TW201404883A - Drop-type high-throughput thermal circulation system - Google Patents
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Abstract
Description
本發明是有關於一種熱循環系統,特別是指一種液滴型高通量熱循環系統。 The present invention relates to a thermal cycle system, and more particularly to a droplet type high throughput thermal cycle system.
目前在檢測DNA上最常用的方法,就是將DNA進行聚合酶連鎖反應(Polymerase Chain Reaction,PCR)。PCR主要以三個不斷依序重複之步驟進行,變性(denature,DNA雙股分離形成單股)→黏合(annealing,引子黏合於單股DNA上的互補位置)→延展(extension,以兩個引子為起點合成新的DNA),PCR完成後進行凝膠電泳來檢測結果。 The most common method currently used to detect DNA is to perform DNA polymerase chain reaction (PCR). PCR is carried out in three steps that are repeated in sequence, denaturation (denature, DNA double-strand separation to form a single strand) → adhesion (annealing, primer binding to a complementary position on a single strand of DNA) → extension (extension, with two primers A new DNA was synthesized as a starting point. After the PCR was completed, gel electrophoresis was performed to detect the result.
目前PCR主要是採用固定式循環加熱器,利用控制器控制加熱器加熱時間及溫度,也就是說,固定式循環加熱器是將樣本固定在同一空間內,將該空間進行溫度變化,以使該空間在不同溫度下以不同時間加熱,達到溫度循環加熱的目的,然而,固定式循環加熱器在升降溫時,需要將PCR混合物以及各種同樣位於該空間內的所有元件皆升降至同一溫度後,才能進行下一步驟,不但浪費時間,也大幅增加實驗成本。因此,如何能只讓PCR混合物升降溫,而使其他非必要加熱物件不需同步升降溫,以節省實驗時間,值得多方思考、研究。 At present, PCR mainly uses a fixed circulation heater, and the controller is used to control the heating time and temperature of the heater. That is to say, the fixed circulation heater fixes the sample in the same space, and changes the temperature of the space to make the The space is heated at different temperatures for different times to achieve the purpose of temperature cycle heating. However, when the fixed circulation heater is used to raise and lower the temperature, it is necessary to raise and lower the PCR mixture and all the components also located in the space to the same temperature. The next step can be carried out, which not only wastes time, but also greatly increases the cost of the experiment. Therefore, how to only let the PCR mixture rise and fall, so that other non-essential heating objects do not need to be synchronized with the temperature rise, in order to save experimental time, it is worth thinking and researching.
因此,本發明之目的,即在提供一種可以有效節省實驗時間與成本的液滴型高通量熱循環系統。 Accordingly, it is an object of the present invention to provide a droplet type high throughput thermal cycle system that can effectively save experimental time and cost.
於是,本發明液滴型高通量熱循環系統,供容放並加熱混合有多數磁珠且呈液滴狀的待測樣本,該液滴型高通量熱循環系統包含一圍繞界定出一移動空間的外殼、一能於該移動空間內移動的移動裝置,及一加熱裝置。 Thus, the droplet type high-throughput thermal cycle system of the present invention is configured to accommodate and heat a sample to be tested mixed with a plurality of magnetic beads and having a droplet shape, the droplet type high-throughput thermal cycle system comprising a surrounding defining one a housing of the moving space, a mobile device movable within the moving space, and a heating device.
該移動裝置包括一動力源、一受該動力源驅動而於該移動空間內往復移動的載台,及一設置於該載台上而隨該載台移動的承載單元,其中,該承載單元具有一設置於該載台上的盒體、一可拆離地蓋設於該盒體上且形成有一開口的蓋體、一嵌設於該蓋體之開口的濾光片、一設置於該盒體內的磁吸件,及一置放於該磁吸件上且對應該濾光片位置的承載盤,該承載盤具有多個用以容放待測樣本的容置部。 The mobile device includes a power source, a stage driven by the power source to reciprocate in the moving space, and a carrying unit disposed on the stage and moving with the stage, wherein the carrying unit has a box disposed on the stage, a cover body detachably disposed on the box body and having an opening, a filter embedded in the opening of the cover body, and a filter disposed on the box a magnetic member in the body, and a carrier plate disposed on the magnetic member and corresponding to the position of the filter, the carrier having a plurality of receiving portions for receiving the sample to be tested.
