Device for preparing stationary phase chip for enzymatic gene synthesis

Abstract

The utility model provides a kind of preparation device of fixed phase chip for enzyme method gene synthesis, belong to enzymatic method gene synthesis technical field, including shell, chip fixing frame and upper cover, shell top is open and inside forms chip reaction pool, shell side portion has liquid inlet hole and liquid outlet hole, liquid inlet hole and liquid outlet hole are respectively used to pass pipeline communication peristaltic pump, peristaltic pump is used to push reaction liquid flow through chip reaction pool and form circulating flow;Chip fixing frame is placed in the inside of shell chip reaction pool, and chip fixing frame has multiple chip fixing slots suitable for accommodating multiple phase chips;Upper cover is sealingly connected to the top of shell and is suitable for covering top opening, so that chip reaction pool forms closed space.The preparation device of fixed phase chip for enzyme method gene synthesis provided by the utility model can produce medium batch chips, meet the use, improve yield and save cost.

Description

Technical Field

[0001] This invention belongs to the field of enzymatic gene synthesis technology, and more specifically, relates to a device for preparing a stationary phase chip for enzymatic gene synthesis. Background Technology

[0002] With the rapid development of biotechnology in recent years, the third-generation gene synthesis technology, namely enzyme-catalyzed DNA synthesis technology, has gradually moved from the laboratory research and development stage to the industrial production stage. As a result, the amount of synthetic stationary phase required for this technology has also increased rapidly. However, the existing equipment for preparing stationary phase chips for enzyme gene synthesis cannot be used to prepare medium-batch stationary phase chips and cannot meet the needs. Therefore, it is necessary to develop large-scale stationary phase preparation technology and dedicated equipment. Utility Model Content

[0003] The purpose of this invention is to provide a device for preparing stationary phase chips for enzymatic gene synthesis, which aims to solve the technical problem that existing equipment for preparing stationary phase chips for enzymatic gene synthesis cannot be used to prepare medium-batch stationary phase chips.

[0004] To achieve the above objectives, the technical solution adopted by this utility model is: to provide an apparatus for preparing a stationary phase chip for enzymatic gene synthesis, comprising: The outer casing has an open top and forms a chip reaction pool inside. The side of the outer casing has a liquid inlet and a liquid outlet. The liquid inlet and the liquid outlet are respectively used to connect to a peristaltic pump through a pipe. The peristaltic pump is used to push the reaction liquid through the chip reaction pool and form a circulating flow. A chip holder is placed inside the chip reaction pool of the housing, and the chip holder has multiple chip fixing slots suitable for accommodating multiple phase chips; The top cover is sealed to the top of the housing and is adapted to seal the top opening so that the chip reaction cell forms a closed space.

[0005] In one possible implementation, the chip holder has a bottom and a top, the chip fixing slot is located at the top of the chip holder and extends into the chip holder in the depth direction, the bottom of the chip holder is located near the bottom of the housing, and the top of the chip holder is located near the top of the housing.

[0006] In one possible implementation, a row of chip fixing slots is arranged on the top of the chip holder near its opposite ends, and each row of chip fixing slots includes a plurality of chip fixing slots arranged at equal intervals.

[0007] In one possible implementation, a perforated hole is provided between the two rows of chip mounting slots, penetrating the top and bottom of the chip mounting bracket.

[0008] In one possible implementation, the bottom of the chip holder is provided with a plurality of pillars suitable for supporting the chip holder, the top of the pillars is connected to the bottom of the chip holder, the bottom of the pillars is used to contact the inner bottom wall of the housing, and the pillars are used to create a gap between the chip holder and the inner bottom wall of the housing.

[0009] In one possible implementation, a lifting lug is connected to the top corner of the chip holder, the lifting lug being used to lift the chip holder.

[0010] In one possible implementation, the outer casing and the top cover are sealed together by fasteners.

[0011] In one possible implementation, the outer shell includes a sheath and an inner liner fitted inside the sheath, with the chip holder placed inside the inner liner. The sheath is made of stainless steel, and both the inner liner and the chip holder are made of polytetrafluoroethylene (PTFE).

[0012] In one possible implementation, the top cover is made of stainless steel.

[0013] In one possible implementation, the top of the outer casing is provided with a groove, and the bottom of the upper cover is provided with a protrusion, the protrusion and the groove being connected to each other.

