CN211255777U - Automatic solid-phase synthesis system for oligomer - Google Patents
Automatic solid-phase synthesis system for oligomer Download PDFInfo
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- CN211255777U CN211255777U CN201922439337.3U CN201922439337U CN211255777U CN 211255777 U CN211255777 U CN 211255777U CN 201922439337 U CN201922439337 U CN 201922439337U CN 211255777 U CN211255777 U CN 211255777U
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Abstract
The utility model discloses an automatic solid-phase synthesis system for oligomer, which comprises a reagent distribution system, a pressure chamber, a reaction vessel, a plate frame for installing the reaction vessel and a control system; the reagent distribution system comprises a distribution pipe, a distribution pipe mounting bracket and a constant pressure chamber, wherein the distribution pipe is arranged on the distribution pipe mounting bracket, one end of the distribution pipe is provided with a square opening, the other end of the distribution pipe is provided with a conical distribution nozzle, the constant pressure chamber is filled with inert gas, and the distribution pipe is positioned in the constant pressure chamber; the pressure chamber is a movable pressure chamber; the plate frame for installing the reaction vessel is a micro-titer array-hole matrix type flat plate, is used for installing the reaction vessel and is placed in a pressure chamber for reaction during operation; the control system is used for automatically controlling the work of the reagent distribution system, the pressure chamber and the reaction container. The utility model discloses but at every turn accurate control is used for the synthesis of oligomer to 0.5ul reagent addition, and the low material consumption volume when realizing the small-scale synthesis can accurately carry out the collection of oligomer, cross contamination between the composition when avoiding collecting.
Description
Technical Field
The utility model relates to a biological gene field, concretely relates to automatic solid phase synthesis system of oligomer.
Background
Solid phase synthesis of oligomers has been carried out for many years using automated synthesizers, which vary in design depending on the type and scale of synthesis. Early instruments used completely closed reaction wells and were capable of synthesizing only small amounts of oligomer at a time, and these instruments consumed large amounts of reagents and were unable to meet the ever-increasing demand for low-cost, short-time production of oligomers.
In recent years, open reaction vessel designs have been applied to a variety of instruments, typically pipette synthesis columns or plate wells, which can synthesize more oligomers, typically from 12 to 96. However, these instruments (e.g., applied biosystems 3900 synthesizers) are relatively inefficient at controlling the reagents flowing through the reaction vessels because the reagents are added in much greater amounts than are required for the reaction.
Another market-driven need is the desire to synthesize oligomers comprising special and expensive building blocks, such as RNA and RNA/DNA containing modified building blocks, which typically require longer reaction times, particularly to minimize the building blocks required to drive the completion of a given coupling reaction. Conventional systems require multiple dispensing of reagents to allow the synthesis medium to be in contact with the reaction reagents for extended periods of time. Other systems optimize the reaction by controlling the rate of reagent flow through the synthesis medium, but they are more focused on the scale of synthesis where large amounts of reagent are required for each reaction. These methods are effective for the scale of synthesis envisaged, but there is still a need for new instruments based on open reaction vessels in order to achieve the following technical problems:
(1) greatly reducing the consumption of materials for small-scale synthesis, eliminating or reducing the movement time without influencing the synthesis quality, and not reducing the reaction time;
(2) facilitating downstream processing of post-synthesis oligomers to facilitate more compliance with 384 or higher density specifications;
(3) when the collecting plate and the final composition are collected, the composition splashes due to the long distance between the collecting plate and the final composition and the gas passes through the middle of the collecting plate, so that the cross contamination of the composition is caused.
SUMMERY OF THE UTILITY MODEL
In order to solve the technical problems, the utility model provides an automatic solid-phase synthesis system for oligomers, which comprises a reagent distribution system, a pressure chamber, a reaction vessel, a plate frame for installing the reaction vessel and a control system;
the reagent distribution system comprises a distribution pipe, a distribution pipe mounting bracket and a constant pressure chamber, wherein the distribution pipe is arranged on the distribution pipe mounting bracket, one end of the distribution pipe is provided with a square opening, the other end of the distribution pipe is provided with a conical distribution nozzle, the constant pressure chamber is filled with inert gas, and the distribution pipe is positioned in the constant pressure chamber;
the pressure chamber is a movable pressure chamber;
the top of the reaction vessel is provided with a reagent inlet, the bottom of the reaction vessel is provided with a waste liquid outlet, and the reagent inlet is used for introducing a reagent to be reacted into the reaction vessel; the waste liquid discharge port is used for discharging the waste liquid after reaction;
the plate frame for installing the reaction vessel is a micro-titer array-hole matrix type flat plate, is used for installing the reaction vessel and is placed in a pressure chamber for reaction during operation;
the control system is used for automatically controlling the work of the reagent distribution system, the pressure chamber and the reaction container.
