TWI309259B - - Google Patents

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Publication number
TWI309259B
TWI309259B TW95107430A TW95107430A TWI309259B TW I309259 B TWI309259 B TW I309259B TW 95107430 A TW95107430 A TW 95107430A TW 95107430 A TW95107430 A TW 95107430A TW I309259 B TWI309259 B TW I309259B
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TW
Taiwan
Prior art keywords
temperature
wafer
circuit
control
unit
Prior art date
Application number
TW95107430A
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Chinese (zh)
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TW200734453A (en
Inventor
zong-min Xie
jin-xing Luo
Gwo Bin Lee
Original Assignee
Univ Nat Cheng Kung
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Priority to TW095107430A priority Critical patent/TW200734453A/en
Publication of TW200734453A publication Critical patent/TW200734453A/en
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Publication of TWI309259B publication Critical patent/TWI309259B/zh

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  • Automatic Analysis And Handling Materials Therefor (AREA)

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1309259 九、發明說明: 【發明所屬之技術領域】 本發明是有關於一種微型聚合酶連鎖反應裝置,特別 是指一種不易受環境溫度影響之微型聚合酶連鎖反應裂置 【先前技術】 聚合酶連鎖反應(Polymerase Chain Reacti〇n,以下簡稱 PCR)是一種利用酵素對特定基因做體外或試管内(卜 Vitro)大量合成的技術,乃為分子生物領域帶來革命性的大 轉變,並加速了生物科技領域的研究腳步,更重要的是目 前PCR已被廣泛地應用在學術、工業和醫學的研究上。 PCR主要是藉由溫度的控制’將去氧核糖核酸(dna)之 雙螺旋,經過變性(Denaturati〇n)、緩冷配對(Anneal)與 複製(Extension)等三個步驟重複多次的循環,將標定的 DNA序列(target sequence)放大至數百萬倍,簡單來說, P^R就是-個熱循環作用,上述步驟分別會在高溫區、低 /皿區及中皿區進行’乃需要極佳的溫度控制,以經過正峰 的溫程循環,讓DNA達到複製放大的目標,反應時溫度控 制精確度通常會在1〜代以内,因此,溫度控㈣會影響到 =應結果’特別是對利用微機電製程技術生產之微流體生 4檢測晶片而言’溫度的準確性與均勻度更是重要。 圖所不 種習知微型聚合酶連鎖反應裝置1,用 於提供PCR三個步驟所需的溫度,並包含:一晶片U '二1309259 IX. Description of the invention: [Technical field of the invention] The present invention relates to a micro-polymerase chain reaction device, in particular to a micro-polymerase chain reaction cleft which is not susceptible to environmental temperature [Prior Art] Polymerase chain The reaction (Polymerase Chain Reacti〇n, hereinafter referred to as PCR) is a technology that uses enzymes to synthesize specific genes in vitro or in vitro (Vitro). It is a revolutionary transformation in the field of molecular biology and accelerates biology. Research in the field of science and technology, more importantly, PCR has been widely used in academic, industrial and medical research. PCR is mainly carried out by the temperature control 'the double helix of deoxyribonucleic acid (dna), repeated three steps of denaturation (Denaturati〇n), slow cooling pairing (Anneal) and replication (Extension). Amplify the calibrated DNA sequence to millions of times. In simple terms, P^R is a thermal cycle. The above steps are performed in the high temperature zone, the low/dish zone and the middle zone respectively. Excellent temperature control, through the temperature cycle of the positive peak, let the DNA reach the target of replication amplification, the temperature control accuracy during the reaction is usually within 1~ generation, therefore, the temperature control (4) will affect the result should be 'special It is more important for the accuracy and uniformity of temperature for microfluidic 4 detection wafers produced using MEMS process technology. There is no known micro-polymerase chain reaction device 1 for providing the temperature required for three steps of PCR, and comprises: a wafer U 'two

