CN107523494A - A kind of fluid system and the nucleic acid sequencing system with the fluid system - Google Patents
A kind of fluid system and the nucleic acid sequencing system with the fluid system Download PDFInfo
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- CN107523494A CN107523494A CN201710879637.6A CN201710879637A CN107523494A CN 107523494 A CN107523494 A CN 107523494A CN 201710879637 A CN201710879637 A CN 201710879637A CN 107523494 A CN107523494 A CN 107523494A
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- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
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Abstract
The present invention relates to a kind of fluid system and the nucleic acid sequencing system with the fluid system, the fluid system include frame structure, pan straddle, reagent container, suction pipe, reagent selector valve manifold, first sensor, second sensor, rotary bracket, fixed support, thermoelectric cooling element and control system；When reagent container inserts pan straddle, reagent container collision rotary bracket rotates rotary bracket, when pan straddle is promoted to reagents loaded position, rotary bracket and fixed support trigger first sensor and second sensor respectively, can be by suction pipe and reagent selector valve manifold by the agent transfer in reagent container to miscellaneous part when the signal Confirmation reagent container that control system receives first sensor and second sensor loads completely, simple to operate and cost is cheap, can be widely applied in electronics and technical field of optical detection.
Description
Technical field
The present invention is on the fluid system a kind of flow suitable for nucleic acid sequencing and the nucleic acid with the fluid system
Sequencing system, it is related to electronics and technical field of optical detection.
Background technology
In order to preferably grasp mankind's coding, it is necessary to the genome of the mankind be gained more insight into, by decoding genome institute
The information of carrying, it is able to detect that the unfavorable factor that may influence human health and virus or the specificity and variability of bacterium
Influence to the mankind, in addition, genetic disease can also be predicted to a certain extent by decoding the information entrained by genome.
Therefore, human genome and its all features are fully understood by, gene and some health status are connected, disease can be entered
Row sufficiently treatment, and improving to health so that acology is developed, and further improves the health status of the mankind,
Enable the mankind more long-lived.The studies above obviously can also be carried out in animal and plant, to allow exploitation to be used to improve disease
The genetic technique of the crop of malicious resistance and the loss in the whole crop of certain areas is avoided, or allow the work in non-traditional environment
Thing grows, such as：In desert area maize planting.At present, on human genome or the understanding of any other species gene group
Complete far away.
As described above, it is necessary to develop more technologies for being used for nucleic acid sequencing, to find that individual i.e. animal and plant is surveyed
Sequence common ground and correlation, so as to realize the complete understanding to genome.It there are in the prior art for nucleic acid sequencing
Device, but the device has the shortcomings that costly and time-consuming, hinder genome and be referred to as the genome sequence of genotype with
The research of the common relation of known physical features (being referred to as phenotype).These researchs are usually using from thousands of personal letters
Breath, so as to statistically effectively and related, this needs billions of individual nucleotides are sequenced, and (each human genome has 3,000,000,000
Nucleotides), and the common relation of each information with multiple clinically relevant features is analyzed, but existing nucleic acid sequencing apparatus
This demand can not be met.
The content of the invention
In view of the above-mentioned problems, and sequencing quick fluid system low it is an object of the invention to provide a kind of cost and with should
The nucleic acid sequencing system of fluid system.
To achieve the above object, the present invention takes following technical scheme：A kind of fluid system, it is characterised in that the fluid
System include frame structure, pan straddle, reagent container, suction pipe, reagent selector valve manifold, first sensor, second sensor,
Thermoelectric cooling element and control system；The frame structure is formed by fixedly connecting by top plate, bottom plate and support bar, the framework knot
The surrounding of structure sets front side board, back side panel, left plate and right plate to form body structure respectively；It is provided with the body structure
The pan straddle, the pan straddle both ends are fixedly connected with the left plate and right plate by elevating mechanism respectively, described
Front side board connects the elevating mechanism by connecting rod and forms manually operated door, and the connecting rod promotes the lift when acting
Structure, which acts, make it that the pan straddle is moved up and down in the body structure；Activity plugs described in the pan straddle
Reagent container, the suction pipe is arranged at intervals on the top plate, position and quantity corresponding to the suction pipe, the pan straddle top
Portion is arranged at intervals with through hole and the reagent container head clearance is provided with reagent storage recess, the top plate side fixed setting
With reagent selector valve manifold described in the suction pipe quantity identical, each reagent selector valve manifold connects corresponding described respectively
Suction pipe；Whether insert the pan straddle for detecting the reagent container described first is fixedly installed in the top plate rearward end
Sensor and the second sensor that reagents loaded position whether is reached for detecting the pan straddle, on the back side panel
It is provided with the thermoelectric cooling element；The first sensor, second sensor and thermoelectric cooling element are electrically connected described
Control system.
