CN106635772B

CN106635772B - Multichannel sequencing reaction small chamber and multichannel sequencing reaction device

Info

Publication number: CN106635772B
Application number: CN201510733672.8A
Authority: CN
Inventors: 盛司潼; 冯传发
Original assignee: Individual
Current assignee: Individual
Priority date: 2015-11-03
Filing date: 2015-11-03
Publication date: 2019-07-02
Anticipated expiration: 2035-11-03
Also published as: WO2017076013A1; CN106635772A

Abstract

The present invention relates to biochemical sequencing equipment technical field, a kind of multichannel sequencing reaction small chamber and multichannel sequencing reaction device are provided；The multichannel sequencing reaction small chamber includes the first slide and the second slide to fit, first slide is used to form a plurality of hollow reaction channel with the second slide, the both ends of the reaction channel are respectively provided with the reagent buffer area for accommodating reagent, it is provided with the reagent inlet being connected to reagent buffer area on first slide or the second slide, is additionally provided with the reagent exit being connected to reagent buffer area on first slide or the second slide；The beneficial effect of multichannel sequencing reaction small chamber of the invention is: by the design of reagent buffer area, the structure of multichannel sequencing reaction small chamber simplified, is cleaned convenient for the inside to multichannel sequencing reaction small chamber, it is very convenient；Can repeatedly use, compared with the existing technology in disposable reaction chamber, greatly reduce the cost of equipment.

Description

Multichannel sequencing reaction small chamber and multichannel sequencing reaction device

Technical field

The present invention relates to biochemical equipment field, it is more particularly related to a kind of multichannel sequencing reaction small chamber and Multichannel sequencing reaction device.

Background technique

Gene sequencing technology develops very swift and violent in recent years.It is different from first generation sequencing technologies " Capillary Electrophoresis order-checking ", Current gene sequencing technology is to detect nucleic acid by gene sequencer, obtains nucleic acid sequence by data processing.And in base Because including an important equipment -- sequencing reaction small chamber in sequenator.

Sequencing reaction small chamber is for carrying out sequencing reaction.In the gene sequencer of the prior art, sequencing reaction small chamber tool There is an intermediate reaction channel wide, both ends are narrow, when being sequenced, it is anti-that the sample to be tested handled well is fixed on sequencing first Small interior is answered, sequencing reaction reagent is then injected into, which flows through sequencing reaction small chamber by reaction channel, sends out with sample to be tested Raw sequencing reaction.After sequencing reaction, sequencing signal is acquired by signal pickup assembly, by the data processing in later period from And obtain gene order.

Since gene sequencing is the operation in nanometer scale, the preparation for instrument processing precision and various biochemical materials Required precision is all very high, and the requirement to temperature, reagent dosage, the time control of biochemical reaction etc. is also very strict.And it is exactly Due to above-mentioned limitation, in the gene sequencer of the prior art, designed sequencing reaction small chamber is single channel.When needs pair When multiple samples to be tested are sequenced, multiple sequencing reaction can only be carried out respectively, this makes the efficiency that Multi-example is sequenced very It is low.

Low efficiency is sequenced to Multi-example in view of the sequencing reaction small chamber in single channel, therefore the sequencing for designing multichannel is anti- Answer cell.Multichannel sequencing reaction small chamber in the prior art has multiple reaction channels, can be simultaneously in multiple reaction channels Sequencing reaction is carried out simultaneously.Since each reaction channel is required to be passed through reagent, each reaction chamber individually has examination Agent import and reagent exit, and it is connected with pipeline on reagent entry port and reagent exit, for flowing into and out for reagent.It is existing The structure of multichannel sequencing reaction small chamber in technology it is very cumbersome with it is complicated, and cleaning when need by more root canal roads carry out Disassembly, it is very inconvenient, it is also easy to poor sealing occur in disassembly and assembling process, causes to occur during sequencing reaction The case where leakage.

Therefore the multichannel sequencing reaction small chamber and degree channel sequencing reaction device for needing one kind new, can simplify multichannel The structure of sequencing reaction small chamber facilitates the disassembly and cleaning of sequencing reaction small chamber.

Summary of the invention

The purpose of the present invention is to provide a kind of multichannel sequencing reaction small chambers, it is intended to solve sequencing reaction in the prior art Cell structure is complicated, is not easy to the problem of being dismantled and being cleaned.

In order to realize goal of the invention, multichannel sequencing reaction small chamber includes: the first slide and the second glass including fitting Piece, first slide are used to form a plurality of hollow reaction channel with the second slide, and the both ends of the reaction channel are set respectively There is the reagent buffer area for accommodating reagent, is provided with the examination being connected to reagent buffer area on first slide or the second slide Agent entrance is additionally provided with the reagent exit being connected to reagent buffer area on first slide or the second slide.

Wherein, first slide is located above the second slide, and the reaction channel and reagent buffer area are arranged at the The lower surface of one slide, the reagent inlet are the through-hole being set on the first slide or the second slide, and the reagent exit is The through-hole being set on the first slide or the second slide.

Wherein, first slide is located above the second slide, and the reaction channel and reagent buffer area are arranged at the The upper surface of two slides, the reagent inlet are the through-hole being set on the first slide or the second slide, and the reagent exit is The through-hole being set on the first slide or the second slide.

Wherein, first slide is located above the second slide, and the lower surface of first slide is provided with multiple strips The groove of shape after the second slide is fitted on the first slide lower surface, constitutes hollow react with the strip-shaped groove Channel；The reagent setting buffers are set to the first slide in the lower surface of the first slide and the upper surface of the second slide On reagent buffer area shape it is identical as the shape for the reagent buffer area being set on the second slide, when the first slide is fitted in When on the second slide, the reagent buffer area being set on the first slide and the reagent buffer area kissing being set on the second slide It closes.

Wherein, first slide is located above the second slide, the lower surface of first slide and the second slide it is upper Surface is provided with the multiple strip-shaped grooves to match, and after the first slide and the second slide fit, the strip to match is recessed Slot constitutes hollow reaction channel；Reagent setting buffers in the lower surface of the first slide and the upper surface of the second slide, and The shape for the reagent buffer area being set on the first slide is identical as the shape for the reagent buffer area being set on the second slide, when When first slide is fitted on the second slide, the reagent buffer area that is set on the first slide and it is set to the second slide On reagent buffer area match.

Wherein, the shape of the reagent inlet and reagent exit is identical as the shape of reagent buffer area.

Wherein, first slide is fitted closely by coverslip and drain piece, and second slide is glass slide, institute Drain piece is stated between coverslip and glass slide, the drain on piece is provided with the through-hole of strip, the reaction channel by Coverslip, the through-hole of strip and glass slide enclose；Or

First slide is coverslip, and second slide is fitted closely by drain piece and glass slide, described to lead Liquid on piece is provided with the through-hole of strip, and the reaction channel is enclosed by coverslip, the through-hole of strip and glass slide.

Further, the reagent buffer area is that the through-hole of drain on piece is arranged in or is setting on the cover slip logical Hole.

Further, reagent buffer area semicircular in shape, reagent buffer area have arc-shaped edges and straight line, and described slow The straight line for rushing area is located at close to the side of the reaction channel.

Further, the reagent buffer area is triangular in shape.

In addition, the invention also provides a kind of, the multichannel sequencing reaction with above-mentioned multichannel sequencing reaction small chamber is filled It sets, it is made of multichannel sequencing reaction small chamber, cell upper element and cell lower component, in which:

The cell upper element includes feed pathway and liquid outlet channel；

The cell lower component includes cell upper cover and cell pedestal, and the cell pedestal is used to place the multi-pass Road sequencing reaction small chamber, the cell upper cover are mounted on cell pedestal；

The cell upper element is for being mounted on cell lower component, and the feed pathway of the cell upper element It is connected to the reagent inlet of the multichannel sequencing reaction small chamber, the liquid outlet channel and the multichannel of the cell upper element The reagent exit of sequencing reaction small chamber is connected to.