銜接U 11的連接單元12、—電連接該等連接單元U 1309259 的循環溫度控制單元13,及—安裝在晶# 11T方的散熱器 |4。该循環溫度控制單元13能將所量測到之晶片u溫度訊 號加以處理,若晶片11溫度較低於一設定溫度時,即會驅 動加熱該晶片11,又若晶片11溫度較高於該設定溫度時, 則會停止加熱晶片u,而讓晶片u上的熱量由散熱器14 散熱,用以控制使晶片u趨近於該設定溫度。 雖然習知微型聚合酶連鎖反應裝置1可提供PCR晶片 11反應所需的溫度’然而,由於晶片11周圍之環境溫度並 未被控制變更,所以暴露在此環境中之晶片u容易受到環 境恤度影響,因此晶片u溫度之精準性及穩定度較難以提 尚,導致PCR反應時間、結果受到影響。 例如當環境處於一較低溫的冷氣房内時,晶片n的加 熱升溫的速率就會較慢,甚至很難升溫到設定溫度,反之 /當環境處於較高溫度時’晶片溫的速率就會趨緩, 很難快速降溫到設定溫度。所以習知的微型聚合酶連鎖反 應,置i很容易受到環境的影響,進而影響到循環溫度控 制單元13的循環設定時間。 【發明内容】 因此,本發明之目的,即在提供一種具有較佳之溫度 控制效果的不易受環境溫度影響之微 彳双玉眾合酶連鎖反應裝 於是,本發明不易受環境溫度影響之微型聚合酶連鎖 至少—_該晶片的連接單元 、—定溫單元,及-電連接該連接單元之控制單元。該控 1309259 制單元用於感測並控制該晶片,使晶片上的溫度可於設定 值間準確的循環。該定溫單元是位於晶片旁邊,並包括一 控制%境溫度的環境溫度控制電路,用以給予晶片周圍一 固定溫度’讓晶片㈣之環境溫度趨近於一設定溫度。 【實施方式】 有關本發明之前述及其他技術内容、特點與功效,在 乂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。 如圖2與圖3所示,本發明微型聚合酶連鎖反應裝置 之較佳實施例包含:—晶片2、二連接單元3、—定溫單元 4、一控制單元5、一輸入輪出單元6,及一散熱器7。 該晶片2為一 PCR晶片,是以微機電製程製成之生物 曰曰片由於晶片2構造並非本發明重點,所以在此不再詳 細說明。 該等連接單元3銜接在晶片2之兩側,在本實施例中 疋使用pci插槽式的方式進行連結,亦即該晶片2之側邊 是插,在連接單元3中,不僅能便於電連接晶片2,亦可快 速且簡易地進行晶片2更換。 該定溫單元4包括一控制環境為一固定溫度的環境溫 度控制電路41。在本實施例中可以使用例如TE c〇〇ier的元 件進行袁*兄咖度控帝j ’以達到具有較佳之溫度控制效果。 該控制單元5是電連接該連接單元3與環境溫度控制 電路=1’能用於感測控制使晶片2趨近一設定溫度,並包 括里測晶片2溫度的溫度訊號處理電路組5丨、_接收並 7 1309259 運算該溫度訊號量測電路組51傳來之訊息的微處理器52、 '接t微處理H 52指令以控制使晶片2溫度趨近設定溫度 的溫度循環控制電路53、一電連接微處理器52以控制周邊 元件(圖未示)的周邊元件控制電路54,及一電連接微處理器 52以控制輸人輪出單元6的輸人輸出單元控制電路^。 該溫度訊號處理電路組51具有—用於#|取晶片2上所 量測到之電子訊號的訊號擷取電路511、一降低内部或外部 雜訊的前遽波電路512、-㈣所得訊號準位並提高該訊號 的訊號與雜訊比(SNR)之訊號準位調整電路513、一將處理 過之訊號放大的訊號放大電路514,及—將放大訊號轉換並 傳送至微處理器52之數位類比轉換電路515。而該微處理 52亦電連接該環境溫度控制電路41。 該溫度循環控制電路53即為一訊號回饋控制電路,乃 用於處理訊號的輸出輸入及控制理論的嵌入,以回饋訊號 致使溫度保持在設定溫度循環的參數曲線上。該周邊元件 控制電路54是用於控制外接周邊^件,例如閥門、幫浦、 風扇......等,用以使該晶片2加熱或降溫,當然亦可以採 用加熱器來加熱,並使用壓縮機或循環水流冷卻,在此不 再詳細說明。 该輸入輸出單元6電連接該輸入輸出單元控制電路55 ,並包括一供操作者將所需之設定溫度與固定溫度輸入該 :处理H 52的輸入件61,及一能顯示該微處理_ 52控制 溫度之資訊的輸出件62 盤,該輸出件62為一液 。在本實施例中該輸入件61為一鍵 晶顯示器,一般PCR系統共有三類 1309259 操作參數:溫度、時間、循環次數’我們可以經由輸入件 61將操作參數輸人,而後即可透過輸出件62逐一顯示pcR 的進行流程與目前狀態。 該散熱器7安裝在該晶片2底部,且電連接該控制單 元5之周邊元件控制電路54 ’能被控制而用以使晶片:散 熱。 操作人員將晶片2插接在連接單元3上,將設定溫度 之參數鍵入輸入件6卜此時訊號擷取電路511即可量測擷 取晶片2之溫度訊息’並將此訊息經過前據波電路512、訊 號準位調整電路513、訊號放大電路514與數位類比轉換電 路515之後’再傳送至微處理器52,該微處理器52會將此 訊息與設定溫度比對,並經過處理之後,即會傳訊啟動周 邊元件控制電路54,使晶片2升溫或降溫,若晶片2溫度 較低於設定溫度時,即會驅動加熱該晶片2,又若晶片2溫 度較高於該設定溫度時,則會停止加熱晶片2,而;晶片: 上的熱量由散熱器7散熱,用以控制使晶片2趨近於該設 定溫度。同時操作人員亦將該固^溫度之參數鍵入該輸入 件6!。’而該微處理器52即會控制該環境溫度控制電路41 ’使操作環境定溫於該固定溫度。 參閱圖4,進-步說明有關晶片2與定溫單元4的且體 結構關係,此處所㈣之晶Μ 2又可稱作微型加熱晶片, 該晶片2具有_由詞、⑦或是高分子材料製成之基板?! 、安裝在基板21頂部之至少—微型加熱器22與至少—微 蜇溫度感測器23,以乃一忠驻Α娜亦丨上血 及女裝在微型加熱Is 22與微型溫度 9 1309259 感測器23上方之微型反應槽24。微型加熱器22盘微型、田 度感測器23係以金屬製成’惟其溫度感測及加熱控制流= 為一般技術,所以在此不再詳細說明。該微型反應槽Μ可 使用高分子材料或是直接在基板21上加卫而得,乃用於承 中該定溫單元4為一塊安裝 在該晶片2底部的加熱平台,其面積略大於該晶片2之: 板2卜當然在設計上其構造及安裝位置不以本實施例驗 〇 、須進一步說明的是,這類型的晶片2由於體積小,所 以晶片2本身將容易受到環境溫度的影響,進而造成本 溫度場的改變’因此在晶片2上之微型反應槽24加孰時, 若外界溫度有大幅度的昇降情況時,晶片2本身的溫度亦 會大幅改變,故而當外界溫度劇烈變化時,晶片2本身浪 度的均句性與穩定度將會大幅下降。因此,若能在定溫: π 4上維持_較溫度,—般是設定為高於室溫但低於晶 片2上微型反應槽24的操作溫度,將可大幅提高其晶片2 之熱均勻性與敎度,並可保有晶片2的微小性與升降溫 效能。 皿 J說月·田日曰片2進行一個熱循環時(如聚合酶連 鎖反應),因為外界溫度的劇烈變化,可能導致系統啟動時 =:=應期間晶片2本身的溫度發生相當大的誤差, 片2在熱循環過程中,因受到外界溫度改變的 於使聚合酶連鎖反應失敗。這時若使㈣定溫單元4 , 即可將^ 2底部的環境溫度控制於贼,即所設定之固 10 1309259 定溫度,對該微型晶片2而言,確能 .碩此侍到—個較穩定的加 ',,、衣兄’於初始溫度校正時即可在4〇t的環境進行,而告 此系統在室外或溫度較易發生變化之環境時,由於定溫: 兀4的固定溫度控制於4〇。 持在-個較穩定的狀態下,口有 〜卜,、有曰曰片2之微型反應槽24的 區域進行高速熱循環的動作,如此可減少該區域上溫 =誤=提供給生物檢體在晶片2中進行聚合酶連鎖反 二時:個穩定的環境,進而提高此生物晶片2的效能。因 此右使用此方式,僅需要,丨旦 僅需要夕里之熱能維持晶片2周邊的溫 能提升這類型晶片2的溫度均勻性與穩定性,亦 °保有&類型晶片2的快速升降溫特性。 ▲本案發明人為證實此設計概念之可行性,乃進行下述 §式驗··如附件1所千,杳& 2 ,, 斤不冑驗叙(本發明)是將兩片可分別控制 ’’、、日日A、B(即分別為晶片2、定溫單元4)上、下属人 後放=散熱片c(即散熱器7)上方,其設計係兩晶片: 片=:之情形,而對照組(習知)則是將-晶“(即晶 ^ Α —散熱片C (即散熱器14)上方,所以僅有單一 的情形。如附件2所示,係測試作為特定晶片( 對照組(見熱相圖⑷ 動㈣方式實現 然後再以晶片A、Β同時動作之 凊形實現實驗組(見熱相圖(b)、⑷)。 數據可知,當Γ片圖(Ba)與(b),比較兩圖及其左下角所顯示之 -度此畔上并θ加熱動作時,會令晶片A(即晶片2)的 遍許上升’也就是對照組之晶片•晶片⑴溫度略低 1309259 於實驗組晶片A(即晶片2)的溫度。為了驗證實驗組具有較 佳的抗環境溫度變異特性,乃模擬環境溫度產生變化的情 況,直接在散熱片附近通入氣流(如附件2假想線箭頭所示) ,使其產生劇烈的環境溫度變化,再分別測得對照組與實 驗組之熱相圖,由熱相圖(c)與(d)得知,在通入氣體的情況 下,對照組的溫度整體下降約大於2。