Method for causing synthesis reaction between reagent and packing material, and device
By controlling the flow direction and volume of the reagent liquid in the synthesis container and using a method of multiple circulations through the reaction packing, the problems of low reagent utilization and low product purity were solved, achieving efficient reagent utilization and improved product purity, and reducing synthesis costs.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- INSCINSTECH CO LTD
- Filing Date
- 2025-08-12
- Publication Date
- 2026-07-30
AI Technical Summary
Existing technologies suffer from low utilization rates of chemical reagents, low product purity, and high synthesis costs. In particular, unreacted reagents are discharged with residual liquid during nucleic acid synthesis, leading to reagent waste and reduced product purity.
By controlling the flow direction and volume of the reagent liquid in the synthesis container, and using a method of multiple circulations through the reaction packing, the reagent and packing are ensured to fully contact and react. This includes the reaction liquid flowing through the packing once, then flowing through the packing again in the reverse direction, and the portion that does not flow in the reverse direction is treated as effluent. This process is repeated until the remaining reagent is discharged.
It improved reagent utilization, significantly enhanced product purity, reduced synthesis costs, and achieved controllability of the reaction process and mixed conversion effect.
Smart Images
Figure CN2025114021_30072026_PF_FP_ABST
Abstract
Description
A method and apparatus for causing a synthesis reaction between reagents and fillers. Technical Field
[0001] This invention relates to the field of synthetic processing technology, specifically to a method and equipment for causing a synthetic reaction between reagents and fillers. Background Technology
[0002] In the fields of chemical synthesis and biotechnology, a wide variety of chemical reactions and processes are involved, which extensively utilize various chemical reagents and fillers (synthetic supports). These processes typically involve injecting specific chemical reagents into a reaction vessel via a liquid injection unit to react with the filler material or other reactants within the vessel. However, existing technologies have certain limitations in terms of reagent use and residual liquid disposal.
[0003] In current technologies, the injection of chemical reagents and the removal of residual liquid are typically non-selective. That is, during the chemical reaction, both reacted and unreacted reagents are removed together, as shown in Figure 1. Taking nucleic acid synthesis as an example, existing nucleic acid synthesis techniques generally employ column synthesis, as shown in Figure 1. This method injects key chemical reagents, such as A / G / C / T monomer reagents corresponding to four different bases and acetonitrile reagents, into the synthesis container through a liquid injection unit. This promotes the chemical reaction between the reagents and the linkage sites on the solid-phase carrier packing material within the synthesis container, gradually constructing the target nucleic acid sequence. However, in this process, regardless of whether the chemical reagents injected into the synthesis container have completely reacted, they are directly discharged through the drain pipe.
[0004] This approach leads to several significant problems: First, the utilization rate of chemical reagents is generally low, as unreacted reagents are discharged along with the residual liquid and cannot be effectively utilized in the current or subsequent synthesis processes; second, the purity of the synthesized products is affected, as the presence of these components reduces the purity of the final product; and third, the overall synthesis cost is high, as the waste of reagents and product purity issues require more reagent input and subsequent purification steps during the synthesis process, thereby increasing costs.
[0005] The specific reasons affecting the purity of the synthesized product are as follows: Each time any reagent A / G / C / T is added to the synthesis container, the added reagent must connect to a linker site on the packing material inside the synthesis container through the synthesis reaction. The packing material inside the synthesis container contains many linker sites (hereinafter referred to as units). Assuming that during the addition of monomer A, two units (let's call them unit X and unit Y) are selected from the packing material, unit X reacts with reagent A, but unit Y does not. Then, reagents G, C, and T are added, and units X and Y react with reagents G, C, and T. At this point, two products are synthesized: product 1 synthesized on unit X has the sequence AGCT, while product 2 synthesized on unit Y has the sequence GCT. Based on the above reasons, conventional synthesis techniques reduce the utilization rate of chemical reagents and the purity of the final nucleic acid product, thus limiting the application and development of synthesis techniques in a wider range of fields to some extent.
[0006] Therefore, one of the technical problems to be solved by the present invention is how to improve the purity of the product, that is, how to synthesize products with the desired base sequence on each filler unit. Summary of the Invention
[0007] Therefore, the technical problem to be solved by the present invention is to overcome the problems of low reagent utilization, low product purity and high synthesis cost in the prior art, and to provide a new method and equipment for making reagents and fillers undergo a synthesis reaction.
