CN106047684B - A kind of digitlization nucleic acid augmentative instrument - Google Patents

A kind of digitlization nucleic acid augmentative instrument Download PDF

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Publication number
CN106047684B
CN106047684B CN201610178269.8A CN201610178269A CN106047684B CN 106047684 B CN106047684 B CN 106047684B CN 201610178269 A CN201610178269 A CN 201610178269A CN 106047684 B CN106047684 B CN 106047684B
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China
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thermoelectric
cooler
cabinet
nucleic acid
temperature controller
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CN201610178269.8A
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Chinese (zh)
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CN106047684A (en
Inventor
俞育德
任鲁风
魏清泉
刘文文
刘元杰
刘勇
李钊
王小青
蒋莉娟
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大连胤瑞生物医学仪器有限责任公司
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Publication of CN106047684A publication Critical patent/CN106047684A/en
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Abstract

A kind of digitlization nucleic acid augmentative instrument, including cabinet, wherein the cabinet is internally provided with temperature controller and blower fan module, and the blower fan module includes thermoelectric (al) cooler;The thermoelectric (al) cooler is set to the side of the cabinet, and the temperature controller is set to the other side of the cabinet close to the thermoelectric (al) cooler, and the temperature controller is electrically connected with the thermoelectric (al) cooler, the temperature for thermoelectric (al) cooler described in real-time control;The thermoelectric (al) cooler is set to cabinet inside using the push-pull structure for going out after advancing or going out before laggard.The digitlization nucleic acid augmentative instrument overall structure of the present invention is simple, easy to operate;The arrangement of each component is best, has not only saved the space of single unit system, but also reduces production cost;Wherein temperature cycles may be implemented with temperature controller in thermoelectric (al) cooler, accurately control denaturation, annealing and elongating temperature, time and the recurring number of template, may be implemented to expand the required accuracy controlling for quickly raising and reducing temperature.

Description

A kind of digitlization nucleic acid augmentative instrument

Technical field

The present invention relates to nucleic acid amplification technologies field more particularly to a kind of digitlization nucleic acid augmentative instruments.

Background technology

Nucleic acid amplification technologies, (Polymerase Chain Reaction are referred to as especially digital polymerase chain reaction technique PCR), it is a kind of molecular biotechnology for expanding specific DNA molecular segment, it is using DNA molecular as template, by a pair of of people The specific oligonucleotide primers of work synthesis, pass through archaeal dna polymerase enzymatic reaction, rapid amplifying specific DNA molecular segment, in biology There is extremely important effect on.As it is using more and more extensive, the requirement to nucleic acid augmentative instrument (such as PCR instrument) is more next It is higher.For example, for PCR instrument, compared with traditional round pcr, the application for digitizing round pcr is more and more extensive, number Word round pcr can provide the accurate quantification data of denier template, the preceding library of sequencing is quantitative, low abundance mRNA detections and There is significant advantage and irreplaceability in the applications such as rare DNA mutation detection and the micro Research on differences of copy number.Number Change round pcr and so that searching the work for having valuable low abundance template data in traditional technology in a large amount of sample datas becomes It is abnormal simple, it is diagnosed so as to being rapidly engaged in such as cancer and early detection, the early screening of fetus genetic disease, DNA Or even the innovation works such as individual medical treatment.This technology has irreplaceable effect compared to traditional technology field, and several recently Forward position and the hot spot for becoming international research year, have important scientific meaning and application value.

It must be provided simultaneously with biochemical condition and Thermal cycling conditions during PCR amplification, need to accurately control template Denaturation, annealing and elongating temperature, time and recurring number.But traditional PCR instrument is porous type heating instrument mostly, and in reality It is not that can fill every time in, the reagent of different number can be generally heated according to actual demand, thus generates different Heating load, and then change heat circulating system thermal resistance hot melt, in the process if ignoring the variation of heating load, it will Lead to PCR reaction failures, and then makes Thermal cycling conditions during PCR amplification that can not accurately control the denaturation of template, annealing With elongating temperature, time and recurring number.

Chinese invention patent (201210012865.0:A kind of PCR instrument of high temperature control precision) disclose a kind of high temperature control essence The PCR instrument of degree includes the load information transfer module being connect with control circuit, and the load information transfer module is to sensor temperature Information is handled, and obtains the correspondence relationship information between invisible spectro temperature of reagent information and sensor temperature information, and will The correspondence relationship information is sent to control circuit, controls fan and thermoelectric cooler.

