Preparation control method based on droplet microfluidics technology

Abstract

The present invention relates to a preparation control method based on droplet microfluidics technology. According to the preparation parameters input before preparation, the propulsion speed of the syringe piston handle corresponding to each input is calculated, and the first driver is controlled to drive the propulsion member according to the propulsion speed to achieve stable output of the solution in the syringe; and by monitoring the real-time position of the propulsion member, the amount of solution output is calculated in real time, thereby controlling the preparation process and realizing automated preparation. The present invention not only avoids the instability of traditional equipment, but also prevents reagent contamination; it can automatically, accurately and stably prepare according to process requirements, with high efficiency, good process accuracy and product consistency.

Description

Technical Field

[0001] The invention relates to a preparation control method based on droplet microfluidics technology, which is applicable to the technical field of laboratory biological vaccine preparation. Background Art

[0002] Droplet microfluidics is a biological vaccine preparation technology that can realize biochemical reactions, rapid mixing of reagents, and synthesis of microparticles. It is widely used in industries such as biological vaccines and pharmaceutical processing. The current microfluidic preparation equipment can usually be divided into production type and experimental type. The structure of the production type equipment is relatively large and complex, suitable for high flow rate and high throughput production conditions, while the structure of the experimental type equipment is mostly small, mainly to meet the test needs of a small amount of reagents in the laboratory. The structural principle of the existing experimental preparation equipment is usually similar to that of the production type equipment. It is composed of a preparation chip, a liquid supply tube with at least two output ends connected to the preparation chip, and a liquid pump. During preparation, the input end of the liquid supply tube needs to be passed into a test tube containing the raw material solution, and the solution in the test tube is sucked into the liquid supply tube by the liquid pump, and then the input end of the liquid supply tube is closed by a valve, and the output end is opened, and then the solution in the liquid supply tube is pushed into the preparation chip at a certain rate by the liquid pump for mixing.

[0003] However, due to the influence of factors such as liquid pressure and temperature during the preparation process, it is difficult to ensure the stability of the flow rate and flow rate of the liquid when the solution is output by the liquid pump. The production equipment can monitor the liquid pump in real time through sensors, but the experimental equipment is limited by its structure and function, and the total preparation volume is small. It cannot adjust the preparation process in real time like the production equipment. Therefore, the preparation accuracy and product consistency of the existing experimental preparation equipment are difficult to guarantee. In order to overcome the above problems, the applicant previously applied for a microfluidic droplet preparation device with a publication number of CN221359932U, which uses an external syringe instead of a liquid supply tube, and outputs the solution by using a driver to drive the propeller to push the syringe piston handle to avoid the instability of the liquid pump outputting the solution. However, since the driving method of the above-mentioned device is completely different from the liquid pump output, there is still a lack of a preparation control method for the above-mentioned microfluidic droplet preparation device in the prior art. Summary of the invention

[0004] In order to solve the defects of the above-mentioned prior art, the present invention proposes a preparation control method based on droplet microfluidics technology. The technical solution adopted by the present invention is: a preparation control method based on droplet microfluidics technology, adopting a droplet microfluidics preparation system, the preparation system includes a preparation chip having at least two input ports detachably connected to the cone head of a syringe containing a solution required for preparation, and an output port for outputting a mixed solution product, a driving component whose number is the same as the number of the input ports and is used to drive the syringe connected to the input port to pump out the solution, a collection component for collecting the product, and a main control module for controlling the operation of the preparation system, the driving component includes a pusher that is slidably arranged and pushes the syringe piston handle by sliding, a first driver for driving the pusher to slide, and a first driver that is arranged on the pusher and is used to monitor the pusher. A pressure sensor is used to measure the pressure applied by the piston handle of the syringe to the feed product. The collection component includes at least one first container for collecting good products, at least one second container for collecting defective products, and a second driver for controlling the positions of the first container and the second container so that one of them is connected to the output port of the preparation chip. The first driver, the pressure sensor and the second driver are all electrically connected to the main control module. An external disposable syringe is used instead of the liquid supply tube, and the first driver drives the propeller to advance the syringe piston handle. Not only can the stability of the first driver driving the propeller ensure the stability of the solution pumped out of the syringe, thereby ensuring the preparation accuracy and consistency of the prepared product, but also the workload of cleaning and sterilization after the preparation is completed, thereby improving the preparation efficiency and avoiding the contamination that is easily caused when preparing reagents of different processes.

