KR20080052220A - Apparatus for pcr using a disposable polymer chip and natural convection and method the same - Google Patents

Abstract

A natural convection apparatus for PCR(polymerase chain reaction) is provided to transfer automatically a sample by supplying periodical temperature changes to a sample through natural convection with a disposable polymer chip having a loop type channel, so that a portable PCR apparatus is accomplished. A natural convection apparatus for PCR comprises: a polymer chip(100) having a loop type microchannel connected to a plurality of channels, wherein a sample is filed into the microchannel; a plurality of heating metal portion(300) for transferring the heat by contacting with the loop type microchannel of the polymer chip; a temperature controller(500) connected to the heating metal portion for maintaining the temperatures of heating metal portion differently; a heater(420) connected to the heating metal portion and temperature controller for supplying the heat to the heating metal portion by the temperature controller; and a temperature sensor(400) connected to the heating metal portion and temperature controller. Further, the plurality of channels contain a dissociation channel, an annealing channel and an extension channel.

Description

[0001] The present invention relates to a natural convection PCR apparatus using a disposable polymer chip,

1 is a schematic diagram of a natural convection PCR apparatus using a disposable polymer chip according to the present invention.

2 is a sectional view taken along the line A-A 'shown in Fig.

3 is a plan view schematically illustrating the shape of a disposable polymer chip and a channel according to the present invention.

4 is a schematic illustration of a substrate adhering process for forming a channel of a disposable polymer chip according to the present invention.

FIG. 5 is an explanatory view schematically showing a process of moving a sample to a channel of a disposable polymer chip according to the present invention. FIG.

6 is a conceptual view of a capillary stop valve of a disposable polymer chip according to the present invention.

7 is a computer simulation result of a sample flow in a channel due to natural convection of the disposable polymer chip according to the present invention.

FIG. 8 is an explanatory diagram of a change in PCR time according to the orientation of the disposable polymer chip according to the present invention. FIG.

9 is a schematic plan view with a gas tight plate to prevent evaporation of a sample of a disposable polymer chip according to the present invention.

10 is a schematic plan view showing a sample pretreatment section for PCR at the inlet end of the disposable polymer chip according to the present invention.

DESCRIPTION OF REFERENCE NUMERALS

100: polymer chip 105: polymer chip flow substrate

110: polymer chip cover plate 111: hole

200: channel 210 of polymer chip: dissociation channel

220: Extension channel 230: Annealing channel

241: dissociation-annealing connection channel 242: extended-dissociation connection channel

243: Annealing-extended connection channel 244: Insulation hole

250: capillary stop valve 260: inlet

270: outlet 280: outlet connecting channel

290: inlet connection channel 300: heating metal part

310: heating metal block 320: heating metal pin

330: heating metal contact 400: temperature sensor

410: heater wire 420: heater

500: Temperature controller 600: Airtight plate

700:

The present invention relates to a natural convection PCR apparatus using a disposable polymer chip and a method thereof. More particularly, the present invention relates to a method for forming a looped channel on a polymer chip and contacting each channel with a heated metal portion maintained at a different temperature to provide a cyclic temperature To a natural convection PCR apparatus using the disposable polymer chip and a method thereof.

In general, biochips, biosensors, and chemical sensors for biochemical analysis require that a predetermined reaction be performed by applying a constant temperature change to a sample. Various heating methods have been proposed for this purpose. As a representative example of a device that reacts by applying a constant temperature change, there is a DNA amplification device that amplifies DNA by adding an enzyme to a DNA template and applying a constant temperature cycling.

More specifically, the temperature cycling is to change the temperature to two or three different temperatures. That is, denaturation to separate the DNA double helix, annealing to arrange for the DNA template to find a complementary pair, and temperature extension for DNA growth. PCR (Polymerase Chain Reaction) is the amplification of DNA by this temperature change.

