High-flux automatic preparation system based on microchannel

Abstract

The invention discloses a microchannel-based high-flux automatic preparation system, which comprises a control system, a microreaction assembly, a switcher, a product assembly and a waste liquid assembly, the microreaction assembly is connected with the switcher, the switcher is located between the product assembly and the waste liquid assembly, and the control system is connected with the microreaction assembly, the switcher and the product assembly. After raw materials enter the micro-reaction assembly to be mixed to prepare LNP, products are output to the product assembly, the product assembly collects various different products and subsequently detects the collected products, after LNP preparation is completed every time, the micro-reaction assembly is automatically cleaned, and cleaning waste liquid enters the waste liquid assembly to be recycled. According to the invention, full-process automation of experimental operation is realized, operations such as sample preparation, instrument cleaning and sample separation and detection are automatically carried out, complexity and errors of manual operation are greatly reduced, the experimental efficiency is improved, and the purposes of high-throughput preparation and screening are realized.

Description

Technical Field

[0001] The invention belongs to the technical field of microchannel reactors, and in particular relates to a high-throughput automatic preparation system based on microchannels. Background Art

[0002] The characteristic of a microchannel reactor is that the reaction site is a channel with an extremely small inner diameter. The fluid flows in the channel, which has a better effect in mixing or synthesis. In combination with ultrasonic vibration, it can achieve instantaneous uniform mixing of materials and efficient heat transfer. Therefore, many reactions that cannot be achieved in conventional reactors can be achieved in microchannel reactors.

[0003] Microchannel reactors can realize the synthesis of substances and the mixing of materials. For example, microchannel reactors can be used to prepare LNP. LNP lipid nanoparticles are a nanoscale drug delivery system based on lipid self-assembly. They have excellent biocompatibility, stability and targeting, and can significantly improve the solubility and bioavailability of drugs. At present, the most commonly used technology in the preparation of nano lipid particles is the collision jet mixing technology. Later, ultrasonic microfluidics technology was also developed to be applied to the preparation process of lipid nanoparticles.

[0004] At present, there are still many problems in the preparation of lipid nanoparticles using ultrasonic microfluidics, such as the relatively complex preparation process, the large workload before and after the preparation, and the inability to achieve rapid and efficient screening of a large number of LNP candidate drugs. In addition, there are also the problems of dead volume and particle blockage in conventional microchannel reactors. The existence of dead volume in microchannel reactors can lead to problems such as reagent waste, increased experimental errors, and further reduction in screening efficiency. If a high-throughput screening platform can be proposed to solve the above problems, it will be beneficial to the research of LNP candidate drugs and the preparation of LNP. Summary of the invention

[0005] In order to solve the above technical problems, the purpose of the present invention is to provide a high-throughput automatic preparation system based on microchannels, which can realize the full automation of experimental operations, automatically perform operations such as sample preparation, instrument cleaning, sample separation and detection, greatly reduce the tediousness and errors of manual operations, improve experimental efficiency, and achieve the purpose of high-throughput preparation and screening.

[0006] In order to achieve the above-mentioned invention object, the technical solution adopted by the present invention is as follows:

[0007] A high-throughput automatic preparation system based on a microchannel, comprising a control system, a micro-reaction component, a switch, a product component and a waste liquid component;

[0008] The micro-reaction assembly comprises a micro-reactor, a side conveyor, an end conveyor and an ultrasonic generator, the ultrasonic generator is connected to the micro-reactor, a reaction channel and an output channel are arranged in the micro-reactor, the output channel is communicated with the middle part of the reaction channel, the output channel is communicated with the switch, and based on the connection point between the output channel and the reaction channel, the reaction channel is divided into a first sub-channel on the left and a second sub-channel on the right;

[0009] Along the material flow direction, the plurality of side conveyors are all connected to the first branch channel, and a one-way valve is arranged at the connection between the side conveyor and the first branch channel, an end conveyor is arranged at the outer end of the first branch channel, a two-inlet and one-outlet switching valve is arranged between the end conveyor and the first branch channel, the two inlets of the switching valve are respectively connected to the end conveyor and the compressed gas delivery pipe, the outlet of the switching valve is connected to the first branch channel, and a one-way valve is arranged at the connection between the switching valve and the first branch channel;

