WO2022127927A1 - 一种液相自动化合成仪 - Google Patents

一种液相自动化合成仪 Download PDF

Info

Publication number
WO2022127927A1
WO2022127927A1 PCT/CN2021/139399 CN2021139399W WO2022127927A1 WO 2022127927 A1 WO2022127927 A1 WO 2022127927A1 CN 2021139399 W CN2021139399 W CN 2021139399W WO 2022127927 A1 WO2022127927 A1 WO 2022127927A1
Authority
WO
WIPO (PCT)
Prior art keywords
module
liquid
sampling
automatic
pipeline
Prior art date
Application number
PCT/CN2021/139399
Other languages
English (en)
French (fr)
Inventor
叶新山
姚文龙
熊德彩
Original Assignee
北京大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 北京大学 filed Critical 北京大学
Priority to US18/268,314 priority Critical patent/US20240036013A1/en
Priority to EP21905849.2A priority patent/EP4220150A4/en
Priority to JP2023535356A priority patent/JP2023552601A/ja
Publication of WO2022127927A1 publication Critical patent/WO2022127927A1/zh

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/24—Automatic injection systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/16—Injection
    • G01N30/20—Injection using a sampling valve
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/26—Conditioning of the fluid carrier; Flow patterns
    • G01N30/28—Control of physical parameters of the fluid carrier
    • G01N30/30—Control of physical parameters of the fluid carrier of temperature
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0006—Controlling or regulating processes
    • B01J19/004—Multifunctional apparatus for automatic manufacturing of various chemical products
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00599—Solution-phase processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00686—Automatic
    • B01J2219/00689—Automatic using computers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00709—Type of synthesis
    • B01J2219/00711—Light-directed synthesis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00722—Nucleotides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00725—Peptides