Wherein, the cell upper element further includes bottom plate, thermal insulation board, cooling piece, heat-conducting plate and temperature sensor；Its In

The thermal insulation board is fixed on the lower section of bottom plate, and the middle part of the thermal insulation board has through-hole, and the cooling piece is set to In the through-hole of thermal insulation board, and the upper surface of the cooling piece is in contact with the lower surface of bottom plate；

The heat-conducting plate is fixed on the lower section of cooling piece, and the upper surface of heat-conducting plate is in contact with the lower surface of cooling piece, when When cell upper element is mounted in cell lower component, the lower surface of the heat-conducting plate connects with multichannel sequencing reaction small chamber Touching；

The temperature sensor is used to detect the temperature of the multichannel sequencing reaction small chamber；

The feed pathway and liquid outlet channel are respectively the through-hole through the bottom plate, thermal insulation board and heat-conducting plate.

Further, the middle part of the cell upper cover has through-hole, and the cell upper element is mounted on cell lower part group When on part, the thermal insulation board and heat-conducting plate of the cell upper element are protruded into the through-hole of cell upper cover, and the heat-conducting plate is tightly attached to On multichannel sequencing reaction small chamber, and the feed pathway is connected to the reagent inlet of multichannel sequencing reaction small chamber, it is described go out Liquid channel is connected to the reagent exit of multichannel sequencing reaction small chamber.

Further, the cell upper element further includes top plate and heat sink, and the top plate is arranged above bottom plate, institute Heat sink is stated between top plate and bottom plate and is fixed on the bottom plate, the heat sink has several radiating fins.

Further, the bottom plate and thermal insulation board are connected by screw to, and are provided with steel pipe among the screw, which is For feed pathway and liquid outlet channel.

Further, seal gasket is additionally provided on the heat-conducting plate, and seal gasket is set to the outlet of feed pathway The inlet at place and liquid outlet channel, when the cell upper element is mounted in cell lower component, the seal gasket is close to In on multichannel sequencing reaction small chamber.

Wherein, it is elasticly connected with briquetting below the cell upper cover, the briquetting is pressed in multichannel sequencing reaction small chamber On.

Wherein, buckle is provided on the cell on lid, the buckle is for being stuck in the cell pedestal.

Further, it is provided with through-hole on the cell upper element, the through-hole is for shooting light field figure, for seeing Whether the magnetic bead distribution in cell is uniform.

From the foregoing, it will be observed that the present invention passes through the design of reagent buffer area, the structure of multichannel sequencing reaction small chamber is simplified, just It is cleaned in the inside to multichannel sequencing reaction small chamber, it is very convenient, it reduces and is dismantling and occurring in assembling process Poor sealing and cause the case where leakage occur during sequencing reaction；It can repeatedly use in actual use, Disposable reaction chamber in compared with the existing technology, greatly reduces the cost of equipment.

Detailed description of the invention

Fig. 1, Fig. 2 are the structural representation in the multichannel sequencing reaction small chamber of an example of the present invention about reaction channel Figure.

Fig. 3, Fig. 4 are the structural representation in another exemplary multichannel sequencing reaction small chamber of the invention about reaction channel Figure.

Fig. 5 is the structural schematic diagram in another exemplary multichannel sequencing reaction small chamber of the invention about reaction channel.

Fig. 6 a is the structural schematic diagram in another exemplary multichannel sequencing reaction small chamber of the invention about reaction channel.

Fig. 6 b is the structural schematic diagram in another exemplary multichannel sequencing reaction small chamber of the invention about reaction channel.

Fig. 7 is the structural schematic diagram in the multichannel sequencing reaction small chamber of an example of the present invention about reagent buffer area；

Fig. 8 is the structural representation in another exemplary multichannel sequencing reaction small chamber of the invention about reagent buffer area Figure.

Fig. 9 is the structural representation in another exemplary multichannel sequencing reaction small chamber of the invention about reagent buffer area Figure.

Figure 10 a, Figure 10 b are the knot in another exemplary multichannel sequencing reaction small chamber of the invention about reagent buffer area Structure schematic diagram.

Figure 11 a, Figure 11 b are in the multichannel sequencing reaction small chamber of an example of the present invention about reagent buffer area shape Two kinds of structural schematic diagrams.

Figure 12 a, Figure 12 b, Figure 12 c are in multichannel sequencing reaction small chamber of the invention about reagent inlet and reagent exit Three kinds of exemplary diagrams.

Figure 13 a is the knot in the multichannel sequencing reaction small chamber of an example of the present invention about reagent inlet and reagent exit Structure schematic diagram.

Figure 13 b is in another exemplary multichannel sequencing reaction small chamber of the invention about reagent inlet and reagent exit Structural schematic diagram.

Figure 14 is the structural schematic diagram of the multichannel sequencing reaction device of an example of the present invention.

Figure 15 is the vertical section structure of cell upper element in another exemplary multichannel sequencing reaction device of the invention Schematic diagram.

Figure 16 is the vertical section structure schematic diagram of another exemplary multichannel sequencing reaction device of the invention.

Figure 17 is the vertical section structure schematic diagram of another exemplary multichannel sequencing reaction device of the invention.

Specific embodiment

In order to make the objectives, technical solutions, and advantages of the present invention clearer, with reference to the accompanying drawings and embodiments, right The present invention is further elaborated.

The present invention proposes first embodiment, and the present embodiment proposes a kind of multichannel sequencing reaction small chamber, which surveys Sequence reaction small chamber makes multiple samples while carrying out sequencing reaction, realizes multichannel sequencing reaction small chamber and is sequenced in parallel.It is described Multichannel sequencing reaction small chamber includes the first slide and the second slide to fit, and first slide is used for and the second slide shape At a plurality of hollow reaction channel, the both ends of the reaction channel are respectively provided with the reagent buffer area for accommodating reagent, described The reagent inlet being connected to reagent buffer area is provided on first slide or the second slide, on first slide or the second slide It is additionally provided with the reagent exit being connected to reagent buffer area.

In the present embodiment, the reagent inlet is connected to the pipeline of supply reagent, reagent exit and the pipe for excluding reagent Road connection.Multiple samples to be tested are fixed on the inner wall of the reaction channel between the first slide and the second slide, are passed through The pipeline of supply reagent is passed through reagent in multichannel sequencing reaction small chamber, and before reagent enters reaction channel, reagent first can Into being located in the reagent buffer area of reaction channel one end, after the filling of reagent buffer area, reagent enters in multiple lead to simultaneously again In empty reaction channel, sequencing reaction occurs simultaneously with sample to be tested in multiple reaction channels, overcomes traditional sequencing reaction Small interior can only single sample be sequenced, the problem under efficiency is relatively low；Hereafter it is another then to flow out into reaction channel for reagent In the reagent buffer area of one end, after reagent collects in the reagent buffer area, it is discharged from the pipeline of discharge reagent.Since reagent is slow The presence in area is rushed, reagent buffer area can store a certain amount of reagent, and it is slow that reagent can be flowed into before reagent is passed through reaction channel It rushes in area, reagent buffer area is conducive to the air being uniformly discharged in a reaction channel, inside pressure when reagent enters reaction channel Power one to, reagent can uniformly pass through each reaction channel, thus ensure that the uniformity of each reaction channel flow velocity with And diffusible uniformity.