[0008] To solve the above-mentioned technical problems, the present invention provides a method for synthesizing a reagent and a filler, characterized by the following steps: Step S1, providing a reagent liquid containing the reagent and a synthesis container loaded with a reaction filler, and adding a predetermined first volume of the reagent liquid into the synthesis container; Step S2, allowing a portion of a predetermined second volume of the reagent liquid to flow through the reaction filler to obtain a primary reaction solution; Step S3, allowing a portion of a predetermined third volume of the primary reaction solution to flow back through the reaction filler to obtain a secondary reaction solution, and the remaining portion of the primary reaction solution that does not flow back through the reaction filler becomes a discharge liquid detached from the reaction filler, the fourth volume of the discharge liquid being the difference between the second volume and the third volume; Step S4, after repeating steps S2 to S3 multiple times, discharging the remaining reagent liquid in the synthesis container.
[0009] In one embodiment of the present invention, the first volume of the reaction liquid added to the synthesis container in step S1 is set as V1, and step S2 further includes: setting the second volume of the primary reaction liquid as V2, the size of V2 is obtained by the following relationship: V2=X·V1 / n, where n is an integer greater than 1, and 1<X<n.
[0010] In one embodiment of the present invention, step S3 further includes: setting the third volume of the secondary reaction liquid as V3, the size of V3 is obtained by the following relationship: V3=(X-1)·V1 / n, setting the volume of the discharged liquid detached from the reaction packing as V4, then V4=V2-V3=V1 / n.
[0011] In one embodiment of the present invention, the number of repetitions of steps S2 to S3 in step S4 depends on the values of n and X, and is positively correlated with the value of n and negatively correlated with the value of X.
[0012] In one embodiment of the present invention, in step S4, the number of repetitions of steps S2 to S3 is at most the integer obtained by rounding down the calculation result of (n-X+1).
[0013] In one embodiment of the present invention, in step S2, a portion of the reagent liquid flows through the reaction packing at a first velocity Vx ranging from 5 to 100 μl / s; in step S3, a portion of the primary reaction liquid flows back through the reaction packing at a second velocity Vy ranging from 5 to 100 μl / s.
[0014] In one embodiment of the present invention, in step S2, a portion of the reagent liquid flows through the reaction packing and remains still for a first time T1 to obtain the primary reaction solution; in step S3, a portion of the primary reaction solution flows in the reverse direction through the reaction packing again and remains still for a second time T2 to obtain the secondary reaction solution.
[0015] This invention also provides a reagent filler synthesis and processing apparatus, comprising: a liquid injection unit, a synthesis container, and a liquid driving unit, wherein the liquid injection unit is connected to a memory storing a reagent liquid containing the reagent, the synthesis container is loaded with reaction filler, and the liquid injection unit is used to add the reagent liquid into the synthesis container; the liquid driving unit is connected to the synthesis container and is used to control the flow and flow direction of the reagent liquid in the synthesis container; the reagent filler synthesis and processing apparatus performs reagent filler synthesis and processing by performing the following steps:
[0016] a. The reagent liquid of a preset first volume is added into the synthesis container through the liquid injection unit;
[0017] b. A portion of the reagent liquid of a preset second volume is passed through the reaction packing material by the liquid driving unit to obtain a primary reaction solution;
[0018] c. A portion of the primary reaction liquid of a preset third volume is reversed and flows through the reaction packing again through the liquid driving unit to obtain a secondary reaction liquid. The other portion of the primary reaction liquid that does not flow through the reaction packing becomes the discharge liquid that is separated from the reaction packing. The fourth volume of the discharge liquid is the difference between the second volume and the third volume.
[0019] d. After repeating steps b to c multiple times by the liquid driving unit, the remaining reagent liquid in the synthesis container is discharged.
[0020] In one embodiment of the present invention, the reagent filler synthesis and processing equipment includes a plurality of liquid injection units, a plurality of synthesis containers, and a plurality of liquid driving units, wherein the plurality of liquid injection units and the plurality of synthesis containers are arranged in a one-to-one correspondence, and any synthesis container is connected to one of the liquid driving units.
[0021] In one embodiment of the present invention, the liquid driving unit includes a pump body and two docking nozzles, both of which are disposed on the pump body. One of the docking nozzles is connected to the synthesis container, and the other docking nozzle is connected to the discharge liquid collection device.