Definitions

  • the invention relates to the technical field of experimental equipment, in particular to a liquid-phase automatic synthesizer.
  • Liquid phase experiments are an essential part of academic research. Existing liquid phase experiments all require manual quantitative addition to the reaction fusion, and the mixed solution is obtained by manually controlling the stirring reaction. In the process of testing the mixed solution, it is also necessary to manually add the reaction solution to the monitor for testing, and the monitoring report generated by the monitor needs to be manually sorted and checked, which makes the entire liquid phase experimental monitoring process time-consuming and labor-intensive.
  • Pipeline transfer sampling At present, there are polypeptide solid-phase synthesizers and oligosaccharide solid-phase synthesizers and automatic Solid Phase Extractor etc. Its advantages are that the system is airtight, safe, free from external interference and systemic; its disadvantages are long research and development cycles and high design and development costs for a single finished product. There are two ways to design it: 1.
  • the components are purchased and assembled, which can be flexibly adjusted and modified to facilitate the integration of programs (syringe pump unit, multi-channel switching valve, light source, low temperature circulation, magnetic stirring, etc., and online monitoring), but also requires Redesign requires a long period of time and requires talents from all walks of life, and there are many factors that affect the operation results after assembly. 2. Transformation and upgrading from commercial similar products, that is, appropriate transformation of mature automation products, short cycle and no need for too much manpower, can ensure normal work, but because mature products have mature software control systems developed by their own patents, program integration is troublesome , without source code, may need to redesign the integrated board. 2.
  • Automatic pipetting and sampling At present, there are mature automatic pipetting workstations for sale on the market (prices range from 100,000 to 400,000), which can be purchased directly and modified slightly. Its advantages are that it is simple, fast, and can directly solidify manual operations on the instrument; the disadvantage is that all operations need to be replaced by robotic arms, with high failure rate and large space. It is also a mature product, and the program integration is inconvenient.
  • temperature and illumination control is also an important part of the experiment during the liquid phase experiment.
  • two quartz reactors are often used for solution reaction, and it is difficult to carry out side reactions in a low temperature tank of -80 °C.
  • a long arc mercury lamp light source and a quartz cold trap are generally used as the light source device.
  • the lamp cannot be turned on) is higher than the temperature of the low temperature tank (-80°C), which makes it difficult to accurately control the temperature of the low temperature tank.
  • a separate set of low temperature circulation device needs to be equipped to turn on the mercury lamp in time. If you forget to turn on the cold trap The mercury lamp is turned on by the low temperature circulation device, and with the mercury lamp being turned on and irradiated for a long time, there is a very high risk of fire.
  • the cold trap In order to solve the above problems, in the irradiation method, although the long-arc mercury light source and the cold trap made of quartz are used, the cold trap needs to be placed horizontally, and the ultraviolet light is irradiated on the reactor from top to bottom, and the reactor is placed in the ethanol / Dry ice in a cryogenic bath dewar.
  • This method is easy to control the temperature and is stable, and the synthesis effect of the model reaction is consistent with the previous laboratory side-illumination method, or even slightly better, but it still needs to cool the cold trap and additionally open the low-temperature circulation device of the cold trap, which is not easy to assemble the instrument and is not safe. And the utilization rate of UV light is very low, and additional UV protection devices are required.
  • the purpose of the present invention is to provide a liquid-phase automatic synthesizer, so as to realize the automation of liquid-phase synthesis experiments and further improve the experimental efficiency and experimental precision of the liquid-phase synthesis experiments.
  • the present invention provides the following scheme:
  • a liquid phase automatic synthesizer comprising: an automatic sampling system, a liquid phase synthesis auxiliary system, an automatic liquid phase synthesis monitoring system and a host computer;
  • the automatic sample introduction system, the liquid-phase synthesis auxiliary system and the liquid-phase synthesis automatic monitoring system are all connected with the upper position electromechanically;
  • the automatic sampling system is used to complete the automatic sampling operation according to the sampling instruction of the host computer; the liquid phase synthesis auxiliary system is used to complete the reaction solution according to the temperature control instruction and the illumination control instruction of the host computer. Temperature and illumination control; the automatic monitoring system is used to monitor the reaction solution and generate a monitoring report; the upper computer generates an experimental analysis result according to the monitoring report.
  • a novel reactor is also included;
  • the novel reactor is respectively connected with the pipeline of the automatic sampling system, the liquid phase synthesis auxiliary system and the liquid phase synthesis automatic monitoring system.
  • the novel reactor comprises: a bottle mouth, a bottle body, a sample inlet, an exhaust outlet, a sample outlet, a circulating liquid outlet and a circulating liquid inlet;
  • the bottle body sequentially includes a reaction inner tank, a temperature circulation layer and a vacuum layer from the inside to the outside; the tank bottom of the reaction inner tank is a circular arc structure;
  • the sampling port is communicated with the reaction liner
  • Both the circulating liquid outlet and the circulating liquid inlet are communicated with the temperature circulating layer, and the circulating liquid outlet and the circulating liquid inlet are arranged diagonally.
  • the automatic sampling system includes: an inert gas delivery module, a sampling channel switching module, a quantitative module, a disposal module and a liquid storage module;
  • Both the liquid storage module and the sampling channel switching module are connected to the inert gas delivery module through pipelines; the quantitative module is respectively connected to the sampling channel switching module and the disposal module through pipelines; The liquid module is connected with the sampling channel switching module through a pipeline;
  • the inert gas delivery module, the sampling channel switching module and the quantitative module are all electrically connected to the upper position;
  • the inert gas delivery module is used to deliver the internally stored inert gas to the liquid storage module and the sampling channel switching module through pipelines respectively; the sampling channel switching module is used to extract the stored inert gas in the liquid storage module.
  • the upper computer is used to control the opening and closing of the inert gas delivery module and the quantitative module, and is used to control the sampling channel switching module to perform channel switching.
  • the sampling channel switching module includes: a first multi-channel switching valve and a second multi-channel switching valve;
  • the first multi-channel switching valve is connected to M of the liquid storage bottles through pipelines;
  • the second multi-channel switching valve is connected to N-M of the liquid storage bottles through pipelines;
  • the quantitative module includes: a syringe pump unit, a pressure sensor, a flow meter and a second solenoid valve unit;
  • the inlet of the syringe pump unit is connected to the sampling channel switching module through a pipeline; the outlet of the syringe pump unit is connected to the flowmeter through a pipeline; the flowmeter is connected to the disposal module through a pipeline;
  • the second solenoid valve unit is arranged on the connection pipeline between the flowmeter and the treatment module; the pressure sensor is arranged on the connection pipeline between the syringe pump unit and the flowmeter; the second solenoid valve The unit, the pressure sensor and the flowmeter are all electrically connected to the upper position;
  • the disposal module includes: a solution pipe and a waste liquid bottle;
  • the sample inlet of the novel reactor and the liquid inlet of the waste product are connected to the second solenoid valve unit through pipelines;
  • the solution pipe is connected to the circulating liquid of the novel reactor through pipelines port connection;
  • the second solenoid valve unit is used to close the connection pipeline between the flowmeter and the new reactor when the solution in the new reactor reaches a set amount, and open the flowmeter and the waste gas.
  • the syringe pump unit includes: a first syringe pump and a second syringe pump;
  • the first syringe pump is connected with a channel in the first multi-channel switching valve through a pipeline; the second syringe pump is connected with a channel in the second multi-channel switching valve through a pipeline; the The range of the first syringe pump is smaller than the range of the second syringe pump.
  • the liquid phase synthesis auxiliary system includes: a mixing device and a temperature control device;
  • the novel reactor is placed on the mixing device, and both the mixing device and the temperature control device are electrically connected with the upper position.
  • the temperature control device includes: an ultraviolet light source and a low temperature circulator;
  • the liquid outlet of the low temperature circulator is connected with the circulating liquid inlet pipeline; the liquid inlet of the low temperature circulator is connected with the circulating liquid outlet pipeline; the ultraviolet light source is used for irradiating the novel reactor;
  • the mixing device includes: an automatic stirrer and a constant temperature plate;
  • Both the automatic stirrer and the thermostatic plate are electrically connected to the upper computer; the automatic stirrer is used to stir the mixed liquid in the novel reactor according to the stirring instruction in the upper computer; on the automatic stirrer; the thermostatic plate was used to keep the temperature of the novel reactor constant.
  • the liquid phase synthesis automatic monitoring system includes: a sampling module, a power module, a monitoring and analysis module and a cleaning module;
  • the sampling module is connected with the power module pipeline; the power module is connected with the monitoring and analysis module pipeline; the sampling module, the power module and the monitoring and analysis module are all connected with the upper electromechanical;
  • the sampling module is used to absorb the reaction solution contained in the novel reactor;
  • the power module is used to provide suction force for the sampling module according to the suction instruction in the upper computer, and is used to inject the absorbed reaction solution into
  • the monitoring and analysis module is configured to transmit the monitoring report to the host computer after generating the monitoring report according to the reaction solution; the host computer generates the analysis result according to the monitoring report;
  • the cleaning module is respectively connected with the sampling module and the power module pipeline.
  • the sampling module includes: a stainless steel needle, a slide rail and a turntable;
  • the stainless steel needle is connected to the power module through a first pipeline; the first pipeline is arranged on the slide rail, and the slide rail and the horizontal line are at a set angle; the stainless steel needle is fixedly arranged on the One end of the slide rail, and the other end of the slide rail is a free end; the slide rail is used to drive the stainless steel needle to slide, and the stainless steel needle is used to probe into the novel reactor to absorb the reaction solution; the The slide rail is fixedly arranged on the turntable; the turntable and the slide rail are both electromechanically connected with the upper position;
  • the power module includes: a power pump; the power pump is a syringe pump or the plunger pump;
  • the power pump is respectively connected with the sampling module and the monitoring and analysis module pipeline;
  • the monitoring and analysis module is a high performance liquid chromatograph
  • the cleaning module includes: a first liquid container, a second liquid container and a solenoid valve;
  • the stainless steel needle sucks the cleaning liquid in the first liquid container; the second liquid container, the power module and the monitoring and analysis module are all connected with the solenoid valve pipeline.
  • the present invention discloses the following technical effects:
  • the liquid-phase automatic synthesizer provided by the present invention is provided with an automatic sampling system, a liquid-phase synthesis auxiliary system, an automatic liquid-phase synthesis monitoring system and a host computer, and the automatic sampling system is set according to the sampling instruction of the host computer.
  • the liquid phase synthesis auxiliary system completes the temperature and illumination control of the reaction solution according to the temperature control instruction and the illumination control instruction of the host computer
  • the automatic monitoring system monitors the reaction solution and generates a monitoring report
  • the upper computer generates experimental analysis results according to the monitoring report, so as to complete the automatic process from sample injection to report generation in the liquid phase experiment process, thereby reducing the experimental labor cost and improving the experimental efficiency.
  • Fig. 1 is the structural block diagram of liquid phase automatic synthesizer provided by the invention