Sequencing reaction small chamber in the prior art with multiple channels, since with multiple reaction channels, each is anti- The entrance and exit in channel is answered to be required to access conduit, for flowing into and out for reagent；The sequencing reaction small chamber of this structure Structure it is very cumbersome with it is complicated, when cleaning sequencing reaction small chamber, need to dismantle in more root canal roads, very not It is convenient, it is also easy to poor sealing occur in disassembly and assembling process, causes the case where leakage occur during sequencing reaction.And Multichannel sequencing reaction small chamber in the present embodiment, due to the setting of reagent buffer area, it is only necessary to which it is slow that a root canal road accesses reagent Rush area, so that it may which the sequencing reaction for completing multiple channels simplifies the structure of multichannel sequencing reaction small chamber；In addition, needing To sequencing reaction small chamber carry out disassembly, cleaning when, it is only necessary to dismantle the feed liquor that one is connected to reagent inlet pipeline and one and The pipeline for going out liquid of reagent exit connection, so that it may the inside of sequencing reaction small chamber is cleaned, it is very convenient, it reduces There is the case where leakage during disassembly and the poor sealing that occurs in assembling process cause sequencing reaction.It is actually using Can repeatedly use in the process, compared with the existing technology in disposable reaction chamber, the present invention greatly reduces equipment Cost.

It is described in detail below for all parts of multichannel sequencing reaction small chamber.

(1) reaction channel about multichannel sequencing reaction small chamber.

For the reaction channel of multichannel sequencing reaction small chamber, the invention proposes an examples, as shown in Figure 1 and Figure 2, institute Stating multichannel sequencing reaction small chamber includes the first slide 10 and the second slide 20 to fit, and Fig. 1 is the first slide 10 and second The schematic cross-section of slide 20, Fig. 2 are the schematic perspective view of the first slide 10, and first slide 10 is located at the second slide 20 tops, first slide 10 are used to form a plurality of hollow reaction channel 101, and the reaction channel with the second slide 20 101 both ends are respectively provided with the reagent buffer area 102 for accommodating reagent, and in this example, the reaction channel 101 and reagent are slow The lower surface that area 102 is arranged at the first slide 10 is rushed, specifically, being provided with strip on the bottom surface of first slide 10 Groove, after the second slide 20 covers on the first slide 10 and the groove of strip forms the reaction channel of closed hollow structure 101, the lower surface of the first slide 10 is arranged in reagent buffer area 102.In addition, being provided on first slide 10 slow with reagent The reagent inlet 103 and reagent exit 104 that area 102 is respectively communicated with are rushed, in this example, the reagent inlet 103 and reagent go out Mouth 104 is the through-hole being arranged on the first slide 10.

As shown in Figure 1, the inner wall of reaction channel 101 is used to fix multiple samples to be tested in the reaction channel 101, The quantity of reaction channel 101 can be set as needed, such as can be the sequencing reaction small chamber in six channels, be also possible to eight The sequencing reaction small chamber in channel, shown in Fig. 2 is the first slide 10 of six channel sequencing reaction small chambers.In this example, Reagent inlet 103 is connected to the pipeline of supply reagent, and reagent exit 104 is connected to the pipeline of discharge reagent, it is contemplated that reagent Flowing, before carrying out sequencing reaction, preferably places sequencing reaction small chamber, and reagent inlet 103 is located below vertically.Into When row sequencing reaction, the reagent buffer area at reagent inlet 103 is initially entered by the reagent that reagent inlet 103 injects 102, after persistently injecting reagent, after reagent is filled with the reagent buffer area 102 at reagent inlet 103, it can just enter six simultaneously In reaction channel 101, sequencing reaction is carried out with the sample to be tested being fixed in reaction channel 101 respectively, is then out and enters In the reagent buffer area 102 at reagent exit 102, after reagent collects in the reagent buffer area 102, from the pipe of discharge reagent It is discharged in road, persistently injects reagent, reagent is then constantly flowed through from reaction channel 101, and sequencing reaction occurs with sample to be tested. Due to the presence of reagent buffer area 102, before reagent is passed through reaction channel 101, or after the outflow of reaction channel 101, reagent Buffer area 102 can store a certain amount of reagent, ensure that the uniformity and diffusivity of each 101 flow velocity of reaction channel Uniformity.This invention simplifies the structures of multichannel sequencing reaction small chamber, are needing to dismantle sequencing reaction small chamber When cleaning, it is only necessary to dismantle the pipeline for the feed liquor that one is connected to reagent inlet 103 and what one was connected to reagent exit 104 goes out The pipeline of liquid, after the first slide 10 is separated with the second slide 20, so that it may to the reaction channel 101 of sequencing reaction small chamber, Reagent buffer area 102, reagent inlet 103 and reagent exit 104 are cleaned, very convenient, while being reduced and being dismantled Cause the case where leakage occur during sequencing reaction with the poor sealing occurred in assembling process.Carry out the first slide and When the installation of the second slide, since reagent inlet, reagent exit, reaction channel and reagent buffer area are arranged at the first slide On, therefore very convenience is installed.

As shown in Figure 3, Figure 4, for the reaction channel of multichannel sequencing reaction small chamber, the invention also provides an example, The multichannel sequencing reaction small chamber includes the first slide 10 and the second slide 20 to fit, and Fig. 3 is 10 He of the first slide The schematic cross-section of second slide 20, Fig. 4 are the schematic perspective view of the first slide 10 and the second slide 20, first glass Piece 10 is located at 20 top of the second slide, and first slide 10 is used to form a plurality of hollow reaction channel with the second slide 20 101, and the both ends of the reaction channel 101 are respectively provided with the reagent buffer area 102 for accommodating reagent.Specifically, originally showing In example, the upper surface of second slide 20 has the groove of multiple strips, when the first slide 10 is fitted in the second slide 20 When upper, the groove of strip and the first slide 10 enclose and constitute hollow reaction channel 101, and the both ends of reaction channel 101 It is connected to reagent buffer area 102, the lower surface of the first slide 10 is arranged in reagent buffer area 102.In addition, first slide 10 On be provided with the reagent inlet 103 and reagent exit 104 being respectively communicated with reagent buffer area 102, and the reagent inlet 103 It is the through-hole being arranged on the first slide 10 with reagent exit 104.

The inner wall of the reaction channel 101 of hollow structure is for fixing multiple samples to be tested, reagent inlet 103 and supply reagent Pipeline connection, reagent exit 104 be discharged reagent pipeline be connected to.Before carrying out sequencing reaction, sequencing reaction small chamber is erected It is straight to place, and reagent inlet 103 is located below.When carrying out sequencing reaction, the reagent injected by reagent inlet 103 is first Into the reagent buffer area 102 being located at reagent inlet, after persistently injecting reagent, it is slow that reagent is filled with the reagent at reagent inlet It after rushing area 102, can just enter in multiple reaction channels 101 simultaneously, be then out and enter the reagent being located at reagent exit 104 In buffer area 102, after reagent collects in the reagent buffer area 102, it is discharged from the pipeline of discharge reagent, due to reagent buffer area 102 presence, before reagent is passed through reaction channel 101, or after the outflow of reaction channel 101, reagent buffer area 102 can Store a certain amount of reagent, thus ensure that each 101 flow velocity of reaction channel uniformity and diffusible uniformity. This invention simplifies the structures of multichannel sequencing reaction small chamber, unusual when needing to carry out disassembly, cleaning to sequencing reaction small chamber It is convenient, while reducing the poor sealing occurred in disassembly and assembling process and leakage occur during causing sequencing reaction Situation.In this example, since the lower surface of the first slide 10 is arranged in reagent buffer area 102, multiple strip-shaped groove settings exist On second slide 20, relative to the reagent buffer area and reaction channel for processing different structure on same slide, this programme drop Low difficulty of processing.

