Microfluidic chip with reagent quantitative liquid taking unit and control method
By designing a microfluidic chip with quantitative liquid dispensing for miniaturized detection systems, and by designing a microfluidic chip with a reagent quantitative liquid dispensing unit, the technical problems of quantitative liquid dispensing microfluidic chips in portable biological detection devices are solved. The patent specification provides a microfluidic chip with a reagent quantitative liquid dispensing unit, which solves the problems of high manufacturing cost, structural complexity, and control methods in existing technologies, and achieves full integration, automation, and application for rapid on-site diagnosis.
Patent Information
- Application Number
- CN202410829849.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-06-25
- Publication Date
- 2026-01-27
- Estimated Expiration
- 2044-06-25
AI Technical Summary
Existing microfluidic chips suffer from high cost and complex structure in quantitative liquid extraction, making them unsuitable for portable biochemical analysis devices.
Design a microfluidic chip with a reagent quantitative dispensing unit. The fluid volume can be simply and accurately quantitatively controlled by the volume difference between the liquid supply tube and the reagent flow chamber. It can be driven by external pressure without the need for microvalves or peristaltic pumps. The sampling and quantitative sampling can be achieved by combining the bevel needle and rubber stopper.
It reduces the manufacturing cost of microfluidic chips, has a simple structure, is suitable for portable biochemical analysis devices, and achieves fully integrated, automated and standardized quantitative liquid extraction.
Smart Images

Figure CN118698620B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biological detection device design technology, specifically relating to a microfluidic chip with a reagent quantitative dispensing unit and its control method. Background Technology
[0002] In recent years, microfluidic technology has been widely applied in biomedicine, chemical analysis and detection, and other fields. As a novel technological platform, microfluidic systems control the flow of minute samples through tiny channels, pathways, and valves, offering advantages such as small sample volume, high automation, and fast analysis speed. These systems play a crucial role in laboratory research, medical diagnostics, and drug development. However, in analytical testing, reagent preparation and sample collection and transfer are critical steps. In quantitative biochemical analysis, accurately controlling the volume of trace solutions directly affects the accuracy of test results; therefore, the precision of quantitative liquid extraction is essential for accurate biochemical analysis. Traditional large-scale analytical instruments, such as fully automated biochemical analyzers and immunoassay analyzers, use plunger pumps to control sampling needles to extract samples for collection and quantification. These devices are limited in accuracy in liquid addition range due to their structural characteristics and have high hardware requirements. Therefore, they are mainly used in large-scale automated equipment and are difficult to integrate into portable biochemical analysis devices. Another method involves professionals adding liquid using pipettes or droppers. This method also has many drawbacks, mainly because pipettes have high precision but are expensive, while droppers are cheaper but their precision is difficult to guarantee.
[0003] With increasing health demands, traditional central laboratory testing can no longer meet the growing testing needs. People require testing anytime, anywhere, leading to a significant demand for integrated, automated, and miniaturized testing systems. To achieve this goal, developing quantitative liquid sampling technologies suitable for portable analysis has become crucial.
[0004] To address the following issues in existing technologies: Traditional central laboratories require specialized equipment and control systems such as plunger pumps and pipettes, which occupy space and require a large number of professional personnel, making integration and automation impossible. The earliest common microfluidic chips utilize highly elastic PDMS material to fabricate multilayer microfluidic chips, integrating microvalve and peristaltic pump control structures to achieve quantitative dispensing of trace samples. However, this chip requires cumbersome manufacturing processes and complex microvalve control systems, resulting in high cost and complexity. The quantitative liquid dispensing structure mentioned in patent CN112147356A uses a liquid-carrying rod to achieve solution delivery and switching, reducing structural complexity and manufacturing costs, but still cannot achieve precise quantitative dispensing of trace solutions. The sample quantification unit used in patent CN108663531B utilizes centrifugal force to accurately achieve sequential driving and volumetric quantification of fluids in a sample to a specific area, but it is limited by the chip design requiring specific external driving conditions, making standardization and integration impossible.