  • Fig. 2 is the structural representation of liquid phase automatic synthesizer provided by the invention.
  • FIG. 3 is a schematic structural diagram of a novel reactor provided in an embodiment of the present invention.
  • FIG. 4 is a schematic structural diagram of an automatic sample injection system provided by an embodiment of the present invention.
  • FIG. 5 is a schematic structural diagram of a liquid phase synthesis auxiliary system provided in an embodiment of the present invention.
  • FIG. 6 is a schematic structural diagram of a liquid-phase synthesis automatic monitoring system provided in an embodiment of the present invention.
  • FIG. 7 is a physical diagram of a liquid-phase automated synthesizer provided in an embodiment of the present invention.
  • 1 automatic sampling system 1-1 inert gas delivery module, 1-11 inert gas storage, 1-12 pressure regulating filter, 1-13 first solenoid valve unit, 1-131 first two-way solenoid valve, 1- 132 second two-way solenoid valve, 1-133 three-way solenoid valve, 1-2 sampling channel switching module, 1-21 first multi-channel switching valve, 1-22 second multi-channel switching valve, 1-3 quantitative module, 1-31 Syringe Pump Unit, 1-311 First Syringe Pump, 1-312 Second Syringe Pump, 1-32 Pressure Sensor, 1-33 Flow Meter, 1-34 Second Solenoid Valve Unit, 1-4 Disposal Module, 1-41 New Reactor, 1-42 Solution Tube, 1-43 Waste Liquid Bottle, 1-5 Liquid Storage Module, 1-51 Liquid Storage Bottle, 2- Liquid Phase Synthesis Auxiliary System, 2-1 Temperature Control Device, 2 -11 UV light source, 2-12 low temperature circulator, 2-2 mixing device, 2-21 automatic stirrer, 2-22 constant temperature plate, 3- liquid phase synthesis automatic monitoring system, 3-1
  • the purpose of the present invention is to provide a liquid-phase automatic synthesizer, so as to realize the automation of liquid-phase synthesis experiments and further improve the experimental efficiency and experimental precision of the liquid-phase synthesis experiments.
  • the liquid-phase automatic synthesizer provided by the present invention includes: an automatic sampling system 1 , a liquid-phase synthesis auxiliary system 2 , a liquid-phase synthesis automatic monitoring system 3 and a host computer 5 .
  • the automatic sampling system 1 , the liquid-phase synthesis auxiliary system 2 and the liquid-phase synthesis automatic monitoring system 3 are all electrically connected to the upper computer 5 .
  • the automatic sampling system 1 is used to complete the automatic sampling operation according to the sampling instruction of the upper computer 5 .
  • the liquid phase synthesis auxiliary system 2 is used to complete the temperature and illumination control of the solution to be reacted according to the temperature control instruction and the illumination control instruction of the upper computer 5 .
  • An automatic monitoring system is used to monitor the reaction solution and generate a monitoring report.
  • the upper computer 5 generates experimental analysis results according to the monitoring report.
  • the present invention correspondingly provides a new type of reactor 1-41 as a supporting reactor of the entire liquid-phase automatic synthesizer.
  • the novel reactor 1-41 provided by the present invention has advantages that other existing reactors cannot match, it can also be used in other experimental equipment.
  • novel reactors 1-41 provided by the present invention are respectively connected with the automatic sampling system 1 , the liquid phase synthesis auxiliary system 2 and the liquid phase synthesis automatic monitoring system 3 pipelines.
  • the new reactor 1-41 includes: bottle mouth 1-411, injection port 1-412, exhaust port 1-413, sampling port 1-414, bottle body 1-415 and circulating liquid Port 1-416.
  • the injection port 1-412 is at a set angle (preferably 60°) with the bottle body 1-415.
  • the exhaust port 1-413 and the injection port 1-412 are arranged symmetrically with the center line of the bottle mouth 1-411 as the center.
  • the space included angle between the center line of the sampling port 1-414 and the center line of the exhaust port 1-413 is 60°. The setting of this specific angle is also to prevent the reaction liquid from splashing out of the reactor during the stirring process.
  • the bottle body 1-415 sequentially includes a reaction liner 1-4151, a temperature circulation layer 1-4152 and a vacuum layer 1-4153 from the inside to the outside.
  • the bottom of the reaction liner 1-4151 is a circular arc structure.
  • the sampling port 1-414 communicates with the reaction inner tank 1-4151.
  • the circulation liquid outlet 1-416 and the circulation liquid inlet are both communicated with the temperature circulation layer 1-4152, and the circulation liquid outlet 1-416 and the circulation liquid inlet are arranged diagonally.
  • the bottle mouth 1-411 is provided with an upper cover 1-417 or the bottle mouth 1-411 is set as a sealing structure.
  • the set upper cover 1-417 is preferably a high light transmittance quartz plate.
  • the provided novel reactor 1-41 preferably further includes a sealing clip.
  • the sealing clip is used to clamp the bottle mouth 1-411 and the upper cap 1-417.
  • the sealing clip is a double-jacketed eggplant-shaped structure. Specifically, two flanged clips can be used, and the two flanged clips can be improved so that the shape formed between the two flanged clips is changed from a U-shaped to an eggplant-shaped.
  • the automatic sampling system 1 includes: an inert gas delivery module 1-1, a sampling channel switching module 1-2, a quantitative module 1-3, a disposal module 1-4 and a liquid storage module 1- 5.
  • Both the liquid storage module 1-5 and the sampling channel switching module 1-2 are connected to the inert gas delivery module 1-1 through pipelines.
  • the quantitative module 1-3 is respectively connected with the sampling channel switching module 1-2 and the disposal module 1-4 through pipelines.
  • the liquid storage module 1-5 is connected to the sampling channel switching module 1-2 through a pipeline.
  • the inert gas delivery module 1-1, the sampling channel switching module 1-2 and the quantitative module 1-3 are all electrically connected to the upper computer 5.
  • the inert gas delivery module 1-1 is used to deliver the internally stored inert gas to the liquid storage module 1-5 and the sampling channel switching module 1-2 through pipelines, respectively.
  • the sampling channel switching module 1-2 is used to extract the to-be-reacted solution stored in the liquid storage module 1-5, and to switch the channel for extracting the to-be-reacted solution.
  • the quantitative module 1-3 is used to determine the amount of the solution to be reacted injected into the treatment module 1-4.
  • the upper computer 5 is used to control the opening and closing of the inert gas delivery module 1-1 and the quantitative module 1-3, and is used to control the sampling channel switching module 1-2 to perform channel switching.
  • All other external devices can be controlled by the host computer 5 through a communication protocol with a programmable logic controller (Programmable Logic Controller, PLC) for program control to meet the normal operation of the automation program.
  • PLC programmable logic controller
  • the above-mentioned inert gas delivery module 1-1 includes: an inert gas storage 1-11, a pressure regulating filter 1-12 and a first solenoid valve unit 1-13.
  • the inert gas storage 1-11 is respectively connected with the liquid storage module 1-5 and the sampling channel switching module 1-2 through pipelines.
  • the pressure regulating filter 1-12 and the first solenoid valve unit 1-13 are arranged on the connecting pipeline of the inert gas storage 1-11 and the liquid storage module 1-5, or arranged on the inert gas storage 1-11 and the sampling channel switching module 1-2 on the connecting line.
  • the first solenoid valve unit 1-13 includes: a first two-way solenoid valve 1-131, a second two-way solenoid valve 1-132 and a three-way solenoid valve 1-133.
  • the first two-way solenoid valve 1-131 and the three-way solenoid valve 1-133 are arranged on the connection pipeline between the inert gas storage 1-11 and the sampling channel switching module 1-2.
  • the second two-way solenoid valve 1-132 is arranged on the connection pipeline between the inert gas storage 1-11 and the liquid storage module 1-5.
  • the number of pressure regulating filters 1-12 is two, and the two pressure regulating filters 1-12 are respectively disposed on the connection pipeline between the inert gas storage 1-11 and the sampling channel switching module 1-2 and the inert gas On the connecting pipeline between the accumulator 1-11 and the liquid storage module 1-5.
  • the above liquid storage module 1-5 includes N liquid storage bottles 1-51.
  • Each liquid storage bottle 1-51 is connected with the inert gas delivery module 1-1 through a pipeline.
  • the bottom of the liquid storage bottle 1-51 is conical or arc-shaped.
  • Each liquid storage bottle 1-51 includes: a first channel opening, a second channel opening, a third channel opening and a bottle cap.
  • the first channel port is used to connect with the sampling channel switching module 1-2 through a pipeline.
  • the second channel port is used to connect with the inert gas delivery module 1-1 through a pipeline.
  • the third channel port is used to discharge the gas or liquid in the liquid storage bottle 1-51.
  • the bottle cap is screwed to the bottle mouth 1-411 of the liquid storage bottle 1-51.
  • the inert gas is slightly positive pressure to fill each liquid storage bottle 1-51, so as to avoid the negative pressure of the closed liquid storage bottle 1-51 due to the reduction of liquid, which will affect the accuracy of injection.
  • liquid storage bottles 1-51 There are preferably four kinds of liquid storage bottles 1-51 provided by the present invention: 10 mL pointed bottom liquid storage bottle, 20 mL pointed bottom liquid storage bottle, 500 mL round bottom liquid storage bottle and 125 mL two-neck liquid storage bottle.
  • the 10mL and 20mL pointed bottom liquid storage bottles are mainly used to reserve block samples and reagent catalysts.
  • the pointed bottom is designed to allow the pipeline to reach 1-512 at the bottom of the bottle to avoid the loss and waste of the reserve liquid.
  • the internal thread design is convenient for custom-made polytetrafluoroethylene. Vinyl fluoride cap.
  • the 500mL round-bottomed liquid storage bottle is mainly used to store ultra-dry organic solvents, and the 125mL two-necked bottle is mainly used to store organic solvents for diluting the reaction solution, or even waste liquid.
  • the injection port 1-412 on the side is mainly for the insertion and extraction of the sampling needle during online monitoring.
  • All the liquid storage bottles 1-51 are made of transparent tube-sealed glass with pressure resistance. The main purpose of not using brown or black is to facilitate the user of the instrument to observe the remaining amount of the storage liquid.
  • the custom cap design to match the custom reservoir bottle 1-51 has undergone repeated exploration, verification and modification.
  • the bottle cap has three channels, which are for ventilation, liquid flow and air release.
  • the bottle cap In order to ensure the stability of the concentration of the stock solution and the accuracy of automatic sample injection, the bottle cap must be tightly sealed, convenient for on-off, corrosion-resistant and durable.
  • the on-off switch is embedded inside the bottle cap, and the bottom of the bottle cap is thinned and connected with an inverted cone to ensure that the compaction seal does not need a sealing ring and the connection is tight.
  • the tightness of the connecting line gets the initial custom cap. After repeated tests, it was found that there was liquid leakage at the on-off switch embedded in the initial bottle cap. Therefore, an ordinary elastic sealing gasket was added to the on-off switch. This gasket is outside the bottle cap and does not require corrosion resistance. Teflon three-channel compact cap.
  • the above sampling channel switching module 1-2 includes: a first multi-channel switching valve 1-21 and a second multi-channel switching valve 1-22.
  • the first multi-channel switching valve 1-21 is connected with M liquid storage bottles 1-51 through pipelines.
  • the second multi-channel switching valve 1-22 is connected with N-M liquid storage bottles 1-51 through pipelines.
  • Two ten-channel switching valves can be connected in parallel or cross-connected to different sizes of storage bottles 1-51.
  • the 10th channel of the two switching valves is always connected to the inert gas
  • the 9th channel is connected to the commonly used ultra-dry solvent (such as dichloromethane)
  • the 8th channel is connected to the secondary ultra-dry solvent (such as acetonitrile or toluene, etc.)
  • other channels can be independent or cross-connected with different or the same stock solution without cross-contamination.
  • the injection volume of less than or close to 1mL is connected to the first multi-channel switching valve 1-21, and the injection volume greater than or close to 1 mL is connected to the second multi-channel switching valve 1-22.
  • Each channel number of the multi-channel switching valve needs to be One-to-one correspondence with the substances in each liquid storage bottle 1-51.
  • the inert gas storage 1-11 is used to depressurize and filter the pressure through the pressure reducing valve and the pressure regulating filter 1-12 in turn, so as to provide positive pressure and clean the pipeline.
  • the above-mentioned quantitative module 1-3 includes: a syringe pump unit 1-31, a pressure sensor 1-32, a flow meter 1-33 and a second solenoid valve unit 1-34.
  • the inlet of the syringe pump unit 1-31 is connected to the sampling channel switching module 1-2 through a pipeline.
  • the outlet of the syringe pump unit 1-31 is connected to the flow meter 1-33 through a pipeline.
  • the flow meters 1-33 are connected to the disposal modules 1-4 by pipelines.
  • the second solenoid valve unit 1-34 is arranged on the connection pipeline between the flow meter 1-33 and the treatment module 1-4.
  • the pressure sensor 1-32 is arranged on the connecting line between the syringe pump unit 1-31 and the flow meter 1-33.
  • the second solenoid valve unit 1-34, the pressure sensor 1-32 and the flow meter 1-33 are all electrically connected to the upper computer 5.
