A one-way valve structure on a centrifugal microfluidic chip

Abstract

The application discloses a one-way valve structure on a centrifugal micro-fluidic chip, which is applied to an amplification area on the chip; the chip comprises a bottom plate, a bare chip, a sealing layer and a bonding layer; the amplification area comprises a measuring cavity and an amplification cavity which are arranged on the lower surface of the bare chip; the lower surface of the bare chip is provided with a one-way valve inlet flow channel which is communicated with the measuring cavity, and the upper surface of the bare chip is also provided with a first groove which is arranged at the position corresponding to the other end of the one-way valve inlet flow channel. The radial centrifugal force is used to open the plugging piece to realize the distribution of the liquid; after the distribution is completed, the backflow liquid acts on the other side of the plugging piece, thereby plugging the flow channel, so that the function of the one-way valve is realized; in addition, the backflow of the liquid can be prevented by cooperating with the plugging piece through the lower ram device after the distribution is completed.

Description

Technical Field

[0001] This invention relates to the field of microfluidics, and more particularly to a one-way valve structure on a centrifugal microfluidic chip. Background Technology

[0002] Centrifugal microfluidics integrates microfluidic structures on a centrifuge platform, utilizing centrifugal force to drive and manipulate the movement of microdroplets or microfluidics. This technology combines principles from fluid mechanics, mechanical engineering, and bioanalysis, and has many potential applications, particularly in biomedicine, biochemical analysis, and clinical diagnostics.

[0003] In centrifugal microfluidic systems, valves are a crucial component for achieving precise control of microfluidics. The function of valves is to adjust or interrupt fluid flow on the rotating centrifuge platform to perform operations such as sample processing, mixing, and separation. Common valve structures used in centrifugal microfluidic systems include:

[0004] 1) Rotary Valves: These typically consist of a rotating disk with tiny channels. The angle of the rotating disk controls the path of the fluid. When the channels on the rotating disk are aligned with specific positions, fluid is allowed to pass through; otherwise, the fluid is blocked. Rotary valves are commonly used for sample dispensing, mixing, and separation.

[0005] 2) Diaphragm Valves: Diaphragm valves consist of a resilient diaphragm that changes the state of the passage by applying pressure to the diaphragm. When pressure is applied to the diaphragm, the diaphragm deforms, opening the passage; when the pressure decreases, the diaphragm returns to its original shape, closing the passage. This valve structure is typically used to achieve rapid fluid control.

[0006] 3) Switching Valves: Switching valves control fluid flow through mechanical or electromagnetic switches. These valve structures can be used to switch fluid paths between different channels to enable sample processing and analysis.

[0007] 4) Paraffin-wax valves: The phase change properties of paraffin can be used to control the flow in microfluidic channels. By heating or cooling paraffin, its state can be changed, thereby controlling the fluid flow in the microchannels.

[0008] 5) Passive Valves: Passive valves are structures that control fluid flow by passively altering the channel geometry or surface tension within a microfluidic chip. These valves typically do not require external energy input and have relatively simple structures, such as siphon valves and capillary valves.

[0009] In summary, existing valve structures on microfluidic platforms can be broadly categorized into active and passive valves. Active valves, including rotary valves, diaphragm valves, on / off valves, and paraffin valves, typically require external mechanical components to operate. These valves demand high precision in their design and fit with the mechanical components, or they rely on external fields such as electric, temperature, or magnetic fields to control their state. These valves often have specific material requirements. Furthermore, phase change valves, such as those made of paraffin, are generally not reusable. Meanwhile, passive valves typically require high precision in their manufacturing process or surface treatments to achieve on / off control. Summary of the Invention

[0010] The purpose of this invention is to provide a one-way valve structure on a centrifugal microfluidic chip, which uses radial centrifugal force to push open the sealing member to achieve liquid distribution. After the distribution is completed, the backflow liquid will act on the other side of the sealing member, thereby blocking the flow channel, thus realizing the function of a one-way valve. In addition, after the distribution is completed, a lowering device can be used in conjunction with the sealing member to ensure that the liquid cannot flow back.