[0014] The beneficial effects of the apparatus for preparing stationary phase chips for enzymatic gene synthesis provided by this utility model are as follows: Compared with the prior art, the apparatus for preparing stationary phase chips for enzymatic gene synthesis of this utility model includes a shell, a chip holder, and a top cover. The top of the shell is open and a chip reaction pool is formed inside. The side of the shell has a liquid inlet and a liquid outlet, which are respectively used to connect to a peristaltic pump through pipes. The peristaltic pump is used to push the reaction liquid through the chip reaction pool and form a circulating flow. The chip holder is placed inside the chip reaction pool of the shell and has multiple chip fixing slots suitable for accommodating multiple phase chips. The top cover is sealed to the top of the shell and is suitable for sealing the top opening, so that the chip reaction pool forms a closed space. This utility model can prepare and produce chips in medium batches, meet the needs of use, increase output, and save costs. Attached Figure Description

[0015] To more clearly illustrate the technical solutions in the embodiments of this utility model, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this utility model. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0016] Figure 1A schematic diagram of the structure of the apparatus for preparing a stationary phase chip for enzymatic gene synthesis provided in this embodiment of the present invention in its usage state; Figure 2 An exploded view of the apparatus for preparing a stationary phase chip for enzymatic gene synthesis provided in this embodiment of the present invention; Figure 3 A schematic diagram of the chip holder structure of the apparatus for preparing a stationary phase chip for enzymatic gene synthesis provided in this embodiment of the present invention; Figure 4 A schematic diagram of the outer shell structure of the apparatus for preparing a stationary phase chip for enzymatic gene synthesis provided in an embodiment of this utility model; Figure 5 A schematic diagram of the upper cover structure of the apparatus for preparing a stationary phase chip for enzymatic gene synthesis provided in an embodiment of this utility model; Figure 6 This is a schematic diagram of the chip structure contained in the apparatus for preparing a stationary phase chip for enzymatic gene synthesis provided in an embodiment of the present invention.

[0017] Explanation of reference numerals in the attached figures: 10. Outer shell; 11. Chip reaction cell; 12. Liquid inlet; 13. Liquid outlet; 14. Sheath; 15. Inner liner; 16. Groove; 20. Chip holder; 21. Chip mounting slot; 22. Recess; 23. Hole; 24. Support; 25. Lifting lug; 30. Top cover; 31. Protrusion; 40. Pipe; 50. Peristaltic pump; 60. Chip. Detailed Implementation

[0018] To make the technical problems, technical solutions, and beneficial effects of this utility model clearer, the present utility model will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present utility model and are not intended to limit the present utility model.

[0019] The inventors discovered that the existing equipment used for preparing stationary phases in enzyme-catalyzed DNA synthesis technology cannot meet the requirements for preparing medium-batch chips 60, and it is difficult to rapidly increase the amount of stationary phase used in synthesis. Therefore, the inventors improved upon the existing technology, iterated on its advantages and made up for its disadvantages, and designed the preparation device for stationary phase chips for enzyme gene synthesis of this utility model. This invention develops a large-scale stationary phase preparation device, while increasing the preparation throughput, to meet the needs of the rapid development of enzyme-catalyzed DNA synthesis technology.

[0020] This invention belongs to the field of enzymatic gene synthesis technology in synthetic biology manufacturing, specifically a device for preparing stationary phase chips for enzymatic gene synthesis, which can be used to prepare medium-batch stationary phase chips.

[0021] Please refer to the following: Figures 1 to 6 The present invention provides a device for preparing a stationary phase chip for enzymatic gene synthesis. The device includes a housing 10, a chip holder 20, and a top cover 30. The housing 10 has an open top and forms a chip reaction pool 11 inside. The housing 10 has an inlet hole 12 and an outlet hole 13 on its side. The inlet hole 12 and the outlet hole 13 are respectively connected to a peristaltic pump 50 through a pipe 40. The peristaltic pump 50 is used to push the reaction liquid through the chip reaction pool 11 and form a circulating flow. The chip holder 20 is placed inside the chip reaction pool 11 of the housing 10 and has multiple chip fixing slots 21 suitable for accommodating multiple phase chips 60. The top cover 30 is sealed to the top of the housing 10 and is suitable for sealing the top opening, so that the chip 60 reaction pool 11 forms a closed space.

[0022] The apparatus for preparing stationary phase chips for enzymatic gene synthesis provided by this invention, compared with the prior art, fixes multiple chips 60 on a chip holder 20, places the chip holder 20 inside the chip reaction cell 11 of the outer shell 10, and then seals the top opening of the outer shell 10 with a top cover 30, so that the inside of the chip reaction cell 11 forms a closed space. By using an external peristaltic pump 50, the reaction liquid can be pushed to circulate in the chip reaction cell 11 and form a circulation. This invention can prepare medium batches of chips 60 to meet the needs of use, increase output and save costs. Based on the prior art, this invention has improved its advantages and compensated for its disadvantages, while increasing the preparation throughput to meet the needs of the rapid development of enzyme-catalyzed DNA synthesis technology.

