CN114797706A - Multichannel parallel secondary reaction centrifugal micro-fluidic chip - Google Patents
Multichannel parallel secondary reaction centrifugal micro-fluidic chip Download PDFInfo
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- CN114797706A CN114797706A CN202210461409.8A CN202210461409A CN114797706A CN 114797706 A CN114797706 A CN 114797706A CN 202210461409 A CN202210461409 A CN 202210461409A CN 114797706 A CN114797706 A CN 114797706A
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- 238000010517 secondary reaction Methods 0.000 title claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 122
- 239000007788 liquid Substances 0.000 claims abstract description 111
- 239000002699 waste material Substances 0.000 claims abstract description 29
- 238000004891 communication Methods 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 9
- 238000007039 two-step reaction Methods 0.000 abstract description 4
- 238000000034 method Methods 0.000 description 9
- 230000008569 process Effects 0.000 description 8
- 238000010586 diagram Methods 0.000 description 6
- 230000001133 acceleration Effects 0.000 description 5
- 230000000630 rising effect Effects 0.000 description 4
- 230000009471 action Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000001360 synchronised effect Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0053—Details of the reactor
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/28—Moving reactors, e.g. rotary drums
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
Abstract
The application discloses a multichannel parallel secondary reaction centrifugal microfluidic chip, which comprises a first connecting channel, a second connecting channel and a third connecting channel; the front end of the first connecting channel is provided with an inlet, and the tail end of the first connecting channel is provided with a second siphon valve and a waste liquid cavity; the second connecting channel is communicated with a second-stage reaction cavity; the first end of the third connecting channel is communicated with the first connecting channel, the second end of the third connecting channel is communicated with the first end of the first-stage reaction cavity, a first air pressure balancing channel communicated with the second end of the second connecting channel is also arranged, and a buffer cavity is arranged between the first end and the second end of the third connecting channel; and the second end of the first-stage reaction cavity is provided with a first siphon valve communicated with the first end of the second connecting channel. The multichannel parallel secondary reaction centrifugal microfluidic chip can meet the requirements of two-step reaction of double reagents; the multi-channel parallel quantitative distribution and residence of the first-stage reaction cavity and the controllable conveying from the first-stage reaction cavity to the second-stage reaction cavity are realized.
Description
Technical Field
The application relates to the technical field of centrifugal microfluidic chips, in particular to a multichannel parallel secondary reaction centrifugal microfluidic chip.
Background
The centrifugal micro-fluidic chip is a micro-fluidic system for detecting and analyzing liquid flow, and integrates the parts such as valves, flow pipelines, mixers, reactors, separation devices and the like involved in the chemical analysis process on a CD-shaped chip in a miniaturized manner, and uses centrifugal force as liquid flow driving force.
The parallel reaction detection channel of the existing centrifugal microfluidic chip only comprises a first-stage reaction structure, and only a single reagent can be used, so that the detection performance and the application range of the chip are greatly limited. Taking biochemical detection as an example, the problems of endogenous interference, low stability and accuracy and the like exist in the reaction process of a single reagent, and the single reagent is gradually replaced by double reagents on the traditional large-scale equipment.
Therefore, how to provide a multi-channel parallel secondary reaction centrifugal microfluidic chip that solves the above technical problems to meet the development requirements of dual reagents is a technical problem that needs to be solved by those skilled in the art.
Disclosure of Invention
The multi-channel parallel secondary reaction centrifugal micro-fluidic chip can meet the requirements of two-step reaction of double reagents; the multi-channel parallel quantitative distribution and residence of the first-stage reaction cavity and the controllable conveying from the first-stage reaction cavity to the second-stage reaction cavity are realized.
In order to achieve the above object, the present application provides a centrifugal microfluidic chip with multiple channels and parallel secondary reactions, comprising:
the front end of the first connecting channel is provided with an inlet, and the tail end of the first connecting channel is provided with a second siphon valve and a waste liquid cavity; and
the second connecting channel is communicated with the second-stage reaction cavity; and
and the first end of the third connecting channel is communicated with the first end of the first-stage reaction cavity, the second end of the third connecting channel is communicated with the first end of the second-stage reaction cavity, the first pressure balance channel is communicated with the second end of the second connecting channel, a buffer cavity is arranged between the first end and the second end of the third connecting channel, and the second end of the first-stage reaction cavity is provided with a first siphon valve communicated with the first end of the second connecting channel.
