CN207552287U - A kind of micro-fluidic chip and chip assembly - Google Patents

A kind of micro-fluidic chip and chip assembly Download PDF

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Publication number
CN207552287U
CN207552287U CN201721215118.1U CN201721215118U CN207552287U CN 207552287 U CN207552287 U CN 207552287U CN 201721215118 U CN201721215118 U CN 201721215118U CN 207552287 U CN207552287 U CN 207552287U
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China
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control
liquid
state
waste liquid
circulation pipeline
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CN201721215118.1U
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Chinese (zh)
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刘鹏
耿智
顾寅
周文兴
杨毅
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Hangzhou Zijing Biological Co ltd
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Beijing Jie Gold Chong Gene Technology Co Ltd
Tsinghua University
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Abstract

The utility model discloses a kind of micro-fluidic chip and chip assembly, it is related to microfluidic art, it can realize integrated, the fully integrated operation of sample preparation and amplification separation in detection of nucleic acids, the operation for making detection of nucleic acids is more convenient, improves the efficiency of detection of nucleic acids.The micro-fluidic chip includes being used to implement the liquid reagent liquid storage unit of sample introduction, the extraction amplification unit for expanding isolated sample to be checked and the devil liquor recovery unit for recycling detection waste liquid successively;Wherein, liquid storage unit includes multiple liquid storage devices and the first circulation duct connected with the liquid outlet of each liquid storage device, the first control piece is equipped between each liquid outlet and the first circulation duct, first control piece is used to control the conducting state of liquid outlet, when any liquid storage device is in pressurized state, corresponding first control piece is in opening, remaining first control piece is in closed state.Micro-fluidic chip and chip assembly provided by the utility model are used for detection of nucleic acids.

Description

Micro-fluidic chip and chip assembly
Technical Field
The utility model relates to a micro-fluidic technology field especially relates to a micro-fluidic chip and chip subassembly.
Background
The microfluidic chip technology is a highly integrated technology which can automatically complete the whole analysis process by integrating basic operations such as sample preparation, amplification separation, heating detection and the like of nucleic acid in the biological, chemical and medical analysis processes on a micron-scale chip. However, since the sample preparation process requires strict control of sequential sample injection of multiple reaction reagents, it is not easy to implement in a micro-fluidic chip with a small volume and a complex structure, and thus the micro-fluidic chip in the prior art can only implement amplification separation and heating detection of nucleic acid, and the sample preparation process needs to be performed in a separate external device, for example, an external liquid storage tank is used to complete sample preparation, and then the obtained sample is connected with the micro-fluidic chip through a hose, so that the micro-fluidic chip can complete operations such as amplification separation and heating detection after obtaining the sample.
Although the problem that multiple reaction reagents are sequentially injected can be well solved by adopting an external liquid storage tank, the method is not enough in actual operation, and because the interface design of the microfluidic chip is very tiny, the connection of the flexible pipe is time-consuming and labor-consuming at every time, so that the operation process of nucleic acid detection is complex, and the detection efficiency is low.
SUMMERY OF THE UTILITY MODEL
An object of the utility model is to provide a micro-fluidic chip and chip subassembly can realize among the nucleic acid testing integration, the full integrated operation of sample preparation and amplification separation, makes the operation of nucleic acid testing more convenient, has promoted nucleic acid testing's efficiency.
In order to achieve the above object, an aspect of the present invention provides a microfluidic chip, including a liquid storage unit for sequentially injecting a liquid reagent, an extraction and amplification unit for obtaining a sample to be detected by amplification and separation, and a waste liquid recovery unit for recovering a detection waste liquid, wherein the liquid storage unit, the extraction and amplification unit, and the waste liquid recovery unit are sequentially connected; wherein,
the liquid storage unit comprises a plurality of liquid storages and first circulation pipelines communicated with liquid outlets of the liquid storages, a first control piece is arranged between each liquid outlet and each first circulation pipeline and used for controlling the communication state of the liquid outlets, when any one of the liquid storages is in a pressurization state, the corresponding first control piece is in an opening state, and the rest first control pieces are in a closing state.
Preferably, the extraction and amplification unit comprises an amplification chamber for extracting amplified nucleic acid to obtain a sample to be detected, one end of the amplification chamber is communicated with the first circulation pipeline through a second control element, the other end of the amplification chamber is communicated with the waste liquid recovery unit through a third control element, the second control element is used for controlling the communication state of the first circulation pipeline and the amplification chamber, and the third control element is used for controlling the communication state of the second circulation pipeline and the waste liquid recovery unit.
Preferably, the extraction and amplification unit further comprises a first pressurization part for controlling the state of the second control element, and a second pressurization part for controlling the state of a third control element;
when positive air pressure is applied to the second control member and the third control member through the first pressurizing portion and the second pressurizing portion, respectively, the second control member and the third control member are both in an open state;
when negative air pressure is applied to the second control member and the third control member by the first pressurizing portion and the second pressurizing portion, respectively, both the second control member and the third control member are in a closed state.