For the reaction channel of multichannel sequencing reaction small chamber, as shown in figure 5, the invention also provides an example, it is described Multichannel sequencing reaction small chamber includes the first slide 10 and the second slide 20 to fit, and Fig. 5 is the first slide 10 and the second glass The schematic cross-section of piece 20, the first slide 10 are located at 20 top of the second slide, and the first slide 10 is used for and the formation of the second slide 20 A plurality of hollow reaction channel 101, and the both ends of the reaction channel 101 are respectively provided with the reagent buffer area for accommodating reagent 102.Specifically, in this example, the upper surface of the lower surface of first slide 10 and the second slide 20 is provided with strip The groove of shape, after the first slide 10 and the second slide 20 fit, the groove and the second slide of strip on the first slide 10 Strip-shaped groove on 20 is adapted, and constitutes hollow reaction channel 101, and the reagent buffer area 102 is set to the first slide Lower surface, reaction channel is connected to reagent buffer area 102.When first slide 10 is fitted on the second slide 20, Using encapsulation process, leakage is prevented.Further, the examination being respectively communicated with reagent buffer area is provided on the first slide 10 Agent entrance 103 and reagent exit 104, and reagent inlet 103 and reagent exit 104 are that leading on the first slide 10 is arranged in Hole.When carrying out sequencing reaction, the reagent at reagent inlet 103 is initially entered by the reagent that reagent inlet 103 injects Buffer area 102, persistently inject reagent after, after reagent is filled with the reagent buffer area 102 at reagent inlet 103, just can and meanwhile into Enter in multiple reaction channels 101, carries out sequencing reaction, sequencing reaction while realizing multiple samples with sample to be tested.The present invention The structure for simplifying multichannel sequencing reaction small chamber, it is very convenient when needing to carry out disassembly, cleaning to sequencing reaction small chamber.

For the reaction channel 101 of multichannel sequencing reaction small chamber, as shown in Figure 6 a, the invention also provides an example, The multichannel sequencing reaction small chamber makes multiple samples while carrying out sequencing reaction, and it is flat to realize multichannel sequencing reaction small chamber Row sequencing.Multichannel sequencing reaction small chamber includes the first slide 10 and the second slide 20 to fit, and first slide 10 is used In forming a plurality of hollow reaction channel 101 with the second slide 20, the both ends of the reaction channel 101 are respectively provided with receiving The reagent buffer area 102 of reagent is provided with the reagent inlet being respectively communicated with reagent buffer area 102 on first slide 10 103 and reagent exit 104, in this example, as shown in figure 8, first slide 10 is closely pasted by coverslip 30 and drain piece 40 It closes, second slide 20 is glass slide 50, and the drain piece 40 is between coverslip 30 and glass slide 50；It is described to lead The through-hole of strip is provided on liquid piece 40, when coverslip 30 and glass slide 50 are fitted in the upper and lower surface of drain piece respectively, It is enclosed with the through-hole of strip and constitutes the reaction channel 101；It is provided with through-hole on the drain piece 40, when 30 He of coverslip When glass slide 50 is fitted in the upper and lower surface of drain piece respectively, reagent buffer area 102 is constituted with through-hole enclosing.Carry out Before sequencing reaction, the multichannel sequencing reaction small chamber in the present embodiment is placed on sequencing device vertically, reagent inlet 103 with It is passed through the pipeline connection of reagent, reagent exit 104 is connected to the pipeline of outflow reagent, and multiple samples to be tested are fixed on drain piece Reaction channel 101 inner wall on, before reagent enters reaction channel 101, reagent first can enter be located at reaction channel 101 1 In the reagent buffer area 102 at end, after reagent buffer area 102 is filled, reagent can just enter the reaction channel of drain piece 40 simultaneously In 101, sequencing reaction occurs simultaneously with sample to be tested in multiple reaction channels 101, overcomes in traditional sequencing reaction small chamber Can only single sample be sequenced, the problem under efficiency is relatively low.Hereafter reagent flows out into the examination of the reaction channel other end In agent buffer area 102, after reagent collects in the reagent buffer area 102, it is discharged from the pipeline of discharge reagent.Since reagent buffers The presence in area 102, reagent buffer area 102 can store a certain amount of reagent, can flow into examination before reagent is passed through reaction channel In agent buffer area 102, reagent buffer area 102 is conducive to the air being uniformly discharged in a reaction channel 101, and reagent enters reaction Always, reagent can uniformly pass through each reaction channel to internal pressure, therefore ensure that each reaction channel 101 when channel The uniformity of flow velocity and diffusible uniformity.Multichannel sequencing reaction small chamber of the invention and sequencing in the prior art Reaction small chamber compares, and simplifies the structure of multichannel sequencing reaction small chamber；It is clear needing to carry out dismantling to sequencing reaction small chamber When washing, the pipeline for being connected into reagent inlet 103 and reagent exit 104 need to only be dismantled, by coverslip 30, drain piece 40 and glass slide After 50 separation, so that it may the inside of sequencing reaction small chamber is cleaned, it is very convenient, it is passed through due to only needing to dismantle one The pipeline of the pipeline of reagent and an outflow reagent is reduced and is being torn open compared to the sequencing reaction small chamber for needing to dismantle more root canal roads It unloads and causes the case where leakage occur during sequencing reaction with the poor sealing that occurs in assembling process.

As shown in Figure 6 b, for multichannel sequencing reaction small chamber, the invention also provides an example, the multichannel sequencing Reaction small chamber includes the first slide 10 and the second slide 20 to fit, and first slide 10 is used for and the formation of the second slide 20 A plurality of hollow reaction channel 101, the both ends of the reaction channel 101 are respectively provided with the reagent buffer area for accommodating reagent 102, the reagent inlet 103 and reagent exit 104 being respectively communicated with reagent buffer area 102 are provided on first slide 10, In this example, first slide 10 is coverslip 30, and second slide 20 is closely pasted by drain piece 40 and glass slide 50 It closes, the drain piece 40 is between coverslip 30 and glass slide 50；The logical of strip is provided on the drain piece 40 Hole encloses with the through-hole of strip when coverslip 30 and glass slide 50 are fitted in the upper and lower surface of drain piece respectively and constitutes institute The reaction channel 101 stated；It is additionally provided with through-hole on drain piece 40, when coverslip 30 and glass slide 50 are fitted in drain piece respectively When upper and lower surface, reagent buffer area 102 is constituted with through-hole enclosing.Before carrying out sequencing reaction, multichannel is sequenced anti- Cell is answered to be placed on sequencing device vertically, reagent inlet 103 is connected to the pipeline for being passed through reagent, reagent exit 104 and outflow The pipeline of reagent is connected to, and multiple samples to be tested are fixed on the inner wall of reaction channel 101 of drain piece 40, is entered in reagent anti- Before answering channel 101, reagent can enter in the reagent buffer area 102 of 101 one end of reaction channel first, by reagent buffer area After 102 fillings, reagent can just enter simultaneously in the reaction channel 101 of drain piece 40, with sample to be tested in multiple reaction channels 101 Sequencing reaction occurs simultaneously.In the example described in Fig. 6 a, Fig. 6 b, the through-hole of strip is provided on drain piece 40, and It is fitted on drain piece 40 by coverslip 30 and glass slide 50, is enclosed with the through-hole of strip and constitute reaction channel 101.But it needs It is noted that the groove of multiple strips can be set on the upper surface or lower surface of the drain piece 40, when When the groove of the upper surface setting strip of drain piece 40, coverslip 30 is fitted in drain on piece, constitutes with the groove of strip Hollow reaction channel, to the lower surface of drain piece setting strip groove when, glass slide is fitted in drain on piece, with length The groove of bar shaped constitutes hollow reaction channel.

In above-mentioned any scheme, the quantity of reaction channel 101 can according to need carry out sequencing reaction to test sample The quantity of product is adjusted, and reaction small chamber all has six reaction channels in above-mentioned example.The structure of the reaction channel 101 Without concrete restriction, the cross section of reaction channel 101 can be semicircle or rectangular or other shapes, but it should be recognized that In general, sample to be tested needs to be fixed on burnishing surface, convenient for leading to after the progress of sequencing reaction and sequencing reaction for reacting The cleaning in road, therefore, in the example described in Fig. 1, Fig. 2, sample to be tested is fixed on the upper surface of the second slide 20, for reaction The then simultaneously no requirement (NR) of the shape in channel；In example described in Fig. 3, Fig. 4 and in example described in Fig. 5, sample to be tested is fixed on In strip-shaped groove on second slide 20, therefore, the bottom surface of strip-shaped groove is a burnishing surface, furthermore, it is contemplated that reaction is logical The difficulty of processing in road 101 and the cleaning difficulty of reaction channel 101, the corner of strip-shaped groove can be set to an arc Face reduces the difficulty of processing of multichannel sequencing reaction small chamber by the design of this structure, and it is anti-to be easy to implement multichannel sequencing The batch production for answering cell, in cleaning, the arcwall face of strip-shaped groove is more convenient for cleaning.

