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CN-121988247-A - Solid phase synthesizer

CN121988247ACN 121988247 ACN121988247 ACN 121988247ACN-121988247-A

Abstract

The disclosure provides a reaction cup for a solid phase synthesizer, the solid phase synthesizer and a control method thereof, wherein the reaction cup comprises a reaction cup body, a reaction cup base with clamping and supporting functions, an inlet for introducing liquid and/or gas is formed in the outer portion of a cavity of the reaction cup base, a groove structure is formed in the reaction cup body, a protruding structure matched with the groove structure is arranged in the cavity of the reaction cup base, and the groove structure is clamped with the protruding structure and used for fixing the reaction cup body on the reaction cup base. In addition, the inlet formed in the reaction cup base is beneficial to adding some related substances into the reaction cup from the adding direction different from the reaction cup body, so that the synthesis quality is further improved.

Inventors

  • CHEN BOLIN
  • TAN BAOFENG
  • JIANG QIUYU
  • HUA WEIWEN

Assignees

  • 江苏金斯瑞生物科技有限公司

Dates

Publication Date
20260508
Application Date
20251105
Priority Date
20241106

Claims (20)

  1. 1. The reaction cup for the solid phase synthesizer comprises a reaction cup body and is characterized by further comprising a reaction cup base with clamping and supporting functions, wherein an inlet for introducing liquid and/or gas is formed in the outer part of a cavity of the reaction cup base; The reaction cup comprises a reaction cup body, and is characterized in that a groove structure is arranged on the reaction cup body, a protruding structure matched with the groove structure is arranged in a cavity of the reaction cup base, and the groove structure is clamped with the protruding structure and used for fixing the reaction cup body on the reaction cup base.
  2. 2. The cuvette for a solid phase synthesizer according to claim 1, wherein the outside of the chamber of the cuvette base is provided with a reagent inlet and a gas inlet, respectively.
  3. 3. The cuvette for solid phase synthesizer according to claim 2, wherein when the cuvette is used for polypeptide synthesis, a reaction raw material or a washing reagent is added through the cuvette body, a deprotection reagent is added through the reagent inlet, and a gas is blown through the gas inlet drum for mixing the reaction raw material or isolating air or participating in the reaction.
  4. 4. The cuvette for a solid phase synthesizer according to claim 1, wherein only a gas inlet is provided outside the chamber of the cuvette base.
  5. 5. The cuvette for solid phase synthesizer according to claim 4, wherein when the cuvette is used for polypeptide synthesis, gas is blown in through the gas inlet drum for mixing reaction raw materials or isolating air or participating in reaction.
  6. 6. The cuvette for a solid phase synthesizer according to any one of claims 1 to 5, wherein a sealing element is provided outside the mouth of the cuvette body or inside the cavity of the cuvette base.
  7. 7. The cuvette for a solid phase synthesizer according to any one of claims 1 to 5, wherein the cuvette base comprises a clamping member for clamping the cuvette body mouth and a support member for supporting the cuvette body, the clamping member and the support member being connected; the protruding structure is arranged on the inner wall of the clamping piece, and the inlet is arranged on the supporting piece.
  8. 8. The cuvette for solid phase synthesizer according to claim 7, wherein a plurality of the protruding structures are provided along the extending direction of the clamping member, and each of the protruding structures is provided with one of the groove structures on the outer wall of the cuvette body bottleneck.
  9. 9. A solid phase synthesizer, characterized by comprising the reaction cup for the solid phase synthesizer according to any one of claims 1 to 8, further comprising a liquid injection module, a liquid discharge module and an oscillation module; The liquid injection module is used for injecting reaction raw materials or washing reagents or deprotection reagents into the reaction cup; the liquid discharging module is used for discharging liquid flowing out through the reaction cup; The oscillation module is used for uniformly mixing substances in the reaction cup.
  10. 10. The solid phase synthesizer according to claim 9, further comprising a thermal cycle module, wherein the thermal cycle module is attached to the reaction cup and is connected to a heating device; and the thermal circulation module is used for circulating the heating medium to flow when the heating equipment is started so as to realize temperature control of the reaction cup.
  11. 11. The solid phase synthesizer of claim 9 further comprising a nitrogen control assembly; And the nitrogen control assembly is used for controlling the blowing of nitrogen into the reaction cup.
  12. 12. The solid phase synthesizer of claim 9, wherein the drainage module comprises a drainage check valve; the liquid discharge one-way valve is connected with the reaction cup and used for one-way discharging liquid flowing out through the reaction cup.
  13. 13. The solid phase synthesizer according to any one of claims 9 to 12, wherein the number of reaction cups is plural.
  14. 14. The solid phase synthesizer according to any one of claims 9 to 12 wherein the priming module comprises a priming control component and a plurality of priming tubes connected to the priming control component; The liquid injection control assembly is used for injecting mother liquor into the corresponding liquid injection pipe based on a high-pressure liquid injection mode so as to inject reaction raw materials or washing reagents or deprotection reagents into the reaction cup through the liquid injection pipe.
  15. 15. The solid phase synthesizer of claim 14, wherein the injection control assembly comprises a high pressure pump and a high pressure valve; the high-pressure pump and the high-pressure valve are connected in series, and are used for realizing the flow of mother liquor to the corresponding liquid injection pipe through the high-pressure valve when the high-pressure pump is started.
  16. 16. The solid phase synthesizer of claim 15, wherein the injection control assembly further comprises a rebound safety protection device.
  17. 17. The solid phase synthesizer according to claim 14, wherein the plurality of filling pipes are provided in pairs at both ends of the reaction cup.
  18. 18. The solid phase synthesizer of claim 14, wherein the plurality of injection tubes comprises four injection tubes; The four liquid injection pipes are used for simultaneously adding reaction raw materials or washing reagents to the two reaction cups.
  19. 19. A method of controlling a solid phase synthesizer, characterized by being applied to the solid phase synthesizer according to any one of claims 9 to 18, the method comprising: responding to a starting instruction aiming at a target synthesis task in a user operation page, and acquiring an execution program corresponding to the target synthesis task; and executing a plurality of subtasks under the target synthesis task according to the execution program to obtain a synthesis reactant.
  20. 20. The method according to claim 19, wherein the plurality of subtasks includes a pumping subtask, a deprotection subtask, a washing subtask, and a condensation subtask, and the performing the plurality of subtasks under the target synthesis task according to the execution program includes: Draining the liquid in the reaction cup by starting a negative pressure pump in response to the execution operation for the pumping subtask; adding a deprotection reagent to the reaction cup in response to an execution operation for the deprotection sub-task; Adding a washing reagent into a reaction cup in response to an execution operation for the washing subtask, and discharging liquid in the reaction cup when a washing end condition is reached; In response to the execution of the condensation subtask, adding reaction raw materials and condensation reagents into the reaction cup to perform a solid-phase synthesis reaction, and after the solid-phase synthesis reaction, executing the pumping subtask, the deprotection subtask and the washing subtask again until a synthesis reactant is obtained.

