Microfluidic chips and immunoassay instruments

Abstract

This application relates to microfluidic chips and immunoassay instruments, which have a microfluidic chamber formed in the main body. The microfluidic chamber includes a first valve-controlled structure, a second valve-controlled structure, a third valve-controlled structure, a fourth valve-controlled structure, a first liquid chamber, a second liquid chamber, a first reaction chamber, a detection reaction chamber, and a waste liquid chamber. The first liquid chamber, the first valve-controlled structure, the first reaction chamber, the fourth valve-controlled structure, and the waste liquid chamber are sequentially connected and arranged from closest to furthest from the center of rotation. The second liquid chamber, the second valve-controlled structure, the detection reaction chamber, the third valve-controlled structure, and the waste liquid chamber are also sequentially connected and arranged. By designing a matching first liquid chamber, second liquid chamber, first reaction chamber, and detection reaction chamber, it is suitable for time-delayed one-step and two-step detection schemes requiring precise quantification of two reactions. This allows the microfluidic chip to be matched with time-delayed one-step and two-step immunoassay reactions, further broadening the versatility of microfluidic chips, especially disk-type microfluidic chips.

Description

Technical Field

[0001] This application relates to the field of microfluidic chips, and in particular to microfluidic chips and immunoassay instruments. Background Technology

[0002] Microfluidic chips are microanalytical systems that integrate sample pretreatment, mixing, reaction, separation, and detection into one or more chips. Analytical instruments using microfluidic chips can replace a significant amount of traditional laboratory work.

[0003] Furthermore, microfluidic chips offer advantages such as small sample volume, simple operation, and the ability to accurately complete the entire process from sample preparation to result display in a short time, effectively overcoming experimental errors caused by manual operation in traditional laboratory work. Therefore, microfluidic chips are finding increasing applications in fields such as chemical analysis, DNA sequencing, protein analysis, single-cell analysis, single-molecule analysis, food safety, environmental monitoring, and drug screening.

[0004] However, most traditional microfluidic disk chips are designed to achieve biochemical reactions. The few microfluidic disk chips that are adapted to immune reactions are only suitable for one-step processes. There is a lack of microfluidic chips, especially disk chips, that are adapted to delayed one-step processes. Summary of the Invention

[0005] Therefore, it is necessary to provide a microfluidic chip and an immunoassay instrument.

[0006] In one embodiment, a microfluidic chip includes a body having a center of rotation and a microfluidic chamber formed therein;

[0007] The microfluidic chamber includes a first valve-controlled structure, a second valve-controlled structure, a third valve-controlled structure, a fourth valve-controlled structure, a first liquid chamber, a second liquid chamber, a first reaction chamber, a detection reaction chamber, and a waste liquid chamber;

[0008] The first liquid chamber, the first valve-controlled structure, the first reaction chamber, the fourth valve-controlled structure, and the detection reaction chamber are sequentially connected in order of distance from the rotation center, and the second liquid chamber, the second valve-controlled structure, the detection reaction chamber, the third valve-controlled structure, and the waste liquid chamber are sequentially connected in order.

[0009] The aforementioned microfluidic chip, through the design of a first liquid chamber, a second liquid chamber, a first reaction chamber, and a detection reaction chamber that work together, is suitable for time-delayed one-step and two-step detection schemes that require precise quantification of two reactions. This enables time-delayed one-step or two-step microfluidic detection, allowing the microfluidic chip to be matched with time-delayed one-step and two-step immune reactions, further broadening the versatility of microfluidic chips, especially disk-type microfluidic chips.

[0010] In one embodiment, the first liquid chamber and the first valve-controlled structure are located on one side of the body, while the second liquid chamber, the second valve-controlled structure, the first reaction chamber, the fourth valve-controlled structure, the detection reaction chamber, the third valve-controlled structure, and the waste liquid chamber are located on the other side of the body; or...

[0011] The first liquid chamber, the first valve-controlled structure, the first reaction chamber, and the fourth valve-controlled structure are located on one side of the main body, while the second liquid chamber, the second valve-controlled structure, the detection reaction chamber, the third valve-controlled structure, and the waste liquid chamber are located on the other side of the main body; or,

[0012] The first liquid chamber, the first valve-controlled structure, the first reaction chamber, the fourth valve-controlled structure, the detection reaction chamber, the third valve-controlled structure, and the waste liquid chamber are located on one side of the main body, while the second liquid chamber and the second valve-controlled structure are located on the other side of the main body; or,

[0013] The first valve control structure, the second valve control structure, the third valve control structure, the fourth valve control structure, the first liquid chamber, the second liquid chamber, the first reaction chamber, the detection reaction chamber, and the waste liquid chamber are all located on the same side of the main body.

[0014] In one embodiment, the first valve control structure is configured to close at a speed lower than a preset first rotational speed;

[0015] The second valve control structure is configured to close at speeds below a preset second rotational speed;

[0016] The third valve control structure is configured to close at a speed lower than a preset third rotation speed to control the flow of liquid in the first reaction chamber to the waste liquid chamber;

[0017] Wherein, the preset first speed is not higher than the preset second speed, and both the preset first speed and the preset second speed are lower than the preset third speed.

[0018] In one embodiment, the distances from the center of rotation are arranged from closest to farthest.

[0019] The inlet of the first valve-controlled structure is connected to the bottom end of the first liquid chamber, and the inlet of the second valve-controlled structure is connected to the bottom end of the second liquid chamber; or...

