A laboratory automation liquid path transmission module and its control method

Abstract

The present invention discloses a laboratory automation liquid path transmission module and its control method. The liquid path transmission module includes at least two groups of pump-valve modules, a control module and a terminal. The pump-valve module at least includes an injection pump A, a reversing valve A, an injection pump B and a reversing valve B. The injection pump A and the injection pump B are respectively connected to the pump-valve interfaces of the reversing valves A and B. The cross-pump interfaces of the injection pump A and the injection pump B are interconnected by pipelines. The reversing valve A or the reversing valve B also has a sample interface connected to the medicine and an instrument interface connected to the inlet and outlet of the instrument module. When the cross-pump interfaces of the injection pump A and the injection pump B are connected, the control module controls the piston rod of the injection pump A to move downward while the piston rod of the injection pump B moves upward at the same rate. The present invention uses the liquid path transmission module to integrally connect multiple instrument modules across regions, realizing the automatic step-by-step progress of experimental operations.

Description

Technical Field

[0001] The present invention relates to a laboratory automated liquid path transmission module and a control method therefor. Background Art

[0002] In existing laboratories, most of the experimental operations need to be carried out manually for assembly and operation, which greatly depends on the experience and proficiency of the experimental personnel. During the operation process, due to the different operation methods of the personnel, the yield stability of the product is poor. In some dangerous experimental operations, there are safety hazards and it is possible to cause damage to the person and property. Therefore, it is necessary to further change the traditional experimental operation method.

[0003] CN113495165A discloses a continuous liquid injection system and a control method therefor, which realizes continuous injection of a protected sample by means of alternating operation of multiple injection pumps. In essence, it realizes sampling and injection in succession within an extremely short time by the cooperation of a pump and a valve. Although it can realize liquid feeding in an almost continuous manner, its use also has limitations: this method can only be applied to a single operation. In essence, it is to inject samples into a single detection chamber or dispersed operation units by means of the alternating continuous operation mode of a double pump. It cannot realize the integration of operation units and cross-region fluid connection, cannot meet the cross-region integration of multiple operation units, and cannot realize the automated progress of experimental operations, with great limitations in use. At the same time, the injection pumps of this patent are all connected to the same injection pump, resulting in large wear on the valve body, and the liquid transmission path is short, with great limitations in use and cannot be applied to complex experimental operation processes.

[0004] Therefore, how to improve the structure of the liquid path transmission module and realize the automated operation of multi-step experimental processes, thereby maintaining the stability of reaction conditions and increasing the yield of the product becomes very important. Summary of the Invention

[0005] In order to solve the above technical problems, the purpose of the present invention is to provide a laboratory automated liquid path transmission module and a control method therefor.

[0006] The present invention is realized through the following technical solutions: A laboratory automated liquid path transmission module, including a pump valve module (1), a control module (2) and a terminal (3), the control module (2) is communicatively connected to the terminal (3), the pump valve module (1) at least includes an injection pump A, a reversing valve A, an injection pump B and a reversing valve B, both the reversing valve A and the reversing valve B are multi-channel valve bodies, and the connection of different channels is realized by the rotation of the rotor in the valve body; the injection pump A and the injection pump B are respectively directly connected to the pump valve interfaces (A1) of the reversing valve A and the pump valve interface of the reversing valve B, and the cross-pump interface (A2) of the injection pump A is interconnected with the cross-pump interface (B2) of the injection pump B by a pipeline, and the reversing valve A or the reversing valve B also has a sample interface connected to the drug and an instrument interface connected to the inlet and outlet of the instrument module;

[0007] The control module (2) is electrically connected to the injection pump A, the reversing valve A, the injection pump B and the reversing valve B, and the control module (2) can control the switching of the connection between different interfaces of the reversing valve A or the reversing valve B; when the cross-pump interface (A2) of the injection pump A is connected to the cross-pump interface (B2) of the injection pump B, the control module controls the piston rod of the injection pump A to move downward while the piston rod of the injection pump B moves upward at the same rate.

[0008] Preferably, the instrument interface of the reversing valve A or the reversing valve B can be combined and connected with one or several of a reaction module, a mixing module, an extraction module, a rotary evaporation module, a distillation device or a drying and filtering module.

[0009] Preferably, the sample interface of the reversing valve A is connected to the drug, two of the instrument interfaces (A5, A6) of the reversing valve A are respectively connected to the interface (P1) of a three-way valve (P) and the outlet (S12) of the reaction module, the other two interfaces (P2, P3) of the three-way valve are respectively connected to the inlet (S11) of the reaction module and the first inlet (S21) of the mixing module, and the other two instrument interfaces (A7, A8) of the reversing valve A are respectively connected to the inlet (S31) and the outlet (S32) of the extraction module; the sample interface of the reversing valve B is connected to the drug, and one of the instrument interfaces (B6) of the reversing valve B is connected to the second inlet (S22) of the mixing module, and the other two instrument interfaces (B7, B8) of the reversing valve are respectively connected to the inlet (S41) and the outlet (S42) of the drying and filtering module; the mixing module also has a mixing channel (S23), and the outlet of the mixing channel is connected to the inlet (S11) of the reaction module.

[0010] Preferably, the pump valve module (1) further includes an injection pump C and a reversing valve C. The injection pump C is connected to the pump valve interface (C1) of the reversing valve C, and the cross-pump interface (C2) of the reversing valve C is connected to the other cross-pump interface (B7’) of the reversing valve B.

