Chip holder for oligonucleotide synthesis

Abstract

The utility model provides a chip support for oligonucleotide synthesis, which comprises a bearing platform, a supporting frame is arranged on the bearing platform, the supporting frame is used for supporting a chip, the bearing platform is also provided with a reagent recovery hole in the supporting frame, and the reagent recovery hole is connected with a first negative pressure pump; and the bearing platform is configured to enable the reaction reagent to flow through the hole in the chip from top to bottom under suction when the first negative pressure pump generates negative pressure. The utility model has the beneficial effects that the reagent recovery hole is matched with the first negative pressure pump to generate negative pressure, so that the reaction reagent passes through the hole on the chip in a flowing manner from top to bottom under the suction force.

Description

Technical Field

[0001] The utility model relates to the technical field of chemical synthesis equipment, in particular to a chip bracket for oligonucleotide synthesis. Background Art

[0002] High-throughput inkjet synthesizers utilize semiconductor chip technology and inkjet printing techniques to synthesize oligonucleotides, revolutionizing traditional oligonucleotide synthesis methods and significantly improving synthesis efficiency and throughput. The chip holder is a core module in high-throughput inkjet synthesizers, and different synthesizers utilize different chip holders in terms of structure and function.

[0003] For example, U.S. Patent Publication No. US10773232B2 discloses a de novo gene library synthesis method. The chip holder used in this patent also serves as a reaction chamber. A lid is placed on the chip supported by the lower chip holder to form a closed area, allowing the upper and lower surfaces of the chip (wafer) to be immersed in reagents to achieve chemical reactions. This design uses the capillary and osmotic principles of liquids to complete the synthesis reaction of oligonucleotides within the chip wells (pore diameter or microstructure gap 5-80μm). However, a disadvantage of this patent is that the reagents are in a static state during the synthesis reaction, and all reaction wells share a pool of reagents. This may cause unreacted monomers dissolved in the wells to flow into other wells to form heterochains, causing liquid contamination, which can reduce the purity of the final product and affect the synthesis quality.

[0004] Therefore, it is necessary to study a chip support for oligonucleotide synthesis to solve the above problems or alleviate the impact of the above problems. Utility Model Content

[0005] The utility model provides a chip holder for oligonucleotide synthesis, which generates negative pressure through a reagent recovery hole in cooperation with a first negative pressure pump, so that the reaction reagent flows from top to bottom through the holes on the chip under suction, thereby effectively solving the above-mentioned problems or alleviating the effects of the above-mentioned problems.

[0006] The chip holder for oligonucleotide synthesis of the present invention may include a carrier platform, a support frame is provided on the carrier platform, the support frame is used to support the chip, and a reagent recovery hole is further provided in the support frame on the carrier platform, and the reagent recovery hole is connected to the first negative pressure pump;

[0007] The supporting platform is constructed so that when the first negative pressure pump generates negative pressure, the reaction reagent flows from top to bottom through the holes on the chip under suction.

[0008] In one embodiment, the reagent recovery hole is connected to the first negative pressure pump through a reagent recovery tube, and a first mounting hole for mounting the reagent recovery tube is opened on one side of the supporting platform, and the first mounting hole is connected to the reagent recovery hole.

[0009] In one embodiment, the carrier platform is provided with a plurality of drainage columns evenly distributed in the support frame, and the drainage columns can guide the reaction reagents passing through the chip to flow to the reagent recovery hole.

[0010] In one embodiment, the support frame includes a first support frame and a second support frame, the first support frame is located in the second support frame, and an edge groove is formed between the first support frame and the second support frame.

[0011] In one embodiment, the supporting platform is provided with a vacuum pumping hole at the bottom of the edge groove, and the vacuum pumping hole is connected to a second negative pressure pump;

[0012] The supporting platform is constructed so that when the second negative pressure pump generates negative pressure, a vacuum environment is formed between the edge groove and the chip, so as to fix the chip.