[0020] The inlet of the third valve-controlled structure is connected to the bottom of the detection reaction chamber; or...

[0021] The inlet of the fourth valve-controlled structure is connected to the bottom of the first reaction chamber.

[0022] For example, in one embodiment, the bottom of the first reaction chamber is higher than the top of the detection reaction chamber in order of distance from the rotation center from near to far.

[0023] In one embodiment, the first valve-controlled structure, the second valve-controlled structure, and the third valve-controlled structure are steam traps or capillary valves; or...

[0024] The fourth valve-controlled structure is a siphon valve; or...

[0025] The first liquid chamber and the second liquid chamber are metering chambers used for metering liquid; or,

[0026] The first reaction chamber and the detection reaction chamber are each pre-filled with reaction reagents; or,

[0027] The volume of the detection reaction chamber is greater than or equal to the sum of the volumes of the first liquid chamber and the second liquid chamber; or,

[0028] The volume of the waste liquid chamber is greater than or equal to the sum of the volumes of the first liquid chamber and the second liquid chamber.

[0029] In one embodiment, the fourth valve-controlled structure is a siphon valve, and the surface of the fourth valve-controlled structure is a hydrophilic layer;

[0030] In order of increasing distance from the rotation center, the outlet of the fourth valve-controlled structure is connected to the uppermost end of the detection reaction chamber, and the uppermost end of the fourth valve-controlled structure is higher than the uppermost end of the first reaction chamber.

[0031] In one embodiment, the first liquid chamber and the second liquid chamber are metering chambers, and the volumes of the first liquid chamber and the second liquid chamber are the same or different.

[0032] In one embodiment, the shape of the first reaction chamber is selected from one of the following: partially elliptical, partially circular, elliptical, circular, trapezoidal, pear-shaped, rectangular, and regular polygonal; or,

[0033] The volume of the first reaction chamber is greater than or equal to the volume of the first liquid chamber; or,

[0034] The shape of the detection reaction chamber is selected from one of the following: partially elliptical, partially circular, elliptical, circular, trapezoidal, pear-shaped, rectangular, and regular polygonal; or...

[0035] The shape of the detection reaction chamber is set according to the photodetector; or...

[0036] The volume of the detection reaction chamber is greater than the volume of the first liquid chamber, the volume of the first reaction chamber, and the volume of the second liquid chamber; or,

[0037] The shape of the waste liquid chamber is selected from one of the following: partially elliptical, partially circular, elliptical, circular, trapezoidal, rectangular, and regular polygonal; or...

[0038] The volume of the waste liquid chamber is greater than or equal to the sum of the volumes of the first liquid chamber, the second liquid chamber, the first reaction chamber, and the detection reaction chamber.

[0039] For example, in one embodiment, the volume of the first reaction chamber is 1.5 to 2 times the volume of the first liquid chamber.

[0040] For example, in one embodiment, the volume of the detection reaction chamber is greater than or equal to 1.5 times the volume of the first liquid chamber, the volume of the detection reaction chamber is greater than or equal to 1.5 times the volume of the second liquid chamber, and the volume of the detection reaction chamber is greater than or equal to 1.5 times the volume of the first reaction chamber.

[0041] In one embodiment, the microfluidic chip is a disk-type microfluidic chip.

[0042] For example, in one embodiment, the microfluidic chip is a single-disk microfluidic chip.

[0043] In one embodiment, the bottom of the first reaction chamber is higher than the top of the detection reaction chamber, arranged from closest to furthest from the center of rotation.

[0044] In one embodiment, an immunoassay instrument includes a centrifuge and a microfluidic chip as described in any embodiment, the microfluidic chip being disposed on the rotating shaft of the centrifuge. Attached Figure Description

[0045] To more clearly illustrate the technical solutions in the embodiments of this application or the conventional technology, the drawings used in the description of the embodiments or the conventional technology will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0046] Figure 1 This is a schematic diagram of the structure of an embodiment of the microfluidic chip described in this application.

[0047] Figure 2 This is a schematic diagram of another embodiment of the microfluidic chip described in this application.

[0048] Figure 3 for Figure 2 A partial structural schematic diagram of the embodiment shown.

[0049] Figure 4 for Figure 3 The illustrated embodiment is shown in the following diagram.

[0050] Reference numerals: microfluidic chip 100, body 110, rotation center 120, microfluidic chamber 130, first valve control structure 131, second valve control structure 132, third valve control structure 133, fourth valve control structure 134, first liquid chamber 135, second liquid chamber 136, first reaction chamber 137, detection reaction chamber 138, waste liquid chamber 139, centrifugation direction 140, liquid 200. Detailed Implementation

[0051] To make the above-mentioned objectives, features, and advantages of this application more apparent and understandable, the specific embodiments of this application are described in detail below with reference to the accompanying drawings. Many specific details are set forth in the following description to provide a thorough understanding of this application. However, this application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of this application. Therefore, this application is not limited to the specific embodiments disclosed below.

[0052] It should be noted that when a component is referred to as being "fixed to" or "set on" another component, it can be directly on the other component or there may be an intermediate component. When a component is considered to be "connected to" another component, it can be directly connected to the other component or there may be an intermediate component present. The terms "vertical," "horizontal," "upper," "lower," "left," "right," and similar expressions used in this application's specification are for illustrative purposes only and do not represent the only possible implementation.

[0053] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this application, "multiple" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0054] In this application, unless otherwise expressly specified and limited, "above" or "below" the second feature can mean that the first feature is in direct contact with the second feature, or that the first feature and the second feature are in indirect contact through an intermediate medium. Furthermore, "above," "over," and "on top" the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.

