CN109825431A - Oligonucleotides assemble in situ instrument - Google Patents
Oligonucleotides assemble in situ instrument Download PDFInfo
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- CN109825431A CN109825431A CN201910204884.5A CN201910204884A CN109825431A CN 109825431 A CN109825431 A CN 109825431A CN 201910204884 A CN201910204884 A CN 201910204884A CN 109825431 A CN109825431 A CN 109825431A
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- oligonucleotides
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- 108091034117 Oligonucleotide Proteins 0.000 title claims abstract description 48
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Abstract
The problem of the present invention provides a kind of oligonucleotides assemble in situ instrument, are related to bioscience research and applied technical field, more to solve oligonucleotides assembling steps existing in the prior art to a certain extent, cumbersome, low efficiency.The oligonucleotides assemble in situ instrument includes: the accommodating vessel for placing sample to be assembled；Temperature control mechanism limits including limit groove body and the temperature-controlled package being connected with limit groove body and is provided with multiple limit cavitys for being used to place accommodating vessel on groove body, and limit cavity has opening upward；Micro-fluidic liquid distributor including liquid-conveying ducts and fluid-directing needle, liquid-conveying ducts are connected to by pumping installations with reagent reservoirs；The mobile mechanism being connect with micro-fluidic liquid distributor.For completing oligonucleotides assemble in situ process, overall process is automatically performed the oligonucleotides assemble in situ instrument, is operated convenient, high-efficient.
Description
Technical field
The present invention relates to bioscience research and applied technical fields, more particularly, to a kind of oligonucleotides assemble in situ
Instrument.
Background technique
Oligonucleotides, short nucleotide (including DNA DNA or the ribose of usually a kind of 10-200 base
Nucleotide in nucleic acid RNA), oligonucleotides can be docked easily with their complementary strand, so being often used as probe
The structure for determining DNA or RNA is frequently used for during genetic chip, electrophoresis, fluorescence in situ hybridization etc..
The DNA of oligonucleotide synthesis can be used for chain polymerization reaction, can amplify the segment for determining nearly all DNA, at this
Oligonucleotides is combined as the complementary fragment marked in primer and DNA during a, is made the duplicate of DNA.
Gene chemical synthesis package technique principle is simple, easy-to-use, but operating process is complicated, and whole process generally requires experience reaction
System is prepared, the amplification of upper machine, digestion connection, error correction, assembling, complex for operation step, expend a large amount of human and material resources and when
Between, the development of gene synthesis technology is limited, the needs of high-throughput large fragment DNA assembling are unable to satisfy.
Summary of the invention
The purpose of the present invention is to provide a kind of oligonucleotides assemble in situ instrument, to solve the prior art to a certain extent
Present in oligonucleotides assembling steps it is more, it is cumbersome, the technical issues of low efficiency.
Oligonucleotides assemble in situ instrument provided by the invention, comprising:
Vessel are accommodated, including the ontology with inner cavity, and are covered on the top cover of the opening of the inner cavity, the inner cavity
For placing sample to be assembled；
Temperature control mechanism, including limit groove body and the temperature-controlled package being connected with the limit groove body, the limit groove body
On be provided with it is multiple for place it is described accommodating vessel limit cavitys, the limit cavity have be open；
Micro-fluidic liquid distributor, including liquid-conveying ducts, and the fluid-directing needle being connected to the liquid-conveying ducts, the drain
Needle includes into liquid needle and drain needle, and the liquid-conveying ducts are connected to by pumping installations with multiple reagent reservoirs；
Mobile mechanism, the mobile mechanism are connected to the micro-fluidic liquid distributor, for controlling the miniflow draining
Body distributor is mobile so that the fluid-directing needle is inserted into the inner cavity after passing through the top cover for accommodating vessel.
In the above-mentioned technical solutions, further, the mobile mechanism includes bracket, attachment beam, driver and lead screw, institute
It states driver to be installed on the bracket, the attachment beam is provided with and the matched threaded hole of the lead screw, the lead screw and institute
Attachment beam to be stated to be threadedly engaged, the driver is connect with the lead screw, for driving the lead screw to rotate, the attachment beam and institute
State micro-fluidic liquid distributor connection.
