CN103992938B - gene amplification device - Google Patents
gene amplification device Download PDFInfo
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- CN103992938B CN103992938B CN201410210884.3A CN201410210884A CN103992938B CN 103992938 B CN103992938 B CN 103992938B CN 201410210884 A CN201410210884 A CN 201410210884A CN 103992938 B CN103992938 B CN 103992938B
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- heat
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- gene amplification
- amplification device
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L7/00—Heating or cooling apparatus; Heat insulating devices
- B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
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- Chemical & Material Sciences (AREA)
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- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention provides a kind of gene amplification device, described gene amplification device comprises heating system and cooling system, heating system comprises heating source and heat conducting module, heating source is ceramic heater or paster power resistor, cooling system comprises the first liquid pipeline of offering in heat conducting module, heat sink, circulation line, cooling fluid and circulating pump, by circulating pump control cooling fluid at first liquid pipeline, in the close access that second liquid pipeline and circulation line form, circulate or stop, realize the rapid temperature rise and drop of heat conducting module, the temperature homogeneity of module has greatly improved.
Description
Technical field
The present invention relates to polymerase chain reaction device, particularly relate to a kind of gene amplification device.
Background technology
In biology field, polymerase chain reaction is extensively approved, is the tool of a kind of DNA of explorationThere is the effective means of high reliability. DNA in sample, under reagent coordinates, carries out under specified temp programTemperature cycles reaction, can obtain the fragment amplification of 2 Nth power quantity at short notice, makes to detect verySensitive.
Gene amplification equipment based on polymerase chain reaction technique has become the basis of biology field kindProperty and necessary equipment. Gene amplification equipment comprises gene-amplificative instrament and fluorescence quantitative polymerase chain reaction inspection conventionallyThe large class of examining system two, the core of these two large kind equipments is all to adopt polymerase chain reaction technique.
Tradition gene amplification equipment can meet the polymerase chain reaction of general low sensitivity reagent. But along withPolymerase chain reaction technique is in the expanded application of every field, the extension of the technology degree of depth, and reaction principleFurther refinement, has proposed more and more higher requirement to the technical performance of instrument. Tradition gene amplification equipment masterStream all adopts semiconductor cooler as heating source and refrigeration source, conventionally adopts aluminium alloy, copper alloy or heat pipeThe radiator of type also dispels the heat by the air-cooled form of direct blower fan, and such gene amplification equipment is to carry out temperature quickWhen sense reagent or high-resolution experiment, often can not obtain desirable result, affect in clinical, scientific research, inspectionThe application of testing occasion, is mainly reflected in:
1. semiconductor cooler temperature performance influence factor is numerous, and control measures are few, and mechanism's mounting process is wantedAsk higher. Its refrigeration heating properties of semiconductor cooler not only with material behavior, the material arrangement of original paper selfCharacteristic, thermal power distribution, flatness, welding procedure etc. are relevant, also equal with mounting plane degree, pressure distributionStructure and the environmental correclations such as even property, interface Heat Conduction Material, environment steam, radiating surface operating mode. Therefore to bring into playMaximum performance has certain difficulty, and the different lot number uniformity of maintenance equipment also acquire a certain degree of difficulty.
2. be the technology of a high low-temperature circulating due to polymerase chain reaction, in reagent, enzymatic activity is to decay in time, due to the requirement of user's detection efficiency and promptness, determined that gene amplification equipment must be one simultaneouslyThe rapid temperature rise and drop system of high-speed cruising as far as possible. In this case, the condition of work of semiconductor coolerBe quick-cooling, heating circulation, use state class to be similar to temperature match curing conditions test fatigue life. Repeatedly, after circulation, partly leadThe bearing structure of system cooler element can become flexible, its thermo-contact and thermal stress conditions and easily change,Aggravation performance degradation, therefore general actual life of only tens thousand of circulations.
