The present disclosure relates to the field of biological detection technology, and in particular to a microfluidic chip.
The microfluid control technology may realize the accurate control and manipulation of micro-droplets. The digital microfluid control based on the dielectric wetting technology adopts an electrical signal to drive, which has the advantages of strong driving force, simple and convenient operation and control, simple chip structure, high automation degree and the like, and is an important component of a lab-on-a-chip system.
Digital Microfluidics (DMF) utilizes the electrowetting principle of droplets on a hydrophobic surface, and applies a control signal to an electrode array to cause a contact angle of the droplets to change, thereby realizing the accurate control of the droplets. Compared with the conventional flow channel type microfluidic chip, a power source of the digital microfluidic chip is an electric signal, and the digital microfluidic chip does not need a micro pump, a micro valve and other driving devices, and the chip structure and control are simple. The micro-channels in the digital microfluidic chip are not complex, a moving path of the droplets may be controlled by timing, and a plurality of micro droplets may be operated in parallel, improving the flux. The amount of the consumed reagent is less. The digital microfluidic chip has great advantages in the aspects of analysis scale, response speed, high flux and the like, and has wide research and application in the fields of biology, chemistry, medicine and the like.
The invention aims to solve at least one of technical problems in the prior art and provides a microfluidic chip.
The embodiment of the present disclosure provides a microfluidic chip, including a middle region and a peripheral region surrounding the middle region; the middle region includes a liquid storage region and a detection region; the microfluidic chip includes a first substrate and a second substrate opposite to each other; the first substrate includes a first base plate and a first electrode layer on a side of the first base plate proximal to the second substrate; the second substrate includes a second base plate and a second electrode layer on a side of the second base plate proximal to the first substrate; wherein
a liquid storage tank and a liquid inlet are on a side of the first base plate proximal to the second substrate, the liquid inlet penetrates through a bottom of the liquid storage tank; the liquid storage tank and the liquid inlet are both in the liquid storage region;
a cross section of the liquid storage tank taken along a thickness direction of the first substrate and a direction parallel to a direction in which the liquid storage region points towards the detection region has a first side proximal to the detection region; the first side has a first end point and a second end point, and the first end point is farther away from the second substrate than the second end point; an extending direction of a line connecting the first end point and the second end point is inclined with respect to an axial direction of the liquid inlet, and a distance from the first end point to an axis of the liquid inlet is smaller than a distance from the second end point to the axis of the liquid inlet.
In some embodiments, the first side is a straight side.
In some embodiments, an angle θ between the extending direction of the line connecting the first end point and the second end point and the axial direction of the liquid inlet is 30° or −60°.
In some embodiments, an interlayer dielectric layer is on a side of the second electrode layer distal to the second base plate; an angle between the extending direction of the line connecting the first end point and the second end point and the axial direction of the liquid inlet is θ:
tan θ>2d(F−G)/ε0 εrV2, where ε0 represents a vacuum dielectric constant; εr represents a relative dielectric constant of the interlayer dielectric layer; d is a thickness of the interlayer dielectric layer; F represents a support force applied by the interlayer dielectric layer on a droplet to be detected; G represents the gravity of the droplet to be detected; V represents a voltage value applied to the second electrode layer.
In some embodiments, the liquid inlet includes a first port and a second port, and the liquid inlet is communicated with the liquid storage tank through the first port; an orthographic projection of the first port on the second base plate at least partially overlaps an orthographic projection of the second electrode layer on the second base plate.
In some embodiments, an orthographic projection of an edge of the second electrode layer on the second base plate passes through a center of the orthographic projection of the first port on the second base plate; or
the orthographic projection of the edge of the second electrode layer on the second base plate is in contact with an edge of the orthographic projection of the first port on the second base plate.
In some embodiments, the liquid inlet includes a first port and a second port opposite to each other, and the liquid inlet is communicated with the liquid storage tank through the first port; an orthographic projection of the second port on the second base plate covers an orthographic projection of the first port on the second base plate.
In some embodiments, the microfluidic chip further includes a liquid inlet column; the liquid inlet column and the liquid inlet are coaxially arranged; the liquid inlet includes a first port and a second port opposite to each other, and the liquid inlet is communicated with the liquid storage tank through the first port; the liquid inlet column includes a third port and a fourth port opposite to each other; the third port of the liquid inlet column is connected with the second port of the liquid inlet.
