CN113544515A

CN113544515A - Microfluidic structure, microfluidic system, microfluidic method and method for manufacturing microfluidic structure

Info

Publication number: CN113544515A
Application number: CN202080000166.7A
Authority: CN
Inventors: 胡立教; 张玙璠; 袁春根; 崔皓辰
Original assignee: BOE Technology Group Co Ltd; Beijing BOE Health Technology Co Ld
Current assignee: BOE Technology Group Co Ltd; Beijing BOE Health Technology Co Ld
Priority date: 2020-02-21
Filing date: 2020-02-21
Publication date: 2021-10-22
Also published as: WO2021164021A1

Abstract

A microfluidic structure is provided. The microfluidic structure includes: an inlet; a plurality of microchambers; and a microchannel connected to the inlet and to the plurality of microchambers. The microchannel includes a trunk and a plurality of branches connecting the plurality of microchambers with the trunk, respectively. The plurality of branches are arranged in succession along the length of the trunk, and are connected to the trunk at a plurality of branch points arranged in succession along the length of the trunk, respectively. Two adjacent microchambers of the plurality of microchambers are spaced apart from each other by at least two adjacent branch points of the plurality of branch points.

Description

Microfluidic structure, microfluidic system, microfluidic method and method for manufacturing microfluidic structure

Technical Field

The present disclosure relates to microfluidic technologies, and in particular, to a microfluidic structure, a microfluidic system, a microfluidic method, and a method for manufacturing a microfluidic structure.

Background

The microfluidic chip is a microchip on which various processes including biological analysis, chemical analysis, and medical analysis are performed. For example, biological analysis on microfluidic chips includes sample preparation, dilution, reaction, separation, and detection with respect to substances. The micro-fluidic chip can be used for automatically completing the treatment of the detection substance in the micro-fluidic chip.

The microfluidic chip technology has the advantages of high analysis precision, high analysis speed, light weight, thinness, less reagent consumption, high integration level, high automation degree and repeated use, and has huge potential markets in the fields of biology, chemistry, medicine and the like.

Among the detection techniques for microfluidic chips, optical detection is the most widely used and most effective technique. Methods for optical detection include fluorescence detection, detection using ultraviolet-visible absorption spectroscopy, chemiluminescence detection, bioluminescence detection, and raman scattering detection. For example, detection using ultraviolet-visible absorption spectroscopy can not only detect a substance but also perform other analyses of the substance, including quantitative analysis, structural analysis, functional group identification, and the like.

Disclosure of Invention

In one aspect, the present invention provides a microfluidic structure comprising: an inlet; a plurality of microchambers; and a microchannel connected to the inlet and to the plurality of microchambers; wherein the microchannel comprises a trunk and a plurality of branches connecting the plurality of microchambers with the trunk, respectively; the plurality of branches are arranged in succession along the length of the trunk and are connected to the trunk at a plurality of branch points arranged in succession along the length of the trunk, respectively; and two adjacent microchambers of the plurality of microchambers are spaced apart from each other by at least two adjacent branch points of the plurality of branch points.

Optionally, at a respective one of the plurality of branch points, the portion of the trunk in the upstream immediately adjacent to the respective one of the plurality of branch points, the portion of the respective one of the plurality of branches in the downstream immediately adjacent to the respective one of the branch points, and the portion of the trunk in the downstream immediately adjacent to the respective one of the plurality of branch points divide the microfluidic structure into three non-overlapping regions comprising a first region, a second region, and a third region, wherein the first region is located between the portion of the trunk in the upstream immediately adjacent to the respective one of the plurality of branch points and the portion of the respective one of the plurality of branches in the downstream immediately adjacent to the respective one of the plurality of branch points, the second area is located between a portion of the trunk in an immediately upstream and a portion of the trunk in an immediately downstream vicinity of the one of the plurality of branch points, and the third area is located between a portion of the one of the plurality of branches in an immediately downstream vicinity of the one of the plurality of branch points and a portion of the trunk in an immediately downstream vicinity of the one of the plurality of branch points; a first side of the first zone and a second side of the first zone form a first included angle α, 90 degrees ≦ α ≦ 270 degrees, in the first zone, wherein the first side of the first zone follows a first liquid passing direction of the portion of the trunk in an upstream immediately adjacent to the respective one of the plurality of branch points and abuts the portion of the trunk in an upstream immediately adjacent to the respective one of the plurality of branch points, and the second side of the first zone follows a second liquid passing direction of the portion of the respective one of the plurality of branches in a downstream immediately adjacent to the respective one of the plurality of branch points and abuts the portion of the respective one of the plurality of branches in a downstream immediately adjacent to the respective one of the plurality of branch points; a third side of a second region and a fourth side of the second region forming a second included angle β in the second region, 0 degrees < β ≦ 120 degrees, the third side of the second region along the first liquid passing direction of the portion of the backbone in the immediately upstream of the respective one of the plurality of branch points and immediately adjacent to the portion of the backbone in the immediately upstream of the respective one of the plurality of branch points, the fourth side of the second region along a third liquid passing direction of the portion of the backbone in the immediately downstream of the respective one of the plurality of branch points and immediately adjacent to the portion of the backbone in the immediately downstream of the respective one of the plurality of branch points; and alpha is greater than beta.

Alternatively, 165 degrees ≦ α ≦ 195 degrees, and 75 degrees ≦ β ≦ 105 degrees.

Optionally, the microfluidic structure further comprises a plurality of outlets respectively connected to the plurality of microchambers.

Optionally, the microfluidic structure further comprises a gas-permeable, liquid-impermeable membrane covering the plurality of outlets, the membrane allowing air to vent from the plurality of microchambers while retaining liquid inside the plurality of microchambers.

Optionally, the microfluidic structure further comprises: a waste outlet for draining liquid in the trunk; and a waste microchamber connecting the waste outlet and the microchannel.

Optionally, the microfluidic structure further comprises a waste branch connecting the waste microchamber to the backbone; wherein the proximal branch of the plurality of branch points, the proximal branch of the plurality of branches, and the waste branch are connected to the backbone; wherein, at the immediately adjacent branch point, the portion of the trunk in the upstream immediately adjacent to the immediately adjacent branch point, the portion of the immediately adjacent branch, and the portion of the waste liquid branch divide the microfluidic structure into three non-overlapping regions including a fourth region between the portion of the trunk in the upstream immediately adjacent to the immediately adjacent branch point and the portion of the immediately adjacent branch, a fifth region between the portion of the trunk in the upstream immediately adjacent to the immediately adjacent branch point and the portion of the waste liquid branch, and a sixth region between the portion of the immediately adjacent branch and the portion of the waste liquid branch; a fifth side of the fourth region and a sixth side of the fourth region form a third included angle γ in the fourth region, 90 degrees ≦ γ ≦ 270 degrees, wherein the fifth side of the fourth region is along a fourth liquid passing direction of the portion of the trunk in an upstream immediately adjacent to the immediately adjacent branch point and abuts against the portion of the trunk in an upstream immediately adjacent to the immediately adjacent branch point, and the sixth side of the fourth region is along a fifth liquid passing direction of the portion of the immediately adjacent branch and abuts against the portion of the immediately adjacent branch; a seventh side of the fifth region and an eighth side of the fifth region form a fourth angle e in the fifth region, 0 degrees < e ≦ 120 degrees, wherein the seventh side of the fifth region is along the fourth liquid passing direction of the portion of the trunk in the upstream immediately adjacent to the branch point and is next to the portion of the trunk in the upstream immediately adjacent to the branch point, and the eighth side of the fifth region is along the sixth liquid passing direction of the portion of the waste liquid branch and is next to the portion of the waste liquid branch; and gamma is greater than epsilon.

Alternatively, 165 degrees ≦ γ ≦ 195 degrees, and 75 degrees ≦ ε ≦ 105 degrees.

Optionally, the immediately adjacent branch is a last branch of the plurality of branches arranged consecutively in sequence; the immediately adjacent branch point is a last branch point of the plurality of branch points arranged successively in order; and the waste liquid branch and the waste liquid microchamber are spaced from the inlet by a trunk connected to the plurality of branches.

Optionally, the plurality of microchambers is a plurality of detection chambers, a respective one of the plurality of detection chambers being optically coupled to the detector.

In another aspect, the present invention provides a microfluidic system comprising a microfluidic structure as described herein or manufactured by the methods described herein and one or more sensing circuits.

In another aspect, the invention provides a microfluidic method comprising: receiving a liquid from an inlet of a microfluidic structure; and delivering different portions of the liquid to the plurality of microchambers, respectively, in a time sequence, through a microchannel connected to the inlet and to the plurality of microchambers; wherein the microchannel comprises a trunk and a plurality of branches connecting the plurality of microchambers with the trunk, respectively; the plurality of branches are arranged in succession along the length of the trunk and are connected to the trunk at a plurality of branch points arranged in succession along the length of the trunk, respectively; and two adjacent microchambers of the plurality of microchambers are spaced apart from each other by at least two adjacent branch points of the plurality of branch points; delivering different portions of the liquid through the microchannel in a time sequence to the plurality of microchambers, respectively, comprises: moving the liquid from the inlet to the stem; and delivering the different portions of the liquid into the plurality of branches, respectively, in a time sequence.