Further, the position corresponding to the suction pipe and quantity, it is arranged at intervals with the top plate described for supporting
The tip rack of suction pipe.
Further, handle is provided with the manually operated door, the manually operated door and top plate leading section are correspondingly set
It is equipped with for detecting 3rd sensor and/or the actuator whether manually operated door is closed, the described 3rd passes
Sensor and/or actuator also electrically connect the control system.
Further, corresponding to the first sensor and second sensor, rotation is provided with the top of the pan straddle
Ask frame and fixed support；When the reagent container inserts the pan straddle, the reagent container collides the rotary bracket
So that the rotary bracket rotation, when the pan straddle is promoted to reagents loaded position, the rotary bracket triggers institute
First sensor is stated, the fixed support triggers the second sensor；When the reagent container is not inserted into the pan straddle,
The rotary bracket remains stationary position, when the pan straddle is promoted to reagents loaded position, the rotary bracket is not
The first sensor can be triggered, the fixed support triggers the second sensor.
Further, the front end of the reagent container is provided with two grooves, the left and right/of the reagent container or upper and lower ends
Be provided with more than one alignment guide, the left and right/or upper and lower ends in the pan straddle be provided with it is described right
The alignment guiding element that quasi- guides fitting uses, the reagent container top are provided with the protectiveness bonding worn for the suction pipe
Paper tinsel, it is additionally provided with for identifying the lot number of reagent in the reagent container, build date or original producton location on the reagent container
Identify label.
Further, the elevating mechanism includes two slider guides, two sliding blocks and two telescope supports；It is each described flexible
Support uses parallelogram lever, and two slider guides are longitudinally spaced to be arranged on the left plate or right plate,
The inner of two slider guides is flexibly connected the pan straddle by a sliding block, and the outer end of two sliding blocks connects
The top mobile terminal of a telescope support is connect, mobile terminal is fixedly connected with institute on the outside of the telescope support of the manually operated door
One end of connecting rod is stated, the other end of the connecting rod is fixedly connected with the manually operated door, and the bottom of the telescope support is consolidated
Fixed end is fixedly connected with the left plate or right plate.
Further, the back side panel uses conductive metal plate, after the thermoelectric cooling element on the back side panel
Side is provided with heat abstractor.
Further, the position corresponding to the through hole and quantity, the pan straddle top are provided with sleeve, the suction
Pipe is stretched into the reagent container through the corresponding sleeve and through hole；The forward upper of the frame structure is additionally provided with thin
Wall.
Further, the top plate bottom is provided with illuminating lamp, and the illuminating lamp also electrically connects the control system.
A kind of nucleic acid sequencing system, it is characterised in that the nucleic acid sequencing system includes fluid system, flow control valve, stream
Dynamic pond, excitation system, detecting system, the first peristaltic pump, the second peristaltic pump and waste liquid box, wherein, it is provided with the flow cell
First flow and second flow channel；All reagent selector valve manifolds of the fluid system are all connected with entering for the flow control valve
Mouthful, two outlets of the flow control valve connect the first flow and second flow channel respectively, and the first flow is through described the
One peristaltic pump connects the waste liquid box, and the second flow channel connects the waste liquid box, the flow cell through second peristaltic pump
Inside it is provided with and excites the nucleotide sequence marked in the flow cell in reagent to produce described in the excitation source of fluorescence for providing
Excitation system and the detecting system detected for fluorescence signal caused by the nucleotide sequence to mark.
For the present invention due to taking above technical scheme, it has advantages below：1st, fluid system of the invention is due to setting
There are pan straddle, elevating mechanism, connecting rod, first sensor, second sensor, rotary bracket and fixed support, when reagent holds
When device inserts pan straddle, reagent container collision rotary bracket rotates rotary bracket, closes manually operated door pan straddle quilt
It is promoted to reagents loaded position so that rotary bracket and fixed support trigger first sensor and second sensor respectively, work as control
The signal Confirmation reagent container that system processed receives first sensor and second sensor when loading completely can by suction pipe and
For reagent selector valve manifold by the agent transfer in reagent container to miscellaneous part, simple to operate and cost is cheap, is surveyed for nucleic acid
It can also meet quick demand is sequenced in sequence system.The 2nd, protective adhesive foil is set at the top of reagent container of the invention, can
To ensure the freshness of liquid reagent in reagent storage recess, prevent liquid reagent from polluting and overflowing, and sensitivity can also be protected
Reagent is from illumination.3rd, back side panel of the invention uses metallic plate with good conductivity, passes through the heat being arranged on the metallic plate
Reagent in reagent container is heated or cooled electric cooling element, the fluid system of the present invention is adapted to different examinations
Agent preservation condition and use demand.4th, the forward upper that sleeve and frame structure are provided with the top of pan straddle of the invention is set
There is thin-walled, sleeve and thin-walled constitute the basic protection mechanism for preventing personal injury, can prevent from working as and not tried in body structure
During agent container, user by hand insert reagent container in due to the sharp of suction pipe and caused by personal injury, add protection factor.