[0010] Along the material flow direction, the plurality of side conveyors are all connected to the second branch channel, and a one-way valve is arranged at the connection between the side conveyor and the second branch channel, an end conveyor is arranged at the outer end of the second branch channel, a two-inlet and one-outlet switching valve is arranged between the end conveyor and the second branch channel, the two inlets of the switching valve are respectively connected to the end conveyor and the compressed gas delivery pipe, the outlet of the switching valve is connected to the second branch channel, and a one-way valve is arranged at the connection between the switching valve and the second branch channel;

[0011] The side conveyor inputs liquid raw materials into the reaction channel, and the end conveyor inputs cleaning liquid into the reaction channel;

[0012] The switch is located between the product component and the waste liquid component, and transports the material in the output channel to the product component or the waste liquid component;

[0013] The product assembly includes a material receiving orifice plate and a plane moving mechanism, wherein the material receiving orifice plate is arranged on the plane moving mechanism, and the plane moving mechanism controls the movement of the material receiving orifice plate;

[0014] The control system is respectively connected with the side conveyor, the end conveyor, the switcher and the plane moving mechanism.

[0015] Preferably, the reaction channel is a linear channel or a zigzag channel.

[0016] Preferably, the length of the first sub-channel is the same as or different from the length of the second sub-channel.

[0017] Preferably, the direction in which the side conveyor outside the first sub-channel inputs materials is the same as the direction in which the materials flow in the first sub-channel, and the direction in which the side conveyor outside the second sub-channel inputs materials is the same as the direction in which the materials flow in the second sub-channel.

[0018] Preferably, the switch includes a base and a switching motor and a hose arranged on the base, the transmission shaft of the switching motor is connected to the hose, one end of the hose is connected to the output channel of the microreactor, and the switching motor controls the rotation of the hose so that the other end of the hose is in the product component or in the waste liquid component.

[0019] Preferably, the receiving orifice plate includes one or more of a 24-well plate, a 48-well plate, a 96-well plate, and a 384-well plate.

[0020] Preferably, the number of the material receiving orifice plates on the planar moving mechanism is greater than or equal to two.

[0021] Preferably, the planar moving mechanism includes a transverse screw rod, a transverse motor, a longitudinal screw rod, a longitudinal motor and a connecting plate, the transverse motor is connected to the transverse screw rod, the longitudinal motor is connected to the longitudinal screw rod, the longitudinal screw rod is arranged on the screw rod nut member of the transverse screw rod, the longitudinal screw rod is controlled by the transverse screw rod to move transversely, and the connecting plate is arranged on the screw rod nut member of the longitudinal screw rod, and the connecting plate is controlled by the longitudinal screw rod to move longitudinally.

[0022] Preferably, the waste liquid component includes a waste liquid collection tank.

[0023] Preferably, the number of the waste liquid collection tanks is one or more.

[0024] Beneficial effects:

[0025] The present invention realizes the automation of experimental design and integrates automated liquid processing, which can realize the actual automatic addition and mixing of raw materials and the automatic distribution of prepared samples. The present invention can automatically and accurately control the volume and flow rate of the liquid according to the preset experimental scheme parameters to ensure the accuracy and repeatability of the experiment. In combination with a robot or a robotic arm, the present invention can realize the full automation of experimental operations, automatically perform operations such as sample preparation, instrument cleaning, and sample separation and detection, which greatly reduces the tediousness and errors of manual operations, improves experimental efficiency, and achieves the purpose of high-throughput preparation and screening. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Shown is an overall schematic diagram of the present invention;

[0027] Figure 2 Shown is a schematic diagram of the micro-reaction assembly of the present invention.

[0028] Figure numerals: 1-microreactor, 2-ultrasonic generator, 3-side conveyor, 4-end conveyor, 5-switching valve, 6-compressed gas delivery pipe, 7-switcher, 8-material receiving orifice plate, 9-plane moving mechanism, 10-waste liquid collecting tank, 11-check valve, 101-first sub-channel, 102-second sub-channel, 103-output channel. DETAILED DESCRIPTION

[0029] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the specific implementation methods of the present invention will be described below with reference to the accompanying drawings. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings and other implementation methods can be obtained based on these drawings without creative work.

[0030] The present invention proposes a high-throughput automatic preparation system based on microchannels, which can precisely control the processes such as fluid control, mixing and reaction at a microscale, solve the problem of dead volume in the mixing or reaction process, and achieve the purpose of high-throughput automatic preparation of lipid nanoparticles. The present invention can be used in the fields of LNP, PLGA, drug synthesis, and customized cosmetic product emulsification.

