to rotate the bonnet 86, so the drive shaft 412 is out of driving engagement with the drive sleeve 413. The above-mentioned disengagement of the driving engagement is achieved, for example, by the driving shaft 412 moving axially along itself, and the specific implementation of the driving shaft 412 and the driving sleeve 413 maintaining the driving connection and disengaging the driving connection will be described later.
Before this, a specific implementation of the driving unit 411 will be described.
Referring to fig. 1 to 5, the driving part 411 includes a first motor 411a and a transmission assembly 411 b.
The transmission assembly 411b drivingly connects the drive shaft 412 to the first motor 411 a. The transmission assembly 411b includes a first pulley 411c, a second pulley 411d, and a conveying belt 411 e. The first pulley 411c is drivingly connected to an output shaft of the first motor 411a, the second pulley 411d is drivingly connected to the drive shaft 412, and the first pulley 411c and the second pulley 411d are connected together by a conveyor belt 411 e. The belt transmission is adopted, so that the power transmission is reliable, and the convenience in arranging various parts is realized.
In some embodiments, the nucleic acid extraction apparatus further comprises a base plate 42, and the base plate 42 serves as a mounting base for all modules, and may be stationary itself or coupled to a stationary device. The flow channel switching module 41 is slidably mounted to the base plate 42. The flow path switching module 41 is brought close to the rotary valve 82 of the chip 80 by sliding the flow path switching module 41 as a whole with respect to the base plate 42.
Referring to fig. 1 to 5, in some embodiments, the flow channel switching module 41 further includes a first bracket 414, a bushing 415, and an elastic member 416. The first bracket 414 is mounted to the base plate 42 as described above and is able to slide or otherwise move relative to the base plate 42. The first support 414 moves to bring the driving portion 411, the driving shaft 412, the driving sleeve 413, and the like together to move toward the chip 80 or away from the chip 80. When the nucleic acid extraction operation is required, the entire flow channel switching module 41 is close to the chip 80. In the nucleic acid extraction process, the relative position of the flow channel switching module 41 to the chip 80 is not changed. When the nucleic acid extraction is completed, the entire flow channel switching module 41 is away from the chip 80.
The first frame 414 may be a plurality of frames or may be a single body. In the embodiments illustrated in fig. 1 to 5, the first bracket 414 is formed by a plurality of plates, and the plates include flat plates and vertical plates, and the number of the flat plates and the number of the vertical plates are respectively set according to needs. The first bracket 414 has a mounting hole 414 a. The boss 415 is mounted to the outside of the driving shaft 412 and inside the mounting hole 414 a. The elastic member 416 is interposed between the boss 415 and the driving boss 413. The driving sleeve 413 is disposed outside the driving shaft 412 and clamped between the elastic element 416 and the free end of the driving shaft 412. Drive sleeve 413 is slidably connected with drive shaft 412.
The driving sleeve 413 is slidable in the axial direction thereof with respect to the driving shaft 412. When the drive sleeve 413 is in a set position relative to the drive shaft 412, the drive sleeve 413 is drivingly connected to the drive shaft 412, which position is also referred to as the drive sleeve 413 being in a drivingly connected position. When the drive sleeve 413 is in another set position relative to the drive shaft 412, the drive connection between the drive sleeve 413 and the drive shaft 412 is broken and the drive shaft 412 no longer transmits a rotational torque to the drive sleeve 413, which position is also referred to as the drive sleeve 413 being in the disengaged position. In some embodiments hereinafter, the drive sleeve 413 is keyed to the drive shaft 412 to enable the drive sleeve 413 to be switched between a drive connected position and a disconnected position.
The elastic member 416 is interposed between the boss 415 and the driving sleeve 413, and the driving sleeve 413 is automatically returned from the separated position to the driving connection position by the elastic member 416. Other functions of the elastic member 416 will be described in detail later.
In some embodiments, the first bracket 414 is mounted to the plate 46, the plate 46 being positioned above the base plate 42, and a gap exists between the plate 46 and the base plate 42 for mounting components to be mounted, which are carried by the base plate 42.
Referring to fig. 20 and 21, specifically, pallet 46 is driven by power transmission 47 to effect sliding movement of pallet 46 relative to base plate 42. By moving carrier 46 relative to base 42, it is achieved that the components mounted to carrier 46 are closer to or farther from chip 80. The power transmission mechanism 47 includes a second motor 471 and a pulley transmission mechanism 472. The second motor 471 is in transmission connection with the pulley transmission 472, so as to drive the sliding of the supporting plate 46 through the rotation of the pulley transmission 472.
The pulley mechanism 472 includes a pulley 472a and a lead screw 472b drivingly connected to the pulley 472 a. The second motor 471 drives the belt wheel 472a to rotate, and the belt wheel 472a drives the screw 472b to rotate. In order to effectively support the lead screw 472b during rotation, each smooth section of the lead screw 472b is provided with a support seat 474 for support. As shown in fig. 21, both ends of the screw 472b are smooth, that is, both ends of the screw 472b are smooth sections M1 and M3, and the middle is a threaded section M2. The support block 474 is connected to the smooth sections M1 and M3 of the lead screw 472b by bearings. Specifically, two support seats 474 are provided, the smooth segment M1 being bearing-connected to one of the support seats 474, and the smooth segment M3 being bearing-connected to the other support seat 474. Threaded section M2 of lead screw 472b is coupled to plate 46 by nut mount 475. One end of the lead screw 472b is a connecting segment M4, and the connecting segment M4 is in driving connection with the pulley 472 a.
