CN109517732A

CN109517732A - Integrated DNA analysis system

Info

Publication number: CN109517732A
Application number: CN201710852605.7A
Authority: CN
Inventors: 王承; 林小靖; 钱宇; 曹健荣
Original assignee: Denuojie Billion (beijing) Biotechnology Co Ltd
Current assignee: Denuojie Billion (beijing) Biotechnology Co Ltd
Priority date: 2017-09-19
Filing date: 2017-09-19
Publication date: 2019-03-26
Anticipated expiration: 2037-09-19
Also published as: CN109517732B

Abstract

The invention discloses a kind of integrated DNA analysis systems, wherein includes: agent delivery system, agent delivery system includes reagent storage means and reagent injection device；Micro-fluidic reaction system, micro-fluidic reaction system includes micro-fluidic chip and micro fluidic device, sample to be analyzed can be added on micro-fluidic chip, reaction reagent in reagent storage means can be injected into micro-fluidic chip by reagent injection device, and micro fluidic device can control the flowing of fluid in micro-fluidic chip；Separation detecting system, separation detecting system includes capillary electrophoresis separation device and fluorescence detection device, reactant on micro-fluidic chip can enter in capillary electrophoresis separation device, and fluorescence detection device can detect the separating resulting in capillary electrophoresis separation device.Integrated DNA analysis system of the invention has the characteristics that integrated function, simple operation, using flexible, detection high-speeding and Mobile portable, can carry out the business application of scale.

Description

Integrated DNA analysis system

Technical field

The present invention relates to DNA analysis detection field more particularly to a kind of integrated DNA analysis systems.

Background technique

DNA analysis technology has wide application field.In basic research field, DNA analysis is mainly used in genome Sequencing, gene expression spectrum analysis, gene mutation and polymorphism analysis etc.；In clinical medicine domain, clinical disease can be carried out Diagnosis, medicament research and development；In judicial expertise field, individual identification and paternity test can be carried out；In agriculture field, animals and plants can be carried out Crossbreeding research, Safety of GM Food detection.

Wherein, by taking medical law fields as an example, with the development of science and technology, forensic dna detection technique has become in one line of public security Body identification, indispensable scientific sharp weapon of fighting crime.In decades, forensic dna detection technique experienced DNA Fingerprinting Map analysis technology, amplified fragment length polymorphism technology, the big technological revolution of mitochondrial DNA detection technique three.It has sent out at present It opens up based on fluorescent marker limited loci STR composite amplification detection technique, mitochondrial DNA detection technique and snp analysis technology The technical system led.

The realization of the above technology be unable to do without corresponding detection platform, and the development of forensic dna detecting instrument determines respectively The practical performance and development speed of kind forensic dna detection technique.Therefore, which is increasingly becoming forensic science field and analysis The research hotspot of instrument field.Indispensable platform and tool, the forensic dna detecting instrument of mainstream are detected as forensic dna It substantially experienced the development of three phases.

First generation DNA detection device results from the eighties in last century, and core technology is plate gel electrophoresis, electrophoresis path By forming comprising being permitted lacunary solid state medium and buffer, DNA molecular completes electrophoresis process in gel, after electrophoretic separation, Fluorescence excitation and photographic analysis are carried out to dyed DNA analysis using UV light source and camera.The DNA Fingerprinting of early stage Figure and AMPFLP, STR allele etc. are all made of plate gel electrophoresis and are detected, and since detection efficiency is low, need a large amount of Technical staff participates in.

Second generation DNA detecting instrument with it is integrated, be automated as basis, start from the last century 90's, be extensive Gene sequencing lay a good foundation.Nineteen ninety-five, American AB company are proposed the flat genetic analyzer of 377 types, poly- using thin layer Acrylamide gel separations of DNA molecules, using Sanger chain termination method, four color fluorescent markers, by reading these four fluorescence The sequence of signal acquisition sample to be tested.The disk electrophoresis paving glue trouble that the instrument uses, therefore it is used Capillary Electrophoresis rapidly The platform of technology replaces.

With the demand growing day by day to extensive, high-throughput DNA analysis instrument, the third generation automates fluorescent capillary Guan Ning Gel electrophoresis analyzer comes into being.New instrument replaces traditional vertical electrophoresis plate with capillary, and vertical slab electrophoresis is overcome to need The shortcomings that manual glue and manual identified swimming lane, makes DNA analysis technology move towards low cost, high-throughput, automation, scale completely Road.Since the heat dissipation area of the unit volume of capillary gel is more much greater than slab gel, DNA points are not only increased The voltage more much higher than slab gel electrophoresis more can be used in the sensitivity and resolution capability of analysis, thus several times improve electricity Swimming speed, increases to the operation of vertical slab electrophoresis 3 times a day 12 times a day, has become most widely used, technology at present most Mature mainstream technology.But the defect of existing equipment mostly various degrees, such as to operation it is professional require it is relatively high, It is unsuitable for layman's use, is difficult to be applied and pushed away on a large scale in conventional forensic dna detection device in a short time Extensively.

Summary of the invention

The purpose of the present invention is to provide one kind to have integrated function, simple operation, using flexible, detection quick Change the integrated DNA analysis system with Mobile portable.

To achieve the above object, integrated DNA analysis system of the invention the specific technical proposal is:

A kind of integration DNA analysis system, wherein include: agent delivery system, agent delivery system includes reagent storage Device and reagent injection device, reagent storage means and reagent injection device are in fluid communication；Micro-fluidic reaction system, it is micro-fluidic anti- Answering system includes micro-fluidic chip and micro fluidic device, and reagent injection device and micro-fluidic chip are in fluid communication, micro-fluidic chip It is connected with micro fluidic device, sample to be analyzed can be added on micro-fluidic chip, and reagent injection device can be by reagent storage means In reaction reagent be injected into micro-fluidic chip, micro fluidic device can control micro-fluidic chip in fluid flowing；Separation inspection Examining system, separation detecting system include capillary electrophoresis separation device and fluorescence detection device, and micro-fluidic chip and capillary are electric Separator of swimming is in fluid communication, and fluorescence detection device is connected with capillary electrophoresis separation device, the reactant on micro-fluidic chip Can enter in capillary electrophoresis separation device, fluorescence detection device can to the separating resulting in capillary electrophoresis separation device into Row detection.

Further, reagent storage means include conventional kit and temperature control kit, and conventional kit includes reagent bottle, energy Enough storages reagent low to ambient temperature requirements；Temperature control kit includes reagent bottle and temperature control device, the adjustable examination of temperature control device The temperature of reagent in agent bottle can store the reagent high to ambient temperature requirements.

Further, temperature control kit includes heat insulation sheath, and reagent bottle is arranged in heat insulation sheath, is provided on heat insulation sheath The inside of protection box body is arranged in temperature control component, reagent bottle, heat insulation sheath and temperature control component.

Further, reagent injection device includes reagent accommodating chamber and automatic propelling device, the reagent of reagent accommodating chamber Entrance and the reagent exit of reagent storage means are in fluid communication, the reagent exit of reagent accommodating chamber and the reagent of micro-fluidic chip Entrance is in fluid communication；Automatic propelling device is connected with reagent accommodating chamber, the reagent in reagent storage means can be added to examination In agent accommodating chamber, and the reagent in reagent accommodating chamber is filled on micro-fluidic chip.

Further, reagent injection device includes multiple syringes vertically arranged side by side, connects one on each syringe A reagent push rod, each reagent push rod are connected with Power Component respectively, and Power Component can respectively drive push component in syringe Reagent is classified and is injected in micro-fluidic chip by middle reciprocating movement.

Further, micro-fluidic chip includes chip body and reaction member, is provided with sample extraction unit on chip body And fluid circuit, sample extraction unit are used for the extraction of reactant；Reaction member fitting is arranged on chip body, reaction member On be provided with conversion zone, the conversion zone on reaction member is connected with the fluid circuit on chip body, reactant and anti- Answer reagent that can be transported in conversion zone by fluid circuit, to complete reaction in conversion zone.

Further, chip body includes accessory blade unit, pipeline blade unit and the control valve blade unit of overlapping setting, accessory It is provided with sample extraction accessory on blade unit, fluid circuit is provided on pipeline blade unit, control is provided on control valve blade unit The control valve member of fluid circuit on-off processed.

Further, it is provided with pipeline cut-off point on the fluid circuit of pipeline blade unit, corresponds to pipeline on control valve blade unit Piping connection hole is provided at the position of cut-off point, piping connection hole is connected with the fluid circuit near pipeline cut-off point, pipe Perforation of the fluid circuit at pipeline cut-off point on road blade unit is realized by piping connection hole.

Further, it is corresponded on control valve blade unit and is provided with opening/shutting valve at the position of pipeline connecting hole, opening/shutting valve can The opening and closing of control piper connecting hole, to realize the perforation and disconnection of corresponding fluid circuit on pipeline blade unit.

Further, micro fluidic device includes chip bearing component and connecting hole opening/closing component, and micro-fluidic chip can be placed On chip bearing component, connecting hole opening/closing component is connected with the piping connection hole in the chip being seated on chip bearing component, The opening and closing in the piping connection hole in controllable chip, to realize the fluid hose being connected on chip with the piping connection hole The connection and disconnection on road.

Further, temperature-controlling module is provided on chip bearing component, micro-fluidic chip is seated in chip bearing component After upper, temperature-controlling module is in contact with micro-fluidic chip, and the reaction temperature on micro-fluidic chip is adjusted.

Further, micro fluidic device includes Mechanical course component, and Mechanical course component is connected with chip bearing component, can be driven Dynamic chip bearing component moves back and forth.

Further, capillary electrophoresis separation device includes Capillary Electrophoresis component and temperature-controlling module, Capillary Electrophoresis Component includes guard assembly, and the inside of guard assembly is arranged in capillary；Temperature-controlling module includes barrier assembly, heating component The inside of barrier assembly is set；Capillary Electrophoresis component and temperature-controlling module contact with each other and can carry out hot transmitting, temperature Heating component in control assembly can carry out temperature adjusting to the capillary in Capillary Electrophoresis component.

Further, it is provided with detection window at the position on guard assembly corresponding to the fluid outlet of capillary, passed through Detection window can detect the electrophoretic separation in capillary.

Further, capillary electrophoresis separation device includes quick lock in component, quick lock in component and Capillary Electrophoresis group Part is connected, by the detachable setting of Capillary Electrophoresis component in integrated DNA analysis system.

Further, capillary electrophoresis separation device includes gel propulsion device, and gel propulsion device includes gel containment chamber Room, temperature-controlled package and automatic propelling device, gel containment chamber is for temporarily storing gel, temperature-controlled package and gel Accommodating chamber is connected, and the gelling temp in gel containment chamber is adjusted, and automatic propelling device is connected with gel containment chamber, can Gel is added in gel containment chamber, and the gel in gel containment chamber is pushed in Capillary Electrophoresis component.

Further, gel propulsion device includes reagent cylinder and reagent push rod, is provided with protecting box on the outside of reagent cylinder, Semiconductor cooler is provided in protecting box, semiconductor cooler is connected with reagent cylinder, and the gel in reagent cylinder is adjusted Temperature, reagent push rod is connected with propulsion assembly, and propulsion assembly can drive reagent push rod to move back and forth in reagent cylinder.

Further, fluorescence detection device includes laser, object lens and spectrometer, laser, object lens and spectrometer sequentially light Road connects, and is provided with the first optical path adjuster, the first optical path between the capillary in laser and capillary electrophoresis separation device The path for the laser that laser issues can be changed in adjuster, is provided with the second optical path adjuster between object lens and spectrometer, and second The path of the fluorescence between object lens and spectrometer can be changed in optical path adjuster.

Further, the first optical path adjuster includes the first plane mirror and the first lens, and the first plane mirror can incite somebody to action The laser of laser transmitting is vertically reflected to capillary direction, and the first lens can focus the laser reflected to capillary direction.

Further, the second optical path adjuster includes second plane mirror, optical filtering and the second lens, the second plane reflection Mirror can vertically reflect the fluorescence that capillary issues to spectrometer direction；Optical filtering can become the fluorescence reflected to spectrometer direction For monochrome；Second lens can focus one-color fluorescence.

Integrated DNA analysis system of the invention has the advantage that

1) each step that DNA is tested and analyzed all is integrated on a compact apparatus, easy to operate, and detection is quick, is being protected Under the premise of demonstrate,proving accuracy, the efficiency of DNA detection is greatly improved, meanwhile, Integral type small-sized equipment also greatlys improve Mobile portability, expand can application places range.

2) unique chip split-type design reduces whole manufacture difficulty under the premise of realizing integrated function And cost, improve reaction effect.

3) original micro fluidic device is realized by the fluid circuit of hierarchical design and matching for control valve To the Precise control of the flowing of reacting fluid on chip, it ensure that that reacts on chip goes on smoothly.

4) the chip reaction system and agent delivery system independently designed, can meet the testing requirements of different number, Improve the flexibility that equipment uses.

5) capillary electrophoresis system of integrated form reduces the difficulty of capillary replacement, improves reaction efficiency, convenient for non- The daily use of professional.

6) from sample to as a result, user is not necessarily to operate in the PCR Lab of standard, it is only necessary to simply be tried Agent is prepared and sample-adding process, subsequent DNA extraction process, PCR process, PCR product mixing and Capillary Electrophoresis process, signal detection Process etc. can all automate progress, and be also equipped with reagent short-term preservation function, can be widely applied to public security, the administration of justice, clinic etc. Field.