5th, the present invention in body structure due to setting light source, and under conditions of outside underlit or deficiency, user can be easy
Ground inserts or removed reagent container, can be widely applied in electronics and technical field of optical detection.
Brief description of the drawings
Fig. 1 is the 3D overviews that fluid system of the present invention is in shutdown state；
Fig. 2 is the 3D overviews that fluid system of the present invention is in door opening state；
Fig. 3 is the front cross-sectional view of fluid system of the present invention；
Fig. 4 is the structural representation of reagent container of the present invention；
Fig. 5 is the schematic cross-section of reagent container of the present invention；
Fig. 6 is the structure and use state diagram of elevating mechanism of the present invention, wherein, Fig. 6 (a) is fluid system of the present invention
Use state diagram in door opening state elevating mechanism, Fig. 6 (b) are that fluid system of the present invention is in shutdown state lift
The use state diagram of structure；
Fig. 7 is the structural representation of thermoelectric cooling element of the present invention and corresponding heat abstractor；
Fig. 8 is the central cross-sectional view that fluid system of the present invention is in door opening state；
Fig. 9 is the central cross-sectional view that fluid system of the present invention is in shutdown state；
Figure 10 be in fluid system of the present invention suction pipe and prevent personal injury basic protection mechanism viewgraph of cross-section；
Viewgraph of cross-section when Figure 11 is the fully-inserted reagent container of suction pipe in fluid system of the present invention；
Figure 12 is the structural representation of nucleic acid sequencing system of the present invention.
Embodiment
Come to carry out the present invention detailed description below in conjunction with accompanying drawing.It should be appreciated, however, that accompanying drawing has been provided only more
Understand the present invention well, they should not be interpreted as limitation of the present invention.In the description of the invention, it is to be understood that
Term " first ", " second " etc. are only used for the purpose of description, and it is not intended that instruction or hint relative importance.
As shown in Fig. 1~3 and Fig. 7~9, fluid system provided by the invention includes frame structure 1, pan straddle 2, lifting
Mechanism 3, reagent container 4, suction pipe 5, tip rack 6, reagent selector valve manifold 7, first sensor 8, second sensor the 9, the 3rd
Sensor and/or actuator 10, thermoelectric cooling element 11 and control system.
Frame structure 1 is formed by fixedly connecting by top plate 1-1, bottom plate 1-2 and support bar, wherein, the surrounding point of frame structure 1
Not She Zhi front side board 1-3, back side panel 1-4, left plate 1-5 and right plate 1-6 form body structure, the back side panel 1- of body structure
4 use metallic plate with good conductivity.
Pan straddle 2 is provided with body structure, the both ends of pan straddle 2 are fixedly connected with case by elevating mechanism 3 respectively
The left plate 1-5 and right plate 1-6 of body structure, the front side board 1-3 of body structure pass through the shape of connecting rod 1-7 connections elevating mechanism 3
Promote the action of elevating mechanism 3 that pan straddle 2 is entered in body structure into manually operated door, when connecting rod 1-7 is acted
Row moves up and down.Activity is inserted with reagent container 4 in pan straddle 2, is arranged at intervals with and is used on the top plate 1-1 of frame structure 1
Support the tip rack 6 of suction pipe 5.Position and quantity corresponding to suction pipe 5, the head clearance of pan straddle 2 be provided with through hole 2-1 and
The head clearance of reagent container 4 is provided with reagent storage recess 4-1, the fixed setting of top plate 1-1 sides and the suction pipe 5 of frame structure 1
Quantity identical reagent selector valve manifold 7, each reagent selector valve manifold 7 connects corresponding suction pipe 5 respectively by pipeline.
