CN220238527U - Microfluidic chip solid-phase peptide synthesizer - Google Patents
Microfluidic chip solid-phase peptide synthesizer Download PDFInfo
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- CN220238527U CN220238527U CN202321410443.9U CN202321410443U CN220238527U CN 220238527 U CN220238527 U CN 220238527U CN 202321410443 U CN202321410443 U CN 202321410443U CN 220238527 U CN220238527 U CN 220238527U
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- peptide synthesis
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- 239000007790 solid phase Substances 0.000 title claims abstract description 24
- 108090000765 processed proteins & peptides Proteins 0.000 title abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 92
- 238000010647 peptide synthesis reaction Methods 0.000 claims abstract description 18
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 10
- 238000010511 deprotection reaction Methods 0.000 claims abstract description 9
- 238000006482 condensation reaction Methods 0.000 claims abstract description 8
- 150000001413 amino acids Chemical class 0.000 claims abstract description 6
- WYTGDNHDOZPMIW-RCBQFDQVSA-N alstonine Natural products C1=CC2=C3C=CC=CC3=NC2=C2N1C[C@H]1[C@H](C)OC=C(C(=O)OC)[C@H]1C2 WYTGDNHDOZPMIW-RCBQFDQVSA-N 0.000 claims description 7
- 238000013461 design Methods 0.000 claims description 5
- 239000011521 glass Substances 0.000 claims description 3
- 239000011347 resin Substances 0.000 abstract description 24
- 229920005989 resin Polymers 0.000 abstract description 24
- 238000003786 synthesis reaction Methods 0.000 abstract description 12
- 230000002457 bidirectional effect Effects 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000007788 liquid Substances 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 230000007797 corrosion Effects 0.000 description 2
- 238000005260 corrosion Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000010532 solid phase synthesis reaction Methods 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000012854 evaluation process Methods 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 238000005461 lubrication Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
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- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940043263 traditional drug Drugs 0.000 description 1
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- Physical Or Chemical Processes And Apparatus (AREA)
Abstract
The utility model relates to a microfluidic chip solid-phase peptide synthesis device which is used in the processes of amino acid condensation reaction and deprotection reaction and comprises a reaction chip, a sample injector and a reverse pusher, wherein a reaction microchannel is arranged in the reaction chip, an inlet of the reaction chip is communicated with an output end of the sample injector through a pipeline A, and an outlet of the reaction chip is communicated with an output end of the reverse pusher through a pipeline B. According to the utility model, the inlet and the outlet of the reaction chip are respectively provided with the sample injector and the reverse pusher, so that the reaction liquid and the immobilized resin perform bidirectional continuous flow circulation reaction in the micro-channel, the reaction is fully contacted, the mixed flow effect is greatly improved, and the efficiency of the synthesis reaction is effectively improved. The reaction micro-channel adopts the smooth treatment of the snake-shaped bent angle, the immobilized resin can smoothly pass through without adhering to the wall, and the immobilized resin is still in good form after long-time reaction, can perform longer-time reaction, is suitable for synthesizing long-chain peptide, and the reaction chip can be repeatedly used, so that the application cost is effectively reduced.
Description
Technical Field
The utility model relates to the technical field of polypeptide synthesis, in particular to a microfluidic chip solid-phase peptide synthesis device.
Background
Currently, microfluidic chip technology has unique advantages in terms of high throughput, low consumption, and rapid synthesis. Compared with the traditional drug development program, a miniaturized and highly controllable environment is provided for the occurrence of biochemical reaction, and when the microfluidic chip solid-phase peptide synthesis and the analysis detection method are integrated, high-throughput screening and evaluation can be performed, so that the time and cost for drug development are effectively reduced, and the method has high value for the economic feasibility of the scale conversion and evaluation process.
However, most of the studies currently available are microfluidic chip solid-phase peptide synthesis performed under a continuous flow fixed bed reaction format, and the following drawbacks mainly exist: (1) When the existing microfluidic chip is used for peptide synthesis, the reaction liquid and the solid phase carrier can only perform unidirectional flow reaction, and the immobilized resin is seriously extruded and aggregated at the outlet position, so that active sites loaded on the resin cannot fully contact and react with the reaction liquid, the condition of resin ball rupture exists, the efficiency of chemical reaction is reduced, and the synthesis of longer peptide chains is difficult to realize. (2) The existing microfluidic chip is used for synthesis reaction, and after synthesis is finished, the immobilized resin in the channel is easy to accumulate and adhere to the wall at the right angle (dead angle) of the channel, and is not easy to discharge, so that the secondary use performance of the chip is reduced or the chip cannot be reused, and the cost of research, development and production is further increased.