[0005] The preparation control method includes:

[0006] S1, the system is initialized, and then the syringes loaded with the solution required for preparation are connected to the input ports of the preparation chip one by one, and the preparation parameters of each input phase of the preparation chip are set in the preparation system, and then the preparation is started; wherein the preparation parameters include the number of input phases involved in the preparation n, the total stroke F of the propeller corresponding to the xth input phase x , the total volume U of the syringe corresponding to the xth input x , the total stroke H of the piston handle of the syringe corresponding to the xth input x , the volume of the discarded liquid of the xth input phase M x , the preparation volume N of the xth input phase x , Set flow rate V of the xth input phase x ; Among them, M x +N x ≤U x, 1<x≤n, and x is an integer representing the number of the input phase; specifically, the volume of discarded liquid refers to the initial preparation stage. Due to the unstable flow rate of the solution in each input phase, the qualified rate of the mixed product is low. Therefore, the product solution output in the initial preparation stage needs to be discarded to prevent affecting the qualified products output later. This part of the solution volume that needs to be discarded is the volume of discarded liquid. System initialization includes the main control module controlling each first driver to drive the propeller to move to the farthest position from the preparation chip, and marking the position as the initial position, which is convenient for the operator to connect the syringe to avoid interference, and it is also convenient to locate the initial point to monitor the propulsion distance of the propeller. Furthermore, the total stroke F of the propeller x It refers to the distance that the pusher moves from the initial position until it contacts the syringe piston handle and pushes the piston handle to pump out all the solution inside the syringe. The total stroke of the syringe piston handle H x Refers to the volume U loaded in the syringe x The distance that the piston handle pushes out all the solution when the piston is filled with solution.

[0007] S2, the main control module controls the first driver to drive the propeller close to the syringe piston handle until the propeller contacts the piston handle and the pressure sensor sends a pressure signal. At the same time, the main control module marks the current position of the propeller as the preparatory position. At this time, the drive component corresponding to the xth input phase is in the preparatory state. Then the main control module determines the distance f between the preparatory position and the initial position. x Calculate the volume G of the solution loaded in the syringe corresponding to the xth input x =[f x -(F x -H x ) ÷H x ×U x ; and the distance L that the piston handle of the corresponding syringe needs to advance to discharge the loaded solution x = F x -f x ; and according to G x and L x Calculate the propulsion speed v of the propulsion element corresponding to the xth input x =L x ÷(G x ÷V x); the pusher can stop automatically after reaching the preparation position through the pressure sensor, without the need for manual control by the operator, ensuring the accuracy of the preparation position; at the same time, the volume of the solution in the syringe is automatically calculated according to the preparation position of the pusher and the relevant model of the syringe used, which also avoids the errors that are easy to be caused by manually entering the amount of solution in the syringe, ensuring the accuracy of parameters; and the propulsion speed of the pusher is calculated according to the set preparation parameters, which can make the pusher stably advance during the preparation process, ensuring the stability and accuracy of the delivered solution, and then ensuring the consistency of the mixed prepared solution.

[0008] S3, the main control module controls the first driver to drive the propulsion member at a propulsion speed v x Push the syringe piston handle, and the main control module monitors the real-time distance between the current position of the pusher and the preparatory position. x , and calculate the actual amount of solution g that has been output x =l x ÷L x ×G x Then the main control module will calculate the actual solution volume g x and the volume of the discarded liquid M x For comparison, if g x <M x , then continue to advance and monitor; if g x ≥M x , then execute step S4; by monitoring the real-time position of the propulsion member, the actual amount of solution output is calculated to facilitate judgment on whether the waste liquid volume has been reached.

