CN209052674U - Loading device and gene sequencing system - Google Patents

Abstract

The utility model provides a kind of loading device, for several liquid reactants to be loaded on naked sequence testing chip, including cover board and pedestal, circular seal groove is opened up on the cover board bottom surface, several flow path grooves for passing through the center of circle are equipped on the inside of the seal groove, the cover board is bonded with the sequence testing chip by being embedded in the sealing element of the seal groove to form cavity, the flow path groove is equipped with liquid outlet and inlet, the inlet or the liquid outlet are connected to the solenoid valve of fluid system, and the solenoid valve is for controlling liquid feeding and drain.The application of the device is not so that sequence testing chip needs expensive encapsulation process, reactant can be loaded directly on naked sequence testing chip, it is convenient to operate, loading procedure bubble-free, it is steady to change liquid, the quality and efficiency that liquid/paving liquid channel is remarkably improved the reagents loaded of overlarge area circle chip are changed by subregion domain construction, is conducive to the automatic biological reaction of quick, big flux.The utility model also provides a kind of gene sequencing system.

Description

Loading device and gene sequencing system

Technical field

The utility model relates to gene technology fields, particularly relate to a kind of for several liquid reactants to be loaded on naked survey The loading device of biochemical reaction, and the gene sequencing system using the device are carried out on sequence chip.

Background technique

This part intends to provides background or context for the embodiments of the present invention stated in claims.This The description at place recognizes it is the prior art not because not being included in this section.

Gene sequencing chip (such as silicon wafer) needs and a variety of different reagents carry out biological respinse and can fix on its surface Or gene molecule or nucleic acid molecules are carried, liquid speed degree is changed, liquid measure is changed, changes the liquid time, change liquid temperature, change liquid during load reagent Stationarity requires strict control, and chip is unable to ingress of air during replacing reagent, so chip loads reaction process It needs to carry out inside the locking device being especially tailored.By taking the load of gene nano sphere molecule (DNB) as an example, prior art It is a kind of closed DNB loading method of silicon wafer, each chip is carried out special processing in advance and encapsulates (chip front side first by this method Fixed position lid sets sheet glass, and edge glue dispensing and packaging makes internal formation runner, and wherein runner both ends, which correspond to, opens up feed liquor on chip Mouth and liquid outlet, and combined chip-glass piece is fixed using frame), DNB or reagent are connected to feed liquor by the chip after encapsulation Mouthful, the syringe drawing liquid through liquid outlet generates negative pressure, and reactant carries out biological respinse from inlet suction passage and after being full of, after Reactant is until the reaction is complete in continuous drawing liquid replacement runner.

The encapsulation process of above-mentioned silicon chip DNB loading method, each chip is complicated, and the precision of runner, leakproofness are wanted Ask high, the scrappage of chip is high when encapsulation；Auxiliary material (sheet glass, frame) demand is big simultaneously, at high cost；Moreover, often One chip is both needed to encapsulation process, is unfavorable for flexibly using, and especially chip is difficult to exclude after air inlet bubble, and packaged glass piece After be unfavorable for carrying out quickly, big throughput automated biological respinse.When especially sequence testing chip is large scale, is round, liquid is easily changed It is insufficient, limitation application.

Utility model content

In view of the foregoing, it is necessary to provide a kind of improved for several liquid reactants to be loaded on naked sequence testing chip On loading device and gene sequencing system, quick, big throughput automated biological respinse can be carried out, for round sequence testing chip It is abundant that liquid can still be changed, improve sequence testing chip utilization rate.

Technical solution provided by the utility model are as follows: a kind of loading device, for liquid reactant to be loaded on sequencing core On piece carries out biochemical reaction, including cover board and pedestal, and circular seal groove, the seal groove inside are opened up on the cover board bottom surface The flow path groove in the center of circle is passed through equipped with several, the cover board is bonded by being embedded in the sealing element of the seal groove with the sequence testing chip To form cavity, the flow path groove is equipped with liquid outlet and inlet, the inlet or the liquid outlet and fluid system Solenoid valve connection, the solenoid valve is for controlling liquid feeding and drain.