[0022] In one embodiment of the present invention, the reagent filler synthesis and processing equipment further includes a control mechanism for controlling the operation of the liquid injection unit and the liquid driving unit in steps a to d.
[0023] In one embodiment of the present invention, the first volume of the reaction liquid added to the synthesis container in step a is set as V1, and step b further includes: setting the second volume of the primary reaction liquid as V2, the size of V2 is obtained by the following relationship: V2 = X·V1 / n, where n is an integer greater than 1, and 1 < X < n; step c further includes: setting the third volume of the secondary reaction liquid as V3, the size of V3 is obtained by the following relationship: V3 = (X-1)·V1 / n, and setting the fourth volume of the discharge liquid detached from the reaction packing as V4, then V4 = V2 - V3 = V1 / n. The user can set the values of V1, n, and X through the control mechanism.
[0024] The technical solution of the present invention has the following advantages compared with the prior art:
[0025] The method and apparatus for synthesizing reagents and fillers described in this invention increase the number of contact times between the reaction liquid and the filler, enabling them to fully react and achieve complete conversion of the residual liquid. This not only improves reagent utilization, thus reducing costs and protecting the environment, but also significantly enhances product purity. Compared to conventional processing technologies, this application offers advantages such as high controllability of the reaction process, thorough mixing and conversion, reduced reagent waste, and improved product quality, providing a new approach to reagent and filler synthesis. Attached Figure Description
[0026] To make the content of this invention easier to understand, the invention will be further described in detail below with reference to specific embodiments and accompanying drawings.
[0027] Figure 1 is a schematic diagram of the existing synthesis equipment;
[0028] Figure 2 is a three-dimensional structural schematic diagram of the reagent and filler synthesis and processing equipment in a preferred embodiment of the present invention;
[0029] Figure 3 is a schematic diagram of the reagent and filler synthesis and processing equipment shown in Figure 2 when the mixed reaction solution is separated from the reaction filler.
[0030] Figure 4 is a schematic diagram of the reagent and filler synthesis and processing equipment shown in Figure 2 when the pre-discharge liquid and the reaction filler are brought into contact again and reacted.
[0031] Explanation of reference numerals in the accompanying drawings: 100, injection unit; 200, synthesis container; 210, packing material; 220, body; 230, connecting pipe; 240, Luer connector; 300, liquid drive unit; 310, pump body; 320, connecting nozzle; 400, reagent liquid. Detailed Implementation
[0032] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, so that those skilled in the art can better understand and implement the present invention. However, the embodiments described are not intended to limit the present invention.
[0033] Example 1
[0034] This embodiment provides a method for causing a synthetic reaction between reagents and fillers, which is used for the synthesis and processing of oligonucleotides or peptides, and includes the following steps:
[0035] Step S1: Provide a reagent liquid containing the reagent and a synthesis container loaded with reaction filler, and add a preset first volume of the reagent liquid into the synthesis container;
[0036] Furthermore, in this embodiment, the first volume V1 of the reagent liquid can be configured as, for example, 150 μl, which can be used for the synthesis reaction in a synthesis container containing filler.
[0037] Step S2: A portion of the reagent liquid of a preset second volume is allowed to flow through the reaction packing to obtain a primary reaction solution; further, in this embodiment, the reagent liquid inside the synthesis container flows out from its bottom so that a portion of the reagent liquid is separated from the reaction packing to become a primary reaction solution.
[0038] Furthermore, in this embodiment, step S2 further includes:
[0039] Let the second volume of the primary reaction solution be V2, and the value of V2 is obtained by the following relationship:
[0040] V2 = X·V1 / n, where n is an integer greater than 1, and 1 < X < n. Based on this, the second volume of the primary reaction solution can be changed by adjusting the values of n and X according to actual needs.
[0041] Specifically, in this embodiment, n is set to 3, and X is preferably 2, so that the reaction process can balance reaction efficiency and synthesis effect. In different embodiments, the specific settings of n and X can be adaptively adjusted according to actual reaction requirements. This invention does not impose specific limitations on this, but in order to significantly improve product purity, X is preferably set between 1.5 and 2.5. Based on this, V2 = 100 μl in this embodiment. At this time, 50 μl of reagent liquid remains in the synthesis container after step S2.