Optionally, when a portion of liquid is first moved to a respective one of the plurality of branch points, a majority of the portion of liquid is distributed into the respective one of the plurality of branches and a minority of the portion of liquid is distributed to a portion of the trunk in a downstream immediately adjacent to the respective one of the plurality of branch points; when the one of the plurality of branches is filled with liquid, the liquid is directed to a portion of the trunk in a downstream immediately adjacent to the one of the plurality of branch points.

Optionally, the method further comprises: controlling a liquid passing direction at the one of the plurality of branch points of the liquid such that the liquid in a portion of the trunk in an upstream immediately upstream of the one of the plurality of branch points has a first liquid passing direction, the liquid in a portion of one of the plurality of branches in a downstream immediately downstream of the one of the plurality of branch points has a second liquid passing direction, and the liquid in a portion of the trunk in a downstream immediately downstream of the one of the plurality of branch points has a third liquid passing direction; wherein the first liquid passing direction, the second liquid passing direction, and the third liquid passing direction divide the microfluidic structure into three non-overlapping regions at the one corresponding branch point of the plurality of branch points, the three non-overlapping regions including a first region, a second region, and a third region, the first region being located between the first liquid passing direction and the second liquid passing direction, the second region being located between the first liquid passing direction and the third liquid passing direction, the third region being located between the second liquid passing direction and the third liquid passing direction; a first side of the first area along the first liquid passing direction and a second side of the first area along the second liquid passing direction form a first included angle a in the first area; and a third side of the second region along the first liquid passing direction and a fourth side of the second region along the third liquid passing direction form a second included angle β in the second region; wherein a liquid passing direction of the liquid at the corresponding one of the plurality of branch points is controlled such that α is larger than β, 90 degrees ≦ α ≦ 270 degrees, and 0 degrees ≦ β ≦ 120 degrees).

Optionally, 165 degrees ≦ α ≦ 195 degrees, 75 degrees ≦ β ≦ 105 degrees.

Optionally, the method further comprises: discharging air from the plurality of microchambers while retaining liquid inside the plurality of microchambers through a plurality of outlets respectively connected to the plurality of microchambers.

Optionally, the method further comprises: releasing liquid from the trunk to a waste outlet through a waste branch; wherein, at an immediately adjacent branch point of the plurality of branch points, the immediately adjacent branch of the plurality of branches and the waste branch are connected to the trunk.

Optionally, the method further comprises: controlling a liquid passing direction of the liquid at the immediately adjacent branch point such that the liquid in a portion of the trunk in an immediately upstream of the immediately adjacent branch point has a fourth liquid passing direction, the liquid in the immediately adjacent branch portion has a fifth liquid passing direction, and the liquid in the waste liquid branch portion has a sixth liquid passing direction; wherein, at the immediately adjacent branch point, the fourth liquid passing direction, the fifth liquid passing direction, and the sixth liquid passing direction divide the microfluidic structure into three non-overlapping regions including a fourth region, a fifth region, and a sixth region, wherein the fourth region is located between the fourth liquid passing direction and the fifth liquid passing direction, the fifth region is located between the fourth liquid passing direction and the sixth liquid passing direction, and the sixth region is located between the fifth liquid passing direction and the sixth liquid passing direction; a fifth side of the fourth region along the fourth liquid passing direction and a sixth side of the fourth region along the fifth liquid passing direction form a third angle γ in the fourth region; a seventh side of the fifth area along the fourth liquid passing direction and an eighth side of the fifth area along the sixth liquid passing direction form a fourth angle epsilon in the fifth area; and controlling the liquid passing direction of the liquid at the adjacent branch point so that gamma is greater than epsilon, 90 degrees or more and gamma is less than or equal to 270 degrees, and 0 degree < epsilon is less than or equal to 120 degrees.

Optionally, the method further comprises: detecting a target substance at a respective one of the plurality of microchambers.

In another aspect, the present invention provides a method of fabricating a microfluidic structure, comprising: forming an inlet; forming a plurality of microchambers; and forming a microchannel connected to the inlet and to the plurality of microchambers; wherein forming the microchannel comprises: forming a trunk and forming a plurality of branches respectively connecting the plurality of microchambers with the trunk; the plurality of branches are arranged in succession along the length of the trunk and are connected to the trunk at a plurality of branch points arranged in succession along the length of the trunk, respectively; and two adjacent microchambers of the plurality of microchambers are spaced apart from each other by at least two adjacent branch points of the plurality of branch points.

Drawings

The following drawings are merely examples for illustrative purposes in accordance with various disclosed embodiments and are not intended to limit the scope of the present disclosure.

Fig. 1 is a perspective view of a microfluidic structure in some embodiments according to the present disclosure.

Fig. 2A is a schematic structural view of a microfluidic structure in some embodiments according to the present disclosure.

Fig. 2B is a schematic structural view of a microfluidic structure in some embodiments according to the present disclosure.

Fig. 3 is a schematic diagram illustrating the structure of a microchannel in some embodiments according to the present disclosure.

Fig. 4 is a schematic diagram illustrating the structure of a microchannel in some embodiments according to the present disclosure.

Fig. 5 is a perspective view of a partial structure of a microfluidic structure in some embodiments according to the present disclosure.

Fig. 6 is a schematic diagram illustrating the structure of a microchannel in some embodiments according to the present disclosure.

Fig. 7 is a schematic diagram illustrating the structure of a microchannel in some embodiments according to the present disclosure.

Fig. 8 is a schematic diagram illustrating the structure of a microchannel in some embodiments according to the present disclosure.

Fig. 9 is a schematic structural view of a microfluidic structure in some embodiments according to the present disclosure.

Fig. 10 is a schematic diagram illustrating a movement speed of a liquid in a microfluidic structure in a plan view in some embodiments according to the present disclosure.

Fig. 11 is a schematic diagram illustrating the speed of movement of a liquid in a microfluidic structure in a perspective view in some embodiments of the present disclosure.

Fig. 12 is a schematic diagram illustrating a moving speed of a liquid in a microfluidic structure in a plan view in some embodiments of the present disclosure.

Fig. 13 is a schematic diagram illustrating the speed of movement of a liquid in a microfluidic structure in perspective view in some embodiments of the present disclosure.

Fig. 14 is a flow chart illustrating a microfluidic method in some embodiments according to the present disclosure.

Fig. 15 is a flow diagram illustrating a method of fabricating a microfluidic structure in accordance with some embodiments of the present disclosure.

Detailed Description

The present disclosure will now be described more specifically with reference to the following examples. It should be noted that the following description of some embodiments presented herein is for the purpose of illustration and description only. It is not intended to be exhaustive or to be limited to the precise form disclosed.

In a process of detecting a plurality of substances in different microchambers of the same microfluidic structure, a detection signal for detecting one microchamber may become noise in a process of detecting another microchamber using a different detection signal.

Accordingly, the present disclosure provides, among other things, a microfluidic structure, a microfluidic system, a microfluidic method, and a method of manufacturing a microfluidic structure that substantially obviate one or more problems due to limitations and disadvantages of the related art. In one aspect, the present disclosure provides a microfluidic structure. In some embodiments, the microfluidic structure comprises an inlet; a plurality of microchambers; and a microchannel connected to the inlet and to the plurality of microchambers. Optionally, the microchannel includes a trunk and a plurality of branches connecting the plurality of microchambers with the trunk, respectively. Optionally, the plurality of branches are successively arranged along the length of the trunk, and are connected to the trunk at a plurality of branch points successively arranged along the length of the trunk, respectively. Optionally, two adjacent microchambers of the plurality of microchambers are spaced apart from each other by at least two adjacent branch points of the plurality of branch points.

Fig. 1 is a perspective view of a microfluidic structure in some embodiments according to the present disclosure. Referring to fig. 1, in some embodiments, a microfluidic structure includes an inlet 10. For example, liquid is input to the microfluidic structure through inlet 10. Optionally, the microfluidic structure further comprises a plurality of microchambers 20. Optionally, the liquid in a corresponding one of the plurality of microchambers 20 is detected by a detector. Alternatively, reagents are provided in the plurality of micro chambers 20 to react with different portions of the liquid respectively transferred to the plurality of micro chambers 20.

In some embodiments, the microfluidic structure includes a microchannel 30 connected to the inlet 10 and to the plurality of microchambers 20, e.g., the microchannel 30 connecting the inlet 10 to each of the plurality of microchambers 20. Fig. 2A is a schematic structural view of a microfluidic structure in some embodiments according to the present disclosure. Alternatively, referring to fig. 2A, the microchannel 30 includes a trunk 31 and a plurality of branches 32 respectively connecting the plurality of microchambers 20 with the trunk 31. Optionally, the backbone 31 has a curved shape. For example, the stem 31 has a waveform shape. In another example, the stem 31 has a zigzag shape as shown in fig. 2A.

Fig. 2B is a schematic structural view of a microfluidic structure in some embodiments according to the present disclosure. Alternatively, referring to fig. 2A and 2B, the plurality of microchambers 20 includes a first microchamber 201, a second microchamber 202, and a third microchamber 203. For example, the first microchamber 201, the second microchamber 202 and the third microchamber 203 are arranged in succession along the length of the stem 31. Optionally, the plurality of branch points BP includes a first branch point BP1, a second branch point BP2, and a third branch point BP 3. For example, the first branch point BP1 corresponds to the first microchamber 201, the second branch point BP2 corresponds to the second microchamber 202, and the third branch point BP3 corresponds to the third microchamber 203.

