Reaction device

Abstract

The utility model discloses a reaction device which mainly comprises a feeding flow path, a discharging flow path, a reaction flow path and a detection flow path, when a first flow path setting device is in a circulating state and a second flow path setting device is in a non-bypass state, the reaction device activates a first closed-loop and circulating flow path, and under the condition, the first closed-loop and circulating flow path is activated by the detection flow path. The reaction device which is closed-loop and circularly operated enables the whole reaction to be free of dead angles, avoids the problem of incomplete reaction caused by incomplete contact, remarkably improves the synthesis efficiency, saves reagents and reduces the reaction cost at the same time. In addition, the dosage of the reagent can be further controlled through a high-precision pump, and the accuracy of the dosage of the reagent is guaranteed.

Description

Technical Field

[0001] The utility model relates to the technical field of synthesis, and particularly relates to a reaction device. Background Art

[0002] In existing synthesis devices that use inert gas as power, such as polypeptide synthesis, the inert gas is used to transfer liquid substances in the device, and at the same time, a liquid level sensing device is used to measure the volume of substances to control their usage.

[0003] In the prior art, the solution mixing methods during the reaction mainly include the following several types: 1) Using inert gas for bubbling to mix the reaction solution; 2) Using a mechanical device to perform a 180° flip to mix the reaction solution; 3) Using a mechanical device to perform a 360° stirring to mix the reaction solution.

[0004] It should be noted that none of the above mixing methods can achieve close to or reach 100% full mixing, which leads to limited synthesis scale. At the same time, the above mixing methods also result in low synthesis efficiency and large reagent loss, and these disadvantages further lead to high synthesis costs. In addition, when transferring liquid substances through gas power, the liquid level sensing and metering method has a large deviation, making it difficult to accurately control the liquid usage, which further leads to many problems such as the difficulty in efficiently and accurately implementing the synthesis process. Summary of the Utility Model

[0005] Aiming at the problems in the prior art, the utility model provides a reaction device, a method for solid-phase polypeptide synthesis, a medium and a device.

[0006] On the one hand, the utility model discloses a reaction device, comprising:

[0007] A reaction flow path with a reactor, which is used for substances to flow into the reactor and then flow out,

[0008] A feed flow path, which is used for the reaction device to input substances,

[0009] A discharge flow path, which is used for the reaction device to discharge substances, and,

[0010] A detection flow path, which is used for detecting the substances flowing through,

[0011] Wherein,

[0012] When the reaction device is in the circulation mode, the reaction device activates the first closed-loop and circulating flow path, so that substances act in a circulating manner in the reactor. Among them, the first closed-loop and circulating flow path includes: a first flow path setting device, a system pump, a second flow path setting device, a reaction flow path, and a detection flow path.

[0013] Preferably, when the first flow path setting device is set to the circulation state and the second flow path setting device is set to the non-bypass state, the reaction device is in the circulation mode.

[0014] Preferably, when the reaction device is in the feeding and discharging mode, the reaction device activates the feeding flow path, and the activated feeding flow path is connected to the reaction flow path, wherein,

[0015] the feeding flow path includes: an inlet valve, a system pump, and a second flow path setting device; or,

[0016] the feeding flow path includes: an inlet valve, a first flow path setting device, a system pump, and a second flow path setting device.

[0017] Preferably, when the reaction device is in the feeding and discharging mode, the reaction device activates the discharging flow path, and the activated discharging flow path is connected from the reaction flow path, wherein the discharging flow path at least includes: a second flow path setting device, a detection flow path, and a first flow path setting device.

[0018] Preferably, before the circulation mode, the reaction device activates the feeding flow path.

[0019] Preferably, when the first flow path setting device is in the non-circulation state and the second flow path setting device is in the non-bypass state, the reaction device is in the feeding and discharging mode.

[0020] Preferably, when the reaction device is in the feeding and discharging mode, the feeding flow path, the reaction flow path, and the discharging flow path form a first open-loop flow path.

[0021] Preferably, when the second flow path setting device is in the non-bypass state, the reaction flow path can operate in the forward flushing mode or the reverse flushing mode.

[0022] Preferably, the system pump includes a high-precision metering pump.

[0023] Preferably, the detection flow path includes a conductivity detector and / or an ultraviolet detector, wherein,

[0024] the conductivity detector is used to detect the substances flowing through the flow path;

[0025] the ultraviolet detector is used to detect the substances flowing through the flow path.

[0026] Preferably, both the first flow path setting device and the second flow path setting device include control components, which are used to activate different flow paths, and the control components include at least 1 valve.

[0027] Preferably, the discharging flow path further includes: a back pressure valve,

[0028] along the direction of the substance flow in the flow path, the back pressure valve is located before the substance discharge outlet.

[0029] Preferably, when the reaction device is in the bypass mode, the reaction device activates the flow path of the second open loop, and the activated flow path of the second open loop bypasses the reaction flow path, wherein the flow path of the second open loop at least includes: an inlet valve, a system pump, a second flow path setting device, a detection flow path, and a first flow path setting device.

[0030] Preferably, when the first flow path setting device is in the non-circulating state and the second flow path setting device is in the bypass state, the reaction device is in the bypass mode.

[0031] Preferably, when the reaction device is in the premixing mode, the reaction device further includes a premixing flow path so that at least two substances are premixed before entering the reaction flow path, wherein the premixing flow path includes a premixing container.

[0032] Preferably, when the reaction device is in the premixing mode, the reaction device activates the second closed-loop and circulating flow path, wherein,

[0033] The second closed-loop and circulating flow path includes: a first flow path setting device, a system pump, and a premixing flow path,

[0034] The premixing flow path further includes a third flow path setting device.

[0035] Preferably, the volume of the premixing container is smaller than the volume of the reactor.

[0036] Preferably, when the reactor includes a synthesis column, the volume of the premixing container is 2 / 3 of the column volume of the reactor.

[0037] Preferably, the first flow path setting device includes any one of the following rotary valves: a 7-port valve, a 5-port valve; and / or, the second flow path setting device includes any one of the following rotary valves: a 7-port valve, a 4-port valve;

[0038] Or,

[0039] The second flow path setting device includes a column position valve, and the column position valve includes: a single-column position valve or a multi-column position valve.

[0040] Preferably, the inlet valve includes a first inlet valve and a second inlet valve,

[0041] The system pump includes a first system pump and a second system pump, wherein,

[0042] The first branch of the feed flow path includes a first inlet valve and a first system pump,

[0043] The second branch of the feed flow path includes a second inlet valve and a second system pump.

