A liquid adding device of a high-throughput gene synthesizer

Abstract

A liquid adding device of a high-throughput gene synthesizer belongs to the field of DNA recombination technology, comprising a mounting plate, wherein a mounting area is arranged on the mounting plate, and a liquid adding assembly is arranged in the mounting area; the liquid adding assembly comprises a liquid adding base, a liquid adding piece is inserted and mounted on the liquid adding base, a liquid outlet of the liquid adding piece is provided with a liquid outlet piece for controlling the liquid outlet amount, and the liquid adding pieces are arranged in an array on the liquid adding base; the liquid adding assembly is combined in an array mode to be suitable for various scene requirements, and the time for liquid adding is significantly shortened on the premise of arranging multiple liquid adding assemblies, so that the synthesis efficiency is improved.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of DNA recombination technology, and particularly relates to a liquid adding device of a high-throughput gene synthesizer. BACKGROUND

[0002] At present, artificially synthesized DNA is the only way to know the directional modification of gene sequences, and is widely applied to multiple fields such as protein modification and life science, nucleic acid drugs, enzyme engineering, gene detection, gene therapy and the like.

[0003] Most of the DNA synthesizers on the market at present adopt the phosphite amide chemical synthesis method to synthesize DNA, and four steps of deprotection, activation coupling, capping and oxidation are performed, and different chemical reagents need to be used in each step. The deprotection reagent is mainly trichloroacetic acid solution (TCA), the four monomer reagents are T, G, C and A, the activation reagent is ACT, the capping reagents are CAPA and CAPB, the oxidation reagent is mainly iodine solution (Ox), and the cleaning reagent is mainly acetonitrile solution (ACN). The traditional multi-well synthesis plate is usually 8x12 wells (96 flux) or 16x24 wells (384 flux), and in the synthesis process, after the synthesis carrier (usually CPG column) is preloaded in each well of each synthesis plate, the synthesis plate is placed in the instrument to start synthesis; the corresponding reagent needs to be added to each well to ensure that the reagent and the carrier in each synthesis well of the synthesis plate fully react. For the 96 flux or 384 flux synthesizer, multiple liquid adding nozzles are used to simultaneously add liquid to a row of wells, and for most synthesizers, each reagent is divided into 8 or 16 liquid adding nozzles for liquid adding, the distance between the nozzles is 9 mm, and the liquid adding frequency is 12 times or 48 times, which can meet the demand.

[0004] However, for the 1536 flux synthesizer, the synthesis plate has 32x48 wells, and the distance between the wells is 2.25 mm. If each reagent still uses a 9 mm interval nozzle for liquid adding, the liquid adding module needs to run back and forth a total of four times to add reagents to the 1536 wells, which will cause problems such as too long liquid adding time and low synthesis efficiency. Therefore, for high-throughput synthesizers, a high-density liquid adding nozzle is urgently needed to solve this problem. SUMMARY

[0005] The purpose of the present application is to provide a liquid adding device of a high-throughput gene synthesizer to solve the problems raised in the background art.

[0006] To achieve the above purpose, the present application provides the following technical scheme:

[0007] The application discloses a liquid adding device of a high-throughput gene synthesizer.

[0008] Compared with the prior art, the technical scheme has the following effects:

[0009] The arrayed liquid adding assembly is combined in multiple specifications to be applicable to various scene requirements, and the liquid adding time is significantly shortened on the premise of arranging multiple liquid adding assemblies, so that the synthesis efficiency is improved.

[0010] Preferably, the liquid adding piece is a liquid adding pipe.

[0011] Preferably, the liquid outlet piece is a steel needle.

[0012] Preferably, the liquid outlet end of the steel needle is subjected to hole expansion treatment, and an outer wall surface of the steel needle is coated with a Teflon coating.

[0013] Preferably, the liquid adding base is detachably connected with a clamping block through bolts, the clamping block is internally hollow and provided with a premixing cavity, two liquid adding pipes are interference-fitted on the clamping block, the liquid outlet ends of the two liquid adding pipes and the bottom end surface of the premixing cavity have a gap, the liquid inlet end of the liquid outlet piece is inserted into the clamping block, and the liquid inlet end of the liquid outlet piece is flush with the bottom end surface of the premixing cavity.

[0014] Preferably, a plurality of liquid adding pipes are arrayed and inserted into the liquid adding base, and the liquid outlet ends of the liquid adding pipes are all inserted with steel needles. DETAILED DESCRIPTION

[0015] Figure 1 is a schematic diagram of the overall structure of the application;

[0016] Figure 2 is a schematic diagram of the overall structure of the first liquid adding assembly in the application;

[0017] Figure 3 is an enlarged schematic diagram of the partial cross-sectional structure of the first liquid adding assembly in the application;

[0018] Figure 4 is a first schematic diagram of the overall structure of the second liquid adding assembly in the application;

[0019] Figure 5 is a second schematic diagram of the overall structure of the second liquid adding assembly in the application;

[0020] Figure 6 is a schematic diagram of the cross-sectional structure of the second liquid adding assembly in the application. Detailed Implementation

[0021] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0022] Example:

[0023] like Figures 1-6 The liquid addition device of a high-throughput gene synthesizer shown includes a mounting plate 1, on which a mounting area 10 is provided. The mounting area 10 is arrayed with liquid addition components. By increasing the density of the liquid addition components, the liquid addition time is significantly shortened and the synthesis efficiency is improved. The liquid addition components include a liquid addition base, on which liquid addition elements are arrayed. The liquid addition elements have a liquid outlet end for controlling the liquid output. More specifically, in this embodiment, the liquid addition element and the liquid outlet are a liquid addition tube and a steel needle, respectively. Compared with existing liquid addition devices, in this embodiment, the liquid addition components are provided in two types.