Alternatively, referring to fig. 2A, the plurality of branches 32 are sequentially arranged along the length of the trunk 31, and the plurality of branches 32 are respectively connected to the trunk 31 at a plurality of branch points BP that are sequentially arranged along the length of the trunk 31. Alternatively, the trunk 31 having a curved shape is curved at a plurality of branch points BP. In one example, the stem 31 has a zigzag shape, and each of the plurality of branch points BP corresponds to a turning point of the zigzag shape.

Alternatively, two adjacent microchambers of the plurality of microchambers 20 are spaced apart from each other by at least two adjacent branch points of the plurality of branch points BP. Optionally, two adjacent microchambers of the plurality of microchambers 20 are on two opposite sides of the stem 31. For example, referring to fig. 2B, the first microchamber 201 and the second microchamber 202 are microchambers immediately adjacent to each other, and the first branch point BP1 and the second branch point BP2 are branch points immediately adjacent to each other. The first and second microchambers 201 and 202 are spaced apart from each other by a first branch point BP1 and a second branch point BP 2.

Fig. 3 is a schematic diagram illustrating the structure of a microchannel in some embodiments according to the present disclosure. Fig. 4 is a schematic diagram illustrating the structure of a microchannel in some embodiments according to the present disclosure. Referring to fig. 2A, 3 and 4, in some embodiments, at a respective one of the plurality of branch points BP, the first portion P1 of the stem 31 in the upstream immediately adjacent to the respective one of the plurality of branch points BP, the second portion P2 of the respective one of the plurality of branches 32 in the downstream immediately adjacent to the respective one of the plurality of branch points BP, and the third portion P3 of the stem 31 in the downstream immediately adjacent to the respective one of the plurality of branch points BP divide the microfluidic structure into three non-overlapping regions.

Optionally, the three non-overlapping regions include a first region R1, a second region R2, and a third region R3. Optionally, the first region R1 is located between the first portion P1 of the stem 31 in the upstream immediately adjacent to a respective one of the plurality of branch points BP and the second portion P2 of a respective one of the plurality of branches 32 in the downstream immediately adjacent to the respective one of the plurality of branch points BP. Alternatively, the second region R2 is located between the first part P1 of the stem 31 in the immediately upstream and the third part P3 of the stem 31 in the immediately downstream of the one of the plurality of branch points BP. Optionally, the third region R3 is located between the second part P2 of a respective one of the plurality of branches 32 immediately downstream of the respective one of the plurality of branch points BP and the third part P3 of the stem 31 in immediately downstream of the respective one of the plurality of branch points BP.

Optionally, the first side S1 of the first region R1 and the second side S2 of the first region R1 form a first included angle α in the first region R1, 90 degrees ≦ α ≦ 270 degrees, e.g., 90 degrees ≦ α ≦ 140 degrees, 140 degrees ≦ α ≦ 190 degrees, 190 degrees ≦ α ≦ 240 degrees, and 240 degrees ≦ α ≦ 270 degrees, wherein the first side S1 of the first region R1 passes along the first liquid passing direction D1 of the first portion P1 of the backbone 31 immediately upstream of the one of the plurality of branch points BP and immediately upstream of the first portion P1 of the backbone 31 in immediately upstream of the one of the plurality of branch points BP, and the second side S2 of the first region R1 passes along the second liquid passing direction D2 of the second portion P2 of the one of the plurality of branch points 32 immediately downstream of the one of the plurality of branch points BP, And the second portion P2 of a corresponding one of the plurality of branches 32 immediately downstream of the corresponding one of the plurality of branch points BP. Optionally, the first included angle α is in a range of 110 degrees to 130 degrees, for example, the first included angle α is 120 degrees. Optionally, the first included angle α is in a range of 140 degrees to 160 degrees, for example, the first included angle α is 150 degrees. Optionally, the first included angle α is in a range of 170 degrees to 190 degrees, for example, the first included angle α is 180 degrees.

Referring to fig. 3, optionally, the first liquid passing direction D1 and the second liquid passing direction D2 are the same. Referring to fig. 4, optionally, the first liquid passing direction D1 and the second liquid passing direction D2 are different.

Alternatively, with reference to FIGS. 2A, 3 and 4, the third side S3 of the second region R2 and the fourth side S4 of the second region R2 form a second included angle β in the second region R2, 0 degrees < β ≦ 120 degrees, e.g., 0 degrees < β ≦ 20 degrees, 20 degrees ≦ β ≦ 40 degrees, 40 degrees ≦ β ≦ 60 degrees, 60 degrees ≦ β ≦ 80 degrees, 80 degrees ≦ β ≦ 100 degrees, 100 degrees ≦ β ≦ 120 degrees, wherein the third side S3 of the second region R2 passes along the first liquid passing direction D1 of the first portion P1 of the stem 31 in the upstream immediately adjacent to the one of the plurality of branch points BP and the first portion P1 of the first side P86531 in the upstream immediately adjacent to the one of the plurality of branch points BP, and the fourth side S637 of the second region R2 passes along the third liquid passing direction D3 of the third portion P3 of the downstream branch points P6854 of the branch points P in the immediately adjacent to the one of the plurality of branch points BP, And is immediately adjacent to the third portion P3 of the stem 31 in the immediately downstream position from the corresponding one of the plurality of branch points BP. Optionally, the second included angle β is in the range of 20 degrees to 40 degrees, for example, the second included angle β is 30 degrees. Optionally, the second included angle β is in the range of 50 degrees to 70 degrees, for example, the second included angle β is 60 degrees. Optionally, the second included angle β is in a range of 80 degrees to 100 degrees, for example, the second included angle β is 90 degrees.

Optionally, α is greater than β.

Alternatively, 165 degrees ≦ α ≦ 195 degrees, such as 165 degrees ≦ α ≦ 175 degrees, 175 degrees ≦ α ≦ 185 degrees, and 185 degrees ≦ α ≦ 195 degrees. Alternatively, 75 degrees ≦ β ≦ 105 degrees, such as 75 degrees ≦ β ≦ 85 degrees, 85 degrees ≦ β ≦ 95 degrees, and 95 degrees ≦ β ≦ 105 degrees.

Optionally, the first included angle α and the second included angle β may be adjusted to control the speed of movement of the liquid into the plurality of microchambers 20.

Fig. 5 is a perspective view of a partial structure of a microfluidic structure in some embodiments according to the present disclosure. In some embodiments, referring to fig. 1, 2A, and 5, the microfluidic structure further comprises a plurality of outlets 40 connected to the plurality of microchambers 20, respectively.

In some embodiments, referring to fig. 1 and 2A, the microfluidic structure further comprises a gas-permeable, liquid-impermeable membrane 50 covering the plurality of outlets 40, the membrane 50 allowing air to escape from the plurality of microchambers 20 but retaining liquid within the plurality of microchambers 20. For example, the liquid-impermeable, gas-permeable membrane 50 is configured to have a microporous structure that allows air to pass through, but prevents liquid from passing through.

For example, referring to fig. 1, 2A and 5, when a liquid enters a respective one of the plurality of microchambers 20, air in the respective one of the plurality of microchambers 20 is pushed out of the respective one of the plurality of microchambers 20 to a respective one of the plurality of outlets 40 by a portion of the liquid entering the respective one of the plurality of microchambers 20. The portion of liquid may eventually enter a respective one of the plurality of outlets 40 and push air in the respective one of the plurality of outlets 40 out of the microfluidic structure through the gas-permeable, liquid-impermeable membrane 50.

Referring to fig. 1, the microfluidic structure further comprises a sealing membrane 60 located on a side of the microchannel 30 remote from the plurality of outlets 40 (e.g., on a bottom side of the microfluidic structure for sealing the bottom side of the microfluidic structure). For example, the connection point between a respective one of the plurality of outlets 40 and a respective one of the plurality of microchambers 20 is closer to the top side of the respective one of the plurality of microchambers 20 (e.g., the side of the respective one of the plurality of microchambers 20 distal from the sealing membrane 60). Optionally, the sealing film 60 is a composite film.

In some embodiments, referring to fig. 1 and 2A, the microfluidic structure further comprises a waste outlet 41 for releasing liquid in the backbone 31; and a waste microchamber 21 optionally connecting the waste outlet 41 and the microchannel 30. Optionally, referring to fig. 2A, the microfluidic structure further comprises a waste liquid branch 33 connecting the waste liquid microchamber 21 to the trunk 31. For example, liquid moves sequentially from the trunk 31 to the waste branch 33, the waste microchamber 21 and the waste outlet 41, so that air, reaction waste and excess reactants in the trunk 31 can leave the microfluidic structure, e.g., be pushed out of the waste outlet 41 from the waste microchamber 21.

Fig. 6 is a schematic diagram illustrating the structure of a microchannel in some embodiments according to the present disclosure. In some embodiments, referring to fig. 6, the plurality of branches 32 further includes an immediately adjacent branch 321, and the plurality of branch points BP further includes an immediately adjacent branch point BP 0. Alternatively, the waste liquid branch 33 and the immediately adjacent branch 321 of the plurality of branches 32 are connected to the trunk 31 at the immediately adjacent branch point BP0 of the plurality of branch points BP.

