CN206553527U - sequence detection system - Google Patents

Abstract

The utility model discloses a kind of Sequence Detection System.Sequence Detection System includes fluid means, the Sequence Detection System includes fluid means, the fluid means includes valve component and drive component, the valve component includes the first valve and the second valve, first valve and the reaction unit connection, first valve includes the stator and rotor that can be connected, first valve has common port, there are multiple ports on the stator, there is connectivity slot on the rotor, by rotating the rotor common port can be made to be connected with port at least one described by the connectivity slot, the multiple port includes first port, second valve can be directly connected to the first port, first reagent and/or the first buffer solution.In above-mentioned Sequence Detection System, using first the first valve of buffer solution for cleaning, that is, the first reagent in the first valve can be replaced before rotor, can avoid rotor switch different reagents when cross pollution risk.

Description

Sequence Detection System

Technical field

The utility model is related to sequencing technology field, more particularly to a kind of Sequence Detection System.

Background technology

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

Using based on biochemical reaction carry out sequence platform during sequencing, it is necessary on reaction unit Biochemical reaction is carried out, for example, needs that different reagents is incorporated on chip and reacted together or successively using liquid-way system. At present, to make the liquid-way system compact efficient in platform, liquid-way system switches input/output reagent using the first valve.

The first presently commercially available valve, due to its design feature, inevitably occurs different when different reagents switch The reagent of degree intersects or is mixed into, i.e. reagent cross pollution.Reagent cross pollution can influence the progress of reaction, especially for that The reaction of a little reactions required amount of reagent very little in itself, such as single-molecule sequencing, the cross pollution of reagent is fatal.

Therefore, how to reduce or avoid the reagent cross pollution in fluid path, as it is to be solved the problem of.

Utility model content

The utility model embodiment is intended at least solve one of technical problem present in correlation technique or at least carried For a kind of useful business selection.Find and contemplate based on the fractionation research below to the structure of the first valve, inventor makes The utility model.

Current the first valve on the market, also referred to as sampling valve, multiposition valve, rotary valve or revolving valve, are used as sample collection, liquid The part of body sample introduction or stream conversion etc..Its composition generally comprises stator and rotor, passes through combining closely for stator and rotor, energy It is enough to form effectively sealing.

First valve has common port, and common port is the port that different stream liquid into or outs can all pass through, and common port is located at On stator and/or rotor, there is one or more of the other port on stator and/or rotor.By the rotation of rotor, it can realize The connection of rotor and stator path, so that common port and other ports have been connected, to reach the function of selection sample introduction or shunting.The General configuration/standard configurations of one valve are more logical selection type, i.e., in the process of running, only a port is connected with common port.

Common port is connected with other ports, generally require by one or several public structures being arranged on rotor come Connection.When having liquid in the public structure, due to the rotation of rotor, rotor and stator connect seal interface relatively live Dynamic, inevitably at least a portion liquid in public structure can be brought to the place outside public structure, i.e. stream and change When, it can inevitably make the liquid that a upper stream is carried in next stream liquid, and if follow-up opposite direction stream conversion, again meeting The next stream liquid for being mixed with a stream liquid is set to be brought in the liquid of lower stream；Even if in this way, micro be mixed into, producing Cross pollution be difficult to control to, influence to be difficult to estimate.

Inventor in the result that the manual result of comparative analysis and upper machine are determined, repetition test and checking device system All parts are associated and the fractionation to the structure of the first valve based on more than is studied, it is determined that the above, due to public affairs when stream change At least a portion liquid in co-structured is incorporated into the i.e. next course of reaction of next stream, the i.e. cross pollution of reagent, to sequence Measurement result produces the unfavorable influence for being difficult to expect.Therefore, the utility model embodiment provides a kind of Sequence Detection System.

A kind of Sequence Detection System of the utility model embodiment, is controlled, the sequence to sequencing reaction Determining reaction includes the first biochemical reaction, and first biochemical reaction is carried out using the first reagent on reaction unit.The sequence Row measurement system includes control device and fluid means, and the control device connects the fluid means, the fluid means bag Include valve component and drive component.The valve component includes the first valve and the second valve, first valve and the reaction unit Connection, first valve includes the stator and rotor that can be connected, and first valve has on common port, the stator with multiple There is connectivity slot on port, the rotor, can make the common port and at least one described port by rotating the rotor Connected by the connectivity slot, the multiple port include first port, second valve can be directly connected to the first port, First reagent and/or the first buffer solution.

