CN210287188U - Automatic change polypeptide reaction system - Google Patents
Automatic change polypeptide reaction system Download PDFInfo
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- CN210287188U CN210287188U CN201822096163.0U CN201822096163U CN210287188U CN 210287188 U CN210287188 U CN 210287188U CN 201822096163 U CN201822096163 U CN 201822096163U CN 210287188 U CN210287188 U CN 210287188U
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- 238000006243 chemical reaction Methods 0.000 title claims abstract description 74
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 44
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 42
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 42
- 230000008859 change Effects 0.000 title abstract description 5
- 239000007788 liquid Substances 0.000 claims abstract description 47
- 238000004140 cleaning Methods 0.000 claims abstract description 22
- 238000002360 preparation method Methods 0.000 claims abstract description 22
- 238000001514 detection method Methods 0.000 claims abstract description 20
- 238000003860 storage Methods 0.000 claims abstract description 12
- 238000012544 monitoring process Methods 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 238000005303 weighing Methods 0.000 claims abstract description 10
- 238000007599 discharging Methods 0.000 claims abstract description 9
- 238000000825 ultraviolet detection Methods 0.000 claims abstract description 5
- 238000010532 solid phase synthesis reaction Methods 0.000 claims description 16
- 238000005406 washing Methods 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 6
- 230000007246 mechanism Effects 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 7
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 239000011347 resin Substances 0.000 abstract description 4
- 229920005989 resin Polymers 0.000 abstract description 4
- 150000001413 amino acids Chemical class 0.000 abstract description 3
- RSWGJHLUYNHPMX-UHFFFAOYSA-N 1,4a-dimethyl-7-propan-2-yl-2,3,4,4b,5,6,10,10a-octahydrophenanthrene-1-carboxylic acid Chemical compound C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 abstract description 2
- 238000003756 stirring Methods 0.000 abstract description 2
- 239000012530 fluid Substances 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000003746 solid phase reaction Methods 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000009434 installation Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 238000011165 process development Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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- Physical Or Chemical Processes And Apparatus (AREA)
- Peptides Or Proteins (AREA)
Abstract
The utility model discloses an automatic change polypeptide reaction system comprises solvent storage tank, join in marriage fluid reservoir, retort, weighing module, level sensor, automatic feed system, automatic discharge system, temperature control system, reaction degree detecting system, online cleaning system. The quantitative liquid feeding device is controlled by a weighing module and a liquid level sensor, and automatically and quantitatively feeds liquid to a reaction tank from a solvent storage tank and a liquid preparation tank. After reaction resin and amino acid are added, stirring is started automatically, and in the reaction process, a temperature sensor collects the temperature of the liquid medicine in the tank and sends the temperature to a temperature control system, so that the temperature of the liquid medicine in the reaction tank is controlled accurately. And monitoring the degree of the polypeptide synthesis reaction in real time through online ultraviolet detection and online K detection. After the reaction is finished, discharging through an automatic discharging system, and collecting the peptide resin. The cleaning degree is monitored by online conductivity detection and online pH detection and automatic cleaning is carried out. By adopting the automatic equipment, the labor intensity of workers is greatly reduced, and the operation precision and stability are improved.
Description
Technical Field
The utility model relates to an automatic reaction system, in particular to an automatic polypeptide solid phase synthesis system.
Background
In the field of polypeptide solid phase synthesis, the existing automatic polypeptide synthesizer realizes quantitative material transfer from a storage tank to a reaction kettle through a flowmeter, but the precision of a common vortex shedding flowmeter is insufficient, so that the stability of process control is influenced. If a mass flowmeter with higher precision is adopted, the cost is very high; the mass flow meter is limited by field installation space, and vertical installation of the mass flow meter is difficult to realize due to inconvenience in fixation; if horizontal installation can have the washing dead angle, brought certain degree of difficulty for the clean verification of system's pipeline, increased system pollution's risk.