[0042] Furthermore, in this embodiment, the discharge rate Vx of the primary reaction solution is 8–12 μl / s. It should be noted that in this embodiment, the discharge rate Vx is obtained by observing the change in product purity under different discharge rates. Specifically, in this embodiment, the purity of the corresponding synthesized products is detected sequentially under multiple uniformly gradient discharge rate conditions, and the optimal discharge rate Vx is obtained after comparison. This results in relatively faster product processing efficiency and relatively higher purity. For conventional synthesis and processing, the range of Vx is generally configured as 5–100 μl / s.
[0043] Furthermore, to ensure that the reaction reagents can fully contact the packing material and undergo a synthesis reaction, in this embodiment, a portion of the reagent liquid flows through the reaction packing material and remains stationary for a first time T1 to obtain the primary reaction solution. In different embodiments, the preset value of the first time T1 can be adjusted accordingly based on different chemical reactions and experimental tests; this invention does not impose specific limitations on this.
[0044] Step S3: A portion of the primary reaction liquid with a preset third volume is reversed and flows through the reaction packing again to obtain a secondary reaction liquid. The other portion of the primary reaction liquid that does not flow through the reaction packing becomes the discharge liquid that is removed from the reaction packing. The fourth volume of the discharge liquid is the difference between the second volume and the third volume.
[0045] Further, in this embodiment, step S3 further includes: setting the third volume of the secondary reaction liquid as V3, the value of V3 being obtained by the following relationship: V3 = (X-1)·V1 / n; and setting the fourth volume of the discharged liquid detached from the reaction packing as V4, then V4 = V2 - V3 = V1 / n. This achieves the goal of simultaneously carrying out the residual liquid re-reaction and the discharge liquid collection. In this document, the term residual liquid refers to the reagent liquid that has come into contact with and reacted with the reaction packing.
[0046] Specifically, in this embodiment, both V3 and V4 are 50 μl. At this time, 50 μl of discharge liquid is obtained after step S3, and the liquid volume in the synthesis container is 100 μl. Specifically, it is composed of the remaining 50 μl of reagent liquid in the synthesis container in step S2 and the secondary reaction liquid returned to the synthesis container in step S3.
[0047] Furthermore, the reflux rate Vy of the portion of the primary reaction solution flowing back through the reaction packing is 6–10 μl / s. Similarly, for conventional synthesis processes, Vy is typically configured in the range of 5–100 μl / s.
[0048] Furthermore, in step S3, a portion of the primary reaction solution flows back through the reaction packing material and remains stationary for a second time T2 to obtain the secondary reaction solution. This increases the contact time between the reagents and the packing material in part of the primary reaction solution, thereby improving the actual utilization rate. In different embodiments, the preset second time T2 can be adjusted according to the type of reagent and environmental parameters; this invention does not impose specific limitations on this.
[0049] Step S4: After repeating steps S2 to S3 multiple times, drain the remaining reagent liquid from the synthesis container.
[0050] According to the method of the present invention, steps S2 and S3 can be considered as one cycle. Those skilled in the art will understand that when the cycle consisting of steps S2 and S3 is repeated multiple times, depending on the different values of n and X, some of the reagent liquid may come into contact with the packing material and react more than twice. Therefore, the terms "primary reaction liquid" and "secondary reaction liquid" herein refer to a portion of the reagent liquid coming into contact with the packing material for the first time and reacting, and then coming into contact with the packing material for the second time and reacting, rather than limiting the actual number of contacts and reactions spanning multiple cycles.
[0051] Furthermore, in this embodiment, the number of repetitions of steps S2 to S3 depends on the values of n and X, is positively correlated with the value of n, and negatively correlated with the value of X. The specific parameter values can be freely set according to actual processing requirements.
[0052] Specifically, since the monomer reagents used in the coupling stage of chemical synthesis are expensive, when used in the coupling stage, the number of repetitions (cycles) of steps S2 to S3 can be increased by appropriately increasing n and decreasing X, thereby increasing the utilization rate of monomer reagents and reducing experimental costs. On the other hand, the reagents such as acetonitrile required for deprotection, oxidation, and capping stages are relatively inexpensive, and the number of repetitions (cycles) of steps S2 to S3 can be reduced by appropriately decreasing n and increasing X, or even eliminating the need for cycling.
[0053] Furthermore, in this embodiment, in step S4, an upper limit can be set for the number of repetitions of steps S2 to S3. The number of repetitions of steps S2 to S3 is at most the integer obtained by rounding down the calculation result of (n-X+1).
