CN113694975A - Micro-fluidic sorting chip based on memory alloy and sorting method thereof - Google Patents
Micro-fluidic sorting chip based on memory alloy and sorting method thereof Download PDFInfo
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- CN113694975A CN113694975A CN202111003375.XA CN202111003375A CN113694975A CN 113694975 A CN113694975 A CN 113694975A CN 202111003375 A CN202111003375 A CN 202111003375A CN 113694975 A CN113694975 A CN 113694975A
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Abstract
The invention discloses a micro-fluidic sorting chip based on memory alloy.A main runner of a fluid channel layer is provided with an inlet at one end and an outlet at the other end, a sheath flow module and a detection module are sequentially arranged between the inlet and the outlet of the main runner, and sorting outlets I and II are arranged at the other ends of a sorting runner I and a sorting runner II; the separation layer is provided with a communication hole II and a communication hole I which correspond to the separation outlet II and the separation outlet I in position; the sorting layer is also provided with a micro valve hole and a waste liquid outlet hole which correspond to the positions of the sorting outlet II and the sorting outlet I, the micro valve hole is communicated with the target outlet hole through a flow channel positioned at the lower layer of the sorting layer, the micro valve is sequentially embedded into the micro valve hole, the communication hole II and the sorting outlet II from top to bottom, the micro valve is provided with memory alloy, and the opening and the closing of the distribution channel II are realized by utilizing the characteristics of the memory alloy so as to realize the high-flux sorting of target cells.
Description
Technical Field
The invention belongs to the technical field of cell sorting, and particularly relates to a micro-fluidic sorting chip based on memory alloy and a sorting method thereof.
Background
After dissociation of most biological tissues, a mixed cell suspension containing a plurality of different cell types is usually obtained. However, scientists are often interested in studying a single target type of cell in a large population of cells. The second step in the single cell sorting process is therefore to separate the mixed cell suspension into one type of cell suspension. The most common cell sorting methods are fluorescence activated cell sorting, flow cytometry and magnetic activated cell sorting, and have the disadvantages that the instruments are expensive, the complex cell surface markers increase the sample pretreatment time, the cell viability is reduced, the sample pollution risk is reduced and the like, and the adaptability of the microfluidic cell sorting platform is limited, but the limitations enable the microfluidic cell sorting platform to obtain a certain development space.
The advent of microfluidic cell sorting technology has broken through some of the limitations of fluorescence activated cell sorting. Compared with the traditional cell sorting method, the microfluidic device is essentially more beneficial to cell sorting. The miniaturization of the microfluidic equipment reduces the reagent consumption in laboratory operation and improves the portability; the operation steps of the experiment are simplified in the microfluidic chip, and meanwhile, the risk of cell sample pollution is reduced.
Disclosure of Invention
In order to solve the problems, the invention provides a micro-fluidic sorting chip based on memory alloy, which realizes the opening and closing of a shunting channel II by utilizing the characteristics of the memory alloy so as to realize the high-flux sorting of target cells.
In order to achieve the above purpose, the invention adopts a technical scheme as follows:
the invention provides a micro-fluidic sorting chip based on memory alloy, which is sequentially provided with a fluid channel layer, an isolation layer and a sorting layer from bottom to top, wherein the fluid channel layer is provided with a main flow channel, one end of the main flow channel is provided with an inlet, the other end of the main flow channel is provided with an outlet communicated with one end of a sorting flow channel I and one end of a sorting flow channel II, a sheath flow module and a detection module are sequentially arranged between the inlet and the outlet of the main flow channel, the other end of the sorting flow channel I is provided with a sorting outlet I, and the other end of the sorting flow channel II is provided with a sorting outlet II; the separation layer and the separation layer are provided with a hole inlet and a sheath liquid hole corresponding to the positions of the inlet and the sheath flow module, and the separation layer is also provided with a communication hole II and a communication hole I corresponding to the positions of the separation outlet II and the separation outlet I; the sorting layer is also provided with a micro valve hole and a waste liquid outlet hole which correspond to the sorting outlet II and the sorting outlet I, the micro valve hole is communicated with the target outlet hole through a flow channel positioned at the lower layer of the sorting layer, the micro valve is sequentially embedded into the micro valve hole, the communication hole II and the sorting outlet II from top to bottom, the micro valve is provided with memory alloy, the target outlet hole is used for outputting target cells, and the waste liquid outlet hole is used for outputting non-mesh single cells;
the memory alloy, the detection module and the sheath flow module are connected with a control circuit.