Further, the sealing element is bonded with the edge of the sequence testing chip.

Further, the end of each flow path groove is close to the seal groove.

Further, the flow path groove is equipped with 2, and right-angled intersection is in the center point.

Further, the point of intersection of the flow path groove is equipped with an inlet.

Further, the end of each flow path groove is equipped with the first liquid outlet.

Further, the second liquid outlet is equipped on the inside of the seal groove arc side midpoint between adjacent 2 the first liquid outlets.

Further, the inlet, first liquid outlet are used for the stream under the control of the corresponding solenoid valve The paving liquid of road slot changes liquid.

Further, the inlet, second liquid outlet are under the control of the corresponding solenoid valve for along described Flow path groove tiles liquid until being full of cavity.

Further, the pedestal is circle, and the base top surface offers arc groove and strip groove, and the strip groove is hung down The middle part of the arc groove is directly intersected at, the end line of the arc groove intersects with the strip groove.

The utility model further provides for a kind of gene sequencing system, impregnates reaction test system, packet for naked sequence testing chip Fluid system and the loading device are included, the fluid system includes solenoid valve, and the open and close of the solenoid valve are used In the feed liquor and liquid out that control the loading device.

Compared with prior art, provided by the utility model for several liquid reactants to be loaded on naked sequence testing chip Loading device, including cover board and pedestal open up circular seal groove on the cover board bottom surface, are equipped with number on the inside of the seal groove Item passes through the flow path groove in the center of circle, and the cover board is bonded by being embedded in the sealing element of the seal groove with the sequence testing chip to be formed Cavity, the flow path groove are equipped with liquid outlet and inlet, the solenoid valve of the inlet or the liquid outlet and fluid system Connection, the solenoid valve is for controlling liquid feeding and drain.The application of the device is not so that sequence testing chip needs at expensive encapsulation Reason, reactant can be loaded directly on naked sequence testing chip, and at low cost, it is convenient to operate, and loading procedure is simple, and efficiently, bubble-free is changed Liquid is steady；Liquid/paving liquid channel, which is changed, by subregion domain construction is remarkably improved overlarge area circle chip (greater than 30000mm²) The quality and efficiency of reagents loaded are conducive to the automatic biological reaction of quick, big flux；It can using its gene sequencing system Automatically differential responses agent is loaded on naked sequence testing chip, so that it is carried gene molecule or nucleic acid molecules, not only increases circle The utilization rate of sequence testing chip, reaction flux is big, expanded application.

Detailed description of the invention

Utility model will be further described in detail below with reference to the attached drawings and specific embodiments.

Fig. 1 is the perspective view of the loading device of one embodiment of the utility model.

Fig. 2 is the exploded view of loading device shown in FIG. 1.

Fig. 3 is another angle decomposition figure of loading device shown in FIG. 1.

Fig. 4 is the bottom view of cover board shown in FIG. 1.

Description of symbols:

The utility model embodiment that the following detailed description will be further explained with reference to the above drawings.

Specific embodiment

In order to be more clearly understood that the above objects, features, and advantages of the utility model embodiment, below with reference to attached The utility model is described in detail in figure and specific embodiment.It should be noted that in the absence of conflict, the application Embodiment in feature can be combined with each other.

Many details are explained in the following description in order to fully understand the utility model embodiment, it is described Embodiment be only a part of embodiment of the utility model, rather than whole embodiment.Based in the utility model Embodiment, every other embodiment party obtained by those of ordinary skill in the art without making creative efforts Formula belongs to the range of the utility model embodiment protection.

Unless otherwise defined, all technical and scientific terms used herein and belong to the utility model embodiment The normally understood meaning of those skilled in the art is identical.Terminology used in the description of the utility model herein It is only for the purpose of describing specific embodiments, it is not intended that in limitation the utility model embodiment.