[0009] S4, the main control module controls the first driver to stop driving the propulsion member, and controls the second driver to connect the first container with the output port of the prepared chip, and then controls the first driver to continue driving the propulsion member at a propulsion speed v x Push the syringe piston handle; when the output solution volume has reached the waste solution volume, the second driver automatically switches the collection container to distinguish the waste solution from the qualified solution to be collected, thereby realizing automated preparation and collection.

[0010] S5. The main control module continuously monitors the real-time distance l x And the actual solution volume g x , and the actual solution volume g x With preparation volume N x For comparison, if g x <N x , then continue to advance and monitor; if any input phase g x ≥M x, the main control module controls all the first drivers to stop driving the propulsion element and ends the preparation; after switching the collection container, it enters the normal preparation process, and judges the preparation progress of each input phase by real-time monitoring of the actual output solution volume. When the actual solution volume of any input phase reaches the preparation volume, all the input phases involved in the preparation are controlled to stop delivering the solution to prevent the amount of solution pre-extracted in the syringe from causing an error in the mixing ratio of the product, thereby ensuring product quality.

[0011] Through the above-mentioned preparation control method, after the operator sets the preparation parameters such as the waste liquid volume, preparation volume, and set flow rate in the preparation system according to the preparation process, the preparation system can automatically convert the preparation parameters into system operation instructions, and drive the syringe to output the solution for preparation at a uniform and stable propulsion speed, avoiding the problem of poor stability of traditional liquid pumps and being easily affected by factors such as solution pressure and temperature, thereby ensuring preparation accuracy and consistency of the prepared products.

[0012] Furthermore, in step S1, the system initialization further includes the main control module controlling the second driver to connect the second container to the output port of the preparation chip. The second driver drives the second container to connect to the output port of the preparation chip to facilitate the collection of waste products in the subsequent preparation stage.

[0013] Furthermore, in step S2, the method in which the main control module controls the driving component corresponding to the x-th input phase to enter the preparatory state includes: the main control module sends a start signal to the first driver, and the first driver drives the propeller to approach the syringe piston handle according to the start signal, and when the pressure sensor detects the pressure between the propeller and the piston handle, the main control module controls the first driver to stop driving and records the number of positions y, and marks the current position of the propeller as the preparatory position. The position of the propeller is controlled by the signal generated by the pressure sensor to ensure the accuracy of the preparatory position of the propeller, avoiding the problem of manual control of the propeller, which is prone to errors.

[0014] Furthermore, the preparation parameters also include the trigger pressure value Q of the xth input phase x In step S2, the method in which the main control module controls the driving component corresponding to the xth input phase to enter the preparatory state also includes: when the pressure sensor detects the pressure generated between the propulsion member and the piston handle, real-time monitoring of the actual pressure value p of the pressure applied by the piston handle to the propulsion member x And send it to the main control module, the main control module determines the actual pressure value p in real time x Is it less than the trigger pressure value Q? x If not, the main control module controls the first driver to stop driving. By setting the trigger pressure threshold of the pressure sensor, the propeller is controlled to stop moving when the pressure applied by the piston handle reaches a certain value, ensuring the accurate preparation position of the propeller and avoiding false triggering caused by improper installation of the syringe.

[0015] Furthermore, between step S2 and step S3, the following steps are also included:

[0016] Step S2.1: The main control module compares the number of in-place pushers y with n. If y < n, the current step is repeated. Otherwise, step S3 is executed. By comparing the number of in-place pushers in each input phase with the number of input phases involved in the preparation, it is ensured that all pushers of all input phases have reached the preparation position before proceeding to the next step of preparation to avoid errors in the preparation process.

[0017] Furthermore, the preparation parameters also include the pressure threshold P of the xth input phase x Steps S2 to S5 also include: the pressure sensor monitors the actual pressure value p of the pressure applied by the piston handle to the propulsion member in real time x And send it to the main control module, the main control module determines the actual pressure value p in real time x Is it less than the pressure threshold P? x If not, the main control module controls all first drivers to stop running. By setting the pressure threshold and monitoring the actual pressure value collected by the pressure sensor in real time, it is ensured that when a certain input phase is blocked and the solution pressure exceeds the normal value, the machine can be automatically shut down in time to avoid production accidents.

