CN209065879U

CN209065879U - Sequence Detection System

Info

Publication number: CN209065879U
Application number: CN201821236750.9U
Authority: CN
Inventors: 吴平; 颜钦; 姜泽飞; 周志良
Original assignee: SHENZHEN HANHAI GENE BIOTECHNOLOGY CO Ltd
Current assignee: Genemind Biosciences Co Ltd
Priority date: 2018-08-01
Filing date: 2018-08-01
Publication date: 2019-07-05
Anticipated expiration: 2028-08-01

Abstract

The utility model discloses a kind of Sequence Detection Systems, Sequence Detection System includes control device, fluid means and imaging device, control device is for controlling imaging device and fluid means, fluid means includes valve component and driving assembly, valve component includes rotary valve, rotary valve includes the stator and rotor that can be connected to, rotary valve has common port, there are multiple ports on stator, there is connectivity slot on rotor, rotor, which can rotate, is connected to common port by connectivity slot with a port, multiple ports include first group of port and second group of port, first group of port includes first port and second port, first port connects the first reagent, second port connects the second reagent, second group of port includes third port and the 4th port, first port, second port, third port and the 4th port be by rotor preset rotation direction successively Arrangement, third port connect the first reagent, and the 4th port connects the second reagent, and common port connects reaction unit.

Description

Sequence Detection System

Technical field

The utility model relates to sequencing technology field more particularly to a kind of Sequence Detection Systems.

Background technique

Sequencing is sequenced, the measurement including nucleic acid sequence.Microarray dataset on the market includes that generation sequencing is flat at present Platform, two generation microarray datasets and three generations's microarray dataset.

Using the platform for carrying out sequence based on biochemical reaction during sequencing, need on reaction unit Biochemical reaction is carried out, such as needs to introduce different reagents on chip together or successively using liquid channel system and react. Currently, to make the liquid channel system compact efficient in platform, liquid channel system is all made of valve body to switch input/output reagent.

Currently, reagent needed for biochemical reaction is more, the even micro intersection of the intersection of some reagents may be serious Influence reaction progress perhaps reaction as a result, the cross contamination for therefore how avoiding or reducing between different reagents becomes Problem to be solved.

Utility model content

Inventors have found that using the fluid path with commercially available rotary valve in order to every kind of reagent in plurality of reagents successively into When row input and output, the influence of pipeline residual is excluded, can always have a kind of a certain amount of reagent in a kind of lower reagent, it is right It is impacted by the reaction of reagent a kind of under this.To solve this problem, based on the fractionation research below to the structure of rotary valve It was found that, imagine and test, inventor makes the utility model.

Rotary valve on the market, also referred to as sampling valve, multiposition valve or revolving valve at present, as sample acquisition, Liquid sample introduction Or the component of flow path conversion etc..Its composition generally comprises stator and rotor, by combining closely for stator and rotor, is capable of forming Effectively sealing.

Generally, rotary valve has common port, and common port is the port that different flow path liquid into or out can all pass through, public Mouth is located on stator and/or rotor, has one or more of the other port on stator and/or rotor.Pass through the rotation of rotor, energy The connection for enough realizing rotor and stator access selects sample introduction or shunting to reach to be connected to common port and other ports Function.General configuration/standard configurations of rotary valve be multi-pass selection type, i.e., in the process of running, only a port with it is public Mouth connection.

Common port is connected to other ports, generally require one or several public structures by being arranged on rotor come Connection.When having liquid in the public structure, the seal interface that is connected due to the rotation of rotor, rotor and stator it is relatively living Dynamic, inevitably at least part liquid in public structure can be brought to the place except public structure, i.e., turn in flow path When changing, can inevitably make in next flow path liquid have a upper flow path liquid, and if subsequent opposite direction flow path convert, again The next flow path liquid for being mixed with a flow path liquid can be made to be brought in the liquid of lower flow path；In this way, the cross contamination generated It is difficult to control, influences to be difficult to estimate.Herein, deserving to be called " the public structure " stated is connectivity slot.

For this purpose, the utility model embodiment provides a kind of pair of Sequence Detection System.

A kind of Sequence Detection System of the utility model embodiment controls sequencing reaction, and sequence is surveyed Fixed reaction carries out on reaction unit, and reaction unit is placed in removable microscope carrier, sequencing reaction include the first sequencing reaction and Second sequencing reaction, Sequence Detection System include control device, fluid means and imaging device, control device connecting fluid device And imaging device, for control device for controlling imaging device and fluid means, fluid means includes valve component and driving assembly, Valve component includes rotary valve, and rotary valve includes the stator and rotor that can be connected to, and rotary valve has common port, has on stator more A port has connectivity slot on rotor, and rotor, which can rotate, is connected to common port by connectivity slot with a port, multiple ports First group of port and second group of port including respectively corresponding the first sequencing reaction and the second sequencing reaction, first group of port includes First port and second port, first port connect the first reagent of the first sequencing reaction base extension, second port connection Second reagent of excision, second group of port include third port and the 4th port, first port, second port, third port It is to be arranged successively by the preset rotation direction of rotor with the 4th port, third port connects the second sequencing reaction base extension First reagent, the 4th port connect the second reagent, and common port connects reaction unit.

In above system, the stator and rotor that can be connected to by rotary valve, so that the first reagent and the second reagent can be in sequences The different phase of column measurement reaction is passed through into reaction unit, and therefore, the system is by simple apparatus structure and control liquid Body disengaging sequence, can largely reduce the pollution between different type substrate or between different substrate combinations.

The additional aspect and advantage of the utility model embodiment will be set forth in part in the description, partially will be under Become obvious in the description in face, or is recognized by the practice of the utility model embodiment.

Detailed description of the invention

The above-mentioned and/or additional aspect and advantage of the utility model embodiment are from combination following accompanying drawings to embodiment Description in will be apparent and be readily appreciated that, in which:

Fig. 1 is the flow diagram for the method for the utility model embodiment controlled sequencing reaction；

Fig. 2 is the flow passage structure schematic diagram of the Sequence Detection System of the utility model embodiment；

Fig. 3 is another flow passage structure schematic diagram of the Sequence Detection System of the utility model embodiment；

Fig. 4 is the port of the rotary valve of the utility model embodiment and the relation schematic diagram of common port；

Fig. 5 is the port of the rotary valve of the utility model embodiment and another relation schematic diagram of common port；

Fig. 6 is the port of the rotary valve of the utility model embodiment and the another relation schematic diagram of common port；

Fig. 7 is the functional block diagram of the Sequence Detection System of the utility model embodiment.

Specific embodiment

The embodiments of the present invention is described below in detail, the example of the embodiment is shown in the accompanying drawings, wherein Same or similar label indicates same or similar element or element with the same or similar functions from beginning to end.Lead to below It crosses the embodiment being described with reference to the drawings to be exemplary, is only used for explaining the utility model, and should not be understood as practical to this Novel limitation.

In the description of the present invention, it should be understood that term " first ", " second " are used for description purposes only, and It cannot be understood as indicating or implying relative importance or implicitly indicate the quantity of indicated technical characteristic.It defines as a result, The feature of " first ", " second " can explicitly or implicitly include one or more feature.In the utility model Description in, the meaning of " plurality " is two or more, unless otherwise specifically defined.

In the description of the present invention, it should be noted that unless otherwise clearly defined and limited, " connection " should be done It broadly understood, for example, it may be being fixedly connected, may be a detachable connection, or be integrally connected；It can be mechanical connection, It is also possible to be electrically connected or can be in communication with each other；It can be directly connected, can also can be indirectly connected through an intermediary The interaction relationship of connection or two elements inside two elements.It for the ordinary skill in the art, can be with The concrete meaning of above-mentioned term in the present invention is understood as the case may be.

Following disclosure provides many different embodiments or example is used to realize the different structure of the utility model. In order to simplify the disclosure of the utility model, hereinafter to the component of specific examples and being set for describing.In addition, the utility model Can in different examples repeat reference numerals and/or reference letter, this repetition be for purposes of simplicity and clarity, Body does not indicate the relationship between discussed various embodiments and/or setting.