[0023] Existing equipment cannot produce medium-batch quantities of chips 60 in a single operation. However, this invention, through its design, can meet the requirements for medium-batch chip 60 production. In this embodiment, the chip 60 is a phase-phase chip, or a liquid-phase chip, based on a multi-index parallel detection platform using Luminex xMAP technology, enabling high-throughput and high-sensitivity biomolecular analysis. The chip holder 20 has 40 chip mounting slots 21, accommodating medium-batch chip 60 production. Separating the chip holder 20 from the chip reaction cell 11 allows for rapid, integrated transfer of the chips 60, improving the uniformity of chip preparation. This invention optimizes the structure of the chip holder 20, making chip 60 placement more convenient and reducing the range of shaking.

[0024] Specifically, the height of the chip holder 20 is less than the depth of the chip reaction cell 11, while not affecting the connection and sealing of the top cover 30 to the outer casing 10. The peristaltic pump 50 has an inlet and an outlet, which are respectively connected to one end of two pipes 40. The peristaltic pump 50 is used to pump liquid and circulate the liquid.

[0025] In this embodiment, both the inlet hole 12 and the outlet hole 13 are sealed to one end of the pipe 40, while the other end of the pipe 40 is used to connect to the peristaltic pump 50. The peristaltic pump 50 can pump liquid (reaction liquid). One pipe 40 is used to input liquid into the chip reaction pool 11, and the other pipe is used to discharge liquid from the inside of the chip reaction pool 11 to the outside, realizing the flow and circulation of liquid, so that the liquid flows in the chip reaction pool 11 and increases the uniformity of chip 60 preparation. In this embodiment, the outer shell 10 is rectangular, and a rectangular chip reaction pool 11 is formed inside. Generally, the bottom of the outer shell 11 is set downward and the top is set upward. That is, after the chip holder 20 is placed inside the chip reaction pool 11, its bottom is also set downward and its top is set upward.

[0026] In some embodiments, please refer to Figures 2 to 3 The chip holder 20 has a bottom and a top. Chip fixing slots 21 are located at the top of the chip holder 20 and extend inwards in the depth direction, meaning the depth direction of the chip fixing slots 21 is downwards. The bottom of the chip holder 20 is close to the bottom of the outer casing 10, and the top of the chip holder 20 is close to the top of the outer casing 10. The depth of the chip fixing slot 21 is greater than its length, and it is vertically arranged. The chip 60 is inserted into the chip fixing slot 21 from the top or one side. Multiple chip fixing slots 21 are evenly spaced along the inner side of the long side of the chip holder 20.

[0027] Chip fixing slots 21 are located on the top of the chip holder 20, near both ends. Chip fixing slots 21 are part of the top structure. Since the outer casing 10 is cuboid, the chip holder 20 is also cuboid. In this embodiment, the chip holder 20 can be viewed as having a cuboid recess 22 excavated in the center of its top, with chip fixing slots 21 located on both sides of the recess 22, along the long side of the chip holder 20. The top of the chip fixing slots 21 and the sides near the recess 22 are open, facilitating the placement of the chip 60 inside the chip fixing slots 21.

[0028] Preferably, a drain hole is provided at the bottom of the housing 10. This drain hole is used to drain the liquid inside the housing 10. When the drain hole is not in use, it can be sealed with a plug to prevent the liquid inside the housing 10 from leaking out.

[0029] In this embodiment, the four corners of the outer shell 10 and the upper cover 30 are all rounded.

[0030] To achieve the fabrication of medium-batch stationary phase chips 60 to meet usage requirements, please refer to some embodiments. Figures 2 to 3The chip holder 20 has a row of chip fixing slots 21 arranged near its opposite ends on its top. Each row of chip fixing slots 21 includes multiple chip fixing slots 21 arranged at equal intervals. In this embodiment, two rows of chip fixing slots 21 are arranged at intervals. The width of the chip fixing slots 21 is matched with the chip 60, so that the chip 60 can be inserted into the chip fixing slot 21. After multiple chips 60 are installed into multiple chip fixing slots 21 one by one, the multiple chips 60 are arranged in rows. In actual use, multiple chips 60 can be filled, or an appropriate number of chips 60 can be installed according to the actual situation.

[0031] The number of chip fixed slots 21 in each column is 20, that is, there are 20 chip fixed slots 21 in total, and a total of 40 chip fixed slots 21 in the two columns.