Detailed description of the invention

Fig. 1 is the structural schematic diagram of a specific example of integrated DNA analysis system of the invention；

Fig. 2 is the front view of the integrated DNA analysis system in Fig. 1；

Fig. 3 is the left view of the integrated DNA analysis system in Fig. 1；

Fig. 4 is the right view of the integrated DNA analysis system in Fig. 1；

Fig. 5 is the rearview of the integrated DNA analysis system in Fig. 1；

Fig. 6 is the structural schematic diagram of the micro-fluidic chip in integrated DNA analysis system of the invention；

Fig. 7 is the pipeline perspective view of the micro-fluidic chip in Fig. 6；

Fig. 8 is the broken away view of the micro-fluidic chip in Fig. 6；

Fig. 9 is the structural schematic diagram of the top flat in Fig. 8；

Figure 10 is the structural schematic diagram of the accessory piece in Fig. 8；

Figure 11 is the structural schematic diagram of the confuser in Fig. 8；

Figure 12 is the structural schematic diagram of the dust piece in Fig. 8；

Figure 13 is the structural schematic diagram of the valve opening piece in Fig. 8；

Figure 14 is the structural schematic diagram of the egative film in Fig. 8；

Figure 15 is the structural schematic diagram of the reaction plate in Fig. 8；

Figure 16 is the structural schematic diagram of the micro fluidic device in integrated DNA analysis system of the invention；

Figure 17 is the broken away view of the micro fluidic device in Figure 16；

Figure 18 is the structural schematic diagram of the Mechanical course platform in Figure 17；

Figure 19 is the structural representation of the first embodiment of the reagent storage means in integrated DNA analysis system of the invention Figure；

Figure 20 is the structural representation of the second embodiment of the reagent storage means in integrated DNA analysis system of the invention Figure；

Figure 21 is the broken away view of the reagent storage means in Figure 20；

Figure 22 is the structural schematic diagram of the reagent injection device in integrated DNA analysis system of the invention；

Figure 23 is that the reagent injection device in Figure 22 omits the structural schematic diagram after panel；

Figure 24 is the structural schematic diagram of the reagent interface arrangement in Figure 22；

Figure 25 is the structural schematic diagram of the slide assemblies in Figure 22；

Figure 26 is the structural schematic diagram of the capillary electrophoresis separation system in integrated DNA analysis system of the invention；

Figure 27 is the structural schematic diagram of the Capillary Electrophoresis box in Figure 26；

Figure 28 is the broken away view of the Capillary Electrophoresis box in Figure 27；

Figure 29 is the structural schematic diagram of the capillary heating box in Figure 26；

Figure 30 is the broken away view of the capillary heating box in Figure 29；

Figure 31 is the structural schematic diagram of the cassette electromagnetic locking device in Figure 26；

Figure 32 is the broken away view of the cassette electromagnetic locking device in Figure 31；

Figure 33 is the structural schematic diagram of the gel Automatic Propulsion System in integrated DNA analysis system of the invention；

Figure 34 is the side view of the gel Automatic Propulsion System in Figure 33；

Figure 35 is the broken away view of the gel Automatic Propulsion System in Figure 33；

Figure 36 is the structural schematic diagram of the fluorescence detecting system in integrated DNA analysis system of the invention.

Specific embodiment

In order to be better understood by the purpose of the present invention, structure and function, with reference to the accompanying drawing, to a kind of one of the invention Change DNA analysis system and does further detailed description.

Compared to traditional DNA analysis equipment, the integrated DNA analysis system integration of the invention sample extraction, PCR are anti- It answers, be separated by electrophoresis, the almost all step during the DNA analyses such as fluorescence detection, making the analytic process of DNA can be in an entirety It is completed in equipment, greatly improves the usage scenario of equipment, can be widely applied to the fields such as public security, the administration of justice, clinic.

According to functional regional division, integrated DNA analysis system of the invention includes agent delivery system, micro-fluidic reaction System, separation detecting system.Wherein, agent delivery system is for storing required various examinations in integrated DNA analysis system Agent, and be selectively delivered in each component as needed, to meet the needs of equipment operation；Micro-fluidic reaction system mainly into Processing of row sample, such as extraction, the PCR reaction of DNA etc., prepare for subsequent separation detection；Separation detecting system is used for DNA fragmentation is separated by electrophoresis, and carries out fluorescence detection, is needed with completing detection.Also, it is noted that of the invention The complementary structure such as control system, power-supply system is provided in integrated DNA analysis system, accordingly also to reach equipment operation Automation.

Micro-fluidic reaction system

Micro-fluidic reaction system includes micro-fluidic chip and micro fluidic device, wherein micro-fluidic chip is the core of integrated form Piece can be integrated with the various operations and functions of DNA analysis, such as the capture and washing of DNA, DNA cloning thereon；Micro fluidic device For controlling the fluid flowing in micro-fluidic chip, to assist micro-fluidic chip to realize above-mentioned integrated form operation.

Specifically, micro-fluidic chip theoretically can integrated bio, chemistry, medical analysis process sample preparation, anti- Multiple basic operation units such as answer, separate, detecting, but due to the limitation of technology development, excessive operating procedure is integrated at one The accuracy of experimental result, accuracy are reduced, the using effect of whole chip is had a greatly reduced quality, therefore Be only capable of in the laboratory scientific research stage, can not scale business application.Micro-fluidic chip in the present invention is only integrated with DNA and mentions It takes and reacts two step units with PCR, under the premise of realizing small integrated, it is ensured that good using effect.

Compared to existing monoblock type micro-fluidic chip, the micro-fluidic chip in the present invention includes two parts, first is that chip Ontology, second is that reaction member.Wherein, chip body is the main part of micro-fluidic chip, is integrated with sample extraction unit, fluid Pipeline etc.；Reaction member is special conversion zone, for realizing PCR reaction step.Chip body and reaction are single in the present invention Member is two components of independent design, flexible design can be carried out as needed in material and in shape, by core after molding Piece ontology and reaction member combine the micro-fluidic chip constituted in the present invention.

Be designed in this way be most biochemical reactions is considered all to have the material of reaction vessel and shape special requirement, and These special materials, which may not be able to be used to the production chip body of scale or special shape, to be facilitated It is made on conventional die ontology, may such as there is the problems such as difficulty of processing is big, material cost is high, using effect is poor. By taking PCR reacts as an example, can significantly it be improved instead using the reaction vessel that PP material (polypropylene, Polypropylene) makes Answer effect, but compared to conventional chip material, PP material there are difficulty of processing it is big, material cost is high the problems such as, be unsuitable for answering Use entire micro-fluidic chip, and micro-fluidic chip of the invention is by making chip body and reaction member split-type design, it can Reaction member is made using only PP material, it is good to solve the problems, such as this, the using effect of micro-fluidic chip is improved significantly.

In addition, the individually designed shape that can also make conversion zone of reaction member is more flexible, without considering chip The problems such as processing complexity of ontology, because inevitably to design many supplementary structures, such as fluid circuit on chip body Deng.Or by taking PCR reacts as an example, by verification experimental verification, the reaction zone shape of S type can significantly improve reaction effect, if The conversion zone that this type is made on chip body will not only solve the problems, such as chip manufacture mold, also solve conversion zone The problem of closing, increases the difficulty of processing of chip entirety, and then can easily make on reaction member in the present invention should Shape is reacted, because greatly reducing the complexity of manufacture craft on reaction member almost without additional supplementary structure.

Meanwhile the reaction member of independent design is also convenient for accurately temperature control, because the PCR in micro-fluidic chip reacts Requirement for temperature is more stringent, and the existing reaction member being integrated on chip body is paid no attention to very much in terms of temperature control Think, independent reaction member is used in the present invention, the reaction member flexible design temperature control device can be directed to, and make temperature control device Contact with reaction member is more convenient, greatly improves the temperature control effect of reaction member.

For the chip body in the present invention, to further decrease manufacture difficulty, chip body be can be by multiple groups piece Body unit is formed by stacking, for example, can by top flat unit, accessory blade unit, pipeline blade unit, channel blade unit, valve opening blade unit, Egative film unit, which is sequentially overlapped, to be composed.The labyrinth of chip body can be disassembled and as a result, by different piece body units It realizes, the installation space of each accessory unit is such as made on top flat unit and accessory blade unit, in pipeline blade unit and channel Basic fluid circuit is made on blade unit, and fluid circuit is made on valve opening blade unit and egative film unit and controls valve member, it is convenient The standardization of factory, mass production.Each body unit that batch making goes out, which is uniformly carried out overlapping processing, can be completed tool Have a production of the chip of labyrinth, the overlapping processing method of each body unit can there are many, such as bonding, bonding.

Sample extraction unit, fluid circuit unit and discharging of waste liquid list are mainly integrated on chip body in the present invention Member.Wherein, sample extraction unit can complete the extraction of sample, reacting fluid may be implemented in chip sheet in fluid circuit unit Reacting fluid extra on chip body can be absorbed in flowing, discharging of waste liquid unit on body.

By taking DNA is extracted as an example, sample extraction unit can use a variety of extracting modes, if FTA test paper extracts, FTA test paper As a patented technology of Whatman company, it is Promethean application at room temperature the acquisition, transport, purifying of DNA and RNA and Storage, all working are completed on a card, are very suitable to be applied to miniaturization, on integrated micro-fluidic chip.In addition, Existing paramagnetic particle method extraction can also be used, and paramagnetic particle method nucleic acid extraction is mentioned by a kind of novel nucleic acids of carrier of nano biological magnetic bead Technology is taken, nucleic acid molecules can occur specific recognition and be combined with the silicone hydroxyl of magnetic bead surfaces, be sent out under the action of external magnetic field Raw aggregation or dispersion thoroughly get rid of in traditional nucleic acid extraction process and the process hand-manipulated such as are centrifuged, extract supernatant, to realize The automation of nucleic acid is extracted.The sample extraction unit on micro-fluidic chip of the invention can use the energy of any one as a result, The mode of sample is extracted in enough automations, to reach the requirement of integrated automation.

Fluid circuit unit is mainly used for connecting each component units on micro-fluidic chip, with realize sample and Flowing of the reagent between each component units.For fluid circuit unit, main includes two aspects, first is that the drive of fluid It is dynamic, i.e., how to drive sample and reagent to flow in fluid circuit, second is that how the control of fluid, i.e., control sample and reagent exists Flow direction in fluid circuit.

Micro-fluidic chip in the present invention uses Micropump mainly to realize the driving of fluid, wherein machinery can be used in Micropump Micropump, such as centrifugal force Micropump, heat power Micropump, mems electrostatic pump, aerodynamic force Micropump, electromagnetism Micropump, piezoelectric micropump, bimetallic memory Alloy Micropump etc., mechanical Micropump is capable of providing the low-flow fluid to match with the fluid channel on micro-fluidic chip and conveys, special Not Shi He high molecular material class chip simple interfacial assembly.Certainly, according to the actual situation, can also using on-mechanical Micropump come The driving flowed on micro-fluidic chip is realized, as electric field power-driven pump, capillarity Micropump, biological effect Micropump, magnetic fluid are dynamic Power pump, optical drive pump, based on gravity-driven pump, chemical action Micropump etc..

Be for the control of micro-fluidic chip upper fluid flowing, in the present invention by the special designing of fluid circuit and with The micro-valve structure that is used cooperatively realize.Wherein, a plurality of fluid circuit is provided on chip body, every fluid circuit is all Can on micro-fluidic chip a certain operation or conversion zone be connected, so that fluid reagent can be flowed to by this fluid circuit The operation or conversion zone.And the fluid communication between two operations or conversion zone then needs respectively accordingly fluid circuit elder generation Row is in fluid communication, and is provided with flowing connecting hole on chip body of the invention between two accordingly fluid circuit, open or The connection or disconnection of two fluid circuits can be realized by being closed the flowing connecting hole.

The open or close of flowing connecting hole can be accomplished in several ways, for example, being arranged in the side of flowing connecting hole Resilient structural layer is applied on resilient structural layer at position corresponding with a certain flowing connecting hole by external force, can make bullet Property structure sheaf seal up the flowing connecting hole, realize the closure of the flowing connecting hole, accordingly two fluid circuits flowing connect It connects and off-state is just presented at hole, fluid reagent just can not flow between two fluid circuits；And after external force is cancelled, elasticity Structure sheaf can automatically reset, and make to flow connecting hole opening, and accordingly two fluid circuits will pass through flowing connecting hole and present Connected state, fluid reagent can be flowed between two fluid circuits.Wherein, the external force being applied on resilient structural layer It can be realized by solenoid valve, air rammer etc..

Based on above description, the micro fluidic device in the present invention includes chip bearing component and connecting hole opening/closing component, In, chip bearing component be in order to load above-mentioned micro-fluidic chip, on micro-fluidic chip operation and reaction provide one it is steady Fixed platform, connecting hole opening/closing component are then to be connected with micro-fluidic chip, or be specifically and the flowing on micro-fluidic chip Connecting hole is connected, and for controlling the opening and closing for flowing connecting hole on micro-fluidic chip, and then reaches on micro-fluidic chip The flowing of fluid is controlled.

Chip bearing component is preferably flatlike structure, and major function is exactly to carry chip, it is contemplated that chip loads It needs precisely to connect with connecting hole opening/closing component after to chip bearing component, so should be arranged on chip bearing component corresponding Link slot or link block, chip can be directly seated on the link slot or link block, to guarantee that subsequent chip and connecting hole open and close The accurate connection of component.Loading based on chip routine is accustomed to, and is preferably provided with corresponding link slot on chip bearing component, can The accuracy for enough guaranteeing chip mounting location, also can guarantee stability when chip subsequent operation and the saving to space.

Chip bearing component is usually to be horizontally disposed with, and the link slot being arranged thereon is also horizontal configuration, and chip is loaded into It is also basic after in link slot to guarantee each interregional relative independentability on chip in this way in being horizontally arranged, and avoid weight Influence of the power effect to operation and reaction.But according to different situations, sometimes also can be vertical by chip bearing component or oblique set It sets, chip mostly can be also presented vertical or oblique at this time, and in this case, loading fixing of the chip in link slot is with regard to outstanding It is important.