[0031] "High throughput" here refers to the ability of the system to automatically process, prepare and detect a large number of samples in a short period of time. This high-throughput capability is achieved through the system's automated processing capabilities, which can significantly improve experimental efficiency and reduce the tediousness and errors of manual operations. Specifically, the present invention utilizes microchannel technology to enable multiple samples to be automatically prepared one after another, thereby achieving a higher sample processing volume per unit time, achieving the purpose of high-throughput preparation and screening. Here, the sample preparation throughput of the high-throughput system should be greater than 60 samples / hour, that is, the preparation of more than 60 samples of different properties can be completed within one hour.

[0032] The high-throughput automatic preparation system based on microchannel includes a control system, a micro-reaction component, a switch 7, a product component and a waste liquid component, wherein the micro-reaction component is connected to the switch 7, the switch 7 is between the product component and the waste liquid component, the control system is connected to the micro-reaction component, the switch 7 and the product component, the raw material enters the micro-reaction component for mixing and preparing the sample, and then outputs the product to the product component, the product component collects a variety of different products and subsequently detects the collected products, and after each sample preparation is completed, the micro-reaction component is automatically cleaned, and the cleaning waste liquid enters the waste liquid component for recycling. The technical scheme of the present invention is described in detail below.

[0033] The micro-reaction assembly includes a micro-reactor 1, a side conveyor 3, an end conveyor 4 and an ultrasonic generator 2. Figure 1-2As shown, a plurality of side conveyors 3 are installed on the side of the microreactor 1 , two end conveyors 4 are arranged at the two ends of the microreactor 1 , and the ultrasonic generator 2 is connected to the microreactor 1 .

[0034] A reaction channel and an output channel 103 are arranged in the microreactor 1. The reaction channel is a linear channel. The output channel 103 is connected to the middle part of the reaction channel. The output channel 103 is connected to the switch 7. Based on the connection point between the output channel 103 and the reaction channel, the reaction channel is divided into a first sub-channel 101 on the left and a second sub-channel 102 on the right. It is easy to understand that the first sub-channel 101 and the second sub-channel 102 are directly connected. The direction of the first sub-channel 101 toward the output channel 103 is the direction of material flow in the first sub-channel 101, and the direction of the second sub-channel 102 toward the output channel 103 is the direction of material flow in the second sub-channel 102.

[0035] A plurality of side conveyors 3 are arranged on the side of the first sub-channel 101. Along the material flow direction, the plurality of side conveyors 3 are all connected to the first sub-channel 101, and a one-way valve 11 is arranged at the connection between the side conveyor 3 and the first sub-channel 101. An end conveyor 4 is arranged at the outer end of the first sub-channel 101, i.e., the end of the first sub-channel 101 away from the second sub-channel 102. A two-inlet and one-outlet switching valve 5 is arranged between the end conveyor 4 and the first sub-channel 101. The two inlets of the switching valve 5 are respectively connected to the end conveyor 4 and the compressed gas delivery pipe 6, and the outlet of the switching valve 5 is connected to the first sub-channel 101, and a one-way valve 11 is arranged at the connection between the switching valve 5 and the first sub-channel 101.

[0036] A plurality of side conveyors 3 are arranged on the side of the second sub-channel 102. Along the material flow direction, the plurality of side conveyors 3 are all connected to the second sub-channel 102, and a one-way valve 11 is arranged at the connection between the side conveyor 3 and the second sub-channel 102. An end conveyor 4 is arranged at the outer end of the second sub-channel 102, i.e., the end of the second sub-channel 102 away from the first sub-channel 101. A two-inlet and one-outlet switching valve 5 is arranged between the end conveyor 4 and the second sub-channel 102. The two inlets of the switching valve 5 are respectively connected to the end conveyor 4 and the compressed gas delivery pipe 6, and the outlet of the switching valve 5 is connected to the second sub-channel 102, and a one-way valve 11 is arranged at the connection between the switching valve 5 and the second sub-channel 102.

[0037] It is easy to understand that the compressed gas delivery pipe 6 is connected to an external gas compressor such as an air compressor, and the gas compressor provides clean and dry compressed gas for the present invention. In the present invention, the compressed gas can be compressed air or other pure compressed gases, such as compressed oxygen, compressed nitrogen, compressed inert gas, etc., depending on the preparation needs.