該加熱裝置包括一控制器,及三個分別電連接於該控制器且設置於該外殼的移動空間內的加熱單元,所述加熱單元是位於該移動裝置的上方而用以加熱該承載單元,其中,每一加熱單元具有一圍繞壁、一由該圍繞壁所圍繞界定的加熱空間,及一固設於該圍繞壁上且電連接於該控制器而用以加熱該加熱空間的加熱件。 The heating device comprises a controller, and three heating units respectively electrically connected to the controller and disposed in the moving space of the outer casing, the heating unit is located above the mobile device for heating the carrying unit, Wherein each heating unit has a surrounding wall, a heating space defined by the surrounding wall, and a heating member fixed to the surrounding wall and electrically connected to the controller for heating the heating space.
本發明之功效在於:利用該載台帶動待測樣本於不同加熱單元所形成的溫區之間移動,有效節省升降溫所需之時間與成本,且透過該承載單元之濾光片與磁吸件的設計,可以提高加熱效率,並避免待測樣本有偏離位置的情形發生。 The utility model has the advantages that the sample is driven to move between the temperature zones formed by different heating units, thereby effectively saving the time and cost required for the temperature rise and fall, and the filter and the magnetic material passing through the load bearing unit The design of the part can improve the heating efficiency and avoid the situation where the sample to be tested is out of position.
有關本發明之前述及其他技術內容、特點與功效,在以下配合參考圖式之一個較佳實施例的詳細說明中,將可清楚的呈現。 The above and other technical contents, features and advantages of the present invention will be apparent from the following detailed description of the preferred embodiments.
參閱圖1與圖2,為本發明液滴型高通量熱循環系統之較佳實施例,包含一外殼2、一能相對於該外殼2移動的移動裝置3,及一加熱裝置4。 Referring to Figures 1 and 2, a preferred embodiment of a droplet type high throughput thermal cycle system of the present invention comprises a housing 2, a moving device 3 movable relative to the housing 2, and a heating device 4.
該外殼2包括一基座21、兩個對應地設置於該基座21兩側的側壁22,及一由該基座21與該二側壁22共同界定的移動空間23。 The housing 2 includes a base 21, two side walls 22 correspondingly disposed on opposite sides of the base 21, and a moving space 23 defined by the base 21 and the two side walls 22.
該移動裝置3包括一設置於該基座21內的動力源31、一受該動力源31驅動而於該移動空間23內沿著移動方向X往復移動的載台32,及一設置於該載台32上而隨該載台32移動的承載單元33。 The mobile device 3 includes a power source 31 disposed in the base 21, a stage 32 driven by the power source 31 to reciprocate in the moving space 23 along the moving direction X, and a loading platform 32 disposed on the mobile device 31. A load bearing unit 33 on the table 32 that moves with the stage 32.
參閱圖2、3,該承載單元33具有一設置於該載台32上的盒體331、一可拆離地蓋設於該盒體331上且形成有一開口330的蓋體332、一嵌設於該蓋體332之開口330的濾光片333、一設置於該盒體331內的磁吸件334,及一置放於該磁吸件334上且對應該濾光片333位置的承載盤335,該承載盤335具有多個容置部336,所述容置部336用以容放混合有多數磁珠6且呈液滴狀的待測樣本5。 Referring to FIGS. 2 and 3, the carrying unit 33 has a casing 331 disposed on the carrier 32, a cover 332 detachably disposed on the casing 331 and having an opening 330 formed therein. a filter 333 for the opening 330 of the cover 332, a magnetic member 334 disposed in the case 331, and a carrier plate disposed on the magnetic member 334 corresponding to the position of the filter 333 335. The carrier 335 has a plurality of accommodating portions 336 for accommodating the sample 5 to be tested mixed with a plurality of magnetic beads 6 and having a droplet shape.
