A pressurized microfluidic chip

Abstract

The present application relates to the technical field of microfluidic chip, and particularly relates to a pressurized microfluidic chip. The present application provides a pressurized microfluidic chip, which comprises a chip main body, a one-way valve, a pressurizing unit, a reaction unit and an exhaust unit. The one-way valve is located on the chip main body, the liquid inlet of the one-way valve is connected with the sample inlet on the chip main body through the internal pipeline in the chip main body, the liquid outlet of the one-way valve is communicated with the liquid inlet of the reaction unit through the internal pipeline in the chip main body, the liquid outlet of the reaction unit is communicated with the exhaust unit, and the exhaust unit is also communicated with the pressurizing unit. The one-way valve is used for limiting the one-way flow of liquid from the liquid inlet to the liquid outlet. The present application provides a pressurized microfluidic chip, which can prevent the production of bubbles in the amplification process.

Description

Technical Field

[0001] This invention relates to the field of microfluidic chip technology, and in particular to a pressure boosting microfluidic chip. Background Technology

[0002] Microfluidic chips are a technology platform that manipulates nanoliters to picoliters of fluid within micrometer-level channels (typically 10-500 micrometers wide). They are also known as "lab-on-a-chip" or micro total analysis systems (μ-TAS). Their core objective is to integrate sampling, reaction, separation, and detection operations from chemical and biological laboratories onto a chip of just a few square centimeters, achieving automated and miniaturized analysis.

[0003] When conducting detection and analysis, real-time fluorescence PCR detection is mainly used. During the detection process, the microfluidic chip is prone to bubble formation at high temperatures during sample addition and amplification, which affects the accuracy of subsequent optical measurement results.

[0004] Therefore, in order to address the above problems, there is an urgent need for a microfluidic chip that can prevent the formation of bubbles during the amplification process. Summary of the Invention

[0005] This invention provides a pressurized microfluidic chip that can prevent the formation of bubbles during the amplification process.

[0006] In a first aspect, embodiments of the present invention provide a pressurized microfluidic chip, comprising a chip body, a one-way valve, a pressurization unit, a reaction unit, and an exhaust unit;

[0007] The one-way valve is located on the chip body. The inlet of the one-way valve is connected to the sample inlet on the chip body through an internal pipe inside the chip body. The outlet of the one-way valve is connected to the inlet of the reaction unit through an internal pipe inside the chip body. The outlet of the reaction unit is connected to the exhaust unit, and the exhaust unit is also connected to the pressurization unit. The one-way valve is used to restrict the unidirectional flow of liquid from the inlet to the outlet.

[0008] The pressurization unit has a volume change structure. During the sample injection stage, the volume of the pressurization unit increases to allow the sample to enter the reaction unit. During the amplification stage, the volume of the pressurization unit decreases to pressurize the liquid in the reaction unit.

[0009] In one possible design, the one-way valve includes a valve seat, a valve body, and a valve cover;

[0010] The valve seat is cylindrical, with one end fixed to the surface of the chip body and the other end sealed by the valve cover. The outlet of the internal pipe connected to the sample inlet and the inlet of the internal pipe connected to the reaction unit are both connected to the interior of the valve seat. The valve body is located inside the valve seat and connected to the chip body. The valve body is hollow inside, with one end open and the other end closed. The closed end is formed by the abutting of two inclined plate edges. The open end of the valve body is fastened to the outlet of the internal pipe connected to the sample inlet, forming the liquid inlet of a one-way valve. The inlet of the internal pipe connected to the reaction unit is located between the valve body and the valve seat. The space formed by the valve body, the valve seat, and the valve cover is the liquid outlet.

[0011] In one possible design, the pressurization unit includes a sleeve and an airbag;

[0012] One end of the sleeve is fixed to the chip body, wherein one end of the internal pipe communicating with the exhaust unit is located inside the sleeve, and the airbag is sealed to the end of the sleeve away from the chip body;

[0013] Before sample injection, the air bladder is recessed into the sleeve. During the sample injection stage, the air bladder inflates to provide space for liquid to enter the reaction unit. During the amplification stage, the air bladder is pressed to increase the gas pressure inside the reaction unit.