The top plate 1-1 rearward ends fixed setting first sensor 8 and second sensor 9 of frame structure 1, corresponding to two sensings
Device, the top of pan straddle 2 are provided with rotary bracket 2-2 for triggering first sensor 8 and for triggering second sensor 9
Fixed support 2-3.Manually operated door is closed, elevating mechanism 3 drives pan straddle 2 to move upwards, fixed support 2-3 and rotation
Bracket 2-2 is in propradation, and whether second sensor 9 reaches reagents loaded position for detection container support 2, work as container
When support 2 is promoted to reagents loaded position, fixed support 2-3 triggering second sensor 2-3, first sensor 8 is used to detect
Whether reagent container 4 inserts pan straddle 2, and when reagent container 4 inserts pan straddle 2, reagent container 4 collides rotary bracket 2-
2 cause rotary bracket 2-2 rotations, and when pan straddle 2 is promoted to reagents loaded position, rotary bracket 2-2 can trigger the
One sensor 8, when reagent container 4 is not inserted into pan straddle 2, rotary bracket 2-2 will remain in about 30 degree of resting position, when
When pan straddle 2 is promoted to reagents loaded position, rotary bracket 2-2 can not trigger first sensor 8.Manually operated door and frame
The top plate 1-1 leading sections of frame structure 1 are correspondingly arranged on 3rd sensor and/or actuator 10, are for detecting manually operated door
It is no to be closed.
Some thermoelectric cooling elements 11 are provided with the back side panel 1-4 of body structure.First sensor 8, second sensor
9th, 3rd sensor and/or actuator 10 and thermoelectric cooling element 11 are electrically connected control system.
In a preferred embodiment, handle 1-8 can be provided with manually operated door.
In a preferred embodiment, first sensor 8, second sensor 9 and 3rd sensor and/or actuator
10 can use magnetic sensor, optical sensor or mechanical pick-up device.
In a preferred embodiment, as seen in figures 3-5, reagent container 4 can use rectangular parallelepiped structure, and reagent holds
The front end of device 4 is provided with the two groove 4-2 for being easy to reagent container 4 to be inserted and removed from manually from pan straddle 2, reagent container 4
Left and right/or upper and lower ends be provided with more than one alignment guide 4-3, left and right/or upper and lower ends in pan straddle 2
It is provided with the alignment guiding element 2-4 being used cooperatively with alignment guide 4-3.The top of reagent container 4 is provided with what is worn for suction pipe 5
Protectiveness adhesive foil 4-4, protectiveness adhesive foil 4-4 can use astrafoil or aluminium foil made of adhesive or non-adhesive,
The freshness of liquid reagent in reagent storage recess 4-1 can be ensured, prevent liquid reagent from polluting and overflowing, and can also be protected
Sensitive agents can be configured from illumination, reagent storage recess 4-1 shape and size according to actual conditions, each reagent
Storage recess 4-1 can also have different shape and size, to adapt to different reagent volume demands.In addition, reagent container 4
Top is additionally provided with identification label 4-5, for identifying lot number, build date or original producton location of reagent etc. in the reagent container 4, knows
Distinguishing label 4-5 can use bar code, Quick Response Code, RFID label tag, contact electronic tag or non-contact electronic lable.
In a preferred embodiment, as shown in fig. 6, elevating mechanism 3 includes two slider guide 3-1, two sliding block 3-2
Parallelogram lever is used with two telescope support 3-3, each telescope support 3-3, two slider guide 3-1 are longitudinally spaced to be set
Put on the left plate 1-5 or right plate 1-6 of body structure, the inner of two slider guide 3-1 passes through sliding block 3-2 activities
Pan straddle 2 is connected, two sliding block 3-2 outer end connects the top mobile terminal of a telescope support 3-3, close to stretching for manually operated door
Contracting support 3-3 outside mobile terminal is fixedly connected with connecting rod 1-7 one end, and the connecting rod 1-7 other end is fixedly connected with manual behaviour
Make door, telescope support 3-3 bottom fixing end is fixedly connected with the left plate 1-5 or right plate 1-6 of body structure.Manually operated door
During closing, telescope support 3-3 is acted on by connecting rod 1-7 and telescope support 3-3 foldings and extended, telescope support 3-3 elongations
While band movable slider 3-2 slider guide 3-1 act, realize the motion of the vertical direction of pan straddle 2.
In a preferred embodiment, as shown in fig. 7, the rear side of each thermoelectric cooling element 11 is provided with heat abstractor
12, heat abstractor 12 can use water-cooled dissipation heat abstractor or fan heat sink etc..The quantity of thermoelectric cooling element 11
It can be needed and changed according to temperature of reagent with size, it can be various sizes in different types of embodiment.Radiating
The quantity and size of device 12 be able to can not also be changed with respective change.