Foregoing invention increases a load information transfer module, and the loading information module is by arriving calorifics information equivalence It is corresponding between sensor temperature information and the temperature of reagent information in test tube in the case of different loads to determine in electrical model Then the information of the correspondence is sent to control circuit by relationship, to control fan, thermoelectric cooler etc. to temperature of reagent It is adjusted.But the accuracy that foregoing invention adjusts temperature of reagent is not high, and can not achieve and quickly raise and reduce temperature Regulation and control.Moreover, PCR instrument overall construction is not compact enough, influences to radiate, be also unfavorable for installation and maintenance.

Invention content

The object of the present invention is to provide a kind of digitlization nucleic acid augmentative instruments, to overcome in prior art described above extremely A kind of few problem.

In order to achieve the above objectives, the present invention provides a kind of digitlization nucleic acid augmentative instrument, including cabinet, wherein

The cabinet is internally provided with temperature controller and blower fan module, and the blower fan module includes thermoelectric (al) cooler;

The thermoelectric (al) cooler is set to the side of the cabinet, and the temperature controller is set to close to the thermoelectric (al) cooler The other side of the cabinet, the temperature controller are electrically connected with the thermoelectric (al) cooler, for thermoelectricity described in real-time control The temperature of cooler;

The thermoelectric (al) cooler is set to cabinet inside using the push-pull structure for going out after advancing or going out before laggard.

According to a preferred embodiment of the invention a, the thermoelectric (al) cooler includes cooling fin, cooling fin and fan two, The cooling fin and the material of cooling fin are aluminium flake, and are respectively arranged on the not homonymy of the thermoelectric (al) cooler;The fan two It is set to the bottom surface of the cooling fin and the cooling fin.

According to a preferred embodiment of the invention a, the upper surface of the thermoelectric (al) cooler is equipped with chip slot, the core Film trap is fixed on the thermoelectric (al) cooler by trip bolt;Chip is equipped in the chip slot;

The upper surface of the cabinet be equipped with groove, the groove is identical with the chip groove shape, and the groove and The chip slot is coaxially arranged.

According to a preferred embodiment of the invention a, control assembly is additionally provided in the cabinet, the control assembly is tight The adjacent temperature controller is set in the cabinet, and the control assembly is arranged with the temperature controller homonymy;It is described Control assembly is connected with temperature controller control.

According to a preferred embodiment of the invention a, the side of the cabinet is additionally provided with power switch, and the power supply is opened It closes and is arranged with the temperature controller homonymy, the control assembly is electrically connected with the power switch.

According to a preferred embodiment of the invention a, it is additionally provided with rotary switch module in the cabinet, passes through fixation Piece is fixedly connected on the control assembly.

According to a preferred embodiment of the invention a, power supply module and serial ports switch are additionally provided in the cabinet, it is described Power supply module and serial ports switch set on the opposite side of the temperature controller, the power supply module for realizing electric current conversion.

According to a preferred embodiment of the invention a, the digitlization nucleic acid augmentative instrument further includes microscope, described aobvious Micro mirror includes eyepiece and object lens;The microscope with screw by being tightly fixed on the upper surface of the cabinet.

According to a preferred embodiment of the invention a, the digitlization nucleic acid augmentative instrument further includes fluorescent moieties, described Fluorescent moieties are set between the object lens and chip, are located at the underface of object lens;

The fluorescent moieties can rotate, and rotation angle is 0-180 °;The fluorescent moieties include external power supply and filter Mating plate.

According to a preferred embodiment of the invention a, the shape of the upper surface of the cabinet is rectangle or circle.

According to the above-mentioned technical solution, digitlization nucleic acid augmentative instrument of the invention has the advantages that:

(1) digitlization nucleic acid augmentative instrument single unit system provided by the invention is simple in structure, easy to operate;Each component therein Location arrangements mode it is best, connection line is most short, has not only saved the space of single unit system, but also reduces production cost;

(2) temperature cycles may be implemented in the thermoelectric (al) cooler in the present invention, temperature controller, accurately control the change of template Property, annealing and elongating temperature, time and recurring number, may be implemented quickly to raise and reduce the accurate of temperature needed for nucleic acid amplification Regulation and control;

(3) thermoelectric (al) cooler in the present invention is arranged using plug-type mode, that is, the arrangement for going out or going out before laggard after advancing Mode facilitates the dismounting of thermoelectric (al) cooler, is installed on repair;The reality of chip may be implemented in the arrangement of thermoelectric (al) cooler internal structure When radiate, ensure chip be in best operating temperature;

(4) digitlization nucleic acid augmentative instrument provided by the invention can carry out the huge single sample template of quantity individual Nucleic acid amplification and analysis have high sensitivity and absolute quantitation ability.