[0024] To better understand the structure of the liquid addition assembly in this embodiment, the structures of the two types of liquid addition assemblies in this embodiment will be described in detail below:

[0025] The first type: single-tube liquid addition method, referred to as the first liquid addition mechanism 3 in this embodiment. The first liquid addition mechanism 3 includes a first liquid addition support 30. An installation area 31 is provided on the rod of the first liquid addition support 30. The installation area 31 is arrayed with installation grooves 310, and a first liquid addition tube 33 is inserted into the installation grooves 310. To enhance the stability of the first liquid addition tube 33 during installation, a reinforcing block 35 is fitted onto the tube body of the first liquid addition tube 33 housed within the installation groove 310. Simultaneously, for aesthetic purposes, a cap 32 is bolted to the upper end face of the installation area 31 to conceal the opening of the installation groove 310. Furthermore, the tube body of the first liquid addition tube 33 passes through the cap 32, combined with… Figure 6 It is known that a first steel needle 34 is inserted into the outlet end of the first liquid addition tube 33. The first steel needle 34 is hollow inside and has openings at both ends, which are used to guide the reagent in the first liquid addition tube 33 out.

[0026] The second type is a double-pipe liquid adding mode, referred to as a second liquid adding mechanism 2 in the embodiment, which comprises a second liquid adding support 20, the second liquid adding support 20 is provided with a mounting area 21, a plurality of clamping blocks 22 are arranged in the mounting area 21, the clamping blocks 22 are detachably installed on the mounting area 21 through bolts 220, two plug-in holes are arranged on the clamping blocks 22, and second liquid adding pipes 23 are plugged into the plug-in holes. It should be noted that the mounting area 21 is internally hollow and provided with a premixing cavity, that is, the mounting area 21 corresponding to the downward extension of the clamping block 22 is provided with the premixing cavity. The purpose of this arrangement is that, when multiple reagents are needed, compared with the single-pipe liquid adding mode, multiple liquid injection is needed, but the present mode can realize simultaneous liquid injection, significantly improving the liquid injection time. At the same time, since the multiple reagents can be premixed in the premixing cavity, the coupling between the reagents is improved, and the premixing cavity is provided with a sealing ring to prevent the mixed reagents in the premixing cavity from leaking. The bottom end of the clamping block 22 is plugged into a second steel needle 24, the upper end of the second steel needle 24 extends into the premixing cavity, and the lower end of the second steel needle 24 is expanded and treated to have a bell mouth structure 240.

[0027] In the embodiment, whether the first type or the second type, or even a combination of the two, is used, the purpose of high-throughput and rapid liquid adding is achieved by using an array mode. At the same time, whether the first steel needle 34 or the second steel needle 24, both are made of medical stainless steel, and the liquid outlet ends of both are expanded and treated, and the outer wall is sprayed with a Teflon coating to solve the problem of liquid dripping after liquid adding.

[0028] Secondly, the detachable mode of bolt connection can realize combination according to actual needs, improving the flexibility of the device itself.

[0029] In the description of the present application, it should be understood that the terms "center", "transverse", "upper", "lower", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer" and the like indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and therefore cannot be understood as indicating or implying that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as limiting the present application. In addition, the terms "first", "second" are only for the purpose of description, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the technical features indicated. Therefore, the features limited by "first", "second" can explicitly or implicitly include one or more of the features. In the description of the present application, unless otherwise stated, the meaning of "several" is two or more. In addition, the term "includes" and any variation thereof is intended to cover non-exclusive inclusion.

[0030] The application is illustrated by the examples, and the device can be modified and improved in several ways without departing from the principle thereof. It should be pointed out that any technical solution obtained by using equivalent substitution or equivalent transformation, etc. falls within the protection scope of the application.

Claims

1. A liquid adding device of a high-throughput gene synthesizer, comprising a mounting plate (1), wherein a mounting area (10) is arranged on the mounting plate (1), and characterized in that: Array is provided with liquid adding assembly in the installation area (10); the liquid adding assembly includes liquid adding base, liquid adding piece is inserted and mounted on the liquid adding base, liquid outlet end of the liquid adding piece is provided with liquid outlet piece for controlling liquid outlet amount, and the liquid adding piece array is provided on the liquid adding base; The clamping block (22) is detachably connected to the liquid adding base through the bolt (220), the inside of the liquid adding base in the corresponding position of the clamping block (22) is hollowly provided with premixing cavity, and two liquid adding pipes are interference-fitted on the clamping block (22), and there is gap between the liquid outlet end of the two liquid adding pipes and the bottom end surface of the premixing cavity, the liquid inlet end of the liquid outlet piece is inserted and mounted on the clamping block (22), and the liquid inlet end of the liquid outlet piece is flush with the bottom end surface of the premixing cavity.

2. The liquid adding device of the high-throughput gene synthesizer according to claim 1, characterized in that: The liquid adding piece is liquid adding pipe.

3. The liquid adding device of a high-throughput gene synthesizer according to claim 2, characterized in that: The liquid outlet piece is steel needle.

4. The liquid adding device of the high-throughput gene synthesizer according to claim 3, characterized in that: The liquid outlet end of the steel needle is treated by hole expansion, and the outer wall surface of the steel needle is coated with a layer of Teflon coating.

5. The liquid adding device of a high-throughput gene synthesizer according to claim 3 or 4, characterized in that: Array is inserted and mounted with several liquid adding pipes on the liquid adding base, and the liquid outlet end of the several liquid adding pipes is inserted and mounted with steel needle.

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