Fig. 7 is a schematic diagram illustrating the structure of a microchannel in some embodiments according to the present disclosure. Fig. 8 is a schematic diagram illustrating the structure of a microchannel in some embodiments according to the present disclosure. In some embodiments, referring to fig. 6, 7 and 8, immediately adjacent to the branch point BP0, the portion P4 of the stem 31 in the upstream immediately adjacent to the branch point BP0, the portion P5 immediately adjacent to the branch 321 and the portion P6 of the waste liquid branch 33 divide the microfluidic structure into three non-overlapping regions. The three non-overlapping regions include a fourth region R4, a fifth region R5, and a sixth region R6, wherein the fourth region R4 is located between a portion P4 of the stem 31 in the upstream immediately adjacent to the branch point BP0 and a portion P5 of the stem immediately adjacent to the branch point 321, the fifth region R5 is located between a portion P4 of the stem 31 in the upstream immediately adjacent to the branch point BP0 and a portion P6 of the waste liquid branch 33, and the sixth region R6 is located between a portion P5 of the stem immediately adjacent to the branch point BP0 and a portion P6 of the waste liquid branch 33.

Optionally, a fifth side S5 of the fourth region R4 and a sixth side S6 of the fourth region R4 form a third included angle γ in the fourth region R4 of 90 degrees ≦ γ ≦ 270 degrees, e.g., 90 degrees ≦ γ ≦ 140 degrees, 140 degrees ≦ γ ≦ 190 degrees, 190 degrees ≦ γ ≦ 240 degrees, and 240 degrees ≦ γ ≦ 270 degrees, wherein the fifth side S5 of the fourth region R4 lies along the fourth liquid passing direction D4 of the portion P4 of the stem 31 immediately upstream of the branch point BP0 and immediately upstream of the portion P4 of the stem 31 immediately upstream of the branch point BP0, and the sixth side S6 of the fourth region R4 lies along the fifth liquid passing direction D5 of the portion P5 immediately upstream of the branch 321 and immediately adjacent to the portion P5 of the branch 321. Optionally, the third included angle γ is in a range of 110 degrees to 130 degrees, for example, the third included angle γ is 120 degrees. Optionally, the third included angle γ is in a range of 140 degrees to 160 degrees, for example, the third included angle γ is 150 degrees. Optionally, the third included angle γ is in a range of 170 degrees to 190 degrees, for example, the third included angle γ is 180 degrees.

Referring to fig. 7, the fourth liquid passing direction D4 is the same as the fifth liquid passing direction D5. Referring to fig. 8, the fourth liquid passing direction D4 and the fifth liquid passing direction D5 are different.

Alternatively, referring to FIGS. 6, 7 and 8, the seventh side S7 of the fifth region R5 and the eighth side S8 of the fifth region R5 form a fourth included angle ε, 0 degrees < ε ≦ 120 degrees, for example, 0 degrees < ε ≦ 20 degrees, 20 degrees ≦ ε ≦ 40 degrees, 40 degrees ≦ ε ≦ 60 degrees, 60 degrees ≦ ε ≦ 80 degrees, 80 degrees ≦ ε ≦ 100 degrees, 100 degrees ≦ ε ≦ 120 degrees, in the fifth region, the seventh side S7 of the fifth region R5 along the fourth liquid passing direction D4 of the portion P4 of the stem 31 in the immediately upstream of the branch point BP0 and the portion P4 of the stem 31 in the immediately upstream of the branch point BP0, and the eighth side S8 of the fifth region R5 along the sixth liquid passing direction D6 of the portion P6 of the waste liquid branch 33 and the portion P6 of the waste liquid branch 33. Optionally, the fourth angle e is in the range of 20 degrees to 40 degrees, for example the fourth angle e is 30 degrees. Optionally, the fourth angle epsilon is in the range of 50 degrees to 70 degrees, for example, the fourth angle epsilon is 60 degrees. Optionally, the fourth angle epsilon is in the range of 80 degrees to 100 degrees, e.g., the fourth angle epsilon is 90 degrees.

Optionally, γ is greater than ε.

Alternatively, 165 degrees ≦ γ ≦ 195 degrees, such as 165 degrees ≦ γ ≦ 175 degrees, 175 degrees ≦ γ ≦ 185 degrees, and 185 degrees ≦ γ ≦ 195 degrees. Alternatively, 75 degrees ≦ ε ≦ 105 degrees, such as 75 degrees ≦ ε ≦ 85 degrees, 85 degrees ≦ ε ≦ 95 degrees, and 95 degrees ≦ ε ≦ 105 degrees.

Optionally, the third angle γ and the fourth angle ε may be adjusted to control a speed of movement of a portion of the liquid into a respective one of the plurality of microchambers and the waste microchamber.

Optionally, the immediately adjacent branch 321 is the last branch of the plurality of branches 32 arranged consecutively in sequence. Alternatively, the immediately adjacent branch point BP0 is the last branch point of the plurality of branch points BP arranged successively in order. Optionally, the waste branch 33 and the waste microchamber 21 are spaced from the inlet 10 by a trunk 31 connected to a plurality of branches 32.

Fig. 9 is a schematic structural view of a microfluidic structure in some embodiments according to the present disclosure. In some embodiments, referring to fig. 9, the plurality of microchambers 20 is a plurality of detection chambers. Optionally, a respective one of the plurality of detection chambers is optically coupled to the detector 70. Optionally, the area corresponding to the waste microchamber 21 is free of any detector 70. Optionally, the microfluidic structure is a structure in a detection chip. Alternatively, a plurality of micro chambers 20 in the detection chip are previously provided with different reagents for detecting different substances or different characteristics of the sample.

A plurality of microchambers 20 may be used to perform various functions. For example, the plurality of microchambers 20 can include an analysis chamber, a reaction chamber, and a sequencing chamber. For example, multiple detection chambers can be used to perform enzymatic analysis (e.g., glucose and lactate assays), DNA analysis (e.g., DNA sequencing, polymerase chain reaction PCR, autonomous sequence replication 3SR), protein analysis, and chemical synthesis analysis.

Optionally, the microfluidic structure comprises a plurality of detection signal providers configured to provide a plurality of detection signals to the plurality of microchambers, respectively. For example, the plurality of detection signal providers are a plurality of light sources that emit light having different wavelength ranges. Optionally, the plurality of detection signals are respectively transmitted through the plurality of microchambers and respectively reach the plurality of detectors, and one corresponding detector in the plurality of detectors is controlled to perform detection processing to detect a change in one corresponding detection signal in the plurality of detection signals. The plurality of microchambers are sequentially filled with liquid along the length of the trunk, and thus, a respective one of the plurality of detectors can operate for a specified period of time that will not completely overlap with another period of time during which another detector operates, thereby detecting a change in a respective one of the plurality of detection signals.

By arranging the plurality of branches in succession in sequence along the length of the trunk, the liquid entering the inlet can sequentially fill the plurality of microchambers connected to the plurality of branches, respectively. Because the plurality of microchambers are filled sequentially and continuously along the length of the stem, different microchambers are filled in different time periods in a chronological order (e.g., the different time periods at least do not completely overlap). Thus, detectors optically coupled to different microchambers, respectively, can detect the following reaction products, respectively: the reaction products are formed by filling portions of the liquid in different microchambers respectively at different time periods (e.g., in a time sequence and optionally non-overlapping time periods) and at different locations corresponding to the different microchambers. As a result, the detection window time used by the detector may be reduced, and the amount of work required to process the amount of data collected from the detection process may be reduced. The need for computational resources required to process the amount of data collected from the detection process may be reduced.

For example, during the detection process, the detection signal is applied to a respective one of the plurality of microchambers, and a respective one of the plurality of detectors corresponding to the respective one of the plurality of microchambers detects a change in the detection signal. In order to detect different substances or different properties of substances, which are located in different microchambers, respectively, different detection signals may be applied to different microchambers, respectively. When different detection signals are applied simultaneously, crosstalk between the different detection signals may adversely affect the results of the detection process. The microfluidic chip structure described herein allows different microchambers to be filled at different time periods, so that different detectors can detect different microfluidic microchambers at different time periods, and thus cross-talk between different detection signals used in different detection processes can be prevented. Optionally, the different detection signals comprise different light rays having different wavelength ranges.

The moving speed of the liquid entering the microfluidic structure can be accurately controlled, so that the time spent by the liquid moving from the inlet to different microchambers and filling the different microchambers can be accurately calculated, and the detection processing of the detector can be accurately controlled to different positions corresponding to different microchambers in different time periods. In one example, different detectors are provided corresponding to different microchambers. In another example, the detector is configured to move to different positions to detect different microchambers in different time periods.

In one example, a plurality of microchambers are provided with different reactants in advance, and a sample in the form of a liquid flowing through a microchannel is provided. Different portions of the liquid are delivered to the plurality of microchambers, respectively. The microfluidic structures described herein fill portions of a sample into multiple microchambers at different (e.g., non-overlapping) time periods in a time sequential manner, thereby minimizing cross-contamination between different reactants in the multiple microchambers.

In a process of filling a plurality of micro chambers in a conventional microfluidic structure, before the micro chambers are completely filled, a liquid flows into the micro chambers and is mixed with a reagent disposed in the micro chambers to form a mixed liquid. In conventional microfluidic structures, due to turbulence in the microchamber, a portion of the mixed liquid may flow out of the microchamber into the next microchamber, which may lead to contamination between the microchambers.

