Microchannel-based liquid mixing chip and method

文档序号:1823648 发布日期:2021-11-12 浏览:24次 中文

阅读说明:本技术 基于微通道的液体混合芯片和方法 (Microchannel-based liquid mixing chip and method ) 是由 冯一鸣 张罗 卜晨 于 2021-08-24 设计创作,主要内容包括:本发明提供了基于微通道的液体混合芯片及方法,所述液体混合芯片包括基底和电极,所述基底采用绝缘材料;多个暂存模块设置在所述基底上,用于暂存液体;所述电极设置在所述暂存模块的外侧;阻碍模块设置在所述暂存模块和电极之间,用于阻碍所述暂存模块上的液体与所述电极接触;多个微通道的入口设置在所述暂存模块和电极之间,出口连通混合腔;混合腔设置在所述基底上。本发明具有液体消耗量少等优点。(The invention provides a liquid mixing chip based on a micro-channel and a method, wherein the liquid mixing chip comprises a substrate and an electrode, and the substrate is made of an insulating material; the temporary storage modules are arranged on the substrate and used for temporarily storing liquid; the electrode is arranged on the outer side of the temporary storage module; the blocking module is arranged between the temporary storage module and the electrode and is used for blocking the liquid on the temporary storage module from contacting with the electrode; inlets of the micro-channels are arranged between the temporary storage module and the electrodes, and outlets of the micro-channels are communicated with the mixing cavity; a mixing chamber is disposed on the base. The invention has the advantages of less liquid consumption and the like.)

1. The liquid mixing chip based on the micro-channel comprises a substrate and an electrode, wherein the substrate is made of an insulating material; characterized in that, the liquid mixing chip further comprises:

the temporary storage modules are arranged on the substrate and used for temporarily storing liquid; the electrode is arranged on the outer side of the temporary storage module;

the blocking module is arranged between the temporary storage module and the electrode and is used for blocking liquid on the temporary storage module from contacting with the electrode;

the inlets of the micro-channels are arranged between the temporary storage module and the electrodes, and the outlets of the micro-channels are communicated with the mixing cavity;

a mixing chamber disposed on the base.

2. The fluid mixing chip of claim 1, wherein the number of mixing chambers is multiple, any mixing chamber is connected to multiple temporary modules through micro-channels, and the temporary modules connected to any two mixing chambers are different.

3. The liquid mixing chip of claim 2, wherein a plurality of electrodes surround the same temporary storage module, and an inlet of a microchannel is provided between any one of the electrodes and the temporary storage module; the outlets of the micro-channels connected with the same temporary storage module are communicated with different mixing cavities.

4. The liquid mixing chip of claim 1, wherein the inlet of the microchannel is disposed at the obstruction module.

5. The liquid mixing chip of any one of claims 1 to 4, wherein the blocking module employs a hydrophobic layer disposed on the substrate surface between the staging module and the electrode.

6. The liquid mixing chip according to any one of claims 1 to 4, wherein the staging module is a hydrophilic layer disposed on the substrate surface.

7. The liquid mixing chip according to any one of claims 1 to 4, wherein the temporary storage module is a groove formed on the substrate, an inner diameter of the groove becomes larger from bottom to top, and an inner diameter of the electrode is larger than a maximum inner diameter of the groove.

8. The liquid mixing chip of claim 7, wherein a plurality of staging modules are disposed around the mixing chamber.

9. The liquid mixing method of the liquid mixing chip according to any one of claims 1 to 8, comprising the steps of:

(A1) the charged body contacts the liquid in the temporary storage module;

(A2) an electric field is formed between the charged body and the electrodes, and liquid in the temporary storage module overcomes the obstruction module and contacts the electrodes;

under the action of the electric field, the liquid enters the micro-channel;

(A3) the liquid delivered by each micro-channel is received in the mixing cavity, and the liquid is mixed in the mixing cavity.

10. The liquid mixing method according to claim 9, wherein in the step (a1), a plurality of liquids to be mixed are selected, and the microchannel and the mixing chamber are selected according to the selected liquids;

in step (a2), power is supplied to the electrode corresponding to the selected microchannel according to the microchannel.

Technical Field

The present invention relates to liquid mixing, and more particularly to microchannel-based liquid mixing chips and methods.

Background

The micro-reaction system has the characteristics of small liquid consumption, large flux, high reaction speed, easy integration and the like, and is widely applied to actual clinical diagnosis and large-scale drug screening, such as POCT, protein crystallization and the like. Existing microreaction systems often require complex chip structures or use pipettes for droplet operations when dealing with multiple sample mixing. This leads to increased chip design costs and potential cross-contamination, and more importantly, the chip design is more complicated and the likelihood of cross-contamination increases as more liquid mixtures are processed.