[0013] In one embodiment, the vacuum exhaust hole is connected to the second negative pressure pump through a vacuum adsorption tube, and a second mounting hole for mounting the vacuum adsorption tube is provided on one side of the supporting platform, and the second mounting hole is connected to the vacuum exhaust hole.

[0014] In one embodiment, the chip holder further includes a washing liquid base, which is disposed around the outer side of the carrying platform, and a washing liquid tank is formed between the carrying platform and the side wall of the washing liquid base.

[0015] In one embodiment, a waste liquid recovery interface corresponding to the bottom of the washing liquid tank is opened on the side wall of the washing liquid base, and the waste liquid recovery interface is connected to the waste liquid bottle through a waste liquid recovery pipe.

[0016] In one embodiment, the bottom of the washing liquid tank is a slope, and the slope is inclined downward toward the waste liquid recovery interface.

[0017] In one embodiment, the side wall of the washing liquid base is also provided with a reagent recovery interface corresponding to the first mounting hole and a vacuum adsorption interface corresponding to the second mounting hole. The reagent recovery interface is used to match the installation of the reagent recovery tube, and the vacuum adsorption interface is used to match the installation of the vacuum adsorption tube.

[0018] The chip holder for oligonucleotide synthesis provided by the present invention has at least the following beneficial effects compared with the prior art:

[0019] The present invention's chip holder for oligonucleotide synthesis uses a support frame to support the mounted chip. A first negative pressure pump generates negative pressure through reagent recovery holes, causing the reaction reagents to flow downward through the holes on the chip under suction. This allows the reaction reagents to flow through the holes on the chip, maintaining a state of fluid renewal during the reaction process. Compared to existing methods of allowing reagents to sit in a static state, this method improves reaction efficiency and effectively prevents contamination from liquid crosstalk in the static reagents, improving the purity of the final product and ensuring synthesis quality. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] The present invention will be described in more detail below based on embodiments with reference to the accompanying drawings.

[0021] Figure 1 This is a schematic diagram of the three-dimensional structure of the chip holder according to an embodiment of the present invention;

[0022] Figure 2 This is a top view of the chip holder according to an embodiment of the present invention;

[0023] Figure 3 This is a side view of the chip holder according to an embodiment of the present invention;

[0024] Figure 4 yes Figure 1 A schematic diagram of the structure is enlarged in part I;

[0025] Figure 5 yes Figure 3 A cross-sectional view of AA;

[0026] Figure 6 yes Figure 3 A cross-sectional view of the middle BB;

[0027] Figure 7 It is a structural schematic diagram of the connection between the chip holder and the negative pressure pump in an embodiment of the utility model.

[0028] In the drawings, like parts are given like reference numerals, but the drawings are not necessarily drawn to scale.

[0029] Reference numerals:

[0030] 1-carrying platform, 2-support frame, 3-reagent recovery hole, 4-first mounting hole, 5-reagent recovery tube, 6-first negative pressure pump, 7-first waste liquid bottle, 8-drainage column, 9-first support frame, 10-second support frame, 11-edge groove, 12-edge protrusion, 13-positioning groove, 14-vacuum exhaust hole, 15-second mounting hole, 16-vacuum adsorption tube, 17-second negative pressure pump, 18-second waste liquid bottle, 19-washing liquid base, 20-washing liquid trough, 21-waste liquid recovery interface, 22-reagent recovery interface, 23-vacuum adsorption interface, 24-fixing column, 25-screw hole, 26-two-position three-way solenoid valve, 27-waste liquid recovery tube. DETAILED DESCRIPTION

[0031] The present invention will be further described below with reference to the accompanying drawings.

[0032] like Figures 1 to 7 As shown, the chip holder for oligonucleotide synthesis of the present invention may include a carrier 1, a support frame 2 is provided on the carrier 1, the support frame 2 is used to support the chip, and the carrier 1 is further provided with a reagent recovery hole 3 in the support frame 2, and the reagent recovery hole 3 is connected to a first negative pressure pump 6;

[0033] The carrier platform 1 is constructed so that when the first negative pressure pump 6 generates negative pressure, the reaction reagent flows from top to bottom through the holes on the chip under suction.