Chip fixing structure can be provided on chip loading assembly, if be only by direct chip placing in link slot, Situations such as usually will appear shaking, requires to influence for relatively high microfluidic system bigger for fining, and chip is fixed Structure is to guarantee the laden stability of chip to carry out additional fixation to the chip being loaded into link slot.This core Piece fixed structure is preferably realized using simple structure, a rotation snap-gauge such as is arranged on the side of link slot, directly by core Piece is firmly stuck in link slot, or further saves space, Elastic buckle, chip can be arranged in the inside of link slot When being loaded into link slot, directly snapped onto link slot by Elastic buckle.Since such fixed structure is more, as long as can Meet that chip, which is fixed, structure is simple, saves space selectively to use.

Chip just needs to be connected with connecting hole opening/closing component after being fixed on chip loading assembly, and connecting hole opening/closing component can To use solenoid valve, because solenoid valve sensitivity with higher, and technology is more mature, is very suitable to be applied to miniflow Control field.Specifically can be, the plunger of solenoid valve be inserted into the flowing connecting hole on chip, by plunger it is flexible come The opening and closing of control flowing connecting hole, for example, plunger is inserted into flowing connecting hole, flowing connection hole is in closing shape State, accordingly off-state is just presented in flowing connection hole in two flow lines, and fluid reagent just can not be in two flow ducts It is flowed between road；When plunger is removed from flowing connecting hole, flowing connecting hole is in the open state, accordingly two flow lines Connected state will be presented by flowing connecting hole, fluid reagent can be flowed between two flow lines.

Alternatively, elastic knot is also provided between flowing connecting hole and the plunger of solenoid valve on chip Structure layer, to realize the opening and closing of flowing connecting hole by resilient structural layer.Specifically: plunger is close to resilient structural layer When, can squeeze on resilient structural layer with flowing connecting hole relative to position at, resilient structural layer will deformation occurs, and then stifled Flowing connecting hole is clogged, flowing connecting hole is in close state, accordingly two flow lines are just in flowing connection hole Existing off-state, fluid reagent just can not flow between two flow lines；When plunger is far from resilient structural layer, elastic construction Layer can return to original state, and flowing connecting hole is just in the open state, and accordingly two flow lines will be connected by flowing It connects hole and connected state is presented, fluid reagent can be flowed between two flow lines.

The above is that connecting hole opening/closing component is described by taking solenoid valve as an example, can also use other in the present invention Structure realizes, such as surges or air rammer, as long as can reach the work of the flowing connecting hole on closure or openness chip With.

Setting of the connecting hole opening/closing component relative to the position property of can choose of chip loading assembly, usually there is two groups of settings Mode, first is that the lower section for the link slot being located on chip loading assembly, after chip is loaded into link slot, connecting hole opening/closing component It is inserted into the flowing connecting hole on chip from the bottom of chip；Second is that the top for the link slot being located on chip loading assembly, After chip is loaded into link slot, connecting hole opening/closing component is from the flowing connecting hole being inserted on chip at the top of chip.Extremely In selecting which kind of mode, generally to need to be inserted into from bottom based on the concrete form of chip, such as the flowing connecting hole of chip, then select First way is selected, needs to be inserted into from top, then selects the second way.Sometimes it can also consider the overall structure of micro fluidic device Arrangement, if chip loading assembly and connecting hole opening/closing component are stationarily connected to together or relatively independently be arranged, Yi Jixin The upper space of piece loading assembly or the size of lower space etc..

Solenoid valve class connecting hole opening/closing component would generally generate certain heat in movement, due to micro fluidic device Internal relative closure is also provided with radiating subassembly for the normal operation for guaranteeing internal each component, especially solenoid valve, dissipates Hot component can radiate to the internal component of micro fluidic device, and radiating mode preferably uses airflow radiating, with structure letter It is single, it is easy to accomplish effect, be relatively specific for the heat dissipation of solenoid valve.But if being realized using the mechanical structure of other forms The opening and closing of connecting hole is flowed on chip, can also be using the radiating mode for being suitable for the mechanical structure, such as water-cooling may There is better effect than airflow radiating.

After flowing to relevant conversion zone by the fluid reagent on connecting hole opening/closing component control chip, it can carry out Relevant reaction, after the completion of extracting such as DNA, PCR reaction reagent and the DNA extracted flow to PCR reaction zone together, can start PCR reaction.Since the reaction on chip mostly has specific requirement to temperature, thus for guarantee chip on react it is normal into It goes, temperature-controlling module should be also set in micro fluidic device, pass through the temperature reacted on the adjustable chip of temperature-controlling module.

Wherein, the setting position of temperature-controlling module should be determined based on the position of conversion zone on chip, with guarantee pair Reaction temperature is precisely controlled on chip.For example, temperature-controlling module should correspond to if conversion zone is located at the end of chip The position opposite with the end of chip is set, and if conversion zone is located at the middle part of chip, temperature-controlling module reply It should be provided in the opposite position in the middle part of chip, and preferably, temperature-controlling module is directly contacted with chip, to guarantee heat The accuracy of conduction.

Since chip is fixedly disposed in the link slot of chip loading assembly in the present invention, so temperature-controlling module is answered It is arranged relative to link slot, if conversion zone is located at top on fruit chip, then temperature-controlling module may be provided at the upper of link slot Side, in order to which the conversion zone at the top of chip is in contact, if conversion zone is located at bottom on fruit chip, then temperature-controlling module can The lower section of link slot is set or is set up directly on the bottom surface of link slot, in order to which the conversion zone of chip bottom is in contact. Wherein, temperature-controlling module preferably uses semiconductor cooler, and semiconductor cooler (Thermo Electric Cooler) is Made of Peltier effect using semiconductor material, have the characteristics that small in size, low energy consumption, Cooling rate is fast, and refrigeration, The rate of heating and refrigeration, heating, can all be determined by current direction and size, easy to use.

For convenience of replacement chip or other maintenances are carried out, Mechanical course component can be set, Mechanical course component can be to micro- Each component in flow control apparatus is moved, and facilitates operation to remove integral device.Wherein, since it is desired that replacing chip, so It is mobile that more frequently mainly chip loading assembly, Mechanical course component can individually control chip loading assembly, When needing to carry out chip replacement, chip loading assembly is individually removed from integral device, meanwhile, in order to facilitate other component Maintenance can also individually control or combination be controlled to it such as connecting hole opening/closing component, temperature-controlling module or radiating subassembly System.

In view of the globality and stability of micro fluidic device, general chip loading assembly, connecting hole opening/closing component, temperature Control assembly and radiating subassembly are fixed together, so Mechanical course component generally is intended to carry out displacement control to its entirety System.Wherein, Bit andits control mainly includes lateral displacement control and length travel control, and length travel control is to adjust each group The height of part, facilitates the separation or combination of each component and integral device, and lateral displacement control is to set each component from whole Standby horizontal removal, to replace chip or carry out other maintenances.

The structure type of Mechanical course component is more universal, it will usually including power mechanism, sliding equipment etc., micro-fluidic dress Each component set can be fixed in sliding equipment, and power mechanism drives sliding equipment mobile, and each component can be driven lateral Or longitudinal movement.Wherein, it because integral device is typically all square structure, can also generally all place when in use in the plane, And it is both provided with corresponding component, such as reagent pipeline etc. above integral device core piece loading assembly, so would generally be first Vertically move each component, to be separated with the associated component in integral device, then consider further that it is laterally moved out from integral device, It is operated with the replacement etc. for carrying out chip.

Agent delivery system

Agent delivery system includes reagent storage means and reagent injection device, wherein reagent storage means will be for that will set Standby required reagent provisional classifications store, and reagent storage means for being connected by reagent injection device with accordingly apparatus assembly It is logical, reagent is injected relevant device component as needed, make to react smooth.

Specifically, reagent storage means include two kinds, one is conventional reagent the storage box, for temporarily store for Ambient temperature requires lower reagent, such as buffer；Another kind is with temperature controlled reagent the storage box, for temporarily depositing It puts to the higher reagent of extraneous temperature requirement, such as archaeal dna polymerase.It wherein, can be with for the first conventional reagent the storage box It generally only include reagent bottle, conduit etc. using reagent the storage box common in this field；Second of temperature control reagent is stored Box can be and increase temperature control device on the basis of general reagent the storage box, such as add heat insulation sheath, half in the outside of reagent bottle Conductor refrigerator etc., to meet the requirement to temperature.

Reagent injection device is for connecting mentioned reagent storage device and micro-fluidic chip, wherein reagent injection device packet Reagent accommodating chamber is included, reagent accommodating chamber is for temporarily storing the fluid reagent that be filled on chip, generally in this field In, reagent accommodating chamber all can use syringe form, both ensure that in this way reagent filling when it is easy to operate, can also make Structure simplifies as far as possible, and can also have a control well for reagent adding amount.But it can also be using other forms, such as Reagent in kit can be filled on chip by kit by way of pumping, and certainly, such mode also has very It is more, only common or syringe form in practice at present.

The reagent inlet of reagent accommodating chamber can be in fluid communication with reagent storage means, the fluid examination in reagent storage means Agent can be filled into advance in reagent accommodating chamber, be then filled on chip by reagent accommodating chamber again.Wherein, reagent accommodates Generally control valve can be all set between chamber and reagent storage means, to control reagent as needed into reagent accommodating chamber Conveying, it is contemplated that the amount of reagent needed for micro-fluidic chip, it is preferred to use solenoid valve is controlled, and can guarantee reagent in this way The Precise control of filling.As a result, when needing to add reagent into reagent accommodating chamber, corresponding solenoid valve, reagent are opened It can be transported to from reagent storage means in reagent accommodating chamber.

After reagent is added to reagent accommodating chamber, so that it may according to the reaction needs on chip, corresponding reagent be filled Onto chip, wherein reagent inlet on the reagent exit and chip of reagent accommodating chamber is in fluid communication, reagent accommodating chamber with Generally control valve can be also set between chip, be preferably all using electricity to control conveying of the reagent on chip as needed Magnet valve, to guarantee the Precise control of reagent filling.As a result, when needing for the reagent in reagent accommodating chamber to be filled on chip When, corresponding solenoid valve is opened, reagent can be transported on chip from reagent accommodating chamber.

Since reagent accommodating chamber usually can all use the form of syringe, so when needing to add the reagent in syringe When infusing on chip, the reagent in syringe can be released by the push rod of promotion syringe, push rod downlink.It considers The push rod of the demand of automation, syringe can be connected with Power Component, and Power Component can be according to the automatic driving push rod of predetermined condition Downlink.Wherein, Power Component generally uses the combining form of motor, sliding block, and sliding block is fixedly connected with the push rod of syringe, electricity Machine can drive sliding block to slide on corresponding sliding rail, to drive the push rod upstream or downstream of syringe, by reagent from injection It is released in device.And if using kit and delivery pump combining form, be that reagent is directly controlled by delivery pump to chip The time of upper filling and amount of reagent are based on cost consideration, preferably still use the form of syringe.

Due to preferably controlling the filling of reagent by the way of Power Component driving push rod, so will be to push rod Moving distance is controlled, and to avoid the excessive movement of push rod, leads to the damage of syringe or push rod, because micro-fluidic chip is determined The small volume for having determined syringe, it is relatively fragile for also meaning that syringe and push rod all.For the moving distance of push rod, It can be controlled using a variety of modes, default moving distance such as is carried out to Power Component, pass through the dynamic of control Power Component Sensing device is arranged to indirectly control the moving distance of push rod, or in the movement routine of push rod in power output, directly to pushing away The moving distance of bar is detected, and this mode may be more accurate and timely.

Above-mentioned sensing device can use the form of sensor, such as photoelectric sensor, be provided with induction targets on push rod, It is provided with inductive component in the movement routine of push rod, when the critical localisation of push rod downlink, inductive component can sense push rod On induction targets, and then generate inductive signal, to know that push rod arrived critical localisation.Wherein, the critical localisation master of push rod It to include two, first is that position when lower limit by row, i.e. push rod all release the reagent in syringe, at this time push rod and injection The overlapping region of device is in maximum value；Second is that the position upper limit by row, i.e. push rod will be filled reagent in syringe when, push rod at this time Minimum value is in the overlapping region of syringe.Since the uplink of push rod can carry out controlling it by many simpler modes Block is arranged in extreme position such as at the upper limit by row of push rod, so general be only arranged in push rod volume downlink extreme position incudes Device, because of the bottom of the lower guild contact syringe of push rod, it has not been convenient to the structures such as block be arranged.

In view of reagent accommodating chamber preferably uses the form of syringe, and syringe usually only has a reagent connection Mouthful, filling of reagent of the reagent in the addition and syringe into syringe on chip will pass through the reagent connector, institute It, can be by syringe by reagent interface module a reagent interface module can be set at the reagent connector of syringe Reagent connector be connected to respectively with reagent storage means, chip fluid.As be provided on reagent interface module main interface channel, And the reagent input channel and reagent output channel being in fluid communication respectively with main interface channel, wherein main interface channel and note Reagent connector in emitter is in fluid communication, and reagent input channel and reagent storage means are in fluid communication, reagent output channel with Chip fluid connection, can so realize the connection of syringe Yu reagent storage means, chip.

When needing to add reagent into syringe, the solenoid valve between syringe and reagent storage means is opened, is closed Solenoid valve between syringe and chip, reagent storage means, reagent interface module, syringe three will be in fluid communication, and lead to Power Component driving push rod uplink is crossed, the reagent in reagent storage means can input logical by the reagent on reagent interface module Road is inhaled into syringe；When needing to fill reagent on chip, the solenoid valve between syringe and chip is opened, is closed Solenoid valve between syringe and reagent storage means, syringe, reagent interface module, chip three will be in fluid communication, and lead to Power Component driving push rod downlink is crossed, the reagent in syringe can be pushed away by the reagent output channel on reagent interface module It is sent in chip.Sucking and release system due to above-mentioned entire reagent are all relative closures, it is possible to effectively be prevented The entrance of air, avoids and generates bubble in syringe.

