CN221117405U

CN221117405U - Chip sequencing system for rapid sample injection

Info

Publication number: CN221117405U
Application number: CN202322894668.2U
Authority: CN
Inventors: 杜灵国; 万明明; 乔朔
Original assignee: Saina Biotechnology Guangzhou Co ltd
Current assignee: Saina Biotechnology Guangzhou Co ltd
Priority date: 2023-10-27
Filing date: 2023-10-27
Publication date: 2024-06-11
Anticipated expiration: 2033-10-27

Abstract

The application discloses a chip sequencing system for rapid sample injection, which comprises a reagent supply device, a rotary valve device, a chip device, a pumping power source device, an electromagnetic valve device, a pushing power source device and a waste liquid storage device; wherein the reagent supply device is used for providing reagents required by the test; the rotary valve device is used for controlling the delivery of different reagents; the chip device is used for placing a chip to be tested; the liquid pumping power source device is used for providing power for the reagent supply device so as to pump the corresponding reagent; the electromagnetic valve device is used for controlling the trend of an output pipeline of the chip device; the pushing and hydraulic power source device is used for providing a preset type of reagent; the waste liquid storage device is used for storing waste liquid and preventing environmental pollution. The application can realize rapid sample injection, effectively improve the liquid feeding speed, effectively avoid bubbles and liquid leakage, ensure the sequencing quality, realize higher sequencing flux and sequencing quality output and realize faster sequencing time.

Description

Chip sequencing system for rapid sample injection

Technical Field

The disclosure relates to the technical field of gene chip sequencing, in particular to a chip sequencing system for rapid sample injection.

Background

Gene sequencing is a novel gene detection technology capable of analyzing and determining gene sequences from blood or human body appendages and predicting the possibility of suffering from various diseases, such as cancers or leukemia, and the like. Gene sequencing related products and techniques have evolved from laboratory studies to clinical use, a gene chip or a sequencing chip is a chip for gene sequencing, a variety of gene sequencing chips have been developed at present, prototypes of the gene chip are proposed in the middle of 80 s, and the sequencing principle of the gene chip is a hybridization sequencing method, i.e., a method of determining a nucleic acid sequence by hybridization with a set of nucleic acid probes of known sequences, and probes of target nucleotides of known sequences are immobilized on a substrate surface. When the nucleic acid sequence with fluorescent mark in the solution is complementary matched with the nucleic acid probe in the corresponding position on the gene chip, one group of completely complementary probe sequences is obtained through determining the fluorescent intensity, and the sequence of the nucleic acid to be detected can be recombined.

Because the sequencing reagent is basically used by switching a plurality of reagents, the narrow pipeline and the thin cavity are adopted by the liquid path disclosed in the prior art, so that the size of a chip is required to be in a certain range, and the corresponding liquid inlet component is also required to be kept at a certain liquid inlet speed; however, along with the increase of diversity of research and development and test and sequencing quantity, the requirement on the detection period of a single chip is shorter, but if the liquid inlet speed is forcibly increased in the scheme disclosed in the prior art, the absolute value of negative pressure at the inlet of the chip is increased, so that the connecting piece (namely a rubber pad) at the liquid inlet of the chip is leaked, gas can enter from the outside, bubbles appear in liquid entering the flow channel of the chip, the detection result is influenced, the detection result is inaccurate, and the obtained sequencing image is inaccurate even the corresponding sequencing detection fails.

Disclosure of utility model

In view of the above, the embodiments of the present disclosure provide a chip sequencing system for rapid sample injection, which at least partially solves the problem in the prior art that the liquid feeding speed cannot be improved.

The embodiment of the disclosure provides a chip sequencing system for rapid sample injection, comprising:

a reagent supply device comprising a plurality of reagent supply assemblies;

rotary valve means connected to each of said reagent supply assemblies;

The chip device is provided with a chip liquid inlet and a chip liquid outlet, and the chip liquid inlet is connected with the rotary valve device;

a waste liquid storage device;

The liquid pumping power source device is provided with a liquid pumping inlet and a liquid pumping outlet connected with the waste liquid storage device and is used for controlling the corresponding liquid of the reagent supply device to be pumped;

The electromagnetic valve device is provided with a first opening, a second opening and a third opening, the first opening is connected with the liquid outlet of the chip, the second opening is connected with the liquid suction inlet, and the third opening is connected with the waste liquid storage device;

The hydraulic pushing power source device comprises a first power source component, a second power source component, a third power source component, a first liquid supply component, a second liquid supply component and a third liquid supply component, wherein the first power source component, the second power source component and the third power source component are respectively in one-to-one correspondence with the first liquid supply component, the second liquid supply component and the third liquid supply component;

The liquid pushing ports of the first power source assembly, the second power source assembly and the third power source assembly are respectively and correspondingly connected with different valve ports of the rotary valve device.

Optionally, the reagent supply device comprises a plurality of amplification reagent supply bottles, a plurality of sequencing reagent supply bottles, a unwinding reagent supply bottle and a joint primer reagent supply bottle.

