A microfluidic device

Abstract

This invention discloses a microfluidic device, comprising a main body, a micromixing device, a liquid delivery device, and a liquid receiving device. The main body includes an opening and a receiving cavity, with the opening communicating with the receiving cavity. The micromixing device, the liquid delivery device, and the liquid receiving device are all housed within the receiving cavity. The micromixing device includes at least two inlets, a microchannel, and at least one outlet. The inlets and outlets are connected via the microchannel. The liquid delivery device delivers raw material liquid into the inlets, and the liquid receiving device receives the microfluidic mixture from the outlet. This invention features a simple structure, high degree of automation, convenient operation, and high preparation accuracy. Using the micromixing device to prepare microfluidic mixtures allows for automated and precise control of the inlet volume and inlet speed of the raw material liquids, with a total flow rate up to 120 ml / min, enabling precise control of the ratio and temperature between the various raw material liquids. The liquid receiving device can automatically switch between the collection tube and the waste liquid tube, achieving continuous production of multiple doses.

Description

Technical Field

[0001] This invention relates to the field of microfluidic control, and more particularly to a microfluidic device primarily used for the preparation of nanomedicines and microspheres. Background Technology

[0002] Microfluidics is a technique that uses microchannels (tens to hundreds of micrometers in size) to precisely control and manipulate microscale fluids or small volumes of fluids, especially for micrometer and submicrometer structures.

[0003] The early concept of microfluidics involved fabricating gas chromatographs on silicon wafers using photolithography. This concept has since expanded to include microfluidic capillary electrophoresis systems and microreactors. One of the key characteristics of microfluidics is its unique fluid properties at the microscale, such as laminar flow and droplet formation. Leveraging these unique fluid phenomena, microfluidics can achieve a range of microfabrications and micromanipulations that are difficult to accomplish using conventional methods. Currently, microfluidics is considered to have enormous development potential and broad application prospects in biological and medical research.

[0004] However, the current common flow control chip boxes have relatively complex structures and high costs, and some can only be used once, resulting in great waste and high research and development costs for research units or personnel.

[0005] Currently, there is a lack of systematic automated microfluidic preparation equipment in China. For liquid delivery devices, there are a series of issues such as how to accurately control and automatically and dynamically control the inlet volume and inlet speed of the raw material liquid, how to heat the raw material liquid and set a certain temperature or temperature curve, how to easily remove and reposition the raw material liquid, how to achieve multi-dose continuous preparation to realize automated continuous production, and how to ensure that the raw material liquid and microfluidic mixture do not leak during the preparation process.

[0006] Therefore, this patent provides a new technical solution to address the above problems. Summary of the Invention

[0007] To address the technical problems existing in the prior art, this invention provides a microfluidic device that is simple in structure, easy to use, capable of continuous automated operation, and offers high preparation precision and high flow rate. The specific technical solution is as follows:

[0008] A microfluidic device includes a main body, a micromixing device, a liquid delivery device, and a liquid receiving device;

[0009] The main body of the device includes an opening and a receiving cavity. The opening is connected to the receiving cavity. The micro-mixing device, the liquid delivery device, and the liquid receiving device are all housed in the receiving cavity. The micro-mixing device includes a microchannel, at least one liquid inlet, and at least one liquid outlet. The liquid inlet and the liquid outlet are connected through the microchannel. The liquid delivery device cooperates with the liquid inlet and can deliver raw material liquid into the liquid inlet. The liquid receiving device corresponds to the liquid outlet and can receive the microfluidic mixture from the liquid outlet.

[0010] As a preferred embodiment of the microfluidic device described in this patent, the main body of the device further includes a support body, which is housed in the receiving cavity. The support body has a box groove and at least one liquid delivery hole. The box groove is connected to the liquid delivery hole. The micro-mixing device is snapped into the box groove, and the liquid inlet of the micro-mixing device corresponds to the liquid delivery hole.

[0011] The liquid delivery device includes at least one liquid delivery pipe, which can contain raw material liquid.

[0012] As a preferred embodiment of the microfluidic device described in this patent, the liquid receiving device includes a liquid receiving slider and a liquid receiving tube. The liquid receiving slider is slidably mounted on the support body. The liquid receiving slider has a waste liquid tank and at least two slots. The waste liquid tank is arranged between two adjacent slots and can receive waste liquid from the outlet. The liquid receiving tube is snapped into the slot and can receive the microfluidic mixture from the outlet.

[0013] The microchannel structures include T-shaped structures, Y-shaped structures, cross-shaped structures, SHM fishbone structures, and Tesla structures.

[0014] As a preferred embodiment of the microfluidic device described in this patent, the microchannel includes at least one liquid inlet microchannel and at least one mixing microchannel. The liquid inlet corresponds one-to-one with the liquid inlet microchannel. One end of the liquid inlet microchannel is connected to the liquid inlet, the other end of the liquid inlet microchannel is connected to one end of the mixing microchannel, and the other end of the mixing microchannel is connected to the liquid outlet.

[0015] As a preferred embodiment of the microfluidic device described in this patent, it also includes a telescopic extrusion device, which corresponds to the liquid delivery tube and is located on the side of the liquid delivery tube away from the micro-mixing device. The telescopic extrusion device can push the raw material liquid in the liquid delivery tube to the liquid inlet.

[0016] The support body, equipped with a liquid delivery hole, can rotate.

[0017] As a preferred embodiment of the microfluidic device described in this patent, the liquid delivery device further includes a heating structure, which can heat the liquid delivery hole, and the liquid delivery hole can conduct heat to the raw material liquid in the liquid delivery tube;

[0018] As a preferred embodiment of the microfluidic device described in this patent, the support body with the liquid delivery hole can rotate and stop at any position.

[0019] As a preferred embodiment of the microfluidic device described in this patent, the support body is rotatably connected to the device body, or

[0020] The supporting body includes a movable part and a fixed part. The fixed part is fixedly disposed on the main body of the device. The movable part can rotate around the fixed part. The movable part is provided with a first arc-shaped part, and the fixed part is provided with a second arc-shaped part. The first arc-shaped part and the second arc-shaped part together form a liquid delivery hole.

[0021] As a preferred embodiment of the microfluidic device described in this patent, the liquid delivery device further includes a sleeve, and liquid delivery tubes of different volumes are snapped into the liquid delivery hole through the sleeve.

[0022] As a preferred embodiment of the microfluidic device described in this patent, the micro-mixing device has at least two fixing slots, and a protruding structure is provided in the box slot. The micro-mixing device is housed in the box slot, and the protruding structure is snapped into the fixing slot.

[0023] As a preferred embodiment of the microfluidic device described in this patent, the swirling flow structure microchannel is a swirling flow microchannel formed by connecting multiple S-shaped microchannels end to end in sequence.

[0024] Compared with the prior art, the microfluidic device described in this patent has at least one or more of the following beneficial effects:

[0025] (1) The microfluidic device described in this patent has a simple structure, high degree of automation, convenient operation, and high preparation accuracy. It uses a micro-mixing device to prepare microfluidic mixtures. By automatically and precisely controlling the amount and speed of the raw material liquid entering the micro-mixing device, the ratio between the raw material liquids can be precisely controlled. In addition, the different receiving tubes of the receiving device can be automatically switched, which can realize the continuous preparation of multiple doses of the prepared microfluidic mixture. It can not only be used for experimental or small-batch product production, but also for process scale-up and application in production.

[0026] (2) The micro-mixing device is equipped with microchannels. By setting the shape (including straight, curved, circumferential or swirling flow, etc.), structure (including but not limited to T-shaped structure, Y-shaped structure, cross-shaped structure, SHM fishbone structure, Tesla structure and swirling flow structure) and inner diameter of the microchannels, the flow rate and velocity of the raw material liquid are controlled, as well as the mixing, and / or coating, and / or proportional configuration, and / or separation, and / or sorting, and / or purification of the mixed liquid, etc., so as to accurately prepare the ideal microfluidic mixture, especially for the preparation of nano-encapsulation of nucleic acid drugs or vaccines.

[0027] (3) The micromixing device is equipped with a sealing ring to ensure a sealed connection between the first and second outlets of the microfluidic chip and the inlet and outlet of the housing, respectively, preventing liquid spillage, which would not only affect the experimental results but also contaminate the raw materials or products to be prepared again. The micromixing device is equipped with a limiting post to limit and fix the microfluidic chip, preventing leakage or blockage caused by the microfluidic chip sliding and misalignment. The micromixing device is equipped with a handle end for pushing the micromixing device into the housing groove by holding the handle end, or pushing the micromixing device to rotate the support body that holds the micromixing device. The handle end is provided to prevent slippage and facilitate operation.