Due to being integrated with a variety of reactions on micro-fluidic chip, thus on chip needed for reagent type be also it is a variety of, in order to Realize chip on plurality of reagents automatic filling, can with the setting multiple groups reagent accommodating chamber and reagent driving means of array, Every group reagent accommodating chamber and reagent driving means be all it is relatively independent, respectively and in different reagent storage means and chip Different reagent inlets be in fluid communication, to realize the filling of plurality of reagents, and every group reagent accommodating chamber and reagent push Device should be also individually to control, to realize the control to the filling of multiple reagents.Certainly, if every kind of reagent is all that sequence adds The case where entering, being not in two or more reagents while filling can also control all reagents by a Power Component Driving means and reagent accommodating chamber can save space in this way and avoid the complication of structure.

Separation detecting system

Separation detecting system includes capillary electrophoresis separation device and fluorescence detection device, wherein capillary electrophoresis separation Device is the occurrence of equipment of gel electrophoresis, for realizing the electrophoretic separation of DNA fragmentation；Fluorescence detection device and Capillary Electrophoresis point It is used from matched with devices, to realize the fluorescence detection to DNA fragmentation.

Specifically, capillary electrophoresis separation system includes Capillary Electrophoresis component, temperature-controlling module, quick lock in group Part, and the gel propulsion device injected for realizing gel in capillary.Wherein, Capillary Electrophoresis component is for accommodating capillary Pipe provides a reliable and stable environment for electrophoretic separation, avoids capillary in use or the damage in replacement；Temperature Control assembly can be provided for Capillary Electrophoresis component electrophoretic separation when temperature control, with guarantee electrophoretic separation it is smooth into Row；Quick lock in component is in order to which Capillary Electrophoresis component to be temporarily locked in integral device, to facilitate the replacement of capillary.

Wherein, Capillary Electrophoresis component includes capillary and the guard assembly for protecting capillary, and capillary can be adopted It is usually adopted with commercial product such as the elastic vitreous silica capillary that Polymicro Technologies (PT) company produces It is drawn with artificial vitreous silica semi-finished product, similar also can be used the hot quartz in day, Pyrex, a variety of plastics or melting Silicon materials synthetic manufactures, this depends primarily on actual application demand.

Carrier of the capillary as electrophoretic separation, is preferably arranged in a curve way the inside of guard assembly, forms smooth radian, Reach the optimum efficiency of electrophoretic separation, it is of course also possible to capillary be seated in the inside of guard assembly using other modes, such as The capillary being of a straight line type directly is arranged in the inside etc. of guard assembly.In addition, usually, a Capillary Electrophoresis component Inside is provided only with a capillary, but sometimes, in order to improve analysis throughput or analysis efficiency, can also use more hairs Tubule is in parallel arranged to form the form of bundle of capillary tubes.

Guard assembly outside capillary mainly plays the role of protecting capillary, and concrete form can be using protection Shell, capillary are directly seated in the inside of protection shell, protect shell and capillary to form an entirety, in this way can not only The effect that protection capillary avoids damage to is played, but also can effectively improve the substitute mode of capillary.If in capillary electricity Exposed capillary is directly used in separation system of swimming, it is when requiring replacement, extremely careful since capillary belongs to consumables It fractures or is crushed to avoid it, but when the inside that protection shell is arranged in capillary forms an entirety, it is whole directly to replace this Body component.

Due to being provided with a guard assembly in the present invention on the outside of capillary, so in order to meet the need of subsequent detection It wants, detection window should be provided on guard assembly, fluorescence detection device can be made in capillary by the detection window Electrophoretic separation tested and analyzed.Wherein, the requirement based on DNA analysis device miniaturization, fluorescence detection device should contract as far as possible Small size, therefore the fluorescence detection device in the present invention is in addition to including the tradition such as laser, object lens, spectrometer in existing equipment Outside component, it is additionally provided with optical path adjusting component, optical path adjusting component includes plane mirror, lens or optical filtering etc., passes through light Road, which adjusts component, can change the optical line between laser and object lens, and is arranged by the relative position between each component, Reach the requirement of miniaturization.

Capillary Electrophoresis component is alternatively provided in integral device, is replaced for convenience, should be set in integral device It is equipped with quick lock in component, Capillary Electrophoresis component can be made to be quickly locked in integral device using quick lock in component, And when requiring replacement, also easily Capillary Electrophoresis component can be removed from integral device.Wherein, quick lock in component can To be existing elastic latching structure, Capillary Electrophoresis component, which is directly inserted into the elasticity latching structure, can be realized locking, or Person's quick lock in component is also possible to regular screw threads closing component structure, and Capillary Electrophoresis component is directly threaded into the screw thread closing component structure i.e. Locking can be achieved, certain similar structures are there are also very much, as long as being that by quick lock in.

It is corresponding, the structure matched with quick lock in component, such as fast lock should be also provided on Capillary Electrophoresis component Determine component use solenoid component control elastic latching structure, then on Capillary Electrophoresis component need to set with lock head component The position of the locking holes being interlocked, the locking holes should determine according to installation site of the Capillary Electrophoresis component in integral device It is fixed, the edge of Capillary Electrophoresis component is typically set.It, can be with as a result, by the above-mentioned closing component structure being used cooperatively Realize the quick-replaceable of Capillary Electrophoresis component.

There can be special requirement to temperature during Capillary Electrophoresis, for example, temperature influence separation reproducibility and separation Efficiency, control temperature can regulate and control the size of electroosmotic flow, and temperature increases, and buffer viscosity reduces, the light base dissociation capability of tube wall silicon Enhancing, electric osmose speed become larger, and analysis time shortens, and analysis efficiency improves, but such as temperature is excessively high, then can cause capillary column internal diameter Increase to the temperature difference, joule heating effect enhancing, column effect reduces, and separative efficiency can also reduce.So in capillary electrophoresis separation system Also it can be all provided with temperature-controlling module, temperature-controlling module is mainly adjusted the temperature of capillary, to guarantee electrophoresis Process is gone on smoothly.

It wherein, is the inside that guard assembly has been set based on the capillary in the present invention, so temperature control will become It is not quite alike with existing way, such as can be used and be directly sticked the mode of temperature-controlling module in the outside of guard assembly, this Kind mode can not only shorten heat transfer path, and the convenient temperature to capillary quickly adjust and controlled, greatly reduces Experimental period, but also the effect being supported to Capillary Electrophoresis component can be played, because temperature-controlling module is generally all It is to be directly anchored on the whole.

Temperature-controlling module is preferably located at the side of Capillary Electrophoresis component in integral device, shape and Capillary Electrophoresis The shape of component matches, when Capillary Electrophoresis component is locked in integral device, temperature-controlling module and Capillary Electrophoresis Component fits, and is controlled using contact heat conductien the temperature of capillary.Wherein, the heating group in temperature-controlling module Heating structure common in this field can be used in part, such as resistance-type heating plate, and preferably uses ultra-thin resistance heating plate, with In the case where the heating effect needed for realizing, it can significantly reduce energy consumption and save space, provide branch for the miniaturization of integral device It holds.

Due to the miniaturization feature of integral device, the distance of each component can be relatively small in equipment, in order to avoid to entirety The other component of equipment impacts, and the outside of heating component should be provided with barrier assembly, and barrier assembly can mainly play Heating component is supported, and provides the environment of relative closure for heating component.Wherein, the set-up mode of barrier assembly can be with analogy The set-up mode of protective casing outside above-mentioned capillary is made into monolithic construction or Demountable etc., and is using When temperature-controlling module barrier assembly and the guard assembly of Capillary Electrophoresis component can contact with each other and carry out hot transmitting.

In order to guarantee heat transfer effect, the guard assembly of the barrier assembly of temperature-controlling module and Capillary Electrophoresis component is all The material production that heat-transfer effect should be selected to compare, and make capillary and heating component close to the side to contact with each other as far as possible, with contracting Short heat transfer path.Meanwhile heat-conducting pad, heat conductive pad are also provided between temperature-controlling module and Capillary Electrophoresis component Piece may be provided on Capillary Electrophoresis component, may also be arranged on temperature-controlling module, it is contemplated that using effect, heat-conducting pad is most It is to be arranged on Capillary Electrophoresis component well, so that temperature to be uniformly transmitted on capillary.

To realize, gel is automatically injected in capillary, further includes gel propulsion device in the present invention, wherein gel promotes Device includes gel containment chamber, and gel containment chamber is for temporarily storing the gel that be filled on capillary.Generally at this In field, gel containment chamber all can use syringe form, both ensure that in this way gel filling when it is easy to operate, also can Simplify structure as far as possible, and can also have a control well for the adding amount of gel.

The reagent inlet and gel storage device of gel containment chamber are in fluid communication, and reagent exit and capillary fluid connect It is logical.Gel in gel storage device can be pre-added in gel containment chamber, then according to capillary electrophoresis system It needs, gel is filled into capillary in time.Wherein, temperature-controlled package, temperature tune are provided in reagent accommodating chamber The temperature of the gel in the adjustable reagent accommodating chamber of component is saved, so that gel is in ideal storage temperature, is convenient for gel The storage of interim low temperature, the characteristic of specific structure, gel based on reagent accommodating chamber, temperature-controlled package is preferably using partly leading The form of chiller.

Temperature-controlled package can directly be in contact with reagent accommodating chamber, to guarantee its temperature control effect, such as when reagent holds When chamber of receiving uses the form of syringe, temperature-controlled package can wrap laying and set in the outside of syringe, directly to injection Gel in device carries out temperature control.But, it is contemplated that stability of the reagent accommodating chamber when storing gel and injection, preferably , it is provided with support component between temperature-controlled package and reagent accommodating chamber, is set as the outside of syringe is directly coated It is equipped with support component, temperature-controlled package is in contact with support component, transfers heat to reagent accommodating chamber by support component Room, although this mode may make temperature control, speed is slowed down, and the stability of package entirety considers, this hair This mode is still preferably used in bright.

In order to be permanently kept the temperature of the gel in reagent accommodating chamber in OK range, reagent accommodating chamber It may be provided with heat insulation module on the outside of room, heat insulation module is preferably directly contacted with reagent accommodating chamber, namely is located at support component Between reagent accommodating chamber, if the outside of syringe directly winds setting heat insulation module, to maintain in syringe for a long time Gel temperature.Certainly, heat insulation module can be while maintaining the gelling temp in reagent accommodating chamber, also can be to temperature The heat transfer for adjusting component impacts, but in comparison, heat insulation module is directly arranged in the outside of reagent accommodating chamber The whole using effect of meeting more advantageous installation, and the effect of protection reagent accommodating chamber can also be played, avoid support component etc. Reagent accommodating chamber is caused to damage.

Due to the demand of heat transfer, reagent accommodating chamber, heat insulation module, support component and temperature-controlled package can be close Be set together, guard assembly should be set in its whole outside, to prevent each group part by extraneous interference and damage.Its In, guard assembly can be by all coated settings of reagent accommodating chamber, heat insulation module, support component and temperature-controlled package, to protect Protection effect is demonstrate,proved, reagent accommodating chamber just needs to connect by connecting pipe with reagent storage means and capillary fluid as a result, The connecting pipe should also meet the needs of heat preservation, to prevent gel temperature when flowing through the connecting pipe from changing, especially Reagent accommodating chamber and intercapillary connecting pipe.It should be noted that if reagent accommodating chamber uses the shape of syringe Formula, then heat insulation module, support component, temperature-controlled package, guard assembly can be provided only on the main part of syringe, avoid Keep structure excessively complicated, influences whole using effect.

Since reagent accommodating chamber usually can all use the form of syringe, so when needing gel being added to syringe In or when the gel in syringe is filled into capillary, can be realized by pushing the push rod of syringe, on push rod Gel in reagent storage means can be drawn into syringe by row, and the gel in syringe can be pushed to capillary by push rod downlink Guan Zhong.In view of the demand of automation, the push rod of syringe can be connected with Power Component, and Power Component can be according to predetermined condition certainly The movement of dynamic driving push rod.Wherein, Power Component generally uses the combining form of motor, sliding block, the push rod of sliding block and syringe It is fixedly connected, motor can drive sliding block to slide on corresponding sliding rail, to drive the push rod upstream or downstream of syringe.

Each step that integrated DNA analysis system of the invention tests and analyzes DNA all integrates operation on one device Convenient, detection is quick, under the premise of guaranteeing accuracy, greatly improves the efficiency of DNA detection, can be widely applied to public affairs The fields such as peace, the administration of justice, clinic, integrated DNA analysis system of the invention can sufficiently meet its easy to operate, detection efficiently It is required that.

With reference to the accompanying drawing 1 to Figure 36, a certain preferred embodiment of integrated DNA analysis system of the invention is said It is bright.

As shown in Figures 1 to 5, integrated DNA analysis system of the invention includes agent delivery system, micro-fluidic reaction system System and separation detecting system.Wherein, agent delivery system includes reagent storage means 100 and reagent injection device 200, micro-fluidic Reaction system includes micro-fluidic chip 300 and micro fluidic device 400, and separation detecting system includes 500 He of capillary electrophoresis Fluorescence detection device 600, specifically, reagent storage means 100 pass through reagent injection device 200 and 300 phase of micro-fluidic chip Even, the reagent in reagent storage means 100 can be transported on micro-fluidic chip 300 by reagent injection device 200, to complete phase The operation answered, and flowing of the reagent on micro-fluidic chip 300 is controlled by micro fluidic device 400, micro-fluidic chip 300 On reactant can be flowed into capillary electrophoresis 500, to be separated by electrophoresis, and pass through matching used fluorescence detection 600 pairs of results of device detect.