In above-mentioned Sequence Detection System, the first buffer solution can be made to flow into the first valve so that in connectivity slot before rotor Liquid before rotor by the first buffer solution substitute, in other words, the first valve rotor rotation before, using to target sequence Row determine first buffer solution of the reaction without influence and instead of the first reagent in connectivity slot, it is to avoid connect in rotor rotation process Original reagent is brought to the other positions of the linkage interface of stator and rotor in groove, and then when having avoided the different reagents of switching The risk of cross pollution.

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

Brief description of the drawings

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

Fig. 1 is the high-level schematic functional block diagram of the Sequence Detection System of the utility model embodiment；

Fig. 2 is the schematic flow sheet for reacting sequencing the method being controlled of the utility model embodiment；

Fig. 3 is the structural representation of the Sequence Detection System of the utility model embodiment；

Fig. 4 is the relation schematic diagram of port, connectivity slot and the common port of the first valve of the utility model embodiment；

Fig. 5 is the structural representation of the valve component of the utility model embodiment；

Fig. 6 is the structural representation of the test platform of the utility model embodiment；

Fig. 7 is the schematic diagram of one group of test data obtained by the test platform of the utility model embodiment；

Fig. 8 is the schematic diagram of another group of test data obtained by the test platform of the utility model embodiment；

Fig. 9 is the contrast schematic diagram of the different test datas obtained by the test platform of the utility model embodiment；

Figure 10 is that another flow for reacting sequencing the method being controlled of the utility model embodiment is illustrated Figure.

Embodiment

Embodiment of the present utility model is described below in detail, the example of the embodiment is shown in the drawings, wherein Same or similar label represents same or similar element or the element with same or like function from beginning to end.Lead to below It is exemplary to cross the embodiment being described with reference to the drawings, and is only used for explaining the utility model, and it is not intended that to this practicality New limitation.

In description of the present utility model, it is to be understood that term " first ", " second " are only used for describing purpose, and It is not intended that indicating or implying relative importance or the implicit quantity for indicating indicated technical characteristic.Thus, define One or more feature can be expressed or be implicitly included to the feature of " first ", " second ".In the utility model Description in, " multiple " are meant that two or more, unless otherwise specifically defined.

, it is necessary to which explanation, unless otherwise clearly defined and limited, " connection " should be done in description of the present utility model It broadly understood, for example, it may be being fixedly connected or being detachably connected, or be integrally connected；Can mechanically connect, Can also electrically connect or can be in communication with each other；Can be joined directly together, can also be indirectly connected to by intermediary, Ke Yishi The connection of two element internals or the interaction relationship of two elements.For the ordinary skill in the art, can be with Concrete meaning of the above-mentioned term in the utility model is understood as the case may be.

Following disclosure provides many different embodiments or example is used for realizing different structure of the present utility model. In order to simplify disclosure of the present utility model, hereinafter to the parts of specific examples and description is set for.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, its Body does not indicate the relation between discussed various embodiments and/or setting.

" sequencing " same determining nucleic acid sequence alleged by the utility model embodiment, including DNA sequencing and/or RNA Sequencing, including long segment sequencing and/or short-movie section sequencing.Alleged " sequencing reaction " same to sequencing reaction.Usually, in core In the measure of acid sequence, a base or a certain types of base, alleged alkali can be determined by a wheel sequencing reaction Base is selected from least one of A, T, C, G and U.It is alleged in the sequencing reaction being sequenced when being sequenced and/or connecting while in synthesis A wheel sequencing reaction include extension (base extension), information (/ IMAQ of taking pictures) and group and cut off (cleave).Alleged " nucleotide analog " is substrate, also referred to as terminator (terminator), is A, T, C, G and/or U Analog, base complementrity principle and certain types of base pairing can be followed, while next nucleotides/bottom can be terminated Thing is attached on template strand.

It please join Fig. 1 to Fig. 3, the utility model embodiment provides a kind of Sequence Detection System 300, and sequencing is reacted It is controlled, sequencing reaction includes the first biochemical reaction, and the first biochemical reaction is using the first reagent 11 in reaction unit 40 It is upper to carry out.

Sequence Detection System 300 includes fluid means 100, and fluid means 100 includes valve component 10 and drive component 50.

Valve component 10 includes the first valve 20 and the second valve 30, and the first valve 20 and reaction unit 40 are connected, and the first valve 20 is wrapped The stator and rotor that can be connected are included, the first valve 20, which has to have on common port, stator, has connectivity slot on multiple ports, rotor 21, by rotor common port can be made to be connected with least one port by connectivity slot 21, multiple ports include first end Mouth 22, the second valve 30 can be directly connected to first port 22, the first reagent 11 and/or the first buffer solution 60.