[0005] Using the microfluidic quantitative liquid dispensing reagent tube assembly and its usage method provided by this invention, truly integrated, automated, and standardized quantitative analysis can be achieved. Based on a simple external pressure drive, it enables precise quantification and on-demand use of trace reagents, and can be combined with a microfluidic chip system for rapid on-site diagnosis. Summary of the Invention
[0006] This invention provides a microfluidic chip with a reagent quantitative sampling unit and a control method, which can solve the technical problems of existing microfluidic chips with reagent quantitative sampling that use microvalves and peristaltic pumps, which are costly, complex in structure, and unsuitable for portable biochemical analysis devices.
[0007] To address the above problems, the present invention provides a microfluidic chip with a reagent quantitative dispensing unit, comprising:
[0008] A reagent quantitative dispensing unit includes: a unit body, wherein a reagent flow chamber and a reagent quantitative chamber are formed within the unit body, the reagent flow chamber and the reagent quantitative chamber are connected through a flow channel, wherein the reagent flow chamber is selectively connected to a supply pipe, and the fluid volume contained in the supply pipe is greater than the volume of the reagent flow chamber.
[0009] In some embodiments, the reagent metering chamber is further provided with a septum stopper, and a reconstitution channel is formed on the wall of the reagent metering chamber. The position of the flow channel is higher than the top inlet of the reconstitution channel, and the top surface of the septum stopper is higher than the top inlet of the reconstitution channel but lower than the flow channel. Bottom stoppers are provided in the bottom ports of both the reagent metering chamber and the reagent flow channel, and the space between the septum stopper and the bottom stopper is pre-filled with the reagent to be reconstituted.
[0010] In some embodiments, an upper rubber stopper is provided in the top port of the reagent metering chamber, and a reagent metering space is formed between the upper rubber stopper and the partition rubber stopper. An overflow channel is also formed on the cavity wall of the reagent metering chamber, and a waste liquid chamber is also formed in the unit body. The overflow channel is connected to the waste liquid chamber.
[0011] In some embodiments, the reagent metering chamber is further provided with a partition rubber stopper, an exhaust hole is formed on the wall of the reagent metering chamber, a bottom rubber stopper is provided in the bottom port of both the reagent metering chamber and the reagent flow passage, an upper rubber stopper is provided in the top port of the reagent metering chamber, the bottom surface of the partition rubber stopper is higher than the flow passage and the exhaust hole, and a reagent pre-positioning chamber for accommodating the first reagent is formed between the partition rubber stopper and the upper rubber stopper.
[0012] In some embodiments, a reagent to be reconstituted is pre-filled between the partition stopper and the bottom stopper.
[0013] In some embodiments, the reagent flow chamber is a cylindrical cavity with a diameter of D, and D≥4mm.
[0014] In some embodiments, the microfluidic chip further includes a chip lower part, which has a reagent communication channel and multiple beveled needles communicating with the reagent communication channel, each beveled needle corresponding to a bottom rubber plug.
[0015] This invention also provides a control method for a microfluidic chip, used to manipulate the aforementioned microfluidic chip with a reagent quantitative dispensing unit, comprising: pressing down an upper rubber stopper disposed within the liquid supply tube along its axial direction to the bottom of the liquid supply tube, so that all fluid in the liquid supply tube flows out while the upper rubber stopper seals the beveled needle corresponding to the liquid supply tube; then, pressing down an upper rubber stopper disposed within the reagent quantitative cavity along its axial direction to the bottom of the cavity so that the beveled needle disposed at the bottom of the reagent quantitative cavity passes through the corresponding bottom rubber stopper and the partition rubber stopper in sequence, the upper rubber stopper of the reagent quantitative cavity seals the beveled needle, and the fluid containing the reagent to be reconstituted and the first reagent sequentially enter the collection tube.
[0016] The present invention also provides a microfluidic chip with a reagent quantitative dispensing unit, comprising: a reagent quantitative dispensing unit, including: a unit body, wherein a sampling quantitative cavity and a waste liquid overflow cavity are formed within the unit body, the sampling quantitative cavity is connected to the waste liquid overflow cavity, the sampling quantitative cavity is selectively connected to a supply tube and a collection tube, and the fluid volume contained in the supply tube is greater than the volume of the sampling quantitative cavity.