Description of the drawings

Fig. 1 is a kind of overall structure figure for digitlization nucleic acid augmentative instrument that a specific embodiment of the invention provides;

Fig. 2 is a kind of side view for digitlization nucleic acid augmentative instrument that a specific embodiment of the invention provides;

Fig. 3 is a kind of overall structure of the explosion figure for digitlization nucleic acid augmentative instrument that a specific embodiment of the invention provides;

Reference numeral has following meaning in figure:

1:Eyepiece;2:Object lens;3:Fluorescent moieties;4:Blower fan module;5:Groove;6:Temperature controller;7:Control assembly;8: Serial ports switchs;9:Power supply module;10:Cabinet;11:Fixinig plate;12:Rotary switch module;13:Power switch;18:RS232 connects Connect device;19:Fuse;20:Power outlet;14:Thermoelectric (al) cooler;15:Fan one;16:Cooling fin;17:Cooling fin;21:Core Film trap.

Specific implementation mode

The present invention provides a kind of digitlization nucleic acid augmentative instrument, including cabinet, wherein the cabinet is internally provided with temperature control Device processed and blower fan module, the blower fan module include thermoelectric (al) cooler;The thermoelectric (al) cooler is set to the side of the cabinet, institute State temperature controller close to the thermoelectric (al) cooler be set to the sequenator splice cabinet the other side, the temperature controller with The thermoelectric (al) cooler electrical connection, the temperature for thermoelectric (al) cooler described in real-time control;Before the thermoelectric (al) cooler uses The push-pull structure for going out after or going out before laggard is set to cabinet inside.

For thermoelectric (al) cooler, the thermoelectric (al) cooler is plug-type, using the arrangement that goes out before going out after advance or being laggard Mode facilitates the dismounting of thermoelectric (al) cooler, is installed on repair;

The thermoelectric (al) cooler includes cooling fin, cooling fin and fan two, and the cooling fin and the cooling fin are all made of Aluminium flake, and it is respectively arranged on the not homonymy of the thermoelectric (al) cooler;The fan two is set to the cooling fin and the cooling fin Bottom surface can make cooling fin and cooling fin rapid cooling, and then realize the real-time heat dissipation to chip;

The upper surface of the thermoelectric (al) cooler is equipped with chip slot, and the chip slot is fixed on the thermoelectricity by trip bolt On cooler;Chip is equipped in the chip slot;

The upper surface of the cabinet be equipped with groove, the groove is identical with the chip groove shape, and the groove and The chip slot is coaxially arranged.

Preferably, the thermoelectric (al) cooler is preferably 40mm × 40mm.

Preferably, the upper surface of the thermoelectric (al) cooler is additionally provided with chip encapsulating device, in the chip encapsulating device Set the PT100 thermistors for 1mm there are one thickness;The temperature of chip can feed back to the temperature by the thermistor Controller.

In addition, being additionally provided with microscope in the cabinet comprising eyepiece and object lens;The microscope passes through trip bolt It is fixed on the upper surface of the cabinet.

In addition, being additionally provided with fluorescent moieties in the cabinet, it is set between the object lens and chip, is being located at object lens just Lower section.

Preferably, the fluorescent moieties can rotate, and rotation angle is 0-180 °.

Preferably, the fluorescent moieties include external power supply and filter set, the filter set by exciter filter, Two to color separation film, transmitting filter set at.Exciter filter and transmitting optical filter are vertical at 90 degree, and two divide excitation equally to color separation film Optical filter and right angle formed by transmitting optical filter, two to color separation film and microscopical optical axis at 45 degree of angles.

Preferably, rectangle or circle can be used in the shape of the upper surface of the cabinet.

In addition, the side of the cabinet is additionally provided with power switch, the power switch and the temperature controller homonymy cloth It sets.

In addition, control assembly, rotary switch module, fixinig plate, power supply module and serial ports switch are additionally provided in the cabinet, The control assembly is set to close to the temperature controller in the cabinet, and the control assembly and the temperature control homonymy Arrangement.

Preferably, the control assembly is connected with temperature controller control, can control the startup of temperature controller With closing;The control assembly is electrically connected with the power switch.

Preferably, the rotary switch module is fixedly connected on the control assembly by the fixinig plate.

Preferably, the power supply module is set to the opposite side of the temperature controller, the power supply with serial ports switch The conversion of electric current may be implemented in component.