DNA is mainly integrated with as shown in Fig. 6 to Figure 15, on micro-fluidic chip 300 to extract and two steps of PCR amplification, packet Include the top flat 301 being sequentially superimposed, accessory piece 302, confuser 303, dust piece 304, valve opening piece 305, egative film 306 and reaction plate 307.Wherein, the size and shape of top flat 301, accessory piece 302, confuser 303, dust piece 304, valve opening piece 305, egative film 306 Identical, overlapping constitutes chip body, and chip body is the bearing assembly of micro-fluidic chip 300, is integrated with sample on chip body This extraction region, fluid circuit and discharging of waste liquid region；Reaction plate 307 is attached on chip body, is micro-fluidic chip 300 Reaction component is formed with conversion zone, the fluid hose on conversion zone and chip body in reaction plate 307 in reaction plate 307 Road is connected.

These, it is preferred to the top flat 301 of compositing chip ontology, accessory piece 302, confuser 303, dust piece 304, valve Material selection PET material (the polyethylene terephthalate Polyethylene of hole piece 305, egative film 306 Terephthalate), PET material has excellent physical mechanical property in wider temperature range, and long-term use temperature can Up to 120 DEG C, electrical insulating property is excellent, or even under high-temperature high-frequency, electrical property is still preferable, creep resistance, fatigue durability, rub resistance Property, dimensional stability are all fine, are highly suitable as the material of main part of chip, have the advantages that easy to process, cheap.

Meantime, it is preferable that the material selection PP material (polypropylene Polypropylene) of reaction plate 307, wherein PP Material density is small, and intensity, rigidity, hardness, heat resistance are superior to low pressure polyethylene, can use, have good at 150 DEG C of highest or so Good dielectric properties and high-frequency insulation, and do not influenced by humidity, but become fragile when low temperature, it is not wear-resisting, easy to aging.The processing of PP material Difficulty is not suitable as the material of main part of chip, but for PCR reaction, can be significant using PP material production reaction vessel Raising reaction efficiency, therefore in the present embodiment, reaction plate 307 is made of PP material.

Specifically, top flat 301 is the upper case chip of micro-fluidic chip 300, primarily serves the effect of encapsulating chip ontology. Wherein, the internal structure of corresponding micro-fluidic chip 300 in this present embodiment, be formed on top flat 301 sample adding mouth 308, Hydrophobic exhaust outlet 309, reaction plate thermovent 310, reagent adding mouth 311 and reactant delivery port 312.

Sample adding mouth 308 is connected with the sample extraction region on chip body, and blood sample to be processed can be by sample Adding mouth 308 is added on chip, and sealed cover slip 313 is provided at sample adding mouth 308；Hydrophobic exhaust outlet 309 and chip sheet Hydrophobic exhaust gas region on fluid circuit in body is connected, and hydrophobic vent fittings 314 are provided at hydrophobic exhaust outlet 309, with For the exhaust in fluid circuit；Reaction plate thermovent 310 is connected with the reaction plate 307 being attached on chip body, is used for The connection of reaction plate 307 and external environment, to facilitate heat dissipation；On fluid circuit in reagent adding mouth 311 and chip body Reagent inlet is connected, and for the filling of reaction reagent in fluid circuit, wherein reagent adding mouth 311 has multiple, each reagent A kind of corresponding reagent of adding mouth 311；Connecting conduit 315 is provided at reactant delivery port 312, reactant delivery port 312 can lead to It crosses connecting conduit 315 to be connected with subsequent reactions equipment (capillary), for the reactant on micro-fluidic chip 300 to be transported to In follow-up equipment.

Accessory piece 302 is located at the lower section of top flat 301, for providing installation space for each accessory on micro-fluidic chip 300, Such as sample extraction accessory 316, discharging of waste liquid accessory 317.Wherein, it is contemplated that the thickness of the difficulty of processing, accessory piece 302 is not easy It is too big, so in order to guarantee that each accessory has enough installation spaces, the quantity of accessory piece 302 can by multiple, such as two, Three etc., there are two accessory pieces 302 for setting in the present embodiment.

The internal structure of corresponding micro-fluidic chip 300 in this present embodiment and the structure of above-mentioned top flat 301, accessory piece Be formed on 302 sample extraction accessory installing zone 318, hydrophobic exhaust outlet 309, reaction plate thermovent 310, reagent adding mouth 311, Reactant delivery port 312, discharging of waste liquid accessory installing zone 319.Wherein, on sample extraction accessory installing zone 318 and top flat 301 Sample adding mouth 308 is corresponding, for installing sample extraction accessory 316；Discharging of waste liquid accessory installing zone 319 is for installing waste liquid Outlet fitting 317.

It should be noted that sample extraction accessory 316 preferably uses FTA test paper, FTA test paper conduct in the present embodiment One patented technology of Whatman company, Promethean acquisition, transport, purifying and the storage for applying DNA and RNA at room temperature, All working is completed on a card.Certainly, sample extraction accessory 316 can also use similar paramagnetic particle method extraction assembly Deng as long as being that by the extraction of sample.In addition, discharging of waste liquid accessory 317 is preferably using with fluid absorption function Paper etc., to facilitate installation.

Confuser 303 is located at the lower section of accessory piece 302, is the carrying sheet body of fluid circuit 320, fluid reagent is mainly in pipe It is flowed in fluid circuit 320 on road piece 303, to realize the flowing between each functional area.Meanwhile confuser 303 also with Accessory piece 302 provides installation space together for each accessory, in order to the connection of each accessory and fluid circuit 320.

The internal structure of corresponding micro-fluidic chip 300 in this present embodiment and the structure of above-mentioned accessory piece 302, confuser Fluid circuit 320, sample extraction accessory installing zone 318, reaction plate thermovent 310, the installation of discharging of waste liquid accessory are formed on 303 Area 319.Wherein, the sample extraction accessory installing zone 318 on accessory piece 302 and confuser 303 and sample extraction accessory 316 are total It is same to form sample extraction region；Discharging of waste liquid accessory installing zone 319 and waste liquid row on accessory piece 302 and confuser 303 It puts accessory 317 and together forms discharging of waste liquid region；Reagent inlet, hydrophobic exhaust gas region, reaction are provided on fluid circuit 320 Object outlet, fluid circuit 320 can connect each functional area, to facilitate stream of the reacting fluid between each functional area It is dynamic.

It is extracted corresponding to the DNA integrated on micro-fluidic chip 300 and PCR amplification operates, the reagent on fluid circuit 320 enters Mouth includes eluent entrance 321, PCR reagent entrance 322, corresponds to subsequent electrophoresis and detection operation, the examination of fluid circuit 320 Agent entrance can also include marker entrance 323.Wherein, the eluent entrance 321 on fluid circuit 320 and sample extraction region It is connected, is flushed out the reactant extracted in sample extraction region from the eluent that eluent entrance 321 inputs with utilizing Come；PCR reagent entrance 322 is connected with the conversion zone in reaction plate 307, the PCR reagent inputted from PCR reagent entrance 322 It can be flowed into the conversion zone in reaction plate 307 with from together with the reactant that sample extraction region flushes out, it is anti-to carry out PCR It answers；Marker entrance 323 is connected with the reactant exit 324 on fluid circuit 320, and marker can be by marker entrance 323 It is delivered to reactant exit 324 along fluid circuit 320 after input, and by reactant exit 324, reactant delivery port 312, connection Conduit 315 is transported to subsequent consersion unit.

In the present embodiment, the fluid circuit 320 on confuser 303 includes: connection sample extraction region and hydrophobic exhaust area The first fluid pipeline 325 in domain；Connect the second fluid pipeline 326 of PCR reagent entrance 322 and hydrophobic exhaust gas region；Connection is dredged The third fluid circuit 327 of water exhaust gas region and conversion zone；Connect the 4th fluid hose of conversion zone and reactant exit 324 Road 328；5th fluid circuit 329 of linker entrance 323 and reactant exit 324；And connection sample extraction region With the discharging of waste liquid pipe in discharging of waste liquid region, conversion zone and discharging of waste liquid region, reactant exit 324 and discharging of waste liquid region Road 330.Wherein, the third fluid circuit 327 for connecting hydrophobic exhaust gas region and conversion zone is preferably two, in order to reaction zone Reactant is sufficient filling in domain.

In the present embodiment, the fluid circuit 320 between any two functional area on confuser 303 is simultaneously non-through, and It is to disconnect, i.e., is formed with pipeline cut-off point on fluid circuit 320, fluid can not directly passes through the fluid on confuser 303 Pipeline 320 flows between each functional area, but will be by means of following dust piece 304 and valve opening piece 305, to facilitate to micro- The flowing of 300 upper fluid of fluidic chip is precisely controlled.

Dust piece 304 is located at the lower section of confuser 303, is in order to which the perforation to the fluid circuit 320 on confuser 303 mentions It connects for transition, the flowing of 300 upper fluid of micro-fluidic chip is precisely controlled with realizing.Corresponding in this present embodiment micro- The structure of the internal structure of fluidic chip 300 and above-mentioned confuser 303, be formed on dust piece 304 transition connecting hole group 331, Conversion zone connecting hole 332 and reaction plate thermovent 310.

Wherein, transition connecting hole group 331 corresponds to the pipeline cut-off point setting of the fluid circuit 320 on confuser 303, often A transition connecting hole group 331 includes two adjacent connecting holes, and each connecting hole is disconnected with the pipeline on fluid circuit 320 respectively The fluid circuit 320 of point two sides is connected；Conversion zone connecting hole 332 is connected with the conversion zone in reaction plate 307, is used for Reacting fluid is transported in the conversion zone in reaction plate 307.

Valve opening piece 305 is located at the lower section of dust piece 304, for realizing the perforation of the fluid circuit 320 on confuser 303. The internal structure of corresponding micro-fluidic chip 300 in this present embodiment and the structure of above-mentioned confuser 303, dust piece 304, valve opening Valve opening 333, conversion zone connecting hole 332 and reaction plate thermovent 310 are formed on piece 305.

Wherein, the transition connecting hole group 331 that valve opening 333 corresponds on dust piece 304 is arranged, each transition connecting hole group 331 be all connected with a valve opening 333 namely transition connecting hole group 331 in two adjacent connecting holes respectively with 333 phase of valve opening Connection, fluid circuit 320 can be realized in the perforation of pipeline cut-off point by transition connecting hole group 331, valve opening 333 as a result,.

Specifically, the first fluid pipeline 325 corresponding to connection sample extraction region and hydrophobic exhaust gas region, is formed with First valve opening 334；Corresponding to the third fluid circuit 327 for connecting hydrophobic exhaust gas region and conversion zone, it is formed with the second valve opening 335；Corresponding to the 4th fluid circuit 328 of connection conversion zone and reactant exit 324, it is formed with third valve opening 336；It is corresponding It is arranged in connection sample extraction region and discharging of waste liquid region, conversion zone and discharging of waste liquid region, reactant exit 324 and waste liquid The discharging of waste liquid pipeline 330 for putting region, is formed with the 4th valve opening 337.

Egative film 306 is located at the lower section of valve opening piece 305, is the lower case chip of micro-fluidic chip 300.It corresponds in this present embodiment Micro-fluidic chip 300 internal structure and above-mentioned valve opening piece 305 structure, be formed with conversion zone connecting hole on egative film 306 332 and reaction plate thermovent 310.

Meanwhile opening and closing control is carried out to the valve opening 333 on valve opening piece 305 in order to realize, egative film 306 preferably has elasticity, Correspond on egative film 306 at the position of the valve opening 333 on valve opening piece 305 as a result, and apply external force, egative film 306 can be made to occur Deformation, and then egative film 306 is made to block the valve opening 333 on valve opening piece 305, make fluid circuit 320 in the perforation of pipeline cut-off point It disconnects.It should be noted that the above-mentioned external force for being applied to egative film 306 can by with the matching used micro-fluidic dress of micro-fluidic chip 300 400 are set to apply, such as the valve opening 333 corresponded on valve opening piece 305 in micro fluidic device 400 is provided with solenoid valve, passes through The opening and closing of valve opening 333 can be realized in the lifting of solenoid valve.

Reaction plate 307 is located at the lower section of egative film 306, is special reaction vessel, and size and shape can be according to not sympathizing with Condition flexible setting, in addition, may be provided with protection gasket 338 between reaction plate 307 and egative film 306.It corresponds in this present embodiment The internal structure of micro-fluidic chip 300 and the structure of said chip ontology are formed with conversion zone 339, reaction in reaction plate 307 Object entrance 340 and reactant exit 341.

Wherein, in order to improve the effect that PCR reacts, the shape of the conversion zone 339 in reaction plate 307 preferably uses S type. The conversion zone 339 of S type is connected by reactant entrance 340 with 339 connecting hole 332 of conversion zone corresponding on chip body Logical, reactant can flow into conversion zone by fluid circuit 320, conversion zone connecting hole 332, reactant entrance 340 as a result, 339, to carry out PCR reaction.And the product after reacting can pass through corresponding conversion zone on reactant exit 341, chip body Connecting hole 332, fluid circuit 320 are transported to the reactant exit 324 on confuser, and then pass through reactant delivery port 312, connect It connects conduit 315 and is transported to subsequent consersion unit.