With continued reference to fig. 20 and 21, the base plate 42 is fixed with a guide rail 473, and the guide rail 473 serves as a linear guide for the sliding movement of the supporting plate 46.
The provision of the pallet 46 realizes layering of the installation space above the bottom plate 42, so that the installation-related components can be more reasonably arranged in the height direction, thereby reducing the planar size of the nucleic acid extracting apparatus and making the structure thereof more compact and reasonable. Also, after the pallet 46 is positioned, all of the components carried by the pallet 46 may move with the pallet 46. That is, a pallet 46 drive mechanism is provided that enables common movement of the pallet 46 and all components carried by the pallet 46. The movement mode is more stable and reliable, the number of required driving mechanisms is small, and the control mode is simpler.
Referring to fig. 5, a bushing 415 is disposed between the outer wall of the driving shaft 412 and the mounting hole 414a, and the bushing 415 is made of a graphite sliding block to achieve smooth rotation of the driving shaft 412. Furthermore, the bushing 415 serves as a positioning member for one end of the elastic member 416, which will be described later, and thus, the installation and positioning of the elastic member 416 are simplified.
The manner in which the drive sleeve 413 is drivingly connected and disconnected from the drive shaft 412 is described below.
As shown in fig. 4 and 5, and fig. 8 and 9, the end of the driving shaft 412 is provided with a projection 412 b. The driving sleeve 413 is provided with a key groove 413 b. The free end of the projection 412b is provided with a first catch column 412c described below. The other end of the projection 412b is adjacent to the key groove 413b, and the key groove 413b is adjacent to the projection 412b in the axial direction of the drive shaft 412. The projection 412b is configured to restrain the driving sleeve 413 to prevent the driving sleeve 413 from falling off from the free end of the driving shaft 412. The key 417 is installed in the key groove 413 b. The key slot 413b extends through at least one side edge of the driving sleeve 413 in the axial direction, so that the key 417 can smoothly slide out of the key slot 413b when necessary, and the driving sleeve 413 is disconnected from the driving shaft 412. The drive sleeve 413 is fitted outside the key 417, i.e., in the circumferential direction of the drive shaft 412. The right side of the driving sleeve 413 abuts against a first end of the elastic member 416, and a second end of the elastic member 416 abuts against a sleeve 415 fixed to the driving shaft 412. The sleeve 415 remains stationary relative to the drive shaft 412. The sleeve 415 is a graphite slider. The resilient member 416 comprises a spring that is always in compression.
When the driving sleeve 413 does not abut against the valve cap 86 of the rotary valve 82 of the chip 80, the driving sleeve 413 is restrained between the protrusion 412b and the spring under the force of the spring. When the entire driving shaft 412 and the driving sleeve 413 are driven by the outside to move towards the chip 80 to the position where the driving sleeve 413 abuts against the valve cover 86, the driving sleeve 413 drives the valve cover 86 to rotate from the pre-tightening position to the sealing matching position. In this process, there are two implementation forms, and the first implementation form is: when the valve cover 86 contacts the valve seat 83, the retainer 46 does not move and the components fixedly attached to the retainer 46 do not move. Because the valve cover 86 abuts against the elastic member 416, and the elastic member 416 is a compression spring, under the action of the elastic force of the elastic member 416, the valve cover 86 has a certain displacement along the self-axial direction, and the displacement enables the valve cover 86 to rotate from the pre-tightening position to the sealing engagement position. In the process of rotating the valve cover 86 from the pre-tightening position to the sealing engagement position, the rotating power comes from the driving shaft 412, and at this time, the driving shaft 412 is kept in driving connection with the driving sleeve 413, so that the rotating power can be transmitted to the driving shaft 412 via the driving portion 411 and then to the driving sleeve 413. The second implementation manner is as follows: the entire driving shaft 412 and the driving sleeve 413 are driven by the external environment to continuously move towards the chip 80. In some embodiments of the present invention, the first implementation manner is taken as an example.
When the valve cover 86 is in a sealing engagement with the valve seat 83, with the valve cover 86 abutting the valve seat 83, there is no further axial movement of the valve cover 86. In this case, the entire driving shaft 412 is continuously moved toward the chip 80 by the outside, which causes the elastic member 416 to be further pressed by the driving sleeve 413 which cannot move continuously, the compression amount of the elastic member 416 becomes larger, and the distance between the driving sleeve 413 and the sleeve 415 becomes smaller. The drive shaft 412 and the key 417 continue to move axially toward the chip 80 and the drive sleeve 413 is progressively disengaged from the key 417, thereby achieving a driving disengagement of the drive sleeve 413 from the drive shaft 412 when the drive sleeve 413 is fully disengaged from the key 417.
Subsequently or simultaneously, the first catching column 412c of the driving shaft 412 forms a shaft hole driving fit with the first catching hole 851 of the rotor 85. Subsequently, when the driving shaft 412 is rotated, the driving sleeve 413 will not rotate, and the rotor 85 will be driven by the driving shaft 412 to realize the valve position switching.
The above-described procedure achieves that the drive sleeve 413 is configured to be movable relative to the drive shaft 412 in its own axial direction to switch between the drive connection position and the disconnection position.