[0011] Preferably, the sample interface of the reversing valve A is connected to the drug. The two instrument interfaces (A7’, A9’) of the reversing valve A are respectively connected to the inlet (S11) and the outlet (S12) of the reaction module. A distillation device (S6) is further installed on the reaction module. The distillation device (S6) is connected to the reaction module (S1) through a communication path (S61). The outer layer of the communication path (S61) is coated with a heat-insulating layer. The distillation device (S6) has a connecting bottle body (S62). The outlet (S63) of the connecting bottle body is connected to another instrument interface (A8’) of the reversing valve A; the reversing valve B has a sample interface, and two of its instrument interfaces (B4’, B5’) are respectively connected to the inlet (S31) and the outlet (S32) of the extraction module. The other two interfaces (B8, B9) of the reversing valve B are respectively connected to the outside and the collection bottle (k3); the reversing valve C has a sample interface (C3), and three of its instrument interfaces (C4, C5, C7) are respectively connected to the inlet (S41) and the outlet (S42) of the drying and filtering module and the rotary evaporation module. One of the outlets of the rotary evaporation module is connected to the product collection bottle, and the other outlet is connected to the intermediate bottle (k1). The intermediate bottle (k1) is connected to the interface (C6) of the reversing valve C.

[0012] Preferably, the drying and filtering module includes a drying and filtering bottle body and an air extraction device. A sand core (43) is arranged inside the drying and filtering bottle body. A drying agent is placed on the sand core (43). An air extraction channel (45) is arranged on the side wall of the drying and filtering bottle body. The air extraction channel (45) is connected to the air extraction device. The air extraction channel (45) has an extending channel (46) extending into the drying and filtering bottle body. The end of the extending channel (46) is provided with the air extraction port (47). The extending channel (46) extends towards the side wall of the drying and filtering bottle body where the air extraction channel (45) is arranged, and its inner diameter gradually decreases in the extending direction of the air extraction port (47).

[0013] The present invention also provides a control method for a laboratory automated liquid path transmission module. The control method includes the following steps:

[0014] Step S10: Obtain the volume parameter of the terminal;

[0015] Step S20: In the initial state, the control module (2) controls the pump valve module (1) to start operating. The pump valve module (1) sucks a fixed amount of liquid for inlet. Among them, the pump valve module (1) at least includes an injection pump A, a reversing valve A, an injection pump B, and a reversing valve B;

[0016] Step S30: Control the reversing valve A and the reversing valve B to reverse and communicate with each other simultaneously. While the piston rod of the injection pump A moves downward, the piston rod of the injection pump B moves upward at the same rate, and all the liquid in the injection pump A is transferred and transported into the injection pump B;

[0017] Step S40: Control the rotor of the reversing valve B to rotate so that the interface between the injection pump B and the reversing valve B is connected. The piston rod of the injection pump B moves downward to push the liquid inside it out to the corresponding position.

[0018] Preferably, the instrument interface of the pump valve module can be connected to different instrument modules. The different instrument modules and the terminal are communicatively connected through a communication interface. When starting, enter the comparison mode, including the following steps:

[0019] Set the connection methods of different instrument modules on the display interface of the terminal (3);

[0020] The terminal (3) receives the signals sent by the assembled different instrument modules through their respective communication interfaces and parses them;

[0021] Compare the set connection method with the parsed connection method to determine whether the connection method is correct. If it is correct, enter the experimental mode. If it is incorrect, give corresponding prompts on the terminal.

[0022] Preferably, the different instrument modules are connected through a connection pipeline. An identification device is provided on the connection pipeline, and the identification device is communicatively connected to the terminal.

[0023] Preferably, the application program at the terminal uses the Bayesian theory to predict the reaction products. By inputting experimental data into the prediction model for calculation and prediction, and then comparing the corresponding experimental data with the prediction results to judge the accuracy of the model, and continuously iterating and optimizing until the accuracy reaches the set standard.

[0024] The present invention also provides a control method for a laboratory automated liquid path transmission module, including a liquid path transmission module. The pump valve module at least includes first, second, and third groups of pump valve modules (1A, 1B, 1C) that are bidirectionally connected to each other. The first and third groups of pump valve modules (1A, 1C) are connected to each other. The steps for the terminal to automatically search for the shortest path include:

[0025] Step 1: Establish a node graph based on the connection paths of the pump valve module;

[0026] Step 2: Use the node graph to search all paths starting from the starting point of the path. After the search is completed, add the starting point of the path to the list of nodes that have completed the search;

[0027] Step 3: If the path searched in Step 2 does not reach the end point of the path, continue the search with the intermediate connection point as the node, and at the same time add the searched intermediate connection point to the list of nodes that have completed the search until the end point of the path is reached;

[0028] Step 4: Obtain the shortest path by calculating the number of nodes in the searched path.

[0029] The present invention uses a liquid path transmission module to integrally connect and connect multiple instrument modules across regions, automatically execute the instructions of the terminal, and realize the automatic step-by-step progress of experimental operations. It can perform refined operation processing on various experimental processes hierarchically. In this way, not only can the cross-region transmission of liquids be realized, but also the stable output of products can be maintained. Brief Description of the Drawings

[0030] In order to more clearly illustrate the technical solutions of the present invention, the accompanying drawings required for the description of the embodiments or the prior art will be briefly introduced below. Obviously, the accompanying drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, other accompanying drawings can be obtained based on these drawings without creative efforts.

[0031] Figure 1 and Figure 2 is a schematic structural diagram of the laboratory automation liquid path transmission module according to Embodiment 1 of the present invention.

[0032] Figure 3 is a schematic cross-sectional view of the reversing valve A or the reversing valve B of the present invention.

[0033] Figure 4 is a flowchart of the control method of the laboratory automation liquid path transmission module of the present invention.

[0034] Figure 5 is a side view of the reaction module in another embodiment of the present invention.

[0035] Figure 6 The structural diagram of the drying and filtering module in another embodiment of the present invention.

[0036] Figure 7 is a schematic structural diagram of the laboratory automation liquid path transmission module according to Embodiment 2 of the present invention.

[0037] Figure 8This is another cross - regional connection method of the laboratory automation liquid path transmission module of the present invention. Detailed implementation manners

[0038] The following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention.

[0039] The present invention designs a laboratory automation liquid path transmission module, which can be combined with experimental instrument hardware with different functions to form different experimental combinations. This liquid path transmission module can combine different functional experimental instruments across regions and achieve cross - regional connection of different liquid paths.