The heating method for providing the PCR temperature change is roughly classified into two types. One is a method of changing the temperature of a sample by applying a temperature change externally to a sample which is charged in the chamber and the other is a method of transferring the temperature to a sample by transferring the sample to an environment having a desired temperature condition. Here, in the case of changing the external temperature environment to the stopped sample, there is an advantage that the additional fluid control operation is not necessary since the sample is stopped. However, in order to change the external temperature environment, it takes a lot of time when the external environment has a large heat capacity, and the control operation for temperature change is additionally required, which is complicated.

On the other hand, in the case of the method of applying the temperature change by transferring the sample, since the external temperature environment is kept constant, there is an advantage that the temperature can be changed quickly and accurately, but the problem of requiring the fluid control operation for transferring the sample .

Therefore, as a method to overcome the disadvantages of the above-mentioned two methods, a method of periodically applying a temperature change to a sample is a method of using a natural convection to pass a constant temperature range without needing an additional external fluid control operation To quickly and accurately change the temperature of the sample.

The natural convection is a flow phenomenon resulting from the generation of buoyancy due to the density change of the fluid generated by the heat generated by the fluid placed under the gravity field. When the fluid is placed in a relatively cool and hot external environment, downward and upward flows occur, respectively. In PCR, the denaturation is 90-97 ° C, annealing is 50-65 ° C, and extension is 68-74 ° C, depending on the type of DNA sample to be amplified. Therefore, the natural convection flow can be generated by using the temperature difference, and the flow is naturally generated in the presence of the gravitational field, so that the fluid control operation for transferring the sample from the outside can be omitted .

Methods and apparatus for PCR using natural convection are known, and methods and apparatus for PCR using natural convection according to the known methods will be described below.

Examples of PCR using natural convection include, but are not limited to, US 6586233 "Convectively driven PCR thermal-cycling", US 2004/0152122 "Method and apparatus for amplification of nucleic acid sequences using thermal convection" -0025027 " PCR apparatus using Marangoni convection and PCR method using the same ". In the above-mentioned " Convectively driven PCR thermal-cycling ", a method of performing PCR temperature cycling using a convection generated by pressing a pouch-type sample reservoir in a heating block heated by two separate temperature trenches is presented And the pouch-shaped sample reservoir is inserted into the groove in the heating block. In the above-mentioned " Method and apparatus for amplifying nucleic acid sequences using thermal convection ", a relatively high temperature region is installed at a low height, a relatively low temperature region is installed at a high height, A method and an apparatus have been proposed in which PCR is carried out by spatially changing the temperature in a sample to generate convection, and "PCR apparatus using Marangoni convection and PCR method using the same" , And a PCR apparatus and a method using a convection phenomenon by the surface tension of margarine surface generated at the interface of the sample are proposed.

In addition, a paper published in Anal. Chem., Vol. 76, entitled "Thermosiphon-based PCR reactor: Experiment and modeling," was published in the paper, And a loop is formed by a tube at the center thereof, thereby performing PCR.

However, the above-mentioned known patent documents and papers disclose a method and an apparatus in which PCR is performed by using a pouch-type sample reservoir or tube and applying a local spatial temperature change to generate natural convection, In case of using a tube, it is inconvenient to inject the sample, or the tube must be replaced when reused, and it is difficult to produce multiple samples. In addition, the spatial temperature change is a structure that is difficult to efficiently remove heat interference, and there is a problem that the sample is heated to a desired temperature in each temperature range by attempting local heating on the side of the sample volume, .

SUMMARY OF THE INVENTION The present invention has been made in order to solve the above problems, and it is an object of the present invention to provide a method of forming a loop type channel on a polymer chip and bringing the heated metal part, The present invention provides a natural convection PCR apparatus using the disposable polymer chip and a method thereof, in which a flow due to convection is generated so as to provide a periodic temperature change to the sample.

Another object of the present invention is to provide a PCR device which can be used as an element which can be manufactured at low cost by using a polymer substrate and which can be used as a portable PCR device without external flow control and requiring only simple temperature control, A natural convection PCR apparatus using the disposable polymer chip and a method thereof, which precisely realizes the temperature change of the sample by preventing the interference, and the sample is completely filled with the capillary flow without the air layer in the loop type microchannel, .