Conventional microreaction systems generally employ the following structure:

1. in the closed microfluidic chip structure, different reaction liquids are injected into a specific pipeline to flow by using external power (such as an injection pump) so that different micro-volume reactions can be mixed. Multiple plunger pumps are often required to achieve precise mixing of multiple liquids, increasing the cost of the overall instrument and making miniaturization of the instrument difficult.

2. The upper surface of the open chip structure is covered by oil to prevent the evaporation of trace liquid. When liquid mixing is carried out, a trace liquid charger is used for sucking liquid drops in the coring sheet for mixing, cross contamination is introduced by the method, the method is limited by the number of sample applicators, and the reaction flux is difficult to improve.

The controllable electrowetting technology is that a plurality of controllable circuits are integrated under a chip, and the contact angle of liquid drops is changed by changing the dotted state in the circuits, so that the operations of moving and separating the liquid drops are realized.

Disclosure of Invention

In order to overcome the defects in the prior art, the invention provides a liquid mixing chip based on a micro-channel.

The purpose of the invention is realized by the following technical scheme:

the liquid mixing chip based on the micro-channel comprises a substrate and an electrode, wherein the substrate is made of an insulating material; the liquid mixing chip further comprises:

the temporary storage modules are arranged on the substrate and used for temporarily storing liquid; the electrode is arranged on the outer side of the temporary storage module;

the blocking module is arranged between the temporary storage module and the electrode and is used for blocking liquid on the temporary storage module from contacting with the electrode;

the inlets of the micro-channels are arranged between the temporary storage module and the electrodes, and the outlets of the micro-channels are communicated with the mixing cavity;

a mixing chamber disposed on the base.

The invention also aims to provide a liquid mixing method, and the aim is realized by the following technical scheme:

according to the liquid mixing method of the liquid mixing chip of the invention, the liquid mixing method comprises the following steps:

(A1) the charged body contacts the liquid in the temporary storage module;

(A2) an electric field is formed between the charged body and the electrodes, and liquid in the temporary storage module overcomes the obstruction module and contacts the electrodes;

under the action of the electric field, the liquid enters the micro-channel;

(A3) the liquid delivered by each micro-channel is received in the mixing cavity, and the liquid is mixed in the mixing cavity.

Compared with the prior art, the invention has the beneficial effects that:

1. the liquid consumption is less;

by means of the arrangement of the temporary storage module and the electrodes, liquid can be temporarily stored in the temporary storage module only by nano-upgrading, when mixing is needed, the temporarily stored liquid can enter the micro-channel by using an electrophoresis technology, and the using amount of the liquid is obviously reduced;

2. high flux;

a plurality of temporary storage modules are designed on the same chip, different liquids exist, and the capillary electrophoresis array is matched to realize the mixing of various liquids, so that the analysis flux is obviously improved;

3. the structure is simple, and the cost is low;

the nano-liter liquid is conveyed by utilizing the capillary electrophoresis technology, an expensive pump is not needed, and the structural complexity and the cost are reduced;

4. selecting multiple mixing modes;

the same module of keeping in corresponds a plurality of microchannels for different mixing chambers connect different modules of keeping in, the mixture of different liquid has been realized, if utilize first mixing chamber to realize first, the mixture of second and third kind of liquid, the module of keeping in of first kind of liquid utilizes first microchannel and first mixing chamber intercommunication, it is first to utilize the second mixing chamber to realize, the mixture of fourth kind of liquid, the module of keeping in of first kind of liquid utilizes second microchannel and second mixing chamber intercommunication, the selection of liquid mixing mode has been realized.

Drawings

The disclosure of the present invention will become more readily understood with reference to the accompanying drawings. As is readily understood by those skilled in the art: these drawings are only for illustrating the technical solutions of the present invention and are not intended to limit the scope of the present invention. In the figure:

FIG. 1 is a schematic diagram of a liquid mixing chip according to an embodiment of the invention;

FIG. 2 is another schematic diagram of a liquid mixing chip according to an embodiment of the invention.

Detailed Description

Fig. 1-2 and the following description depict alternative embodiments of the invention to teach those skilled in the art how to make and reproduce the invention. Some conventional aspects have been simplified or omitted for the purpose of teaching the present invention. Those skilled in the art will appreciate that variations or substitutions from these embodiments will be within the scope of the invention. Those skilled in the art will appreciate that the features described below can be combined in various ways to form multiple variations of the invention. Thus, the present invention is not limited to the following alternative embodiments, but is only limited by the claims and their equivalents.