Further, the control circuit includes an electrode set.
The invention also provides a sorting method of the micro-fluidic sorting chip based on the memory alloy, which comprises the following steps:
s1, injecting cell sap from an inlet;
s2, the cells are arranged in a single row under the action of the sheath flow module and move towards the outlet direction along the main flow channel, and a detection module is used for detecting whether target cells appear or not;
s3, when target cells appear, the control circuit controls the memory alloy to be electrified, the memory alloy is contracted and deformed to pull the bottom of the micro valve upwards, the sorting flow channel II is opened at the moment, and the cells flow out along a sorting outlet II, a communication hole II, the micro valve hole, the flow channel and the target outlet of the sorting flow channel II and reach the cell collecting pool; when target cells do not appear, the control circuit controls the memory alloy to be powered off, the memory alloy recovers deformation, the sorting flow channel II is closed at the moment, and the cells flow out along the sorting outlet I, the communication hole I and the waste liquid outlet of the sorting flow channel I and reach the waste liquid pool.
Compared with the prior art, the technical scheme of the invention has the following advantages:
the microfluidic sorting chip has the advantages that the opening and closing of the shunting channel II are realized by utilizing the characteristics of the memory alloy, so that the high-flux sorting of target cells is realized, the structure is simple, the use is convenient and fast, and the risk of cell sample pollution is reduced.
Drawings
FIG. 1 is a top view of a memory alloy based microfluidic sorting chip according to an embodiment of the present invention;
FIG. 2 is a top view of a fluid channel layer in accordance with an embodiment of the present invention;
FIG. 3 is a top view of an isolation layer in an embodiment of the invention;
FIG. 4 is a bottom view of a sorting layer in accordance with an embodiment of the present invention;
FIG. 5 is an isometric view of a microvalve and a memory alloy in accordance with an embodiment of the present invention;
reference numerals: the device comprises a fluid channel layer 1, a main channel 1-1, an inlet 1-2, a separation channel I1-3, a separation channel II 1-4, an outlet 1-5, a separation outlet I1-6, a separation outlet II 1-7, an isolation layer 2, a separation layer 3, a communication hole II 2-1, a communication hole I2-2, a micro valve hole 3-1, a waste liquid outlet 3-2, a target outlet 3-3, a channel 3-4, a sheath flow module 4, a detection module 5, an inlet 6, a sheath liquid hole 7, a micro valve 8 and a memory alloy 9
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, 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 invention.
As shown in fig. 1-4, the invention provides a micro-fluidic sorting chip based on memory alloy, which is provided with a fluid channel layer 1, an isolation layer 2 and a sorting layer 3 in sequence from bottom to top, wherein the fluid channel layer 1 is provided with a main channel 1-1, one end of the main channel 1-1 is provided with an inlet 1-2, the other end is provided with an outlet 1-5 communicated with one end of the sorting channel i 1-3 and one end of the sorting channel i 1-4, a sheath flow module 4 and a detection module 5 are sequentially arranged between the inlet 1-2 and the outlet 1-5 of the main channel 1-1, the other end of the sorting channel i 1-3 is provided with a sorting outlet i 1-6, and the other end of the sorting channel i 1-4 is provided with a sorting outlet ii 1-6; the separation layer 2 and the separation layer 3 are provided with an inlet hole 6 and a sheath liquid hole 7 corresponding to the positions of the inlets 1-2 and the sheath flow module 4, and the separation layer 2 is also provided with a communication hole II 2-1 and a communication hole I2-2 corresponding to the positions of the separation outlets II 1-6 and the separation outlets I1-6; the sorting layer 3 is also provided with a micro valve hole 3-1 and a waste liquid outlet hole 3-2 corresponding to the positions of a sorting outlet II 1-6 and a sorting outlet I1-6, the micro valve hole 3-1 is communicated with the target outlet hole 3-3 through a flow channel 3-4 positioned at the lower layer of the sorting layer 3, a micro valve 8 is sequentially embedded into the micro valve hole 3-1, a communicating hole II 2-1 and the sorting outlet II 1-6 from top to bottom, a memory alloy 9 passes through the micro valve 8, the target outlet hole 3-3 is used for outputting target cells, and the waste liquid outlet hole 3-2 is used for outputting non-target single cells;
the memory alloy 9, the detection module 5 and the sheath flow module 4 are connected with a control circuit.