[0028] (4) The support body is provided with a first arc-shaped part and a second arc-shaped part. The second arc-shaped part can rotate, which makes it easy to take out and place the liquid delivery tube. The second arc-shaped part has a circular section that firmly fixes the liquid delivery tube and an arc-shaped section with an arc angle greater than 180°, so that the arc-shaped section can also firmly lock the liquid delivery tube and / or the tube sleeve to prevent it from loosening or falling off, thus achieving the purpose of both making it easy to take out and place the liquid delivery tube and firmly locking the liquid delivery tube.

[0029] (5) The liquid delivery device is equipped with a heating structure, which can heat the raw material liquid. As needed, the heating temperature, heating time and other conditions can be set to broaden the experimental conditions and provide more preparation conditions for the product preparation method. It is also equipped with a temperature sensor and control system, which facilitates precise control of the heating start / end time, heating temperature and heating duration, and facilitates precise control of preparation conditions, thereby helping to prepare microfluidic mixtures with higher precision, purity and better stability.

[0030] (6) The supporting body of the liquid delivery hole can be rotated. It can rotate around the main body of the equipment by means of the supporting body rotating, or the supporting body is provided with a fixed part and a movable part that can rotate around the fixed part, so that the liquid delivery hole can be rotated. This makes it easy to install the liquid delivery pipe into or remove it from the liquid delivery hole. After being rotated, it is easy to see whether the liquid delivery pipe is firmly installed into the liquid inlet, ensuring that the raw material liquid is not leaked when it is delivered into the micro-mixing device, and ensuring the stable preparation of microfluidic mixture. In addition, the rotating part is preferably a damping shaft or a universal damper, which can make the liquid delivery hole rotate to any position as needed, making the operation very convenient and greatly improving the user experience.

[0031] (7) The liquid delivery device is also equipped with a telescopic extrusion device, which can automatically control the extrusion of the raw material liquid into the liquid delivery pipe of the micro-mixing device without manual operation, facilitating stable and uniform delivery of the raw material liquid and enabling quantitative control of the delivered raw material liquid. It is equipped with a pressure sensor that can automatically sense whether the liquid delivery pipe is in contact with the telescopic extrusion device, facilitating control of the delivery speed of the raw material liquid, i.e., quantitative control of the flow rate and velocity of the delivered raw material liquid, and facilitating control of the delivery ratio between different raw material liquids. It is equipped with a control system that, in addition to controlling the opening, closing, and rotation speed of the drive structure, can also, in conjunction with the pressure value detected by the pressure sensor in the extrusion delivery pipe, adjust the rotation speed and direction of the drive structure in a timely manner according to settings or needs, to precisely control or dynamically change the flow rate and velocity of the delivered raw material liquid.

[0032] (8) A liquid receiving device is equipped with a liquid receiving slider, which can be fitted with multiple liquid receiving tubes. The multiple liquid receiving tubes are switched by sliding the liquid receiving slider to collect the microfluidic mixture, facilitating continuous operation. During the production process, the liquid receiving tubes that have been used for collection can be removed, and new liquid receiving tubes can be installed to continue collecting the microfluidic mixture. A waste liquid tank is provided on the liquid receiving slider to collect the droplets flowing out of the outlet when switching between different liquid receiving tubes, keeping the device clean and ensuring that the prepared microfluidic mixture is not contaminated. The liquid receiving device is equipped with a drive device and a spring, which can drive the liquid receiving slider to move back and forth along the slide bar, thereby realizing automatic switching of the liquid receiving tubes and improving work efficiency. A spring is provided on the other side of the drive device, so that the liquid receiving slider can automatically return to its initial position after operation, facilitating continuous operation of the drive device and precise control of the movement position of the liquid receiving slider.

[0033] (9) The microfluidic device described in this patent can not only be used for screening low flow rate nanomedicine formulations in the early stage with a flow rate range of 1-20 ml / min, but also breaks through the problem that traditional microfluidic devices cannot be scaled up. The maximum flow rate can support up to 120 ml / min.

[0034] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description

[0035] To more clearly illustrate the technical solution of the present invention, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0036] Figure 1 This is an exploded structural diagram of the microfluidic device described in this patent;

[0037] Figure 2 yes Figure 1 A schematic diagram of the R-section structure in the diagram;

[0038] Figure 3 This is a three-dimensional structural diagram of the microfluidic device described in this patent;

[0039] Figure 4 yes Figure 1 A three-dimensional structural diagram of the main body of the equipment, the liquid delivery pipe, and the liquid receiving pipe;

[0040] Figure 5 yes Figure 1 A three-dimensional structural diagram of the main body of the equipment, the liquid delivery pipe, and the liquid receiving pipe;

[0041] Figure 6 yes Figure 1 A three-dimensional structural diagram of the main support structure, the liquid receiving pipe, and the sleeve.

[0042] Figure 7 yes Figure 1 A three-dimensional structural diagram of the central support body, microfluidic chip box, and liquid receiving tube;

[0043] Figure 8 yes Figure 1 A three-dimensional structural diagram of the central support structure and the liquid receiving pipe;

[0044] Figure 9 yes Figure 8 A schematic diagram of the AA-direction cross-section;

[0045] Figure 10 yes Figure 7 A three-dimensional structural diagram of the flipped state;

[0046] Figure 11 yes Figure 10 A schematic diagram of the cross-sectional structure along direction B;

[0047] Figure 12 This is an exploded structural diagram of another embodiment of the main body of the device described in this patent;

[0048] Figure 13 yes Figure 12 A three-dimensional structural diagram of the main body of the equipment;

[0049] Figure 14 yes Figure 13 Schematic diagram of the cross-sectional structure along the middle A direction;

[0050] Figure 15 yes Figure 12 A three-dimensional structural diagram of the central support body and the microfluidic chip box;

[0051] Figure 16 yes Figure 12 A three-dimensional structural diagram of the main supporting structure;

[0052] Figure 17 yes Figure 12 Front view diagram of the main supporting structure;

[0053] Figure 18 This is an exploded structural diagram of the liquid delivery pipe described in this patent;

[0054] Figure 19 This is a three-dimensional structural diagram of the liquid delivery tube described in this patent;

[0055] Figure 20 This is a three-dimensional structural schematic diagram of the sleeve described in this patent from one perspective;

[0056] Figure 21 This is a three-dimensional structural diagram of the liquid delivery tube described in this patent from another perspective;

[0057] Figure 22 This is a three-dimensional structural diagram of the liquid-receiving slider described in this patent;

[0058] Figure 23 This is a three-dimensional structural diagram of the liquid receiving tube described in this patent;

[0059] Figure 24 This is an exploded structural diagram of the microfluidic chip cassette described in this patent.

[0060] Figure 25 This is a three-dimensional structural diagram of the microfluidic chip box described in this patent;

[0061] Figure 26 yes Figure 25 A schematic diagram of the planar structure along direction A;

[0062] Figure 27 yes Figure 25 A schematic diagram of the cross-sectional structure along direction B in the diagram;

[0063] Figure 28 This is a three-dimensional structural diagram of the microfluidic chip box described in this patent from one perspective.

[0064] Figure 29 This is a three-dimensional structural diagram of the microfluidic chip box described in this patent from another perspective;

[0065] Figure 30 This is a three-dimensional structural diagram of the microfluidic chip in the microfluidic chip box described in this patent from one perspective.

[0066] Figure 31 This is a three-dimensional structural diagram of the microfluidic chip in the microfluidic chip box described in this patent from another perspective;

[0067] Figure 32 This is a three-dimensional structural diagram of the lid of the microfluidic chip box described in this patent.