However, in the microfluidic structure described herein, once a respective one of the plurality of microchambers is completely filled, the liquid pressure at the respective one of the plurality of microchambers is greater than the liquid pressure at the portion of the stem in the downstream immediately adjacent to the respective one of the plurality of branch points, the liquid will continue to flow along the stem to the next microchamber, and the interaction between a portion of the liquid (e.g., the mixed liquid) in the respective one of the plurality of microchambers and a portion of the liquid in the stem is substantially reduced, which prevents the mixed liquid from flowing out of the respective one of the plurality of microchambers.

In the microfluidic structures described herein, a much shorter duration (e.g., 1-1.2 seconds) is required for the liquid to completely fill a respective one of the plurality of microchambers, and the relatively fast fill process effectively prevents contamination between the microchambers. In addition, the mixing process of the liquid and the reagent in a corresponding one of the plurality of micro chambers is performed within 1 second to 1.2 seconds, during which the detector can perform the detection process. This enables the detector to detect the reaction between the liquid (e.g., biological sample) and the reagent in a timely manner (e.g., at the peak of the reaction).

In some embodiments, the moving speed of the liquid may be controlled by adjusting an acute angle between the trunk in an upstream immediately adjacent to a corresponding one of the plurality of branch points and the trunk in a downstream immediately adjacent to the corresponding one of the plurality of branch points.

In some embodiments, the moving speed of the liquid may be controlled by adjusting an angle between the stem in an upstream immediately adjacent to a respective branch point of the plurality of branch points and a respective branch in a downstream immediately adjacent to a respective branch point of the plurality of branch points. An angle between a trunk in an upstream immediately adjacent to the one of the plurality of branch points and the one of the plurality of branches in a downstream immediately adjacent to the one of the plurality of branch points does not cover the following area: the region has a skeleton in a downstream immediately adjacent to the corresponding one of the plurality of branch points.

In one example, referring to fig. 3, the first included angle α is 180 degrees and the second included angle β is 90 degrees. Fig. 10 is a schematic diagram illustrating a moving speed of a liquid in a microfluidic structure in plan view in some embodiments according to the present disclosure. Fig. 11 is a schematic diagram illustrating a moving speed of a liquid in a microfluidic structure in a perspective view in some embodiments according to the present disclosure. Referring to fig. 10 and 11, the darker the color, the slower the liquid moves. The plurality of microchambers are a plurality of pressure relief ports. Referring to fig. 2A, 2B, 3, 10, and 11, a part of the liquid flows from the inlet 10 to the first microchamber 201, and a part of the liquid flows to the second microchamber 202. The speed of the portion of the liquid flowing from the inlet 10 to the first microchamber 201 is much greater than the speed of the portion of the liquid flowing from the first branch point BP1 to the second microchamber 202. The first microchamber 201 is filled before the second microchamber 202 is completely filled, and the completely filled first microchamber 202 and the completely filled second microchamber 202 may be detected at different time periods (optionally, non-overlapping time periods), thereby eliminating or significantly reducing cross-talk between the different signals detected in the first microchamber 201 and the second microchamber 202, respectively. In one example, cross-contamination between first microchamber 201 and second microchamber 202 may be eliminated or substantially reduced.

In another example, referring to fig. 4, the first included angle α is 150 degrees and the second included angle β is 90 degrees. Fig. 12 is a schematic diagram illustrating a moving speed of a liquid in a microfluidic structure in a plan view in some embodiments of the present disclosure. Fig. 13 is a schematic diagram illustrating a moving speed of a liquid in a microfluidic structure in a perspective view in some embodiments of the present disclosure. Referring to fig. 2A, 2B, 3, 12 and 13, the velocity of a portion of the liquid flowing from the inlet 10 to the first microchamber 201 is much greater than the velocity of a portion of the liquid flowing from the first branch point BP1 to the second microchamber 202. The first microchamber 201 is completely filled before the second microchamber 202 is completely filled, and the completely filled first microchamber 201 and the completely filled second microchamber 202 may be detected in different time periods (optionally, non-overlapping time periods), thereby eliminating or significantly reducing cross-talk between the different signals detected in the first microchamber 201 and the second microchamber 202, respectively. In one example, cross-contamination between first microchamber 201 and second microchamber 202 may be eliminated or substantially reduced.

To allow the upstream microchamber (e.g., first microchamber) to be filled with liquid before the liquid changes its direction towards the downstream microchamber (e.g., second microchamber), optionally, the second included angle β is decreased to increase the resistance to flow of liquid to the downstream microchamber, e.g., the second included angle β is 60 degrees, 45 degrees, or 30 degrees; optionally, the first angle α is increased to reduce the resistance of the liquid to flow to the upstream microchamber, e.g., the first angle α is 120 degrees, 150 degrees, or 180 degrees.

In another aspect, the present disclosure also provides a microfluidic system. In some embodiments, a microfluidic system includes a microfluidic structure described herein and one or more sensing circuits.

In another aspect, the present disclosure also provides a microfluidic method. Fig. 14 is a flow chart illustrating a microfluidic method in some embodiments according to the present disclosure. In some embodiments, referring to fig. 14, a microfluidic method includes receiving a liquid from an inlet of a microfluidic structure; and delivering different portions of the liquid to the plurality of microchambers, respectively, in a time sequence, through a microchannel connected to the inlet and to the plurality of microchambers. Optionally, the microchannel includes a trunk and a plurality of branches connecting the plurality of microchambers with the trunk, respectively. Optionally, the plurality of branches are successively arranged along the length of the trunk, and are connected to the trunk at a plurality of branch points successively arranged along the length of the trunk, respectively. Optionally, two adjacent microchambers of the plurality of microchambers are spaced apart from each other by at least two adjacent branch points of the plurality of branch points.

In some embodiments, delivering different portions of the liquid to the plurality of microchambers, respectively, in a time sequence, through the microchannel comprises: moving the liquid from the inlet to the stem; and delivering the different portions of the liquid to the plurality of branches, respectively, in a time sequence.

When a portion of the liquid first moves to a respective one of the plurality of branch points, a majority of the portion of the liquid is distributed into the respective one of the plurality of branches, and a minority of the portion of the liquid is distributed into a portion of the trunk in a downstream immediately adjacent to the respective one of the plurality of branch points; and when the one of the plurality of branches is filled with liquid, the liquid is directed to a portion of the trunk in a downstream immediately adjacent to the one of the plurality of branch points.

In some embodiments, referring to fig. 2A, 3 and 4, the microfluidic method further comprises: the liquid passing direction at a respective one of the plurality of branch points BP is controlled such that the liquid in the first portion P1 of the trunk 31 in the immediately upstream of said respective one of the plurality of branch points BP has a first liquid passing direction D1, the liquid in the second portion P2 of the respective one of the plurality of branches 32 in the immediately downstream of said respective one of the plurality of branch points BP has a second liquid passing direction D2, and the liquid in the third portion P3 of the trunk 31 in the immediately downstream of said respective one of the plurality of branch points BP has a third liquid passing direction D3.

Optionally, the first liquid passing direction D1, the second liquid passing direction D2, and the third liquid passing direction D3 divide the microfluidic structure into three non-overlapping regions at the one corresponding branch point of the plurality of branch points BP, including a first region R1 between the first liquid passing direction D1 and the second liquid passing direction D2, a second region R2 between the first liquid passing direction D1 and the third liquid passing direction D3, and a third region R3 between the second liquid passing direction D2 and the third liquid passing direction D3.

Optionally, a first side S1 of the first region R1 along the first liquid passing direction D1 and a second side S2 of the first region R1 along the second liquid passing direction D2 form a first included angle α in the first region R1.

Alternatively, the third side S3 of the second region R2 along the first liquid passing direction D1 and the fourth side S4 of the second region R2 along the third liquid passing direction D3 form a second included angle β in the second region R2.

Optionally, a liquid passing direction of the liquid at a corresponding one of the plurality of branch points is controlled such that α is larger than β.

Alternatively, 90 degrees ≦ α ≦ 270 degrees, e.g., 90 degrees ≦ α ≦ 140 degrees, 140 degrees ≦ α ≦ 190 degrees, 190 degrees ≦ α ≦ 240 degrees, 240 degrees ≦ α ≦ 270 degrees. Optionally, the first included angle α is in a range of 110 degrees to 130 degrees, for example, the first included angle α is 120 degrees. Optionally, the first included angle α is in a range of 140 degrees to 160 degrees, for example, the first included angle α is 150 degrees. Optionally, the first included angle α is in a range of 170 degrees to 190 degrees, for example, the first included angle α is 180 degrees.

Alternatively, 0 degrees < β ≦ 120 degrees, such as 0 degrees < β ≦ 20 degrees, 20 degrees ≦ β ≦ 40 degrees, 40 degrees ≦ β ≦ 60 degrees, 60 degrees ≦ β ≦ 80 degrees, 80 degrees ≦ β ≦ 100 degrees, 100 degrees ≦ β ≦ 120 degrees. Optionally, the second included angle β is in a range of 20 degrees to 40 degrees, for example, the second included angle β is 30 degrees. Optionally, the second included angle β is in a range of 50 degrees to 70 degrees, for example, the second included angle β is 60 degrees. Optionally, the second included angle β is in the range of 80 degrees to 100 degrees, for example, the second included angle is 90 degrees β.