[0011] To achieve the above objectives, the following technical solution is adopted:

[0012] A one-way valve structure on a centrifugal microfluidic chip is applied to the amplification region of the chip. The chip includes a substrate, a die, a sealing layer, and an adhesive layer. The amplification region includes a measurement cavity and an amplification cavity formed on the lower surface of the die. A one-way valve inlet channel with one end connected to the measurement cavity is formed on the lower surface of the die. A first groove is formed on the upper surface of the die at the corresponding position of the other end of the one-way valve inlet channel. A one-way valve inlet through-hole connected to the other end of the one-way valve inlet channel is formed in the first groove, and a one-way valve is movably arranged in the first groove for blocking the one-way valve. A sealing element for the inlet through-hole; the die has a one-way valve outlet channel with one end connected to the amplification chamber, and a one-way valve outlet through-hole connected to the other end of the one-way valve outlet channel; the adhesive layer is arranged on the upper surface of the die corresponding to the amplification area, and the adhesive layer also has a perforated hole; the first groove is located inside one end of the perforated hole, and the one-way valve outlet through-hole is located inside the other end of the perforated hole; the sealing layer covers the adhesive layer, and a gap channel connected to the first groove and the one-way valve outlet through-hole is left between the lower surface of the sealing layer and the perforated hole.

[0013] Furthermore, the one-way valve outlet channel is located on the upper surface of the bare plate.

[0014] Furthermore, the one-way valve outlet channel is located on the lower surface of the bare plate.

[0015] Furthermore, both the first groove and the sealing element are cylindrical in shape; the diameter of the sealing element is larger than the diameter of the one-way valve inlet orifice, but smaller than the diameter of the first groove.

[0016] Furthermore, the first groove has a hemispherical structure, and the sealing element has a spherical structure; the diameter of the sealing element is larger than the diameter of the one-way valve inlet orifice, and smaller than the diameter of the first groove.

[0017] Furthermore, both the inlet and outlet ports of the one-way valve are opened in the vertical direction.

[0018] Furthermore, it also includes a lower pestle device arranged above the first groove.

[0019] By adopting the above solution, the beneficial effects of the present invention are:

[0020] 1) This invention adds a blocking component in the vertical direction of the liquid flow path, and then utilizes the characteristic that the liquid acts on different positions of the blocking component during the exchange process at the inner and outer diameter positions, so that the blocking component is in two states of opening and blocking the flow channel, thereby realizing the function of a one-way valve. The overall design and assembly are simple, and the number of flow channel holes can be changed according to the actual requirements of the blocking effect. Moreover, there are multiple options for the blocking component according to structural differences, making it highly versatile.

[0021] 2) This invention does not require external field force or surface treatment. It uses radial centrifugal force to push open the sealing component to achieve liquid distribution. After the distribution is completed, the return liquid will act on the other side of the sealing component, thereby blocking the flow channel. That is, it only uses the liquid acting on different positions of the sealing component in motion and static states to achieve the passage and cut-off of fluid, which is simple and efficient.

[0022] 3) The lower pestle device can be used in conjunction with the sealing component to ensure that the liquid cannot flow back and improve the sealing effect. Attached Figure Description

[0023] Figure 1 This is a top view of the one-way valve structure of the present invention;

[0024] Figure 2 This is a schematic diagram of the structure of the first embodiment of the present invention;

[0025] Figure 3 for Figure 2 A partial cross-sectional view;

[0026] Figure 4 This is a schematic diagram of the liquid flow direction according to the first embodiment of the present invention;

[0027] Figure 5 This is a schematic diagram of the structure of the second embodiment of the present invention;

[0028] Figure 6 This is a schematic diagram of the liquid flow direction according to the second embodiment of the present invention;

[0029] Figure 7 This is a schematic diagram of the liquid flow direction according to the third embodiment of the present invention;

[0030] Figure 8 This is a schematic diagram of the chip structure for practical application of the present invention;

[0031] The following are explanations of the labels in the attached diagram:

[0032] 1. Base plate; 2. Die; 3. Sealing layer; 4. Adhesive layer; 5. Measurement chamber; 6. Amplification chamber; 7. One-way valve inlet channel; 8. First groove; 9. One-way valve inlet through hole; 10. Sealing component; 11. One-way valve outlet channel; 12. One-way valve outlet through hole; 13. Hole; 14. Slit channel; 101. Central shaft; 102. Pre-set reagent storage area; 103. Liquid mixing area; 104. Sorting area; 105. Waste liquid chamber; 106. Amplification area. Detailed Implementation

[0033] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments.