[0038] In the present invention, the timing of the side conveyor 3 injecting the raw material into the first sub-channel 101 / the second sub-channel 102 can be controlled. Since the pressure and flow rate of the injected raw material are known, and the lengths of the first sub-channel 101 and the second sub-channel 102 are known, precise control can be achieved by controlling the injection time. Figure 2 As shown, a plurality of side conveyors 3 are arranged on the side of the first sub-channel 101 along the material flow direction, with the side conveyor 3 farthest from the output channel 103 as the starting point, and the distance between the injection points of any two side conveyors 3 on the first sub-channel 101 is determined. When the injection pressure and flow rate are known, the speed of the raw material flowing on the first sub-channel 101 can also be determined. The raw material is input from a side conveyor 3 to the first sub-channel 101, and the time for the raw material to flow to any side conveyor 3 behind is known. Therefore, the present invention can realize accurate control of the preparation through different injection timings of multiple raw materials. The side conveyor 3 of the second sub-channel 102 has the same function as the side conveyor 3 of the first sub-channel 101.

[0039] A one-way valve 11 is provided between the side conveyor 3 and the first sub-channel 101 / the second sub-channel 102 and its function is to prevent the raw material or the material in the channel from flowing back.

[0040] In the present invention, the inner diameters of the reaction channel and the output channel 103 are 0.5-8 mm.

[0041] The present invention is particularly suitable for preparing LNP. For ease of explanation, the invention takes the preparation of lipid nanoparticles LNP encapsulating drugs as an example. The drugs are dissolved in organic matter, which is easy to understand. Water-soluble drugs can also be dissolved in the aqueous phase. The encapsulation of the drugs is also achieved by collision mixing. The present invention is also applicable to the synthesis of drugs or other substances.

[0042] In the present invention, the reaction channel is divided into two left and right sub-channels. The first sub-channel 101 and the second sub-channel 102 can be used and injected with raw materials at the same time, or only the sub-channel on one side can be injected with raw materials. Specifically, the present invention includes but is not limited to the following mixing methods:

[0043] Mixing method 1: Only the first sub-channel 101 or the second sub-channel 102 is used to realize the two-phase collision to realize LNP self-assembly, and the lipid organic phase and the aqueous phase containing the drug are injected through different side conveyors 3. The organic phase collides with the aqueous phase, and the lipid and the drug are precipitated, completing the encapsulation of the drug by the lipid to form lipid nanoparticles.

[0044] Mixing method 2: Use the first sub-channel 101 and the second sub-channel 102 at the same time to achieve three-phase collision to achieve LNP self-assembly. For example, the water phase and the drug-containing organic phase are first injected into the first sub-channel 101 for collision and mixing, so that the drug is precipitated first, and the lipid-containing organic phase is injected into the second sub-channel 102. The mixed solution containing the drug precipitated particles flows forward to the output channel 103 and collides with the lipid-containing organic phase. The lipid precipitation encapsulates the drug particles to form lipid nanoparticles.

[0045] Mixing method three: Use the first sub-channel 101 and the second sub-channel 102 at the same time to achieve two-phase collision to realize LNP self-assembly. The first sub-channel 101 is respectively injected with organic raw materials such as lipids and drugs required for LNP self-assembly, and first mixed to form an organic phase. The second sub-channel 102 is injected with the aqueous phase required for LNP self-assembly. Along the flow direction of the materials, the organic phase and the aqueous phase collide and mix, and the lipids encapsulate the drugs to form lipid nanoparticles.

[0046] It is easy to understand that the first sub-channel 101 and the second sub-channel 102 converge at the output channel 103. The output channel 103 is a place with lower pressure in the microreactor 1. The material will enter the output channel 103 and be discharged instead of entering the adjacent sub-channel. Especially when compressed gas is input, it is even less likely that the material will enter the adjacent sub-channel.

[0047] The switching valve 5 connected to the end conveyor 4 is used to control the input of compressed gas and the input of cleaning liquid. After the side conveyor 3 completes the step of injecting raw materials, the switching valve 5 switches to the compressed gas delivery pipe 6 to input compressed gas, and the compressed gas pushes the mixed material forward, thereby maximizing the reduction of the dead volume material retained in the microreactor 1. Generally, after all the raw materials are completely injected into the first sub-channel 101 / the second sub-channel 102, the compressed gas is input. It is easy to understand that the input of compressed gas and the input process of raw materials are staggered, and the timing of raw material injection is not affected by the input of compressed gas.