3. the one side of semiconductor cooler (working face) is with the heat conducting module in test tube hole, another side (inoperativeFace) radiator is housed, semiconductor cooler self is a heat conduction path, therefore semiconductor coolerTemperature and the distributing homogeneity thereof of each face to another side impacts. In gene amplification equipment, heat radiationThe Temperature Distribution of device face just has remarkable impact to the heat distribution of working face heat conducting module. Radiator face is also with conventionallyHave blower fan to carry out forced air cooling, in the case, due to radiator shape, fin distribution, edge effect,Radiating airflow path, end face flow distribution, airway resistance etc. inconsistent, makes the non-work of semiconductor coolerMake the heat distribution complex genesis of face, though there are some producers to adopt heat-pipe radiator to carry out improvement in performance, theseEven if factor can not effectively be eliminated through some indemnifying measure.
4. relevant to first few items statement, radiator effective area used is less than normal, volume is large, weight is large, heat passesLead efficiency low, blower fan also brings larger noise. Poor temperature uniformity, the heating and cooling efficiency of heat conducting module are low,Cause being applied to responsive to temperature reagent and high-resolution experiment.
Summary of the invention
Based on this, be necessary carrying out responsive to temperature reagent or high-resolution for above-mentioned traditional gene amplification equipmentThe problem that can not obtain ideal effect when rate experiment, provides a kind of gene amplification device.
A kind of gene amplification device, comprises heating system and cooling system, and described heating system comprises heating sourceAnd heat conducting module, described heating source heats reaction reagent by heat conducting module, and described heating source is that pottery addsHot device or paster power resistor, described cooling system comprises first liquid pipeline, the use in heat conducting module, offeredIn distributing the heat sink, circulation line, cooling fluid of heat energy and for promoting the circulating pump of described coolant flow,In described heat sink, be provided with the second liquid pipeline being communicated with described circulation line, described first liquid pipeline,Second liquid pipeline and described circulation line are communicated with formation close access.
In an embodiment, described heat conducting module is provided with first interface and the second interface therein, and describedOne interface and the second interface are communicated with described first liquid pipeline with described circulation line, described first interface andThe quantity of the second interface is at least 1, and described first liquid pipeline inner track can be parallel or serial or bifurcatedOr turnover or merging.
In an embodiment, described heat sink is provided with the first heat radiation interface and the second heat radiation interface, institute thereinState the first heat radiation interface and described the second heat radiation interface by described second liquid pipeline and described circulation line companyLogical, the quantity of described the first heat radiation interface and the second heat radiation interface is at least 1, described second liquid pipeline insidePath can be parallel or serial or bifurcated or turnover or merging.
In an embodiment, described ceramic heater is by exchanging or direct current supply therein.
In an embodiment, described heating source is for to fill by paster power resistor by leading heat-curable glue thereinThe insulation calandria that the array being arranged in forms.
In an embodiment, described heat sink is provided with radiating fin therein.
Therein in an embodiment, described cooling fluid do not solidify in the time of 0 degree Celsius, in the time of 100 degrees CelsiusDo not seethe with excitement, between 0 degree Celsius to 100 degrees Celsius, be liquid state.
In an embodiment, described cooling fluid is engine fluid therein.
In an embodiment, described circulation line is Thermostable flexible hose therein.
In an embodiment, described cooling system also comprises blower fan therein.
Said gene amplification device comprises heating system and cooling system, and heating system comprises heating source and heat conductionModule, heating source is ceramic heater or paster power resistor, cooling system comprises to be offered in heat conducting moduleFirst liquid pipeline, heat sink, circulation line, cooling fluid and circulating pump, by circulating pump control cooling fluidIn the close access forming at first liquid pipeline, second liquid pipeline and circulation line, circulate or stop,Realize the rapid temperature rise and drop of heat conducting module, the temperature homogeneity of module has greatly improved.
Brief description of the drawings
Fig. 1 is the schematic diagram of gene amplification device in present embodiment;
Fig. 2 is the schematic diagram of heat conducting module in present embodiment;
Fig. 3 is the schematic diagram of heat sink in present embodiment.
Detailed description of the invention
For above-mentioned purpose of the present invention, feature and advantage can be become apparent more, below in conjunction with accompanying drawing pairThe specific embodiment of the present invention is described in detail. Set forth in the following description a lot of details withBe convenient to fully understand the present invention. But the present invention can come real to be a lot different from alternate manner described hereExecute, those skilled in the art can do similar improvement without prejudice to intension of the present invention in the situation that, therefore thisThe bright restriction that is not subject to following public specific embodiment.