要特別說明的是,於本實施例中,該載台32與該盒體331並非以一體式的方式繪示,但於實際製造時,也可使該盒體331與載台32為一體式設計,不以此為限。 It should be particularly noted that, in this embodiment, the stage 32 and the box body 331 are not shown in an integrated manner, but in the actual manufacturing, the box body 331 and the stage 32 may be integrated. Design, not limited to this.
再參閱圖1與圖2,該加熱裝置4包括一控制器41, 及三個分別電連接於該控制器41且設置於該移動空間23內的加熱單元42,所述加熱單元42是用以加熱容置於該承載單元33內的待測樣本5。其中,每一加熱單元42具有一連接於該二側壁22之間且截面呈倒U形的圍繞壁421、一由該圍繞壁421所圍繞界定的加熱空間422、一固設於該圍繞壁421上且電連接於該控制器41而用以加熱該加熱空間422的加熱件423,及兩個貼設於該圍繞壁421上且互相對應的反射鏡片424。每一圍繞壁421具有一彎弧段425,及二由該彎弧段425兩端向下延伸的直立段426,該二反射鏡片424是分別貼設於該二直立段426上。於本實施例中,所述加熱件423為紅外線燈管。 Referring again to FIGS. 1 and 2, the heating device 4 includes a controller 41. And a heating unit 42 that is electrically connected to the controller 41 and disposed in the moving space 23, and the heating unit 42 is configured to heat the sample 5 to be tested and accommodated in the carrying unit 33. Each of the heating units 42 has a surrounding wall 421 connected between the two side walls 22 and having an inverted U-shaped cross section. A heating space 422 defined by the surrounding wall 421 is fixed to the surrounding wall 421. The heating member 423 is electrically connected to the controller 41 for heating the heating space 422, and two reflecting mirrors 424 are attached to the surrounding wall 421 and correspond to each other. Each of the surrounding walls 421 has a curved section 425 and two upright sections 426 extending downwardly from opposite ends of the curved section 425. The two reflecting mirrors 424 are respectively attached to the two straight sections 426. In this embodiment, the heating member 423 is an infrared lamp.
為了方便說明,特別將所述加熱單元42分別以編號42a、42b、42c做區分,將所述加熱空間422分別以編號422a、422b、422c做區分,而所述加熱件423分別以編號423a、423b、423c做區分。於本實施例中,以該控制器41分別控制加熱件423a的溫度為95℃、加熱件423b的溫度為55℃,以及加熱件423c的溫度為72℃,而使所述加熱件423a、423b、423c分別加熱所述加熱空間422a、422b、422c而趨近於95℃、55℃,及72℃。要說明的是,上述溫度只是本實施例所設定之實驗條件,可以視各種不同的實驗條件而改變所述加熱件423a~c的溫度,來調整所述加熱空間422a~c的溫度。同時,定義95℃的加熱空間422a為變性區(denaturation)、而55℃的加熱空間422b則為黏合區(annealing),72℃的加熱空間422c為延展區(extension)。當 然,亦可以視實際需求,而使加熱空間422b為延展區,加熱空間422c為黏合區,同時配合實驗條件改變加熱空間422b、422c之溫度,不以本實施例所揭露者為限。 For convenience of description, the heating unit 42 is specifically distinguished by numbers 42a, 42b, and 42c, and the heating spaces 422 are respectively distinguished by numbers 422a, 422b, and 422c, and the heating members 423 are respectively numbered 423a. 423b, 423c make a distinction. In the present embodiment, the controller 41 controls the temperature of the heating member 423a to be 95 ° C, the temperature of the heating member 423b to 55 ° C, and the temperature of the heating member 423c to 72 ° C, respectively, so that the heating members 423a, 423b And 423c respectively heats the heating spaces 422a, 422b, and 422c to approach 95 ° C, 55 ° C, and 72 ° C. It should be noted that the above temperature is only the experimental condition set in the embodiment, and the temperature of the heating elements 423a-c can be changed according to various experimental conditions to adjust the temperature of the heating spaces 422a-c. Meanwhile, the heating space 422a defining 95 ° C is denaturation, and the heating space 422 b of 55 ° C is an annealing, and the heating space 422 c of 72 ° C is an extension. when However, depending on the actual needs, the heating space 422b is an extension area, and the heating space 422c is an adhesion area, and the temperature of the heating spaces 422b and 422c is changed in accordance with experimental conditions, which is not limited to those disclosed in the embodiment.