[0017] In some embodiments, the sampling quantitative cavity is a cylindrical cavity with a diameter of D, and D≥4mm; and / or, the sealing push rod of the sampling quantitative cavity has a plunger body, the shape of which matches the sampling quantitative cavity.
[0018] The present invention provides a microfluidic chip and control method with a reagent quantitative dispensing unit, which has the following beneficial effects:
[0019] By utilizing the difference between the fluid volume contained in the supply tube and the volume of the reagent flow chamber, a simple and precise quantitative control of the amount of fluid to be sampled can be achieved. This eliminates the need for microvalves or peristaltic pumps used in existing technologies for sample quantification, greatly reducing the manufacturing cost of microfluidic chips. The structure is simple and easy to operate, making it particularly suitable for applications in portable biochemical analysis devices.
[0020] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description
[0021] To more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings in the following description are merely exemplary, and those skilled in the art can derive other embodiments based on the provided drawings without creative effort.
[0022] The structures, proportions, sizes, etc. illustrated in this specification are only for the purpose of assisting those skilled in the art in understanding and reading the content disclosed herein, and are not intended to limit the conditions under which the present invention can be implemented. Therefore, they have no substantial technical significance. Any modifications to the structure, changes in the proportions, or adjustments to the size, without affecting the effects and objectives that the present invention can produce, should still fall within the scope of the technical content disclosed in the present invention.
[0023] Figure 1 This is a three-dimensional structural schematic diagram (expanded) of a microfluidic chip with a reagent quantitative dispensing unit according to an embodiment of the present invention;
[0024] Figure 2 This is a schematic diagram of the internal structure of the reagent quantitative dispensing unit in Embodiment 1 of the present invention. The arrows in the diagram indicate the flow direction of the solution or gas.
[0025] Figure 3 This is a schematic diagram of the internal structure of the reagent quantitative dispensing unit in Embodiment 2 of the present invention. The arrows in the diagram indicate the flow direction of the solution or gas.
[0026] Figure 4This is a schematic diagram of the internal structure of the microfluidic chip with a reagent quantitative dispensing unit in Embodiment 3 of the present invention. ①②③ in the figure show the order of applying axial downward pressure (i.e., thrust), and the arrows in the figure show the flow direction of the solution or gas.
[0027] Figure 5 This is a schematic diagram of the internal structure of the reagent quantitative liquid dispensing unit in Embodiment 4 of the present invention. The arrows in the figure indicate the flow direction of the solution or gas.
[0028] The reference numerals in the attached figures are as follows:
[0029] 1. Unit body; 11. Reagent flow chamber; 12. Reagent metering chamber; 121. Reagent to be reconstituted; 122. Isolation stopper; 1221. Reconstitution channel; 1222. Vent hole; 124. Bottom stopper; 125. Upper stopper; 1251. Plunger body; 126. Overflow channel; 127. Waste liquid chamber; 128. Reagent pre-filling chamber; 13. Flow channel; 21. Supply tube; 22. Chip lower part; 221. Bevel needle; 222. Reagent connecting channel; 23. Collection tube; 24. Chip body; 25. Chip top cover; 51. Sampling metering chamber; 52. Waste liquid overflow chamber; 53. Sealing push rod; 531. Plunger body. Detailed Implementation
[0030] 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 only some embodiments of the present invention, and not all embodiments. The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit the present invention or its application or use. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0031] 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.
[0032] It should be understood that the term "and / or" used in this article is merely a description of the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, and B existing alone. Additionally, the character " / " in this article generally indicates that the preceding and following related objects have an "or" relationship.
[0033] Unless otherwise specifically stated, the relative arrangement, numerical expressions, and values of the components and steps set forth in these embodiments do not limit the scope of the invention. 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 figures denote similar items; therefore, once an item is defined in one figure, it need not be further discussed in subsequent figures.