Disclosure of Invention
The utility model aims to provide a microfluidic chip solid-phase peptide synthesis device applied to the deprotection reaction and amino acid condensation reaction process of polypeptide solid-phase synthesis, which can enable reaction liquid and a solid-phase carrier to fully contact and react, and the reaction chip can be reused.
In order to achieve one of the above purposes, the technical scheme adopted by the utility model is as follows: the utility model provides a microfluidic chip solid-phase peptide synthesizer, is used in amino acid condensation reaction and deprotection reaction in-process, and this synthesizer includes reaction chip, injector and contrary propeller, be equipped with reaction microchannel in the reaction chip, the entry of reaction chip communicates to the output of injector through pipeline A, the export of reaction chip communicates to the output of contrary propeller through pipeline B.
Preferably, the volume of the reverser is greater than the maximum volume of solution flowing into the reverser interior.
Preferably, the reverser is arranged vertically and above the injector.
Preferably, the reaction microchannel employs a serpentine microchannel and its turns employ a smooth corner design.
Preferably, the reaction chip is made of glass.
The second purpose of the utility model is to provide a microfluidic chip solid-phase peptide synthesis device applied to the whole process of polypeptide solid-phase synthesis, which can make the reaction liquid and the solid-phase carrier fully contact and react.
In order to achieve the second purpose, the utility model adopts the following technical scheme: the utility model provides a microfluidic chip solid-phase peptide synthesizer, includes reaction chip, injector, contrary propeller and tee bend filter, be equipped with snakelike microchannel in the reaction chip, reaction chip's entry communicates to the output of injector through pipeline A, reaction chip's export communicates to tee bend filter through pipeline B, tee bend filter's first export communicates to contrary propeller's output, tee bend filter's second export is the reaction liquid export, combine the valve on the tee bend filter, the valve is used for controlling second export switch or is used for switching on one of first export and second export.
Preferably, the volume of the reverser is greater than the maximum volume of solution flowing into the reverser interior.
Preferably, the reverser is arranged vertically and above the injector.
Preferably, the reaction microchannel employs a serpentine microchannel and its turns employ a smooth corner design.
Compared with the prior art, the utility model has the following beneficial effects:
according to the utility model, the inlet and the outlet of the reaction chip are respectively provided with the sample injector and the reverse pusher, so that the reaction liquid and the immobilized resin perform bidirectional continuous flow circulation reaction in the micro-channel, the reaction is fully contacted, the mixed flow effect is greatly improved, and the efficiency of the synthesis reaction is effectively improved; after the reaction is finished, the immobilized resin can be smoothly and completely discharged from the reaction chip without residue, and the reaction chip can be reused, so that the application cost is effectively reduced.
According to the utility model, through designing and preparing the internal channel structure of the microfluidic chip reactor and smoothly processing the serpentine bent angle, the immobilized resin can smoothly pass through the bent angle, the wall hanging condition is avoided, the immobilized resin is still in good form after long-time reaction, almost no damage condition is caused, and the reaction can be carried out for a longer time, so that the method is suitable for synthesizing long-chain peptide.
Drawings
FIG. 1 is a schematic diagram of the synthesis apparatus according to example 1 of the present utility model.
FIG. 2 is a schematic diagram of the synthesis apparatus according to embodiment 2 of the present utility model.
The marks in the figure: 10. a reaction chip; 20. a sample injector; 30. a reverse pusher; 40. a three-way filter head; 100. reaction microchannels.
Detailed Description
In order to make the above features and advantages of the present utility model more comprehensible, embodiments accompanied with figures are described in detail below.