(2) about the reagent buffer area of multichannel sequencing reaction small chamber.

In the above-mentioned any scheme illustrated for reaction channel, the reagent buffer area 102 is arranged at first On the lower surface of slide 10.For reagent buffer area 102, the invention also provides an example, multichannel described in the example is surveyed Sequence reaction small chamber includes the first slide 10 and the second slide 20 to fit, and Fig. 7 is section of the first slide 10 and the second slide 20 Face schematic diagram, first slide 10 are located at 20 top of the second slide, and first slide 10 is used for and the formation of the second slide 20 A plurality of hollow reaction channel 101, and the both ends of the reaction channel 101 are respectively provided with the reagent buffer area for accommodating reagent 102.In this example, the upper surface of the second slide 20 is arranged in the reaction channel 101, still, any one in above-mentioned scheme Kind can be applicable in this example about the scheme of 101 position of reaction channel, then not to the position of reaction channel in this example It is described in detail again.The reagent buffer area 102 is the groove being arranged on the second slide 20, when the first slide 10 covers After on second slide 20, the reagent inlet 103 and reagent exit 104 being set on the first slide 10 then with reagent buffer area 102 Connection, meanwhile, the two ends of reaction channel 101 are connected to reagent buffer area 102 respectively.Before carrying out sequencing reaction, it will be sequenced Reaction small chamber is placed vertically, and reagent inlet 103 is located below, convenient for the air when carrying out sequencing reaction inside discharge, When carrying out sequencing reaction, the reagent injected by reagent inlet 103 can fill the reagent buffer area at reagent inlet 103 first 102, it can just enter in multiple reaction channels 101 simultaneously, sequencing reaction while realizing multiple samples.

As shown in figure 8, for the reagent buffer area 102 of multichannel sequencing reaction small chamber, the invention also provides an example, In this example, the lower surface of the first slide 10, for the position of reaction channel 101, above-mentioned is arranged in the reaction channel 101 The position of reaction channel 101 in meaning scheme can be applicable in this example, therefore then not to reaction channel 101 in this programme Position be described in detail.The reagent buffer area 102 is lower surface and the second slide 20 that the first slide 10 is arranged in Upper surface groove, and the shape for the groove being set on the first slide 10 and the shape of groove that is set on the second slide 20 Shape is identical, and when the first slide 10 is fitted on the second slide 20, groove matches, and constitutes reagent buffer area 102.Described The reagent inlet 103 and reagent exit 104 being respectively communicated with reagent buffer area 102 are provided on one slide 10, in this example, The reagent inlet 103 and reagent exit 104 are the through-hole being arranged on the first slide 10.It, will before carrying out sequencing reaction Sequencing reaction small chamber is placed vertically, and reagent inlet 103 is located below.It should be noted that not sequencing reaction small chamber only Carry out sequencing reaction can be placed vertically, when sequencing reaction small chamber is horizontally arranged, can also be completed sequencing reaction, be originally explanation Signified sequencing reaction small chamber places a kind of only preferable scheme vertically in book.When carrying out sequencing reaction, entered by reagent The reagents of 103 injection of mouth can fill the reagent buffer area 102 at reagent inlet 103 first, and it is logical just to enter simultaneously multiple reactions In road 101, sequencing reaction while realizing multiple samples.In this example, since longitudinal depth of reagent buffer area 102 is greater than The depth of reaction channel 101, therefore even if carrying out sequencing reaction when the multichannel sequencing reaction small chamber in this example is horizontal positioned, When being passed through reagent by reagent inlet 103, reagent will not be directly entered reaction channel 101, but be introduced into reagent buffering Area 102, after the reagent buffer area 102 being located on the second slide 20 is full of reagent, reagent can just enter reaction channel 101 simultaneously It is interior.

As shown in figure 9, for the reagent buffer area 102 of multichannel sequencing reaction small chamber, the invention also provides an example, In this example, the multichannel sequencing reaction small chamber includes the first slide 10 and the second slide 20 to fit, first glass Piece 10 is fitted closely by coverslip 30 and drain piece 40, and second slide 20 is glass slide 50, the drain piece 40 Between coverslip 30 and glass slide 50, the reagent being respectively communicated with reagent buffer area 102 is provided on the coverslip piece 30 Entrance 103 and reagent exit 104；The through-hole of strip is provided on the drain piece 40, when coverslip 30 and glass slide 50 divide When not being fitted in the upper and lower surface of drain piece, is enclosed with the through-hole of strip and constitute the reaction channel 101；The drain piece It is provided with through-hole on 40, and is arranged fluted on the glass slide 50, through-hole is adapted with the groove shapes, when lid glass When piece 30 and glass slide 50 are fitted in the upper and lower surface of drain piece 40 respectively, through-hole matches with the groove, described in composition Reagent buffer area 102.Such structure of reagent buffer area, multichannel sequencing reaction small chamber are in vertical placement status either When horizontal positioned state, reagent buffer area 102 can store certain reagent, and reagent will not be directly entered reaction channel 101, Ensure that each 101 flow velocity of reaction channel uniformity and diffusible uniformity.

As described in Figure 10 a, Figure 10 b, for the reagent buffer area 102 of multichannel sequencing reaction small chamber, the present invention is also proposed One example, the multichannel sequencing reaction small chamber include the first slide 10 and the second slide 20 to fit, first glass Piece 10 is fitted closely by coverslip 30 and drain piece 40, and second slide 20 is glass slide 50, the drain piece 40 Between coverslip 30 and glass slide 50；It is provided with through-hole on the coverslip 30, which is reagent buffer area 30.Such as figure Shown in 10b, the through-hole of strip is provided on the drain piece 40, when coverslip 30 is fitted in the upper surface of drain piece 40, When glass slide 50 is fitted in the lower surface of drain piece 40, the through-hole of strip is the reaction channel 101 for foring sealing, in lid glass It when piece 30 is bonded with drain piece 40, glass slide 50 with drain piece 40, needs to be sealed processing, prevents from be sequenced instead At once there is the case where leakage.In this example, reagent buffer area 102 and reaction channel 101 are arranged in coverslip 30 respectively On upper and drain piece 40, so that the processing of reagent buffer area 102 and reaction channel 102 is more simple, the efficiency of processing is improved. It is anti-to simplify multichannel sequencing to multichannel sequencing reaction small chamber of the invention compared with sequencing reaction small chamber in the prior art Answer the structure of cell.When being cleaned, coverslip 30 is removed from drain piece 40, by drain piece 40 from glass slide 50 On remove, coverslip 30, drain piece 40 and glass slide 50 are cleaned respectively, can be directly to the reagent on coverslip 30 Reaction channel 101 on buffer area 102 and drain piece 40 is cleaned, very convenient.