In the above-mentioned technical solutions, further, one end of the lead screw is connect with the driver, and the other end passes through axis
It holds and is connect with the holder pivots.
In any of the above-described technical solution, further, pass through sealing ring between the ontology and top cover of the accommodating vessel
It is tightly connected.
It further include mounting plate further in any of the above-described technical solution, the mobile mechanism and the temperature control mechanism
It is mounted on the mounting plate.
In the above-mentioned technical solutions, further, the limit groove body is installed at the top of the mounting plate, the temperature tune
Section component is installed between the limit groove body and the mounting plate, and the temperature control mechanism further includes radiating subassembly, the heat dissipation
Component is installed on the mounting plate bottom.
In any of the above-described technical solution, further, the micro-fluidic liquid distributor further includes micro-fluidic plate, described
Liquid-conveying ducts are set on the micro-fluidic plate, and the fluid-directing needle is installed on the bottom of the micro-fluidic plate.
In any of the above-described technical solution, further, the liquid-conveying ducts include into liquid channel and apocenosis passage, it is described
Enter liquid channel with it is each it is described enter liquid needle be connected to, the apocenosis passage is connected to each drain needle.
In the above-mentioned technical solutions, further, the fluid-directing needle is in array-like on the micro-fluidic liquid distributor
Distribution, it is described enter liquid channel and the apocenosis passage respectively include the first access, alternate path and tributary circuit, described first is logical
The quantity on road be it is multiple, each first access be connected to the alternate path respectively, the alternate path and pumping installations company
It connects, first access is connected to by the tributary circuit with fluid-directing needle, the extending direction of first access and described second
The extending direction of access is vertical, it is described enter liquid channel the first access it is parallel with the first access of the apocenosis passage and staggeredly point
Cloth.
It further include driving mechanism and magnetic part further, the driving mechanism is used in any of the above-described technical solution
Drive the magnetic part close to or far from the accommodating vessel, the magnetic part is used to that the magnetic bead in the accommodating vessel to be driven to move
It is dynamic.
Compared with the existing technology, oligonucleotides assemble in situ instrument of the present invention has the advantage that
In use, sample to be assembled is placed in accommodating vessel to oligonucleotides assemble in situ instrument of the present invention
Interior, accommodating vessel are placed in the limit chamber body of limit groove body.Mobile mechanism drives micro-fluidic liquid distributor to close to accommodating
The direction of vessel is mobile, so that fluid-directing needle passes through the inner cavity of insertion accommodating vessel after the top cover for accommodating vessel.Pumping installations can
The reagent in reagent reservoirs to be transported in the liquid-conveying ducts of micro-fluidic liquid distributor, liquid flow to along liquid-conveying ducts and leads
At liquid needle, and it is sent into accommodating vessel via the liquid needle that enters of fluid-directing needle.
Due to reagent reservoirs quantity be it is multiple, a variety of not same liquids can be imported into accommodating vessel by pumping installations
Interior, pumping installations can will also accommodate the liquid in vessel and be extracted out by fluid-directing needle.
The addition and discharge of a variety of different reagents may be implemented using oligonucleotides assemble in situ instrument provided by the present application, and
It can be according to assembling process regulating and controlling temperature, so that the sample to be assembled in accommodating vessel is at preference temperature always.
It therefore, can be single without using other equipment auxiliary using oligonucleotides assemble in situ instrument provided by the present application
The many more manipulations such as oligonucleotide hybridization, connection, amplification, assembling and error correction are continuously finished in accommodating vessel, can prevent from polluting, are shown
Work improves efficiency.
Detailed description of the invention
It, below will be to specific in order to illustrate more clearly of the specific embodiment of the invention or technical solution in the prior art
Embodiment or attached drawing needed to be used in the description of the prior art be briefly described, it should be apparent that, it is described below
Attached drawing is some embodiments of the present invention, for those of ordinary skill in the art, before not making the creative labor
It puts, is also possible to obtain other drawings based on these drawings.