[0034] In the description of this invention, it should be understood that the orientation or positional relationship indicated by directional terms such as "front, back, up, down, left, right", "horizontal, vertical, horizontal" and "top, bottom" is generally based on the orientation or positional relationship shown in the accompanying drawings, and is only for the convenience of describing this invention and simplifying the description. Unless otherwise stated, these directional terms do not indicate or imply that the device or element referred to must have a specific orientation or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation on the scope of protection of this invention; the directional terms "inner" and "outer" refer to the inner and outer contours relative to the outline of each component itself.
[0035] 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.
[0036] 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 should not be construed as limiting the scope of protection of this invention.
[0037] See Figures 1 to 5As shown, according to an embodiment of the present invention, a microfluidic chip with a reagent quantitative dispensing unit is provided, comprising:
[0038] See also Figures 2 to 4 As shown, the reagent quantitative dispensing unit includes: a unit body 1, in which a reagent flow chamber 11 and a reagent dispensing chamber 12 are formed. The reagent flow chamber 11 and the reagent dispensing chamber 12 are connected through a flow channel 13. The reagent flow chamber 11 is selectively connected to a liquid supply pipe 21, and the fluid volume contained in the liquid supply pipe 21 is greater than the volume of the reagent flow chamber 11. Thus, the amount of fluid that enters through the aforementioned flow channel 13 and is contained in the aforementioned reagent dispensing chamber 12 is the final quantitative value that needs to be sampled.
[0039] In this technical solution, the difference between the fluid volume contained in the liquid supply tube 21 and the volume of the reagent flow chamber 11 is used to achieve simple and accurate quantitative control of the amount of fluid to be sampled. This eliminates the need for microvalves or peristaltic pumps in existing technologies to achieve quantitative sampling, greatly reducing the manufacturing cost of microfluidic chips. The structure is simple and easy to operate, making it particularly suitable for application in portable biochemical analysis devices.
[0040] Example 1:
[0041] See details Figure 2 As shown, the reagent quantitative dispensing unit is specifically a quantitative dispensing unit that achieves quantitative dispensing based on air expulsion. It has an exhaust port 1222 on the cavity wall of the reagent quantitative chamber 12. A bottom rubber plug 124 is set in the bottom port of the reagent quantitative chamber 12, and an upper rubber plug 125 is set in the top opening. At the same time, a bottom rubber plug 124 is also set in the top port of the reagent flow chamber 11. The upper rubber plug 125 not only seals the top opening of the reagent quantitative chamber 12, but also serves as a driving carrier for external pressure (such as pressure applied by a pressure rod). The exhaust port 1222 is connected to the external atmospheric pressure (a membrane that is breathable but not water-permeable can be set inside to ensure that the sample or reagent fluid (solution) does not leak out), so that the fluid can smoothly enter the dispensing quantitative chamber. It is understood that during use, the liquid level of the solution to be quantified in the reagent quantitative chamber 12 does not exceed the position of the exhaust port 1222. The aforementioned bottom rubber stopper 124 can seal the corresponding chamber while also cooperating with the corresponding oblique needle 221 to form a flow control. That is, when the oblique needle 221 pierces from the bottom to the top of the bottom rubber stopper 124, the solution is released and connected. When the oblique needle 221 is inside the bottom rubber stopper 124, it is sealed to cut off the connection.
[0042] The specific usage can be as follows:
[0043] The first method: The volume of the solution (reagent or sample, etc.) in the supply tube 21 is known. The solution is completely discharged by using the air in the tube. At this time, the reagent flow chamber is full of solution, and the excess solution discharged into the reagent metering chamber is the solution that needs to be quantitatively taken (i.e., quantitative sampling).
[0044] The second method involves using the known volume of the solution (reagent or sample, etc.) in the supply tube 21. By using the air inside the tube to drive a certain downward stroke, the solution is precisely controlled to be discharged in a certain quantity, thereby obtaining a quantitative solution.