Further, the waste liquid recovery unit includes the waste liquid pond, and with the second circulation pipeline of the inlet intercommunication of waste liquid pond, the one end of second circulation pipeline is passed through the third control with the amplification cavity intercommunication, the other end of second circulation pipeline pass through the fourth control with the inlet intercommunication, the fourth control be used for controlling the inlet with the conducting state of second circulation pipeline.
Preferably, the first control piece and the fourth control piece are both sheet-shaped elastic membranes, and each sheet-shaped elastic membrane comprises a single-side fixing part and a first elastic movable part; wherein,
one end of a single-side fixed part of the first control piece is fixedly connected with the outer wall of the liquid storage device, the other end of the single-side fixed part is fixedly connected with the first elastic movable part, when the first control piece is in an opening state, the first elastic movable part is separated from the liquid outlet, so that the liquid outlet is in a conducting state with the first circulation pipeline, and when the first control piece is in a closing state, the first elastic movable part is attached to the liquid outlet, so that the liquid outlet is in a sealed and isolated state with the first circulation pipeline;
the one end of the unilateral fixed part of fourth control with the outer wall fixed connection in waste liquid pond, the other end of unilateral fixed part with first elasticity movable part fixed connection works as when the fourth control is in the open mode, first elasticity movable part with the inlet separation makes the inlet with second circulation pipeline is in the on-state, works as when the fourth control is in the closed mode, first elasticity movable part with the inlet laminating makes the inlet with second circulation pipeline is in airtight isolated state.
Preferably, the second control part and the third control part are both T-shaped elastic diaphragms, and each T-shaped elastic diaphragm comprises an isolation fixing part and a second elastic moving part; wherein,
the isolation fixing part of the second control part is fixed on the first circulation pipeline, two ends of the second elastic moving part of the second control part are respectively fixed on the outer walls of two sides of the first pressurizing part, and when the second control part is in an opening state, the second elastic moving part of the second control part is separated from the isolation fixing part of the second control part, so that the first circulation pipeline and the amplification chamber are in a conduction state;
and when the third control part is in an open state, the second elastic movable part of the third control part is separated from the isolation fixing part of the third control part, so that the second circulation pipeline and the amplification chamber are in a conduction state.
Preferably, the reservoir is a conical funnel-shaped structure, a suspension ball is arranged in the reservoir, and the diameter of the suspension ball is d1The diameter of the liquid outlet is d2And d is1>d2
Further, the thickness of the first control part is 0.05-1.5 mm, and the interval between the adjacent first control parts is 0.5-1.5 mm.
Preferably, a clamping groove is formed in one side face of the microfluidic chip, and clamping columns corresponding to the clamping groove are arranged on the opposite face of the side face.
Compared with the prior art, the utility model provides a micro-fluidic chip has following beneficial effect:
the utility model provides an among the micro-fluidic chip, by the stock solution unit, draw amplification unit and waste liquid recovery unit to constitute, wherein, the stock solution unit includes a plurality of reservoir and first circulation pipeline, through set up first control between the liquid outlet of each reservoir and first circulation pipeline, when continuously applying forward atmospheric pressure to arbitrary reservoir, the first control of being connected with the liquid outlet of this reservoir will be in the state of continuously opening under the effect of forward atmospheric pressure, promptly this reservoir switches on with first circulation pipeline, make the liquid reagent in this reservoir can flow into first circulation pipeline under the effect of forward atmospheric pressure, and after the liquid reagent in this reservoir gets into first circulation pipeline, through the drainage of first circulation pipeline, this liquid reagent can contact with other first control in first circulation pipeline, and provide reverse pressure to the first control of contact with it, therefore, the rest of the first control parts are in an adherence state under the action of reverse pressure, at the moment, the liquid reagent in the liquid reservoirs corresponding to the rest of the first control parts and the first circulation pipeline are in a closed isolation state, and then the liquid reagent flows through the extraction and amplification unit and is recovered to the waste liquid recovery unit, so that the sample introduction of the liquid reagent is completed.
It is thus clear that use the utility model provides a micro-fluidic chip adds the liquid reagent that corresponds in a plurality of reservoir, only through the control to arbitrary reservoir state of pressurizeing, can realize controlling the appearance of advancing of liquid reagent in this reservoir, and is further, through the control to a plurality of reservoirs state of pressurizeing in proper order, just can realize advancing the control of appearance in proper order to multiple liquid reagent. Therefore, compare in prior art, the utility model provides a stock solution unit has simple structure, controls multiple liquid reagent and advances the reliability height of appearance in proper order and can not take place advantages such as crosstalk, in addition, through with the stock solution unit, draw amplification unit and waste liquid recovery unit and communicate the setting in proper order, can realize the integration of nucleic acid detection, integrate the operation, have the convenience of preferred and higher detection efficiency.