  • the syringe pump unit 1-31 includes: a first syringe pump 1-311 and a second syringe pump 1-312.
  • the first syringe pump 1-311 is connected to a channel in the first multi-channel switching valve 1-21 through a pipeline.
  • the second syringe pump 1-312 is connected to a channel in the second multi-channel switching valve 1-22 through a pipeline.
  • the range of the first syringe pump 1-311 is smaller than the range of the second syringe pump 1-312.
  • injection is performed by the pipeline connected to the small-range syringe pump (ie, the first syringe pump 1-311).
  • the pipeline connected by the large-range syringe pump ie, the second syringe pump 1-312
  • the syringe on the syringe pump can be replaced, the minimum is 500uL, the maximum is 25mL, and the number of switching valves and syringe pumps can be increased modularly for expansion.
  • Each pipeline is a syringe pump to provide injection power.
  • Each pipeline has its own syringe pump and the high-precision flowmeter 1-33 behind it to cooperate, double control to ensure the accuracy of the injection, and the flowmeter 1-33 is used between the syringe pump and the flowmeter 1-33.
  • the measurement is used as the final injection volume.
  • One reason for this setting is that the accuracy of the syringe pump itself (1%) is lower than the accuracy of the flowmeter 1-3333 itself (2 ⁇ ).
  • the second is that the syringe pump cannot identify air bubbles or whether there is a reserve liquid, and the metering difference between the gas and liquid of the flowmeter 1-33 is large. When the gas passes through, the measurement change can be fed back to the flowmeter 1-33 and the syringe pump. Double self-correction.
  • the above-mentioned disposal module 1-4 includes: a novel reactor 1-41, a solution pipe 1-42 and a waste liquid bottle 1-43.
  • the injection port 1-412 of the novel reactor 1-41 and the liquid inlet of the waste liquid product are connected to the second solenoid valve unit 1-34 through pipelines.
  • the solution pipe 1-42 is connected to the exhaust port 1-413 of the novel reactor 1-41 through a pipeline.
  • the second solenoid valve unit 1-34 is used to close the connection pipeline between the flowmeter 1-33 and the new reactor 1-41, and open the flowmeter 1-41 when the solution in the new reactor 1-41 reaches the set amount. 33 Connecting pipes to waste bottles 1-43.
  • the solenoid valve next to the flowmeter 1-33 will immediately switch the excess to-be-reacted solution to the waste liquid bottle 1-43 to ensure that it enters the new reaction.
  • the injection volume of devices 1-41 is accurate. After each sample injection, an instruction on whether to perform pipeline cleaning can be programmed in the host computer 5 as required, and the waste liquid from the pipeline cleaning also enters the waste liquid bottle 1-43. Connected to the liquid inlet of the new reactor 1-41 is an oil bubbler that can prevent back suction. The purpose of this is to ensure that the air pressure in the new reactor 1-41 is normal and no foreign gas or water vapor will enter. This reactor type further meets the airtightness requirement of the entire automatic sampling system 1 .
  • the above-mentioned liquid phase synthesis auxiliary system 2 includes: a temperature control device 2-1 and a mixing device 2-2.
  • a software program is implanted in the upper computer 5, and the software program is used to control the specific work flow of the mixing device 2-2 and the temperature control device 2-1.
  • the novel reactor 1-41 is placed on the mixing device 2-2, and both the mixing device 2-2 and the temperature control device 2-1 are electrically connected to the upper computer 5.
  • the above temperature control device 2-1 includes: an ultraviolet light source 2-11 and a low temperature circulator 2-12.
  • the liquid outlet of the cryogenic circulator 2-12 is connected with the pipeline of the circulating liquid inlet 1-416.
  • the liquid inlet of the cryogenic circulator 2-12 is connected with the pipeline of the circulating liquid outlet.
  • the UV light source 2-11 is used to illuminate the novel reactor 1-41.
  • the ultraviolet light source 2-11 is preferably a mercury lamp light source of the CEL-M series.
  • the mixing device 2-2 includes an automatic stirrer 2-21 and a constant temperature plate 2-22.
  • Both the automatic stirrer 2-21 and the constant temperature plate 2-22 are electrically connected with the upper computer 5 .
  • the automatic stirrer 2-21 is used to stir the mixed liquid in the new reactor 1-41 according to the stirring instruction in the upper computer 5.
  • the new reactor 1-41 was placed on the automatic stirrer 2-21.
  • the automatic stirrer 2-21 is provided on the thermostatic plate 2-22.
  • the rotation of the automatic stirrer 2-21 drives the rotation of the new reactor 1-41, so as to realize the stirring function through the action of centrifugal force.
  • Thermostat plate 2-22 is used to keep the temperature of novel reactor 1-41 constant.
  • the automatic stirrer 2-21 in the present invention can also be a stirring rod, which is arranged above the novel reactor 1-41 to mix the solution evenly by stirring the mixed liquid in the reactor.
  • the liquid phase synthesis automatic monitoring system 3 includes: a sampling module 3-1, a power module 3-2 and a monitoring and analysis module 3-3.
  • the sampling module 3-1 is connected with the power module 3-2 by pipeline.
  • the power module 3-2 and the monitoring and analysis module 3-3 are connected by pipeline.
  • the sampling module 3-1, the power module 3-2 and the monitoring and analysis module 3-3 are all electrically connected to the upper computer 5.
  • the sampling module 3-1 is used to absorb the reaction solution contained in the novel reactor 1-41.
  • the power module 3-2 is used to provide suction force for the sampling module 3-1 according to the suction instruction in the upper computer 5, and is used to inject the suctioned reaction solution into the monitoring and analysis module 3-3.
  • the monitoring and analysis module 3-3 is used to transmit the monitoring report to the upper computer 5 after generating the monitoring report according to the reaction solution.
  • the upper computer 5 generates analysis results according to the monitoring report.
  • the above sampling module 3-1 includes: a stainless steel needle, a slide rail and a turntable.
  • the stainless steel needle is connected to the power module 3-2 through the first pipeline.
  • the first pipe is arranged on the slide rail, and the slide rail and the horizontal line form a set angle (preferably 60°).
  • the stainless steel needle is fixedly arranged at one end of the slide rail, and the other end of the slide rail is a free end.
  • the slide rail is used to drive the stainless steel needle to slide, and the stainless steel needle is used to probe into the new reactor 1-41 to absorb the reaction solution.
  • the slide rail is fixed on the turntable. Both the turntable and the slide rail are electrically connected with the upper computer 5 .
  • the slide rail includes a slide plate and a support frame.
  • the sliding plate moves down the support frame so that the stainless steel needle is inserted into the novel reactor 1-41 to draw the reaction solution.
  • the support frame is fixed on the turntable, and the turntable can drive the entire slide rail to rotate, so that the stainless steel needle can absorb the liquid in different containers.
  • the slide rail is fixed with the position of the new reactor 1-41 and can be adjusted up and down.
  • a sliding track may be provided on the sliding rail to fix the first conduit.
  • the turntable (machining module) drives the support slide rail to rotate to different positions at a certain angle in different directions and stay there.
  • Stainless steel needles are preferably 9# needles in the present invention.
  • a pierceable sealing rubber pad and an organic filter head are also arranged.
  • the selection specifications of organic filter heads include 0.22um, 0.45um and 0.8um.
  • the above-mentioned power module 3-2 includes: a power pump.
  • the power pump is a syringe pump or a plunger pump.
  • the power pump selected in the present invention has a strong suction force and also has a reverse suction function.
  • the purpose of setting the suck-back function is to facilitate the cleaning of the pipelines of the entire liquid phase synthesis automatic monitoring system 3 .
  • the power pump is connected to the sampling module 3-1 and the monitoring and analysis module 3-3 pipelines respectively.
  • the above-mentioned monitoring and analysis module 3-3 is preferably a high performance liquid chromatograph (HPLC).
  • HPLC high performance liquid chromatograph
  • the liquid chromatograph is improved as follows: disassemble and adjust the sample injection part, connect with the online sample injection six-way valve through loop, receive the short-circuit signal of the upper computer 5 to control the trigger operation, and run the If the method is fixed and selected, it will be automatically flushed after the method is run.
  • the high performance liquid chromatograph gives a report in TXT format according to the extracted reaction solution sample, for the upper computer 5 to extract data and generate an analysis report.
  • the liquid phase synthesis automatic monitoring system 3 provided by the present invention further includes a cleaning module 3-4.
  • the cleaning module 3-4 is respectively connected to the sampling module 3-1 and the power module 3-2 with pipelines.
  • the cleaning module 3-4 includes: a first liquid container 3-41, a second liquid container 3-42 and a solenoid valve 3-43.
  • the stainless steel needle can absorb the cleaning liquid in the first liquid container 3-41.
  • the second liquid container 3-42, the power module 3-2 and the monitoring and analysis module 3-3 are all connected with the solenoid valve 3-43 in a pipeline. After the power module 3-2 sucks the cleaning liquid in the second liquid container 3-42 into the power pump through the suction function, it can be injected into the monitoring and analysis module 3-3 to clean it.
  • the cleaning solution used in the present invention is preferably an organic solvent.
  • the solenoid valve 3-43 is preferably an online sample injection six-way valve (high pressure flow path switching valve). It is equivalent to the injection six-way valve of the high-performance liquid sampler, connecting the loop of the HPLC and the waste liquid. The difference between it and the six-way valve in HPLC is that it is online alone and is controlled by the host computer 5 or HPLC.
  • liquid phase synthesis automatic monitoring system 3 provided by the present invention to automatically sample, monitor and report and analyze the reaction solution, it is necessary to rely on a software program.
  • the specific advantages of the liquid phase synthesis automatic monitoring system 3 provided by the present invention will be described in detail below in conjunction with the software program implanted in the upper computer 5 . Since the key point of the present invention is to protect the hardware structure, only the spiritual level is explained for the software control part.
  • the present invention utilizes Shimadzu's DB version (database version) to analyze the liquid phase, reserves short-circuit joints for control triggering, combines with the short-circuit signal from the upper computer 5 to the PLC to control the liquid phase to run automatically as required, and automatically generates a PDF version after the running is completed.
  • the TXT report of the report and the ASCII code of the original data, the upper computer 5 extracts the TXT report.
  • reaction principle of "pre-activation” as an example, whether it is a common activation method or a light-mediated activation method, after the donor is activated, "sampling monitoring” needs to monitor whether the donor is fully activated, that is, activation monitoring, and then give Feedback of activation results, if it is not fully activated, continue to activate or activate repeatedly or continue to activate by light; if it is fully activated, add receptors, enter the "reaction time", and “sample to monitor” whether the receptors completely disappear after a certain time and temperature. Whether a new compound is formed, that is, reaction monitoring, and then give feedback on the reaction result. Whether the receptor remains is the key to judging whether to continue the next cycle reaction.
  • the receptor still remains, continue to prolong the reaction time or increase the reaction temperature to continue the reaction. If the receptor has disappeared or is below a certain limit, it can continue by default. For the next cycle, the activation reaction can be continued and monitored. Consider terminating the automated synthesis if the receptor persists above a certain limit.
  • each system provided by the present invention is organically integrated, and the obtained liquid-phase automatic synthesizer is shown in Figure 7.
  • the length, width and height of the liquid-phase automatic synthesizer under this combination are 600cm.
  • This assembly method is not the only assembly method of the liquid-phase automated synthesizer provided by the present invention, and the combination methods that can be obtained by those skilled in the art in combination with the above contents of the present invention all belong to the protection scope of the present invention.
  • the liquid-phase automatic synthesizer is provided with a power distribution cabinet to provide electrical energy for the entire liquid-phase automatic synthesizer.
  • the liquid phase automatic synthesizer provided by the present invention has a multi-layer structure inside, and each layer structure is provided with a door, and the door is provided with a stainless steel handle.
  • the material of the door is mostly brown plexiglass, so that the operator can observe the internal experiment process while blocking light and heat.
  • the door is divided into a lower door, a side door and an upper door, and the side door includes a left door and a right door.
  • Each door is provided with a door suction and a door hole to ensure the sealing of the entire liquid phase automatic synthesizer.
  • a linear slide rail is also provided below the liquid storage modules 1-5, and the linear slide rail is fixed on the bottom plate.
  • the liquid storage module 1-5 and the mixing device 2-2 are separated by side baffles.