Fig. 1 is the structural schematic diagram that oligonucleotides assemble in situ instrument provided in an embodiment of the present invention is in the first visual angle；
Fig. 2 is the structural schematic diagram that oligonucleotides assemble in situ instrument provided in an embodiment of the present invention is in the second visual angle；
Fig. 3 is the structural schematic diagram that oligonucleotides assemble in situ instrument provided in an embodiment of the present invention is in third visual angle；
Fig. 4 is the structural schematic diagram that oligonucleotides assemble in situ instrument provided in an embodiment of the present invention is in the 4th visual angle；
Fig. 5 is the structural schematic diagram that oligonucleotides assemble in situ instrument provided in an embodiment of the present invention is in the 5th visual angle；
Fig. 6 is the structural schematic diagram that oligonucleotides assemble in situ instrument provided in an embodiment of the present invention is in the 6th visual angle；
Fig. 7 is the structural schematic diagram that oligonucleotides assemble in situ instrument provided in an embodiment of the present invention is in the 7th visual angle；
Fig. 8 is the structural schematic diagram that oligonucleotides assemble in situ instrument provided in an embodiment of the present invention is in the 8th visual angle；
Fig. 9 is the structural schematic diagram that oligonucleotides assemble in situ instrument provided in an embodiment of the present invention is in the 9th visual angle；
Figure 10 is the structural schematic diagram of drain pipeline in oligonucleotides assemble in situ instrument provided in an embodiment of the present invention.
In figure: 10- accommodates vessel；20- limits groove body；The micro-fluidic liquid distributor of 30-；31- enters liquid channel；32- drain
Channel；41- enters liquid needle；42- drain needle；50- pumping installations；60- reagent reservoirs；61- positioning seat；70- mobile mechanism；71- branch
Frame；72- pedestal；73- driver；74- lead screw；75- attachment beam；80- semiconductor cooler；81- heat sink；82- fan；91-
Power supply mechanism；92- controller；93- solenoid valve block.
Specific embodiment
Technical solution of the present invention is clearly and completely described below in conjunction with attached drawing, it is clear that described implementation
Example is a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, ordinary skill
Personnel's every other embodiment obtained without making creative work, shall fall within the protection scope of the present invention.
In the description of the present invention, it should be noted that term " center ", "upper", "lower", "left", "right", "vertical",
The orientation or positional relationship of the instructions such as "horizontal", "inner", "outside" be based on the orientation or positional relationship shown in the drawings, merely to
Convenient for description the present invention and simplify description, rather than the device or element of indication or suggestion meaning must have a particular orientation,
It is constructed and operated in a specific orientation, therefore is not considered as limiting the invention.In addition, term " first ", " second ",
" third " is used for descriptive purposes only and cannot be understood as indicating or suggesting relative importance.
In the description of the present invention, it should be noted that unless otherwise clearly defined and limited, term " installation ", " phase
Even ", " connection " shall be understood in a broad sense, for example, it may be being fixedly connected, may be a detachable connection, or be integrally connected；It can
To be mechanical connection, it is also possible to be electrically connected；It can be directly connected, can also can be indirectly connected through an intermediary
Connection inside two elements.For the ordinary skill in the art, above-mentioned term can be understood at this with concrete condition
Concrete meaning in invention.
As shown in figs. 1-9, oligonucleotides assemble in situ instrument provided in an embodiment of the present invention, comprising: accommodating vessel 10, temperature
Control mechanism, micro-fluidic liquid distributor 30, mobile mechanism 70, pumping installations 50 and reagent reservoirs 60, in which:
Accommodating vessel 10 includes the ontology with inner cavity, and is covered on the top cover of the opening of inner cavity, and inner cavity is for putting
Set sample to be assembled.Specifically, the top cover for accommodating vessel is arranged there are two through-hole, one of them is used to be inserted into liquid needle, another
It is a to be used to be inserted into drain needle.
It is red in a kind of optional embodiment, it is connected through a screw thread between top cover and ontology, and be provided on the outside of top cover
Non-slip texture.
Temperature control mechanism includes the temperature-controlled package for limiting groove body 20 and being connected with limit groove body 20, limits and sets on groove body 20
Multiple limit cavitys for being used to place accommodating vessel 10 are equipped with, limit cavity has opening.In a kind of embodiments possible, limit
The top cover of the opening up setting of position cavity, accommodating vessel 10 is exposed to the opening.Accordingly, micro-fluidic liquid distributor 30
In the upper area of limit groove body 20, micro-fluidic liquid distributor 30 may make fluid-directing needle insertion accommodating vessel after moving down
10.Specifically, the opening for limiting cavity can be arranged vertically upward, can also tilt upward setting, and the opening for limiting cavity is excellent
It is selected as set-up mode vertically upward.
