CN210176770U - Apparatus for solid phase synthesis of polypeptides - Google Patents
Apparatus for solid phase synthesis of polypeptides Download PDFInfo
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- CN210176770U CN210176770U CN201920435251.0U CN201920435251U CN210176770U CN 210176770 U CN210176770 U CN 210176770U CN 201920435251 U CN201920435251 U CN 201920435251U CN 210176770 U CN210176770 U CN 210176770U
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Abstract
The utility model discloses an equipment for solid phase synthesis of polypeptide, it includes: at least one reservoir of amino acid; at least two condensation agent reservoirs; a multi-channel switching device; a peristaltic pump; a liquid measuring device; a transfer device; a reactor; and a deprotecting agent reservoir. The utility model discloses a pipeline blockage problem has been solved at all to equipment to design compactness, occupation space volume greatly reduced practice thrift the cost.
Description
Technical Field
The utility model relates to a polypeptide synthesis field, in particular to a solid phase synthesis's equipment for polypeptide.
Background
Polypeptides are compounds formed by the dehydration condensation of α -amino acids and their peptide bonds.
In the solid-phase synthesis method, a natural amino acid in which a relevant functional group is protected with a specific protecting group is selected as a raw material. During synthesis, the reaction is initiated on a solid support. The steps of deprotection, activation, crosslinking and the like are repeatedly carried out, so that peptide bonds are formed between the amino acids and are connected to the solid phase carrier one by one to form polypeptide chains.
In existing apparatus for solid phase synthesis of polypeptides, a gas such as nitrogen is typically used as the liquid transfer driving substance. In the apparatus having such a structure, when the reaction in the reaction vessel is waited for, a part of the raw material amino acid solution is fed and then retained in the pipe, and the amino acid solution in the pipe is precipitated for a long time. The amino acid precipitation can block the pipeline, and if the pipeline is not cleaned in time, the reaction can be stopped unpredictably, so that the efficiency of polypeptide synthesis is greatly influenced.
Therefore, an apparatus for solid phase synthesis of polypeptides that prevents the occurrence of amino acid precipitation is required.
SUMMERY OF THE UTILITY MODEL
In one aspect, the present invention provides an apparatus for solid phase synthesis of a polypeptide, the apparatus comprising:
at least one amino acid reservoir for storing an amino acid solution;
at least two condensation agent reservoirs for storing a condensation agent;
a multi-channel switching device having a plurality of inlets and one outlet, and allowing a fluid channel to be formed between any one of the plurality of inlets and the outlet while no fluid channel is formed between the other inlets and the outlet;
a peristaltic pump;
a liquid measuring device;
a transfer device;
a reactor; and
a deprotection agent reservoir for storing a deprotection agent,
wherein the content of the first and second substances,
each of the at least one amino acid reservoir and each of the at least two condensing agent reservoirs are in fluid communication with an inlet of the multi-channel switching device,
the outlet of the multi-channel switching device is in fluid communication with one port of the peristaltic pump,
the other port of the peristaltic pump is in fluid communication with the inlet of the dosing device,
the outlet of the liquid measuring device is communicated with the inlet of the transfer device in a fluid mode,
the outlet of the transfer device is in fluid communication with the reactor and
the deprotecting agent reservoir is in fluid communication with the reactor.
Optionally, the multi-channel switching device is a multi-channel switching valve.
Optionally, the multi-channel switching device is a plurality of multi-channel switching valves connected in series.
Optionally, the apparatus further comprises at least one cleaning liquid reservoir, each of the at least one cleaning liquid reservoirs being in fluid communication with a respective most upstream inlet of the multi-channel switching device.
Optionally, the dosing device has a level sensor.
Optionally, the reactor is a two-pass reactor.
Optionally, the apparatus further comprises a motor configured to allow the reactor to be inverted.
Optionally, the apparatus further comprises a cutting fluid reservoir in fluid communication with the reactor.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly described below. It is obvious that the drawings in the following description are only some embodiments of the invention, and that for a person skilled in the art, other drawings can be derived from them without inventive effort.