[0048] After completing one preparation process, the side conveyor 3 remains closed, the switching valve 5 switches to the end conveyor 4, and the cleaning liquid is input. The cleaning liquid is input to both end conveyors 4 to clean the first sub-channel 101 and the second sub-channel 102, and the cleaning liquid is finally discharged through the output channel 103. After the cleaning is completed, the switching valve 5 switches to the compressed gas delivery pipe 6 again, and the compressed gas is input again to discharge all the residual cleaning liquid.

[0049] The reaction channel is a linear channel or a zigzag channel, and one end of the output channel 103 is connected to the reaction channel, that is, the reaction channel and the output channel 103 form a T-shaped channel structure or a Y-shaped channel structure, so that the reaction channel is divided into a first sub-channel 101 and a second sub-channel 102. It is easy to understand that the first sub-channel 101 and the second sub-channel 102 are both linear channels. When the reaction channel is a zigzag channel, the output channel 103 is connected to the bend of the reaction channel.

[0050] It should be noted that in the present invention, the reaction channel is preferably straight, that is, the angle between the first sub-channel 101 and the second sub-channel 102 is 180°. The advantage of this structure is that the materials in the first sub-channel 101 and the second sub-channel 102 collide with each other to the maximum extent, avoiding the generation of other component forces, and facilitating cleaning. It is easy to understand that the reaction channel can also be a broken line type, and the angle between the first sub-channel 101 and the second sub-channel 102 is an obtuse angle, such as 90 to 180°, which is designed according to experimental requirements and is not specifically limited by the present invention.

[0051] Preferably, the direction in which the side conveyor 3 outside the first sub-channel 101 inputs materials is the same as the direction in which the materials flow in the first sub-channel 101, and the direction in which the side conveyor 3 outside the second sub-channel 102 inputs materials is the same as the direction in which the materials flow in the second sub-channel 102. Figure 2 As shown, the side conveyors 3 are all inclined to reduce the resistance of raw material injection. After the raw materials are injected, the raw materials flow forward along the material flow direction.

[0052] In the present invention, the length of the first sub-channel 101 is the same as or different from the length of the second sub-channel 102. It is easy to understand that even if the lengths of the first sub-channel 101 and the second sub-channel 102 are different, by controlling the timing of injecting raw materials by the side conveyor 3, the materials in the first sub-channel 101 and the second sub-channel 102 collide and mix.

[0053] The ultrasonic generator 2 is connected to the microreactor 1. It is easy to understand that the connection method between the ultrasonic generator 2 and the microreactor 1 is similar to that of the existing ultrasonic microchannel reaction device. For example, the ultrasonic generator 2 is connected to the microreactor 1 based on the center position of the microreactor 1. The ultrasonic generator 2 provides uniform and stable ultrasonic vibration for the microreactor 1, so that the materials in the reaction channel and the output channel 103 generate ultrasonic cavitation, and promote the mixing or reaction of the raw materials in the microreactor 1.

[0054] In the present invention, the side conveyor 3 and the end conveyor 4 are conventional pressure feeding devices, such as injection pumps, and the injection flow rate and feed amount of the injection pump are convenient to control.

[0055] The inlet of the switch 7 is connected to the output channel 103 of the microreactor 1, and the switch 7 outputs the material to the product component or the waste liquid component. It is easy to understand that the function of the switch 7 is to change the flow direction of the material. The material of the microreactor 1 can enter the product component or the waste liquid component through the switch 7. For example, when the product synthesis performance is not up to standard during cleaning or in the initial stage, the switch 7 is switched to be connected to the waste liquid component, and the cleaning liquid or waste liquid generated in the microreactor 1 enters the waste liquid component. When the synthetic sample meets the standard, the switch 7 is switched to be connected to the product component, and the qualified sample enters the product component for collection.

[0056] The switch 7 is an existing conventional mechanism, and the present invention does not make specific restrictions. The present invention proposes two common switch 7 below. For example, the switch 7 is a two-input and one-output switching valve 5, or the switch 7 is a structure in which a switching motor cooperates with a hose to rotate. Specifically, the switch 7 includes a base and a switching motor and a hose arranged on the base. The transmission shaft of the switching motor is connected to the hose, one end of the hose is connected to the output channel 103 of the microreactor 1, and the hose is controlled to rotate by the switching motor. The other end of the hose can be in the product component or in the waste liquid component.

