:：v 1295375 九、發明說明： 【發明所屬之技術領域】 本發明係為二種生物晶片微流管道之被動閥内流體驅 動方法，尤其疋指-種具有無需將電流或熱能與樣本液 體，或試劑液體接觸的特點，可將樣本液體或試劑液體受 電流或熱能影響的因素減低之生物晶片微流管道之被動闕 内流體驅動方法。 【先前技術】 藝、# ’微機電系統應用於生物或化學分析是近年來受重 視的研究領域之-，其目標就是將過去需要昂貴儀器、耗 時、耗費人力的生物或化學吩析或製程能在此微小系統上 來執行，這種裝置統稱為生物晶片〔Biochip〕，它的優點 包括：樣品量與測試時間大幅減少，同時又能提供平行快 __且崎低分㈣製程成本，由料種晶片可以很 5㈣造所崎㈣畢可雜棄，聽以絲賴管不乾 柯能產生之二次污染問題。又，生物晶片技術的運用範 圍很廣，譬如在新藥品發展、基因工程、環境監督、及臨 床疾病診斷上均可能會有革命性的運用。在晶片中被分析 及操作的流體以液體媒介為主，例如··血液、體液、尿液 等’因此在晶片中要設計各種微小元件，以執行分析工作 中所需的混合、萃取、加熱、冷卻、檢體判讀等流程，而 連接各種元件的流體管道直徑大約在100〜400//ΧΠ的範 圍’所以稱為微流管道〔MicroChannel〕，而管道中的各種 微小元件，稱為微流體〔microfluidics〕，或微流子。 而驅動微流管道中之液體流動的技術，可以微小之機 1295375 構〔微膈膜、微懸樑、微葉輪〕，再輸入電能使微機構擺動 或轉動以驅動液體流動，是為微幫浦〔Micro Pump〕達成， 或是利用液體表面張力達成；即將微流管道製造成小到一 定的尺度〔約70/zm以下〕，液體與管壁間的介面力〔表面 張力、毛細力〕對液體流動的影響將大於與液體質量有關 的力〔例如慣性力、重力〕。 此外，較複雜的檢驗、分析、或製程需要使晶片中的 液體在設定的區域滯留，再續流，或需要使不同管路的液 體，依照設計的順序在晶片微流管道内流動；而目前這種 控制流動順序或使液體續流的方式有：（i)在微管道中製 造微電極，需要使液體續流時，就對電極通電使液體電解 產生氣泡，以氣泡壓力推動液體；（ii)或將微管道晶片置 於旋轉機器上用離心力驅使液體續流；（iii)將液體介面間 的表面張力藉由加熱、通電、加入介面活性劑等方法使液 體與管壁介面間的接觸角改變，促使液體續流。 然而，綜觀上述可以控制液體流動順序或使被阻擋的 液體續流的方式，其皆需將電流或熱能與樣本液體或試劑 液體接觸，使得樣本液體或試劑液體受電流或熱能影響的 因素大幅升高，而影響液體的分析結果。 【發明内容】 今，發明人為解決上述情形，故而研創出本發明之生 物晶片微流管道之被動閥内流體驅動方法。 就本發明生物晶片微流管道之被動閥内流體驅動方 法，其主要係利用光源來驅動微流體系統中之被動閥運 作，它可以使依照所要求的反應或檢測步驟在生物晶片微 1295375 流管道内流動之樣本液體或試劑液體，由被動閥阻擋在被 動閥内’待完成等待或化學反應後，再以光源驅動被動閥 壁面之光觸媒反應，以依序打開被動閥，使被阻檔之樣本 液體或試劑液體再流出被動閥，以利後續之反應或檢測， 且當光源停止照射後，又可使被動閥回復關閉狀態。 【實施方式】 首先’利用流體之表面張力〔Surface Tension〕驅使 液體在微流管道内依照指定的順序或方向流動，譬如設計 微流管道擴張，則能使液體自然地滯留在管道中，或在管 道中設計特殊之幾何形狀，使液體僅自然地順向通過管 道，這種微流管道上的幾何形狀設計，類似於管路中的閥 門，又由於沒有可動元件，所以稱為被動閥。請參閱第一 圖所示，本發明係有關於一種利用光源來驅動生物晶片之 微流體系統中被動閥運作之方法，其中，在下晶片〔Lower Chip〕（1)上設置微流體系統中的微流管道（11)、呈幾何形 狀的被動閥（12)、一可注入樣本液體或試劑液體之注入槽 (14)及一儲存反應後之液體樣本或試劑之儲存槽（15)，且 在被動閥（12)的周壁被覆一層厚度為4〜13//m的奈米光觸 媒薄膜（13)，該奈米光觸媒薄膜（13)係採用粒徑為20〜50nm 之二氧化鈦粉末製成，而在上晶片〔Upper Chip〕（2)上設 有可發出380nm波長之紫外光源（21)與順序控制電路 (22);據此，即可在上、下晶片（2)、（1)所組成的生物晶 片之微流管道（11)上進行檢測，且在檢測的過程中，可利 用呈幾何形狀之被動閥（12)所採用不同的擴張角設計，來 阪擋樣本液體或試劑液體，使樣本液體或試劑液體依照所 1295375 要求的步驟在被動閥（12)内等待，或在被動閥（12)内進行 所需之化學反應，當等待時間或化學反應時間結束後，則 由順序控制電路（22)使被動閥（12)上方的紫外光源（21)發 光，使得被動閥（12)壁面上的奈米光觸媒薄膜（13)作用， 改變樣本液體或試劑液體在被動閥（12)壁面上的親水性關 係’使其接觸角改變，令被動閥（12)阻擋的液體依序流出 被動閥（12)，並儲存於儲存槽（15)内，以接著後續之反應 或檢測。 <實施例> 將去離子水〔DI water〕滴到具有奈米級的二氧化鈦 粉末薄膜的玻璃表面，經陽光照射，會使其表面的二氧化 鈦粉末受陽光中紫外線作用，產生光觸媒反應，使去離子 也逐漸轉變成更趨親水性；而且若停止陽光照射，其表面 又會慢慢變回疏水性；如第二圖所示，係水滴初始滴到具 奈米光觸媒薄膜的玻璃表面，其之接觸角為17·2° ，第三 圖係水滴滴到具奈米光觸媒薄膜（13)的玻璃表面，且經日 照5分鐘後，其之接觸角為11· Γ ，第四圖係水滴滴到具 奈米光觸媒薄（13)膜的玻璃表面，經日照1〇分鐘後之接觸 角7 · 2 ，由於以上的試驗可得到水滴在具奈米光觸媒薄膜 (13)的玻璃表面之平均接觸角及水滴在一般玻璃表面之接 觸角與日照時間之關係〔參第五圖〕，其中，當陽光照射一 未具有奈米光觸媒薄膜的一般玻璃表面時，去離子水之接 觸角保持33.3°，不受陽光照射時間增加而改變其接觸角。 經由以上的實施說明，可知僅有特定波長範圍的光線 〔 380nm〕才能激發被動閥（12)壁面上的奈米光觸媒薄膜 8 1295375 (13)作甩，並據此開啟被動閥（12)，使樣本液體或試劑液 體續流，而當光停止照射時，奈米光觸媒薄膜（13)作用消 失，被動閥（12)又回復到關閉狀態。 此外，由於本發明無需將電流或熱能與樣本液體或試 劑液體接觸，使得本發明之樣本液體或試劑液體受電流或 熱能影響的因素能夠大幅減低，提昇樣本液體或試劑液體 更準確的檢測結果。 另，請參閱第六圖所示，為本發明之另一實施，例其 係於下晶片（1)上設置微流體系統中的微流管道（11)、呈幾 何形狀的被動閥（12)、二注入槽（16)、（17)及一儲存反應 後之液體樣品或試劑之儲存槽（15)，此二注入槽（16)、（17) 可分別注入樣本液體與試劑，使它們流到被動閥（12)進行 反應，待反應完成後，打開紫外光源（21)，使反應後的液 體流出被動閥（12)以做後續之處理。 綜上所述，本發明實施例確能達到所預期之使用功 效’又其所揭露之具體構造，不僅未曾見諸於同類產品中， 亦未曾公開於申請前，誠已完全符合專利法之規定與要 求’爰依法提出發明專利之申請，懇請惠予審查，並賜准 專利，則實感德便。 1295375 【圖式簡單說明】 第一圖··本發明之微流體系統的管道與被動閥及紫外 光源與順序控制電路位置圖 第二圖：係水滴初始滴到具奈米光觸媒薄膜的玻璃表 面之圖 第三圖：係水滴滴到具奈米光觸媒薄膜的玻璃表面， 且經日照5分鐘後之圖 第四圖：係水滴滴到具奈米光觸媒薄膜的玻璃表面經 ，日照10分鐘後之圖 第五圖··係水滴在奈米光觸媒薄膜的玻璃表面之平均 接觸角與日照時間之關係圖 第六圖··係本發明之另一實施 【主要元件符號說明】 (1) 下晶片 (11) 微流管道 (12) 被動閥 (13) 奈米光觸媒薄膜 (14) 注入槽 (15) 儲存槽 (16) 注入槽 (17) 注入槽 (2) 上晶片 (21) 紫外光源 (22) 順序控制電路 10::v 1295375 IX. Description of the Invention: [Technical Field] The present invention is a passive in-valve fluid driving method for two kinds of biochip microfluidic pipes, in particular, a type of liquid having no need for current or thermal energy and sample liquid. Or the characteristic of the liquid contact of the reagent, the passive in-situ fluid driving method of the biochip microfluidic