[0044] Preferably, the reaction device realizes the mixed input of multiple solutions in any of the following ways:

[0045] 1) The inlet valve is a multi-port valve. The ports of the multi-port valve that need to mix and input multiple solutions are connected to electromagnetic proportional valves to achieve the input of at least two different solutions. Among them, the ratio between the solutions is controlled by the switching time of the electromagnetic proportional valves. The electromagnetic proportional valves include at least three two-way valves or two three-way valves;

[0046] 2) In the feed flow path, at least one additional pump other than the system pump is added. The additional pump is connected through an electromagnetic proportional valve to achieve the proportional input of at least two different solutions. Among them, the ratio between the solutions is controlled by the switching time of the electromagnetic proportional valves. The electromagnetic proportional valves include at least three two-way valves or two three-way valves;

[0047] 3) The inlet valve is a multi-port valve. When the first solution is input through one port of the multi-port valve, the other solutions are arranged adjacent to each other in sequence at the ports next to this port according to the order of the ports of the multi-port valve. During feeding, the liquid inlet ports are quickly switched in sequence.

[0048] Preferably, the second inlet valve is one or more.

[0049] When there are multiple ones, one of the second inlet valves is a first-level second inlet valve, and

[0050] the first-level second inlet valve is directly connected to the second system pump.

[0051] The remaining second inlet valves are connected to the second system pump via the first-level second inlet valve.

[0052] Preferably, when the first flow path setting device is in a non-circulating state, the system pump transports the substances input through the inlet valve;

[0053] When the first flow path setting device is in a circulating state, the system pump transports the substances flowing out of the reactor.

[0054] Preferably, the reaction device is used for solid-phase peptide synthesis.

[0055] Preferably, the substances include any of the following: deprotection reagent, coupling reagent, capping reagent, cleaning reagent.

[0056] Preferably, at different stages of peptide synthesis, the reaction device uses the feed flow path to input the substances corresponding to different stages to carry out peptide synthesis.

[0057] Preferably, when the reaction device is used for solid-phase peptide synthesis, for the coupling stage, the first closed-loop and circulating flow path can be activated.

[0058] On the other hand, the present utility model also discloses a method for solid-phase synthesis of polypeptides using the reaction device described in any one of the foregoing, including:

[0059] Coupling stage:

[0060] Input amino acids and activator respectively through the first system pump and the second system pump. When the first flow path setting device is in the circulating state and the second flow path setting device is in the non-bypass state, recycle the amino acids and activator in the first closed-loop and circulating flow path according to the set circulation conditions to achieve full contact of the reagents in the reactor.

[0061] On the other hand, the present utility model also discloses a computer-readable storage medium,

[0062] The computer-readable storage medium stores computer instructions, and when the computer instructions are executed by a processor, the method for solid-phase synthesis of polypeptides described in any one of the foregoing is implemented.

[0063] Finally, the present utility model also discloses an electronic device, including:

[0064] A processor and a memory, wherein,

[0065] The memory stores computer instructions, and the computer instructions are executed by the processor so that the electronic device implements the method for solid-phase synthesis of polypeptides described in any one of the foregoing.

[0066] In the present utility model, when the first flow path setting device is in the circulating state and the second flow path setting device is in the non-bypass state, the reaction device activates the first closed-loop and circulating flow path. In this case, the reaction device operating in a closed-loop and circulating manner makes the entire reaction free of dead corners, increases the contact time, avoids the problem of incomplete reaction caused by incomplete contact, significantly improves the synthesis efficiency, saves reagents at the same time, and reduces the cost of the reaction. In addition, the present utility model can further control the dosage of the reagent through a high-precision pump to ensure the accuracy of the reagent dosage. BRIEF DESCRIPTION OF THE DRAWINGS

[0067] In order to more clearly illustrate the technical solutions of the embodiments of the present utility model, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the drawings in the following description exemplarily show some embodiments of the present utility model.

[0068] Figure 1A In one embodiment of the present utility model, a schematic diagram of the circulation mode of the reaction device;

[0069] Figure 1B In another embodiment of the present utility model, when the reaction device is in the circulation mode, a specific flow path schematic diagram of forward and reverse flushing;

[0070] Figure 2A In another embodiment of the present utility model, when the reaction device is in the feeding and discharging mode, after activating the feeding flow path, it is a schematic diagram of the connection between the feeding flow path and the reaction flow path, and when the reaction device activates the discharging flow path, it is a schematic diagram of the connection between the reaction flow path and the discharging flow path;

[0071] Figure 2B In another embodiment of the present utility model, it is a specific flow path schematic diagram of the forward and reverse flushing of the reaction device in the feeding and discharging mode;

[0072] Figure 3 In another embodiment of the present utility model, when the reaction device is in the bypass mode, it is a schematic diagram of the flow path of the second open loop;

[0073] Figure 4 In another embodiment of the present utility model, it is a specific flow path schematic diagram when the reaction device is in the premixing mode;

[0074] Figures 5A to 5C In the present utility model, it is a schematic diagram of different implementation manners for realizing the mixed input of multiple solutions;

[0075] Figures 6A to 6E In another embodiment of the present utility model, it is a schematic diagram of the reaction device for solid-phase synthesis of polypeptides respectively implementing the processes of de-capping and DMF cleaning after de-capping, coupling in amino acids and activators, coupling cyclic reaction and DMF cleaning after cyclic reaction, capping and DMF cleaning after capping.

[0076] Through the above-mentioned drawings, specific embodiments of the present utility model have been shown, and there will be more detailed descriptions hereinafter. These drawings and textual descriptions are not intended to limit the scope of the concept of the present utility model in any way, but to illustrate the concept of the present utility model to those skilled in the art by referring to specific embodiments. Detailed Embodiments

[0077] The following combines the attached Figures 1A to 6E to elaborate in detail on the preferred embodiments of the present utility model, so that the advantages and features of the present utility model can be more easily understood by those skilled in the art, thereby making a clearer and more definite definition of the protection scope of the present utility model.

[0078] It should be noted that in this text, relational terms such as first and second are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprising", "including", "having" or any other variants thereof are intended to cover non-exclusive inclusion, such that a process, method, article or device comprising a series of elements not only includes those elements, but also includes other elements not expressly listed, or elements inherent to such process, method, article or device. Without further limitation, elements defined by the statements "comprising...", "having..." do not exclude the existence of additional elements in the process, method, article or device comprising the elements.

[0079] See Figure 1A , in one embodiment, the present utility model discloses a reaction device, comprising:

[0080] A reaction flow path having a reactor, which is used for substances to flow into the reactor and then flow out,

[0081] A feed flow path, which is used for the reaction device to input substances,

[0082] A discharge flow path, which is used for the reaction device to discharge substances, and,

[0083] A detection flow path, which is used for detecting the substances flowing through,

[0084] Wherein,

[0085] When the reaction device is in a circulation mode, the reaction device activates a first closed-loop and circulating flow path so that substances act in a circulating manner in the reactor, wherein the first closed-loop and circulating flow path includes: a first flow path setting device, a system pump, a second flow path setting device, a reaction flow path, and a detection flow path.

[0086] For the above embodiment, see Figure 1A, it can be understood that since the first closed-loop and circulating flow path has the characteristics of being closed-loop and circulating, and incorporates the first flow path setting device, the system pump connected to the first flow path setting device, the second flow path setting device, the reaction flow path, and the detection flow path, there are no dead corners in the reaction in the entire reactor, the contact time is increased, the problem of incomplete reaction caused by incomplete contact is avoided, the synthesis efficiency is significantly improved, and at the same time, reagents are saved and the reaction cost is reduced. Since the first closed-loop and circulating flow path enables the reaction device to recycle reagents during the reaction process, increases the contact time, and makes the reaction have no dead corners in the reactor, it can be understood that the above reaction device that can operate in the circulation mode can be used in all suitable scenarios involving biological and chemical reactions and solve the problems of reaction dead corners and incomplete reactions.