[0054] In this embodiment, after repeating steps S2 to S3 three times, the remaining 50 μl of reagent liquid in the synthesis container is completely drained, thus completing one complete reagent and filler synthesis reaction process. Therefore, after repeating steps S2 to S3 three times, the remaining 50 μl of reagent liquid in the synthesis container is less than the second volume V2—100 μl in step 2. If steps 2 to 3 are performed again at this point, the reagent liquid in the synthesis container will be completely drained in step 2, and the filler will still be exposed to air after step 3, which is undesirable because it is an invalid cycle. Therefore, as mentioned above, an upper limit can be set for the number of repetitions of steps S2 to S3. In this embodiment, since n is 3 and X is 2, the maximum number of repetitions of steps S2 to S3 is the integer obtained by rounding down the result of (n-X+1) = 3.
[0055] Furthermore, the method for causing the reagents and fillers to undergo a synthetic reaction disclosed in this embodiment is applicable to, for example, nucleic acid synthesis and processing. Specifically, it can be used in various stages of nucleic acid synthesis, including coupling, deprotection, oxidation, and capping, and is particularly suitable for the coupling stage. Different types of reagents are used in each stage of nucleic acid synthesis, because the coupling stage requires expensive ATCG monomer reagents, while the deprotection, oxidation, and capping stages require relatively inexpensive reagents such as acetonitrile.
[0056] Furthermore, based on the above process, this embodiment can improve the efficiency of nucleic acid synthesis and processing, significantly reduce reagent consumption and processing costs, and has practical significance for nucleic acid synthesis and processing. In addition, the above process is applicable to costly chemical reagent synthesis reactions, and can also be applied to stages such as deprotection, oxidation, and capping, thereby achieving the goal of cost reduction and efficiency improvement.
[0057] Example 2
[0058] Referring to Figure 2, this embodiment provides a reagent-filler synthesis reaction apparatus, which includes a liquid injection unit 100, a synthesis container 200, and a liquid driving unit 300. The liquid injection unit 100 is connected to a memory storing a reagent liquid containing the reagent, and is used to inject the reagent liquid 400 into the synthesis container 200. It can be connected to a reagent container storing reagents required for the synthesis reaction. The synthesis container 200 contains a reaction filler 210 and provides a synthesis reaction space for the filler 210 and the reagent liquid 400. The filler 210 is disposed within the... Inside the body 220 of the synthesis container 200; a liquid driving unit 300 is connected to the synthesis container 200 and is used to control the flow and flow direction of the reagent liquid in the synthesis container 200 to realize the circulation reaction or discharge of the liquid. The liquid driving unit 300 includes a pump body 310 and two docking nozzles 320. The docking nozzles 320 are both disposed on the pump body 310. One of the docking nozzles 320 is connected to the outlet end of the synthesis container 200, and the other docking nozzle 320 is connected to a discharge liquid collection device (not shown).
[0059] The specific steps for synthesizing reagent filler 210 using the aforementioned reagent filler synthesis reaction equipment are as follows:
[0060] Step a: Add a preset first volume of reagent liquid 400 into the synthesis container 200 through the liquid injection unit 100.
[0061] Further, referring to Figures 3 and 4, in this embodiment, the reagent filler 210 synthesis and processing equipment may include multiple liquid injection units 100, multiple synthesis containers 200, and multiple liquid driving units 300, wherein the multiple liquid injection units 100 and the multiple synthesis containers 200 are arranged in a one-to-one correspondence, and any synthesis container 200 is connected to one of the liquid driving units 300, thereby enabling multiple synthesis reactions to be carried out simultaneously to multiply the synthesis and processing efficiency of the reagent filler 210.
[0062] Furthermore, the synthesis container 200 in this embodiment is configured as a cylindrical structure. In different embodiments, its specific shape can be adjusted according to actual usage requirements. In addition, besides the liquid injection unit 100, other devices can be used to add the reagents required for the synthesis reaction from the reagent container into the synthesis container 200. This invention does not impose specific limitations on this.
[0063] Specifically, in this embodiment, the first volume V1 of the reagent liquid 400 added by any injection unit 100 to the corresponding synthesis container is configured as, for example, 150 μl, that is, 150 μl of reagent liquid 400 enters the corresponding synthesis container 200 through multiple injection units 100.
[0064] Step b: A portion of the reagent liquid 400 of a preset second volume is made to flow through the reaction packing 210 via the liquid driving unit 300 to obtain a primary reaction solution.