Optionally, the first liquid supply assembly comprises an oil-sealed reagent storage bottle;

the second liquid supply assembly comprises a buffer cleaning liquid storage bottle;

The third liquid supply assembly comprises an oil seal cleaning reagent storage bottle.

Optionally, the first power source component is connected with the oil seal reagent storage bottle through a first pipeline;

The second power source assembly is connected with the buffer cleaning liquid storage bottle through a second pipeline;

The third power source assembly is connected with the oil seal cleaning reagent storage bottle through a third pipeline;

the oil seal reagent storage bottle is connected with the rotary valve device through a fourth pipeline;

the buffer cleaning liquid storage bottle is connected with the rotary valve device through a fifth pipeline;

The oil seal cleaning reagent storage bottle is connected with the rotary valve device through a sixth pipeline;

the rotary valve device is connected with the chip device through a seventh pipeline;

The chip device is connected with the electromagnetic valve device through an eighth pipeline;

the electromagnetic valve device is connected with the waste liquid storage device through a ninth pipeline;

The electromagnetic valve device is connected with the liquid pumping power source device through a tenth pipeline;

the liquid pumping power source device is connected with the waste liquid storage device through an eleventh pipeline.

Optionally, the inner diameter of the first pipeline is D1, and the length of the first pipeline is L1; d1 is more than 0.3mm, L1 is more than 0 and less than 1000mm;

the inner diameter of the second pipeline is D2, and the length of the second pipeline is L2;

the inner diameter of the third pipeline is D3, and the length of the third pipeline is L3;

the inner diameter of the fourth pipeline is D4, and the length of the fourth pipeline is L4;

The inner diameter of the fifth pipeline is D5, and the length of the fifth pipeline is L5;

The inner diameter of the sixth pipeline is D6, and the length of the sixth pipeline is L6;

the inner diameter of the seventh pipeline is D7, and the length of the seventh pipeline is L7;

D7＝D6＝D5＝D4＝D3＝D2＝D1，L7＝L6＝L5＝L4＝L3＝L2＝L1；

The inner diameter of the eighth pipeline is D8, and the length of the eighth pipeline is L8; d8 is more than D1, L8 is less than 50mm;

The inner diameter of the ninth pipeline is D9, and D9 is more than D8.

Optionally, an elastic rubber pad is arranged above the liquid inlet of the chip, and the elastic rubber pad is provided with a through hole.

Optionally, the elastic rubber pad includes a first columnar section and a second columnar section, the outer diameter of the second columnar section is larger than the outer diameter of the first columnar section, and the height of the second columnar section is smaller than the height of the first columnar section;

A first through hole is formed in the first columnar section, and a second through hole communicated with the first through hole is formed in the second columnar section;

The end part of the first columnar section, which is far away from the second columnar section, is convexly provided with a first circular ring structure, the outer diameter of the first circular ring structure is smaller than that of the first columnar section, and the inner diameter of the first circular ring structure is larger than that of the first through hole;

The second cylindrical section is far away from the end part of the first cylindrical section and protrudes to be provided with a second circular ring structure, the outer diameter of the second circular ring structure is smaller than that of the second cylindrical section, and the inner diameter of the second circular ring structure is larger than that of the second through hole.

Optionally, in the first working state, the first liquid supply assembly, the first power source assembly, the rotary valve device, the chip device, the electromagnetic valve device and the waste liquid storage device are communicated, and the internal pressure at the elastic rubber pad is higher than the external pressure;

in a second working state, the second liquid supply assembly, the second power source assembly, the rotary valve device, the chip device, the electromagnetic valve device and the waste liquid storage device are communicated, and the internal pressure at the elastic rubber pad is higher than the external pressure;

In a third working state, the third liquid supply assembly, the third power source assembly, the rotary valve device, the chip device, the electromagnetic valve device and the waste liquid storage device are communicated, and the internal pressure at the elastic rubber pad is higher than the external pressure;

in a fourth working state, the reagent supply device, the rotary valve device, the chip device, the electromagnetic valve device, the liquid pumping power source device and the waste liquid storage device are communicated, and the internal pressure at the elastic rubber pad is smaller than the external pressure.

Optionally, the first power source assembly, the second power source assembly and the third power source assembly are arranged in the same structure.

Optionally, the pushing flow rates of the first power source assembly, the second power source assembly and the third power source assembly are all larger than the drawing power flow rate of the drawing power source device.

According to the chip sequencing system for rapid sample injection disclosed by the application, through the arrangement of the pumping power source device and the pushing power source device, the positive pressure sample injection design is adopted for the reagent with larger viscosity, so that the problem of air leakage caused by overlarge flow resistance is successfully solved, the acceleration of the fluid process is successfully realized, air leakage is not generated in a pipeline, the high-quality reaction effect and the data volume are ensured, the whole reaction period is effectively shortened, and the detection efficiency is provided. The application can realize rapid sample injection, effectively improve the liquid feeding speed, effectively avoid bubbles and liquid leakage, ensure the sequencing quality, realize higher sequencing flux and sequencing quality output and realize faster sequencing time.