So-called " sequencing " the same determining nucleic acid sequence of the utility model embodiment, including DNA sequencing and/or RNA Sequencing, including long segment sequencing and/or short-movie section sequencing.So-called " sequencing reaction " same to sequencing reaction.Generally, in core In the measurement of acid sequence, a base can be measured by a wheel sequencing reaction, alleged base in A, T, C, G and U extremely Few one kind.In the sequencing reaction for being sequenced in synthesis and/or being sequenced in connection, so-called sequencing reaction includes extension (base extension), information collect (/ Image Acquisition of taking pictures) and group excision (cleave).So-called " nucleotide analog " i.e. bottom Object, also referred to as terminator (terminator) are the analog of A, T, C, G and/or U, can follow base complementrity principle and spy Determine the base pairing of type while can terminate on next nucleotide/Binding Capacity to template strand.

It please join Fig. 1, Fig. 2 and Fig. 3, the utility model embodiment provides a kind of pair of sequencing and reacts the side controlled Method, sequencing reaction carry out on reaction unit 40, and reaction unit 40 can be placed in removable microscope carrier 80, utilize sequencing system System controls sequencing reaction, and sequencing reaction includes that the first sequencing reaction that sequence carries out and the second sequencing are anti- Answer, the first sequencing reaction and the second sequencing reaction include the steps that following sequence carries out: base extends, Image Acquisition and cuts It removes.

Using the progress base extension of the first reagent, the first reagent of the first sequencing reaction and the second sequencing reaction is not identical, It is cut off using the second reagent.Alleged first reagent includes at least one nucleotide analog, alleged nucleotide analog packet Include the analog of following several nucleotides: adenyl-deoxyribonucleotide (A), thymidylic acid (T), cytimidine deoxidation Nucleotide (C), guanine deoxyribonucleoside sour (G) and uracil deoxynucleotide (U).

Sequence Detection System includes fluid means 100, and fluid means 100 includes valve component 29 and driving assembly 50.Valve Body component 29 includes rotary valve 70, and rotary valve 70 includes the stator 81 and rotor that can be connected to, and rotary valve 70 has common port 71, fixed There are multiple ports on son 81, there is connectivity slot 72 on rotor, common port 71 and a port can be made to connect by rotating rotor Logical, multiple ports include the first group of port and second group of port for respectively corresponding the first sequencing reaction and the second sequencing reaction, the One group of port includes first port 1 and second port 2, and first port 1 connects the first reagent of the first sequencing reaction, second port 2 the second reagents of connection, second group of port includes third port 3 and the 4th port 4, first port 1, second port 2, third port 3 and the 4th port 4 be arranged successively by the preset rotation direction of rotor, third port 3 connect the second sequencing reaction first examination Agent, the 4th port 4 connect the second reagent, common port 71 connect reaction unit 40, method comprising steps of

I), first port 1 is connected to common port 71 using driving assembly 50, pass through the first reagent of the first sequencing reaction Rotary valve 70 enters reaction unit 40, to realize that the base of the first sequencing reaction extends；

Ii), second port 2 is connected to common port 71 using driving assembly 50, enter the second reagent through rotary valve 70 Reaction unit 40, to realize the excision of the first sequencing reaction；

Iii), third port 3 is connected to common port 71 using driving assembly 50, make the first reagent of the second sequencing reaction Enter reaction unit 40 through rotary valve 70, to realize that the base of the second sequencing reaction extends；

Iv), the 4th port 4 is connected to common port 71 using driving assembly 50, enter the second reagent through rotary valve 70 Reaction unit 40, to realize the excision of the second sequencing reaction.

In the above method, before the first reagent for making the second sequencing reaction enters reaction unit 40 through rotary valve 70, lead to The rotation in one direction of rotor is crossed, so that connectivity slot 72 is connected to first port 1 to input the first reagent of the first sequencing reaction, connects Rotation switching make link slot 72 be connected to second port 2 to input the second reagent, in connectivity slot 72 and connectivity slot can be made Wholly or largely first sequencing reaction in the sealing surface region 73 being brought to because of rotation between rotor and stator 81 in 72 The first reagent substituted by the second reagent, the first reagent that high degree reduces the first sequencing reaction is brought to the second sequencing Reaction, while the first reagent for also avoiding the second sequencing reaction will not be brought in the first reagent of the first sequencing reaction, It avoids or high degree reduces cross contamination between different first reagents.This method is for needing to control in each round The sequencing reaction of different type substrate or different substrate combinations is added in sequence, and particularly suitable, this method relies on simple device Structure and control liquid disengaging sequence, can largely reduce between different type substrate or different substrate combinations it Between pollution.

Specifically, when carrying out the base extension of the first sequencing reaction, connectivity slot 72 is connected to first port 1 and common port 71, And then first port 1 is made to be connected to reaction unit 40, make the first reagent of the first sequencing reaction through rotary valve using driving assembly 50 70 enter in reaction unit 40 the base extension for carrying out the first sequencing reaction.Connection is flowed through in the first reagent of the first sequencing reaction The first reagent of the first sequencing reaction can be remained when slot 72, in connectivity slot 72.Later, using driving assembly 50 along default rotation Direction rotor is so that connectivity slot 72 is connected to second port 2 and common port 71, and then second port 2 is made to be connected to reaction unit 40.When carrying out the excision of the first sequencing reaction, the second reagent is set to enter reaction unit 40 through rotary valve 70 using driving assembly 50 The interior excision for carrying out the first sequencing reaction.On the one hand, it rotates in a one way-direction in rotor connectivity slot 72 is connected to first port 1 When switching to connection second port 2, first reagent a part of the first sequencing reaction in connectivity slot 72 can remain in rotor and Sealing surface region 73 (region as shown in Figure 4) between stator 81, on the other hand, the second reagent of excision flows through connectivity slot When 72, first reagent another part of the first sequencing reaction in connectivity slot 72 can entirely or partly be taken away.In this way, utilizing Simple device and liquid input and output control can be greatly decreased the first reagent strip of the first sequencing reaction to the second sequencing Pollution caused by first reagent of reaction can be avoided first examination of first reagent to the first sequencing reaction of the second sequencing reaction It is polluted caused by agent.

In some embodiments, reaction unit 40 can be chip, be equipped with plurality of passages (channel) in reaction unit 40 To accommodate sample.Driving assembly 50 may include motor and pump, and motor connection rotor simultaneously is used to drive rotor rotation so that connectivity slot Different port on 72 connection stators 81.Pump connection reaction unit 40, and for generating negative pressure in the channel of reaction unit 40 To drive reagent to enter in reaction unit 40 and siphon away reagent out of reaction unit 40, and stop generating negative pressure, so that reagent It stays in and carries out biochemical reaction in reaction unit 40.In addition, the reagent being pumped away can be recycled by being pumped into waste fluid container 60. Removable microscope carrier 80 can drive reaction unit 40 to carry out in the movement of the direction XY of diagram with the different zones for adjusting reaction unit 40 Image Acquisition.Removable microscope carrier 80 can also drive reaction unit 40 to move upwards in the side perpendicular to X/Y plane, to adjust image Object distance when acquisition.

In the utility model embodiment, rotor preset rotation direction is Fig. 2 and clockwise direction shown in Fig. 3.? That is the movement of rotary valve 70, when Yao Liantong second port 2, needs first to be connected to first port 1, Yao Liantong third port 3 When need first to be connected to second port 2 etc..It is appreciated that in other embodiments, rotor preset rotation direction can be other Direction, counter clockwise direction as shown in Figures 2 and 3, port can be selected from multiple ports again according to direction of rotation, herein not Make concrete restriction.