[0045] In this embodiment, the solution with a volume of 50 μL or more is used; preferably, see [reference needed]. Figure 2 As shown, the diameter D1 of the reagent flow chamber 11 should be no less than 4 mm to prevent air bubbles introduced from the supply tube 21 from forming an air column in the reagent flow chamber 11, which would lead to inaccurate quantification. More optimally, the connection between the reagent flow chamber 11 and the reagent quantification chamber 12 is treated with a hydrophilic coating, and the reagent flow chamber 11 is machined with rounded corners or bevels to allow air bubbles to rise along the flow channel wall and be smoothly discharged.
[0046] Example 2:
[0047] See details Figure 3 As shown, based on Example 1, the reagent metering chamber 12 is further provided with a septum stopper 122. A reconstitution channel 1221 is formed on the wall of the reagent metering chamber 12. The position of the flow channel 13 is higher than the top inlet of the reconstitution channel 1221, and the top surface of the septum stopper 122 is higher than the top inlet of the reconstitution channel 1221 but lower than the flow channel 13. Bottom stoppers 124 are provided in the bottom ports of both the reagent metering chamber 12 and the reagent flow channel 11. The septum stopper 122 and the reconstitution channel 1221 are connected in a series of steps. The space between the bottom rubber stoppers 124 is pre-filled with the reagent 121 to be reconstituted. The top port of the reagent metering chamber 12 is provided with an upper rubber stopper 125. The upper rubber stopper 125 and the partition rubber stopper 122 form a reagent metering space. An overflow channel 126 is also formed on the cavity wall of the reagent metering chamber 12. A waste liquid chamber 127 is also formed in the unit body 1. The aforementioned waste liquid chamber 127 can, for example, be arranged around the outer periphery of the reagent flow chamber 11 and the reagent metering chamber 12. The overflow channel 126 is connected to the waste liquid chamber 127.
[0048] The aforementioned reagent 121 to be reconstituted can specifically be lyophilized reaction microspheres; however, other reagents can be selected in other specific detection procedures. This technical solution is suitable for solutions of 10 μL or more.
[0049] In this technical solution, a sampling and quantitative space for the solution is formed between the partition rubber stopper 122 and the upper rubber stopper 125, and the reagent to be reconstituted 121 is pre-loaded between the bottom rubber stopper 124 and the partition rubber stopper 122, so as to realize the quantitative reconstitution of the solution while reconstituted the reagent in the microfluidic chip.
[0050] It is understandable that the aforementioned reagent flow chamber 11, reagent metering chamber 12, and waste liquid chamber 127 are assembled from corresponding inner tubes and outer sleeves, and the connection points should be properly sealed, for example, by setting corresponding sealing O-rings to prevent the solution from leaking out.
[0051] In specific operation, first press down the upper rubber stopper 125 in the corresponding liquid supply tube 21 to allow the solution inside to enter the reagent flow chamber 11. After the reagent flow chamber 11 is filled with solution (its volume is known), the excess solution will enter the sampling and quantitative space between the aforementioned partition rubber stopper 122 and the upper rubber stopper 125 through the flow channel 13. Since there is an overflow channel 126 on the cavity wall, the excess solution and gas will enter the waste liquid chamber 127 through it. The solution retained in the aforementioned sampling and quantitative space is the required solution volume. Then press down the reagent quantitative chamber. The upper rubber stopper 125 inside 12 moves downward. The upper rubber stopper 125 is pushed by the aforementioned quantitative solution to the partition rubber stopper 122. The partition rubber stopper 122 moves downward. During the downward movement of the partition rubber stopper 122, the quantitative solution enters the space below the partition rubber stopper 122 through the reconstitution channel 1221 and mixes with the reagent 121 to be reconstituted inside. The upper rubber stopper 125 continues to move downward and finally delivers the solution mixed with the reagent 121 to the subsequent chamber, such as the collection tube 23, through the corresponding bevel needle 221 and reagent communication channel 222.
[0052] It should be noted that since the overflow channel 126 in this embodiment can both vent air and overflow the solution, the diameter of the reagent flow chamber 11 in this embodiment is not limited. Even if bubbles are generated during the flow process, it will not lead to inaccurate quantification of the solution in the sampling and quantification space.