The positive pressure liquid inlet disclosed by the application can effectively reduce flow resistance and improve liquid inlet speed and liquid inlet quality; because the viscosity of the liquid is far greater than that of the gas, the pressure difference required by the passing sealing pressing surface is larger, so that the leakage of the liquid cannot be generated, and the generation of bubbles and leakage can be effectively avoided by positive pressure, namely, the gas cannot enter at the joint of the sealing rubber gaskets through the introduction of the pushing hydraulic power source device.

The foregoing description is only an overview of the disclosed technology, and may be implemented in accordance with the disclosure of the present disclosure, so that the above-mentioned and other objects, features and advantages of the present disclosure can be more clearly understood, and the following detailed description of the preferred embodiments is given with reference to the accompanying drawings.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present disclosure, and other drawings may be obtained according to these drawings without inventive effort to a person of ordinary skill in the art.

Fig. 1 is a schematic diagram of an embodiment of the present application.

Fig. 2 is a schematic perspective view of an elastic rubber pad in the present application.

Fig. 3 is another angular schematic view of the elastic rubber pad in the present application.

Reference numerals illustrate:

1. A first pipeline; 2. a second pipeline; 3. a third pipeline; 4. a fourth pipeline; 5. a fifth pipeline; 6. a sixth pipeline; 7. a seventh pipeline; 8. an eighth pipeline; 9. a ninth pipeline; 10. a tenth pipeline; 11. an eleventh pipeline;

100. A reagent supply device; 200. a rotary valve device; 300. a chip device; 310. a first cylindrical section; 320. a second cylindrical section; 330. a first annular structure; 340. a second ring structure; 400. a pumping power source device; 500. a solenoid valve device; 610. a first power source assembly; 620. a first liquid supply assembly; 710. a second power source assembly; 720. a second liquid supply assembly; 810. a third power source assembly; 820. a third liquid supply assembly; 900. a waste liquid storage device.

Detailed Description

The present disclosure is described in further detail below with reference to the drawings and the embodiments. It is to be understood that the specific embodiments described herein are merely illustrative of the relevant content and not limiting of the present disclosure. It should be further noted that, for convenience of description, only a portion relevant to the present disclosure is shown in the drawings.

In addition, embodiments of the present disclosure and features of the embodiments may be combined with each other without conflict. The technical aspects of the present disclosure will be described in detail below with reference to the accompanying drawings in conjunction with embodiments.

Unless otherwise indicated, the exemplary implementations/embodiments shown are to be understood as providing exemplary features of various details of some ways in which the technical concepts of the present disclosure may be practiced. Thus, unless otherwise indicated, features of the various implementations/embodiments may be additionally combined, separated, interchanged, and/or rearranged without departing from the technical concepts of the present disclosure.

The use of cross-hatching and/or shading in the drawings is typically used to clarify the boundaries between adjacent components. As such, the presence or absence of cross-hatching or shading does not convey or represent any preference or requirement for a particular material, material property, dimension, proportion, commonality between illustrated components, and/or any other characteristic, attribute, property, etc. of a component, unless indicated. In addition, in the drawings, the size and relative sizes of elements may be exaggerated for clarity and/or descriptive purposes. While the exemplary embodiments may be variously implemented, the specific process sequences may be performed in a different order than that described. For example, two consecutively described processes may be performed substantially simultaneously or in reverse order from that described. Moreover, like reference numerals designate like parts.

When an element is referred to as being "on" or "over", "connected to" or "coupled to" another element, it can be directly on, connected or coupled to the other element or intervening elements may be present. However, when an element is referred to as being "directly on," "directly connected to," or "directly coupled to" another element, there are no intervening elements present. For this reason, the term "connected" may refer to physical connections, electrical connections, and the like, with or without intermediate components.

For descriptive purposes, the present disclosure may use spatially relative terms such as "under … …," under … …, "" under … …, "" lower, "" above … …, "" upper, "" above … …, "" upper "and" side (e.g., as in "sidewall") to describe one component's relationship to another (other) component as illustrated in the figures. In addition to the orientations depicted in the drawings, the spatially relative terms are intended to encompass different orientations of the device in use, operation, and/or manufacture. For example, if the device in the figures is turned over, elements described as "under" or "beneath" other elements or features would then be oriented "over" the other elements or features. Thus, the exemplary term "below … …" may encompass both an orientation of "above" and "below". Furthermore, the device may be otherwise positioned (e.g., rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. Furthermore, when the terms "comprises" and/or "comprising," and variations thereof, are used in the present specification, the presence of stated features, integers, steps, operations, elements, components, and/or groups thereof is described, but the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof is not precluded. It is also noted that, as used herein, the terms "substantially," "about," and other similar terms are used as approximation terms and not as degree terms, and as such, are used to explain the inherent deviations of measured, calculated, and/or provided values that would be recognized by one of ordinary skill in the art.