In some embodiments, incorporated by reference to Fig. 4, based on the rotary valve with multiple ports, include in conjunction with sequencing reaction The step of feed liquor sequence, keep first port 1 and second port 2 adjacent, second port 2 and third port 3 are adjacent, third port 3 and the 4th port 4 it is adjacent, can be realized and while avoiding or be greatly decreased the cross contamination between the first reagent rotor is revolved The stroke turned is shorter, convenient for quickly sequencing.It is appreciated that in other embodiments, first port 1, second port 2, third Other ports of multiple ports also may be selected in port 3 and the 4th port 4, need to only guarantee first port 1, second port 2, third end The 3 and the 4th 6 port 4 of mouth is arranged successively by rotor preset rotation direction.

Carry out sequencing reaction base extend, Image Acquisition and excision when, rotor along preset rotation direction rotate with according to The secondary operation completing different reagents and entering in reaction unit 40 through rotary valve 70.

In addition, in some embodiments, DNA is sequenced, reaction substrate A, T, C are similar with tetra- kinds of nucleotide of G Object, at least there are three types of substrates to have at least one fluorescent marker (fluorescent dye/luminophore) in four kinds of substrates, polymerize anti- Answer/base extension when, when on Binding Capacity to DNA template chain, under the excitation of specific wavelength laser, can issue glimmering Light, Sequence Detection System be based on conversion and/or acquire these optical signals and not same substrate order of addition (if having) with measure DNA sequence dna.In a specific example, there are two types of fluorescent marker, both of which therein to have a kind of fluorescence mark for four kinds of substrate bands Note, in addition both of which has another fluorescent marker, and the first reagent of the first sequencing reaction is the reagent comprising two kinds of substrates, should Two kinds of substrates in first reagent have different fluorescent markers, and the first reagent of the second sequencing reaction is to include other two kinds of bottoms The reagent of object, for two kinds of substrates in first reagent with different fluorescent markers, a wheel sequencing reaction includes the first sequencing Reaction and the second sequencing reaction, the first sequencing reaction carry out carrying out after the completion of the second sequencing reaction, the second sequencing reaction after the completion First sequencing reaction, is repeated by this.Reaction is flowed into the reaction substrate that control extends the base of the second sequencing reaction When in device 40, it will need to add again after the luminophore excision on the reaction substrate (terminator) of the base of the first sequencing reaction extension The terminator for adding the base of the second sequencing reaction to extend.For example, making the first of the first sequencing reaction to try incorporated by reference to above-mentioned example After agent is input in reaction unit 40, Image Acquisition can be carried out to reaction unit 40.It, need to be by the first sequencing after the completion of Image Acquisition The first reagent of the second sequencing reaction is added after the luminophore excision of first reagent of reaction again.

In some embodiments, incorporated by reference to Fig. 2 and Fig. 3, multiple port distributions are rounded, common port 71 and circular shape concentric Setting.In this way, connectivity slot when multiple ports of rounded distribution and common port 71 and circular shape concentric setting ensure that rotor 72 accuracys being connected to corresponding port and common port 71.

In some embodiments, incorporated by reference to Fig. 2 and Fig. 3, connectivity slot 72 is in linear.It is being connected in this way, agent liquid can be reduced Flow path in slot 72, and then realize and guarantee quickly sequencing.It specifically, can be with shorter path in linear connectivity slot 72 Connection is located at port and the common port 71 at 72 both ends of connectivity slot.In the utility model example, linear is linear.

In some embodiments, valve component includes the first valve 30, and second port 2 passes through the first valve 30 and the second reagent It is connected, the 4th port 4 is connected by the first valve 30 with the second reagent.In this way, the second reagent can be provided to different ports, subtract Pipeline connection is lacked, has simplified the fluid path in Sequence Detection System, has been conducive to problem investigation maintenance, is conducive to industrial production.

In the utility model embodiment, the first valve 30 includes a total mouth and multiple points of mouths, it will be understood that the first valve 30 quantity for dividing mouth quantity to be no less than sequencing reaction, for example, the first valve 30 divides mouth number when the quantity of sequencing reaction is 2 Amount no less than 2.

For example, the first valve 30 includes a Zong Kou and four points of mouths, that is to say, that one in the utility model example First valve 30 can provide the second reagent to most four sequencing reactions.Specifically, in the utility model example, the first valve 30 Four points of mouths be separately connected second port 2, the 4th port 4, the 14th port 14 and the 16th port 16, the first valve 30 it is total Mouth the second reagent of connection.Therefore, when connectivity slot 72 is connected to common port 71 and corresponding port, second examination of the driving of driving assembly 50 Agent flows through the first valve 30 and rotary valve 70 enters reaction unit 40.

In some embodiments, Sequence Detection System includes imaging device, method comprising steps of using imaging device into Row Image Acquisition.In this way, Sequence Detection System can facilitate user to carry out Image Acquisition to the sample in reaction unit 40.

Specifically, imaging device may include light emitting device and camera.By taking the first sequencing reaction and the second sequencing reaction as an example, When in the first reagent to reaction unit 40 for having added the first sequencing reaction, issues and swash using light emitting device (such as laser) Shine to reaction unit 40, to excite luminophore to issue fluorescence, and taken pictures using camera to acquire fluorescence, and formed image with Carry out sequencing.After the completion of taking pictures, the second reagent is added so that the will be added again after the luminophore excision in reaction unit 40 First reagent of two sequencing reactions, then carry out the Image Acquisition of the second sequencing reaction.

In some embodiments, Image Acquisition is carried out using third reagent, first group of port includes by default rotation side To the first port 1, fifth port 5 and second port 2 being arranged successively, second group of port includes successively arranging by preset rotation direction Third port 3, the 6th port 6 and the 4th port 4 of column, method include: carry out i) after and carry out ii) before, utilize Driving assembly 50 is connected to fifth port 5 with common port 71, and third reagent is made to enter reaction unit 40 through rotary valve 70, to realize The Image Acquisition of first sequencing reaction；Carry out iii) after and carry out iv) before, make the 6th port using driving assembly 50 6 are connected to common port 71, and third reagent is made to enter reaction unit 40 through rotary valve 70, to realize that the image of the second sequencing reaction is adopted Collection.

The presence of third reagent makes the sample in reaction unit 40 can be by preferably acquisition figure after base extension Picture.Specifically, third reagent can reduce the photobleaching effect of sample and/or resist and is quenched, the band that the first reagent can be made to include It after the Binding Capacity to template strand of luminophore, under the excitation of laser, shines more stable, is conducive to Image Acquisition, especially singly The acquisition of a molecule tiny signal.

Specifically, in some embodiments, when sequencing reaction includes the first sequencing reaction and that sequence carries out When two sequencing reactions, incorporated by reference to Fig. 2 and Fig. 3, first port 1, fifth port 5, second port 2, third port 3, the 6th port 6 It is arranged successively with the 4th port 4 by preset rotation direction.In base extension, Image Acquisition and the excision for carrying out sequencing reaction, Rotor is sequentially completed the operation that different reagents enter through rotary valve 70 in reaction unit 40 along preset rotation direction rotation.

In some embodiments, the first sequencing reaction and the second sequencing reaction include the steps that following sequence carries out: Base extension, the first washing, Image Acquisition and excision.In this way, the first reagent remained in connectivity slot 72 can be mostly It is taken away by the first washing, further reduces the cross contamination of the first reagent of different sequencing reactions.

In some embodiments, the first washing is carried out using the 4th reagent, first group of port includes by default rotation side To first port 1, the 7th port 7 and the second port 2 being arranged successively, second group of port includes successively arranging by preset rotation direction Third port 3, the 8th port 8 and the 4th port 4 of column, method include: carry out i) after and carry out ii) before, utilize Driving assembly 50 is connected to the 7th port 7 with common port 71, and the 4th reagent is made to enter reaction unit 40 through rotary valve 70, to realize First washing of the first sequencing reaction；Carry out iii) after and carry out iv) before, make the 8th port using driving assembly 50 8 are connected to common port 71, and the 4th reagent is made to enter reaction unit 40 through rotary valve 70, to realize that the first of the second sequencing reaction washes It washs.