[0087] Furthermore, it can be understood that since in the circulation mode, the reaction device is for the recycling of the reagents used in the reaction, therefore, preferably, after a reaction is completed in the reactor, starting from the reagents flowing out of the reactor, the first closed-loop and circulating flow path is activated, so as to continuously circulate the reagents flowing out of the reactor in the first closed-loop and circulating flow path. It is precisely for this reason that Figure 1A an exemplary illustration shows that the circulation arrow starts after the reaction flow path.

[0088] In another embodiment, the system pump includes a high-precision metering pump.

[0089] Thus, the present utility model ingeniously combines the system pump, especially the high-precision metering pump, into the relevant flow path of the reaction device to achieve precise control of the reagents, thereby overcoming many problems in the prior art, such as large deviation in the liquid level induction metering method when transferring liquid substances by gas power, difficult to accurately control the liquid dosage, and difficult to efficiently and accurately implement the synthesis process. In this embodiment, the system pump provides power for the reagent delivery and at the same time controls the delivery dosage of the reagents to ensure the accuracy of the reagent dosage during the reaction. According to specific needs, the system pump can be selected as a plunger pump or a diaphragm pump, etc.

[0090] See Figure 1B , it should be noted that in one embodiment,

[0091] When the first flow path setting device is set to the circulation state and the second flow path setting device is set to the non-bypass state, the reaction device is in the circulation mode. At this time, the reaction device activates the first closed-loop and circulating flow path.

[0092] See Figure 1B , in another embodiment,

[0093] The detection flow path includes a conductivity detector and / or an ultraviolet detector, wherein,

[0094] A conductivity detector for detecting substances flowing through a flow path;

[0095] An ultraviolet detector for detecting substances flowing through a flow path.

[0096] Specifically, the conductivity detector detects based on conductivity, while the ultraviolet detector detects based on ultraviolet light.

[0097] In another embodiment,

[0098] The reactor is a synthesis column;

[0099] The reactor includes a single or multiple synthesis columns,

[0100] When there are multiple synthesis columns, they are in an alternative mode, and only one synthesis column is connected at any given time.

[0101] It can be understood that in this embodiment, multiple synthesis columns share any flow path other than the reactor in the reaction device in an alternative manner, which helps to efficiently utilize the reaction device.

[0102] Further referring to Figure 2A 、 Figure 2B , which describes through multiple embodiments that in other modes of the reaction device of the present invention besides the circulation mode, such as in the feeding and discharging mode, the feeding flow path and the discharging flow path of the reaction device can be activated. Specifically:

[0103] On the one hand, in combination with Figure 2A 、 Figure 2B , where

[0104] When the reaction device is in the feeding and discharging mode, the reaction device activates the feeding flow path, and the activated feeding flow path is connected to the reaction flow path. Among them, the feeding flow path at least includes: an inlet valve, a system pump, and a second flow path setting device;

[0105] When the reaction device is in the feeding and discharging mode, the reaction device can also activate the discharging flow path, and the activated discharging flow path is connected from the reaction flow path. Among them, the discharging flow path at least includes: a second flow path setting device, a detection flow path, and a first flow path setting device.

[0106] On the other hand, it can be learned from Figure 2B that the system pump of the present invention can include a first system pump and a second system pump, and the inlet valve can also include a first inlet valve and a second inlet valve. That is to say, referring to Figure 2B , in a specific embodiment, the first branch of the feeding flow path includes a first inlet valve and a first system pump, and the second branch of the feeding flow path includes a second inlet valve and a second system pump.

[0107] Exemplarily, such asFigure 2B As shown, the first branch and the second branch of the feed flow path converge via a three-way valve, and a pressure sensor is also provided at the convergence point; among them, in the second branch of the feed flow path, Figure 2B When the second inlet valve and the second system pump of... form a feed flow path via the second flow path setting device and are connected to the reaction flow path, this feed flow path does not necessarily require the first flow path setting device; furthermore, it can be further found that in the first branch of the feed flow path, compared with the second branch of the feed flow path, the first flow path setting device also constitutes a part of the activated feed flow path;

[0108] In addition, in combination with Figure 2B as shown,

[0109] Both the first flow path setting device and the second flow path setting device include at least one valve, so that through the functions of the two, the corresponding flow paths in the reaction device are activated. It can be understood that the first flow path setting device and the second flow path setting device can be any implementation manner as long as they can activate the corresponding flow paths such as the first closed-loop and circulating flow path, the feed flow path, the discharge flow path, etc.

[0110] In another embodiment, the first flow path setting device includes at least one circulation valve, and the second flow path setting device includes at least one column position valve, where the column position valve and the circulation valve can be rotary valves.

[0111] Exemplarily,

[0112] The first flow path setting device includes any one of the following rotary valves: a 7-port valve, a 5-port valve, and / or

[0113] The second flow path setting device includes any one of the following rotary valves: a 7-port valve, a 4-port valve;

[0114] Or,

[0115] The second flow path setting device includes a column position valve, and the column position valve includes a single-column position valve or a multi-column position valve.

[0116] Regarding the reaction device in the above feeding and discharging mode, it should be further noted that

[0117] Regarding the feed flow path: In the second branch of the feed flow path, refer to Figure 2B , the reagent enters successively through the corresponding inlet valve (the second inlet valve), the corresponding system pump (the second system pump), and the feed flow path formed by the second flow path setting device. Since the feed flow path is connected to the inlet of the reaction flow path at this time, the reagent finally enters the reactor in the reaction flow path; in the first branch of the feed flow path, refer to Figure 2B, the reagent enters successively through the corresponding inlet valve (the first inlet valve), the first flow path setting device, the corresponding system pump (the first system pump), and the second flow path setting device to form a feed flow path. Since the feed flow path is connected to the inlet of the reaction flow path at this time, the reagent can finally enter the reactor in the reaction flow path;

[0118] Regarding the discharge flow path: According to the process parameters set by the reaction device, during discharge, it successively passes through the second flow path setting device, the detection flow path, and the first flow path setting device from the outlet of the reaction flow path, and finally discharges, for example, discharges to Figure 2B the waste liquid container in

[0119] In another embodiment,

[0120] The discharge flow path further includes: a back pressure valve,

[0121] Along the direction of the material flow in the flow path, the back pressure valve can be located after the second flow path setting device and before the waste liquid container, or, along the direction of the material flow in the flow path, the back pressure valve is located before the material discharge outlet. For this embodiment, the back pressure valve can be used for pressure control of the reaction device. Regarding Figure 2B the example shown, the setting of the back pressure valve improves the safety of the entire reaction device during operation, especially the combined use of the back pressure valve and the pressure sensor.