In above-mentioned Sequence Detection System, before rotor the first buffer solution 60 can be made to flow into the first valve 20 so that connection Liquid in groove 21 is substituted before rotor by the first buffer solution 60, in other words, before the rotor rotation of the first valve 20, profit With first buffer solution 60 of the reaction without influence is determined on target sequence it instead of the first reagent 11 in connectivity slot 21, it is to avoid Original reagent is brought to the other positions of the linkage interface of stator and rotor in connectivity slot 21 in rotor rotation process, and then returns The risk of cross pollution when having kept away switching different reagents.

Specifically, because first port 22 is connected with the second valve 30 so that the first reagent 11 and the first buffer solution 60 are optional Enter first port 22 through the second valve 30 with selecting, therefore, before rotor, the first buffer solution 60 can be made to instead of connectivity slot 21 In the first reagent 11, and then produce a desired effect.For example, Sequence Detection System can be infused according to the following steps：

S11, makes first port 22 be connected by connectivity slot 21 with common port；

S12, makes the second valve 30 connect the first reagent 11 and first port 22；

S13, makes the first reagent 11 enter reaction unit 40 through the second valve 30 and the first valve 20 successively using drive component 50, To carry out the first biochemical reaction；

S14, before rotor, makes the second valve 30 connect the first buffer solution 60 and first port 22；

S15, makes the first buffer solution flow through the second valve 30 and the first valve 20 successively using drive component 50.

In some embodiments, Sequence Detection System 300 includes control device 302, the connection valve body group of control device 302 Part 10 and drive component 50, control device 302 are used for the operation of application valve body component 10 and drive component 50.

Specifically, control device 302 can control the first valve 20 rotor rotation, and the second valve 30 opening and closing, And control drive component 50 makes the first reagent 11 and the first buffer solution 60 enter the second valve 30 and the first valve 20.

In some embodiments, reaction unit 40 can be chip, and reaction unit 40 carries sample.Incorporated by reference to Fig. 3, instead Device 40 is answered to include first module 41 and second unit 42, each unit includes plurality of passages (channel), can be respectively the The passage of one unit 41 and the passage of second unit 42 are carried out in different types of sequencing reaction, the passage of first module 41 Sequencing reaction and the sequencing in the passage of second unit 42 react be stagger, it is nonsynchronous, be mutually independent of each other. For example, when needing to carry out biochemical reaction to the sample in first module 41, fluid means 100 can be conveyed instead to first module 41 The reagent of application, now, will not make identical reagent enter second unit 42, vice versa.

In the utility model embodiment, Fig. 3 please be join, each unit correspondence is connected with first valve 20.Specifically, The common port of first valve 20 connects corresponding unit so that the reagent exported from the common port of the first valve 20 can enter corresponding Unit carries out biochemical reaction.In this way, the process of sequencing can be accelerated.

In some embodiments, before sequencing reaction is carried out, the first module 41 and second of reaction unit 40 is single The sample for needing sequencing is fixed on the surface of the passage of member 42, the sample for treating sequencing is, for example, to have double-strand or list The DNA of chain structure.

Between first reagent 11 and the second valve 30, between the first buffer solution 60 and the second valve 30, port and the second valve 30 it Between, between the second valve 30 and the first valve 20 and/or between the first valve 20 and reaction unit 40 can connect and connect by flexible pipe, such as This, flexible pipe can make the configuration of fluid path more flexible.

In some embodiments, the first valve 20 can be multiple-way valve.In some embodiments, the second valve 30 can be threeway Valve, such as three-way magnetic valve, the normally closed port and normally open of three-way magnetic valve respectively connected the reagent and buffer solution that need to add. In some embodiments, the first valve 20 can be rotary valve, in this way, reacting the Sequence Detection System being controlled to sequencing 300 have a wide range of application.

In the utility model embodiment, " being directly connected to " is referred between the second valve 30 and first port 22, second Connected between the reagent 11 of valve 30 and first, between the second valve 30 and the first buffer solution 60 by pipeline, the second valve 30 and first end Do not have between mouthfuls 22, between the second valve 30 and the first reagent 11, between the second valve 30 and the first buffer solution 60 other valves or in Between component.

In some embodiments, common port is opened on stator, multiple ports around common port set, and common port with One end correspondence of connectivity slot 21 is connected.In other embodiments, common port is opened on rotor, and positioned at connectivity slot 21 One end.

In the utility model embodiment, step S11 is implemented before step S12, in other embodiments, step S12 can be implemented before step S11, or step S11 and step S12 can be implemented simultaneously.

Alleged buffer solution for liquid pH can be maintained to a certain degree in the solution of particular range, be weak acid, weak base and/or in Property solution.In some embodiments, the first buffer solution is do not influence the first biochemical reaction and/or sequencing to react other The solution of biochemical reaction.