For the first sequencing reaction, rotated by preset rotation direction in rotor so that connectivity slot 72 is from connection first port 1 When switching to seven port 7 of connection, the first reagent of the first sequencing reaction can largely remain between rotor and stator 81 Sealing surface region, greatly reduce the first reagent of the first sequencing reaction and the first reagent of the second sequencing reaction intersects dirt Dye.

It should be pointed out that the 4th reagent is the cleaning agent on target sequencing reaction without influence.

In some embodiments, the first sequencing reaction and the second sequencing reaction include the steps that following sequence carries out: Base extension, the first washing, the second washing, Image Acquisition and excision.In this way, the first reagent remained in connectivity slot 72 can It is mostly taken away by the first washing, further reduces the cross contamination of the first reagent of different sequencing reactions, meanwhile, second Washing step is buffer to be added, and so-called buffer is that can maintain liquid pH value in the solution of particular range to a certain degree, For weak acid, weak base and/or neutral solution.In some embodiments, buffer is solution of the target sequencing reaction without influence.

In some embodiments, the first washing is carried out using the 4th reagent, carries out the second washing using the 5th reagent, the One group of port includes the first port 1 being arranged successively by preset rotation direction, the 7th port 7, the 9th port 9 and second port 2, Second group of port includes the third port 3 being arranged successively by preset rotation direction, the 8th port 8, the tenth port 10 and the 4th end Mouth 4, method include: before washing after carrying out i) with progress second, to make the 7th port 7 and common port 71 using driving assembly 50 Connection makes the 4th reagent enter reaction unit 40 through rotary valve 70, to realize the first washing of the first sequencing reaction；

After carry out first is washed and before progress ii), connect the 9th port 9 and common port 71 using driving assembly 50 It is logical, so that the 5th reagent is entered reaction unit 40 through rotary valve 70, to realize the second washing of the first sequencing reaction；

Carrying out iii) later and before the second washing of progress, make the 8th port 8 and common port 71 using driving assembly 50 Connection makes the 4th reagent enter reaction unit 40 through rotary valve 70, to realize the first washing of the second sequencing reaction；

After carry out first is washed and before progress iv), make the tenth port 10 and common port 71 using driving assembly 50 Connection makes the 5th reagent enter reaction unit 40 through rotary valve 70, to realize the second washing of the second sequencing reaction.

For the first sequencing reaction, rotated by preset rotation direction in rotor so that connectivity slot 72 is from connection first port 1 When switching to seven port 7 of connection, the first reagent of the first sequencing reaction can largely remain between rotor and stator 81 Sealing surface region, further, rotor by preset rotation direction rotate so that connectivity slot 72 from connection 7 company of switching to of the 7th port When logical nine port 9, the first reagent of the first sequencing reaction can further remain in the sealing surface area between rotor and stator 81 Domain, and then the cross contamination of the first reagent of the first sequencing reaction and the first reagent of the second sequencing reaction is greatly reduced.

In some embodiments, it is mesh that the 4th reagent, which is cleaning agent and the 5th reagent on target sequencing reaction without influence, Mark buffer of the sequencing reaction without influence.

In some embodiments, the first sequencing reaction and the second sequencing reaction include the steps that following sequence carries out: Base extension, Image Acquisition, excision and capped.

Specifically, the group/key being exposed after so-called capped predominantly blocking group excision.In one example, Can be sulfydryl by the group after luminophore that light and/or chemical ablation can be broken, being exposed, by it is capped as by plus Enter alkylating reagent, sulfydryl can be protected not oxidized.

In some embodiments, be capped using the 6th reagent, first group of port include by preset rotation direction according to First port 1, second port 2 and the tenth Single port 11 of secondary arrangement, second group of port include successively arranging by preset rotation direction Third port 3, the 4th port 4 and the tenth Two-port netwerk 12 of column, method include: to carry out ii) later and before progress iii), benefit The tenth Single port 11 is connected to common port 71 with driving assembly 50, and the 6th reagent is made to enter reaction unit 40 through rotary valve 70, To realize the capped of the first sequencing reaction；Carrying out iv) after, make the tenth Two-port netwerk 12 and common port 71 using driving assembly 50 Connection makes the 6th reagent enter reaction unit 40 through rotary valve 70, to realize the capped of the second sequencing reaction.

In some embodiments, sequencing reaction includes the first sequencing reaction, the second sequencing reaction that sequence carries out With third sequencing reaction, third sequencing reaction includes the steps that surveying with the first sequencing reaction or with the second sequencing reaction, first First reagent of sequence reaction, the second sequencing reaction and third sequencing reaction is all different, and multiple ports further include that corresponding third is surveyed The third group port of sequence reaction, third group port includes the 13rd port 13 and the 14th being arranged successively by preset rotation direction Port 14, first group of port, second group of port and third group port are arranged successively by preset rotation direction, and the 13rd port 13 connects The first reagent of third sequencing reaction is connect, the 14th port 14 connects the second reagent, and method further comprises the steps of:

V) iv is being carried out) after, the 13rd port 13 is connected to common port 71 using driving assembly 50, and third is sequenced First reagent of reaction enters reaction unit 40 through rotary valve 70, to realize that the base of third sequencing reaction extends；

Vi) be connected to the 14th port 14 with common port 71 using driving assembly 50, make the second reagent through rotary valve 70 into Enter reaction unit 40, to realize the excision of third sequencing reaction.

In this way, making the method controlled sequencing reaction more efficient.Meanwhile it can also be greatly decreased in this way The cross contamination of first reagent of the first reagent and third sequencing reaction of the second sequencing reaction.

Specifically, in certain present embodiments, incorporated by reference to Fig. 5, first port 1 and second port 2 are adjacent, second port 2 and third port 3 it is adjacent, third port 3 and the 4th port 4 are adjacent, and the 4th port 4 and the 13rd port 13 are adjacent, the 13rd Port 13 and the 14th port 14 are adjacent, so that the stroke of rotor rotation is shorter, convenient for quickly sequencing.It is appreciated that other In embodiment, first port 1, second port 2, third port 3, the 4th port 4, the 13rd port 13 and the 14th port 14 Other ports of multiple ports also may be selected, need to only guarantee first port 1, second port 2, third port 3, the 4th port 4, the 13 ports 13 and the 14th port 14 are arranged successively by rotor preset rotation direction.

In base extension, Image Acquisition and the excision for carrying out sequencing reaction, rotor is rotated along rotor preset rotation direction To be sequentially completed different reagents through the operation in the entrance reaction unit 40 of rotary valve 70.

In some embodiments, when sequencing reaction includes that sequentially the first sequencing reaction of progress, the second sequencing are anti- When should be with third sequencing reaction, third group port includes the 13rd port the 13, the 17th being arranged successively by preset rotation direction Port 17 and the 14th port 14, incorporated by reference to Fig. 2 and Fig. 3, first port 1, fifth port 5, second port 2, third port 3, Preset rotation direction is pressed successively in 6th port 6, the 4th port 4, the 13rd port 13, the 17th port 17 and the 14th port 14 Arrangement.In base extension, Image Acquisition and the excision for carrying out sequencing reaction, rotor is rotated in a clockwise direction to be sequentially completed Different reagents enter the operation in reaction unit 40 through rotary valve 70.17th port 17 connects third reagent.