In addition, the existing polypeptide synthesis system does not monitor the reaction degree in the reaction kettle in the production process, and the change of the weight and the volume of the resin in the peptide chain extension process cannot be known, so that the stability control of process development and continuous production is not facilitated. And when deviation occurs, the deviation cannot be found in time, and only the coupling of all amino acids is finished, so that waste is caused. After the reaction is finished, pollution is not avoided, secondary production is influenced, the cleaning of a reaction device is particularly important, and the existing polypeptide synthesis system has no complete on-line detection and automatic cleaning system.
Meanwhile, the existing equipment has low automation degree, and the collected solid reaction product can only pass through a sieve plate of the reaction kettle which is manually disassembled and assembled firstly, and then is transferred, so that the labor intensity is high, and the equipment is not beneficial to large-batch industrial production.
Disclosure of Invention
For solving the problem that exists, the utility model provides a reduction artifical intensity of labour with functions such as automatic business turn over material, on-line monitoring polypeptide synthesis reaction degree, on-line monitoring and self-cleaning is favorable to the automatic polypeptide solid phase synthesis system of industry large-scale production.
An automatic polypeptide solid phase synthesis system comprises a solvent storage tank, a liquid preparation tank, a reaction tank, a weighing module, an automatic feeding system, a temperature control system, a reaction degree monitoring system, an automatic discharging system and an online cleaning system.
Preferably, the automatic polypeptide solid phase synthesis system is provided with a DMF divided pulse type washing pipeline, piperidine is required to be added for protection after the polypeptide is synthesized in one step, and then after the polypeptide is washed by DMF, the polypeptide can be synthesized in the next step after no piperidine residue is left.
By additionally arranging the DMF divided into one pulse type washing pipeline, the separate control of synthesis and washing is realized, meanwhile, the process of manually adding a DMF solvent is reduced, and the working efficiency and the production safety are improved.
Preferably, the automatic polypeptide solid phase synthesis system is provided with a stirrer in the liquid preparation tank and the reaction tank, a weighing module and a liquid level sensor outside, and the automatic feeding system is composed of a solvent storage tank, a liquid preparation tank and a reaction tank which are connected with each other through a pipeline, a pump and a switch.
The real-time weight and volume of the liquid medicine in the tank can be determined through the weighing module and the liquid level sensor; through automatic feed system, automatic from solvent storage tank and join in marriage liquid tank ration liquid feeding to retort, be favorable to in time discovering the deviation, improve technology stability.
Preferably, temperature sensors are arranged in a liquid preparation tank and a reaction tank of the automatic polypeptide solid phase synthesis system, and the temperature sensors and the temperature control unit form a temperature control system together.
After automatic feeding, the control program starts stirring to react, and temperature sensor gathers liquid medicine temperature in the retort and sends to temperature control system in the reaction process, through temperature regulation, realizes the accurate control of liquid medicine temperature in the retort.
Preferably, the reaction degree monitoring system of the automatic polypeptide solid phase synthesis system consists of pipeline type online ultraviolet detection and online K detection. The real-time monitoring of The solid-phase reaction degree of The polypeptide is realized by an online ultraviolet detection device and an online K detection (The Kaiser Test) device, and The reaction is stopped in time according to The detection condition.
Preferably, a reaction tank of the automatic polypeptide solid phase synthesis system is provided with a rotary supporting mechanism and an automatic discharge port to form an automatic discharge system. Through rotatory supporting mechanism, make the retort slope ejection of compact, ensure that the smooth ejection of compact of jar interior solid-liquid is to no residue, both reduced the loss, avoid operating personnel directly to tear the cauldron open again, contact organic solvent and volatile matter accord with the EHS requirement.
Preferably, the automatic discharging system of the automatic polypeptide solid phase synthesis system can directly discharge and collect reaction products, and can also be connected with a drying system through a pipeline to form reaction-filtration-drying integration.
Preferably, the online cleaning system of the automated polypeptide solid phase synthesis system consists of an online conductivity detection device and an online pH detection device. The cleaning degree of the reaction tank is detected by detecting the conductivity and the pH value of the liquid for cleaning the reaction tank, and automatic cleaning is started until the conductivity of the liquid in the reaction tank is close to the conductivity of the purified water and the pH value is close to 7.
The automatic reaction system is suitable for other solid-phase reactions besides polypeptide solid-phase synthesis reactions.
