CN102517206B

CN102517206B - Gene sequencing device and system

Info

Publication number: CN102517206B
Application number: CN201110460749.0A
Authority: CN
Inventors: 盛司潼
Original assignee: Individual
Current assignee: Individual
Priority date: 2011-12-31
Filing date: 2011-12-31
Publication date: 2015-06-03
Anticipated expiration: 2031-12-31
Also published as: CN102517206A

Abstract

The invention relates to the field of genetic engineering, in particular to a gene sequencing device and a gene sequencing system. The gene sequencing device comprises a sample preparation component, a liquid conduction component, a sample loading component, a temperature control component, an image acquisition component and a control component. The gene sequencing system comprises a sample preparation control module, a liquid conduction control module, a reaction control module, a temperature control module, an image acquisition control module and a control module. By adopting the gene sequencing device and the gene sequencing system, the integration from sample preparation to data processing can be realized, and full automation of gene sequencing can also be realized. Meanwhile, the high-pass and low-cost gene sequencing can be realized.

Description

A kind of gene sequencing Apparatus and system

Technical field

The present invention relates to genetically engineered field, more particularly, relate to a kind of gene sequencing Apparatus and system.

Background technology

Since the Human Genome Project is implemented, the development of gene sequencing technology is very swift and violent, initial pure manual order-checking replace by the instrumentation of semi-automation, Automatic Control is then following Developing mainstream.In order-checking efficiency and cost, from first man genoid group order-checking use 13 year, cost 3,500,000,000 dollars, to only 1 year consuming time of second human genome order-checking, cost 7,000 ten thousand dollars, progress is significant.And the reduction of the raising of the efficiency that checks order and order-checking cost, the sequence measurement not only with current is relevant, more closely bound up with various sequencing device.

The sequencing equipment mainly gene chip sequencing device of current appearance.Utilize this device to check order, first need to prepare pin storehouse, then by special mini sprinkler, respectively different probe solutions is put at substrate surface successively according to the order be ranked in advance, and make probe be fixed on substrate surface by physics and chemistry effect.The device of this gene chip order-checking and the process of order-checking are: gene chip is made up of multiple micro fluid reaction passage, and channel surface has the DNA sequencing library that molecule is formed.Microfluidic gene chip is closely linked by two-layer substrate and is formed, there is microstructure centre, the fluid reaction pond of composition channel-type, and fluid input and output hole, underlying substrate is transparent material, there are thousands of minute solid particles on the subsurface material surface relative with micro fluid reaction pond, are connected with lower floor transparent substrates by chemical bond.Minute solid particles is fixed with a large amount of nucleic acid molecule.Biochemical reaction in microfluidic channel, then the sequence detecting the nucleic acid molecule on molecule with optical detection means.

Above-mentioned when utilizing biochip technology to check order, extraction, the sequencing reaction of this biochip sequencing device sequencing reagent control all by manually carrying out, and this makes level of automation extremely low, manual efficiency, accuracy rate all Shortcomings.In addition, the DNA sequencing fragment quantity to be measured that can fix is very limited, and generally only have the order of magnitude of several thousand to 10,000, sequencing throughput is lower, and order-checking efficiency has much room for improvement; In addition, the flux just because of once sequencing is lower, and when will reach the flux of necessarily even more than one hundred million order of magnitude, and the amount of reagent utilizing this device to check order to consume is just very large, causes order-checking cost very high.

Therefore need a kind of new gene sequencing device, order-checking level of automation can be improved, and can sequencing throughput be improved, reduce order-checking cost further; Meanwhile, need a kind of new gene sequencing system, the full-automation of checking order can be realized, thus reduce labour cost, raise the efficiency.

Summary of the invention

The object of the present invention is to provide a kind of gene sequencing device, be intended to solve in prior art the problem that level of automation is low, sequencing throughput is low, order-checking cost is high.

In order to realize goal of the invention, gene sequencing device of the present invention comprises sample preparation module, liquid conductive assembly, load sample assembly, temperature control assembly, adopts figure assembly and control unit.

Wherein, described sample preparation module, is connected with load sample assembly, for the preparation of testing sample, and is fixed on by testing sample on load sample assembly; Described liquid conductive assembly, is connected with load sample assembly, for storing and transmission reagent; Described load sample assembly, for fixing testing sample, and receives the reagent of liquid conducting subassembly transmission, makes testing sample carry out sequencing reaction with the reagent received; Meanwhile, described load sample assembly also adopts figure position for determining; Described temperature control assembly, is connected with load sample assembly, for regulating the temperature of sequencing reaction in load sample assembly; Describedly adopt figure assembly, be connected with load sample assembly, for adopting the view data of figure position described in obtaining; Described control unit, is connected respectively with sample preparation module, liquid conductive assembly, load sample assembly, temperature control assembly and Cai Tu assembly, for controlling the operation of coupled each assembly.

Wherein, corresponding reagent comprises the kind of reagent and the amount of reagent.

Wherein, described gene sequencing device also comprises data handling component, described data handling component with adopt figure assembly and control unit is connected respectively, for receiving and processing the view data of adopting figure assembly and gathering.

Wherein, described data handling component can for the equipment utilizing electronics principle to process data according to a series of instruction.

Preferably, this data handling component is computer.

Wherein, liquid conductive assembly comprises reagent platform and pump.This reagent platform is positioned at the side of pump, is connected with pump by conduit, for holding the multiple reagent for drawing; This pump for extracting the reagent in reagent platform, and by reagent delivery in load sample assembly.

Wherein, liquid conductive assembly also comprises mechanical manipulator, and it is positioned at the top of reagent platform or is positioned at the side of reagent platform, is connected with pump by conduit, for extracting corresponding reagent in pump from reagent platform.

Wherein, all tubes connection is passed through between described pump and load sample assembly, between pump and mechanical manipulator, between pump and reagent platform.

Wherein, reagent platform comprises damping fluid pedestal and reagent pedestal.This damping fluid pedestal is for holding the damping fluid needed for sequencing reaction; This reagent pedestal is connected with damping fluid pedestal, for holding the reagent except damping fluid needed for sequencing reaction.

Wherein, above-mentioned damping fluid pedestal is the pedestal at least one hole, and reagent pedestal is the pedestal at least one hole.

Above-mentioned load sample assembly comprises sample table and locating device.This sample table is used for fixing testing sample, and receives the reagent of liquid conducting subassembly transmission, makes testing sample carry out sequencing reaction with the reagent received; This locating device and sample table and/or adopt figure assembly and be connected, for Quality control platform and/or the displacement of adopting figure assembly, thus determine to adopt figure position.

Wherein, sample table comprises sequencing reaction small chamber, for fixing testing sample, makes the reagent that testing sample and liquid conductive assembly transmit carry out sequencing reaction.

During order-checking, be fixed on sequencing reaction small chamber by physics or chemical action by testing sample (being also DNA fragmentation), form short label array, an array point represents a kind of DNA fragmentation, is called DNA fragmentation array.Can form the array of up to ten million even more than one hundred million points in this sequencing reaction small chamber, be also array point.

Wherein, DNA fragmentation can directly be fixed on sequencing reaction small chamber, also can be fixed on sequencing reaction small chamber by globule.

Wherein, above-mentioned DNA fragmentation or the globule being fixed with DNA fragmentation are fixed on slide, and slide is fixed on sequencing reaction small chamber, form the chamber of sequencing reaction small chamber.

Wherein, above-mentioned locating device comprises horizontal movement device and vertical movement device.This horizontal movement device is connected with sample table, for regulate sample table himself position in the plane; This vertical movement device and sample table, adopt figure assembly and be connected, for regulating sample table and adopting the distance between figure assembly.