[0068] The components are as follows: 1-Equipment body, 2-Microfluidic chip box, 3-Liquid delivery device, 4-Liquid receiving device, 5-Telescopic extrusion device, 11-Opening, 12-Receiving cavity, 13-Supporting body, 131-Box groove, 132-Slide rod, 1321-Slide rod hole, 133-Rotation hole, 134-Limiting wing, 135-Heating tank, 136-Through groove, 137-Flip handle, 14-Equipment shell, 15-Equipment cover, 151-Equipment cover handle, 16-Placement rack, 161-Placement hole, 17-Equipment receiving hole, 18-Power button. 21-Box body, 22-Microfluidic chip, 23-Box cover, 211-Receptive cavity, 2111-Chip slot, 2112-Annular groove, 2113-Inlet sealing groove, 2114-Outlet sealing groove, 2115-Limiting post, 2116-Inner annular protrusion, 2117-Outer annular protrusion, 212-Inlet port, 2121-Inlet column, 213-Outlet port, 2131-Outlet column, 214-Handle end, 2141-Protrusion, 221-Inlet microchannel, 2211-First inlet microchannel, 2212-Second inlet microchannel 222-Mixing microchannel, 223-First opening, 224-Second opening, 226-Limiting hole, 231-Annular retaining strip, 232-Fixing groove, 241-Sealing ring, 31-Liquid delivery tube, 32-Liquid delivery hole, 33-Tube sleeve, 34-Rotating shaft, 301-Moving part, 302-Fixing part, 311-Solution cylinder, 3111-Solution chamber, 3112-Liquid delivery head, 312-Push-pull rod, 321-First arc-shaped part, 322-Second arc-shaped part, 3211-Arch-shaped segment, 3212-Circular segment, 3213-Limiting ring 331-Limiting ring, 3311-Arc groove, 41-Liquid receiving slider, 42-Liquid receiving pipe, 411-Perforation, 412-Card slot, 413-Waste liquid tank, 421-Card ring, 43-Drive device, 431-Drive rod, 51-Slide rail, 52-Sliding structure, 53-Drive structure, 521-Lead screw hole, 522-Sliding body, 5221-Sensing hole, 5222-Sensor groove, 5223-Pressure hole, 523-Moving piece, 524-Sensing element, 531-Lead screw, 54-Pressure sensor, 55-Fixing plate. Detailed Implementation

[0069] Embodiments of the present invention are described in detail below, examples of which are illustrated in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0070] In the description of this invention, it should be understood that the terms "upper," "lower," "top," "bottom," "one end," "one side," and "the other side," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, and are only for the convenience of describing the invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of the invention. In the description of this invention, "a plurality of" means two or more, unless otherwise explicitly specified.

[0071] In the description of this invention, unless otherwise explicitly specified and limited, the terms "provided with", "equipped with", "connected", "provided with", "fixed", etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to two elements. The specific meaning of the above terms in this invention should be understood according to the specific circumstances.

[0072] Example

[0073] Please see Figure 1-32 ,like Figure 1-32 As shown, the microfluidic device includes a device body 1, a microfluidic chip box 2, a liquid delivery device 3, and a liquid receiving device 4;

[0074] The main body 1 of the device includes an opening 11 and a receiving cavity 12. The opening 11 is connected to the receiving cavity 12. The microfluidic chip box 2, the liquid delivery device 3, and the liquid receiving device 4 are all housed in the receiving cavity. The microfluidic chip box 2 includes at least two liquid inlets 212, a microchannel, and at least one liquid outlet 213. The liquid inlets 212 and the liquid outlet 213 are connected through the microchannel. The liquid delivery device 3 cooperates with the liquid inlets 212 and can deliver raw material liquid into the liquid inlets 212. The liquid receiving device 4 corresponds to the liquid outlet 213 and can receive the microfluidic mixture from the liquid outlet 213.

[0075] The main body 1 of the device also includes a support body 13, which is housed within the receiving cavity 12. The support body 13 has a housing groove 131 and at least one liquid delivery hole 32. The housing groove 131 and the liquid delivery hole 32 are located on different end faces of the support body 13. The housing groove 131 communicates with the liquid delivery hole 32. The microfluidic chip cassette 2 is snapped into the housing groove 131, and the liquid inlet 212 of the microfluidic chip cassette 2 corresponds to the liquid delivery hole 32. In this example, the axial direction of the housing groove 131 is perpendicular to the axial direction of the liquid delivery hole 32, and the axial directions of the multiple liquid delivery holes 32 are consistent. The liquid delivery hole 32 is located below the housing groove 131. At least one slide rod 132 is detachably mounted on the support body 13, and the slide rod 132 and the housing groove 131 are located on the same side of the support body 13.

[0076] The liquid delivery device 3 includes at least one liquid delivery pipe 31 and at least one liquid delivery hole 32. The liquid delivery pipe 31 is housed within the liquid delivery hole 32 and is sealed to the liquid inlet 212. The liquid delivery pipe 31 can push the raw material liquid into the liquid inlet 212 of the microfluidic chip cassette 2. Preferably, the liquid delivery device 3 further includes a heating structure that can heat the liquid delivery hole 32. The liquid delivery hole 32 is a heat-conducting liquid delivery hole that can conduct heat to the raw material liquid within the liquid delivery pipe 31. Preferably, the liquid delivery device 3 further includes a flipping structure, and the support body 13 is rotatably connected to the device body 1 via a rotating shaft or universal joint. Preferably, the volume of the liquid delivery tube 31 that can hold the raw material liquid includes, but is not limited to, 0.5ml-20ml. The outer diameter of the liquid delivery tube 31 with different volumes is different, so a sleeve 33 is provided. The sleeve 33 matches the liquid delivery tube 31, and the liquid delivery tube 31 can be snapped into the liquid delivery hole 32 through the sleeve 33.

[0077] The liquid receiving device 4 includes a support body 13, a liquid receiving slider 41, and a liquid receiving tube 42. At least one slide rod 132 is detachably installed on the support body 13. The liquid receiving slider 41 is sleeved on the slide rod 132 and can slide along the slide rod 132. The liquid receiving slider 41 has at least two slots 412 and a waste liquid tank 413. The waste liquid tank 413 is arranged between two adjacent slots 412 and can receive the microfluidic mixture from the liquid outlet 213. The liquid receiving tube 42 has a liquid receiving cavity with one end open. The liquid receiving tube 42 is snapped into the slot 412 and corresponds to the liquid outlet 213. The liquid receiving tube 42 can receive the microfluidic mixture from the liquid outlet 213.

[0078] The microchannel includes at least two liquid inlet microchannels 221 and at least one mixing microchannel 222. The liquid inlet 212 corresponds one-to-one with the liquid inlet microchannel 221. One end of the liquid inlet microchannel 221 is connected to the liquid inlet 212, and the other end of the liquid inlet microchannel 221 is connected to one end of the mixing microchannel 222. The other end of the mixing microchannel 222 is connected to the liquid outlet 213.

[0079] The microfluidic device also includes a device housing 14 and a device cover 15. The device housing 14 is fitted onto the device body 1 and has an opening that corresponds to the opening 11 of the device body 1. The device cover 15 is disposed at the opening. In this example, the device cover 15 is rotatably connected to the device housing 14. The device cover 15 is provided with a device handle 151, which allows for easy opening of the device cover 15 by holding the device handle 151. In this example, the device housing is also provided with a power button 18, which controls the device to be turned on and off.

[0080] It also includes a placement rack 16, which is fixedly disposed within the receiving cavity 12, such as... Figure 12 As shown, the placement rack 16 can also be fixedly mounted on the side wall of the equipment housing 14, such as... Figure 13 As shown, the placement rack 16 has multiple placement holes 161, and the tube sleeve 33 is placed in the placement holes 161.

[0081] Liquid delivery device

[0082] The liquid delivery device 3 is used to deliver the raw material liquid to the microfluidic chip box of the microfluidic device according to a certain proportion and quantity, temperature and other control requirements, so as to obtain a microfluidic mixture.

[0083] Please see Figure 1 and Figure 5-21 As shown in the figure, the liquid delivery device includes a support body 13 and at least one liquid delivery pipe 31;

[0084] The support body 13 has at least one through-hole 32 for liquid delivery, such as Figure 6 and Figure 15 As shown, the liquid delivery hole 32 is located below the liquid inlet 212 of the microfluidic chip cassette 2, and the liquid delivery hole 32 corresponds to the liquid inlet 212. In this example, there are two liquid delivery holes 32. Of course, the liquid delivery hole 32 includes, but is not limited to, two. Depending on user needs, experimental needs, or production needs, one or more holes can be provided. In this example, a limiting annular groove 3213 is provided at the end of the liquid delivery hole 32 away from the liquid inlet 212. The liquid delivery hole 32 can be designed as an integral part, such as... Figure 12-17 As shown, the liquid delivery port 32 can also be designed as a separate unit, such as... Figure 1 and Figure 5-11 As shown.

[0085] Preferably, the support body 13 is provided with a heating structure, which can heat the liquid delivery hole 32. The microfluidic device also includes a control system, which includes a heating control module. The heating structure is communicatively connected to the heating control module, and the heating control module can control the opening and closing of the heating structure, the heating temperature, and the heating time. In the example, the heating structure is a heating plate, which is fixed to the side of the support body 13 away from the slide bar 132. The liquid delivery hole 32 is a heat-conducting liquid delivery hole, which can conduct heat to the raw material liquid in the liquid delivery tube 31. Preferably, the heating plate is only added to the liquid delivery hole 32 part of the support body 13, and the other parts of the support body 13 do not conduct heat to the liquid delivery hole 32 part, that is, they are heat-insulated. The heating structure can heat the raw material liquid. As needed, the heating temperature, heating time, and other conditions can be set to broaden the experimental conditions and provide more preparation conditions for the product preparation method.