Example 1
As shown in fig. 1, this embodiment provides a microfluidic chip solid-phase peptide synthesis device, which is used in the process of amino acid condensation reaction and deprotection reaction, the synthesis device includes a reaction chip 10, a sample injector 20 and a reverse pusher 30, a reaction micro-channel 100 is disposed in the reaction chip 10, an inlet of the reaction chip 10 is connected to an output end of the sample injector 20 through a pipeline a, an outlet of the reaction chip 10 is connected to an output end of the reverse pusher 30 through a pipeline B, a granular solid-borne resin is disposed in the reaction micro-channel 100 and is not fixed, during the condensation reaction or deprotection reaction, a reaction solution (deprotection solution or activated amino acid solution) is fed into the reaction micro-channel 100 through the sample injector 20, and then the bidirectional push-pull action of the sample injector 20 and the reverse pusher 30 is utilized to make the reaction solution and the solid-borne resin reciprocally mix in the reaction micro-channel 100, the pipeline a and the pipeline B and perform corresponding reaction, and the reaction solution and the active site on the solid-borne resin are fully contacted and reacted, thereby the efficiency of the synthesis reaction is effectively improved.
In this embodiment, the reaction chip 10 is made of glass, has high corrosion resistance, and has excellent performance of stable synthesis for a long time, and can directly observe the situation in the internal reaction microchannel 100 from the outside. The pipeline A and the pipeline B can be made of Teflon materials, and have excellent chemical stability, corrosion resistance, sealing performance and high lubrication non-tackiness.
The reaction micro-channel 100 inside the reaction chip 10 of the embodiment adopts a serpentine micro-channel and the corner thereof adopts a smooth corner design, in the reaction process, the immobilized resin is dispersed in the reaction liquid and uniformly flows dynamically in the reaction micro-channel 100, and due to the smooth treatment of the serpentine corner, the immobilized resin can smoothly pass through the corner when flowing through the corner, the adhesion wall hanging condition is avoided, the immobilized resin is still in an intact form after long-time reaction, almost no damage condition is avoided, and the reaction can be performed for a longer time, thereby being suitable for synthesizing long-chain peptide. After the reaction is finished, the reaction micro-channel 100 is filled with the washing liquid such as DMF through the injector 20, so that the immobilized resin can be smoothly and completely discharged out of the reaction chip 10 without residue, the reaction chip 10 can be reused, and the application cost is effectively reduced.
In this embodiment, the injector 20 includes a syringe and a syringe pump for pushing and pulling the syringe, the syringe is a needleless syringe, the syringe is mounted on a housing platform of the syringe pump, a plunger head of the syringe is abutted against an output end of the syringe pump, and a pushing speed of the syringe is controlled and adjusted by the syringe pump, so as to adjust a dosage, a speed and a direction of the given medicine. The output tube head of the injector is detachably connected with the pipeline A. The reverse pusher 30 also adopts a syringe pump to control a syringe, and the installation mode is the same as that of the syringe. In other examples, the thrust reverser 30 may also be designed to be a syringe only.
The loading capacity of the injector 20 is far greater than the volume of the reaction micro-channel 100 of the reaction chip 10, for example, the volume of the reaction micro-channel 100 is 1 ml and the capacity of the injector 20 is 30 ml, so that the mixed flow of the reaction liquid and the solid-borne resin in the reaction micro-channel 100 is obvious. In addition, in order to enhance the mixed flow effect, the capacity of the reverse pusher 30 is larger than the maximum volume of the solution flowing into the reverse pusher 30, and the solid-liquid-gas three-phase mixed flow is formed in the pipeline and the reaction microchannel 100 during the bidirectional pushing and pulling process of the injector 20 and the reverse pusher 30; as a preferred example, the injector 20 of the present embodiment is horizontally disposed, and the back-up device 30 is vertically disposed and higher than the injector 20, so that part of air can be better retained in the back-up device 30, which is helpful for the mixed flow of solid, liquid and gas.
In this embodiment, the inlet and outlet ends of the reaction chip 10 are respectively provided with the sample injector 20 and the reverse pusher 30, so that the reaction liquid and the solid-supported resin perform a bidirectional continuous flow circulation reaction in the reaction microchannel 100, and the reaction is fully contacted. After the reaction is finished, the reverse pusher 30 is removed from the pipeline B, and the immobilized resin can be smoothly and completely discharged out of the reaction chip 10 under the pushing action of injecting the solvent into the injector 20, so that the reaction chip 10 can be reused, and the application cost is effectively reduced.