Fig. 1 shows a schematic diagram of an apparatus for solid phase synthesis of polypeptides according to an embodiment of the present invention.
Fig. 2 shows a schematic diagram of a device expanded on the basis of the apparatus for solid-phase synthesis of polypeptides according to the embodiment of the present invention of fig. 1.
Figure 3 shows a schematic diagram of a more specific apparatus for solid phase synthesis of polypeptides according to an embodiment of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiment of the present invention, all other embodiments obtained by a person skilled in the art without creative work belong to the protection scope of the present invention.
Fig. 1 shows a schematic diagram of an apparatus for solid phase synthesis of polypeptides according to an embodiment of the present invention. It includes: at least one amino acid reservoir 8, at least two condensing agent reservoirs 6, a multi-channel switching device 3, a peristaltic pump 5, a liquid measuring device 12, a transfer device 14, a reactor 4 and a deprotection agent reservoir 21.
The amino acid reservoir 8 and the condensing agent reservoir 6 are used to store synthetic raw materials for the polypeptide reaction, and may be referred to as raw material reservoirs. The amino acid reservoir 8 is at least one, but may be plural, but is represented by a square in fig. 1. In the present invention, the number of the amino acid reservoirs is not particularly limited, and may be 1, 2, 3, 4, 5 or more, for example, up to 24. Multiple amino acid reservoirs 8 can be used to store different kinds of amino acid solutions to synthesize polypeptides comprising multiple amino acid monomers. The condensation agent reservoir 6 is at least two, but there may also be a plurality, but it is indicated by a block in fig. 1. Since typically at least two condensing agents are required for polypeptide synthesis, there are at least two reservoirs of condensing agent in the system. In the present invention, the number of the condensing agent reservoirs is not particularly limited. It may be 2 and used to store two different condensing agents, a first condensing agent and a second condensing agent, respectively.
Polypeptide synthesis typically requires the use of two condensing agents in sequence to accomplish the amino acid condensation. An example of the first and second condensing agents in a system is DIC and oxyma. The reaction scheme is schematically shown below.
Through the above-shown procedure, polypeptides were synthesized from amino acids in a solid phase. Other examples of first/second condensing agent systems may also be HCTU/DIEA, HATU/DIEA, and the like. HATU and HCTU are structurally similar, with the same principle, but with higher HATU activity.
The raw material liquid reservoirs are connected with one end of a peristaltic pump 5 through a multi-channel switching device 3. The multi-channel switching device 3 has a plurality of inlets and one outlet, and allows a fluid channel to be formed between any one of the plurality of inlets and the outlet while no fluid channel is formed between the other inlets and the outlet. The multi-channel switching device 3 may be a multi-channel switching valve, for example a 6-channel switching valve. When the raw material reservoir is large, then a plurality of multi-channel switching valves connected in series may be used to form the multi-channel switching device 3, the outlet of the upstream multi-channel switching valve being connected to one inlet of the downstream multi-channel switching valve, and wherein the outlet of the most downstream one of the multi-channel switching valves is directly connected to the peristaltic pump 5. In fig. 1, the multichannel switching device 3 is represented by a block. The utility model discloses in, do not do the special restriction to the number of multichannel diverter valve. The multi-channel switching device 3 ensures that only one stock reservoir is in fluid communication with the peristaltic pump 5 at a time. It should be noted that when the multi-channel switching device 3 is formed using a plurality of multi-channel switching valves connected in series, each multi-channel switching valve is divided into upstream and downstream in the flow path due to the presence of the pipe connecting each multi-channel switching valve in series. The liquid flowing in from the most upstream multi-channel switching valve will flow through all of the series pipes. The inlets are equivalent for the same multi-channel switching valve.