Referring to fig. 5, in some embodiments, the flow path switching module 41 further includes a limit snap ring 418. The first bracket 414 is mounted with a driving part 411 and a driving shaft 412. The first bracket 414 is mounted to the base plate 42, and the first bracket 414 is mounted to the base plate 42, such as directly to the base plate 42 or via the bracket 46 described above. The first bracket 414 has a mounting hole 414 a. The driving shaft 412 is installed in the installation hole 414 a. A retaining snap ring 418 is mounted to the first bracket 414 and is rotatably coupled to the drive shaft 412. The limit snap ring 418 is configured to limit the movement of the drive shaft 412 relative to the mounting hole 414a in the axial direction of the drive shaft 412, i.e., so that the drive shaft 412 does not move relative to the mounting hole 414a in the axial direction of the drive shaft 412.
With continued reference to fig. 4 and 5, in order to more conveniently measure the rotation angle of the driving shaft 412, the flow channel switching module 41 further includes an angle measuring assembly 419, the angle measuring assembly 419 being located at an end of the driving shaft 412 away from the chip 80, the angle measuring assembly 419 being configured to detect the rotation angle of the driving shaft 412.
The angle measuring component 419 uses, for example, a hall sensor. The hall sensor support 419a is mounted to the first bracket 414, and the hall element 419b is mounted to the hall sensor support 419 a.
As described above, the nucleic acid extracting apparatus further includes a base plate 42, and the flow channel switching module 41 is slidably mounted on the base plate 42. The first bracket 414 is slidably mounted to the base plate 42, and the driving part 411 is also mounted to the first bracket 414. The first support 414 can be driven to slide relative to the base plate 42 by a motor drive or an electric slide, etc.
It will be appreciated here that in some embodiments, a pallet 46 is provided above the base plate 2. In this case, both the flow path switching module 41 and the ultrasonic module 43 may be mounted on the support plate 46. The supporting plate 46 moves to drive the flow channel switching module 41 and the ultrasonic module 43 to integrally move, so that the flow channel switching module 41 and the ultrasonic module 43 are integrally close to or far away from the chip 80.
It is also understood that if the support plate 46 is not provided, a driving mechanism may be provided for each of the flow channel switching module 41 and the ultrasonic module 43 to move closer to or away from the chip 80.
Referring to fig. 1-3, the ultrasound module 43 is described below.
The ultrasonic module 43 serves as a vibration source to transmit ultrasonic vibration to the liquid in the reaction chamber 87 for ultrasonically lysing cells and uniformly mixing reagents and magnetic beads.
In some embodiments, the nucleic acid extraction device further comprises an ultrasound module 43, the ultrasound module 43 comprising an ultrasound transducer 431 and a second bracket 432. The ultrasonic transducer 431 is movably mounted to a second bracket 432. The second bracket 432 may be a separate bracket and fixed to the base plate 42; alternatively, the second bracket 432 is part of the base plate 42.
In some embodiments, where a pallet 46 is provided, then a second bracket 432 is carried by the pallet 46, the second bracket 432 may be a separate bracket and secured to the pallet 46; alternatively, second leg 432 is part of tray 46.
Referring to fig. 16, in some embodiments, an ultrasonic transducer 431 is mounted to a second bracket 432 by a clamp 435. The ultrasonic transducer 431 is detachably connected to the clamp 435, and the ultrasonic transducer 431 and the clamp 435 move in synchronization.
Ultrasonic transducer 431 is used to abut reaction chamber 87 to facilitate the reaction of reaction chamber 87. When second support 432 moves with pallet 46 toward chip 80, ultrasonic transducer 431 is moved synchronously until ultrasonic transducer 431 is adjacent to reaction chamber 87 of chip 80. The energy released by the ultrasonic transducer 431 is used for separating nucleic acid from the sample in the reaction chamber 87 and mixing the reagent and the magnetic beads uniformly.
Referring to fig. 1 to 3, in order to facilitate controlling the magnitude of the force of the ultrasonic transducer 431 against the reaction chamber 87 of the chip 80, the ultrasonic module 43 further includes a third bracket 433 and a force measuring assembly 434. The third holder 433 is slidably mounted to the second holder 432, and the ultrasonic transducer 431 is slidably mounted to the third holder 433. The force measuring assembly 434 is mounted to the end of the third support 433 remote from the ultrasonic transducer 431. Wherein the ultrasonic transducer 431 is configured to be slidable relative to the third bracket 433 to a position abutting against the load cell 434.
When the second support 432 is moved towards the chip 80, the force-measuring unit 434 with the third support 433 fixed to the third support 433 and the ultrasonic transducer 431 slidably connected to the third support 433 are moved towards the chip 80 simultaneously. When the whole is moved to the state where the driving shaft 412 abuts against the rotor 85 of the chip 80, the ultrasonic transducer 431 does not abut against the chip 80. Next, the third motor 436 drives the third support 433, the force measuring assembly 434 carried by the third support 433, the clamp 435 fixing the ultrasonic transducer 431, and the ultrasonic transducer 431 to continue to advance until the ultrasonic transducer 431 first abuts against the chip 80, and under the abutting force applied by the chip 80, the ultrasonic transducer 431 cannot continue to move, while the third support 433 still moves. This results in a gradual decrease in the distance of the ultrasonic transducer 431 from the force measuring assembly 434. After the ultrasonic transducer 431 abuts against the force measuring assembly 434, the force measuring assembly 434 can accurately measure the magnitude of the acting force applied by the ultrasonic transducer 431 to the reaction cavity 87 of the chip 80 according to the principle that the magnitudes of the force and the reaction force are equal. The displacement of the third holder 433 is controlled by the force measuring unit 434, and when the force measured by the force measuring unit 434 satisfies a predetermined value, the force measuring unit 434 feeds the force back to the controller, and the controller stops the third motor 436.
