Microfluidic valve control system and microfluidic chip

Abstract

The present invention discloses a microfluidic valve control system and a microfluidic chip. The microfluidic valve control system includes a first capillary channel for connecting between a first cavity and a second cavity of the microfluidic chip, wherein, 0.5 mm ≤ the length L1 of the first capillary channel ≤ 20 mm, 0.01 mm ≤ the width W1 of the first capillary channel ≤ 2 mm, and 0.01 mm ≤ the depth H1 of the first capillary channel ≤ 2 mm. The microfluidic valve control system of the present invention relies on the appropriate combination and arrangement of at least one group of capillary channels and upstream and downstream chambers. Due to the different three-dimensional dimensions of the capillary channels, different liquid surface tensions and fluid resistances will be exhibited. These differences can realize the function as a valve control unit, and with the drive of an appropriate centrifugal force, the timing position control of the microfluid in the chip is achieved, that is, the liquid is in a blocked state in the cavity or the liquid is transferred from the upstream cavity to the downstream cavity within a determined time period.

Description

Technical Field

[0001] The present invention relates to the field of microfluidics, and particularly to a microfluidic valve control system and a microfluidic chip. Background Art

[0002] Most of the current automated analysis instruments for sample detection evolve the steps of sampling, reagent injection, sample / reagent mixing, constant temperature incubation, signal detection, result data processing and output in the analysis process by imitating the manual operation process into automated machinery. However, automation leads to large size, high complexity and high cost of the automated analysis equipment, and it is prone to failures and requires frequent regular maintenance and servicing. At the same time, in many cases, due to the particularity of the samples such as strong infectivity, easy contamination, easy inactivation, etc., professional detection environments such as central laboratories in large hospitals, P2 / P3 laboratories, etc. are often required. In terms of operation, due to the high degree of specialization of the equipment and the high requirements for professional experimental operations, it comprehensively results in that the personnel operating the equipment need to have extremely strong professional qualities, be very familiar with the entire operation process (instrument + manual), and have a certain ability to predict and avoid potential risks that may lead to detection failure or unreliable results, and be able to cope with various emergencies temporarily. It can be seen that the traditional automated analysis instruments lead to high detection costs, low detection efficiency, poor detection controllability, and cannot meet the needs of on-site sampling analysis and detection, rapid detection or patient self-testing, etc.

[0003] Currently, many companies at home and abroad have begun to combine sample detection with microfluidic technology. By taking advantage of the high integration and miniaturization of microfluidic technology, the detection of traditional automated analytical instruments has been reduced, resulting in a dual reduction in the usage of reagents and samples and a decrease in detection costs. At the same time, as a relatively closed and highly integrated reaction carrier, the microfluidic chip is more likely to prevent cross-contamination during the detection process and greatly reduces the requirements for the size and complexity of the instrument it cooperates with, thereby reducing manual intervention errors and equipment maintenance costs. To achieve the detection function, an integrated microfluidic chip needs to fix or transfer the liquid to a specific position at a specific time and, according to the requirements of the detection methodology, sequentially complete processes such as reagent mixing, sample reaction, and generation of detectable signals. These three processes often need to be separated due to different detection objects and are in a serial process relationship, that is, the next step will only be entered after the previous step is completely completed. Therefore, during the operation of each step, some special structures and components within the chip are required to prevent the liquid from advancing, overflowing, etc., so as to avoid process errors or abnormal reaction results caused by premature triggering of subsequent processes or premature mixing of reagents in different steps. Common microfluidic blocking structures include: wax valves, mechanical valves, or soluble membrane valves, etc. For the above three types of valves, additional components or relatively complex and difficult-to-implement processes need to be added to the chip during the chip preparation process. At the same time, the wax valve or soluble membrane valve is only a single-use valve and cannot achieve the repeated use of the valve and complex multi-valve combination functions. The usability of this expensive structure is greatly reduced for complex reagent detection. Although the mechanical valve can be used multiple times, its operability is not strong and additional equipment components need to be added for cooperation. If multi-stage valve control is required, in addition to the increased complexity of the chip itself, the complexity of the equipment and the control difficulty of the multi-stage valve system also increase, and the repeatability and stability of the system are insufficient. Summary of the Invention

[0004] Based on this, it is necessary to provide a microfluidic valve control system to address the problems of difficult maintenance, easy contamination, difficulty in quantifying tiny liquids, and inability to simultaneously control multiple fluids in traditional large-scale equipment mechanical liquid transfer systems, as well as the problems of inability to achieve repeated use of valves and low usability of complex multi-valve combination functions in wax valves or soluble membrane valves in current other microfluidic controls, poor operability of mechanical valves, and the need for additional equipment components for cooperation.

[0005] A microfluidic valve control system includes a first capillary channel, which is used to connect between the first cavity and the second cavity of the microfluidic chip. Among them, 0.5 mm ≤ the length L1 of the first capillary channel ≤ 20 mm, 0.01 mm ≤ the width W1 of the first capillary channel ≤ 2 mm, and 0.01 mm ≤ the depth H1 of the first capillary channel ≤ 2 mm.

[0006] In some of these embodiments, the microfluidic valve control system further includes a second capillary channel... an Nth capillary channel, where N≥2. The first capillary channel is used to connect between a first cavity of the microfluidic chip and a second cavity of the microfluidic chip. The second capillary channel is used to connect between the second cavity and a third cavity of the microfluidic chip. The Nth capillary channel is used to connect between the Nth cavity of the microfluidic chip and the (N + 1)th cavity of the microfluidic chip. Among them, the first cavity, the second cavity... the Nth cavity and the (N + 1)th cavity are sequentially distributed in order from the rotation center outwards. Among them, 0.5mm ≤ the length L1 of the first capillary channel ≤ the length L2 of the second capillary channel ≤... ≤ the length LN of the Nth capillary channel ≤ 20mm, 2mm ≥ the width W1 of the first capillary channel ≥ the width W2 of the second capillary channel ≥... ≥ the width WN of the Nth capillary channel ≥ 0.01mm, 2mm ≥ the depth H1 of the first capillary channel ≥ the depth H2 of the second capillary channel ≥... ≥ the depth HN of the Nth capillary channel ≥ 0.01mm.

[0007] In some of these embodiments, the microfluidic valve control system further includes a first air duct, a second air duct... an Nth air duct. The first air duct is used to connect the second cavity. The second air duct is used to connect the third cavity. The Nth air duct is used to connect to the (N + 1)th cavity.

[0008] In some of these embodiments, the microfluidic valve control system further includes a branch capillary channel. One end of the branch capillary channel is used to connect to a liquid inlet of the microfluidic chip. The other end of the branch capillary channel is used to connect to the Mth cavity of the microfluidic chip, where 2≤M≤N. The length Lmao of the branch capillary channel ≥ the length L(M - 1) of the (M - 1)th capillary channel connected to the Mth cavity at the same radial position; the width Wmao of the branch capillary channel ≥ the width W(M - 1) of the (M - 1)th capillary channel connected to the Mth cavity at the same radial position; the depth Hmao of the branch capillary channel ≥ the depth H(M - 1) of the (M - 1)th capillary channel connected to the Mth cavity at the same radial position.