[0053] Example 3:
[0054] See details Figure 4As shown, based on Example 1, the reagent metering chamber 12 is further provided with a partition rubber stopper 122. A vent hole 1222 (which may contain a membrane that is permeable to air but impermeable to liquid) is formed on the wall of the reagent metering chamber 12. Bottom rubber stoppers 124 are provided in the bottom ports of both the reagent metering chamber 12 and the reagent flow chamber 11. An upper rubber stopper 125 is provided in the top port of the reagent metering chamber 12. The bottom surface of the partition rubber stopper 122 is higher than the flow channel 13 and the vent hole 1222. A reagent pre-positioning chamber 128 for containing the first reagent is formed between the partition rubber stopper 122 and the upper rubber stopper 125. A reagent 121 to be reconstituted is pre-loaded between the partition rubber stopper 122 and the bottom rubber stopper 124. The reagent flow chamber 11 is a cylindrical cavity with a diameter of D, where D ≥ 4 mm, which effectively prevents the formation of an air column within the reagent flow chamber 11, thereby ensuring the accuracy of the sample quantification.
[0055] In this embodiment, the air in the supply tube 21 drives the complete discharge of a known volume of solution, the reagent flow chamber 11 is filled with solution, and the excess solution discharged into the reagent metering chamber 12 is the solution to be metered.
[0056] In a specific application scenario, the aforementioned first reagent is DEPC water, and both the supply tube 21 and the collection tube 23 can be conventional standard reagent tubes. Specifically, the supply tube 21 is a conventional standard reagent tube used to inject the reaction elution buffer, which contains a pathogen or human nucleic acid substance to be detected, obtained by silica gel membrane column extraction or magnetic bead extraction. In practical applications, a portion of the elution buffer is typically used as a nucleic acid sample template for PCR amplification. The collection tube 23 is a conventional standard reagent tube used to receive the final reaction reagent mixture for the next step of heating and cycling amplification.
[0057] The following is for Figure 5 The microfluidic chip shown illustrates its loading and the process of quantitative liquid dispensing and reconstitution:
[0058] a) Reagent tube assembly loading process (i.e., microfluidic chip assembly process):
[0059] The corresponding reagent tubes are made of materials such as PMMA and PP, and the transparency is determined according to the storage conditions of the pre-loaded reagents. The first step is to load the inner tube for liquid extraction, and to seal it by connecting the rubber stopper 122 to the upper part of the tube wall flow channel 13. After installing the DEPC water and the upper rubber stopper 125, the lyophilized microspheres or solution reagents (primers, probes, and enzyme raw materials for the PCR reaction system, etc.) that need to be pre-loaded are loaded sequentially from the bottom, and the bottom rubber stopper 124 is then sealed.
[0060] b) Quantitative liquid collection and reconstitution process:
[0061] When using this component, the first standard reagent tube is pressed down to puncture the bevel needle 221, releasing the eluent into the quantitative dispensing unit. The eluent flows through the reagent flow chamber 11 until it is fully filled, and the overflowing solution is the required quantitative eluent, which is then reconstituted with the lyophilized microspheres pre-loaded in the reagent dispensing chamber 12. Subsequently, the upper rubber stopper 125 of the quantitative dispensing unit, under the pressure of the external push rod, causes the fluid in the reagent tube to continuously move downwards. The isolation rubber stopper 122 is punctured by the bevel needle 221, and DEPC water enters the collection tube 23 through the bevel needle 221. The upper rubber stopper 125 further descends to seal the top of the bevel needle 221, facilitating the injection of the solution from the collection tube 23.
[0062] This component can be used for quantitative dispensing of micro-solutions ranging from 10 to 100 μL, and is compatible with bubble and waste liquid handling. It requires minimal external drive conditions, and its internal structure is easy to manufacture and operate, even for non-professionals. It eliminates the need for costly devices such as plunger pumps, reducing costs. Furthermore, the quantified sample can be combined with other structures on the chip for subsequent analysis, forming a complete sample processing and analysis system, facilitating integration and portability.