[0034] Reference Figures 1 to 8 As shown, this invention provides a one-way valve structure on a centrifugal microfluidic chip, applied to the amplification region of the chip; the chip includes a substrate 1, a bare die 2, a sealing layer 3, and an adhesive layer 4; the amplification region includes a measurement cavity 5 and an amplification cavity 6 formed on the lower surface of the bare die 2, and a one-way valve inlet channel 7 with one end connected to the measurement cavity 5 is formed on the lower surface of the bare die 2, and a first groove 8 is formed on the upper surface of the bare die 2 corresponding to the other end of the one-way valve inlet channel 7; a one-way valve inlet through hole 9 connected to the other end of the one-way valve inlet channel 7 is formed in the first groove 8, and a one-way valve inlet through hole for blocking the one-way valve inlet through hole is also movably arranged in the first groove 8. The die 2 has a sealing element 10; one end of the die 2 is connected to the amplification chamber 6 and a one-way valve outlet channel 11 is provided on the die 2, and the other end of the die 2 is connected to the one-way valve outlet channel 11 and a one-way valve outlet through hole 12 is provided on the die 2; the adhesive layer 4 is arranged on the upper surface of the die 2 corresponding to the amplification area, and the adhesive layer 4 is also provided with a hollow hole 13; the first groove 8 is located in one end of the hollow hole 13, and the one-way valve outlet through hole 12 is located in the other end of the hollow hole 13; the sealing layer 3 covers the adhesive layer 4, and a gap channel 14 connected to the first groove 8 and the one-way valve outlet through hole 12 is left between the lower surface of the sealing layer 3 and the hollow hole 13.

[0035] In the entire nucleic acid detection process, after the elution buffer containing the target nucleic acid enters amplification chamber 6, the high temperature during amplification causes the liquid inside the chamber to expand, thus causing it to exit amplification chamber 6 and affecting the amplification results. Therefore, a valve structure needs to be added to the inlet of amplification chamber 6 to ensure that the elution buffer can enter smoothly but cannot be discharged. Therefore, it is necessary to study a one-way valve structure on a centrifugal microfluidic platform for sealing amplification chamber 6 in nucleic acid detection chips.

[0036] Continue to refer to Figure 1 As shown, the eluent needs to flow from the measurement chamber 5 into the amplification chamber 6. When the chip is stationary, and the eluent undergoes heating and cooling amplification in the amplification chamber 6, the liquid must remain within the amplification chamber 6 and cannot flow back into the measurement chamber 5. To achieve this function, this invention proposes a one-way valve design. Utilizing the positional differences of the sealing element 10 within the structure under different states, the flow and shut-off of the liquid within the inlet and outlet channels are achieved.

[0037] Specifically, in one embodiment, as described above, the one-way valve structure of the present invention includes a first groove 8, a one-way valve inlet channel 7, a one-way valve inlet through hole 9, a sealing member 10, a one-way valve outlet through hole 12, a one-way valve outlet channel 11, etc. Meanwhile, a hollow area, i.e. a hollow hole 13, is provided on the adhesive layer 4. The purpose is to allow the sealing member 10 to move up and down in the first groove 8, rather than being fixed to the bottom of the adhesive layer 4. At the same time, a gap channel 14 is generated between the sealing layer 3 and the adhesive layer 4 in the hollow area to allow liquid to flow.

[0038] In this embodiment, such as Figures 2 to 4 As shown, the one-way valve outlet channel 11 is located on the upper surface of the bare die 2. When the eluent enters the amplification chamber 6 while the centrifuge disc is rotating at high speed, the liquid, under the action of centrifugal force, pushes up the sealing element 10 in the first groove 8 through the one-way valve inlet channel 7 and the one-way valve inlet through hole 9. The liquid then flows along the gap channel 14 between the sealing layer 3 and the adhesive layer 4 through the one-way valve outlet channel 11 and enters the amplification chamber 6. After all the eluent has entered the amplification chamber 6, the centrifugal microfluidic chip determines the stop position through the positioning device. At this time, the temperature control device in the instrument clamps the amplification area and proceeds to the next amplification cycle. During this process, the temperature in the amplification chamber 6 will rise. When the eluent expands due to heat, it flows inward through the one-way valve outlet channel 11. At this time, the upper surface of the sealing component 10 is squeezed by the backflowing liquid, thus adhering tightly to the bottom of the first groove 8 and blocking the one-way valve inlet hole 9, thereby achieving the liquid sealing effect. Since the chip is in a static state during the amplification process, in order to better prevent liquid backflow, a lowering device can be added inside the instrument. During the amplification process, the lowering device moves downward, contacts the sealing layer 3, and applies downward force, so that the sealing component 10 presses more tightly against the one-way valve inlet hole 9 to ensure that the liquid cannot flow back.