[0040] Specifically, referring to Attached Figure 1 ~Attached Figure 3 , a laboratory automation liquid path transmission module includes a pump - valve module 1, a control module 2 and a terminal 3. The control module 2 is electrically connected to the pump - valve module 1. Among them, two groups of pump - valve modules 1 at least include an injection pump A, a reversing valve A, an injection pump B and a reversing valve B. The injection pump A or B may include a driving structure, a lead screw, a slider and a syringe. The output shaft of the driving structure is connected to the lead screw, and the slider is arranged on the lead screw. The slider is connected to the piston rod of the syringe. Taking the driving structure as a motor as an example, according to different instructions issued by the control module, the motor is controlled to rotate in different directions. When the motor rotates clockwise, it drives the lead screw to rotate, and the slider on the lead screw moves upward, pulling the piston rod of the syringe upward. The volume of part of the gas in the syringe cavity becomes larger, and the air pressure decreases. While the external atmospheric pressure remains unchanged, the atmospheric pressure presses the liquid into the cavity, realizing the extraction of the liquid. On the contrary, when the motor rotates counter - clockwise, the piston rod of the syringe moves downward, the pressure in the syringe cavity increases, and the liquid is discharged along the passage, realizing the liquid discharge of the injection pump. The reversing valve A or B is a multi - channel valve body, which includes a plurality of channel interfaces. A rotor d is arranged in the reversing valve, and different channel interfaces are connected during the rotation of the rotor, so as to switch to different channels. Taking the middle interface as a common channel as an example, the outlet of the injection pump A is connected to the pump - valve interface A1 of the reversing valve A, and the outlet of the injection pump B is connected to the pump - valve interface B1 of the reversing valve B. At the same time, the cross - pump interface A2 of the reversing valve A and the cross - pump interface B2 of the reversing valve B are connected to each other by a pipeline.

[0041] The control module 2 and the terminal 3 use a communication device (such as Bluetooth wireless communication, WiFi wireless communication, and USB, etc.) to perform information interaction and transmission; the terminal 3 is, for example, a mobile phone, a PC, or a tablet, etc. An application program is installed in the terminal 3. The user inputs corresponding parameters on the display interface of the application program and issues a command to the control module 2. After the control module 2 parses the command, it can control the two groups of pump-valve modules 1 to operate simultaneously and cooperate with each other to complete the transmission of the liquid. Taking the sample interface A3 of the reversing valve A being connected to a certain reactant as an example, the above control module 2 controls the two groups of pump-valve modules 1 to start. The rotor of the reversing valve A rotates so that the pump-valve interface A1 of the reversing valve A is connected to the sample interface A3. The sample interface A3 of the reactant is used for the inflow of the reactant or medicine, and the piston rod of the syringe pump A moves upward to extract a certain volume of liquid; then, the control makes the rotor of the reversing valve A continue to rotate so that the pump-valve interface A1 of the reversing valve A is connected to its cross-pump interface A2. At the same time, the pump-valve interface B1 of the reversing valve B is connected to its cross-pump interface B2, that is, the syringe pump A and the syringe pump B are connected to each other. The control makes the piston rod of the syringe pump A move downward and the piston rod of the syringe pump B move upward at the same rate, so as to realize the transmission of the liquid across the pump-valve. After that, the rotor of the reversing valve B continues to rotate, and the piston rod of the reversing valve B slides downward to press the liquid out to the corresponding reaction flask or other operating positions.

[0042] The terminal 3 is installed with a target application program, which can display the information shown during the operation of the pump-valve module at the display interface and can also facilitate the user to set its parameters accordingly; in order to ensure that the pump-valve module can accurately extract a quantitative volume of liquid, taking the sample interface A3 of the reversing valve A being connected to a certain reactant as an example, referring to the appendix Figure 3 , the control method of the laboratory automation liquid path transmission module is as follows:

[0043] Step S10: Obtain the volume parameter of the terminal;

[0044] Step S20: In the initial state, the control module 2 controls the pump-valve module 1 to start operating, and the pump-valve module 1 sucks a quantitative

[0045] liquid for inflow.

[0046] In one embodiment, before step S20, the pump valve module 1 will pre-extract a certain amount of air and then suck a quantitative amount of liquid for inlet. The volume of air extracted by the pump valve module 1 is preset in the terminal in advance. The pre-extracted air volume is at least equal to the volume of the path between the injection pump A and the inlet of the reactant, preventing the gas in the pipeline from affecting the accuracy of the quantitative extraction of the pump valve module and ensuring that the volume extracted in the injection pump can reach the preset volume parameter. Further, in another embodiment, in order to reduce the volume of air and make the liquid fill the pipeline as much as possible, before step S20, the pump valve module 1 can also be preset to first extract a small amount of liquid and discharge it to the waste liquid interface, so that the sample liquid can fill the pipeline as much as possible, thereby reducing the influence of air in the case of different pipeline specifications.

[0047] Step S30: Control the reversing valve A and the reversing valve B to reverse and communicate simultaneously. The piston rod of the injection pump A moves downward while the piston rod of the injection pump B moves upward at the same rate, and all the liquid in the injection pump A is transferred and transported into the injection pump B.

[0048] In this step, in order to ensure that the pushing and sucking volumes of the two are the same, the pump valve module transmits the moving position or distance information of the two syringes of the same specification to the terminal in real time for comparison, ensuring that the two operate at the same rate and can monitor the working state in a timely manner, and extending the service life of the pump valve module.

[0049] Step S40: The rotor of the reversing valve B rotates, so that the injection pump B is connected to the outlet of the reversing valve B, and the piston rod of the injection pump B moves downward to push the liquid inside it to the corresponding position.

[0050] After step S40, the injection pump A can also be used to suck a preset volume of air into its cavity, and then the reversing valve A and the reversing valve B are connected to each other. The piston rod of the injection pump A moves downward while the piston rod of the injection pump B moves upward at the same rate, so as to discharge the residual liquid in the pipeline into the injection pump B, and then discharge the residual liquid to the corresponding position, ensuring the accuracy of the extracted liquid volume. The laboratory automation liquid path transmission module of the present invention is formed by connecting at least two groups of pump valve modules in series, and the two groups of pump valve modules work simultaneously to realize the cross-pump and cross-region transmission of liquid, and realize the accurate liquid inlet of the pump valve module through the setting of the target application program at the terminal.