The control principle of the microfluidic sorting chip is as follows: cell sap is injected from the inlet 1-2, the control circuit controls the sheath flow module 4 to work at the moment, and the sheath flow module 4 works to enable the cells to be arranged in a single row and move towards the outlet 1-5 along the main flow channel 1-1 at intervals; at the moment, the detection module 5 detects each cell in turn, the detection module 5 can be a trained deep learning module or an electrode group, when target cells are not identified, the sorting outlet II 1-6 is sealed, the sorting outlet I1-6 is connected with the atmospheric pressure, so that non-target cells can flow out along the sorting outlet I1-6, the communication hole I2-2 and the waste liquid outlet 3-2 of the sorting flow channel I1-3 and reach a waste liquid pool, when the target cells are identified, the control circuit applies voltage to two ends of the memory alloy 9, when the memory alloy 9 is heated to the transition temperature by current, the shape memory alloy 9 can contract and shorten the length, so that the bottom layer of the micro valve 8 can be pulled upwards, the micro valve 8 is opened, and the micro valve hole 3-1 is blocked by the top of the micro valve 8, therefore, the target cells flow out along the sorting outlet II 1-6, the communication hole II 2-1, the micro valve hole 3-1, the flow channel 3-4 and the target outlet hole 3-3 and reach the cell collecting pool;
in the invention, the sorting outlet II 1-6, the communicating hole II 2-1, the micro valve hole 3-1 and the micro valve 8 are in sealed connection, the sorting outlet I1-6, the communicating hole I2-2 and the waste liquid outlet 3-2 are in nested connection, so that the leakage of cell liquid can be effectively prevented, and similarly, the inlet 1-2 and the inlet 6 are also in nested connection, and the sheath liquid hole 7 is also in nested connection.
The invention also provides a sorting method of the micro-fluidic sorting chip based on the memory alloy, which comprises the following steps:
s1, injecting cell sap from an inlet 1-2;
s2, the cells are arranged in a single row under the action of the sheath flow module 4 and move along the main flow channel 1-1 to the outlet 1-5 direction, and a detection module 5 is used for detecting whether target cells appear or not;
s3, when target cells appear, the control circuit controls the memory alloy 9 to be electrified, the memory alloy 9 is contracted and deformed to pull the bottom of the micro valve 8 upwards, the sorting flow channel I1-4 is opened at the moment, and the cells flow out along the sorting outlet II 1-6, the communication hole II 2-1, the micro valve hole 3-1, the flow channel 3-4 and the target outlet hole 3-3 of the sorting flow channel I1-4 and reach the cell collecting pool; when target cells do not appear, the control circuit controls the memory alloy 9 to be powered off, the memory alloy 9 restores to deform, the sorting flow channel I1-4 is closed at the moment, and the cells flow out along the sorting outlet I1-6, the communication hole I2-2 and the waste liquid outlet 3-2 of the sorting flow channel I1-3 and reach the waste liquid pool.