Landscapes

  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

一种液相自动化合成仪，通过设置自动进样系统（1）、液相合成辅助系统（2）、液相合成自动监测系统（3）和上位机（5），并使得自动进样系统（1）根据上位机（5）的进样指令完成自动进样操作，液相合成辅助系统（2）根据上位机（5）的温度控制指令和光照控制指令完成对待反应溶液的温度和光照控制，液相合成自动监测系统（3）对反应溶液进行监测，生成监测报告，上位机（5）根据监测报告生成实验分析结果，以完成液相实验过程中从进样到生成报告的自动化过程，进而降低实验人力成本、提高实验效率。

Description

一种液相自动化合成仪
本申请要求于2020年12月19日提交中国专利局、申请号为202011508994.X、发明名称为“一种液相自动化合成仪”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本发明涉及实验设备技术领域，特别是涉及一种液相自动化合成仪。
背景技术
液相实验是进行学术研究必不可少的环节。现有的液相实验均需要人工对待反应融合进行定量添加，并且，人工控制搅拌反应的方式得到混合溶液。在对混合溶液进行检测的过程中，也需要人工将反应液添加到监测仪中进行检测，并且，监测仪生成的监测报告需要人工整理核对，这就导致整个液相实验监测过程费时费力。
基于此，现有技术中提供了部分自动进样装置，其进样方式主要包括两种：一、管路转移进样：目前市场上有多肽固相合成仪和寡糖固相合成仪及自动固相萃取仪等。它的优点是体系密闭、安全、外界无干扰与系统性强；缺点是研发周期长、单个成品的设计与研制成本高。它的设计的途径有两个：1、组件购买组装，可灵活调整和修改，便于集成程序(注射泵单元、多通道切换阀、光源、低温循环、磁力搅拌等及在线监测)，但亦需要重新设计，周期长，需要各方面人才，且组装后运行结果存在较多影响因素。2、从商业化的相似产品改造升级，即适当改造成熟自动化产品，周期短且不需要太多的人力，可保证正常工作，但由于成熟产品有自己专利研发的成熟软件控制系统，程序集成麻烦，没有源代码，可能需要重新设计集成板。二、自动移液进样：目前市面上有成熟的自动移液工作站出售(价格在10-40万)，可直接进行购买稍加改造即可。它的优点是简单、快速、可直接将手动操作固化到仪器上；缺点是所有操作需要机械臂代替，故障率高、空间大，同样是成熟产品，程序集成不便。
此外，在进行液相实验过程中控温和控制光照也是实验的重要环节，现有的实验液相合成过程中多采用两口石英反应器进行溶液反应，并且难以在-80℃低温槽内进行侧照的方式进行实验。在侧照过程中，一般采用 长弧汞灯光源和石英材质的冷阱作为光源装置，该光源装置需要给石英冷阱配套低温循环装置，以使循环温度(-20℃，太低温度下汞灯无法启动)高于低温槽的温度(-80℃)，这就造成低温槽的温度很难准确控制，同时需要单独配备一套低温循环装置在开启汞灯前及时开启，如果忘记开启冷阱的低温循环装置而开启汞灯，随着汞灯的开启和长时间照射，则有着非常高的失火风险。
为了解决上述存在的问题，在进行照射方式时，虽然使用长弧汞灯光源和石英材质的冷阱，但是需要将冷阱横置，紫外光自上而下照射反应器，反应器置于乙醇/干冰的低温浴杜瓦瓶中。此方式易控温且稳定，模型反应合成效果与之前实验室侧照方式一致，甚至略好，但仍需要给冷阱降温并额外开启冷阱的低温循环装置，不易于仪器的组装，不安全且紫外光的利用率非常低，还需要额外的紫外防护装置。
因此，提供一种能够实现液相实验自动化的具有高效率、高精度的液相自动合成装置，是本领域亟待解决的一个技术难题。
发明内容
本发明的目的是提供一种液相自动化合成仪，以实现液相合成实验的自动化、进而提高液相合成实验的实验效率和实验精度。
为实现上述目的，本发明提供了如下方案：
一种液相自动化合成仪，包括：自动进样系统、液相合成辅助系统、液相合成自动监测系统和上位机；
所述自动进样系统、所述液相合成辅助系统和所述液相合成自动监测系统均与所述上位机电连接；
所述自动进样系统用于根据所述上位机的进样指令完成自动进样操作；所述液相合成辅助系统用于根据所述上位机的温度控制指令和光照控制指令完成对待反应溶液的温度和光照控制；所述自动监测系统用于对反应溶液进行监测，生成监测报告；所述上位机根据所述监测报告生成实验分析结果。
优选地，还包括新型反应器；
所述新型反应器分别与所述自动进样系统、所述液相合成辅助系统和 所述液相合成自动监测系统管路连接。
优选地，所述新型反应器包括：瓶口、瓶身、进样口、排气口、取样口、循环出液口和循环进液口；
所述进样口与所述瓶身间呈设定角度；所述排气口和所述进样口以所述瓶口的中心线为中心对称设置；
所述瓶身由内及外依次包括反应内胆、温度循环层和真空层；所述反应内胆的胆底为圆弧形结构；
所述取样口与所述反应内胆连通；
所述循环出液口和所述循环进液口均与所述温度循环层连通，且所述循环出液口和所述循环进液口对角设置。
优选地，所述自动进样系统包括：惰性气体输送模块、取样通道切换模块、定量模块、处置模块和储液模块；
所述储液模块和所述取样通道切换模块均通过管路与所述惰性气体输送模块连接；所述定量模块通过管路分别与所述取样通道切换模块和所述处置模块连接；所述储液模块通过管路与所述取样通道切换模块连接；
所述惰性气体输送模块、所述取样通道切换模块和所述定量模块均与所述上位机电连接；
所述惰性气体输送模块用于将内部存储的惰性气体分别通过管路输送给所述储液模块和所述取样通道切换模块；所述取样通道切换模块用于提取所述储液模块中存储的待反应溶液，并用于切换提取所述待反应溶液的通道；所述定量模块用于确定注入所述处置模块中的待反应溶液量；
所述上位机用于控制所述惰性气体输送模块和所述定量模块的开启和关闭，并用于控制所述取样通道切换模块进行通道切换。
优选地，所述取样通道切换模块包括：第一多通道切换阀和第二多通道切换阀；
所述第一多通道切换阀通过管路与M个所述储液瓶连接；所述第二多通道切换阀通过管路与N-M个所述储液瓶连接；
所述定量模块包括：注射泵单元、压力传感器、流量计和第二电磁阀 单元；
所述注射泵单元的入口通过管路与所述取样通道切换模块连接；所述注射泵单元的出口通过管路与所述流量计连接；所述流量计通过管路与所述处置模块连接；所述第二电磁阀单元设置在所述流量计与所述处置模块的连接管路上；所述压力传感器设置在所述注射泵单元与所述流量计的连接管路上；所述第二电磁阀单元、所述压力传感器和所述流量计均与所述上位机电连接；
所述处置模块包括：溶液管和废液瓶；
所述新型反应器的进样口和所述废液品的进液口均通过管路与所述第二电磁阀单元连接；所述溶液管通过管路与所述新型反应器的循环进液口连接；
所述第二电磁阀单元用于当所述新型反应器中溶液达到设定量时，关闭所述流量计与所述新型反应器间的连接管路，并开启所述流量计与所述废液瓶的连接管路；
优选地，所述注射泵单元包括：第一注射泵和第二注射泵；
所述第一注射泵通过管路与所述第一多通道切换阀中的一通道连接；所述第二注射泵通过管路与所述第二多通道切换阀中的一通道连接；所述第一注射泵的量程小于所述第二注射泵的量程。
优选地，所述液相合成辅助系统，包括：混合装置和控温装置；
所述新型反应器置于所述混合装置上，所述混合装置和所述控温装置均与所述上位机电连接。
优选地，所述控温装置包括：紫外光源和低温循环器；
所述低温循环器的出液口与所述循环进液口管路连接；所述低温循环器的入液口与所述循环出液口管路连接；所述紫外光源用于照射所述新型反应器；
所述混合装置包括：自动搅拌器和恒温盘；
所述自动搅拌器和所述恒温盘均与所述上位机电连接；所述自动搅拌器用于根据所述上位机中的搅拌指令搅拌所述新型反应器中的混合液；所 述新型反应器置于所述自动搅拌器上；所述恒温盘用于保持所述新型反应器的温度恒定。
优选地，所述液相合成自动监测系统，包括：取样模块、动力模块、监测分析模块和清洗模块；
所述取样模块与所述动力模块管路连接；所述动力模块和所述监测分析模块管路连接；所述取样模块、所述动力模块和所述监测分析模块均与所述上位机电连接；
所述取样模块用于吸取所述新型反应器中盛装的反应溶液；所述动力模块用于根据所述上位机中的吸取指令为所述取样模块提供吸取力，并用于将吸取的反应溶液注入所述监测分析模块中；所述监测分析模块用于根据反应溶液生成监测报告后，将所述监测报告传输给所述上位机；所述上位机根据所述监测报告生成分析结果；
所述清洗模块分别与所述取样模块和所述动力模块管路连接。
优选地，所述取样模块包括：不锈钢针头、滑轨和转盘；
所述不锈钢针头通过第一管道与所述动力模块连接；所述第一管道设置在所述滑轨上，且所述滑轨与水平线间呈设定角度；所述不锈钢针头固定设置在所述滑轨的一端，所述滑轨的另一端为自由端；所述滑轨用于带动所述不锈钢针头进行滑动，所述不锈钢针头用于探入所述新型反应器中吸取反应溶液；所述滑轨固定设置在所述转盘上；所述转盘和所述滑轨均与所述上位机电连接；
所述动力模块包括：动力泵；所述动力泵为注射泵或所述柱塞泵；
所述动力泵分别与所述取样模块和所述监测分析模块管路连接；
所述监测分析模块为高效液相色谱仪；
所述清洗模块包括：第一盛液器、第二盛液器和电磁阀；
所述不锈钢针头吸取所述第一盛液器中的清洗液；所述第二盛液器、所述动力模块和所述监测分析模块均与所述电磁阀管路连接。
根据本发明提供的具体实施例，本发明公开了以下技术效果：
本发明提供的液相自动化合成仪，通过设置自动进样系统、液相合成 辅助系统、液相合成自动监测系统和上位机，并使得所述自动进样系统根据所述上位机的进样指令完成自动进样操作，所述液相合成辅助系统根据所述上位机的温度控制指令和光照控制指令完成对待反应溶液的温度和光照控制，所述自动监测系统对反应溶液进行监测，生成监测报告，所述上位机根据所述监测报告生成实验分析结果，以完成液相实验过程中从进样到生成报告的自动化过程，进而降低实验人力成本、提高实验效率。
说明书附图
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动性的前提下，还可以根据这些附图获得其他的附图。
图1为本发明提供的液相自动化合成仪的结构框图；