Example 1:

FIG. 1 shows a schematic configuration of a microchannel-based liquid mixing chip according to an embodiment of the present invention, which includes, as shown in FIG. 1:

the substrate 11, the substrate 11 adopts the insulating material;

a plurality of temporary storage modules, such as a first temporary storage module 21, a second temporary storage module 41, a third temporary storage module 51 and a fourth temporary storage module 61, which are disposed on the substrate 11 for temporarily storing liquid;

electrodes, such as the first electrode 21, the second electrode 42, the third electrode 52, and the fourth electrode 62, are disposed at the outer side of the buffer module;

the blocking module is arranged between the temporary storage module and the electrode and is used for blocking liquid on the temporary storage module from contacting with the electrode;

a plurality of microchannels, such as a first microchannel 31, a second microchannel 33, a third microchannel 35, and a fourth microchannel 37, with inlets (such as a first inlet 32, a second inlet 34, a third inlet 36, and a fourth inlet 38) of the microchannels disposed between the staging module and the electrodes and outlets communicating with a first mixing chamber 81;

a first mixing chamber 81, wherein the first mixing chamber 81 is arranged on the substrate 11, and a plurality of temporary storage modules surround the first mixing chamber 81.

In order to increase the mixing flux, further, the mixing chambers are multiple, such as the first mixing chamber 81 and other mixing chambers, any mixing chamber is connected with multiple temporary storage modules through micro-channels, and the temporary storage modules connected with any two mixing chambers are different.

In order to adapt to the mixing of one liquid and other different liquids, furthermore, a plurality of electrodes surround the same temporary storage module, and an inlet of a micro-channel is arranged between any electrode and the temporary storage module; the outlets of the micro-channels connected with the same temporary storage module are communicated with different mixing cavities.

In order to prevent liquid on the buffer module from entering the microchannels when not mixed, further, the inlets of the microchannels are arranged at the blocking module.

In order to reduce the structural complexity and improve the reliability, the blocking module further adopts a hydrophobic layer, and the hydrophobic layer is arranged on the surface of the substrate between the temporary storage module and the electrode.

In order to reduce the structural complexity and improve the reliability, the temporary storage module is a hydrophilic layer disposed on the surface of the substrate.

In order to reduce the structural complexity and improve the reliability, the temporary storage module is a groove formed on the substrate, the inner diameter of the groove is increased from bottom to top, and the inner diameter of the electrode is larger than the maximum inner diameter of the groove.

The liquid mixing method of the embodiment of the present invention, that is, the working method of the liquid mixing chip of the embodiment of the present invention, includes the steps of:

(A1) the charged body contacts the liquid in the temporary storage module;

(A2) an electric field is formed between the charged body and the electrodes, and liquid in the temporary storage module overcomes the obstruction module and contacts the electrodes;

under the action of the electric field, the liquid enters the micro-channel;

(A3) the liquid delivered by each micro-channel is received in the mixing cavity, and the liquid is mixed in the mixing cavity.

In order to achieve mixing between the same liquid and different liquids, further, in step (a1), selecting a plurality of liquids to be mixed, and selecting a microchannel and a mixing chamber according to the selected liquids;

in step (a2), power is supplied to the electrode corresponding to the selected microchannel according to the microchannel.

Example 2:

an application example of the microchannel-based liquid mixing chip and the method according to embodiment 1 of the present invention.

In this application example, as shown in fig. 1, a plurality of ring-shaped electrodes including a first electrode 22, a second electrode 42, a third electrode 52, and a fourth electrode 62 are formed on the surface of a substrate 11 by sputtering or the like using insulating glass as the substrate 11;

four temporary storage modules, including the first temporary storage module 21, the second temporary storage module 41, the third temporary storage module 51 and the fourth temporary storage module 61, the structure of each temporary storage module is: a groove is processed on the substrate 11 at the inner side of the annular electrode, the inner diameter of the groove is enlarged from bottom to top, and the inner diameter of the annular electrode is larger than the maximum inner diameter of the groove (the inner diameter of the top end of the groove); the area of the tank adjacent to the electrode 31 is provided with an obstruction module, such as a hydrophobic layer, so that liquid is prevented from contacting the electrode when no sample is fed;

microchannels including a first microchannel 31, a second microchannel 33, a third microchannel 35 and a fourth microchannel 37, each having a hydrophilic layer on an inner wall thereof, inlets (such as a first inlet 32, a second inlet 34, a third inlet 36 and a fourth inlet 38) of the microchannels being provided at the blocking module;

the first mixing chamber 81 is connected to the respective buffer module via a first microchannel 31, a second microchannel 33, a third microchannel 35 and a fourth microchannel 37.