[0014] In one possible design, the airbag sequentially includes a cylindrical portion, a connecting portion, and a curved portion; wherein the protrusion of the curved portion faces the chip body;

[0015] The end of the cylindrical portion away from the connecting portion is fixed to the sleeve, and the thickness of the connecting portion is thinner than that of the cylindrical portion and the curved portion, respectively.

[0016] In one possible design, the cylindrical portion has an annular protrusion perpendicular to its axis near its port, the sleeve has a circular groove, one end of the cylindrical portion is inserted into the circular groove, the annular protrusion covers the end face of the sleeve, and the circular groove is pre-filled with sealant.

[0017] In one possible design, the airbag is made of silicone.

[0018] In one possible design, the reaction unit includes multiple reaction chambers, each of which is connected to the liquid outlet of the one-way valve and the exhaust unit through different internal channels.

[0019] In one possible design, the internal channel connecting the exhaust unit and the reaction unit has a waterproof and breathable membrane covering the channel opening.

[0020] In one possible design, the waterproof and breathable membrane is made of materials including PTFE composite membrane, PP nonwoven fabric, TPU, or PE.

[0021] Secondly, embodiments of the present invention provide a detection method based on any of the above-mentioned pressurized microfluidic chips, the detection method comprising:

[0022] During the sample introduction stage, the liquid to be tested is injected through the sample inlet, allowing the liquid to enter the reaction unit through the one-way valve; wherein, the gas in the reaction unit is discharged into the exhaust unit, and the gas in the exhaust unit enters the pressurization unit, increasing the volume of the pressurization unit;

[0023] During the amplification phase, the pressurization unit is compressed so that the pressure is transmitted to the reaction unit through the exhaust unit.

[0024] Compared with the prior art, the present invention has at least the following beneficial effects:

[0025] In this embodiment, the test liquid is added through the injection port and enters the reaction unit via a one-way valve. Gas within the reaction unit enters the pressurization unit via an exhaust unit, increasing its volume. Since the one-way valve only allows liquid to enter the reaction unit, the liquid entering the unit will not flow backwards through the valve to the outside, ensuring the airtightness of the test liquid within the reaction unit. During the amplification phase, the pressurization unit provides pressure by compressing its volume. This pressure is transmitted to the reaction unit via the exhaust unit, placing the test liquid within the reaction unit at a higher pressure. The increased pressure raises its boiling point, thus preventing bubble formation within the reaction unit, where normal atmospheric pressure would normally be close to boiling and prone to bubble production. Attached Figure Description

[0026] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0027] Figure 1 This is a first-view structural schematic diagram of a pressure-boosting microfluidic chip provided in an embodiment of the present invention;

[0028] Figure 2This is a schematic diagram of a pressure-boosting microfluidic chip from a second perspective, provided in an embodiment of the present invention.

[0029] Figure 3 This is a front view schematic diagram of a pressure boosting microfluidic chip provided in an embodiment of the present invention;

[0030] Figure 4 is a diagram illustrating a detection process for a liquid to be tested according to an embodiment of the present invention, including... Figure 4a , Figure 4b , Figure 4c and Figure 4d ;

[0031] Figure 5 This is a schematic diagram of a one-way valve with downstream flow provided in an embodiment of the present invention; wherein, the arrow indicates the direction of liquid flow;

[0032] Figure 6 This is a schematic diagram of a one-way valve reversing flow structure provided in an embodiment of the present invention; wherein, the arrow direction indicates the liquid flow direction;

[0033] Figure 7 This is a schematic diagram of a flow-through umbrella valve provided in an embodiment of the present invention;

[0034] Figure 8 This is a schematic diagram of a reverse flow structure of an umbrella valve provided in an embodiment of the present invention;

[0035] Figure 9 This is a schematic diagram of a Belleville valve with downstream flow provided in an embodiment of the present invention;

[0036] Figure 10 This is a schematic diagram of a Belleville valve reversing flow provided in an embodiment of the present invention.