〇,而實驗組僅下降不 到1°C,如此可證實當晶片B動作時,確能讓晶片A之溫 度場較不受環境溫度之干擾,而使晶片A不易受環境之影 響導致降低其效能,因此本發明之定溫單& 4確能= 定周遭環境溫度,讓曰曰“ 2周圍之環境溫度趨近於一設: 溫度之功效。 田上通說明可知,本發明微型聚合酶連鎖反應裝置在 設計上,是藉由定溫單元4創造出一個恒溫的環境,使晶 片2持續在相同溫度下操作,而不會受到外在環境例如: 乳、電風扇’或大熱天等的影響,例如將設定溫度定在乃 以溫’此溫度並不會隨晶片2的升、降溫度而改變,亦 即疋溫單元4的溫度設定靼曰片, 仲滋… 溫度相互獨立,使晶片2 ^籠罩在定溫單元4關造之㈣環境中,能提昇 ▲度的精準性與穩定度,並 ^ , 立了週整晶# 2升溫與降溫的速 率,在驗複㈣能具有最佳的表現,所以本發明= 實能夠達到本發明之目的因ΤΓ溫度控制效果’確 之創新,更可供產業上;本發明不❹前所未有 惟以上所述者,僅為本發明之較佳實施例而已,當不 12 1309259 能以此限定本發明實施之範圍,即大凡依本發明申請專利 範圍及發明說明内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内。 【圖式簡單說明】 圖1是一種習知微型聚合酶連鎖反應裝置之一側視示 意圖, 圖2是本發明之不易受環境溫度影響之微型聚合酶連 鎖反應裝置的一較佳實施例的一側視示意圖;及 圖3疋β玄較佳實施例的一系統電路方塊流程示意圖; 及 圖4是該較佳實施例的一侧視示意圖,說明有關一晶 片與一定溫單元的具體結構關係。 附件1是有關實驗組與對照組之簡單結構的比對示意 圖。 附件2是有關實驗組與對照組測試晶片上溫度場之熱 相圖比對。 13 1309259 【主要元件符號說明】 2 .....晶片 21 ·…基板 22·…微型加熱器 23····微型溫度感測器 24…··微型反應槽 3 .....連接單元 4 •…定溫單元 41····環境溫度控制電路 5 ••…控制單元 5 1 · · · ·溫度訊號處理電路組 511,,訊號擷取電路 512··前濾波電路 513 ·. 訊號準位調整電路 514 · 訊號放大電路 515 ., 數位類比轉換電路 52,… 微處理器 53… 溫度循環控制電路 54··· 周邊元件控制電路 55.·· 輸入輸出單元控制電路 6 ·… 輸入輸出單元 61… 輸入件 62 ··· 輪出件 7 * " 散熱器 14The connection unit 12 that connects the U 11 , the circulation temperature control unit 13 that electrically connects the connection units U 1309259, and the radiator 4 that is mounted on the crystal # 11T side. The circulating temperature control unit 13 can process the measured wafer u temperature signal. If the temperature of the wafer 11 is lower than a set temperature, the wafer 11 is driven to be heated, and if the temperature of the wafer 11 is higher than the setting. At the temperature, the heating of the wafer u is stopped, and the heat on the wafer u is dissipated by the heat sink 14 to control the wafer u to approach the set temperature. Although the conventional micro-polymerase chain reaction device 1 can provide the temperature required for the reaction of the PCR wafer 11 'however, since the ambient temperature around the wafer 11 is not controlled to be changed, the wafer u exposed to the environment is susceptible to environmental exposure. Influence, so the accuracy and stability of the wafer u temperature is difficult to mention, resulting in PCR reaction time and results are affected. For example, when the environment is in a lower temperature air-conditioned room, the heating rate of the wafer n will be slower, and it is even difficult to heat up to the set temperature. Conversely, when the environment is at a higher temperature, the rate of the wafer temperature will tend to increase. Slow, it is difficult to quickly cool down to the set temperature. Therefore, the conventional micro-polymerase chain reaction is very susceptible to environmental influences, which in turn affects the cycle set time of the circulation temperature control unit 13. SUMMARY OF THE INVENTION Accordingly, it is an object of the present invention to provide a micro-polymerization of a micro-small double-zinc synthase having a temperature control effect which is less susceptible to environmental temperature and which is less susceptible to environmental temperature. The enzyme linkage is at least - the connection unit of the wafer, the temperature control unit, and the control unit electrically connected to the connection unit. The control 1309259 unit is used to sense and control the wafer so that the temperature on the wafer can be accurately cycled between set values. The tempering unit is located next to the wafer and includes an ambient temperature control circuit for controlling the ambient temperature to impart a fixed temperature around