Above-mentioned temperature control assembly comprises heating and cooling device and temperature measuring equipment.This temperature measuring equipment, for measuring the temperature of load sample assembly in real time; This heating and cooling device, is connected respectively with temperature measuring equipment, load sample assembly, and for regulating the temperature of load sample assembly, the temperature that this heating and cooling device can be measured according to temperature measuring equipment carries out work to the temperature of load sample assembly.This heating and cooling device work makes the temperature of load sample assembly arrive the temperature of acquiescence or the temperature of setting.

Wherein, temperature control assembly, by regulating the temperature of load sample assembly, controls the carrying out of sequencing reaction.

Wherein, this temperature measuring equipment is also for measuring the temperature of gene sequencing device inside.

Wherein, temperature control assembly also comprises air exhausting device.This air exhausting device is used for the air flowing inside and outside gene sequencing device.Also namely realized the exchange of the inner air and outer air of gene sequencing device by air exhausting device, thus the temperature in gene sequencing device is controlled in the temperature range of setting.

After above-mentioned temperature measuring equipment measures the temperature of described instrument internal, the temperature recorded is issued control unit, control unit produces the work order of air exhausting device according to the temperature data measured, air exhausting device carries out work according to work order, thus realize adjustment to gene sequencing device internal temperature, thus ensure that gene sequencing device internal temperature is in its temperature range of allowing of normally working.

The above-mentioned figure of adopting assembly comprises light-emitting device, prism group and photographic means.This light-emitting device is connected with load sample assembly, for providing the light of specific wavelength, to excite the testing sample with marker in load sample assembly; This prism group, between light-emitting device and load sample assembly, is filtered for the light sent light-emitting device, and carries out optical path adjusting; This photographic means is positioned at load sample assembly side, for gathering the view data of figure position.

Wherein, above-mentioned light-emitting device can launch the light of different wave length.

When sequencing reaction, the reagent of sequencing reaction carries marker, and this carries the reagent of marker and testing sample reacts, and after reaction terminates, forms the testing sample carrying marker; Then carry the testing sample of marker by the rayed of the specific wavelength utilizing light-emitting device to send, the testing sample carrying marker just can be luminous; Adopt the testing sample that carry marker of figure assembly to luminescence carry out acquisition of image data with this again.

Wherein, light-emitting device also comprises optical gate, between light-emitting device and load sample assembly, for blocking exciting light when not needing excitation light irradiation.

Wherein, described photographic means comprises multiplying arrangement and claps map device.The image of figure position adopted by this multiplying arrangement for amplifying; This bat map device is positioned at the side of multiplying arrangement, for being adopted the view data of figure position by multiplying arrangement shooting.

Wherein, the magnification of this multiplying arrangement is not limit, and is preferably 20 to 100 times.Preferred, magnification is between 40 times to 100 times.

In order to better realize object of the present invention, this gene sequencing device also can comprise: data handling component, and adopts figure assembly and is connected, for receiving and processing the view data of adopting figure assembly and gathering.

Wherein, this data handling component comprises data transmission device and data analysis set-up.This data transmission device is connected with photographic means and data analysis set-up, for adopting the image data transmission of figure assembly collection to data analysis set-up; This data analysis set-up, for the treatment of view data.

Wherein, data transmission device can be arbitrarily for connecting two equipment and can transmitting the device of data.Preferably, data transmission device is data line.In order to better realize object of the present invention, gene sequencing system of the present invention comprises sample preparation control module, liquid conductive control module, reaction controlling module, temperature control module, adopts figure control module and control module.

Wherein, described sample preparation control module, is connected with control module, prepares assembly prepare testing sample for Quality control, and controls testing sample and be fixed on load sample assembly; Described liquid conductive control module, is connected with control module, for controlling extraction and the transmission of liquid in liquid conductive assembly; Described reaction controlling module, is connected with control module, for controlling the carrying out of sequencing reaction, and determines the position of adopting figure; Described temperature control module, is connected with control module, for controlling the temperature of sequencing reaction; Describedly adopting figure control module, be connected with control module, gathering image for controlling to adopt figure assembly; Described control module, for controlling the operation of connected each module.

Wherein, described system also comprises a data processing module, for the treatment of the view data of adopting the collection of figure assembly.

Wherein, the data processing module of gained also comprises data transmission module and data analysis module.Described data transmission module, is connected with data analysis module, for control data transmission to data analysis module; Described data analysis module, for receiving the data of data transmission module transmission, and carries out analysis and treament to data.Compared with prior art, present invention achieves the automatization from sample preparation to data processing whole process, thus significantly improve order-checking efficiency; Also improve sequencing throughput simultaneously, and reduce order-checking cost and human cost.

Accompanying drawing explanation

Fig. 1 is the structural representation of gene sequencing device in one embodiment of the invention;

Fig. 2 is the structural representation of gene sequencing device in another embodiment of the present invention;

Fig. 3 is the structural representation of liquid conductive assembly in one embodiment of the invention;

Fig. 4 is the structural representation of reagent platform in one embodiment of the invention;

Fig. 5 is the structural representation of liquid conductive assembly in another embodiment of the present invention;

Fig. 6 is the structural representation of liquid conductive assembly in another embodiment of the present invention;

Fig. 7 is the structural representation of liquid conductive assembly in another embodiment of the present invention;

Fig. 8 is the structural representation of load sample assembly in one embodiment of the invention;

Fig. 9 is the structural representation of sample table in one embodiment of the invention;

Figure 10 is the structural representation of sequencing reaction small chamber in one embodiment of the invention;

Figure 11 is the block schematic illustration of locating device in one embodiment of the invention;

Figure 12 is the structural representation of locating device in one embodiment of the invention;

Figure 13 is the structural representation of locating device in another embodiment of the present invention;

Figure 14 is the structural representation of locating device in another embodiment of the present invention;

Figure 15 is the structural representation of temperature control assembly in one embodiment of the invention;

Figure 16 is the structural representation of temperature control assembly in another embodiment of the present invention;

Figure 17 is the structural representation of air exhausting device in one embodiment of the invention;

Figure 18 is the structural representation of air exhausting device in another embodiment of the present invention;

Figure 19 is the structural representation adopting figure assembly in one embodiment of the invention;

Figure 20 is the structural representation of photographic means in one embodiment of the invention;

Figure 21 is the structural representation of light-emitting device in one embodiment of the invention;

Figure 22 is the light path transmission structure schematic diagram of light-emitting device in another embodiment of the present invention;

Figure 23 is the structural representation of prism group in one embodiment of the invention;

Figure 24 is the structural representation of data handling component in one embodiment of the invention;

Figure 25 is the use schema of gene sequencing device in one embodiment of the invention;

Figure 26 is the control texture schematic diagram of gene sequencing system in one embodiment of the invention;

Figure 27 is the structural representation of gene sequencing system in another embodiment of the present invention;

Figure 28 is the structural representation of data processing module in one embodiment of the invention.

Embodiment

In order to make object of the present invention, technical scheme and advantage clearly understand, below in conjunction with drawings and Examples, the present invention is further elaborated.

Fig. 1 shows the structural representation of the gene sequencing device in one embodiment of the invention, and it comprises:

(1) sample preparation module 1, is connected with load sample assembly 3, for the preparation of testing sample, and is fixed on load sample assembly by testing sample.

(2) liquid conductive assembly 2, is connected with load sample assembly 3, for storing and transmission reagent.

(3) load sample assembly 3, for fixing testing sample, and receives the reagent of liquid conducting subassembly 2 transmission, makes testing sample carry out sequencing reaction with the reagent received; Meanwhile, load sample assembly 3 also adopts figure position for determining.

(4) temperature control assembly 4, is connected with load sample assembly 3, and for regulating the temperature of sequencing reaction in load sample assembly 3, being convenient to sequencing reaction can carry out smoothly.

