CN209052673U - Loading device and gene sequencing system - Google Patents

Abstract

The utility model provides a kind of loading device and gene sequencing system, the device is used to several liquid reactants loading on naked sequence testing chip, including cover board and pedestal, fan-shaped seal groove is offered on the cover board bottom surface, flow path groove is equipped on the inside of the straight flange of the seal groove, the cover board is bonded the sequence testing chip by the edge of the seal groove and forms fan-shaped cavity, several liquid outlets are equipped on the inside of the seal groove arc side, the flow path groove is equipped with inlet close to central angle, the inlet or the liquid outlet are connected to the solenoid valve of fluid system, 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.

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, offers fan-shaped seal groove on the cover board bottom surface, the seal groove it is straight Flow path groove is equipped on the inside of side, the cover board is bonded the sequence testing chip by the edge of the seal groove and forms fan-shaped cavity, Be equipped with several liquid outlets on the inside of the seal groove arc side, the flow path groove is equipped with inlet close to central angle, the inlet or The liquid outlet is connected to the solenoid valve of fluid system, and the solenoid valve is for controlling liquid feeding and drain.

Further, the seal groove be equipped with several, the edge dispensing subregion of each seal groove, and with the sequencing Chip fitting.

Specifically, the seal groove is equipped with identical 4, and each radian is 90 °, and each seal groove is a quarter Circle, straight flange and the equal dispensing of arc side are closed, and are bonded with the sequence testing chip.

Further, the circle that the seal groove is encircled into is bonded with the edge of the sequence testing chip.

Further, the flow path groove is equipped with several, and each flow path groove is parallel with a straight flange of the seal groove, And both ends are respectively close to the central angle and an arc angle of the seal groove.

Further, the flow path groove is equipped with two to intersect vertically, and intersection point is equipped with a feed liquor close to the central angle Mouthful, the flow path groove is respectively equipped with the first liquid outlet and the second liquid outlet close to the end of the arc angle.

Further, third liquid outlet is equipped on the inside of the arc side midpoint of each seal groove.

Further, the inlet, first liquid outlet, second liquid outlet the corresponding solenoid valve control The lower paving liquid for being used for the flow path groove of system changes liquid.

Further, the inlet, the third 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 Include fluid system and the loading device, the fluid system electromagnetism connected with the automatic program control set The opening and closing of valve.

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 offer fan-shaped seal groove on the cover board bottom surface, on the inside of the straight flange of the seal groove Equipped with flow path groove, the cover board is bonded the sequence testing chip by the edge of the seal groove and forms fan-shaped cavity, described close Be equipped with several liquid outlets on the inside of sealing groove arc side, the flow path groove is equipped with inlet close to central angle, the inlet or it is described go out Liquid mouth is 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 so that sequencing Chip does not need expensive encapsulation process, and reactant can be loaded directly on naked sequence testing chip, and at low cost, it is convenient to operate, load Process is simple, and efficiently, it is steady to change liquid for bubble-free；Liquid/paving liquid channel, which is changed, by subregion domain construction is remarkably improved overlarge area circle Shape chip (is greater than 30000mm²) reagents loaded quality and efficiency, be conducive to quick, big flux automatic biological reaction； Differential responses agent can be loaded on naked sequence testing chip automatically using its gene sequencing system, it is made to carry gene molecule or core Acid molecule not only increases the utilization rate of round sequence testing chip, and 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 partial enlarged view of cover board shown in Fig. 2.

Description of symbols:

Loading device	100
		Cover board	10
Glue	11
		Seal groove	15
Flow path groove	16
		Inlet	161
First liquid outlet	162
		Second liquid outlet	163
Third liquid outlet	164
		Pedestal	30
Sequence testing chip	50

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 10,50 (edge of sequence testing chip from top to bottom Glue 11 be bonded), pedestal 30.

Referring to Figure 4 together, the cover board 10 is rectangular, and seal groove 15 is offered on bottom surface.It is close in present embodiment Sealing groove 15 is the fan-shaped groove on 10 bottom surface of cover board, which is equipped with 4, each is in the circle (sector) of a quarter, arc Angle is 90 °, is encircled into circle, and the corresponding glue 11 is circular ring shape, and intermediate provided with cross, and glue 11 is set to 4 sealings On the profile of slot 15, and its bottom contacts at the edge and centre of the sequence testing chip 50, thus the cover board 10, the sequencing Chip 50, the seal groove 15, the fitting of the glue 11 form 4 independent fan-shaped cavitys, the cover board 10 and the sequencing core Gap control between piece 50 is in the micron-scale (for the cavity of conventional vessel, the gap is minimum).The glue 11 and institute Adhesion between sequence testing chip 50 is stated, does not influence the sequencing reaction etc. of the subsequent sequence testing chip 50.

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

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 Straight flange on the inside of.In present embodiment, it is equipped with runner on the inside of each 15 straight flange of seal groove, and is intersected at central angle and forms 1 Right angle flow path groove 16, that is to say, that flow path groove 16 is equipped with 4, contains 1 in the seal groove 15 of each sector, each is at L Shape；Close to the central angle and arc angle of the seal groove 15, the effect of flow path groove 16 is effectively to arrange for the end of the flow path groove 16 Except gas, sequence testing chip 50 is contacted with air when avoiding changing liquid, and liquid is guided to flow to.