Usually, the sealing of the first valve 20 is substantially by the end face seal between stator and rotor, in rotor, even Agent liquid in groove 21 can be between the stator and the rotor sealing surface have residual.As shown in figure 4, carrying out the first biochemical reaction When, the first reagent 11 as the port 1 of first port 22, connectivity slot 21 and common port 0 through entering reaction unit 40.And needing When carrying out other biochemical reactions, when the first reagent 11 in connectivity slot 21 is not cleaned, when rotor from port 1 goes to port When 2, the first reagent 11 in connectivity slot 21 can remain on the region between port 1 and port 2 (the delta in such as Fig. 4 Domain), the first reagent 11 of these residuals can pollute the other reagents entered through other ports with the rotation of rotor.So, It please join Fig. 3 and Fig. 5, triple valve is externally connected with the port of stator, before rotor, triple valve is connected the first buffer solution 11 With first port 22, and using drive component 50 the first buffer solution 60 is set to flow through the second valve and the first valve 20 successively, and then to even First reagent 11 of residual is cleaned in groove 21, significantly improves the situation of cross pollution.It is appreciated that this practicality is new In type example, the second valve 30 may include that triple valve V1-V8's is one or more.First port 22 may include one in the 1-8 of port It is individual or multiple.

Illustrate the cross pollution performance before and after improving to test below.In this test, the first valve 20 is with rotary valve Exemplified by illustrate.

First, existing two rotary valve of in the market is chosen, and builds test platform as shown in fig. 6, utilizing test platform Assess the cross pollution performance of two rotary valve (calling rotary valve A1 and rotary valve B1 in the following text).Incorporated by reference to Fig. 5, select close to port 1,2 and 8 is connected to fluorometric reagent 1 as test, port 1, and port 2 and port 8 are buffer solution, reaction unit flow cell There are two parallel passage A and B, test operation details is as follows：

(1) selection reaction unit flow cell passage A, makes fluorometric reagent 1 flow through passage A, so using drive component 50 After turn clockwise rotor, with port switching, make the communications ports 2 of connectivity slot 21 and common port 0, make excess using drive component 50 Buffer solution enter rotary valve through port 2, it is ensured that rotary valve include in the fluid path including common port 0 and connectivity slot 21 fluorescence examination Agent 1 is all cleaned up；

(2) fluid path is switched to reaction unit flow cell passage B, first taken using single molecule fluorescence detection system Passage B background, statistics fluorescence points n1；Then rotate counterclockwise rotor, makes the switching of connectivity slot 21 be communicated to port 8, that is, holds Mouth 8 is connected with common port 0, a certain amount of buffer solution is entered rotary valve through port 8 using drive component 50 and is flowed to reaction dress Flow cell passage B is put, the same regions of single molecule fluorescence detection system photographs passage B, statistics fluorescence points n2 is used；

(3) it is buffer solution due to enter rotary valve through port 2 and port 8, unstressed configuration point, therefore n2-n1 is that can be considered Rotary valve from port 1 be switched to port 2 (clockwise) be switched to again during port 8 (counterclockwise) caused by cross pollution, N2-n1 be fluorescence points increase must be fluorometric reagent 1 be mixed into through port 8 entrance buffer solution in and be detected it is glimmering Spot number, therefore the numerical value can assess cross pollution order of severity when rotating Vavle switching.

It is the initial data of 8 groups of tests shown in Fig. 7, it can be seen that either rotary valve A1 or rotary valve B1, all can not The cross pollution of reagent is avoided, because the pollution occurs in rotor, therefore is passed through after fluorometric reagent 1, even if connectivity slot 21 be switched to port 2 carry out rotary valve cleaning after be switched to port 8 again, can not also avoid all the time fluorometric reagent 1 be mixed into through end Mouthfuls 8 buffer solutions entered and produce pollution, therefore, common cleaning process also can not thoroughly solve problem.It should be noted that In Fig. 7, in the block diagram shown in same test group, n1 data, the post on the right before the histogram graph representation rotation on the left side Shape figure represents the data of n2 after rotation.