In some embodiments, the reaction device further comprises a gas pressure balancing channel arranged in the first-stage reaction chamber, the third connecting channel and the waste liquid chamber.
In some embodiments, the air pressure balancing channel comprises:
the third pressure balance channel and the fourth pressure balance channel are communicated with the first-stage reaction cavity; and
a fifth air pressure balance passage communicating with a second end of the third connecting passage; and
a second air pressure balance channel communicated with the waste liquid cavity;
when the third connecting channel is adjacent to the first-stage reaction cavity, only one of the fifth air pressure balancing channel and the third air pressure balancing channel is needed.
In some embodiments, the number of the third connecting channels is plural, a plurality of the third connecting channels are distributed along the first connecting channel, and repeating units including the third or fifth pressure equalizing channel, the first-stage reaction chamber, the fourth pressure equalizing channel, the first siphon valve, the second connecting channel, the second-stage reaction chamber, and the first pressure equalizing channel are distributed between adjacent third connecting channels.
In some embodiments, the first connecting channel is in the shape of a circular ring, the center of the circular disk and the center of rotation of the chip coincide, the third connecting channels are in the shape of radiating toward the center of rotation of the chip on the circular ring, and the repeating units are all equidistant from the center of rotation of the chip.
In some embodiments, a plurality of the third connecting channels are equally distributed on the circle of the first connecting channels.
In some embodiments, a distance between a center of a vent hole of the air pressure balance channel and the rotation axis of the chip is not less than a minimum distance R1 between a side of the first air pressure balance channel far from the rotation axis of the chip and the rotation axis of the chip, a minimum distance R2 between a side of the second siphon valve far from the rotation axis of the chip and the rotation axis of the chip, a distance between a side of the third connecting channel and the first-stage reaction chamber communicating position far from the rotation axis of the chip and a minimum distance R3 between the first air pressure balance channel and the third connecting channel communicating position close to the rotation axis of the chip, a maximum distance R11 between the buffer chamber close to the rotation axis of the chip and the minimum distance R6 between the buffer chamber far from the rotation axis of the chip and a maximum distance R7 between the buffer chamber far from the rotation axis of the chip and the rotation axis of the chip, a distance between the second siphon valve and the waste liquid chamber communicating position The distance R8 between the position and the chip rotation axis is not more than the distance R10 between the center of the first connecting channel and the chip rotation axis.
In some embodiments, the minimum distance R3 between the edge of the third connecting channel, which is far away from the rotation axis of the chip, and the first-stage reaction chamber is less than or equal to the distance R9 between the center of the first-stage reaction chamber and the rotation axis of the chip, and the minimum distance R10 between the edge of the third connecting channel, which is far away from the rotation axis of the chip, and the chip.
Compared with the background technology, the multichannel parallel secondary reaction centrifugal microfluidic chip provided by the application comprises a first connecting channel, a first air pressure balance channel, a first-stage reaction cavity, a first siphon valve, a second connecting channel, a second-stage reaction cavity, a third connecting channel, a waste liquid cavity and a second siphon valve; the front end of the first connecting channel is provided with an inlet, and the tail end of the first connecting channel is provided with a second siphon valve and a waste liquid cavity; the second connecting channel is communicated with a second-stage reaction cavity; the first end of the third connecting channel is communicated with the first connecting channel, and the second end of the third connecting channel is communicated with the first end of the first-stage reaction cavity and is also provided with a first air pressure balancing channel communicated with the second end of the second connecting channel; and the second end of the first-stage reaction cavity is provided with a first siphon valve communicated with the first end of the second connecting channel.
