Micro-fluidic chip
By designing interconnected injection holes, droplet formation chambers, droplet paving chambers, bubble convergence chambers and drainage holes in the microfluidic chip, and utilizing the guide surface and guide cavity structure, the problem of decreased detection accuracy caused by residual bubbles was solved, and efficient detection of fully closed operations was achieved.
Patent Information
- Application Number
- CN202422758326.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-12
- Publication Date
- 2025-10-28
- Estimated Expiration
- 2034-11-12
AI Technical Summary
Existing microfluidic chips are prone to generating bubbles during droplet generation and PCR reaction, resulting in decreased detection accuracy and detection failure, and cannot meet the requirements of full-process closed operation.
A microfluidic chip is designed, which includes a chip body and a sealing layer. The chip is constructed to form an injection hole, a droplet formation cavity, a droplet flattening cavity, a bubble gathering cavity and a drainage hole that are connected in sequence. The inner wall of the droplet flattening cavity is provided with a guide surface, and the bubble gathering cavity is provided with a guide cavity and a guide hole. Bubbles can quickly gather and be discharged from the drainage hole under the action of buoyancy to avoid bubble residue.
It effectively avoids the residue of bubbles in the droplet paving chamber and prevents bubbles from disturbing the droplets during high and low temperature cycles, improves the quantitative accuracy and reliability of the detection, and meets the needs of closed operation throughout the entire process.
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Figure CN223475055U_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of testing consumables technology, and more specifically, to a microfluidic chip. Background Technology
[0002] Droplet digital PCR systems often employ a split-process approach, where droplet generation, PCR reaction, and droplet detection are performed on separate instruments. This approach makes it difficult to achieve a fully closed-loop operation, which does not meet the requirements for clinical diagnostic analysis.
[0003] With the continuous development of microfluidic chip technology, more and more instruments are adopting microfluidic chips that integrate droplet generation, droplet spreading, PCR reaction cycling, and droplet detection into a single, fully automated process. However, existing microfluidic chips still need to address the adverse effects caused by air bubbles generated during droplet generation and PCR reaction cycling. Once air bubbles are generated, they continuously increase and decrease in size during high and low temperature cycling in PCR, thus disturbing the droplets, causing large-area droplet fusion, affecting quantitative accuracy, and even leading to detection failure. Utility Model Content
[0004] The main objective of this application is to provide a microfluidic chip to solve the problem of residual air bubbles affecting detection in the prior art.
[0005] This application provides a microfluidic chip, which includes a chip body and a sealing layer. The chip body and the sealing layer are sealed together and are constructed to form a liquid injection hole, a droplet forming cavity, a droplet spreading cavity, a bubble gathering cavity and a liquid drainage hole that are connected in sequence.
[0006] The inner wall of the droplet spreading cavity has a guiding surface, which is used to guide the bubbles in the droplet spreading cavity to move towards the bubble converging cavity. The bubbles entering the bubble converging cavity are discharged from the microfluidic chip through the drain hole.
[0007] Furthermore, the bubble converging cavity includes a guide cavity and a guide hole that are interconnected. The end of the guide cavity away from the guide hole is connected to the droplet spreading cavity, and the top wall of the guide cavity is inclined along the droplet spreading cavity toward the guide hole. The end of the guide hole away from the guide cavity is connected to the drain hole.
[0008] Furthermore, the top wall of the guiding cavity includes a first sub-wall, a second sub-wall, and a third sub-wall. The first sub-wall and the third sub-wall are located on opposite sides of the second sub-wall along the direction of the droplet spreading cavity toward the guiding hole, and the first sub-wall, the second sub-wall, and the third sub-wall are inclined along the direction of the droplet spreading cavity toward the guiding hole.
[0009] And / or, the guide hole gradually decreases in diameter at least partially toward the drain hole.
[0010] Furthermore, the guide hole includes a first hole and a second hole, the second hole being connected between the first hole and the drain hole;
[0011] The diameter of the first hole gradually decreases towards the direction of the second hole, and the diameter of the second hole is less than or equal to the minimum diameter of the first hole.
[0012] Furthermore, the diameter of the second hole is smaller than the diameter of the drain hole.
[0013] Furthermore, the diameter of the second hole gradually decreases towards the first hole, and the minimum diameter of the second hole is less than or equal to the minimum diameter of the first hole.
[0014] Furthermore, the first sub-wall and the third sub-wall are symmetrically disposed on opposite sides of the second sub-wall along the direction of the droplet spreading cavity toward the guide hole, and the side of the first sub-wall, the second sub-wall and the third sub-wall away from the droplet spreading cavity are respectively connected to the hole wall of their respective guide holes.
[0015] Furthermore, the second sub-wall is recessed and connected between the first sub-wall and the third sub-wall along the direction of the guide hole toward the drain hole, and the first sub-wall and the third sub-wall are inclined toward the second sub-wall respectively.
[0016] Furthermore, the angle of inclination of the guide surface relative to the horizontal plane is 0.5° to 3°;
[0017] And / or, the inclination angle of the first sub-wall relative to the horizontal plane is 0.6° to 5°;
[0018] And / or, the inclination angle of the second sub-wall relative to the horizontal plane is 0.6° to 5°;
[0019] And / or, the inclination angle of the third sub-wall relative to the horizontal plane is 0.6° to 5°.
