阅读说明：本技术 基因测序系统中向基因芯片加载试剂的方法 (Method for loading reagent to gene chip in gene sequencing system ) 是由 不公告发明人 于 2020-06-30 设计创作，主要内容包括：本发明涉及一种基因测序系统中向基因芯片加载试剂的方法。包括,将基因芯片置入盛装有试剂的容器中,且试剂淹没基因芯片,使容器形成负压。本发明通过使容器形成负压,以排出基因芯片的流道内的空气,同时,容器中的试剂在负压的作用下被吸入基因芯片的流道内,实现将试剂均匀并充分地加载至基因芯片的流道内,提高测序结果的准确性。(The invention relates to a method for loading a reagent to a gene chip in a gene sequencing system. Comprises placing the gene chip into a container containing the reagent, and submerging the gene chip with the reagent to make the container form negative pressure. The invention discharges the air in the flow channel of the gene chip by making the container form negative pressure, and simultaneously the reagent in the container is sucked into the flow channel of the gene chip under the action of the negative pressure, thereby realizing that the reagent is uniformly and fully loaded into the flow channel of the gene chip, and improving the accuracy of the sequencing result.)

1. A method for loading a reagent into a gene chip in a gene sequencing system, comprising placing the gene chip into a container containing the reagent, wherein the reagent submerges the gene chip, the method further comprising: the container is brought to a negative pressure.

2. The method for loading a reagent into a gene chip in a gene sequencing system according to claim 1, wherein: the method of creating a negative pressure in the container includes evacuating the container after sealing the container.

3. The method for loading a reagent into a gene chip in a gene sequencing system according to claim 1, wherein: and starting timing after the container forms negative pressure, and inflating the container after the preset time is reached until the air pressure in the container is recovered to the normal pressure.

4. The method for loading a reagent into a gene chip in a gene sequencing system according to claim 3, wherein:

providing a lifting cylinder and a taking and placing part for selectively grabbing or releasing the gene chip, wherein the taking and placing part is fixedly arranged on a piston rod of the lifting cylinder;

the container is provided with a cavity for containing the reagent and an opening part communicated with the cavity for the gene chip to enter and exit the cavity;

the taking and placing part is arranged to seal the mouth part of the container after the taking and placing part is driven to descend by the lifting cylinder;

the taking and placing part is provided with an air exhaust hole and an air charging hole which are both communicated with the containing cavity when the taking and placing part plugs the mouth part of the container;

the air extraction hole is connected with an air extraction device which is used for extracting air in the cavity so as to enable the cavity to form negative pressure;

the inflation hole is connected with an inflation device for inflating air into the cavity.

5. The method for loading reagents into a gene chip in a gene sequencing system according to claim 4, wherein:

the mouth part and the cavity of the container are both in circular hole shapes, the diameter of the mouth part is larger than that of the cavity, and a container step surface is formed at the joint of the mouth part and the cavity;

the taking and placing part comprises an upper column and a lower column which are connected with each other, the upper column and the lower column are both cylindrical, the diameter of the upper column is larger than that of the lower column, and a taking and placing part step surface is formed at the joint of the upper column and the lower column;

the diameter of the lower column is smaller than that of the cavity, and the lower column is inserted into the cavity when the taking and placing part plugs the mouth part of the container;

the diameter of the upper column is larger than that of the cavity and smaller than that of the opening, and the upper column is inserted into the opening when the taking and placing part seals the opening of the container;

an elastic sealing ring is sleeved outside the lower column;

the elastic sealing ring is clamped between the step surface of the container and the step surface of the taking and placing part when the taking and placing part seals the opening part of the container;

the air suction hole and the air inflation hole are both arranged on the end surface of the lower column.

6. The method for loading reagents into a gene chip in a gene sequencing system according to claim 5, wherein: and an air pressure sensor for measuring the air pressure in the cavity is arranged on the end surface of the lower column.

7. The method for loading reagents into a gene chip in a gene sequencing system according to claim 6, wherein:

providing a chip frame, wherein the gene chip is fixedly arranged on the chip frame in a detachable mode;

the top of the chip frame is provided with a top iron body;

the lower column of the taking and placing part is provided with a taking and placing part slot for inserting the top of the chip frame, and the notch of the taking and placing part slot is arranged on the end surface of the lower column;

an electromagnet is arranged in the lower column of the taking and placing part;

the electromagnet attracts a top iron body inserted into the top of the chip frame of the pick-and-place section slot when the electromagnet is powered on.

8. The method for loading reagents into a gene chip in a gene sequencing system according to claim 7, wherein: the gene sequencing system for implementing the method of loading the reagent to the gene chip comprises a guide rail, a sliding seat which can be glidingly arranged on the guide rail and a sliding seat driving mechanism which is arranged between the sliding seat and the guide rail and drives the sliding seat to slide along the guide rail, wherein the cylinder body of the lifting cylinder is fixedly arranged on the sliding seat;

the guide rail, the sliding seat driving mechanism, the lifting cylinder and the taking and placing part form a chip carrying device.

Technical Field

The invention relates to a method for loading a reagent to a gene chip in a gene sequencing system.

Background

The essence of a gene is a DNA fragment with a genetic effect that controls a biological trait. The gene sequencing can quickly and accurately acquire biological genetic information, reveal the complexity and diversity of a genome and play an important role in life science research; similarly, gene sequencing is of great importance and value to clinical medicine, and the research on the mechanism and clinical diagnosis of many diseases gradually depends on gene sequencing technology.