In the use process of the multichannel parallel secondary reaction centrifugal microfluidic chip, the chip firstly rotates at a constant speed, the superior liquid flows into the third connecting channel through the first connecting channel, the communicating positions of the buffer cavity and the third connecting channel with the first air pressure balance channel are sequentially filled with the liquid, the liquid continuously rises in the third connecting channel and flows into the first-stage reaction cavity after being higher than the communicating position with the first reaction cavity, and the liquid level of the third connecting channel temporarily stops rising; because the air pressure channel is closed and is influenced by air pressure, liquid does not flow into the first siphon valve from the first-stage reaction cavity, the liquid continuously flows into the first-stage reaction cavity until the first-stage reaction cavity is filled with the liquid, and the liquid is quantitatively distributed to the first-stage reaction cavity and stays in the first-stage reaction cavity; after the first-stage reaction cavity is filled, the liquid level of the third connecting channel is continuously raised until the liquid passes through the second siphon valve and is injected into the waste liquid cavity; until the liquid at the upper level is not injected into the first connecting channel any more, the liquid level of the third connecting channel begins to descend until the distance between the liquid level and the rotating axis is equal to the distance between the outlet of the siphon valve in the waste liquid cavity and the rotating axis, at the moment, the air pressure channel is opened again, the buffer cavity is in an empty state, the chip decelerates, and the residual liquid in the first connecting channel and the third connecting channel flows into the buffer cavity to ensure the smoothness of the air pressure channel; the chip is accelerated again and then rotates at a constant speed, and then the liquid in the first-stage reaction cavity can be driven to pass through the first siphon valve and enter the second-stage reaction cavity.
The multichannel parallel secondary reaction centrifugal microfluidic chip can meet the requirements of two-step reaction of double reagents; the multi-channel parallel quantitative distribution and residence of the first-stage reaction cavity and the controllable conveying from the first-stage reaction cavity to the second-stage reaction cavity are realized.
Drawings
In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings needed to be used in the description of the embodiments or the prior art will be briefly introduced below, it is obvious that the drawings in the following description are only embodiments of the present application, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.
Fig. 1 is a schematic structural diagram of a multichannel parallel secondary reaction centrifugal microfluidic chip provided in an embodiment of the present application;
fig. 2 is a schematic positional relationship diagram of a multichannel parallel secondary reaction centrifugal microfluidic chip provided in an embodiment of the present application;
fig. 3 is a schematic structural diagram of a multichannel parallel secondary reaction centrifugal microfluidic chip including a typical upper-stage structure provided in an embodiment of the present application.
Wherein:
1-a first connecting channel, 2-a first air pressure balancing channel, 3-a first-stage reaction cavity, 4-a first siphon valve, 5-a second connecting channel, 6-a second-stage reaction cavity, 7-a third connecting channel, 8-a second air pressure balancing channel, 9-a waste liquid cavity, 10-a second siphon valve, 11-a buffer cavity, 12-a third air pressure balancing channel, 13-a fourth air pressure balancing channel, 14-a fifth air pressure balancing channel, 15-a third siphon valve and 16-a mixing cavity.
Detailed Description
The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application, and it is obvious that the described embodiments are only a part of the embodiments of the present application, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.
In order to enable those skilled in the art to better understand the scheme of the present application, the present application will be described in further detail with reference to the accompanying drawings and the detailed description.
Referring to fig. 1, fig. 1 is a schematic structural diagram of a centrifugal microfluidic chip for multi-channel parallel secondary reaction according to an embodiment of the present disclosure.
In a first specific embodiment, the application provides a centrifugal microfluidic chip for multi-channel parallel two-stage reaction, which mainly comprises a first connecting channel 1, a first air pressure balance channel 2, a first-stage reaction chamber 3, a first siphon valve 4, a second connecting channel 5, a second-stage reaction chamber 6, a third connecting channel 7, a waste liquid chamber 9 and a second siphon valve 10.
The front end of the first connecting channel 1 is provided with an inlet, the front end inlet can be used for liquid to enter, and the source of the liquid can be a superior mechanism; the tail end of the first connecting channel 1 is provided with a second siphon valve 10 and a waste liquid cavity 9, and the second siphon valve 10 is positioned between the tail end of the first connecting channel 1 and the waste liquid cavity 9. The second connecting channel 5 is communicated with a second-stage reaction chamber 6. The first end of the third connecting channel 7 is communicated with the first connecting channel 1; the second end of the third connecting channel 7 is communicated with the first end of the first-stage reaction cavity 3, and is also provided with a first air pressure balancing channel 2 communicated with the second end of the second connecting channel 5; a buffer chamber 11 is arranged between the first end and the second end of the third connecting channel 7. The second end of the first-stage reaction chamber 3 is provided with a first siphon valve 4 communicated with the first end of the second connecting channel 5.