[0037] In the picture:

[0038] 1-Chip body;

[0039] 11-Inlet;

[0040] 2-Check valve;

[0041] 21-Valve seat;

[0042] 22-Valve body;

[0043] 23-Valve cover;

[0044] 3-Boost unit;

[0045] 31-Sleeve;

[0046] 32-Airbags;

[0047] 4-Reaction unit;

[0048] 5-Exhaust unit;

[0049] 51-Waterproof and breathable membrane. Detailed Implementation

[0050] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0051] In the description of the embodiments of the present invention, unless otherwise expressly specified and limited, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance; unless otherwise specified or stated, the term "multiple" refers to two or more; the terms "connected," "fixed," etc., should be interpreted broadly. For example, "connected" can be a fixed connection, a detachable connection, an integral connection, or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium. Those skilled in the art can understand the specific meaning of the above terms in the present invention according to the specific circumstances.

[0052] In this specification, it should be understood that the directional terms such as "upper" and "lower" used in the description of the embodiments of the present invention are used to describe the angles shown in the accompanying drawings and should not be construed as limiting the embodiments of the present invention. Furthermore, in the context, it should also be understood that when it is mentioned that one element is connected "upper" or "lower" to another element, it can be directly connected to the other element "upper" or "lower," or indirectly connected to the other element "upper" or "lower" through an intermediate element.

[0053] like Figures 1 to 3 As shown, this embodiment of the invention provides a pressurized microfluidic chip, including a chip body 1, a one-way valve 2, a pressurization unit 3, a reaction unit 4, and an exhaust unit 5;

[0054] One-way valve 2 is located on chip body 1. The liquid inlet of one-way valve 2 is connected to the sample inlet 11 on chip body 1 through an internal pipe inside chip body 1. The liquid outlet of one-way valve 2 is connected to the liquid inlet of reaction unit 4 through an internal pipe inside chip body 1. The liquid outlet of reaction unit 4 is connected to exhaust unit 5. Exhaust unit 5 is also connected to pressurization unit 3. One-way valve 2 is used to restrict the liquid from flowing unidirectionally from the liquid inlet to the liquid outlet.

[0055] The pressurization unit 3 is a volume-changing structure. During the sample injection stage, the volume of the pressurization unit 3 increases to allow the sample to enter the reaction unit 4. During the amplification stage, the volume of the pressurization unit 3 decreases to pressurize the liquid in the reaction unit 4.

[0056] In this embodiment, the test liquid is added through the injection port 11. The test liquid enters the reaction unit 4 through the one-way valve 2. The gas in the reaction unit 4 enters the pressurization unit 3 through the exhaust unit 5. After the gas enters the pressurization unit 3, the volume of the pressurization unit 3 increases. Since the one-way valve 2 only allows liquid to enter the reaction unit 4, the liquid entering the reaction unit 4 will not reverse through the one-way valve 2 and come into contact with the outside, ensuring the sealing of the test liquid in the reaction unit 4. During the amplification stage, the volume of the pressurization unit 3 is compressed to provide pressure. The pressure is transmitted to the reaction unit 4 through the exhaust unit 5, so that the test liquid in the reaction unit 4 is in a higher pressure state. After the pressure increases, its boiling point also increases. In this way, the reaction unit 4, which is normally close to boiling and prone to producing bubbles, no longer produces bubbles.

[0057] Please refer to Figure 5 and Figure 6 In some embodiments of the present invention, the one-way valve 2 includes a valve seat 21, a valve body 22, and a valve cover 23;

[0058] The valve seat 21 is cylindrical, with one end fixed to the surface of the chip body 1 and the other end sealed by the valve cover 23. The outlet of the internal pipe connected to the sample inlet 11 and the inlet of the internal pipe connected to the reaction unit 4 are both connected to the inside of the valve seat 21. The valve body 22 is located inside the valve seat 21 and connected to the chip body 1. The valve body 22 is hollow inside, with one end open and the other end closed. The closed end is formed by the abutting of two inclined plate edges. The open end of the valve body 22 is fastened to the outlet of the internal pipe connected to the sample inlet 11. The open end of the valve body 22 forms the liquid inlet of the one-way valve 2. The inlet of the internal pipe connected to the reaction unit 4 is located between the valve body 22 and the valve seat 21. The space formed by the valve body 22, the valve seat 21 and the valve cover 23 is the liquid outlet.