In a preferred embodiment, as shown in figure 8, the forward upper of frame structure 1 is provided with thin-walled 1-9, prevent
Hand enters suction pipe 5 above pan straddle 2, increases protection factor.
In a preferred embodiment, as shown in Fig. 8, Figure 10, glued to pierce through protectiveness when pan straddle 2 is lifted
Close paper tinsel 4-4, the end set of suction pipe 5 it is more sharp, if not doing the safeguard procedures of correlation, hand may prick by suction pipe 5,
Cause to injure, therefore the position corresponding to through hole 2-1 and quantity, the top of pan straddle 2 are provided with sleeve 2-5, suction pipe 5 passes through phase
Sleeve 2-5 and through hole 2-1 is answered to stretch into reagent container 4.
In a preferred embodiment, as shown in Figure 10, the top plate 1-1 bottoms of frame structure 1 are additionally provided with illuminating lamp
1-10, illuminating lamp 1-10 can use LED, Halogen lamp LED or other light sources, so as in outside underlit or insufficient condition
Under so that reagent container 4 can conveniently insert or remove pan straddle 2, and illuminating lamp 1-10 is also electrically connected connected control system.
In a preferred embodiment, as shown in Figure 10, Figure 11, difference can be used according to the type of reagent, suction pipe 5
Length, with the types of agents used in suitable for reagent container 4, i.e. suction pipe 5 can be designed to reagent storage recess 4-1 bottom
Contact and contactless two kinds.
As shown in figure 12, the present invention also provides a kind of nucleic acid sequencing system, and the nucleic acid sequencing system includes above-mentioned fluid
System, flow control valve 13, flow cell 14, excitation system, detecting system, the first peristaltic pump 15, the second peristaltic pump 16 and waste liquid
Box 17, wherein, first flow 14-1 and second flow channel 14-2, the first peristaltic pump 15 and the second peristaltic pump are provided with flow cell 14
Reversal valve can be provided with 16；All reagent selector valve manifolds 7 of fluid system pass through pipeline connecting passage control valve 13
Import, two outlets of flow control valve 13 connect first flow 14-1 and second flow channel 14-2, first flow respectively by pipeline
14-1 connects waste liquid box 17 by pipeline through the first peristaltic pump 15, and second flow channel 14-2 is connected by pipeline through the second peristaltic pump 16
Waste liquid box 17, excitation system and detecting system are provided with flow cell 14, and excitation system is excited in flow cell 14 for offer and tried
The nucleotide sequence marked in agent produces the excitation source of fluorescence, and detecting system is used to believe fluorescence caused by the nucleotide sequence of mark
Number detected, complete nucleic acid sequencing.
In a preferred embodiment, detecting system can be made up of the different optical elements of various properties, including but
Filter, pipe lens, relay lens and the camera of different wave length are not limited to, camera can be CCD or CMOS, and can hold
Row sector scanning, line scanning or TDI scannings.Detecting system can include more than one camera, more than one filter or
Any combination of above-mentioned all elements.For the process, flow cell 14 is placed in sample stage, camera, filter and thoroughly
Moved in x and y direction while mirror remains stationary, the motion of sample stage is synchronous with camera shooting image, to ensure
Correct image capture.The image that will then be captured using specific image procossing, the position of each nucleic acid cluster is found, it is determined that often
The fluorescence that individual filter receives, and determine the glimmering photosynthetic nucleic acid base received based on each filter.Finally, by determination
The information of alkali cardinal sum reliability will be recorded in standard format files.
In a preferred embodiment, excitation system can use laser or LED light source, and quantity is not limited, can
Selected with actually using.Excitation system can be according to the excitation wavelength demand of fluorescent dye, there is provided the exciting light of different wave length.