[0009] In some of these embodiments, the first capillary channel has a linear structure, a curved structure or a tortuous structure; and / or

[0010] The second capillary channel has a linear structure, a curved structure or a tortuous structure; and / or ...

[0012] And / or, the Nth capillary channel has a linear structure, a curved structure or a tortuous structure.

[0013] In some of these embodiments, the range of centrifugation parameters for controlling the transfer of the liquid reagent from the upstream cavity to the downstream cavity includes pipetting centrifugation parameters: centrifugal rotation speed of 100 rpm - 2000 rpm; acceleration and deceleration of 500 - 20000 rpm / s; mixing centrifugation parameters: centrifugal rotation speed of 100 rpm - 2000 rpm; acceleration and deceleration of 500 - 20000 rpm / s; swing angle of 10° - 3600°; swing pause time of 0 - 10000 ms; number of swings of 0 - 1000 times.

[0014] Another object of the present invention is also to provide a microfluidic chip.

[0015] A microfluidic chip includes a chip substrate and the microfluidic valve control system described above. The chip substrate includes a first cavity, a second cavity... an (N + 1)-th cavity. The first cavity, the second cavity... the N-th cavity and the (N + 1)-th cavity are sequentially distributed outward from the rotation center of the chip substrate. The first capillary channel is connected between the first cavity and the second cavity of the microfluidic chip, the second capillary channel is connected between the second cavity and the third cavity of the microfluidic chip, and the N-th capillary channel is connected between the N-th cavity and the (N + 1)-th cavity of the microfluidic chip.

[0016] In some of these embodiments, air holes are provided on the chip substrate, and the first air channel, the second air channel... the N-th air channel of the microfluidic valve control system communicate with the air holes.

[0017] In some of these embodiments, the first air channel, the second air channel... the N-th air channel of the microfluidic valve control system are respectively connected to one of the air holes, or one or several of the first air channel, the second air channel... the N-th air channel of the microfluidic valve control system share one of the air holes for connection.

[0018] In some of these embodiments, the height of the first capillary channel, the height of the second capillary channel... the height of the N-th capillary channel are the same relative to the bottom surface of the chip substrate.

[0019] In some of these embodiments, at least one of the top regions of the first capillary channel, the top regions of the second capillary channel... the top regions of the N-th capillary channel is close to the upper surface of the chip substrate, and at least one of the bottom regions of the first capillary channel, the bottom regions of the second capillary channel... the bottom regions of the N-th capillary channel is close to the lower surface of the chip substrate.

[0020] The above-mentioned microfluidic valve control system relies on the appropriate combination and arrangement of at least one group of capillary channels (with a certain length and shape and a huge difference in cross-sectional area between the capillary channels and the cross-sectional area of the connected chambers). Due to the different three-dimensional dimensions of the capillary channels, different liquid surface tensions and fluid resistances will be exhibited. These differences can realize the function of a valve control unit. Coupled with the driving of an appropriate centrifugal force, the microfluidic timing position control within the chip is realized, that is, the liquid is blocked in the chamber or the liquid is transferred from the upstream chamber to the downstream chamber within a certain period of time. The microfluidic valve control system of the present invention solves the problem in the existing technology that additional components need to be added to the chip or relatively complex and difficult-to-implement processes are required during the preparation of the microfluidic chip to achieve valve control. The microfluidic valve control system of the present invention can realize the function of repeated use of valves that cannot be achieved by a single valve through the combination and matching of multiple capillary channels, and the implementation process is simple. It can be combined with each other to achieve systematic and linkage complex fluid control, with stronger operability, and solves the disadvantages of some existing valves that require additional equipment components to cooperate for use, complex chip and equipment structures, and insufficient valve repeatability and stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the drawings in the following description are only some embodiments of the present application. For those skilled in the art, without creative efforts, other drawings can be obtained based on these drawings.

[0022] In order to more completely understand the present application and its beneficial effects, the following will be described in conjunction with the drawings. Among them, the same reference numerals in the following description represent the same parts.

[0023] Figure 1 Schematic diagram of a partial structure of a microfluidic chip according to an embodiment of the present invention;

[0024] Figure 2 Schematic diagram of a partial structure of a microfluidic chip according to an embodiment of the present invention;

[0025] Figure 3 Schematic diagram of a partial structure of a microfluidic chip according to an embodiment of the present invention;

[0026] Figure 4 Schematic diagram of a partial structure of a microfluidic chip according to an embodiment of the present invention;

[0027] Figure 5 Schematic diagram of a capillary channel structure according to an embodiment of the present invention;

[0028] Figure 6 Schematic diagram of a capillary channel structure according to an embodiment of the present invention;

[0029] Figure 7 Schematic diagram of the capillary channel structure according to an embodiment of the present invention;

[0030] Figure 8 Schematic diagram of a partial cross-sectional structure of a microfluidic chip according to an embodiment of the present invention;

[0031] Figure 9 Schematic diagram of a partial cross-sectional structure of a microfluidic chip according to an embodiment of the present invention;

[0032] Figure 10 Schematic diagram of a partial cross-sectional structure of a microfluidic chip according to an embodiment of the present invention;

[0033] Figure 11 Schematic diagram of a partial cross-sectional structure of a microfluidic chip according to an embodiment of the present invention.

[0034] Description of reference numerals

[0035] 101, First cavity; 102, Second cavity; 103, Third cavity; 104, Fourth cavity;

[0036] 201, First capillary channel; 202, Second capillary channel; 203, Third capillary channel; 204, Fourth capillary channel;

[0037] 301, First air passage; 302, Second air passage; 303, Third air passage;

[0038] 401, Air hole;

[0039] 501, First branch cavity; 502, Second branch cavity;

[0040] 600, Branch capillary channel; 601, First branch channel; 602, Second branch channel;

[0041] 701, First branch air passage;

[0042] 801, First liquid sac / first liquid bag; 802, Second liquid sac / second liquid bag;

[0043] 901, First liquid inlet; 902, Second liquid inlet;

[0044] 21, First freeze-dried reagent group; 22, Second freeze-dried reagent group; 23, Third freeze-dried reagent group. Detailed implementation manners

[0045] To make the above objects, features, and advantages of the present invention more apparent and understandable, the following describes the specific embodiments of the present invention in detail with reference to the accompanying drawings. Many specific details are set forth in the following description to facilitate a full understanding of the present invention. However, the present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without departing from the spirit of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed below.

[0046] In the description of the present invention, it should be understood that the terms "center", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential", etc. indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings. These are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation. Therefore, it should not be construed as a limitation of the present invention.

[0047] In addition, the terms "first" and "second" are used only for descriptive purposes and cannot be construed as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, features defined with "first" and "second" may explicitly or implicitly include at least one of such features. In the description of the present invention, "a plurality" means at least two, such as two, three, etc., unless otherwise specifically defined.