[0055] Unless otherwise defined, all technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in this application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The term "and / or" as used in this application includes any and all combinations of one or more of the associated listed items.

[0056] This application discloses a microfluidic chip and an immunoassay analyzer, which includes some or all of the technical features of the following embodiments; that is, the microfluidic chip and immunoassay analyzer include some or all of the following structures. In one embodiment of this application, a microfluidic chip includes a body having a center of rotation and a microfluidic chamber formed therein; the microfluidic chamber includes a first valve-controlled structure, a second valve-controlled structure, a third valve-controlled structure, a fourth valve-controlled structure, a first liquid chamber, a second liquid chamber, a first reaction chamber, a detection reaction chamber, and a waste liquid chamber; the first liquid chamber, the first valve-controlled structure, the first reaction chamber, the fourth valve-controlled structure, and the waste liquid chamber are sequentially connected and arranged in order of distance from the center of rotation from near to far, and the second liquid chamber, the second valve-controlled structure, the detection reaction chamber, the third valve-controlled structure, and the waste liquid chamber are sequentially connected and arranged in order. The aforementioned microfluidic chip, through the design of a matching first liquid chamber, second liquid chamber, first reaction chamber, and detection reaction chamber, is suitable for time-delayed one-step and two-step detection schemes requiring precise quantification of two reactions. This enables time-delayed one-step or two-step microfluidic detection, allowing the microfluidic chip to be matched with time-delayed one-step and two-step immune reactions, further broadening the versatility of microfluidic chips, especially disk-type microfluidic chips. The following section will combine... Figures 1 to 4 The microfluidic chip will be described in detail below.

[0057] In one embodiment, a microfluidic chip 100, such as Figure 1 As shown, it includes a body 110 with a rotation center 120 and a microfluidic chamber 130 is formed in the body 110; in the illustrated embodiment, the rotation center 120 of the microfluidic chip 100 is located outside the body 110, and the microfluidic chip 100 is a disk-type microfluidic chip, and multiple microfluidic chips 100 can be placed in a rotating system.

[0058] Exemplarily, in one embodiment, a microfluidic chip 100 such as Figure 2As shown, the microfluidic chip 100 is a single-disk microfluidic chip, the body 110 is circular, and the rotation center 120 is located in the body 110 and is the center of the circle of the body 110. In this embodiment, the microfluidic chip 100 has only one microfluidic chamber 130 in its body 110; in other embodiments, the microfluidic chip 100 may also have two or more microfluidic chambers 130 in its body 110, and the embodiments of this application do not impose additional restrictions on this.

[0059] Combination Figure 2 and Figure 3 In various embodiments, the microfluidic chamber 130 includes a first valve-controlled structure 131, a second valve-controlled structure 132, a third valve-controlled structure 133, a fourth valve-controlled structure 134, a first liquid chamber 135, a second liquid chamber 136, a first reaction chamber 137, a detection reaction chamber 138, and a waste liquid chamber 139; combined with Figure 4 In this embodiment, the first liquid chamber 135 and the second liquid chamber 136 are used for metering liquid 200; the valve control structure, including the first valve control structure 131, the second valve control structure 132, the third valve control structure 133, and the fourth valve control structure 134, is used for transferring liquid 200; taking the fourth valve control structure 134 as an example, the fourth valve control structure 134 is used to transfer liquid 200 in the first reaction chamber 137 to the detection reaction chamber 138 under specific conditions. The first reaction chamber 137 and the detection reaction chamber 138 are used for reactions such as immune reactions, and reaction reagents for the reaction can be pre-set in the first reaction chamber 137 and the detection reaction chamber 138. The waste liquid chamber 139 is used to receive waste liquid.

[0060] Furthermore, in the microfluidic chamber 130, the first liquid chamber 135 and the second liquid chamber 136 are closest to the rotation center 120 relative to other structures, while the waste liquid chamber 139 is farthest from the rotation center 120 relative to other structures.

[0061] Specifically, the first liquid chamber 135, the first valve-controlled structure 131, the first reaction chamber 137, the fourth valve-controlled structure 134, and the detection reaction chamber 138 are sequentially connected in order of distance from the rotation center 120, and the second liquid chamber 136, the second valve-controlled structure 132, the detection reaction chamber 138, the third valve-controlled structure 133, and the waste liquid chamber 139 are sequentially connected in order of distance from the rotation center 120; that is, in the centrifugal direction 140, the first liquid chamber 135, the first valve-controlled structure 131, the first reaction chamber 137, the fourth valve-controlled structure 134, and the detection reaction chamber 138 are sequentially connected in order of distance from the rotation center 120, and the second liquid chamber 136, the second valve-controlled structure 132, the detection reaction chamber 138, the third valve-controlled structure 133, and the waste liquid chamber 139 are sequentially connected in order of distance from the rotation center 120.

[0062] With this structural design, under rotating conditions, the first liquid chamber 135, the first valve control structure 131, and the first reaction chamber 137 form a pre-reaction system. The resulting preliminary reactants enter the detection reaction chamber 138 via the fourth valve control structure 134. At this time, the second valve control structure 132 can be opened in conjunction with this, or the second valve control structure 132 can be opened in advance. The substances in the second liquid chamber 136 enter the detection reaction chamber 138 via the second valve control structure 132, react with the preliminary reactants, and obtain the final reactants. After the detection reaction chamber 138 completes the detection, the final reactants enter the waste liquid chamber 139 via the third valve control structure 133.