Further, on the basis of above-mentioned any scheme, for the shape of reagent buffer area 102, the invention proposes One example, as shown in fig. 11a, 102 semicircular in shape of reagent buffer area, reagent buffer area 102 have arc-shaped edges and straight line, The straight line of the buffer area 102 is located at close to the side of the reaction channel 101.By the design of such structure, when will be more After channel sequencing reaction small chamber is vertically arranged on sequencing device, as shown in fig. 11a, reagent is being injected toward reagent buffer area 102 During, since reagent buffer area 102 is designed as semicircle, the flow velocity of the point of A shown in Figure 11 a, B point and C point is more uniform, So that the flow velocity of any position is more uniform in reagent buffer area 102, to ensure that the equal of each 101 flow velocity of reaction channel Even property and diffusible uniformity；Make the sequencing reaction in multiple reaction channels 101 while carrying out.It should be noted that Above-mentioned scheme does not constitute any restrictions, the size and shape and root of reagent buffer area 102 to the structure of reagent buffer area 102 It is designed according to actual needs, such as reagent buffer area 102 can use square or rectangular, scheme shown in Figure 11 a is only For a preferable example.It as shown in figure 11b, is another example of reagent buffer area 102, in the example, the reagent buffer area 102 is triangular in shape, during injecting reagent toward reagent buffer area 102, by the design of triangular structure, guarantees each The uniformity of a 101 flow velocity of reaction channel and diffusible uniformity；Keep the sequencing reaction in multiple reaction channels 101 same Shi Jinhang.

(3) about reagent inlet and reagent exit.

For the position of reagent inlet 103 and reagent exit 104, in addition to reagent inlet 103 and examination in the above-described embodiments Except in the case of agent outlet 104 is arranged on the first slide 10, the present invention also provides an examples, as figure 12 a shows, multichannel Sequencing reaction small chamber includes the first slide 10 and the second slide 20 to fit, and the first slide 10 is used for and the formation of the second slide 20 A plurality of hollow reaction channel, the both ends of the reaction channel are respectively provided with the reagent buffer area for accommodating reagent；This example In, reaction channel and reagent buffer area in above-mentioned example can be applicable in this example, therefore for reaction channel and examination Agent buffer area, in this example then without detailed description；The upper table of the first slide 10 is arranged in the reagent inlet 103 The lower surface of the second slide 20 is arranged in face, the reagent exit 104, and reagent is passed through from reagent inlet 103 on the first slide 10, Reaction channel is flowed through, and is flowed out from the reagent exit 104 on the second slide 20.

For the position of reagent inlet and reagent exit, as shown in Figure 12b, the invention also provides an example, multichannels Sequencing reaction small chamber includes the first slide 10 and the second slide 20 to fit, is had for multichannel sequencing reaction small chamber anti- Channel and reagent buffer area are answered, the reaction channel and reagent buffer area in above-mentioned example can be applicable in this example, therefore For reaction channel and reagent buffer area in this example then without detailed description；In this example, the reagent inlet 103 The lower surface of second slide 20 is set, and reagent exit 104 is set to the upper surface of the first slide 10, passes through past second slide 20 Reagent inlet be passed through reagent, reagent after flowing through reaction channel, from the second slide 20 reagent exit 103 flow out.

As shown in fig. 12 c, for the position of reagent inlet 103 and reagent exit 104, the invention also provides an example, Multichannel sequencing reaction small chamber includes the first slide 10 and the second slide 20 to fit, likewise, in the present embodiment, for The reaction channel and reagent buffer area that multichannel sequencing reaction small chamber has are not explained in detail, 103 He of reagent inlet Reagent exit 104 is arranged on the bottom surface of the second slide 20, and when carrying out sequencing reaction, reagent is from the reagent on the second slide 20 Entrance 103 is passed through, the reacted channel of reagent flow, is flowed out from the reagent exit of the second slide 104.For reagent inlet and reagent The setting of the position of outlet, can according to the actual situation depending on, the present invention is not to the position of reagent inlet 103 and reagent exit 104 It sets and carries out any restriction.In the example described in Figure 12 a, Figure 12 b, since the second slide 20 is arranged in reagent inlet 103 Lower surface is carrying out sequencing reaction, when multichannel sequencing reaction small chamber is in horizontal positioned state, by reagent inlet 103 to Reagent is injected in reaction channel, reagent collects in reagent buffer area, will not be directly entered in reaction channel, therefore, reagent inlet It is arranged at the second slide lower surface, is applicable to the horizontal positioned feelings for carrying out sequencing reaction of multichannel sequencing reaction small chamber Condition.

It is to be arranged first in above-mentioned arbitrary scheme for the shape of reagent inlet 103 and reagent exit 104 Through-hole on slide 10 or the second slide 20, in addition, being directed to the shape of reagent inlet 103 and reagent exit 104, the present invention is also An example is proposed, as depicted in fig. 13 a, in this example, when the reagent inlet 103 and reagent exit being set on the first slide 10 When 104 shape is identical as the shape of the reagent buffer area 102, the reagent inlet 103 and reagent exit 104 are also just etc. It is same as the reagent buffer area 102.In order to be illustrated to such technical solution, as depicted in fig. 13 a, the program is in Fig. 1 Shown in the extension that carries out on the basis of scheme, but it should be recognized that not carried out to reaction channel 101 in this programme any It limits.Unlike scheme shown in FIG. 1, in the program, the reagent inlet 103 and reagent being set on the first slide 10 go out The shape of mouth 104 is identical as the shape of reagent buffer area 102.In general, multichannel sequencing reaction small chamber needs are vertically placed on It is sequenced in instrument, and is passed through reagent from below, help to empty the air in multichannel sequencing reaction small chamber.It is anti-when be sequenced At once, when injecting reagent to (i.e. reagent buffer area 102) at reagent inlet 103 by injecting the pipeline of reagent, since reagent enters Mouthful 103(reagent buffer area 102) shared by region it is relatively large, therefore reagent will not be directly entered in reaction channel 101, first Reagent can be full of reagent buffer area 102, continue after injecting reagent, and reagent enters in multiple reaction channels 101 simultaneously, logical with reacting Sample to be tested in road 101 carries out sequencing reaction.Likewise, for the position of reagent inlet 103 and reagent exit 104, at this Specific restriction is had no in scheme, for example, work as the lower surface that reagent inlet 103 is set to the second slide 20, and reagent exit 104 When being set to the upper surface of the first slide 20, as illustrated in fig. 13b, the shape and reagent of reagent inlet 103 and reagent exit 104 are slow The shape for rushing area 102 is identical, and in this scheme, the multichannel sequencing reaction small chamber can be directly horizontally arranged, by past Reagent inlet 103(, that is, reagent buffer area 102) it is passed through reagent, downward due to reagent inlet 103, reagent reagent full first Buffer area 102(, that is, reagent inlet 103), reagent will not be directly entered in reaction channel 103, and this structure helps to be discharged Air inside multichannel sequencing reaction small chamber；After persistently injecting reagent, reagent enters in multiple reaction channels 101 simultaneously, with Sample to be tested in reaction channel 101 carries out sequencing reaction.

In addition, on the basis of above-mentioned any scheme, to the material of first slide 10 and the second slide 20 without It limits, the material of the second slide 10 and the second slide 20 can be glass, PMMA, PC, PE any of them.Wherein the second glass Piece 20 can not only firmly fix sample, prevent sample when reaction from falling off and reducing flux, and light can smoothly lead to The second slide 20 is crossed, allows to carry out and adopts adopting figure component and capable of taking clearly sequencing image for figure, to be the raising of flux Provide sound assurance.Further, when first slide 10 is made of coverslip 30 and drain piece 40, the second slide is When glass slide or the first slide be coverslip, when the second slide is made of drain piece and glass slide, to the coverslip 30, Without limiting, the material of coverslip 30, drain piece 40 and glass slide 50 can be the material of drain piece 40 and glass slide 50 Glass, PMMA, PC, PE or other materials, in addition, drain piece 40 can also use stainless steel substrates or silica gel piece.

In any scheme of above-mentioned multi-channel reaction cell, use is also provided on multichannel sequencing reaction small chamber In the Mark point of picture registration positioning, and the shape of the Mark point is not limited in cross shape, as long as clear convenient for identification ?.The setting of Mark point has been convenient for adopting map device and has carried out adopting the processing synthesis after figure, improved picture quality.