In the utility model embodiment, before rotor, the second valve 30 is set to connect the first buffer solution 60 and first end Mouth 22, and the first buffer solution 60 is flowed through the second valve 30 and the first valve 20 successively using drive component 50, above-mentioned intersection can be improved Pollution condition.Specifically, Fig. 5 please be join, illustrated so that the second valve 30 is three-way magnetic valve as an example.The normally closed port of three-way magnetic valve The reagent and buffer solution for needing to add are respectively connected with normally open, (now port 1 is connected for example, electric on magnetic valve V1 Reagent 1), after reagent 1 introduces rotary valve by drive component 50, immediately close magnetic valve V1 (the now connection of port 1 bufferings Liquid), in the connectivity slot 21 for washing a small amount of buffer solutions (determining specific amount according to pipeline situation) using drive component 50 The reagent 1 remained, there will be no reagent 1 to remain in rotation after so cleaning, then during rotor switching different port On the end face of rotary valve, although residual is buffer solution, but buffer solution on biochemical reaction without influence, this Sequence Detection System 300 can Avoided in other words due to reagent cross pollution caused by rotary valve rotation with substantially reducing.

Similarly, using single molecule fluorescence detection system, the cross pollution situation after improving, initial data such as Fig. 8 are assessed It is shown.The comparison of n2-n1 before and after improving is as shown in Figure 9.As known to Fig. 9, it can be seen that compared to rotary valve A1 before and B1, the Sequence Detection System 300 of the utility model embodiment make it that the cross pollution of rotary valve is obviously improved, The Sequence Detection System 300 of the utility model embodiment prevents reagent cross pollution from source, is especially suitable for applying right The very sensitive occasion of micro cross pollution, such as unimolecule gene sequencing instrument system.It should be noted that in Fig. 8, same In block diagram shown in individual test No., n1 data before the histogram graph representation rotation on the left side, the histogram graph representation rotation on the right N2 data afterwards.In Fig. 9, in the block diagram shown in same test group, the n2-n1 after the histogram graph representation improvement on the left side Data, rotary valve A1 n2-n1 data before middle histogram graph representation improves, the histogram graph representation on the right rotates before improving Valve B1 n2-n1 data.

In some embodiments, Figure 10 please be join, sequencing reaction includes the second biochemical reaction, and the second biochemical reaction is adopted Carried out with the second reagent 12 on reaction unit 40, valve component 10 includes the 3rd valve 31, multiple ports include second port 23, 3rd valve 31 can be directly connected to second port 23, the second reagent 12 and/or the second buffer solution.

In this way, the Sequence Detection System of the utility model embodiment can be applied to need progress many in sequencing reacts Individual different types of biochemical reaction, expands the application of the Sequence Detection System of the utility model embodiment.

Specifically, the Sequence Detection System of present embodiment can be infused according to the following steps：

S16, rotor makes connectivity slot 21 connect second port 23 and common port；

S17, makes the 3rd valve 31 connect the second reagent 12 and second port 23；

S18, makes the second reagent 12 enter reaction unit 40 through the 3rd valve 31 and the first valve 20 successively using drive component 50, To carry out the second biochemical reaction；

S19, before rotor, makes the 3rd valve 31 connect the second buffer solution and second port 23；

S20, makes the second buffer solution flow through the 3rd valve 31 and the first valve 20 successively using drive component 50.

Specifically, in the utility model example, incorporated by reference to Fig. 5, second port 23 may include one in the 1-8 of port or Multiple, the 3rd valve 31 may include one or more of triple valve V1-V8.It is pointed out that the second valve 30 and the 3rd valve 31 The different valves in triple valve V1-V8 should be selected.First port 22 and second port 23 answer the different port in selection port 1-8.

It should be noted that the second buffer solution is does not influence the solution of the first biochemical reaction, the first buffer solution 60 is not shadow Ring the solution of the second biochemical reaction.In the utility model embodiment, " being directly connected to " can refer to the solution of embodiment of above Release.

In the utility model Fig. 3 example, the second buffer solution and the first buffer solution 60 are same buffer solution.Certainly, Two buffer solutions and the first buffer solution are alternatively chosn to different buffer solutions.In one example, the first buffer solution and the second buffering Liquid is same buffer solution, be " 150mM HEPES, 150mM NaCl, pH=7.0 " buffer solution, to sequencing reaction not Influence.

In some embodiments, one of port 70 of the stator of the first valve 20 can be connected with outside air, with side Just air is introduced pipeline is carried out to remove agent liquid.

In the utility model embodiment, step S16 is implemented before step S17, in other embodiments, step S17 can be implemented before step S16, or step S16 and step S17 can be implemented simultaneously.

In some embodiments, the first biochemical reaction includes extension.

Specifically, extension is to be connected to based on base complementrity, by specific substrates on the sample for treating sequencing, and The type with reference to upper substrate is determined using the detectable group carried on substrate, to determine sequence.In one example, may be used Detection moiety includes fluorophor, can send fluorescence under the laser of specific wavelength.