[0086] In a preferred embodiment, the support body 13 is further provided with a temperature sensor, which can detect the temperature of the liquid delivery hole 32; the temperature sensor is communicatively connected to the heating control module, which can receive the temperature of the liquid delivery hole 32 detected by the temperature sensor, so as to accurately control the heating temperature and improve the accuracy of experiments or product preparation.

[0087] The liquid delivery tube 31 is housed within the liquid delivery hole 32, and the liquid delivery tube 31 corresponds one-to-one with the liquid inlet 212. The liquid delivery tube 31 includes a solution cylinder 311 and a push-pull rod 312. Figure 18-19 As shown, the solution cylinder 311 has a solution cavity 3111 open at both ends, which can accommodate the raw material liquid. The push-pull rod 312 can move within the solution cavity 3111. The push-pull rod 312 extends into and is accommodated within the solution cavity 3111 from one end. A hollow liquid delivery head 3112 is provided at the end of the solution cylinder 311 away from the push-pull rod 312. The inner diameter of the liquid delivery head 3112 is smaller than the inner diameter of the solution cylinder 311. The push-pull rod 312 can push the raw material liquid sequentially through the liquid delivery head 3112 and the liquid inlet 212 into the microfluidic chip cassette 2. In this example, the outer diameter of the liquid delivery head 3112 is larger than the inner diameter of the liquid inlet 212 of the microfluidic chip cassette 2, and the outer diameter of the liquid delivery head 3112 is not larger than the inner diameter of the liquid inlet 212 of the microfluidic chip cassette 2. The liquid delivery head 3112 extends into the liquid inlet 212. In the example, a sealing gasket is provided at one end of the push-pull rod 312 near the liquid delivery head 3112. The sealing gasket can seal the raw material liquid in the solution chamber 3111. The sealing gasket is preferably a rubber gasket, but other elastic sealing gaskets are also possible.

[0088] In one embodiment, such as Figure 12-17 As shown, the liquid delivery hole 32 is an integral design, and the support body 13 is rotatably connected to the device body 1. The support body 13 can rotate or flip around the device body 1, and the heating element is fixed to the side of the support body 13 away from the slide rod 132. In one example, the support body 13 is rotatably connected to the device body 1 via a rotating shaft. The rotating shaft is preferably a damped rotating shaft, but it can also be a non-damped rotating shaft. The sidewall of the support body 13 has symmetrically arranged rotating holes 133, and the device body 1 has device receiving holes 17. The device receiving holes 17 correspond one-to-one with the rotating holes 133. One end of the rotating shaft is fixedly housed in the rotating hole 133, and the other end is fixedly housed in the placement hole 17. In another example, the support body 13 is rotatably connected to the device body 1 via a universal damper. This universal damper allows for more flexible rotation, more diverse rotation angles and directions, and is more convenient to use. The support body is designed to be flip-up, facilitating the removal of the liquid delivery tube 31 from or placement within the liquid delivery hole 32. A limiting wing 134 is provided on the side of the support body 13 away from the liquid delivery hole 32. The limiting wing 134 abuts against the device body 1, allowing the support body 13 to be placed against the opening of the device body 1.

[0089] In another embodiment, such as Figure 1 and Figure 5-11As shown, the liquid delivery hole 32 is a split design. The supporting body 3 includes a movable part 301 and a fixed part 302. The movable part 301 is rotatably connected to the fixed part 302 and can rotate around the fixed part 302. The movable part 301 is provided with a first arc-shaped part 321, and the fixed part 302 is provided with a second arc-shaped part 322. The first arc-shaped part 321 and the second arc-shaped part 322 together form the liquid delivery hole 32. A heating groove 135 is provided on the side of the fixed part 302 away from the movable part 301. The heating element is fixedly disposed in the heating groove 135. Preferably, the heating element only heats the second arc-shaped part 322 on the fixed part 302, and the other parts of the fixed part 302 and the movable part 301 are not heated. They are heat-insulated from the second arc-shaped part 322 on the fixed part 302. In the example, the first arc-shaped portion 321 includes an arc-shaped segment 3211 and a circular segment 3212 along the axial direction. The arc-shaped segment 3211 is located at the end of the liquid delivery hole 32 away from the microfluidic chip cassette 2. The second arc-shaped portion 322 matches the arc-shaped segment 3211. Preferably, the arc angle of the arc segment 3211 is in the range of 180°-360°. The arc segment 3211 can prevent the liquid delivery tube 31 from loosening or falling out of the liquid delivery hole 32. Preferably, the arc angle of the arc segment 3211 is in the range of 180°-270°. Setting the arc angle range allows the liquid delivery hole 32 to both hold the liquid delivery tube 31 and facilitate the removal and placement of the liquid delivery tube 31. In the example, the fixed part is vertically fixed, and when the moving part 301 is flipped to a near-horizontal state, it facilitates the placement or removal of the liquid delivery tube 31. After the liquid delivery tube 31 is placed, the moving part 301 moves to contact the fixed part 302. At this time, the first arc-shaped part 321 and the second arc-shaped part 322 together form a complete liquid delivery hole 32. Then, the liquid delivery tube 31 can be automatically or manually pressed to deliver raw material liquid to the inlet according to the needs or requirements of the experiment. In the example, the moving part 301 is rotatably connected to the fixed part 302 through a rotating shaft, especially a damped rotating shaft or a universal damper. Of course, a non-damped rotating shaft or other rotating parts can also be used. Any component that can enable the rotation of the moving part 301 is within the scope of protection of this patent. In the example, the support body 1 is provided with a flip handle 137, which makes it easier to flip the moving part 301. The flip structure facilitates the installation and removal of the liquid delivery tube when flipped, making the equipment operation more convenient.

[0090] In another embodiment, the liquid delivery device further includes a sleeve 33, such as Figure 6 and Figure 20-21 As shown;

[0091] The sleeve 33 is a hollow tube open at both ends. The liquid delivery tube 31 is fastened to the liquid delivery hole 32 through the sleeve 33. A limiting ring 331 is fitted on one end of the sleeve 33. The sleeve 33 is housed in the liquid delivery hole 32. The limiting ring 331 abuts against the opening of the liquid delivery hole 32. The outer diameter of the sleeve 33 is the same as the inner diameter of the liquid delivery hole 32. The inner diameter of the sleeve 33 is the same as the outer diameter of the liquid delivery tube 31. The length of the sleeve 33 is not greater than the length of the liquid delivery hole 32. In this example, the volume range of the liquid delivery tube 31 that can hold the raw material liquid is including but not limited to 0.5ml-20ml. The outer diameters of the liquid delivery tubes 31 with different volumes are different. Therefore, liquid delivery tubes 31 with different volumes are equipped with matching sleeves 33. The inner diameters of the sleeves 33 with different specifications are different. The outer diameters of the sleeves 33 with different specifications are all the same. The outer diameter of the sleeve 33 is the same as the inner diameter of the liquid delivery hole 32. Preferably, the inner diameters of the delivery tubes 31 with different volumes are also different. The volume of the raw material liquid contained in the delivery tubes 31 includes, but is not limited to, 0.5ml, 1ml, 2ml, 3ml, 5ml, 7ml, 8ml, 10ml, 12ml, 15ml, 18ml, and 20ml. In the example, two inwardly recessed arc-shaped grooves 3311 are symmetrically formed on the limiting ring 331. The limiting ring 331 matches the limiting ring groove 3213, and the limiting ring 331 is housed within the limiting ring groove 3213. The arc-shaped grooves 3311 are aesthetically pleasing and facilitate the removal and placement of the delivery tubes 31. The delivery hole 32 is designed as a single piece, and the side wall of the limiting ring groove 3213 has a handle groove. The tube sleeve 33 is snapped into the delivery hole 32, and the limiting ring 331 is housed within the limiting ring groove 3213. The handle groove facilitates the removal of the tube sleeve 33 from the handle groove, making operation convenient.

[0092] The device is equipped with a tubing sleeve to accommodate delivery tubing of different volumes and models. The delivery tubing can be any commercially available medical syringe (excluding needles), eliminating the need for custom-made tubing and reducing costs.

[0093] Wetted device

[0094] The liquid receiving device 4 is mainly used to receive the microfluidic mixture prepared by the microfluidic device, and of course, it also includes the collection of waste liquid.

[0095] Please see Figure 1-2 , Figure 4-13 , Figure 15-17 and Figure 22-23 As shown in the figure, the liquid receiving device includes a support body 13, a liquid receiving slider 41, and a liquid receiving pipe 42;

[0096] At least one slide rod 132 is detachably mounted on the support body 13. The support body 13 is provided with a plurality of slide rod holes 1321. The slide rod holes 1321 and the box groove 131 are located on the same side of the support body 13. The slide rod holes 1321 are located below the box groove 131. The end of the slide rod 132 is detachably mounted in the slide rod hole 1321. In the example, there are two slide rods 132, and the two slide rods 132 are axially aligned.