In the using process of the multichannel parallel secondary reaction centrifugal microfluidic chip, the chip firstly rotates at a constant speed, the upper-level liquid flows into the third connecting channel 7 through the first connecting channel 1, the liquid level of the liquid in the third connecting channel 7 gradually rises under the action of centrifugal force, the buffer cavity 11, the communication position of the third connecting channel 7 and the first air pressure balance channel 2 are sequentially filled, then the liquid flows into the first-level reaction cavity 3, and the liquid level of the third connecting channel 7 temporarily stops rising; because the communication position of the third connecting channel 7 and the first air pressure balance channel 2 is filled with liquid, the air pressure channel is closed and is influenced by air pressure, the liquid does not flow into the first siphon valve 4 from the first-stage reaction cavity 3, the liquid continuously flows into the first-stage reaction cavity 3 until the first-stage reaction cavity 3 is filled with the liquid, and the liquid is quantitatively distributed to the first-stage reaction cavity 3 and stays; after the first-stage reaction cavity 3 is filled, the liquid level of the third connecting channel 7 begins to rise again until the liquid passes through the second siphon valve 10 and is injected into the waste liquid cavity 9; until the liquid at the upper level is not injected into the first connecting channel 1 any more, the liquid level of the third connecting channel 7 begins to descend until the distance between the liquid level in the third connecting channel 7 and the rotating axis is equal to the distance between the outlet of the second siphon valve 10 in the waste liquid cavity 9 and the rotating axis, at the moment, the air pressure channel is opened again, the buffer cavity 11 is in an empty state, the chip decelerates, and the liquid in the first connecting channel 1 and the liquid in the third connecting channel 7 flow into the buffer cavity 11, so that the air pressure channel is ensured to be in an open state; the liquid in the first-stage reaction cavity 3 can be driven to pass through the first siphon valve 4 and enter the second-stage reaction cavity 6 by accelerating again and then rotating at a constant speed, so that controllable conveying is realized.
The multichannel parallel secondary reaction centrifugal microfluidic chip can meet the requirements of two-step reaction of double reagents; the shunting quantification and the residence of the multi-channel parallel first-stage reaction cavity 3 and the controllable conveying from the first-stage reaction cavity 3 to the second-stage reaction cavity are realized.
It should be noted that the communication position may be an interface or a connection channel, and the communication position also belongs to the description scope of the embodiment.
In some embodiments, the chip further comprises a gas pressure equalization channel disposed in the first-stage reaction chamber 3, the third connecting channel 7 and the waste liquid chamber 9.
Further, the air pressure equalizing channels include a second air pressure equalizing channel 8, a third air pressure equalizing channel 12, a fourth air pressure equalizing channel 13, and a fifth air pressure equalizing channel 14.
It should be noted that the air pressure balancing channel should be provided with a vent hole communicated with the outside; for example, the air pressure balance channels other than the first air pressure balance channel 2 are all structures provided with vent holes communicated with the outside, and the first air pressure balance channel 2 is communicated with other air pressure balance channels, and may not be separately communicated with the outside.
The third pressure balance channel 12 and the fourth pressure balance channel 13 are communicated with the first-stage reaction cavity 3, the fifth pressure balance channel 14 is communicated with the second end of the third connecting channel 7, and the second pressure balance channel 8 is communicated with the waste liquid cavity 9. It should be noted that, when the third connecting channel 7 is adjacent to the first-stage reaction chamber 3, only one of the fifth air pressure balance channel 14 and the third air pressure balance channel 12 is used; illustratively, the third connecting channel 7 shares the third pressure balance channel 12 with the first-stage reaction chamber 3, and the fifth pressure balance channel 14 is not provided.