In order to accomplish the above object, the present invention provides a polymer chip in which a loop-type microchannel to which a plurality of channels are connected is formed and a sample is charged into a channel; A plurality of heating metal parts for contacting the loop type microchannel of the polymer chip to transfer heat; A temperature controller connected to the plurality of heating metal parts and maintaining the plurality of heating metal parts at different constant temperatures; A heater connected to the plurality of heating metal parts and the temperature controller and supplying heat to the heating metal part by a temperature controller; And a temperature sensor connected to the plurality of heated metal parts and the temperature controller. The present invention also provides a natural convection PCR apparatus using the disposable polymer chip.

The loop-type microchannel includes an inlet through which the sample flows, a plurality of channels, a connection channel connecting the channels and flowing the sample, and an outlet through which the sample flows.

The loop type microchannel further includes a capillary stop valve for filling the sample in the channel without the air layer.

In addition, the plurality of channels include a dissociation channel, an annealing channel, and an extension channel.

The polymer chip is formed by adhering a polymer film and a flow path substrate on which channels are formed by injection molding or hot embossing. The adhesion between the flow channel substrate and the polymer film is made by a lamination method and an adhesive bonding. In addition, the polymer chip prevents the surface of the channel from being biologically, chemically, and optically processed and adsorbing components such as biomolecules in the heating fluid to the channel surface.

The heated metal portion being connected to the heater and being heat-transferred from the heater; A heated metal pin connected to be protruded from the heated metal block and heat-transferred from the heated metal block; And one side of which is connected to the heated metal pin and the other side of which is in contact with the channel of the polymer chip.

Further, the heated metal part is formed in a slot shape so that the heated metal block, the heated metal pin, and the heated metal contact part are integrated and the polymer chip can be inserted. The heating metal block is maintained at a constant temperature by a heater, a temperature controller, and a temperature sensor. A sample in the loop-type microchannel is heated to a predetermined temperature by the heating metal block, So that the sample flows along the loop and the temperature changes sequentially.

The heating metal part further includes a heat insulating material for fixing the thermal metal block to minimize thermal interference between the heated metal blocks maintained at different temperatures, and a heating metal block is fixed and installed between the heat insulating materials.

The heater may be a film heater, a ceramic heater, or a rod heater.

The polymer chip is mounted at an angle with respect to the direction of gravitational field so that the natural convection PCR time is adjusted.

The natural convection PCR apparatus using the disposable polymer chip according to the present invention further comprises a fluorescence detector for obtaining a PCR result in real time using the polymer chip.

The polymer chip may be made of a polymer such as polymethylmethacrylate (PMMA), polycarbonate (PC), cycloolefin copolymer (COC), polyamide (PA), polyethylene (PE) , Polypropylene (PP), polyphenylene ether (PPE), polystyrene (PS), polyoxymethylene (POM), polyetheretherketone (PEEK), polytetrafluoroethylene Polytetrafluoroethylene (PTFE), polyvinylchloride (PVC), polyvinylidene fluoride (PVDF), polybutylene terephthalate (PBT), fluorinated ethylenepropylene (FEP) And perfluoroalkoxyalkane (PFA).

The present invention is a natural convection PCR method using a disposable polymer chip including the polymer chip, a heated metal part, a temperature controller, a heater, and a temperature sensor. The heated convection PCR method uses a heater, a temperature controller and a temperature sensor, And heating the sample in the looped microchannel to a predetermined temperature through the heating metal part to cause natural convection by the heating so that the sample flows along the loop by the natural convection so that a sequential temperature change A natural convection PCR method using a disposable polymer chip.

In addition, the natural convection PCR apparatus using the disposable polymer chip according to the present invention can be used as an inexpensive multi-productable device using a polymer substrate, requires no external flow control device, requires only simple temperature control, It can be used as a device.

Since the polymer chip is manufactured in the form of a microchannel, the flow of the sample is smooth, the interference or resistance is small, and the sample is completely filled with the capillary flow without the air layer in the loop type microchannel. .

In addition, a loop type microchannel is formed on a polymer substrate capable of multi-fabrication, and thermal interference of the heated metal part is prevented, thereby realizing a temperature change of the sample accurately.