The force applied by the ultrasonic transducer 431 to the reaction chamber 87 of the chip 80 (i.e., the magnitude of the force measured by the force measuring assembly 434) is related to the displacement of the third support 433. Second leg 432 has stopped moving before the force is precisely adjusted. The magnitude of the force applied by the ultrasonic transducer 431 to the reaction chamber 87 of the chip 80 is adjusted by the displacement amount of the third support 433 relative to the second support 432. When the force applied by the ultrasonic transducer 431 to the reaction chamber 87 of the chip 80 meets the requirement, the relative position of the ultrasonic transducer 431 and the chip 80 and the force between the two are unchanged, the second support 432 stops sliding, and the third support 433 also stops sliding. During the nucleic acid extraction process, the ultrasonic transducer 431 is fixed in position with respect to the chip 80, that is, the position of the second support 432 is kept constant with respect to the base plate 42, and the third support 433 is also kept constant with respect to the second support 432. If the transmission effect of the ultrasonic vibration needs to be changed, whether the force applied by the ultrasonic transducer 431 to the reaction chamber 87 of the chip 80 is changed or not, namely the displacement of the third support 433 relative to the second support 432, can be selected according to the needs.
The following describes how to precisely control the conditions of the ejection of the chips 80 and the amount of displacement of the pallet 46 relative to the chips 80 in those embodiments where the pallet 46 is present. The discharging of the chip 80 needs to satisfy the following conditions: with blade 46 away from chip 80, ultrasonic transducer 431 no longer abuts chip 80.
Referring to fig. 17, in some embodiments, the nucleic acid extraction device is provided with a first trigger assembly 48. The first trigger assembly 48 includes a first photoelectric switch 481 and a first blade 482. The first photoelectric switch 481 is fixed to the base plate 42, and the first stopper 482 is fixed to the support plate 46. First trigger assembly 48 is configured to control the amount of displacement of blade 46 relative to chip 80. Specifically, two operations are involved: one is how to determine the closest distance that the carrier 46 can move to the die 80 at the beginning of the test to determine whether the drive sleeve 413 is in driving connection with the valve cap 86. When the first trigger assembly 48 is triggered, the supporting plate 46 is advanced a set number of steps to ensure that the driving sleeve 413 is just in driving connection with the valve cover 86, and the valve cover 86 is still in a primary sealing state, i.e., the valve cover 86 is still in a pre-tightening position. While the drive shaft 412 is not yet in driving connection with the rotor 85 of the chip 80. Second, how to determine whether the carrier 46 has moved away from the chip 80 at the end of the test.
For the first operation, the first shutter 482 is located in the detection area of the first photoelectric switch 481 when the first photoelectric switch 481 is triggered as the calculation starting point. From this position as a calculation starting point, precisely controlling the number of steps of the second motor 471 for driving the movement of the pallet 46 relative to the base plate 42 achieves precisely controlling the amount of displacement by which the pallet 46 is advanced. When the forward displacement of the pallet 46 meets the requirement, the pallet 46 is halted. Under the action of the resilient member 416 described above, there is some axial displacement of the valve cover 86 in itself, which causes the valve cover 86 to rotate from the pre-tensioned position to the sealing engagement position. In the process of rotating the valve cover 86 from the pre-tightening position to the sealing engagement position, the rotating power comes from the driving shaft 412, and at this time, the driving shaft 412 is kept in driving connection with the driving sleeve 413, so that the rotating power can be transmitted to the driving shaft 412 through the driving part 411 and then transmitted to the driving sleeve 413. The carriage 46 then moves back until the first opto-electronic switch 481 is again triggered, indicating that the carriage 46 has been reset. The blade 46 then advances from the position where the first opto-electronic switch 481 is activated to a position where the second opto-electronic switch 491, described below, is activated, in which the drive shaft 412 is in driving connection with the rotor 85. This position is a position where the valve position of the chip 80 can be switched. Throughout the testing process, drive shaft 412 remains in driving communication with rotor 85. After the entire test is completed, the chip 80 needs to be taken out of the bin. A second operation is required at this point. The second operation is that when the supporting plate 46 moves from the nearest position to the chip 80 to the first photoelectric switch 481 and is triggered by the first stop 482 again, it indicates that the supporting plate 46 has retreated to the original position. In this case, one of the conditions for the binning of the chips 80 has been met.
It should be noted that the above-mentioned control process is not the only implementation manner, and by setting a suitable control program and parameters, it can be realized that the pallet 46 can be switched from the state in which the valve seat 83 is driven to the state in which the rotor 85 is driven by one advance, without the need of reciprocating the pallet 46 to determine the starting point of the linear displacement and the rotational movement.