[0097] The liquid-receiving slider 41 is provided with at least one through hole 411 and at least two slots 412, such as Figure 22 As shown, the perforation 411 is perpendicular to the slot 412. The slide rod 132 passes through the perforation 411 and is detachably mounted on the support body 13. The liquid receiving slider 41 can slide on the slide rod 132. The liquid receiving tube 42 has a liquid receiving cavity with one end open, such as... Figure 1-2 and Figure 4-11 As shown, the liquid receiving tube 42 is snapped into the slot 412. The liquid receiving tube 42 is located below the liquid outlet 213 of the microfluidic chip box, with its opening facing upwards. The microfluidic chip box 2 includes an inlet 212, a microchannel, and an outlet 213. The raw material liquid enters through the inlet 212, passes through the microchannel to form a microfluidic mixture, and flows out through the outlet 213. In this example, the inner diameter of the perforation 411 matches the outer diameter of the slide bar 132. There are two perforations 411 and two slide bars 132 to stabilize the liquid receiving slider 41, thereby stabilizing the liquid receiving tube 42 and preventing leakage of the microfluidic mixture inside. In this example, there are two slots 412. Of course, the slots 412 include, but are not limited to, two; there may be one or more. The liquid receiving tube can also be divided into a collection tube for collecting the microfluidic mixture and a waste liquid collection tube. In addition, centrifuge tubes can be used directly for receiving liquid to reduce costs, but it is not limited to centrifuge tubes. Any receiving tube that can receive microfluidic mixtures is acceptable.

[0098] Preferably, a through groove 136 is formed on the support body 13, the through groove 136 is disposed between two slide rod holes 1321 on the same side of the support body 13, the axial direction of the through groove 136 is consistent with the axial direction of the slide rod 132, and a retaining ring 421 is provided on the side of the liquid receiving pipe 42 near the opening end, such as Figure 23 As shown, the retaining ring 421 abuts against the retaining groove 412, and the retaining ring 421 can prevent the liquid receiving tube 42 from sliding out of the retaining groove 412.

[0099] Waste liquid tanks 413 are provided between two adjacent slots 412. The waste liquid tanks 413 are aligned with the axial direction of the slots 412 and have their openings facing upwards. The waste liquid tanks 413 can receive droplets flowing out of the outlet 212 when switching the liquid inlet pipe. The waste liquid tanks 413 can keep the support body 13 and the receiving cavity 12 clean, thus preventing the prepared microfluidic mixture from being contaminated.

[0100] In a preferred embodiment, a spring is fitted onto the slide rod 132. The spring is located on one side of the liquid-receiving slider 41. One end of the spring abuts against the support body 13, and the other end of the spring abuts against the liquid-receiving slider 41. The spring can abut against the liquid-receiving slider 41 at one end of the slide rod 132. The end of the slide rod 132 away from the spring is marked as the initial position of the liquid-receiving slider 41. The spring abuts against one side of the liquid-receiving slider 41. During the sliding process of the liquid-receiving slider 41, the sliding position of the liquid-receiving slider 41 can be precisely controlled by the spring's abutment. Furthermore, after the liquid-receiving slider 41 finishes sliding, the spring, through its elastic force, abuts against the liquid-receiving slider 41 at its initial position, causing the liquid-receiving slider 41 to automatically reset without manual adjustment to the initial position. This facilitates continuous operation of the liquid-receiving device 4 and enables automated production.

[0101] In a preferred embodiment, the liquid receiving device 4 further includes a driving device 43, such as... Figure 2 , Figure 4-5 and Figure 12-13 As shown, the driving device 43 has a driving rod 431, which is accommodated in the receiving cavity 12. The driving device is mounted on the side wall of the main body of the equipment. The driving rod 431 is located on the side of the liquid receiving slider 41 away from the spring. The driving rod 431 and the liquid receiving slider 41 are coaxially arranged. The driving device can drive the driving rod 431 to move toward the liquid receiving slider 41. The driving rod 431 passes through the through groove 136 to drive the liquid receiving slider 41 to move away from the driving rod 431. Preferably, the driving rod 431 and the liquid receiving slider 41 are coaxially arranged. The drive device controls the extension distance of the drive rod 431, which, in conjunction with the spring on the other side of the liquid receiving slider 41, controls the sliding position of the liquid receiving slider 41. Sliding the liquid receiving slider 41 to different positions allows switching of the liquid receiving tube 42 within different slots to below the liquid outlet 213 of the microfluidic chip cartridge. The control system also includes a liquid receiving control module, which is communicatively connected to the drive device 43. This module controls the forward and backward movement of the drive rod 431. Switching between different liquid receiving tubes 42 via the drive device facilitates automated continuous operation and helps improve production efficiency.

[0102] Telescopic extrusion device

[0103] The telescopic extrusion device 5 is used to extrude and push the raw material liquid in the liquid delivery tube 31 into the microfluidic chip cassette. The telescopic extrusion device is fixed in the receiving cavity 12. In this example, two telescopic extrusion devices 5 are symmetrically arranged in the receiving cavity.

[0104] Please see Figure 1 , Figure 4-5 and Figure 12-14 As shown in the figure, the telescopic extrusion device includes a slide rail 51, a sliding structure 52 and a driving structure 53;

[0105] The slide rail 51 is fixed to the inner wall of the equipment body 1, and two slide rails 51 are symmetrically fixed to the inner wall of the equipment body 1.

[0106] The sliding structure 52 is slidably engaged with the slide rail 51, and the sliding structure 52 can slide along the slide rail 51. In one embodiment, the sliding structure 52 is provided with a slide groove, which is fitted onto the slide rail 51, and the sliding structure 52 slides on the slide rail 51 through the slide groove. In another embodiment, the slide rail 51 is provided with a slide rail groove, and a slider is provided on the side of the sliding structure 52 near the slide rail 51. The slider is accommodated in the slide rail groove, and the sliding structure 52 moves within the slide rail groove through the slider.

[0107] The driving structure 53 can drive the sliding structure 52 to move along the slide rail 51. The driving structure 53 includes a motor and a lead screw 531 fixedly connected to the motor. The lead screw 531 is provided with an external thread. The sliding structure 52 has a lead screw hole 521 along the sliding direction. The inner wall of the lead screw hole 521 is provided with an internal thread that matches the external thread. The sliding structure 52 passes through the lead screw hole 521 and is sleeved on the lead screw 531. The motor drives the lead screw 531 to rotate, and the rotating lead screw can drive the sliding structure 52 to move along the slide rail. The telescopic extrusion device 5 can automatically control the extrusion of the liquid delivery tube to deliver raw material liquid into the microfluidic chip cassette without manual operation, which facilitates stable and uniform delivery of raw material liquid and allows for quantitative control of the delivered raw material liquid.

[0108] Preferably, a pressure sensor 54 is installed on the sliding structure 52, and the pressure sensor 54 can detect the pressure of the sliding structure 52 pushing the liquid receiving pipe 31.

[0109] In the example, the sliding structure 52 includes a sliding body 522 and a movable piece 523. The movable piece 523 is movably mounted on the sliding body 522. The sliding body 522 and the liquid delivery pipe 31 are located on opposite sides of the movable piece 523. The movable piece 523 corresponds to the liquid delivery pipe 31 of the liquid delivery device 3. Under the driving action of the driving structure, the sliding structure 52 can move towards the liquid delivery pipe 31, and the movable piece 523 abuts against the liquid delivery pipe 31. The pressure sensor 54 is fixedly mounted on the sliding body 522. The pressure sensor 54 abuts against the movable piece 523 and can sense and detect the contact between the movable piece 523 and the liquid delivery pipe. The shape of the movable piece 523 includes, but is not limited to, square, circular, rhomboid, triangular, polygonal, elliptical, or other regular or irregular shapes. In the example, the side of the sliding body 522 near the slide rail 51 is perpendicular to the side of the sliding body 522 near the movable piece 523. A pressure sensor is installed to accurately detect the pressure of the extrusion device 5 pressing the liquid delivery pipe 31, which facilitates the control of the speed of conveying raw material liquid. That is, it can quantitatively control the flow rate and velocity of the conveyed raw material liquid, and facilitate the control of the delivery ratio between different raw material liquids.

[0110] In one embodiment, such as Figure 4-5 As shown, one end of the movable piece 523 is movably connected to the sliding body 522 via a pivot. A sensing hole 5221 is provided on the side of the sliding body 522 near the movable piece 523. The pressure sensor 54 is housed within the sensing hole 5221 and abuts against the movable piece 523. In this example, the axial direction of the sensing hole 5221 is consistent with the axial direction of the lead screw 531.