[0020] Furthermore, the top wall of the droplet spreading cavity is the guiding surface, wherein the guiding surface is an inclined surface and slopes along the injection hole toward the drainage hole.
[0021] Furthermore, the guiding surface is the top wall of the droplet spreading cavity, and there is a first stepped surface between the top wall of the guiding cavity and the guiding surface. The first stepped surface is used to block the air bubbles in the guiding cavity from moving into the droplet spreading cavity.
[0022] Alternatively, the guiding surface may be the top wall of the droplet spreading cavity, and the top wall of the guiding cavity may be connected to the guiding surface.
[0023] Furthermore, the chip body has a first light-transmitting surface, which is opposite to the guiding surface and located on the side of the guiding surface away from the droplet spreading cavity;
[0024] The first light-transmitting surface and the guiding surface are parallel to each other.
[0025] Furthermore, the chip body includes an upper chip layer and a lower chip layer, wherein the upper chip layer is configured to form the liquid injection hole and the liquid drainage hole, the lower chip layer is connected between the upper chip layer and the sealing layer, and the upper chip layer, the lower chip layer and the sealing layer together form the droplet forming cavity, the droplet spreading cavity and the bubble converging cavity.
[0026] Furthermore, the chip body and the sealing layer together form a PCR reaction unit, wherein the PCR reaction unit includes the injection hole, the droplet forming chamber, the droplet spreading chamber, the bubble gathering chamber and the drain hole connected in sequence;
[0027] Alternatively, the chip body and the sealing layer are jointly constructed to form multiple independent PCR reaction units, wherein each PCR reaction unit includes the injection hole, the droplet forming chamber, the droplet spreading chamber, the bubble gathering chamber and the drain hole that are connected in sequence.
[0028] Furthermore, the droplet forming cavity includes a main channel, a branch channel, and a droplet forming channel. The main channel connects the injection hole and the branch channel. The multiple droplet forming channels are respectively connected between the branch channel and the droplet spreading cavity, and one end of each droplet forming channel connected to the droplet spreading cavity is funnel-shaped.
[0029] Furthermore, the lower layer of the chip and / or the upper layer of the chip are configured to form a guide portion extending to the droplet tiling cavity, and at least one of the guide portions is disposed between two adjacent droplet forming channels, the guide portion being used to guide the droplet to move towards the center of the droplet tiling cavity.
[0030] Furthermore, the guide portion is fixedly connected to the sealing layer so that the sealing layer is sealed to the side of the lower layer of the chip away from the upper layer of the chip.
[0031] Furthermore, the sealing layer is glass or a thin film, the direction from the injection hole to the drainage hole is a first direction, and the direction perpendicular to the first direction is a second direction;
[0032] Wherein, the flow channel and the bubble converging cavity are located on opposite sides of the droplet spreading cavity along the first direction, and a plurality of droplet forming channels are respectively connected between the flow channel and the droplet spreading cavity along the first direction; or, the flow channel includes a first sub-flow channel and a second sub-flow channel, the first sub-flow channel and the second sub-flow channel are located on opposite sides of the droplet spreading cavity along the second direction, the droplet forming channel includes a first sub-droplet forming channel and a second sub-droplet forming channel, a plurality of first sub-droplet forming channels are respectively connected between the first sub-flow channel and the corresponding droplet spreading cavity along the second direction, and a plurality of second sub-droplet forming channels are respectively connected between the second sub-flow channel and the corresponding droplet spreading cavity along the second direction.
[0033] Furthermore, the sealing layer has a second light-transmitting surface, which corresponds to the droplet spreading cavity, and the guiding surface is inclined relative to the second light-transmitting surface.
[0034] This application constructs a sequentially interconnected system of injection holes, droplet forming chambers, droplet spreading chambers, bubble converging chambers, and drainage holes by using a sealed chip body and a sealing layer. A guiding surface is provided on the inner wall of the droplet spreading chamber to guide the bubbles within it towards the bubble converging chamber. This allows the bubbles in the droplet spreading chamber to move rapidly towards the bubble converging chamber under buoyancy, and after accumulating or merging in the bubble converging chamber, they are directly discharged from the microfluidic chip through the drainage hole. This prevents bubbles from remaining in the droplet spreading chamber and undergoing volume changes during high and low temperature processing, which could disturb the droplets and cause adjacent droplets to merge, affecting the detection results. Attached Figure Description
[0035] The drawings described herein are used to provide a further understanding of the present application and constitute a part of the present application. The illustrative embodiments of the present application and their descriptions are used to explain the present application and do not constitute an improper limitation on the present application. In the drawings:
[0036] Figure 1 This is a schematic diagram of the overall microfluidic chip in one embodiment of the present application, showing the first direction and the second direction.
[0037] Figure 2 for Figure 1 A sectional view along the A-A1 direction.
[0038] Figure 3 This is a schematic diagram of the chip body in one embodiment of this application.
[0039] Figure 4 for Figure 3 A sectional view along the B-B1 direction.
[0040] Figure 5 for Figure 3 A sectional view along the C-C1 direction.
[0041] Figure 6 for Figure 3 A sectional view along the D-D1 direction.
[0042] Figure 7 This is a schematic diagram of the chip body in another embodiment disclosed in this application.