Drawings
FIG. 1 is a schematic diagram of an automated polypeptide solid phase reaction system according to an embodiment of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention are described in detail below with reference to the accompanying drawings in the embodiments of the present invention. The described embodiments are only some embodiments of the invention, not all embodiments. Other embodiments formed by similar replacement, modification or combination based on the present embodiment belong to the protection scope of the present invention.
The embodiment provides an automatic polypeptide solid-phase synthesis system, as shown in fig. 1, which comprises an ① solvent storage tank, a ② liquid preparation tank, a ③ reaction tank, a ④ weighing module, an automatic feeding system, a temperature control system, a reaction degree monitoring system, an automatic discharging system and an online cleaning system, wherein after reaction resin and amino acid are added into the reaction tank, coupling reagents and deprotection reagents can be respectively prepared in the liquid preparation tanks 1 and 2, the weighing module and a ⑤ liquid level detector determine the real-time weight and volume of liquid medicines in the liquid preparation tank and the reaction tank, quantitative liquid is automatically added from the solvent storage tank to the liquid preparation tank through the automatic feeding system, and then quantitative liquid is sequentially added from the liquid preparation tank to the reaction tank.
When the primary coupling deprotection needs to wash the pipeline and the deprotection reagent in the reaction tank so as to avoid influencing the next coupling reaction, the automatic polypeptide solid phase synthesis system is provided with ⑥ DMF pulse washing pipelines which are divided into one path, and after the washing by the DMF, the next synthesis can be carried out after the deprotection reagent is ensured to have no residue.
In the process of liquid preparation and reaction, the influence of temperature on polypeptide reaction is large, so that an ⑦ temperature sensor is arranged, the change of temperature is monitored and collected in real time and transmitted to a ⑧ temperature control system, the temperature is kept in a proper range through proper regulation and control, the ⑨ stirrer is automatically started by the system, liquid medicine and reactants in a tank are fully mixed and react, and ⑩ online ultraviolet detection and reaction are carried out in the reaction process
And performing on-line K detection (The Kaiser Test), realizing real-time monitoring of The solid-phase reaction degree of The polypeptide, and stopping The reaction at any time according to The detection condition. After the reaction is finished, by
The supporting mechanism is rotated to ensure that the reaction tank is obliquely discharged, and solid and liquid in the tank pass through
The discharge hole discharges smoothly. Meanwhile, the discharge port is connected with the drying system through a pipeline, and a reaction product in the tank can be directly transferred to the drying system to carry out the next procedure, so that the reaction-filtration-drying integration is formed, and the loss of manpower and material resources is reduced.
After the polypeptide solid phase synthesis reaction is finished, a liquid preparation tank, a reaction tank and a pipeline of the system are cleaned and monitored by an online cleaning system. The on-line cleaning system comprises
On-line conductivity detection and
and (3) online pH detection, wherein the online conductivity detection unit detects the conductivity of the liquid for cleaning the reaction tank, the online pH detection unit detects the pH value of the liquid for cleaning the reaction tank, the online pH detection unit and the online pH detection unit simultaneously feed back the cleaning degree of the system, automatic cleaning is started until the conductivity of the liquid in the reaction tank is close to the conductivity of the purified water and the pH value is close to 7, and the system is automatically cleaned after the condition that the cleaning is finished is indicated.
Claims (10)
1. An automatic polypeptide reaction system is characterized in that the automatic polypeptide solid phase synthesis system comprises a solvent storage tank, a liquid preparation tank, a reaction tank, a weighing module, an automatic feeding system, a temperature control system, a reaction degree monitoring system, an automatic discharging system and an online cleaning system; the solvent storage tank, the liquid preparation tank and the reaction tank are connected with one another through pipelines; the weighing module is connected with the liquid preparation tank and the reaction tank; the automatic feeding system is connected with the agent storage tank, the liquid preparation tank and the reaction tank; the temperature control system is connected with the liquid preparation tank and the reaction tank; the reaction degree monitoring system is connected with the reaction tank; the automatic discharging system is connected with the reaction tank; the online cleaning system is connected with the liquid preparation tank and the reaction tank.