In some embodiments, sequencing reaction include sequence carry out the first sequencing reaction, the second sequencing reaction, Third sequencing reaction and the 4th sequencing reaction, third sequencing reaction and the 4th sequencing reaction include the steps that anti-with the first sequencing It answers or with the second sequencing reaction, the first sequencing reaction, the second sequencing reaction, third sequencing reaction and the 4th sequencing reaction First reagent is all different, and multiple ports further include the 4th sequencing reaction of third group port and correspondence of corresponding third sequencing reaction The 4th group of port, third group port includes the 13rd port 13 and the 14th port being arranged successively by preset rotation direction 14, the 4th group of port includes the 15th port 15 and the 16th port 16 being arranged successively by preset rotation direction, first group of end Mouth, second group of port, third group port and the 4th group of port are arranged successively by preset rotation direction, the 13rd port 13 connection the First reagent of three sequencing reactions, the 14th port 14 connect the second reagent, and the 15th port 15 connects the 4th sequencing reaction First reagent, the 16th port 16 connect the second reagent, and method further comprises the steps of:

Vi) be connected to the 14th port 14 with common port 71 using driving assembly 50, make the second reagent through rotary valve 70 into Enter reaction unit 40, to realize the excision of third sequencing reaction；

Vii the 15th port 15) is connected to common port 71 using driving assembly 50, tries the first of the 4th sequencing reaction Agent enters reaction unit 40 through rotary valve 70, to realize that the base of the 4th sequencing reaction extends；

Viii the 16th port 16) is connected to common port 71 using driving assembly 50, makes the second reagent through rotary valve 70 Into reaction unit 40, to realize the excision of the 4th sequencing reaction.

In this way, the type of sequencing reaction can be increased, so that the method controlled sequencing reaction is more efficient.Together When, the intersection that the first reagent of the second sequencing reaction and the first reagent of third sequencing reaction can also be greatly decreased in this way is dirty Dye, and the cross contamination of the first reagent of third sequencing reaction and the first reagent of the 4th sequencing reaction is greatly decreased.

Specifically, in some embodiments, incorporated by reference to Fig. 6, first port 1 and second port 2 are adjacent, second port 2 Adjacent with third port 3, third port 3 and the 4th port 4 are adjacent, and the 4th port 4 and the 13rd port 13 are adjacent, the 13rd end The 13 and the 14th port 14 of mouth is adjacent, and the 14th port 14 and the 15th port 15 are adjacent, the 15th port 15 and the 16th end Mouth 16 is adjacent, so that the stroke of rotor rotation is shorter, convenient for quickly sequencing.It is appreciated that in other embodiments, first end Mouthful 1, second port 2, third port 3, the 4th port 4, the 13rd port 13, the 14th port 14, the 15th port 15 and the Other ports of multiple ports also may be selected in 16 ports 16, need to only guarantee first port 1, second port 2, third port 3, the Rotation side is preset by rotor in four ports 4, the 13rd port 13, the 14th port 14, the 15th port 15 and the 16th port 16 To being arranged successively.

In a specific example, four kinds of reaction substrates have a same fluorescent marker, and first, second, third, fourth First reagent of sequencing reaction is respectively the reagent for including a kind of substrate, and a wheel sequencing reaction includes the first sequencing reaction, second Sequencing reaction, third sequencing reaction and the 4th sequencing reaction, the first sequencing reaction carry out the second sequencing reaction, the second survey after the completion Sequence carries out third sequencing reaction after the reaction was completed, carries out the 4th sequencing reaction, the 4th sequencing reaction after the completion of third sequencing reaction The first sequencing reaction is carried out after the completion, is repeated by this.

This method is designed and is controlled by simple fluid path structure, and rotary valve is always according to one during making sequencing reaction The rotation of direction of rotation can avoid the reagent being separated by between sequencing reaction intersection from being mixed into, such as first and third, the second and substantially Reagent intersection between 4th sequencing reaction is mixed into, and the reagent intersection that can be greatly reduced between adjacent sequencing reaction is mixed into, As the reagent between first and second, second and the sequencing reaction of third, third and fourth, the 4th and first intersects.

In some embodiments, when sequencing reaction includes that sequentially the first sequencing reaction of progress, the second sequencing are anti- It answers, third sequencing reaction and when four sequencing reactions, third group port includes the 13 be arranged successively by preset rotation direction Port 13, the 17th port 17 and the 14th port 14, the 4th group of port includes the tenth be arranged successively by preset rotation direction Five ports 15, the 18th port 18 and the 16th port 16, incorporated by reference to Fig. 2 and Fig. 3, first port 1, fifth port 5, second end Mouth 2, third port 3, the 6th port 6, the 4th port 4, the 13rd port 13, the 17th port 17, the 14th port the 14, the tenth Five ports 15, the 18th port 18 and the 16th port 16 are arranged successively by preset rotation direction.In the alkali for carrying out sequencing reaction When base extension, Image Acquisition and excision, rotor is rotated in a clockwise direction to be sequentially completed different reagents through rotary valve 70 and enter Operation in reaction unit 40.17th port 17 connects third reagent, and the 18th port 18 connects third reagent.

In some embodiments, Fig. 2 please be join, valve component 29 includes two rotary valves 70 and two the first valves 30, instead Answering device 40 includes first unit 41 and second unit 42, and first unit 41 connects the common port 71 of one of rotary valve 70, It includes the second valve 35, third valve 36 and that second unit, which connects 71,29 valve component 29 of common port that 42 connect another rotary valve 70, Four valves 37, the second valve 35 connect the first reagent of two rotary valves 70 and the first sequencing reaction, and third valve 36 connects two rotations First reagent of valve 70 and the second sequencing reaction, the 4th valve 37 connect the second reagent and two the first valves 30, each first valve 30 Connect second port 2 and the 4th port 4 of a rotary valve 70.

In this way, different types of sequencing can be carried out in the channel of first unit 41 and the channel of second unit 42 respectively It reacts, it is to be staggered that the sequencing reaction in the channel of first unit 41 is reacted with the sequencing in 42 channel of second unit , it is nonsynchronous, be mutually independent of each other, and then shorten time of sequencing reaction.For example, needing to first unit 41 On sample when carrying out the base of the first sequencing reaction and extending, fluid means 100 can convey the of reaction to first unit 41 First reagent of one sequencing reaction, at this point, identical reagent will not be made to enter second unit 42, vice versa.

Specifically, in the utility model embodiment, the first reagent of the first sequencing reaction is delivered to two through the second valve 35 First reagent of two first ports 1 of a rotary valve 70, the second sequencing reaction is delivered to two rotary valves 70 through third valve 36 Two third ports 3, the second reagent is delivered to two the first valves 30 through the 4th valve 37.

In some instances, the second valve 35, third valve 36 and the 4th valve 37 are triple valve.

In the embodiment shown in figure 2, sequencing reaction includes the first sequencing reaction, the second sequencing that sequence carries out Reaction, third sequencing reaction and the 4th sequencing reaction, each sequencing reaction include the steps that following sequence carries out: base extension, First washing, the second washing, Image Acquisition, excision and capped.

Corresponding to the first sequencing reaction, along rotor preset rotation direction, first group of port includes first port 1, the 7th end The 7, the 9th port 9 of mouth, fifth port 5, second port 2 and the tenth Single port 11.It is default along rotor corresponding to the second sequencing reaction Direction of rotation, second group of port include third port 3, the 8th port 8, the tenth port 10, the 6th port 6, the 4th port 4 and Ten Two-port netwerks 12.Corresponding to third sequencing reaction, along rotor preset rotation direction, third group port include the 13rd port 13, 19th port 19, the 20th port 20, the 17th port 17, the 14th port 14, the 20th Single port 21.Corresponding to the 4th Sequencing reaction, along rotor preset rotation direction, the 4th group of port includes the 15th port 15, the 20th Two-port netwerk the 22, the 20th Three ports 23, the 18th port 18, the 16th port 16 and the 24th port 24.

Valve component 29 further includes the 6th valve 51, the 7th valve 52, the 8th valve 53, the 9th valve 54, the tenth valve 55 and the 11st Valve 56, the quantity of the first valve 30 are 10, and the 6th valve 51 connects the first reagent and two rotary valves 70 of third sequencing reaction Two the 13rd ports 13, the 7th valve 52 connect the 4th sequencing reaction the first reagent and two the 15th of two rotary valves 70 Port 15.8th valve 53 connects third reagent and two the first valves 30, and the 9th valve 54 connects the 6th reagent and two the first valves 30, Tenth valve 55 connects the 4th reagent and two the first valves 30, and the 11st valve 56 connects the 5th reagent and two the first valves 30.