以下則配合實驗的進行說明本發明的使用方式,首先,準備雙股DNA作為模板(template),並確認一段能與該雙股DNA部分互補的片段,將該片段、模板,以及含有磁珠6的反應試劑混合後形成待測樣本5,再將待測樣本5置於該承載盤335的容置部336內,並將一層礦物油7覆蓋於待測樣本5上。其中,所述磁珠6的表面為親水性,因此磁珠6移動時,可以帶動液滴狀的待測樣本5移動。 Hereinafter, the mode of use of the present invention will be described in conjunction with an experiment. First, a double-stranded DNA is prepared as a template, and a fragment complementary to the double-stranded DNA portion is confirmed, and the fragment, the template, and the magnetic beads are included. After the reaction reagents are mixed, the sample 5 to be tested is formed, and the sample 5 to be tested is placed in the accommodating portion 336 of the carrier tray 335, and a layer of mineral oil 7 is covered on the sample 5 to be tested. Wherein, the surface of the magnetic bead 6 is hydrophilic, so when the magnetic bead 6 moves, the droplet-shaped sample 5 to be tested can be moved.
接著,經由該控制器41調整所述加熱空間422a~c所需的溫度,再使該動力源31驅動該載台32,使該載台32與移動裝置3於該移動空間23內移動並依序通過變性區→黏合區→延展區而完成聚合酶連鎖反應(PCR)的一次循環,並且使載台32再回到變性區而重複進行上述移動順序,該載台32與移動裝置3停留於上述區域的時間可視實際情況進行調整。 Next, the controller 41 adjusts the temperature required for the heating spaces 422a-42, and the power source 31 drives the stage 32 to move the stage 32 and the moving device 3 in the moving space 23. The sequence of the polymerase chain reaction (PCR) is completed through the denaturation zone→adhesion zone→extension zone, and the above-mentioned moving sequence is repeated by returning the stage 32 to the denaturation zone, and the stage 32 and the mobile device 3 stay at The time in the above area can be adjusted according to the actual situation.
要說明的是,該載台32與移動裝置3移動至每一加熱單元42下方時,該承載單元33之濾光片333是會對應位於每一加熱件423的下方,而由於每一加熱件423為紅外線燈管,於加熱時散發熱輻射,並配合所述反射鏡片424的設置,讓熱能可以集中並通過該濾光片333,而對待測樣本5進行加熱。另外,由於待測樣本5中主要成分為水,而水的吸收頻譜在1450nm和1950nm有兩個高吸收波長, 因此於本實施例中,該濾光片333可選用兩種規格,一種是可讓1400nm-1500nm之波長通過,另一種則是可讓1900nm-2000nm的波長通過,以對所述待測樣本5產生最好的加熱效果。 It should be noted that when the stage 32 and the moving device 3 are moved under each heating unit 42, the filter 333 of the carrying unit 33 is correspondingly located below each heating member 423, and each heating member is 423 is an infrared lamp tube, which radiates heat radiation when heated, and cooperates with the arrangement of the reflective lens 424 to allow heat energy to be concentrated and passed through the filter 333, and the sample to be tested 5 is heated. In addition, since the main component of the sample 5 to be tested is water, the absorption spectrum of water has two high absorption wavelengths at 1450 nm and 1950 nm. Therefore, in this embodiment, the filter 333 can be used in two sizes, one can pass the wavelength of 1400 nm to 1500 nm, and the other can pass the wavelength of 1900 nm to 2000 nm to the sample to be tested 5 Produces the best heating effect.