Gene sequencing system, for detecting the sequence rule of the base-pair on gene molecule or nucleic acid molecules, analysis prediction disease Disease and risk.The system will be by that will be sequenced core dissolved with the different liquids reactant load of gene molecule or nucleic acid molecules On piece is sufficiently reacted, so that sequence testing chip surface carries several gene molecules or nucleic acid molecules main chain according to certain rules, then Group on each main chain is subjected to base pairing one by one, fluorescent marker, is taken pictures, to obtain complete sequence.It wherein will be molten It is primary committed step that solution, which has the different liquids reactant of gene molecule or nucleic acid molecules to be loaded on sequence testing chip, after determining The sequencing throughput and sequencing quality of phase.

Because sequence testing chip 50 needs and a variety of different reagents carry out biological respinse, existing pre-packaged chip loading method, envelope It is high and cumbersome to fill processing cost, scrappage is high, the utilization rate of sequence testing chip 50 is low, and can not prevent the entrance of bubble, will affect The progress (sequence testing chip 50 is unable to ingress of air in reaction) of biochemical reaction is unfavorable for quick, big throughput automated biological respinse. Easily to change liquid insufficient for the conventional liquid method of changing in the arc side area of especially circular sequence testing chip, so the utility model is set accordingly The loading device 100 of circular cover-plate type is counted.

The overall structure of the loading device 100 to the utility model is made into detailed elaboration below with reference to Fig. 1 to Fig. 4.

The device 100 carries out biochemical reaction for loading on liquid reactant on sequence testing chip, application is so that sequencing Chip 50 does not need expensive encapsulation process, and reactant can be loaded directly on naked sequence testing chip 50, and at low cost, it is convenient to operate.

Fig. 1 shows the main structure of the device 100, specifically includes that

Cover board 10 is covered on sequence testing chip 50, forms sealing structure with sequence testing chip 50；

Pedestal 30 supports sequence testing chip 50 from bottom；

Sequence testing chip 50 is placed between cover board 10 and pedestal 30, for round (being not shown in the figure, be sealed in inside).

For sealing structure is described in detail, integrally-built internal component shown in FIG. 1 is decomposed along longitudinal direction, such as Fig. 2 and Fig. 3 It is shown.

In present embodiment, which is successively arranged cover board 10, sealing element 11, sequencing core from top to bottom Piece 50, pedestal 30.

Referring to Figure 4 together, the cover board 10 is rectangular, and circular seal groove 15 is offered on bottom surface.This embodiment party In formula, 15 cross section of seal groove is circle, and longitudinal section is T-shaped structure, and the cross section of the corresponding sealing element 11 is also circle, Longitudinal section is T-shaped structure, in the embeddable seal groove 15 of sealing element 11；Meanwhile 11 bottom of sealing element contacts at the sequencing On the edge of chip 50, and the cover board 10 is locked with the pedestal 30 come regulating sealing gap, thus the lid by screw Plate 10, the sealing element 11, the sequence testing chip 50 form circular cavity, between the cover board 10 and the sequence testing chip 50 Gap control in the micron-scale (for the cavity of conventional vessel, the gap is minimum).

It is appreciated that the shape of the seal groove 15, sealing element 11 is not limited to present embodiment；The seal groove 15 Quantity is not limited to present embodiment；In other embodiments, the shape of the cavity is not limited to circle, can be arc Or other.In other embodiments, the sealing element 11 can be fitted on the inside of the edge of the sequence testing chip 50, it is only necessary to be sealed ?.

As shown in figure 4, being additionally provided with flow path groove 16 on 10 bottom surface of cover board, the flow path groove 16 is set to the seal groove 15 Inside, including several grooves across its center of circle, the end of each groove is close to the seal groove 15.In present embodiment, It is equipped with cross runner on the inside of seal groove 15, and is intersected in the center point, that is to say, that seal groove 15 is divided into 4 by flow path groove 16 A fan-shaped region, the effect of flow path groove 16 be effectively to exclude gas, and sequence testing chip 50 is contacted with air when avoiding changing liquid, and is drawn Drain body flow direction.