[0048] In the present invention, unless otherwise clearly defined and limited, the terms "mounted", "connected", "coupled", "fixed", etc. shall be construed broadly. For example, it may be a fixed connection, a detachable connection, or integrated; it may be a mechanical connection or an electrical connection; it may be directly connected or indirectly connected through an intermediate medium, and it may be the internal communication of two elements or the interaction relationship between two elements, unless otherwise clearly limited. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0049] In the present invention, unless otherwise clearly defined and limited, the first feature being "on" or "under" the second feature may be that the first and second features are in direct contact, or the first and second features are indirectly in contact through an intermediate medium. Moreover, the first feature being "above", "over" and "on top of" the second feature may be that the first feature is directly above or obliquely above the second feature, or merely indicates that the first feature has a higher horizontal height than the second feature. The first feature being "under", "beneath" and "underneath" the second feature may be that the first feature is directly below or obliquely below the second feature, or merely indicates that the first feature has a lower horizontal height than the second feature.

[0050] It should be noted that when an element is referred to as "fixed to" or "disposed on" another element, it can be directly on the other element or there may also be an intermediate element. When an element is considered to be "connected to" another element, it can be directly connected to the other element or there may be an intermediate element at the same time. The terms "vertical", "horizontal", "upper", "lower", "left", "right" and similar expressions used herein are only for illustrative purposes and do not represent the only implementation.

[0051] In the description of the present invention, the meaning of "several" is more than one, the meaning of "multiple" is more than two, and understandings such as "greater than", "less than", "exceeding" do not include the present number, and understandings such as "above", "below", "within" include the present number. If there is a description of "first" and "second", it is only for the purpose of distinguishing technical features and cannot be understood as indicating or implying relative importance or implicitly indicating the quantity of the indicated technical features or implicitly indicating the sequence relationship of the indicated technical features.

[0052] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the technical field to which the present invention belongs. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0053] The embodiment of the present application provides a microfluidic valve control system to solve the problems that traditional wax valves or soluble film valves cannot achieve the reuse of valves and the low usability of complex multi-valve combinations, and the poor operability of mechanical valves and the need for additional equipment components to cooperate. The following will be described in conjunction with the drawings.

[0054] The microfluidic valve control system provided by the embodiment of the present application, for example, please refer to Figure 1 as shown in Figure 1 is a partial structural schematic diagram of the microfluidic chip provided by the embodiment of the present application. The microfluidic valve control system of the present application can be used for the valve control of a microfluidic chip. Specifically, the microfluidic valve control system of the present application can be applied to microfluidic control, including but not limited to the diversion, blocking, transfer, mixing, release, etc. of fluids. The microfluidic valve control system of the present application can replace traditional large pipetting equipment, platforms or workstations.

[0055] In order to more clearly illustrate the structure of the microfluidic valve control system, the microfluidic valve control system will be introduced below in conjunction with the drawings.

[0056] For example, please refer to Figure 1As shown, a microfluidic valve control system includes a first capillary channel 201, and the first capillary channel 201 is used to connect between a first cavity 101 and a second cavity 102 of a microfluidic chip. Among them, 0.5 mm ≤ the length L1 of the first capillary channel 201 ≤ 20 mm, 0.01 mm ≤ the width W1 of the first capillary channel 201 ≤ 2 mm, and 0.01 mm ≤ the depth H1 of the first capillary channel 201 ≤ 2 mm.

[0057] In some embodiments, the microfluidic valve control system further includes a second capillary channel 202... an Nth capillary channel, where N ≥ 2. The first capillary channel 201 is used to connect between a first cavity 101 and a second cavity 102 of the microfluidic chip, the second capillary channel 202 is used to connect between the second cavity 102 and a third cavity 103 of the microfluidic chip, and the Nth capillary channel is used to connect between the Nth cavity and the (N + 1)th cavity of the microfluidic chip. Among them, the first cavity 101, the second cavity 102... the Nth cavity, and the (N + 1)th cavity are sequentially distributed in order from the rotation center outwards. Among them, 0.5 mm ≤ the length L1 of the first capillary channel 201 ≤ the length L2 of the second capillary channel 202 ≤... ≤ the length LN of the Nth capillary channel ≤ 20 mm, 2 mm ≥ the width W1 of the first capillary channel 201 ≥ the width W2 of the second capillary channel 202 ≥... ≥ the width WN of the Nth capillary channel ≥ 0.01 mm, and 2 mm ≥ the depth H1 of the first capillary channel 201 ≥ the depth H2 of the second capillary channel 202 ≥... ≥ the depth HN of the Nth capillary channel ≥ 0.01 mm.

[0058] Preferably, 0.5 mm ≤ the length L1 of the first capillary channel 201 ≤ the length L2 of the second capillary channel 202 ≤... ≤ the length LN of the Nth capillary channel ≤ 20 mm, 0.01 mm ≤ the width W1 of the first capillary channel 201 = the width W2 of the second capillary channel 202 =... = the width WN of the Nth capillary channel ≤ 2 mm, and 2 mm ≥ the depth H1 of the first capillary channel 201 ≥ the depth H2 of the second capillary channel 202 ≥... ≥ the depth HN of the Nth capillary channel ≥ 0.01 mm.

[0059] In some embodiments, the microfluidic valve control system further includes a first air channel 301, a second air channel 302... an Nth air channel provided on a chip substrate. The first air channel 301 is used to connect the second cavity 102, the second air channel 302 is used to connect the third cavity 103, and the Nth air channel is used to connect the (N + 1)th cavity.

[0060] In some embodiments, refer to Figure 3As shown, the microfluidic valve control system further includes a branch capillary channel 600 disposed on the chip substrate. One end of the branch capillary channel 600 is used to connect to the liquid inlet of the microfluidic chip, and the other end of the branch capillary channel 600 is used to connect to the Mth cavity of the microfluidic chip, where 2 ≤ M ≤ N. The length L_mao of the branch capillary channel 600 ≥ the length L_(M - 1) of the (M - 1)th capillary channel connected to the Mth cavity at the same radial position. The width W_mao of the branch capillary channel 600 ≥ the width W_(M - 1) of the (M - 1)th capillary channel connected to the Mth cavity at the same radial position; the depth H_mao of the branch capillary channel 600 ≥ the depth H_(M - 1) of the (M - 1)th capillary channel connected to the Mth cavity at the same radial position. That is to say, on the chip substrate of the microfluidic chip, around the rotation center of the chip substrate, the length of the Nth capillary channel at the same radius position is not greater than the length of the branch capillary channel 600 at this position (the same radial position, see Figure 4 the radius trajectory shown by the dashed line in the figure), the width of the Nth capillary channel at the same radius position is not greater than the width of the branch capillary channel 600 at this position (the same radial position), and the depth of the Nth capillary channel at the same radius position is not greater than the depth of the branch capillary channel 600 at this position (the same radial position).

[0061] In some embodiments, see Figures 5 - 7 As shown, the first capillary channel 201 has a linear structure, a curved structure, or a meandering structure.

[0062] In some embodiments, the second capillary channel 202 has a linear structure, a curved structure, or a meandering structure.

[0063] In some embodiments, the Nth capillary channel has a linear structure, a curved structure, or a meandering structure.

[0064] In some embodiments, the range of centrifugal parameters when controlling the transfer of the liquid reagent from the upstream cavity to the downstream cavity includes pipetting centrifugal parameters: centrifugal rotation speed 100 rpm - 2000 rpm; acceleration and deceleration 500 - 20000 rpm / s; mixing centrifugal parameters: centrifugal rotation speed 100 rpm - 2000 rpm; acceleration and deceleration 500 - 20000 rpm / s; swing angle 10° - 3600°; swing pause time 0 - 10000 ms; swing frequency 0 - 1000 times.