Referring to fig. 18, in some embodiments, the nucleic acid extraction device is provided with a second trigger assembly 49. The second triggering device 49 includes a second photoelectric switch 491 and a second shutter 492. The second photoelectric switch 491 is fixed to the base plate 42, and the second shutter 492 is fixed to the support plate 46. Second trigger assembly 49 is configured to determine whether drive shaft 412 is just in driving connection with rotor 85. The carriage 46 is moved from when the first trigger assembly 48 is triggered to when the second trigger assembly 49 is triggered. After the second trigger assembly 49 is triggered, the pallet 46 stops moving. The position where drive shaft 412 is in driving connection with rotor 85, also referred to as drive shaft 412 being in a driving position. When the drive shaft 412 is in this drive position, the drive shaft 412 has been brought into driving connection with the rotor 85, and the drive sleeve 413 is no longer in driving connection with the drive shaft 412, so that the drive sleeve 413 no longer transmits rotational power to the valve cover 86. The position may be determined experimentally. When the second photoelectric switch 491 is triggered, that is, the second blocking piece 492 is located in the detection area of the second photoelectric switch 491, the valve cover 86 is already located at the sealing matching position, the valve cover 86 is no longer driven to rotate, and the driving shaft 412 and the rotor 85 form a driving connection, which realizes that the valve position communication state of the rotary valve 82 is adjusted as required in the subsequent testing process to meet the testing requirement.
Referring to fig. 19, in some embodiments, the nucleic acid extraction device is provided with a third trigger assembly 40. The third triggering assembly 40 includes a third photoelectric switch 401 and a third shutter 402. The third photoelectric switch 401 is fixed to the support plate 46, and the third stopper 402 is fixed to the third holder 433. Third trigger assembly 40 is configured to determine whether ultrasonic transducer 431 is located at a home position, which is a position where ultrasonic transducer 431 does not abut against chip 80.
In the control process, the ultrasonic transducer 431 is reset to a position where it does not contact the chip 80, and then the supporting plate 46 is reset. When these conditions are met, it is indicated that the chip 80 can be taken out of the bin. Then the chip 80 is driven to be delivered out of the warehouse by the chip clamping device for lifting the bearing chip 80.
In some embodiments, the nucleic acid extraction apparatus further comprises a controller (not shown) as described above, and the controller is electrically connected to at least one of the first trigger assembly 48, the second trigger assembly 49, and the third trigger assembly 40 to perform corresponding operations according to the detection result of each trigger assembly.
The flow driving module 44 is described below.
Referring to FIGS. 1 to 3 and 7, in some embodiments, the nucleic acid extracting apparatus further includes a liquid flow driving module 44, and the liquid flow driving module 44 includes a fourth support 441, a power source 442, and an adsorption member 443. The suction member 443 is attached to the fourth frame 441; one end of the suction member 443 is drivingly connected to the power source 442, and the other end is open. The power source 442 may be mounted to the fourth support 441, or to the platform 46, or to the base plate 42.
Referring to fig. 1, in some embodiments, the suction member 443 includes a suction tube 443a and a suction nozzle 443b in communication with a first end of the suction tube 443 a. The second end of the suction pipe 443a communicates with the power source 442. The power source 442 employs, for example, a pump to supply suction power to the suction nozzle 443b through the suction pipe 443 a. The suction nozzle 443b is made of a relatively soft material so as to achieve sealed communication between the suction nozzle 443b and the suction port 88 of the chip 80.
The fourth bracket 441 may be fixed with the above first bracket 414 or share one bracket. After the driving shaft 412 of the channel switching module 41 is drivingly connected to the rotor 85 of the chip 80, the adsorbing member 443 needs to be connected to the suction port 88 of the chip 80 before nucleic acid extraction is performed. That is, the other end of the suction member 443 is hermetically connected to the suction port 88 of the chip 80. In addition, since the fourth support 441 is fixed to the first support 414, the fourth support 441 moves along with the movement of the first support 414, and the fluid driving module 44 can also move forward when the first support 414 moves forward, thereby saving a first motor. When the first support 414 is advanced, the suction nozzle 443b of the fluid driving module 44 is also pressed against the suction port 88 of the chip, so as to achieve a sealed connection. Therefore, it is not necessary to provide a separate driving motor for the fourth support 441, and thus one motor is saved, so that the number of power equipment required for the nucleic acid isolation apparatus is reduced, and the weight reduction of the product is facilitated.
Referring to FIGS. 9 to 12, the suction port 88 of the chip 80 communicates with the reaction chamber 87. By applying negative pressure to the suction port 88, negative pressure can be formed in the reaction chamber 87 to allow the fluid to flow smoothly into the inside of the reaction chamber 87. A buffer chamber 801 may be provided between the pumping port 88 of the chip 80 and the reaction chamber 87 to reduce the possibility that fluid is pumped to the outside of the chip 80.
Referring to fig. 1-3 and 6, the magnetic attraction module 45 is described.
In some embodiments, the nucleic acid extraction device further comprises a magnetic attraction module 45. After the substance in the reaction chamber 87 is separated into nucleic acid and other components, the magnetic module 45 can discharge the other components in the reaction chamber 87, and the magnetic beads with the nucleic acid adsorbed thereon are retained. After all the nucleic acid extraction reactions in the reaction chamber 87 are completed, the substances in the reaction chamber are divided into a nucleic acid solution and waste magnetic beads, and the waste magnetic beads can be left by the magnetic module 45, and only the nucleic acid solution is extracted.
Referring to fig. 6, the magnetic module 45 includes a magnet 451 and a driving member 452, and the driving member 452 is drivingly connected to the magnet 451 to switch the magnet 451 between an operating position and a home position. Specifically, the magnet 451 rotates in a plane perpendicular to the surface of the chip 80 to switch the magnet 451 between the operating position and the home position.