In the utility model embodiment, alleged the first reagent is terminator reagent, i.e. reaction substrate, including A, T, C and G base analogues, specifically, alleged base analogue are that the structure of terminator terminates group-connection list for A/T/C/G- Member-luminophore, i.e. the first alleged reagent is (to call A examinations in the following text comprising the A- reagents for terminating group-connection unit-luminophore Agent), comprising T- terminate group-connection unit-luminophore reagent (calling T reagents in the following text), include C- terminate group-connection list The reagent (calling C reagents in the following text) of member-luminophore and/or comprising G- terminate group-connection unit-luminophore reagent (call G in the following text Reagent).Termination group therein be light and/or chemistry can cleavable groups, substrate is made with hair by connection unit (linker) Light group.

In a specific example, the luminophores of four kinds of terminator institute bands is the same structure or sent when being excited The detectable light of the same color, four kinds of base analogues are contained in different reagent bottles respectively.During sequencing, sequentially add One kind in A, T, C and G terminator, every four kinds of terminators reaction is referred to as a circulation.The reagent bottle for holding different terminators leads to Triple valve, the first valve is crossed to be connected with reaction unit.

Illustrate below in conjunction with Fig. 5 in an example of the present utility model, the adding procedure of mentioned reagent.

In Figure 5, reagent 1 is A reagents, and reagent 2 is T reagents, and reagent 3 is C reagents, and reagent 4 is G reagents.Prolonged Electric on triple valve V1 when stretching reaction, triple valve V2-V8 is closed, the connection of port 1 A reagents, communications ports 1 of connectivity slot 21 and public Mouth 0, drive component 50 makes A reagents be reacted through triple valve V1 and the first valve 20 into reaction unit 40 is interior, in rotor Before, triple valve V1 is closed, and the connection of port 1 buffer solution, drive component 50 makes buffer solution flow through triple valve V1 and the first valve 20.Rear Continuous when need to change T reagents, C reagents, G reagents and/or the other reagents of addition, rotor makes connectivity slot 21 connect common port 0 With corresponding port, and carried out according to above-mentioned process.

In some embodiments, the second biochemical reaction is cut off including group.

Specifically, need to be by the terminator of a upper structure when terminator of addition different structure is in reaction unit 40 The terminator of another structure is added after luminophore excision again.For example, incorporated by reference to above-mentioned example, adding A reagents to reaction When in device 40, exciting light is sent to reaction unit 40 using light-emitting device (such as laser), to excite luminophore to send Fluorescence, and taken pictures using imaging device to gather fluorescence, and form image to carry out sequencing.After the completion of taking pictures, A need to be tried Other reagents are added again after the luminophore excision of agent.Further, in this example embodiment, reagent 5 (is called in the following text for the reagent of excision Cut off reagent).Therefore, in some embodiments, Sequence Detection System 300 includes imaging device 102, and imaging device 102 is used Taken pictures in sequencing reaction.

After the completion of taking pictures, when addition excision reagent, rotor makes the communications ports 5 of connectivity slot 21 and common port 0, three Electric on port valve V5, triple valve V1-V4 and V6-V8 are closed, and the connection of port 5 excision reagent, drive component 50 makes excision reagent through three Port valve V5 and the first valve 20, which enter, carries out excision reaction in reaction unit 40, before rotor, triple valve V5 is closed, port 5 Buffer solution is connected, drive component 50 makes buffer solution flow through triple valve V5 and the first valve 20.

In some embodiments, extension is carried out using ligase and/or polymerase.

In some embodiments, the second biochemical reaction includes capping.

Specifically, it is alleged to cap the group/key being exposed after predominantly blocking group excision.In one example, First biochemical reaction includes extension, and the second biochemical reaction is cut off including group, and base can be broken by light and/or chemical ablation After group, the group being exposed is sulfydryl, by capping such as by adding alkylating reagent, sulfydryl can be protected not oxidized.

Incorporated by reference to above-mentioned example, further, in this example embodiment, reagent 6 (is called in the following text to cap added reagent and caps examination Agent).When addition caps reagent, rotor makes electric on the communications ports 6 of connectivity slot 21 and common port 0, triple valve V6, threeway Valve V1-V5 and V7-V8 are closed, and the connection of port 6 caps reagent, and drive component 50 makes to cap reagent through triple valve V6 and the first valve 20 Reaction is capped in into reaction unit 40, before rotor, triple valve V6 is closed, the connection of port 6 buffer solution, driving group Part 50 makes buffer solution flow through triple valve V6 and the first valve 20.