[0063] As can be seen from the above description, although the above embodiments are essentially two-step methods, they only require one microfluidic chip. In one system, two reactions requiring precise quantification can be achieved through a single centrifugation operation, thus improving detection efficiency. They are compatible with three immunological methodologies: one-step, delayed one-step, and two-step methods, and can be adapted to more projects. Some embodiments may also be referred to as delayed one-step detection or two-step detection, that is, providing both delayed one-step and two-step detection schemes, thereby realizing microfluidic detection of delayed one-step and two-step immunological methods. This allows the microfluidic chip 100 to be matched with delayed one-step and two-step immunological reactions, further broadening the versatility of the microfluidic chip 100, especially the disc-type microfluidic chip.

[0064] Exemplarily, in one embodiment, such as Figure 4As shown, the second liquid chamber 136 contains liquid 200, which can be functionally categorized as a reaction solution, diluent, and cleaning solution. In other embodiments, the first liquid chamber 135 may also contain liquid 200. For stringent reaction conditions, the liquid 200 contained in the first liquid chamber 135 and the second liquid chamber 136 is precisely quantified. In one embodiment, the first reaction chamber 137 and / or the detection reaction chamber 138 may also contain liquid 200 to participate in the reaction, dilute the solute, or perform cleaning. This structural design facilitates the implementation of two separately controlled reactions within the same centrifugation operation without replacing the microfluidic chip 100. Therefore, it provides a microfluidic detection scheme compatible with both two-step and delayed one-step methods, which not only improves the efficiency of immunoassay detection but also enhances the precision of the detection results and reduces the amount of microfluidic chip 100 required.

[0065] In one embodiment, the first valve control structure 131 is configured to close at a speed lower than a preset first rotational speed; the second valve control structure 132 is configured to close at a speed lower than a preset second rotational speed; and the third valve control structure 133 is configured to close at a speed lower than a preset third rotational speed, thereby controlling the flow of liquid 200 in the first reaction chamber 137 to the waste liquid chamber 139; wherein the preset first rotational speed is not higher than the preset second rotational speed, and both the preset first rotational speed and the preset second rotational speed are lower than the preset third rotational speed. For example, the preset first rotational speed is the same as the preset second rotational speed, and both the preset first rotational speed and the preset second rotational speed are lower than the preset third rotational speed. Exemplarily, in one embodiment, the preset first rotational speed is 500 rpm, i.e., 500 revolutions per minute; the preset second rotational speed is 800 rpm; and the preset third rotational speed is 1000 rpm; that is, the preset first rotational speed is lower than the preset second rotational speed, and the preset second rotational speed is lower than the preset third rotational speed. Alternatively, the preset first rotational speed is 800 rpm, the preset second rotational speed is 800 rpm, and the preset third rotational speed is 1000 rpm; that is, the preset first rotational speed is the same as the preset second rotational speed, and both the preset first rotational speed and the preset second rotational speed are lower than the preset third rotational speed. Alternatively, the preset first rotational speed is 1000 rpm, the preset second rotational speed is 2000 rpm, and the preset third rotational speed is 3000 rpm. Other embodiments follow the same principle and will not be elaborated further. The specific preset first rotational speed, the preset second rotational speed, and the preset third rotational speed can be set or adjusted according to actual conditions, and the embodiments of this application do not impose additional restrictions in this regard. This design, through simple centrifugation speed control, can realize the on / off control of the first valve control structure 131, the second valve control structure 132, and the third valve control structure 133, thereby completing the time-delayed one-step and two-step detection schemes requiring precise quantitative analysis of two reactions, offering advantages of convenience, practicality, and speed.

[0066] Exemplarily, the liquid transfer process achieved by the microfluidic chip 100 through rotational speed control is described as follows: The second liquid enters the second liquid chamber 136 from the back channel and enters the first reaction chamber 137 under the action of the second rotational speed; and under the action of the second rotational speed, the second liquid will not pass through the fourth valve control structure 134, at which time the fourth valve control structure 134 is in a closed state. When the microfluidic chip 100 stops rotating, the second liquid passes through the fourth valve control structure 134 under capillary action, at which time the fourth valve control structure 134 is in a closed state, and the second liquid enters the detection reaction chamber 138 from the first reaction chamber 137 under the action of the second rotational speed; after the second liquid has been incubated in the detection reaction chamber 138, it enters the waste liquid chamber 139 under the action of the third rotational speed; similarly, the first liquid enters the first liquid chamber 135 from the front channel and enters the detection reaction chamber 138 under the action of the first rotational speed; after the first liquid has been incubated in the detection reaction chamber 138, it enters the waste liquid chamber 139 under the action of the third rotational speed.