The driving part 452 is a steering engine, and the steering engine is fixed on the bottom plate 42 through a steering engine mounting seat 453. The rotating shaft of the steering engine is fixed with the magnet fixing piece 454. The rotation of the rotating shaft of the steering engine drives the magnet fixing part 454 to rotate synchronously. The magnet 451 is mounted to the magnet holder 454.
The operation position of the magnet 451 refers to a position where the magnet 451 can adsorb magnetic beads in the reaction chamber 87 of the chip 80. The home position of the magnet 451 refers to a position where the magnet 451 cannot adsorb magnetic beads in the reaction chamber 87 of the chip 80. When the rotating shaft of the steering engine rotates for a certain angle, such as 90 degrees, the magnet 451 stands up, and the center of the end face of the magnet 451 facing to the chip 80 is consistent with and contacts with the geometric center of the reaction cavity 87. The magnet 451 attracts magnetic beads in the reagent.
Magnetic beads are small particles with a diameter of the order of micrometers that have superparamagnetism. The magnetic beads have reversible adsorption capacity to nucleic acid (including DNA and RNA) under certain conditions; and other impurities such as protein and the like are not adsorbed by the magnetic beads and remain in the solution. Magnetism is inhaled module 45 and is cooperated the magnetic bead design, and magnetism is inhaled module 45 and is used for gathering the magnetic bead, carries out magnetic separation to magnetic bead and liquid, can leave the magnetic bead that takes nucleic acid like this, and drains away the waste liquid. Therefore, the magnetic module 45 collects the magnetic beads when necessary, and prevents the magnetic beads from being taken away.
Referring to fig. 1 to 13, the embodiment of the present invention further provides a nucleic acid extraction device, including a chip 80 and the nucleic acid extraction device according to any one of the technical embodiments of the present invention. The chip 80 includes a chip body 81 and a rotary valve 82 provided on the chip body 81.
As described above, the rotary valve 82 includes the valve seat 83, the seal 84, the rotor 85, and the valve cover 86. The valve seat 83 is fixedly connected with the chip body 81, the valve cover 86 is rotatably connected with the valve seat 83, and the rotor 85 is rotatably clamped between the valve seat 83 and the valve cover 86.
A plurality of flow channels are provided inside the chip body 81. The drive shaft 412 is drivingly connected to the rotor 85 and the drive sleeve 413 is drivingly connected to the valve cover 86. Wherein the rotary valve 82 is configured to switch the communication state between the two flow passages by the rotation of the rotor 85, and the rotary valve 82 is configured to rotate the valve cover 86 in the pre-tightening position to the seal engagement position by the rotation of the valve cover 86. When the valve cover 86 is in the pre-tensioned position, the seal 84 is hardly squeezed. When the valve cap 86 is in the sealing engagement position, the seal 84 is compressed to reduce the likelihood of leakage during operation of the rotary valve 82.
Referring to fig. 10 to 13, in some embodiments, the valve seat 83 is configured to be annular, and an edge of the valve seat 83 is provided with a first catching groove 831 and a second catching groove 832 which are communicated, and the second catching groove 832 is located at a side of the first catching groove 831 facing the chip body 81, and specifically, referring to fig. 15, an upper edge of the second catching groove 832 is located at a side of the upper edge of the first catching groove 831 facing the chip body 81. It should be noted that the first locking notch 831 and the second locking notch 832 may also adopt other structures to meet the following matching requirements. The inner wall of the valve cover 86 is provided with a fastener 862. When the valve cover 86 is in the pre-tightening position, the latch 862 is engaged with the first engaging slot 831. When the valve cover 86 is in the sealed engagement position, the catch 862 engages the second detent 832.
Referring to fig. 13, a first clamping step 833 is disposed on an inner wall of the first locking groove 831, and the first clamping step 833 is a downward protrusion shown in fig. 13. The first clamping step 833 is used to prevent the latch 862 from coming out of the first slot 831, i.e., prevent the first clamping from failing.
Referring to fig. 14 and 15, the inner wall of the second catching groove 832 is provided with a second catching step 834, and the second catching step 834 is a protrusion part in the direction toward the edge of the valve seat 83 as illustrated in fig. 13. Second catch step 834 is used to prevent the catch 862 from disengaging from the second catch 832, i.e., to prevent failure of the secondary catch.
Referring to fig. 10-13, in some embodiments, first and second detents 831, 832 are provided in multiple sets spaced apart along the circumference of valve seat 83. Correspondingly, a plurality of fasteners 862 are arranged on the inner wall of the driving sleeve 413, and one fastener 862 corresponds to one set of the first locking slot 831 and the second locking slot 832.
As described above, in some embodiments, the free end of the driving shaft 412 is provided with the first retaining column 412c, the rotor 85 is provided with the first retaining hole 851, and the first retaining column 412c is matched with the first retaining hole 851 to realize the driving connection between the driving shaft 412 and the rotor 85.
The shapes, the numbers and the distribution manners of the first retaining columns 412c and the first retaining holes 851 are selected to achieve reliable driving connection between the driving shaft 412 and the rotor 85.
As described above, in some embodiments, the free end of the driving sleeve 413 is provided with the second retaining column 413a, the valve cover 86 is provided with the second retaining hole 861, and the second retaining column 413a is matched with the second retaining hole 861.
The shapes, the number and the distribution mode of the second clamping columns 413a and the second clamping holes 861 are selected in various ways, so that the driving sleeve 413 and the valve cover 86 can be connected in a reliable driving mode.