pipeline which can reduce the influence of the current or the thermal energy of the sample liquid or the reagent liquid. [Prior Art] EI, # 'Micro-Electro-Mechanical Systems for biological or chemical analysis is a research field that has received much attention in recent years - the goal is to use biological or chemical characterization or processes that used to require expensive instruments, time-consuming and labor-intensive It can be implemented on this tiny system. This device is collectively called Biochip. Its advantages include: the sample volume and test time are greatly reduced, while providing parallel fast __ and low-segment (four) process cost. The kind of wafer can be very 5 (four) made by Saki (four) Bi can be discarded, listening to the secondary pollution problem caused by the filthy tube. In addition, biochip technology can be used in a wide range of applications, such as new drug development, genetic engineering, environmental monitoring, and clinical disease diagnosis. The fluids analyzed and operated in the wafer are mainly liquid media, such as blood, body fluids, urine, etc. 'Thus various small components are designed in the wafer to perform the mixing, extraction, heating, and Cooling, sample interpretation and other processes, and the fluid pipe connecting various components is about 100~400//ΧΠ, so it is called MicroChannel, and various tiny components in the pipe are called microfluidics. Microfluidics], or microfluidics. The technology for driving the liquid flow in the microfluidic pipeline can be micro-machine 1295375 [micro-film, micro-cantilever, micro-impeller], and then input electric energy to make the micro-mechanism swing or rotate to drive the liquid flow, which is for the micro-pull [ Micro Pump is achieved by using liquid surface tension; that is, the microfluidic pipe is made to a small scale (about 70/zm or less), and the interfacial force between the liquid and the pipe wall (surface tension, capillary force) is on the liquid flow. The effect will be greater than the force associated with the quality of the liquid (eg inertial force, gravity). In addition, more complex inspections, analyses, or processes require that the liquid in the wafer be retained in the set area, then re-free, or that the liquid in different lines needs to flow in the microfluidic flow of the wafer in the order of design; The manner in which the flow sequence is controlled or the liquid is freewheeled is: (i) the microelectrode is fabricated in the microchannel, and when the liquid needs to be freewheeled, the electrode is energized to cause the liquid to electrolyze to generate bubbles, and the bubble pressure pushes the liquid; Or placing the microchannel wafer on a rotating machine to drive the liquid to flow freely; (iii) bringing the surface tension between the liquid interfaces by heating, energizing, adding an surfactant, etc. to make the contact angle between the liquid and the tube wall interface Change, causing the liquid to continue to flow. However, looking at the above-mentioned manner in which the flow sequence of the liquid can be controlled or the flow of the blocked liquid is continued, the current or thermal energy needs to be brought into contact with the sample liquid or the reagent liquid, so that the influence of the current or the heat of the sample liquid or the reagent liquid is greatly increased. High, and affect the analysis results of the liquid. SUMMARY OF THE INVENTION Nowadays, in order to solve the above-mentioned situation, the inventors have developed a passive in-valve fluid driving method of the biochip microfluidic pipe of the present invention. The passive in-valve fluid driving method of the biochip microfluidic pipeline of the present invention mainly