[0065] Furthermore, in this embodiment, the body 220 of the synthesis container 200 is connected to the docking nozzle 320 via a connecting pipe 230, and the body 220 is provided with a Luer connector 240 to connect the outlet end of the synthesis container 200 to the connecting pipe 230.
[0066] In other embodiments, in addition to the liquid drive unit 300, other types of pumps or double-acting cylinders may be used to control the flow and direction of the reagent liquid 400, and the present invention does not impose specific limitations on this.
[0067] In this embodiment, the volume of the primary reaction solution is set as V2, where the value of V2 is obtained by the following formula:
[0068] V2 = X·V1 / n, where n is an integer greater than 1, and 1 < X < n. Based on this, the second volume of the primary reaction solution can be changed by adjusting the values of n and X according to actual needs.
[0069] Specifically, in this embodiment, n is set to 3, and X is preferably 2, so that the reaction process can balance reaction efficiency and synthesis effect. In different embodiments, the specific settings of n and X can be adaptively adjusted according to actual reaction requirements. This invention does not impose specific limitations on this, but in order to significantly improve product purity, X is preferably set between 1.5 and 2.5. Based on this, in this embodiment, V2 = 100 μl, at which point 50 μl of reagent liquid 400 remains in the synthesis container 200.
[0070] Furthermore, in this embodiment, the discharge rate Vx of the primary reaction solution is 8–12 μl / s. It should be noted that in this embodiment, the discharge rate Vx is obtained by observing the change in product purity under different discharge rates. Specifically, in this embodiment, the purity of the corresponding synthesized products is detected sequentially under multiple uniformly gradient discharge rate conditions, and the optimal discharge rate Vx is obtained after comparison. This results in relatively faster product processing efficiency and relatively higher purity. For conventional synthesis and processing, the range of Vx is generally configured as 5–100 μl / s.
[0071] Furthermore, to ensure that the reaction reagents can fully contact the packing material 210 and undergo a synthesis reaction, in this embodiment, a portion of the reagent liquid 400 flows through the reaction packing material 210 and remains stationary for a first time T1 to obtain the primary reaction solution. In different embodiments, the preset value of the first time T1 can be adjusted accordingly based on different chemical reactions and experimental tests; this invention does not impose specific limitations on this.
[0072] Step c: The liquid driving unit 300 causes a portion of the primary reaction liquid of a preset third volume to flow back through the reaction packing 210 in the synthesis container 200 to obtain a secondary reaction liquid. At the same time, the liquid driving unit 300 causes another portion of the primary reaction liquid that did not flow back through the reaction packing 210 to become a discharge liquid detached from the reaction packing 210. The fourth volume of the discharge liquid is the difference between the second volume and the third volume.
[0073] Furthermore, in this embodiment, step c further includes: setting the third volume of the secondary reaction liquid as V3, the value of V3 being obtained by the following relationship: V3 = (X-1)·V1 / n; setting the fourth volume of the discharged liquid detached from the reaction packing 210 as V4, then V4 = V2 - V3 = V1 / n. This achieves the goal of simultaneously carrying out the residual liquid re-reaction and product collection.
[0074] Specifically, in this embodiment, both V3 and V4 are 50 μl. At this time, after step c, 50 μl of discharge liquid is obtained, and the liquid volume in the synthesis container 200 is 100 μl. Specifically, it is composed of the remaining 50 μl of reagent liquid 400 in the synthesis container 200 in step b and the secondary reaction liquid returned to the synthesis container 200 in step c.
[0075] Furthermore, the secondary reaction liquid flows back through the reaction packing 210 in the synthesis vessel 300 via a liquid-driven unit at a reflux rate Vy of 6–10 μl / s for a portion of the primary reaction liquid. Similarly, for conventional synthesis processes, Vy is typically configured in the range of 5–100 μl / s.
[0076] Furthermore, in step c, a portion of the primary reaction solution flows back through the reaction packing 210 and remains stationary for a time T2 to obtain the secondary reaction solution. This increases the contact time between the reagents in the primary reaction solution and the packing 210, thereby improving the actual utilization rate. In different embodiments, the preset second time T2 is adjusted according to the type of reagent and environmental parameters; this invention does not impose specific limitations on this.
[0077] Step d: After repeating steps b to c multiple times by the liquid driving unit 300, the remaining reagent liquid 400 in the synthesis container 200 is discharged.