[0034] Specifically, the carrier platform 1 serves as the core part of the entire chip holder. The support frame 2 is fixedly arranged on the carrier platform 1. The support frame 2 matches the chip. Its shape and size can be designed according to the specific specifications of the chip to ensure that the chip can be firmly placed on the support frame 2, while facilitating the rapid installation and removal of the chip. On the carrier platform 1, located in the internal area of the support frame 2, a reagent recovery hole 3 is provided. The reagent recovery hole 3 can ensure that under the action of negative pressure, the reaction reagent can be sucked in and collected, and the reagent recovery hole 3 is connected to a first negative pressure pump 6 through a pipeline. The first negative pressure pump 6 is responsible for generating a stable negative pressure environment during the synthesis process.

[0035] In the specific oligonucleotide synthesis process, the chip is first placed on the support frame 2 and confirmed to be stable and correct. The first negative pressure pump 6 is started to generate a negative pressure environment. Under the action of negative pressure, the reaction reagents are accurately guided to each hole on the chip, and a specific reaction occurs in the hole. After the reaction is completed, the remaining reagents and possible by-products can be driven by negative pressure to quickly flow through the holes on the chip into the reagent recovery hole 3 on the carrier 1, and finally be extracted and collected by the first negative pressure pump 6.

[0036] Overall, the chip holder for oligonucleotide synthesis of the present invention supports the mounting of the chip via a support frame 2, and then generates negative pressure through the reagent recovery hole 3 in conjunction with the first negative pressure pump 6, so that the reaction reagents are sucked from top to bottom in a flowing manner through the holes on the chip. In this way, the reaction reagents flow through the holes on the chip and are in a state of flow renewal during the reaction process, ensuring the uniformity and consistency of the reaction process. Compared with existing static reagents, the reaction efficiency is higher, and it can effectively avoid liquid contamination in the static reagents, improve the purity of the final product, and ensure the quality of the synthesis.

[0037] It should be noted that there can be multiple reagent recovery holes 3, and multiple reagent recovery holes 3 can be evenly distributed on the carrier 1. The number, size and position of the reagent recovery holes 3 can be optimized according to the layout of the holes on the chip and the flow characteristics of the reaction reagents.

[0038] Furthermore, the number of the reagent recovery hole 3 can be one, and it is arranged in the middle of the supporting platform 1.

[0039] In one example, the reagent recovery hole 3 is connected to the first negative pressure pump 6 through the reagent recovery tube 5 , and a first mounting hole 4 for mounting the reagent recovery tube 5 is provided on one side of the supporting platform 1 , and the first mounting hole 4 is connected to the reagent recovery hole 3 .

[0040] Specifically, if Figure 5 As shown, the reagent recovery hole 3 is a vertically arranged L-shaped structure, the first mounting hole 4 is a horizontally arranged mounting hole, the reagent recovery tube 5 is inserted into the first mounting hole 4, and the first mounting hole 4 is connected to the reagent recovery hole 3, that is, the reagent recovery tube 5 is connected to the reagent recovery hole 3, and then connected to the first negative pressure pump 6 through the reagent recovery tube 5, thereby realizing the connection between the reagent recovery hole 3 and the first negative pressure pump 6. It should be noted that when there are multiple reagent recovery holes 3, the lower ends of the multiple reagent recovery holes 3 are connected to the first mounting hole 4 after being gathered inside the carrier 1.

[0041] Furthermore, the inner diameter of the first mounting hole 4 is larger than the inner diameter of the reagent recovery hole 3, and a limiting portion is formed at the connection between the first mounting hole 4 and the reagent recovery hole 3, so that the reagent recovery tube 5 can be installed in a limited position when inserted into the first mounting hole 4.

[0042] Furthermore, a first waste liquid bottle 7 may be provided on the reagent recovery pipe 5 between the first negative pressure pump 6 and the reagent recovery hole 3. The reaction reagent passes through the reagent recovery hole 3 and then flows into the first waste liquid bottle 7 through the reagent recovery pipe 5 for collection.