Preferably, RS232 connectors, fuse and power outlet are additionally provided on the cabinet.

To make the objectives, technical solutions, and advantages of the present invention clearer, below in conjunction with specific embodiment, and reference Attached drawing, the present invention is described in further detail.

As shown in Figure 1, Fig. 1 is a kind of overall structure figure of digitlization nucleic acid augmentative instrument provided by the invention, wherein number It includes that microscope, fluorescent moieties 3, blower fan module 4, groove 5, temperature controller 6, control assembly 7, serial ports are opened to change nucleic acid augmentative instrument Close 8, power supply module 9, cabinet 10, fixinig plate 11, rotary switch module 12 and power switch 13;Wherein microscope includes eyepiece 1 With object lens 2;Blower fan module 4 includes thermoelectric (al) cooler 14, and the thermoelectric (al) cooler 14 includes fan two, cooling fin 16 and cooling fin 17;The upper surface of thermoelectric (al) cooler 14 is equipped with chip slot 21, chip is equipped in chip slot 21, and chip slot 21 is by fastening spiral shell Nail is fixed on thermoelectric (al) cooler 14.In addition, core amplification instrument further includes RS232 connectors 18, fuse 19 and power outlet 20.

Wherein, microscope is set to the upper surface of cabinet 10, and is fixed on the cabinet 10 by trip bolt;Fluorescent moieties 3 are set between object lens 2 and chip, and positioned at the underface of object lens 2;Fluorescent moieties 3 include external power supply and filter set, described Filter set from exciter filter, two to color separation film, transmitting filter set at.Exciter filter is with transmitting optical filter at 90 degree Vertically, two divide exciter filter and right angle formed by transmitting optical filter equally to color separation film, and two to color separation film and microscopical optical axis At 45 degree of angles.The upper surface of cabinet 10 can be rectangle or circle, and end face is equipped with groove 5 thereon.

Blower fan module 4 is set to the inside of cabinet 10 with temperature controller 6, and blower fan module 4 includes thermoelectric (al) cooler 14, thermoelectricity Cooler 14 is set to the side of cabinet 10, the other side of the temperature controller 6 close to thermoelectric (al) cooler 14 and set on cabinet 10;Thermoelectricity The upper surface of cooler 14 is equipped with chip slot 21, is equipped with silicon base chip in chip slot 21, chip slot 21 is fixed by trip bolt In thermoelectric (al) cooler 14;The upper surface of cabinet 10 is equipped with groove 5, and groove 5 is identical as the shape of chip slot 21, and groove 5 and core Film trap 21 is coaxially arranged.

As shown in Fig. 2, Fig. 2 is a kind of side view for digitlization nucleic acid augmentative instrument that a specific embodiment of the invention provides, Wherein digital polymerase chain reaction instrument further includes RS232 connectors 18, fuse 19 and power outlet 20.

As shown in figure 3, it is the overall structure of the explosion figure that a specific embodiment of the invention digitizes nucleic acid augmentative instrument, thermoelectricity Cooler 14 includes cooling fin 16, cooling fin 17 and fan two, and wherein cooling fin 16 and cooling fin 17 is all made of aluminium flake, and respectively Positioned at the not homonymy of thermoelectric (al) cooler 14;Fan two be set to cooling fin 17 and cooling fin 16 bottom surface, can make cooling fin with it is cold But piece rapid cooling, and then realize the real-time heat dissipation to chip.

Cabinet 10 is laterally equipped with power switch 13, and power switch 13 is arranged with 6 homonymy of temperature controller;In cabinet 10 also Equipped with control assembly 7, rotary switch module 12, fixinig plate 11, power supply module 9 and serial ports switch 8, wherein control assembly 7 close to Temperature controller 6 is arranged, and controls connection composition temperature control system with temperature controller 6, controls the real time temperature of chip;Control Component 7 processed is electrically connected with power switch 13, and power switch 13 can control the startup and closing of control assembly 7.

Rotary switch module 12 is connected to by fixinig plate 11 in control assembly 7;Power supply module 9 and serial ports switch 8 are set to The conversion of electric current may be implemented in the opposite side of temperature controller 6, power supply module 9;Be additionally provided on cabinet 10 RS232 connectors 18, Fuse 19 and power outlet 20.

Chip in chip slot 21 is made of the micro reaction pool array of silicon base chip, is that reagent realizes core with template to be measured The physical support of acid amplification, reagent are completed into hole in the micro reaction pool of chip with template to be measured, detach, position and quantify.