[0065] Another object of the present invention also lies in providing a microfluidic chip.

[0066] A microfluidic chip includes a chip substrate and a microfluidic valve control system disposed on the chip substrate. The chip substrate includes a first cavity 101, a second cavity 102... an (N + 1)-th cavity. The first cavity 101, the second cavity 102... the N-th cavity and the (N + 1)-th cavity are sequentially distributed outward from the rotation center of the chip substrate. Reagents can be pre-stored in the first cavity 101, the second cavity 102... the (N + 1)-th cavity. The types, properties and numbers of the reagents can be inconsistent. The reagents can be freeze-dried reagents, air-dried / dried reagents, encapsulated liquid reagents, etc. Specific requirements are set and adjusted according to each reaction step of the biological detection process. In order to enable the transfer of liquid between each reaction chamber (the first cavity 101, the second cavity 102... the (N + 1)-th cavity), a liquid reagent needs to be introduced into the N-th cavity. The introduction of the liquid reagent can be through an external device sampling system or manually with the aid of tools, or by puncturing the encapsulated liquid reagent in the chamber or applying appropriate pressure to squeeze the upper liquid sac / liquid bag of the chip, and the pre-stored liquid reagent therein is introduced into the cavity through the break at the bottom of the liquid sac / liquid bag or introduced into the corresponding N-th cavity via a drainage channel. If a liquid reagent is introduced into a cavity pre-storing a solid reagent (freeze-dried reagent, air-dried / dried reagent), the solid reagent will be dissolved by the liquid reagent. The same liquid reagent can be introduced multiple times in the same cavity or between different cavities. Similarly, different types of reagents can also be introduced multiple times in the same cavity or between different cavities. The order of liquid introduction into the cavity can also be programmed to specify the order and process according to the biological test requirements.

[0067] In some embodiments, when the first cavity 101, the second cavity 102... the (N + 1)-th cavity are used to contain solid reagents, there will be columnar structures in the cavities; preferably, after the reagents are introduced into these cavities, a left-right back-and-forth oscillation mode or a one-way acceleration-deceleration switching motion mode can be performed to promote the dissolution and mixing of the solid reagents.

[0068] The first capillary channel 201 is connected between the first cavity 101 and the second cavity 102 of the microfluidic chip, the second capillary channel 202 is connected between the second cavity 102 and the third cavity 103 of the microfluidic chip, and the N-th capillary channel is connected between the N-th cavity and the (N + 1)-th cavity of the microfluidic chip.

[0069] In some embodiments, air holes 401 are provided on the chip substrate, and the first air channel 301, the second air channel 302... the N-th air channel of the microfluidic valve control system communicate with the air holes 401.

[0070] In some of these embodiments, the first air passage 301, the second air passage 302... the Nth air passage of the microfluidic valve control system are respectively in communication with a pore 401, or one or several of the first air passage 301, the second air passage 302... the Nth air passage of the microfluidic valve control system share a pore 401 for communication.

[0071] In some of these embodiments, the height of the first capillary channel 201, the height of the second capillary channel 202... the height of the Nth capillary channel are the same relative to the bottom surface of the chip substrate.

[0072] In some of these embodiments, at least one of the first capillary channel 201, the second capillary channel 202... the Nth capillary channel is close to the upper surface of the chip substrate, and at least one of the first capillary channel 201, the second capillary channel 202... the Nth capillary channel is close to the lower surface of the chip substrate. For example, in one specific example, refer to Figure 8 As shown, the top regions of the first capillary channel 201, the second capillary channel 202... the Nth capillary channel are all close to the upper surface of the chip substrate. For example, in another specific example, refer to Figure 9 As shown, the bottom regions of the first capillary channel 201, the second capillary channel 202... the Nth capillary channel are all close to the lower surface of the chip substrate. For example, in another specific example, refer to Figure 10 As shown, the top region of the first capillary channel 201 is close to the upper surface of the chip substrate, the bottom region of the second capillary channel 202 is close to the lower surface of the chip substrate, and the top regions of the third capillary channel 203 are all close to the upper surface of the chip substrate. For example, in another specific example, refer to Figure 11 As shown, the top region of the first capillary channel 201 is close to the upper surface of the chip substrate, the bottom region of the second capillary channel 202 is close to the lower surface of the chip substrate, the top regions of the third capillary channel 203 are all close to the upper surface of the chip substrate, and the top regions of the fourth capillary channel 204 are all close to the upper surface of the chip substrate.

[0073] In some of these embodiments, refer to Figure 4As shown, the chip substrate also includes branched microfluidics, which includes a first branched cavity 501, a second branched cavity 502... an Nth branched cavity. The microfluidic valve control system also includes a first branch channel 601, a second branch channel 602... an (N - 1)th branch channel provided on the chip substrate. The microfluidic valve control system also includes a first branch air channel, a second branch air channel... an (N - 1)th branch air channel provided on the chip substrate. The first branched cavity 501, the second branched cavity 502... the Nth branched cavity are sequentially distributed outward from the rotation center of the chip substrate. Reagents can be pre-stored in the first branched cavity 501, the second branched cavity 502... the Nth branched cavity. The types, properties, and numbers of the reagents can be inconsistent. The reagents can be freeze-dried reagents, air-dried / dried reagents, encapsulated liquid reagents, etc. The first branch channel 601 is connected between the first branch cavity and the second branch cavity of the microfluidic chip. The second branch channel 602 is connected between the second branch cavity and the third branch cavity of the microfluidic chip. The (N - 1)th branch channel is connected between the (N - 1)th branch cavity and the Nth branch cavity of the microfluidic chip. Multiple branched microfluidics can be provided on the microfluidic chip. The last branched cavity (the Nth branched cavity) of the branched microfluidics is finally connected to the (N + 1)th cavity. Among them, 0.5 mm ≤ the length L_branch1 of the first branch channel 601 ≤ the length L_branch2 of the second branch channel 602 ≤... ≤ the length L_branch(N - 1) of the (N - 1)th branch channel ≤ 20 mm, and 2 mm ≥ the width W_branch1 of the first branch channel 601 ≥ the width W_branch2 of the second branch channel 602 ≥ ... ≥ the width W_branch(N - 1) of the (N - 1)th branch channel ≥ 0.01 mm, and 2 mm ≥ the depth H_branch1 of the first branch channel 601 ≥ the depth H_branch2 of the second branch channel 602 ≥... ≥ the depth H_branch(N - 1) of the (N - 1)th branch channel ≥ 0.01 mm. And, the length L_branch(N - 1) of the (N - 1)th branch channel = the length of the capillary channel in the same radial direction.

[0074] It should be noted that the biological reaction processes occurring in the above-mentioned first cavity 101, second cavity 102... (N + 1)th cavity, first branched cavity 501, second branched cavity 502... Nth branched cavity include but are not limited to: biochemistry, immunology, molecule, cell culture, drug screening, organ-on-a-chip, metal ion detection, food / raw material residue detection, etc.