[0043] Figure 8 for Figure 7 A sectional view along the E-E1 direction.
[0044] The above figures include the following reference numerals:
[0045] Microfluidic chip 100, chip body 10, upper chip layer 11, guiding surface 111, first receiving part 112, second receiving part 113, first light-transmitting surface 114, LOGO position 115, identification position 116, PCR reaction unit identification position 117, lower chip layer 12, guiding part 121, support part 13, sealing layer 20, second light-transmitting surface 21, injection hole 30, droplet forming cavity 40, main channel 41, branch channel 42, first sub-branch channel 421 Second sub-diversion channel 422, third sub-diversion channel 423, droplet forming channel 43, first sub-droplet forming channel 431, second sub-droplet forming channel 432, funnel-shaped 433, droplet spreading cavity 50, bubble converging cavity 60, guiding cavity 61, first sub-wall 611, second sub-wall 612, third sub-wall 613, guiding hole 62, first stepped surface 63, first hole 621, second hole 622, third hole 623, drain hole 70, second stepped surface 71. Detailed Implementation
[0046] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other. This application will now be described in detail with reference to the accompanying drawings and embodiments.
[0047] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments according to this application. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.
[0048] Unless otherwise specifically stated, the relative arrangement, numerical expressions, and values of the components and steps described in these embodiments do not limit the scope of this application. It should also be understood that, for ease of description, the dimensions of the various parts shown in the drawings are not drawn to actual scale. Techniques, methods, and devices known to those skilled in the art may not be discussed in detail, but where appropriate, such techniques, methods, and devices should be considered part of the specification. In all examples shown and discussed herein, any specific values should be interpreted as merely exemplary and not as limitations. Therefore, other examples of exemplary embodiments may have different values. It should be noted that similar reference numerals and letters in the following drawings denote similar items; therefore, once an item is defined in one drawing, it need not be further discussed in subsequent drawings.
[0049] Please see Figure 1-5 As shown, this application provides a microfluidic chip 100, which includes a chip body 10 and a sealing layer 20. The chip body 10 and the sealing layer 20, which are sealed together, are configured to form a liquid injection hole 30, a droplet forming cavity 40, a droplet spreading cavity 50, a bubble converging cavity 60 and a liquid drainage hole that are connected in sequence.
[0050] The injection port 30 is used to sequentially inject an oil phase and a sample phase into the chip body 10. The oil phase, after entering the chip body 10 through the injection port 30, flows through the droplet forming cavity 40 and the droplet spreading cavity 50, completely filling both 40 and 50, and at least partially filling the injection port 30, the bubble gathering cavity 60, and the drain port 70. The sample phase is an aqueous phase.
[0051] The droplet forming cavity 40 divides the injected sample phase into droplets of uniform size based on the principle of stepped emulsification. The droplet spreading cavity 50 is used to contain the droplets. Specifically, after the sample phase enters the chip body 10 through the injection hole 30, it will come into contact with the oil phase and be enveloped by the oil phase, and then be dispersed into droplets of uniform size when passing through the droplet forming cavity 40.
[0052] Please refer to the following: Figure 2 As shown, during the addition of the oil phase or the sample phase, air bubbles carried in the oil phase or the sample phase will enter the droplet spreading cavity 50 along with the oil phase or the sample phase. The inner wall of the droplet spreading cavity 50 has a guiding surface 111, which is used to guide the air bubbles in the droplet spreading cavity 50 to move towards the bubble converging cavity 60, thereby preventing air bubbles from remaining in the droplet spreading cavity 50.
[0053] The bubble converging chamber 60 connects the droplet spreading chamber 50 and the drain hole 70. When the microfluidic chip 100 is placed horizontally, the bubble converging chamber 60 is at least partially located above the droplet spreading chamber 50, so that bubbles entering the bubble converging chamber 60 from the droplet spreading chamber 50 can directly enter the drain hole 70 from the bubble converging chamber 60 and be discharged from the microfluidic chip 100. This avoids bubbles remaining in the droplet spreading chamber 50 and undergoing volume changes during the high and low temperature treatment process, which would disturb the droplets and cause adjacent droplets to merge, affecting the detection results.
[0054] Furthermore, the chip body 10 includes an upper chip layer 11 and a lower chip layer 12. The upper chip layer 11 forms the injection port 30 and the drainage port 70. The lower chip layer 12 connects the upper chip layer 11 and the sealing layer 20. The upper chip layer 11, the lower chip layer 12, and the sealing layer 20 together form the droplet forming cavity 40, the droplet spreading cavity 50, and the bubble converging cavity 60.
[0055] For further information, please refer to [link / reference]. Figure 2 As shown, when the microfluidic chip 100 is placed horizontally, the sealing layer 20 is located at the bottom, the upper chip layer 11 is located at the top, and the lower chip layer 12 is located between the sealing layer 20 and the upper chip layer 11.
[0056] Furthermore, the top wall of the droplet spreading cavity 50 is the guide surface 111. The guide surface 111 is an inclined surface and is inclined along the direction of the injection hole 30 toward the drainage hole 70 to guide the air bubbles in the droplet spreading cavity 50 toward the air bubble converging cavity 60.