[0039] In another embodiment, the one-way valve outlet channel 11 is formed on the lower surface of the bare plate 2. In this embodiment, as... Figure 5-6 As shown, the one-way valve outlet flow channel 11 is opened on the lower surface of the bare plate 2, which can increase the liquid flow path. That is, both the inlet and outlet of the one-way valve are composed of upper and lower through holes and flow channels, similar to the design described above. Figure 6 As shown, when the chip is in high-speed centrifugal motion, the eluent enters the first groove 8 through the one-way valve inlet channel 7 and the one-way valve inlet through hole 9, lifting the sealing member 10, and then enters the one-way valve outlet through hole 12 along the slit channel 14, and then flows into the amplification chamber 6 through the one-way valve outlet channel 11. When the chip is stationary, the liquid in the amplification chamber 6 expands due to heat and flows back from the one-way valve outlet channel 11. During the backflow, the liquid needs to pass through the one-way valve outlet through hole 12 and enter the first groove 8, which increases the flow path and resistance. The sealing member 10 in the first groove 8 is pressed against the one-way valve inlet through hole 9 below by the force of the backflow liquid, realizing the liquid sealing function.

[0040] In both of the above embodiments, the first groove 8 and the sealing member 10 are cylindrical in shape. The diameter of the sealing member 10 is larger than the diameter of the one-way valve inlet hole 9 and smaller than the diameter of the first groove 8.

[0041] Meanwhile, in another embodiment, the first groove 8 has a hemispherical structure, and the sealing member 10 has a spherical structure; the diameter of the sealing member 10 is larger than the diameter of the one-way valve inlet hole 9, and smaller than the diameter of the first groove 8.

[0042] like Figure 7 As shown, in this embodiment, the sealing element 10 can be a soft ball. The first groove 8 has a hemispherical structure and is connected to the one-way valve inlet hole 9. The diameter of the soft ball is slightly larger than the diameter of the one-way valve inlet hole 9 but smaller than the diameter of the first groove 8. When the one-way valve is open, the liquid pushes the soft ball into the amplification chamber 6. When the one-way valve is closed, the backflowing liquid acts on the upper surface of the soft ball, and the soft ball blocks the one-way valve inlet hole 9 to prevent the liquid from continuing to flow back.

[0043] Furthermore, in a preferred embodiment, both the one-way valve inlet hole 9 and the one-way valve outlet hole 12 are vertically oriented. Additionally, a lowering device positioned above the first groove 8 may be included to act on the sealing member 10, thereby enhancing the sealing function and ensuring that liquid cannot flow back. The components in the expanded area can also be assembled using other methods, such as laser welding or heat sealing. If laser welding is used, the adhesive layer 4 is unnecessary; however, the hollow structure in the middle of the adhesive layer 4 must be avoided during welding to ensure a certain gap between the chip and the sealing layer 3 in this area.

[0044] In a specific case of practical application, such as Figure 8As shown, a microfluidic chip is provided, including a central axis 101, a pre-placed reagent storage area 102, a liquid mixing area 103, a sorting area 104, a waste liquid chamber 105, and an amplification area 106. The experimental detection process is as follows:

[0045] 1) Add the sample to the liquid mixing zone 103;

[0046] 2) The lysis buffer in the pre-prepared reagent storage area 102 is released, mixes with the sample in the liquid mixing area 103, and lyses the sample;

[0047] 3) The lysed sample and lysis buffer pass through the sorting zone 104 and enter the waste liquid chamber 105. During this process, nucleic acid molecules are adsorbed into the silica membrane at the front end of the sorting zone 104.

[0048] 4) The cleaning solution in the pre-set reagent storage area 102 is released, passes through the sorting area 104, and enters the waste liquid chamber 105. During this process, impurities in the silica membrane are carried into the waste liquid chamber 105 by the cleaning solution.

[0049] 5) The elution buffer released from the pre-set reagent storage area 102 passes through the sorting area 104 and enters the amplification area 106. During this process, the nucleic acid molecules in the silica membrane are carried into the amplification area 106 by the elution buffer.