It should be noted that the third air pressure balance channel 12 and the fourth air pressure balance channel 13 are only a specific arrangement manner in the present embodiment, and the number of the channels may be increased according to the requirement, and is not limited to the third air pressure balance channel 12 and the fourth air pressure balance channel 13.
In some embodiments, the number of the third connecting channels 7 is plural, a plurality of the third connecting channels 7 are distributed along the first connecting channel 1, and the repeating unit is distributed between the adjacent third connecting channels 7, and includes a third pressure equalizing channel 12 or a fifth pressure equalizing channel 14, a first-stage reaction chamber 3, a fourth pressure equalizing channel 13, a first siphon valve 4, a second connecting channel 5, a second-stage reaction chamber 6, and a first pressure equalizing channel 2. Wherein the first repeating unit communicating with the front inlet takes the form of a fifth air pressure equalizing channel 14 on the third connecting channel 7 and the third connecting channels 7 of the subsequent other repeating units take the form of third air pressure equalizing channels 12.
In some embodiments, the chip is in the shape of a disk, and the first connecting channel 1 is in the shape of a ring, the center of the disk, and the center of the rotation axis of the chip being coincident.
The third connecting channels 7 are formed on the ring so as to radiate toward the rotation axis of the chip. The distances between the multiple repeating units and the rotation axes of the chips are equal, for example, the distance between the first-stage reaction chamber 3 in the first repeating unit and the rotation axis of the chip is equal to the distance between the first-stage reaction chamber 3 in the second repeating unit and the rotation axis of the chip, the distance between the second-stage reaction chamber 6 in the first repeating unit and the rotation axis of the chip is equal to the distance between the second-stage reaction chamber 6 in the second repeating unit and the rotation axis of the chip, and the descriptions of other structures are similar to this, and are not repeated one by one here.
In some embodiments, the plurality of third connecting channels 7 is equally distributed on the circle of the first connecting channel 1.
It should be emphasized that the specific number of the repeating units is not limited in this embodiment, even though the number of the repeating units shown in fig. 1 is six, this does not mean that the present application can only protect the solution with the number of the repeating units being six, and for the solution with other number, the number may be more than six or less than six, and the present application shall also belong to the protection scope of the present application.
In one specific process description:
the front end liquid flows into the third connecting channels 7 in sequence through the first connecting channel 1, the liquid level in the third connecting channels 7 gradually rises to reach the buffer cavity 11, after the buffer cavity 11 is full of liquid, the liquid level continues to rise to reach the interfaces of the first air pressure balance channel 2 and the third connecting channels 7, the liquid level continues to rise to reach the interfaces of the third connecting channels 7 and the first-stage reaction cavity 3, the liquid flows into the first-stage reaction cavity 3, the liquid level in the third connecting channels 7 temporarily stops rising, and because the interfaces of the first air pressure balance channel 2 and the third connecting channels 7 are full of liquid, the air pressure balance channels are closed. Influenced by the atmospheric pressure, liquid does not flow into first siphon valve 4 from first order reaction chamber 3, and liquid continues to flow into first order reaction chamber 3, and liquid ration is distributed to a plurality of first order reaction chambers 3 and is resident until first order reaction chamber 3 fills up.
After the first-stage reaction cavity 3 is filled with liquid, the liquid level in the third connecting channel 7 continuously rises, the liquid passes through the second siphon valve 10, the liquid starts to be injected into the waste liquid cavity 9, the liquid in the superior structure continuously flows into the waste liquid cavity 9 until the liquid is exhausted, the liquid level in the third connecting channel 7 starts to fall until the liquid level is level with the outlet of the second siphon valve 10 in the waste liquid cavity 9, the liquid level is lower than the boundary of the buffer cavity 11 at the moment, and the buffer cavity 11 and the connections between the buffer cavity 11 and the third air pressure balance channel 12 and between the buffer cavity 11 and the fifth air pressure balance channel 14 are both in an empty state at the moment.
The first air pressure balance channel 2 is connected with a third air pressure balance channel 12 and a fifth air pressure balance channel 14 through a third connecting channel 7, and the air pressure balance channel of the second-stage reaction cavity 6 is opened again. The chip is accelerated again and then rotates at a constant speed, so that the liquid in the first-stage reaction cavity 3 can be driven to pass through the first siphon valve 4 and enter the second-stage reaction cavity 6.