(5) adopt figure assembly 5, be connected with load sample assembly 3, for adopting the view data of figure position described in obtaining.

(6) control unit 6, is connected respectively with sample preparation module 1, liquid conductive assembly 2, load sample assembly 3, temperature control assembly 4 and Cai Tu assembly 5, for controlling the operation of coupled each assembly.

In the present embodiment, when needs extract reagent, sample preparation module 1 receives after control unit 6 prepares the order of testing sample, sample preparation module 1 prepares testing sample, be fixed on slide after testing sample preparation, then, sample preparation module 1 receives after control unit 6 installs the instruction of slide, be then fixed on by sample on load sample assembly 3; Liquid conductive assembly 2 receives after control unit 6 extracts the order of reagent, comprises the kind extracting reagent, the amount extracting reagent, performs and extract reagent, and imported in load sample assembly 3 by the reagent of extraction.Load sample assembly 3 receives reagent; After temperature control assembly 4 receives temperature instruction, comprise the temperature of heating-cooling, perform heating or refrigeration, realize the control to temperature in load sample assembly 3.When figure adopted by needs, adopt figure assembly 5 and receive after control unit 6 gathers the order of image, comprise the position of adopting figure, the number etc. adopting figure, adopt figure assembly 5 and move to the position of adopting figure of specifying.Then collection image is carried out.

The mechanize of the preparation of testing sample, the installation of slide, the extraction of liquid etc. can be realized in the technical scheme of the present embodiment, the integration being prepared into data handling procedure from testing sample of gene sequencing device is achieved from entirety, make the level of automation of gene sequencing high, save manual labor simultaneously, improve the efficiency of gene sequencing.

It should be noted that, the dotted line in figure connects for annexation in logic, includes but not limited to wireless connections.

For the embodiment in Fig. 1, the present invention proposes an embodiment, and sample preparation module 1 comprises a mechanical arm, and when sample is fixed to after on slide, slide is fixed on load sample device by mechanical arm.

Fig. 2 shows the structural representation of the gene sequencing device in another embodiment of the present invention, and it comprises:

(1) sample preparation module 1, is connected with load sample assembly 3, for the preparation of testing sample, and is fixed on load sample assembly by testing sample.Sample preparation module 1 of the present invention can take various ways to prepare sample.In one embodiment, sample preparation module 1 can complete the testing sample preparation sections such as library preparation, amplification: from tissue samples, first extract DNA, and be broken into small segment; Carry out enzyme to cut, obtain the DNA fragmentation of equal length; By DNA fragmentation two ends jointing sequence, obtain DNA short label, be prepared into DNA library; Then DNA short label is connected on microballon, increases in emulsion-based PCR system; Then enrichment obtains testing sample.

(2) liquid conductive assembly 2, is connected with load sample assembly 3, for storing and fluid transfer.

(7) data handling component 7, and adopts figure assembly 5 and control unit 6 is connected respectively, for receiving and processing the view data of adopting figure assembly and gathering.

In the present embodiment, data handling component can be computer.

In the technical scheme of the present embodiment, gene sequencing device achieves full-automatic gene sequencing.By Automated condtrol, substantially increase efficiency and the precision of gene sequencing.

Fig. 3 shows the structural representation of the liquid conductive assembly in one embodiment of the invention, and this liquid conductive assembly comprises reagent platform 21, pump 221 and conduit 222.Wherein:

(1) reagent platform 21 is connected with pump 221 by conduit 222, for holding the relevant reagent of sequencing reaction.

(2) described pump 221 is for extracting the reagent in reagent platform 21, and by reagent delivery in load sample assembly.

Deposit the liquid needed for sequencing reaction in reagent platform 21, comprise all reagent needed for sequencing reaction.Be connected with many conduits 222 between pump 221 and reagent platform 21, conduit 222 one end is inserted in the liquid of reagent platform 21, and the other end is connected with pump 221.When needs extract reagent, pump 221 extracts the reagent of selection to load sample assembly from reagent platform 21.

For reagent platform, the present invention proposes an embodiment, and as shown in Figure 4, reagent platform comprises damping fluid pedestal 212 and reagent pedestal 211.Wherein:

(1) damping fluid pedestal 212, for holding the damping fluid needed for sequencing reaction.

(2) reagent pedestal 211 is connected with damping fluid pedestal 212, for holding the reagent except damping fluid needed for sequencing reaction.

In the present embodiment, when sequencing reaction needs damping fluid, pump 221 extracts required damping fluid from damping fluid pedestal 212, the damping fluid of setting dosage is drawn in load sample assembly, when sequencing reaction needs other reagent, pump 221 chooses required reagent from reagent pedestal 211, by the reagent aspiration of setting dosage in load sample assembly.

In the present embodiment, reagent platform can store plurality of reagents simultaneously, and user once can add required all reagent, avoids the trouble that user frequently adds reagent.

For damping fluid pedestal, the present invention proposes an embodiment, and damping fluid is placed in damping fluid pedestal by reagent bottle.In the present embodiment, damping fluid pedestal can need replacing according to different.Such as: the number of placing reagent bottle as required, the damping fluid pedestal of different hole count is changed; Hold the damping fluid pedestal of the replaceable different hole size of specification of the reagent bottle of damping fluid as required.Also namely damping fluid pedestal can be changed according to the reagent bottle size of required placement and number.

Preferably, the number in the hole of damping fluid pedestal is 6.

Preferably, the size in the hole of damping fluid pedestal is the hole holding 200mL reagent bottle.

In the present embodiment, what hold in reagent pedestal is the reagent except damping fluid needed for sequencing reaction, and the number in the hole that reagent pedestal has is not limit.Meanwhile, the size in the hole on reagent pedestal can be changed according to the specification of Reagent Tube.Also namely, the size in the hole of reagent pedestal and the number in hole unrestricted, can be hyperphoric as required.

Preferably, the size in the hole of reagent pedestal is the hole of the Reagent Tube holding 1.5mL specification.

Preferably, the number in the hole of this reagent pedestal is 96.

For liquid conductive assembly, the present invention proposes another embodiment, and as shown in Figure 5, this assembly can comprise pump 221, mechanical manipulator 23, conduit 222, reagent pedestal 211 and damping fluid pedestal 212.

(1) pump 221 is for extracting the reagent in reagent platform, and by reagent delivery in load sample assembly.

(2) mechanical manipulator 23, it is positioned at the top of reagent platform or is positioned at the side of reagent platform, is connected with pump by conduit, for extracting corresponding reagent in pump from reagent platform.

(3) damping fluid pedestal 212, for holding the damping fluid needed for sequencing reaction.

(4) reagent pedestal 211 is connected with damping fluid pedestal 212, for holding the reagent except damping fluid needed for sequencing reaction.

Wherein, mechanical manipulator 23 is positioned at the top of reagent platform, for extracting corresponding reagent from reagent platform in pump 221 in sequencing procedure.Mechanical manipulator 23 is connected with pump 221 by conduit 222, and mechanical manipulator 23 can move in X, Y, Z space, extracts the reagent in reagent pedestal 211.When needs extract certain reagent, mechanical manipulator 23 accurately navigates to required reagent position in reagent pedestal 211, and extract the reagent of required dosage, be transferred in pump 221 by conduit 222, reagent imports in load sample assembly by pump 221 again.Wherein, pump 221 is also connected with damping fluid pedestal 212 by conduit 222, and the damping fluid extracting setting dosage in damping fluid pedestal 212, to pump 221, is then transferred in load sample assembly through pump 221 again.