Another aspect of the invention provides a microfluidic chip assembly comprising a microfluidic chip according to any one of claims 1 to 9.
The utility model provides a beneficial effect of micro-fluidic chip subassembly with the utility model discloses a micro-fluidic chip's that the first aspect provided beneficial effect is the same, and here is no longer repeated.
Drawings
The accompanying drawings, which are described herein, serve to provide a further understanding of the invention and constitute a part of this specification, and the exemplary embodiments and descriptions thereof are provided for explaining the invention without unduly limiting it. In the drawings:
fig. 1 is a schematic structural diagram of a microfluidic chip according to an embodiment of the present invention;
FIG. 2 is a schematic view of the reservoir of FIG. 1 in one state;
FIG. 3 is a schematic view of another state of the reservoir of FIG. 1;
FIG. 4 is a schematic diagram of the liquid reagent injection process of FIG. 1;
FIG. 5 is a schematic view of the liquid reagent of FIG. 1 with sample stop;
FIG. 6 is a schematic view of another structure of a microfluidic chip according to an embodiment;
fig. 7 is a schematic diagram of a chip assembly composed of a plurality of microfluidic chips according to the second embodiment.
Reference numerals:
1-liquid storage unit, 11-liquid storage device;
12-a liquid outlet, 13-a first control element;
14-first flow-through channel, 2-extraction amplification unit;
21-a first pressurizing part, 22-a second pressurizing part;
23-a second control, 24-a third control;
25-an amplification chamber, 3-a waste liquid recovery unit;
31-a waste liquid pool and 32-a liquid inlet;
33-a fourth control element, 34-a second through-flow duct;
4-clamp column, 5-clamp groove.
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 with reference to the accompanying drawings. It is to be understood that the embodiments described are only some embodiments of the invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by a person skilled in the art without creative efforts all belong to the protection scope of the present invention.
Example one
Referring to fig. 1-5, the microfluidic chip provided in this embodiment includes a liquid storage unit 1 for sequentially injecting a liquid reagent, an extraction and amplification unit 2 for performing amplification and separation to obtain a sample to be detected, and a waste liquid recovery unit 3 for recovering a detection waste liquid, where the liquid storage unit 1, the extraction and amplification unit 2, and the waste liquid recovery unit 3 are sequentially connected; the liquid storage unit 1 includes a plurality of liquid reservoirs 11 and a first circulation pipeline 14 communicated with the liquid outlets 12 of the liquid reservoirs 11, a first control member 13 is disposed between each liquid outlet 12 and the first circulation pipeline 14, the first control member 13 is used for controlling the communication state of the liquid outlets 12, when any one of the liquid reservoirs 11 is in a pressurized state, the corresponding first control member 13 is in an open state, and the other first control members 13 are in a closed state.
As can be seen from the above specific implementation process, the microfluidic chip provided in this embodiment includes a liquid storage unit 1, an extraction and amplification unit 2, and a waste liquid recovery unit 3, wherein the liquid storage unit 1 includes a plurality of liquid reservoirs 11 and a first circulation pipeline 14, and by disposing a first control member 13 between a liquid outlet 12 of each liquid reservoir 11 and the first circulation pipeline 14, when a forward air pressure is continuously applied to any liquid reservoir 11, the first control member 13 connected to the liquid outlet 12 of the liquid reservoir 11 will be in a continuously open state under the action of the forward air pressure, that is, the liquid reservoir 11 is in communication with the first circulation pipeline 14, so that a liquid reagent in the liquid reservoir 11 can flow into the first circulation pipeline 14 under the action of the forward air pressure, and after the liquid reagent in the liquid reservoir 11 enters the first circulation pipeline 14, the liquid reagent can contact with the remaining first control member 13 through drainage of the first circulation pipeline 14, and provides the first control member 13 contacted with it with a reverse pressure, so that the rest of the first control members 13 will be in an adherence state under the action of the reverse pressure, at this time, the liquid reagent in the liquid reservoir 11 corresponding to the rest of the first control members 13 and the first circulation pipeline 14 are in a sealed and isolated state, and then the liquid reagent flows through the extraction and amplification unit 2 and is recovered to the waste liquid recovery unit 3, thereby completing the sample introduction of the liquid reagent.
It can be seen that, with the microfluidic chip provided in this embodiment, the corresponding liquid reagents are added to the plurality of liquid reservoirs 11, and the sample injection of the liquid reagents in the liquid reservoirs 11 can be controlled only by controlling the pressurization state of any one of the liquid reservoirs 11, and further, the control of the sequential sample injection of the plurality of liquid reagents can be realized by sequentially controlling the pressurization states of the plurality of liquid reservoirs 11. Consequently, compare in prior art, the stock solution unit 1 that this embodiment provided has simple structure, controls the multiple liquid reagent reliability of advancing the appearance in proper order and high and can not take place advantages such as crosstalk, in addition, through with stock solution unit 1, draw amplification unit 2 and waste liquid recovery unit 3 and communicate the setting in proper order, can realize the integration of nucleic acid detection, integrate the operation, have the convenience of preferred and higher detection efficiency.