The above examples are merely illustrative of several embodiments of the present invention, and the description thereof is more specific and detailed but not to be construed as limiting the scope of the invention. Various modifications and alterations to this invention will become apparent to those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (3)
1. A micro-fluidic sorting chip based on memory alloy is characterized in that a fluid channel layer (1), an isolation layer (2) and a sorting layer (3) are arranged from bottom to top in sequence, the fluid channel layer (1) is provided with a main flow channel (1-1), one end of the main flow channel (1-1) is provided with an inlet (1-2), the other end of the main flow channel (1-1) is provided with an outlet (1-5) communicated with one end of the separation flow channel I (1-3) and one end of the separation flow channel II (1-4), a sheath flow module (4) and a detection module (5) are sequentially arranged between an inlet (1-2) and an outlet (1-5) of the main flow passage (1-1), the other end of the separation flow channel I (1-3) is provided with a separation outlet I (1-6), the other end of the sorting flow channel II (1-4) is provided with a sorting outlet II (1-7); the isolation layer (2) and the separation layer (3) are provided with a feed hole (6) and a sheath liquid hole (7) corresponding to the positions of the inlet (1-2) and the sheath flow module (4), and the isolation layer (2) is also provided with a communication hole II (2-1) and a communication hole I (2-2) corresponding to the positions of the separation outlet II (1-7) and the separation outlet I (1-6); the sorting layer (3) is also provided with a micro valve hole (3-1) and a waste liquid outlet hole (3-2) which correspond to the positions of a sorting outlet II (1-7) and a sorting outlet I (1-6), the micro valve hole (3-1) and the target outlet hole (3-3) are communicated through a flow channel (3-4) positioned at the lower layer of the sorting layer (3), a micro valve (8) is sequentially embedded into the micro valve hole (3-1), a communication hole II (2-1) and the sorting outlet II (1-7) from top to bottom, the micro valve (8) is provided with a memory alloy (9), the target outlet hole (3-3) is used for outputting target cells, and the waste liquid outlet hole (3-2) is used for outputting non-target single cells;
the memory alloy (9), the detection module (5) and the sheath flow module (4) are connected to a control circuit.
2. The memory alloy-based microfluidic sorting chip of claim 1, wherein the control circuit comprises an electrode set.
3. The sorting method of the microfluidic sorting chip based on the memory alloy according to claim 1, characterized by comprising the following steps:
s1, injecting cell sap from an inlet (1-2);
s2, the cells are arranged in a single row under the action of the sheath flow module (4) and move towards the outlet (1-5) along the main flow channel (1-1), and the detection module (5) is utilized to detect whether target cells appear;
s3, when target cells appear, the control circuit controls the memory alloy (9) to be electrified, the memory alloy (9) is subjected to shrinkage deformation to pull the bottom of the micro valve (8) upwards, the sorting flow channel II (1-4) is opened at the moment, and the cells flow out along the sorting outlet II (1-7) of the sorting flow channel II (1-4), the communication hole II (2-1), the micro valve hole (3-1), the flow channel (3-4) and the target outlet hole (3-3) and reach the cell collecting pool; when target cells do not appear, the control circuit controls the memory alloy (9) to be powered off, the memory alloy (9) restores to deform, the sorting flow channel II (1-4) is closed at the moment, and the cells flow out along the sorting outlet I (1-6), the communication hole I (2-2) and the waste liquid outlet (3-2) of the sorting flow channel I (1-3) and reach the waste liquid pool.
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| CN202111003375.XA CN113694975A (en) | 2021-08-30 | 2021-08-30 | Micro-fluidic sorting chip based on memory alloy and sorting method thereof |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102003560A (en) * | 2010-10-14 | 2011-04-06 | 清华大学 | Normally closed active micro valve for electrically driven shape memory alloy wire |
| CN205556699U (en) * | 2016-04-20 | 2016-09-07 | 大连海事大学 | High flux, full -automatic micro -fluidic chip cell sorting device |
| CN109943475A (en) * | 2019-04-12 | 2019-06-28 | 广西医科大学第一附属医院 | The micro-fluidic sorting chip of one kind and its separation system |
| CN110343603A (en) * | 2019-07-04 | 2019-10-18 | 中国科学院苏州生物医学工程技术研究所 | The micro-fluidic chip for preventing cell from blocking using sheath fluid adverse current |
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- 2021-08-30 CN CN202111003375.XA patent/CN113694975A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102003560A (en) * | 2010-10-14 | 2011-04-06 | 清华大学 | Normally closed active micro valve for electrically driven shape memory alloy wire |
| CN205556699U (en) * | 2016-04-20 | 2016-09-07 | 大连海事大学 | High flux, full -automatic micro -fluidic chip cell sorting device |
| CN109943475A (en) * | 2019-04-12 | 2019-06-28 | 广西医科大学第一附属医院 | The micro-fluidic sorting chip of one kind and its separation system |
| CN110343603A (en) * | 2019-07-04 | 2019-10-18 | 中国科学院苏州生物医学工程技术研究所 | The micro-fluidic chip for preventing cell from blocking using sheath fluid adverse current |
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