One port of the peristaltic pump 5 is in fluid communication with the outlet of the multi-channel switching device 3 and the other port thereof is in fluid communication with the dosing device 12. Typically, the other port is fluidly connected to the top or upper portion of the dosing device 12 so that liquid can fall under gravity into the dosing device and collect at the bottom. Peristaltic pumps are known to achieve bi-directional delivery of fluids. Thus, the peristaltic pump 5 can either pump fluid from a reservoir to the metering device 12 or pump back into its reservoir reaction fluid retained in the line between the metering device 12 and the peristaltic pump 5. The direction in which peristaltic pump 5 delivers liquid to vector liquid device 12 is referred to herein as the forward direction, and the direction in which peristaltic pump 5 delivers liquid to the stock reservoir is referred to as the reverse direction.
In the present invention, the fluid communication means that there is a fluid passage, and fluid control components such as a valve and a pump may be provided on the fluid passage.
The liquid measuring device 12 is used for quantitatively measuring a required raw material liquid. Which may be a conventional container. The dosing device 12 may optionally be equipped with a level sensor. For example, it may be equipped with a photoelectric sensor 13 and signal that the amount of liquid is sufficient when the liquid level in the dosing device 12 reaches the desired level. This signal can then be used as a trigger to stop the peristaltic pump 5 from running in the forward direction and to start running in the reverse direction, thereby automatically controlling the feeding process.
The outlet of the metering device 12 is in fluid communication with the relay device 14. Typically, the metering device 12 is at a higher level than the level of the relay device 14 and is in fluid communication with the top or upper portion of the relay device 14 so that liquid can flow by gravity from the metering device 12 into the relay device 14. The relay device 14 is used to sufficiently premix the reaction raw material liquid before entering the reactor, thereby activating the amino acid.
The relay device 14 is in fluid communication with the reactor 4 so that the mixed reaction liquid can be fed to the reactor 4 and reacted. Typically, the mixed reaction solution is transferred from the transit device 14 to the reactor 4 by means of pipe pressure operated by a peristaltic pump.
The apparatus for solid phase synthesis of polypeptides of the present invention may also comprise other conventional components required in polypeptide synthesis.
The apparatus for solid phase synthesis of polypeptides should also comprise a storage and feed system for the deprotecting agent. The apparatus includes at least a deprotecting agent reservoir in fluid communication with the reactor. The deprotection agent may be, for example, piperidine. The storage and feed system for the deprotecting agent may use peristaltic pumps similar to the feedstock storage and feed system.
The apparatus for solid phase synthesis of polypeptides may further comprise a waste treatment system coupled to the reactor. The waste treatment system may include a pump and a waste collector, among others. The apparatus for solid phase synthesis of polypeptides may further comprise a product collection system coupled to the reactor. The product collection system may include a pump and a product collector, among others. The waste treatment system and the product collection system may share piping.
The apparatus for solid phase synthesis of polypeptides may also include automated feedback and control means as required.
The apparatus of the present invention for solid phase synthesis of polypeptides may include any suitable valve, pump, sensor and flow path design. The pumps of the present invention are preferably peristaltic pumps and thus do not contain any means for driving the liquid flow with gas.
The utility model discloses a characterized in that of a solid phase synthesis's equipment for polypeptide, through adopting the combination of peristaltic pump and multichannel valve to carry out the feeding, can carry the reaction liquid especially amino acid reaction liquid that the retention is in the pipeline between pump and the volume liquid device back to its reservoir to avoid amino acid solution to stop taking place to appear in the pipeline and then arouse the pipeline jam. In addition, compare in the mode that uses gas drive fluid among the prior art, the utility model discloses a feeding mode design is compact, practice thrift cost, occupation space volume greatly reduced.