[0067] In one embodiment, in order of increasing distance from the rotation center 120, the inlet of the first valve-controlled structure 131 connects to the bottommost end of the first liquid chamber 135, and the inlet of the second valve-controlled structure 132 connects to the bottommost end of the second liquid chamber 136. That is, the inlet of the first valve-controlled structure 131 connects to the lowest point of the first liquid chamber 135, which is the position of the first liquid chamber 135 furthest from the rotation center 120. Other embodiments follow the same principle and will not be elaborated further. In one embodiment, in order of increasing distance from the rotation center 120, the inlet of the third valve-controlled structure 133 connects to the bottommost end of the detection reaction chamber 138. In one embodiment, in order of increasing distance from the rotation center 120, the inlet of the fourth valve-controlled structure 134 connects to the bottommost end of the first reaction chamber 137. In one embodiment, in order of increasing distance from the rotation center 120, the bottommost end of the first reaction chamber 137 is higher than the topmost end of the detection reaction chamber 138. For example, in one embodiment, the bottom of the first reaction chamber 137 is higher than the top of the detection reaction chamber 138 in order of distance from the rotation center 120. Traditional methodologies for disc-type microfluidic chips are mostly biochemical reactions, which are difficult to adapt to delayed one-step or two-step immunoreaction processes. This is mainly due to the following limitations: immunoreaction requires precise quantification, multiple rounds of washing, repeated reuse of valve-controlled structures, and two incubation cycles required for delayed one-step or two-step methods. Therefore, two reaction chambers for incubation need to be designed, and the reaction proceeds in a specific order. Furthermore, the process of dispensing liquid from the disc-type microfluidic chip to the reaction chambers is usually controlled by a hydrophobic valve or capillary valve, but neither hydrophobic valves nor capillary valves can effectively control the liquid in both reaction chambers. This application provides a microfluidic chamber design that enables quantitative mixing and reaction by designing a first liquid chamber 135, a second liquid chamber 136, a first reaction chamber 137, and a detection reaction chamber 138 that work together. This design enables the application of a disc-type microfluidic chip with delayed one-step or two-step immunoreaction methods, allowing the microfluidic chip 100 to be matched with more methodologies. This solves the problem that traditional disc-type microfluidic chips are difficult to adapt to delayed one-step and two-step immunoreaction methods, and further broadens the versatility of the microfluidic chip 100, especially the disc-type microfluidic chip.

[0068] In one embodiment, the first valve control structure 131, the second valve control structure 132, and the third valve control structure 133 are hydrophobic valves or capillary valves. In one embodiment, the opening speed of the first valve control structure 131 and the second valve control structure 132 is less than the opening speed of the third valve control structure 133. At low speeds, the first valve control structure 131 and the second valve control structure 132 prevent the liquid 200 in the first liquid chamber 135 and the second liquid chamber 136 (e.g., the metering chamber) from flowing to the reaction chamber, thus achieving the metering function of the metering chamber. The opening speed of the third valve control structure 133 is higher than that of the first valve control structure 131 and the second valve control structure 132, preventing the liquid 200 in the reaction chamber from flowing to the waste liquid chamber 139 when the first valve control structure 131 is opened. The inlet of the first valve control structure 131 should be located at the bottom of the first liquid chamber 135, and the inlet of the second valve control structure 132 should be located at the bottom of the second liquid chamber 136. This design facilitates accurate control of the flow direction of the liquid 200 in the microfluidic chamber 130, ensuring that the reactions in the first reaction chamber 137 and the detection reaction chamber 138 can be precisely quantified according to the design objectives.

[0069] In one embodiment, the fourth valve-controlled structure 134 is a siphon valve. In another embodiment, the fourth valve-controlled structure 134 is a siphon valve, and its surface is a hydrophilic layer. In order of distance from the rotation center 120, the outlet of the fourth valve-controlled structure 134 connects to the uppermost end of the detection reaction chamber 138, and the uppermost end of the fourth valve-controlled structure 134 is higher than the uppermost end of the first reaction chamber 137. That is, the minimum distance between the fourth valve-controlled structure 134 and the rotation center 120 is less than the minimum distance between the first reaction chamber 137 and the rotation center 120. For example, the uppermost end of the fourth valve-controlled structure 134 is higher than the uppermost end of the detection reaction chamber 138, meaning the minimum distance between the fourth valve-controlled structure 134 and the rotation center 120 is less than the minimum distance between the detection reaction chamber 138 and the rotation center 120. The uppermost end is the position closest to the rotation center 120, i.e., the position with the smallest distance from the rotation center 120. In one embodiment, the surface of the fourth valve-controlled structure 134 is made of a hydrophilic material. Under capillary action, liquid 200 can fill the fourth valve-controlled structure 134. The inlet of the fourth valve-controlled structure 134 is located at the bottom of the first reaction chamber 137, and the outlet of the fourth valve-controlled structure 134 is located at the top of the detection reaction chamber 138. The highest point of the fourth valve-controlled structure 134 should be higher than the highest point of the first reaction chamber 137. Compared with traditional hydrophobic valve and capillary valve solutions, this design allows for accurate control of the opening and closing of the fourth valve-controlled structure 134 by controlling the centrifugation speed. This effectively meets the technical requirements of delayed one-step and two-step methods that require two incubations, making the microfluidic chip 100 compatible with both delayed one-step and two-step immune reactions.

[0070] In one embodiment, the first liquid chamber 135 and the second liquid chamber 136 are metering chambers for metering liquid 200; in another embodiment, the first liquid chamber 135 and the second liquid chamber 136 are metering chambers, and their volumes are the same or different. This structural design facilitates the accurate addition of liquid 200 to the first liquid chamber 135 and / or the second liquid chamber 136, controlling the two reactions requiring precise metering from the source, thereby improving the testing precision of the microfluidic chip 100.