In the present embodiment, after mechanical manipulator 23 receives the order of control unit extraction reagent, comprise extract reagent kind, extract the dosage of reagent, mechanical manipulator 23 move to this reagent place corresponding above reagent pedestal 211 position, extract the reagent of corresponding dosage in pump; After pump receives reagent, by reagent delivery in load sample assembly.When pump 221 receives the damping fluid in control unit extraction damping fluid pedestal 212, after comprising position corresponding to damping fluid, dosage needed for damping fluid, pump 221 extracts corresponding damping fluid in pump 221 from damping fluid pedestal 212, is then transferred in load sample assembly.

The present embodiment, achieves the automatization that liquid (comprising reagent, damping fluid) extracts, transmits, substantially increases the level of automation of gene sequencing device and the precision of extracting liquid.

For liquid conductive assembly, the present invention proposes another embodiment, and as shown in Figure 6, this assembly comprises: mechanical manipulator 23, pump 221, reagent pedestal 211, damping fluid pedestal 212.Wherein:

In the present embodiment, mechanical manipulator 23, is positioned at the top of reagent platform, for extracting corresponding reagent to pump 221 from reagent platform in sequencing procedure; Pump 221, for receiving the reagent that mechanical manipulator 23 extracts.Reagent pedestal 211, for holding the reagent except damping fluid; Damping fluid pedestal 212, for holding damping fluid.Wherein, mechanical manipulator 23 is connected with pump 221 by conduit, and mechanical manipulator 23 moves in X, Y, Z space, extracts the reagent in reagent pedestal 211 or the damping fluid in damping fluid pedestal 212.When needs extract certain reagent, mechanical manipulator 23 accurately navigate to this reagent place hole position on, extract this reagent of required dosage, then, by conduit 222 by reagent delivery in pump 221, reagent imports in load sample assembly by pump 221 again.

The present embodiment extracts corresponding reagent or damping fluid in pump by mechanical manipulator, achieves the automatization of Liquid extracting.

In the present invention, the number of mechanical manipulator at least one.The speed of the number of mechanical manipulator extracting liquid is as required selected, and when the fast parallel extraction plurality of liquid of needs, mechanical manipulator can be multiple, can realize parallel and extracting liquid fast.When without speed limit, mechanical manipulator can be one, thus simplifies the structure of gene sequencing device.

For liquid conductive assembly, the present invention proposes another embodiment, and as shown in Figure 7, this assembly comprises two mechanical manipulators 23, pump 221, reagent pedestal 211, damping fluid pedestal 212.Wherein, two mechanical manipulators lay respectively at the top of reagent platform and the side of reagent platform, for extracting corresponding reagent in pump 221 in sequencing procedure from reagent platform.Mechanical manipulator 23 is connected with pump 221 by conduit.An above-mentioned mechanical manipulator 23 is for extracting the reagent in reagent pedestal 211, and mechanical manipulator 23 can move in X, Y, Z space.When needs extract certain reagent, mechanical manipulator 23 accurately navigate to this reagent place hole position on, extract the reagent of required dosage, then, be transferred in pump 221 by conduit 222, reagent imports in load sample assembly by pump 221 again.Another mechanical manipulator 23 above-mentioned is for extracting the reagent in damping fluid pedestal 212, when needs extract certain damping fluid, mechanical manipulator 23 spatially moves at X, Y, Z, navigate to the position at this damping fluid place in damping fluid pedestal 212, and extract the reagent of required dosage, then, by reagent delivery in pump 221, damping fluid imports in load sample assembly by pump 221 again.

The present embodiment adopts two non-interfering extraction reagent of mechanical manipulator 23 and damping fluid, achieves the automatization of Liquid extracting, transmission; Meanwhile, make the speed of Liquid extracting faster.

For load sample assembly, the present invention proposes an embodiment, and as shown in Figure 8, load sample assembly comprises: sample table and locating device.

(1) sample table 31, for fixing testing sample, and receives the reagent of liquid conducting subassembly transmission, makes testing sample carry out sequencing reaction with the reagent received;

(2) locating device 32, is connected with sample table 31, for Quality control platform 31 and/or the displacement of adopting figure assembly, determines to adopt figure position in sample table 31.

In the present embodiment technical scheme, locating device can accurately realize adopting figure location according to the order of control unit, substantially increases the positioning precision of load sample assembly, thus collects clear sequencing image accurately and lay a good foundation for follow-up figure assembly of adopting.

For sample table, the present invention proposes an embodiment, and as shown in Figure 9, sample table comprises support and sequencing reaction small chamber.Wherein:

(1) support 311, for fixing sequencing reaction small chamber 312;

(2) sequencing reaction small chamber 312, for fixing testing sample, makes the reagent that testing sample and liquid conductive assembly transmit carry out sequencing reaction.

Sequencing reaction small chamber 312 is fixed on the support 311 of sample table.Before sequencing reaction starts, be fixed to by the slide being fixed with testing sample on sequencing reaction small chamber 312, sequencing reaction small chamber 312 is fixed on support 311.In this embodiment, being fixed to slide on sequencing reaction small chamber 312 adopts transparent and light transmission is good material to make.

Slide fixing on sequencing reaction small chamber 312 has three pieces, and middle slide is the slide of hollow, and hollow slide side slide is the slide with holes, and the holes of slide with holes is communicated with the hollow space of hollow slide.Form reagent inlet and reagent exit, the part of hollow forms the chamber of sequencing reaction small chamber.The opposite side slide of hollow slide is fixed with testing sample.Also the chamber of i.e. three pieces of slide formation forms the inwall of sequencing reaction small chamber 312.

For sequencing reaction small chamber, the present invention proposes an embodiment, and as shown in Figure 10, sequencing reaction small chamber 312 comprises reagent inlet and reagent exit.Wherein:

(1) reagent inlet 3121, for importing to reagent in sequencing reaction small chamber 312.

(2) reagent exit 3122, for deriving reagent in sequencing reaction small chamber 312.

Wherein, DNA fragmentation to be measured can be fixed on globule, and globule is attached on the inwall of sequencing reaction small chamber 312 side, and DNA fragmentation to be measured also can directly be fixed on the inwall of sequencing reaction small chamber 312 side.

Testing sample 01, namely DNA fragmentation array to be measured or the globule with DNA fragmentation to be measured, be fixed on the inwall of the side of sequencing reaction small chamber 312.The inwall of sequencing reaction small chamber 312 side can be fixed up to ten million even more than one hundred million DNA fragmentation arrays to be measured or the globule with DNA fragmentation to be measured, these up to ten million even more than one hundred million DNA fragmentation arrays to be measured or the globule with DNA fragmentation to be measured define short label array.

Wherein, DNA fragmentation to be measured or globule are attached on the inwall of sequencing reaction small chamber 312 side by chemical reaction or physical action.

When sequencing reaction carries out, reagent flows into from reagent inlet 3121, flows through the inwall of sequencing reaction small chamber 312, after reacting, then flows out from reagent exit 3122 with the testing sample 01 be fixed on the inwall of sequencing reaction small chamber 312 side.

Sequencing reaction small chamber of the present invention fixes thousands of even more than one hundred million DNA fragmentations, achieves gene sequencing device high-throughput, checks order fast; Meanwhile, reagent flows into from reagent inlet and flows out from reagent exit, makes reagent flows have directivity, makes the reagent of flowing and testing sample react more abundant, has saved reagent and reduced cost, also made speed of response accelerate, realized checking order fast.

In the present invention, the area for the sequencing reaction small chamber of the slide of fixing DNA fragmentation to be measured can reach 1000mm ².The density of array point can according to the density needing selection array point of sequencing throughput.