In a kind of optional embodiment, the section of top cover and ontology is circle, and the outer diameter of top cover is greater than ontology
Outer diameter.Accordingly, limit cavity cross-section is also round, and the outer diameter of top cover is greater than the internal diameter of limit cavity, accommodates the sheet of vessel
The outer diameter of body is equal to or slightly less than the internal diameter of limit cavity.So set, holding when that will accommodate vessel and be placed in limit chamber body
The ontology for setting vessel protrudes into limit chamber body, and top cover is located at the external side of limit chamber, bottom margin and the limit groove body of top cover
Top surface contact.
For restraining position ring block convenient for further fixing accommodating vessel, is arranged on limit groove body, stop collar is located at limit groove body
Top surface, and be located at the periphery of limit cavity, the depth of stop collar is less than the height of the top cover of accommodating vessel.So set,
After accommodating vessel are put into limit cavity, the bottom margin of top cover is extend into stop collar, top of the stop collar for accommodating vessel
Lid further functions as position-limiting action.
In use, accommodating vessel 10 are placed in limit chamber body, limiting slot is adjusted by temperature-controlled package
The temperature of body 20, so that suitable environment temperature is provided for accommodating vessel 10, it can be in different times tune by temperature-controlled package
Section be different temperatures, with meets progress assemble in situ during different times for temperature the needs of.
Micro-fluidic liquid distributor 30 is including liquid-conveying ducts and fluid-directing needle, the fluid-directing needle that fluid-directing needle is connected to liquid-conveying ducts,
Fluid-directing needle includes into liquid needle and drain needle, and liquid-conveying ducts are connected to by pumping installations 50 with multiple reagent reservoirs 60.
During use, enter liquid needle and drain needle both pass through through-hole on accommodating vessel top cover after be inserted into Container
In the inner cavity of ware.Pumping installations, which is used to that the reagent in different reagent reservoirs to be passed through to liquid-conveying ducts and enter liquid needle, imported into Container
In ware, the liquid in vessel will be accommodated by being also used for is discharged by liquid-conveying ducts.So set, continuous in same accommodating vessel internal medicine
Be passed through a variety of different reagents, so as to meet carry out assemble in situ during different times reagent demand.
Mobile mechanism 70 is connected to micro-fluidic liquid distributor 30, for control micro-fluidic liquid distributor 30 it is mobile so that
Fluid-directing needle is inserted into its inner cavity after passing through the top cover for accommodating vessel 10.Mobile mechanism 70 drives the micro-fluidic movement of liquid distributor 30
Direction is related to the limit limit opening direction of cavity of groove body 20.When the opening direction of limit cavity is vertically upward, then
Mobile mechanism 70 drives micro-fluidic liquid distributor 30 vertically to move, so that fluid-directing needle can be perpendicularly inserted into Container
In ware.When limit cavity opening tilt upward, then mobile mechanism 70 drive micro-fluidic liquid distributor 30 along with limit
The identical inclined at inclination angles in cavity hatch direction moves up and down.
As shown in Figure 3 and Figure 5, in a kind of embodiments possible of the present embodiment, mobile mechanism includes bracket 71, connection
Beam 75, driver 73 and lead screw 74, driver 73 are installed on bracket 71, and attachment beam 75 is provided with and the matched screw thread of lead screw 74
Hole, lead screw 74 are threadedly engaged with attachment beam 75, and driver 73 is connect with lead screw 74, for driving lead screw 74 to rotate, attachment beam 75
It is connect with micro-fluidic liquid distributor 30.
Specifically, motor can be selected in driver, and the output shaft and lead screw of motor are coaxially connected, after starting motor, motor
Output shaft drives lead screw rotation, since motor is fixed on bracket, in lead screw rotation process, drives attachment beam along lead screw
Axial movement.