[0032] To ensure the flow of the reaction solution within the chip reaction cell 11, in some embodiments, please refer to... Figures 2 to 3 A perforated hole 23 is provided between the two rows of chip fixing slots 21, penetrating the top and bottom of the chip fixing frame 20. Specifically, there are multiple perforated holes 23 arranged in a matrix, covering the area between the two rows of chip fixing slots 21. The function of the perforated holes 23 is to allow liquids (such as modification liquids or reaction liquids) flowing through the inside of the outer shell 10 to pass through the chip fixing frame 20, enabling the liquid to quickly contact the chip 60 and accelerating the dispersion and diffusion of the solution.

[0033] Specifically, the perforation 23 is circular and extends through the top and bottom of the chip holder 20, that is, it is set vertically through the chip holder 20, so that liquid can flow through multiple perforations 23. In this embodiment, the inner diameter of the perforation 23 is larger than the width of the chip fixing slot 21.

[0034] After the chip 60 is inserted into the chip fixing slot 21, the upper end of the chip 60 can be exposed at the top of the chip fixing slot 21, which makes it convenient to put the chip 60 in and take it out.

[0035] The chip 60 has a rectangular plate structure and is usually set vertically inside the chip fixing slot 21. That is, the long side of the chip 60 is set along the height direction of the chip fixing frame 2, and the short side is set along the width direction of the chip fixing frame 2.

[0036] In some embodiments, please refer to Figures 2 to 3The chip holder 20 has multiple support pillars 24 at its bottom, suitable for supporting the chip holder 20. The top of the support pillar 24 is connected to the bottom of the chip holder 20, and the bottom of the support pillar 24 is used to contact the inner bottom wall of the housing 10. The support pillars 24 are used to create a gap between the chip holder 20 and the inner bottom wall of the housing 10. There are four support pillars 24, which are set at the four corners of the bottom of the chip holder 20, and they play a supporting role for the chip holder 20, preventing the bottom of the chip holder 20 from contacting the bottom of the housing 10. This design facilitates the flow of liquid in the chip reaction pool 11.

[0037] To enable the placement and removal of the chip holder 2, in some embodiments, please refer to... Figures 2 to 3 The chip holder 20 is connected to a lifting lug 25 at its top corner. The lifting lug 25 is used to lift the chip holder 20. Since the chip holder 20 is rectangular, there are four lifting lugs 25, which are respectively set at the four corners of the top of the chip holder 20. There is an ear hole in the middle of the lifting lug 25, which makes it easy for the staff to use tweezers or hooks to remove the chip holder 20, that is, to take the chip holder 20 out of the chip reaction pool 11, so as to prevent the repair solution from being contaminated.

[0038] Specifically, the lug 25 is a rectangular plate that is set vertically, with its long side along the height direction of the chip holder 20. Its bottom end is fixedly connected to the upper end of the chip holder 20, or the chip holder 20 can be connected as a whole. The ear hole is set near the upper end of the lug 25 to facilitate the use of tools to clamp or insert into the ear hole, so as to realize the actions of picking up and putting down the chip holder 20.

[0039] In some embodiments, the outer shell 10 and the upper cover 30 are sealed together by fasteners. The number of fasteners is not limited. Specifically, a screw hole or blind hole may be provided on the top of the outer shell 10, and a screw or bolt may be screwed onto the upper cover 30. The screw or bolt is aligned with the screw hole or blind hole. By turning the screw or bolt, it can be screwed into the screw hole or blind hole, thereby achieving a tight connection between the upper cover 30 and the outer shell 10.

[0040] The fasteners mentioned above can be screws or bolts, or other fasteners, to achieve a sealed connection between the top cover 30 and the outer shell 10, prevent the solvent in the modification liquid from evaporating, and make the chip 60 manufacturing process more stable.

[0041] Preferably, a sealing gasket (not shown in the figure) can be provided between the top cover 30 and the outer shell 10. The sealing gasket is rectangular and can seal the gap or slit between the top cover 30 and the outer shell 10, so that a closed space is formed inside the outer shell 10.

[0042] In some embodiments, please refer to Figure 4The outer shell 10 includes a sheath 14 and an inner liner 15 fitted inside the sheath 14. A chip holder 20 is placed inside the inner liner 15. The sheath 14 is made of stainless steel, while the inner liner 15 and the chip holder 20 are both made of polytetrafluoroethylene (PTFE). When the chip reaction cell 11 needs to be heated, heat can be quickly transferred through the outer sheath 14 to the inner liner 15, thus heating the chip reaction cell 11. In this embodiment, the chip reaction cell 11 is formed inside the inner liner 15. The inner liner 15 and the sheath 14 have the same structure, are in contact with each other, and are fitted together, enabling heat transfer.