The application method of the nucleic acid sequencing system of the present invention is further illustrated below, flow cell 14 is placed on sample stage
On, and the nucleotide base reagent for being marked with different dyes is placed in the reagent storage recess 4-1 of reagent container 4, pass through
Rotary bracket 2-2 is rotated in X-axis by reagent container 4, and it is elevated to close manually operated door pan straddle 2, makes rotary bracket 2-2
First sensor 8 and second sensor 9 are triggered respectively with fixed support 2-3, and control system receives first sensor 8 and second and passed
The signal Confirmation reagent container 4 of sensor 9 loads completely, and control system is by receiving 3rd sensor and/or actuator 10
Signal, it is ensured that manually operated door is in completely closed state, and now fluid system prepares to use.Suction pipe 5 is completely submerged in examination
In agent, and reagent can be transferred to other parts of suction pipe 5 and fluid system from reagent container 4.Adjust flow control valve 13
Open state select a certain runner such as first flow 14-1, open the first peristaltic pump 15 and cause reagent from suction pipe 5 and corresponding
Reagent selector valve manifold 7 flow into first flow 14-1, excitation system, which is launched, excites light irradiation first flow 14-1 nucleotides
Base reagent, the marked dyestuff of nucleotide base reagent, which is excited, sends fluorescence, and fluorescence signal is by quilt after imaging system images
Detecting system detects, and detecting system carries out the sequencing that nucleotide base reagent is completed in processing to testing result.
In a preferred embodiment, nucleic acid sequencing can be by synthesis order-checking or by connecting the sequencing carried out, will
Nucleotides and be implanted into it is nucleic acid-templated in, be generally arranged in clone's group of referred to as cluster, wherein cloned copies be by expand one
Use the primary template chain of polymerase chain reaction method.Above two nucleic acid sequencing can be detected using fluorescence probe, its
In each different nucleotide base (A, C, T or G) different dye markers is respectively adopted, these dyestuffs send different wave length
Fluorescence, and the presence of different nucleotide bases can be detected using the combination of match filter.Difference containing fluorescent dye
Base can be simultaneously or separately imaged.If be imaged simultaneously, filter group is needed to use to detect depositing for different dyes respectively
If independent imaging, filter is not being needed, there need not be different dyestuffs on different nucleotide bases yet.For
The other method of sequencing can also be used, such as：When different number of dyestuff is connected to nucleotide base, it is possible to achieve compile
Ink recorder system, when using only two kinds of dyestuffs, two of which nucleotide base receives two kinds of different dyestuffs, trinucleotide base
Receive the mixture of foregoing two kinds of dyestuffs.Tetranucleotide base will not receive any dyestuff, by using this method, only need
Two kinds of colors are read in flow cell 14, reduce the complexity for detecting system, said system can use two inspections
The combination of examining system performs two different colors of detection, such as CCD camera, each detecting system equipped with a kind of dyestuff
Launch wavelength matching filter, an or detecting system by using combination, equipped with wave filter selection device, such as filter
Wheel, it is equipped with the launch wavelength that two optical filters match two kinds of dyestuffs.But this sequence measurement needs to consider：First, the 3rd core
Thuja acid base should receive the aequum of two kinds of dyestuffs, in order to avoid another nucleotide base is detected as by mistake；Second, surveying
When sequence method starts, it is necessary to calibration procedure is performed, to detect the presence in the cluster site of all clusters, because tetranucleotide base
By the dyestuff without attachment, therefore the light of any wavelength will not be launched, will not be detected by equipment.Therefore, detecting system control
Device processed will have to assume tetranucleotide when not detecting dyestuff be present, for this problem, detecting system controller
All cluster positions that will be should be noted on flow cell 14, and if do not detect dye in the known given position that cluster be present
Material, it assumes that tetranucleotide is enclosed.
The various embodiments described above are merely to illustrate the present invention, wherein the structure of each part, connected mode and manufacture craft etc. are all
It can be varied from, every equivalents carried out on the basis of technical solution of the present invention and improvement, should not exclude
Outside protection scope of the present invention.
Claims (10)
- A kind of 1. fluid system, it is characterised in that the fluid system include frame structure, pan straddle, reagent container, suction pipe, Reagent selector valve manifold, first sensor, second sensor, thermoelectric cooling element and control system；The frame structure is formed by fixedly connecting by top plate, bottom plate and support bar, before the surrounding of the frame structure is set respectively Side plate, back side panel, left plate and right plate form body structure；The pan straddle is provided with the body structure, the pan straddle both ends are fixedly connected by elevating mechanism respectively The left plate and right plate, the front side board connect the elevating mechanism by connecting rod and form manually operated door, the company Extension bar promotes the elevating mechanism action so that the pan straddle is moved up and down in the body structure when acting；Institute State activity in pan straddle and plug the reagent container, the suction pipe is arranged at intervals on the top plate, corresponding to the suction pipe Position and quantity, the pan straddle head clearance is provided with through hole and the reagent container head clearance is provided with reagent storage Groove, the top plate side fixed setting and reagent selector valve manifold described in the suction pipe quantity identical, each reagent Selector valve manifold connects the corresponding suction pipe respectively；Whether insert the pan straddle for detecting the reagent container described first is fixedly installed in the top plate rearward end Sensor and the second sensor that reagents loaded position whether is reached for detecting the pan straddle, on the back side panel It is provided with the thermoelectric cooling element；The first sensor, second sensor and thermoelectric cooling element are electrically connected described Control system.