[0050] 6) The elution buffer enters amplification chamber 6 to complete the nucleic acid amplification process, and the presence of the target gene in each chamber is determined by fluorescence detection.

[0051] In step (6), the eluent flows from the measurement chamber 5 into the amplification chamber 6 during the high-speed centrifugal motion of the chip, and mixes thoroughly with the pre-placed lyophilized amplification bulbs in the amplification chamber 6. During this process, the chip is in motion, and the flow path of the eluent is as follows: Figure 4 As shown in (a), the eluent converts the radial centrifugal force into upward pressure within the flow channel orifice, and pushes up the sealing element 10. At this time, the one-way valve is in the open state; subsequently, the eluent flows into the amplification region 106 through the gap between the sealing layer 3 and the chip.

[0052] After mixing, the chip stops moving, and the sealing element 10 in the first groove 8 returns to the bottom of the first groove 8 under the action of gravity; the temperature control component in the instrument clamps the upper and lower surfaces of the chip amplification area 106 for heat transfer, and the amplification program begins; during this process, the temperature of the amplification area 106 can rise to a maximum of 90 degrees Celsius, and the liquid in the amplification chamber 6 expands due to heat, flowing back from the one-way valve outlet channel 11 and the slit channel 14, and acting on the upper surface of the sealing element 10, so that the sealing element 10 adheres tightly to the bottom of the first groove 8, blocking the one-way valve inlet hole 9, preventing further backflow; at this time, the one-way valve is in the closed state, and the liquid flows through as... Figure 4 As shown in (b) of the diagram.

[0053] Since the chip is stationary at this time, in order to ensure the sealing effect of the liquid, a lowering device can be added above the first groove 8 inside the instrument. After the chip is stationary and successfully positioned, the lowering device moves down a certain distance and acts on the sealing layer 3 and the sealing member 10 in the first groove 8 in sequence, so that the sealing member 10 abuts against the one-way valve inlet hole 9, thereby ensuring that the liquid cannot flow back into the one-way valve inlet hole 9.

[0054] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A one-way valve structure on a centrifugal microfluidic chip, applied to the amplification region of the chip; the chip includes a substrate, a die, a sealing layer, and an adhesive layer; the amplification region includes a measurement cavity and an amplification cavity formed on the lower surface of the die, characterized in that, The die has a one-way valve inlet channel on its lower surface, one end of which is connected to the measurement chamber. A first groove is also formed on the upper surface of the die at the corresponding location of the other end of the one-way valve inlet channel. A one-way valve inlet through-hole, connected to the other end of the one-way valve inlet channel, is formed within the first groove, and a sealing element for blocking the one-way valve inlet through-hole is also movably arranged within the first groove. A one-way valve outlet channel, one end of which is connected to the amplification chamber, is formed on the die, and a one-way valve outlet through-hole, connected to the other end of the one-way valve outlet channel, is also formed on the die. An adhesive layer is arranged on the upper surface of the die corresponding to the amplification region, and a perforated hole is formed on the adhesive layer. The first groove is located within one end of the perforated hole, and the one-way valve outlet through-hole is located within the other end of the perforated hole. A sealing layer covers the adhesive layer, and a gap channel, connected to the first groove and the one-way valve outlet through-hole, is left between the lower surface of the sealing layer and the perforated hole. The one-way valve outlet channel is located on the upper surface of the bare plate; The first groove has a hemispherical structure, and the sealing element has a spherical structure; the diameter of the sealing element is larger than the diameter of the one-way valve inlet orifice, but smaller than the diameter of the first groove.

2. The one-way valve structure on the centrifugal microfluidic chip according to claim 1, characterized in that, The one-way valve outlet channel is located on the lower surface of the bare plate.

3. The one-way valve structure on the centrifugal microfluidic chip according to claim 1, characterized in that, Both the first groove and the sealing element are cylindrical in shape; the diameter of the sealing element is larger than the diameter of the one-way valve inlet orifice, but smaller than the diameter of the first groove.

4. The one-way valve structure on the centrifugal microfluidic chip according to claim 1, characterized in that, Both the inlet and outlet ports of the one-way valve are opened in the vertical direction.

5. The one-way valve structure on the centrifugal microfluidic chip according to claim 1, characterized in that, It also includes a lower pestle device arranged above the first groove.

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