[0078] Furthermore, in this embodiment, the number of repetitions of steps S2 to S3 depends on the values of n and X, is positively correlated with the value of n, and negatively correlated with the value of X. The body parameters can be set according to actual processing requirements.
[0079] Specifically, since the monomer reagents used in the coupling stage are expensive, when used in the coupling stage, the number of repetitions (cycles) of steps S2 to S3 can be increased by appropriately increasing n and decreasing X, thereby increasing the utilization rate of monomer reagents and reducing experimental costs. On the other hand, the reagents such as acetonitrile required for deprotection, oxidation, and capping stages are relatively inexpensive. The number of repetitions (cycles) of steps S2 to S3 can be reduced by appropriately decreasing n and increasing X, and they may even be eliminated by directly draining them through a peristaltic pump.
[0080] Furthermore, in this embodiment, in step d, an upper limit can be set for the number of repetitions of steps b to c. The number of repetitions of steps b to c is at most the integer obtained by rounding down the calculation result of (n-X+1).
[0081] In this embodiment, after repeating steps b to c three times, the remaining 50 μl of the reagent liquid 400 in the synthesis container 200 will be completely discharged, thus completing one complete reagent and filler 210 synthesis reaction process.
[0082] Furthermore, in this embodiment, the reagent filler 210 synthesis and processing equipment may also include a control mechanism for controlling the actions of the liquid injection unit 100 and the liquid driving unit 300 in steps a to d. Specifically, the actions of the liquid injection unit 100 adding reagent liquid to the synthesis container 200 in step a, the actions of the liquid driving unit 300 causing a portion of the reagent liquid 400 to flow through the reaction filler 210 in step b, the actions of the liquid driving unit 300 causing a portion of the primary reaction liquid to flow back through the reaction filler 210 in step c, and the actions of the liquid driving unit 300 repeatedly performing steps b to c and discharging the remaining reagent liquid 400 in the synthesis container 200 in step d are all performed under the control of the control mechanism.
[0083] Furthermore, the control mechanism stores a program for executing the above-mentioned reagent filler 210 synthesis reaction method. The liquid injection unit 100, the synthesis container 200, and the liquid driving unit 300 are respectively connected to the control mechanism. In the actual production and processing process, the operator can adjust the above structure in real time through the control mechanism, thereby improving the flexibility of the equipment. The operator can also preset parameters through the control mechanism, thereby improving the automation level of the equipment.
[0084] Furthermore, the user can set values such as V1, n, and X through the control mechanism. Specific preset parameters of the control mechanism include n and X, which limit the number of cycles; the first velocity Vx of a portion of the reagent liquid flowing through the reaction packing; the second velocity Vy of a portion of the primary reaction liquid flowing back through the reaction packing 210; the first time T1 during which a portion of the reagent liquid flows through the reaction packing 210 and remains stationary; the second time T2 during which a portion of the primary reaction liquid flows back through the reaction packing 210 and remains stationary; and the first volume V1 of the reaction liquid added to the synthesis container 200.
[0085] In summary, this invention enhances the contact between the reaction liquid and the packing material 210, ensuring sufficient interaction between the two and thus achieving complete conversion of the residual liquid. This technology not only significantly improves reagent utilization efficiency and achieves cost savings, but also effectively increases the purity of the final product.
[0086] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.
Claims
1. A method of synthesizing a reagent with a filler, characterized by: Includes the following steps: Step S1: Provide a reagent liquid containing the reagent and a synthesis container loaded with reaction filler, and add a preset first volume of the reagent liquid into the synthesis container; Step S2: Pass a portion of the predetermined second volume of the reagent liquid through the reaction packing material to obtain a primary reaction solution; Step S3: A portion of the primary reaction liquid of a preset third volume is reversed and flows through the reaction packing again to obtain a secondary reaction liquid. The other portion of the primary reaction liquid that does not flow through the reaction packing becomes the discharge liquid that is separated from the reaction packing. The fourth volume of the discharge liquid is the difference between the second volume and the third volume. Step S4: After repeating steps S2 to S3 multiple times, drain the remaining reagent liquid from the synthesis container.
2. The method for causing a synthesis reaction between the reagent and the filler according to claim 1, characterized in that: Let V1 be the first volume of the reaction liquid added to the synthesis container in step S1. Step S2 further includes: setting the second volume of the primary reaction solution as V2, the value of V2 being obtained by the following formula: V2 = X·V1 / n, where n is an integer greater than 1, and 1 < X < n.