As described above, the first retaining column 412c and the first retaining hole 851 are used to realize the reliable driving connection between the driving shaft 412 and the rotor 85. The second retaining column 413a and the second retaining hole 861 are used for realizing reliable driving connection between the driving sleeve 413 and the valve cover 86.
The drive shaft 412 is drivingly connected to the rotor 85 for effecting switching of the valve positions of the rotary valve 82, and the drive sleeve 413 is drivingly connected to the valve cover 86 for effecting screwing of the valve cover 86 from the pre-tensioned position to the sealing engagement position. The two driving connections do not exist simultaneously, and in the working process, the driving connection between the driving sleeve 413 and the valve cover 86 is firstly realized, namely, the valve cover 86 is firstly screwed from the pre-tightening position to the sealing matching position, and then the driving connection between the driving shaft 412 and the rotor 85 is realized. During the use of the product, the driving connection between the driving sleeve 413 and the valve cover 86 is completed at the beginning, after the valve cover 86 is screwed to the sealing matching position, the driving sleeve 413 is connected with the driving shaft 412 in a key way, at this time, although the driving sleeve 413 and the valve cover 86 are in a connecting state, no rotating power is transmitted to the valve cover 86 from the driving sleeve 413.
In the nucleic acid extraction process, the rotary valve 82 is involved in a plurality of valve position switching operations. The drive shaft 412 is always in driving connection with the rotor 85, and the drive shaft 412 is always capable of transmitting rotational power like the rotor 85.
The nucleic acid detection system provided by the embodiment of the invention meets the requirements of full-automatic integration and high integration of nucleic acid detection, bedside detection, instant detection and random detection, and is not only suitable for small equipment capable of instant detection and random detection, but also suitable for large equipment with full-automatic integration and high integration. Therefore, the nucleic acid detection system provided by the technical scheme has strong universality and wide application scene.
In the description of the embodiments of the present invention, it should be understood that the terms "central", "longitudinal", "lateral", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc. indicate orientations or positional relationships based on those shown in the drawings, and are only for convenience of description and simplicity of description, but do not indicate or imply that the devices or elements being referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus, are not to be considered as limiting the scope of the present invention.
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: it is to be understood that modifications may be made to the technical solutions described in the foregoing embodiments, or equivalents may be substituted for some of the technical features thereof, but such modifications or substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims (24)

1. A nucleic acid extraction device, comprising:
a flow channel switching module (41) comprising a driving part (411), a driving shaft (412) and a driving sleeve (413); the driving shaft (412) is in driving connection with the driving part (411); the drive sleeve (413) is configured to switch between a drive connection position and a disconnection position; wherein the drive shaft (412) is in driving connection with the drive sleeve (413) when the drive sleeve (413) is in a driving connection position; -when the drive sleeve (413) is in the disengaged position, the drive shaft (412) is drivingly disconnected from the drive sleeve (413);
the drive sleeve (413) is configured to be movable relative to the drive shaft (412) along its own axial direction to switch between a drive connection position and a disconnection position;
wherein the drive sleeve (413) is configured to be in driving connection with a valve cap (86) of a rotary valve (82) of the chip (80).
2. The nucleic acid extraction device according to claim 1, wherein the flow channel switching module (41) further comprises:
a first bracket (414) having a mounting hole (414a), the drive shaft (412) being mounted to the mounting hole (414 a); and
an elastic member (416) interposed between the first bracket (414) and the driving sleeve (413);
wherein, the driving sleeve (413) is sleeved outside the driving shaft (412) and is connected with the driving shaft (412) in a sliding way.
3. The nucleic acid extraction device according to claim 2, wherein the flow channel switching module (41) further comprises:
a bushing (415) mounted to an outside of the driving shaft (412) and located inside the mounting hole (414 a); the elastic piece (416) is clamped between the shaft sleeve (415) and the driving sleeve (413).
4. The nucleic acid extraction apparatus according to claim 2, wherein the drive sleeve (413) is provided with a key groove (413b) that penetrates the drive sleeve (413) itself in the axial direction, and the drive shaft (412) is provided with a key (417); the key groove (413b) is fitted with the key (417).
5. The nucleic acid extraction apparatus according to claim 4, wherein an end of the drive shaft (412) is provided with a projection (412b), and the projection (412b) is configured to position the drive sleeve (413).
6. The nucleic acid extraction apparatus according to claim 4, wherein the drive section (411) includes:
a first motor (411 a); and
a transmission assembly (411b) drivingly connecting the drive shaft (412) with the first motor (411 a).
7. The nucleic acid extraction device according to claim 3, wherein the flow channel switching module (41) further comprises:
a limit snap ring (418) mounted to the first bracket (414) and rotatably coupled to the drive shaft (412); the limit snap ring (418) is configured to limit movement of the drive shaft (412) relative to the mounting hole (414a) along an axial direction of the drive shaft (412).
8. The nucleic acid extraction device according to claim 1, wherein the flow channel switching module (41) further comprises:
an angle measurement assembly (419) mounted to the drive shaft (412) and configured to detect a rotational angle of the drive shaft (412).
9. The nucleic acid extraction apparatus according to claim 1, further comprising:
a base plate (42), the flow channel switching module (41) being slidably mounted to the base plate (42).
10. The nucleic acid extraction apparatus according to claim 9, characterized by further comprising:
a pallet (46) slidably mounted to the base plate (42); the runner switching module (41) is carried by the carrier (46).