It is appreciated that the flow path groove 16 not necessarily straight groove, can be arc, involute etc., only need to be formed Cavity is simultaneously divided region by runner, and synchronous load can shorten waiting time, improve efficiency.

It is further seen that, the flow path groove 16 is equipped with inlet 161, each runner in center of circle intersection from Fig. 4 The end of slot 16 is respectively provided with 1 the first liquid outlet 162, the inlet 161 or first liquid outlet 162 by threaded hole and Pipeline is connected to the outside of the cover board 10.The inside at the 15 arc side midpoint of the seal groove between the first adjacent liquid outlet 162 Equipped with 1 the second liquid outlet 163.In present embodiment, there is 2 flow path grooves 16 to intersect vertically, center of circle point of intersection be equipped with 1 into Liquid mouth 161,4 ends of flow path groove 16 are respectively provided with 1 the first liquid outlet 162, any 2 the first adjacent liquid outlets 162 it Between be equipped with 1 the second liquid outlet 163, also have 4 in total.The inlet 161 or the liquid outlet (162,163) and fluid system The solenoid valve of system is connected to, and the solenoid valve is for controlling liquid feeding and drain.

It is appreciated that the quantity of the flow path groove 16, inlet 161, liquid outlet (162,163) is not limited to this embodiment party Formula can be divided into 5 regions or 6 regions or more such as when the area of chip is very big, need to only meet quick, abundant paving Liquid and change liquid.

As shown in figure 3, the pedestal 30 be it is rectangular, match with cover board 10.30 top surface of pedestal offers arc groove And strip groove, the strip groove are vertically intersected on the middle part of the arc groove, the end line of the arc groove and the bar shaped Slot intersection.

The sequence testing chip 50 is placed on the pedestal 30, and top surface is surrounded to form cavity by cover board 10 and sealing element 11.This In embodiment, sealing element 11 fits in the edge of sequence testing chip 50, and the sequence testing chip 50 of cavity sealing area is circle, described Sequence testing chip 50 is set to 30 interior surface of pedestal, and specifically, the strip groove is used to place the clamping piece of sequence testing chip 50, It is fixed on the back side of sequence testing chip 50 in a manner of adhesion, convenient for taking, does not pollute the survey for having loaded gene molecule or nucleic acid molecules 50 surface of sequence chip.

It is appreciated that sealing element 11 can fit on the inside of the edge of sequence testing chip 50, need to set depending on actual needs.

The liquid feeding process work of the loading device of the utility model 100 is further specifically illustrated below.

Step 1: for the first time when liquid feeding (paving liquid), opening corresponding solenoid valve, suck liquid, remove pipeline air；

Step 2: opening inlet 161, the corresponding solenoid valve of the first liquid outlet 162, and close in step 1 and be used to be vented Solenoid valve, liquid from inlet 161 flows to the first liquid outlet 162 along flow path groove 16 and full of flow path groove 16；

Step 3: when liquid reaches the first liquid outlet 162, closing the corresponding solenoid valve of the first liquid outlet 162, and open the The corresponding solenoid valve of two liquid outlet 163, liquid are that equably enclosed flows to the second liquid outlet 163 to starting point with flow path groove 16, directly To cavity is paved with, wait for fully reacting quietly.

The liquid process work that changes of the loading device of the utility model 100 is further specifically illustrated below.

Step 1: opening the solenoid valve for exhaust, suck new liquid, replace the liquid (waste liquid) reacted in pipeline；

Step 2: inlet 161, the corresponding solenoid valve of the first liquid outlet 162 are opened, and closes the solenoid valve for exhaust, Liquid flows to the first liquid outlet 162 along flow path groove 16, while waste liquid is extracted out or squeezed out from the first liquid outlet 162, arranges from pipeline Out；

Step 3: when liquid arrival first liquid outlet 162, closing the corresponding solenoid valve of the first liquid outlet 162, and open The corresponding solenoid valve of the second liquid outlet 163 is opened, liquid is starting point with flow path groove 16, and equably enclosed flows to the second liquid outlet 163, while waste liquid is extracted out or is squeezed out from the second liquid outlet 164, is discharged from pipeline, liquid to be changed is complete, closes the inlet 161 and the corresponding solenoid valve of second liquid outlet 163, wait for fully reacting quietly.