Referring to fig. 1, the application discloses a chip sequencing system for rapid sample injection, which comprises a reagent supply device 100, a rotary valve device 200, a chip device 300, a pumping power source device 400, a solenoid valve device 500, a pushing power source device and a waste liquid storage device 900, wherein the reagent supply device 100 is used for providing reagents required by a test; the rotary valve device 200 is used to control the delivery of different reagents; the chip device 300 is used for placing a chip to be tested; the liquid pumping power source device 400 is used for providing power for the reagent supplying device 100 so as to pump the corresponding reagent; the electromagnetic valve device 500 is used for controlling the trend of the output pipeline of the chip device 300; the pushing and hydraulic power source device is used for providing a preset type of reagent; the waste liquid storage device 900 is used for storing waste liquid, and prevents environmental pollution.

In this embodiment, the predetermined type of reagent provided by the pushing force source device is higher in viscosity than the reagent provided by the reagent supplying device.

Further, the reagent supplying apparatus 100 includes several reagent supplying components; in this embodiment, the reagent supply device 100 includes a plurality of amplification reagent supply bottles, a plurality of sequencing reagent supply bottles, a unwinding reagent supply bottle, and a linker primer reagent supply bottle (i.e., primer supply bottle).

The rotary valve device 200 is connected to a plurality of reagent supply assemblies, respectively, and in this embodiment, the rotary valve device 200 includes a common port and a plurality of liquid inlet ports, where the liquid inlet ports are selectively communicated with the common port in an operating state, i.e. only one liquid inlet port is communicated with the common port in the operating state. Wherein, the public port is the export, and a plurality of amplification reagent supply bottles, a plurality of sequencing reagent supply bottles, unwinding reagent supply bottles, joint primer reagent supply bottles are connected with corresponding feed liquor valve ports respectively, and in this embodiment, the total number of feed liquor valve ports is greater than the total number of amplification reagent supply bottles, sequencing reagent supply bottles, unwinding reagent supply bottles and joint primer reagent supply bottles.

The chip device 300 is used for accommodating a DNA sequence to be sequenced and generating a sequencing chemical reaction in the chip; the chip is internally provided with a cavity, and the cavity is provided with an access hole, so that reagent exchange with the outside is facilitated; the inner surface of the chip cavity is smooth or has array type micro pits, and the sequencing reaction can occur on the surface or in the micro pits.

In this embodiment, the inlet and outlet holes of the cavity are a chip liquid inlet and a chip liquid outlet, the chip liquid inlet is connected with the rotary valve device 200, i.e. is connected with a common port, and the rotary valve device 200 can control the reagent input corresponding to the liquid inlet valve port, i.e. the reagent input to the chip device 300 through the common port.

The pumping power source device 400 has a pumping inlet and a pumping outlet connected to the waste liquid storage device 900 for controlling the corresponding liquid pumping of the reagent supply device 100.

The electromagnetic valve device 500 is provided with a first opening, a second opening and a third opening, wherein the first opening is connected with the liquid outlet of the chip, the second opening is connected with the liquid suction inlet, and the third opening is connected with the waste liquid storage device 900; when the first opening and the second opening are opened, the whole system extracts the reagent in the reagent supply device 100 through the liquid extraction power source device 400, so that the extracted reagent enters the chip device 300, namely, the whole system provides liquid extraction force; when the first opening is communicated with the third opening, the whole system pushes the target reagent through the liquid pushing power source device, so that the target reagent is pushed into the chip device 300, and the liquid pushing force provided for the whole system is ensured.

The hydraulic power source pushing device comprises a first power source component 610, a second power source component 710, a third power source component 810, a first liquid supply component 620, a second liquid supply component 720 and a third liquid supply component 820, wherein the first power source component 610, the second power source component 710 and the third power source component are respectively in one-to-one correspondence with the first liquid supply component 620, the second liquid supply component 720 and the third liquid supply component 820; the fluid ports of the first power source assembly 610, the second power source assembly 710, and the third power source assembly 810 are respectively connected with different valve ports of the rotary valve device 200.

The chip sequencing system for rapid sample injection disclosed by the application can rapidly supply various reagents through the connection of the reagent supply device 100 and the rotary valve device 200; the existence of a plurality of reagent supply assemblies can simultaneously provide different reagents, thereby saving the time for reagent replacement and supporting the requirements of various sequencing experiments. Second, the chip device 300 has a liquid inlet and a liquid outlet, and is connected to the rotary valve device 200, so that the sample can rapidly enter the chip, and analysis and sequencing can be performed in the chip, and the efficiency and accuracy of sequencing can be greatly improved by using the chip device 300. In addition, the liquid suction inlet of the liquid suction power source device 400 and the liquid suction outlet connected to the waste liquid storage device 900 are used for controlling the liquid suction of the reagent supply device 100, so that the accurate supply of the reagent and the smooth removal of the sample can be ensured, thereby avoiding the possibility of cross contamination and confusion. In addition, the solenoid valve device 500 has three openings, which are connected to the chip liquid outlet, the liquid suction inlet, and the waste liquid storage device 900, respectively. By controlling the opening and closing of the electromagnetic valve, the smooth in-out of the sample and the storage of the waste liquid can be realized, so that the operation of the system is simpler and more convenient and efficient. Finally, the hydrodynamic force source device includes a plurality of power source components and fluid supply components that are correspondingly coupled to the ports of the rotary valve device 200 to provide sufficient pressure and power to ensure smooth flow and transport of the sample and reagents. In summary, the chip sequencing system with rapid sample injection has various beneficial effects, including rapid reagent supply, efficient sample injection, accurate liquid extraction, convenient operation and stable transportation, and improves the sequencing efficiency and accuracy.