[0075] The above-mentioned microfluidic valve control system can be used to control liquid reagents or mixed liquid reagents in a microfluidic chip. Among them, the mixed liquid reagent is a mixture of a liquid reagent / diluent, etc., which dissolves other solid reagent components (lyophilized reagent / dried reagent). Whether it is a single liquid reagent or a mixed liquid reagent, its components include but are not limited to the following components: water (ultrapure water, deionized water, etc.), electrolytes (cations and anions required for reagent components, such as buffer pairs), proteins or amino acids and their derivatives (antigens, antibodies, enzymes, and other proteins or amino acids that meet the reaction requirements), nucleic acids and their derivatives, sugars and their derivatives (monosaccharides, disaccharides, and polysaccharides such as glucose, trehalose, sucrose, lactose, and galactose), high molecular polymers (such as PEG2000), inhibitors (such as EDTA), surfactants, preservatives, and other additives. The viscosity range of the above-mentioned mixed liquid reagent at 20 °C is 0-20000 Cps.

[0076] In the present invention, various combination strategies can be achieved by changing the surface properties in the capillary channel and combining the three-dimensional size matching of the channels. Usually, the two main surface property change strategies are to hydrophilize or hydrophobize the channel. The hydrophilized channel is more conducive to the infiltration of liquid in the capillary channel, and the required centrifugal force and centrifugal motion parameters (the combination of centrifugal force, centrifugal time, and centrifugal acceleration) can be appropriately reduced to complete the transfer of the reagent from the upstream cavity to the downstream cavity or to draw out the liquid reagent from the liquid sac / liquid bag. The hydrophobized channel can enhance the blocking ability of the liquid reagent and hinder the liquid from infiltrating the capillary channel. Therefore, a certain centrifugal force and centrifugal motion parameters (the combination of centrifugal force, centrifugal time, and centrifugal acceleration) are required to enable the liquid to break through the capillary channel and transfer from the upstream cavity to the downstream cavity. Among them, the hydrophilic and hydrophobic reagent types are as follows: ① hydrophilic reagents: selected from at least one of polyvinylpyrrolidone, polyethylene glycol, hyaluronic acid, sodium polyacrylate, polyacrylamide, sodium alginate, and polyvinyl alcohol; hydrophobic reagents: selected from at least one of fluorinated alkanes, fluorinated methyl ethers, fluorinated furans, etc.

[0077] Example 1

[0078] This example provides a microfluidic chip.

[0079] A microfluidic chip includes a chip substrate and a microfluidic valve control system.

[0080] The chip substrate includes a first cavity 101, a second cavity 102... an Nth cavity, and an N+1th cavity. The first cavity 101, the second cavity 102... the Nth cavity, and the N+1th cavity are sequentially distributed outward from the rotation center of the chip substrate.

[0081] The microfluidic valve control system includes a first capillary channel 201, a second capillary channel 202... an Nth capillary channel disposed on a chip substrate. The first capillary channel 201 is connected between a first cavity 101 and a second cavity 102. The second capillary channel 202 is connected between the second cavity 102 and a third cavity 103 of the microfluidic chip. The Nth capillary channel is connected between the Nth cavity of the microfluidic chip and the (N + 1)th cavity of the microfluidic chip.

[0082] 0.5 mm ≤ the length L1 of the first capillary channel 201 ≤ the length L2 of the second capillary channel 202 ≤... ≤ the length LN of the Nth capillary channel ≤ 20 mm, 2 mm ≥ the width W1 of the first capillary channel 201 ≥ the width W2 of the second capillary channel 202 ≥... ≥ the width WN of the Nth capillary channel ≥ 0.01 mm, 2 mm ≥ the depth H1 of the first capillary channel 201 ≥ the depth H2 of the second capillary channel 202 ≥... ≥ the depth HN of the Nth capillary channel ≥ 0.01 mm.

[0083] A plurality of air holes 401 are disposed on the chip substrate. For example, a first air hole, a second air hole... an Nth air hole.

[0084] The microfluidic valve control system includes a first air channel 301, a second air channel 302... an Nth air channel disposed on the chip substrate. One end of the first air channel 301 is connected to the second cavity 102. One end of the second air channel 302 is connected to the third cavity 103. One end of the Nth air channel is connected to the (N + 1)th cavity. Further, the other end of the first air channel 301 communicates with the first air hole, and the extending direction of the first air channel 301 is opposite to that of the first capillary channel 201. The other end of the second air channel 302 communicates with the second air hole, and the extending direction of the second air channel 302 is opposite to that of the second capillary channel 202. The other end of the (N - 1)th air channel communicates with the (N - 1)th air hole, and the extending direction of the (N - 1)th air channel is opposite to that of the (N - 1)th capillary channel. The other end of the Nth air channel communicates with the Nth air hole, and the extending direction of the Nth air channel is opposite to that of the Nth capillary channel. Or, as shown in Figure 1 the figure, the Nth air channel and the (N - 1)th air channel communicate with the (N - 1)th air hole together.

[0085] In this embodiment, as shown in Figure 1As shown in the figure, a liquid reagent is introduced into the first cavity 101 through a fluid inlet of the liquid sac / liquid bag (it can also be introduced from the liquid inlet through the equipment sampling system or manually); (2) With appropriate centrifugal pipetting parameters, the liquid reagent breaks through the first capillary channel 201 and enters the second cavity 102, and the liquid reagent does not break through the second capillary channel 202 during this process; (3) With appropriate mixing parameters, the introduced liquid reagent is melted and mixed with the freeze-dried reagent in the second cavity 102, and the liquid reagent does not break through the second capillary channel 202 during this process; (4) With appropriate centrifugal pipetting parameters, the mixed reagent breaks through the second capillary channel 202 and enters the third cavity 103. And so on, by controlling appropriate centrifugal parameters, it can be ensured that the liquid reagent enters the next adjacent cavity from the previous cavity without breaking through the third cavity.

[0086] Example 2

[0087] This embodiment provides a microfluidic chip.

[0088] A microfluidic chip includes a chip substrate and a microfluidic valve control system.

[0089] The chip substrate includes a first cavity 101, a second cavity 102, and a third cavity 103. The first cavity 101, the second cavity 102, and the third cavity 103 are sequentially distributed outward from the rotation center of the chip substrate.

[0090] See Figure 2 As shown in the figure, the microfluidic valve control system includes a first capillary channel 201 and a second capillary channel 202 provided on the chip substrate. The first capillary channel 201 is connected between the first cavity 101 and the second cavity 102, and the second capillary channel 202 is connected between the second cavity 102 and the third cavity 103 of the microfluidic chip.

[0091] 0.5 mm ≤ the length L1 of the first capillary channel 201 ≤ the length L2 of the second capillary channel 202 ≤ 20 mm, 2 mm ≥ the width W1 of the first capillary channel 201 ≥ the width W2 of the second capillary channel 202 ≥ 0.01 mm, 2 mm ≥ the depth H1 of the first capillary channel 201 ≥ the depth H2 of the second capillary channel 202 ≥ 0.01 mm.

[0092] A gas hole 401 is provided on the chip substrate.

[0093] The microfluidic valve control system includes a first air passage 301 and a second air passage 302 provided on the chip substrate. One end of the first air passage 301 is connected to the second cavity 102, and one end of the second air passage 302 is connected to the third cavity 103. Further, the other end of the first air passage 301 communicates with the air hole 401, and the extending direction of the first air passage 301 is opposite to that of the first capillary channel 201. The other end of the second air passage 302 communicates with the air hole 401, and the extending direction of the second air passage 302 is opposite to that of the second capillary channel 202.