Specifically, referring to fig. 4 and 5, the extraction and amplification unit 2 in the above embodiment includes an amplification chamber 25 for extracting amplified nucleic acid to obtain a sample to be detected, one end of the amplification chamber 25 is communicated with the first circulation duct 14 through a second control member 23, the other end of the amplification chamber 25 is communicated with the waste liquid recovery unit 3 through a third control member 24, the second control member 23 is used for controlling the conduction state of the first circulation duct 14 and the amplification chamber 25, and the third control member 24 is used for controlling the conduction state of the second circulation duct 34 and the waste liquid recovery unit 3.
The extraction and amplification unit 2 further comprises a first pressurization unit 21 for controlling the state of the second control element 23, and a second pressurization unit 22 for controlling the state of the third control element 24; when positive air pressure is applied to the second control member 23 and the third control member 24 by the first pressurizing portion 21 and the second pressurizing portion 22, respectively, both the second control member 23 and the third control member 24 are in the open state; when negative air pressure is applied to the second control member 23 and the third control member 24 by the first pressure portion 21 and the second pressure portion 22, respectively, both the second control member 23 and the third control member 24 are in the closed state.
The waste liquid recovery unit 3 comprises a waste liquid tank 31 and a second circulation pipeline 34 communicated with a liquid inlet 32 of the waste liquid tank 31, one end of the second circulation pipeline 34 is communicated with the amplification chamber 25 through a third control part 24, the other end of the second circulation pipeline 34 is communicated with the liquid inlet 32 through a fourth control part 33, and the fourth control part 33 is used for controlling the conduction state of the liquid inlet 32 and the second circulation pipeline 34.
As can be seen from the above specific implementation process, in the microfluidic chip provided in this embodiment, when any one of the reservoirs 11 is in a conducting state with the first circulation channel 14, the second control element 23 and the third control element 24 are also in an open state through the synchronous control of the first pressure part 21 and the second pressure part 22, so that the liquid reagent in the reservoir 11 rapidly flows into the first circulation channel 14 under the action of the forward air pressure and flows into the amplification chamber 25 without obstruction, the waste liquid filtered by the amplification chamber 25 is directly discharged into the second circulation channel 34, and the waste liquid flows along the second circulation channel 34 to the liquid inlet 32 of the waste liquid pool 31 to contact with the fourth control element 33, so that the fourth control element 33 is in an open state under the action of the surface pressure, and the waste liquid can be recovered in the waste liquid pool 31; in the same way, when continuously applying forward atmospheric pressure to any liquid storage device 11 in proper order, can realize corresponding liquid reagent and flow into amplification chamber 25 in proper order to retrieve the waste liquid that produces to waste liquid pond 31 in proper order, consequently, use the micro-fluidic chip that this embodiment provided, not only realized the integration of nucleic acid detection, integrated the operation, can concentrate the waste liquid and retrieve in addition, reduce environmental pollution.
It is necessary to supplement that the amplification chamber 25 of the extraction amplification unit 2 is provided with a chemically modified glass fiber filter paper, so that after the liquid reagent flows through the amplification chamber 25, the nucleic acid in the liquid reagent can be captured after being filtered by the glass fiber filter paper; according to the principle that one liquid storage device 11 only stores one liquid reagent, the number of the liquid storage devices 11 can be freely increased or decreased according to the type of the liquid reagent for experiments in the specific implementation process. In addition, the volume of the reservoir 11 and the volume of the first circulation line 14 and the second circulation line 34 are not particularly limited in this embodiment, and those skilled in the art can make appropriate selections for the specifications of the required reservoir 11, the first circulation line 14, the second circulation line 34 and the waste liquid pool 31 according to the detection requirement. Illustratively, the volume of the liquid reservoir 11 is 10 to 500 microliters, the volumes of the first circulation pipe 14 and the second circulation pipe 34 are both 1 to 10 milliliters, and the volume of the waste liquid tank 31 is 10 to 20 milliliters.
Referring to fig. 2 and 3, the liquid reservoir 11 is a conical funnel-shaped structure, and a floating ball is disposed in the liquid reservoir 11, and the diameter of the floating ball is d1The diameter of the liquid outlet 12 is d2And d is1>d2. Through the arrangement of the suspension ball, when the liquid reagent exists in the liquid reservoir 11, the suspension ball floats on the water surface; when the liquid reagent in the liquid storage device 11 completely flows out, the suspension ball can block the liquid outlet 12 of the conical liquid storage device 11, so that gas is prevented from entering the first fluid channel, the use reliability of the micro-fluidic chip is ensured, and the effect of saving the liquid reagent is also achieved.