For the sequencing throughput of sequencing reaction small chamber, the present invention proposes an embodiment.DNA fragmentation to be measured is directly fixed in sequencing reaction small chamber.When the density of array point is 1 × 10 ⁵individual/mm ², then the number of fixable array point can reach more than one hundred million.When the density of array point is 2 × 10 ⁵individual/mm ², then the number of fixable array point can reach 200,000,000.Also namely sequencing reaction small chamber of the present invention, compared with traditional sequencing device, substantially increases sequencing throughput, because flux is once high, thus improves the efficiency of order-checking.When sequencing reaction, the amount of reagent in input sequencing reaction small chamber is identical, but the flux of order-checking is high, thus reduces the cost of order-checking.

For the sequencing throughput of sequencing reaction small chamber, the present invention proposes another embodiment.The diameter of the globule of fixing DNA fragmentation to be measured is preferably between 0.5 nanometer to 100 nanometers.When the area of the sequencing reaction small chamber 312 for fixing globule is 500mm ²time, the diameter of globule is 10 μm, fixes globule with the filling ratio of 50%, and the number of fixing globule can reach more than 2,000 ten thousand.Also namely sequencing throughput can reach more than 2,000 ten thousand.In the technical scheme of the present embodiment, the sequencing throughput of sequencing reaction small chamber is high, thus makes in the identical order-checking time, and the sequence that order-checking obtains is many, also namely improves order-checking efficiency.Meanwhile, when sequencing reaction, the amount of reagent in input sequencing reaction small chamber is identical, but the flux of order-checking is high, thus reduces the cost of order-checking.

For locating device, the present invention proposes an embodiment, and as shown in figure 11, this locating device comprises horizontal movement device 321 and vertical movement device 322.Wherein:

(1) horizontal movement device 321 is connected with sample table 31, for regulate sample table 31 position in the plane.

(2) vertical movement device 322 is connected with sample table 31 and Cai Tu assembly, for the position regulating sample table 31 and adopt between figure assembly 5.

Locating device in the present embodiment regulates the position of sample table and Cai Tu assembly according to the instruction of control unit, and relative and manual shift, substantially increases the precision of location and the efficiency of location.

For locating device, the present invention proposes another embodiment, and as shown in figure 12, this locating device comprises horizontal movement device 321 and vertical movement device 322.Horizontal movement device 321 is connected with sample table 31, for regulating the position of sample table 31 place plane; Vertical movement device 322, is connected with sample table 31, for regulating the position of sample table 31, makes sample table 31 and the distance of adopting between figure assembly 5 is best adopt figure site.

For locating device, the present invention proposes another embodiment, and as shown in figure 13, this locating device comprises horizontal movement device 321 and vertical movement device 322.Horizontal movement device 321 is connected with sample table 31, for regulating the position of sample table 31 place plane; Vertical movement device 322, and adopts figure assembly 5 and is connected, and for regulating the position of adopting figure assembly 5, makes sample table 31 and the distance of adopting between figure assembly 5 is best adopt figure site.

For locating device, the present invention proposes another embodiment, and as shown in figure 14, this locating device comprises horizontal movement device 321 and vertical movement device 322.Horizontal movement device 321 is connected with sample table 31, for regulating the position of sample table 31 place plane; Vertical movement device 322, is connected with sample table 31 and multiplying arrangement 531, regulates the position of sample table 31 and Cai Tu assembly 5 simultaneously, makes sample table 31 and the distance of adopting between figure assembly 5 is best adopt figure site.

The adjustment of the vertical movement device 322 pairs of positions in the present embodiment realizes by autofocus adjustment, can achieve the automatization of adopting location, figure position.

For temperature control assembly, the present invention proposes an embodiment, and as shown in figure 15, temperature control assembly comprises temperature measuring equipment 42 and heating and cooling device 41.Wherein:

(1) temperature measuring equipment 42 is for measuring the temperature of load sample assembly in real time.

(2) heating and cooling device 41, is connected respectively with temperature measuring equipment 42, load sample assembly, carries out work according to the temperature that temperature measuring equipment is measured to the temperature of load sample assembly.

When after the temperature arranging load sample assembly, the temperature of load sample assembly measured by temperature measuring equipment 42, and measured temperature value is issued control unit, control unit is according to the temperature data received, send the work order of heating and cooling device, heating and cooling device 41 carries out work according to instruction, performs the instruction of heating or refrigeration.This heating and cooling device 41 is positioned at load sample assembly side, comprises at least one refrigerator.Preferably, in above-described embodiment, the number of refrigerator is 2.

In the present embodiment, sequencing reaction needs to carry out in certain temperature range, and the temperature of heating and cooling device 41 pairs of load sample assemblies accurately controls, and sequencing reaction can be carried out smoothly.

For temperature control assembly, the present invention proposes another embodiment, and as shown in figure 16, temperature control assembly comprises temperature measuring equipment 42, heating and cooling device 41 and air exhausting device 43.Wherein, temperature measuring equipment 42 is for the temperature of the temperature and instrument internal of measuring load sample assembly in real time.The temperature of the load sample assembly recorded is issued control unit by temperature measuring equipment 42, and control unit, according to the temperature data received, sends the work order of heating and cooling device, and heating and cooling device 41 carries out work according to instruction, performs the instruction of heating or refrigeration; The temperature of instrument internal is issued control unit by temperature measuring equipment 42, and control unit, according to the temperature data received, sends the work order of air exhausting device 43.Air exhausting device 43 carries out work according to instruction.Air exhausting device 43, the inner air and outer air achieving gene sequencing device exchanges, and the temperature in gene sequencing device is adjusted in temperature range that gene sequencing device normally works.

Temperature control assembly in the present embodiment not only achieves the Automated condtrol of temperature, and the gentle normal operation of the fast lifting achieving load sample assembly and gene sequencing device.

For the structure of air exhausting device, the present invention proposes an embodiment, and as shown in figure 17, air exhausting device comprises multiple exhaust fan 431, and the number of exhaust fan 431 is preferably: 1 ~ 10.Wherein, exhaust fan 431 is positioned at the bottom of gene sequencing device, side or rear portion.Preferred, the number of exhaust fan 431 is 4, is arranged on two sides, bottom and rear portions of instrument respectively.

For the structure of air exhausting device, the present invention proposes another embodiment, and as shown in figure 18, air exhausting device comprises exhaust fan 431, scatterer 432, refrigerator 433 and loose wind device 434.Wherein:

(1) exhaust fan 431, for discharging the heat in refrigerator 433.

(2) scatterer 432, for leaving the heat transmission of refrigerator 433.

(3) refrigerator 433, for lowering the temperature to gene sequencing device.

(4) loose wind device 434, inner for the cryogenic energy of refrigerator 433 side being evenly delivered to gene sequencing device.

In the present embodiment, loose wind device 434 held against heat sink 432, refrigerator 433 is between loose wind device 434 and scatterer 432, and exhaust fan 431 is positioned over the side of scatterer 432.When appliance requires is lowered the temperature, refrigerator 433 is started working, and the one side of refrigerator 433 is low temperature, another side is high temperature; Cryogenic air around refrigerator 433 low temperature face enters in instrument by loose wind device 434, after the high temperature air of refrigerator 433 high temperature face enters scatterer 432, the high temperature air of scatterer 432 is discharged instrument by exhaust fan 431, thus reaches the object of temperature in lowering apparatus.In this embodiment, air exhausting device can be positioned at the bottom of gene sequencing device, side, top or rear portion.The number of air exhausting device can arrange 1 ~ 5.Preferably, the number of air exhausting device 43 is 2, is all installed on the top of instrument.The number of refrigerator 433 is 1 ~ 5.Preferably, the number of this refrigerator 433 is 3.

The technical scheme of the present embodiment can realize the fast cooling of gene sequencing device, thus saves the time of sequencing reaction, also namely substantially increases the efficiency of sequencing reaction.

For the structure of adopting figure assembly, the present invention proposes an embodiment, as shown in figure 19, adopts figure assembly and comprises light-emitting device 51, prism group 52 and photographic means 23.Wherein:

(1) this light-emitting device 51 is connected with load sample assembly, for providing the light of specific wavelength, to excite the testing sample with marker in load sample assembly.