- 2. a kind of fluid system as claimed in claim 1, it is characterised in that position and quantity corresponding to the suction pipe, institute State the tip rack being arranged at intervals with top plate for supporting the suction pipe.
- 3. a kind of fluid system as claimed in claim 1, it is characterised in that be provided with handle on the manually operated door, institute State manually operated door and top plate leading section and be correspondingly arranged on whether be closed for detecting the manually operated door Three sensors and/or actuator, the 3rd sensor and/or actuator also electrically connect the control system.
- 4. a kind of fluid system as claimed in claim 1, it is characterised in that sensed corresponding to the first sensor and second Device, rotary bracket and fixed support are provided with the top of the pan straddle；When the reagent container inserts the pan straddle, the reagent container collides the rotary bracket and causes the rotation support Frame rotates, and when the pan straddle is promoted to reagents loaded position, the rotary bracket triggers the first sensor, institute State fixed support and trigger the second sensor；When the reagent container is not inserted into the pan straddle, the rotary bracket is protected Resting position is held, when the pan straddle is promoted to reagents loaded position, the rotary bracket can not trigger described first Sensor, the fixed support trigger the second sensor.
- 5. a kind of fluid system as claimed in claim 1, it is characterised in that it is recessed that the front end of the reagent container is provided with two Groove, the left and right/of the reagent container or upper and lower ends are provided with more than one alignment guide, in the pan straddle Left and right/or upper and lower ends are provided with the alignment guiding element being used cooperatively with the alignment guide, are set at the top of the reagent container The protectiveness adhesive foil worn for the suction pipe is equipped with, is additionally provided with the reagent container for identifying in the reagent container Lot number, build date or the identification in the original producton location label of reagent.
- A kind of 6. fluid system as claimed in claim 1, it is characterised in that the elevating mechanism include two slider guides, Two sliding blocks and two telescope supports；Each telescope support uses parallelogram lever, and two slider guides are longitudinally spaced to be arranged on the left side On side plate or right plate, the inner of two slider guides is flexibly connected the pan straddle by a sliding block, and two The outer end of the sliding block connects the top mobile terminal of a telescope support, on the outside of the telescope support of the manually operated door Mobile terminal is fixedly connected with one end of the connecting rod, and the other end of the connecting rod is fixedly connected with the manually operated door, described The bottom fixing end of telescope support is fixedly connected with the left plate or right plate.
- 7. a kind of fluid system as described in any one of claim 1 to 6, it is characterised in that the back side panel uses electric conductivity Metallic plate, the thermoelectric cooling element rear side on the back side panel are provided with heat abstractor.
- 8. a kind of fluid system as described in any one of claim 1 to 6, it is characterised in that corresponding to the position of the through hole And quantity, the pan straddle top are provided with sleeve, the suction pipe passes through the corresponding sleeve and through hole to stretch into the reagent In container；The forward upper of the frame structure is additionally provided with thin-walled.
- 9. a kind of fluid system as described in any one of claim 1 to 6, it is characterised in that the top plate bottom is provided with photograph Bright lamp, the illuminating lamp also electrically connect the control system.
- 10. a kind of nucleic acid sequencing system, it is characterised in that the nucleic acid sequencing system is included as described in any one of claim 1 to 9 Fluid system, flow control valve, flow cell, excitation system, detecting system, the first peristaltic pump, the second peristaltic pump and waste liquid box, Wherein, first flow and second flow channel are provided with the flow cell；All reagent selector valve manifolds of the fluid system are all connected with the import of the flow control valve, the flow control valve Two outlets connect the first flow and second flow channel respectively, the first flow is described useless through first peristaltic pump connection Liquid box, the second flow channel connect the waste liquid box through second peristaltic pump, are provided with the flow cell sharp for providing The nucleotide sequence marked in sending out flow cell described in reagent produces the excitation system of the excitation source of fluorescence and for mark The detecting system that fluorescence signal caused by the nucleotide sequence of note is detected.