utilizes a light source to drive a passive valve operation in a microfluidic system, which can make a flow path in the biochip micro 1295375 according to a required reaction or detection step. The sample liquid or reagent liquid flowing inside is blocked by the passive valve in the passive valve. After waiting for the chemical reaction, the light source drives the photocatalyst reaction of the passive valve wall surface to sequentially open the passive valve to make the sample of the blocked file. The liquid or reagent liquid flows out of the passive valve to facilitate subsequent reaction or detection, and when the light source stops emitting, the passive valve can be returned to the closed state. [Embodiment] Firstly, the surface tension of the fluid is used to drive the liquid to flow in the microflow duct according to a specified sequence or direction. For example, if the microfluidic tube is designed to expand, the liquid can be naturally retained in the pipeline, or The special geometry of the pipe is designed so that the liquid only passes naturally through the pipe. The geometry of the microfluidic pipe is similar to that of a valve in a pipeline, and because it has no moving components, it is called a passive valve. Referring to the first figure, the present invention relates to a method for operating a passive valve in a microfluidic system using a light source to drive a biochip, wherein a microfluidic system is provided on a lower chip (1). a flow conduit (11), a passive passive valve (12), an injection tank (14) into which a sample liquid or reagent liquid can be injected, and a storage tank (15) for storing a liquid sample or reagent after the reaction, and in a passive The peripheral wall of the valve (12) is coated with a nano photocatalyst film (13) having a thickness of 4 to 13/m, and the nano photocatalyst film (13) is made of titanium dioxide powder having a particle diameter of 20 to 50 nm. The upper chip (2) is provided with an ultraviolet light source (21) capable of emitting a wavelength of 380 nm and a sequence control circuit (22); accordingly, a creature composed of the upper and lower wafers (2) and (1) The microfluidic tube (11) of the wafer is tested, and during the detection process, the divergent angle design of the passive valve (12) can be used to block the sample liquid or the reagent liquid to make the sample liquid Or reagent liquid according to the requirements of 1295375 Waiting in the passive valve (12) or performing the required chemical reaction in the passive valve (12). When the waiting time or chemical reaction time is over, the sequential control circuit (22) causes the passive valve (12) to be above. The ultraviolet light source (21) emits light, so that the nano photocatalyst film (13) on the wall of the passive valve (12) acts to change the hydrophilic relationship of the sample liquid or the reagent liquid on the wall of the passive valve (12) to change the contact angle thereof. The liquid blocked by the passive valve (12) sequentially flows out of the passive valve (12) and is stored in the storage tank (15) for subsequent reaction or detection. <Examples> Deionized water [DI water] was dropped onto the surface of a glass of a titanium dioxide powder film having a nanometer level, and the surface of the titanium dioxide powder was subjected to ultraviolet rays in sunlight to cause a photocatalytic reaction. Deionization is also gradually transformed into more hydrophilic; and if the sunlight is stopped, the surface will slowly return to hydrophobicity; as shown in the second figure, the water droplets are initially dropped onto the glass surface of the photocatalyst film with nanometers. The contact angle is 17·2°, and the third figure drops onto the glass