[0018] Furthermore, the preparation system further includes a storage module electrically connected to the main control module. Steps S2 to S5 further include: the main control module receives the actual pressure value p x Upload to the storage module for storage. The storage module can record and save the real-time pressure data fed back by the syringe piston handle on the pusher during the preparation process, so that the operator can retrieve the data for discussion later, find problems, improve the process, etc.

[0019] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:

[0020] The preparation control method based on droplet microfluidics technology of the present invention adopts a disposable syringe in the preparation system to replace the traditional liquid supply tube, and adopts a first driver and a propeller to cooperate with the syringe to output the solution, which not only avoids the instability of using a liquid pump to output the solution in traditional equipment, but also prevents the risk of reagent contamination due to inadequate cleaning; and, through the control method and the preparation system, the preparation parameters input by the operator can be automatically converted into control instructions for controlling the operation of the preparation system, so that the preparation system can automatically, accurately and stably advance the preparation process according to the process requirements, which can not only ensure the preparation efficiency, but also ensure the accuracy of the preparation process and the consistency of the product. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Hereinafter, some specific embodiments of the present invention will be described in detail in an exemplary and non-limiting manner with reference to the accompanying drawings. The same reference numerals in the accompanying drawings indicate the same or similar components or parts. It should be understood by those skilled in the art that these drawings are not necessarily drawn to scale. In the accompanying drawings:

[0022] Figure 1 is a system architecture diagram of an embodiment of the present invention;

[0023] Figure 2 yes Figure 1 Schematic diagram of the structure of the preparation system in the embodiment shown Figure 1 ;

[0024] Figure 3 yes Figure 1 Schematic diagram of the structure of the preparation system in the embodiment shown Figure 2 ;

[0025] The reference numerals are described as follows:

[0026] 1. Prepare chip; 2. Drive component; 21. Propelling member; 22. First driver; 23. Pressure sensor; 3. Collection component; 31. First container; 32. Second container; 33. Second driver; 4. Main control module; 5. Storage module. DETAILED DESCRIPTION

[0027] The technical solution of the present invention will be described clearly and completely below in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] In addition, the technical features involved in the different embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0029] Reference Figure 1-3This embodiment provides a preparation control method based on droplet microfluidics technology, using a droplet microfluidics preparation system, the preparation system includes a preparation chip 1, a drive component 2, a collection component 3, and a main control module 4. The preparation chip 1 has at least two input ports, each of which is detachably connected to the cone head of a syringe, and each syringe is filled with a solution required for preparation. In actual production, the specific syringe and solution type used in the preparation can be selected according to demand. The preparation chip 1 also has an output port for outputting a mixed solution product. The number of drive components 2 is consistent with the number of input ports, and is used to drive the syringe connected to the input port to pump out the solution. The drive component 2 includes a pusher 21 that is slidably arranged and pushes the syringe piston handle by sliding, a first driver 22 for driving the pusher 21 to slide, and a pressure sensor 23 that is arranged on the pusher 21 and is used to monitor the pressure applied by the syringe piston handle to the pusher 21. The collection component 3 is used to collect products, including at least one first container 31 for collecting good products, at least one second container 32 for collecting defective products, and a second driver 33 for controlling the positions of the first container 31 and the second container 32 so that one of them is connected to the output port of the preparation chip 1. The first driver 22, the pressure sensor 23 and the second driver 33 are all electrically connected to the main control module 4; the main control module 4 controls the operation of the entire preparation system. An external disposable syringe is used instead of the liquid supply tube, and the first driver 22 drives the propeller 21 to advance the syringe piston handle. This not only ensures the stability of the syringe pumping out the solution through the stability of the driving of the propeller 21 by the first driver 22, thereby ensuring the preparation accuracy and consistency of the prepared product, but also reduces the workload of cleaning and sterilization after the preparation is completed, improves the preparation efficiency, and avoids the contamination that is easily caused when preparing reagents of different processes.