Second valve 35, third valve 36, the 4th valve 37, the 6th valve 51, the 7th valve 52, the 8th valve 53, the 9th valve 54, the tenth valve 55 and the 11st valve 56 includes a Zong Kou and two points of mouths.

7th port 7, the 8th port 8, the 19th port 19 and the 20th Two-port netwerk 22 connect the 4 of same first valve 30 A point of mouth, total mouth of same first valve 30 connect a point of mouth of the tenth valve 55, the 4th examination of total mouth connection of the tenth valve 55 Agent.

9th port 9, the tenth port 10, the 20th port 20 and the 23rd port 23 connect same first valve 30 4 points of mouths, total mouth of same first valve 30 connect a point of mouth of the 11st valve 56, total mouth connection of the 11st valve 56 the Five reagents.

Fifth port 5, the 6th port 6, the 17th port 17 and the 18th port 18 connect 4 of same first valve 30 Divide mouth, total mouth of same first valve 30 connects a point of mouth of the 8th valve 53, and total mouth of the 8th valve 53 connects third reagent.

Second port 2, the 4th port 4, the 14th port 14 and the 16th port 16 connect 4 of same first valve 30 Divide mouth, total mouth of same first valve 30 connects a point of mouth of the 4th valve 37, and total mouth of the 4th valve 37 connects the second reagent.

Tenth Single port 11, the tenth Two-port netwerk 12, the 20th Single port 21 and the 24th port 24 connect same 4 points of mouths of one valve 30, total mouth of same first valve 30 connect a point of mouth of the 9th valve 54, and total mouth of the 9th valve 54 connects Connect the 6th reagent.

6th valve 51, the 7th valve 52, the 8th valve 53, the 9th valve 54, the tenth valve 55 and the 11st valve 56 are triple valve, the One valve 30 includes a total mouth and 4 points of mouths, and rotary valve 70 is 28 mouthfuls of rotary valves.Therefore, in the embodiment shown in figure 2, The quantity of triple valve is 9, and the quantity of the first valve 30 is 10.

Reaction unit 40 includes first unit 41 and second unit 42.First unit 41 connects the public of a rotary valve 70 Mouth 71, second unit 42 connect the common port 71 of another rotary valve 70.

Driving assembly 50 includes eight townhouses pump, and 4 pumps in eight townhouses pump connect first unit 41, and another 4 pumps connect the Two units 42 are to generate negative pressure in the channel of first unit 41 and second unit 42 respectively.The use of eight townhouses pump can save instrument Device installation space and saving cost, and the use of solenoid valve can be reduced, reduce failure rate.Eight townhouses pump can be eight townhouse Thomas The noise of pump, eight townhouse Thomas pump is smaller, and vibration is smaller, realizes quick sequencing reaction.

After first reagent needed for the base extension of each sequencing reaction is pumped into, the rotor of rotary valve 70 can be by default Complete the first washing, the second washing, the addition of third reagent, excision in direction of rotation (clockwise direction as shown in Figure 2) (cleave) and the process of capped (cap), residual of the terminator of the first reagent in rotary valve 70 are largely limited to rotor First reagent cross contamination of different sequencing reactions can be preferably minimized by the sealing surface region between stator 81.

In some embodiments, base provided by the first reagent of the first sequencing reaction is A, the second sequencing reaction Base provided by first reagent is G, and base provided by the first reagent of third sequencing reaction is C, the 4th sequencing reaction Base provided by first reagent is T.Second reagent is the reagent C l of excision, and third reagent is the reagent I of Image Acquisition, 4th reagent is the reagent R of the first washing, and the 5th reagent is the reagent B of the second washing, and the 6th reagent is capped examination Agent Ca.

It is appreciated that in other embodiments, the first sequencing reaction, the second sequencing reaction, third sequencing reaction and the Base provided by first reagent of four sequencing reactions can also change, for example, the first reagent of the first sequencing reaction is mentioned The base of confession is T, and base provided by the first reagent of the second sequencing reaction is G, and the first reagent of third sequencing reaction is mentioned The base of confession is C, and base provided by the first reagent of the 4th sequencing reaction is A etc..

Preferably, the first reagent A, T, C, G, the second reagent, third reagent and the 6th reagent can be placed in the environment of refrigeration, 4th reagent and the 5th reagent can be placed in the environment of room temperature.

In some embodiments, Fig. 3 please be join, valve component 29 includes the 5th valve 38, and reaction unit 40 includes first single Member 41 and second unit 42, the 5th valve 38 connect common port 71 and first unit 41, and connection common port 71 and second unit 42.

In this way, different types of sequencing can be carried out in the channel of first unit 41 and the channel of second unit 42 respectively It reacts, it is to be staggered that the sequencing reaction in the channel of first unit 41 is reacted with the sequencing in 42 channel of second unit , it is nonsynchronous, be mutually independent of each other, and then shorten time of sequencing reaction.For example, needing to first unit 41 On sample when carrying out the base of the first sequencing reaction and extending, fluid means 100 can be to the conveying reaction of first unit 41 with first First reagent of sequencing reaction, at this point, identical reagent will not be made to enter second unit 42, vice versa.

Specifically, the 5th valve 38 is optionally connected to common port 71 and first unit 41, or connection common port 71 and the Two units 42, when the 5th valve 38 is connected to common port 71 and first unit 41, reagent can be under the driving of driving assembly 50 through revolving Rotary valve 70 and the 5th valve 38 enter first unit 41 and carry out sequencing reaction, at this point, common port 71 is not connected to second unit 42, examination Agent will not enter second unit 42.When the 5th valve 38 is connected to common port 71 and second unit 42, reagent can be with driving assembly 50 Driving under enter second unit 42 through rotary valve 70 and the 5th valve 38 and carry out sequencing reaction, at this point, common port 71 with first singly Member 41 is not connected to, and reagent will not enter first unit 41.

In the utility model embodiment, the 5th valve 38 is three way rotary valves.

In the embodiment shown in fig. 3, sequencing reaction includes the first sequencing reaction, the second sequencing that sequence carries out Reaction, third sequencing reaction and the 4th sequencing reaction, each sequencing reaction include the steps that following sequence carries out: base extension, First washing, the second washing, Image Acquisition, excision and capped.Corresponding to the first sequencing reaction, along rotor preset rotation direction, First group of port includes first port 1, the 7th port 7, the 9th port 9, fifth port 5, second port 2 and the tenth Single port 11.Corresponding to the second sequencing reaction, along rotor preset rotation direction, second group of port includes third port 3, the 8th port 8, Ten ports 10, the 6th port 6, the 4th port 4 and the tenth Two-port netwerk 12.Corresponding to third sequencing reaction, along the default rotation of rotor Direction, third group port include the 13rd port 13, the 19th port 19, the 20th port 20, the 17th port the 17, the 14th Port 14, the 20th Single port 21.Corresponding to the 4th sequencing reaction, along rotor preset rotation direction, the 4th group of port includes the 15 ports 15, the 20th Two-port netwerk 22, the 23rd port 23, the 18th port 18, the 16th port 16 and the 24th Port 24.

Valve component 29 includes 5 the first valves 30, and the first valve 30 includes a total mouth and 4 points of mouths.Rotary valve 70 is 28 Mouth rotary valve.

7th port 7, the 8th port 8, the 19th port 19 and the 20th Two-port netwerk 22 connect the 4 of same first valve 30 Total mouth of a point of mouth, same first valve 30 connects the 4th reagent.

9th port 9, the tenth port 10, the 20th port 20 and the 23rd port 23 connect same first valve 30 Total mouth of 4 points of mouths, same first valve 30 connects the 5th reagent.

Fifth port 5, the 6th port 6, the 17th port 17 and the 18th port 18 connect 4 of same first valve 30 Divide mouth, total mouth of same first valve 30 connects third reagent.

Second port 2, the 4th port 4, the 14th port 14 and the 16th port 16 connect 4 of same first valve 30 Divide mouth, total mouth of same first valve 30 connects the second reagent.