[0122] In addition, the back pressure valve can also avoid large fluctuations in the ultraviolet detector during detection caused by instantaneous pressure relief.

[0123] In another embodiment,

[0124] Before the circulation mode, the reaction device activates the feed flow path.

[0125] It can be understood that before the circulation mode, the reaction device activates the feed flow path for the following situation: before the first closed-loop and circulating flow path of the reaction device is activated, it is necessary to first achieve the entry of the reagent into the reaction flow path. Further, it can also be understood that the discharge flow path can be activated for discharging after the circulation mode. If it is necessary to input another reagent after the circulation mode so that it enters the reaction flow path, then, after the circulation mode, activate the feed flow path, and then the discharge flow path can also be activated as needed.

[0126] Combined with Figure 2B In another embodiment,

[0127] When the first flow path setting device is in a non-circulating state and the second flow path setting device is in a non-bypass state, the reaction device is in the feeding and discharging mode.

[0128] See Figure 2B Further, in another embodiment,

[0129] When the reaction device is in the feeding and discharging mode, the feeding flow path, the reaction flow path, and the discharging flow path form a first open-loop flow path.

[0130] It can be understood that this situation means that: under the combined action of the first flow path setting device and the second flow path setting device of the reaction device, the reagent flows along the first open-loop flow path: enters the reaction flow path through the feeding flow path, and the substance after passing through the reactor further passes through the discharging flow path and is finally discharged.

[0131] Combined with the multiple embodiments described above, it can be found that the feeding flow path is operably connected to the reaction flow path, and the discharging flow path is operably connected from the reaction flow path.

[0132] In another embodiment, refer to Figure 1B 、 Figure 2B ,

[0133] When the second flow path setting device is in the non-bypass state, by setting the second flow path setting device, the reaction flow path can work in the forward flushing mode or the reverse flushing mode.

[0134] For this embodiment, it should be noted that Figure 1B 、 Figure 2B The forward flushing and reverse flushing modes are schematically shown in a diagrammatic way: when the reagent enters from above the reactor and then flows out from below the reactor, it can be considered as the flow direction of the reagent in the forward flushing mode. The reagent flows along the second flow path setting device and the reaction flow path in a clockwise direction; the reverse flushing mode means that: the reagent enters from below the reactor and then flows out from above the reactor, and the reagent flows along the second flow path setting device and the reaction flow path in a counterclockwise direction. It can be known from Figure 2B that whether it is the forward flushing mode or the reverse flushing mode, assuming that the reaction device is currently in the feeding and discharging mode and the feeding flow path and the discharging flow path are activated, then, after flowing out of the reaction flow path, it flows into the discharging flow path.

[0135] The present utility model additionally introduces a backflush mode to enable the reaction device to adapt to different process production requirements and provide an additional option. The reaction solution flows from bottom to top, which can reduce the concentration reduction caused by dilution of the reaction solution during forward flushing, thereby improving the actual utilization rate of materials. During application, parameters such as the sequence and number of forward flushing and backflushing can be set according to different process requirements. It should be particularly noted that for this embodiment, since the working mode of the second flow path setting device and the reaction flow path involves the cooperation of the two, they need to cooperate in the forward flushing mode and also in the backflushing mode. For example, when the second flow path device is a valve, corresponding settings need to be made to the valve to change the flow path direction. Therefore, it is not recommended to add other components, devices, or functional units between the second flow path setting and the reaction flow path. At the same time, it should be noted that Figure 1B 、 Figure 2B In the embodiments shown in

[0136] and other various embodiments of the present utility model, along the direction of material flow, the components, devices, or functional units that pass through successively on each flow path have their inherent logic and cannot be set arbitrarily.

[0137] Furthermore, in combination with the forward flushing mode and the backflushing mode described in the previous embodiments, it can be understood that in the backflushing mode, the inlet of the reaction flow path is actually the outlet of the reaction flow path in the forward flushing mode.

[0138] It should be particularly noted that whether the second flow path setting device and the reaction flow path work in the forward flushing mode or the backflushing mode, it is only a different cooperative setting between the second flow path setting device and the reaction flow path. In these two different working modes, in the entire reaction device, except that the second flow path setting device and the reaction flow path have the corresponding forward flushing mode and backflushing mode corresponding to clockwise and counterclockwise, for other parts of the flow paths such as the first closed-loop and circulating flow path or the first open-loop flow path, the flow direction of the reagent therein can always remain unchanged.

[0139] It can be understood that the flow path of the first open loop and the first closed-loop and circulating flow path described above belong to different time periods and different modes in terms of timing. For example, the circulating mode of the reaction device and the feeding and discharging mode of the reaction device are different modes. However, according to different process requirements, since the first flow path setting device and the second flow path setting device can work or be set in different states, the first closed-loop and circulating flow path can be switched to the first open-loop flow path. Similarly, the first open-loop flow path can also be switched to the first closed-loop and circulating flow path.

[0140] It should be noted that the reaction device in the present utility model not only includes the circulating mode and the feeding and discharging mode disclosed in the previous different embodiments, but also includes a bypass mode.

[0141] See Figure 3 , in another embodiment,

[0142] When the reaction device is in the bypass mode, the reaction device activates the second open-loop flow path, and the activated second open-loop flow path bypasses the reaction flow path. Among them, the second open-loop flow path at least includes: an inlet valve, a system pump, a second flow path setting device, a detection flow path, and a first flow path setting device.

[0143] For the reaction device in the bypass mode, it should be further explained that in combination with Figure 3 , it can be further found that in the second open-loop flow path, the reagent successively passes through the inlet valve, the first flow path setting device, the system pump, the second flow path setting device, the detection flow path, returns to the first flow path setting device, and finally is discharged.

[0144] For this embodiment, depending on the specific process requirements, a typical application scenario is that the reagent flows in the second open-loop flow path and does not flow through the reaction flow path. For example, when the reaction device is used for solid-phase peptide synthesis, in the synthesis preparation stage, the reagent can be filled in the relevant pipelines, and this filling process is completed without passing through the reactor, avoiding contact with the resin in the reactor when it is unnecessary.

[0145] In another embodiment,

[0146] When the first flow path setting device is in a non-circulating state and the second flow path setting device is in a bypass state, the reaction device is in the bypass mode.

[0147] This embodiment further confirms that the utility model utilizes the first flow path setting device and the second flow path setting device in linkage and coordination to realize different working modes of the reaction device. Combined with the foregoing, it can be found that the first flow path setting device has at least two different states, namely, a circulation state and a non-circulation state, and the second flow path setting device has at least a non-bypass state and a bypass state, wherein the non-bypass state is further divided into two working modes, namely, forward flushing and back flushing. Therefore, combined with the circulation mode, feed and discharge mode, and bypass mode described above, assuming that when the feed flow path is activated in the feed and discharge mode, the discharge flow path is also activated, then the reaction device of the utility model has at least the following 5 working modes:

[0148] 1) Cyclic mode and positive rush;

[0149] 2) Cyclic mode with recoil;

[0150] 3) Infeed and outfeed mode and positive flushing;

[0151] 4) Infeed and outfeed mode with backflushing;

[0152] 5) Bypass mode.