Optionally, the apparatus for solid phase synthesis of polypeptides of the present invention further comprises a washing liquid reservoir 9 connected to the most upstream inlet of the multi-channel switching device 3. When a plurality of amino acids are used in the present invention for the synthesis of polypeptide, after each amino acid is attached, the peristaltic pump 5, the liquid measuring device 12, the relay device 14, the reactor 4, and the resin carrier therein need to be cleaned for the next synthesis or cleavage. At this time, the cleaning liquid is caused to flow through the entire flow path by providing the multi-channel switching device 3, and cleaning is performed. The most upstream is provided to enable cleaning of the entire flow path. When the multi-channel switching device 3 is only one multi-channel switching valve, any one of the inlets is the most upstream inlet. When the multichannel switching device 3 is a multichannel switching valve connected in series, the most upstream inlet is any one of the inlets of the most upstream multichannel switching valve. The cleaning solution used for preparation for the next synthesis and the cleaning solution used for preparation for cutting may be different cleaning solutions. The cleaning liquid reservoir 9 is at least one, but may be a plurality, but is represented by a block in fig. 1.
Optionally, the apparatus for solid phase synthesis of polypeptides of the present invention further comprises a cutting fluid storage and feed system. The cutting fluid is used for cutting the finally synthesized polypeptide from the solid carrier. The cutting fluid storage and feed system may use peristaltic pumps similar to the stock storage and feed system. However, since the cutting fluid does not have the problem of clogging the pipes, other feeding means are also contemplated.
Optionally, the apparatus for solid phase synthesis of polypeptides of the present invention further comprises a product wash reservoir for storing the product wash. After the cleavage is complete, the cleavage solution containing the product is discharged from the reactor, but some reaction product comprising the polypeptide remains in the reactor. The product wash is used to wash the reactor and resin to avoid product waste.
Fig. 2 shows a schematic diagram of a device expanded on the basis of the apparatus for solid-phase synthesis of polypeptides according to the embodiment of the present invention of fig. 1.
Wherein, three amino acid liquid reservoirs 8 are included1、82、83(ii) a Two condensing agent reservoirs 61、62(ii) a A cleaning liquid reservoir 9 connected to the multi-channel valve 3; a photoelectric liquid level sensor 13 disposed in the liquid measuring device 12; a deprotecting agent reservoir 21 fluidly connected to reactor 4; a motor 17 which can turn the reactor 4 up and down; a waste liquid collector 23 for storing waste liquid; and a cutting fluid reservoir 25 storing cutting fluid.
In this context, the numerical subscripts of the parts are used to distinguish the same kind of parts. For example, 81、82、83For first, second and third amino acid reservoirs.
The device operation mode is: first the multi-channel valve 3 is switched to the amino acid reservoir 8 where the first amino acid is stored1And the peristaltic pump 5 is operated in the forward direction to deliver the first amino acid to the vector liquid device 12. When the amount of the first amino acid in the equivalent liquid device 12 reaches a preset value, the amount is detected by the photoelectric liquid level sensor, the peristaltic pump is controlled to run reversely, and the amino acid solution retained between the peristaltic pump 5 and the equivalent liquid device 12 is sent back to the amino acid reservoir 81In (1). A metered amount of the amino acid solution is transferred from the metering device 12 to the relay device 14. Subsequently, the multi-channel valve 3 is switched to the condensing agent reservoir 6 storing the first condensing agent1And the peristaltic pump 5 is enabled to run in the forward direction, so that the first condensing agent is conveyed to the liquid metering device 12. When the amount of the first condensing agent in the liquid measuring device 12 reaches a preset value, the photoelectric liquid level sensor detects the amount of the first condensing agent, the peristaltic pump is controlled to run reversely, and the first condensing agent reserved between the peristaltic pump 5 and the liquid measuring device 12 is sent back to the condensing agent reservoir 61In (1). A metered amount of the first condensing agent is transferred from the dosing device 12 to the relay device 14. Subsequently, the multi-channel valve 3 is switched to the condensing agent reservoir 6 storing the second condensing agent2And the peristaltic pump 5 is enabled to run in the forward direction, so that the second condensing agent is conveyed to the liquid metering device 12. When the amount