Alternatively, 165 degrees ≦ α ≦ 195 degrees, e.g., 165 degrees ≦ α ≦ 175 degrees, 175 degrees ≦ α ≦ 185 degrees, and 185 degrees ≦ α ≦ 195 degrees, and 75 degrees ≦ β ≦ 105 degrees, e.g., 75 degrees ≦ β ≦ 85 degrees, 85 degrees ≦ β ≦ 95 degrees, 95 degrees ≦ β ≦ 105 degrees.

In some embodiments, referring to fig. 2A, the microfluidic method further comprises: air is discharged from the plurality of micro chambers 20 while the liquid is retained in the plurality of micro chambers 20 through the plurality of outlets 40 respectively connected to the plurality of micro chambers 20. Because the air in a respective one of the plurality of microchambers 20 is pushed by a portion of the liquid out of a respective one of the plurality of microchambers 20 through a respective one of the plurality of outlets 40, the respective one of the plurality of microchambers 20 is filled with the portion of the liquid.

In some embodiments, referring to fig. 6, 7 and 8, the microfluidic method further comprises: liquid is released from the main trunk 31 to the waste outlet 41 through the waste branch 33. Optionally, the waste liquid branch 33 and the immediately adjacent branches of the plurality of branches 32 are connected to the backbone 31 at the immediately adjacent branch point BP0 of the plurality of branch points BP.

In some embodiments, the microfluidic method further comprises controlling the liquid passage direction of the liquid immediately at the branch point BP0 such that the liquid in the portion P4 of the stem 31 in the upstream immediately adjacent to the branch point BP0 has a fourth liquid passage direction D4, the liquid in the portion P5 immediately adjacent to the branch 321 has a fifth liquid passage direction D5, and the liquid in the portion P6 of the waste liquid branch 33 has a sixth liquid passage direction D6.

Alternatively, immediately adjacent to the branch point BP0, the fourth liquid passing direction D4, the fifth liquid passing direction D5 and the sixth liquid passing direction D6 divide the microfluidic structure into three non-overlapping regions including a fourth region R4 between the fourth liquid passing direction D4 and the fifth liquid passing direction D5, a fifth region R5 between the fourth liquid passing direction D4 and the sixth liquid passing direction D6, and a sixth region R6 between the fifth liquid passing direction D5 and the sixth liquid passing direction D6.

Alternatively, the fifth side S5 of the fourth region R4 along the fourth liquid passing direction D4 and the sixth side S6 of the fourth region R4 along the fifth liquid passing direction D5 form a third included angle γ in the fourth region R4.

Alternatively, the seventh side S7 of the fifth region R5 along the fourth liquid passing direction D4 and the eighth side S8 of the fifth region R5 along the sixth liquid passing direction D6 form a fourth included angle ∈ in the fifth region R5.

Optionally, the liquid passing direction of the liquid at the point immediately adjacent to the branch point is controlled such that γ is greater than ε.

Optionally 90 degrees ≦ γ ≦ 270 degrees, e.g., 90 degrees ≦ γ ≦ 140 degrees, 140 degrees ≦ γ ≦ 190 degrees, 190 degrees ≦ γ ≦ 240 degrees, and 240 degrees ≦ γ ≦ 270 degrees, optionally the third included angle γ is in the range of 110 degrees to 130 degrees, e.g., the third included angle γ is 120 degrees. Optionally, the third included angle γ is in a range of 140 degrees to 160 degrees, for example, the third included angle γ is 150 degrees. Optionally, the third included angle γ is in a range of 170 degrees to 190 degrees, for example, the third included angle γ is 180 degrees.

Alternatively, 0 degrees < ε ≦ 120 degrees, e.g., 0 degrees < ε ≦ 20 degrees, 20 degrees ≦ ε ≦ 40 degrees, 40 degrees ≦ ε ≦ 60 degrees, 60 degrees ≦ ε ≦ 80 degrees, 80 degrees ≦ ε ≦ 100 degrees, 100 degrees ≦ ε ≦ 120 degrees. Optionally, the fourth angle e is in the range of 20 degrees to 40 degrees, e.g. the fourth angle e is 30 degrees. Optionally, the fourth angle ε is in a range of 50 degrees to 70 degrees, for example, the fourth angle is 60 degrees. Optionally, the fourth angle e is in the range of 80 degrees to 100 degrees, e.g. the fourth angle e is 90 degrees.

Alternatively, 165 degrees ≦ γ ≦ 195 degrees, e.g., 165 degrees ≦ γ ≦ 175 degrees, 175 degrees ≦ γ ≦ 185 degrees, and 185 degrees ≦ γ ≦ 195 degrees, and 75 degrees ≦ ε ≦ 105 degrees, e.g., 75 degrees ≦ ε ≦ 85 degrees, 85 degrees ≦ ε ≦ 95 degrees, and 95 degrees ≦ ε ≦ 105 degrees.

In some embodiments, the microfluidic method further comprises: detecting a target substance at a respective one of the plurality of microchambers. Examples of microfluidic methods also include, but are not limited to, sequencing of a substance (e.g., sequencing of DNA molecules), detecting a reaction between a target substance and a reagent, analyzing the target substance. For example, multiple microchambers can be used to perform enzymatic analysis (e.g., glucose and lactate assays), DNA analysis (e.g., DNA sequencing, polymerase chain reaction PCR, autonomous sequence replication 3SR), protein analysis, and chemical synthesis analysis.

By arranging the plurality of branches in succession in sequence along the length of the trunk, the liquid entering the inlet can sequentially fill the plurality of microchambers connected to the plurality of branches, respectively. Because the plurality of microchambers are sequentially filled along the length of the stem, different microchambers are filled in different time periods (e.g., different time periods at least do not completely overlap) in chronological order. Thus, detectors optically coupled to different microchambers, respectively, can detect the following reaction products, respectively: the reaction products are formed by filling portions of the liquid in different microchambers respectively at different time periods (e.g., in a time sequence and optionally non-overlapping time periods) and at different locations corresponding to the different microchambers. As a result, the detection window time used by the detector may be reduced, and the amount of work required to process the amount of data collected from the detection process may be reduced. The need for computational resources required to process the amount of data collected from the detection process may be reduced.

For example, during the detection process, the detection signal is applied to a respective one of the plurality of microchambers, and a respective one of the plurality of detectors corresponding to the respective one of the plurality of microchambers detects a change in the detection signal. In order to detect different substances or different properties of substances in different microchambers, respectively, different detection signals may be applied to different microchambers, respectively. When different detection signals are applied simultaneously, crosstalk between the different detection signals may adversely affect the results of the detection process. The microfluidic methods described herein allow different microchambers to be filled at different time periods, so that different detectors can detect different microfluidic microchambers at different time periods, which can prevent cross-talk between different detection signals used in different detection processes. Optionally, the different detection signals comprise different light rays having different wavelength ranges.

The moving speed of the liquid entering the microfluidic structure can be accurately controlled, so that the time spent by the liquid moving from the inlet to different microchambers and filling the different microchambers can be accurately calculated, and the detector can be accurately controlled to perform detection processing on different positions corresponding to the different microchambers in different time periods. In one example, different detectors are provided corresponding to different microchambers. In another example, the detector is configured to move to different positions to detect different microchambers in different time periods.

In one example, a plurality of microchambers are provided with different reactants in advance, and a sample is provided in the form of a liquid flowing through a microchannel. Different portions of the liquid are delivered to the plurality of microchambers, respectively. The microfluidic structures described herein fill portions of a sample into multiple microchambers at different (e.g., non-overlapping) time periods in a time sequential manner, thereby minimizing cross-contamination between different reactants in the multiple microchambers.

However, in the microfluidic structures described herein, once a respective one of the plurality of microchambers is completely filled, the liquid pressure at the respective one of the plurality of microchambers is greater than the liquid pressure at the portion of the trunk in the downstream immediately adjacent to the respective one of the plurality of branch points, the liquid will continue to flow along the trunk to the next microchamber, and the interaction between the portion of the liquid (e.g., the mixed liquid) in the respective one of the plurality of microchambers and the portion of the liquid in the trunk is substantially reduced, which prevents the mixed liquid from flowing out of the respective one of the plurality of microchambers.

In the microfluidic structures described herein, a much shorter duration (e.g., 1-1.2 seconds) is required for the liquid to completely fill a respective one of the plurality of microchambers, and the relatively fast fill process effectively prevents contamination between the microchambers. In addition, the mixing process between the liquid and the reagent in a corresponding one of the plurality of micro-chambers is performed within 1 second to 1.2 seconds, during which the detector may perform the detection process. This enables the detector to detect the reaction between the liquid (e.g., biological sample) and the reagent in a timely manner (e.g., at the peak of the reaction).

In some embodiments, the moving speed of the liquid may be controlled by adjusting an angle between the stem in an upstream immediately adjacent to a respective branch point of the plurality of branch points and a respective branch in a downstream immediately adjacent to the respective branch point of the plurality of branch points. An angle between a trunk in an upstream immediately adjacent to the one of the plurality of branch points and the one of the plurality of branches in a downstream immediately adjacent to the one of the plurality of branch points does not cover the following area: the region has a skeleton in a downstream immediately adjacent to the respective one of the plurality of branch points.