[0043] In one example, Figure 1 、 Figure 2 and Figure 4As shown, the carrier platform 1 is provided with a plurality of drainage columns 8 evenly distributed in the support frame 2 , and the drainage columns 8 can guide the reaction reagents after passing through the chip to flow to the reagent recovery hole 3 .

[0044] Specifically, after the reaction reagents flow from top to bottom through the holes on the chip, they tend to accumulate as larger droplets on the lower side of the chip, causing cross-contamination. However, after the drainage posts 8 are provided, the reaction reagents, after passing through the holes on the chip, come into contact with the drainage posts 8 and flow downstream to the reagent recovery holes 3, effectively preventing them from accumulating on the lower side of the chip. The number and size of the drainage posts 8 can be set accordingly according to the holes on the chip.

[0045] Furthermore, the drainage column 8 can be a vertically erected cylinder with a diameter in the range of 0.5 to 1 mm, and its top surface is lower than the mounting plane of the support frame 2. In this way, the top surface of the drainage column 8 is small, which facilitates the downward drainage of the reaction reagents without hindering the installation of the chip.

[0046] In one example, Figure 2 As shown, the support frame 2 includes a first support frame 9 and a second support frame 10 . The first support frame 9 is located inside the second support frame 10 , and an edge groove 11 is formed between the first support frame 9 and the second support frame 10 .

[0047] Specifically, the first support frame 9 and the second support frame 10 form an internal and external fit to achieve stable support for the chip and prevent the middle part of the chip from being depressed by force; and a side groove 11 is formed between the first support frame 9 and the second support frame 10. The side groove 11 and the chip installed on the support frame 2 form a closed space, and then cooperate with the vacuum exhaust hole 14 to form a vacuum environment, so that the chip is subjected to a pressure difference between the positive pressure above and the negative pressure below, so as to be fixed on the support frame 2.

[0048] Furthermore, the carrier platform 1 is designed with edge protrusions 12 around the edge of the second support frame 10 to limit the horizontal installation position of the chip, increase the accuracy and stability of chip placement, and positioning grooves 13 are provided at the corners of the edge protrusions 12 to facilitate the removal and placement of the chip.

[0049] In one example, the carrier platform 1 is provided with a vacuum pumping hole 14 at the bottom of the edge groove 11 , and the vacuum pumping hole 14 is connected to the second negative pressure pump 17 ;

[0050] The carrier platform 1 is constructed so that when the second negative pressure pump 17 generates negative pressure, a vacuum environment is formed between the edge groove 11 and the chip, so as to fix the chip.

[0051] Specifically, on the supporting platform 1, a vacuum exhaust hole 14 is opened at the bottom of the edge groove 11. The vacuum exhaust hole 14 is connected to the second negative pressure pump 17 through a pipeline. The second negative pressure pump 17 is responsible for sucking the space surrounded by the edge groove 11 and the chip into a vacuum environment, so that the chip can be stably fixed on the support frame 2 due to the pressure difference formed by the positive pressure above and the negative pressure below.

[0052] In one example, Figure 6 As shown, the vacuum exhaust hole 14 is connected to the second negative pressure pump 17 through the vacuum adsorption tube 16 , and a second mounting hole 15 for mounting the vacuum adsorption tube 16 is opened on one side of the supporting platform 1 , and the second mounting hole 15 is connected to the vacuum exhaust hole 14 .

[0053] Specifically, the vacuum exhaust hole 14 is a vertically arranged L-shaped structure, the second mounting hole 15 is a horizontally arranged mounting hole, the vacuum adsorption tube 16 is inserted into the second mounting hole 15, and the second mounting hole 15 is connected to the vacuum exhaust hole 14, that is, the vacuum adsorption tube 16 is connected to the vacuum exhaust hole 14, and then connected to the second negative pressure pump 17 through the vacuum adsorption tube 16, thereby realizing the connection between the vacuum exhaust hole 14 and the second negative pressure pump 17.