The course of work of micro-fluidic chip 300 of the invention are as follows: firstly, apply the corresponding region in external force to egative film 306, With all valve openings 333 on close valve orifice piece 305, it is in an off state corresponding fluid circuit 320 on dust piece 304；Its It is secondary, blood sample to be measured is matched by the sample extraction that the sample adding mouth 308 on top flat 301 is added in sample extraction region On part 316；Then, the first valve opening 334 on valve opening piece 305 is opened, so that between sample extraction region and hydrophobic exhaust gas region First fluid pipeline 325 be in breakthrough status, while being passed through eluent from eluent entrance 321, DNA can be from sample extraction It is eluted out on sample extraction accessory 316 in region, and flows to hydrophobic exhaust gas region；Then, on close valve orifice piece 305 First valve opening 334 opens the second valve opening 335, makes the third fluid circuit 327 between hydrophobic exhaust gas region and conversion zone 339 In breakthrough status, DNA and PCR reagent are entered in the conversion zone 339 in reaction plate 307 by third fluid circuit 327；It connects , the second valve opening 335 on close valve orifice piece 305 makes the conversion zone 339 in reaction plate 307 become isolation chamber, to carry out PCR reaction；Finally, PCR is after the reaction was completed, third valve opening 336 is opened, so that the of conversion zone 339 and reactant exit 324 Four fluid circuits 328 are in breakthrough status, and the reactant in conversion zone 339 can flow to reactant exit 324, while mark certainly Object entrance 323 is passed through marker, so the DNA and marker after amplification can enter subsequent capillary, is separated by electrophoresis Operation.Wherein, in whole process, if waste liquid is excessive, optionally open the 4th valve opening 337 so that sample extraction region with Waste liquid between discharging of waste liquid region, conversion zone 339 and discharging of waste liquid region, reactant exit 324 and discharging of waste liquid region The perforation of 330 selectivity of discharge pipe, makes excess fluid enter discharging of waste liquid region.

As shown in Figure 16 to 18, micro fluidic device 400 includes microfluidic control box 401 and Mechanical course platform 402, In, microfluidic control box 401 can realize the carrying of micro-fluidic chip 300, anti-on the flowing control of fluid and chip in chip Answer the control of temperature；Mechanical course platform 402 can realize the movement of microfluidic control box 401, so that the replacement of chip is more Add simplicity.

Further, microfluidic control box 401 includes chip platform 403 and carrying bottom frame 404, wherein carrying 404 structure of bottom frame At the main body frame of microfluidic control box 401, the setting of chip platform 403 is on carrying bottom frame 404, for carrying chip.Its In, chip platform 403 is plank frame, is provided with chip containing groove 405, chip containing groove on the top surface of plank frame 405 be Open architecture, and the shape of shape and chip matches, and chip can be directly seated in chip containing groove 405.It is excellent Choosing, it is subsequent to fluid to guarantee due to " loaded " position of the chip in chip containing groove 405 accuracy with higher Flowing control, be also provided with position correction component in chip containing groove 405, column such as corresponding with the groove on chip Shape protrusion can make the placement of chip more accurate easy using position correction component.

The side of chip containing groove 405 is provided with chip locking device 406, and chip locking device 406 is conventional turns Dynamic locking-type structure after chip placement is in chip containing groove 405, can be rotated chip locking device 406, so that chip is locked Chip is pressed in chip containing groove 405 by device 406 securely, guarantees chip when fixing and the operation that chip loads Stability.Alternatively, elastic latching structure can also be set directly in chip containing groove 405, and chip is placed on chip Can be completed locking after in containing groove 405, in this way can more convenient chip replacement, also can avoid in chip platform 403 Extra component is arranged in other positions, saves space.

Temperature-controlling module 407 is provided in chip containing groove 405, wherein temperature-controlling module 407 is arranged in core Corresponding with the reaction plate 307 on above-mentioned micro-fluidic chip 300 on the bottom surface of piece containing groove 405, chip placement holds in chip After setting in groove 405, temperature-controlling module 407 is directly contacted with the reaction plate 307 on micro-fluidic chip 300, to adjust reaction The temperature of conversion zone 339 on piece 307 guarantees being normally carried out for reaction.In the present embodiment, temperature-controlling module 407 includes that This heat-conducting pad connected, semiconductor cooler, and the temperature being arranged between heat-conducting pad and semiconductor cooler Sensor, after chip placement is in chip containing groove 405, heat-conducting pad is directly in contact with chip, semiconductor cooler pair Reaction temperature on chip is adjusted.

Multiple intermediate interface channels 408 are additionally provided on the bottom surface of chip containing groove 405, intermediate interface channel 408 passes through Wear the setting of chip platform 403, wherein multiple intermediate interface channels 408 on 405 bottom surface of chip containing groove with it is more on chip A valve opening 333 corresponds.Correspondingly, multiple solenoid valves 409 are provided on the carrying bottom frame 404 of 403 lower section of chip platform, Wherein, it carries and is provided with multiple solenoid valve mounting holes 410 on the bottom surface 414 of bottom frame 404, solenoid valve 409 is mounted vertically in In solenoid valve mounting hole 410, multiple centres on 405 bottom surface of laying and chip containing groove of multiple solenoid valves 409 connect Road 408 is connected to correspond, the top plunger of solenoid valve 409 pass through after corresponding intermediate interface channel 408 with above-mentioned miniflow Egative film 306 on control chip 300 is in contact, and can drive the position lifting that valve opening 333 is corresponded on egative film 306, to realize to core The corresponding valve opening 333 of on piece opens or closes.

Radiator 413 is additionally provided in microfluidic control box 401, radiator 413 is used for entire microfluidic control Box 401 radiates, and prevents it from can not work normally because of high temperature.Wherein, radiator 413 includes installation 412 He of shell The radiator fan 411 being embedded on installation shell, installation shell 412 coats the outside that carrying bottom frame 404 is arranged in, to form phase To closed space, solenoid valve 409 is located in the enclosure space, and the side wall of installation shell 412 is arranged in radiator fan 411 On, and radiating airflow is enable to cover solenoid valve 409, it is preferred to use the mode of face is arranged, and is dissipated with saving space and improving The thermal efficiency.

Mechanical course platform 402 includes horizontal displacement device and vertical displacement device, wherein microfluidic control box 401 is solid It is fixed to be arranged in horizontal displacement device and vertical displacement device, it can realize that microfluidic control box 401 exists by horizontal displacement device The movement of horizontal direction can realize the movement of microfluidic control box 401 in the vertical direction by vertical displacement device,

Wherein, horizontal displacement device includes horizontal sliders 415 and first motor 416, and horizontal sliders 415 include fixing The sliding rail of setting and the sliding part being used cooperatively with sliding rail, sliding rail may be selected to be fixed on pedestal base part, as mobile base Plinth, sliding part are to be slidably matched with sliding rail, and first motor 416 is connected with sliding part, the carrying bottom frame on microfluidic control box 401 404 are fixed on sliding part, and as a result, under the driving of first motor 416, sliding part can drive entire microfluidic control box 401 move back and forth along sliding rail, to realize moving horizontally for microfluidic control box 401.

Vertical displacement device equally includes vertical sliding part 417 and the second motor 418, and vertical sliding part 417 includes fixing The sliding rail of setting and the sliding part being used cooperatively with sliding rail, sliding rail may be selected to be fixed on pedestal base part, as mobile base Plinth, sliding part are to be slidably matched with sliding rail, and the second motor 418 is connected with sliding part, microfluidic control box 401 and horizontal displacement dress It sets and is fixed on sliding part together, as a result, under the driving of the second motor 418, sliding part can drive entire microfluid control Box 4011 and horizontal displacement device processed are moved back and forth along sliding rail, to realize the vertically movable of microfluidic control box 401.

In the present embodiment, vertical displacement device is to need that microfluidic control box 401 and horizontal displacement device one is driven to start shipment Dynamic, so the sliding rail in horizontal displacement device is fixed in the first frame 419, horizontal displacement device is relative to the first frame Frame 419 moves horizontally microfluidic control box 401.Meanwhile sliding part and the fixed company of the first frame 419 in vertical displacement device It connects, sliding rail is fixedly connected with the second frame 420, the sliding as a result, under the driving of the second motor 418, in vertical displacement device Part can drive the first frame 419 and the microfluidic control box 401 and horizontal displacement device that are arranged on the first frame 419 phase together It is vertically movable for the second frame 420.

As shown in Figure 19 to Figure 21, reagent storage means 100 of the invention include two kinds, one is conventional kit 101, One is temperature control kits 102.Conventional kit 101 mainly includes reagent bottle and conduit, for storing to temperature as shown in figure 19 Spend the reagent without too high request, such as buffer；Temperature control kit 102 as shown in Figure 20 and Figure 21, including keeps the temperature box body, examination Agent bottle and conduit, for storing the reagent relatively high to temperature requirement, such as archaeal dna polymerase.

Specifically, heat preservation box body includes heat insulation sheath 103, temperature control component 104 and protection box body 105, wherein reagent bottle 106 are fixed in heat insulation sheath 103, the preservation for liquid；Temperature control component 104 is fixed on heat insulation sheath 103, for controlling The temperature of liquid in reagent bottle 106 processed；Heat insulation sheath 103 is installed in protection box body 105, the heat preservation for reagent bottle 106.

Heat insulation sheath 103 is fastened by two shells with half arc inner wall, which is used to reagent bottle 106 bottle body wraps, and the mouth cylindrical part of reagent bottle 106 protrudes from the upper surface of heat insulation sheath 103；The outer wall of heat insulation sheath 103 It is provided with temperature control component 104, which includes semiconductor cooler and temperature sensor, and semiconductor cooler has The advantages such as temperature is adjustable, small in size, low energy consumption.

Heat insulation sheath 103 and temperature control component 104 setting protection box body 105 in, protection box body 105 include preceding box body 107, The top of back plate 108 and box cover 109, the rear open of preceding box body 107, preceding box body 107 is equipped with notch, and heat insulation sheath 103 is embedding In the inner cavity of preceding box body 107, notch is passed through for the mouth cylindrical part of reagent bottle 106, before back plate 108 is fixed on after box body 107 Side seals the open side of preceding box body 107, and the upper end of back plate 108 upwardly extends, and box cover 109 is arranged in 107 notches of preceding box body Place, box cover 109 are used to seal mouth cylindrical part, and the rear side of box cover 109 is connected to the extending part of back plate 108, is arranged in reagent bottle Conduit 111 in 106 is stretched out from box cover 109.Moreover it is preferred that being equipped with backing plate between back plate 108 and preceding box body 107 110, backing plate 110 is equipped with recess portion, and temperature control device is arranged on the rear side outer wall of heat insulation sheath 103, and recess portion is used to accommodate temperature control Device.

As shown in Figure 22 to Figure 25, reagent injection device 200 includes installation panel 201, installs the first side of panel 201 On be vertically provided with multiple syringes 202 side by side, a reagent push rod 203, reagent push rod are connected on each syringe 202 203 can move back and forth inside syringe 202, by the inside of reagent inhalation syringe 202 or by the reagent inside syringe 202 Push out.Wherein, every group of syringe 202 and reagent push rod 203 are all relatively independent, the injection being arranged side by side by multiple groups The filling of plurality of reagents on chip may be implemented in device 202 and reagent push rod 203.

The lower part for installing the first side of panel 201 is provided with reagent interface arrangement 204, right on reagent interface arrangement 204 One group of syringe interface channel 205, reagent input channel 206 and reagent output channel should be both provided in each syringe 202 207, wherein syringe interface channel 205 is arranged on the top surface of reagent interface arrangement 204, and the setting of reagent input channel 206 exists On the side of reagent interface arrangement 204, reagent output channel 207 is arranged on the bottom surface of reagent interface arrangement 204, reagent input Channel 206 and reagent output channel 207 are in fluid communication with syringe interface channel 205 respectively.

Each syringe interface channel 205 on reagent interface arrangement 204 is corresponding with the syringe 202 of top, note The bottom of emitter 202 is inserted into the syringe interface channel 205 on reagent interface arrangement 204, and the reagent of syringe 202 connects Mouth is in fluid communication with syringe interface channel 205.Reagent input channel 206 and reagent storage on reagent interface arrangement 204 fill Reagent exit on 100 is set to be in fluid communication, and the reagent exit in reagent input channel 206 and reagent storage means 100 it Between interface channel on be provided with the first solenoid valve 208；In reagent output channel 207 and chip on reagent interface arrangement 204 Reagent inlet be in fluid communication, and it is same on the interface channel between the reagent inlet in reagent output channel 207 and chip It is provided with second solenoid valve.

The reagent interface on syringe 202 passes through the syringe interface channel 205 on reagent interface arrangement 204, examination as a result, Reagent exit in agent input channel 206 and reagent storage means 100 is in fluid communication；Reagent interface on syringe 202 passes through The examination on syringe interface channel 205, reagent output channel 207 and above-mentioned micro-fluidic chip 300 on reagent interface arrangement 204 Agent entrance is in fluid communication.When on the interface channel between the reagent exit in reagent input channel 206 and reagent storage means 100 The first solenoid valve 208 when opening, the reagent in reagent storage means 100 can pass through the reagent in reagent storage means 100 Reagent in outlet, the reagent input channel 206 on reagent interface arrangement 204, syringe interface channel 205, syringe 202 connects Mouth flows into syringe 202, to realize the addition of reagent in syringe 202.Reagent in reagent output channel 207 and chip When second solenoid valve on interface channel between entrance is opened, the reagent in syringe 202 can be by syringe 202 The reagent on syringe interface channel 205, reagent output channel 207, chip on reagent interface, reagent interface arrangement 204 enters Mouth flows into chip, to realize the filling of reagent in chip.

The bottom of syringe 202 is inserted into the syringe interface channel 205 on reagent interface arrangement 204, can not only The bottom of syringe 202, can also be arranged in relatively fixedly and install by the purpose for playing connection reagent storage means 100 and chip On panel 201.Meanwhile installing and being additionally provided with syringe clamping device 209 in the top of reagent interface arrangement 204 on panel 201, Corresponding to holding holes are both provided at the position of each syringe 202 on syringe clamping device 209, syringe 202, which can block, to be set It, can jail by reagent interface arrangement 204 and syringe clamping device 209 in the holding holes on syringe clamping device 209 Admittedly by syringe 202 setting installation panel 201 on.Preferably, the position of the holding holes on syringe clamping device 209 The top or middle and upper part of corresponding syringe 202, in this way, the bottom of syringe 202 is fixed by reagent interface arrangement 204, injection The middle and upper part of device 202 is fixed by syringe clamping device 209, in this way when reagent push rod 203 moves back and forth in syringe 202 When, it is ensured that the stability of syringe 202.