of the second condensing agent in the liquid measuring device 12 reaches a preset value, the photoelectric liquid level sensor detects the amount of the second condensing agent, the peristaltic pump is controlled to run reversely, and the second condensing agent which is reserved between the peristaltic pump 5 and the liquid measuring device 12 is sent back to the condensing agent reservoir 62In (1). In this case, it is also possible not to operate in reversePeristaltic pump, i.e. not returning the retention second condensing agent to the condensing agent reservoir 62In this case, the flow path cleaning described later is immediately waited for. However, from the point of view of saving agent, the choice is to return the retention second condensing agent to the condensing agent reservoir 62In (1). A metered amount of the second condensing agent is transferred from the dosing device 12 to the relay device 14. It should be noted that in the above process, the sequence of the steps of reversely operating the peristaltic pump and the steps of transferring the liquid from the liquid measuring device 12 to the transfer device 14 can be arbitrary. That is, the completed dosing fluid may be transferred from the dosing device to the relay device before, after, or simultaneously with returning the retained fluid to the raw material reservoir. The present invention does not limit this sequence. The first amino acid, the first condensing agent and the second condensing agent are mixed well in the relay device 14 to form a mixture, and reacted to activate the amino acid. The mixture is transferred from the transfer device 14 to the reactor 4. The motor 17 is actuated to flip the reactor 4 up and down to allow the mixture to react with the solid support therein. After the reaction, the waste liquid is discharged to the waste liquid collector 23. Subsequently, the multi-channel valve 3 is switched to be communicated with the cleaning liquid reservoir 9, so that the peristaltic pump 5 runs in the forward direction, and the flow path is fully cleaned. The cleaned waste liquid is discharged to the waste liquid collector 23. To this end, the synthesis of the first amino acid in the polypeptide is completed. Subsequently, a deprotection agent is supplied from the deprotection agent reservoir 21 to the reactor to deprotect the carboxyl group of the existing polypeptide chain. The cleaning process is then repeated.
The above procedure was repeated except that a solution from the amino acid reservoir 8 was used2To complete the synthesis of the second amino acid in the polypeptide. The above procedure was repeated again, except using a reservoir 8 from the amino acid3To complete the synthesis of the third amino acid in the polypeptide.
Finally, the polypeptide is cleaved from the solid support using the cleavage solution from the cleavage solution reservoir 25 to obtain a crude peptide solution. The crude peptide is removed from the reactor 4 and subjected to subsequent processing.
As described above, the apparatus for solid-phase synthesis of polypeptides of the present invention utilizes a peristaltic pump in combination with a multi-channel switching valve, thereby solving the problem of blockage of the tubing due to retention of amino acids in the conventional apparatus for solid-phase synthesis of polypeptides. Furthermore, the utility model discloses a device design is compact, needn't use gas drive system, has practiced thrift space and cost greatly. At the same time, the peristaltic pump may also provide higher feed accuracy.
Figure 3 shows a schematic diagram of a more specific apparatus for solid phase synthesis of polypeptides according to an embodiment of the present invention.
In FIG. 3, 24 amino acid reservoirs 8 are provided1To 824Which are connected in batches to a multi-channel switching valve 32To 36. Multi-channel switching valve 3 here6To 32Are connected in series in sequence. I.e. multi-channel switching valve 36Is connected to the multi-channel switching valve 35An inlet, multi-channel switching valve 35Is connected to the multi-channel switching valve 34And so on. Multi-channel switching valve 32Is in turn connected to a multi-channel switching valve 31An inlet of (2). Multi-channel switching valve 31To 36Are all 6-channel switching valves which together form a multi-channel switching device. Two cleaning liquid reservoirs 9 are also provided1And 92For storing DMF and DCM, respectively, and connected to the most upstream multi-channel switching valve 36. Furthermore, five condensation agent reservoirs 61To 65Is connected to a multi-channel switching valve 31Respectively, for storing DIC, Oxyma, HATU, HCTU, DIEA. It will be appreciated that the connection of the reservoir to the multi-channel switching valve may vary. Due to the series relationship of the six-channel switching valves, only one reservoir can be in fluid communication with the peristaltic pump 5 at a time by their switching positions.