[0153] Therefore, the reaction device of the utility model has a sufficiently rich working mode, can be used in a variety of scenarios and complex process control, and can still achieve a reaction without dead angles and sufficient reaction, and can further achieve precise control of reagents by introducing a high-precision metering pump in a specific position of the flow path, so as to overcome the technical problems in the prior art. It can be understood that the control software involved in the process control can control the first setting device of the flow path, the second setting device of the flow path, the system pump, etc. to work in the corresponding state according to different process conditions, for example, the first setting device of the flow path works in a non-circulating state, the second setting device of the flow path works in a non-bypass state, and the system pump is turned on. When the process conditions change, it is only necessary to update the relevant parameters of the control software and / or update the control software.

[0154] Furthermore, in another embodiment, the present invention also discloses an additional sixth mode, namely the premixing mode, wherein:

[0155] When the reaction device is in the premixing mode, the reaction device activates a second closed-loop and circulating flow path so that at least two reagents are premixed before entering the reaction flow path, wherein the second closed-loop and circulating flow path includes: a first flow path setting device, a system pump, and a premixing flow path.

[0156] For this embodiment, it should be noted that it once again reflects the feature of the reuse of components, devices or functional units in the flow path in the present utility model. For example, the first flow path setting device and the system pump in this embodiment are not only used for the circulation mode described above, but also for the feeding and discharging mode and the premixing mode. Since the first flow path setting device, the system pump and the premixing flow path form a second closed-loop and circulating flow path, for at least two reagents to participate in the reaction, such as the reagents fed from the first and second inlet valves respectively, when they flow in the second closed-loop and circulating flow path, they can be premixed to facilitate the subsequent efficient and high-quality implementation of the reaction in the reactor. In addition, it can be found that the second closed-loop and circulating flow path may not include a detection flow path, which is to maximize the avoidance of reagent waste during the premixing process. In this case, when the premixing mode ends can depend on the time parameter corresponding to the premixing mode. It can also be understood that the control of each mode of the reaction device disclosed in the present utility model can be controlled by the time parameter corresponding to each mode, and for multiple modes involving a detection flow path, it can also be assisted by manual control or fully automatic control according to the detection results of the detection flow path according to the requirements of different processes.

[0157] Further, referring to Figure 4 , which gives a more specific embodiment regarding the premixing mode. Exemplarily, the premixing flow path including a premixing container and a third flow path setting device, together with the first flow path setting device and the system pump (such as the first system pump) connected to the first flow path setting device, constitutes a second closed-loop and circulating flow path. Among them, at P1 and P2 in the figure, there is the ability to switch various local flow paths, for example, valves can be set to achieve the corresponding flow path control. During cyclic premixing, settings are made at P1, and the substance flowing out of the premixer returns to the first flow path setting device and is circulated through the system pump. When the premixing is completed, settings are made at P1 to connect the premixing flow path with the second flow path setting device, and the reagents that have been premixed in the premixing container are transported to the reaction flow path.

[0158] Regarding the premixing flow path, exemplarily, as Figure 4 shown,

[0159] the premixing flow path includes a third flow path setting device and a premixing container.

[0160] In another embodiment, the volume of the premixing container is smaller than the volume of the reactor. Preferably, when the reactor includes a synthesis column, the volume of the premixing container is 2 / 3 of the column volume of the reactor.

[0161] The purpose of the above additional limitation on the volume of the premixing container is that when the reagent (or other substances) in the premixing container needs to be input into the reactor after premixing, it will not cause overflow and waste from the reactor.

[0162] In another embodiment,

[0163] The third flow path setting device includes a control device, the control device includes at least one valve, the valve includes a rotary valve, and after the reaction device completes premixing, the premixing container, the third flow path setting device, the second flow path setting device, and the reaction flow path form a series flow path to input the premixed reagent into the reactor.

[0164] Furthermore, for the reaction device of the present invention, considering the aforementioned circulation mode, feeding and discharging mode, bypass mode, and premixing mode, among them,

[0165] When the first flow path setting device is in a non-circulation state, the reagent transported by the system pump is the reagent input via the inlet valve;

[0166] When the first flow path setting device is in a circulation state, the reagent transported by the system pump is the reagent flowing out of the reactor or the premixing container.

[0167] Exemplarily, when the first flow path setting device, the second flow path setting device, and the third flow path setting device are all rotary valves, the states of the first flow path setting device, the second flow path setting device, and the third flow path setting device are changed by means of pipelines and internal dark grooves of the rotary valve, so that the reaction device is in different working modes, such as circulation mode, feeding and discharging mode, bypass mode, and premixing mode.

[0168] In order to further improve the feeding capacity of the feeding flow path of the reaction device of the present invention, in another embodiment, the inlet valve is a multi-port valve, and the feeding flow path further includes an electromagnetic proportional valve.

[0169] Furthermore, the reaction device further realizes the simultaneous input of multiple solutions in any of the following ways:

[0170] 1) Refer to Figure 5A , taking the first inlet valve as an example, this inlet valve is a multi-port valve, and the ports of the multi-port valve that require almost simultaneous input of multiple solutions are connected to the electromagnetic proportional valve to realize the input of at least two reagents. Among them, the ratio between the reagents is controlled by the switching time of the electromagnetic proportional valve. For example, two different reagents are realized through one three-way electromagnetic proportional valve, and three reagents enter the system in proportion through two three-way or three two-way electromagnetic proportional valves;

[0171] For example, as Figure 5AAs shown, when ports 2 and 10 of the inlet valve need to use 2 or 3 reagents to enter the system almost at the same time, this requirement is achieved through the electromagnetic proportional valves 1, 2, and 3;

[0172] 2) See Figure 5B , for the feed flow path, at least one other additional pump is added in addition to the system pump, the system pump and the other additional pumps are connected via a three-way valve 1, and at least one electromagnetic proportional valve is connected to the other additional pumps to achieve at least two different reagents to be input in proportion to each other; similarly, for example, two different reagents can be realized through one three-way electromagnetic proportional valve, and three reagents can be realized to enter the system in proportion through two three-way or three two-way electromagnetic proportional valves;

[0173] 3) See Figure 5C Taking the first inlet valve as an example, the inlet valve is a multi-port valve. When the first solution is input through one port of the multi-port valve, the other solutions are arranged in sequence at the ports next to the port according to the order of the ports of the multi-port valve. The inlet ports are switched quickly in sequence during feeding.

[0174] For example, Figure 5C In the case where two solutions need to be input simultaneously into ports 2 and 10, when HOBT (1-hydroxybenzotriazole) is input through port 2 of the first inlet valve, DIC (N,N'-diisopropylcarbodiimide) is input through port 3; when HBTU (2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate) is input through port 10, DIEA (diisopropylethylamine) is input into port 9, thereby realizing almost simultaneous input of HBTU and DIEA, and almost simultaneous input of DIC and HOBT.