When the pushing hydraulic power source device is used for supplying the reagent, taking the starting of the first power source assembly 610 as an example for describing in detail, the first power source assembly 610 extracts the reagent from the first liquid supply assembly 620, and the positive pressure reagent is temporarily stored in the cavity of the first power source assembly 610 in a negative pressure mode; when the reagent is used, the solenoid valve device 500 is switched to communicate with the waste liquid storage device 900, and the liquid inlet valve port in the rotary valve device 200 is switched to communicate with the first power source assembly 610, so that a complete passage is formed. The first power source assembly 610 inputs high viscosity liquid into the interior of the chip device 300 through the rotary valve device 200; then, the waste liquid outputted from the chip device 300 enters the waste liquid storage device 900 through the electromagnetic valve device 500, and positive pressure sample injection is realized.

In the present embodiment, the pushing flow rates of the first power source module 610, the second power source module 710, and the third power source module 810 are all greater than the pumping power flow rate of the pumping power source device 400.

In this embodiment, the first fluid supply assembly 620 includes a vial for storing a fluid-tight reagent for providing the fluid-tight reagent; the second liquid supply assembly 720 includes a buffer cleaning liquid storage bottle for providing a buffer cleaning liquid; the third liquid supply assembly 820 includes a grease cleaning reagent storage bottle for providing a grease cleaning reagent.

The first power source assembly 610 is connected with the oil-sealed reagent storage bottle through a first pipeline 1; the second power source component 710 is connected with the buffer cleaning liquid storage bottle through a second pipeline 2; the third power source assembly 810 is connected with the oil seal cleaning reagent storage bottle through a third pipeline 3; the oil-sealed reagent storage bottle is connected with the rotary valve device 200 through a fourth pipeline 4; the buffer cleaning liquid storage bottle is connected with the rotary valve device 200 through a fifth pipeline 5; the oil seal cleaning reagent storage bottle is connected with the rotary valve device 200 through a sixth pipeline 6; the rotary valve device 200 is connected with the chip device 300 through a seventh pipeline 7; the chip device 300 is connected with the electromagnetic valve device 500 through an eighth pipeline 8; the electromagnetic valve device 500 is connected with the waste liquid storage device 900 through a ninth pipeline 9; the electromagnetic valve device 500 is connected with the pumping power source device 400 through a tenth pipeline 10; the pumping power source device 400 is connected to the waste liquid storage device 900 through an eleventh line 11.

Wherein the inner diameter of the first pipeline 1 is D1, and the length of the first pipeline 1 is L1; d1 is more than 0.3mm,0 is more than 0 and L1 is less than 1000mm.

The inner diameter of the second pipeline 2 is D2, the length of the second pipeline 2 is L2, the inner diameter of the third pipeline 3 is D3, the length of the third pipeline 3 is L3, the inner diameter of the fourth pipeline 4 is D4, the length of the fourth pipeline 4 is L4, the inner diameter of the fifth pipeline 5 is D5, the length of the fifth pipeline 5 is L5, the inner diameter of the sixth pipeline 6 is D6, the length of the sixth pipeline 6 is L6, the inner diameter of the seventh pipeline 7 is D7, and the length of the seventh pipeline 7 is L7.

D7＝D6＝D5＝D4＝D3＝D2＝D1，L7＝L6＝L5＝L4＝L3＝L2＝L1。

The inner diameter of the eighth pipeline 8 is D8, and the length of the eighth pipeline 8 is L8; d8 is greater than D1, L8 is less than 50mm.

The ninth pipeline 9 has an inner diameter D9, D9 > D8.

In this embodiment, the hydrodynamic power source device is preferably a syringe pump or peristaltic pump to power the flow of reagent.

In this embodiment, the rotary valve device 200 is a single rotary valve, and it should be noted that the rotary valve device 200 further includes a plurality of rotary valves connected in series to meet the input requirement of a large amount of reagents.

According to the chip sequencing system for rapid sample injection disclosed by the application, through the arrangement of the pumping power source device 400 and the pushing power source device, the design of positive pressure sample injection is adopted for reagents with larger viscosity, so that the problem of air leakage caused by overlarge flow resistance is successfully solved, the acceleration of a fluid process is successfully realized, air leakage is not generated in a pipeline, the high-quality reaction effect and data volume are ensured, the whole reaction period is effectively shortened, and the detection efficiency is provided.

Referring to fig. 1 and fig. 2 and3, an elastic rubber pad is arranged above the liquid inlet of the chip, and the elastic rubber pad is provided with a through hole.

The elastic rubber pad includes a first cylindrical section 310 and a second cylindrical section 320, the outer diameter of the second cylindrical section 320 is greater than the outer diameter of the first cylindrical section 310, and the height of the second cylindrical section 320 is less than the height of the first cylindrical section 310.