(2) prism group 52 is between light-emitting device and load sample assembly, filters for the light sent light-emitting device, and carries out optical path adjusting;

(3) photographic means 23 is positioned at load sample assembly side, for gathering the view data of figure position.

In the present embodiment, when adopting figure, light-emitting device 51 sends exciting light, is regulated, make exciting light inject load sample assembly by prism group 52 pairs of light paths, and photographic means 23 pairs of load sample assemblies carry out IMAQ.

In the technical scheme of the present embodiment, prism group achieves the light filtering light-emitting device and send, and can regulate light path, thus ensures that the light of enough light arrives load sample assembly, and the light arriving load sample assembly is purer.This provides guarantee for photographic means photographs image clearly.

For the structure of photographic means, the present invention proposes an embodiment, and as shown in figure 20, photographic means comprises multiplying arrangement 531 and claps map device 532.Multiplying arrangement 531 is for amplifying the image adopting figure position in load sample assembly; Clap the side that map device 532 is positioned at multiplying arrangement 531, for being taken the view data of adopting figure position in load sample assembly by multiplying arrangement 531.When sequencing reaction carries out or after sequencing reaction terminates, imaging device carries out imaging to the image in load sample assembly, clap map device and the image in load sample assembly is gathered.What the technical scheme of the present embodiment can realize gene sequencing device collects image clearly automatically.

The multiple of the multiplying arrangement in the present invention is not limit.The magnification of multiplying arrangement is selected according to the sharpness of the image of shooting and the size in region of shooting image.When region that is less demanding to sharpness but the image of needs shooting is larger, adopt the multiplying arrangement that magnification is low.When sharpness is required high but the region of image of shooting is not limited time, adopt the multiplying arrangement that magnification is high.Preferably, the magnification of this multiplying arrangement 531 is preferably 20 to 100 times.Preferred, the magnification of this multiplying arrangement 531 is 50 times.

Bat map device in the present invention is for directly can be converted to analog current signal arbitrarily by optical signalling, current signal, through amplifying and analog to digital conversion, realizes the acquisition of image, the bat map device of transmission is all applicable to the bat map device that uses in the present invention.

For bat map device, the present invention proposes an embodiment, and clapping map device can be CCD (Charge-coupled Device, charge coupled cell) or CID (charge injection device, charge-injection detector(CID)).

In the present invention, clap the pixel of map device without particular restriction.Sharpness according to the image of required shooting is selected.Preferably, the pixel of this bat map device is at least 3,000,000 pixels.Preferred, the pixel of this bat map device is 4,000,000 pixels.

For light-emitting device, the present invention proposes an embodiment, and this light-emitting device is a mercury lamp, and the testing sample on excited sample platform is luminous.In one embodiment, in sequencing reaction, after testing sample is combined with the reagent carrying marker, form the testing sample carrying marker, the light that mercury lamp sends makes the testing sample carrying marker luminous.

For light-emitting device, the present invention proposes another embodiment, and this light-emitting device is a laser apparatus, the testing sample after the laser radiation utilizing laser apparatus to send and the reagent carrying marker react, and this testing sample carrying marker is luminous.

About the testing sample reacted with the reagent carrying marker, form the method for carrying the testing sample of marker, can referenced patent CN201010155269.9.

It should be noted that, the testing sample carrying marker, when receiving the light of certain wavelength, can send fluorescence.Anyly the light source of excitation labeling thing luminescence all can be applicable to the present invention.Protection scope of the present invention is not limited to the light source in above-described embodiment.

For the structure of adopting figure assembly, the present invention proposes an embodiment, and as shown in figure 21, this is adopted figure assembly and comprises light-emitting device 51, claps map device 532, prism group 52 and multiplying arrangement 531.Wherein:

(1) light-emitting device 51, is connected with load sample assembly, for providing the light of specific wavelength, to excite the testing sample with marker in load sample assembly.

(2) prism group 52, between light-emitting device and load sample assembly, filters for the light sent light-emitting device, and carries out optical path adjusting.

(3) multiplying arrangement 531, for amplifying the image adopting figure position.

(4) clap map device 532, be positioned at the side of multiplying arrangement, for being adopted the view data of figure position by multiplying arrangement shooting.

In the present embodiment, multiplying arrangement 531 is connected with load sample assembly 3, and prism group 52 is positioned at the side of multiplying arrangement 531, and clap the side that map device 532 is positioned at prism group 52, light-emitting device 51 is positioned at the opposite side of prism group 52.Wherein, the light that light-emitting device 51 sends, filters through prism group 52, then reflects through prism group 52, is irradiated on load sample assembly 3 by multiplying arrangement 531.After the irradiation of the light after the testing sample carrying marker in load sample assembly 3 is filtered, the testing sample carrying marker is luminous, the light that the testing sample carrying marker sends, through multiplying arrangement 531 and prism group 52, arrives and claps map device 532, claps map device 532 and carries out image taking.

For the structure of adopting figure assembly, the present invention proposes another embodiment, and as shown in figure 22, this is adopted figure assembly and comprises light-emitting device 51, claps map device 532, prism group 52, multiplying arrangement 531 and optical gate 513.Wherein:

(2) optical gate 513, described optical gate between light-emitting device and load sample assembly, for blocking exciting light when not needing excitation light irradiation.

(3) prism group 52, between light-emitting device and load sample assembly, filters for the light sent light-emitting device, and carries out optical path adjusting.Multiplying arrangement 531, for amplifying the image adopting figure position.

In the present embodiment, multiplying arrangement 531 is connected with load sample assembly 3, and prism group 52 is positioned at the side of multiplying arrangement 531, claps the side that map device 532 is positioned at prism group 52, light-emitting device 51 is positioned at the opposite side of prism group 52, and optical gate 513 is between light-emitting device 51 and prism group 52.When figure clapped by needs, open optical gate 513, after light-emitting device 51 sends light, light injects prism group 52, and prism group 52 filters out specific light, then after the reflection of prism group 52, by multiplying arrangement 531 on load sample assembly 3.In load sample assembly, after the testing sample carrying marker receives specific rayed, the testing sample carrying marker is luminous, and the light that the testing sample carrying marker sends arrives after multiplying arrangement 531 and prism group 52 claps map device 532, claps map device 532 and gathers image.When not needing light, the optical gate 513 being positioned at light-emitting device 51 side just can block light-emitting device 51, and light-emitting device 51 can not be irradiated in load sample assembly 3.

Technical scheme of the present invention achieves gene sequencing device by prism group filter light, adjustment light path, the exciting light arrived in load sample assembly is made to be monochromatic excitation light, thus the light making testing sample send is purer, make the image clapping map device shooting more clear; Meanwhile, after adopting figure position and determining, after bat map device receives the instruction of bat figure, gather image, realize automation collection image; In addition, when not needing light, utilize optical gate to block, avoid exciting light irradiate prism group for a long time and damage prism, thus extend the work-ing life of prism group.

For prism group, the present invention proposes an embodiment, as shown in figure 23, this prism 522 is fixed on prism bracket 521, prism bracket 521 is fixed with multiple prism 522, and prism 522 is provided with can the spectral filter of filter specific wavelengths, spectral filter on each prism 522 is identical or different, when needing the light of certain specific wavelength, rotating prism, enabling prism filter out the light of specific wavelength.Wherein, in this prism group, the number of fixed prism 522 can be 3 ~ 9.Preferably, in this prism group, the number of fixed prism 522 is 3.

For data handling component, the present invention proposes an embodiment, and as shown in figure 24, data handling component comprises data transmission device 71 and data analysis set-up 72.