[0030] The preparation control method includes:

[0031] S1, system initialization, then the syringes loaded with the solution required for preparation are connected to the input ports of the preparation chip 1 one by one, and the preparation parameters of each input phase of the preparation chip 1 are set in the preparation system, and then the preparation is started; wherein the preparation parameters include the number of input phases involved in the preparation n, the total stroke F of the propeller corresponding to the xth input phase x , the total volume U of the syringe corresponding to the xth input x , the total stroke H of the piston handle of the syringe corresponding to the xth input x , the volume of the discarded liquid of the xth input phase M x , the preparation volume N of the xth input phase x , Set flow rate V of the xth input phase x ; Among them, M x +N x ≤U x, 1<x≤n, and x is an integer representing the number of the input phase; specifically, the volume of discarded liquid refers to the initial stage of preparation. Due to the unstable flow rate of the solution in each input phase, the qualified rate of the mixed product is low. Therefore, it is necessary to discard the product solution output in the initial stage of preparation to prevent affecting the qualified products output later. The volume of this part of the solution that needs to be discarded is the volume of discarded liquid. System initialization includes the main control module controlling each first driver to drive the propeller to move to the farthest position from the preparation chip, and marking the position as the initial position, which is convenient for the operator to connect the syringe to avoid interference, and it is also convenient to locate the initial point to monitor the propulsion distance of the propeller. Furthermore, the total stroke Fx of the propeller refers to the distance the propeller is pushed from the initial position until it abuts against the syringe piston handle and pushes the piston handle to pump out all the solution in the syringe; and the total stroke H of the syringe piston handle x The syringe is loaded with a volume U x When the solution is pumped out, the piston handle pumps out the distance required to advance all the solution. At the same time, the main control module 4 controls the second driver 33 to connect the second container 32 with the output port of the preparation chip, so as to collect the waste product in the subsequent preparation early stage.

[0032] S2, the main control module 4 controls the first driver 22 to drive the propeller 21 to approach the syringe piston handle until the propeller 21 abuts against the piston handle and the pressure sensor 23 sends a pressure signal. At the same time, the main control module 4 marks the current position of the propeller 21 as the preparatory position. At this time, the drive assembly 2 corresponding to the x-th input phase is in the preparatory state. Then the main control module 4 determines the distance f between the preparatory position and the initial position. x Calculate the volume G of the solution loaded in the syringe corresponding to the xth input x =[f x -(F x -H x )]÷H x ×U x ; and the distance L that the piston handle of the corresponding syringe needs to advance to discharge the loaded solution x = F x -f x ; and according to G x and L x Calculate the propulsion speed v of the propulsion member 21 corresponding to the xth input x =L x ÷(G x ÷V x); the pusher 21 can stop automatically after reaching the preparation position through the pressure sensor 23, without the need for manual control by the operator, ensuring the accuracy of the preparation position; at the same time, the volume of the solution in the syringe is automatically calculated according to the preparation position of the pusher and the relevant model of the syringe used, which also avoids the errors that are easy to be caused by manually entering the amount of solution in the syringe, ensuring the accuracy of parameters; and the propulsion speed of the pusher 21 is calculated according to the set preparation parameters, so that the pusher 21 can be stably advanced during the preparation process, ensuring the stability and accuracy of the delivered solution, and then ensuring the consistency of the mixed prepared solution.

[0033] S3, the main control module 4 controls the first driver 22 to drive the propulsion member 21 at a propulsion speed v x Push the syringe piston handle, and the main control module 4 monitors the real-time distance l between the current position of the propulsion member 21 and the preparatory position in real time x , and calculate the actual amount of solution g that has been output x =l x ÷L x ×G x Then the main control module 4 will calculate the actual solution volume g x and the volume of the discarded liquid M x For comparison, if g x <M x , then continue to advance and monitor; if g x ≥M x , then execute step S4; by monitoring the real-time position of the propeller 21, the actual amount of solution output is calculated to facilitate judgment on whether the waste liquid volume has been reached.