The first through hole is formed in the first cylindrical section 310, and the second through hole communicated with the first through hole is formed in the second cylindrical section 320, so that liquid can be conveniently introduced.

The end of the first cylindrical section 310 far away from the second cylindrical section 320 is convexly provided with a first circular ring structure 330, the outer diameter of the first circular ring structure 330 is smaller than the outer diameter of the first cylindrical section 310, and the inner diameter of the first circular ring structure 330 is larger than the diameter of the first through hole.

The end of the second cylindrical section 320 far away from the first cylindrical section 310 is convexly provided with a second annular structure 340, the outer diameter of the second annular structure 340 is smaller than the outer diameter of the second cylindrical section 320, and the inner diameter of the second annular structure 340 is larger than the diameter of the second through hole.

In the first operating state, the first liquid supply assembly 620, the first power source assembly 610, the rotary valve device 200, the chip device 300, the solenoid valve device 500, and the waste liquid storage device 900 are communicated, and the internal pressure at the elastic rubber pad is greater than the external pressure.

In the second operating state, the second liquid supply assembly 720, the second power source assembly 710, the rotary valve device 200, the chip device 300, the solenoid valve device 500, and the waste liquid storage device 900 are communicated, and the internal pressure at the elastic rubber pad is greater than the external pressure.

In the third operating state, the third liquid supply assembly 820, the third power source assembly 810, the rotary valve device 200, the chip device 300, the solenoid valve device 500, and the waste liquid storage device 900 are communicated, and the internal pressure at the elastic rubber pad is greater than the external pressure.

In the fourth operating state, the reagent supplying apparatus 100, the rotary valve apparatus 200, the chip apparatus 300, the solenoid valve apparatus 500, the pumping power source apparatus 400, and the waste liquid storage apparatus 900 are communicated, and the internal pressure at the elastic rubber pad is smaller than the external pressure.

Further, the first power source component, the second power source component and the third power source component are arranged in the same structure.

Further, the outer side of the first columnar section is also provided with a plurality of vertical edges, so that the positioning during installation is convenient, and the coaxiality is ensured.

In addition, the chip sequencing system for rapid sample injection also comprises sensors such as pressure, flow rate and the like, and is used for monitoring whether the fluid system operates normally.

Further, the chip sequencing system for rapid sample injection also comprises a temperature control system for controlling reagents, chips or other components of the sequencer, so that the smooth progress of the sequencing reaction is ensured; the temperature control system of the chip has the functions of heating and refrigerating, so that the sequencing reaction can be accelerated or inhibited by the temperature; the temperature control system of the reagent bin is mainly used for refrigerating the reagent and preventing the sequencing reagent from deteriorating at normal temperature.

Further, the chip sequencing system for rapid sample injection further comprises an optical imaging system for detecting fluorescent signals in the chip subjected to sequencing reaction. The optical imaging system may excite and collect fluorescent signals in the sequencing chip, thereby identifying sequencing reactions occurring in the chip. In addition, the optical imaging system also comprises an automatic focusing component, so that the imaging system can be ensured to be in an in-focus state in the imaging process, and the quality of the produced image is ensured. The optical system has various adjustment means for ensuring alignment of the components of the imaging system and alignment of the imaging system with the chip.

Further, the chip sequencing system for rapid sample injection also comprises a data processing system for processing the image generated by the optical imaging system, converting the image signal into read-out gene sequences and outputting reference information such as sequence quality.

Further, a chip, a fluid, a temperature control system, an optical system and the like in the chip sequencing system for rapid sample injection are combined, different sequencing kits are selected according to the sequencing condition requirements of samples, so that 2+2 ECC sequencing or 1*4 sequencing is realized, and better sequencing quality is realized.

In this embodiment, the thickness of the chip is 30 micrometers to 200 micrometers, and the length is 50mm or more.

In the prior art, the sample introduction involves the introduction of various liquids into the flow cell, and due to the high definition of the flow cell in the chip device, bubbles can easily affect the accuracy of sample introduction and the effective reaction area in the cavity, thereby causing sequencing throughput and quality loss.

According to the sealing theory, the sealing element (namely the elastic rubber cushion in the prior art) is clamped between the two sides to be connected, and the solid at the two sides and the sealing element generate larger contact area by applying pressure to the sealing element, so that the leakage of a well-connected and sealed passage can be effectively blocked due to the size of the contact area and the material property of the sealing element. The passageway often fills the medium to realize the transmission of material, and the power that produces the transmission is the pressure differential of upstream and downstream, and has respective pressure value in the different positions of passageway, and this pressure is recorded as pressure value PA in the sealing member with the inboard of the contact surface of both sides solid, and the outside of this contact surface produces pressure value PB, and when the pressure differential of both is less than certain threshold value, produces better sealed effect, when the pressure differential of both is greater than certain threshold value, easily produces the leakage.