In the loop type microchannel of the polymer substrate according to the present invention, the sample is completely filled with only the capillary flow without the air layer, and the sample can smoothly flow.

In addition, the polymer chip according to the present invention is easy to be directly applied to various sensors that can be formed on a plane using a two-dimensional polymer substrate. In addition, in the heating method, the polymer chip is locally heated only in the loop-type microchannel according to the two-side contact so that thermal interference is minimized, only a very simple temperature controller is required, and a small and light- To provide a natural convection PCR apparatus.

Hereinafter, the configuration, functions, and effects of the natural convection PCR apparatus using the disposable polymer chip according to the present invention and preferred embodiments of the method will be described in detail.

FIG. 1 is a view for explaining an embodiment of a natural convection PCR apparatus using the disposable polymer chip of the present invention, and FIG. 2 is a sectional view taken along the line A-A 'shown in FIG. As shown in the figure, the natural convection PCR apparatus comprises a polymer chip 100, a heating metal part 300, a temperature controller 500, a heater 420, and a temperature sensor 400.

The polymer chip 100 is formed by combining a flow channel substrate 105 and a polymer chip cover plate 110 on which a plurality of looped microchannels 200 (shown in FIGS. 3 and 5) are connected.

The plurality of heated metal parts 300 are for contacting and transferring heat to the looped microchannels of the polymer chip and include a heated metal block 310, a heated metal pin 320, and a heated metal contact 330 . The plurality of heating metal blocks 310 are for receiving heat from the heater 420 and transferring heat to the channels. The heating metal pins 320 are connected to the heating metal block 310, It is preferable to be formed of a metal having high thermal conductivity so that heat can be easily transmitted to the channel. The heated metal contact portion 330 protrudes from the heated metal pin and contacts both outer surfaces of the plurality of channels 210, 220 and 230 of the polymer chip 100 to heat the heated metal block 310 to the channel of the polymer chip 100 .

As described above, the heating metal block 310, the heating metal pin 320, and the heating metal contacting part 330 forming the heating metal part 300 are integrally formed into a slot shape so that the polymer chip can be fitted .

In addition, the heated metal pins 320 may be connected to a plurality of the heating metal blocks 310 to form a plurality of slots, thereby mounting many polymer chips at the same time. In addition, it is preferable that the heating metal block 310 is fixed and installed with a heat insulating material interposed therebetween so that thermal interference between the metal heating blocks maintained at different temperatures is minimized and fixed.

It is preferable that the contact surfaces of the heating metal contact parts 310, which are in contact with the channels of the polymer chip 100, are in contact with each other without forming an air layer at the contact parts, so that the surfaces are smoothly processed to facilitate heat transfer.

The temperature controller 500 is for maintaining the plurality of heated metal blocks 310 at a constant temperature, that is, for PCR, through the heater 420 and the temperature sensor 400.

The heater 420 is for heating a plurality of heating metal blocks 310 and is coupled to or inserted into a plurality of heating metal blocks and is connected to the temperature controller 500 through a heater wire 410 . Further, the heater 420 according to the present invention preferably comprises one of a film heater, a ceramic heater, and a rod heater.

The temperature sensor 400 is for detecting the temperature of the heated metal block and is connected to the plurality of heated metal blocks 310 and the temperature controller 500.

2, the natural convection PCR apparatus using the disposable polymer chip according to the present invention includes the heating metal block 310, the heating metal pin 310, and the heating metal contact 330, The polymer chip 100 is mounted in a slot-shaped space formed by the metal pins 100 and the heated metal pins are spatially separated from each other to remove thermal interference. In addition, since only the heated metal contacts 330 are in contact with the polymer chip, interference between different temperature zones on the polymer chip 100 is minimized.