[0034] In an optional embodiment, the method for the main control module 4 to monitor the current position of the propulsion member 21 in real time is: a position sensor is set on the propulsion member 21, and the main control module 4 starts the position sensor to record the initial point when marking the initial position of the propulsion member 21, and then the main control module 4 reads the position information collected by the position sensor in real time to calculate the distance between the initial position and the preparatory position, and the real-time distance between the subsequent real-time position of the propulsion member and the preparatory position;

[0035] In another optional implementation scheme, the method for the main control module 4 to monitor the current position of the propulsion member 21 in real time is: the first driver 22 is set as a servo motor, and the distance that the servo motor can drive the propulsion member 21 to advance in a single signal pulse is preset according to the transmission structure (such as a screw transmission structure) between the first driver 22 and the propulsion member 21, and then the main control module 4 records the number of signal pulses sent to the first driver 22 in real time, and calculates the real-time distance of the propulsion member 21.

[0036] S4, the main control module 4 controls the first driver 22 to stop driving the propulsion member 21, and controls the second driver 33 to connect the first container 31 with the output port of the preparation chip 1, and then controls the first driver 22 to continue driving the propulsion member 21 at a propulsion speed v x Push the syringe piston handle; when the output solution volume has reached the waste solution volume, the second driver 33 automatically switches the collection container to distinguish the waste solution from the qualified solution to be collected, thereby realizing automated preparation and collection.

[0037] S5, the main control module 4 continuously monitors the real-time distance l x And the actual solution volume g x , and the actual solution volume g x With preparation volume N x For comparison, if g x <N x , then continue to advance and monitor; if any input phase g x ≥N x , the main control module 4 controls all the first drivers 22 to stop driving the propeller 21 and ends the preparation; after switching the collection container, the normal preparation process is entered, and the actual output solution volume is monitored in real time to judge the preparation progress of each input phase. When the actual solution volume of any input phase reaches the preparation volume, all the input phases involved in the preparation are controlled to stop delivering the solution to prevent the amount of solution pre-extracted in the syringe from being wrong, which may cause an error in the mixing ratio of the product and ensure product quality.

[0038] In a more preferred embodiment, in step S2, the method in which the main control module 4 controls the drive component 2 corresponding to the x-th input phase to enter a preparatory state includes: the main control module 4 sends a start signal to the first driver 22, and the first driver 22 drives the thruster 21 to approach the syringe piston handle according to the start signal. When the pressure sensor 23 detects the pressure generated between the thruster 21 and the piston handle, the main control module 4 controls the first driver 22 to stop driving and records the number of positions y, and marks the current position of the thruster 21 as the preparatory position. The position of the thruster 21 is controlled by the signal generated by the pressure sensor 23 to ensure that the preparatory position of the thruster 21 is accurate, thereby avoiding the problem of errors that are prone to occur when manually controlling the thruster 21.

[0039] In a more preferred embodiment, the preparation parameters also include the trigger pressure value Q of the xth input phase x In step S2, the method in which the main control module controls the driving component corresponding to the xth input phase to enter the preparatory state also includes: when the pressure sensor detects the pressure generated between the propulsion member and the piston handle, real-time monitoring of the actual pressure value p of the pressure applied by the piston handle to the propulsion member x And send it to the main control module, the main control module determines the actual pressure value p in real time xIs it less than the trigger pressure value Q? x If not, the main control module controls the first driver to stop driving. By setting the trigger pressure threshold of the pressure sensor, the propeller is controlled to stop moving when the pressure applied by the piston handle reaches a certain value, ensuring the accurate preparation position of the propeller and avoiding false triggering caused by improper installation of the syringe.

[0040] In a more preferred embodiment, the step between step S2 and step S3 further includes:

[0041] Step S2.1, the main control module 4 compares the number of in-place components y with n. If y<n, the current step is repeated. Otherwise, step S3 is executed. By comparing the number of in-place components in each input phase with the number of input phases involved in the preparation, it is ensured that the next step of preparation is carried out only after all the components of the input phases have reached the preparation position, so as to avoid errors in the preparation process.