In some embodiments, the microfluidic chip further includes a liquid inlet column; the liquid inlet column and the liquid inlet are coaxially arranged; the liquid inlet includes a first port and a second port opposite to each other, and the liquid inlet is communicated with the liquid storage tank through the first port; the liquid inlet column includes a third port and a fourth port opposite to each other; an orthographic projection of the third port of the liquid inlet column on the second base plate is in an orthographic projection of the fourth port on the second base plate.
In some embodiments, the first port and the second port of the liquid inlet have a same aperture.
In some embodiments, a sealant is between the first substrate and the second substrate and in the peripheral region and surrounds the middle region.
In some embodiments, a first receiving groove is on a side of the first base plate proximal to the second substrate, and the sealant is in the first receiving groove.
In some embodiments, a conductive component is between the first substrate and the second substrate and in the peripheral region, and is configured to electrically connecting the first electrode layer with a connection pad on the second substrate.
In some embodiments, a second receiving groove is on a side of the first base plate proximal to the second substrate, and the conductive component is in the second receiving groove.
In some embodiments, a support structure is between the first substrate and the second substrate, and is configured to maintain a cell gap between the first substrate and the second substrate.
In some embodiments, a gas outlet is on the first base plate and penetrates through the first base plate in a thickness direction.
In some embodiments, a first hydrophobic layer is on a side of the first electrode layer proximal to the second substrate; and
a second hydrophobic layer is on a side of the second electrode layer proximal to the second substrate.
To enable one of ordinary skill in the art to better understand technical solutions of the present disclosure, the present disclosure will be further described in detail below with reference to the accompanying drawings and exemplary embodiments.
Unless defined otherwise, technical or scientific terms used herein should have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure belongs. The terms of “first”, “second”, and the like herein are not intended to indicate any order, quantity, or importance, but rather are used for distinguishing one element from another. Further, the terms of “a”. “an”, “the”, or the like used herein does not denote a limitation of quantity, but rather denote the presence of at least one element. The term of “comprising”, “including”, or the like, means that the element or item preceding the term contains the element or item listed after the term and the equivalent thereof, but does not exclude the presence of other elements or items. The terms “connected”, “coupled”, and the like are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect connections. The terms “upper”, “lower”, “left”, “right”, and the like are used only for indicating relative positional relationships, and when the absolute position of an object being described is changed, the relative positional relationships may also be changed accordingly.
Since the trend of the first side L1 of the cross section of the liquid storage tank 112 shown in
In some examples, there is an angle θ between the trend of the first side L1 of the cross section of the liquid storage tank 112 shown in
In some examples, the microfluidic chip further includes an interlayer dielectric layer 23 disposed on a side of the second electrode layer 22 distal to the second base plate 21; the angle between the extending direction of the line connecting the first end point and the second end point of the first side L1 and the direction of the axis of the liquid inlet 111 is θ; tan θ>2d(F−G)/ε0 εr V2, where ε0 represents a vacuum dielectric constant, εr represents the relative dielectric constant of the interlayer dielectric layer; d is a thickness of the interlayer dielectric layer 23; F represents a support force applied by the interlayer dielectric layer 23 on the droplet to be detected; G represents the gravity of the droplet to be detected; V represents a voltage value applied to the second electrode layer. The interlayer dielectric layer may be a single-layer film, such as a polyimide film. Alternatively, the interlayer dielectric layer may also be a composite film of a polyimide film and a hydrophobic layer layer.
In some examples, the liquid storage tank 112 on the first base plate 11 may be a rectangular-like tank, i.e., having four side walls and a bottom wall; or may also be a cylindrical-like tank, i.e. having only one side wall and one bottom wall. The embodiment of the present disclosure will be described by taking an example in which the liquid storage tank 112 has four side walls and a bottom wall. For example: two side walls arranged opposite to each other in the direction that the liquid storage region Q11 points towards the detection region Q12 are respectively a first side wall and a second side wall, and the other pair of side walls arranged opposite to each other is a third side wall and a fourth side wall; wherein, a dihedral angle between the bottom wall and the second side wall, the third side wall or the fourth side wall is 90 degrees or approximately 90 degrees, and a dihedral angle between the bottom wall and the first side wall is an obtuse angle, for example in the range of 120 to 150 degrees. For example, the dihedral angle between the first side wall and the bottom wall is 135°. It should be noted that the dihedral angles described above refer to interior angles of the liquid storage tank 112. Alternatively, in the embodiment of the present disclosure, the second side wall, the third side wall and the fourth side wall may be disposed obliquely with respect to the bottom wall. In some examples, the dihedral angle between the bottom wall and the second side wall, the third side wall or the fourth side wall may be equal to the dihedral angle between the first side wall and the bottom wall.