Preferably, a control valve and a pressure reducing valve are arranged in the pressure chamber, and the control valve is used for accurately controlling the reaction dosage of the reagent in the distribution pipe; the pressure reducing valve is used for controlling the pressure required in the pressure chamber, and the control system is connected with the control valve and the pressure reducing valve.
Preferably, the reaction container further comprises a collecting plate provided with a plurality of collecting holes, wherein the collecting plate is positioned below the plate frame for installing the reaction container and is used for collecting substances after reaction of the reaction container.
Preferably, the collecting device further comprises a collecting plate up-and-down moving device for automatically adjusting the position of the collecting plate in the up-and-down direction.
Preferably, the reaction vessel and the plate frame for mounting the reaction vessel together form a 384-well plate or 1536-well plate, and the distance between two adjacent reaction wells on the 384-well plate or 1536-well plate is 2.25mm-4.5 mm.
Preferably, the distribution pipe mounting bracket is a strip with a threaded hole, a plurality of distribution pipes are arranged on the distribution pipe mounting bracket, and the inner diameter of the threaded hole is matched with the outer diameter of the distribution pipe.
Preferably, the conical dispensing nozzle of the dispensing tube is made of a soft inert tube, the soft inert tube material comprising polytetrafluoroethylene.
Preferably, the center of the distribution pipe coincides with the center of two adjacent reaction wells on the 384-well plate, and each distribution pipe corresponds to one reaction well and is used for introducing the reagent in the distribution pipe into the reaction well.
Preferably, the amount of reagent dispensed in each time in the dispensing tube is 0.1ul-10 ul. More preferably, the amount of reagent dispensed per time in the dispensing tube is 0.5 ul.
Preferably, after the reagent in the distribution tube is introduced into the reaction well, the pressure chamber moves to one side, and the 384-well plate, the distribution tube and the pressure chamber space together form a pressure liquid discharge chamber for discharging the reagent in the distribution tube introduced into the reaction well for oligomer synthesis.
The utility model discloses the beneficial effect who brings does: the reagent distribution system of the utility model is in one-to-one correspondence with the 384 pore plates, and the center of each distribution pipe coincides with the centers of two adjacent reaction holes on the 384 pore plates, and through the control system and the distribution pipe is in the condition of the constant pressure chamber, the reagent addition amount of 0.1ul-10ul can be accurately controlled each time for the synthesis of the oligomer, the low material consumption during the small-scale synthesis is realized, and the adjacent distance is only 4.5mm millimeters, so that the small-distance movement of the distribution pipe can be convenient for realizing the synthesis work of the next row of reaction holes; meanwhile, the movable pressure chamber can enable a 384 pore plate in the pressure chamber to move into a pressure drainage chamber formed by the pressure chamber after receiving a reagent of a distribution pipe, so that an oligomer in a reaction hole is discharged under the pressurization of inert gas, further, the collection plate and the collection plate up-down moving device are used, the automatic adjustment of the position between the collection plate and the 384 pore plate can be realized, the collection of the oligomer is realized by accurately aligning the collection hole in the collection plate and the hole in the 384 pore plate, the cross contamination between compositions during collection is avoided, and the collection plate up-down moving device is suitable for the collection application of various up-down size distances, so that the collection application range is enlarged.
Drawings
FIG. 1 is a schematic diagram of an automated solid-phase oligomer synthesis system according to the present invention;
FIG. 2 is a schematic diagram of the structure of an automated solid-phase oligomer synthesis system according to the present invention;
FIG. 3 is a schematic diagram showing the operation of the distribution pipe in the automated solid-phase oligomer synthesis system of the present invention;
FIG. 4 is a schematic diagram of a 384-well plate structure in an automated solid-phase oligomer synthesis system according to the present invention;
Detailed Description
The present invention will be further described with reference to the following specific drawings.
As shown in fig. 1 and 2, there is provided an automated solid phase synthesis system for oligomers, comprising a reagent dispensing system 1, a pressure chamber 2, a 384-well plate 3, wherein the 384-well plate 3 comprises a reaction vessel 31 (corresponding to a reaction well on the 384-well plate) and a plate holder 32 for mounting the reaction vessel, a control system 4, a collection plate 51 having a plurality of collection wells formed therein, and a collection plate up-and-down moving device 52 for automatically adjusting the position of the collection plate 5 in the up-and-down direction;
wherein: the reagent distribution system 1 comprises a plurality of distribution pipes 11, a distribution pipe mounting bracket 12 for mounting the distribution pipes 11, and a constant pressure chamber 13, wherein the upper ends of the distribution pipes 11 are provided with square openings, the lower ends are provided with conical distribution nozzles, and the distribution nozzles are made of soft inert pipes (such as polytetrafluoroethylene materials or other materials with similar functions); the dispensing tube mounting bracket 12 is made of a hard material such as anodized aluminum or polyphenylene sulfide (PPS), Polyetheretherketone (PEEK), etc., and has a strip shape with a threaded hole having an inner diameter matching the outer diameter of the dispensing tube 11, and the dispensing nozzle can be screwed into the threaded hole formed in the dispensing tube mounting bracket 12 without a preliminary screw process.