[0042] In a more preferred embodiment, the preparation parameters also include the pressure threshold P of the xth input phase. x Steps S2 to S5 also include: the pressure sensor 23 monitors the actual pressure value p of the pressure applied by the piston handle to the propulsion member 21 in real time x And send it to the main control module 4, the main control module 4 determines the actual pressure value p in real time x Is it less than the pressure threshold P? x If not, the main control module 4 controls all first drivers 22 to stop running. By setting the pressure threshold and monitoring the actual pressure value collected by the pressure sensor in real time, it is ensured that when a certain input phase is blocked and the solution pressure exceeds the normal value, the machine can be automatically shut down in time to avoid production accidents.

[0043] In a more preferred embodiment, the preparation system further comprises a storage module 5 electrically connected to the main control module 4, and steps S2 to S5 further comprise: the main control module 4 receives the actual pressure value p x The data is uploaded to the storage module 5 for storage. The storage module 5 can record and save the real-time pressure data fed back by the syringe piston handle on the pusher during the preparation process, so that the operator can retrieve the data for discussion later, find problems, improve the process, etc.

[0044] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:

[0045] The preparation control method based on droplet microfluidics technology of the present invention adopts a disposable syringe in the preparation system to replace the traditional liquid supply tube, and adopts a first driver and a propeller to cooperate with the syringe to output the solution, which not only avoids the instability of using a liquid pump to output the solution in traditional equipment, but also prevents the risk of reagent contamination due to inadequate cleaning; and, through the control method and the preparation system, the preparation parameters input by the operator can be automatically converted into control instructions for controlling the operation of the preparation system, so that the preparation system can automatically, accurately and stably advance the preparation process according to the process requirements, which can not only ensure the preparation efficiency, but also ensure the accuracy of the preparation process and the consistency of the product.

[0046] The above embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with this technology to understand the contents of the present invention and implement them accordingly. They cannot be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A preparation control method based on droplet microfluidics technology, characterized in that: A droplet microfluidics preparation system is used, the preparation system comprising a preparation chip (1) having at least two input ports detachably connected to the cone head of a syringe containing a solution required for preparation and an output port for outputting a mixed solution product, a driving component (2) having the same number as the input ports and used to drive the syringes connected to the input ports to pump out the solution, a collecting component (3) for collecting the product, and a main control module (4) for controlling the operation of the preparation system, wherein the driving component (2) comprises a pusher (21) which is slidably arranged and pushes the syringe piston handle by sliding, and a first pusher for driving the pusher (21) to slide. a driver (22), a pressure sensor (23) disposed on the pushing member (21) and used for monitoring the pressure exerted on the pushing member (21) by the syringe piston handle, the collection component (3) comprising at least one first container (31) for collecting good products, at least one second container (32) for collecting bad products, and a second driver (33) for controlling the positions of the first container (31) and the second container (32) so that one of them is connected to the output port of the preparation chip (1), the first driver (22), the pressure sensor (23) and the second driver (33) are all electrically connected to the main control module (4); The preparation control method comprises: S1, system initialization, then connecting the syringes loaded with the solution required for preparation to the input ports of the preparation chip (1) one by one, and setting the preparation parameters of each input phase of the preparation chip (1) in the preparation system, and then starting preparation; wherein the preparation parameters include the number of input phases involved in the preparation n, the total stroke F of the propulsion member (21) corresponding to the xth input phase x , the total volume U of the syringe corresponding to the xth input x , the total stroke H of the piston handle of the syringe corresponding to the xth input x , the volume of the discarded liquid of the xth input phase M x , the preparation volume N of the xth input phase x , Set flow rate V of the xth input phase x ; Among them, M x +N x ≤U x , 1<x≤n, the system initialization includes the main control module (4) controlling each first driver (22) to drive the propulsion member (21) to move to the farthest position from the prepared chip (1), and marking the position as the initial position; S2, the main control module (4) controls the first driver (22) to drive the propeller (21) to approach the syringe piston handle until the propeller (21) abuts against the piston handle and the pressure sensor (23) sends a pressure signal. At the same time, the main control module (4) marks the current position of the propeller (21) as the preparation position. At this time, the drive component (2) corresponding to the xth input phase is in the preparation state. Then, the main control module (4) adjusts the distance f between the preparation position and the initial position according to the distance f between the preparation position and the initial position. x Calculate the volume G of the solution loaded in the syringe corresponding to the xth input x =[f x -(F x -H x )]÷H x ×U x ; and the distance L that the piston handle of the corresponding syringe needs to advance to discharge the loaded solution x = F x -f x ; and according to G x and L x Calculate the propulsion speed v of the propulsion member (21) corresponding to the xth input x =L x ÷(G x ÷V x ); S3, the main control module (4) controls the first driver (22) to drive the propulsion member (21) at a propulsion speed v x The syringe piston handle is pushed, and at the same time the main control module (4) monitors in real time the real-time distance l between the current position of the propulsion member (21) and the preparatory position x , and calculate the actual amount of solution g that has been output x =l x ÷L x ×G x , and then the main control module (4) converts the actual solution volume g x and the volume of the discarded liquid M x For comparison, if g x <M x , then continue to advance and monitor; if g x ≥M x , then execute step S4; S4, the main control module (4) controls the first driver (22) to stop driving the propulsion member (21), controls the second driver (33) to connect the first container (31) to the output port of the preparation chip (1), and then controls the first driver (22) to continue driving the propulsion member (21) at a propulsion speed v x Push the syringe plunger handle; S5, the main control module (4) continuously monitors the real-time distance l x And the actual solution volume g x , and the actual solution volume g x With preparation volume N x For comparison, if g x <N x , then continue to advance and monitor; if any input phase g x ≥N x , the main control module (4) controls all first drivers (22) to stop driving the propulsion members (21), thereby ending the preparation.