It is further seen that, each flow path groove 16 is equipped with inlet 161 close to the end of central angle, each from Fig. 2 The flow path groove 16 is equipped with the first liquid outlet 162 and the second liquid outlet 163, the inlet 161 or institute close to the end of arc angle State the outside that liquid outlet is connected to the cover board 10 by threaded hole with pipeline.Arc of each seal groove 15 far from the flow path groove 16 Third liquid outlet 164 is equipped on the inside of the midpoint of side.In present embodiment, 1 161 He of inlet is equipped in each seal groove 15 3 liquid outlets (162,163,164) and 1 flow path groove 16, the inlet 161 or the liquid outlet (162,163,164) It is connected to the solenoid valve of fluid system, the solenoid valve is for controlling liquid feeding and drain.Correspondingly glue 11 is equipped with 1, is annulus Shape, centre are cross, are the profile dispensing in seal groove 15 in practical operation, are bonded after cured with sequence testing chip 50.

It is appreciated that the quantity of liquid outlet (162,163,164) is not limited to present embodiment；In other embodiments In, the position of the inlet 161, quantity are not limited to present embodiment.

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 glue 11.This implementation In mode, glue 11 fits in the edge of sequence testing chip 50, and the sequence testing chip 50 of cavity sealing area is circle, the sequence testing chip 50 are set to 30 interior surface of pedestal, and specifically, the strip groove is used to place the clamping piece of sequence testing chip 50, with adhesion side Formula is fixed on the back side of sequence testing chip 50, convenient for taking, does not pollute the sequence testing chip 50 for having loaded gene molecule or nucleic acid molecules Surface.

It is appreciated that glue 11 can fit on the inside of the edge of sequence testing chip 50, 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 first liquid outlet 162, the corresponding solenoid valve of the second liquid outlet 163, and close step The solenoid valve for exhaust in rapid 1, liquid flow to the first liquid outlet 162 and second along flow path groove 16 from inlet 161 and go out liquid Mouth 163；

Step 3: when liquid is full of flow path groove 16, the first liquid outlet 162 of closing and the corresponding electromagnetism of the second liquid outlet 163 Valve, and open the corresponding solenoid valve of third liquid outlet 164, liquid are that starting point equably tiles, flows to third and go out with flow path groove 16 Liquid mouth 164 waits for fully reacting quietly until being paved with.

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: opening inlet 161, the first liquid outlet 162, the corresponding solenoid valve of the second liquid outlet 163, and close and use In the solenoid valve of exhaust, liquid flows to the first liquid outlet 162 and the second liquid outlet 163 along flow path groove 16, while waste liquid is from first It extracts out or squeezes out in liquid outlet 162 and the second liquid outlet 163, be discharged from pipeline；

Step 3: when liquid reaches first liquid outlet 162 and the second liquid outlet 163, closing 162 He of the first liquid outlet The corresponding solenoid valve of second liquid outlet 163, and the corresponding solenoid valve of third liquid outlet 164 is opened, liquid is with flow path groove 16 Point equably tiles, flows to third liquid outlet 164, while waste liquid is extracted out or squeezed out from third liquid outlet 164, arranges from pipeline Out, liquid to be changed is complete, closes the inlet 161 and the corresponding solenoid valve of the third liquid outlet 164, waits 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 The opening and closing of solenoid valve 40 described in automatic program control of the system system by setting；

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 (9)

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, fan-shaped seal groove is offered on the cover board bottom surface, is equipped with flow path groove, institute on the inside of the straight flange of the seal groove It states cover board and the cavity that the sequence testing chip forms sector is bonded by the edge of the seal groove, set on the inside of the seal groove arc side There are several liquid outlets, the flow path groove is equipped with inlet, the inlet or the liquid outlet and fluid system close to central angle Solenoid valve connection, the solenoid valve is for controlling liquid feeding and drain.

2. loading device according to claim 1, it is characterised in that: the seal groove is equipped with several, each sealing The edge dispensing subregion of slot, and be bonded with the sequence testing chip.

3. loading device according to claim 2, it is characterised in that: the circle and the sequencing core that the seal groove is encircled into The edge of piece is bonded.

4. loading device according to claim 1, it is characterised in that: the flow path groove is equipped with several, each stream Road slot is parallel with a straight flange of the seal groove, and both ends are respectively close to the central angle and an arc angle of the seal groove.

5. loading device according to claim 4, it is characterised in that: the flow path groove is equipped with two to intersect vertically, hands over Point is equipped with an inlet close to the central angle, and the flow path groove is respectively equipped with first close to the end of the arc angle and goes out liquid Mouth and the second liquid outlet.

6. loading device according to claim 5, it is characterised in that: be equipped with third on the inside of the arc side midpoint of each seal groove Liquid outlet.

7. loading device according to claim 6, it is characterised in that: the inlet, first liquid outlet, described Two liquid outlets for the paving liquid of the flow path groove or change liquid under the control of the corresponding solenoid valve.

8. loading device according to claim 7, it is characterised in that: the inlet, the third liquid outlet are corresponding For tiling liquid until being full of cavity along the flow path groove under the control of the solenoid valve.

9. a kind of gene sequencing system, it is characterised in that: including fluid system and as described in any one of claims 1 to 8 Loading device, the fluid system is with the opening and closing of the connected solenoid valve of the automatic program control that sets.