另外,由於所述待測樣本5內含有磁珠6,再搭配該磁吸件334用以吸附所述磁珠6,因此該承載單元33被該載台32帶動移動時,透過該磁吸件334可以避免所述待測樣本5偏離或是移位。而由於礦物油7的沸點高於100℃,因此將礦物油7覆蓋於待測樣本5上,可避免待測樣本5於進行反應時蒸發,不必另外使用任何形式的上蓋,節省加工的成本與時間。 In addition, since the magnetic sample 6 is contained in the sample to be tested 5, and the magnetic member 334 is used to adsorb the magnetic bead 6, the magnetic bearing member 33 is moved by the carrier 32, and the magnetic member is transmitted through the magnetic member. 334 can prevent the sample 5 to be tested from being deviated or shifted. Since the boiling point of the mineral oil 7 is higher than 100 ° C, the mineral oil 7 is covered on the sample 5 to be tested, so that the sample 5 to be tested can be prevented from evaporating during the reaction, and it is not necessary to additionally use any form of the upper cover, thereby saving the processing cost and time.
綜上所述,本發明液滴型高通量熱循環系統,利用該載台32帶動所述待測樣本5於不同加熱單元42所形成的溫區之間移動,有效節省升降溫所需之時間與成本,配合每一加熱單元42之加熱件423配合反射鏡片424的設計,能對所述待測樣本5產生最好的加熱效果,而由於透過該磁吸件334用以吸附所述待測樣本5內的磁珠6,使該承載單元33被該載台32帶動移動時,可以避免所述待測樣本5偏離或是移位,故確實能達成本發明之目的。 In summary, the droplet type high-throughput thermal cycle system of the present invention uses the stage 32 to drive the sample 5 to be tested to move between the temperature zones formed by the different heating units 42, thereby effectively saving the temperature required for lifting and lowering. Time and cost, in conjunction with the design of the heating member 423 of each heating unit 42 in conjunction with the reflective lens 424, the best heating effect can be produced on the sample 5 to be tested, and the magnetic member 334 is used to adsorb the When the magnetic beads 6 in the sample 5 are measured to move the carrying unit 33 by the stage 32, the sample 5 to be tested can be prevented from being displaced or displaced, so that the object of the present invention can be achieved.
惟以上所述者,僅為本發明之較佳實施例而已,當不能以此限定本發明實施之範圍,即大凡依本發明申請專利範圍及發明說明內容所作之簡單的等效變化與修飾,皆仍屬本發明專利涵蓋之範圍內。 The above is only the preferred embodiment of the present invention, and the scope of the invention is not limited thereto, that is, the simple equivalent changes and modifications made by the scope of the invention and the description of the invention are All remain within the scope of the invention patent.