Tenth Single port 11, the tenth Two-port netwerk 12, the 20th Single port 21 and the 24th port 24 connect same Total mouth of 4 points of mouths of one valve 30, same first valve 30 connects the 6th reagent.

Reaction unit 40 includes first unit 41 and second unit 42.First unit 41 connects one of the 5th valve 38 out Mouthful, second unit 42 connects another outlet of the 5th valve 38.

After first reagent needed for the base extension of each sequencing reaction is pumped into, the rotor of rotary valve 70 can be by default Complete the first washing, the second washing, the addition of third reagent, excision in direction of rotation (clockwise direction as shown in Figure 3) (cleave) and the process of capped (cap), residual of the terminator of the first reagent in rotary valve 70 are largely limited to rotor First reagent cross contamination of different sequencing reactions can be preferably minimized by the sealing surface region between stator 81.

In the utility model embodiment, the switching of two units is realized using three way rotary valves.Compared to two Position-3-way solenoid valve, three way rotary valve internal dead volumes are almost nil, it is not necessary to worry the reagent cross contamination between two units. The utility model embodiment can avoid the use of triple valve, reduces connector connection quantity, reduces costs simultaneously.

It should be pointed out that avoid the lines in attached drawing from causing attached drawing unclear too much, in figure 2 and figure 3, Mou Xiefa It is not shown with the pipeline line of the pipeline line of certain port and certain valves and certain reagents.Art technology Personnel are appreciated that the company that above-mentioned pipeline line can be had a clear understanding of according to the above-mentioned explanation to the utility model embodiment It connects.

It please join Fig. 7, a kind of Sequence Detection System 300 of the utility model embodiment controls sequencing reaction System, the sequencing reaction carry out on reaction unit 40, and reaction unit 40 is placed in removable microscope carrier 80, sequencing reaction Including the first sequencing reaction and the second sequencing reaction.

Sequence Detection System 300 includes control device 302, fluid means 100 and imaging device 200, and control device 302 connects The fluid means 100 and imaging device 200 are connect, control device 302 is for controlling imaging device 200 and fluid means, fluid Device 100 includes valve component 29 and driving assembly 50,

Valve component 29 includes rotary valve 70, and rotary valve 70 includes the stator 81 and rotor that can be connected to, and rotary valve 70 has Common port 71 has multiple ports on stator 81, has connectivity slot 72 on rotor, rotor, which can rotate, makes common port 71 and one Port is connected to by connectivity slot 72, and multiple ports include first group of end for respectively corresponding the first sequencing reaction and the second sequencing reaction Mouth and second group of port, first group of port include first port 1 and second port 2, and first port 1 is for connecting the first sequencing instead The first reagent of base extension is answered, second port 2 is used to connect the second reagent of excision, and second group of port includes third end Mouth 3 and the 4th port 4, first port 1, second port 2, third port 3 and the 4th port 4 are the preset rotation direction by rotor It is arranged successively, third port 3 is used to connect the first reagent of the second sequencing reaction base extension, and the 4th port 4 is for connecting Second reagent, common port 71 connect reaction unit 40.

In above system 300, the stator 81 and rotor that can be connected to by rotary valve 70, so that the first reagent and the second reagent It can be passed through in the different phase that sequencing reacts into reaction unit 40, therefore, the system 300 is for needing to control each The sequencing reaction of different type substrate or different substrate combinations is sequentially added in wheel, particularly suitable, the system 300 is by simple Apparatus structure and control liquid disengaging sequence, can largely reduce between different type substrate or different substrates Pollution between combination.

It should be noted that reacting the method controlled to sequencing in any of the above-described embodiments and examples Technical characteristic and the explanation and illustration of beneficial effect be also applied for the Sequence Detection System 300 of present embodiment, it is superfluous to avoid It is remaining, it is no longer developed in details herein.

In some embodiments, fluid means 100 includes flow control unit, the control of 302 connecting fluid of control device Unit, flow control unit are electrically connected valve component 29 and driving assembly 50 and are transported with application valve body component 29 and driving assembly 50 Row.

Specifically, flow control unit can receive the control signal of control device 302, and according to control signal to valve body group Other components of part 29, driving assembly 50 and fluid means 100 are controlled.In this way, in this way can be by the portion of control device 302 Point function executes realization by flow control unit, reduces the load of control device 302.Flow control unit can be including The devices such as single-chip microcontroller, computer processor or central control processor improve effect, it can be achieved that 100 automatic running of fluid means Rate.

In some embodiments, flow control unit and control device 302 can be integrated in a component, module or device In, to improve the integrated level of Sequence Detection System 300, reduce cost.

In some embodiments, control device 302 includes the unit of control fluid means, controls the unit of fluid means Valve component 29 and driving assembly 50 is electrically connected to run with application valve body component 29 and driving assembly 50.

Specifically, the unit for controlling fluid means can receive externally input control signal, and according to control signal to valve Other components of body component 29, driving assembly 50 and fluid means 100 are controlled.In this way, in this way can be by control device 302 Partial function realization is executed by the unit of control fluid means, reduce the interference between 302 each unit of control device.Control The unit of fluid means processed can be including devices such as single-chip microcontroller, computer processor or central control processors, it can be achieved that flowing 100 automatic running of body device, improves efficiency.

In some embodiments, control device 302 may also include other units, for example, control device 302 includes control The unit of imaging device.

In some embodiments, valve component 29 includes the first valve, and second port 2 passes through the first valve and the second reagent phase Even, the 4th port 4 is connected by the first valve with the second reagent.

In some embodiments, first group of port includes the first port the 1, the 5th being arranged successively by preset rotation direction Port 5 and second port 2, second group of port include the third port 3 being arranged successively by preset rotation direction, 6 and of the 6th port 4th port 4, fifth port 5 and the 6th port 6 are used to be passed through the third reagent of Image Acquisition.

In some embodiments, first group of port includes the first port the 1, the 7th being arranged successively by preset rotation direction Port 7 and second port 2, second group of port include the third port 3 being arranged successively by preset rotation direction, 8 and of the 8th port 4th port 4, the 7th port 7 and the 8th port 8 are used to be passed through the first sequencing reaction and the first washing of the second sequencing reaction is used The 4th reagent.

In some embodiments, first group of port includes the first port the 1, the 7th being arranged successively by preset rotation direction Port 7, the 9th port 9 and second port 2, second group of port include the third port 3 being arranged successively by preset rotation direction, Eight ports 8, the tenth port 10 and the 4th port 4, the 7th port 7 are used to be passed through the 4th of the first washing of the first sequencing reaction Reagent, the 8th port 8 are used to be passed through the 4th reagent of the first washing of the second sequencing reaction, and the 9th port 9 is for being passed through the 5th reagent of the second washing of one sequencing reaction, the tenth port 10 are used to be passed through the second washing of the second sequencing reaction 5th reagent

In some embodiments, first group of port includes the first port 1, second being arranged successively by preset rotation direction Port 2 and the tenth Single port 11, second group of port include the third port 3 being arranged successively by preset rotation direction, the 4th port 4 With the tenth Two-port netwerk 12, the tenth Single port 11 is used to be passed through the 6th capped reagent of the first sequencing reaction, the tenth Two-port netwerk 12 For being passed through the 6th capped reagent of the second sequencing reaction.

In some embodiments, sequencing reaction includes third sequencing reaction and the 4th sequencing reaction, multiple ports It further include the third group port and the 4th group of port of corresponding 4th sequencing reaction of corresponding third sequencing reaction, third group port packet The 13rd port 13 and the 14th port 14 being arranged successively by preset rotation direction are included, the 4th group of port includes by default rotation The 15th port 15 and the 16th port 16 that direction is arranged successively, first group of port, second group of port, third group port and Four groups of ports are arranged successively by preset rotation direction, and the 13rd port 13 is used to connect the first reagent of third sequencing reaction, the For connecting the second reagent, the 15th port 15 is used to connect the first reagent of the 4th sequencing reaction for 14 ports 14, and the 16th Port 16 is for connecting the second reagent.