In the present embodiment, the axial direction of lead screw is with the opening of limit cavity towards identical.When the opening of limit cavity is perpendicular
When directly setting up, the axial direction of lead screw is vertical direction, i.e., along the y axis.So set, cooperating driver and lead screw
Attachment beam can be driven to move up and down along the y axis, so that micro-fluidic liquid distributor be driven to move up and down.Micro-fluidic liquid distribution
Device is located at the top of limit groove body, and fluid-directing needle can be inserted into corresponding accommodating vessel after moving down by micro-fluidic liquid distributor,
Each accommodating vessel respectively correspond two fluid-directing needles, one of them be into liquid needle, for accommodating vessel in be passed through liquid, it is another
A is drain needle, for that will accommodate the discharge of the liquid in vessel.
In the other embodiments of the present embodiment, mobile mechanism includes: bracket, attachment beam, driver, driver difference
It is connected with bracket and attachment beam, driver directly drives attachment beam along straight reciprocating motion.Driver be hydraulic cylinder or cylinder,
Cylinder part is fixedly connected with bracket, and pusher portion is connect with attachment beam, and push rod is mobile relative to bracket, so that attachment beam be driven to move
It is dynamic.
To improve the stability of lead screw during rotation, mitigate the shake of lead screw radial direction, in a kind of preferred embodiment
In, one end of lead screw is connect with driver, and the other end is connect with holder pivots.Specifically, lead screw can be turned by bearing and bracket
Dynamic connection, bearing holder (housing, cover) is loaded on lead screw, and the inner ring of bearing is fixedly connected with lead screw, and outer ring and the bracket of bearing are fixed.
Further, as shown in figure 5, bracket 71 includes pedestal 72, it is arranged on pedestal 72 fluted, bearing is embedded at groove
It is interior.
To improve the stability in micro-fluidic liquid distributor moving process, in a kind of optional embodiment, bracket edge
It is vertically arranged with guide groove, attachment beam is provided with guide pad, and guide pad slidable fit is in guide groove.So set, in driver
During driving attachment beam mobile, guide pad slides in guide groove, and guide groove plays guiding for guide pad and limit is made
With avoiding in moving process attachment beam from shake occur, shake or offset, so that it is mobile to improve micro-fluidic liquid distributor
Stability in the process.
In order to further increase stability of the attachment beam in moving process, bracket includes two pillars, the bottom of pillar
It is provided with pedestal, the area of pedestal is greater than pillar, is provided with hole on pedestal, can be consolidated pedestal and other structures by bolt
It is fixed, so that bracket is more preferably fixed.A driver is respectively fixedly connected on two pillars, the both ends of attachment beam are respectively set
There is a threaded hole, the both ends that two drivers pass through the lead screw and attachment beam that respectively connect respectively are threadedly engaged.Connect mobile
During connecing beam, the synchronous driving of two drivers.
Alternatively, two lead screws rotation positioned at attachment beam both ends can also be driven using only a driver.Citing comes
It says, transmission gear is arranged on two lead screws, is sequentially connected between two transmission gears by transmission belt, driver can drive
One of lead screw rotation, the lead screw drive another lead screw to rotate by transmission belt.
In any of the above-described technical solution, further, accommodates and sealed between the ontology of vessel and top cover by sealing ring
Connection.The sealing performance that accommodating vessel can be improved is arranged such.It is provided with detent in accommodating vessel, for fixing sample to be assembled
Product, such as biochip.
For convenient for fixed mobile mechanism and temperature control mechanism, it further includes mounting plate, mobile mechanism that oligonucleotides assemble in situ, which is set,
Mounting plate is mounted on temperature control mechanism.
Specifically, limit groove body is installed at the top of mounting plate, and the temperature-controlled package in temperature control mechanism connects with limit groove body
Touching, in a specific embodiment, temperature-controlled package are installed between limit groove body and mounting plate.
Temperature-controlled package may include semiconductor cooler (Thermoe l ectr i c Coo l er, abbreviation TEC),
Semiconductor cooler is made of the Peltier effect using semiconductor material.TEC includes some p-types and N-type pair, they pass through
Electrode connects together, and is clipped between two ceramic electrodes；When there is electric current to flow through from TEC, the heat that electric current generates can be from
The other side is passed in the side of TEC, " heat " side and " cold " side is generated on TEC, here it is the heating of TEC and refrigeration principle.Therefore,
It can be freezed using semiconductor cooler, can also be heated.