To sum up, using the loading procedure of the device, simply, efficiently, loading procedure bubble-free, it is steady to change liquid, by large area Liquid is changed in the fluid injection of chip subregion, and loading efficiency is high, load and reaction is more abundant, is conducive to the automatic biological of quick, big flux Reaction.

The gene sequencing system of the application provided by the utility model loading device 100, further includes fluid system, the stream System system is equipped with solenoid valve, and the solenoid valve is connect with the loading device；In present embodiment, the solenoid valve divides liquid feed valve And liquid valve, the liquid feed valve are connected into valve port with storage bottle, pump；The liquid feed valve goes out valve port and the inlet 161 with pipeline connection；Similarly, the liquid outlet (162,163), the liquid valve into valve port, the liquid valve go out valve port, Liquid pump, waste liquid bottle are conducted.

Various liquid reactants can be loaded on naked sequence testing chip 50 by the system automatically, not only increase sequence testing chip 50 Utilization rate, reaction flux it is big, can by large-area chips surface efficiently, sufficiently change liquid, extend round sequence testing chip 50 Using；And the needs of repeated authentication test can be realized in single, and testing efficiency is high, and test result is more acurrate；It automates simultaneously Loading procedure control, is designed, so that the systematic error of repeated loading is small, test result is more reliable in conjunction with seal cavity.

Embodiment of above is only to illustrate the technical solution of the utility model embodiment rather than limits, although referring to more than The utility model embodiment is described in detail in better embodiment, those skilled in the art should understand that, it can It is modified with the technical solution to the utility model embodiment or equivalent replacement should not all be detached from the utility model embodiment The spirit and scope of technical solution.

Claims (10)

1. a kind of loading device carries out biochemical reaction for loading on liquid reactant on sequence testing chip, it is characterised in that: packet Cover board and pedestal are included, circular seal groove is opened up on the cover board bottom surface, several is equipped on the inside of the seal groove and passes through the center of circle Flow path groove, the cover board are bonded with the sequence testing chip by being embedded in the sealing element of the seal groove to form cavity, the stream Road slot is equipped with liquid outlet and inlet, and the inlet or the liquid outlet are connected to the solenoid valve of fluid system, the electricity Magnet valve is for controlling liquid feeding and drain.

2. loading device according to claim 1, it is characterised in that: paste at the edge of the sealing element and the sequence testing chip It closes.

3. loading device according to claim 1, it is characterised in that: the end of each flow path groove is close to the sealing Slot.

4. loading device according to claim 3, it is characterised in that: the flow path groove is equipped with 2, and right-angled intersection is in the center of circle Place.

5. loading device according to claim 4, it is characterised in that: the point of intersection of the flow path groove is equipped with an inlet.

6. loading device according to claim 5, it is characterised in that: the end of each flow path groove is equipped with first and goes out liquid Mouthful.

7. loading device according to claim 6, it is characterised in that: the sealing between adjacent 2 the first liquid outlets The second liquid outlet is equipped on the inside of slot arc side midpoint.

8. loading device according to claim 7, it is characterised in that: the inlet, first liquid outlet are corresponding It is used for the paving liquid of the flow path groove under the control of the solenoid valve or changes liquid.

9. loading device according to claim 8, it is characterised in that: the inlet, second liquid outlet are corresponding For tiling liquid until being full of cavity along the flow path groove under the control of the solenoid valve.

10. a kind of gene sequencing system, it is characterised in that: including fluid system and such as any one of claims 1 to 9 institute The loading device stated, the fluid system include solenoid valve, and the open and close of the solenoid valve are for controlling the load dress The feed liquor set and liquid out.