In another aspect, the present disclosure also provides a method of manufacturing a microfluidic structure. Fig. 15 is a flow diagram illustrating a method of fabricating a microfluidic structure in some embodiments according to the present disclosure. In some embodiments, referring to fig. 15, a method of fabricating a microfluidic structure comprises: forming an inlet; forming a plurality of microchambers; and forming a microchannel connected to the inlet and to the plurality of microchambers. Optionally, forming the microchannel comprises: forming a trunk and forming a plurality of branches respectively connecting the plurality of microchambers with the trunk. Optionally, the plurality of branches are arranged successively along the length of the trunk, and the plurality of branches are connected to the trunk at a plurality of branch points arranged successively along the length of the trunk, respectively. Optionally, two adjacent microchambers of the plurality of microchambers are spaced apart from each other by at least two adjacent branch points of the plurality of branch points.

In some embodiments, at a respective one of the plurality of branch points, the portion of the trunk in the upstream immediately adjacent to the respective one of the plurality of branch points, the portion of the respective one of the plurality of branches in the downstream immediately adjacent to the respective one of the plurality of branch points, and the portion of the trunk in the downstream immediately adjacent to the respective one of the plurality of branch points are formed to divide the microfluidic structure into three non-overlapping regions including a first region between the portion of the trunk in the upstream immediately adjacent to the respective one of the plurality of branch points and the portion of the respective one of the plurality of branches in the downstream immediately adjacent to the respective one of the plurality of branch points, a second region between the portion of the trunk in the upstream immediately adjacent to the respective one of the plurality of branch points and the portion of the trunk in the downstream immediately adjacent to the respective one of the plurality of branch points, and a third region between the first region and the second region Between portions of the trunk in a downstream immediately adjacent to the one respective branch point of the plurality of branch points, the third area being located between a portion of the one respective branch of the plurality of branches in a downstream immediately adjacent to the one respective branch point of the plurality of branch points and a portion of the trunk in a downstream immediately adjacent to the one respective branch of the plurality of branch points.

Optionally, a first side of the first region and a second side of the first region form a first included angle α, 90 degrees ≦ α ≦ 270 degrees, in the first region, the first side of the first region being along a first liquid passing direction of the portion of the trunk in the upstream immediately adjacent to the respective one of the plurality of branch points and being immediately adjacent to the portion of the trunk in the upstream immediately adjacent to the respective one of the plurality of branch points, the second side of the first region being along a second liquid passing direction of the portion of the respective one of the plurality of branches in the downstream immediately adjacent to the respective one of the plurality of branch points and being immediately adjacent to the respective one of the plurality of branch points.

Optionally, a third side of the second region and a fourth side of the second region form a second included angle β, 0 degrees < β ≦ 120 degrees, in the second region, the third side of the second region being along the first liquid passing direction of the portion of the backbone in the immediately upstream of the respective one of the plurality of branch points and being immediately adjacent to the portion of the backbone in the immediately upstream of the respective one of the plurality of branch points, the fourth side of the second region being along the third liquid passing direction of the portion of the backbone in the immediately downstream of the respective one of the plurality of branch points and being immediately adjacent to the portion of the backbone in the immediately downstream of the respective one of the plurality of branch points.

Optionally, α is greater than β.

In some embodiments, a method of fabricating a microfluidic structure comprises: a plurality of outlets respectively connected to the plurality of microchambers are formed.

In some embodiments, a method of fabricating a microfluidic structure comprises: a gas-permeable, liquid-impermeable membrane is disposed to cover the plurality of outlets, allowing air to be expelled from the plurality of microchambers while retaining liquid inside the plurality of microchambers.

In some embodiments, a method of fabricating a microfluidic structure comprises: forming a waste liquid outlet for releasing liquid in the trunk; and forming a waste microchamber connecting the waste outlet and the microchannel.

In some embodiments, a method of fabricating a microfluidic structure comprises: a waste branch is formed connecting the waste microchamber to the main. Optionally, a waste branch and an immediately adjacent branch of the plurality of branches are formed to connect to the trunk at an immediately adjacent branch point of the plurality of branch points.

Optionally, at the immediately adjacent branch point, the portion of the trunk in the upstream immediately adjacent to the immediately adjacent branch point, the portion of the immediately adjacent branch, and the portion of the waste liquid branch are formed to divide the microfluidic structure into three non-overlapping regions including a fourth region between the portion of the trunk in the upstream immediately adjacent to the immediately adjacent branch point and the portion of the immediately adjacent branch, a fifth region between the portion of the trunk in the upstream immediately adjacent to the immediately adjacent branch point and the portion of the waste liquid branch, and a sixth region between the portion of the immediately adjacent branch and the portion of the waste liquid branch.

Optionally, a fifth side of the fourth region and a sixth side of the fourth region form a third angle γ in the fourth region, 90 degrees ≦ γ ≦ 270 degrees, the fifth side of the fourth region being along a fourth liquid passing direction of the portion of the trunk in the immediately upstream of the immediately adjacent branch point and abutting the portion of the trunk in the immediately upstream of the immediately adjacent branch point, the sixth side of the fourth region being along a fifth liquid passing direction of the portion of the immediately adjacent branch and abutting the portion of the immediately adjacent branch.

Optionally, a seventh side of a fifth region and an eighth side of the fifth region form a fourth angle ∈ 0 degrees < ≦ 120 degrees in the fifth region, the seventh side of the fifth region being along a fourth liquid passing direction of the portion of the trunk in an upstream immediately upstream of the immediately adjacent branch point and being immediately adjacent to the portion of the trunk in an upstream immediately upstream of the immediately adjacent branch point, the eighth side of the fifth region being along a sixth liquid passing direction of the portion of the waste liquid branch and being immediately adjacent to the portion of the waste liquid branch.

Optionally, γ is greater than ε.

Alternatively, 165 degrees ≦ γ ≦ 195 degrees, 75 degrees ≦ ε ≦ 105 degrees.

In some embodiments, the immediately adjacent branch is formed as the last branch of the plurality of branches arranged in succession in turn. The immediately adjacent branch point is formed as the last branch point among a plurality of branch points arranged in succession in order. The waste liquid branch and the waste liquid microchamber are formed to be spaced apart from the inlet by a trunk connected to the plurality of branches.

In some embodiments, the plurality of microchambers is formed as a plurality of detection chambers. Optionally, a respective one of the plurality of microchambers is optically coupled to the detector.

The foregoing descriptions of embodiments of the present disclosure have been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the disclosure to the precise form or exemplary embodiments disclosed. The foregoing description is, therefore, to be considered illustrative rather than restrictive. Obviously, many modifications and variations will be apparent to practitioners skilled in the art. The embodiments were chosen and described in order to explain the principles of the disclosure and its best mode practical application to enable one skilled in the art to understand the disclosure for various embodiments and with various modifications as are suited to the particular use or implementation contemplated. It is intended that the scope of the disclosure be defined by the following claims and their equivalents, and that all terms are to be given their broadest reasonable meaning unless otherwise indicated. Thus, the terms "disclosure," "present disclosure," and the like, do not necessarily limit the scope of the claims to particular embodiments, and reference to exemplary embodiments of the disclosure is not meant to limit the disclosure, and no such limitation is to be inferred. The present disclosure is to be limited only by the spirit and scope of the appended claims. Furthermore, these claims may refer to the use of "first," "second," etc., these words being followed by a noun or element. These terms should be understood as nomenclature and should not be construed as limiting the number of elements modified by these nomenclature, unless a specific number has been given. Any advantages and benefits described may not apply to all embodiments of the disclosure. It should be understood that variations may be made in the described embodiments by those skilled in the art without departing from the scope of the present disclosure as defined by the appended claims. Furthermore, no element or component in the present disclosure is intended to be dedicated to the public regardless of whether the element or component is explicitly recited in the appended claims.

Claims

1. A microfluidic structure comprising:

an inlet;

a plurality of microchambers; and

a microchannel connected to the inlet and to the plurality of microchambers;

wherein the microchannel comprises a trunk and a plurality of branches connecting the plurality of microchambers with the trunk, respectively;

the plurality of branches are arranged in succession along the length of the trunk and are connected to the trunk at a plurality of branch points arranged in succession along the length of the trunk, respectively; and

two adjacent microchambers of the plurality of microchambers are spaced apart from each other by at least two adjacent branch points of the plurality of branch points.

2. The microfluidic structure according to claim 1, wherein, at a respective one of the plurality of branch points, the portion of the trunk in the upstream immediately adjacent to the respective one of the plurality of branch points, the portion of the respective one of the plurality of branches in the downstream immediately adjacent to the respective one of the branch points, and the portion of the trunk in the downstream immediately adjacent to the respective one of the plurality of branch points divide the microfluidic structure into three non-overlapping regions including a first region, a second region, and a third region, wherein the first region is located between the portion of the trunk in the upstream immediately adjacent to the respective one of the plurality of branch points and the portion of the respective one of the plurality of branches in the downstream immediately adjacent to the respective one of the plurality of branch points, the second area is located between a portion of the trunk in an upstream immediately upstream of the respective one of the plurality of branch points and a portion of the trunk in a downstream immediately downstream of the respective one of the plurality of branch points, and the third area is located between a portion of the respective one of the plurality of branches immediately downstream of the respective one of the plurality of branch points and a portion of the trunk in a downstream immediately downstream of the respective one of the plurality of branch points;

A first side of the first zone and a second side of the first zone form a first included angle α, 90 degrees ≦ α ≦ 270 degrees, in the first zone, wherein the first side of the first zone follows a first liquid passing direction of the portion of the trunk in an upstream immediately adjacent to the respective one of the plurality of branch points and abuts the portion of the trunk in an upstream immediately adjacent to the respective one of the plurality of branch points, and the second side of the first zone follows a second liquid passing direction of the portion of the respective one of the plurality of branches in a downstream immediately adjacent to the respective one of the plurality of branch points and abuts the portion of the respective one of the plurality of branches in a downstream immediately adjacent to the respective one of the plurality of branch points;

a third side of a second region and a fourth side of the second region forming a second included angle β in the second region, 0 degrees < β ≦ 120 degrees, the third side of the second region along the first liquid passing direction of the portion of the backbone in the immediately upstream of the respective one of the plurality of branch points and immediately adjacent to the portion of the backbone in the immediately upstream of the respective one of the plurality of branch points, the fourth side of the second region along a third liquid passing direction of the portion of the backbone in the immediately downstream of the respective one of the plurality of branch points and immediately adjacent to the portion of the backbone in the immediately downstream of the respective one of the plurality of branch points; and is

Alpha is greater than beta.