[0054] It should be noted that there may be multiple vacuum exhaust holes 14 , and the lower ends of the multiple vacuum exhaust holes 14 are connected to the second mounting hole 15 after being collected inside the supporting platform 1 .

[0055] Furthermore, the inner diameter of the second mounting hole 15 is larger than the inner diameter of the vacuum exhaust hole 14 , and a limiting portion is formed at the connection between the second mounting hole 15 and the vacuum exhaust hole 14 so that the vacuum adsorption tube 16 can be installed in a limited position when inserted into the second mounting hole 15 .

[0056] Furthermore, a second waste liquid bottle 18 can be provided on the vacuum adsorption tube 16 between the second negative pressure pump 17 and the vacuum exhaust hole 14, so that when the chip holder is cleaned, the waste liquid used for cleaning can pass through the vacuum exhaust hole 14 and then flow into the second waste liquid bottle 18 through the vacuum adsorption tube 16 for waste liquid collection.

[0057] In one example, the chip holder further includes a washing liquid base 19 , which is disposed around the outer side of the carrier 1 , and a washing liquid tank 20 is formed between the side walls of the carrier 1 and the washing liquid base 19 .

[0058] Specifically, the wash base 19 has a groove structure, and the carrier 1 is fixedly mounted in the middle of the wash base 19. The sidewalls of the wash base 19 surround the carrier 1 and form a wash tank 20. This prevents the reaction reagents used in the synthesis process from overflowing the carrier 1, while facilitating the cleaning of the carrier 1 and allowing the waste liquid after cleaning to be collected through the wash tank 20.

[0059] In one example, Figures 1 to 3 As shown, a waste liquid recovery port 21 is provided on the side wall of the washing liquid base 19 corresponding to the bottom of the washing liquid tank 20. The waste liquid recovery port 21 is connected to the waste liquid bottle via a waste liquid recovery pipe 27. The arrangement of the waste liquid recovery port 21 facilitates the installation of the waste liquid recovery pipe 27, so that the waste liquid from the washing can be collected by connecting the waste liquid recovery pipe 27 to the waste liquid bottle.

[0060] Furthermore, if Figure 5 and Figure 6 As shown, the bottom of the washing liquid tank 20 is an inclined surface, which is inclined downwardly towards the waste liquid recovery interface 21. This is convenient for waste liquid to gather towards the waste liquid recovery interface 21 under the effect of gravity, and then to be convenient to be passed into the waste liquid bottle by the waste liquid recovery pipe 27.

[0061] It should be noted that the waste liquid recovery pipe 27 can also be connected to a negative pressure pump after the waste liquid bottle to form a negative pressure to suck the waste liquid in the washing liquid tank 20. Figure 7 As shown, the waste liquid recovery pipe 27 can also share a set of waste liquid bottles and negative pressure pumps with the reagent recovery pipe 5, namely the first waste liquid bottle 7 and the first negative pressure pump 6. A two-position three-way solenoid valve 26 is provided on the waste liquid recovery pipe 27 and the reagent recovery pipe 5, and the waste liquid recovery pipe 27 and the reagent recovery pipe 5 are respectively connected to the two inlets of the two-position three-way solenoid valve 26, and the outlet of the two-position three-way solenoid valve 26 is connected to the first waste liquid bottle 7 and the first negative pressure pump 6. In this way, the two-position three-way solenoid valve 26 switches to the waste liquid recovery pipe 27 when discharging waste liquid, and switches to the reagent recovery pipe 5 when reacting. After switching, the other way is closed, thereby ensuring that the synthesis operation and the cleaning operation can be carried out accordingly.

[0062] In one example, Figure 1 and Figure 3 As shown, the side wall of the washing liquid base 19 is also provided with a reagent recovery interface 22 corresponding to the first mounting hole 4 and a vacuum adsorption interface 23 corresponding to the second mounting hole 15. The reagent recovery interface 22 is used to match the installation of the reagent recovery tube 5, and the vacuum adsorption interface 23 is used to match the installation of the vacuum adsorption tube 16.