2. The preparation control method based on droplet microfluidics technology according to claim 1, characterized in that: In step S1, the system initialization further includes the main control module (4) controlling the second driver (33) to connect the second container (32) to the output port of the prepared chip.

3. The preparation control method based on droplet microfluidics technology according to claim 1, characterized in that: In step S2, the method in which the main control module (4) controls the drive component (2) corresponding to the xth input phase to enter a preparatory state comprises: the main control module (4) sends a start signal to the first driver (22), and the first driver (22) drives the propeller (21) to approach the syringe piston handle according to the start signal; when the pressure sensor (23) detects that pressure is generated between the propeller (21) and the piston handle, the main control module (4) controls the first driver (22) to stop driving and records the number of positions y, and marks the current position of the propeller (21) as the preparatory position.

4. The preparation control method based on droplet microfluidics technology according to claim 3, characterized in that: The preparation parameters also include the trigger pressure value Q of the xth input phase x In step S2, the method in which the main control module (4) controls the driving component (2) corresponding to the xth input phase to enter the ready state further includes: when the pressure sensor (23) detects that pressure is generated between the propulsion member (21) and the piston handle, real-time monitoring of the actual pressure value p of the pressure applied by the piston handle to the propulsion member (21) x The pressure is sent to the main control module (4), and the main control module (4) determines the actual pressure value p in real time. x Is it less than the trigger pressure value Q? x If not, the main control module (4) controls the first driver (22) to stop driving.

5. The preparation control method based on droplet microfluidics technology according to claim 3, characterized in that: The steps between step S2 and step S3 also include: Step S2.1: The main control module (4) compares the number of in-place items y with n. If y<n, the current step is repeated; otherwise, step S3 is executed.

6. The preparation control method based on droplet microfluidics technology according to claim 1, characterized in that: The preparation parameters also include the pressure threshold P of the xth input phase x Steps S2 to S5 also include: the pressure sensor (23) monitors in real time the actual pressure value p of the pressure applied by the piston handle to the propulsion member (21). x The pressure is sent to the main control module (4), and the main control module (4) determines the actual pressure value p in real time. x Is it less than the pressure threshold P? x If not, the main control module (4) controls all first drivers (22) to stop running.

7. The preparation control method based on droplet microfluidics technology according to claim 6, characterized in that: The preparation system further comprises a storage module (5) electrically connected to the main control module (4), and steps S2 to S5 further comprise: the main control module (4) receives the actual pressure value p x Upload to the storage module (5) for storage.

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