[0051] The above-mentioned automated liquid path transmission module can be combined with different instrument modules to form different equipment combinations for cross-regional instrument or drug connection. In one embodiment, the control module 2 of the automated liquid path transmission module can be used as a master control module to communicate with the terminal 3, and the relevant circuits of other combined-connected instruments are connected to the control module 2. The control module is used as a central control platform to parse instructions and control corresponding instruments. When the control module 2 receives an instruction from the terminal 3, the control module 2 parses the instruction and then controls each combined instrument or pump valve module to operate individually or cooperatively, so as to complete the specified relevant reactions or operations.

[0052] In one embodiment, corresponding communication interfaces can also be set on each connected instrument. These communication interfaces can communicate with the terminal 3 separately. After the user sets the corresponding reaction connection combination method on the terminal 3, the user assembles the instruments according to the corresponding reaction connection combination method. When the device is started, it first enters the comparison mode. The respective communication units in the combined instrument devices first send their signals to the terminal 3. The terminal 3 compares the connection method of the combined instruments with the pre-set connection method to determine whether the connection is correct, and then starts the experimental mode operation of the system to prevent the user's connection error from affecting the operation of the system and the output result of the product. Among them, if the terminal determines that the connection method is correct, it enters the experimental mode; if it is determined to be incorrect, a corresponding prompt is given at the terminal. Further, an identification device can also be set at the connection pipeline of each combined instrument. For example, the automatic identification of the pipeline is realized by using the RFID method, and the corresponding connection information is transmitted to the terminal 3 for display, and the dynamic connection of each step is displayed in real time and compared accordingly, so as to more intuitively display the connection information and be able to feedback and find errors in time.

[0053] In addition, in order to obtain the optimal reaction conditions for various reaction operations, the application program at the terminal can use Bayesian theory to predict the product of the reaction, and obtain the optimized conditions of the reaction and a higher product yield from it. By inputting the experimental data into the prediction model for calculation and prediction, and then comparing the corresponding experimental data with the prediction results to judge the accuracy of the model, and continuously iterating and optimizing until the accuracy reaches the set standard.

[0054] Embodiment 1

[0055] Refer to the appendix Figure 1 , by combining the laboratory automated liquid path transmission module with the reaction module S1, mixing module S2, extraction module S3, and drying and filtering module S4 to form a laboratory automated system, under the mode of automatic control, the preparation of Grignard reagent is realized, which can not only maintain the stable output of the product, but also the whole experimental process is automated, with high intelligence and simple operation.

[0056] Refer to the attached Figure 1 , the sample interfaces A3 and A4 of the reversing valve A are respectively connected to the pharmaceutical diethyl ether g1 and sulfuric acid g2, and the interface A5 of the reversing valve A is connected to the first inlets S21 of the reaction module S1 and the mixing module S2 through the three-way valve P. The outlet S12 of the reaction module S1 is connected to the interface A6 of the reversing valve A through a pipeline; in addition, the two interfaces A7 and A8 of the reversing valve A are respectively connected to the inlet S31 and the outlet S32 of the extraction module S3, and the interface A9 of the reversing valve A is a waste liquid channel for discharging the waste liquid out of the system; the sample interfaces B3, B4 and B5 of the reversing valve B are respectively connected to the pharmaceutical n-butyl bromide g3, acetone g4 and 30% sodium carbonate g5, and another interface B6 of the reversing valve B is connected to the second inlet S22 of the mixing module S2. In addition, the interfaces B7 and B8 of the reversing valve B are respectively connected to the inlet S41 and the outlet S42 of the drying and filtering module S4, and the interface B9 of the reversing valve B is a waste liquid channel for discharging the corresponding waste liquid out of the system. The interface P1 of the above three-way valve P is connected to the interface A5 of the reversing valve A, and the interfaces P2 and P3 of the corresponding three-way valve are respectively connected to the inlet S11 of the reaction module and the first inlet S21 of the mixing module S2. The liquids in the two inlets S21 and S22 of the mixing module are mixed in the mixing channel S23 and then flow from the mixing channel to the inlet S11 of the reaction module. The mixing channel S23 is in a curved state, and it can ensure that the liquids at the two inlets are fully mixed evenly in the mixing channel through the extended mixing path setting, so as to ensure the smooth progress of the reaction of the system.

[0057] The above reaction module S1 has multiple openings, one of which is the inlet S11, a stirring device S10 is arranged in one of the openings, and a reflux device can be arranged in another opening; a jacket S13 can be sleeved outside the bottle body of the reaction module S1, and the jacket S13 can realize the high and low temperature control in the reaction module through the circulating connection mode of the circulating oil inlet and the circulating oil outlet with the temperature circulation device; of course, in other reactions, the reaction module S1 can also be placed in a sand bath pot for heating, refer to the attached Figure 5 , at the outlet of the reaction module S1, the liquid at the outlet is pumped out by a sampling pipeline, and the sampling pipeline is composed of a straight pipe channel f1 and an extension channel f2. The extension channel f2 extends out along the outer peripheral contour of the bottle body of the reaction module, and the outlet of the extension channel f2 is connected to the interface A6 of the reversing valve A.

[0058] A conductivity meter 5 is placed at the outlet S32 of the extraction module S3. The conductivity meter 5 includes a positive electrode tube 51 and a negative electrode tube 52. The positive electrode tube 51 and the negative electrode tube 52 can be spaced apart from each other in a physically non-contact manner by using a plurality of tetrafluoro pipe connectors. The middle parts of the positive electrode tube 51 and the negative electrode tube 52 are respectively provided with a positive electrode through groove and a negative electrode through groove for liquid to flow in. The positive electrode tube 51 and the negative electrode tube 52 are connected to the control system by wires. Preferably, the aperture (diameter) of the positive electrode through groove and the negative electrode through groove is 2-3 mm. Taking the separation of the organic phase and the aqueous phase as an example, since the conductivity of the organic phase and the aqueous phase differ by 5-6 orders of magnitude, a numerical mutation will occur when they flow through the positive and negative through grooves, and then it is possible to quickly judge whether the liquid flowing through the pipeline is the organic phase or the aqueous phase through the conductivity mutation between the two liquid phases, without manual judgment operation, and automatically separate the two phases into different liquid bottles, which is fast and convenient.