3. The method for causing a synthesis reaction between the reagent and the filler according to claim 2, characterized in that: Step S3 further includes: Let the third volume of the secondary reaction solution be V3, and the value of V3 is obtained by the following relationship: V3 = (X-1)·V1 / n, Let the fourth volume of the effluent detached from the reaction packing be V4, then V4 = V2 - V3 = V1 / n.
4. The method for causing a synthetic reaction between the reagent and the filler according to claim 3, characterized in that: In step S4, the number of repetitions of steps S2 to S3 depends on the values of n and X, and is positively correlated with the value of n and negatively correlated with the value of X.
5. The method for causing a synthetic reaction between the reagent and the filler according to claim 3, characterized in that: In step S4, the number of repetitions of steps S2 to S3 is at most the integer obtained by rounding down the calculation result of (n-X+1).
6. The method for causing a synthesis reaction between the reagent and the filler according to claim 1, characterized in that: In step S2, a portion of the reagent liquid flows through the reaction packing at a first velocity Vx ranging from 5 to 100 μl / s; in step S3, a portion of the primary reaction liquid flows back through the reaction packing at a second velocity Vy ranging from 5 to 100 μl / s.
7. The method for causing a synthesis reaction between the reagent and the filler according to claim 1, characterized in that: In step S2, a portion of the reagent liquid flows through the reaction packing and remains still for a first time T1 to obtain the primary reaction solution; in step S3, a portion of the primary reaction solution flows through the reaction packing again in the reverse direction and remains still for a second time T2 to obtain the secondary reaction solution.
8. A reagent and filler synthesis and processing apparatus, characterized in that: include: The system comprises a liquid injection unit, a synthesis container, and a liquid drive unit, among which... The injection unit is connected to a memory that stores a reagent liquid containing the reagent, and the synthesis container is loaded with reaction packing material. The injection unit is used to add the reagent liquid into the synthesis container. The liquid driving unit is connected to the synthesis container and is used to control the flow and flow direction of the reagent liquid in the synthesis container; The reagent filler synthesis and processing equipment performs reagent filler synthesis and processing by executing the following steps: Step a: Add a preset first volume of the reagent liquid into the synthesis container through the liquid injection unit; Step b: A portion of the reagent liquid of a preset second volume is flowed through the reaction packing material by the liquid driving unit to obtain a primary reaction solution; Step c: Using the liquid driving unit, a portion of the primary reaction liquid of a preset third volume is reversed and flows through the reaction packing again to obtain a secondary reaction liquid. The other portion of the primary reaction liquid that does not flow through the reaction packing becomes the discharge liquid that is separated from the reaction packing. The fourth volume of the discharge liquid is the difference between the second volume and the third volume. Step d: After repeatedly performing steps b to c by the liquid driving unit, the remaining reagent liquid in the synthesis container is discharged.
9. The reagent and filler synthesis and processing equipment according to claim 8, characterized in that: The reagent filler synthesis and processing equipment includes multiple liquid injection units, multiple synthesis containers, and multiple liquid driving units, wherein the multiple liquid injection units and the multiple synthesis containers are arranged in a one-to-one correspondence, and any synthesis container is connected to one of the liquid driving units.
10. The reagent and filler synthesis and processing equipment according to claim 8, characterized in that: The liquid drive unit includes a pump body and two connectors, both of which are disposed on the pump body. One connector is connected to the synthesis container, and the other connector is connected to the discharge liquid collection device.
11. The reagent and filler synthesis and processing equipment according to claim 8, characterized in that: The reagent filler synthesis and processing equipment also includes a control mechanism for controlling the operation of the liquid injection unit and the liquid driving unit in steps a to d.
12. The reagent and filler synthesis and processing equipment according to claim 11, characterized in that: Let the first volume of the reaction liquid added to the synthesis container in step a be V1. Step b further includes: setting the second volume of the primary reaction solution as V2, the size of V2 is obtained by the following relationship: V2=X·V1 / n, where n is an integer greater than 1, and 1<X<n; Step c further includes: defining the third volume of the secondary reaction liquid as V3, the value of V3 being obtained by the following relationship: V3 = (X-1)·V1 / n; defining the fourth volume of the effluent detached from the reaction packing as V4, then V4 = V2 - V3 = V1 / n. Users can set the values of V1, n, and X through the control mechanism.