[0043] In this embodiment, a protective sleeve 14 is provided on the outer wall of the inner liner 15, which also provides the inner liner 15 with a certain explosion-proof performance. It can be regarded as the protective sleeve 14 wrapping around the inner liner 15.

[0044] In some embodiments, the top cover 30 is made of stainless steel, which enables heat transfer, and the length and width dimensions of the top cover 30 match the length and width dimensions of the outer shell 10.

[0045] To achieve a sealed connection between the top cover 30 and the outer casing 10 and to improve the sealing performance after the connection, in some embodiments, please refer to... Figures 4 to 5 The top of the outer shell 10 is provided with a groove 16, and the bottom of the upper cover 30 is provided with a protrusion 31. The protrusion 31 and the groove 16 are connected to each other. Both the protrusion 31 and the groove 16 are elongated strips, forming a rectangle, and are provided along the edge of the outer shell 10 or the upper cover 30. They can be fitted together to form a better seal between the outer shell 10 and the upper cover 30.

[0046] This invention can produce 40 chips at a time, with 20 fixed slots per row of chips. Compared with the prior art, the chip production output can be increased by 3 times, and the output can be further increased by recycling, thus saving manufacturing costs.

[0047] The above description is only a preferred embodiment of the present utility model and is not intended to limit the present utility model. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present utility model should be included within the protection scope of the present utility model.

Claims

1. An apparatus for preparing a stationary phase chip for enzymatic gene synthesis, characterized in that, include: The outer casing has an open top and forms a chip reaction pool inside. The side of the outer casing has a liquid inlet and a liquid outlet. The liquid inlet and the liquid outlet are respectively used to connect to a peristaltic pump through a pipe. The peristaltic pump is used to push the reaction liquid through the chip reaction pool and form a circulating flow. A chip holder is placed inside the chip reaction pool of the housing, and the chip holder has multiple chip fixing slots suitable for accommodating multiple phase chips; The top cover is sealed to the top of the housing and is adapted to seal the top opening so that the chip reaction cell forms a closed space.

2. The apparatus for preparing a stationary phase chip for enzymatic gene synthesis as described in claim 1, characterized in that, The chip holder has a bottom and a top. The chip fixing slot is located at the top of the chip holder and extends into the chip holder in the depth direction. The bottom of the chip holder is close to the bottom of the housing, and the top of the chip holder is close to the top of the housing.

3. The apparatus for preparing a stationary phase chip for enzymatic gene synthesis as described in claim 2, characterized in that, The chip mounting bracket has a row of chip mounting slots arranged near its opposite ends on the top, and each row of chip mounting slots includes multiple chip mounting slots arranged at equal intervals.

4. The apparatus for preparing a stationary phase chip for enzymatic gene synthesis as described in claim 3, characterized in that, A perforated hole is provided between the two rows of chip fixing slots, penetrating the top and bottom of the chip fixing frame.

5. The apparatus for preparing a stationary phase chip for enzymatic gene synthesis as described in any one of claims 2-4, characterized in that, The bottom of the chip holder is provided with a plurality of pillars suitable for supporting the chip holder. The top of the pillar is connected to the bottom of the chip holder, and the bottom of the pillar is used to contact the inner bottom wall of the housing. The pillar is used to create a gap between the chip holder and the inner bottom wall of the housing.

6. The apparatus for preparing a stationary phase chip for enzymatic gene synthesis as described in any one of claims 1-4, characterized in that, The chip holder is equipped with a lifting lug at the top corner, which is used to lift the chip holder.

7. The apparatus for preparing a stationary phase chip for enzymatic gene synthesis as described in any one of claims 1-4, characterized in that, The outer shell and the upper cover are sealed together by fasteners.

8. The apparatus for preparing a stationary phase chip for enzymatic gene synthesis as described in any one of claims 1-4, characterized in that, The outer shell includes a sheath and an inner liner fitted inside the sheath. The chip holder is placed inside the inner liner. The sheath is made of stainless steel, and the inner liner and the chip holder are both made of polytetrafluoroethylene.

9. The apparatus for preparing a stationary phase chip for enzymatic gene synthesis as described in any one of claims 1-4, characterized in that, The top cover is made of stainless steel.

10. The apparatus for preparing a stationary phase chip for enzymatic gene synthesis as described in any one of claims 1-4, characterized in that, The top of the outer shell is provided with a groove, and the bottom of the upper cover is provided with a protrusion, which cooperates with the groove.

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