The residual liquid in the first connecting channel 1 and the third connecting channel 7 flows into the buffer cavity 11 in the acceleration and deceleration process, so that the air pressure balance channel is prevented from being blocked by the liquid in the acceleration and deceleration process. The multi-channel parallel secondary reaction structure liquid first-stage reaction cavity 3 is divided, quantified and resident, and controllable and synchronous conveying to the second-stage reaction cavity 6 is realized.
Referring to fig. 2, fig. 2 is a schematic diagram of a position relationship of a multi-channel parallel two-stage reaction centrifugal microfluidic chip according to an embodiment of the present disclosure.
In this embodiment, the distance between the center of the vent hole of the air pressure balance channel and the rotation axis of the chip is not less than the minimum distance R1 between the edge of the first air pressure balance channel 2 away from the rotation axis of the chip and the minimum distance R2 between the edge of the second siphon valve 10 away from the rotation axis of the chip and the rotation axis of the chip is not less than the minimum distance R3 between the edge of the first reaction channel 7 and the first-stage reaction chamber 3 which are communicated with each other and away from the rotation axis of the chip and the rotation axis of the chip is not less than the maximum distance R11 between the edge of the buffer chamber 11 close to the rotation axis of the chip and the maximum distance R7 between the edge of the buffer chamber 11 away from the rotation axis of the chip and the waste liquid chamber 9 (i.e. the outlet of the siphon valve) between the second siphon valve 10 and the waste liquid chamber 9 which are communicated with each other and not more than the center of the first connection channel 1 and the chip rotation axis of the chip R10.
The minimum distance R3 between the edge of the communication position of the third connecting channel 7 and the first-stage reaction cavity 3, which is far away from the rotation axis of the chip, and the rotation axis of the chip is not less than that R9 between the center of the second-stage reaction cavity 6 and the rotation axis of the chip is not more than that R10 between the center of the first connecting channel 1 and the rotation axis of the chip.
Referring to fig. 3, fig. 3 is a schematic structural diagram of a multi-channel parallel secondary reaction centrifugal microfluidic chip including a typical upper-level structure according to an embodiment of the present disclosure.
It should be noted that the multichannel parallel two-stage reaction centrifugal microfluidic chip shown in fig. 1 may adopt not only the upper-stage structure shown in fig. 3, but also other upper-stage structures, and shall also fall within the scope of the present embodiment.
In a specific embodiment, the upper structure comprises a mixing chamber 16 and a third siphon valve 15, the mixing chamber 16 is located in the middle of the disc, and the mixing chamber 16 is communicated with the front end opening of the first connecting channel 1 through the third siphon valve 15.
In one specific process description:
the mixing chamber 16 is connected with the first connecting channel 1 through the third siphon valve 15, the chip rotates at a constant speed after accelerating, the liquid in the mixing chamber 16 is acted by the Euler in the accelerating process to generate tangential acceleration, the tangential acceleration crosses the third siphon valve 15 to enter the first connecting channel 1, the disc rotates at a constant speed to generate pressure difference at two ends of the siphon valve, and the liquid continuously enters the first connecting channel 1 from the mixing chamber 16.
Through the first connecting channel 1, enter a plurality of third connecting channels 7 in proper order, and the second siphon valve 10, receive centrifugal force, liquid is full of the position of keeping away from the rotation axis at first, the liquid level in the third connecting channel 7 rises gradually, liquid reaches the buffer chamber 11 at first, continue to rise after filling up, reach the interface of first atmospheric pressure balanced passageway 2 and third connecting channel 7, continuously flow into third connecting channel 7, continue to rise, reach the interface with first order reaction chamber 3, liquid flows into first order reaction chamber 3, liquid level in third connecting channel 7 and the second siphon valve 10 stops rising temporarily, continuously flow into first order reaction chamber 3, because the interface of first atmospheric pressure balanced passageway 2 and third connecting channel 7 is full of liquid, atmospheric pressure balanced passageway seals. Liquid does not flow from the first stage reaction chamber 3 into the first siphon valve 4 under the influence of the gas pressure.