11. The nucleic acid extraction apparatus according to claim 10, further comprising:
a first trigger assembly (48) comprising a first photoelectric switch (481) and a first blade (482); the first photoelectric switch (481) is fixed to the base plate (42), and the first stopper (482) is fixed to the support plate (46); the first trigger assembly (48) is configured to control an amount of displacement of the pallet (46) relative to the base plate (42).
12. The nucleic acid extraction apparatus according to claim 10, further comprising:
a second trigger assembly (49) comprising a second photoelectric switch (491) and a second shutter (492); the second photoelectric switch (491) is fixed on the bottom plate (42), and the second blocking piece (492) is fixed on the supporting plate (46); the second trigger assembly (49) is configured to determine whether the drive shaft (412) is in a drive position.
13. The nucleic acid extraction apparatus according to claim 10, further comprising:
a third trigger assembly (40) comprising a third photoelectric switch (401) and a third shutter (402); the third photoelectric switch (401) is fixed to the support plate (46), and the third shutter (402) is fixed to an ultrasonic module (43) of the nucleic acid extraction apparatus; the third trigger assembly (40) is configured to determine whether the ultrasound module (43) is in a home position.
14. The nucleic acid extraction apparatus according to claim 1, further comprising:
an ultrasound module (43) comprising an ultrasound transducer (431) and a second mount (432); the ultrasonic transducer (431) is movably mounted to the second bracket (432).
15. The nucleic acid extraction apparatus according to claim 14, wherein the ultrasound module (43) further comprises:
a third mount (433) slidably mounted to the second mount (432), the ultrasonic transducer (431) slidably mounted to the third mount (433); and
a force measuring assembly (434) mounted at an end of the third bracket (433) remote from the ultrasonic transducer (431);
wherein the ultrasonic transducer (431) is configured to be slidable relative to the third bracket (433) into a position abutting the load cell assembly (434).
16. The nucleic acid extraction apparatus according to claim 1, further comprising:
a liquid flow driving module (44) including a fourth frame (441), a power source (442), and an adsorption member (443); the suction member (443) is attached to the fourth bracket (441); one end of the adsorption part (443) is in driving connection with the power source (442), and the other end is open.
17. The nucleic acid extraction apparatus according to claim 1, further comprising:
the magnetic attraction module (45) comprises a magnet (451) and a driving part (452), wherein the driving part (452) is in driving connection with the magnet (451) so that the magnet (451) can be switched between a working position and an original position.
18. A nucleic acid detection system, comprising:
a chip (80) including a chip body (81) and a rotary valve (82) provided to the chip body (81); the rotary valve (82) comprises a valve seat (83), a seal (84), a rotor (85) and a valve cover (86); the valve seat (83) is fixedly connected with the chip body (81), the valve cover (86) is rotatably connected with the valve seat (83), the rotor (85) is rotatably clamped between the valve seat (83) and the valve cover (86), and the sealing element (84) is positioned between the valve seat (83) and the rotor (85); a plurality of flow channels are arranged in the chip body (81); and
the nucleic acid isolation apparatus as claimed in any one of claims 1 to 17, wherein the drive shaft (412) is drivingly connected to the rotor (85), and the drive sleeve (413) is drivingly connected to the valve cover (86);
wherein the rotary valve (82) is configured to switch a communication state between the two flow passages by rotation of the rotor (85), and the rotary valve (82) is configured to rotate the valve cover (86) in a pre-tightening position to a seal engagement position by rotation of the valve cover (86).
19. The nucleic acid detecting system according to claim 18, wherein the valve seat (83) is configured to be annular, an edge of the valve seat (83) is provided with a first notch (831) and a second notch (832) which are communicated, and the second notch (832) is located on a side of the first notch (831) facing the chip body (81); a buckle (862) is arranged on the inner wall of the valve cover (86); when the valve cover (86) is in a pre-tightening position, the buckle (862) is matched with the first clamping groove (831); the catch (862) mates with the second catch (832) when the valve cap (86) is in the sealed mating position.
20. The nucleic acid detecting system according to claim 19, wherein the first notch (831) and the second notch (832) are provided in plural sets at intervals along a circumferential direction of the valve seat (83).
21. The nucleic acid detecting system according to claim 19, wherein a free end of the drive shaft (412) is provided with a first retaining column (412c), the rotor (85) is provided with a first retaining hole (851), and the first retaining column (412c) is engaged with the first retaining hole (851).
22. The nucleic acid detecting system according to claim 19, wherein a free end of the drive sleeve (413) is provided with a second retaining column (413a), and the valve cover (86) is provided with a second retaining hole (861), the second retaining column (413a) being engaged with the second retaining hole (861).
23. The nucleic acid detecting system according to claim 19, wherein a free end of the drive shaft (412) is provided with a first catching column (412c), the rotor (85) is provided with a first catching hole (851), a free end of the drive sleeve (413) is provided with a second catching column (413a), and the valve cover (86) is provided with a second catching hole (861);
wherein, the following two cooperation states can be selectively selected and exist: the first clamping column (412c) is matched with the first clamping hole (851), and the second clamping column (413a) is matched with the second clamping hole (861).
24. The nucleic acid detecting system according to claim 18, wherein when the drive shaft (412) is brought into driving connection with the rotor (85) of the chip (80), the other end of the adsorbing member (443) of the liquid flow driving module (44) of the nucleic acid extracting apparatus is sealingly connected to the suction port (88) of the chip (80).
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