3 is a plan view schematically showing the shapes of disposable polymer chips and channels according to the present invention. As shown in the figure, the polymer chip channel 200 includes a denaturation channel 210, an annealing channel 230, and an extension channel 220 for three temperature regions for PCR. And the channels are looped by a dissociation-annealing connection channel 241, an extension-dissociation connection channel 242 and an annealing-extension connection channel 243. Further, an inlet 260, an outlet 270, and connection channels 280 and 290 are further formed for the inflow and outflow of the sample. Also, the channel of the polymer chip according to the present invention is provided with a capillary stop valve 250 in the channel for charging the sample into the loop-shaped channel without clogging of the sample by the air layer. Also, in order to minimize thermal interference between channels, a heat insulating hole 244 is formed by removing the center portion of the closed curved cross section of the loop type channel.

4 is a schematic illustration of a substrate adhering process for forming a channel of a disposable polymer chip according to the present invention. As shown in the drawing, the channel is formed on the flow path substrate 105 by a method such as injection molding and hot embossing, and the channel substrate has a hole 111 corresponding to the inlet 260 and the outlet 270, The chip cover plate 110 is bonded to form a polymer chip. In addition, it is preferable that the flow channel substrate 105 and the chip cover plate 110 are bonded by a lamination method and an adhesive bonding.

As a material for forming the polymer chip, a material such as polymethylmethacrylate (PMMA), polycarbonate (PC), cycloolefin copolymer (COC), polyamide (PA), polyethylene polyethylene, PE), polypropylene (PP), polyphenylene ether (PPE), polystyrene (PS), polyoxymethylene (POM), polyetheretherketone Polytetrafluoroethylene (PTFE), polyvinylchloride (PVC), polyvinylidene fluoride (PVDF), polybutyleneterephthalate (PBT), fluorinated ethylenepropylene, FEP), and perfluoroalkoxyalkane (PFA).

The channel of the polymer chip 100 may be formed by hot embossing, injection molding, casting, stereolithography, laser ablation, rapid prototyping, ), Silkscreen as well as Numerical Control (NC) machining.

In addition, it is preferable that the channel of the polymer chip 100 be biologically, chemically, and optically treated so that components such as biomolecules in the heating fluid are adsorbed on the channel surface.

FIG. 5 is an explanatory view schematically showing a process of moving a sample to a channel of the disposable polymer chip according to the present invention. As shown in the drawing, the loop-type microchannel 200 is provided with a capillary stop valve 250 for charging the sample without the air layer.

More specifically, as shown in FIGS. 5A, 5B, and 5C, the sample introduced from the inlet 260 of the channel 200 fills the inlet connection channel 290, The sample introduced into the dissociation-annealing connection channel 241 is stopped by the capillary stop valve 250 formed at the end. 5 (d) and 5 (e), the sample moving to the dissociation channel 210 flows into the annealing channel 230 and the extension channel 220 through the connection channels 242 and 243, Type microchannel 200 is charged. And then flows into the outlet connection channel 280 and the outlet 270 in contact with the sample stopped at the capillary stop valve 250. Also, in the course of filling the sample, the microchannel can be completely filled with the sample without clogging by the air layer.

 6 is a conceptual diagram of a capillary stop valve of a disposable polymer chip according to the present invention. As shown in FIG. 6A, the capillary stop valve 250 according to the present invention shown in FIG. 6A has a case in which a stepped portion is formed in the channel height direction as shown in FIG. 6B, The capillary force can be stopped through the case where the width of the channel 241 is enlarged as shown in (c) of FIG. In addition, if the above two effects are used at the same time, the sample can be more stably stopped, and it is preferable that the capillary stop valve 250 is mounted in this form.

7 is a computer simulation result of the flow of a sample in a channel by natural convection of the disposable polymer chip according to the present invention. As shown in the figure, upward flow is generated in the channel 200 due to relatively high temperature in the dissociation channel 210, and a downward flow is generated due to a relatively low temperature in the annealing channel 230. Also, the channel 200 of the polymer chip according to the present invention is connected in a loop shape, and it can be confirmed that a constant flow is generated in each channel.

FIG. 8 is an explanatory view of a change in PCR time according to the orientation of the disposable polymer chip according to the present invention. As shown in FIG. 8A, the natural convection determines the intensity of flow in proportion to the size of the gravitational field. Therefore, when the polymer chip 100 of the present invention is inclined at a certain angle (?) With respect to the gravitational field g PCR time can be varied. Also, as shown in Fig. 8 (b), the flow becomes slower as the inter-chip angle in the direction of the gravity field becomes larger.