[0071] In one embodiment, the first reaction chamber 137 and the detection reaction chamber 138 are respectively pre-filled with reaction reagents. The reaction chamber, including the first reaction chamber 137 and the detection reaction chamber 138, contains the reagent to be reacted, i.e., the reaction reagent. The reaction reagent can be liquid, solid, or a solid-liquid mixture, etc. Exemplarily, in one embodiment, the reaction reagent is one or more of solid reagents, lyophilized reagents, liquid reagents, and solid-phase reagents adsorbed onto the chamber. Exemplarily, in one embodiment, the reaction reagent is encapsulated in the first reaction chamber 137 and / or the detection reaction chamber 138 for release under preset conditions, including at least one of centrifugal speed and ambient temperature. With this structural design, the reaction reagent has a relatively long shelf life and is less likely to be transferred to other locations before the valve-controlled structure is opened, thus avoiding affecting the accuracy of the two reactions.

[0072] In one embodiment, the shape of the first reaction cavity 137 is selected from one of the following: partially elliptical, partially circular, elliptical, circular, trapezoidal, pear-shaped, rectangular, and regular polygonal; or, in one embodiment, the volume of the first reaction cavity 137 is greater than or equal to the volume of the first liquid cavity 135. Exemplarily, in one embodiment, the volume of the first reaction cavity 137 is 1.5 to 2 times the volume of the first liquid cavity 135. In one embodiment, the shape of the first reaction cavity 137 can be circular, square, pear-shaped, rectangular, etc., and its volume should be greater than the volume of the first liquid cavity 135, more preferably 1.5 to 2 times the volume of the first liquid cavity 135. The first reaction cavity 137 is closer to the center of the microfluidic disk chip than the detection reaction cavity 138, and more preferably, the bottom of the first reaction cavity 137 is higher than the top of the detection reaction cavity 138. This structural design ensures that the reaction in the first reaction chamber 137 starts first, completes first, and obtains preliminary reactants. Then, after adjusting the centrifugation speed, the fourth valve control structure 134 is opened, and the preliminary reactants enter the detection reaction chamber 138. At this time, the substances in the second liquid chamber 136 can be simultaneously introduced into the detection reaction chamber 138 through the second valve control structure 132. Alternatively, the substances in the second liquid chamber 136 can be introduced into the detection reaction chamber 138 in advance through the second valve control structure 132, and then the reaction and detection are completed in the detection reaction chamber 138.

[0073] In one embodiment, the shape of the detection reaction cavity 138 is selected from one of the following: partially elliptical, partially circular, elliptical, circular, trapezoidal, pear-shaped, rectangular, and regular polygonal; or, in one embodiment, the shape of the detection reaction cavity 138 is set according to the photodetector. In one embodiment, the shape of the detection reaction cavity 138 can be various shapes such as circular, square, pear-shaped, and rectangular, and its shape matches the photodetector. In one embodiment, the volume of the detection reaction cavity 138 is greater than the volume of the first liquid cavity 135, the volume of the first reaction cavity 137, and the volume of the second liquid cavity 136, that is, the volume of the detection reaction cavity 138 is greater than the volume of the second liquid cavity 136, the volume of the detection reaction cavity 138 is greater than the volume of the first liquid cavity 135, and the volume of the detection reaction cavity 138 is greater than the volume of the first reaction cavity 137. More preferably, the volume of the detection reaction cavity 138 is 1.5 to 2 times the larger of the volumes of the second liquid cavity 136 and the first liquid cavity 135. In one embodiment, the volume of the detection reaction chamber 138 is greater than or equal to the sum of the volumes of the first liquid chamber 135 and the second liquid chamber 136; in another embodiment, the volume of the detection reaction chamber 138 is greater than or equal to the sum of the volumes of the first liquid chamber 135, the first reaction chamber 137, and the second liquid chamber 136. In one embodiment, the volume of the detection reaction chamber 138 is greater than or equal to 1.5 times the volume of the first liquid chamber 135, the volume of the detection reaction chamber 138 is greater than or equal to 1.5 times the volume of the second liquid chamber 136, and the volume of the detection reaction chamber 138 is greater than or equal to 1.5 times the volume of the first reaction chamber 137. For example, in one embodiment, the volume of the detection reaction chamber 138 is greater than or equal to 1.5 to 2 times the sum of the volumes of the first liquid chamber 135 and the second liquid chamber 136; or, the volume of the detection reaction chamber 138 is greater than or equal to 1.5 to 2 times the larger of the volumes of the first liquid chamber 135 and the second liquid chamber 136. This structural design is suitable for two reactions requiring precise quantification, ensuring that the second reaction is accurately controlled within the detection reaction chamber 138, preventing any liquid from overflowing, and finally controlling its entry into the waste liquid chamber 139.

[0074] In one embodiment, the waste liquid chamber 139 is used to receive the liquid 200 discharged from the detection reaction chamber 138, and its shape can be circular, elliptical, square, rectangular, or other shapes. In one embodiment, the shape of the waste liquid chamber 139 is selected from one of the following: partially elliptical, partially circular, elliptical, circular, trapezoidal, rectangular, and regular polygonal. In one embodiment, the volume of the waste liquid chamber 139 is greater than or equal to the sum of the volumes of the first liquid chamber 135 and the second liquid chamber 136. In one embodiment, the volume of the waste liquid chamber 139 is greater than or equal to the sum of the volumes of the first liquid chamber 135, the second liquid chamber 136, the first reaction chamber 137, and the detection reaction chamber 138. This structural design facilitates the concentration of all the reacted liquid in the waste liquid chamber 139, making cleaning easier after the detection is completed.