Preferably, referring to fig. 1, in the micro-fluidic chip provided in this embodiment, the liquid outlets 12 of the micro-fluidic chip are linearly arranged along the horizontal direction, and each of the liquid outlets 12 is located right above the first flow channel 14; by adopting the arrangement mode, the space utilization rate of each part can be improved, the volume of the microfluidic chip is further reduced, and the miniaturization and popularization of the microfluidic chip are facilitated.
With reference to fig. 4 and 5, in the microfluidic chip of the above embodiment, the first control part 13 and the fourth control part 33 are both sheet-shaped elastic diaphragms, and each sheet-shaped elastic diaphragm includes a single-side fixed part and a first elastic movable part; wherein,
one end of a single-side fixed part of the first control piece 13 is fixedly connected with the outer wall of the liquid reservoir 11, the other end of the single-side fixed part is fixedly connected with a first elastic movable part, when the first control piece 13 is in an opening state, the first elastic movable part is separated from the liquid outlet 12, so that the liquid outlet 12 is in a conduction state with the first circulation pipeline 14, and when the first control piece 13 is in a closing state, the first elastic movable part is attached to the liquid outlet 12, so that the liquid outlet 12 and the first circulation pipeline 14 are in a closed isolation state;
one end of the unilateral fixed part of the fourth control member 33 is fixedly connected with the outer wall of the waste liquid tank 31, the other end of the unilateral fixed part is fixedly connected with the first elastic movable part, when the fourth control member 33 is in an open state, the first elastic movable part is separated from the liquid inlet 32, so that the liquid inlet 32 and the second circulation pipeline 34 are in a conduction state, and when the fourth control member 33 is in a closed state, the first elastic movable part is attached to the liquid inlet 32, so that the liquid inlet 32 and the second circulation pipeline 34 are in a closed isolation state.
In specific implementation, the single-side fixing portion of the sheet-shaped elastic membrane may be fixedly connected to the outer wall of the liquid reservoir 11, referring to fig. 4, when a forward air pressure is applied to the liquid reservoir 11, the pressure of the forward air pressure may push the liquid reagent to flow to the liquid outlet 12 of the liquid reservoir 11 and form a pushing force on the surface of the elastic moving portion, and when the pushing force is greater than the deformation force of the elastic moving portion itself, the elastic moving portion at this time may be separated from the liquid outlet 12 of the liquid reservoir 11, that is, the liquid outlet 12 of the liquid reservoir 11 and the first circulation pipe 14 are in a conduction state; on the contrary, referring to fig. 5, when the application of the positive air pressure to the liquid reservoir 11 is stopped, the elastic movable portion maintains the attachment state with the liquid outlet 12 of the liquid reservoir 11 under the action of its own deformation force, and at this time, can perform the function of hermetically isolating the liquid outlet 12 of the liquid reservoir 11.
It can be seen that when the first control member 13 is an elastic diaphragm, the reliable control of the separation or attachment of the first elastic movable portion and the liquid outlet 12 can be achieved only by controlling the applied forward air pressure by utilizing the good recovery performance of the elastic diaphragm itself. Preferably, a gap is arranged between adjacent sheet-shaped elastic membranes, the diameter of the gap is 0.5-1.5 mm, and the distance d between the gap and the liquid outlet 12 is more than or equal to 0.5 mm, compared with a mode that the gap and the liquid outlet 12 are arranged in a contact manner, the arrangement structure can improve the sealing and isolating performance when the elastic movable part is attached to the liquid outlet 12. The thickness of the first control part 13 is 0.05-1.5 mm, and the interval between adjacent first control parts 13 is 0.5-1.5 mm.
When the sheet-shaped elastic membrane is used as the fourth control element 33, the single-side fixed part of the sheet-shaped elastic membrane can be fixedly connected with the outer wall of the waste liquid tank 31, after the waste liquid flows into the second circulation pipeline 34, the positive air pressure applied by any liquid reservoir 11 can push the waste liquid to flow into the liquid inlet 32 of the waste liquid tank 31 and form a thrust on the surface of the first elastic movable part, if the thrust is greater than the deformation force of the first elastic movable part, the elastic movable part at the moment can be separated from the liquid inlet 32 of the waste liquid tank 31, namely, the liquid inlet 32 of the waste liquid tank 31 and the second circulation pipeline 34 are in a conduction state, so that the waste liquid flows into the waste liquid tank 31 to be recovered; when stopping to exert forward atmospheric pressure to arbitrary reservoir 11, consider that the waste liquid self gravity of retrieving in waste liquid pond 31 may be greater than the self deformation power of elasticity movable part, thereby force the inlet 32 separation of elasticity movable part and waste liquid pond 31, lead to the waste liquid to flow back to the emergence of the 34 circumstances of second circulation pipeline, this embodiment sets up a supporting block on the second circulation pipeline 34 that corresponds in inlet 32 below, can avoid the waste liquid in the waste liquid pond 31 to rely on self gravity to oppress the condition that elasticity movable part leads to separating with inlet 32 and take place under the effect of supporting block, thereby the effectual effect that prevents the waste liquid backward flow that plays.