Microfluidics is the subject of liquid control on the micro-nano scale (or millimeter-scale), our chip has a 1mm diameter glass through-hole, the flow cell thickness is 10 to 500 microns, half of the tubing is also the inner diameter less than 1mm, these dimensions will produce some flow characteristics of the microfluidics. The seal cannot generally be compressed too much because excessive compression can produce a large lateral deformation and even the passage of the seal becomes small or blocked. When the compression amount is not large, the leakage threshold value of the contact surface is low. The smaller flow cell thickness and smaller line internal diameter will create greater fluid resistance and, according to flow resistance theory, the pressure required to control the stable flow of liquid in the line and flow cell will be related to the flow resistance of the entire passageway. In theory, the flow resistance of a pipeline is defined as the wallpaper of the pressure difference and the average flow rate at two ends, particularly to rectangular and circular cross sections, and has different empirical formulas,

Rectangular cross section: Wherein D is the height of the flow channel, W is the width of the flow channel, deltaX is the length of the flow channel, deltaP is the pressure drop between two points of the flow channel, Q is the volume flow, and v is the kinematic viscosity.

Circular cross section: Wherein R is the radius of the flow channel.

From the above flow resistance equation, it can be calculated that a pressure difference of about 80kPa is required to achieve a flow rate of 50 microliters per second in the entire passage, and this pressure difference has a pressure of about-50 kPa in the vicinity of the contact surface of the seal member, and a pressure difference of about-50 kPa is generated with the atmospheric pressure outside the contact surface, so that it is easy for the outside leakage air bubbles to come out.

If a positive pressure design is adopted, in order to maintain the flow rate of 50 microliters per second, a pressure difference of about 80kPa is still required, the pressure difference is about 50kPa near the contact surface of the sealing element, and a pressure difference of more than 50kPa is generated with the atmospheric pressure outside the contact surface, and the viscosity of liquid is far greater than that of gas, so that the pressure difference required by the sealing pressing surface passing through the sealing element is larger, and the leakage of the liquid is avoided; therefore, the positive pressure can effectively avoid the generation of bubbles and liquid leakage, namely, through the scheme disclosed by the application, the liquid inlet speed can be effectively improved, and meanwhile, the generation of bubbles and liquid leakage can be effectively avoided.

In the description of the present specification, reference to the terms "one embodiment/manner," "some embodiments/manner," "example," "a particular example," "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment/manner or example is included in at least one embodiment/manner or example of the application. In this specification, the schematic representations of the above terms are not necessarily for the same embodiment/manner or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments/modes or examples. Furthermore, the various embodiments/modes or examples described in this specification and the features of the various embodiments/modes or examples can be combined and combined by persons skilled in the art without contradiction.

Furthermore, the terms "first," "second," and the like, are used for descriptive purposes only and are not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include at least one such feature. In the description of the present application, the meaning of "plurality" means at least two, for example, two, three, etc., unless specifically defined otherwise.

It will be appreciated by those skilled in the art that the above-described embodiments are merely for clarity of illustration of the disclosure, and are not intended to limit the scope of the disclosure. Other variations or modifications will be apparent to persons skilled in the art from the foregoing disclosure, and such variations or modifications are intended to be within the scope of the present disclosure.

Claims

1. A chip sequencing system for rapid sample injection, comprising:

A reagent supply device (100) comprising a number of reagent supply assemblies;

A rotary valve device (200) connected to a plurality of the reagent supply assemblies;

A chip device (300) having a chip liquid inlet and a chip liquid outlet, the chip liquid inlet being connected to the rotary valve device (200);

a waste liquid storage device (900);

A liquid pumping power source device (400) provided with a liquid pumping inlet and a liquid pumping outlet connected with the waste liquid storage device (900) and used for controlling the corresponding liquid pumping of the reagent supply device (100);

A solenoid valve device (500) having a first opening, a second opening and a third opening, wherein the first opening is connected with the chip liquid outlet, the second opening is connected with the liquid suction inlet, and the third opening is connected with the waste liquid storage device (900);

The hydraulic pushing power source device comprises a first power source component (610), a second power source component (710), a third power source component (810), a first liquid supply component (620), a second liquid supply component (720) and a third liquid supply component (820), wherein the first power source component (610), the second power source component (710) and the three power source components are respectively in one-to-one correspondence with the first liquid supply component (620), the second liquid supply component (720) and the third liquid supply component (820);

The liquid pushing ports of the first power source assembly (610), the second power source assembly (710) and the third power source assembly (810) are respectively and correspondingly connected with different valve ports of the rotary valve device (200).

2. The chip sequencing system for rapid sample injection according to claim 1, wherein the reagent supply device (100) comprises a number of amplification reagent supply bottles, a number of sequencing reagent supply bottles, a unwinding reagent supply bottle, a linker primer reagent supply bottle.

3. The chip sequencing system for rapid sample injection of claim 1, wherein said first liquid supply assembly (620) comprises an oil-sealed reagent storage bottle;

The second liquid supply assembly (720) includes a buffer cleaning liquid storage bottle;

The third liquid supply assembly (820) includes a grease sealed cleaning reagent storage bottle.