图2为本发明提供的液相自动化合成仪的结构示意图；
图3为本发明实施例提供的新型反应器的结构示意图；
图4为本发明实施例提供的自动进样系统的结构示意图；
图5为本发明实施例提供的液相合成辅助系统的结构示意图；
图6为本发明实施例提供的液相合成自动监测系统的结构示意图；
图7为本发明实施例提供的液相自动化合成仪的实物图。
符号说明：
1自动进样系统，1-1惰性气体输送模块，1-11惰性气体存储器，1-12调压过滤器，1-13第一电磁阀单元，1-131第一二通电磁阀，1-132第二二通电磁阀，1-133三通电磁阀，1-2取样通道切换模块，1-21第一多通道切换阀，1-22第二多通道切换阀，1-3定量模块，1-31注射泵单元，1-311第一注射泵，1-312第二注射泵，1-32压力传感器，1-33流量计，1-34第二电磁阀单元，1-4处置模块，1-41新型反应器，1-42溶液管，1-43废液瓶，1-5储液模块，1-51储液瓶，2-液相合成辅助系统，2-1控温装置，2-11紫外光源，2-12低温循环器，2-2混合装置，2-21自动搅拌器，2-22恒温盘，3-液相合成自动监测系统，3-1取样模块，3-2动力模块，3-3监测分析模块，3-4清洗模块，3-41第一盛液器，3-42第二盛液器，3-43电磁阀，1-411瓶口，1-412进样口，1-413排气口，1-414取样口，1-415 瓶身，1-4151反应内胆，1-4152温度循环层，1-4153真空层，1-416循环出液口，1-417上盖，5上位机。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
本发明的目的是提供一种液相自动化合成仪，以实现液相合成实验的自动化、进而提高液相合成实验的实验效率和实验精度。
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合附图和具体实施方式对本发明作进一步详细的说明。
如图1所示，本发明提供的液相自动化合成仪，包括：自动进样系统1、液相合成辅助系统2、液相合成自动监测系统3和上位机5。
自动进样系统1、液相合成辅助系统2和液相合成自动监测系统3均与上位机5电连接。
自动进样系统1用于根据上位机5的进样指令完成自动进样操作。液相合成辅助系统2用于根据上位机5的温度控制指令和光照控制指令完成对待反应溶液的温度和光照控制。自动监测系统用于对反应溶液进行监测，生成监测报告。上位机5根据监测报告生成实验分析结果。
因采用液相自动化合成仪进行液相实验的过程中，需要机器对反应器中的溶液进行搅拌，现有的反应器在搅拌过程中极易发生喷溅，并且，在进行某些低温实验时，现有的反应器外壁极易产生水汽而导致无法直接对反应器中的反应溶液进行观察。所以，基于本发明提供的液相自动化合成仪，本发明对应提供了一种新型反应器1-41以作为整个液相自动化合成仪的配套反应器。当然，因本发明提供的新型反应器1-41具有其他现有反应器无法匹及的优点，也可以用于其他实验设备。
本发明提供的新型反应器1-41分别与自动进样系统1、液相合成辅助系统2和液相合成自动监测系统3管路连接。
如图3所示，该新型反应器1-41包括：瓶口1-411，进样口1-412，排气口1-413，取样口1-414，瓶身1-415和循环出液口1-416。
进样口1-412与瓶身1-415间呈设定角度(优选为60°)。排气口1-413和进样口1-412以瓶口1-411的中心线为中心对称设置。取样口1-414的中心线与排气口1-413的中心线间的空间夹角为60°，这一具体角度的设置也是为了杜绝反应液在搅拌过程中喷溅到反应器外。
瓶身1-415由内及外依次包括反应内胆1-4151、温度循环层1-4152和真空层1-4153。反应内胆1-4151的胆底为圆弧形结构。
取样口1-414与反应内胆1-4151连通。
循环出液口1-416和循环进液口均与温度循环层1-4152连通，且循环出液口1-416和循环进液口对角设置。
并且在瓶口1-411上设置有上盖1-417或将瓶口1-411设置为密封结构。设置的上盖1-417优选为高透光率石英片。在瓶口1-411上设置有上盖1-417时，为了提高密封性，提供的新型反应器1-41还优选包括密封夹。密封夹用于夹接瓶口1-411和上盖1-417。密封夹为双夹套茄型结构，具体的可以采用两个法兰夹，对两个法兰夹进行改进，使两个法兰夹间形成的形状由U型变为茄型。
如图4所示，本发明提供的自动进样系统1包括：惰性气体输送模块1-1、取样通道切换模块1-2、定量模块1-3、处置模块1-4和储液模块1-5。
储液模块1-5和取样通道切换模块1-2均通过管路与惰性气体输送模块1-1连接。定量模块1-3通过管路分别与取样通道切换模块1-2和处置模块1-4连接。储液模块1-5通过管路与取样通道切换模块1-2连接。
惰性气体输送模块1-1、取样通道切换模块1-2和定量模块1-3均与上位机5电连接。
惰性气体输送模块1-1用于将内部存储的惰性气体分别通过管路输送给储液模块1-5和取样通道切换模块1-2。取样通道切换模块1-2用于提取储液模块1-5中存储的待反应溶液，并用于切换提取待反应溶液的通道。定量模块1-3用于确定注入处置模块1-4中的待反应溶液量。
上位机5用于控制惰性气体输送模块1-1和定量模块1-3的开启和关闭，并用于控制取样通道切换模块1-2进行通道切换。
其他的外接设备都可以通过通讯协议由上位机5控制可编程逻辑控制器(Programmable Logic Controller，PLC)进行程序控制以满足自动化程序的正常运行。
其中，上述惰性气体输送模块1-1包括：惰性气体存储器1-11、调压过滤器1-12和第一电磁阀单元1-13。
惰性气体存储器1-11通过管路分别与储液模块1-5和取样通道切换模块1-2连接。调压过滤器1-12和第一电磁阀单元1-13设置在惰性气体存储器1-11与储液模块1-5的连接管路上，或设置在惰性气体存储器1-11与取样通道切换模块1-2的连接管路上。
其中，第一电磁阀单元1-13包括：第一二通电磁阀1-131、第二二通电磁阀1-132和三通电磁阀1-133。
第一二通电磁阀1-131和三通电磁阀1-133设置在惰性气体存储器1-11与取样通道切换模块1-2的连接管路上。第二二通电磁阀1-132设置在惰性气体存储器1-11与储液模块1-5的连接管路上。
优选地，调压过滤器1-12的个数为两个，两个调压过滤器1-12分别设置在惰性气体存储器1-11与取样通道切换模块1-2的连接管路上和惰性气体存储器1-11与储液模块1-5的连接管路上。
上述储液模块1-5包括N个储液瓶1-51。
每一储液瓶1-51均与惰性气体输送模块1-1通过管路连接。储液瓶1-51的瓶底为锥形或弧形。
每一储液瓶1-51均包括：第一通道口、第二通道口、第三通道口和瓶盖。
第一通道口用于通过管路与取样通道切换模块1-2连接。第二通道口用于通过管路与惰性气体输送模块1-1连接。第三通道口用于排出储液瓶1-51中的气体或液体。
瓶盖与储液瓶1-51的瓶口1-411螺纹连接。
惰性气体微正压充满每一储液瓶1-51，以避免密闭的储液瓶1-51因液体的减少而产生负压，进而影响进样的准确度。
本发明提供的储液瓶1-51优选有四种：10mL尖底储液瓶，20mL尖底储液瓶，500mL圆底储液瓶和125mL两口储液瓶。10mL和20mL尖底储液瓶主要为储备砌块样品和试剂催化剂，尖底设计目的是让管路通到瓶底1-512避免储备液的损失和浪费，内螺纹设计方便配合定制的聚四氟乙烯瓶盖。500mL圆底储液瓶主要为储备超干的有机溶剂，125mL两口瓶主要为储备稀释反应液的有机溶剂，甚至废液。侧面的进进样口1-412主要为在线监测时取样针的插入和拔出。所有的储液瓶1-51均为透明封管玻璃材质，具备耐压能力，未采用棕色或者黑色主要目的是便于仪器使用者观察储备液的剩余量。
从自动进样的整体结构中可以看出，在合成仪的研发过程中，除了最核心的反应器和光源及自动化进样与上位机5软件的密切配合，还有起辅助和基础作用的定制配件设计，主要是各种储液瓶1-51和相应的瓶盖。
与定制储液瓶1-51匹配的定制瓶盖设计经历了反复的探索、验证和修改。前文提到瓶盖有三个通道，分别为了通气、通液和放气。为了保证储备液的浓度稳定和自动进样的准确性，必须要求瓶盖密封严格，方便通断，耐腐蚀和耐用。通过增加四氟瓶盖的长度，在瓶盖内部镶嵌通断开关，瓶盖底部变细和倒锥连接，保证压实密封无需密封圈且连接紧密，瓶盖上方通过三角型布置倒锥连接保证连接管路的密封性得到初始定制瓶盖。经过反复测试发现，该初始瓶盖内部镶嵌的通断开关处有漏液想象，故又在通断开关处增加普通的弹性密封垫圈，此垫圈在瓶盖外部，无需要求耐腐蚀功能，即得到四氟三通道压实性瓶盖。
上述取样通道切换模块1-2包括：第一多通道切换阀1-21和第二多通道切换阀1-22。
第一多通道切换阀1-21通过管路与M个储液瓶1-51连接。第二多通道切换阀1-22通过管路与N-M个储液瓶1-51连接。
两个十通道切换阀可以平行或者交叉连接不同规格的储液瓶1-51。为方便使用，将两个切换阀的第10通道一直连接惰性气体，第9通道连 接常用的超干溶剂(比如二氯甲烷)，第8通道连接次用的超干溶剂(比如乙腈或者甲苯等)，其他的各个通道可以分别独立或者交叉连接不同或相同的储备液，不会出现交叉污染的现象。
一般根据实验需要进样量小于或者接近1mL的连接第一多通道切换阀1-21，大于或者接近1mL的连接第二多通道切换阀1-22，多通道切换阀种的每个通道号需要和各个储液瓶1-51内的物质一一对应。而惰性气体存储器1-11则通过减压阀和调压过滤器1-12依次降压并过滤使用，起到提供正压和清洗管路的作用。
上述定量模块1-3包括：注射泵单元1-31、压力传感器1-32、流量计1-33和第二电磁阀单元1-34。
注射泵单元1-31的入口通过管路与取样通道切换模块1-2连接。注射泵单元1-31的出口通过管路与流量计1-33连接。流量计1-33通过管路与处置模块1-4连接。第二电磁阀单元1-34设置在流量计1-33与处置模块1-4的连接管路上。压力传感器1-32设置在注射泵单元1-31与流量计1-33的连接管路上。第二电磁阀单元1-34、压力传感器1-32和流量计1-33均与上位机5电连接。