[0057] Furthermore, the upper chip layer 11 protrudes away from the lower chip layer 12 to form a first receiving portion 112 and a second receiving portion 113 spaced apart from each other, wherein the first receiving portion 112 forms the injection hole 30 and the second receiving portion 113 forms the drainage hole 70.
[0058] The injection hole 30 is located above the droplet forming cavity 40 and the droplet spreading cavity 50 to ensure that the injected liquid completely fills the droplet forming cavity 40 and the droplet spreading cavity 50. The drain hole 70 is located above the droplet forming cavity 40, the droplet spreading cavity 50 and the bubble converging cavity 60 to ensure that the bubbles in the bubble converging cavity 60 can be directly discharged through the drain hole 70.
[0059] Furthermore, in one embodiment, the upper chip layer 11 and the lower chip layer 12 are integrally formed, and the sealing layer 20 is a transparent thin film made of glass or polymer material. The sealing layer 20 and the side of the lower chip layer 12 away from the upper chip layer 11 can be sealed together by, but is not limited to, bonding, welding, thermoforming, and chemical bonding.
[0060] For further information, please refer to [link / reference]. Figure 2 As shown, the bubble converging cavity 60 includes a guide cavity 61 and a guide hole 62 that are interconnected. The end of the guide cavity 61 away from the guide hole 62 is connected to the droplet spreading cavity 50, and the top wall of the guide cavity 61 is inclined along the droplet spreading cavity 50 towards the guide hole 62, so that bubbles guided from the droplet spreading cavity 50 to the guide cavity 61 can continue to be guided towards the guide hole 62 through the guide cavity 61. The end of the guide hole 62 away from the guide cavity 61 is connected to the drain hole 70.
[0061] Further, please refer to Figure 4-6 As shown, the top wall of the guide cavity 61 includes a first sub-wall 611, a second sub-wall 612, and a third sub-wall 613. The first sub-wall 611 and the third sub-wall 613 are located on opposite sides of the second sub-wall 612 along a first direction from the droplet spreading cavity 50 toward the guide hole 62. That is, the first sub-wall 611, the second sub-wall 612, and the third sub-wall 613 are connected sequentially along a second direction, wherein the second direction is perpendicular to the first direction.
[0062] Furthermore, the first sub-wall 611, the second sub-wall 612, and the third sub-wall 613 are inclined along the droplet spreading cavity 50 toward the guide hole 62. This ensures that bubbles moving from the droplet spreading cavity 50 to the first sub-wall 611, the second sub-wall 612, and the third sub-wall 613 will move along the corresponding first sub-wall 611, second sub-wall 612, or third sub-wall 613 toward the guide hole 62, thereby preventing bubbles from remaining in the guide cavity 61 and thus preventing bubbles from returning from the guide cavity 61 to the droplet spreading cavity 50 during high and low temperature processes.
[0063] Furthermore, in one embodiment, the first sub-wall 611 and the third sub-wall 613 are symmetrically disposed on opposite sides of the second sub-wall 612 along the direction of the droplet spreading cavity 50 toward the guide hole 62. This allows bubbles within the droplet spreading cavity 50 to move stably toward the guide cavity 61 corresponding to the first sub-wall 611 or the third sub-wall 613, thereby reducing or avoiding turbulence in the movement direction of bubbles within the droplet spreading cavity 50.
[0064] Furthermore, the first sub-wall 611, the second sub-wall 612, and the third sub-wall 613, each located away from the droplet spreading cavity 50, are respectively connected to the wall of their respective guide holes 62. This effectively increases the communication space between the guide cavity 61 and the guide hole 62, allowing the air bubbles in the guide cavity 61 to move more smoothly into the guide hole 62.
[0065] Furthermore, in one embodiment, the guiding surface 111 is the top wall of the droplet spreading cavity 50, and a first stepped surface 63 is provided between the top wall of the guiding cavity 61 and the guiding surface 111. The first stepped surface 63 is used to block the air bubbles in the guiding cavity 61 from moving towards the droplet spreading cavity 50.
[0066] Furthermore, the first sub-wall 611, the second sub-wall 612 and the third sub-wall 613 each have a first stepped surface 63 between them and their respective corresponding guide surfaces 111.
[0067] Furthermore, the second sub-wall 612 is recessed along the guide hole 62 towards the drain hole 70 and connected between the first sub-wall 611 and the third sub-wall 613, with the first sub-wall 611 and the third sub-wall 613 inclined towards the second sub-wall 612 respectively. This causes at least a portion of the bubbles entering the guide cavities 61 corresponding to the first sub-wall 611 and the third sub-wall 613 to first enter the guide cavity 61 corresponding to the second sub-wall 612, thereby causing more bubbles to accumulate in the guide cavity 61 corresponding to the second sub-wall 612. This increases the likelihood that these accumulated bubbles will merge into larger bubbles. Therefore, the merged large bubble has greater buoyancy to overcome surface tension, gravity, and viscosity, thus moving more smoothly towards the guide hole 62.
[0068] In another embodiment, the guiding surface 111 is the top wall of the droplet spreading cavity 50, and the top wall of the guiding cavity 61 is connected to the guiding surface 111. This allows the air bubbles in the droplet spreading cavity 50 to move smoothly into the guiding cavity 61 and, under the action of the inclined top wall of the guiding cavity 61, move towards the guiding hole 62.