Preferably, referring to fig. 4 and 5, in the microfluidic chip in the above embodiment, the second control part 23 and the third control part 24 are both T-shaped elastic diaphragms, and each T-shaped elastic diaphragm includes an isolation fixing part and a second elastic moving part; wherein, the isolated fixing part of the second control member 23 is fixed on the first circulation duct 14, two ends of the second elastic moving part of the second control member 23 are respectively fixed on the outer walls of two sides of the first pressurization part 21, when the second control member 23 is in an open state, the second elastic moving part of the second control member 23 is separated from the isolated fixing part of the second control member 23, so that the first circulation duct 14 and the amplification chamber 25 are in a conduction state;
the isolation fixing part of the third control 24 is fixed on the second circulation duct 34, both ends of the second elastic movable part of the third control 24 are respectively fixed on the outer walls of both sides of the second pressurization part 22, and when the third control 24 is in the open state, the second elastic movable part of the third control 24 is separated from the isolation fixing part of the third control 24, so that the second circulation duct 34 and the amplification chamber 25 are in the conduction state.
According to the above implementation process, when the second control member 23 and the third control member 24 are both T-shaped elastic diaphragms, the first and second flow channels 14 and 34 can be controlled to be respectively connected/disconnected with the amplification chamber 25 by controlling the pressurization states of the first and second pressurization parts 21 and 22.
It should be added that the single-side fixing portion of the sheet-shaped elastic membrane is fixedly connected to the outer wall of the liquid reservoir 11/waste liquid tank 31 and the T-shaped elastic membrane is fixedly connected to the outer wall of the first pressurizing portion 21/second pressurizing portion 22 in various manners, for example, chemically fixedly connected by a process of contact surface modification and pressing, or physically fixedly connected by an adhesive or the like. In addition, in order to make the sheet-shaped elastic diaphragm and the T-shaped elastic diaphragm have a strong deformation force, the sheet-shaped elastic diaphragm and the T-shaped elastic diaphragm are made of one or more materials of polydimethylsiloxane, fluororubber and silicone rubber, for example.
It is understood that the materials for the liquid reservoir 11, the waste liquid pool 31, the first circulation line 14 and the second circulation line 34 may be the same or different, and the present embodiment is not limited thereto; illustratively, when the materials of the liquid reservoir 11, the waste liquid pool 31, the first circulation pipe 14 and the second circulation pipe 34 are the same, one or two of ceramics, glass and plastics can be selected as the materials for manufacturing the liquid reservoir 11, the waste liquid pool 31, the first circulation pipe 14 and the second circulation pipe 34.
In order to facilitate the control of the pressurization state of each liquid reservoir 11, please refer to fig. 6, a pressurization unit connected to each liquid reservoir 11 is further provided in this embodiment, where the pressurization unit includes a positive pressure pump, a negative pressure pump, a first gate and a second gate, the positive pressure pump is respectively communicated with the input ends of the first gate and the second gate, the negative pressure pump is communicated with the second gate, the output end of the first gate is respectively communicated with the liquid inlets of the plurality of liquid reservoirs 11 through corresponding via holes on the sealing cover plate, and the output end of the second gate is respectively communicated with the first pressurization part 21 and the second pressurization part 22 through corresponding via holes on the sealing cover plate; the first gate is used to gate any one of the reservoirs 11 so that the corresponding reservoir 11 is in a pressurized state; the second gating means is configured to gate the first pressurizing unit 21 and the second pressurizing unit 22 at the same time, so that both the first pressurizing unit 21 and the second pressurizing unit 22 are in a pressurized or negative pressure state.
The pressurization control unit of the microfluidic chip further comprises a gating control module, wherein the input end of the first gating device and the input end of the second gating device are respectively connected with the output end of the gating control module; the gating control module is used for providing a control signal to the first gating device and/or the second gating device according to the detection operation flow, so that the first gating device and/or the second gating device are gated according to the control signal.