[0094] In this embodiment, as shown in Figure 2 : (1) The liquid sac / liquid bag introduces a liquid reagent into the first cavity 101 through the fluid inlet (it can also be introduced from the liquid inlet through the device sample addition system or manually); (2) With appropriate centrifugal pipetting parameters, the liquid reagent breaks through the first capillary channel 201 and enters the second cavity 102, and the liquid reagent does not break through the second capillary channel 202 during this process; (3) With appropriate mixing parameters, the introduced liquid reagent is melted and mixed with the freeze-dried reagent in the second cavity 102, and the liquid reagent does not break through the second capillary channel 202 during this process; (3) With appropriate centrifugal pipetting parameters, the mixed reagent breaks through the second capillary channel 202 and enters the third cavity 103.

[0095] Embodiment 3

[0096] This embodiment provides a microfluidic chip.

[0097] A microfluidic chip includes a chip substrate and a microfluidic valve control system.

[0098] The chip substrate includes a first cavity 101, a second cavity 102, a third cavity 103, and a fourth cavity 104. The first cavity 101, the second cavity 102, and the third cavity 103 are sequentially distributed outward from the rotation center of the chip substrate.

[0099] As shown in Figure 3 : The microfluidic valve control system includes a first capillary channel 201, a second capillary channel 202, and a third capillary channel 203 provided on the chip substrate. The first capillary channel 201 is connected between the first cavity 101 and the second cavity 102, the second capillary channel 202 is connected between the second cavity 102 and the third cavity 103, and the third capillary channel 203 is connected between the third cavity 103 and the fourth cavity 104.

[0100] 0.5 mm ≤ the length L1 of the first capillary channel 201 ≤ the length L2 of the second capillary channel 202 = the length L3 of the third capillary channel 203 ≤ 20 mm, 0.01 mm ≤ the width W1 of the first capillary channel 201 = the width W2 of the second capillary channel 202 = the width W3 of the third capillary channel 203 ≤ 2 mm, 2 mm ≥ the depth H1 of the first capillary channel 201 ≥ the depth H2 of the second capillary channel 202 ≥ the depth H3 of the third capillary channel 203 ≥ 0.01 mm.

[0101] A gas hole 401 is provided on the chip substrate.

[0102] The microfluidic valve control system includes a first air passage 301, a second air passage 302, and a third air passage 303 provided on the chip substrate. One end of the first air passage 301 is connected to the second cavity 102, one end of the second air passage 302 is connected to the third cavity 103, and one end of the third air passage 303 is connected to the fourth cavity 104. Further, the other end of the first air passage 301 communicates with the gas hole 401, and the extending direction of the first air passage 301 is opposite to that of the first capillary channel 201. The other end of the second air passage 302 communicates with the gas hole 401, and the extending direction of the second air passage 302 is opposite to that of the second capillary channel 202. The other end of the third air passage 303 communicates with the gas hole 401, and the extending direction of the third air passage 303 is opposite to that of the third capillary channel 203.

[0103] The microfluidic valve control system further includes a branch capillary channel 600 provided on the chip substrate. One end of the branch capillary channel 600 is used to connect to the liquid inlet of the microfluidic chip, and the other end of the branch capillary channel 600 is used to connect to the third cavity 103 of the microfluidic chip. The length Lmao of the branch capillary channel 600 ≥ the length L2 of the second capillary channel at the same radial position. The width Wmao of the branch capillary channel 600 ≥ the width W2 of the second capillary channel at the same radial position; the depth Hmao of the branch capillary channel 600 ≥ the depth H2 of the second capillary channel at the same radial position. The length Lmao of the branch capillary channel 600 can be determined according to the required liquid drainage speed.

[0104] In this embodiment, refer to Figure 3As shown, (1) The second liquid sac / second liquid bag 802 first passes through the second fluid inlet and then introduces the liquid reagent into the third cavity 103 along the branch capillary channel 600. During this process, the liquid reagent does not break through the third capillary channel 203; (2) With appropriate mixing parameters, the introduced liquid is fully re-melted and mixed with the second lyophilized reagent group 22 in the third cavity 103. During this process, the liquid reagent does not break through the third capillary channel 203; (3) The first liquid sac / first liquid bag 801 introduces the liquid reagent into the first cavity 101 through the first fluid inlet. During this process, the liquid reagent does not break through the first capillary channel 201, and the liquid reagent in the third cavity 103 does not break through the third capillary channel 203; (4) With appropriate mixing parameters, the introduced liquid is fully re-melted and mixed with the first lyophilized reagent group 21 in the first cavity 101. During this process, the liquid reagent does not break through the first capillary channel 201, and the liquid reagent in the third cavity 103 does not break through the third capillary channel 203; (5) With appropriate centrifugal pipetting parameters, the mixed reagent in the first cavity 101 breaks through the first capillary channel 201 and enters the second cavity 102, but the mixed reagent in the third cavity 103 still remains in the third cavity 103 and does not break through the third capillary channel 203; (6) With appropriate mixing parameters, the air-dried / dried reagent group in the second cavity 102 is dissolved and mixed by the mixed liquid reagent introduced in the previous step. During this process, the mixed liquid reagent does not break through the second capillary channel 202, and the liquid reagent in the third cavity 103 does not break through the third capillary channel 203; (7) With appropriate centrifugal pipetting parameters, the mixed reagent in the second cavity 102 breaks through the second capillary channel 202 and enters the third cavity 103. During this process, the mixed liquid does not break through the third capillary channel 203; (8) With appropriate mixing parameters, the final mixed liquid completes incubation and reaction in the third cavity 103. During this process, the mixed liquid does not break through the third capillary channel 203; (9) With appropriate centrifugal pipetting parameters, the mixed reagent in the third cavity 103 breaks through the third capillary channel 203 and enters the fourth cavity 104.

[0105] Alternatively, in this embodiment, refer to Figure 3As shown in the figure, (1) the first liquid sac / first liquid bag 801 introduces a liquid reagent into the first cavity 101 through the first fluid inlet; at the same time, the second liquid sac / second liquid bag 802 first passes through the second fluid inlet and then introduces the liquid reagent into the third cavity 103 along the branch capillary channel 600. During this process, the liquid reagent does not break through the first capillary channel 201 and the third capillary channel 203; (2) with appropriate mixing parameters, the introduced liquid is fully re-melted and mixed with the first lyophilized reagent group 21 in the first cavity 101; at the same time, the introduced liquid is fully re-melted and mixed with the second lyophilized reagent group 22 in the third cavity 103. During this process, the mixed liquid reagent in both cavities does not break through the first capillary channel 201 and the third capillary channel 203; (3) with appropriate centrifugal pipetting parameters, the mixed reagent in the first cavity 101 breaks through the first capillary channel 201 and enters the second cavity 102, but the mixed reagent in the third cavity 103 still remains in the third cavity 103 and does not break through the third capillary channel 203; (4) with appropriate mixing parameters, the air-dried / dried reagent group in the second cavity 102 is dissolved and mixed by the mixed liquid reagent introduced in the previous step. During this process, the mixed liquid reagent does not break through the second capillary channel 202, and the liquid reagent in the third cavity 103 does not break through the third capillary channel 203; (5) with appropriate centrifugal pipetting parameters, the mixed reagent in the second cavity 102 breaks through the second capillary channel 202 and enters the third cavity 103. During this process, the mixed liquid does not break through the third capillary channel 203; (6) with appropriate mixing parameters, the final mixed liquid completes incubation and reaction with the already mixed reagent in the third cavity 103. During this process, the mixed liquid does not break through the third capillary channel 203; (7) with appropriate centrifugal pipetting parameters, the mixed reagent in the third cavity 103 breaks through the third capillary channel 203 and enters the fourth cavity 104.