[0069] Furthermore, the guide surface 111 has an inclination angle of 0.5° to 3° relative to the horizontal plane. This facilitates the guidance of air bubbles within the droplet spreading cavity 50 towards the guide cavity 61, while effectively controlling the volume of the droplet spreading cavity 50. This avoids the need to inject excessive oil phase during detection and effectively controls the overall volume of the microfluidic chip 100, preventing waste of raw materials used in preparing the chip body 10.
[0070] The first sub-wall 611 has an inclination angle of 0.6° to 5° relative to the horizontal plane, the second sub-wall 612 has an inclination angle of 0.6° to 5° relative to the horizontal plane, and the third sub-wall 613 has an inclination angle of 0.6° to 5° relative to the horizontal plane. This facilitates the guidance of air bubbles within the guide cavity 61 towards the guide hole 62, effectively controls the volume of the guide cavity 61, avoids the need to inject excessive oil phase during detection, and effectively controls the overall volume of the microfluidic chip 100, avoiding waste of raw materials used in preparing the chip body 10.
[0071] Furthermore, the guide hole 62 has a gradually decreasing diameter at least partially towards the drain hole 70. This causes multiple air bubbles entering the guide hole 62 to converge towards the center, and may result in bubble stacking, thereby promoting the fusion of these converged air bubbles into larger bubbles, which in turn facilitate the movement of these larger bubbles towards the drain hole 70.
[0072] For further information, please refer to [link / reference]. Figure 2 and Figure 4 As shown, in one embodiment, the guide hole 62 includes a first hole 621 and a second hole 622, with the second hole 622 communicating between the first hole 621 and the drain hole 70. The first hole 621 has a gradually decreasing diameter towards the second hole 622, making it a variable-diameter hole, thereby facilitating the guidance of air bubbles located in the first hole 621 towards the second hole 622.
[0073] Furthermore, when the microfluidic chip 100 is placed horizontally, the second hole 622 is located above the first hole 621. Preferably, the second hole 622 is located directly above the first hole 621, so that the air bubble in the first hole 621 can move smoothly into the second hole 622.
[0074] In one embodiment, the second hole 622 is a constant diameter hole, and the diameter of the second hole 622 is equal to the minimum diameter of the first hole 621. This allows the second hole 622 to connect with the minimum diameter portion of the first hole 621.
[0075] In another embodiment, the second hole 622 is a constant diameter hole, and the diameter of the second hole 622 is smaller than the minimum diameter of the first hole 621, thereby creating a third hole 623 at the minimum diameter of the second hole 622 and the first hole 621. The third hole 623 facilitates mold preparation and demolding during injection molding of the integral chip body 10.
[0076] Preferably, the diameter of the third hole 623 gradually decreases along the direction from the first hole 621 toward the second hole 622.
[0077] Furthermore, the diameter of the second hole 622 is smaller than the diameter of the drain hole 70. This results in a second stepped surface 71 at the connection between the second hole 622 and the drain hole 70, which makes it difficult for air bubbles entering the drain hole 70 to return to the guide hole 62 due to the obstruction of the second stepped surface 71.
[0078] Furthermore, in one embodiment, the diameter of the second hole 622 gradually decreases towards the first hole 621, making the second hole 622 a variable diameter hole. The minimum diameter of the second hole 622 is less than or equal to the minimum diameter of the first hole 621.
[0079] By setting the second hole 622 as a variable diameter hole, when the microfluidic chip 100 is placed horizontally for detection (e.g., during the process of cooling from a high temperature to a low temperature), the second hole 622, as a variable diameter hole, will restrict the movement of bubbles located in the second hole 622 and / or in the drain hole 70 toward the first hole 621.
[0080] In addition, by setting the second hole 622 as a variable diameter hole, and the variable diameter direction of the second hole 622 is opposite to that of the first hole 621, it is also convenient to demold when the chip body 10 is injection molded as an integral piece.
[0081] For further information, please refer to [link / reference]. Figure 1-2 As shown, in one embodiment, the chip body 10 has a first light-transmitting surface 114, which is opposite to the guiding surface 111 and located on the side of the guiding surface 111 away from the droplet spreading cavity 50. During detection, the light source passes through the first light-transmitting surface 114 through the upper layer 11 of the chip and enters the droplet spreading cavity 50, and then exits from the sealing layer 20 corresponding to the bottom wall of the droplet spreading cavity 50.
[0082] Furthermore, the first light-transmitting surface 114 and the guiding surface 111 are parallel to each other. This ensures that the optical path of the light source is substantially consistent when passing through the upper layer 11 of the chip.
[0083] Furthermore, in one embodiment, the chip body 10 and the sealing layer 20 are jointly constructed to form a PCR reaction unit. The PCR reaction unit includes, in sequence, the injection port 30, the droplet forming chamber 40, the droplet spreading chamber 50, the bubble converging chamber 60, and the drain port 70.
[0084] In another embodiment, the chip body 10 and the sealing layer 20 are jointly constructed to form a plurality of independent PCR reaction units. Each of the PCR reaction units includes, in sequence, the injection port 30, the droplet forming chamber 40, the droplet spreading chamber 50, the bubble gathering chamber 60, and the drain port 70.