Reciprocating movement of the reagent push rod 203 in syringe 202 is by motor 210, slide assemblies 211 and sliding rail 212 It realizes, wherein motor 210 is connected with slide assemblies 211, and slide assemblies 211 are slidably arranged on sliding rail 212, and Slide Group Part 211 is connected with reagent push rod 203, and motor 210 can drive slide assemblies 211 to move back and forth on sliding rail 212 as a result, in turn Slide assemblies 211 can drive reagent push rod 203 to move back and forth in syringe 202.It should be noted that every group of syringe 202 It is all correspondingly arranged on one group of motor 210, slide assemblies 211 and sliding rail 212 with reagent push rod 203, to facilitate to every group of syringe 202 and reagent push rod 203 independent control.

Panel is installed in the detection of extreme position when moving back and forth inside syringe 202 to realize to reagent push rod 203 It is provided with optical sensor 213 in 201 first side, corresponds to the optical sensor 213 on slide assemblies 211 and is provided with inspection Piece 214 is surveyed, optical sensor 213 and detection lug 214 are worked with photoelectric effect principle.Wherein, optical sensor 213 is arranged In the movement routine of reagent push rod 203, and correspond to the downlink extreme position of reagent push rod 203, slide assemblies 211 drive examination When agent 203 downlink of push rod, detection lug 214 can pass through optical sensor 213 when reagent push rod 203 reaches downlink extreme position, And then sensing signal is generated in optical sensor 213, and downlink extreme position arrived with visualizingre agent push rod 203, it is electric at this time Machine 210 will stop driving.

The specific work process of reagent injection device 200 are as follows: firstly, opening reagent input channel 206 and reagent storage dress The first solenoid valve 208 on the interface channel between the reagent exit on 100 is set, is closed on reagent output channel 207 and chip Reagent inlet between interface channel on second solenoid valve；Secondly, motor 210 drives slide assemblies 211 along sliding rail 212 Row, slide assemblies 211 will drive reagent push rod 203 in 202 inside uplink of syringe, and then will be in reagent storage means 100 Inside reagent inhalation syringe 202, after the completion of reagent addition, close in reagent input channel 206 and reagent storage means 100 The first solenoid valve 208 on interface channel between reagent exit；Then, the reagent type filled as needed on chip, Open the second solenoid valve on the interface channel between the reagent inlet on corresponding reagent output channel 207 and chip；Then, Motor 210 drives slide assemblies 211 along 212 downlink of sliding rail, and slide assemblies 211 will drive reagent push rod 203 in syringe 202 Subordinate's row, and then the reagent in syringe 202 is pushed on chip in accordingly reagent inlet, to meet reaction or operation Demand.

As shown in Figure 26 to Figure 35, capillary electrophoresis 500 includes Capillary Electrophoresis box 501, capillary heating box 502, quick-connect mechanism 503 and gel propulsion device 504, wherein Capillary Electrophoresis box 501 accommodates capillary 505 Sub-assembly, for the execution unit of electrophoretic separation；Capillary heating box 502 is the sub-assembly for accommodating heating plate 506, for electrophoresis point The component adjusted from offer temperature；Quick-connect mechanism 503 is to set the detachable entirety that is locked in of Capillary Electrophoresis box 501 Standby upper component, to facilitate the replacement of Capillary Electrophoresis box 501；Gel propulsion device 504 in capillary 505 gel from Dynamic injection.

Further, Capillary Electrophoresis box 501 includes electrophoresis box body 507, and in the form of sheets, inside is formed with appearance to electrophoresis box body 507 Receive space, capillary 505 is arranged in the accommodation space of electrophoresis box body 507, and electrophoresis box body 507 can play guarantor to capillary 505 Shield effect.Wherein, electrophoresis box body 507 is composed of first shell 508 and second shell 509, and capillary 505 is located at first Between shell 508 and second shell 509, and protection gasket 510 is also provided between first shell 508 and capillary 505, Protection gasket 510 can select the foam pad either gasket made of other elastic materials, for providing capillary 505 Further protection.

The U-shaped bending of capillary 505, the main part of capillary 505 are all located in electrophoresis box body 507, wherein capillary The length of the fluid inlet end of pipe 505 is greater than the length of fluid outlet, as a result, when capillary 505 is arranged in electrophoresis box body 507 When middle, the fluid inlet end of capillary 505 can be stretched out from electrophoresis box body 507, to facilitate the filling of fluid in capillary 505. Simultaneously as the fluid inlet end of capillary 505 is stretched out from electrophoresis box body 507, so on the fluid inlet end of capillary 505 It is preferred that being arranged with protection sleeve pipe 511, protection sleeve pipe 511 can protect the fluid inlet end of capillary 505, avoid using Or the damage of capillary 505 is caused in moving process.

At the position of fluid outlet corresponding to capillary 505, it is provided with detection window 512 on electrophoresis box body 507, examines Surveying window 512 is in order to facilitate the fluorescence detection device 600 in 505 electrophoretic apparatus 500 of capillary to the electrophoresis in capillary 505 Separation is observed namely laser can enter the detection to carry out signal by detection window 512.Accordingly, due to capillary 505 at detection window 512 be relatively exposed, so closing assembly 549 should be provided at detection window 512, need into When row detection, the closing assembly 549 is removed, makes detection window 512 in opened condition, the laser in fluorescence detection device 600 is just It can enter, to carry out the detection of signal, after detection, closing assembly 549 is installed at detection window 512, so that inspection It is in closed state to survey window 512, capillary 505 is avoided to have an accident damage.

Side in second shell 509 close to capillary heating box 502 is provided with heat-conducting pad 513, works as Capillary Electrophoresis When box 501 is installed in integral device, the side that heat-conducting pad 513 is provided on Capillary Electrophoresis box 501 can add with capillary Hot box 502 is bonded to each other, and by the way that heat-conducting pad 513 is arranged, capillary 505 can be made to be heated evenly during the work time, and lead The distance between heat pad piece 513 and capillary 505 are shorter, are greatly improved heating efficiency, and then improve conventional efficient.In addition, Quick clamping groove 514 is also provided on electrophoresis box body 507, quick clamping groove 514 is used for and the quick clamping in integral device Part is attached, in order to quick disassembly and installation of the Capillary Electrophoresis box 501 in integral device.

Capillary heating box 502 include heating box body 515, heat box body 515 shape preferably with above-mentioned electrophoresis box body 507 Shape match, also in the form of sheets, heating box body 515 inside formed accommodating chamber, heating plate 506 be arranged in the accommodating chamber In, heating box body 515 can play protective action to heating plate 506, avoid heating plate 506 from being destroyed, but also can prevent The temperature of heating plate 506 impacts other component.

Wherein, heating box body 515 includes bottom plate 516, and bottom plate 516 has heat transfer property, when heating box body 515 and above-mentioned electricity When swimming box body 507 is in contact, bottom plate 516 can be in contact with the heat-conducting pad 513 on electrophoresis box body 507, to realize the biography of heat It passs.Preferably, heating plate 506 is fixed on bottom plate 516, to shorten the heat transmitting road between capillary 505 as far as possible Diameter, heating plate 506 is located at the middle position of bottom plate 516, and is connected with temperature sensor 517, and temperature sensor 517 passes through letter Number wiring 518 is connect with control system, to realize the real-time monitoring to the temperature of heating plate 506.Wherein, in the present embodiment, add The case where hot plate 506 preferably uses ultra-thin resistance heating plate, and thickness may be designed as 10-20mm, the heating effect needed for realizing Under, it not only can significantly reduce energy consumption, but also the purpose of miniaturization may be implemented.

Bottom plate 516 is connected with braced frame 519, and braced frame 519 is frame-type structure, bottom plate 516 and braced frame 519 Edge be correspondingly arranged on locked component 520, can be connected bottom plate 516 and braced frame 519 are fixed by locked component 520 It connects.Wherein, corresponding to cavity is formed at the position of heating plate 506 in braced frame 519, braced frame 519 and bottom plate 516 connect After connecing, the heating plate 506 on bottom plate 516 is located at the central cavity of braced frame 519, it is preferred that bottom plate 516 and support frame Protection bed course 521 is provided between frame 519, protection bed course 521 can be made of cystosepiment or other elastic materials, neonychium Layer 521 can form protection to heating plate 506, temperature sensor 517.

Bottom plate 516 can be arranged on the outside after being fixedly connected with braced frame 519 protection shell 522, protection shell 522 with Bottom plate 516 can be connected with by the way of with braced frame 519 using snapping or card, and protection shell 522 makes the heating on bottom plate 516 Plate 506 and temperature sensor 517 be in the environment of a relative closure, avoids and interferes with each other with external environment.This Outside, the edge of braced frame 519 is also provided with locking connector 523, can be added capillary by the locking connector 523 Hot box 502 is fixed in integral device.

Quick-connect mechanism 503 includes locking bottom frame 524, and one end of locking bottom frame 524 is provided with lock swinging chute 526, Snap close piece 525, the quick clamping on snap close piece 525 and above-mentioned Capillary Electrophoresis box 501 are movably set in lock swinging chute 526 Slot 514 is used cooperatively, and snap close piece 525 can move back and forth in lock swinging chute 526, to realize to Capillary Electrophoresis box 501 Release and locking.Wherein, the corresponding position on the bottom of snap close piece 525 and lock swinging chute 526 is respectively formed with rotation axis Hole, rotational axis hole are internally provided with shaft, and snap close piece 525 can be around the shaft reciprocally swinging.

The other end on locking bottom frame 524 is provided with actuator mounting plate 527, and the end of solenoid component 528 may pass through It is fixedly connected after mounting hole on actuator mounting plate 527 with locking assembly 529, solenoid component 528 is fixed on locking On bottom frame 524.Wherein, the end of the plunger 530 of solenoid component 528 is provided with drive connection part 531, in snap close piece 525 Top, which is provided with, is drivingly connected hole, and drive connection part 531 can be connected with the drive connection hole on snap close piece 525, solenoid component 528 plunger 530 can drive snap close piece 525 to swing by drive connection part 531, to discharge Capillary Electrophoresis box 501.

Block washer 532, block pad are provided at the position of snap close piece 525 on the plunger 530 of solenoid component 528 The side of circle 532 is in contact with snap close piece 525, and reset spring 533 is provided between the other side and actuator mounting plate 527, multiple Position spring 533 is set on the plunger 530 of solenoid component 528.As a result, when needing to open snap close piece 525, solenoid component 528 plunger 530 can drive snap close piece 525 to swing by drive connection part 531, and snap close piece 525 can connect with block washer 532 Touching, and block washer 532 and reset spring 533 are squeezed, so that reset spring 533 is in compressive deformation state；It is locked when needing to be closed When fastener 525, the deformation power that can directly be saved bit by bit using reset spring 533 pushes block washer 532, and then makes snap close piece 525 It resets.

Gel propulsion device 504 includes syringe 534, protecting box 535, semiconductor cooler 536 and propulsion assembly 537, Wherein, syringe 534 by the gel in gel storage device for sucking and being pushed in capillary 505；Protecting box 535 is arranged In the outside of syringe 534, can play a protective role to syringe 534；Protecting box 535 is arranged in semiconductor cooler 536 The temperature of the gel in syringe 534 can be adjusted in inside；Propulsion assembly 537 is connected with syringe 534, can control automatically Gel in reagent storage means 100 is sucked and is pushed in capillary 505 by syringe 534 processed.

Syringe 534 includes reagent cylinder 537 and reagent push rod 538, wherein reagent push rod 538 is inserted into reagent cylinder It in 537, and can be moved back and forth in reagent cylinder 537, reagent cylinder 537 is for storing gel, and reagent push rod 538 will be for that will coagulate Glue sucking reagent cylinder 537 is released from reagent cylinder 537.

Protecting box 535 includes protection shell, supporting block and heat insulation sheath 539, wherein protection shell, supporting block and heat preservation Sheath 539 is sequentially arranged the outside of the reagent cylinder 537 in syringe 534, plays the gel temperature adjusted in reagent cylinder 537 The effect of degree, protection reagent cylinder 537.Specifically, the coated outside that reagent cylinder 537 is arranged in of heat insulation sheath 539, can be with Make the suitable temperature that is maintained at of the gel long period in reagent cylinder 537, while reagent cylinder 537 can also be avoided by other Component damage is such as supported block and scratches or press from both sides and splits.Wherein, heat insulation sheath 539 can be two panels arc part, two panels arc Heat insulation sheath 539 is bonded the outside that reagent cylinder 537 is arranged in, and certainly, heat insulation sheath 539 can also use banded structure, directly Connect the outside that reagent cylinder 537 is arranged in winding.

Supporting block includes the first supporting block 541 and the second supporting block 542, and the first supporting block 541 and the second supporting block 542 are detained It is located at the outside of reagent cylinder 537 and heat insulation sheath 539, support can be played the role of to reagent cylinder 537 and clamped, simultaneously also Heat insulation sheath 539 can be closely fitted in the outside of reagent cylinder 537.Certainly, the first supporting block 541 and the second supporting block 542 may be alternatively configured integral structure, directly be set in the outside of reagent cylinder 537 and heat insulation sheath 539, but in view of assembling and The convenience of disassembly, preferably split type structure.