Referring to
In some examples, the liquid storage tank 112 have a depth of about 200 μm to 500 μm and a volume of 5 μl to 100 μl. The depth of the liquid storage tank 112 may be reasonably designed to increase the storage capacity for the reaction liquid, so that the reagent amount entering the detection region Q12 is increased, and times of manually adding samples are effectively reduced.
In the embodiment of the present disclosure, the liquid inlet 111 penetrates through the bottom wall of the liquid storage tank 112, and the liquid inlet 111 may be cylindrical, conical, a combination of cylindrical and conical, and the like. Alternatively, a shape of the liquid inlet 11 needs to match a shape of a tip for the reaction liquid, so that the reaction liquid may be dropped into the liquid storage tank 112. The liquid inlet 111 according to the embodiment of the present disclosure is specifically described below.
In one example, as shown in
In another example,
In an example,
In some examples,
In some examples, no matter which structure is adopted for the liquid inlet 111 on the first base plate 11, an orthographic projection of the first port 111 of the liquid inlet 111 on the second base plate 21 at least partially overlaps an orthographic projection of the second electrode layer 22 on the second base plate 21. That is, the reaction liquid entering the liquid storage tank 112 through the liquid inlet 111 may contact the second electrode layer 22, so as to ensure that the reaction liquid may be driven to move after the voltage is applied to the second electrode layer 22. For example: an orthographic projection of an edge of the second electrode layer 22 on the second base plate 21 passes through a center of the orthographic projection of the first port 1111 of the liquid inlet 111 on the second base plate 21. Alternatively, the orthographic projection of the first port 1111 of the liquid inlet 111 on the second base plate 21 is in contact with an edge of the orthographic projection of the second electrode layer 22 on the second base plate 21.
Three exemplary positional relationships between the liquid inlet 111 and the second electrode layer 22 are given below. In the drawings, it will be described by only taking an example in which the first port 111 of the liquid inlet 111 is a circular port. Alternatively, it should be understood that the first port 1111 of the liquid inlet 111 may be other shapes, for example: rectangular, oval, etc.
In an example,
In another example,
In another example,
It should be noted that only three schematic diagrams are shown to illustrate the positional relationship between the second electrode layer 22 and the liquid inlet 111 as above. In practical applications, there may be a distance between the orthographic projection of the first port 1111 of the liquid inlet 111 on the second base plate 21 and an edge of the second electrode layer 22, but the distance is necessarily satisfied such that an electric field force generated by applying the voltage to the second electrode layer 22 may drive the reaction liquid dropped through the liquid inlet 111 to move towards the detection region Q12.
In some examples, a sealant 200 is disposed in the peripheral region Q2 between the first substrate and the second substrate of the microfluidic chip to seal the microfluidic chip. The sealant 200 includes, but is not limited to, UV adhesive or double-sided adhesive. In addition, a certain cell gap is formed by aligning and assembling the first substrate and the second substrate and is used for providing a space for generating, splitting, and the like of micro-droplets of the reaction liquid. In order to avoid the volatilization of the reaction liquid and the reduction of the driving voltage, silicone oil and fluorinated liquid are generally filled between the first substrate and the second substrate. In some examples, in order to prevent the sealant 200 from reacting with the silicone oil and the fluorinated liquid, a first receiving groove 20 surrounding the middle region Q1 is formed in the peripheral region Q2 of the first base plate 11, and the sealant 200 is formed in the first receiving groove 20. For example: the first receiving groove 20 and the first base plate 11 are formed as a single-piece structure, and may for example be formed by injection molding. In some examples, a depth of the first receiving groove 20 is about 50 μm to 2 mm. In an alternative manner, the depth of the first receiving groove 20 is set according to a thickness of the sealant 200, and with reference to the requirements on the cell gap between the first substrate and the second substrate.