It should be noted that, when element is called as " being fixed on " another element, it can be directly at anotherOn individual element or also can have an element placed in the middle. When an element is considered to " connection " another yuanPart, it can be directly connected to another element or may have centering elements simultaneously.
Unless otherwise defined, all technology and the scientific terminology using herein and belong to technology of the present inventionThe implication that the technical staff in field understands is conventionally identical. The art using in description of the present invention hereinLanguage, just in order to describe the object of specific embodiment, is not intended to be restriction the present invention. Use hereinTerm " and/or " comprise one or more relevant Listed Items arbitrarily with all combinations.
Please refer to Fig. 1, Fig. 2 and Fig. 3, present embodiment provides a kind of gene amplification device 100. This geneAmplification device 100 comprises heating system and cooling system, and heating system is for to reaction reagent heating, coolingSystem is for lowering the temperature to reaction reagent. Heating system comprises heating source 130 and heat conducting module 110. Heating source130 and heat conducting module 110 between be connected by heat-conducting medium 120, heat-conducting medium 120 is loose by heating source 130The thermal energy transfer of sending is to heat conducting module 110, heat conducting module 110 again by thermal energy transfer to reaction reagent. CoolingSystem comprise the first liquid pipeline 111 offered in heat conducting module 110, heat sink 140, circulation line 150,Cooling fluid and circulating pump 160, heat sink 140 distributes for the heat energy that collecting plate is collected, circulation line150 is resistant to elevated temperatures flexible pipe, and what in present embodiment, use is platinum silicon sulfide sebific duct. In heat sink 140, establishThere is the second liquid pipeline 141 being communicated with circulation line 150, first liquid pipeline 111, second liquid pipeline141 are connected with circulation line 150, form a close access, and cooling fluid circulates in this close access,Heat energy on heat conducting module 110 and the heating source 130 that heat conducting module 110 is collected is loose by heat sink 140Be dealt in air. Such gene amplification device is without adopting semiconductor cooler can realize high speed heating and coolingWith excellent module temperature homogeneity.
Heating source 130 is ceramic heater or paster power resistor. Heating source 130 can be attached to heat conduction mouldPiece 110 bottoms, also can be embedded into inside. The resistance of resistance can be according to heat conducting module 110 Temperature DistributionRule is adjusted and is set, to produce suitable heating power, heat conducting module 110 is obtained highlyTemperature homogeneity, and make the gene amplification reaction experiment of reaction reagent obtain high consistency.
In the time adopting ceramic heater as heating source 130, ceramic heater is by exchanging or direct current supply.In the time adopting paster power resistor as heating source 130, paster power resistor is arranged in array, and by leadingHeat-curable glue is filled this array, makes it to form an insulation calandria, and this insulation calandria is adding nowThermal source, certainly, also can use other similar heater members. Between heating source 130 and heat conducting module 110Be provided with heat-conducting medium 120, the heat energy that heating source 130 sends passes to heat conducting module by heat-conducting medium 120110, thus reach the effect to reaction reagent heating.
In heat conducting module 110, offer first liquid pipeline 111, and be also provided with and can supply on heat conducting module 110First interface 112 and the second interface 113 that cooling fluid flows into and flows out. First interface 112 and the second interface 113The first liquid pipeline of establishing in heat conducting module 110 111 and circulation line 150 are coupled together, make coolingLiquid can flow smoothly between first liquid pipeline 111 and circulation line 150. First interface 112 and secondThe quantity of interface 113 can be one or more. In first liquid pipeline 111 in heat conducting module 110Path can be walk abreast, serial, bifurcated, turnover, merging. Particularly cooling when forming cross-modality turnoverWhen liquid, can make the reaction reagent on heat conducting module 110 obtain highly consistent dynamic temperature variation, makeThe uniformity of gene magnification experimental result is ensured. When at needs, reaction reagent being carried out when cooling, by flowingCooling fluid through this heat conducting module 110 is directly taken away the heat energy that heat conducting module 110 is collected, and makes heat conducting moduleIt is maximum that 110 rate of temperature fall reaches, thereby reach, reaction reagent carried out to cooling effect.