Second supporting block 542 is in contact with semiconductor cooler 536, and the heat that semiconductor cooler 536 generates can pass through Second supporting block 542 passes to reagent cylinder 537, is adjusted with the temperature to the gel in reagent cylinder 537.As a result, Two supporting blocks 542 should have thermal conduction characteristic, and in view of the uniformity of heat transmitting, the second supporting block 542 and semiconductor refrigerating It may be provided with heat-conducting pad 543 between device 536.Wherein, semiconductor cooler 536 is with small in size, low energy consumption, Cooling rate is fast The characteristics of, heat-conducting pad 543, which is arranged, between semiconductor cooler 536 and the second supporting block 542 can make heat transfer more equal It is even, improve the precision to the control of chip reaction temperature；Meanwhile semiconductor cooler 536 can also be with 517 phase of temperature sensor Even, the real time temperature detection to semiconductor cooler 536 can be realized by temperature sensor 517.

Protecting shell includes first shell 544 and second shell 545, and first shell 544 and second shell 545 be located in branch The outside of bracer and semiconductor cooler 536 makes supporting block, semiconductor cooler 536, heat insulation sheath 539 and reagent cylinder 537 In a relatively closed space, avoid by extraneous interference and damage.Wherein, protection shell is designed to split type knot Structure is also primarily to the convenience of assembling, disassembly.

It should be noted that protection shell is the outer of the coated main part that reagent cylinder 537 is arranged in the present embodiment Side, is only the outside that reagent interface and push rod entrance are located at protection shell on reagent cylinder 537, the reagent on reagent cylinder 537 Interface is directly connected with connecting bend 540, can change the flow direction of gel by connecting bend 540, and can connect various pipes Road connector.Aforesaid way primarily to connection and operation convenience, it is of course also possible to which reagent cylinder 537 is all arranged In the inside of protection shell, reagent push rod 538 just needs to be inserted into reagent cylinder 537 after protection shell as a result, even Elbow is connect to be also required to be connected after protection shell with the reagent interface of reagent cylinder 537.

Propulsion assembly 537 includes sliding rail 546, sliding block 547 and driving motor 548, wherein driving motor 548 and sliding block 547 It is connected, sliding block 547 is slidably arranged on sliding rail 546, and sliding block 547 is connected with reagent push rod 538, and driving motor 548 can as a result, Driving sliding block 547 moves back and forth on sliding rail 546, and then sliding block 547 can drive reagent push rod 538 past in reagent cylinder 537 It is multiple mobile.Specifically, sliding rail 546 can be fixed in protecting box 535, and the extending direction of sliding rail 546 and syringe 534 Setting direction be parallel to each other；One end of sliding block 547 is fixedly connected with reagent push rod 538, and the other end is slidably arranged in sliding rail 546 On；Driving motor 548 can also be fixed in protecting box 535, and the motor shaft of driving motor 548 is fixedly connected with sliding block 547.

As a result, when needing for the gel in gel storage device to be added in reagent cylinder 537, pass through driving motor For 548 band movable sliders 547 along 546 uplink of sliding rail, sliding block 547 can drive the uplink in reagent cylinder 537 of reagent push rod 538, with Suck gel；When needing for the gel in reagent cylinder 537 to be pushed in capillary 505, is driven and slided by driving motor 548 Block 547 is along 546 downlink of sliding rail, and sliding block 547 can drive the downlink in reagent cylinder 537 of reagent push rod 538, to release gel.

Fluorescence detection device 600 includes laser 601, the first optical path adjuster 602, fixed bracket 603, object lens 604, the Two optical path adjusters 605 and spectrometer 606.Laser 601 is used to provide light source, and the setting of the first optical path adjuster 602 is swashing The front end of light device 601, including the first plane mirror and the first lens, wherein the first plane mirror is used to laser The laser vertical direction to the left of 601 transmittings emits, and the laser that the first lens are used to emit vertical direction to the left focuses.This Outside, the left side of the first optical path adjuster 602 is fixed with baffle 607, and baffle 607 upwardly extends, and baffle 607 is equipped with logical for laser The through-hole crossed.

The left side of the first optical path adjuster 602 is arranged in fixed bracket 603, and fixed bracket 603 is used to fixed capillary 505, capillary 505 is in laser focus position, and laser action can be tried when on capillary 505 with the fluorescence in capillary 505 Agent is had an effect, and fluorescence is generated, it is preferred that the lower front of baffle 607 is fixed with link block 608, and fixed bracket 603 is fixed On the link block 608.

Object lens 604 are in the left side of laser 601 and are arranged in parallel with laser 601, are supported by N-type bracket 609, object lens 604 are used to collect the fluorescence of the sending of capillary 505.The rear end of object lens 604, including second is arranged in second optical path adjuster 605 Plane mirror, optical filtering and the second lens, wherein second plane mirror be used to by the direction of fluorescence change into vertically to On, optical filtering is used to becoming fluorescence vertically upward into monochromatic, and the second lens are used to focus one-color fluorescence.Spectrometer 606 is set It sets in the upper end of the second optical path adjuster 605, spectrometer 606 is used to carry out spectrum analysis to the one-color fluorescence after focusing.

Each step that integrated DNA analysis system of the invention tests and analyzes DNA all integrates operation on one device Convenient, detection is quick, under the premise of guaranteeing accuracy, greatly improves the efficiency of DNA detection；Unique chip is split type Design, under the premise of realizing integrated function, reduces whole manufacture difficulty and cost, improves reaction effect；It is original The micro fluidic device of property is realized by the fluid circuit of hierarchical design and matching for control valve to reaction stream on chip The Precise control of the flowing of body ensure that that reacts on chip goes on smoothly；The chip reaction system that independently designs and Agent delivery system can meet the testing requirements of different number, improve the flexibility that equipment uses；The capillary electricity of integrated form Swimming system reduces the difficulty of capillary replacement, reaction efficiency is improved, convenient for the daily use of layman.

The present invention is further described by specific embodiment above, it should be understood that, here specifically Description, should not be construed as the restriction for the essence of the present invention with range, and one of ordinary skilled in the art is reading this explanation The various modifications made after book to above-described embodiment belong to the range that the present invention is protected.

Claims

1. a kind of integration DNA analysis system characterized by comprising

Agent delivery system, agent delivery system include reagent storage means and reagent injection device, reagent storage means and examination Agent injection device is in fluid communication；

Micro-fluidic reaction system, micro-fluidic reaction system include micro-fluidic chip and micro fluidic device, reagent injection device with it is micro- Fluidic chip is in fluid communication, and micro-fluidic chip is connected with micro fluidic device, and sample to be analyzed can be added on micro-fluidic chip, examination Reaction reagent in reagent storage means can be injected into micro-fluidic chip by agent injection device, and micro fluidic device can control miniflow Control the flowing of fluid in chip；

Separation detecting system, separation detecting system include capillary electrophoresis separation device and fluorescence detection device, micro-fluidic chip It is in fluid communication with capillary electrophoresis separation device, fluorescence detection device is connected with capillary electrophoresis separation device, micro-fluidic chip On reactant can enter in capillary electrophoresis separation device, fluorescence detection device can be in capillary electrophoresis separation device Separating resulting is detected.

2. integration DNA analysis system according to claim 1, which is characterized in that reagent storage means include conventional examination Agent box and temperature control kit, conventional kit include reagent bottle, can store the reagent low to ambient temperature requirements；Temperature control reagent Box includes reagent bottle and temperature control device, and temperature control device is adjusted the temperature of reagent in reagent bottle, can store and want to environment temperature Seek high reagent.

3. integration DNA analysis system according to claim 2, which is characterized in that temperature control kit includes heat insulation sheath, Reagent bottle setting is provided with temperature control component, reagent bottle, heat insulation sheath and the setting of temperature control component in heat insulation sheath, on heat insulation sheath In the inside of protection box body.

4. integration DNA analysis system according to claim 1, which is characterized in that reagent injection device includes that reagent holds Receive chamber and automatic propelling device, the reagent inlet of reagent accommodating chamber and the reagent exit of reagent storage means are in fluid communication, The reagent exit of reagent accommodating chamber and the reagent inlet of micro-fluidic chip are in fluid communication；Automatic propelling device and reagent accommodating chamber Room is connected, and the reagent in reagent storage means can be added in reagent accommodating chamber, and by the examination in reagent accommodating chamber Agent is filled on micro-fluidic chip.

5. integration DNA analysis system according to claim 4, which is characterized in that reagent injection device includes erecting side by side To multiple syringes of setting, connect a reagent push rod on each syringe, each reagent push rod respectively with Power Component It is connected, Power Component can respectively drive push component and move back and forth in syringe, and reagent is classified and injects micro-fluidic chip In.

6. integration DNA analysis system according to claim 1, which is characterized in that micro-fluidic chip includes chip body And reaction member, sample extraction unit and fluid circuit are provided on chip body, sample extraction unit is mentioned for reactant It takes；Reaction member fitting is arranged on chip body, and conversion zone, the conversion zone on reaction member are provided on reaction member It is connected with the fluid circuit on chip body, reactant and reaction reagent can be transported in conversion zone by fluid circuit, To complete reaction in conversion zone.

7. integration DNA analysis system according to claim 6, which is characterized in that chip body includes overlapping setting Accessory blade unit, pipeline blade unit and control valve blade unit are provided with sample extraction accessory, pipeline blade unit on accessory blade unit On be provided with fluid circuit, be provided on control valve blade unit control fluid circuit on-off control valve member.

8. integration DNA analysis system according to claim 7, which is characterized in that on the fluid circuit of pipeline blade unit It is provided with pipeline cut-off point, is corresponded on control valve blade unit and is provided with piping connection hole at the position of pipeline cut-off point, pipeline connects It connects hole to be connected with the fluid circuit near pipeline cut-off point, the passing through at pipeline cut-off point of the fluid circuit on pipeline blade unit Cross piping connection hole all to realize.

9. integration DNA analysis system according to claim 8, which is characterized in that correspond to pipeline on control valve blade unit Opening/shutting valve is provided at the position of connecting hole, opening/shutting valve can control the opening and closing in piping connection hole, to realize pipeline The perforation and disconnection of corresponding fluid circuit on blade unit.

10. integration DNA analysis system according to claim 1, which is characterized in that micro fluidic device includes chip bearing Component and connecting hole opening/closing component, micro-fluidic chip can be placed on chip bearing component, connecting hole opening/closing component be seated in Piping connection hole in chip on chip bearing component is connected, and can control the opening and closing in the piping connection hole in chip, To realize the connection and disconnection of the fluid circuit being connected on chip with the piping connection hole.

11. integration DNA analysis system according to claim 10, which is characterized in that be provided on chip bearing component Temperature-controlling module, after micro-fluidic chip is seated on chip bearing component, temperature-controlling module is in contact with micro-fluidic chip, Reaction temperature on adjustable micro-fluidic chip.

12. integration DNA analysis system according to claim 10, which is characterized in that micro fluidic device includes mechanical control Component processed, Mechanical course component are connected with chip bearing component, can the reciprocating movement of driving chip bearing assembly.

13. integration DNA analysis system according to claim 1, which is characterized in that capillary electrophoresis separation device includes Capillary Electrophoresis component and temperature-controlling module, Capillary Electrophoresis component include guard assembly, and capillary is arranged in guard assembly Inside；Temperature-controlling module includes barrier assembly, and the inside of barrier assembly is arranged in heating component；Capillary Electrophoresis component and Temperature-controlling module contacts with each other and can carry out hot transmitting, and the heating component in temperature-controlling module can be to Capillary Electrophoresis component In capillary carry out temperature adjusting.

14. integration DNA analysis system according to claim 13, which is characterized in that correspond to capillary on guard assembly It is provided with detection window at the position of the fluid outlet of pipe, the electrophoretic separation in capillary can be carried out by detection window Detection.

15. integration DNA analysis system according to claim 13, which is characterized in that capillary electrophoresis separation device packet Quick lock in component is included, quick lock in component is connected with Capillary Electrophoresis component, and Capillary Electrophoresis component is detachable It is arranged in integrated DNA analysis system.

16. integration DNA analysis system according to claim 13, which is characterized in that capillary electrophoresis separation device packet Gel propulsion device is included, gel propulsion device includes gel containment chamber, temperature-controlled package and automatic propelling device, and gel holds Chamber of receiving is connected for temporarily storing gel, temperature-controlled package with gel containment chamber, is adjusted in gel containment chamber Gelling temp, automatic propelling device are connected with gel containment chamber, can be added to gel in gel containment chamber, and will coagulate Gel in glue accommodating chamber is pushed in Capillary Electrophoresis component.

17. integration DNA analysis system according to claim 16, which is characterized in that gel propulsion device includes reagent Cylinder and reagent push rod are provided with protecting box on the outside of reagent cylinder, are provided with semiconductor cooler, semiconductor system in protecting box Cooler is connected with reagent cylinder, and the temperature of the gel in reagent cylinder is adjusted, and reagent push rod is connected with propulsion assembly, propulsion group Part can drive reagent push rod to move back and forth in reagent cylinder.

18. integration DNA analysis system according to claim 1, which is characterized in that fluorescence detection device includes laser Device, object lens and spectrometer, sequentially optical path connects for laser, object lens and spectrometer, in laser and capillary electrophoresis separation device Capillary between be provided with the first optical path adjuster, the path for the laser that laser issues can be changed in the first optical path adjuster, The second optical path adjuster is provided between object lens and spectrometer, the second optical path adjuster can be changed glimmering between object lens and spectrometer The path of light.

19. integration DNA analysis system according to claim 18, which is characterized in that the first optical path adjuster includes the One plane mirror and the first lens, the laser that the first plane mirror can emit laser are vertically anti-to capillary direction It penetrates, the first lens can focus the laser reflected to capillary direction.

20. integration DNA analysis system according to claim 18, which is characterized in that the second optical path adjuster includes the Two plane mirrors, optical filtering and the second lens, the fluorescence that second plane mirror can issue capillary is to spectrometer direction Vertical reflection；The fluorescence reflected to spectrometer direction can be become monochromatic by optical filtering；Second lens can focus one-color fluorescence.