The deprotecting agent reservoir 21, waste collector 23, and cutting fluid reservoir 25 of FIG. 3 are described above. In figure 3 appropriate valves v and pumps p are provided in their flow paths to deliver the liquid streams.
In FIG. 3 there are two reactors 41And 42Also known as a two pass reactor. The advantage of the double reactor is that while one reactor is reacting, the other reactor is performing the steps of cleaning, etc. When the reaction of the reactor for carrying out the reaction is completed and the step of cleaning is carried out, the other reactor can carry out the reaction. The cross reaction mode reduces the standby time and improves the reaction efficiency. More reactors may be provided.
Also shown in fig. 3 is a reactant collector 27 for storing the crude peptide. Which shares the same reactor outlet as the waste collector 23 and switches flow paths with switching valves as necessary.
Also shown in fig. 3 is a product purge reservoir 29.
The operation of the apparatus of FIG. 3 is illustrated below by way of example of a single condensation-deprotection and cleavage reaction of a polypeptide.
Standing for 30s to activate amino acid, opening valve and pump below transfer device 14, and transferring the mixture of activated glycine and condensing agent into reactor 4 as required1And 42Any one of them. Reactor 41And 42Two reaction vials which may be dual channel reactors. After the mixture is transferred, the rear motor continuously turns over up and down, and the activated amino acid and the resin are fully mixed and reacted. After the reaction is finished, a valve and a pump below the reactor are opened, and redundant reaction liquid enters a waste liquid barrel. The multi-channel switching valve is then switched to allow the cleaning liquid reservoir 9 to be filled1Is communicated with the peristaltic pump 5, and conveys cleaning solution N, N-dimethyl-formamide (DMF) into a measuring device 12, then into a transfer device 14 and then into a reaction bottle. The motor is started, and the resin and the reaction bottle are cleaned in a vertically reversed way. After a period of time, the waste liquid is directed into the waste liquid collector by opening the valve and the pump.
Deprotection is performed after the coupling is complete. The deprotection agent piperidine was transferred to the reaction flask. The flow path may be provided with a peristaltic pump, a liquid measuring device, a sensor, and the like. After the transfer, the motor is started, the reaction liquid is discharged into a waste liquid collector after being turned and mixed for a period of time, and then the DMF cleaning step is repeated to clean the reaction bottle and the resin in the reaction bottle.
Subsequently, the entire procedure described above may be repeated from the amino acid reservoir 82To deliver the next amino acid for polypeptide synthesis. The amino acid reservoir may store, for example, alanine (Ala), leucine (Leu), isoleucine (Ile), valine (Val), proline (Pro), phenylalanine (Phe), methionine (Met), tryptophan (Trp), serine (Ser), glutamine (gin), threonine (Thr), cysteine (Cys), asparagine (Asn), tyrosine (Tyr), aspartic acid (Asp), glutamic acid (Glu), lysine (Lys), arginine (Lys), or the likeAnd amino acid (Arg), histidine (His), and the like. Other condensing agents may be used as desired. For example, 2- (7-benzotriazol oxide) -N, N, N ', N' -tetramethyluronium Hexafluorophosphate (HATU), 6-chlorobenzotriazole-1, 1, 3, 3-tetramethyluronium Hexafluorophosphate (HCTU), Diisopropylethylamine (DIEA), 1-hydroxy-7-azobenzotriazol (HOAt), etc.