[0175] At the same time, exemplary, in order to further improve the feeding capacity of the feeding flow path, see Figure 4 , in another embodiment,

[0176] There are one or more second inlet valves. When there are more than one second inlet valve, one of the second inlet valves is a first-level second inlet valve, and,

[0177] The first-level second inlet valve is directly connected to the second system pump,

[0178] The remaining second inlet valves are connected to the second system pump via the first-stage second inlet valve.

[0179] As mentioned above, in another embodiment,

[0180] The reaction device is used for solid phase synthesis of polypeptides.

[0181] It can be understood that when the reaction device is used for solid-phase peptide synthesis, preferably, the reagent includes any one of the following: de-capping reagent, coupling reagent, capping reagent, and washing reagent. More preferably, at different stages of peptide synthesis, the reaction device inputs the reagents corresponding to different stages through the feeding flow path to carry out peptide synthesis.

[0182] In another embodiment,

[0183] When the reaction device is used for solid-phase peptide synthesis, for the coupling stage, the first closed-loop and circulating flow path can be activated.

[0184] For this embodiment, due to problems such as inefficient utilization and waste of reagents in the coupling stage and dead corners in the reaction caused by the solid-phase peptide synthesis device represented by the existing peptide synthesizer, the present utility model specifically activates the first closed-loop and circulating flow path of the reaction device for the coupling stage.

[0185] In another embodiment,

[0186] When the reaction device is used for solid-phase peptide synthesis, for the capping stage, the first closed-loop and circulating flow path can also be activated.

[0187] In this way, as long as the process requires, the reaction device of the present utility model can also improve the utilization rate of reagents in the capping stage and achieve full reaction in the capping stage.

[0188] In another embodiment,

[0189] When the reaction device is used for solid-phase peptide synthesis, for the de-capping stage, both the first system pump and the second system pump can operate, and the first flow path setting device is in a non-circulating state.

[0190] That is to say, in the de-capping stage, the reaction device can not only activate the feeding flow path, but also make both the first system pump and the second system pump operate, so that both the first branch and the second branch of the feeding flow path can operate.

[0191] In another embodiment,

[0192] When the inlet valve includes a first inlet valve and a second inlet valve,

[0193] The reagents input by the first inlet valve include any one or any combination of the following: activator, DCM (dichloromethane), DMF (dimethylformamide), capping reagent B (cap B), de-capping reagent, methanol, MTBE (methyl tert-butyl ether),

[0194] The reagents input by the second inlet valve include any one or any combination of the following: DMF, various amino acids, capping reagent A (Cap A), de-capping reagent.

[0195] On the other hand, the utility model also discloses a method for solid phase synthesis of polypeptides using the reaction device described in any one of the above items, comprising:

[0196] Coupling stage:

[0197] Amino acids and activators are respectively input through the first system pump and the second system pump. When the first flow path setting device is in a circulation state and the second flow path setting device is in a non-bypass state, the amino acids and activators in the first closed-loop and circulating flow path are recycled according to the circulation conditions set by the process to achieve full contact of the reagents in the reactor.

[0198] In another embodiment, the method further comprises:

[0199] Hat-off phase:

[0200] The corresponding decapping reagent is input through the first system pump and / or the second system pump. When the first setting device of the flow path is in a circulation state and the second setting device of the flow path is in a non-bypass state, the time node when the deprotection in the reactor ends is automatically determined by detecting the flow path.

[0201] In another embodiment, the method further comprises:

[0202] Blocking phase:

[0203] Capping reagent B (Cap B) and capping reagent A (Cap A) are respectively input through the first system pump and the second system pump, and capping is performed in the reactor when the first flow path setting device is in a non-circulation state and the second flow path setting device is in a non-bypass state.

[0204] In another embodiment, the method further comprises:

[0205] Pre-mixing stage:

[0206] After the corresponding reagents are respectively input through the first system pump and the second system pump, before the reagents are circulated in the first closed-loop and circulating flow path in the coupling stage, at least two reagents in the second closed-loop and circulating flow path are fully premixed by circulation according to the circulation conditions set in the process.

[0207] In another embodiment, the method further comprises:

[0208] Cleaning stage:

[0209] After the corresponding cleaning reagents are respectively input through the first system pump and the second system pump, when the first flow path setting device is in a non-circulating state and the second flow path setting device is in a non-bypass state, the reaction device activates the feed flow path and the discharge flow path, and cleans the reactor and pipelines of the entire reaction device according to the conditions set by the process in the first open-loop flow path formed by the feed flow path, the reaction flow path, and the discharge flow path.

[0210] It can be understood that for the de-capping stage, coupling stage, capping stage, and premixing stage described above, the cleaning stage can be executed timely according to the needs and the conditions set by the process. For example, first clean, then perform de-capping after cleaning is completed, perform cleaning after de-capping is completed, perform coupling after cleaning, perform cleaning after coupling is completed, and perform capping after cleaning. For all stages except the premixing stage, the substances flowing through the detection flow path are detected by a conductivity detector and / or an ultraviolet detector in the flow path to cooperate with the synthesis process of the reaction device described in the present invention and ensure the synthesis effect.

[0211] Typically, before and after each of the coupling stage, de-capping stage, and capping stage, the inlet valve of the reaction device needs to be switched to the cleaning reagent. When the first flow path setting device is in a non-circulating state and the second flow path setting device is in a non-bypass state, the reaction device is cleaned so that the solution in the flow path is completely replaced with the cleaning solution.

[0212] Specifically, the polypeptide solid-phase synthesis process mainly includes several reaction stages such as de-capping reaction, coupling reaction, and capping reaction. The reaction device that can be used for polypeptide solid-phase synthesis disclosed in the present invention will be further described below in combination with the polypeptide solid-phase synthesis process.

[0213] Figures 6A to 6E It is a schematic diagram of the reaction device for polypeptide solid-phase synthesis of the present invention respectively implementing the de-capping and DMF cleaning process after de-capping, the process of coupling amino acids and activators to complete the reaction, the cyclic reaction included in the coupling and the DMF cleaning process after the cyclic reaction, and the capping and DMF cleaning process after capping. Figures 6A to 6E The change in the flow path reflected is the schematic of the reaction device for the synthesis process of a single amino acid polypeptide. Among them,

[0214] Exemplarily, Figure 6A In the de-capping reaction of, first, the reagent bottle connected to the inlet valve is filled with the corresponding reagent, and an appropriate amount of resin is loaded into the reactor. Then, when performing the de-capping reaction, by adjusting the second inlet valve and the first inlet valve to switch to the DBLK (diisobutyl ketone) reagent bottle, under the condition of activating the feed flow path, DBLK is input into the reactor to remove the protecting group on the resin in the reactor. Optionally, the removal time is determined by the detection result of the detection flow path;

[0215] Exemplarily, Figure 6B is a schematic diagram of cleaning with a DMF cleaning reagent after the deprotection reaction. After the deprotection reaction is completed, the inlet valve is switched to the DMF (dimethylformamide) reagent bottle. In the case where the feed flow path and the discharge flow path are activated, a quantitative amount of DMF reagent is pumped in by two system pumps to perform the DMF cleaning process. Among them, the pumped DMF enters the reactor through the second flow path setting device, is discharged from the reactor, then reaches the conductivity detector and the ultraviolet detector through the second flow path setting device, and then reaches the back pressure valve through the first flow path setting device, and finally is discharged to the outside;