[0106] Example 4

[0107] This example provides a microfluidic chip.

[0108] A microfluidic chip includes a chip substrate and a microfluidic valve control system.

[0109] The chip substrate includes a first cavity 101, a second cavity 102, a third cavity 103, and a fourth cavity 104. The first cavity 101, the second cavity 102, and the third cavity 103 are sequentially distributed outward from the rotation center of the chip substrate.

[0110] See Figure 4As shown in the figure, the microfluidic valve control system includes a first capillary channel 201, a second capillary channel 202, and a third capillary channel 203 provided on a chip substrate. The first capillary channel 201 is connected between a first cavity 101 and a second cavity 102. The second capillary channel 202 is connected between the second cavity 102 and a third cavity 103 of the microfluidic chip. The third capillary channel 203 is connected between the third cavity 103 and a fourth cavity 104 of the microfluidic chip.

[0111] 0.5 mm ≤ the length L1 of the first capillary channel 201 ≤ the length L2 of the second capillary channel 202 = the length L3 of the third capillary channel 203 ≤ 20 mm, 0.01 mm ≤ the width W1 of the first capillary channel 201 = the width W2 of the second capillary channel 202 = the width W3 of the third capillary channel 203 ≤ 2 mm, 2 mm ≥ the depth H1 of the first capillary channel 201 ≥ the depth H2 of the second capillary channel 202 ≥ the depth H3 of the third capillary channel 203 ≥ 0.01 mm.

[0112] An air hole 401 is provided on the chip substrate.

[0113] The microfluidic valve control system includes a first air channel 301, a second air channel 302, and a third air channel 303 provided on the chip substrate. One end of the first air channel 301 is connected to the second cavity 102. One end of the second air channel 302 is connected to the third cavity 103. One end of the third air channel 303 is connected to the fourth cavity 104. Further, the other end of the first air channel 301 communicates with the air hole 401, and the extending direction of the first air channel 301 is opposite to that of the first capillary channel 201. The other end of the second air channel 302 communicates with the air hole 401, and the extending direction of the second air channel 302 is opposite to that of the second capillary channel 202. The other end of the third air channel 303 communicates with the air hole 401, and the extending direction of the third air channel 303 is opposite to that of the third capillary channel 203.

[0114] The microfluidic valve control system further includes a branch capillary channel 600 provided on the chip substrate. One end of the branch capillary channel 600 is used to connect to a liquid inlet of the microfluidic chip, and the other end of the branch capillary channel 600 is used to connect to the third cavity 103 of the microfluidic chip. The length L_mao of the branch capillary channel 600 ≥ the length L2 of the second capillary channel at the same radial position. The width W_mao of the branch capillary channel 600 ≥ the width W2 of the second capillary channel at the same radial position; the depth H_mao of the branch capillary channel 600 ≥ the depth H2 of the second capillary channel at the same radial position. The length L_mao of the branch capillary channel 600 can be determined according to the required liquid drainage speed.

[0115] See Figure 4As shown, the chip substrate further includes branch microfluidics, and the branch microfluidics includes a first branch cavity 501 and a second branch cavity 502. The microfluidic valve control system further includes a first branch channel 601 and a second branch channel 602 disposed on the chip substrate, and the microfluidic valve control system further includes a first branch air passage disposed on the chip substrate. The first branch cavity 501 and the second branch cavity 502 are sequentially distributed outward from the rotation center of the chip substrate. Reagents can be pre-stored in the first branch cavity 501 and the second branch cavity 502, and the types, properties, and numbers of the reagents can be inconsistent. The reagents can be freeze-dried reagents, air-dried / dried reagents, encapsulated liquid reagents, etc. The first branch channel 601 is connected between the first branch cavity and the second branch cavity of the microfluidic chip, and the second branch channel 602 is connected between the second branch cavity and the third cavity 103 of the microfluidic chip. Among them, 0.5 mm ≤ the length L_branch1 of the first branch channel 601 ≤ the length L_branch2 of the second branch channel 602 ≤ 20 mm, 2 mm ≥ the width W_branch1 of the first branch channel 601 ≥ the width W_branch2 of the second branch channel 602 ≥ 0.01 mm, 2 mm ≥ the depth H_branch1 of the first branch channel 601 ≥ the depth H_branch2 of the second branch channel 602 ≥ 0.01 mm. Since the first branch channel 601 and the first capillary channel 201 are located at the same radial position, the length L_branch1 of the first branch channel 601 = the length L1 of the first capillary channel 201, the width W_branch1 of the first branch channel 601 = the width W1 of the first capillary channel 201, and the depth H_branch1 of the first branch channel 601 = the depth H1 of the first capillary channel 201; since the second branch channel 602 and the second capillary channel 202 are located at the same radial position, the length L_branch2 of the second branch channel 602 = the length L2 of the second capillary channel 202, the width W_branch2 of the second branch channel 602 = the width W2 of the second capillary channel 202, and the depth H_branch2 of the second branch channel 602 = the depth H2 of the second capillary channel 202.

[0116] In this embodiment, refer to Figure 4As shown, (1) The first liquid sac / first liquid bag 801 introduces a liquid reagent into the first cavity 101 through the first fluid inlet; simultaneously, the second liquid sac / second liquid bag 802 introduces a liquid reagent into the first branch cavity 501 through the second fluid inlet. During this process, the liquid reagents are retained in the first cavity 101 and the first branch cavity 501; (2) With appropriate mixing parameters, the liquid reagents introduced into the two cavities are respectively fully reconstituted and mixed with the first lyophilized reagent group 21 in the first cavity 101 and the second lyophilized reagent group 22 in the first branch cavity 501. During this process, the mixed liquid reagents in the two cavities do not break through the first cavity 101 and the first branch cavity 501; (3) With appropriate centrifugal pipetting parameters, the mixed reagent in the first cavity 101 breaks through the first capillary channel 201 and enters the second cavity 102. Simultaneously, the mixed reagent in the first branch cavity 501 breaks through the first branch channel 601 and enters the second branch cavity 502; (4) With appropriate mixing parameters, the air-dried / dried reagent group in the second cavity 102 is dissolved and mixed by the mixed liquid reagent introduced in the previous step. During this process, neither of the two parts of the mixed liquid reagent breaks through the second cavity 102 and the second branch cavity 502; (5) With appropriate centrifugal pipetting parameters, the mixed reagent in the second cavity 102 breaks through the second capillary channel 202 and enters the third cavity 103. At the same time, the mixed reagent in the second branch cavity 502 breaks through the second branch channel 602 and also enters the third cavity 103. After this process, the mixed liquid in the third cavity 103 does not break through the third capillary channel 203; (6) With appropriate mixing parameters, the final mixed liquid completes incubation and reaction with the third lyophilized reagent group in the third cavity 103. During this process, the mixed liquid does not break through the third capillary channel 203; (7) With appropriate centrifugal pipetting parameters, the mixed reagent in the third cavity 103 breaks through the third capillary channel 203 and enters the fourth cavity 104.