Description

Solid phase synthesizer Cross Reference to Related Applications The present application claims priority from chinese patent application number 202411579067.5 filed on 6/11/2024, the entire contents of which are incorporated herein by reference. Technical Field The disclosure relates to the technical field of solid phase synthesis, in particular to a solid phase synthesizer. Background Polypeptide is a compound formed by combining a plurality of amino acids through peptide bonds according to a certain arrangement sequence, is a generic term of bioactive substances related to various cell functions in organisms, and is often applied to the fields of functional analysis, antibody research, drug research and the like. The solid phase synthesizer refers to an instrument for synthesizing the above polypeptide. A polypeptide synthesizer is a technical device for realizing polypeptide synthesis by adopting a polypeptide solid-phase synthesis technology. The first real polypeptide synthesizer in the early 1980 s, the solid-phase synthesis of polypeptide is carried out in a rapid development period, so that a multi-mode and various polypeptide synthesizer is developed, and the prior synthesizer, such as 2012, the Baiqi biotechnology (Suzhou) company, discloses a high-throughput polypeptide synthesizer which comprises a bottom box with an upper opening and a reaction plate capable of sealing the opening of the bottom box. (Yao Jiwen et al, methods and apparatus for high throughput polypeptide synthesis, CN 102532252 A,2012.07.04) which saves instrument space, increases more reactors, and increases efficiency of simultaneous polypeptide synthesis. 2022, nanjin New drug development Co., ltd, discloses a temperature control device for a polypeptide synthesizer, which comprises a square shell and a temperature clamping belt, so that the temperature control problem of the polypeptide synthesizer is optimized. (Mei Yan, a polypeptide synthesizer temperature control device, CN 217535873 U,2022.10.04). However, the synthesizers disclosed in the prior art have the defects of high energy consumption, high potential safety hazard, small device flux, low polypeptide synthesis efficiency and high purchase and maintenance cost due to the adoption of electric heating (such as an electric heating wire), and are not suitable for large-scale use due to the adoption of microwaves for promoting polypeptide synthesis. In the solid phase synthesis reaction, a stable environment suitable for the reaction needs to be provided, and the existing polypeptide reaction cup cannot ensure the reaction stability due to the limitation of the structure, so that the reaction stability is poor, and the polypeptide synthesis quality is affected. Disclosure of Invention The invention provides a reaction cup for a solid phase synthesizer, the solid phase synthesizer and a control method thereof, so as to improve the stability in the solid phase synthesis reaction process and further achieve better synthesis quality. In a first aspect, an embodiment of the present disclosure provides a reaction cup for a solid phase synthesizer, including a reaction cup body, and further including a reaction cup base provided with clamping and supporting functions, where an inlet for introducing liquid and/or gas is provided outside a cavity of the reaction cup base; The reaction cup comprises a reaction cup body, and is characterized in that a groove structure is arranged on the reaction cup body, a protruding structure matched with the groove structure is arranged in a cavity of the reaction cup base, and the groove structure is clamped with the protruding structure and used for fixing the reaction cup body on the reaction cup base. In one possible embodiment, the reagent inlet and the gas inlet are respectively arranged outside the cavity of the reaction cup base. And adding a reaction raw material or a washing reagent through the reaction cup body, adding a deprotection reagent through the reagent inlet, blowing gas through the gas inlet drum for uniformly mixing the reaction raw material or isolating air or participating in the reaction. In one possible embodiment, the washing reagent comprises one of dimethylformamide DMF, dichloromethane DCM and methanol, and the deprotection reagent comprises one of piperidine, dibutyl aluminum hydroxide DBU, hydrazine hydrate, diethylamine and dimethylacetamide DMA. In one possible implementation, only the gas inlet is formed outside the cavity of the reaction cup base. In one possible embodiment, a gas is blown through the gas inlet drum for mixing the reaction raw materials or for insulating the air or for participating in the reaction. In one possible embodiment, a sealing element is arranged outside the bottle mouth of the reaction cup body or inside the cavity of the reaction cup base. In one possible embodiment, the reaction cup base comprises a clamping piece for clamping the bottle mouth of the reaction cup body and a suppo