The constant pressure chamber 13 is filled with an inert gas (e.g., argon and/or nitrogen) to eliminate the generation of bubbles in the distribution pipe 11 having a small distribution amount difference.
Wherein: the pressure chamber 2 is a movable pressure chamber, and a control valve 21 and a pressure reducing valve 22 are arranged in the pressure chamber, the control valve 21 can effectively control the reagent dosage of the distribution pipe 11 in the opening and closing time through the effective control of the control system 4, and the pressure reducing valve 22 can be arranged in 1 or more according to the pressure requirement of the pressure chamber, so as to ensure that the pressure in each pressure chamber does not exceed the required level.
Wherein: the distance between two adjacent reaction wells on the 384-well plate 3 was 4.5mm, and when the 384-well plate was used in the horizontal direction, twenty-four wells were provided in each row and sixteen reaction wells were provided in each column. A reagent inlet is arranged at the top of the reaction hole (corresponding to the reaction container 31), a waste liquid outlet is arranged at the bottom of the reaction hole, and the reagent inlet is used for introducing the reagent to be reacted, which is introduced from the distribution pipe 11, into the reaction container 31; the waste liquid discharge port is used for discharging the waste liquid after reaction; the 384-well plate 3 is placed in the pressure chamber 2 during operation.
The center of the distribution pipe 11 coincides with the center of two adjacent reaction wells on the 384-well plate 3, each distribution pipe 11 corresponds to one reaction well (corresponding to the reaction vessel 31) for introducing the reagent in the distribution pipe 11 into the reaction well (corresponding to the reaction vessel 31), sixteen distribution pipes 11 are arranged in the center of the distance of 4.5mm between two adjacent reaction wells of sixteen reaction wells in each row of the 384-well plate in one direction, and twenty-four distribution pipes 11 are arranged in the center of the distance of 4.5mm between two adjacent reaction wells of twenty-four reaction wells in each row of the 384-well plate in the second direction.
The collecting plate 51 has a plurality of collecting holes, and is located below the 384-well plate 3 to collect the reacted substances. Meanwhile, a collecting plate up-down moving device 52 is disposed below the collecting plate 51, and the collecting plate up-down moving device 52 may be an elastic device with a spring to adjust the up-down position of the collecting plate 51.
The utility model discloses in, collecting plate 51 is 96 orifice plate formats (be 8 × 12 matrix format), and wherein the distance between two adjacent collecting hole is 9 mm.
The synthesis of oligomer is carried out by the reagent and the synthesis medium through the automatic solid-phase synthesis system of the utility model, which comprises the following steps:
the synthesis medium needed by oligomer synthesis is injected into the reaction hole (corresponding to the reaction container 31) on the 384-hole plate 3 in advance, the 384-hole plate 3 is put into the pressure chamber 2 in parallel, the distribution pipe 11 is communicated with the upper part of the pressure chamber 2 through the distribution pipe mounting bracket 12, and the structure position state is as follows: sixteen distribution tubes 11 are disposed in the center of the distance of 4.5mm between every two adjacent reaction wells of sixteen rows of the 384-well plate in one direction, and twenty-four distribution tubes 11 are disposed in the center of the distance of 4.5mm between every two adjacent reaction wells of twenty-four rows of the 384-well plate in the second direction. The control system 4 starts to accurately control the opening and closing time of the control valve 21 in the pressure chamber 2, so that reagent introduced into the reaction holes of the 384-pore plate 3 by the distribution pipe 11 is effectively controlled, the specific amount of each reagent is 0.5ul, when the injection of 0.5ul of reagent is completed, the 384-pore plate 3 structural device in the pressure chamber 2 moves to the right side of the pressure chamber 2, a pressure liquid discharge chamber 23 is formed at the right side of the pressure chamber 2 at the moment, the reagent and synthetic medium in the reaction holes of the 384-pore plate 3 effectively react to form oligomer, and the pressure liquid discharge chamber 23 can keep an accurate pressure level by eliminating the inherent pressure difference caused by the change of the number of active holes in the synthesis process, so that the oligomer with different lengths can be effectively synthesized in the same 384-pore plate.