注射泵单元1-31包括：第一注射泵1-311和第二注射泵1-312。
第一注射泵1-311通过管路与第一多通道切换阀1-21中的一通道连接。第二注射泵1-312通过管路与第二多通道切换阀1-22中的一通道连接。第一注射泵1-311的量程小于第二注射泵1-312的量程。
为保证进样的准确度，本发明提供的整个进样系统低于或者接近1mL的进样量时，由小量程注射泵(即第一注射泵1-311)连接的管路进样。高于或者接近1mL的进样量时，由大量程注射泵(即第二注射泵1-312)连接的管路进样，两条管路先平行进行后合二为一进入反应器中。注射泵上的注射器可以更换，最小500uL，最大25mL，且可以模块化增加切换阀和注射泵的数量进行拓展。每一条管路都是注射泵提供进样动力。每一条管路都有各自的注射泵和后面的高精度流量计1-33协同配合，双重控制以保证进样的准确性，且注射泵和流量计1-33之间以流量计1-33的计量作为最终的进样量。进行该设置的原因一是因注射泵本身的 精确度(1％)低于流量计1-3333本身的精确度(2‰)。二是注射泵无法识别气泡或者有无储备液，而流量计1-33在气体和液体之间的计量差别较大，有气体通过时计量变化大能反馈到流量计1-33和注射泵的双重自我修正中。
上述处置模块1-4包括：新型反应器1-41、溶液管1-42和废液瓶1-43。
新型反应器1-41的进样口1-412和废液品的进液口均通过管路与第二电磁阀单元1-34连接。溶液管1-42通过管路与新型反应器1-41的排气口1-413连接。
第二电磁阀单元1-34用于当新型反应器1-41中溶液达到设定量时，关闭流量计1-33与新型反应器1-41间的连接管路，并开启流量计1-33与废液瓶1-43的连接管路。
在高精度流量计1-33控制满足需要的进样量后，紧挨着流量计1-33的电磁阀会将多余的待反应溶液立即切换到废液瓶1-43中，保证进入新型反应器1-41的进样量准确。每次进样后可以根据需要在上位机5中编写是否进行管路清洗指令，管路清洗的废液亦进入到废液瓶1-43中。与新型反应器1-41的进液口相连接的是可以防倒吸的油泡器，这样做的目的是为了保证新型反应器1-41内气压正常且不会有外来气体或水蒸气进入该反应器种，进而达到整个自动进样系统1的密闭性要求。
如图5所示，上述液相合成辅助系统2，包括：控温装置2-1和混合装置2-2。
在上位机5中植入软件程序，该软件程序用于控制混合装置2-2和控温装置2-1的具体工作流程。
新型反应器1-41置于混合装置2-2上，混合装置2-2和控温装置2-1均与上位机5电连接。
上述控温装置2-1包括：紫外光源2-11和低温循环器2-12。
低温循环器2-12的出液口与循环进液口1-416管路连接。低温循环器2-12的入液口与循环出液口管路连接。
紫外光源2-11用于照射新型反应器1-41。在本发明中紫外光源2-11 优选是型号为CEL-M系列的汞灯光源。
混合装置2-2包括自动搅拌器2-21和恒温盘2-22。
自动搅拌器2-21和恒温盘2-22均与上位机5电连接。自动搅拌器2-21用于根据上位机5中的搅拌指令搅拌新型反应器1-41中的混合液。新型反应器1-41置于自动搅拌器2-21上。自动搅拌器2-21设置在恒温盘2-22上。自动搅拌器2-21旋转带动新型反应器1-41旋转，以通过离心力的作用实现搅拌功能。恒温盘2-22用于保持新型反应器1-41的温度恒定。
此外，本发明中的自动搅拌器2-21也可以为一根搅拌棒，设置在新型反应器1-41的上方，以通过搅拌反应器中混合液的方式使溶液混合均匀。
如图6所示，液相合成自动监测系统3，包括：取样模块3-1、动力模块3-2和监测分析模块3-3。
取样模块3-1与动力模块3-2管路连接。动力模块3-2和监测分析模块3-3管路连接。取样模块3-1、动力模块3-2和监测分析模块3-3均与上位机5电连接。
取样模块3-1用于吸取新型反应器1-41中盛装的反应溶液。动力模块3-2用于根据上位机5中的吸取指令为取样模块3-1提供吸取力，并用于将吸取的反应溶液注入监测分析模块3-3中。监测分析模块3-3用于根据反应溶液生成监测报告后，将监测报告传输给上位机5。上位机5根据监测报告生成分析结果。
下面对本发明提供的上述各模块的具体结构进行说明。
上述取样模块3-1包括：不锈钢针头、滑轨和转盘。
不锈钢针头通过第一管道与动力模块3-2连接。第一管道设置在滑轨上，且滑轨与水平线间呈设定角度(优选为60°)。不锈钢针头固定设置在滑轨的一端，滑轨的另一端为自由端。滑轨用于带动不锈钢针头进行滑动，不锈钢针头用于探入新型反应器1-41中吸取反应溶液。滑轨固定设置在转盘上。转盘和滑轨均与上位机5电连接。
其中，滑轨包括滑动板和支撑架。滑动板沿支撑架向下运动，使得不 锈钢针头探入新型反应器1-41中以吸取反应溶液。支撑架固定在转盘上，转盘可带动整个滑轨进行旋转，以便不锈钢针头吸取不同容器中的液体。滑轨是和新型反应器1-41的位置配合固定的，可升降调节。为了使第一管道的固定更加牢固，滑轨上可以设置有滑道以便固定第一导管。转盘(机加工模组)带动支撑滑轨朝不同方向的一定角度转动不同位置并停留。
不锈钢针头在本发明优选9#针头。在不锈钢针和第一导管连接位置处，还设置有可穿刺密闭橡胶垫和有机滤头。其中，有机滤头的选择规格包括0.22um、0.45um和0.8um。使用时，在有机滤头前端用脱脂棉轻微堵塞，相当于初步过滤反应溶液中的分子筛，再通过有机滤头的滤膜过滤满足进液相要求，实现双重过滤，这样能够有效避免堵塞有机滤头。
上述动力模块3-2包括：动力泵。动力泵为注射泵或柱塞泵。本发明中所选用的动力泵在具有较强吸取力的同时，还具有倒吸功能。设置倒吸功能，是为了便于对整个液相合成自动监测系统3的管路进行清洗。
动力泵分别与取样模块3-1和监测分析模块3-3管路连接。
上述监测分析模块3-3优选为高效液相色谱仪(HPLC)。本发明为便于实现自动监测的功能，对该液相色谱仪进行以下改进：拆卸调整进样部分，和在线进样六通阀通过loop连接，接收上位机5的短接信号控制触发运行，运行方法固定选择好，运行方法结束后自动冲洗。高效液相色谱仪依据提取的反应溶液样本给出TXT格式的报告，供上位机5提取数据并生成分析报告。
基于上述内容，为了便于对整个系统进行清洗，本发明提供的液相合成自动监测系统3还包括清洗模块3-4。
清洗模块3-4分别与取样模块3-1和动力模块3-2管路连接。
该清洗模块3-4包括：第一盛液器3-41、第二盛液器3-42和电磁阀3-43。
在转盘带动下，不锈钢针头能够吸取到第一盛液器3-41中的清洗液。第二盛液器3-42、动力模块3-2和监测分析模块3-3均与电磁阀3-43管路连接。动力模块3-2通过倒吸功能将第二盛液器3-42中的清洗液吸入到动力泵中后，可注入监测分析模块3-3中，以便对其进行清洗。本发明 采用的清洗液优选为有机溶剂。
其中，电磁阀3-43优选为在线进样六通阀(高压流路切换阀)。其相当于高效液相进样器的进样六通阀，连接HPLC的loop和废液。其与HPLC中的六通阀的区别在于是它是单独在线，受上位机5或者HPLC的控制。
在本发明中实现的滑轨和转盘的滑动旋转，均是采用现有的伺服电机进行，因其为现有常规技术，在此不再进行赘述。
在本发明采用本发明提供的液相合成自动监测系统3对反应溶液进行自动取样、监测和报告分析的过程中，需要依赖于软件程序。下面结合上位机5中植入的软件程序对本发明提供的液相合成自动监测系统3的具体优点进行详细说明。因本发明的重点在于保护硬件结构，因此针对软件控制部分只做精神层面的说明。
本发明利用岛津的DB版(数据库版)分析液相，预留控制触发的短接接头，结合上位机5给PLC的短接信号控制液相根据需要自动运行，运行结束后自动生成PDF版报告和原始数据的ASCII码的TXT报告，上位机5提取TXT报告。
在上位机5中设置“在线监测”界面，以一直提取最新产生的TXT报告。根据液相的命名方式，使得新产生的TXT报告的命名始终处于上一个TXT报告的下，以方便于上位机5的提取，上位机5提取到新的TXT报告后可以根据内部植入的逻辑关系进行对比、判断和分析。
以“预活化”一釜的反应原理为例，不管是普通活化方式还是光介导活化方式，在给体活化后“取样监测”需要监测给体是否被完全活化，即活化监测，然后给出活化结果反馈，如未活化完全则继续活化或者反复活化或者继续光照活化，如果已完全活化则加入受体，进入“反应时间”，一定时间和温度后“取样监测”受体是否完全消失，同时是否有新化合物生成，即反应监测，然后给出反应结果反馈。受体是否剩余是判断是否继续进行下一步循环反应的关键，如果受体仍有剩余则继续延长反应时间或者升高反应温度以继续反应，如果受体已消失或者低于一定限度可默认继续进行下一个循环，可继续活化反应并监测。如果受体一直存在高于一定限度则考 虑终止自动化合成。
基于以上内容对本发明提供的各个系统进行有机整合，得到的液相自动化合成仪的实物如图7所示，该种组合方式下液相自动化合成仪的长、宽和高分别为870cm、730cm和600cm。此种组装方式不作为本发明提供的液相自动化合成仪的唯一组装方式，本领域技术人员结合本发明上述内容能够得到的组合方式均属于本发明的保护范围。
其中，该液相自动化合成仪中设置有配电柜，以为整个液相自动化合成仪提供电能。并且，为了节约布置空间，本发明提供的该液相自动化合成仪内部为多层结构，对应每一层结构均开设有门，门上设置有不锈钢把手。门的材料多以茶色有机玻璃为主，以便操作人员观察内部实验进程的同时，阻隔光、热。其中，门分为下部门、侧门和上部门，侧门包括左侧门和右侧门。每一门上均设置有门吸和门孔，以确保整个液相自动化合成仪的密封性。
进一步为了便于取拿样品，在储液模块1-5下方还设置有线性滑轨，线性滑轨固定在底板上。采用侧挡板将储液模块1-5和混合装置2-2隔开。
本说明书中各个实施例采用递进的方式描述，每个实施例重点说明的都是与其他实施例的不同之处，各个实施例之间相同相似部分互相参见即可。
本文中应用了具体个例对本发明的原理及实施方式进行了阐述，以上实施例的说明只是用于帮助理解本发明的方法及其核心思想；同时，对于本领域的一般技术人员，依据本发明的思想，在具体实施方式及应用范围上均会有改变之处。综上所述，本说明书内容不应理解为对本发明的限制。