[0216] Exemplarily, Figure 6C is a schematic diagram of the coupling reaction assuming no recycling. When performing the coupling reaction, the second inlet valve is switched to the amino acid reagent bottle, such as A. In the case where the feed flow path is activated, the amino acid is input through the second system pump; the first inlet valve is switched to the activator reagent bottle mouth, such as the DIEA (diisopropylethylamine) mouth shown in the figure. In the case where the feed flow path is activated, the activator is input through the first system pump. Thus, the amino acid and the activator are respectively input into the reactor through two system pumps and the second flow path setting device to perform the coupling reaction. After the coupling reaction, the discharge flow path is activated to discharge the reacted reagent. Then, the inlet valve is switched to the DMF reagent bottle, and the DMF reagent is input through the system pump to perform the cleaning after the coupling reaction. The cleaning process can refer to Figure 6B .

[0217] Figure 6D is a schematic diagram of the flow path of the reaction device of the present utility model in the recycling mode. Typically, it is used for the coupling reaction to achieve the recycling of reagents. Among them,

[0218] When the first flow path setting device is in the recycling state and the second flow path setting device is in the non-bypass state, the reagent flowing out along the reactor and the ultraviolet detector direction after passing through the reactor will no longer flow into the back pressure valve for reagent discharge after passing through the first flow path setting device, but will flow into the first system pump. The reagent is re-input into the reactor through the first system pump for reaction, so as to realize the reaction of the reagent and the resin in the reactor to continuously make full contact, improve the reaction effect, and the recycling time can be set according to relevant process parameters. After the recycling process, the first flow path setting device is switched to the non-recycling state and the state of the second flow path setting device is kept unchanged. Then, the second inlet valve and the first inlet valve are switched to the DMF reagent port to perform the DMF cleaning process. The cleaning process can refer to Figure 6B ;

[0219] Figure 6E is a schematic diagram of the capping reaction of the reaction device of the present utility model that can be used for solid-phase peptide synthesis. Among them,

[0220] During the capping reaction, the second inlet valve and the first inlet valve are respectively switched to the CapA and CapB reagent bottles, and the corresponding reagents are input into the reactor by operating each system pump. The unreacted part on the resin in the reactor and the functional groups to be protected are sealed so that they no longer participate in the subsequent reactions. The time of the capping reaction is determined by the corresponding process parameters.

[0221] During the solid-phase synthesis of polypeptides, the de-capping, coupling, and capping reactions are repeatedly performed in the reaction device for solid-phase synthesis of polypeptides until the last amino acid is synthesized, and the final polypeptide synthesis is completed.

[0222] It should be noted that for Figures 6A to 6E ,

[0223] As described above, the present utility model can also perform premixing before at least two reagents enter the reaction flow path. In addition, during the de-capping, coupling, and capping reactions, and the cyclic reactions included in the coupling reaction, the second flow path setting device and the reaction flow path can be set with forward flushing and / or reverse flushing, and the rules of forward and reverse flushing cooperation according to different needs, such as the order and / or number of forward and reverse flushes.

[0224] In addition, regarding Figures 6A to 6E the meanings of the letter abbreviations at the inlets of the inlet valves, such as A, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, W, Y, etc., all represent different amino acids.

[0225] In another embodiment, for the method of solid-phase synthesis of polypeptides of the present utility model, when performing reagent circulation, the method includes the following steps:

[0226] S1101, inputting a variety of reagents through the inlet valve;

[0227] S1102, providing power for the input of a variety of reagents through the system pump, wherein the system pump is connected to the inlet valve;

[0228] S1103, performing flow path switching through the first flow path setting device for reagent circulation, wherein the first flow path setting device is arranged between the inlet valve and the system pump;

[0229] S1104, further controlling the flow path through the second flow path setting device, wherein the second flow path setting device is connected to the system pump, and the second flow path setting device can work in a non-bypass state or a bypass state according to needs, and the bypass state includes two modes of forward flushing and reverse flushing;

[0230] S1105. Peptide synthesis is carried out through a reactor, and the reactor is connected to a second flow path setting device. Among them, when the first flow path setting device is in a circulating state and the second flow path setting device is in a non-bypass state, the reagent flowing through the reactor enters the system pump through the first flow path setting device for reagent circulation.

[0231] On the other hand, the present utility model also discloses a computer-readable storage medium.

[0232] The computer-readable storage medium stores computer instructions, and when the computer instructions are executed by a processor, the method for solid-phase peptide synthesis described in any one of the foregoing is implemented.

[0233] Finally, the present utility model also discloses an electronic device, including:

[0234] a processor and a memory, where

[0235] the memory stores computer instructions, and the computer instructions are executed by the processor to enable the electronic device to implement the method for solid-phase peptide synthesis described in any one of the foregoing.

[0236] In summary, the present utility model controls the dosage of reaction reagents through a high-precision system pump to ensure the accuracy of reagent dosage; by using the first flow path setting device and the second flow path setting device, the reaction device forms a closed-loop and circulating flow path in the circulation mode, making the entire reaction free of dead ends, increasing the contact time, and avoiding incomplete reactions caused by incomplete contact. At the same time, relevant detectors in the detection flow path are used to detect the reaction process to ensure the synthesis effect.

[0237] When the reaction device of the present utility model is used for solid-phase peptide synthesis, corresponding working modes are switched at different stages of synthesis to complete corresponding functions. In the feeding and discharging mode, the first flow path setting device is an intermediate link between the system pump and the inlet valve for reagent transportation. At this time, the first flow path setting device is in a non-circulating state, and the second flow path setting device is in a non-bypass state; when the first flow path setting device is in a circulating state and the second flow path setting device is in a non-bypass state, the reaction device can realize reagent circulation, so as to achieve a sufficient reaction in the process of peptide generation, improve the peptide generation effect and at the same time improve the utilization rate of reagents.

[0238] In the embodiments provided by the present utility model, it should be understood that the disclosed device can be implemented in other ways. For example, the device embodiments described above are merely illustrative. For example, the division of units is only a logical function division. In actual implementation, there may be other division methods. For example, multiple units or components can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the displayed or discussed mutual coupling or direct coupling or communication connection can be through some interfaces. The indirect coupling or communication connection of devices or units can be in electrical, mechanical or other forms.

[0239] The above are only the embodiments of the present utility model, and do not limit the patent scope of the present utility model accordingly. All equivalent structural transformations made by using the specification and drawings of the present utility model, or directly or indirectly applied in other related technical fields, are equally included in the patent protection scope of the present utility model.