After completion of polypeptide synthesis, before cleavage, the multi-channel switching valve is switched to a washing solution reservoir 9 containing Dichloromethane (DCM)2In communication with peristaltic pump 5. After the peristaltic pump 5 was turned on, the cleaning solution was delivered to the reactor. After the upper and lower parts are turned and cleaned, the waste liquid is transferred into the waste liquid. Repeating for 3-4 times to ensure that the redundant DMF in the reactor is removed. Two or more kinds of cleaning liquids may be used for different cleaning objects, and for example, selection may be made based on solubility of the cleaning objects. Subsequently, the cleavage reagent is transferred from the cleavage solution reservoir to the reaction flask, and the inversion is initiated to start the in-line cleavage of the polypeptide. After 2h, the valves and pumps were opened to transfer the reactants to the reactant collector 27. Finally, trichloroacetic acid (TFA) was delivered from the product wash reservoir 29 to the reaction flask for washing. After the resin is washed, the washing liquid is also collected in the reactant collector 27. And carrying out post-treatment on the collected product to obtain a crude product of the polypeptide.
The foregoing describes particular embodiments of the present invention. The utility model discloses an adopt the combination of peristaltic pump and multichannel valve to carry out the feeding, can carry back its reservoir with the reaction liquid especially amino acid reaction liquid of retention in the pipeline between pump and the volume liquid device to avoid amino acid solution to stop taking place to appear in the pipeline and then arouse the pipeline to block. In addition, compare in the mode that uses gas drive fluid among the prior art, the utility model discloses a feeding mode design is compact, practice thrift cost, occupation space volume greatly reduced.
It will be clear to those skilled in the art that, for convenience and simplicity of description, the foregoing division of the functional modules is merely used as an example, and in practical applications, the above function distribution may be performed by different functional modules according to needs, that is, the internal structure of the device is divided into different functional modules to perform all or part of the above described functions.
The above-mentioned embodiments, further detailed description of the objects, technical solutions and advantages of the present invention, it should be understood that the above-mentioned embodiments are only specific embodiments of the present invention, and are not intended to limit the present invention, and any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (8)
1. An apparatus for solid phase synthesis of a polypeptide, the apparatus comprising:
at least one amino acid reservoir for storing an amino acid solution;
at least two condensation agent reservoirs for storing a condensation agent;
a multi-channel switching device having a plurality of inlets and one outlet, and allowing a fluid channel to be formed between any one of the plurality of inlets and the outlet while no fluid channel is formed between the other inlets and the outlet;
a peristaltic pump;
a liquid measuring device;
a transfer device;
a reactor; and
a deprotection agent reservoir for storing a deprotection agent,
wherein the content of the first and second substances,
each of the at least one amino acid reservoir and each of the at least two condensing agent reservoirs are in fluid communication with an inlet of the multi-channel switching device,
the outlet of the multi-channel switching device is in fluid communication with one port of the peristaltic pump,
the other port of the peristaltic pump is in fluid communication with the inlet of the dosing device,
the outlet of the liquid measuring device is communicated with the inlet of the transfer device in a fluid mode,
the outlet of the transfer device is in fluid communication with the reactor and
the deprotecting agent reservoir is in fluid communication with the reactor.
2. The apparatus of claim 1,
the multi-channel switching device is a multi-channel switching valve.
3. The apparatus of claim 1,
the multi-channel switching device is a plurality of multi-channel switching valves connected in series.
4. The apparatus of claim 1, further comprising at least one cleaning solution reservoir, each of the at least one cleaning solution reservoirs being in fluid communication with a respective most upstream inlet of the multi-channel switching device.
5. The apparatus according to claim 1, wherein the dosing device has a level sensor.
6. The apparatus of claim 1, wherein the reactor is a dual channel reactor.
7. The apparatus of claim 1, further comprising a motor configured to cause the reactor to be inverted.
8. The apparatus of claim 1, further comprising a cutting fluid reservoir in fluid communication with the reactor.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110003306A (en) * | 2019-04-01 | 2019-07-12 | 中国科学技术大学 | The device and method of synthesis in solid state for polypeptide |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110003306A (en) * | 2019-04-01 | 2019-07-12 | 中国科学技术大学 | The device and method of synthesis in solid state for polypeptide |
| CN110003306B (en) * | 2019-04-01 | 2023-11-28 | 中国科学技术大学 | Apparatus and method for solid phase synthesis of polypeptides |
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