Example 2
As shown in fig. 2, the embodiment provides a microfluidic chip solid-phase peptide synthesis device, which comprises a reaction chip 10, a sample injector 20, a reverse pusher 30 and a three-way filter 40, wherein an inlet of the reaction chip 10 is communicated to an output end of the sample injector 20 through a pipeline a, an outlet of the reaction chip 10 is communicated to the three-way filter 40 through a pipeline B, a first outlet of the three-way filter 40 is communicated to an output end of the reverse pusher 30, a second outlet of the three-way filter 40 is a reaction liquid outlet, and a valve is combined on the three-way filter 40 and is used for controlling a second outlet switch or for conducting one of the first outlet and the second outlet.
The reaction chip 10, the sample injector 20, the reverse pusher 30, and the pipes a and B of this embodiment are the same as those of embodiment 1 described above.
In the embodiment, the three-way filter head 40 is arranged at the joint of the reverse pusher 30 and the pipeline B, and by changing the conduction path of the three-way filter head 40, the reaction liquid and the solid-borne resin can be reciprocally mixed in the reaction micro-channel 100, the pipeline A and the pipeline B and react correspondingly by means of the bidirectional push-pull action of the sample injector 20 and the reverse pusher 30 in the deprotection reaction and condensation reaction; the residual liquid or the washing liquid in the reaction micro-channel 100 can be discharged and the immobilized resin can be entrapped under the pushing action of the injector 20 during the washing or draining process. In this embodiment, the solid-supported resin is also trapped and does not enter the inside of the back-pusher 30 during the deprotection reaction and the condensation reaction, but the reaction solution enters the inside of the back-pusher 30.
While the basic principles and main features of the utility model and advantages of the utility model have been shown and described, it will be understood by those skilled in the art that the present utility model is not limited by the foregoing embodiments, which are described in the foregoing description merely illustrate the principles of the utility model, and various changes and modifications may be made therein without departing from the spirit and scope of the utility model as defined in the appended claims and their equivalents.
Claims (9)
1. A microfluidic chip solid-phase peptide synthesis device is used in the amino acid condensation reaction and deprotection reaction process, and is characterized in that: the reaction chip is internally provided with a reaction micro-channel, an inlet of the reaction chip is communicated to an output end of the sample injector through a pipeline A, and an outlet of the reaction chip is communicated to an output end of the reverse pusher through a pipeline B.
2. The microfluidic chip solid phase peptide synthesis device according to claim 1, wherein: the capacity of the reverser is greater than the maximum volume of solution flowing into the reverser.
3. The microfluidic chip solid phase peptide synthesis device according to claim 1, wherein: the reverse pusher is vertically arranged and higher than the sample injector.
4. The microfluidic chip solid phase peptide synthesis device according to claim 1, wherein: the reaction micro-channel adopts a serpentine micro-channel and the turning part adopts a smooth corner design.
5. The microfluidic chip solid phase peptide synthesis device according to claim 1, wherein: the reaction chip is made of glass.
6. A microfluidic chip solid phase peptide synthesis device is characterized in that: including reaction chip, injector, contrary ware and tee bend filter, be equipped with snakelike microchannel in the reaction chip, the entry of reaction chip communicates to the output of injector through pipeline A, the export of reaction chip communicates to the tee bend filter through pipeline B, the first export of tee bend filter communicates to the output of contrary ware, the second export of tee bend filter is the reaction liquid export, combine the valve on the tee bend filter, the valve is used for controlling second export switch or is used for switching on one of first export and second export.
7. The microfluidic chip solid phase peptide synthesis device according to claim 6, wherein: the capacity of the reverser is greater than the maximum volume of solution flowing into the reverser.
8. The microfluidic chip solid phase peptide synthesis device according to claim 6, wherein: the reverse pusher is vertically arranged and higher than the sample injector.
9. The microfluidic chip solid phase peptide synthesis device according to claim 6, wherein: and the turning part of the serpentine micro-channel adopts a smooth bent angle design.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202321410443.9U CN220238527U (en) | 2023-06-05 | 2023-06-05 | Microfluidic chip solid-phase peptide synthesizer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202321410443.9U CN220238527U (en) | 2023-06-05 | 2023-06-05 | Microfluidic chip solid-phase peptide synthesizer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN220238527U true CN220238527U (en) | 2023-12-26 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202321410443.9U Active CN220238527U (en) | 2023-06-05 | 2023-06-05 | Microfluidic chip solid-phase peptide synthesizer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN220238527U (en) |
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2023
- 2023-06-05 CN CN202321410443.9U patent/CN220238527U/en active Active
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