Certainly, other structures also can be selected in temperature-controlled package, such as electric heating piece, electric heating piece are connect with power supply mechanism, supply
Motor structure is electric heating piece generation heat after electric heating piece power supply, the heat transfer that electric heating piece generates to limit groove body, so that limit
The temperature of position groove body increases.At this point, temperature-controlled package may also include refrigeration machine, for limit groove body cooling.
As shown in Figure 1, power supply mechanism 91 can be battery, battery is installed in by mobile mechanism 70.
In order to accelerate to limit the cooling rate of groove body, in a kind of optional embodiment, temperature control mechanism further includes heat dissipation group
Part, radiating subassembly are installed on mounting plate bottom.Radiating subassembly may include heat sink and fan, and heat sink includes contact chip and heat dissipation
Fin, contact chip are connect with mounting plate bottom, and there are certain angle between radiating fin and contact chip, the quantity of radiating fin is
Multiple, multiple radiating fins are spaced apart on contact chip, form heat dissipation channel between multiple radiating fins.Fan is mountable to
By heat sink, heat dissipation channel that the air outlet of fan is formed towards radiating fin.
After starting fan, the flabellum of fan is rotated, to increase the gas flow rates around radiating fin, accelerates hot gas
Diffusion.
As Figure 1-Figure 4, when including semiconductor cooler 80 by temperature-controlled package, semiconductor cooler 80 can be made
For mounting plate use, i.e., limit groove body 20 is installed on to the top of semiconductor cooler 80, radiating subassembly is installed on semiconductor
The bottom of refrigerator 80, specifically, heat sink 81 are connect with the bottom surface of semiconductor cooler 80, and fan 82 is located at heat sink 81
Lower section.
In any of the above-described technical solution, further, micro-fluidic liquid distributor includes micro-fluidic plate, and liquid-conveying ducts are set
It is placed on micro-fluidic plate, fluid-directing needle is installed on the bottom of micro-fluidic plate, and is connected to liquid-conveying ducts.
Specifically, as shown in Figure 10, liquid-conveying ducts include entering liquid channel 31 into liquid channel 31 and apocenosis passage 32 and respectively entering
Liquid needle 41 is connected to, and apocenosis passage 32 is connected to each drain needle 42.
In a specific embodiment, fluid-directing needle is distributed on micro-fluidic liquid distributor in array-like, enters liquid channel
The first access, alternate path and tributary circuit are respectively included with apocenosis passage, the quantity of the first access is multiple, each first access
It being connected to respectively with alternate path, alternate path is connect with pumping installations, and the first access is connected to by tributary circuit with fluid-directing needle, the
The extending direction of one access and the extending direction of alternate path are vertical, enter first access in liquid channel and the first of apocenosis passage is led to
Road is parallel and is interspersed.
For example, junction of the fluid-directing needle on micro-fluidic liquid distributor is multiple rows of, and every row includes multiple intervals point
The fluid-directing needle of cloth, every row's fluid-directing needle is of the same race, for example, the fluid-directing needle in a row is that fluid-directing needle into liquid needle, in a row is equal
For drain needle.The row that the row's group and drain needle for entering liquid needle composition form organizes staggered.It is arranged between adjacent two rows of fluid-directing needles
Have the first access, multiple first accesses are parallel to each other on micro-fluidic liquid distributor, if one of them first access belong into
Liquid channel, then first access adjacent with first access belongs to apocenosis passage.Enter liquid channel and is connected to liquid needle is entered, apocenosis passage
It is connected to drain needle.
Each tributary circuit on micro-fluidic liquid distributor is parallel to each other.
On micro-fluidic liquid distributor, enter that liquid needle is identical as the quantity of drain needle, and enters the quantity of liquid needle, drain needle
Quantity is identical as the limit quantity of groove body upper limit cavity respectively.Each limit cavity is correspondingly arranged on a drain needle and one
Enter liquid needle.
For the ease of placing reagent reservoirs, as shown in Figure 1, optionally, oligonucleotides assemble in situ instrument further includes positioning seat
61, multiple sockets are provided on positioning seat 61, socket is for inserting reagent reservoirs 60.
In a specific embodiment, multiple sockets are provided on positioning seat, multiple sockets are on positioning seat along a row
Or multiple rows of distribution, the internal diameter of different sockets may be the same or different.