[0117] The above-mentioned microfluidic valve control system relies on the appropriate combination and arrangement of at least one group of capillary channels (with a certain length and shape and a huge difference in cross-sectional area between the capillary channels and the cross-sectional area of the connected chambers). Due to the different three-dimensional sizes of the capillary channels, different liquid surface tensions and fluid resistances will be exhibited. These differences can realize the function of a valve control unit. With the drive of an appropriate centrifugal force, the microfluidic timing position control within the chip can be realized, that is, the liquid is blocked in the chamber or the liquid is transferred from the upstream chamber to the downstream chamber within a certain period of time. The microfluidic valve control system of the present invention solves the problem in the existing technology that additional components need to be added to the chip or complex and difficult-to-implement processes need to be carried out during the preparation process of the microfluidic chip to realize valve control; the microfluidic valve control system of the present invention can realize the function of repeated use of valves that cannot be achieved by a single valve through the combination and matching of multiple capillary channels, and the implementation process is simple. It can be combined with each other to realize systematic and linkage complex fluid control, with stronger operability, and solves the shortcomings of some valves in the existing technology that need additional equipment components to cooperate to be used, the chip and equipment structures are complex, and the repeatability and stability of the valves are insufficient.

[0118] In the above embodiments, the descriptions of the respective embodiments have their own emphases. For the parts not detailed in a certain embodiment, reference may be made to the relevant descriptions of other embodiments.

[0119] The technical features of the above embodiments can be combined arbitrarily. For the sake of brevity of description, 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, it should be considered as the scope described in this specification.

[0120] The above embodiments only represent several implementation manners of the present invention, and their descriptions are relatively specific and detailed, but they should not be construed as limiting the scope of the patent of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several deformations and improvements can still be made, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention should be subject to the appended claims.

Claims

1. A microfluidic valve control system, characterized in that, It includes a first capillary channel for connecting between a first cavity and a second cavity of a microfluidic chip, where 0.5 mm ≤ the length L1 of the first capillary channel ≤ 20 mm, 0.01 mm ≤ the width W1 of the first capillary channel ≤ 2 mm, and 0.01 mm ≤ the depth H1 of the first capillary channel ≤ 2 mm; The microfluidic valve control system further includes a second capillary channel... an Nth capillary channel, where N ≥ 2. The first capillary channel is for connecting between a first cavity and a second cavity of the microfluidic chip. The second capillary channel is for connecting between the second cavity and a third cavity of the microfluidic chip. The Nth capillary channel is for connecting between the Nth cavity and the (N + 1)th cavity of the microfluidic chip. Among them, the first cavity, the second cavity... the Nth cavity and the (N + 1)th cavity are sequentially distributed in order from the rotation center outwards. Where 0.5 mm ≤ the length L1 of the first capillary channel ≤ the length L2 of the second capillary channel ≤... ≤ the length LN of the Nth capillary channel ≤ 20 mm, 2 mm ≥ the width W1 of the first capillary channel ≥ the width W2 of the second capillary channel ≥... ≥ the width WN of the Nth capillary channel ≥ 0.01 mm, 2 mm ≥ the depth H1 of the first capillary channel ≥ the depth H2 of the second capillary channel ≥... ≥ the depth HN of the Nth capillary channel ≥ 0.01 mm.

2. The microfluidic valve control system according to claim 1, wherein The microfluidic valve control system further includes a first air channel, a second air channel... an Nth air channel. The first air channel is for connecting the second cavity. The second air channel is for connecting the third cavity. The Nth air channel is for connecting to the (N + 1)th cavity.

3. The microfluidic valve control system according to claim 1, wherein, The microfluidic valve control system further includes a branch capillary channel. One end of the branch capillary channel is for connecting to a liquid inlet of the microfluidic chip. The other end of the branch capillary channel is for connecting to the Mth cavity of the microfluidic chip, where 2 ≤ M ≤ N. The length Lmao of the branch capillary channel ≥ the length L(M - 1) of the (M - 1)th capillary channel connected to the Mth cavity at the same radial position; the width Wmao of the branch capillary channel ≥ the width W(M - 1) of the (M - 1)th capillary channel connected to the Mth cavity at the same radial position; the depth Hmao of the branch capillary channel ≥ the depth H(M - 1) of the (M - 1)th capillary channel connected to the Mth cavity at the same radial position.

4. The microfluidic valve control system according to claim 3, wherein The first capillary channel has a linear structure, a curved structure or a tortuous structure; and / or The second capillary channel has a linear structure, a curved structure or a tortuous structure; and / or... And / or, the Nth capillary channel has a linear structure, a curved structure or a tortuous structure.

5. The microfluidic valve control system according to any one of claims 1-4, characterized in that, The centrifugation parameter ranges for controlling the transfer of liquid reagents from the upstream cavity to the downstream cavity include pipetting centrifugation parameters: centrifugal rotation speed 100 rpm - 2000 rpm; acceleration and deceleration 500 - 20000 rpm / s; mixing centrifugation parameters: centrifugal rotation speed 100 rpm - 2000 rpm; acceleration and deceleration 500 - 20000 rpm / s; swing angle 10° - 3600°; swing pause time 0 - 10000 ms; number of swings 0 - 1000 times.

6. A microfluidic chip, characterized in that, It includes a chip substrate and the microfluidic valve control system according to any one of claims 1 - 5. The chip substrate includes a first cavity, a second cavity... an (N + 1)th cavity. The first cavity, the second cavity... the Nth cavity and the (N + 1)th cavity are sequentially distributed outward from the rotation center of the chip substrate. The first capillary channel is connected between the first cavity and the second cavity of the microfluidic chip, the second capillary channel is connected between the second cavity and the third cavity of the microfluidic chip, and the Nth capillary channel is connected between the Nth cavity and the (N + 1)th cavity of the microfluidic chip.

7. The microfluidic chip according to claim 6, wherein, There are air holes provided on the chip substrate, and the first air channel, the second air channel... the Nth air channel of the microfluidic valve control system communicate with the air holes.

8. The microfluidic chip according to claim 7, wherein The first air channel, the second air channel... the Nth air channel of the microfluidic valve control system communicate with one of the air holes respectively, or one or several of the first air channel, the second air channel... the Nth air channel of the microfluidic valve control system share one of the air holes to communicate.

9. The microfluidic chip according to any one of claims 6 to 8, characterized in that, At least one of the top regions of the first capillary channel, the top regions of the second capillary channel... the top regions of the Nth capillary channel is close to the upper surface of the chip substrate, and at least one of the bottom regions of the first capillary channel, the bottom regions of the second capillary channel... the bottom regions of the Nth capillary channel is close to the lower surface of the chip substrate.

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