[0085] Further, please refer to Figure 7-8 and combined Figure 5 As shown, the droplet forming cavity 40 includes a main channel 41, a branch channel 42, and droplet forming channels 43. The main channel 41 connects the injection hole 30 and the branch channel 42, and the plurality of droplet forming channels 43 respectively connect the branch channel 42 and the droplet spreading cavity 50, and one end of each droplet forming channel 43 that connects to the droplet spreading cavity 50 is funnel-shaped 433.
[0086] Compared with the prior art where a funnel-shaped opening 433 is provided at both ends of each droplet forming channel 43, in this embodiment, only one end of each droplet forming channel 43 that connects to the droplet spreading cavity 50 is funnel-shaped 433, which can simplify the structure of the molding die.
[0087] Furthermore, the lower layer of the chip and / or the upper layer of the chip are configured to form a guide portion 121 extending to the droplet tiling cavity 50, and at least one guide portion 121 is disposed between two adjacent droplet forming channels 43. The guide portion 121 is used to guide the droplet to move towards the center of the droplet tiling cavity 50.
[0088] Furthermore, the guide portion 121 protrudes from the droplet forming channel 43 and extends into the corresponding droplet spreading cavity 50, thereby enabling the droplets formed through the droplet forming channel 43 to move along the second direction toward the center of the droplet spreading cavity 50 under the guidance of the guide portion 121, thereby improving the efficiency of the droplets spreading the droplet spreading cavity 50.
[0089] Furthermore, the guide portion 121 is fixedly connected to the sealing layer 20 so that the sealing layer 20 is sealed to the side of the lower chip layer 12 away from the upper chip layer 11.
[0090] Specifically, since the guide portion 121 is close to the droplet forming channel 43, and the droplet forming channel 43 is jointly constructed by the sealing layer 20, the upper chip layer 11, and the lower chip layer 12, by connecting the sealing layer 20 to the guide portion 121, the structural stability of the droplet forming channel 43 can be effectively guaranteed, thereby ensuring that the generated droplets are of uniform size.
[0091] For further information, please refer to [link / reference]. Figure 7-8As shown, in the first embodiment, the sealing layer 20 is glass or a thin film, the diversion channel 42 and the bubble converging cavity 60 are located on opposite sides of the droplet spreading cavity 50 along the first direction, and a plurality of droplet forming channels 43 are respectively connected between the diversion channel 42 and the droplet spreading cavity 50 along the first direction.
[0092] In the second implementation, please refer to [the relevant documentation]. Figure 3 and Figure 5 As shown, the sealing layer 20 is glass or a thin film, and the diversion channel 42 includes a first sub-diversion channel 421 and a second sub-diversion channel 422. The first sub-diversion channel 421 and the second sub-diversion channel 422 are located on opposite sides of the droplet spreading cavity 50 along the second direction.
[0093] The droplet forming channel 43 includes a first sub-droplet forming channel 431 and a second sub-droplet forming channel 432. A plurality of first sub-droplet forming channels 431 are respectively connected along the second direction between the first sub-diversion channel 421 and the corresponding droplet spreading cavity 50. A plurality of second sub-droplet forming channels 432 are respectively connected along the second direction between the second sub-diversion channel 422 and the corresponding droplet spreading cavity 50.
[0094] Furthermore, the diversion channel 42 also includes a third sub-diversion channel 423, which connects the first sub-diversion channel 421, the second sub-diversion channel 422, and the main channel 41 along the second direction. The main channel 41 connects to the middle of the third sub-diversion channel 423, and the first sub-diversion channel 421 and the second sub-diversion channel 422 connect to both ends of the third sub-diversion channel 423.
[0095] By configuring the first sub-diversion channel 421 and the second sub-diversion channel 422, multiple first sub-droplet forming channels 431 are arranged at intervals along the first direction, and multiple second sub-droplet forming channels 432 are arranged at intervals along the first direction. This ensures that the sample phase, upon entering the droplet spreading cavity 50 from the droplet forming cavity 40, enters from both sides of the droplet spreading cavity 50 along the first direction, rather than from the side of the droplet spreading cavity 50 away from the drain hole 70. Therefore, the travel distance of the droplets within the droplet spreading cavity 50 can be effectively shortened, improving droplet generation efficiency while reducing the proportion of droplet stacking.
[0096] Furthermore, by setting up the first sub-diversion channel 421 and the second sub-diversion channel 422, and by setting the guide portion 121 between two adjacent first sub-droplet forming channels 431 and between two adjacent second sub-droplet forming channels 432, the droplets can be guided to move towards the center of the droplet spreading cavity 50 more efficiently. At the same time, the sealing layer 20 and the partition portion can be connected along the first direction near the bubble converging cavity 60, thereby effectively increasing the connection strength between the droplet spreading cavity 50 and the droplet forming cavity 40.
[0097] Furthermore, compared to the prior art where the diversion channels (first sub-diversion channel 421 and second sub-diversion channel 422) and droplet forming channels (first sub-droplet forming channel 431 and second sub-droplet forming channel 432) are extended to the middle of the droplet spreading cavity 50, this embodiment places the first sub-diversion channel 421 and the second sub-diversion channel 422 on opposite sides of the droplet spreading cavity 50, which avoids occupying the detection area of the droplet spreading cavity 50, thereby helping the testing personnel to more efficiently test each detection area of the droplet spreading cavity 50.