After the first-stage reaction chamber 3 is filled, the liquid level continues to rise, the liquid passes through the second siphon valve 10, the liquid starts to be injected into the waste liquid chamber 9, the liquid in the mixing chamber 16 continuously flows into the waste liquid chamber 9 until the liquid is exhausted, the liquid level in the third connecting channel 7 starts to fall until the liquid level is leveled with the outlet of the second siphon valve 10 in the waste liquid chamber 9, at the moment, the liquid level is lower than the interface of the first air pressure balance channel 2 and the third connecting channel 7 and is also lower than the lower edge of the buffer chamber 11, the air pressure balance channel is connected with the third air pressure balance channel 12 and the air pressure balance channel 14 through the third connecting channel 7, and the air pressure balance channel of the second-stage reaction chamber is opened again. The buffer cavity 11 is in an empty state at the moment, the chip decelerates, and the liquid in the first connecting channel 1 and the liquid in the third connecting channel 7 enter the buffer cavity 11, so that the air pressure balance channel is not sealed, and the quantitative distribution and the residence of the first-stage reaction cavity 3 are realized.
After the first-stage reaction is finished, the chip accelerates again, the liquid in the first-stage reaction cavity 3 generates tangential acceleration under the action of the Euler force, passes through the first siphon valve 4 and enters the second-stage reaction cavity 6. The residual liquid in the first connecting channel 1 and the third connecting channel 7 flows to different buffer cavities 11 under the action of driving force, so that the air pressure balance channel is ensured not to be closed all the time. The synchronous controllable conveying of the first-stage reaction cavity 3 to the second-stage reaction cavity 6 is realized.
Therefore, the shunting quantification and the residence of the first-stage reaction cavity 3 of the liquid with the multichannel parallel second-stage reaction structure are realized, and the synchronous controllable conveying to the second-stage reaction cavity 6 is realized.
It should be noted that many of the components mentioned in this application are either common standard components or components known to those skilled in the art, and their structure and principle are known to those skilled in the art through technical manuals or through routine experimentation.
It is noted that, in this specification, relational terms such as first and second, and the like are used solely to distinguish one entity from another entity without necessarily requiring or implying any actual such relationship or order between such entities.
The multichannel parallel secondary reaction centrifugal microfluidic chip provided by the application is described in detail above. The principles and embodiments of the present application are explained herein using specific examples, which are provided only to help understand the method and the core idea of the present application. It should be noted that, for those skilled in the art, it is possible to make several improvements and modifications to the present application without departing from the principle of the present application, and such improvements and modifications also fall within the scope of the claims of the present application.
Claims (8)
1. A centrifugal micro-fluidic chip of multichannel parallel second-stage reaction is characterized by comprising:
the front end of the first connecting channel (1) is provided with an inlet, and the tail end of the first connecting channel is provided with a second siphon valve (10) and a waste liquid cavity (9); and
the second connecting channel (5) is communicated with a second-stage reaction cavity (6); and
third connecting channel (7), first end intercommunication first connecting channel (1), and the second end both with the first end intercommunication of first order reaction chamber (3), still be provided with first atmospheric pressure balanced passageway (2) of the second end intercommunication of second connecting channel (5), be provided with between the first end of third connecting channel (7) and the second end cushion chamber (11), just the second end of first order reaction chamber (3) be provided with first siphon valve (4) of the first end intercommunication of second connecting channel (5).
2. The multi-channel parallel two-stage reaction centrifugal micro-fluidic chip according to claim 1, further comprising a gas pressure balance channel disposed in the first-stage reaction chamber (3), the third connection channel (7) and the waste chamber (9).
3. The multi-channel parallel two-stage reaction centrifugal microfluidic chip of claim 2, wherein the gas pressure balancing channel comprises:
a third pressure balance channel (12) and a fourth pressure balance channel (13) which are communicated with the first-stage reaction cavity (3); and
a fifth air pressure equalizing channel (14) communicating with a second end of the third connecting channel (7); and
a second air pressure balancing channel (8) communicating with the waste liquid chamber (9);
wherein, when the third connecting channel (7) is adjacent to the first-stage reaction cavity (3), only one of the fifth air pressure balancing channel (14) and the third air pressure balancing channel (12) is arranged.