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| CN201710879637.6A CN107523494B (en) | 2017-09-26 | 2017-09-26 | Fluid system and nucleic acid sequencing system with same |
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| CN201710879637.6A CN107523494B (en) | 2017-09-26 | 2017-09-26 | Fluid system and nucleic acid sequencing system with same |
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| CN107523494A true CN107523494A (en) | 2017-12-29 |
| CN107523494B CN107523494B (en) | 2020-12-04 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115029231A (en) * | 2022-08-12 | 2022-09-09 | 河北巴纳克医疗器械有限公司 | Inspection device for oncology department |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070077645A1 (en) * | 2005-10-04 | 2007-04-05 | Canon Kabushiki Kaisha | Biochemical treatment device with dispensing unit |
| CN202379991U (en) * | 2011-01-10 | 2012-08-15 | 伊鲁米那股份有限公司 | Nucleic acid sequencing system |
| WO2013080939A1 (en) * | 2011-11-28 | 2013-06-06 | 財団法人神奈川科学技術アカデミー | Liquid reflux high-speed gene amplification device |
| CN104328049A (en) * | 2014-11-07 | 2015-02-04 | 天津迈安诊生物技术有限公司 | Eyeball forepart perfusion organ culture multicavity system |
| CN104893967A (en) * | 2013-11-29 | 2015-09-09 | 周琪 | Automatic plasmid extraction device with labor saving function |
| CN105188938A (en) * | 2013-03-14 | 2015-12-23 | 简·探针公司 | Diagnostic systems and methods |
| CN105199951A (en) * | 2015-10-27 | 2015-12-30 | 北京中科紫鑫科技有限责任公司 | Feed liquid supplying system for DNA sequencing instrument |
| CN105408466A (en) * | 2013-08-08 | 2016-03-16 | 伊鲁米那股份有限公司 | Fluidic system for reagent delivery to a flow cell |
| CN206089676U (en) * | 2016-08-31 | 2017-04-12 | 中国疾病预防控制中心传染病预防控制所 | Adopt two -dimentional transmission mode's multiple spot inoculation appearance |
-
2017
- 2017-09-26 CN CN201710879637.6A patent/CN107523494B/en active Active
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070077645A1 (en) * | 2005-10-04 | 2007-04-05 | Canon Kabushiki Kaisha | Biochemical treatment device with dispensing unit |
| CN202379991U (en) * | 2011-01-10 | 2012-08-15 | 伊鲁米那股份有限公司 | Nucleic acid sequencing system |
| WO2013080939A1 (en) * | 2011-11-28 | 2013-06-06 | 財団法人神奈川科学技術アカデミー | Liquid reflux high-speed gene amplification device |
| US20140370492A1 (en) * | 2011-11-28 | 2014-12-18 | Kanagawa Academy Of Science And Technology | Liquid reflux high-speed gene amplification device |
| CN105188938A (en) * | 2013-03-14 | 2015-12-23 | 简·探针公司 | Diagnostic systems and methods |
| CN105408466A (en) * | 2013-08-08 | 2016-03-16 | 伊鲁米那股份有限公司 | Fluidic system for reagent delivery to a flow cell |
| CN104893967A (en) * | 2013-11-29 | 2015-09-09 | 周琪 | Automatic plasmid extraction device with labor saving function |
| CN105018340A (en) * | 2013-11-29 | 2015-11-04 | 江苏省电力公司常州供电公司 | Automatic plasmid extracting apparatus with high extracting quality |
| CN104328049A (en) * | 2014-11-07 | 2015-02-04 | 天津迈安诊生物技术有限公司 | Eyeball forepart perfusion organ culture multicavity system |
| CN105199951A (en) * | 2015-10-27 | 2015-12-30 | 北京中科紫鑫科技有限责任公司 | Feed liquid supplying system for DNA sequencing instrument |
| CN206089676U (en) * | 2016-08-31 | 2017-04-12 | 中国疾病预防控制中心传染病预防控制所 | Adopt two -dimentional transmission mode's multiple spot inoculation appearance |
Non-Patent Citations (2)
| Title |
|---|
| 郭奕斌: "基因诊断中测序技术的应用及优缺点", 《遗传》 * |
| 马建: "基于固态纳米孔基因测序的关键技术研究", 《中国博士学位论文全文数据库基础科学辑》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115029231A (en) * | 2022-08-12 | 2022-09-09 | 河北巴纳克医疗器械有限公司 | Inspection device for oncology department |
| CN115029231B (en) * | 2022-08-12 | 2022-10-28 | 河北巴纳克医疗器械有限公司 | Inspection device for oncology department |
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|---|---|
| CN107523494B (en) | 2020-12-04 |
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