[0063] The quantitative dispensing unit of this component uses a standardized rubber stopper and tube diameter. Standard components are set according to different quantitative requirements. Through cooperation with the bevel needle and rubber stopper, a standardized process and operation of "close-open-close" three states are realized, so as to facilitate the future development of standardized and diversified combination design, and realize the free operation of different quantitative amounts within a single reagent tube component.
[0064] See further Figure 4 As shown, the microfluidic chip also includes a chip lower part 22, which has a reagent communication channel 222 and multiple oblique needles 221 communicating with the reagent communication channel 222. Each oblique needle 221 is respectively disposed corresponding to each bottom rubber stopper 124.
[0065] Furthermore, the present invention also provides a control method for a microfluidic chip, used to manipulate the aforementioned microfluidic chip having a reagent quantitative dispensing unit, comprising:
[0066] The upper rubber plug 125 disposed inside the liquid supply pipe 21 is pressed down along the axial direction to the bottom of the liquid supply pipe 21, so that all the fluid in the liquid supply pipe 21 flows out at the same time, the upper rubber plug 125 seals the oblique needle 221 corresponding to the liquid supply pipe 21.
[0067] Subsequently, the upper rubber stopper 125 inside the reagent metering chamber 12 is pressed down along its axial direction to the bottom of the chamber so that the oblique needle 221 corresponding to the bottom of the reagent metering chamber 12 passes through the corresponding bottom rubber stopper 124 and the partition rubber stopper 122 in sequence. The upper rubber stopper 125 of the reagent metering chamber 12 seals the oblique needle 221. The fluid containing the reagent 121 to be reconstituted and the first reagent enter the collection tube 23 in sequence, thereby realizing the reconstitution of the microfluidic chip and the sequential injection of different reagents. The structural design and operation are extremely simple, and it is especially suitable for application in portable biochemical analysis devices.
[0068] Example 4:
[0069] See details Figure 5 As shown, the present invention also provides a microfluidic chip with a reagent quantitative dispensing unit, which differs from the aforementioned embodiments 1 to 3. It includes: a reagent quantitative dispensing unit comprising: a unit body 1, wherein a sampling quantitative cavity 51 and a waste overflow cavity 52 are formed within the unit body 1. The sampling quantitative cavity 51 is connected to the waste overflow cavity 52. The sampling quantitative cavity 51 is selectively connected to a supply pipe 21 and a collection pipe 23, and the fluid volume contained in the supply pipe 21 is greater than the volume of the sampling quantitative cavity 51, thereby ensuring that the solution retained in the sampling quantitative cavity 51 is the sampled quantitative value. The sampling quantitative cavity 51 is a cylindrical cavity with a diameter of D (i.e., Figure 5 The D3 indicated in the middle, and D≥4mm, can prevent the formation of an air column in the sampling quantitative cavity 51, thereby improving the quantitative accuracy.
[0070] In a preferred embodiment, a sealing push rod 53 is provided in the top port of the sampling metering chamber 51. It can be made of hard metal or hard resin, which has hardness while ensuring sealing performance. The sealing push rod 53 has a plunger body 531. The shape of the plunger body 531 matches the sampling metering chamber 51, so that when the sealing push rod 53 is pressed down, the plunger body 531 can completely push out the solution metered in the sampling metering chamber 51. It is understood that when the sealing push rod 53 is at the end of its downward stroke, it can seal the corresponding bevel needle 221.
[0071] In this technical solution, after the fluid contained in the liquid supply tube 21 enters the sampling and quantitative chamber 51, the excess will be discharged into the waste liquid overflow chamber 52, thereby achieving simple and accurate quantitative control of the amount of fluid to be sampled. It eliminates the need for microvalves or peristaltic pumps in existing technologies to achieve sampling and quantitative control, greatly reducing the manufacturing cost of microfluidic chips. The structure is simple and easy to operate, making it particularly suitable for application in portable biochemical analysis devices.