surface of the photocatalyst film (13), and after 5 minutes of sunlight, the contact angle is 11·Γ, and the fourth picture is a drop of water. On the glass surface with a thin film of nano-photocatalyst (13), the contact angle of 7 · 2 after 1 minute of sunlight, the average contact angle of water droplets on the glass surface of the photocatalyst film (13) can be obtained by the above test. And the relationship between the contact angle of water droplets on the general glass surface and the sunshine time [refer to Figure 5], wherein when the sunlight is irradiated to a general glass surface without a nano photocatalyst film, the contact of deionized water Holding 33.3 °, the irradiation time is increased from the sun changes its contact angle. Through the above description, it can be seen that only light of a specific wavelength range [380 nm] can excite the nano photocatalyst film 8 1295375 (13) on the wall of the passive valve (12), and thereby open the passive valve (12). The sample liquid or reagent liquid continues to flow, and when the light stops, the nano photocatalyst film (13) disappears and the passive valve (12) returns to the closed state. In addition, since the present invention does not require current or thermal energy to be in contact with the sample liquid or the reagent liquid, the factor of the sample liquid or reagent liquid of the present invention which is affected by current or heat energy can be greatly reduced, and the detection result of the sample liquid or the reagent liquid can be improved more accurately. In addition, referring to the sixth embodiment, in another embodiment of the present invention, the microfluidic tube (11) in the microfluidic system is disposed on the lower wafer (1), and the passive valve (12) is geometrically shaped. And two injection tanks (16), (17) and a storage tank (15) for storing the liquid sample or reagent after the reaction, the two injection tanks (16), (17) can respectively inject the sample liquid and the reagent to make them flow The reaction is carried out to the passive valve (12). After the reaction is completed, the ultraviolet light source (21) is turned on, and the reacted liquid flows out of the passive valve (12) for subsequent processing. In summary, the embodiments of the present invention can achieve the expected use efficiency and the specific structure disclosed therein, which has not been seen in similar products, nor has it been disclosed before the application, and has fully complied with the provisions of the Patent Law. With the request for 'claiming an invention patent in accordance with the law, please apply for a review and grant a patent. 1295375 [Simple description of the drawings] First figure · The position of the pipeline and passive valve and the ultraviolet light source and the sequence control circuit of the microfluidic system of the present invention is as follows: the water droplet is initially dropped onto the glass surface of the photocatalyst film with nanometer Figure 3: The water droplets drip onto the surface of the glass with nano-photocatalyst film, and after 5 minutes of sunlight, the fourth picture: the water droplets drip onto the glass surface with nano-photocatalyst film, after 10 minutes of sunshine Fig. 5 is a diagram showing the relationship between the average contact angle of water droplets on the glass surface of the nanophotocatalyst film and the sunshine time. Fig. 6 is another embodiment of the present invention. [Main component symbol description] (1) Lower wafer (11) Microfluidic Pipeline (12) Passive Valve (13) Nano Photocatalyst Film (14) Injection Tank (15) Storage Tank (16) Injection Tank (17) Injection Tank (2) Upper Wafer (21) UV Light Source (22) Sequence Control circuit 10