the wafer to bring the ambient temperature of the wafer (4) to a set temperature. The above and other technical contents, features and effects of the present invention will be apparent from the following detailed description of a preferred embodiment of the accompanying drawings. As shown in FIG. 2 and FIG. 3, the preferred embodiment of the micro-polymerase chain reaction device of the present invention comprises: a wafer 2, a two-connecting unit 3, a temperature-limiting unit 4, a control unit 5, and an input wheel-out unit 6. , and a radiator 7. The wafer 2 is a PCR wafer, and the biochip produced by the microelectromechanical process is not the focus of the present invention, and therefore will not be described in detail herein. The connecting units 3 are connected to the two sides of the wafer 2, and in the embodiment, the connecting is performed by using a pci slot type, that is, the side of the wafer 2 is inserted, and in the connecting unit 3, not only electricity can be facilitated. By connecting the wafer 2, the wafer 2 can be replaced quickly and easily. The temperature control unit 4 includes an ambient temperature control circuit 41 that controls the environment to a fixed temperature. In this embodiment, an element such as TE c〇〇ier can be used for the control of the temperature to achieve a better temperature control effect. The control unit 5 is electrically connected to the connection unit 3 and the ambient temperature control circuit=1' can be used for sensing control to bring the wafer 2 closer to a set temperature, and includes a temperature signal processing circuit group 5 of the temperature of the wafer 2. _Receiving 7 1309259 A microprocessor 52 that operates the information transmitted by the temperature signal measuring circuit group 51, and a 'micro-processing H 52 command to control the temperature cycle control circuit 53 that brings the temperature of the wafer 2 closer to the set temperature. The microprocessor 52 is electrically coupled to the peripheral component control circuit 54 for controlling peripheral components (not shown), and is electrically coupled to the microprocessor 52 for controlling the input output control circuitry of the input and output unit 6. The temperature signal processing circuit group 51 has a signal extraction circuit 511 for taking the electronic signal measured on the chip 2, a front chopper circuit 512 for reducing the internal or external noise, and (4) the obtained signal standard. a signal level adjustment circuit 513 for increasing the signal and noise ratio (SNR) of the signal, a signal amplifying circuit 514 for amplifying the processed signal, and - converting the amplified signal to the digital portion of the microprocessor 52 Analog conversion circuit 515. The microprocessor 52 is also electrically coupled to the ambient temperature control circuit 41. The temperature cycle control circuit 53 is a signal feedback control circuit for processing the output of the signal and embedding the control theory to feedback the signal to maintain the temperature on the parameter curve of the set temperature cycle. The peripheral component control circuit 54 is for controlling an external peripheral component, such as a valve, a pump, a fan, etc., for heating or cooling the wafer 2, and of course, a heater can be used for heating, and Cooling using a compressor or circulating water flow will not be described in detail here. The input/output unit 6 is electrically connected to the input/output unit control circuit 55, and includes an input unit 61 for the operator to input the required set temperature and the fixed temperature: the processing unit 52, and the display of the micro processing_52 An output member 62 that controls the temperature information, the output member 62 being a liquid. In the embodiment, the input member 61 is a key crystal display. Generally, the PCR system has three types of 1309259 operating parameters: temperature, time, and number of cycles. 