[0059] The above-mentioned drying and filtering module S4 includes an upper bottle body 41, a lower bottle body 42 and a pumping device (not shown in the figure). The upper and lower bottle bodies can be connected through a ground glass joint. A sand core 43 is arranged in the upper bottle body 41. A desiccant is placed on the sand core 43. The bottom end of the upper bottle body 41 has a liquid outlet pipe 44, and the liquid outlet pipe extends into the lower bottle body 42. At the same time, a pumping channel 45 is also arranged at the position of the upper bottle body 41 corresponding to the liquid outlet pipe. The pumping device pumps air through the pumping channel 45 to form a pressure difference between the upper and lower bottle bodies, and then filters the dried liquid into the lower bottle body 42 by suction; of course, in another embodiment, refer to the appendix Figure 6 The drying and filtering module S4 may also only include a drying and filtering bottle body 41'. The sand core 43 is placed in the drying and filtering bottle body 41'. A pumping channel 45 is opened on the side of the drying and filtering bottle body 41'. The pumping channel 45 is connected to the pumping device. The pumping device can pump out the gas in the drying and filtering bottle body to form a negative pressure at both ends of the sand core, and then use the negative pressure to press the liquid phase from the upper end of the sand core into the bottom of the bottle body to achieve suction filtration; the pumping channel 45 has an extending channel 46 extending into the drying and filtering bottle body. An air extraction port 47 is opened at the end of the extending channel 46. The extending channel 46 extends towards the side wall of the drying and filtering bottle body where the pumping channel 45 is arranged. Preferably, the inner diameter of the extending channel 46 gradually decreases along the direction of the air extraction port 47. Preferably, the extending channel 46 is arranged in an eagle-beak shape.

[0060] The specific steps for the above-mentioned laboratory automation system to automatically prepare Grignard reagent are as follows:

[0061] During automatic operation, first manually put magnesium chips, iodine tablets, and anhydrous potassium carbonate into the bottle body of the reaction module S1 in advance, and then start the device for operation;

[0062] The injection pump A of the liquid path transmission module pumps 15 ml of ethyl ether into the cavity of the injection pump A through the interface A3 of the reversing valve A, and the corresponding liquid and gas are sequentially transported from the cavity of the injection pump A to the bottle body of the reaction module through the interface A5 of the reversing valve A and the interfaces P1 and P2 of the three-way valve P. Then, the stirring device is started for stirring; 2.6 ml of ethyl ether is extracted into the injection pump A through the reversing valve A and sequentially passes through the interface A5 of the reversing valve A and the interfaces P1 and P3 of the three-way valve P, and then enters the mixing channel S23 of the mixing module through the first inlet S21 of the mixing module for mixing. At the same time, 2.4 ml of n-butyl bromide is pumped into the cavity of the injection pump B through the interface B3 of the reversing valve B. Then, the injection pump B sends the n-butyl bromide into the mixing channel S23 of the mixing module through the interface B6 of the reversing valve B and the inlet S22 of the mixing module, so that the n-butyl bromide and ethyl ether are fully mixed in the mixing channel and then flow into the bottle body of the reaction module. The low-temperature circulation mode is turned on, and the temperature of the reaction module is set to -5°C; then, 5.45 ml of ethyl ether and 6.2 ml of n-butyl bromide are respectively sent into the bottle body of the reaction module along the above path in two times. After the liquid delivery is completed, the low-temperature circulation mode is turned off; 20 ml of ethyl ether is pumped into the cavity of the injection pump A again through the interface A3 of the reversing valve A, and the corresponding liquid and gas are sequentially transported from the cavity of the injection pump A to the bottle body of the reaction module through the interface A5 of the reversing valve A and the interfaces P1 and P2 of the three-way valve P, and wait for a period of time; the low-temperature circulation device is turned on again, the temperature is set to -5°C, and 7.5 ml of diethyl ether is pumped into the mixing channel S23 of the mixing module. At the same time, 5 ml of acetone enters the mixing channel S23 through the interfaces B4 and B6 of the switching valve B and the second inlet S22 of the mixing module for mixing and then enters the reaction module S1. The low-temperature circulation device is turned off. After waiting for a period of time, 100 ml of sulfuric acid is transported to the bottle body of the reaction module through the interfaces A4 and A5 of the switching valve A and the interfaces P1 and P2 of the three-way valve P. Then, the liquid in the reaction module enters the extraction module S3 in sequence from the outlet S12 of the reaction module S1 and the interfaces A6 and A7 of the switching valve A. After waiting for 3 min, 3 - 5 ml of liquid flows into the reaction module S1 from the outlet S32 of the extraction module, the interfaces A8 and A5 of the switching valve A, and the interfaces P1 and P2 of the three-way valve P. Then, the conductivity meter of the extraction module is turned on to conduct conductivity detection on the liquid flowing through the through-channel. Part of the liquid is discharged into the reaction module S1 through the outlet S32 of the extraction module, and the other part of the liquid passes through the interfaces A8 and A2 of the switching valve A and the interfaces B2 and B7 of the switching valve B and enters the drying and filtering module S4. The liquid in the reaction module S1 is pumped into the extraction module S3 in batches. Then, 25 ml of diethyl ether is pumped into the extraction module S3 from the interfaces A3 and A7 of the switching valve A. After starting the stirring equipment and stirring, wait. Then, part of the liquid is moved to the drying and filtering module S4 by means of conductivity detection. The drying and filtering module S4 is started, and the liquid in the bottle body is introduced into the lower bottle body and then into the extraction module from its outlet S42, the interfaces B8 and B2 of the switching valve B, and the interfaces A2 and A7 of the switching valve A. And 30 ml of 30% sodium carbonate solution is introduced into the extraction module through the switching valve B and the switching valve A for stirring and washing. After stirring, let it stand for a period of time, then turn on the conductivity detection, and transfer the final target product to the drying and filtering module S4 for stirring, drying and filtering, so as to obtain the final Grignard reagent product.