[0059] In this embodiment, during sample injection, liquid enters the valve seat 21 from the open end. The liquid compresses the inner surface of the plate it is in contact with, causing the plates to separate, allowing the liquid to exit through the closed end of the valve body 22. During the amplification stage, liquid or gas outside the valve seat 21 compresses the plate, increasing the pressure between the plates and improving the sealing of the closed end.

[0060] Of course, a one-way valve can also have other structures, for example, it can be an umbrella valve ( Figure 7 and Figure 8 ) and Belleville valve ( Figure 9 and Figure 10Diaphragm type, spring type, etc.

[0061] In some embodiments of the present invention, the pressurization unit 3 includes a sleeve 31 and an airbag 32;

[0062] One end of the sleeve 31 is fixed to the chip body 1, wherein one end of the internal pipe connected to the exhaust unit 5 is located inside the sleeve 31, and the airbag 32 is sealed to the end of the sleeve 31 away from the chip body 1.

[0063] Before sample injection, the air bladder 32 is recessed into the sleeve 31. During the sample injection stage, the air bladder 32 inflates to provide space for liquid injection into the reaction unit 4. During the amplification stage, the air bladder 32 is pressed to increase the gas pressure inside the reaction unit 4.

[0064] In this embodiment, the air bladder 32 has the ability to bulge outward and indent inward, thereby changing the volume of the space formed between it, the sleeve 31, and the chip body 1. Before sample injection, the air bladder 32 is indented inward, leaving a certain amount of expansion space for the gas discharged from the reaction unit 4, facilitating the entry of liquid into the reaction unit 4. After sample injection, the gas enters the space formed by the sleeve 31 and the air bladder 32, causing the air bladder 32 to bulge outward. During the amplification stage, pressing the air bladder 32 provides pressure to the reaction unit 4, increasing the internal pressure of the reaction unit 4 by one atmosphere, raising the boiling point of the liquid to about 120°C, which is much higher than the denaturation temperature (95°C) during PCR amplification, thereby reducing the amount of air bubbles.

[0065] In some embodiments of the present invention, the airbag 32 sequentially includes a cylindrical portion, a connecting portion, and a curved portion; wherein the curved portion protrudes towards the chip body 1.

[0066] The end of the cylindrical part away from the connecting part is fixed to the sleeve 31, and the thickness of the connecting part is thinner than that of the cylindrical part and the curved part, respectively.

[0067] In this embodiment, under normal conditions, the curved surface protrudes inward and is concave, which, combined with the thinner connecting portion, allows the airbag 32 to maintain the concave state of the curved surface before sample injection. It should be noted that if the curved surface protrudes upward under normal conditions, due to the elastic material of the airbag 32, even if the curved surface is pressed downward by external force, it will gradually return to the upward protruding state after the pressure is released.

[0068] In some embodiments of the present invention, the cylindrical portion is provided with an annular protrusion perpendicular to its axis near its port, the sleeve 31 is provided with a circular groove, one end of the cylindrical portion is inserted into the circular groove, the annular protrusion covers the end face of the sleeve 31, and a sealant is pre-filled in the circular groove.

[0069] In some embodiments of the present invention, the airbag 32 is made of silicone.

[0070] In some embodiments of the present invention, the reaction unit 4 includes multiple reaction chambers, each of which is connected to the liquid outlet of the one-way valve 2 and the exhaust unit 5 through different internal channels.

[0071] In some embodiments of the present invention, the internal channel connecting the exhaust unit 5 and the reaction unit 4 is covered with a waterproof and breathable membrane 51.

[0072] In this embodiment, the waterproof and breathable membrane 51 allows gas from the reaction unit 4 to pass through it into the exhaust unit 5 without allowing the liquid to be tested to enter the exhaust unit 5. Furthermore, the pressure provided by the pressurization unit 3 can also pass through the waterproof and breathable membrane 51 and act on the liquid to be tested within the reaction unit 4.

[0073] In some embodiments of the present invention, the waterproof and breathable membrane 51 is prepared from materials including PTFE composite membrane, PP nonwoven fabric, TPU or PE.

[0074] Please refer to Figures 4a to 4b This invention provides a detection method based on any of the above-mentioned boosted microfluidic chips. The detection method includes:

[0075] During the sample injection stage, the liquid to be tested is injected through the injection port 11, and the liquid to be tested enters the reaction unit 4 through the one-way valve 2; wherein, the gas in the reaction unit 4 is discharged into the exhaust unit 5, and the gas in the exhaust unit 5 enters the pressurization unit 3, increasing the volume of the pressurization unit 3.