It is pointed out that in some embodiments, the first reagent may include do not have to the biochemical reaction in sequencing The reagent of influence, now, after the reagent enters reaction unit 40 through the second valve and the first valve 20, and before rotor, and The second valve and the first valve 20 need not be flowed through with fliud flushing or buffer solution, in this way, the time of sequencing reaction can be saved.

In some embodiments, drive component 50 includes pump, and pump connects common port by reaction unit 40.

In this way, can realize the driving to reagent and buffer solution using pump, the control of Sequence Detection System 300 is simpler.

Specifically, in the utility model example, pump includes the first pump 51 and the second pump 52, and the first pump 51 is single by first Member 41 connects the common port of one of them the first valve 20, and the second pump 52 connects the public affairs of another the first valve 20 by second unit 42 Mouth, makes the first reagent and the first buffer solution enter first module through the second valve 30 and the first valve 20 successively using the first pump 51 altogether 41, the first reagent and the first buffer solution is entered second unit 42 through the second valve 30 and the first valve 20 successively using the second pump 52.

In this way, can realize that the agent liquid for exporting the first valve 20 is inputted to the first list respectively using the first pump 51 and the second pump 52 Member 41 and/or second unit 42, convenient operation.

Specifically, the first pump 51 and the second pump 52 difference pipeline connection first module 41 and second unit 42, for example, passing through Flexible pipe is connected.

First pump 51 connects the common port of one of them the first valve 20 by first module 41, and the second pump 52 is single by second Member 42 connects the common port of another the first valve 20, during work, and the first pump 51 provides negative pressure to first module 41, so that first Unit 41 obtains the first reagent and/or other doses (including buffer solution and/or other reagents) being connected with the port of the first valve 20 Biochemical reaction and/or cleaning are carried out, after first module 41 has obtained dose liquid, the first pump 51 stops providing negative pressure.

First pump 51 makes any agent liquid enter first module 41, depends on：1) which port connectivity slot 21 connects；With it is 2) right In that port (calling communications ports in the following text) connected with connectivity slot 21, communications ports and which triple valve being connected with communications ports make Plant the connection of agent liquid.For example, making port 1 and examination incorporated by reference to Fig. 5, the communications ports 1 of connectivity slot 21, the triple valve V1 being connected with port 1 Agent 1 is connected, then when the first pump 51 provides negative pressure, and reagent 1 enters first module 41 through triple valve V1 and the first valve 20.

Similarly, the operation of the second pump 52 can join the operation of the first pump 51.

Further, in some embodiments, drive component 50 also includes the 4th valve 53, the 5th valve 54 and waste liquid bottle 55.The pipeline of 4th valve 53 is connected between the first pump 51 and first module 41, while going back pipeline connection waste liquid bottle 55.5th valve 54 Pipeline is connected between the second pump 52 and second unit 42, while going back pipeline connection waste liquid bottle 55.

First pump 51 connects first module 41 or waste liquid bottle 55 through the 4th valve 53, so that the first pump 51 extracts first module 41 After the waste liquid for inside having completed sequencing reaction, waste liquid can be injected to waste liquid bottle 55, so that under the first pump 51 is carried out Negative pressure once is provided to first module 41, to carry out sequencing reaction.5th valve 54 is identical with the 4th 53 structure to be set, herein Repeat no more.In some instances, the 4th valve 53 and the 5th valve 54 can be triple valve.

In some embodiments, fluid means 100 includes control unit, control unit electrical connection valve component 10 and drive Dynamic component 50 is run with application valve body component 10 and drive component 50.

In this way, the Automated condtrol of valve component 10 and drive component 50 can be realized, and then improve efficiency.

Specifically, in the utility model example, control unit electrically connects the first valve 20, the second valve 30, the and of the 3rd valve 31 Drive component 50, to control the first valve 20, the second valve 30, the 3rd valve 31 and drive component 50 to run.Control unit can be bag The devices such as single-chip microcomputer, computer processor or central control processor are included, the first valve 20, triple valve are controlled using control unit V1-V8 and drive component operation, realize the automatic running of fluid means 100, improve efficiency.

In some embodiments, when Sequence Detection System 300 includes control device 302, control unit can receive control The control signal of device 302 processed, and according to control signal to the other of valve component 10, drive component 50 and fluid means 100 Part is controlled.In this way, so by control unit the partial function of control device 302 can be performed into realization, reduce The load of control device 302.In some embodiments, control unit and control device 302 can be integrated in part, a module Or in device, to improve the integrated level of Sequence Detection System 300, reduce cost.

In some embodiments, incorporated by reference to Fig. 3 and Fig. 5, multiple port distributions are rounded, and common port is set with circular shape concentric Put.