[0063] This laboratory automation system uses a liquid path transmission module to integrate and connect multiple instrument modules across regions, automatically execute the instructions of the terminal, and realize the automatic progress of experimental operations. It can perform refined operation processing on various experimental processes hierarchically. In this way, it can not only realize the cross-region transmission of liquids, but also maintain the stable output of products.

[0064] Example 2

[0065] Refer to the appendix Figure 7 , by combining the laboratory automation liquid path transmission module with the reaction module S1, the extraction module S3, the drying and filtering module S4 and the rotary evaporation module S5 to form a laboratory automation system, under the mode of automatic control, the preparation of methyl p-bromobenzoate is realized. It can not only maintain the stable output of products, but also the entire experimental process is automated, with high intelligence and simple operation.

[0066] Refer to the appendixFigure 7 The sample interfaces A3', A4', A5' and A6' of the reversing valve A are respectively connected to the pharmaceutical p-bromobenzoic acid h1, methanol h2, thionyl chloride h3 and 10% sodium hydroxide h4. The interface A7' of the reversing valve A is connected to the inlet S11 of the reaction module S1. A stirring device is installed on the reaction module S1, and a distillation device S6 is installed at one of the openings of the reaction module S1. The distillation device S6 is connected to the opening of the reaction module through a communication path S61. The outer layer of the communication path S61 is coated with a heat-insulating layer (not shown in the figure) to ensure that steam can reach the inside of the distillation device S6 for condensation and reflux and then enter the bottom of the bottle of the distillation device. The distillation device S6 has a connecting bottle body S62, and the outlet S63 of the connecting bottle body is interconnected with the interface A8' of the reversing valve A. In addition, the reversing valve A also has an interface A9', and this interface A9' is connected to the outlet S12 of the reaction module S1. Of course, the reversing valve A can also be provided with a waste liquid outlet as needed to discharge the corresponding waste liquid out of the system. The sample interfaces B3' and B6' of the reversing valve B are respectively connected to saturated brine h5 and water h6. The interfaces B4' and B5' of the reversing valve B are respectively connected to the inlet S31 and the outlet S32 of the extraction module S3. The cross-pump interface B7' of the reversing valve B is cross-pumped and connected to the cross-pump interface C2 of the reversing valve C. The interface B8' of the reversing valve B is a waste liquid outlet, and the interface B9' of the reversing valve B is interconnected with the collection bottle k3. The pump-valve interface C1 of the reversing valve C is connected to the injection pump C, and the sample interface C3 of the reversing valve C is connected to the pharmaceutical dichloromethane. The interfaces C4 and C5 of the reversing valve C are respectively connected to the inlet S41 and the outlet S42 of the drying and filtering module S4. The interface C7 of the reversing valve C is connected to the inlet of the rotary evaporation module S5. The rotary evaporation module S5 is an existing automated rotary evaporation module. One of the outlets of the rotary evaporation module S5 is connected to the product collection bottle, and the other outlet is connected to the intermediate bottle k1. The intermediate bottle k1 is connected to the interface C6 of the reversing valve C, and the liquid in the intermediate bottle is discharged to the corresponding position by an automated method.

[0067] The specific steps for the above laboratory automation system to automatically prepare methyl p-bromobenzoate are as follows:

[0068] When the operation is started, a set volume of p-bromobenzoic acid is transferred from the interface A3' of the reversing valve A to the cavity of the injection pump A, and then it is injected into the bottle body of the reaction module S1 through the interface A7' of the reversing valve A. At the same time, methanol is injected into the bottle body of the reaction module S1 from the interfaces A4' and A7' of the reversing valve A. Then, the stirring device is started for mixing and the temperature in the reaction module is reduced to 5 °C by using the temperature cycling device;

[0069] Thionyl chloride is slowly injected into the reaction module S1 through the interfaces A5' and A7' of the reversing valve A, and then by using the temperature...

[0070] The temperature cycling device raises the temperature in the reaction module to 25 - 30 °C and reacts for 2 h; immediately afterwards, the temperature cycling device raises the temperature to 80 °C for distillation, thereby distilling out the solvent and most of the thionyl chloride. After the distillation ends, the temperature in the reaction module is set to 5 °C;

[0071] Dichloromethane flows into the bottle body of the reaction module S1 across the pump and across regions successively through the interfaces C3, C2 of the switching valve C, the interfaces B7’, B2 of the switching valve B, and the interfaces A2, A7’ of the switching valve A. Water is pumped into the bottle body of the reaction module S1 successively through the interfaces B6’, B2 of the switching valve B and the interfaces A2, A7’ of the switching valve A. And 10% sodium hydroxide solution is pumped into the bottle body of the reaction module S1 through the interfaces A6’, A7’ of the switching valve A. A pH sensor is arranged in the reaction module S1, which can monitor the pH value of the mixed solution in real time until the pH value of the mixed solution is adjusted to 8 - 9;

[0072] The liquid in the reaction module S1 is discharged into the extraction module S3 through the interfaces A9’, A2 of the switching valve A and the interfaces B2, B4’ of the switching valve B, and the temperature cycling device and the stirring device are turned off;

[0073] The conductometer of the extraction module is started. The organic phase in the extraction module S3 enters the container bottle k2 through the interfaces B5’, B7’ of the switching valve B and the interfaces C2, C8 of the switching valve C. At the same time, dichloromethane enters the extraction module through the interfaces C3, C2 of the switching valve C and the interfaces B7’, B4’ of the switching valve B for re-stirring extraction. The extracted organic phase enters the container bottle k2, and the aqueous phase enters the corresponding collection bottle k3 through the interfaces B5’, B9’ of the switching valve B. The organic phase in the container bottle k2 enters the extraction module again through the interfaces C8, C2 of the switching valve C and the interfaces B7’, B4’ of the switching valve B. At the same time, saturated brine is pumped into the extraction module through the interfaces B3’, B4’ of the switching valve B for washing. Then the washed organic phase enters the drying and filtering module S4 through the interfaces B5’, B7’ of the switching valve B and the interfaces C2, C4 of the switching valve C. Then the drying and filtering module S4 is turned on. Anhydrous sodium sulfate is arranged on the sand core of the drying and filtering module. After drying and suction filtration of the filtrate, it is sent into the rotary evaporation module S5 for rotary evaporation operation. After the rotary evaporation ends, the liquid in the intermediate bottle k1 flows into the collection bottle k3 through the interfaces C6, C2 of the switching valve C and the interfaces B7’, B9’ of the switching valve B. Finally, the product in the product bottle is collected, and the corresponding pipelines are cleaned.