[0063] Specifically, the reagent recovery tube 5 is installed in the reagent recovery interface 22 and the first mounting hole 4 by an interference fit, and the vacuum adsorption tube 16 is also installed in the vacuum adsorption interface 23 and the second mounting hole 15 by an interference fit. This can save installation space and ensure the stability of the connection between the reagent recovery tube 5 and the vacuum adsorption tube 16.

[0064] In one example, the washing liquid base 19 is further provided with a plurality of evenly distributed fixing posts 24 in the washing liquid tank 20, and vertically extending screw holes 25 are provided in the fixing posts 24. In this way, the washing liquid base 19 can be fixedly connected to the workbench by passing bolts through the fixing posts 24 and engaging with the screw holes 25.

[0065] While the present invention has been described with reference to preferred embodiments, various modifications may be made and equivalent components may be substituted without departing from the scope of the present invention. In particular, the various technical features described in the various embodiments may be combined in any manner, provided no structural conflicts exist. The present invention is not limited to the specific embodiments disclosed herein, but encompasses all technical solutions within the scope of the claims.

Claims

1. A chip holder for oligonucleotide synthesis, characterized in that: The chip holder includes a carrier platform, a support frame is provided on the carrier platform, the support frame is used to support the chip, and a reagent recovery hole is opened in the support frame of the carrier platform, and the reagent recovery hole is connected to the first negative pressure pump; The supporting platform is constructed so that when the first negative pressure pump generates negative pressure, the reaction reagent flows from top to bottom through the holes on the chip under suction.

2. The chip holder for oligonucleotide synthesis according to claim 1, characterized in that The reagent recovery hole is connected to the first negative pressure pump through a reagent recovery tube. A first mounting hole for mounting the reagent recovery tube is provided on one side of the supporting platform. The first mounting hole is communicated with the reagent recovery hole.

3. The chip holder for oligonucleotide synthesis according to claim 1, characterized in that The carrier platform is provided with a plurality of drainage columns evenly distributed in the support frame, and the drainage columns can guide the reaction reagents after passing through the chip to flow to the reagent recovery hole.

4. The chip holder for oligonucleotide synthesis according to claim 1, characterized in that The support frame includes a first support frame and a second support frame. The first support frame is located in the second support frame, and an edge groove is formed between the first support frame and the second support frame.

5. The chip holder for oligonucleotide synthesis according to claim 4, characterized in that The supporting platform is provided with a vacuum pumping hole at the bottom of the edge groove, and the vacuum pumping hole is connected to the second negative pressure pump; The supporting platform is constructed so that when the second negative pressure pump generates negative pressure, a vacuum environment is formed between the edge groove and the chip, so as to fix the chip.

6. The chip holder for oligonucleotide synthesis according to claim 5, characterized in that The vacuum exhaust hole is connected to the second negative pressure pump through a vacuum adsorption tube. A second mounting hole for mounting the vacuum adsorption tube is provided on one side of the supporting platform. The second mounting hole is connected to the vacuum exhaust hole.

7. The chip holder for oligonucleotide synthesis according to claim 1, characterized in that The chip support further comprises a washing liquid base, which is arranged around the outer side of the carrying platform, and a washing liquid tank is formed between the carrying platform and the side wall of the washing liquid base.

8. The chip holder for oligonucleotide synthesis according to claim 7, characterized in that A waste liquid recovery interface corresponding to the bottom of the washing liquid tank is opened on the side wall of the washing liquid base, and the waste liquid recovery interface is connected to the waste liquid bottle through a waste liquid recovery pipe.

9. The chip holder for oligonucleotide synthesis according to claim 8, characterized in that The bottom of the washing liquid tank is an inclined surface, and the inclined surface is inclined downward toward the waste liquid recovery interface.

10. The chip holder for oligonucleotide synthesis according to claim 7, characterized in that: The side wall of the washing liquid base is also provided with a reagent recovery interface corresponding to the first mounting hole and a vacuum adsorption interface corresponding to the second mounting hole. The reagent recovery interface is used to match the installation of the reagent recovery tube, and the vacuum adsorption interface is used to match the installation of the vacuum adsorption tube.

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