First liquid pipeline 111 both sides connect respectively circulation line 150, another of these two circulation lines 150End is connected with second liquid pipeline 141 both sides respectively, first liquid pipeline 111, second liquid pipeline like this141 and circulation line 150 just formed a close access. Circulating pump 160 is installed on a wherein circulation pipeOn road 150, promote cooling fluid and in close access, flow or stop realizing the heating and cooling to reaction reagent.
Heat sink 140 can be arranged at the optional position of this gene amplification device 100, but its internal structure withWhat heat conducting module 110 was identical offers second liquid pipeline 141, and on heat sink 140, offer can coolingBut liquid flows into and flows out the first heat radiation interface 142 and the second heat radiation interface 143, this first heat radiation interface 142With the second heat radiation interface 143 for second liquid pipeline 141 and circulation line 150 are coupled together, with theOne liquid line 111 forms close access. The quantity of the first heat radiation interface 142 and the second heat radiation interface 143Be at least 1. Path in second liquid pipeline 141 in heat sink 140 can be walk abreast, serial, bifurcated,Turnover, merging. Heat sink 140 is made up of metal material, has high density fin radiating structure. When coolingWhen system is opened, heat sink 140 distributes cooling fluid from the heat energy of collecting plate band.
Circulating pump 160 is installed on circulation line 150, under the control of the signal of telecommunication, promotes in cooling systemCooling fluid flows in close access, can also according to actual needs, strengthen or weaken the stream of cooling fluidMoving heat-exchange capacity. In addition, circulating pump 160 is interior can be added inject cooling liquid and can store a certain amount of liquid,To get rid of the air in close access.
Cooling fluid have in the time of 0 DEG C can not solidify, the vaporization of can not seething with excitement in the time of 100 DEG C, at 0 DEG C to 100 DEG CBetween for example, for liquid and there is corrosion resistant characteristic, engine fluid, the work of certain engine fluidTemperature is subzero 35 degrees Celsius to 107 degrees Celsius. In the present embodiment, cooling fluid is used engine anti-Freeze liquid.
The cooling system of this gene amplification device 100 also comprises blower fan 170, and this blower fan 170 acts on heat sinkOn 140, can strengthen the thermal convection current radiating effect of heat sink 140 and surrounding air, thereby improve rate of temperature fall.
When this gene amplification device 100 is during in heated condition, circulating pump 160 is in closed condition, coolingLiquid remains static in close access, and now the heat energy in heat conducting module 110 can not be cooled and beA large amount of losses of uniting. When gene amplification device 100 is during in the state of cooling, be turned off as heating source 130,Circulating pump 160 is in opening, and the cooling fluid in heat conducting module 110 is by the driving circulation line 150 of flowing throughWith second liquid pipeline 141, carry out convective heat exchange at second liquid pipeline 141 places and surrounding air, and wind170, machine has strengthened the heat exchange action of heat sink 140. Circulate in close access by controlling cooling fluidFlow, heat conducting module 110 temperature are able to rapid decline, thereby drive reaction reagent temperature fast-descending. ThisThe gene amplification device of sample can be realized the utilization ratio of heating source 130, has reduced the load of heating source 130,More energy is directly used in heat conducting module 110, makes heat conducting module 110 heating rate maximums; Meanwhile, coldBut the liquid heat conducting module 110 of directly being flowed through, makes heat conducting module 110 rate of temperature fall maximums.
The above embodiment has only expressed several embodiment of the present invention, and it describes comparatively concrete and detailed,But can not therefore be interpreted as the restriction to the scope of the claims of the present invention. It should be pointed out that for this areaThose of ordinary skill, without departing from the inventive concept of the premise, can also make some distortion andImprove, these all belong to protection scope of the present invention. Therefore, the protection domain of patent of the present invention should be with appendedClaim is as the criterion.