After the oligomer is synthesized, the collection plate 51 having a 96-well plate format is moved below the 384-well plate 3 by the collection plate up-and-down moving device 52, the collection wells on the collection plate 51 are aligned with the reaction wells on the 384-well plate 3, and the collection of the oligomer into the collection wells is effected by pressurizing the pressure difference in the effluent chamber 23.
According to the production requirement, the reagent distribution system 1 can be provided with 1 group or the multi-component distribution pipe 1,384 pore plates can be provided with 2 or more corresponding to the group, and the oligomer is synchronously synthesized and collected according to the principle.
The above description is provided for the purpose of describing the present invention in more detail with reference to the preferred embodiments, and it should not be construed that the present invention is limited to these descriptions, and it will be apparent to those skilled in the art that the present invention can be implemented by various modifications without departing from the spirit and scope of the present invention.
Claims (10)
1. An automated solid phase synthesis system for oligomers, comprising: comprises a reagent distribution system, a pressure chamber, a reaction container, a plate frame for installing the reaction container and a control system;
the reagent distribution system comprises a distribution pipe, a distribution pipe mounting bracket and a constant pressure chamber, wherein the distribution pipe is arranged on the distribution pipe mounting bracket, one end of the distribution pipe is provided with a square opening, the other end of the distribution pipe is provided with a conical distribution nozzle, the constant pressure chamber is filled with inert gas, and the distribution pipe is positioned in the constant pressure chamber;
the pressure chamber is a movable pressure chamber;
the plate frame for installing the reaction vessel is a micro-titer array-hole matrix type flat plate, is used for installing the reaction vessel and is placed in a pressure chamber for reaction during operation;
the control system is used for automatically controlling the work of the reagent distribution system, the pressure chamber and the reaction container.
2. The automated solid phase oligomer synthesis system of claim 1, wherein: a control valve and a pressure reducing valve are arranged in the pressure chamber, and the control valve is used for accurately controlling the reaction dosage of the reagent in the distribution pipe; the pressure reducing valve is used for controlling the pressure required in the pressure chamber, and the control system is connected with the control valve and the pressure reducing valve.
3. The automated solid phase oligomer synthesis system of claim 1, wherein: the collecting plate is positioned below the plate frame for installing the reaction container and is used for collecting substances after reaction of the reaction container.
4. The automated solid phase oligomer synthesis system of claim 3, wherein: the collecting plate up-and-down moving device is used for automatically adjusting the position of the collecting plate in the up-and-down direction.
5. The automated solid phase oligomer synthesis system of claim 2, wherein: the reaction vessel and the plate frame for mounting the reaction vessel jointly form a 384-well plate or a 1536-well plate, and the distance between two adjacent reaction wells on the 384-well plate or the 1536-well plate is 2.25mm-4.5 mm.
6. The automated solid phase oligomer synthesis system of claim 5, wherein: the distribution pipe mounting support is in a strip shape with threaded holes, a plurality of distribution pipes are arranged on the distribution pipe mounting support, and the inner diameters of the threaded holes are matched with the outer diameters of the distribution pipes.
7. The automated solid phase oligomer synthesis system of claim 6, wherein: the conical distribution nozzles of the distribution pipe are made of a soft inert pipe, and the soft inert pipe comprises polytetrafluoroethylene.
8. The automated solid phase oligomer synthesis system of claim 7, wherein: the centers of the distribution pipes coincide with the centers of two adjacent reaction holes on the 384-hole plate, and each distribution pipe corresponds to one reaction hole and is used for introducing the reagent in the distribution pipe into the reaction hole.
9. The automated solid phase oligomer synthesis system of claim 8, wherein: the amount of reagent distributed in each distribution pipe is 0.1ul-10 ul.
10. The automated solid phase oligomer synthesis system of claim 8, wherein: after the reagent in the distributing pipe is introduced into the reaction hole, the pressure chamber moves to one side, and the 384-hole plate, the distributing pipe and the pressure chamber space form a pressurized liquid discharge chamber together, wherein the pressurized liquid discharge chamber is used for discharging the reagent in the distributing pipe introduced into the reaction hole for oligomer synthesis.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201922439337.3U CN211255777U (en) | 2019-12-30 | 2019-12-30 | Automatic solid-phase synthesis system for oligomer |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201922439337.3U CN211255777U (en) | 2019-12-30 | 2019-12-30 | Automatic solid-phase synthesis system for oligomer |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111018931A (en) * | 2019-12-30 | 2020-04-17 | 江苏东玄基因科技有限公司 | Automatic solid-phase synthesis system for oligomer |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111018931A (en) * | 2019-12-30 | 2020-04-17 | 江苏东玄基因科技有限公司 | Automatic solid-phase synthesis system for oligomer |
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