In the specific operation process, when any one or more micro-fluidic chips detect a sample reagent, the gating control module respectively controls the first gating device and the second gating device in a gating manner according to the detection operation flow of the corresponding micro-fluidic chip and the usage amount of the liquid reagent so as to sequentially pressurize the corresponding liquid reservoirs 11 in the corresponding micro-fluidic chip, so that the liquid reagent in each liquid reservoir 11 can sequentially enter the amplification chamber 25, the waste liquid discharged by the amplification chamber 25 can be sequentially recovered in the waste liquid pool 31, thereby realizing the automatic extraction of nucleic acid, and after the liquid reagent in each liquid reservoir 11 of the corresponding micro-fluidic chip is sequentially sampled, the gating control module controls the first gating device to close gating on the micro-fluidic chip, and simultaneously controls the second gating device to gate negative air pressure so that the second control element 23 and the third control element 24 are both in a closed state, thereby preventing the recovered waste liquid from flowing back.
In addition, because the flow rates of the liquid reagents released by the liquid reservoirs 11 within a unit time under the same pressure are the same, the time for the first gating device to pressurize the corresponding liquid reservoir 11 is controlled by the gating control module, so that the release amount of the liquid reagents can be accurately controlled, the dosage of the required liquid reagents can be accurately controlled, and the condition that the experimental result is inaccurate due to the error of the dosage of the supplied liquid reagents in the operation step process is avoided. Illustratively, the first and second gates may be electromagnetic gates commonly used in the art.
It should be noted that the functions of the gating control module are all realized by the existing control element or control circuit, for example, the gating control module may be a C8051F series single chip microcomputer; it should be emphasized that, in this embodiment, only the connection relationship between the C8051F series single chip microcomputer and other hardware is improved, and the improvement of the built-in program in the C8051F series single chip microcomputer is not involved.
In addition, in order to make the microfluidic chip have good expansibility, please refer to fig. 1, in this embodiment, a clamping groove 5 is formed on one side surface of the microfluidic chip, and a clamping column 4 corresponding to the clamping groove 5 is disposed on an opposite surface of the side surface. The clamping column 4 of the nth microfluidic chip can be clamped with the clamping groove 5 of the (n + 1) th microfluidic chip, so that the combined connection of a plurality of microfluidic chips is realized, the number of the microfluidic chips can be increased or decreased automatically according to the detection requirements of users, the simultaneous detection of the plurality of microfluidic chips is realized, the detection efficiency is improved, and the use flexibility is improved.
Example two
Referring to fig. 7, another embodiment of the present invention provides a microfluidic chip assembly comprising a plurality of microfluidic chips according to any one of claims 1 to 9.
Compared with the prior art, the embodiment of the utility model provides a micro-fluidic chip subassembly is the same with the beneficial effect that is used for micro-fluidic chip that above-mentioned embodiment one provided, does not do here and gives unnecessary details.
In the foregoing description of embodiments, the particular features, structures, materials, or characteristics may be combined in any suitable manner in any one or more embodiments or examples.
The above description is only for the specific embodiments of the present invention, but the protection scope of the present invention is not limited thereto, and any person skilled in the art can easily think of the changes or substitutions within the technical scope of the present invention, and all should be covered within the protection scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims (10)

1. A micro-fluidic chip is characterized by comprising a liquid storage unit for realizing sequential sample introduction of liquid reagents, an extraction amplification unit for obtaining a sample to be detected through amplification separation, and a waste liquid recovery unit for recovering detection waste liquid, wherein the liquid storage unit, the extraction amplification unit and the waste liquid recovery unit are sequentially communicated; wherein,
the liquid storage unit comprises a plurality of liquid storages and first circulation pipelines communicated with liquid outlets of the liquid storages, a first control piece is arranged between each liquid outlet and each first circulation pipeline and used for controlling the communication state of the liquid outlets, when any one of the liquid storages is in a pressurization state, the corresponding first control piece is in an opening state, and the rest first control pieces are in a closing state.
2. The microfluidic chip according to claim 1, wherein the extraction amplification unit comprises an amplification chamber for extracting amplified nucleic acid to obtain a sample to be detected, one end of the amplification chamber is communicated with the first flow channel through a second control element, the other end of the amplification chamber is communicated with the waste liquid recovery unit through a third control element, the second control element is used for controlling the conduction state of the first flow channel and the amplification chamber, and the third control element is used for controlling the conduction state of the second flow channel and the waste liquid recovery unit.
3. The microfluidic chip according to claim 2, wherein the extraction amplification unit further comprises a first pressurization part for controlling the state of the second control part, and a second pressurization part for controlling the state of a third control part;
when positive air pressure is applied to the second control member and the third control member through the first pressurizing portion and the second pressurizing portion, respectively, the second control member and the third control member are both in an open state;
when negative air pressure is applied to the second control member and the third control member by the first pressurizing portion and the second pressurizing portion, respectively, both the second control member and the third control member are in a closed state.
4. The microfluidic chip according to claim 2, wherein the waste liquid recovery unit comprises a waste liquid pool and a second flow channel communicated with the liquid inlet of the waste liquid pool, one end of the second flow channel is communicated with the amplification chamber through the third control element, the other end of the second flow channel is communicated with the liquid inlet through a fourth control element, and the fourth control element is used for controlling the communication state of the liquid inlet and the second flow channel.