Claims

1. A reaction device, characterized in that: include: A reaction flow path having a reactor, which is used for materials to flow into the reactor and then flow out, The feed flow path is used to input materials into the reaction device. a discharge flow path for discharging materials from the reaction device, and A detection flow path, which is used to detect the substance flowing through, in, When the reaction device is in the circulation mode, the reaction device activates a first closed-loop and circulating flow path so that the substance acts in the reactor in a cyclic manner, wherein the first closed-loop and circulating flow path includes: a first flow path setting device, a system pump, a second flow path setting device, a reaction flow path, and a detection flow path.

2. The reaction device according to claim 1, characterized in that: When the first flow path setting device is set to a circulation state and the second flow path setting device is set to a non-bypass state, the reaction device is in a circulation mode.

3. The reaction device according to claim 1, characterized in that: When the reaction device is in the feeding and discharging mode, the reaction device activates the feeding flow path, and the activated feeding flow path is connected to the reaction flow path, wherein, The feed flow path includes: an inlet valve, a system pump and a second flow path setting device; or, The feed flow path includes: an inlet valve, a first flow path setting device, a system pump and a second flow path setting device.

4. The reaction device according to claim 3, characterized in that: When the reaction device is in the feeding and discharging mode, the reaction device activates the discharge flow path, and the activated discharge flow path is connected from the reaction flow path, wherein the discharge flow path at least includes: a second flow path setting device, a detection flow path, and a first flow path setting device.

5. The reaction device according to claim 3 or 4, characterized in that: Prior to the recycle mode, the reaction device activates the feed flow path.

6. The reaction device according to claim 1, characterized in that: When the first flow path setting device is in a non-circulation state and the second flow path setting device is in a non-bypass state, the reaction device is in a material loading and unloading mode.

7. The reaction device according to claim 1, characterized in that: When the reaction device is in the feeding and discharging mode, the feeding flow path, the reaction flow path and the discharging flow path form a first open-loop flow path.

8. The reaction device according to claim 1 or 7, characterized in that: When the second flow path setting device is in a non-bypass state, the reaction flow path can operate in a forward flushing mode or a back flushing mode.

9. The reaction device according to claim 1, characterized in that: System pumps include high-precision metering pumps.

10. The reaction device according to claim 1, characterized in that: The detection flow path includes a conductivity detector and / or an ultraviolet detector, wherein: A conductivity detector, which is used to detect substances flowing through the flow path; The ultraviolet detector is used to detect substances flowing through the flow path.

11. The reaction device according to claim 1, characterized in that: The first flow path setting device and the second flow path setting device both include a control component, which is used to activate different flow paths, and the control component includes at least one valve.

12. The reaction device according to claim 4, characterized in that: The discharge flow path also includes: back pressure valve, Along the direction of material flow in the flow path, the back pressure valve is located before the material discharge outlet.

13. The reaction device according to claim 1, characterized in that: When the reaction device is in bypass mode, the reaction device activates the second open-loop flow path, and the activated second open-loop flow path bypasses the reaction flow path, wherein the second open-loop flow path at least includes: an inlet valve, a system pump, a second flow path setting device, a detection flow path, and a first flow path setting device.

14. The reaction device according to claim 13, characterized in that: When the first flow path setting device is in a non-circulation state and the second flow path setting device is in a bypass state, the reaction device is in a bypass mode.

15. The reaction device according to claim 1, characterized in that: When the reaction device is in the premixing mode, the reaction device further comprises a premixing flow path, so that at least two substances are premixed before entering the reaction flow path, wherein the premixing flow path comprises a premixing container.

16. The reaction device according to claim 15, characterized in that: When the reaction device is in the premixing mode, the reaction device activates a second closed-loop and circulating flow path, wherein: The second closed-loop and circulating flow path includes: a first flow path setting device, a system pump, and a premixing flow path. The premixing flow path further comprises a flow path third setting device.

17. The reaction device according to claim 15, characterized in that: The volume of the premixing container is smaller than the volume of the reactor.

18. The reaction device according to claim 15, characterized in that: When the reactor comprises a synthesis column, the volume of the premixing container is 2 / 3 of the column volume of the reactor.

19. The reaction device according to claim 1, characterized in that: The first flow path setting device includes any one of the following rotary valves: a 7-port valve, a 5-port valve; and / or, the second flow path setting device includes any one of the following rotary valves: a 7-port valve, a 4-port valve; or, The second flow path setting device includes a column position valve, and the column position valve includes: a single column position valve or a multi-column position valve.

20. The reaction device according to claim 3, characterized in that: The inlet valve comprises a first inlet valve and a second inlet valve. The system pump includes a first system pump and a second system pump, wherein: The first branch of the feed flow path includes a first inlet valve, a first system pump, The second branch of the feed flow path includes a second inlet valve and a second system pump.

21. The reaction device according to claim 3, characterized in that: The reaction device realizes mixed input of multiple solutions by any of the following methods: 1) The inlet valve is a multi-port valve, and the ports of the multi-port valve that need to mix and input multiple solutions are connected to the electromagnetic proportional valve to achieve the input of at least two different solutions, wherein the ratio between the solutions is controlled by the switching time of the electromagnetic proportional valve, and the electromagnetic proportional valve includes at least three two-way valves or two three-way valves; 2) In the feed flow path, at least one additional pump is added in addition to the system pump, and the additional pump is connected through an electromagnetic proportional valve to achieve proportional input of at least two different solutions, wherein the ratio between the solutions is controlled by the switching time of the electromagnetic proportional valve, and the electromagnetic proportional valve includes at least three two-way valves or two three-way valves; 3) The inlet valve is a multi-port valve. When the first solution is input through one port of the multi-port valve, the other solutions are arranged in sequence at the ports next to the port according to the order of the ports of the multi-port valve. The inlet ports are switched quickly and sequentially during feeding.

22. The reaction device according to claim 20, characterized in that: The second inlet valve is one or more, When there are multiple second inlet valves, one of the second inlet valves is a first-level second inlet valve, and, The first-level second inlet valve is directly connected to the second system pump, The remaining second inlet valves are connected to the second system pump via the first-stage second inlet valve.

23. The reaction device according to claim 1, characterized in that: When the first setting device of the flow path is in a non-circulating state, the system pump delivers the material input through the inlet valve; When the first setting device of the flow path is in a circulation state, the system pump conveys the material flowing out of the reactor.

24. The reaction device according to any one of claims 1 to 4, 6 to 7, 9 to 23, characterized in that: The reaction device is used for solid phase synthesis of polypeptides.

25. The reaction device according to claim 5, characterized in that: The reaction device is used for solid phase synthesis of polypeptides.

26. The reaction device according to claim 8, characterized in that: The reaction device is used for solid phase synthesis of polypeptides.

27. The reaction device according to claim 24, characterized in that: The substance includes any of the following: a decapping reagent, a coupling reagent, a capping reagent, and a cleaning reagent.

28. The reaction device according to claim 24, characterized in that: At different stages of polypeptide synthesis, the reaction device utilizes a feed flow path to input substances corresponding to different stages to synthesize the polypeptide.

29. The reaction device according to claim 24, characterized in that: When the reaction device is used for solid phase synthesis of polypeptides, the first closed-loop and circulating flow path can be activated for the coupling stage.

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