[0111] In another embodiment, such as Figure 12-14As shown, the sliding structure 52 also includes a sensing element 524; a sensor groove 5222 is provided on the sliding body 522, the opening of the sensor groove 5222 faces away from the movable piece 523, the pressure sensor 54 is fixed in the sensor groove 5222, a pressure hole 5223 is provided on the side of the sliding body 522 near the movable piece 523, the pressure hole 5223 is connected to the sensor groove 5222, one end of the sensing element 524 is fixedly connected to the pressure sensor 54, and the other end of the sensing element 524 passes through the pressure hole 5223 and abuts against the movable piece 523. The pressure sensor can detect the pressure value of the movable piece 523 by the resistance value, extrusion force or deformation of the sensing element 524. The pressure value of the movable piece is also the pressure value of the liquid delivery tube squeezed by the sliding structure. It should be noted that the pressure sensor can also detect other physical quantities of the movable piece 523 and / or the sensing element 524 to detect the pressure value of the liquid delivery tube squeezed by the sliding structure. In the example, a pulley is provided at the other end of the sensor 524. The sensor 524 abuts against the movable piece 523 through the pulley. The pulley can reduce the friction between the sensor 524 and the movable piece 523, avoid wear of the sensor 524 and the movable piece 523, extend their service life, and help extend the accuracy of the equipment.

[0112] Preferably, the control system further includes a compression control module. The pressure sensor 54 is communicatively connected to the compression control module, which monitors the pressure value of the pressure sensor 54. The drive structure 53 is also communicatively connected to the compression control module, which controls the opening, closing, rotation speed, and rotation direction of the drive structure 53. The compression control module adjusts the pressure value of the movable plate against the material to be compressed by controlling the drive structure. In this example, there are two telescopic compression devices, and the compression control module controls each device independently. The compression control module, in addition to controlling the opening, closing, and rotation speed of the drive structure, can also adjust the rotation speed and direction of the drive structure in real time, based on the pressure value detected by the pressure sensor in the compression delivery pipe, according to settings or needs, to precisely control or dynamically change the flow rate of the conveyed raw material liquid.

[0113] In the example, a fixed plate 55 is provided inside the receiving cavity 12 of the main body 1 of the equipment. The slide rail 51 and the sliding structure 52 are located above the fixed plate 55, and the driving structure 53 is located below the fixed plate 55. The driving structure 53 is fixedly installed on the fixed plate 55, and the lead screw 531 passes through the fixed plate 55 and is sleeved on the sliding structure 52. The receiving cavity below the fixed plate 55 is designated as an auxiliary machine cavity. An auxiliary machine frame is provided around the auxiliary machine cavity. The auxiliary machine frame can fix and accommodate auxiliary components such as the driving structure. Openings are provided at the front and rear ends of the auxiliary machine frame for installing and removing the auxiliary components such as the driving structure. The driving structure 53 is fixed inside the auxiliary machine cavity. An exhaust port is provided on the side wall of the main body 1. The exhaust port is connected to the auxiliary machine cavity and is equipped with an exhaust fan. The exhaust fan can ventilate and dissipate heat from the auxiliary machine cavity.

[0114] Micro-mixing device

[0115] The micromixing device can prepare a target product, namely a microfluidic mixture, by controlling the flow rate, velocity and / or different microchannel designs of one or more raw material liquids.

[0116] The micro-mixing device includes, but is not limited to, microfluidic chip box, T-type mixing device and metal mixing device, etc. This patent mainly uses microfluidic chip box 2 as an example to introduce the structural features of the micro-mixing device.

[0117] Please see Figure 24-32 ,like Figure 24-32 As shown, the microfluidic chip box 2 includes a box body 21, a microfluidic chip 22, and a box cover 23;

[0118] The box body 21 has a receiving cavity 211 with one end open, such as Figure 26-29As shown, the bottom of the accommodating cavity 211 is provided with a chip slot 2111 and an annular groove 2112. The annular groove 2112 is arranged around the outside of the chip slot 2111. The chip slot 2111 and the annular groove 2112 are spaced apart, that is, the chip slot 2111 and the annular groove 2112 are not connected. The housing 21 has at least two liquid inlets 212 and at least one liquid outlet 213. Both the liquid inlets 212 and the liquid outlet 213 are connected to the chip slot 2111. In the example, the inlet 212 is provided with a hollow inlet column 2121, and the outlet 213 is provided with a hollow outlet column 2131. Both the inlet column 2121 and the outlet column 2131 extend in a direction away from the box body 21, and both the inlet column 2121 and the outlet column 2131 are integrally connected to the box body 21. Preferably, both the inlet 212 and the outlet 213 are circular, and both the inlet column 2121 and the outlet column 2131 are cylindrical. In the example, the inlet 212 and its opening face downwards. The delivery head 3112 of the delivery pipe 31 extends into the delivery column 2121, which can seal and deliver the raw material liquid, preventing the raw material liquid from leaking due to poor contact between the delivery head 3112 and the delivery column 2121. Leakage of the raw material liquid not only affects the ratio between different raw material liquids and the proportion of each component in the prepared microfluidic mixture, but may even prevent the preparation of a qualified microfluidic mixture. Moreover, leakage of the raw material liquid also contaminates the containment cavity. The bottom of the box body 21 is provided with an inner annular protrusion 2116 and an outer annular protrusion 2117. The inner annular protrusion 2116 and the outer annular protrusion 2117 are coaxially arranged, and an annular groove 2112 is formed between the inner annular protrusion 2116 and the outer annular protrusion 2117. The inner annular protrusion 2116 surrounds the chip groove 2111.

[0119] Preferably, the housing 21 is further fixedly connected to a handle end 214, which is located at the end of the housing 21 away from the liquid outlet 213. At least one side surface of the handle end 214 is provided with multiple protrusions 2141, preferably arc-shaped, but of course, the protrusions can be any other shape. In this example, the multiple protrusions 2141 are arranged in an array. The handle end 214 is provided for holding the handle end to push the microfluidic chip box into the housing groove, or to push the microfluidic chip box 2, so that the support body 13 with the microfluidic chip box 2 fastened to it rotates. The protrusions provide an anti-slip function and facilitate operation, but the protrusions are not limited to arc shapes, or even to textured surfaces. Any design that increases friction without causing damage to the hand is within the scope of this patent. In this example, both sides of the handle end 214 are provided with multiple protrusions 2141. In the example, the end of the handle 214 away from the receiving cavity 211 is arc-shaped, and the axis of the arc is parallel to the receiving cavity 211.

[0120] The microfluidic chip 22 is housed within a chip slot 2111. Microchannels are formed within the microfluidic chip 22. The structure of the microchannels may include, but is not limited to, T-shaped, Y-shaped, cross-shaped, SHM (fishbone) structure, Tesla structure, and swirling flow structure, etc., as needed. For example, ... Figure 24 , Figure 26-27 and Figures 30-31 As shown, the microchannel structure is preferably a swirling flow structure. Experiments have confirmed that the swirling flow structure can significantly improve the flow rate, while also providing better encapsulation and dispersion. The microchannel includes at least two inlet microchannels 221 and at least one mixing microchannel 222. The microfluidic chip 22 is provided with at least two first openings 223 and at least one second opening 224. The first openings 223 correspond one-to-one with the inlet microchannels 221, and the second openings correspond one-to-one with the outlets. One end of each inlet microchannel 221 is connected to the first opening 223, and the other end is connected to one end of the mixing microchannel 222. The other end of the mixing microchannel 222 is connected to the second opening 224. In the example, the chip slot... The inner diameter of 2111 is consistent with the outer diameter of the microfluidic chip 22. The first opening 223 and the second opening 224 are both located on the same side of the microfluidic chip 22. The material of the microfluidic chip 22 includes, but is not limited to, polymers, stainless steel and PEEK. The polymers include, but are not limited to, cyclic olefin polymers (COP), cyclic olefin copolymers (COC) and polydimethylsiloxane (PDMS). The fabrication method of the microfluidic chip 22 includes, but is not limited to, material processing methods such as injection molding and precision machining. At the same time, the encapsulation process of the microfluidic chip channel includes, but is not limited to, ultrasonic bonding, thermocompression bonding, laser welding and cold / hot pressure welding.