The invention also provides second embodiment, a kind of multichannel sequencing reaction device is proposed in the present embodiment, is used for It realizes multiple samples while carrying out sequencing reaction.As shown in figure 14, the multichannel sequencing reaction device is by cell upper group Part 60, cell lower component 70 and multichannel sequencing reaction small chamber 80 are constituted, and the multichannel sequencing reaction in the present embodiment is small Room is the multichannel sequencing reaction small chamber in above-mentioned any scheme, therefore in the present embodiment, then multichannel will not be sequenced Reaction small chamber is illustrated.The cell upper element 60 includes feed pathway 601 and liquid outlet channel 602；The cell lower part Component 70 includes cell upper cover 701 and cell pedestal 702, and it is anti-that the cell pedestal 702 is used to place the multichannel sequencing Cell 80 is answered, the cell upper cover 701 is mounted on cell pedestal 702；The cell upper element 60 is for being mounted on cell In lower component 70, and the examination of the feed pathway 601 of the cell upper element 60 and the multichannel sequencing reaction small chamber 80 Agent entrance 103 is connected to, the reagent of the liquid outlet channel 602 of the cell upper element 60 and the multichannel sequencing reaction small chamber 80 104 connection of outlet.In the present embodiment, as shown in figure 14, cell upper cover 701 is mounted on cell pedestal 702, cell upper cover It is provided with and is connected to convenient for feed pathway 601 with 80 reagent inlet 103 of multichannel sequencing reaction small chamber and liquid outlet channel on 701 602 structures being connected to 80 reagent exit 104 of multichannel sequencing reaction small chamber, the structure can be setting in cell upper cover 701 On through-hole, when cell upper element 60, which is mounted on, carries out sequencing reaction in cell lower component 70, feed pathway 601 is direct The reagent inlet 103 of multichannel sequencing reaction small chamber 80 is connected to across through-hole, liquid outlet channel 602 directly through through-hole by connecting Connect the reagent exit 104 in multichannel sequencing reaction small chamber 80.Since cell upper element 60 and cell lower component 70 can be with It is combined and splits, i.e., the multichannel sequencing reaction device is to adopt a split structure design, is realized convenient for it automatic It varies.

On the basis of second embodiment, as shown in figure 15, for the multichannel sequencing reaction device, the present invention is also Propose an example, in this example, multichannel sequencing reaction device by cell upper element 60, cell lower component 70 and Multichannel sequencing reaction small chamber 80 is constituted, and the cell upper element 60 includes feed pathway 601 and liquid outlet channel 602；It is described Cell lower component 70 includes cell upper cover 701 and cell pedestal 702, and the cell pedestal 702 is used to place the multi-pass Road sequencing reaction small chamber 80, the cell upper cover 701 are mounted on cell pedestal 702；The cell upper element 60 is for pacifying In cell lower component 70, and the feed pathway 601 of the cell upper element 60 and the multichannel sequencing reaction are small The reagent inlet 103 of room 80 is connected to, the liquid outlet channel 602 of the cell upper element 60 and the multichannel sequencing reaction small chamber 80 reagent exit 104 is connected to.In this example, as shown in figure 15, the cell upper element 60 further includes bottom plate 603, heat-insulated Plate 604, cooling piece 605 and heat-conducting plate 606；Wherein, the thermal insulation board 604 is fixed on 603 lower section of bottom plate, thermal insulation board 604 Middle part has through-hole, and the cooling piece 605 is set in the through-hole of thermal insulation board 604；The heat-conducting plate 606 is fixed on thermal insulation board 604 and cooling piece 605 lower section；The feed pathway 601 and liquid outlet channel 602 are respectively through the bottom plate 603, heat-insulated The through-hole of plate 604 and heat-conducting plate 606.When cell upper element 60 is mounted in cell lower component 70, feed pathway 601 with The reagent inlet 103 of multichannel sequencing reaction small chamber 80 is connected to, the reagent of liquid outlet channel 602 and multichannel sequencing reaction small chamber 80 104 connection of outlet, it is described since multichannel sequencing reaction small chamber 80 needs to be promoted or reduced in sequencing reaction temperature Heat-conducting plate 606 in cell upper element 60 is in contact with multichannel sequencing reaction small chamber 80, to reach optimal heating or drop The effect of temperature.As shown in figure 15, the lower surface of cooling piece 605 is tightly attached to the upper surface of heat-conducting plate 606, the heating of cooling piece 605 or It when person cools down, is acted on by the transmitting of heat-conducting plate 606, the temperature that cell 80 is answered in multichannel sequencing is raised and lowered, to reach Required temperature.

In addition, the cell upper element 60 further includes a temperature sensor, when cooling piece 605 is to multichannel sequencing reaction When cell is heated up or cooled down, temperature sensor is used to detect the temperature of the multichannel sequencing reaction small chamber, prevents more Channel sequencing reaction small chamber it is too high or too low for temperature.In this example, there is a groove on the upper surface of the heat-conducting plate 606, The temperature sensor 607 is arranged in the groove, and temperature sensor 607 is located at the lower section of the cooling piece 605.It needs to illustrate , the position of temperature sensor 607 is set, above are only a kind of preferable embodiment, the temperature sensor 607 can also be set up directly on multichannel sequencing reaction small chamber, directly survey to the temperature of multichannel sequencing reaction small chamber Amount.In this example, the cooling piece 605 is semiconductor chilling plate, and the temperature sensor 607 is K-type thermocouple, still, The cooling piece 605 is not limited in semiconductor chilling plate, and temperature sensor 607 is not limited to K-type thermocouple.

Further, on the basis of exemplary described in Figure 15, for the cell top of multichannel sequencing reaction device Component 60 and cell lower component 70, the invention also provides an examples, as shown in figure 16, the middle part of the cell upper cover 701 With through-hole, when the cell upper element 60 is mounted in cell lower component 70, the cell upper element 60 it is heat-insulated Plate 604 and heat-conducting plate 606 protrude into the through-hole of cell upper cover 701, and the heat-conducting plate 606 is tightly attached to multichannel sequencing reaction small chamber On 80, and the feed pathway 601 is connected to the reagent inlet 103 of multichannel sequencing reaction small chamber 80, the liquid outlet channel 602 It is connected to the reagent exit 104 of multichannel sequencing reaction small chamber 80.The main function of cell upper element 60 is to pass through cooling piece 605 pairs of multichannel sequencing reaction small chambers 80 are heated up or are cooled down, and such structure of multichannel sequencing reaction device, will be more The heating of channel sequencing reaction small chamber 80 and the part of refrigeration concentrate on cell upper element 60, are convenient for cell upper element 60 With the separation of cell lower component 70, the design of this split type structure is easy to implement automatic sample-changing；Cell lower component 70 is main It is used to fix multichannel sequencing reaction small chamber 80, while cell lower component 70 is also used to automatic point sample, passes through liquid transfer gun head It is directed at the reaction channel 101 of multichannel sequencing reaction small chamber 80, at the uniform velocity point sample, injects detected sample into every reaction channel 101 This.

As shown in figure 17, for multichannel sequencing reaction device, the invention also provides in 3rd embodiment, in this implementation In example, multichannel sequencing reaction device is sequenced anti-by cell upper element 60, cell lower component 70 and above-mentioned multichannel Cell 80 is answered to constitute；Wherein, the cell upper element 60 includes feed pathway 601 and liquid outlet channel 602；The cell lower part Component 70 includes cell upper cover 701 and cell pedestal 702, and it is anti-that the cell pedestal 702 is used to place the multichannel sequencing Cell 80 is answered, the cell upper cover 701 is mounted on cell pedestal 702.Cell upper element 60 further includes bottom plate 603, heat-insulated Plate 604, cooling piece 605, heat-conducting plate 606 and temperature sensor 607；Wherein, the thermal insulation board 604 is fixed under bottom plate 603 The middle part of side, thermal insulation board 604 has through-hole, and the cooling piece 605 is set in the through-hole of thermal insulation board 604, the heat-conducting plate 606 It is fixed on the lower section of thermal insulation board 604 and cooling piece 605, there is a groove on the upper surface of the heat-conducting plate 606, the temperature passes Sensor 607 is arranged in the groove, and temperature sensor 607 is located at the lower section of the cooling piece 605.Further, cell upper cover 701 middle part has through-hole, when the cell upper element 60 is mounted in cell lower component 70, the cell upper element 60 thermal insulation board 604 and heat-conducting plate 606 protrudes into the through-hole of cell upper cover 701, and the heat-conducting plate 606 is tightly attached to multichannel sequencing On reaction small chamber 80.