[0057] The product assembly includes a material receiving orifice plate 8 and a plane moving mechanism 9. The material receiving orifice plate 8 is arranged on the plane moving mechanism 9. The plane moving mechanism 9 controls the movement of the material receiving orifice plate 8 to load product samples prepared under different parameter conditions. The plane moving mechanism 9 is a conventional structure for lateral and longitudinal movement to realize the movement of the material receiving orifice plate 8 on the plane. For example, the plane moving mechanism 9 includes components such as a lateral screw, a lateral motor, a longitudinal screw, a longitudinal motor and a connecting plate. The lateral motor is connected to the lateral screw, and the longitudinal motor is connected to the longitudinal screw. The longitudinal screw is arranged on the screw nut of the lateral screw, and the longitudinal screw is controlled by the lateral screw to move lateral. The connecting plate is arranged on the screw nut of the longitudinal screw, and the connecting plate is controlled by the longitudinal screw to move longitudinally. Thus, the connecting plate realizes lateral and longitudinal movement in the plane, and any material receiving hole on the material receiving orifice plate 8 can be placed in a material receiving position.

[0058] The specifications of the receiving hole plate 8 can be various, for example, the receiving hole plate 8 is a 24-hole plate, a 48-hole plate, a 96-hole plate, a 384-hole plate, etc.

[0059] The waste liquid component includes a waste liquid collecting tank 10. It is easy to understand that there are multiple waste liquid collecting tanks 10, for example, there are two waste liquid collecting tanks 10, which respectively collect cleaning waste liquid and unqualified sample waste liquid, and the flow direction of the waste liquid is controlled by the switch 7.

[0060] The present invention prepares products based on the control of a fully automatic control system to control the electrical equipment in the micro-reaction component, the switch 7 and the product component. According to the formula requirements, the corresponding liquid reaction raw materials are respectively connected to the side conveyor 3, and the side conveyor 3 performs fixed-point quantitative delivery of the raw materials according to the corresponding parameters set by the fully automatic control system. Since a one-way valve 11 is provided in the microreactor 1, even if some side conveyors 3 are empty, it does not affect the delivery of the raw materials by other side conveyors 3, that is, the microreactor 1 as a whole will not leak. The present invention is suitable for the mixing or synthesis reaction of two or more raw materials. The present invention has great compatibility and can be applied to as many kinds of reaction raw materials as required according to actual requirements. The reaction raw materials enter the microreactor 1, and through ultrasonic vibration, the mixing of different liquid raw materials is strengthened, and ultrasonic cavitation is generated in the liquid in the microchannel, and the cavitation bubbles explode in the liquid, and the impact generated will have a crushing effect on each molecular structure of the reaction raw materials, so that the mixing or synthesis reaction is more complete, and the precision of the nanometer level can be achieved. In the present invention, compressed gas is input during the preparation process to reduce the dead volume of materials retained in the microreactor 1, and the microreactor 1 outputs the prepared LNP, which is collected by the product assembly on the receiving orifice plate 8. When a group of LNP preparation is completed, the two end conveyors 4 convey the cleaning liquid to clean the reactor under the condition of ultrasonic vibration, and finally the microreactor 1 is forced to drain and blow dry by compressed gas. The next sample is automatically prepared.

[0061] Taking the 96-well plate as an example, two 96-well plates are set in the product component. When one of the 96-well plates is full of liquid, it will automatically exit the sample receiving position and be replaced by the other 96-well plate. At the same time, an alarm will be issued to notify the experimenter to transfer the full 96-well plate to the subsequent detection process and replace it with a new 96-well plate, thereby realizing continuous connection and sample preparation.

[0062] The embodiments provided by the present invention are described in detail above. Specific examples are used herein to describe the principles and implementation methods of the present invention, and the description of the above embodiments is only used to help understand the core idea of ​​the present invention. It should be pointed out that for ordinary technicians in this technical field, without departing from the principles of the present invention, the present invention can also be improved and modified in a number of ways, and these improvements and modifications also fall within the scope of protection of the claims of the present invention.