In some embodiments, valve component 29 includes two rotary valves 70 and two the first valves, and reaction unit 40 wraps First unit 41 and second unit 42 are included, first unit 41 connects the common port 71 of one of rotary valve 70, second unit 42 The common port 71 of another rotary valve 70 is connected, valve component 29 includes the second valve 35, third valve 36 and the 4th valve 37, the second valve First reagent of 35 connection two rotary valves 70 and the first sequencing reaction, third valve 36 connect two rotary valves 70 and the second sequencing First reagent of reaction, the 4th valve 37 connect the second reagent and two the first valves, and each first valve connects a rotary valve 70 Second port 2 and the 4th port 4.

In some embodiments, valve component 29 includes the 5th valve 38, and reaction unit 40 includes first unit 41 and the Two units 42, the 5th valve 38 connect common port 71, first unit 41 and second unit 42.

It please join Fig. 7, the utility model embodiment provides a kind of pair of sequencing and reacts the device 302 controlled, dress Setting 302 includes:

Storage device 304, for storing data, data include computer executable program；

Processor 306, for executing computer executable program, executing computer executable program includes completing above-mentioned The method of one embodiment.

A kind of computer readable storage medium of the utility model embodiment, for storing the journey executed for computer Sequence, executing program includes the method for completing any of the above-described embodiment.Computer readable storage medium may include: read-only storage Device, random access memory, disk or CD etc..

In the description of this specification, reference term " embodiment ", " certain embodiments ", " schematically implementation What the description of mode ", " example ", " specific example " or " some examples " etc. meant to describe in conjunction with the embodiment or example Particular features, structures, materials, or characteristics are contained at least one embodiment or example of the utility model.In this explanation In book, schematic expression of the above terms are not necessarily referring to identical embodiment or example.Moreover, the specific spy of description Sign, structure, material or feature can be combined in any suitable manner in any one or more embodiments or example.

Expression or logic and/or step described otherwise above herein in flow charts, for example, being considered use In the order list for the executable instruction for realizing logic function, may be embodied in any computer readable storage medium, For instruction execution system, device or equipment (such as computer based system, including the system of processor or other can be from finger Enable the system for executing system, device or equipment instruction fetch and executing instruction) it uses, or combine these instruction execution systems, device Or equipment and use.For the purpose of this specification, " computer readable storage medium " can be it is any may include, store, communicating, Propagate or transfer program for instruction execution system, device or equipment or in conjunction with these instruction execution systems, device or equipment and The device used.

In addition, can integrate in a processing module in each functional unit in each embodiment of the utility model, It is also possible to each unit to physically exist alone, can also be integrated in two or more units in a module.Above-mentioned collection At module both can take the form of hardware realization, can also be realized in the form of software function module.It is described integrated If module is realized and when sold or used as an independent product in the form of software function module, also can store at one In computer-readable storage medium.

Although the embodiments of the present invention has been shown and described above, it is to be understood that above-mentioned embodiment party Formula is exemplary, and should not be understood as limiting the present invention, and those skilled in the art are in the utility model Above embodiment can be changed, be modified in range, replacement and variant.

Claims

1. a kind of Sequence Detection System controls sequencing reaction, which is characterized in that the sequencing reaction is anti- It answers and is carried out on device, the reaction unit is placed in removable microscope carrier, and the sequencing reaction includes the first sequencing reaction and the Two sequencing reactions, the Sequence Detection System include control device, fluid means and imaging device, and the control device connects institute Fluid means and the imaging device are stated, the control device is described for controlling the imaging device and the fluid means Fluid means includes valve component and driving assembly,

The valve component includes rotary valve, and the rotary valve includes the stator and rotor that can be connected to, and the rotary valve has public affairs It is total to mouth, there are multiple ports on the stator, there is connectivity slot on the rotor, the rotor, which can rotate, makes the common port It is connected to a port by the connectivity slot, the multiple port includes respectively corresponding first sequencing reaction and institute State the first group of port and second group of port of the second sequencing reaction, first group of port includes first port and second port, The first port is used to connect the first reagent of the first sequencing reaction base extension, and the second port is for connecting Second reagent of excision, second group of port include third port and the 4th port, the first port, second port, The third port and the 4th port are to be arranged successively by the preset rotation direction of rotor, and the third port is for connecting First reagent of the second sequencing reaction base extension, the 4th port is for connecting second reagent, the public affairs Mouth connects the reaction unit altogether.

2. the system as claimed in claim 1, which is characterized in that the valve component includes the first valve, and the second port is logical It crosses first valve to be connected with second reagent, the 4th port is connected by first valve with second reagent.

3. the system as claimed in claim 1, which is characterized in that first group of port include by the preset rotation direction according to The first port, fifth port and the second port of secondary arrangement, second group of port include pressing the default rotation The third port, the 6th port and the 4th port that direction is arranged successively, the fifth port and the 6th port For being passed through the third reagent of Image Acquisition.

4. the system as claimed in claim 1, which is characterized in that first group of port include by the preset rotation direction according to The first port, the 7th port and the second port of secondary arrangement, second group of port include pressing the default rotation The third port, the 8th port and the 4th port that direction is arranged successively, the 7th port and the 8th port For being passed through the 4th reagent of the first washing of first sequencing reaction and second sequencing reaction.

5. the system as claimed in claim 1, which is characterized in that first group of port include by the preset rotation direction according to The first port, the 7th port, the 9th port and the second port of secondary arrangement, second group of port include by described The third port, the 8th port, the tenth port and the 4th port that preset rotation direction is arranged successively, the 7th end 4th reagent of first washing of the mouth for being passed through first sequencing reaction, the 8th port is for being passed through described second 4th reagent of the first washing of sequencing reaction, the 9th port are used to be passed through the second washing of first sequencing reaction 5th reagent, the tenth port are used to be passed through the 5th reagent of the second washing of second sequencing reaction.

6. the system as claimed in claim 1, which is characterized in that first group of port include by the preset rotation direction according to The first port, the second port and the tenth Single port of secondary arrangement, second group of port include pressing the default rotation Turn the third port, the 4th port and the tenth Two-port netwerk that direction is arranged successively, the tenth Single port is for being passed through The 6th capped reagent of first sequencing reaction, for being passed through, second sequencing reaction is capped to be used the tenth Two-port netwerk The 6th reagent.

7. system as claimed in any one of claims 1 to 6, which is characterized in that the sequencing reaction includes that third sequencing is anti- Should further include with the 4th the multiple port of sequencing reaction the corresponding third sequencing reaction third group port and it is corresponding described in 4th group of port of the 4th sequencing reaction, third group port include the 13rd be arranged successively by the preset rotation direction Port and the 14th port, the 4th group of port include the 15th port being arranged successively by the preset rotation direction and 16 ports, first group of port, second group of port, third group port and the 4th group of port by the preset rotation direction according to Secondary arrangement, the 13rd port are used to connect the first reagent of the third sequencing reaction, and the 14th port is for connecting Second reagent is connect, the 15th port is used to connect the first reagent of the 4th sequencing reaction, the 16th end Mouth is for connecting second reagent.

8. such as claim 1 or the described in any item systems of 3-6, which is characterized in that the valve component includes two rotations Rotary valve and two the first valves, the reaction unit include first unit and second unit, and the first unit connects one of them The common port of the rotary valve, the second unit connect the common port of another rotary valve, the valve body Component includes the second valve, third valve and the 4th valve, and second valve connects described two rotary valves and first sequencing reaction The first reagent, the third valve connects the first reagent of described two rotary valves and second sequencing reaction, the described 4th Valve connects second reagent and described two first valves, and each first valve connects the second port and an of rotary valve Four ports.

9. such as claim 1 or the described in any item systems of 3-6, which is characterized in that the valve component includes the 5th valve, institute Stating reaction unit includes first unit and second unit, and the 5th valve connects the common port, the first unit and described Second unit.