4. The multi-channel parallel two-stage reaction centrifugal micro-fluidic chip according to claim 3, wherein the number of the third connecting channels (7) is plural, a plurality of the third connecting channels (7) are distributed along the first connecting channel (1), and repeating units including the third or fifth air pressure balance channel (12, 14), the first stage reaction chamber (3), the fourth air pressure balance channel (13), the first siphon valve (4), the second connecting channel (5), the second stage reaction chamber (6), and the first air pressure balance channel (2) are distributed among the adjacent third connecting channels (7).
5. The microfluidic chip of claim 4, wherein the microfluidic chip is in the shape of a disk, the first connecting channel (1) is in the shape of a ring, the center of the disk and the axis of rotation of the chip coincide, the third connecting channels (7) are in the shape of radiating toward the axis of rotation of the chip on the ring, and the repeating units are all equidistant from the axis of rotation of the chip.
6. A multi-channel parallel two-stage reaction centrifugal microfluidic chip according to claim 5, characterized in that a plurality of said third connection channels (7) are equally spaced and distributed on the circular ring of said first connection channels (1).
7. The multi-channel parallel secondary reaction centrifugal microfluidic chip according to claim 3, wherein the distance between the center of the vent hole of the air pressure balance channel and the rotation axis of the chip is not less than the minimum distance R1 between the side of the first air pressure balance channel (2) far away from the rotation axis of the chip and the rotation axis of the chip, the minimum distance R2 between the side of the second siphon valve (10) far away from the rotation axis of the chip and the rotation axis of the chip is not less than the minimum distance R3 between the side of the communication position of the third connection channel (7) and the first stage reaction chamber (3) far away from the rotation axis of the chip and the rotation axis of the chip, the maximum distance R11 between the side of the communication position of the third connection channel (7) and the rotation axis of the chip is not less than the maximum distance R6 between the side of the buffer chamber (11) near the rotation axis of the chip and the rotation axis of the chip Less than or equal to buffer chamber (11) keep away from the limit of chip rotatory axle center with the biggest distance R7 of chip rotatory axle center is less than or equal to second siphon valve (10) with waste liquid chamber (9) connected position with the distance R8 of chip rotatory axle center is less than or equal to the center of first connecting channel (1) with the distance R10 of chip rotatory axle center.
8. The multi-channel parallel secondary reaction centrifugal microfluidic chip according to claim 7, wherein the minimum distance R3 between the edge of the third connecting channel (7) communicating with the first-stage reaction chamber (3) and the rotation axis of the chip is not less than R3 and not more than R10 between the center of the first-stage reaction chamber (3) and the rotation axis of the chip is not less than R9 and not more than R10 between the center of the second-stage reaction chamber (6) and the rotation axis of the chip.
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| CN106513063A (en) * | 2016-06-06 | 2017-03-22 | 苏州汶颢芯片科技有限公司 | Centrifugal chip capable of achieving sequential reactions and mixing method thereof |
| CN108479868A (en) * | 2018-03-07 | 2018-09-04 | 清华大学 | Siphon valve and its application process are interrupted for centrifugal type microfludic chip |
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| CN113528295A (en) * | 2021-09-10 | 2021-10-22 | 中国医学科学院北京协和医院 | Microfluidic chip capable of carrying out multi-step time sequence reaction, microfluidic method and application thereof |
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| CN106513063A (en) * | 2016-06-06 | 2017-03-22 | 苏州汶颢芯片科技有限公司 | Centrifugal chip capable of achieving sequential reactions and mixing method thereof |
| CN108479868A (en) * | 2018-03-07 | 2018-09-04 | 清华大学 | Siphon valve and its application process are interrupted for centrifugal type microfludic chip |
| WO2021243882A1 (en) * | 2020-06-04 | 2021-12-09 | 广州万孚生物技术股份有限公司 | Microfluidic chip and in-vitro detection apparatus |
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