5. The microfluidic chip according to claim 4, wherein the first control element and the fourth control element are both sheet-like elastic diaphragms, and each sheet-like elastic diaphragm comprises a single-sided fixed part and a first elastic movable part; wherein,
one end of a single-side fixed part of the first control piece is fixedly connected with the outer wall of the liquid storage device, the other end of the single-side fixed part is fixedly connected with the first elastic movable part, when the first control piece is in an opening state, the first elastic movable part is separated from the liquid outlet, so that the liquid outlet is in a conducting state with the first circulation pipeline, and when the first control piece is in a closing state, the first elastic movable part is attached to the liquid outlet, so that the liquid outlet is in a sealed and isolated state with the first circulation pipeline;
the one end of the unilateral fixed part of fourth control with the outer wall fixed connection in waste liquid pond, the other end of unilateral fixed part with first elasticity movable part fixed connection works as when the fourth control is in the open mode, first elasticity movable part with the inlet separation makes the inlet with second circulation pipeline is in the on-state, works as when the fourth control is in the closed mode, first elasticity movable part with the inlet laminating makes the inlet with second circulation pipeline is in airtight isolated state.
6. The microfluidic chip according to claim 2, wherein the second control part and the third control part are both T-shaped elastic diaphragms, and each T-shaped elastic diaphragm comprises an isolation fixing part and a second elastic moving part; wherein,
the isolation fixing part of the second control part is fixed on the first circulation pipeline, two ends of the second elastic moving part of the second control part are respectively fixed on the outer walls of two sides of the first pressurizing part, and when the second control part is in an opening state, the second elastic moving part of the second control part is separated from the isolation fixing part of the second control part, so that the first circulation pipeline and the amplification chamber are in a conduction state;
and when the third control part is in an open state, the second elastic movable part of the third control part is separated from the isolation fixing part of the third control part, so that the second circulation pipeline and the amplification chamber are in a conduction state.
7. The microfluidic chip according to claim 1, wherein the reservoir has a conical funnel-shaped structure, and a suspension ball having a diameter d is disposed in the reservoir1The diameter of the liquid outlet is d2And d is1>d2
8. The microfluidic chip according to claim 1, wherein the thickness of the first control part is 0.05-1.5 mm, and the interval between adjacent first control parts is 0.5-1.5 mm.
9. The microfluidic chip according to claim 1, wherein a side surface of the microfluidic chip is provided with a clamping groove, and a clamping column corresponding to the clamping groove is arranged on an opposite surface of the side surface.
10. A microfluidic chip assembly comprising a plurality of microfluidic chips according to any one of claims 1 to 9.
CN201721215118.1U 2017-09-20 2017-09-20 A kind of micro-fluidic chip and chip assembly Withdrawn - After Issue CN207552287U (en)

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107541452A (en) * 2017-09-20 2018-01-05 清华大学 A kind of micro-fluidic chip and chip assembly
CN111073811A (en) * 2019-12-24 2020-04-28 深圳市华迈生物医疗科技有限公司 Micro-fluidic chip for real-time fluorescent nucleic acid amplification detection and detection method
CN112795474A (en) * 2021-02-19 2021-05-14 清华大学 Full-integrated multi-index nucleic acid detection micro-fluidic chip
CN112940922A (en) * 2021-02-19 2021-06-11 清华大学 Full-integrated pathogen nucleic acid detection micro-fluidic chip
WO2021237397A1 (en) * 2020-05-25 2021-12-02 杭州梓晶生物有限公司 Fluid control device and fluid control method
WO2023206096A1 (en) * 2022-04-26 2023-11-02 广州国家实验室 Liquid transfer device and multi-path parallel liquid transfer device

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107541452A (en) * 2017-09-20 2018-01-05 清华大学 A kind of micro-fluidic chip and chip assembly
CN107541452B (en) * 2017-09-20 2023-12-15 杭州梓晶生物有限公司 Microfluidic chip and chip assembly
CN111073811A (en) * 2019-12-24 2020-04-28 深圳市华迈生物医疗科技有限公司 Micro-fluidic chip for real-time fluorescent nucleic acid amplification detection and detection method
WO2021237397A1 (en) * 2020-05-25 2021-12-02 杭州梓晶生物有限公司 Fluid control device and fluid control method
CN112795474A (en) * 2021-02-19 2021-05-14 清华大学 Full-integrated multi-index nucleic acid detection micro-fluidic chip
CN112940922A (en) * 2021-02-19 2021-06-11 清华大学 Full-integrated pathogen nucleic acid detection micro-fluidic chip
WO2023206096A1 (en) * 2022-04-26 2023-11-02 广州国家实验室 Liquid transfer device and multi-path parallel liquid transfer device

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