2. The automated polypeptide reaction system of claim 1, wherein the automated polypeptide reaction system is provided with DMF pulsed washing pipes in one path.
3. The automated polypeptide reaction system of claim 1, wherein the liquid preparation tank and the reaction tank are provided with a stirrer, and a weighing module and a liquid level sensor are arranged outside the liquid preparation tank and the reaction tank.
4. The automated polypeptide reaction system of claim 1, wherein the automated feeding system comprises a solvent storage tank, a liquid preparation tank, a reaction tank, a pipeline, a pump and a switch.
5. The automated polypeptide reaction system of claim 1, wherein temperature sensors are disposed in the liquid preparation tank and the reaction tank.
6. The automated polypeptide reaction system of claim 5, wherein the temperature sensor and the temperature control unit together comprise a temperature control system.
7. The automated polypeptide reaction system of claim 1, wherein the reaction level monitoring system comprises a pipeline-type online ultraviolet detection device and an online K detection device.
8. The automated polypeptide reaction system of claim 1, wherein the reaction tank is provided with a rotary supporting mechanism and an automatic discharging port, so as to form an automatic discharging system.
9. The automated polypeptide reaction system of claim 1 or 7, wherein the automated discharge system is connectable to a drying system via a conduit.
10. The automated polypeptide reaction system of claim 1, wherein the online cleaning system is comprised of an online conductivity detection device and an online pH detection device.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201822096163.0U CN210287188U (en) | 2018-12-11 | 2018-12-11 | Automatic change polypeptide reaction system |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201822096163.0U CN210287188U (en) | 2018-12-11 | 2018-12-11 | Automatic change polypeptide reaction system |
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| Publication Number | Publication Date |
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| CN210287188U true CN210287188U (en) | 2020-04-10 |
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|---|---|---|---|
| CN201822096163.0U Active CN210287188U (en) | 2018-12-11 | 2018-12-11 | Automatic change polypeptide reaction system |
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| Country | Link |
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| CN (1) | CN210287188U (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113181851A (en) * | 2021-04-29 | 2021-07-30 | 江苏博驰新材料科技有限公司 | Organic synthesizer intelligent control system based on biological imaging |
| CN114130346A (en) * | 2021-02-02 | 2022-03-04 | 申联生物医药（上海）股份有限公司 | Full-automatic solid-phase organic synthesis modular equipment |
| CN116478812A (en) * | 2023-04-19 | 2023-07-25 | 福建恒杰生物科技有限公司 | Method and equipment for determining antigenicity of collagen peptide |
-
2018
- 2018-12-11 CN CN201822096163.0U patent/CN210287188U/en active Active
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114130346A (en) * | 2021-02-02 | 2022-03-04 | 申联生物医药（上海）股份有限公司 | Full-automatic solid-phase organic synthesis modular equipment |
| CN113181851A (en) * | 2021-04-29 | 2021-07-30 | 江苏博驰新材料科技有限公司 | Organic synthesizer intelligent control system based on biological imaging |
| CN116478812A (en) * | 2023-04-19 | 2023-07-25 | 福建恒杰生物科技有限公司 | Method and equipment for determining antigenicity of collagen peptide |
| CN116478812B (en) * | 2023-04-19 | 2023-10-24 | 福建恒杰生物科技有限公司 | Equipment for determining antigenicity of collagen peptide |
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| Date | Code | Title | Description |
|---|---|---|---|
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20210310 Address after: 518118 No. 14 Jinhui Road, Kengzi Street, Pingshan New District, Shenzhen City, Guangdong Province, No. 7 Building, Shenzhen Biomedical Innovation Industrial Park Patentee after: SHENZHEN JX BIO-PHARMACEUTICAL Co.,Ltd. Address before: 518118 8th floor, building 1, Biomedical Innovation Industrial Park, 14 Jinhui Road, Kengzi street, Pingshan New District, Shenzhen City, Guangdong Province Patentee before: Zhong Xianglong Patentee before: Li Xinyu Patentee before: Wang Hongxin |
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| TR01 | Transfer of patent right |