'We can input the operating parameters through the input member 61, and then pass through the output member. 62 shows the progress and current status of the pcR one by one. The heat sink 7 is mounted on the bottom of the wafer 2, and the peripheral component control circuit 54' electrically connected to the control unit 5 can be controlled to dissipate the wafer. The operator inserts the chip 2 on the connection unit 3, and inputs the parameter of the set temperature into the input unit 6 . At this time, the signal extraction circuit 511 can measure the temperature information of the wafer 2 and pass the message. The circuit 512, the signal level adjusting circuit 513, the signal amplifying circuit 514 and the digital analog converting circuit 515 are then 're-transmitted to the microprocessor 52, and the microprocessor 52 compares the message with the set temperature and after processing, That is, the peripheral component control circuit 54 is activated to raise or lower the temperature of the wafer 2. If the temperature of the wafer 2 is lower than the set temperature, the wafer 2 is driven to be heated, and if the temperature of the wafer 2 is higher than the set temperature, The wafer 2 is stopped to be heated, and the heat on the wafer: is dissipated by the heat sink 7 to control the wafer 2 to approach the set temperature. At the same time, the operator also enters the parameter of the solid temperature into the input member 6!. The microprocessor 52 controls the ambient temperature control circuit 41' to temperature the operating environment to the fixed temperature. Referring to FIG. 4, the relationship between the wafer 2 and the constant temperature unit 4 is described in a step-by-step manner. The wafer 2 (4) herein may also be referred to as a micro-heated wafer, and the wafer 2 has a word, 7 or a polymer. Substrate made of material? ! At least on the top of the substrate 21 - the micro-heater 22 and at least - the micro-temperature sensor 23, is a loyal to the Α 丨 丨 丨 丨 blood and women in the micro heating Is 22 and the micro temperature 9 1309259 sensing The microreactor 24 above the device 23. The micro-heater 22-disc micro-field sensor 23 is made of metal. However, the temperature sensing and heating control flow = the general technique, so it will not be described in detail here. The micro-reaction tank can be obtained by using a polymer material or directly on the substrate 21, and is used for supporting the constant temperature unit 4 as a heating platform mounted on the bottom of the wafer 2, the area of which is slightly larger than the wafer. 2: The board 2 is of course not designed and installed in this embodiment. It should be further explained that this type of wafer 2 is susceptible to environmental temperature due to its small size. Further, the temperature field is changed. Therefore, when the micro-reaction tank 24 on the wafer 2 is twisted, if the outside temperature is greatly raised and lowered, the temperature of the wafer 2 itself is greatly changed, so when the external temperature changes drastically, The uniformity and stability of the wave 2 itself will be greatly reduced. Therefore, if the