In this example, the cell upper element 60 further includes top plate 608 and heat sink 609, and the top plate 608 is arranged Above bottom plate 603, the heat sink 609 is between top plate 608 and bottom plate 603 and is fixed on the bottom plate 603, described Heat sink 609 has several radiating fins, also, the bottom plate 603 and thermal insulation board 604 are connected by screw to, the screw Centre is provided with steel pipe, which is feed pathway 601 and liquid outlet channel 602.In addition, the lower section of the cell upper cover 701 It is elasticly connected with briquetting, the briquetting is pressed on multichannel sequencing reaction small chamber 80, is provided with card in the cell upper cover 701 Button, the buckle, by the effect of buckle, cell upper cover 701 are fastened on described for being stuck in the cell pedestal 702 Cell pedestal 702 on, simultaneously because the effect of the briquetting of cell upper cover 701, by the surrounding of multichannel sequencing reaction small chamber 80 It compresses, prevents sample when leakage and point sample from mutually polluting.

When the cooling piece 605 heats multichannel sequencing reaction small chamber 80, the lower surface of cooling piece 605 is For hot face, the upper surface of cooling piece 605 is huyashi-chuuka (cold chinese-style noodles), and the cooling piece 605 is arranged in the through-hole of thermal insulation board 604, is passed through The effect of thermal insulation board 604 separates huyashi-chuuka (cold chinese-style noodles) and hot face, likewise, when cooling piece 605 to multichannel sequencing reaction small chamber 80 into When row refrigeration, the lower surface of cooling piece 605 is cold, and the upper surface of cooling piece 605 is hot face, and thermal insulation board is by huyashi-chuuka (cold chinese-style noodles) and heat Face separates, and improves the efficiency that cooling piece is heated or freezed.In addition, in order to improve sealing performance, in the heat-conducting plate Seal gasket 90 is additionally provided on 606, and exit and the liquid outlet channel of feed pathway 601 is arranged in the seal gasket 90 602 inlet, which is also fitted on the coverslip 30 of multichannel sequencing reaction small chamber 80, while feed pathway 601 outlet is connected to reagent buffer area 102, and the entrance of liquid outlet channel 602 is connected to reagent buffer area 102.On cell top Two through-holes can be set on top plate 608, heat sink 609, bottom plate 603, thermal insulation board 604 and heat-conducting plate 606 in component 60, Two through-holes are form, shoot light field figure by two forms, for seeing whether magnetic bead distribution is uniform.

The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention Made any modifications, equivalent replacements, and improvements etc., should all be included in the protection scope of the present invention within mind and principle.

Claims

1. a kind of multichannel sequencing reaction small chamber, it is characterised in that: including the first slide and the second slide to fit, described One slide is used to form a plurality of hollow reaction channel with the second slide, and the both ends of the reaction channel are respectively provided with receiving The reagent buffer area of reagent is provided with the reagent inlet being connected to reagent buffer area, institute on first slide or the second slide It states and is additionally provided with the reagent exit being connected to reagent buffer area on the first slide or the second slide；

Wherein, reagent buffer area semicircular in shape, reagent buffer area has arc-shaped edges and straight line, and the buffer area is straight Line side is located at close to the side of the reaction channel.

2. multichannel sequencing reaction small chamber according to claim 1, it is characterised in that: first slide is located at the second glass Piece top, the reaction channel and reagent buffer area are arranged at the lower surface of the first slide, and the reagent inlet is to be set to Through-hole on first slide or the second slide, the reagent exit are the through-hole being set on the first slide or the second slide.

3. multichannel sequencing reaction small chamber according to claim 1, it is characterised in that: first slide is located at the second glass Piece top, the reaction channel and reagent buffer area are arranged at the upper surface of the second slide, and the reagent inlet is to be set to Through-hole on first slide or the second slide, the reagent exit are the through-hole being set on the first slide or the second slide.

4. multichannel sequencing reaction small chamber according to claim 1, it is characterised in that: first slide by coverslip and Drain piece fits closely, and second slide is glass slide, and the drain piece is described between coverslip and glass slide Drain on piece is provided with the through-hole of strip, the reaction channel enclosed by coverslip, the through-hole of strip and glass slide and At；Or

First slide is coverslip, and second slide is fitted closely by drain piece and glass slide, the drain piece On be provided with the through-hole of strip, the reaction channel is enclosed by coverslip, the through-hole of strip and glass slide.

5. multichannel sequencing reaction small chamber according to claim 4, it is characterised in that: the reagent buffer area is that setting exists The through-hole of drain on piece or for through-hole on the cover slip is arranged.

6. a kind of multichannel sequencing reaction device with multichannel sequencing reaction small chamber described in claim 1, feature exist In: it is made of multichannel sequencing reaction small chamber, cell upper element and cell lower component, in which:

The cell upper element includes feed pathway and liquid outlet channel；

The cell lower component includes cell upper cover and cell pedestal, and the cell pedestal is used to place the multichannel and surveys Sequence reaction small chamber, the cell upper cover are mounted on cell pedestal；

The cell upper element is for being mounted on cell lower component, and the feed pathway of the cell upper element and institute The reagent inlet connection of multichannel sequencing reaction small chamber is stated, the liquid outlet channel and the multichannel of the cell upper element are sequenced The reagent exit of reaction small chamber is connected to.

7. multichannel sequencing reaction device according to claim 6, it is characterised in that: the cell upper element further includes Bottom plate, thermal insulation board, cooling piece, heat-conducting plate and temperature sensor；Wherein

The thermal insulation board is fixed on the lower section of bottom plate, and the middle part of the thermal insulation board has through-hole, and the cooling piece is set to heat-insulated In the through-hole of plate, and the upper surface of the cooling piece is in contact with the lower surface of bottom plate；

The heat-conducting plate is fixed on the lower section of cooling piece, and the upper surface of heat-conducting plate is in contact with the lower surface of cooling piece, works as cell When upper element is mounted in cell lower component, the lower surface of the heat-conducting plate is in contact with multichannel sequencing reaction small chamber；

8. multichannel sequencing reaction device according to claim 7, it is characterised in that: the middle part of the cell upper cover has Through-hole, when the cell upper element is mounted in cell lower component, the thermal insulation board and heat-conducting plate of the cell upper element It protrudes into the through-hole of cell upper cover, the heat-conducting plate is tightly attached on multichannel sequencing reaction small chamber, and the feed pathway and more The reagent inlet of channel sequencing reaction small chamber is connected to, and the reagent exit of the liquid outlet channel and multichannel sequencing reaction small chamber connects It is logical.

9. multichannel sequencing reaction device according to claim 7, it is characterised in that: the cell upper element further includes Top plate and heat sink, the top plate are arranged above bottom plate, and the heat sink is between top plate and bottom plate and is fixed on described On bottom plate, the heat sink has several radiating fins.

10. multichannel sequencing reaction device according to claim 7, it is characterised in that: the bottom plate and thermal insulation board pass through Screw connects, and is provided with steel pipe among the screw, which is feed pathway and liquid outlet channel.

11. multichannel sequencing reaction device according to claim 6, it is characterised in that: the lower section bullet of the cell upper cover Property is connected with briquetting, and the briquetting is pressed on multichannel sequencing reaction small chamber.

12. multichannel sequencing reaction device according to claim 6, it is characterised in that: be provided on lid on the cell Buckle, the buckle is for being stuck in the cell pedestal.