[0076] During the expansion phase, the compression booster unit 3 is used to transmit pressure to the reaction unit 4 through the exhaust unit 5.

[0077] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A pressure-boosting microfluidic chip, characterized in that, Includes the chip body, one-way valve, pressurization unit, reaction unit, and exhaust unit; The one-way valve is located on the chip body. The inlet of the one-way valve is connected to the sample inlet on the chip body through an internal pipe inside the chip body. The outlet of the one-way valve is connected to the inlet of the reaction unit through an internal pipe inside the chip body. The outlet of the reaction unit is connected to the exhaust unit, and the exhaust unit is also connected to the pressurization unit. The one-way valve is used to restrict the unidirectional flow of liquid from the inlet to the outlet. The pressurization unit has a volume change structure. During the sample injection stage, the volume of the pressurization unit increases to allow the sample to enter the reaction unit. During the amplification stage, the volume of the pressurization unit decreases to pressurize the liquid in the reaction unit. The pressurization unit includes a sleeve and an airbag; One end of the sleeve is fixed to the chip body, wherein one end of the internal pipe communicating with the exhaust unit is located inside the sleeve, and the airbag is sealed to the end of the sleeve away from the chip body; Before sample injection, the air bladder is recessed into the sleeve. During the sample injection stage, the air bladder inflates to provide space for liquid to enter the reaction unit. During the amplification stage, the air bladder is pressed to increase the gas pressure inside the reaction unit. The airbag comprises a cylindrical portion, a connecting portion, and a curved portion in sequence; wherein the curved portion protrudes towards the chip body; The end of the cylindrical portion away from the connecting portion is fixed to the sleeve, and the thickness of the connecting portion is thinner than that of the cylindrical portion and the curved portion, respectively. The internal channel connecting the exhaust unit and the reaction unit is covered with a waterproof and breathable membrane.

2. The booster microfluidic chip according to claim 1, characterized in that, The one-way valve includes a valve seat, a valve body, and a valve cover; The valve seat is cylindrical, with one end fixed to the surface of the chip body and the other end sealed by the valve cover. The outlet of the internal pipe connected to the sample inlet and the inlet of the internal pipe connected to the reaction unit are both connected to the interior of the valve seat. The valve body is located inside the valve seat and connected to the chip body. The valve body is hollow inside, with one end open and the other end closed. The closed end is formed by the abutting of two inclined plate edges. The open end of the valve body is fastened to the outlet of the internal pipe connected to the sample inlet, forming the liquid inlet of a one-way valve. The inlet of the internal pipe connected to the reaction unit is located between the valve body and the valve seat. The space formed by the valve body, the valve seat, and the valve cover is the liquid outlet.

3. The booster microfluidic chip according to claim 1, characterized in that, The cylindrical portion has an annular protrusion perpendicular to its axis near its port. The sleeve has a circular groove. One end of the cylindrical portion is inserted into the circular groove. The annular protrusion covers the end face of the sleeve. The circular groove is pre-filled with sealant.

4. The booster microfluidic chip according to claim 1, characterized in that, The airbag is made of silicone.

5. The booster microfluidic chip according to claim 1, characterized in that, The reaction unit includes multiple reaction chambers, each of which is connected to the liquid outlet of the one-way valve and the exhaust unit through different internal channels.

6. The booster microfluidic chip according to claim 1, characterized in that, The materials used to prepare the waterproof and breathable membrane include PTFE composite membrane, PP nonwoven fabric, TPU or PE.

7. A detection method, characterized in that, Based on the pressurized microfluidic chip according to any one of claims 1-6, the detection method includes: During the sample introduction stage, the liquid to be tested is injected through the sample inlet, allowing the liquid to enter the reaction unit through the one-way valve; wherein, the gas in the reaction unit is discharged into the exhaust unit, and the gas in the exhaust unit enters the pressurization unit, increasing the volume of the pressurization unit; During the amplification phase, the pressurization unit is compressed so that the pressure is transmitted to the reaction unit through the exhaust unit.

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