[0072] It should be noted that the aforementioned microfluidic chip also includes a chip body 24, which has multiple mounting and positioning cavities. The aforementioned liquid supply tubes 21, liquid collection tubes 23, and quantitative liquid dispensing units 1 are all assembled in each mounting and positioning cavity. The lower chip component 22 is connected to the bottom of the chip body 24, and the top of the chip body 24 is connected to the chip cover 25. The chip cover 25 has through holes corresponding to the positions of the pressing components (such as the upper rubber plug 125 and the sealing push rod 53 mentioned above) in each cavity, for the passage of the push rod and other driving components.
[0073] The above description is merely a preferred embodiment of the present invention and is 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. The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the technical principles of the present invention, and these improvements and modifications should also be considered within the protection scope of the present invention.
Claims
1. A microfluidic chip with a reagent quantitative dispensing unit, characterized in that, include: A reagent quantitative dispensing unit includes: a unit body (1), wherein a reagent flow chamber (11) and a reagent quantitative chamber (12) are formed in the unit body (1), the reagent flow chamber (11) and the reagent quantitative chamber (12) are connected through a flow channel (13), wherein the reagent flow chamber (11) is selectively connected to a liquid supply pipe (21), and the fluid volume contained in the liquid supply pipe (21) is greater than the volume of the reagent flow chamber (11); The reagent metering chamber (12) is also provided with a septum stopper (122). A reconstitution channel (1221) is formed on the wall of the reagent metering chamber (12). The position of the flow channel (13) is higher than the top inlet of the reconstitution channel (1221). The top surface of the septum stopper (122) is higher than the top inlet of the reconstitution channel (1221) but lower than the flow channel (13). Bottom stoppers (124) are provided in the bottom ports of both the reagent metering chamber (12) and the reagent flow channel (11). The space between the septum stopper (122) and the bottom stopper (124) is pre-filled with the reagent (121) to be reconstituted. The reagent metering chamber (12) is also provided with a partition rubber stopper (122). A vent hole (1222) is formed on the wall of the reagent metering chamber (12). Bottom rubber stoppers (124) are provided in the bottom ports of the reagent metering chamber (12) and the reagent flow chamber (11). An upper rubber stopper (125) is provided in the top port of the reagent metering chamber (12). The bottom surface of the partition rubber stopper (122) is higher than the flow channel (13) and the vent hole (1222). A reagent pre-positioning chamber (128) for accommodating the first reagent is formed between the partition rubber stopper (122) and the upper rubber stopper (125). It also includes a chip lower part (22), which has a reagent communication channel (222) and multiple oblique needles (221) communicating with the reagent communication channel (222). Each oblique needle (221) is respectively set to correspond to each bottom rubber plug (124).
2. The microfluidic chip according to claim 1, characterized in that, The reagent metering chamber (12) has an upper rubber stopper (125) in the top port, and a reagent metering space is formed between the upper rubber stopper (125) and the partition rubber stopper (122). An overflow channel (126) is also formed on the cavity wall of the reagent metering chamber (12). A waste liquid chamber (127) is also formed in the unit body (1), and the overflow channel (126) is connected to the waste liquid chamber (127).
3. The microfluidic chip according to claim 1, characterized in that, The reagent flow chamber (11) is a cylindrical cavity with a diameter of D, and D≥4mm.
4. A control method for a microfluidic chip, characterized in that, For controlling the microfluidic chip with a reagent quantitative dispensing unit as described in claim 1, comprising: The upper rubber plug (125) installed inside the liquid supply pipe (21) is pressed down along the axial direction to the bottom of the liquid supply pipe (21) so that all the fluid in the liquid supply pipe (21) flows out at the same time the upper rubber plug (125) seals the oblique needle (221) corresponding to the liquid supply pipe (21). Then, the upper rubber stopper (125) inside the reagent metering chamber (12) is pressed down along the axial direction to the bottom of the chamber so that the oblique needle (221) corresponding to the bottom of the reagent metering chamber (12) passes through the corresponding bottom rubber stopper (124) and the partition rubber stopper (122) in sequence. The upper rubber stopper (125) of the reagent metering chamber (12) seals the oblique needle (221), and the fluid containing the reagent to be reconstituted (121) and the first reagent enter the collecting tube (23) in sequence.
Citation Information
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