Claims (10)

  1. 一种液相自动化合成仪，其特征在于，包括：自动进样系统、液相合成辅助系统、液相合成自动监测系统和上位机；
    所述自动进样系统、所述液相合成辅助系统和所述液相合成自动监测系统均与所述上位机电连接；
    所述自动进样系统用于根据所述上位机的进样指令完成自动进样操作；所述液相合成辅助系统用于根据所述上位机的温度控制指令和光照控制指令完成对待反应溶液的温度和光照控制；所述自动监测系统用于对反应溶液进行监测，生成监测报告；所述上位机根据所述监测报告生成实验分析结果。
  2. 根据权利要求1所述的液相自动化合成仪，其特征在于，还包括新型反应器；
    所述新型反应器分别与所述自动进样系统、所述液相合成辅助系统和所述液相合成自动监测系统管路连接。
  3. 根据权利要求2所述的液相自动化合成仪，其特征在于，所述新型反应器包括：瓶口、瓶身、进样口、排气口、取样口、循环出液口和循环进液口；
    所述进样口与所述瓶口间呈设定角度；所述排气口的中心线与所述瓶口的中心线垂直；
    所述瓶身由内及外依次包括反应内胆、温度循环层和真空层；所述反应内胆的胆底为弧形结构；
    所述取样口与所述反应内胆连通；
    所述循环出液口和所述循环进液口均与所述温度循环层连通，且所述循环出液口和所述循环进液口对角设置。
  4. 根据权利要求2所述的液相自动化合成仪，其特征在于，所述自动进样系统包括：惰性气体输送模块、取样通道切换模块、定量模块、处置模块和储液模块；
    所述储液模块和所述取样通道切换模块均通过管路与所述惰性气体输送模块连接；所述定量模块通过管路分别与所述取样通道切换模块和所 述处置模块连接；所述储液模块通过管路与所述取样通道切换模块连接；
    所述惰性气体输送模块、所述取样通道切换模块和所述定量模块均与所述上位机电连接；
    所述惰性气体输送模块用于将内部存储的惰性气体分别通过管路输送给所述储液模块和所述取样通道切换模块；所述取样通道切换模块用于提取所述储液模块中存储的待反应溶液，并用于切换提取所述待反应溶液的通道；所述定量模块用于确定注入所述处置模块中的待反应溶液量；
    所述上位机用于控制所述惰性气体输送模块和所述定量模块的开启和关闭，并用于控制所述取样通道切换模块进行通道切换。
  5. 根据权利要求4所述的液相自动化合成仪，其特征在于，所述取样通道切换模块包括：第一多通道切换阀和第二多通道切换阀；
    所述第一多通道切换阀通过管路与M个所述储液瓶连接；所述第二多通道切换阀通过管路与N-M个所述储液瓶连接；
    所述定量模块包括：注射泵单元、压力传感器、流量计和第二电磁阀单元；
    所述注射泵单元的入口通过管路与所述取样通道切换模块连接；所述注射泵单元的出口通过管路与所述流量计连接；所述流量计通过管路与所述处置模块连接；所述第二电磁阀单元设置在所述流量计与所述处置模块的连接管路上；所述压力传感器设置在所述注射泵单元与所述流量计的连接管路上；所述第二电磁阀单元、所述压力传感器和所述流量计均与所述上位机电连接；
    所述处置模块包括：溶液管和废液瓶；
    所述新型反应器的进样口和所述废液品的进液口均通过管路与所述第二电磁阀单元连接；所述溶液管通过管路与所述新型反应器的排气口连接；
    所述第二电磁阀单元用于当所述新型反应器中溶液达到设定量时，关闭所述流量计与所述新型反应器间的连接管路，并开启所述流量计与所述废液瓶的连接管路。
  6. 根据权利要求5所述的液相自动化合成仪，其特征在于，所述注射泵单元包括：第一注射泵和第二注射泵；
    所述第一注射泵通过管路与所述第一多通道切换阀中的一通道连接；所述第二注射泵通过管路与所述第二多通道切换阀中的一通道连接；所述第一注射泵的量程小于所述第二注射泵的量程。
  7. 根据权利要求2所述的液相自动化合成仪，其特征在于，所述液相合成辅助系统，包括：混合装置和控温装置；
    所述新型反应器置于所述混合装置上，所述混合装置和所述控温装置均与所述上位机电连接。
  8. 根据权利要求7所述的液相自动化合成仪，其特征在于，所述控温装置包括：紫外光源和低温循环器；
    所述低温循环器的出液口与所述循环进液口管路连接；所述低温循环器的进液口与所述循环出液口管路连接；所述紫外光源用于照射所述新型反应器；
    所述混合装置包括：自动搅拌器和恒温盘；
    所述自动搅拌器和所述恒温盘均与所述上位机电连接；所述自动搅拌器用于根据所述上位机中的搅拌指令搅拌所述新型反应器中的混合液；所述新型反应器置于所述自动搅拌器上；所述恒温盘用于保持所述新型反应器的温度恒定。
  9. 根据权利要求2所述的液相自动化合成仪，其特征在于，所述液相合成自动监测系统，包括：取样模块、动力模块、监测分析模块和清洗模块；
    所述取样模块与所述动力模块管路连接；所述动力模块和所述监测分析模块管路连接；所述取样模块、所述动力模块和所述监测分析模块均与所述上位机电连接；
    所述取样模块用于吸取所述新型反应器中盛装的反应溶液；所述动力模块用于根据所述上位机中的吸取指令为所述取样模块提供吸取力，并用于将吸取的反应溶液注入所述监测分析模块中；所述监测分析模块用于根 据反应溶液生成监测报告后，将所述监测报告传输给所述上位机；所述上位机根据所述监测报告生成分析结果；
    所述清洗模块分别与所述取样模块和所述动力模块管路连接。
  10. 根据权利要求9所述的液相自动化合成仪，其特征在于，所述取样模块包括：不锈钢针头、滑轨和转盘；
    所述不锈钢针头通过第一管道与所述动力模块连接；所述第一管道设置在所述滑轨上，且所述滑轨与水平线间呈设定角度；所述不锈钢针头固定设置在所述滑轨的一端，所述滑轨的另一端为自由端；所述滑轨用于带动所述不锈钢针头进行滑动，所述不锈钢针头用于探入所述新型反应器中吸取反应溶液；所述滑轨固定设置在所述转盘上；所述转盘和所述滑轨均与所述上位机电连接；
    所述动力模块包括：动力泵；所述动力泵为注射泵或柱塞泵；
    所述动力泵分别与所述取样模块和所述监测分析模块管路连接；
    所述监测分析模块为高效液相色谱仪；
    所述清洗模块包括：第一盛液器、第二盛液器和电磁阀；
    所述不锈钢针头吸取所述第一盛液器中的清洗液；所述第二盛液器、所述动力模块和所述监测分析模块均与所述电磁阀管路连接。
PCT/CN2021/139399 2020-12-19 2021-12-18 一种液相自动化合成仪 WO2022127927A1 (zh)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US18/268,314 US20240036013A1 (en) 2020-12-19 2021-12-18 Automated solution-phase synthesizer
EP21905849.2A EP4220150A4 (en) 2020-12-19 2021-12-18 AUTOMATED LIQUID PHASE SYNTHESIZER
JP2023535356A JP2023552601A (ja) 2020-12-19 2021-12-18 液相自動化合成装置

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202011508994.XA CN112666293B (zh) 2020-12-19 2020-12-19 一种液相自动化合成仪
CN202011508994.X 2020-12-19

Publications (1)

Publication Number Publication Date
WO2022127927A1 true WO2022127927A1 (zh) 2022-06-23

Family

ID=75407105

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2021/139399 WO2022127927A1 (zh) 2020-12-19 2021-12-18 一种液相自动化合成仪

Country Status (5)

Country Link
US (1) US20240036013A1 (zh)
EP (1) EP4220150A4 (zh)
JP (1) JP2023552601A (zh)
CN (1) CN112666293B (zh)
WO (1) WO2022127927A1 (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115121209A (zh) * 2022-08-03 2022-09-30 衡阳师范学院 一种光热一体气液混合串联式连续流反应仪器系统
CN115683743A (zh) * 2022-12-30 2023-02-03 山东元禾新材料科技股份有限公司 一种轮胎助剂生产取样设备

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112666364B (zh) * 2020-12-19 2022-04-12 北京大学 一种自动进样系统
CN112666293B (zh) * 2020-12-19 2022-05-13 北京大学 一种液相自动化合成仪
CN114405422B (zh) * 2022-01-19 2023-02-28 中国工程物理研究院激光聚变研究中心 一种制备大直径聚合物微球的流体塑形装置及方法

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016008908A (ja) * 2014-06-25 2016-01-18 株式会社島津製作所 超臨界流体を用いた成分抽出分離装置及び成分抽出分離方法
CN205426779U (zh) * 2016-03-23 2016-08-03 厦门大学 硫离子现场自动分析仪
CN109374908A (zh) * 2018-11-23 2019-02-22 中国科学院上海高等研究院 一种适用于溶液高通量筛选的真空自动样品装置及真空样品室
CN110168362A (zh) * 2017-01-10 2019-08-23 株式会社岛津制作所 色谱装置用控制装置
CN110658140A (zh) * 2019-09-29 2020-01-07 北京海光仪器有限公司 一种用于总磷的化学分析系统
CN111289295A (zh) * 2018-12-06 2020-06-16 洛阳华清天木生物科技有限公司 一种用于生物反应过程在线取样检测装置及其方法
CN112666293A (zh) * 2020-12-19 2021-04-16 北京大学 一种液相自动化合成仪

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004174331A (ja) * 2002-11-25 2004-06-24 Mitsui Chemicals Inc 化合物の自動合成および評価システム
EP1714695B9 (en) * 2005-04-18 2010-09-22 Asahi Kasei Bioprocess, Inc. Automated compound synthesis system and method
CN101234325A (zh) * 2008-02-29 2008-08-06 上海大学 一种光催化反应器
EP2633327B1 (en) * 2010-10-29 2019-11-20 Thermo Fisher Scientific OY System layout for an automated system for sample preparation and analysis
CN104407083B (zh) * 2014-11-28 2016-08-31 天津博纳艾杰尔科技有限公司 全自动分离系统及其在食用油极性组分分离中的应用
CN105891391B (zh) * 2016-06-29 2019-02-12 天津博纳艾杰尔科技有限公司 一种自动进样装置
CN209992372U (zh) * 2019-03-29 2020-01-24 杭州慕迪科技有限公司 一种氨氮总磷二合一在线监测仪
CN210934429U (zh) * 2019-09-25 2020-07-07 西门子（中国）有限公司 废气处理系统
CN111060609A (zh) * 2019-12-06 2020-04-24 厦门大学 一种全自动固相萃取富集的分析装置和分析方法

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016008908A (ja) * 2014-06-25 2016-01-18 株式会社島津製作所 超臨界流体を用いた成分抽出分離装置及び成分抽出分離方法
CN205426779U (zh) * 2016-03-23 2016-08-03 厦门大学 硫离子现场自动分析仪
CN110168362A (zh) * 2017-01-10 2019-08-23 株式会社岛津制作所 色谱装置用控制装置
CN109374908A (zh) * 2018-11-23 2019-02-22 中国科学院上海高等研究院 一种适用于溶液高通量筛选的真空自动样品装置及真空样品室
CN111289295A (zh) * 2018-12-06 2020-06-16 洛阳华清天木生物科技有限公司 一种用于生物反应过程在线取样检测装置及其方法
CN110658140A (zh) * 2019-09-29 2020-01-07 北京海光仪器有限公司 一种用于总磷的化学分析系统
CN112666293A (zh) * 2020-12-19 2021-04-16 北京大学 一种液相自动化合成仪

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP4220150A4 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115121209A (zh) * 2022-08-03 2022-09-30 衡阳师范学院 一种光热一体气液混合串联式连续流反应仪器系统
CN115683743A (zh) * 2022-12-30 2023-02-03 山东元禾新材料科技股份有限公司 一种轮胎助剂生产取样设备

Also Published As

Publication number Publication date
CN112666293B (zh) 2022-05-13
CN112666293A (zh) 2021-04-16
US20240036013A1 (en) 2024-02-01
EP4220150A4 (en) 2024-04-10
JP2023552601A (ja) 2023-12-18
EP4220150A1 (en) 2023-08-02

Similar Documents

Publication Publication Date Title
WO2022127927A1 (zh) 一种液相自动化合成仪
CN204116276U (zh) 全自动毛细管电泳仪的液体输送系统
CN100510742C (zh) 负压进样微流控化学合成反应系统
CN103235074A (zh) 一种高效液相色谱在线分析方法及应用
WO2022127928A1 (zh) 一种自动进样系统
CN110186737A (zh) 一种液基标本制片染色一体机
CN206687716U (zh) 一种自动便携抽血泵
CN219695036U (zh) 智能配液滴定一体仪
CN208742320U (zh) 一种药物分析检测用药物溶解装置
CN217805390U (zh) 一种培养基自动分装装置
WO2022127925A1 (zh) 一种液相合成自动监测系统
CN111999162B (zh) 一种用于测定化学需氧量的原位消解装置
CN209997649U (zh) 一种样品检测分液器
CN219084488U (zh) 一种取样架、加药架以及检测装置
CN208237143U (zh) 一种可精确定量多通阀
CN215812595U (zh) 一种具有控温功能的液相色谱仪
CN213068430U (zh) 一种用于微波管的半自动模块化加液装置
CN203909632U (zh) 一种医学检测设备的流体控制系统
CN219701942U (zh) 基于微流控技术的纳米药物芯片盒和制备设备
CN216798794U (zh) 一种吊瓶式大体积进样固相萃取装置
CN202901347U (zh) 多工况定量取样阀
CN216771197U (zh) 配备自动收集功能的模拟局部给药产品体液循环装置
CN214703587U (zh) 一种具有定量测量的水质分析仪
CN217878536U (zh) 一种放射性惰性气体自动取样装置
CN220961552U (zh) 用于光谱仪器的多功能自动进样器

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21905849

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2021905849

Country of ref document: EP

Effective date: 20230428

WWE Wipo information: entry into national phase

Ref document number: 2023535356

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 18268314

Country of ref document: US

NENP Non-entry into the national phase

Ref country code: DE