[0121] The lid 23 covers the opening of the box body 21, such as... Figure 32As shown, the cover 23 abuts against the microfluidic chip 22 within the chip slot. The cover 23 has an annular retaining strip 231 that engages within the annular groove 2112. In this example, the inner side of the annular retaining strip 231 has an inclined surface, which serves a sealing function, allowing the annular retaining strip 231 to be ultrasonically welded and sealed within the annular groove 2112. The cover 23 has at least two fixing slots 232. When the microfluidic chip box is placed on a microfluidic device, the microfluidic chip box can be fixed to the microfluidic device via these fixing slots, which serve a positioning and fixing function. The side wall of the housing groove 131 is provided with a protruding structure, which corresponds to the fixing groove 232. When the microfluidic chip box is inserted into the housing groove 131, the protruding structure is snapped into the fixing groove 232. In the example, the side wall of the housing groove 131 has a through engagement hole. The fixing member is accommodated in the engagement hole and extends into the housing groove to form a protruding structure, which plays the role of fixing and engaging the microfluidic chip box. Of course, there can be other forms of protruding structures, as long as they can play the role of fixing and engaging the microfluidic chip box.

[0122] The hybrid microchannels include, but are not limited to, straight microchannels, and / or circumferential microchannels, and / or curved microchannels, and / or swirling flow microchannels. In the example, the hybrid microchannel 222 is a swirling flow microchannel. This swirling flow hybrid microchannel is formed by connecting multiple S-shaped microchannel structures end-to-end in sequence. Along the flow direction of the raw material liquid, adjacent S-shaped microchannel structures can be smoothly connected or staggered. They can be staggered inside or outside the preceding S-shaped microchannel structure. In the example, the latter S-shaped microchannel structure is staggered inside the former S-shaped microchannel structure, such as... Figure 30 As shown. The mixing microchannel enables the mixing, and / or coating, and / or proportional preparation, and / or separation, and / or sorting, and / or purification of raw material liquids. By setting the shape, structure, and inner diameter of the microchannel, the microchannel can effectively perform operations such as mixing, and / or coating, and / or proportional preparation, and / or separation, and / or sorting, and / or purification of two or more raw material liquids to achieve the purpose of experimental preparation.

[0123] The liquid inlet microchannel includes, but is not limited to, straight microchannels, and / or circumferential microchannels, and / or curved microchannels, and / or swirling flow microchannels. In this example, the liquid inlet microchannel is a straight microchannel. The liquid inlet microchannel includes a first liquid inlet microchannel 2211 and a second liquid inlet microchannel 2212, the shape and inner diameter of which can be the same or different. The flow rate and velocity of the raw material liquid can be controlled by setting the shape and inner diameter of the liquid inlet microchannel, so that different raw material liquids can achieve better mixing, coating, or other effects after mixing.

[0124] In a preferred embodiment, a sealing structure is further included, wherein a sealing structure is provided between the first opening 223 and the liquid inlet 212, and a sealing structure is provided between the second opening 224 and the liquid outlet 213. In the example, the sealing structure is a sealing ring 241, and at least two liquid inlet sealing grooves 2113 and liquid outlet sealing grooves 2114 are provided at the bottom of the chip slot 2111. The sealing ring 241 is accommodated in both the liquid inlet sealing groove 2113 and the liquid outlet sealing groove 2114. The first opening 223 abuts against the liquid inlet 212 through the sealing ring 241, and the second opening 224 abuts against the liquid outlet 213 through the sealing ring 241. Of course, the sealing ring 241 in the liquid inlet sealing groove 2113 and the sealing ring 241 in the liquid outlet sealing groove 2114 can be the same or different. The sealing ring 241 in the liquid inlet sealing groove 2113 matches the liquid inlet sealing groove 2113, and the sealing ring 241 in the liquid outlet sealing groove 2114 matches the liquid outlet sealing groove 2114. In the example, the liquid inlet sealing groove 2113 is coaxially arranged with the liquid inlet 212, and the liquid outlet sealing groove 2114 is coaxially arranged with the liquid outlet 213. The inner diameter of the liquid inlet sealing groove 2113 is larger than the inner diameter of the liquid inlet 212, and the inner diameter of the liquid outlet sealing groove 2114 is larger than the inner diameter of the liquid outlet 213. The outer diameter of the sealing ring 241 in the liquid inlet sealing groove 2113 is larger than the inner diameter of the first opening 223, and the outer diameter of the sealing ring 241 in the liquid outlet sealing groove 2114 is larger than the inner diameter of the second opening 224. This achieves a sealed connection between the first outlet and the second outlet of the microfluidic chip and the liquid inlet and outlet of the housing, respectively, preventing liquid leakage from the microfluidic chip housing 2. This leakage would not only affect the experimental results but also contaminate the raw materials or microfluidic mixture products in the next preparation.

[0125] In another preferred embodiment, a limiting post 2115 is provided at the bottom of the chip slot 2111, and a through limiting hole 226 is provided on the microfluidic chip 22. The limiting post 2115 is accommodated within the limiting hole 226. The limiting post and the limiting hole 226 can limit the position of the microfluidic chip 22 in the chip slot, so that the first opening corresponds and communicates with the liquid inlet, and the second opening corresponds and communicates with the liquid outlet, preventing misalignment and avoiding leakage or blockage. They also serve to fix the microfluidic chip 22.

[0126] Preferably, the microfluidic chip is mainly used for material mixing and droplet generation, particularly for the preparation of nanomedicines, nanocarriers, and microspheres. Nanomedicines include, but are not limited to, nucleic acid drugs, small molecule nanomedicines, and nanocrystalline drugs; nanocarriers include, but are not limited to, lipid nanoparticles (LNPs), polymers, peptides, and proteins; nucleic acid drugs include, but are not limited to, mRNA, siRNA, circular RNA, and self-replicating RNA; small molecule nanomedicines include, but are not limited to, paclitaxel liposomes and doxorubicin liposomes; and microspheres include, but are not limited to, PLGA microspheres, gel microspheres, and embolic microspheres.

[0127] We tested the fabrication process of encapsulating mRNA drugs with a classic LNP formulation using both the microfluidic device described in this patent and a traditional separately constructed microfluidic device. The LNP used in the formulation was the classic Dlin-MC3 formulation (dissolved in 100% pharmaceutical ethanol), and the encapsulating agent was luciferase mRNA (Luc mRNA), dissolved in water-for-injection buffer at a specific pH value. For confidentiality reasons, the specific formulation concentrations are not disclosed.

[0128] Table 1. Preparation of Classic LNP Formula-Encapsulated mRNA Drugs Using the Patented Device and Traditional Separately Built Microfluidic Devices

[0129]

[0130]

[0131] The PDI mentioned above represents the polymer dispersibility index. The data results confirm that the LNP formulation encapsulated mRNA drug prepared by the microfluidic device of this patent has better dispersibility and higher encapsulation rate, with an encapsulation rate as high as 96% and a dispersibility index of 0.03%. At the same time, it can also achieve a high flow rate of 120 ml / min. Therefore, the microfluidic device of this patent is more effective and practical, and is also more convenient and efficient.

[0132] All the technical features of the above components can be freely combined without conflict. In addition, changes, modifications and alterations to the component structure are also within the scope of protection of this patent.

[0133] The beneficial effects of the microfluidic device described in this patent are:

[0134] (1) The microfluidic device described in this patent has a simple structure, high degree of automation, convenient operation, and high preparation accuracy. It uses a micro-mixing device to prepare microfluidic mixtures. By automatically and precisely controlling the amount and speed of the raw material liquid entering the micro-mixing device, the ratio between the raw material liquids can be precisely controlled. In addition, the different receiving tubes of the receiving device can be automatically switched, which can realize the continuous preparation of multiple doses of the prepared microfluidic mixture. It can not only be used for experimental or small-batch product production, but also for process scale-up and application in production.

[0135] (2) The micro-mixing device is equipped with microchannels. By setting the shape (including straight, curved, circumferential or swirling flow, etc.), structure (including but not limited to T-shaped structure, Y-shaped structure, cross-shaped structure, SHM fishbone structure, Tesla structure and swirling flow structure) and inner diameter of the microchannels, the flow rate and velocity of the raw material liquid are controlled, as well as the mixing, and / or coating, and / or proportional configuration, and / or separation, and / or sorting, and / or purification of the mixed liquid, etc., so as to accurately prepare the ideal microfluidic mixture, especially for the preparation of nano-encapsulation of nucleic acid drugs or vaccines.

[0136] (3) The micromixing device is equipped with a sealing ring to ensure a sealed connection between the first and second outlets of the microfluidic chip and the inlet and outlet of the housing, respectively, preventing liquid spillage, which would not only affect the experimental results but also contaminate the raw materials or products to be prepared again. The micromixing device is equipped with a limiting post to limit and fix the microfluidic chip, preventing leakage or blockage caused by the microfluidic chip sliding and misalignment. The micromixing device is equipped with a handle end for pushing the micromixing device into the housing groove by holding the handle end, or pushing the micromixing device to rotate the support body that holds the micromixing device. The handle end is provided to prevent slippage and facilitate operation.