In amplification process, the thermoelectric (al) cooler 14 in blower fan module 4 can be carried with temperature controller 6 for nucleic acid amplification For Thermal cycling conditions, denaturation, annealing and elongating temperature, time and the recurring number of template can be accurately controlled, may be implemented The regulation and control for quickly raising and reducing temperature needed for nucleic acid amplification.Thermoelectric (al) cooler 14 wherein in blower fan module is using plug-type Mode arranges that the arrangement for going out or going out before laggard after advancing, such arrangement is convenient for the installation of thermoelectric (al) cooler 14, is torn open It unloads and repairs, the arrangement of 14 internal structure of thermoelectric (al) cooler can make chip rapid cooling, and can be with chip position Change and change, improves the efficiency that chip radiates in real time.

A series of detailed description described above is illustrated only for feasible embodiment of the invention, They are not to limit the scope of the invention, in the knowledge that the technical field those of ordinary skill has Interior, the various changes or variation made without departing from the purpose of the present invention all belong to the scope of protection of the present invention.

Claims (8)

1. a kind of digitlization nucleic acid augmentative instrument, including cabinet, which is characterized in that
The cabinet is internally provided with temperature controller and blower fan module, and the blower fan module includes thermoelectric (al) cooler;
The thermoelectric (al) cooler is set to the side of the cabinet, and the temperature controller is set to described close to the thermoelectric (al) cooler The other side of cabinet, the temperature controller are electrically connected with the thermoelectric (al) cooler, for thermoelectric-cooled described in real-time control The temperature of device;
The thermoelectric (al) cooler is set to cabinet inside using the push-pull structure for going out after advancing or going out before laggard;
The thermoelectric (al) cooler includes cooling fin, cooling fin and fan two, and the cooling fin and cooling fin are respectively arranged on the heat The not homonymy of electric cooler;The fan two is set to the bottom surface of the cooling fin and the cooling fin;
The upper surface of the thermoelectric (al) cooler is equipped with chip slot, and the chip slot is fixed on the thermoelectric-cooled by trip bolt Device;Chip is equipped in the chip slot;
The upper surface of the cabinet is equipped with groove, and the groove is identical as the chip groove shape, and the groove and the core Film trap is coaxially arranged;
Further include microscope, the microscope includes eyepiece and object lens;The microscope is fixed on the machine by trip bolt The upper surface of case;
Further include fluorescent moieties, the fluorescent moieties are set between the object lens and chip, are located at the underface of object lens.
2. digitlization nucleic acid augmentative instrument as described in claim 1, which is characterized in that the cooling fin and the material of cooling fin are equal For aluminium flake.
3. digitlization nucleic acid augmentative instrument as described in claim 1, which is characterized in that it is additionally provided with control assembly in the cabinet, The control assembly is set to close to the temperature controller in the cabinet, and the control assembly and the temperature controller Homonymy is arranged;The control assembly is connected with temperature controller control.
4. digitlization nucleic acid augmentative instrument as claimed in claim 3, which is characterized in that the side of the cabinet is additionally provided with power supply and opens It closes, the power switch is arranged with the temperature controller homonymy, and the control assembly is electrically connected with the power switch.
5. digitlization nucleic acid augmentative instrument as claimed in claim 3, which is characterized in that be additionally provided with rotary switch mould in the cabinet Block is fixedly connected on by fixinig plate in the control assembly.
6. as described in claim 1 digitlization nucleic acid augmentative instrument, which is characterized in that be additionally provided in the cabinet power supply module and Serial ports switchs, and the power supply module is with serial ports switch set on the opposite side of the temperature controller, and the power supply module is for real The conversion of existing electric current.
7. digitlization nucleic acid augmentative instrument as described in claim 1, which is characterized in that the fluorescent moieties can rotate, rotation Gyration is 0-180 °;The fluorescent moieties include external power supply and optical filter.
8. digitlization nucleic acid augmentative instrument as described in claim 1, which is characterized in that the shape of the upper surface of the cabinet is square Shape or circle.
CN201610178269.8A 2016-03-25 2016-03-25 A kind of digitlization nucleic acid augmentative instrument CN106047684B (en)

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CN106872432A (en) * 2017-03-30 2017-06-20 杭州晶格科学仪器有限公司 A kind of fluorescence detection device and temperature control method with temperature control mechanism
CN109929753B (en) * 2019-03-14 2019-11-08 宁波胤瑞生物医学仪器有限责任公司 A kind of blower fan module digitizing nucleic acid augmentative instrument

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