4. The chip sequencing system for rapid sample injection according to claim 3, wherein the first power source assembly (610) is connected with the oil-sealed reagent storage bottle through a first pipeline (1);

The second power source assembly (710) is connected with the buffer cleaning liquid storage bottle through a second pipeline (2);

the third power source assembly (810) is connected with the oil seal cleaning reagent storage bottle through a third pipeline (3);

The oil seal reagent storage bottle is connected with the rotary valve device (200) through a fourth pipeline (4);

the buffer cleaning solution storage bottle is connected with the rotary valve device (200) through a fifth pipeline (5);

The oil seal cleaning reagent storage bottle is connected with the rotary valve device (200) through a sixth pipeline (6);

The rotary valve device (200) is connected with the chip device (300) through a seventh pipeline (7);

The chip device (300) is connected with the electromagnetic valve device (500) through an eighth pipeline (8);

The electromagnetic valve device (500) is connected with the waste liquid storage device (900) through a ninth pipeline (9);

The electromagnetic valve device (500) is connected with the liquid pumping power source device (400) through a tenth pipeline (10);

The liquid pumping power source device (400) is connected with the waste liquid storage device (900) through an eleventh pipeline (11).

5. The chip sequencing system for rapid sample injection according to claim 4, wherein the inner diameter of the first pipeline (1) is D1, and the length of the first pipeline (1) is L1; d1 is more than 0.3mm, L1 is more than 0 and less than 1000mm;

the inner diameter of the second pipeline (2) is D2, and the length of the second pipeline (2) is L2;

the inner diameter of the third pipeline (3) is D3, and the length of the third pipeline (3) is L3;

the inner diameter of the fourth pipeline (4) is D4, and the length of the fourth pipeline (4) is L4;

The inner diameter of the fifth pipeline (5) is D5, and the length of the fifth pipeline (5) is L5;

The inner diameter of the sixth pipeline (6) is D6, and the length of the sixth pipeline (6) is L6;

The inner diameter of the seventh pipeline (7) is D7, and the length of the seventh pipeline (7) is L7;

D7＝D6＝D5＝D4＝D3＝D2＝D1，L7＝L6＝L5＝L4＝L3＝L2＝L1；

The inner diameter of the eighth pipeline (8) is D8, and the length of the eighth pipeline (8) is L8; d8 is more than D1, L8 is less than 50mm;

the inner diameter of the ninth pipeline (9) is D9, and D9 is more than D8.

6. The chip sequencing system for rapid sample injection of claim 1, wherein an elastic rubber pad is arranged above the chip liquid inlet, and the elastic rubber pad is provided with a through hole.

7. The chip sequencing system for rapid sample injection of claim 6, wherein the elastic rubber pad comprises a first cylindrical section (310) and a second cylindrical section (320), the outer diameter of the second cylindrical section (320) is larger than the outer diameter of the first cylindrical section (310), and the height of the second cylindrical section (320) is smaller than the height of the first cylindrical section (310);

a first through hole is formed in the first columnar section (310), and a second through hole communicated with the first through hole is formed in the second columnar section (320);

The end part of the first columnar section (310) far away from the second columnar section (320) is convexly provided with a first circular ring structure (330), the outer diameter of the first circular ring structure (330) is smaller than the outer diameter of the first columnar section (310), and the inner diameter of the first circular ring structure (330) is larger than the diameter of the first through hole;

the second cylindrical section (320) is far away from the end part of the first cylindrical section (310) and is provided with a second circular ring structure (340) in a protruding mode, the outer diameter of the second circular ring structure (340) is smaller than that of the second cylindrical section (320), and the inner diameter of the second circular ring structure (340) is larger than that of the second through hole.

8. The chip sequencing system for rapid sample injection according to claim 7, wherein in a first working state, the first liquid supply assembly (620), the first power source assembly (610), the rotary valve device (200), the chip device (300), the electromagnetic valve device (500) and the waste liquid storage device (900) are communicated, and the internal pressure at the elastic rubber pad is higher than the external pressure;

In a second working state, the second liquid supply assembly (720), the second power source assembly (710), the rotary valve device (200), the chip device (300), the electromagnetic valve device (500) and the waste liquid storage device (900) are communicated, and the internal pressure at the elastic rubber pad is higher than the external pressure;

In a third working state, the third liquid supply assembly (820), the third power source assembly (810), the rotary valve device (200), the chip device (300), the electromagnetic valve device (500) and the waste liquid storage device (900) are communicated, and the internal pressure at the elastic rubber pad is higher than the external pressure;

in a fourth working state, the reagent supply device (100), the rotary valve device (200), the chip device (300), the electromagnetic valve device (500), the liquid suction power source device (400) and the waste liquid storage device (900) are communicated, and the internal pressure at the elastic rubber pad is smaller than the external pressure.

9. The chip sequencing system for rapid sample injection of claim 1, wherein the first power source assembly (610), the second power source assembly (710), and the third power source assembly (810) are identically configured.

10. The chip sequencing system for rapid sample injection of claim 9, wherein the push flow rates of the first power source assembly (610), the second power source assembly (710), and the third power source assembly (810) are all greater than the extraction power flow rate of the liquid extraction power source device (400).