2‧‧‧外殼 2‧‧‧ Shell
21‧‧‧基座 21‧‧‧Base
22‧‧‧側壁 22‧‧‧ side wall
23‧‧‧移動空間 23‧‧‧Mobile space
3‧‧‧移動裝置 3‧‧‧Mobile devices
31‧‧‧動力源 31‧‧‧Power source
32‧‧‧載台 32‧‧‧ stage
33‧‧‧承載單元 33‧‧‧ Carrying unit
330‧‧‧開口 330‧‧‧ openings
331‧‧‧盒體 331‧‧‧Box
332‧‧‧蓋體 332‧‧‧ cover
333‧‧‧濾光片 333‧‧‧Filter
334‧‧‧磁吸件 334‧‧‧Magnetic parts
335‧‧‧承載盤 335‧‧‧ Carrying tray
336‧‧‧容置部 336‧‧‧ 容部
4‧‧‧加熱裝置 4‧‧‧ heating device
41‧‧‧控制器 41‧‧‧ Controller
42‧‧‧加熱單元 42‧‧‧heating unit
42a~c‧‧‧加熱單元 42a~c‧‧‧heating unit
421‧‧‧圍繞壁 421‧‧‧ Around the wall
422‧‧‧加熱空間 422‧‧‧heating space
422a~c‧‧‧加熱空間 422a~c‧‧‧heating space
423‧‧‧加熱件 423‧‧‧heating parts
423a~c‧‧‧加熱件 423a~c‧‧‧heating parts
424‧‧‧反射鏡片 424‧‧‧Reflective lenses
425‧‧‧彎弧段 425‧‧‧ curved section
426‧‧‧直立段 426‧‧‧Upright section
5‧‧‧待測樣本 5‧‧‧samples to be tested
6‧‧‧磁珠 6‧‧‧Magnetic beads
7‧‧‧礦物油 7‧‧‧ mineral oil
X‧‧‧移動方向 X‧‧‧ moving direction
圖1是一立體圖,說明本發明液滴型高通量熱循環系統之較佳實施例;圖2是一側視圖,輔助說明圖1;及圖3是一局部立體分解圖,說明一移動裝置之承載單元的細部結構。 1 is a perspective view showing a preferred embodiment of the droplet type high-throughput thermal cycle system of the present invention; FIG. 2 is a side view, which is an explanatory view of FIG. 1; and FIG. 3 is a partial exploded perspective view showing a mobile device The detailed structure of the carrying unit.
2‧‧‧外殼 2‧‧‧ Shell
21‧‧‧基座 21‧‧‧Base
22‧‧‧側壁 22‧‧‧ side wall
23‧‧‧移動空間 23‧‧‧Mobile space
3‧‧‧移動裝置 3‧‧‧Mobile devices
31‧‧‧動力源 31‧‧‧Power source
32‧‧‧載台 32‧‧‧ stage
33‧‧‧承載單元 33‧‧‧ Carrying unit
331‧‧‧盒體 331‧‧‧Box
332‧‧‧蓋體 332‧‧‧ cover
333‧‧‧濾光片 333‧‧‧Filter
4‧‧‧加熱裝置 4‧‧‧ heating device
41‧‧‧控制器 41‧‧‧ Controller
42‧‧‧加熱單元 42‧‧‧heating unit
421‧‧‧圍繞壁 421‧‧‧ Around the wall
422‧‧‧加熱空間 422‧‧‧heating space
423‧‧‧加熱件 423‧‧‧heating parts
424‧‧‧反射鏡片 424‧‧‧Reflective lenses
425‧‧‧彎弧段 425‧‧‧ curved section
426‧‧‧直立段 426‧‧‧Upright section
X‧‧‧移動方向 X‧‧‧ moving direction
Claims (5)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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TW101125822A TWI458828B (en) | 2012-07-18 | 2012-07-18 | Droplet type high throughput thermal cycling system |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
TW101125822A TWI458828B (en) | 2012-07-18 | 2012-07-18 | Droplet type high throughput thermal cycling system |
Publications (2)
Publication Number | Publication Date |
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TW201404883A true TW201404883A (en) | 2014-02-01 |
TWI458828B TWI458828B (en) | 2014-11-01 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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TW101125822A TWI458828B (en) | 2012-07-18 | 2012-07-18 | Droplet type high throughput thermal cycling system |
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TW (1) | TWI458828B (en) |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
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TW331553B (en) * | 1994-09-08 | 1998-05-11 | Inventio Ag | Lift with a roller placard |
JP5205802B2 (en) * | 2007-05-11 | 2013-06-05 | ソニー株式会社 | Real-time PCR device |
EP2584344B1 (en) * | 2009-01-08 | 2021-06-30 | IT-IS International Limited | Optical system for detecting light from polymerase chain reactions |
TWI404570B (en) * | 2009-09-24 | 2013-08-11 | Univ Nat Pingtung Sci & Tech | Reciprocating cycle heater |
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TWI458828B (en) | 2014-11-01 |
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