The liquid mixing method of the embodiment of the present invention, that is, the working method of the liquid mixing chip of the embodiment of the present invention, includes the steps of:

(A1) the charged bodies in a matrix form are respectively contacted with the liquid in the four temporary storage modules;

(A2) electric fields are formed between the charged body and the annular electrode, for example, the electric fields are respectively formed between the first charged body and the first electrode 22, between the second charged body and the second electrode 42, between the third charged body and the third electrode 52, between the fourth charged body and the fourth electrode 62, and the liquid in the temporary storage module overcomes the obstruction module and contacts the annular electrode;

under the effect of the electric field, the temporary storage liquid enters the micro-channel, and the method specifically comprises the following steps: into the first microchannel 31 through the first inlet 32, into the second microchannel 33 through the second inlet 34, into the third microchannel 35 through the third inlet 36 and into the fourth microchannel 37 through the fourth inlet 38;

(A3) the liquid delivered from each microchannel is received in a first mixing chamber 81, and the liquids are mixed in the first mixing chamber 81.

Example 3:

according to an application example of the liquid mixing chip and the method of embodiment 1 of the present invention, the difference from embodiment 2 is:

as shown in fig. 2, part of the outside of the temporary storage module is not a ring electrode, the second electrode 42 and the fifth electrode 43 are respectively arranged on the outside of the second temporary storage module 41 and are isolated from each other, the second inlet 34 corresponds to the second electrode 42, and the fifth inlet 30 corresponds to the fifth electrode 63; the fourth electrode 62 and the sixth electrode 63 are respectively arranged at the outer sides of the fourth temporary storage module 61 and are isolated from each other, the fourth inlet 38 corresponds to the fourth electrode 62, and the sixth inlet 39 corresponds to the sixth electrode 63;

the second temporary storage module 41, the fourth temporary storage module 61, the fifth temporary storage module 71 and the sixth temporary storage module 91 are respectively connected with the second mixing chamber 82 through micro channels.

The liquid mixing method of the embodiment of the present invention, that is, the working method of the liquid mixing chip of the embodiment of the present invention, includes the steps of:

(A1) selecting a plurality of liquids to be mixed, and selecting a microchannel and a mixing cavity according to the selected liquids;

if the liquids in the first temporary storage module 21, the second temporary storage module 41, the third temporary storage module 51 and the fourth temporary storage module 61 are selected to be mixed, the first mixing cavity 81, the first microchannel 31, the second microchannel 33, the third microchannel 35 and the fourth microchannel 37 are selected;

the charged bodies in a matrix form are respectively contacted with the liquid in the four temporary storage modules;

(A2) supplying power to the electrodes corresponding to the selected microchannel, and supplying power to the first electrode 22, the second electrode 42, the third electrode 52 and the fourth electrode 62 (the fifth electrode 43 and the sixth electrode 63 are not supplied), so that electric fields are formed between the charged body and the electrodes, specifically, between the first charged body and the first electrode 22, between the second charged body and the second electrode 42, between the third charged body and the third electrode 52, between the fourth charged body and the fourth electrode 62, respectively, and the liquid in the temporary storage module overcomes the obstruction module and contacts the electrodes;

under the effect of the electric field, the temporary storage liquid enters the micro-channel, and the method specifically comprises the following steps: into the first microchannel 31 through the first inlet 32, into the second microchannel 33 through the second inlet 34, into the third microchannel 35 through the third inlet 36 and into the fourth microchannel 37 through the fourth inlet 38;

(A3) the liquid delivered from each microchannel is received in a first mixing chamber 81, and the liquids are mixed in the first mixing chamber 81.

In the liquid mixing method, if the liquids in the second temporary storage module 41, the fourth temporary storage module 61, the fifth temporary storage module 71 and the sixth temporary storage module 91 are selected for mixing, the second mixing chamber 82 and the micro-channels respectively connected with the second temporary storage module 41, the fourth temporary storage module 61, the fifth temporary storage module 71 and the sixth temporary storage module 91 are selected;

and power is supplied to the electrodes outside the second electrode 42, the fourth electrode 62, the fifth temporary storage module 71 and the sixth temporary storage module 91 (the fifth electrode 43 and the sixth electrode 63 are not supplied with power), so that an electric field is formed between the charged body and the electrodes, and the liquid in the four temporary storage modules respectively enters the second mixing chamber 82 through the micro-channels.

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