When setting is applicable to insert various sizes of reagent reservoirs there are many when various sizes of socket on positioning seat.
Further, as shown in Figure 1, oligonucleotides assemble in situ instrument provided by the present application includes control system, control system
System, control system includes controller 92, and single-chip microcontroller, PLC or CPU can be selected in controller 92.Controller 92 respectively with temperature control mechanism,
Mobile mechanism 70 is connected with pumping installations 50 by signal wire.
Controller is conveyed in preset time control pumping installations to micro-fluidic liquid distributor according to the process flow of setting
One or more of reagents of setting, and control temperature control mechanism and the temperature for accommodating vessel is made to reach default temperature corresponding with journey is improved
Degree.Controller controls mobile mechanism to drive micro-fluidic liquid distributor to move so that fluid-directing needle is inserted into accommodating vessel.
Further, temperature control system further includes temperature sensor, and temperature sensor is installed on limit groove body, for measuring limit
The temperature of position groove body.Temperature sensor is connect with controller, to feed back the actual temperature of limit groove body, in order to which controller is sentenced
Whether the temperature of disconnected limit groove body reaches preset value.
Specifically, in a kind of embodiments possible, the test side of temperature sensor is mountable to the limit of limit groove body
In cavity.It compares and is installed on the lateral surface of limit groove body, be installed on the test side detection of the limit inside cavities of limit groove body
The temperature arrived closer to accommodating vessel local environment temperature.
Further, oligonucleotides assemble in situ instrument further includes cover, accommodating vessel, temperature control mechanism, micro-fluidic liquid point
Orchestration and mobile mechanism are all set in cover.Cover has switching door, and the moment will accommodate vessel, temperature to switching door in off position
Control mechanism, micro-fluidic liquid distributor and mobile mechanism are protected in inside cover.Preferably, cover is made of transparent material, with
Packaging technology process is observed convenient for operator.
Further, as depicted in figs. 1 and 2, pass through solenoid valve between reagent reservoirs 60 and micro-fluidic liquid distributor 30
93 connection of group.It include multiple solenoid valves in solenoid valve block 93, each solenoid valve is connect with controller 92 respectively, in controller 92
It is opened or closed under control action, to control the reagent type flowed into accommodating vessel 10 and dosage.
Oligonucleotides assemble in situ instrument provided in this embodiment passes through gradient hybridization-for realizing oligonucleotides deprotection
Oligonucleotides cascade assembling is realized in error correction-connection-various ways assembling-error correction etc., and hybridizes error correction, albumen error correction using gradient
Etc. multisteps error correction, guarantee the assembled in vitro of efficient fidelity.
Oligonucleotides assemble in situ instrument provided in this embodiment further includes driving mechanism and magnetic part, and driving mechanism is used for band
Dynamic magnetic part moves away from or close to accommodating vessel, and after magnetic part is close to accommodating vessel, magnetic part attracts in accommodating vessel
Magnetic bead, driving mechanism drive magnetic part movement can drive accommodating vessel in magnetic bead accommodating vessel in move, thus into
Row magnetic bead error correction procedure.
Specifically, driving mechanism can drive magnetic bead X-axis, Y-axis and Z-direction mobile.Driving mechanism may include multiple drivings
Part, for example, driving mechanism includes three actuators, respectively the first actuator, the second actuator and third actuator, and the
One actuator is for pushing the second actuator to move along the x axis, and the second actuator is for driving third actuator along the y axis
Mobile, third actuator is connect with magnetic part, for driving magnetic part to move along Z-direction.
Actuator can be hydraulic cylinder or cylinder.
Further, driving mechanism may also include the guide rail being arranged along the x axis, and the second actuator slidable fit is in guide rail
On, and can the X-direction movement under the drive of the first actuator.
Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations；To the greatest extent
Pipe present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that: its according to
So be possible to modify the technical solutions described in the foregoing embodiments, or to some or all of the technical features into
Row equivalent replacement；And these are modified or replaceed, various embodiments of the present invention technology that it does not separate the essence of the corresponding technical solution
The range of scheme.