(1) data transmission device 71 with adopt figure assembly and data analysis set-up is connected respectively, for image data transmission that figure assembly gathers will be adopted to data analysis set-up.

(2) data analysis set-up 72, for analysis of image data.

Described view data includes but not limited to that transmitting device 71 transmits the view data of coming, other data that the are similar or collection of homologous genes sequencing device.Any connection mobile equipment and electronics, can reach data corresponding destination device and all can be used as data transmission device 71.The intelligent electronic device anyly to have automatically, carried out massive values computation and various information processing at high speed all can be used as this data analysis set-up 72.

The technical program makes image real time transfer be processed by data analysis set-up, can realize the automatic business processing of sequencing data, substantially increases the speed of data processing.

For the use of this gene sequencing device, the present invention proposes an embodiment, as shown in figure 25.After preparation of samples completes.First, by fixing for testing sample (globule or DNA fragmentation with DNA fragmentation) (by chemistry or physical action), on slide, slide is fixed on sequencing reaction small chamber, forms the chamber of sequencing reaction small chamber; Then, reagent needed for sequencing reaction in reagent platform or damping fluid are imported in sequencing reaction small chamber by pump, reagent enters from reagent inlet, temperature control assembly controls the temperature in sequencing reaction small chamber, sequencing reaction in sequencing reaction small chamber is carried out smoothly, now, the testing sample of marker can be carried; Then, the reagent of order-checking or damping fluid are derived from reagent exit, and start the view data of taking sequencing reaction; Finally, utilize data handling component, Treatment Analysis is carried out to view data, draw surveyed DNA sequence dna.

Above-mentioned gene sequencing device may be used for various sequence measurement, including but not limited to connection sequencing and synthesis sequencing.Wherein, all sequence measurements, after preparation of samples completes, need sample to be fixed on sequencing reaction small chamber, then, and---adopting figure---data analysis of carrying out sequencing reaction.Various sequence measurement is when carrying out gene sequencing, and the time of the sequencing reagent used, damping fluid, sequencing reaction, the temperature etc. of order-checking are distinguished to some extent; And for the method for acquisition of image data and the means of subsequent data analysis and indifference.

Use connection sequencing to carry out gene sequencing for this gene sequencing device, the present invention proposes an embodiment.First, prepare testing sample, and be fixed on globule by testing sample, globule is fixed on slide by chemistry or physical action, is then fixed in sequencing reaction small chamber by slide, the chamber of form sequencing reaction small chamber.Step 1, by tape label thing reagent delivery in sequencing reaction small chamber, temperature control unit controls the temperature of sequencing reaction small chamber, sequencing reaction can be carried out, utilize base pair complementarity principle, the DNA fragmentation obtained through sequencing reaction carries marker, also namely obtains the DNA fragmentation carrying marker.Step 2, after sequencing reaction completes, extracts a certain amount of damping fluid in reagent platform and, to sequencing reaction small chamber, rinses the reagent carrying marker having neither part nor lot in sequencing reaction, and discharged from reagent exit by damping fluid.Step 3, the DNA fragmentation that fluorescent marker is carried in the optical excitation sent by light-emitting device is luminous, utilizes and claps the fluoroscopic image that map device takes multiple different loci in sequencing reaction small chamber.Wherein, clap map device and clap figure by multiplying arrangement.Repeating step 1, to step 3, checks order until complete all DNA fragmentations.Step 4, by clapping the image data transmission of figure to data handling component, processing data, analyzing the sequence of DNA fragmentation.Wherein, often complete a step 1 and can carry out step 4 to step 3, also can repeatedly carry out step 4 after circulation step 1 to step 3.Above-mentioned often kind of fixing DNA fragmentation is longer, and repeating step 1 is more to the number of times of step 3, and every circulation primary, can record the sequence in a site in sequencing reaction small chamber on DNA fragmentation.Above-mentioned DNA fragmentation is testing sample.Above-mentioned globule can be magnetic bead, steel ball, plastic bead etc.

Figure 27 shows the structural representation of gene sequencing system in one embodiment of the invention, and this system comprises sample preparation control module 10, liquid conductive control module 20, reaction controlling module 30, temperature control module 40, adopts figure control module 50 and control module 60;

(1) sample preparation control module 10, is connected with control module 60, prepares assembly prepare testing sample for Quality control, and controls testing sample and be fixed on load sample assembly.

(2) liquid conductive control module 20, is connected with control module 60, for controlling extraction and the transmission of liquid in liquid conductive assembly.

(3) reaction controlling module 30, is connected with control module 60, for controlling the carrying out of sequencing reaction, and determines the position of adopting figure.

(4) temperature control module 40, is connected with control module 60, for controlling the temperature of sequencing reaction.

(5) adopting figure control module 50, be connected with control module 60, gathering image for controlling to adopt figure assembly.

(6) control module 60, for controlling the operation of connected each module.

The technical scheme of the present embodiment can achieve gene sequencing system and control and adopt from sample preparation, Liquid extracting, reaction controlling, temperature the full-automation that figure controls, and has greatly saved manual labor, meanwhile, has improve the efficiency of gene sequencing.

It should be noted that, the annexation be linked as in logic between modules, includes but not limited to wireless connections.

Figure 27 shows the structural representation of gene sequencing system in another embodiment of the present invention, and this system comprises sample preparation control module 10, liquid conductive control module 20, reaction controlling module 30, temperature control module 40, adopts figure control module 50, control module 60 and data processing module 70;

(1) sample preparation control module 10, is connected with control module 60, prepares assembly 1 prepare testing sample for Quality control, and controls testing sample and be fixed on load sample assembly.

(6) control module 60, for controlling the operation of connected each module.

(7) data processing module 70, is connected with control unit 60, for the treatment of the view data of adopting the collection of figure assembly.

When needs carry out gene sequencing, the instruction starting to prepare testing sample is sent to sample preparation control module 10 by control module 60, after sample preparation control module 10 receives instruction, start execution and prepare testing sample, comprise the vibration of sample preparation module 1, testing sample is fixed on slide, the instruction of installing slide is sent to the mechanical arm of sample preparation module 1 by control module 60, and slide is installed on load sample assembly by mechanical arm; After slide installs, the instruction of Liquid extracting is sent to liquid conductive control module 20 by control module 60, after liquid conductive control module 20 receives instruction, controls liquid conductive assembly extracting liquid in load sample assembly; Whether when Liquid extracting is complete, the instruction of reaction detection is sent to reaction controlling module 30 by control module 60, after reaction controlling module 30 receives instruction, controls the operation of load sample assembly, comprise detection load sample assembly and can normally run; When load sample assembly is normal, temperature controlled instruction is sent to temperature control module 40 by control module 60, after temperature control module 40 receives instruction, controls temperature control assembly and heats load sample assembly or freeze, sequencing reaction can be carried out smoothly; After sequencing reaction, the instruction starting to gather image sends to and adopts figure control module 50 by control module 60, adopts after figure control module 50 receives instruction, controls to adopt the image that figure assembly gathers sequencing reaction; After IMAQ terminates, the instruction starting data processing is issued data processing module 70 by control module 60, and after data processing module 70 receives instruction, control data processing components receives the view data gathered, and processes this view data.

Native system achieves the sample preparation of gene sequencing system, Liquid extracting, reaction controlling, temperature control, adopt figure controls and the automatization of data processing, achieve the full-automation of gene sequencing, meanwhile, greatly save manual labor, improve the efficiency of gene sequencing.

Figure 28 shows the structural representation of data processing module in one embodiment of the invention, and this data processing module comprises data transmission module 701 and data analysis module 702.Wherein:

(1) data transmission module 701, is connected with data analysis module 702, for control data transmission to data analysis module.

(2) data analysis module 702, for receiving the data that data transmission module 701 transmits, and carries out analysis and treament to data.