[0075] In one embodiment, the first liquid chamber 135 and the first valve control structure 131 are located on one side of the body 110, while the second liquid chamber 136, the second valve control structure 132, the first reaction chamber 137, the fourth valve control structure 134, the detection reaction chamber 138, the third valve control structure 133, and the waste liquid chamber 139 are located on the other side of the body 110. As an example, the first liquid chamber 135 and the first valve control structure 131 are both located on the back side of the chip, while the second liquid chamber 136, the second valve control structure 132, the third valve control structure 133, the first reaction chamber 137, the fourth valve control structure 134, the detection reaction chamber 138, and the waste liquid chamber 139 are all located on the front side of the chip. It is understood that the front and back sides of the chip are opposite each other, and either side can be used as the front side. Since the first liquid chamber 135 and the second liquid chamber 136 need to contain liquid 200, after the first liquid chamber 135 and / or the second liquid chamber 136 contain liquid 200, they are sealed with a film or sheet to prevent liquid 200 from splashing out after inversion or high-speed centrifugation. This design makes full use of the thickness of the body 110, making it particularly suitable for detection applications with small reaction liquid volumes. The rational distribution of the first liquid chamber 135, the second liquid chamber 136, the first reaction chamber 137, and the detection reaction chamber 138 significantly reduces the area occupied by the microfluidic chambers 130 on the body 110. When applied to a single-disk microfluidic chip, this allows for a greater number of microfluidic chambers 130 to be placed on a single microfluidic chip 100. Compared to the traditional single-sided distribution design, this embodiment, through a double-sided distribution design, maintains the original detection throughput without increasing the number of microfluidic chambers 130, resulting in a smaller microfluidic chip 100 and a reduction in the weight of the body 110 by approximately 13% to 19%. This not only helps to reduce the product's size and production costs but also reduces the motor load.

[0076] In one embodiment, the first liquid chamber 135, the first valve-controlled structure 131, the first reaction chamber 137, and the fourth valve-controlled structure 134 are located on one side of the body 110, while the second liquid chamber 136, the second valve-controlled structure 132, the detection reaction chamber 138, the third valve-controlled structure 133, and the waste liquid chamber 139 are located on the other side of the body 110; or, in one embodiment, the first liquid chamber 135, the first valve-controlled structure 131, the first reaction chamber 137, the fourth valve-controlled structure 134, and the detection reaction chamber 139 are located on the other side of the body 110. The cavity 138, the third valve control structure 133, and the waste liquid cavity 139 are located on one side of the body 110, while the second liquid cavity 136 and the second valve control structure 132 are located on the other side of the body 110; or, in one embodiment, the first valve control structure 131, the second valve control structure 132, the third valve control structure 133, the fourth valve control structure 134, the first liquid cavity 135, the second liquid cavity 136, the first reaction cavity 137, the detection reaction cavity 138, and the waste liquid cavity 139 are located on the same side of the body 110. Other embodiments follow the same principle and will not be described in detail.

[0077] In one embodiment, an immunoassay analyzer includes a centrifuge and a microfluidic chip 100 as described in any embodiment, the microfluidic chip 100 being disposed on the rotating shaft of the centrifuge. It is understood that since the immunoassay analyzer employs the microfluidic chip 100 as described in any embodiment, it possesses the beneficial technical effects brought about by the microfluidic chip 100, which will not be elaborated upon here.

[0078] As an example, an immunoassay analyzer includes a centrifuge and a microfluidic chip 100. The microfluidic chip 100 includes a body 110 having a rotation center 120 and a microfluidic chamber 130 formed therein. The microfluidic chamber 130 includes a first valve control structure 131, a second valve control structure 132, a third valve control structure 133, a fourth valve control structure 134, a first liquid chamber 135, a second liquid chamber 136, a first reaction chamber 137, a detection reaction chamber 138, and a waste liquid chamber 139. The first liquid chamber 135, the first valve control structure 131, the first reaction chamber 137, the fourth valve control structure 134, and the detection reaction chamber 138 are sequentially connected in order of distance from the rotation center 120, and the second liquid chamber 136, the second valve control structure 132, the detection reaction chamber 138, the third valve control structure 133, and the waste liquid chamber 139 are sequentially connected in order. In this embodiment, the body 110 is disposed on the rotating shaft of the centrifuge, and the rotation center 120 is correspondingly disposed on the rotating shaft. Exemplarily, the body 110 can be directly disposed on the rotating shaft, or it can be indirectly disposed on the rotating shaft through an intermediate component. The embodiments of this application do not impose additional restrictions on this, as long as the centrifuge drives the body 110 to rotate through the rotating shaft, so that the various valve control structures of the microfluidic chamber 130 can be controlled by rotation.

[0079] It should be noted that other embodiments of this application also include microfluidic chips and immunoassay instruments formed by combining the technical features of the above embodiments.

[0080] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0081] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the scope of protection of this application. Therefore, the patent protection scope of this application should be determined by the appended claims.