In this way, multiple ports of rounded distribution and common port set connectivity slot when ensure that rotor with circular shape concentric 21 accuracys connected with corresponding port and common port.

In some embodiments, incorporated by reference to Fig. 3 and Fig. 5, connectivity slot 21 is in linear.In this way, agent liquid can be reduced in connection Flow path in groove 21, and then realize the quick sequencing of guarantee.

Specifically, in linear connectivity slot 21, can with shorter path connection positioned at the port at the two ends of connectivity slot 21 and Common port.In the utility model example, linear is linear.

It please join Fig. 1, the utility model embodiment provides a kind of device 302 being controlled to sequencing reaction, dress Putting 302 includes：

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

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

A kind of computer-readable recording medium of the utility model embodiment, for storing the journey performed for computer Sequence, configuration processor includes the method for completing any of the above-described embodiment.Computer-readable recording medium can include：Read-only storage Device, random access memory, disk or CD etc..

In the description of this specification, reference term " embodiment ", " some embodiments ", " schematically implementation The description of mode ", " example ", " specific example " or " some examples " etc. means with reference to the embodiment or example description Specific features, structure, material or feature are contained at least one embodiment of the present utility model or example.In this explanation In book, identical embodiment or example are not necessarily referring to the schematic representation of above-mentioned term.Moreover, the specific spy of description Levy, structure, material or feature can in an appropriate manner be combined in any one or more embodiments or example.

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

It should be appreciated that each several part of the present utility model can be realized with hardware, software, firmware or combinations thereof. In above-mentioned embodiment, what multiple steps or method can in memory and by suitable instruction execution system be performed with storage Software or firmware are realized.If, and in another embodiment, can be with known in this field for example, realized with hardware Any one of following technology or their combination realize：With the gate for realizing logic function to data-signal The discrete logic of circuit, the application specific integrated circuit with suitable combinational logic gate circuit, programmable gate array (PGA), Field programmable gate array (FPGA) or other circuit structures etc..

In addition, each functional unit in the utility model each embodiment can be integrated in a processing module, Can also be that unit is individually physically present, can also two or more units be integrated in a module.Above-mentioned collection Into module can both have been realized in the form of hardware, it would however also be possible to employ the form of software function module is realized.It is described integrated If module is realized using in the form of software function module and as independent production marketing or in use, can also be stored in one In computer read/write memory medium.

Although embodiment of the present utility model has been shown and described above, it is to be understood that above-mentioned embodiment party Formula is exemplary, it is impossible to be interpreted as to limitation of the present utility model, one of ordinary skill in the art is of the present utility model In the range of above-mentioned embodiment can be changed, change, replace and modification.

Claims (10)

1. a kind of Sequence Detection System, is controlled to sequencing reaction, it is characterised in that the sequencing reaction includes First biochemical reaction, first biochemical reaction is carried out using the first reagent on reaction unit,

The Sequence Detection System includes fluid means, and the fluid means includes valve component and drive component,

The valve component includes the first valve and the second valve, the first valve and the reaction unit connection, the first valve bag The stator and rotor that can be connected are included, first valve has on common port, the stator to have on multiple ports, the rotor and had There is connectivity slot, by rotating the rotor common port and at least one described port can be made to connect by the connectivity slot Logical, the multiple port includes first port, second valve can be directly connected to the first port, first reagent and/ Or first buffer solution.

2. the system as claimed in claim 1, it is characterised in that the sequencing reaction includes the second biochemical reaction, described Second biochemical reaction is carried out using the second reagent on the reaction unit, and the valve component includes the 3rd valve, the multiple Port includes second port, and the 3rd valve can be directly connected to the second port, second reagent and/or the second buffering Liquid.

3. the system as claimed in claim 1, it is characterised in that first valve is multiple-way valve.

4. the system as claimed in claim 1, it is characterised in that second valve is triple valve.

5. the system as claimed in claim 1, it is characterised in that the Sequence Detection System includes imaging device, the imaging Device is used to take pictures to sequencing reaction.

6. the system as claimed in claim 1, it is characterised in that the Sequence Detection System includes control device, the control Device connects the valve component and the drive component, and the control device is used to control the valve component and the driving The operation of component.

7. the system as claimed in claim 1, it is characterised in that the drive component includes pump, the pump passes through the reaction Device connects the common port.

8. the system as claimed in claim 1, it is characterised in that the fluid means includes control unit, described control unit The valve component and the drive component is electrically connected to control the valve component and the drive component to run.

9. the system as claimed in claim 1, it is characterised in that the multiple port distribution is rounded, the common port and institute State circular shape concentric setting.

10. the system as claimed in claim 1, it is characterised in that the connectivity slot is in linear.