3. The microfluidic structure of claim 2, wherein 165 degrees ≦ α ≦ 195 degrees and 75 degrees ≦ β ≦ 105 degrees.

4. The microfluidic structure according to any one of claims 1 to 3, further comprising a plurality of outlets respectively connected to the plurality of microchambers.

5. The microfluidic structure of claim 4, further comprising a gas-permeable, liquid-impermeable membrane covering the plurality of outlets, the membrane allowing air to vent from the plurality of microchambers while retaining liquid inside the plurality of microchambers.

6. The microfluidic structure of any one of claims 1 to 5, further comprising:

a waste outlet for draining liquid in the trunk; and

a waste microchamber connecting the waste outlet and the microchannel.

7. The microfluidic structure of claim 6, further comprising a waste branch connecting the waste microchamber to the backbone;

wherein the proximal branch of the plurality of branch points, the proximal branch of the plurality of branches, and the waste branch are connected to the backbone;

wherein, at the immediately adjacent branch point, the portion of the trunk in the upstream immediately adjacent to the immediately adjacent branch point, the portion of the immediately adjacent branch, and the portion of the waste liquid branch divide the microfluidic structure into three non-overlapping regions including a fourth region between the portion of the trunk in the upstream immediately adjacent to the immediately adjacent branch point and the portion of the immediately adjacent branch, a fifth region between the portion of the trunk in the upstream immediately adjacent to the immediately adjacent branch point and the portion of the waste liquid branch, and a sixth region between the portion of the immediately adjacent branch and the portion of the waste liquid branch;

A fifth side of the fourth region and a sixth side of the fourth region form a third included angle γ in the fourth region, 90 degrees ≦ γ ≦ 270 degrees, wherein the fifth side of the fourth region is along a fourth liquid passing direction of the portion of the trunk in an upstream immediately adjacent to the immediately adjacent branch point and abuts against the portion of the trunk in an upstream immediately adjacent to the immediately adjacent branch point, and the sixth side of the fourth region is along a fifth liquid passing direction of the portion of the immediately adjacent branch and abuts against the portion of the immediately adjacent branch;

a seventh side of the fifth region and an eighth side of the fifth region form a fourth angle e in the fifth region, 0 degrees < e ≦ 120 degrees, wherein the seventh side of the fifth region is along the fourth liquid passing direction of the portion of the trunk in the upstream immediately adjacent to the branch point and is next to the portion of the trunk in the upstream immediately adjacent to the branch point, and the eighth side of the fifth region is along the sixth liquid passing direction of the portion of the waste liquid branch and is next to the portion of the waste liquid branch; and is

Gamma is greater than epsilon.

8. The microfluidic structure of claim 7, wherein 165 degrees ≦ γ ≦ 195 degrees, and 75 degrees ≦ ε ≦ 105 degrees.

9. The microfluidic structure according to any one of claims 7 to 8, wherein the immediately adjacent branch is a last branch of the plurality of branches arranged in series in order;

the immediately adjacent branch point is a last branch point of the plurality of branch points arranged successively in order; and

the waste branch and the waste microchamber are spaced from the inlet by a trunk connected to the plurality of branches.

10. The microfluidic structure of any one of claims 1 to 9, wherein the plurality of microchambers is a plurality of detection chambers, a respective one of the plurality of detection chambers being optically coupled to a detector.

11. A microfluidic system comprising a microfluidic structure according to any one of claims 1 to 10 and one or more sensing circuits.

12. A microfluidic method comprising:

receiving a liquid from an inlet of a microfluidic structure; and

delivering different portions of the liquid to the plurality of microchambers, respectively, in a time sequence, through a microchannel connected to the inlet and to the plurality of microchambers;

two adjacent microchambers of the plurality of microchambers are spaced apart from each other by at least two adjacent branch points of the plurality of branch points;

delivering different portions of the liquid through the microchannel in a time sequence to the plurality of microchambers, respectively, comprises:

moving the liquid from the inlet to the stem; and

delivering the different portions of the liquid into the plurality of branches, respectively, in a time sequence.

13. The method of claim 12, wherein when a portion of liquid is first moved to a respective one of the plurality of branch points, a majority of the portion of liquid is distributed into the respective one of the plurality of branches and a minority of the portion of liquid is distributed to a portion of the trunk in a downstream immediate vicinity of the respective one of the plurality of branch points; and

when the one of the plurality of branches is filled with liquid, the liquid is directed to a portion of the trunk in a downstream immediately adjacent to the one of the plurality of branch points.

14. The method of claim 13, further comprising controlling a liquid passing direction of the liquid at the one of the plurality of branch points such that the liquid in the portion of the trunk in an upstream immediately upstream of the one of the plurality of branch points has a first liquid passing direction, the liquid in the portion of the one of the plurality of branches in a downstream immediately adjacent to the one of the plurality of branch points has a second liquid passing direction, the liquid in the portion of the trunk in a downstream immediately adjacent to the one of the plurality of branch points has a third liquid passing direction;

wherein the first liquid passing direction, the second liquid passing direction, and the third liquid passing direction divide the microfluidic structure into three non-overlapping regions at the one corresponding branch point of the plurality of branch points, the three non-overlapping regions including a first region, a second region, and a third region, the first region being located between the first liquid passing direction and the second liquid passing direction, the second region being located between the first liquid passing direction and the third liquid passing direction, the third region being located between the second liquid passing direction and the third liquid passing direction;

A first side of the first area along the first liquid passing direction and a second side of the first area along the second liquid passing direction form a first included angle a in the first area; and is

A third side of the second region along the first liquid passing direction and a fourth side of the second region along the third liquid passing direction form a second included angle β in the second region;

wherein a liquid passing direction of the liquid at the corresponding one of the plurality of branch points is controlled such that α is larger than β, 90 degrees ≦ α ≦ 270 degrees, and 0 degrees ≦ β ≦ 120 degrees).

15. The method of claim 14, wherein 165 degrees ≦ α ≦ 195 degrees and 75 degrees ≦ β ≦ 105 degrees.

16. The method of any of claims 12 to 15, further comprising: discharging air from the plurality of microchambers while retaining liquid inside the plurality of microchambers through a plurality of outlets respectively connected to the plurality of microchambers.

17. The method of any of claims 12 to 16, further comprising: releasing liquid from the trunk to a waste outlet through a waste branch;

wherein, at an immediately adjacent branch point of the plurality of branch points, the immediately adjacent branch of the plurality of branches and the waste branch are connected to the trunk.

18. The method of claim 17, further comprising: controlling a liquid passing direction of the liquid at the immediately adjacent branch point such that the liquid in a portion of the trunk in an immediately upstream of the immediately adjacent branch point has a fourth liquid passing direction, the liquid in the immediately adjacent branch portion has a fifth liquid passing direction, and the liquid in the waste liquid branch portion has a sixth liquid passing direction;

wherein, at the immediately adjacent branch point, the fourth liquid passing direction, the fifth liquid passing direction, and the sixth liquid passing direction divide the microfluidic structure into three non-overlapping regions including a fourth region, a fifth region, and a sixth region, wherein the fourth region is located between the fourth liquid passing direction and the fifth liquid passing direction, the fifth region is located between the fourth liquid passing direction and the sixth liquid passing direction, and the sixth region is located between the fifth liquid passing direction and the sixth liquid passing direction;

a fifth side of the fourth region along the fourth liquid passing direction and a sixth side of the fourth region along the fifth liquid passing direction form a third angle γ in the fourth region;

A seventh side of the fifth region along the fourth liquid passing direction and an eighth side of the fifth region along the sixth liquid passing direction form a fourth angle epsilon in the fifth region;

and controlling the liquid passing direction of the liquid at the adjacent branch point so that gamma is greater than epsilon, 90 degrees or more and gamma is less than or equal to 270 degrees, and 0 degree < epsilon is less than or equal to 120 degrees.

19. The method of claim 18, wherein 165 degrees ≦ γ ≦ 195 degrees and 75 degrees ≦ ε ≦ 105 degrees.

20. The method of any of claims 12 to 19, further comprising: detecting a target substance at a respective one of the plurality of microchambers.

21. A method of fabricating a microfluidic structure, comprising:

forming an inlet;

forming a plurality of microchambers; and

forming a microchannel connected to the inlet and to the plurality of microchambers;

wherein forming the microchannel comprises: forming a trunk and forming a plurality of branches respectively connecting the plurality of microchambers with the trunk;