Claims

1. A microfluidic chip (100), characterized in that, The body (110) has a rotation center (120) and a micro-fluidic chamber (130) is formed in the body (110); The micro-fluidic chamber (130) comprises a first valve control structure (131), a second valve control structure (132), a third valve control structure (133), a fourth valve control structure (134), a first liquid cavity (135), a second liquid cavity (136), a first reaction cavity (137), a detection reaction cavity (138) and a waste liquid cavity (139); The first liquid cavity (135), the first valve control structure (131), the first reaction cavity (137), the fourth valve control structure (134) and the detection reaction cavity (138) are sequentially connected in communication from near to far from the rotation center (120), and the second liquid cavity (136), the second valve control structure (132), the detection reaction cavity (138), the third valve control structure (133) and the waste liquid cavity (139) are sequentially connected in communication; The first valve control structure (131) is arranged to be closed at a first preset rotation speed; The second valve control structure (132) is arranged to be closed at a second preset rotation speed; The third valve control structure (133) is arranged to be closed at a third preset rotation speed, so as to control the liquid in the detection reaction cavity (138) to flow to the waste liquid cavity (139); The first preset rotation speed is not higher than the second preset rotation speed, and the first preset rotation speed and the second preset rotation speed are both lower than the third preset rotation speed; The inlet of the first valve control structure (131) is connected to the bottom end of the first liquid cavity (135), the inlet of the second valve control structure (132) is connected to the bottom end of the second liquid cavity (136), the inlet of the third valve control structure (133) is connected to the bottom end of the detection reaction cavity (138), the inlet of the fourth valve control structure (134) is connected to the bottom end of the first reaction cavity (137), the outlet of the fourth valve control structure (134) is connected to the upper end of the detection reaction cavity (138), and the upper end of the fourth valve control structure (134) is higher than the upper end of the first reaction cavity (137); The first valve control structure (131), the second valve control structure (132) and the third valve control structure (133) are hydrophobic valves or capillary valves; The fourth valve control structure (134) is a siphon valve, and the surface of the fourth valve control structure (134) is a hydrophilic layer.

2. The microfluidic chip (100) according to claim 1, characterized in that The first liquid cavity (135) and the first valve control structure (131) are formed on one side of the body (110), and the second liquid cavity (136), the second valve control structure (132), the first reaction cavity (137), the fourth valve control structure (134), the detection reaction cavity (138), the third valve control structure (133) and the waste liquid cavity (139) are formed on the other side of the body (110).

3. The microfluidic chip (100) according to claim 1, characterized in that The first liquid cavity (135), the first valve control structure (131), the first reaction cavity (137) and the fourth valve control structure (134) are arranged on one side of the body (110), and the second liquid cavity (136), the second valve control structure (132), the detection reaction cavity (138), the third valve control structure (133) and the waste liquid cavity (139) are arranged on the other side of the body (110).

4. The microfluidic chip (100) according to claim 1, characterized in that The first liquid cavity (135), the first valve control structure (131), the first reaction cavity (137), the fourth valve control structure (134), the detection reaction cavity (138), the third valve control structure (133) and the waste liquid cavity (139) are arranged on one side of the body (110), and the second liquid cavity (136) and the second valve control structure (132) are arranged on the other side of the body (110).

5. The microfluidic chip (100) according to claim 1, characterized in that The first valve control structure (131), the second valve control structure (132), the third valve control structure (133), the fourth valve control structure (134), the first liquid cavity (135), the second liquid cavity (136), the first reaction cavity (137), the detection reaction cavity (138) and the waste liquid cavity (139) are arranged on the same side of the body (110).

6. The microfluidic chip (100) according to claim 1, characterized in that The first liquid cavity (135) and the second liquid cavity (136) are quantitative cavities for quantitatively containing liquid (200).

7. The microfluidic chip (100) according to claim 1, characterized in that The first reaction cavity (137) and the detection reaction cavity (138) are respectively pre-provided with reaction reagents.

8. The microfluidic chip (100) according to claim 1, characterized in that The volume of the detection reaction cavity (138) is greater than or equal to the sum of the volumes of the first liquid cavity (135) and the second liquid cavity (136).

9. The microfluidic chip (100) according to claim 1, characterized in that The volume of the waste liquid cavity (139) is greater than or equal to the sum of the volumes of the first liquid cavity (135) and the second liquid cavity (136).

10. The microfluidic chip (100) according to claim 1, characterized in that The first liquid cavity (135) and the second liquid cavity (136) are quantitative cavities, and the volumes of the first liquid cavity (135) and the second liquid cavity (136) are the same or different.

11. The microfluidic chip (100) according to claim 1, characterized in that The shape of the first reaction cavity (137) is selected from one of partial ellipse, partial circle, ellipse, circle, trapezoid, pear shape, rectangle and regular polygon.

12. The microfluidic chip (100) according to claim 1, characterized in that The volume of the first reaction cavity (137) is greater than or equal to the volume of the first liquid cavity (135).

13. The microfluidic chip (100) according to claim 1, characterized in that The shape of the detection reaction cavity (138) is selected from one of partial ellipse, partial circle, ellipse, circle, trapezoid, pear shape, rectangle and regular polygon.

14. The microfluidic chip (100) according to claim 1, characterized in that The shape of the detection reaction cavity (138) is set according to a light detection device.

15. The microfluidic chip (100) according to claim 1, characterized in that The volume of the detection reaction cavity (138) is greater than the volume of the first liquid cavity (135), the volume of the first reaction cavity (137) and the volume of the second liquid cavity (136).

16. The microfluidic chip (100) according to claim 1, characterized in that The shape of the waste liquid cavity (139) is selected from one of partial ellipse, partial circle, ellipse, circle, trapezoid, rectangle and regular polygon.

17. The microfluidic chip (100) according to claim 1, characterized in that The volume of the waste liquid chamber (139) is greater than or equal to the sum of the volumes of the first liquid chamber (135), the second liquid chamber (136), the first reaction chamber (137), and the detection reaction chamber (138).

18. The microfluidic chip (100) according to any one of claims 1 to 17, characterized in that The microfluidic chip (100) is a disc-type microfluidic chip.

19. An immunoassay instrument, characterized by, The microfluidic chip (100) as claimed in any one of claims 1 to 18 is arranged on a rotating shaft of a centrifuge.

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