FIG. 9 is a schematic plan view of a disposable polymer chip according to the present invention, in which a gas tight plate is attached to prevent the sample from evaporating. As shown in the figure, there is a risk that air bubbles may form in the sample or evaporate by applying heat to the sample during the PCR process. Therefore, the airtight plate 600 may be further attached to the inlet 260 and the outlet 270 to prevent this. The airtight plate 600 is preferably made of a material having elasticity. Further, it is preferable to maintain airtightness by applying an adhesive to one surface or by applying mechanical pressure.

FIG. 10 is a schematic plan view showing a sample pretreatment section for PCR at the inlet end of the disposable polymer chip according to the present invention. As shown in the figure, a sample for PCR may require a preprocessing process for extracting and purifying DNA from a sample depending on the type. For this purpose, it is preferable to provide a sample pretreatment unit 700 at the front end of the inlet 260. The sample pretreatment unit 700 is preferably implemented on a disposable polymer chip as illustrated in FIG. 10, but may be implemented in the form of an external structure attached to the inlet 260.

The natural convection PCR apparatus using the disposable polymer chip according to the present invention may further comprise a fluorescence detector for obtaining a PCR result in real time using the polymer chip. In addition, a fluorescence detection method that can obtain results in real time using the fluorescence detector can be easily implemented by those skilled in the art, and it is obvious that all of the technical implementations using the method are within the scope of the present invention.

The natural convection PCR apparatus using the disposable polymer chip according to the present invention is as described above. In addition, the polymer chip 100, the heated metal part 300, the temperature controller, A natural convection PCR method using a disposable polymer chip including a heater and a temperature sensor, comprising the steps of: maintaining a metal heating block at a constant temperature by using a heater, a temperature controller and a temperature sensor; To a natural convection PCR method using a disposable polymer chip in which natural convection is caused by the heating and a sample flows along a loop by the natural convection to apply a sequential temperature change for PCR .

The natural convection PCR method using the disposable polymer chip according to the present invention can be implemented as a program and stored in a computer readable recording medium (CD-ROM, RAM, ROM, floppy disk, hard disk, magneto-optical disk, etc.) . The storing process can be easily implemented by those skilled in the art.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the invention. The present invention is not limited to the drawings.

According to the present invention, a loop channel is formed on a polymer chip, a heating metal portion maintained at a different temperature is brought into contact with each channel, and a flow due to natural convection is generated in the loop channel, The present invention provides a natural convection PCR apparatus and method using a disposable polymer chip that provides a periodic temperature change, and can be used as a device capable of low-cost multi-fabrication using a polymer substrate. In addition, there is no external flow control, And it is possible to use it as a portable PCR device. By making it in the form of a microchannel, the flow of the sample is smooth and the temperature change of the sample is precisely realized, the interference between the samples is minimized. In the loop type microchannel, Disposable polymer chips that are completely filled with capillary flow and can move the sample smoothly A natural convection PCR apparatus using the same, and a method therefor.

Claims (19)