[0098] Furthermore, in one implementation, please refer to [further details]. Figure 2 As shown, the sealing layer 20 has a second light-transmitting surface 21, which corresponds to the droplet spreading cavity 50, and the guiding surface 111 is inclined relative to the second light-transmitting surface 21. During detection, the light source passes through the sealing layer 20 from the second light-transmitting surface 21 and enters the droplet spreading cavity 50, then is reflected from the top wall of the droplet spreading cavity 50 and exits from the sealing layer 20. In this embodiment, the light emitted by the light source cannot pass through the top wall of the droplet spreading cavity 50.
[0099] For further information, please refer to [link / reference]. Figure 5 As shown, the chip body 10 is also configured to form a plurality of support portions 13 extending into the droplet tiling cavity 50. The plurality of support portions 13 are spaced apart and fixedly connected to the sealing layer 20 respectively, so that the portion of the sealing layer 20 corresponding to the droplet tiling cavity 50 can be stably supported, thereby ensuring the flatness of the portion, so as to facilitate the fluorescence imaging detection of the droplet.
[0100] For further information, please refer to [link / reference]. Figure 1 As shown, the surface of the upper layer 11 of the chip is also provided with a LOGO position 115, an identification position 116, and a PCR reaction unit identification position 117. The LOGO position 115 is used to affix or laser engrave the product LOGO, the identification position 116 can be used to identify the detection item or type, etc., and the PCR reaction unit identification position 117 is used to distinguish each of the PCR reaction units.
[0101] Furthermore, the working principle of this utility model is as follows:
[0102] First, the oil phase is injected from the injection hole 30 such that the injected oil phase fills the main channel 41, the branch channel 42, the droplet forming channel 43, the droplet spreading cavity 50, the bubble converging cavity 60, and at least part of the drain hole 70.
[0103] Then, the sample phase is injected from the injection hole 30 so that the injected sample phase flows through the flow channel and the branch channel 42 and enters the droplet forming channel 43. In the droplet forming channel 43, droplets of the same size are formed based on the principle of step emulsification and then enter the droplet spreading cavity 50. Multiple droplets are spread or partially stacked in the droplet spreading cavity 50.
[0104] Secondly, the microfluidic chip 100 is subjected to high and low temperature cycling heating from one side of the sealing layer 20 to perform PCR reaction cycling on the droplets in the droplet spreading area, and after the PCR reaction cycle is completed, the droplets in the droplet spreading cavity 50 are spread out in a flat state.
[0105] Finally, fluorescence imaging is performed on the spread-out droplets.
[0106] For ease of description, spatial relative terms such as "above," "on top of," "on the upper surface of," "above," etc., are used herein to describe the spatial positional relationship of a device or feature as shown in the figures to other devices or features. It should be understood that spatial relative terms are intended to encompass different orientations in use or operation beyond the orientation of the device as described in the figures. For example, if the device in the figures were inverted, a device described as "above" or "on top of" other devices or structures would subsequently be positioned as "below" or "under" other devices or structures. Thus, the exemplary term "above" can include both "above" and "below." The device may also be positioned in other different ways (rotated 90 degrees or in other orientations), and the spatial relative descriptions used herein will be interpreted accordingly.
[0107] Furthermore, it should be noted that the use of terms such as "first" and "second" to define components is merely for the purpose of distinguishing the corresponding components. Unless otherwise stated, the above terms have no special meaning and therefore cannot be construed as limiting the scope of protection of this application.
[0108] The above are merely preferred embodiments of this application and are not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.
Claims
1. A microfluidic chip, characterized in that, It includes a chip body and a sealing layer. The chip body and the sealing layer are sealed together and are constructed to form a liquid injection hole, a droplet forming cavity, a droplet spreading cavity, a bubble gathering cavity and a liquid drainage hole that are connected in sequence. The inner wall of the droplet spreading cavity has a guiding surface, which is used to guide the bubbles in the droplet spreading cavity to move towards the bubble converging cavity. The bubbles entering the bubble converging cavity are discharged from the microfluidic chip through the drain hole.
2. The microfluidic chip according to claim 1, characterized in that, The bubble gathering chamber includes a guide chamber and a guide hole that are interconnected. The end of the guide chamber away from the guide hole is connected to the droplet spreading chamber, and the top wall of the guide chamber is inclined along the droplet spreading chamber toward the guide hole. The end of the guide hole away from the guide chamber is connected to the drain hole.
3. The microfluidic chip according to claim 2, characterized in that, The top wall of the guide cavity includes a first sub-wall, a second sub-wall, and a third sub-wall. The first sub-wall and the third sub-wall are located on opposite sides of the second sub-wall along the direction of the droplet spreading cavity toward the guide hole, and the first sub-wall, the second sub-wall, and the third sub-wall are inclined along the direction of the droplet spreading cavity toward the guide hole. And / or, the guide hole gradually decreases in diameter at least partially toward the drain hole.
4. The microfluidic chip according to claim 3, characterized in that, The guide hole includes a first hole and a second hole, wherein the second hole is connected between the first hole and the drain hole; The diameter of the first hole gradually decreases towards the direction of the second hole, and the diameter of the second hole is less than or equal to the minimum diameter of the first hole.