temperature can be maintained at a constant temperature: π 4 , which is generally higher than room temperature but lower than the operating temperature of the micro reaction cell 24 on the wafer 2, the thermal uniformity of the wafer 2 can be greatly improved. With the degree of twist, and can maintain the micro-slurry and temperature rise and fall performance of the wafer 2. Dish J said that the month of Tianji 曰 2 to perform a thermal cycle (such as polymerase chain reaction), because the external temperature changes drastically, may cause the system to start =: = should be a considerable error in the temperature of the wafer 2 itself The film 2 failed to cause the polymerase chain reaction to fail due to changes in the outside temperature during the thermal cycle. At this time, if (4) the temperature unit 4 is used, the ambient temperature at the bottom of the ^ 2 can be controlled to the thief, that is, the set temperature of 10 1309259 is fixed, and for the microchip 2, it is indeed possible. The stable addition of ',,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, Controlled at 4〇. Holding in a relatively stable state, the mouth has a ~, the area of the micro-reaction tank 24 with the cymbal 2 performs high-speed thermal cycling, so that the temperature in the area can be reduced = error = provided to the biological specimen The polymerase chain reaction in the wafer 2: a stable environment, thereby improving the performance of the biochip 2. Therefore, if this method is used right, it is only required that the heat of the outer layer of the wafer 2 is maintained to maintain the temperature uniformity and stability of the wafer 2 of the type 2, and the rapid temperature rise and fall characteristics of the wafer type 2 are also maintained. ▲ In order to confirm the feasibility of this design concept, the inventor of the present case conducted the following § test. · As shown in Annex 1, thousands, 杳 & 2,, 斤不胄 ( (the invention) is to control two pieces separately ',, day A, B (that is, wafer 2, fixed temperature unit 4), subordinates, subordinates = heat sink c (ie, heat sink 7), the design is two wafers: slice =: the case, The control group (conventional) is the above-mentioned "crystal" (ie, crystal Α - heat sink C (ie, heat sink 14), so there is only a single case. As shown in Annex 2, the test is a specific wafer (control) The group (see the thermal phase diagram (4) dynamic (four) method is realized and then the experimental group is realized by the simultaneous action of the wafer A and the ( (see the thermal phase diagrams (b), (4)). The data can be seen, when the sputum map (Ba) and b) Comparing the two graphs and the lower left corner of the graph, when the θ heating action is performed, the wafer A (ie, wafer 2) is increased by averaging 'that is, the wafer of the control wafer (1) is slightly lower than the temperature of 1309259. The temperature of the experimental group wafer A (ie, wafer 2). In order to verify that the experimental group has better resistance to ambient temperature variability, it simulates changes in ambient temperature. In the case, the airflow is directly introduced near the heat sink (as indicated by the imaginary line arrow in Appendix 2), causing a severe environmental temperature change, and then the thermal phase diagram of the control group and the experimental group is measured respectively, and the thermal phase diagram (c) And (d) know that in the case of gas introduction, the temperature of the control group as a whole decreases by more than about 2. 