[0074] This laboratory automation system uses a liquid path transmission module to integrally connect and connect multiple instrument modules across regions, and automatically executes the instructions of the terminal, which can not only realize the cross-region transmission of liquids, but also maintain the stable output of products.

[0075] Of course, in other embodiments, the above liquid path transmission module can also be connected to other different instrument modules to form a laboratory automation system for cross-region and cross-pump transmission and reaction. Different connection methods are designed according to different reaction products, and then integrated into an automation system to reduce the intervention of manual operation and monitor various parameters of the reaction in real time, so as to achieve stable product output. Further, the three groups of pump-valve structures in the above embodiments can also be connected in the manner shown in the appendix Figure 8 and use the terminal to search for the shortest path to improve the efficiency of liquid path transmission and reduce the occurrence of liquid retention. The specific details are as follows:

[0076] In order to enable the program in the terminal to automatically find the shortest path, the application program can automatically search and calculate the path and then send the shortest transportation path instruction to the liquid path transmission module for parsing. Refer to the appendix Figure 8 , taking the laboratory automation liquid path transmission including at least the first, second, and third groups of pump-valve modules (1A, 1B, 1C) as an example. The three groups of pump-valve modules 1A, 1B, and 1C are bidirectionally connected to each other, and at the same time, the pump-valve module 1A and the pump-valve module 1C are also connected to each other. During actual operation, the method for automatically searching for the shortest path is as follows:

[0077] Step 1: Establish a node graph according to the connection path of the pump-valve module. The pump-valve module includes at least three or more pump-valve modules;

[0078] Taking the connection path of the three groups of pump-valve modules 1A, 1B, and 1C in the attached figure as an example, its node graph is as follows: 1A-1B,1C, 1B-1A,1C, 1C-1B,1A. Among them, each node graph represents pump-valve modules that are directly connected to each other.

[0079] Step 2: Taking the search for the shortest path from 1A to 1C as an example, use the node graph to start searching for all paths from the starting point (1A) of the path. After the search is completed, add the starting point (1A) of the path to the completed search node list;

[0080] Using the node graph, start searching for the shortest path from 1A to 1C. Starting from node 1A, the connected nodes are 1B and 1C. Then, the first-section paths 1A→1B and 1A→1C can be obtained. Among them, 1A→1C has reached the target. At the same time, we add the node

[0081] 1A to the completed search node list to prevent returning to the original path;

[0082] Step 3: If the path searched in Step 2 does not reach the path end point (such as 1A→1B does not reach the path end point 1C), then use the intermediate connection point (1B) as the intermediate node to continue the search until the path end point (1C) is reached;

[0083] For the unfinished target 1A → 1B, use 1B as the intermediate node to continue the connection. Among them, the connection nodes of 1B are 1A and 1C. Among them, 1A is in the list of nodes that have completed retrieval, and the 1A node can be directly ignored, so as to obtain 1A → 1B → 1C, thus completing the target.

[0084] In this way, by searching all possible paths from 1A to 1C, we obtain two paths: 1A → 1B → 1C and 1A → 1C. After that, by calculating the number of nodes in the two paths, it can be concluded that the path of 1A → 1C is the shortest path. Then the terminal sends the instruction of this shortest path to the liquid path transmission module, so that the liquid path transmission module performs liquid transmission according to this shortest path. By using the above principle, we can also expand its application to three or more groups of pump-valve modules with cross-pump connection, so as to be able to find the shortest path in a relatively complex model, improve the transmission rate and reduce the liquid retention condition in the liquid path.

[0085] The above description shows and describes the preferred embodiments of the present invention. As mentioned before, it should be understood that the present invention is not limited to the form disclosed herein, should not be regarded as excluding other embodiments, but can be used in various other combinations, modifications and environments, and can be changed within the scope of the inventive concept described herein through the above teachings or the techniques or knowledge in related fields. And the changes and alterations made by those skilled in the art without departing from the spirit and scope of the present invention shall fall within the protection scope of the appended claims of the present invention.

Claims

1. An automated laboratory liquid path transfer module, characterized in that It includes a pump-valve module (1), a control module (2) and a terminal (3). The control module (2) is communicatively connected to the terminal (3). The pump-valve module (1) at least includes an injection pump A, a reversing valve A, an injection pump B and a reversing valve B. Both the reversing valve A and the reversing valve B are multi-channel valve bodies, and the connection of different channels is realized by the rotation of the rotor in the valve body. The injection pump A and the injection pump B are respectively directly connected to the pump-valve interface (A1) of the reversing valve A and the pump-valve interface of the reversing valve B. The cross-pump interface (A2) of the injection pump A is interconnected with the cross-pump interface (B2) of the injection pump B by a pipeline. The reversing valve A or the reversing valve B also has a sample interface connected to the drug and an instrument interface connected to the inlet and outlet of the instrument module. The control module (2) is electrically connected to the injection pump A, the reversing valve A, the injection pump B and the reversing valve B. The control module (2) can control the switching of the connection between different interfaces of the reversing valve A or the reversing valve B. When the cross-pump interface (A2) of the injection pump A is connected to the cross-pump interface (B2) of the injection pump B, the control module controls the piston rod of the injection pump A to move downward while the piston rod of the injection pump B moves upward at the same rate, so that all the liquid in the injection pump A is transferred to the injection pump B. And the instrument interfaces of the reversing valve A and the reversing valve B are dynamically combined and connected with one or several of the reaction module, the mixing module, the extraction module, the rotary evaporation module, the distillation device or the drying and filtration module.