In the present embodiment, described data are the view data of adopting the collection of figure assembly.The technical scheme of the present embodiment can realize fast transport and the process of data, thus substantially increases the efficiency of gene sequencing.

Should be noted that, the structure of the gene sequencing Apparatus and system in the present invention is including but not limited to the typical structure in the present invention, and other similar sequencing devices utilizing similarity principle to improve in genetically engineered field and system also can be applied in gene sequencing Apparatus and system set forth in the present invention.

The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, all any amendments done within the spirit and principles in the present invention, equivalent replacement and improvement etc., all should be included within protection scope of the present invention.

Claims

1. a gene sequencing device, is characterized in that, comprises sample preparation module, liquid conductive assembly, load sample assembly, temperature control assembly, adopts figure assembly and control unit;

Described sample preparation module, is connected with load sample assembly, for the preparation of testing sample, and is fixed on by testing sample on load sample assembly;

Described liquid conductive assembly, is connected with load sample assembly, for storing and transmission reagent;

Described load sample assembly, for fixing testing sample, and receives the reagent of liquid conducting subassembly transmission, makes testing sample carry out sequencing reaction with the reagent received; Meanwhile, described load sample assembly also adopts figure position for determining;

Described temperature control assembly, is connected with load sample assembly, for regulating the temperature of sequencing reaction in load sample assembly;

Describedly adopt figure assembly, be connected with load sample assembly, for adopting the view data of figure position described in obtaining;

Described control unit, is connected respectively with sample preparation module, liquid conductive assembly, load sample assembly, temperature control assembly and Cai Tu assembly, for controlling the operation of coupled each assembly;

Described temperature control assembly comprises temperature measuring equipment, heating and cooling device and air exhausting device;

Described temperature measuring equipment, is connected with control unit, for the temperature of the temperature and gene sequencing device inside of measuring load sample assembly, and the temperature recorded is sent to control unit;

Described heating and cooling device, is connected respectively with temperature measuring equipment, load sample assembly, control unit, and the temperature of temperature to load sample assembly according to the load sample assembly of temperature measuring equipment measurement regulates;

Described air exhausting device, is connected with control unit, and for the air flowing inside and outside regulatory gene sequencing device, the inner air and outer air realizing gene sequencing device exchanges;

Described air exhausting device comprises exhaust fan, scatterer, refrigerator and loose wind device;

Described exhaust fan is positioned over the side of scatterer, for discharging the heat in refrigerator;

Described scatterer, for opening the heat transmission of refrigerator;

Described refrigerator between loose wind device and scatterer, for lowering the temperature to gene sequencing device;

Described loose wind device held against heat sink, inner for the cryogenic energy of refrigerator side being evenly delivered to gene sequencing device;

Described liquid conductive assembly comprises reagent platform, pump and mechanical manipulator;

Described reagent platform comprises replaceable damping fluid pedestal and reagent pedestal;

Described replaceable damping fluid pedestal, for holding the damping fluid needed for sequencing reaction;

Described reagent pedestal is connected with damping fluid pedestal, for holding the reagent except damping fluid needed for sequencing reaction;

Described reagent platform is connected with pump by conduit, for holding the relevant reagent of sequencing reaction;

Described pump for extracting the reagent in reagent platform, and by reagent delivery in load sample assembly;

Described mechanical manipulator is positioned at the top of reagent platform or is positioned at the side of reagent platform, is connected with pump by conduit, for extracting corresponding reagent in pump from the reagent pedestal in reagent platform;

Damping fluid in described damping fluid pedestal is directly drawn in pump by conduit;

The described figure of adopting assembly comprises light-emitting device, prism group and photographic means;

Described light-emitting device, is connected with load sample assembly, for providing the light of multiple specific wavelength, to excite the testing sample with marker in load sample assembly;

Described prism group, between light-emitting device and load sample assembly, filters for the light sent light-emitting device, and carries out optical path adjusting;

Described photographic means, is positioned at load sample assembly side, for gathering the view data of figure position.

2. gene sequencing device according to claim 1, it is characterized in that, described gene sequencing device also comprises data handling component, described data handling component with adopt figure assembly and control unit is connected respectively, for receiving and processing the view data of adopting figure assembly and gathering.

3. gene sequencing device according to claim 1 and 2, is characterized in that, described load sample assembly comprises sample table and locating device;

Described sample table is used for fixing testing sample, and receives the reagent of liquid conducting subassembly transmission, makes testing sample carry out sequencing reaction with the reagent received;

Described locating device and sample table and/or adopt figure assembly and be connected, for Quality control platform and/or the displacement of adopting figure assembly, thus determine to adopt figure position.

4. gene sequencing device according to claim 3, is characterized in that, described sample table comprises sequencing reaction small chamber, for fixing testing sample, makes the reagent that testing sample and liquid conductive assembly transmit carry out sequencing reaction.

5. gene sequencing device according to claim 4, it is characterized in that, slide fixing on described sequencing reaction small chamber has three pieces, middle slide is the slide of hollow, hollow slide side slide is the slide with holes, the holes of slide with holes is communicated with the hollow space of hollow slide, form reagent inlet and reagent exit, the part of hollow forms the chamber of sequencing reaction small chamber, the opposite side slide of hollow slide is fixed with testing sample, and the chamber of three pieces of slide formation forms the inwall of sequencing reaction small chamber.

6. gene sequencing device according to claim 3, is characterized in that, described locating device comprises horizontal movement device and vertical movement device;

Described horizontal movement device is connected with sample table, for regulate sample table himself position in the plane;

Described vertical movement device and sample table, adopt figure assembly and be connected, for regulating sample table and adopting the distance between figure assembly.

7. gene sequencing device according to claim 1, is characterized in that, described light-emitting device also comprises optical gate, described optical gate between light-emitting device and load sample assembly, for blocking exciting light when not needing excitation light irradiation.

8. gene sequencing device according to claim 1, is characterized in that, described photographic means comprises multiplying arrangement and claps map device;

Described multiplying arrangement, for amplifying the image adopting figure position;

Described bat map device, is positioned at the side of multiplying arrangement, for being adopted the view data of figure position by multiplying arrangement shooting.

9. gene sequencing device according to claim 2, is characterized in that, described data handling component comprises data transmission device and data analysis set-up;

Described data transmission device, and adopts figure assembly and data analysis set-up is connected respectively, for adopting image data transmission that figure assembly gathers to data analysis set-up;

Described data analysis set-up, for the treatment of view data.

10. based on the gene sequencing system of gene sequencing device according to claim 1, it is characterized in that, described system comprises: sample preparation control module, liquid conductive control module, reaction controlling module, temperature control module, adopt figure control module and control module;

Described sample preparation control module, is connected with control module, prepares assembly prepare testing sample for Quality control, and controls testing sample and be fixed on load sample assembly;

Described liquid conductive control module, is connected with control module, for controlling extraction and the transmission of liquid in liquid conductive assembly;

Described reaction controlling module, is connected with control module, for controlling the carrying out of sequencing reaction, and determines the position of adopting figure;

Described temperature control module, is connected with control module, for the temperature of the temperature and gene sequencing device inside that control sequencing reaction;

Describedly adopting figure control module, be connected with control module, gathering image for controlling to adopt figure assembly;

Described control module, for controlling the operation of connected each module.

11. gene sequencing systems according to claim 10, is characterized in that, described system also comprises data processing module, is connected with control unit, for the treatment of the view data of adopting the collection of figure assembly.

12. gene sequencing systems according to claim 11, is characterized in that, described data processing module comprises data transmission module and data analysis module;

Described data transmission module, is connected with data analysis module, for control data transmission to data analysis module;

Described data analysis module, for receiving the data of data transmission module transmission, and carries out analysis and treament to data.