〇, and the experimental group only drops less than 1 ° C, so that when the wafer B is activated, it is indeed Let the temperature field of the wafer A be less disturbed by the ambient temperature, and the wafer A is not easily affected by the environment, thereby reducing the efficiency. Therefore, the constant temperature single & 4 of the present invention can determine the ambient temperature of the surrounding environment, so that 2 The ambient temperature around is close to one: the effect of temperature. As shown in the description of Tianshangtong, the micro-polymerase chain reaction device of the present invention is designed to create a constant temperature environment by the constant temperature unit 4, so that the wafer 2 continues Operating at the same temperature without being affected by external environments such as: milk, electric fans' or hot weather, such as setting the set temperature to a temperature of 'this temperature does not rise or fall with the wafer 2 Change in temperature, that is, 疋The temperature setting of the unit 4 is 靼曰, 仲... The temperature is independent of each other, so that the wafer 2 ^ is enveloped in the (4) environment of the fixed temperature unit 4, which can improve the accuracy and stability of the ▲ degree, and ^, set a week The rate of temperature rise and temperature drop of the whole crystal #2 can have the best performance in the test (4), so the present invention can achieve the object of the present invention because of the temperature control effect, and it is more industrially available; The foregoing is only the preferred embodiment of the present invention, and is not intended to limit the scope of the practice of the present invention, that is, the simplicity of the scope of the invention and the description of the invention. Equivalent variations and modifications are still within the scope of the invention. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic side view of a conventional micro-polymerase chain reaction device, and FIG. 2 is a schematic view of a preferred embodiment of the micro polymerase chain reaction device of the present invention which is less susceptible to ambient temperature. FIG. 4 is a schematic side view of a preferred embodiment of the preferred embodiment of the present invention; and FIG. 4 is a side view of the preferred embodiment of the present invention, illustrating a specific structural relationship between a wafer and a temperature unit. Annex 1 is a schematic representation of the comparison of the simple structure of the experimental and control groups. Annex 2 is a thermal phase diagram comparison of the temperature field on the test wafer between the experimental and control groups. 13 1309259 [Description of main component symbols] 2 ..... wafer 21 · ... substrate 22 ·... micro heater 23 · · · · micro temperature sensor 24 · · · micro reaction tank 3 ..... connection unit 4 •...Fixed temperature unit 41····Environmental temperature control circuit 5 ••...Control unit 5 1 · · · ·Temperature signal processing circuit group 511, signal extraction circuit 512··Pre-filter circuit 513 ·. Bit adjustment circuit 514 · Signal amplification circuit 515 ., digital analog conversion circuit 52,... Microprocessor 53... Temperature cycle control circuit 54··· Peripheral component control circuit 55.·· Input/output unit control circuit 6 ·... Input/output unit 61... Input 62 ··· Wheeled 7 * " Radiator 14

Claims (1)