2. The automated laboratory liquid path transfer module according to claim 1, characterized in that The sample interface of the reversing valve A is connected to the drug. Two of the instrument interfaces (A5, A6) of the reversing valve A are respectively connected to the interface (P1) of the three-way valve (P) and the outlet (S12) of the reaction module. The other two interfaces (P2, P3) of the three-way valve are respectively connected to the inlet (S11) of the reaction module and the first inlet (S21) of the mixing module. The other two instrument interfaces (A7, A8) of the reversing valve A are respectively connected to the inlet (S31) and the outlet (S32) of the extraction module. The sample interface of the reversing valve B is connected to the drug, and one of the instrument interfaces (B6) of the reversing valve B is connected to the second inlet (S22) of the mixing module. The other two instrument interfaces (B7, B8) of the reversing valve are respectively connected to the inlet (S41) and the outlet (S42) of the drying and filtration module. The mixing module also has a mixing channel (S23), and the outlet of the mixing channel is connected to the inlet (S11) of the reaction module.

3. The automated laboratory liquid path transfer module according to claim 1, characterized in that The pump-valve module (1) also includes an injection pump C and a reversing valve C. The injection pump C is connected to the pump-valve interface (C1) of the reversing valve C. The cross-pump interface (C2) of the reversing valve C is connected to another cross-pump interface (B7’) of the reversing valve B.

4. The automated laboratory liquid path transfer module according to claim 3, characterized in that The sample interface of the reversing valve A is connected to the medicine, and the two instrument interfaces (A7', A9') of the reversing valve A are respectively connected to the inlet (S11) and the outlet (S12) of the reaction module. A distillation device (S6) is also installed on the reaction module. The distillation device (S6) is connected to the reaction module (S1) through a communication path (S61). The outer layer of the communication path (S61) is coated with a heat-insulating layer. The distillation device (S6) has a connecting bottle body (S62), and the outlet (S63) of the connecting bottle body is connected to another instrument interface (A8') of the reversing valve A; the reversing valve B has a sample interface, and two of the instrument interfaces (B4', B5') of the reversing valve B are respectively connected to the inlet (S31) and the outlet (S32) of the extraction module. The other two interfaces (B8, B9) of the reversing valve B are respectively connected to the outside and the collection bottle (k3); the reversing valve C has a sample interface (C3), and three of the instrument interfaces (C4, C5, C7) of the reversing valve C are respectively connected to the inlet (S41) and the outlet (S42) of the drying and filtering module and the rotary evaporation module. One of the outlets of the rotary evaporation module is connected to the product collection bottle, and the other outlet is connected to the intermediate bottle (k1). The intermediate bottle (k1) is connected to the interface (C6) of the reversing valve C.

5. A control method for an automated laboratory liquid path transfer module, characterized in that Including the laboratory automation liquid path transmission module according to any one of claims 1-4, the control method thereof includes the following steps: Step S10: Obtain the volume parameter of the terminal; Step S20: In the initial state, the control module (2) controls the pump valve module (1) to start working, and the pump valve module (1) sucks a fixed amount of liquid for inlet. Among them, the pump valve module (1) at least includes an injection pump A, a reversing valve A, an injection pump B and a reversing valve B; Step S30: Control the reversing valve A and the reversing valve B to reverse and communicate with each other at the same time. While the piston rod of the injection pump A moves downward, the piston rod of the injection pump B moves upward at the same rate, and all the liquid in the injection pump A is transferred and transported into the injection pump B; Step S40: Control the rotor of the reversing valve B to rotate so that the injection pump B is connected to the interface of the reversing valve B, and the piston rod of the injection pump B moves downward to push the liquid inside it to be discharged to the corresponding position.

6. The control method for an automated laboratory liquid path transfer module according to claim 5, characterized in that The instrument interfaces of the pump valve module can be connected to different instrument modules. The different instrument modules are communicatively connected to the terminal through communication interfaces. When starting, enter the comparison mode, including the following steps: Set the connection methods of different instrument modules on the display interface of the terminal (3); The terminal (3) receives the signals sent by the assembled different instrument modules through their respective communication interfaces and performs parsing; Compare the set connection method with the parsed connection method to determine whether the connection method is correct. If it is correct, enter the experimental mode. If it is incorrect, give corresponding prompts on the terminal.

7. The control method for an automated laboratory liquid path transfer module according to claim 6, characterized in that The different instrument modules are connected through connecting pipes. An identification device is arranged on the connecting pipes, and the identification device is communicatively connected to the terminal.

8. The control method for an automated laboratory liquid path transfer module according to claim 6, characterized in that The application program at the terminal uses Bayesian theory to predict reaction products. By inputting experimental data into the prediction model for calculation and prediction, and then comparing the corresponding experimental data with the prediction results to judge the accuracy of the model, and continuously iterating and optimizing until the accuracy reaches the set standard.

9. A control method for an automated laboratory liquid path transfer module, characterized in that Including the liquid path transmission module according to any one of claims 1 to 4, the pump valve module at least includes first, second, and third groups of pump valve modules (1A, 1B, 1C) that are bidirectionally connected to each other. The first and third groups of pump valve modules (1A, 1C) are connected to each other. The steps for the terminal to automatically search for the shortest path include: Step 1: Establish a node graph according to the connection path of the pump valve module; Step 2: Use the node graph to start searching for all paths from the starting point of the path. After the search is completed, add the starting point of the path to the list of nodes that have completed the search; Step 3: If the path searched in Step 2 does not reach the end point of the path, continue the search with the intermediate connection point as the node, and at the same time add the searched intermediate connection point to the list of nodes that have completed the search until the end point of the path is reached; Step 4: Obtain the shortest path by calculating the number of nodes of the searched path.

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