[0137] (4) The support body is provided with a first arc-shaped part and a second arc-shaped part. The second arc-shaped part can rotate, which makes it easy to take out and place the liquid delivery tube. The second arc-shaped part has a circular section that firmly fixes the liquid delivery tube and an arc-shaped section with an arc angle greater than 180°, so that the arc-shaped section can also firmly lock the liquid delivery tube and / or the tube sleeve to prevent it from loosening or falling off, thus achieving the purpose of both making it easy to take out and place the liquid delivery tube and firmly locking the liquid delivery tube.

[0138] (5) The liquid delivery device is equipped with a heating structure, which can heat the raw material liquid. As needed, the heating temperature, heating time and other conditions can be set to broaden the experimental conditions and provide more preparation conditions for the product preparation method. It is also equipped with a temperature sensor and control system, which facilitates precise control of the heating start / end time, heating temperature and heating duration, and facilitates precise control of preparation conditions, thereby helping to prepare microfluidic mixtures with higher precision, purity and better stability.

[0139] (6) The supporting body of the liquid delivery hole can be rotated. It can rotate around the main body of the equipment by means of the supporting body rotating, or the supporting body is provided with a fixed part and a movable part that can rotate around the fixed part, so that the liquid delivery hole can be rotated. This makes it easy to install the liquid delivery pipe into or remove it from the liquid delivery hole. After being rotated, it is easy to see whether the liquid delivery pipe is firmly installed into the liquid inlet, ensuring that the raw material liquid is not leaked when it is delivered into the micro-mixing device, and ensuring the stable preparation of microfluidic mixture. In addition, the rotating part is preferably a damping shaft or a universal damper, which can make the liquid delivery hole rotate to any position as needed, making the operation very convenient and greatly improving the user experience.

[0140] (7) The liquid delivery device is also equipped with a telescopic extrusion device, which can automatically control the extrusion of the raw material liquid into the micro-mixing device through the liquid delivery pipe without manual operation, facilitating stable and uniform delivery of the raw material liquid and enabling quantitative control of the delivered raw material liquid. It is equipped with a pressure sensor to automatically sense whether the liquid delivery pipe is in contact with the telescopic device, facilitating control of the delivery speed of the raw material liquid, i.e., quantitative control of the flow rate and velocity of the delivered raw material liquid, and facilitating control of the delivery ratio between different raw material liquids. It is equipped with a control system, which, in addition to controlling the opening, closing, and rotation speed of the drive structure, can also, in conjunction with the pressure value detected by the pressure sensor in the extrusion delivery pipe, adjust the rotation speed and direction of the drive structure in a timely manner according to settings or needs, to precisely control or dynamically change the flow rate and velocity of the delivered raw material liquid.

[0141] (8) A liquid receiving device is equipped with a liquid receiving slider, which can be fitted with multiple liquid receiving tubes. The multiple liquid receiving tubes are switched by sliding the liquid receiving slider to collect the microfluidic mixture, facilitating continuous operation. During the production process, the liquid receiving tubes that have been used for collection can be removed, and new liquid receiving tubes can be installed to continue collecting the microfluidic mixture. A waste liquid tank is provided on the liquid receiving slider to collect the droplets flowing out of the outlet when switching between different liquid receiving tubes, keeping the device clean and ensuring that the prepared microfluidic mixture is not contaminated. The liquid receiving device is equipped with a drive device and a spring, which can drive the liquid receiving slider to move back and forth along the slide bar, thereby realizing automatic switching of the liquid receiving tubes and improving work efficiency. A spring is provided on the other side of the drive device, so that the liquid receiving slider can automatically return to its initial position after operation, facilitating continuous operation of the drive device and precise control of the movement position of the liquid receiving slider.

[0142] (9) The microfluidic device described in this patent can not only be used for screening low flow rate nanomedicine formulations in the early stage with a flow rate range of 1-20 ml / min, but also breaks through the problem that traditional microfluidic devices cannot be scaled up. The maximum flow rate can support up to 120 ml / min.

[0143] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. In addition, those skilled in the art can combine and integrate the different embodiments or examples described in this specification.

[0144] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications and variations to the above embodiments within the scope of the present invention.

Claims

1. A microfluidic device, characterized in that, It includes the main body of the equipment (1), a micro-mixing device, a liquid delivery device (3), and a liquid receiving device (4). The main body (1) of the device includes an opening (11) and a receiving cavity (12). The opening (11) is connected to the receiving cavity (12). The micro-mixing device, the liquid delivery device (3), and the liquid receiving device (4) are all housed in the receiving cavity. The micro-mixing device includes a microchannel, at least one inlet (212), and at least one outlet (213). The inlet (212) and the outlet (213) are connected through the microchannel. The liquid delivery device (3) cooperates with the inlet (212). The liquid delivery device (3) can deliver the raw material liquid into the inlet (212). The liquid receiving device (4) corresponds to the liquid outlet (213), and the liquid receiving device (4) can receive the microfluidic mixture from the liquid outlet (213); the main body of the device (1) also includes a support body (13), the support body (13) is housed in the receiving cavity (12), the support body (13) is provided with a box groove (131) and at least one liquid delivery hole (32), the box groove (131) is connected to the liquid delivery hole (32), the micro-mixing device is snapped into the box groove (131), and the liquid inlet of the micro-mixing device corresponds to the liquid delivery hole (32); The liquid delivery device (3) includes at least one liquid delivery pipe (31), which is capable of containing raw material liquid. It also includes a telescopic extrusion device (5), which corresponds to the liquid delivery pipe (31). The telescopic extrusion device (5) is located on the side of the liquid delivery pipe (31) away from the micro-mixing device. The telescopic extrusion device (5) can push the raw material liquid in the liquid delivery pipe (31) to the liquid inlet (212). The support body (13) with liquid delivery hole (32) can rotate; The support body (13) is rotatably connected to the equipment body (1) via a rotating shaft or a universal damper. The support body (13) can rotate around the equipment body (1). A limiting wing (134) is provided on the side of the support body (13) away from the liquid delivery hole (32). The limiting wing (134) abuts against the equipment body (1). The limiting wing (134) allows the support body (13) to be placed against the opening of the equipment body (1), or The supporting body (13) includes a movable part and a fixed part. The fixed part is fixedly disposed on the main body of the device. The movable part can rotate around the fixed part. The movable part is provided with a first arc-shaped part. The fixed part is provided with a second arc-shaped part. The first arc-shaped part and the second arc-shaped part together form a liquid delivery hole. The first arc-shaped part (321) includes an arc-shaped segment (3211) and a circular segment (3212) along the axial direction. The arc-shaped segment (3211) is located at the end of the liquid delivery hole (32) away from the microfluidic chip box (2). The second arc-shaped part (322) matches the arc-shaped segment (3211).

2. The microfluidic device according to claim 1, characterized in that, The liquid receiving device (4) includes a liquid receiving slider (41) and a liquid receiving tube (42). The liquid receiving slider (41) is slidably installed on the support body. The liquid receiving slider (41) is provided with a waste liquid tank (413) and at least two slots (412). The waste liquid tank (413) is arranged between two adjacent slots (412). The waste liquid tank (413) can receive waste liquid from the outlet (213). The liquid receiving tube (42) is snapped into the slot (412). The liquid receiving tube (42) can receive microfluidic mixture from the outlet (213). The microchannel structures include T-shaped structures, Y-shaped structures, cross-shaped structures, SHM fishbone structures, Tesla structures, and swirling flow structures.

3. The microfluidic device according to claim 1, characterized in that, The microchannel includes at least one liquid inlet microchannel (221) and at least one mixing microchannel (222). The liquid inlet (212) corresponds one-to-one with the liquid inlet microchannel (221). One end of the liquid inlet microchannel (221) is connected to the liquid inlet (212), and the other end of the liquid inlet microchannel (221) is connected to one end of the mixing microchannel (222). The other end of the mixing microchannel (222) is connected to the liquid outlet (213).

4. The microfluidic device according to claim 1, characterized in that, The liquid delivery device (3) also includes a heating structure, which can heat the liquid delivery hole (32), and the liquid delivery hole can conduct heat to the raw material liquid in the liquid delivery pipe (31).

5. The microfluidic device according to claim 1, characterized in that, The support body (13) with liquid delivery hole (32) can rotate and stop at any position; The liquid delivery device also includes a sleeve (33), and liquid delivery pipes (31) of different volumes are snapped into the liquid delivery hole (32) through the sleeve (33).

6. The microfluidic device according to claim 2, characterized in that, The swirling flow structure is a microchannel composed of multiple S-shaped microchannels connected end to end in sequence.

7. The microfluidic device according to claim 1, characterized in that, The micro-mixing device has at least two fixing slots (232), and a protruding structure is provided in the box slot. The micro-mixing device is housed in the box slot (131), and the protruding structure is snapped into the fixing slot (232).

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