5. The microfluidic chip according to claim 4, characterized in that, The diameter of the second hole is smaller than the diameter of the drain hole.
6. The microfluidic chip according to claim 4, characterized in that, The diameter of the second hole gradually decreases towards the first hole, and the minimum diameter of the second hole is less than or equal to the minimum diameter of the first hole.
7. The microfluidic chip according to claim 3, characterized in that, The first sub-wall and the third sub-wall are symmetrically disposed on opposite sides of the second sub-wall along the direction of the droplet spreading cavity toward the guide hole, and the side of the first sub-wall, the second sub-wall and the third sub-wall away from the droplet spreading cavity are respectively connected to the hole wall of their respective guide holes.
8. The microfluidic chip according to claim 3, characterized in that, The second sub-wall is recessed and connected between the first sub-wall and the third sub-wall along the direction of the guide hole toward the drain hole, and the first sub-wall and the third sub-wall are inclined toward the second sub-wall respectively.
9. The microfluidic chip according to claim 3, characterized in that, The guide surface has an inclination angle of 0.5° to 3° relative to the horizontal plane; And / or, the inclination angle of the first sub-wall relative to the horizontal plane is 0.6° to 5°; And / or, the inclination angle of the second sub-wall relative to the horizontal plane is 0.6° to 5°; And / or, the inclination angle of the third sub-wall relative to the horizontal plane is 0.6° to 5°.
10. The microfluidic chip according to any one of claims 2-9, characterized in that, The top wall of the droplet spreading cavity is the guiding surface, wherein the guiding surface is an inclined surface and slopes along the injection hole toward the drainage hole.
11. The microfluidic chip according to claim 10, characterized in that, The guiding surface is the top wall of the droplet spreading cavity, and there is a first stepped surface between the top wall of the guiding cavity and the guiding surface. The first stepped surface is used to block the air bubbles in the guiding cavity from moving into the droplet spreading cavity. Alternatively, the guiding surface may be the top wall of the droplet spreading cavity, and the top wall of the guiding cavity may be connected to the guiding surface.
12. The microfluidic chip according to claim 10, characterized in that, The chip body has a first light-transmitting surface, which is opposite to the guiding surface and located on the side of the guiding surface away from the droplet spreading cavity; The first light-transmitting surface and the guiding surface are parallel to each other.
13. The microfluidic chip according to any one of claims 1-9, characterized in that, The chip body includes an upper chip layer and a lower chip layer. The upper chip layer is configured to form the injection hole and the drainage hole. The lower chip layer is connected between the upper chip layer and the sealing layer. The upper chip layer, the lower chip layer, and the sealing layer together form the droplet forming cavity, the droplet spreading cavity, and the bubble converging cavity.
14. The microfluidic chip according to claim 13, characterized in that, The chip body and the sealing layer together form a PCR reaction unit, wherein the PCR reaction unit includes the injection hole, the droplet forming chamber, the droplet spreading chamber, the bubble gathering chamber and the drain hole connected in sequence; Alternatively, the chip body and the sealing layer are jointly constructed to form multiple independent PCR reaction units, wherein each PCR reaction unit includes the injection hole, the droplet forming chamber, the droplet spreading chamber, the bubble gathering chamber and the drain hole that are connected in sequence.
15. The microfluidic chip according to claim 13, characterized in that, The droplet forming cavity includes a main channel, a branch channel, and a droplet forming channel. The main channel connects the injection hole and the branch channel. The multiple droplet forming channels connect the branch channels and the droplet spreading cavity, and one end of each droplet forming channel that connects to the droplet spreading cavity is funnel-shaped.
16. The microfluidic chip according to claim 15, characterized in that, The lower layer of the chip and / or the upper layer of the chip are configured to form a guide portion extending to the droplet tiling cavity, and at least one of the guide portions is disposed between two adjacent droplet forming channels, the guide portion being used to guide the droplet to move toward the center of the droplet tiling cavity.
17. The microfluidic chip according to claim 16, characterized in that, The guide portion is fixedly connected to the sealing layer so that the sealing layer is sealed to the side of the lower layer of the chip away from the upper layer of the chip.
18. The microfluidic chip according to claim 15, characterized in that, The sealing layer is glass or a thin film, the direction from the injection hole to the drainage hole is a first direction, and the direction perpendicular to the first direction is a second direction; Wherein, the flow channel and the bubble converging cavity are located on opposite sides of the droplet spreading cavity along the first direction, and a plurality of droplet forming channels are respectively connected between the flow channel and the droplet spreading cavity along the first direction; or, the flow channel includes a first sub-flow channel and a second sub-flow channel, the first sub-flow channel and the second sub-flow channel are located on opposite sides of the droplet spreading cavity along the second direction, the droplet forming channel includes a first sub-droplet forming channel and a second sub-droplet forming channel, a plurality of first sub-droplet forming channels are respectively connected between the first sub-flow channel and the corresponding droplet spreading cavity along the second direction, and a plurality of second sub-droplet forming channels are respectively connected between the second sub-flow channel and the corresponding droplet spreading cavity along the second direction.
19. The microfluidic chip according to claim 13, characterized in that, The sealing layer has a second light-transmitting surface, which corresponds to the droplet spreading cavity, and the guiding surface is inclined relative to the second light-transmitting surface.