A polymer chip in which a loop type microchannel to which a plurality of channels are connected is formed and a sample is charged into a channel; A plurality of heating metal parts for contacting the loop type microchannel of the polymer chip to transfer heat; A temperature controller connected to the plurality of heating metal parts and maintaining the plurality of heating metal parts at different constant temperatures; A heater connected to the plurality of heating metal parts and the temperature controller and supplying heat to the heating metal part by a temperature controller; And And a temperature sensor connected to the plurality of heating metal parts and the temperature controller Natural convection PCR device using disposable polymer chip. The method according to claim 1, The loop- A plurality of channels, an inlet through which the sample flows, a channel through which the sample flows, and an outlet through which the sample flows, Natural convection PCR device using disposable polymer chip. 3. The method of claim 2, The loop- Further comprising a capillary stop valve for filling the sample in the channel without an air layer Natural convection PCR device using disposable polymer chip. 4. The method according to any one of claims 1 to 3, The plurality of channels Including dissociation channels, annealing channels, and extension channels. Natural convection PCR device using disposable polymer chip. The method according to claim 1, The polymer chip A channel substrate on which a channel is formed by injection molding or hot embossing is adhered to a polymer film Natural convection PCR device using disposable polymer chip. 6. The method of claim 5, The adhesion between the flow channel substrate and the polymer film Lamination method and adhesive bonding Natural convection PCR device using disposable polymer chip. 6. The method according to claim 1 or 5, The polymer chip The surface of the channel is biologically, chemically, and optically treated so that components such as biomolecules in the heating fluid are prevented from adsorbing to the channel surface Natural convection PCR device using disposable polymer chip. The method according to claim 1, The heated metal portion A heating metal block connected to the heater and being heat-transferred from the heater; A heated metal pin connected to be protruded from the heated metal block and heat-transferred from the heated metal block; Wherein the one surface comprises a heated metal contact protruding from the heated metal pin and having one side in contact with the channel of the polymer chip Natural convection PCR device using disposable polymer chip. 9. The method of claim 8, The heated metal portion The heated metal block, the heated metal pin, and the heated metal contact are integrated and formed into a multi-slot type in which a plurality of polymer chips can be inserted Natural convection PCR device using disposable polymer chip. 9. The method of claim 8, The heated metal block Maintained at a constant temperature by a heater, a temperature controller and a temperature sensor, The sample in the loop-type microchannel is heated to a predetermined temperature by the heating metal block, and natural convection is generated by the heating, so that the sample flows along the loop and the temperature is sequentially changed Natural convection PCR device using disposable polymer chip. 9. The method of claim 8, The heated metal portion Further comprising a thermal insulation for fixing thermal interference between the heated metal blocks maintained at different temperatures so as to minimize thermal interference, wherein a heating metal block is fixed and installed between the thermal insulation Natural convection PCR device using disposable polymer chip. The method according to claim 1, The heater A film heater, a ceramic heater, and a rod heater. Natural convection PCR device using disposable polymer chip. The method according to claim 1, The plurality of heated metal parts are brought into contact with both sides of the loop-shaped microchannel of the polymer chip, Natural PCR apparatus using disposable polymer chip. The method according to claim 1, The polymer chip And the natural convection PCR time is adjusted at a predetermined angle with respect to the gravitational field direction Natural convection PCR device using disposable polymer chip. The method according to claim 1, The polymer chip Further comprising a gas tight plate for blocking the inlet and the outlet from the outside air in order to prevent air bubbles from being generated or evaporated in the sample during the PCR process Natural convection PCR system using polymer chip. The method according to claim 1, The polymer chip Further comprising a preprocessor provided at the front end of the inlet of the polymer chip for the preprocessing of the sample for PCR Natural convection PCR system using polymer chip. The method according to claim 1, And a fluorescence detector for obtaining a PCR result in real time using the polymer chip Natural convection PCR system using polymer chip. The method according to claim 1, The polymer chip Polyolefins such as polymethylmethacrylate (PMMA), polycarbonate (PC), cycloolefin copolymer (COC), polyamide (PA), polyethylene (PE), polypropylene PP, polyphenylene ether (PPE), polystyrene (PS), polyoxymethylene (POM), polyetheretherketone (PEEK), polytetrafluoroethylene (PTFE) , Polyvinylchloride (PVC), polyvinylidene fluoride (PVDF), polybutyleneterephthalate (PBT), fluorinated ethylenepropylene (FEP), perfluoralkoxyalkane , PFA). ≪ RTI ID = 0.0 >  Natural convection PCR device using disposable polymer chip. A natural convection PCR method using a natural convection PCR apparatus using the disposable polymer chip according to claim 1, A heater, a temperature controller and a temperature sensor are used to maintain the heated metal part at a constant temperature, Contacting the polymer chip on which the loop-shaped microchannel is formed through the heated metal part to heat the sample in the channel to a predetermined temperature, The natural convection is generated by the heating, The natural convection causes the sample to flow along the loop and apply a sequential temperature change for PCR Natural convection PCR method using disposable polymer chip.

Images