In some embodiments, a conductive component 300 is disposed in the peripheral region Q2 between the first substrate and the second substrate of the microfluidic chip, and is used for connecting the first electrode layer 12 with a conductive pad on the second substrate to provide an electrical signal to the first electrode layer 12. For example: the first electrode layer 12 may be a ground electrode, which extends to the peripheral region Q2 to be connected to the conductive component 300, which, in turn, is connected to a ground pad on the second substrate, so that the ground electrode is connected to the ground pad. In some examples, the conductive component 300 includes, but is not limited to, a conductive silver paste or conductive foam. In some examples, the conductive component 300 may be located on a side of the sealant 200 distal to the middle region Q1. For example: the microfluidic chip is quadrilateral, and the conductive component 300 is disposed at each of four corners of the first base plate 11. That is, one conductive component 300 is disposed at each corner. In some examples, a second receiving groove 30 is further disposed on a side of the first base plate 11 close to the second substrate, and the conductive component 30) is disposed in the second receiving groove 30. For example: the second receiving cavity 30 and the first base plate 11 are formed as a single-piece structure, and may be formed by injection molding. In some examples, a depth of the second receiving groove 30 is about 50 μm to 2 mm. In an alternative manner, the depth of the second receiving groove 30 is set according to a thickness of the conductive component 300, and also with reference to the requirements on the cell gap between the first substrate and the second substrate. In some examples, a shape of the second receiving groove 30 includes, but is not limited to, a rectangle, a square, a circle or a polygon, and the number of the second receiving grooves 30 is about 1 to 4.
In some examples, the first substrate includes not only the first electrode layer 12 described above, but also a first hydrophobic layer on a side of the first electrode layer 12 proximal to the second substrate. In this case, the reaction liquid is added into the microfluidic chip through the liquid inlet 111, and after the reaction liquid enters the liquid storage tank 112, the reaction liquid contacts a lower surface of the first substrate. Since the lower surface of the first substrate is provided with the first hydrophobic layer exhibiting hydrophobicity, the reaction liquid is less likely to remain on the lower surface of the first hydrophobic layer, and more likely to enter the liquid storage tank 112. Similarly, the second substrate includes not only the second electrode layer 22, but also a second hydrophobic layer on a side of the second electrode layer 22 proximal to the first substrate. When a voltage is applied to the first electrode layer 12 and the second electrode layer 22 to cause the reaction liquid entering the liquid storage tank 112 to move, since an upper surface of the second substrate is provided with the second hydrophobic layer exhibiting hydrophobicity, the reaction liquid is more easily moved, and the motion resistance of the reaction liquid may be effectively reduced. The first hydrophobic layer and the second hydrophobic laver include, but are not limited to, hydrophobic layers, and may be made of various types of materials, such as Teflon, perfluorinated resin (CYTOP), and other fluoropolymers, which are not limited herein.
In order to facilitate the droplets to enter a liquid cavity, in some examples, the first base plate 11 is provided with a gas outlet 60 penetrating through the first substrate 110 in a thickness direction, as shown in
In some examples, the liquid inlet 111, the liquid storage tank 112, the first receiving groove 20, and the second receiving groove 30 on the first base plate 11 of the first substrate may be formed by micro-machining (e.g., injection molding, laser engraving, sand blasting, etc.).
In order to make the operating principle of the microfluidic chip according to the embodiment of the present disclosure more clear, the operating procedure of the microfluidic chip according to the embodiment of the present disclosure will be described by taking an example in which the structure shown in
Firstly, the reaction liquid is added into the liquid storage tank 112 through the liquid inlet 111 by the tip, as shown in
It should be understood that the above embodiments are merely exemplary embodiments adopted to explain the principles of the present disclosure, and the present disclosure is not limited thereto. It will be apparent to one of ordinary skill in the art that various changes and modifications may be made therein without departing from the spirit and scope of the present disclosure, and such changes and modifications also fall within the scope of the present disclosure.
Number | Date | Country | Kind |
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PCT/CN2020/090005 | May 2020 | CN | national |
Filing Document | Filing Date | Country | Kind |
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PCT/CN2021/074457 | 1/29/2021 | WO |