Claims (10)
1. a kind of oligonucleotides assemble in situ instrument characterized by comprising
Vessel are accommodated, including the ontology with inner cavity, and are covered on the top cover of the opening of the inner cavity, the inner cavity is used for
Place sample to be assembled；
Temperature control mechanism is set on the limit groove body including limit groove body and the temperature-controlled package being connected with the limit groove body
Multiple limit cavitys for being used to place the accommodating vessel are equipped with, the limit cavity has opening；
Micro-fluidic liquid distributor, including liquid-conveying ducts, and the fluid-directing needle being connected to the liquid-conveying ducts, the fluid-directing needle packet
It includes into liquid needle and drain needle, the liquid-conveying ducts are connected to by pumping installations with multiple reagent reservoirs；
Mobile mechanism, the mobile mechanism are connected to the micro-fluidic liquid distributor, for controlling the micro-fluidic liquid point
Orchestration is mobile so that the fluid-directing needle is inserted into the inner cavity after passing through the top cover for accommodating vessel.
2. oligonucleotides assemble in situ instrument according to claim 1, which is characterized in that the mobile mechanism include bracket,
Attachment beam, driver and lead screw, the driver are installed on the bracket, and the attachment beam is provided with to be matched with the lead screw
Threaded hole, the lead screw is threadedly engaged with the attachment beam, and the driver is connect with the lead screw, for driving the silk
Thick stick rotation, the attachment beam are connect with the micro-fluidic liquid distributor.
3. oligonucleotides assemble in situ instrument according to claim 2, which is characterized in that one end of the lead screw and the drive
Dynamic device connection, the other end are connect by bearing with the holder pivots.
4. oligonucleotides assemble in situ instrument according to claim 1, which is characterized in that the ontology of the accommodating vessel and top
It is tightly connected between lid by sealing ring.
5. oligonucleotides assemble in situ instrument according to claim 1, which is characterized in that it further include mounting plate, the movement
Mechanism and the temperature control mechanism are mounted on the mounting plate.
6. oligonucleotides assemble in situ instrument according to claim 5, which is characterized in that the limit groove body is installed on described
At the top of mounting plate, the temperature-controlled package is installed between the limit groove body and the mounting plate, and the temperature control mechanism is also
Including radiating subassembly, the radiating subassembly is installed on the mounting plate bottom.
7. oligonucleotides assemble in situ instrument according to claim 1, which is characterized in that the micro-fluidic liquid distributor is also
Including micro-fluidic plate, the liquid-conveying ducts are set on the micro-fluidic plate, and the fluid-directing needle is installed on the micro-fluidic plate
Bottom.
8. oligonucleotides assemble in situ instrument according to claim 1, which is characterized in that the liquid-conveying ducts include logical into liquid
Road and apocenosis passage, it is described enter liquid channel with it is each it is described enter liquid needle be connected to, the apocenosis passage is connected to each drain needle.
9. oligonucleotides assemble in situ instrument according to claim 8, which is characterized in that the fluid-directing needle is described micro-fluidic
Be distributed on liquid distributor in array-like, it is described enter liquid channel and the apocenosis passage respectively include the first access, alternate path
And tributary circuit, the quantity of first access be it is multiple, each first access is connected to the alternate path respectively, described
Alternate path is connect with pumping installations, and first access is connected to by the tributary circuit with fluid-directing needle, first access
Extending direction it is vertical with the extending direction of the alternate path, it is described enter liquid channel the first access and the apocenosis passage
First access is parallel and is interspersed.
10. oligonucleotides assemble in situ instrument according to claim 1, which is characterized in that further include driving mechanism and magnetism
Part, the driving mechanism is for driving the magnetic part close to or far from the accommodating vessel, and the magnetic part is for driving institute
The magnetic bead stated in accommodating vessel is mobile.
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|---|---|---|---|
| CN201910204884.5A CN109825431A (en) | 2019-03-18 | 2019-03-18 | Oligonucleotides assemble in situ instrument |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910204884.5A CN109825431A (en) | 2019-03-18 | 2019-03-18 | Oligonucleotides assemble in situ instrument |
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Inventor after: Wang Shengqi Inventor after: Xiao Rui Inventor after: Rong Zhen Inventor after: Liu Liyan Inventor after: Peng Yongjin Inventor before: Wang Shengqi Inventor before: Xiao Rui Inventor before: Rong Zhen Inventor before: Zhang Lijie Inventor before: Liu Liyan Inventor before: Peng Yongjin |