Claims

1. A high-throughput automatic preparation system based on microchannels, characterized in that: It includes a control system, a micro-reaction component, a switch (7), a product component and a waste liquid component; The micro-reaction assembly comprises a micro-reactor (1), a side conveyor (3), an end conveyor (4) and an ultrasonic generator (2), wherein the ultrasonic generator (2) is connected to the micro-reactor (1), a reaction channel and an output channel (103) are arranged in the micro-reactor (1), the output channel (103) is connected to the middle part of the reaction channel, the output channel (103) is connected to the switch (7), and based on the connection point between the output channel (103) and the reaction channel, the reaction channel is divided into a first sub-channel (101) on the left and a second sub-channel (102) on the right; Along the material flow direction, the plurality of side conveyors (3) are all connected to the first branch channel (101), and a one-way valve (11) is arranged at the connection between the side conveyor (3) and the first branch channel (101), an end conveyor (4) is arranged at the outer end of the first branch channel (101), a two-inlet and one-outlet switching valve (5) is arranged between the end conveyor (4) and the first branch channel (101), the two inlets of the switching valve (5) are respectively connected to the end conveyor (4) and the compressed gas delivery pipe (6), the outlet of the switching valve (5) is connected to the first branch channel (101), and a one-way valve (11) is arranged at the connection between the switching valve (5) and the first branch channel (101); Along the material flow direction, the plurality of side conveyors (3) are all connected to the second branch channel (102), and a one-way valve (11) is arranged at the connection between the side conveyor (3) and the second branch channel (102); an end conveyor (4) is arranged at the outer end of the second branch channel (102); a two-inlet and one-outlet switching valve (5) is arranged between the end conveyor (4) and the second branch channel (102); the two inlets of the switching valve (5) are respectively connected to the end conveyor (4) and the compressed gas delivery pipe (6); the outlet of the switching valve (5) is connected to the second branch channel (102), and a one-way valve (11) is arranged at the connection between the switching valve (5) and the second branch channel (102); The switch (7) is located between the product component and the waste liquid component, and transports the material in the output channel (103) to the product component or the waste liquid component; The product assembly comprises a material receiving orifice plate (8) and a plane moving mechanism (9), wherein the material receiving orifice plate (8) is arranged on the plane moving mechanism (9), and the plane moving mechanism (9) controls the movement of the material receiving orifice plate (8); The control system is respectively connected to the side conveyor (3), the end conveyor (4), the switch (7) and the plane moving mechanism (9).

2. The microchannel-based high-throughput automatic preparation system according to claim 1, characterized in that: The reaction channel is a linear channel or a zigzag channel.

3. The microchannel-based high-throughput automatic preparation system according to claim 2, characterized in that: The length of the first sub-channel (101) is the same as or different from the length of the second sub-channel (102).

4. The microchannel-based high-throughput automatic preparation system according to claim 2, characterized in that: The direction in which the side conveyor (3) outside the first sub-channel (101) inputs materials is the same as the direction in which the materials flow in the first sub-channel (101), and the direction in which the side conveyor (3) outside the second sub-channel (102) inputs materials is the same as the direction in which the materials flow in the second sub-channel (102).

5. The microchannel-based high-throughput automatic preparation system according to claim 1, characterized in that: The switch (7) comprises a base, a switching motor and a hose arranged on the base, the transmission shaft of the switching motor is connected to the hose, one end of the hose is connected to the output channel (103) of the microreactor (1), and the switching motor controls the rotation of the hose so that the other end of the hose is in the product component or in the waste liquid component.

6. The microchannel-based high-throughput automatic preparation system according to claim 1, characterized in that: The material receiving orifice plate (8) includes one or more of a 24-well plate, a 48-well plate, a 96-well plate, and a 384-well plate.

7. The microchannel-based high-throughput automatic preparation system according to claim 1, characterized in that: The number of the material receiving orifice plates (8) on the plane moving mechanism (9) is greater than or equal to two.

8. The microchannel-based high-throughput automatic preparation system according to claim 1, 6 or 7, characterized in that: The planar moving mechanism (9) comprises a transverse screw rod, a transverse motor, a longitudinal screw rod, a longitudinal motor and a connecting plate, wherein the transverse motor is connected to the transverse screw rod, the longitudinal motor is connected to the longitudinal screw rod, the longitudinal screw rod is arranged on a screw rod nut of the transverse screw rod, the longitudinal screw rod is controlled by the transverse screw rod to move transversely, and the connecting plate is arranged on a screw rod nut of the longitudinal screw rod, the connecting plate is controlled by the longitudinal screw rod to move longitudinally.

9. The microchannel-based high-throughput automatic preparation system according to claim 1, characterized in that: The waste liquid component comprises a waste liquid collecting tank (10).

10. The microchannel-based high-throughput automatic preparation system according to claim 9, characterized in that: The number of the waste liquid collection tanks (10) is one or more.

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