Claims (8)
1. a gene amplification device, comprises heating system and cooling system, and described heating system comprises heatingSource and heat conducting module, described heating source heats reaction reagent by heat conducting module, it is characterized in that, described inHeating source is to fill the insulation that the array that is arranged in by paster power resistor forms and heat by leading heat-curable glueBody, described cooling system comprises the first liquid pipeline offered in heat conducting module, for distributing the heat radiation of heat energyPlate, circulation line, cooling fluid and for promoting the circulating pump of described coolant flow, establish in described heat sinkHave the second liquid pipeline being communicated with described circulation line, described first liquid pipeline, second liquid pipeline andDescribed circulation line is communicated with formation close access.
2. gene amplification device according to claim 1, is characterized in that, on described heat conducting module, establishesHave first interface and the second interface, described first interface and the second interface by described first liquid pipeline with described inCirculation line is communicated with, and the quantity of described first interface and the second interface is at least 1, in described first liquid pipelinePortion path is parallel or serial or bifurcated or turnover or merging.
3. gene amplification device according to claim 1, is characterized in that, described heat sink is provided withOne heat radiation interface and the second heat radiation interface, described the first heat radiation interface dispels the heat interface by described the with described secondTwo liquid lines are communicated with described circulation line, and the quantity of described the first heat radiation interface and the second heat radiation interface extremelyBe 1 less, described second liquid pipeline inner track is parallel or serial or bifurcated or turnover or merging.
4. gene amplification device according to claim 1, is characterized in that, described heat sink is provided withRadiating fin.
5. gene amplification device according to claim 1, is characterized in that, described cooling fluid is taken the photograph 0When family name spends, do not solidify, in the time of 100 degrees Celsius, do not seethe with excitement, between 0 degree Celsius to 100 degrees Celsius, be liquid state.
6. gene amplification device according to claim 5, is characterized in that, described cooling fluid is for startingMachine anti-icing fluid.
7. gene amplification device according to claim 1, is characterized in that, described circulation line is resistance toHigh temperature hose.
8. according to the gene amplification device described in any one in claim 1-7, it is characterized in that, described coldBut system also comprises blower fan.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410210884.3A CN103992938B (en) | 2014-05-19 | 2014-05-19 | gene amplification device |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410210884.3A CN103992938B (en) | 2014-05-19 | 2014-05-19 | gene amplification device |
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| CN103992938A CN103992938A (en) | 2014-08-20 |
| CN103992938B true CN103992938B (en) | 2016-05-25 |
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| CN201410210884.3A Active CN103992938B (en) | 2014-05-19 | 2014-05-19 | gene amplification device |
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| JP7139525B2 (en) * | 2019-05-17 | 2022-09-20 | 株式会社日立ハイテク | automatic analyzer |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001051209A1 (en) * | 2000-01-15 | 2001-07-19 | Eppendorf Ag | Laboratory temperature-regulating device comprising a temperature-controlled thermostatic block |
| EP1710017A1 (en) * | 2005-04-04 | 2006-10-11 | Roche Diagnostics GmbH | Thermocycling of a block comprising multiple sample |
| CN102046291A (en) * | 2008-04-04 | 2011-05-04 | It-Is国际有限公司 | Thermal control system and method for chemical and biochemical reactions |
| CN203855571U (en) * | 2014-05-19 | 2014-10-01 | 苏州东胜兴业科学仪器有限公司 | Gene amplification device |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8828712B2 (en) * | 2007-06-29 | 2014-09-09 | Toppan Printing Co., Ltd. | Genetic detection and determination apparatus and method, gene reactor, and incubator |
| CN102604824A (en) * | 2012-02-29 | 2012-07-25 | 北京工业大学 | Space-oriented mini micro-fluidic real-time fluorescent PCR (Plymerase Chain Reaction) working system |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001051209A1 (en) * | 2000-01-15 | 2001-07-19 | Eppendorf Ag | Laboratory temperature-regulating device comprising a temperature-controlled thermostatic block |
| EP1710017A1 (en) * | 2005-04-04 | 2006-10-11 | Roche Diagnostics GmbH | Thermocycling of a block comprising multiple sample |
| CN102046291A (en) * | 2008-04-04 | 2011-05-04 | It-Is国际有限公司 | Thermal control system and method for chemical and biochemical reactions |
| CN203855571U (en) * | 2014-05-19 | 2014-10-01 | 苏州东胜兴业科学仪器有限公司 | Gene amplification device |
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