13092591309259 2. 3. 、申請專利範圍: 響之微型聚合酶連鎖反應裝置 一種不易受環境溫度影 包含: 一晶片; 至少一銜接該晶片的連接單元; 一定溫單元,位於該晶片旁, 度的環境溫度控制電路,用…匕括㈣%境溫 、田A j电路,用以使該晶片周圍具有—固定 '皿又’讓晶片周圍之環境溫度趨近於-設定溫度;及 -電連接該連接單元之控制單元,該控制單元用於 感測觸該晶片’使晶片上的溫度可於設定值間準破 的痛續。 依據申請專利範圍第1項所述之不易受環境溫度影響之 微型聚合酶連鎖反應裝置,其中,該控制單元包括—量 測晶片溫度的溫度訊號處理電路組、一接收並處理該溫 度訊誠理電路組傳來之訊息的微處理H,及-接受微 處理器私^以控制使晶片溫度趨近設定溫度的溫度循環 控制電路’而該微處理器亦電連接該環境溫度控制電路 ,以控制使環境溫度維持在該固定溫度。 依據申哨專利$&圍帛2項所述之不易受環境溫度影響之 U型聚w酶連鎖反應裝置,其中,該溫度訊號處理電路 組具有用於擷取晶片所量測到之電子訊號的訊號擷取 電路、一降低雜訊的前濾波電路、一調整所得訊號準位 之讯唬準位調整電路,及一將處理過之訊號放大的訊號 放大電路。 15 1309259 忙據申月專圍第3項所述之不易受環境溫度影響之 微型聚合酶連鎖反應裝置,其中,該控制單元更包括一 電連接微處理器的周邊元件控制電路。 5·專利範圍第1項所述之不易受環境溫度影響之 上~連鎖反應裝置,更包含—安裝在該控制單元 輪出單元’該輸入輸出單元包括一輸入件,及 16 1309259 七、指定代表圖: )圖。 控制單元 散熱器 (一) 本案指定代表圖為:第(2 (二) 本代表圖之元件符號簡單說明 2 .....晶片 5···· 3……連接單元 Ί…, 4 .....定溫早元 八、本案若有化學式時,請揭示最能顯示發明特徵的化學式:2. 3. Patent application scope: A micro-polymerase chain reaction device is a type that is not susceptible to ambient temperature: a wafer; at least one connecting unit that connects the wafer; a temperature unit located at the side of the wafer, the ambient temperature The control circuit includes: (4) the ambient temperature, the field A j circuit, so that the periphery of the wafer has a - fixed 'dish and 'the ambient temperature around the wafer is approached - set temperature; and - electrically connected to the connecting unit A control unit for sensing the touch of the wafer 'to make the temperature on the wafer breakable between the set values. According to the micro-polymerase chain reaction device which is not susceptible to environmental temperature according to the first aspect of the patent application, wherein the control unit comprises a temperature signal processing circuit group for measuring the temperature of the wafer, and receiving and processing the temperature information The microprocessor H of the message from the circuit group, and the temperature cycle control circuit that accepts the microprocessor to control the temperature of the wafer to approach the set temperature, and the microprocessor is also electrically connected to the ambient temperature control circuit to control The ambient temperature is maintained at this fixed temperature. The U-shaped poly-wase chain reaction device which is less susceptible to ambient temperature according to the claim of the whistle patent, <2>, wherein the temperature signal processing circuit group has an electronic signal for extracting the wafer The signal acquisition circuit, a pre-filter circuit for reducing noise, a signal level adjustment circuit for adjusting the obtained signal level, and a signal amplification circuit for amplifying the processed signal. 15 1309259 The micro-polymerase chain reaction device which is not susceptible to environmental temperature according to the third item of Shenyue, wherein the control unit further comprises a peripheral component control circuit electrically connected to the microprocessor. 5. The patent range is not susceptible to the influence of ambient temperature. The chain reaction device further includes the installation of the control unit wheel-out unit. The input and output unit includes an input member, and 16 1309259. Figure: ) Figure. Control unit heat sink (1) The representative map of the case is: (2 (2) The symbol of the representative figure is a simple description 2 ..... Wafer 5···· 3...Connecting unit Ί..., 4 .. ... fixed temperature early eight, if there is a chemical formula in this case, please reveal the chemical formula that best shows the characteristics of the invention:
TW095107430A 2006-03-06 2006-03-06 Micropolymerase chain reaction apparatus uneasy to be affected by environment temperature TW200734453A (en)

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