International patent application No. PCT/CN2017/104587 discloses a gene sequencing reaction apparatus and a gene sequencing system, which disclose that a sequencing chip (i.e., a gene chip) is immersed in a reagent so that the reagent is loaded (i.e., injected) into a micro flow channel in the gene chip.

Since the flow channel in the gene chip is very fine and the structure of the flow channel is complicated, the flow resistance to the fluid entering the flow channel is very large. The gene chip is soaked only, so that the reagent is difficult to enter and fill the flow channel, the possibility of gas residue in the flow channel is high, the reagent is difficult to enter the volume occupied by the residual gas, the reagent is loaded unevenly and insufficiently, and the sequencing result is influenced.

Disclosure of Invention

The invention aims to provide a method for loading a reagent to a gene chip in a gene sequencing system, which comprises the steps of putting the gene chip into a container containing the reagent, and submerging the gene chip by the reagent to enable the container to form negative pressure.

The invention discharges the air in the flow channel of the gene chip by making the container form negative pressure, and simultaneously the reagent in the container is sucked into the flow channel of the gene chip under the action of the negative pressure, thereby realizing that the reagent is uniformly and fully loaded into the flow channel of the gene chip, and improving the accuracy of the sequencing result.

Drawings

FIG. 1 is a schematic flow chart showing a method for loading a reagent into a gene chip in the gene sequencing system according to the present invention;

FIG. 2 shows a perspective view of a gene sequencing system of the present invention;

FIG. 3 shows a top view of the gene sequencing system of the present invention;

FIG. 4 shows a perspective view of the conveyor line;

fig. 5 shows an exploded perspective view of the chip frame and carrier;

FIG. 6 shows a perspective view of a chip frame;

FIG. 7 shows an exploded perspective view of a chip frame;

FIG. 8 shows a front view of a chip frame;

FIG. 9 shows a cross-sectional view A-A of FIG. 8;

fig. 10 and 11 show perspective views of the handling device at two different angles, respectively;

FIG. 12 shows an enlarged view of part B of FIG. 10;

fig. 13 shows a front view of the handling device;

FIG. 14 shows an enlarged partial view of portion C of FIG. 13;

FIG. 15 shows a D-D cross-sectional view of FIG. 14;

fig. 16 is a schematic view showing the top of the chip frame inserted into the pick-and-place slot on the basis of fig. 14;

FIG. 17 shows a perspective view of the turntable;

FIG. 18 shows a schematic cross-sectional view of a container;

FIG. 19 shows a schematic view of the access portion being withdrawn from the container;

figure 20 shows a schematic view of the pick and place portion being driven down to close off the mouth of a container on the basis of figure 19;

FIG. 21 shows a schematic view of an optical inspection apparatus of the present invention in which the movable carriage is drawn into the main body;

FIG. 22 is a schematic sectional view of the structure of FIG. 21;

FIG. 23 shows a schematic view of the optical inspection apparatus in which the movable carriage is pushed out of the main body;

FIG. 24 is a schematic sectional view of FIG. 23;

FIG. 25 is a perspective view of the turret mounted on the turret and the turret in a chip loading and unloading position;

FIG. 26 is a schematic view showing the chip frame removed from the turret slot in addition to FIG. 25;

FIG. 27 shows a top view of the moving gantry and the turret mounted thereon, with the turret in a chip handling position;

FIG. 28 shows a cross-sectional view E-E of FIG. 27;

FIG. 29 shows a cross-sectional view F-F of FIG. 27;

fig. 30 shows an enlarged view of part G of fig. 28;

FIG. 31 shows an enlarged view of part H of FIG. 29;

FIG. 32 is a perspective view of the mobile gantry and turret mounted thereon, with the turret in a lighted imaging position;

FIG. 33 is a schematic view of the turret rotated from the chip-handling position to the photoimaging position based on FIG. 30;

FIG. 34 is a schematic view of the parts of FIG. 32 after they have been exploded;

fig. 35 to 38 show the operating principle of the drive mechanism;

FIG. 39 shows a front view of the gene sequencing system of the present invention;

FIGS. 40 to 47 are schematic diagrams showing the operation of the gene sequencing system of the present invention.

Reference numerals:

100 chip carrying and loading, 101 lifting cylinder, 102 pick-and-place part, 103 guide rail, 104 slide seat, 105 detection stop position, 106 pick-and-place stop position, 107 liquid adding stop position, 108 air pumping hole, 109 air charging hole, 110 upper column, 111 lower column, 112 pick-and-place part step surface, 113 elastic sealing ring, 114 lower column end surface, 115 air pressure sensor, 116 pick-and-place part slot and 117 electromagnet;

200 gene chip;

300 optical detection device, 301 main body, 302 moving frame, 303 rotating frame, 304 front of main body, 305 entrance, 306 push-pull mechanism, 307 rotating frame slot, 308 rack, 309 rotating shaft, 310 gear, 311 supporting arm, 312 spring positioning ball, 313 ball, 314 recess, 315 magnet;

400 reagent storage device, 401 turntable, 402 container, 403 cavity, 404 mouth part and 405 container step surface;

500 conveying lines and 501 gene sequencing stations;

600 carrier, 601 carrier slot;

700 chip frame, 701 top iron body, 702 mounting position, 703 bottom iron body.

Detailed Description

The present invention will be described in further detail with reference to the accompanying drawings and specific embodiments.