1287574 九、發明說明： 【發明所屬之技術領域】 本發明係關於一種用於生化反應上的快速加熱裝置，特 別有關於一種用於聚合酶連鎖反應(P〇lymerase chain Reaction， pCR)的加熱裝置。 【先前技術】 因PCR技術的發明，人類在分子生物及生物醫學方面有 更重大的突破。藉由PCR，研究人員能方便地大量增幅一段特 # 定之去氧核糖核酸（DNA)，進而可鑑定特定基因存在與否， 並可偵測基因是否有異常，舉凡對遺傳疾病、細菌、病毒檢驗， 乃至於親子鑑定與法醫學上之鑑定。 PCR之關鍵技術在於短時間内，在雙股分離(Denature)、 引子雜父(Annealing)、DNA合成(Extension)的三個溫度區間(一 般疋93〜95 C、30〜65°C、65〜75°C) ’依序進行三段反應，重 複約20〜30次，以放大特定DNA序列，其中，昇/降溫需要 十分快速，若昇降溫速度過慢，或溫度不準確就容易產生非特 鲁 異產物（non-specific products )，而干擾檢驗結果。 目前有許多加熱方式，如US 5,475,61〇號專利係利用加 熱金屬塊並採取接觸方式將熱量傳遞至試管内，但由於金屬塊 熱質里（thermalmass)非常大，因此很難快速地昇降溫。 US 5,720,923、US 6,852,986號專利提供了另一種加熱方 式。其係利用加熱板預熱流體，再以騎或傳導方式加熱，使 熱能傳入至試管，以達到加溫目的，但同樣因為流體之熱質量 較大，因此較難快速變換溫度。 1287574 除傳導、對流方式外，另外有以紅外線輻射、鎢絲燈等 非接觸方式加熱，如TW 564,887、US 6,833,536號專利，其可 選擇性地配合濾、光鏡以加強集中熱源，可減少加熱體積而能使 加熱及冷卻速率提昇，然而這種加熱方式容易產生溫度過高的 現象，不易精確控制溫度。 另外有以白金、鎳、鉻、或鈦等金屬薄膜電阻加熱線圈 裝置進行接觸式加熱，如TW451，〇52號專利。其直接將熱源 傳送至反應試劑，此加熱裝置適合微型晶片使用，因微小化使 得加熱體積變小，其熱容量亦隨之減少，進而可增加昇溫的速 率，但晶片製造成本高昂。 職是之故，發明人鑑於習知技術之設計缺失，乃經悉心 試驗與研究，並一本鎮而不捨之精神，終發明出本案「用於生 物化學反應的加熱裝置及加熱方法」，以下為本案之簡要說明。 【發明内容】 本發明之一種態樣係有關於一種加熱生物化學反應中反 應物及/或生成物之裝置，其包括：一用以承裝該反應物及/ 或生成物的容器；一設置於該容器上的磁性物質；以及一裝設 於该容器周圍之磁場變化裝置，而該磁場變化裝置可使該磁性 物質產生熱能以加熱該反應物及/或生成物。 磁性物質可設置於與反應物及/或生成物接觸的容器内 侧上及/或不與反應物及/或生成物接觸的容器外側上。可利用 塗佈的方式將磁性物質設置於容器上，一般傳統的塗佈方式均 可適用於本發明，其中較佳的有帶狀塗佈、斜向塗佈等塗佈方 式0 1287574 磁性物質除設置於容器壁内及/或容器壁外之外，亦可設 置於容器的壁中，可與容器原料充分混合後一併射出成型為壁 中含磁性物質的容器。 如剞述之裝置可進一步包括一與該反應物及/或生成物 混合成一混合物的螢光物質，該混合物可依反應程度被激發出 相對應光強度的螢光。 無論磁性物質設置於容器的位置為何，較佳的情況，於 磁性物質設置於容器上後，該容器仍可透光，如此，螢光物質 發出的螢光可透過容器。更可於容器外設置一螢光偵測器感測 螢光，可精確掌握反應的進程。 本發明之另一種態樣係有關於一種加熱生物化學反應中 反應物及/或生成物之裝置，其包括··一用以承裝該反應物及/ 或生成物的容器；一設置於該反應物及/或生成物中的磁性物 質；以及一裝設於該容器周圍之磁場變化裝置，而該磁場變化 裝置可使該磁性物質產生熱能以加熱該反應物及/或生成物。 如前述本發明之另一種態樣中，磁性物質可分散於反應 物及/或生成物中，且分散後，光仍可透過磁性物質和該反應 物及/或生成物的混合物。 如前述本發明之另一種態樣中，該裝置可進一步包括一 與該反應物及/或生成物混合成一混合物的螢光物質，該混合 物可依反應程度被激發出相對應光強度的螢光。且由於磁性物 質分散後仍可允許光透過，因此，分散的螢光物質所發出的螢 光便可透過容器。更可於容器外設置一螢光偵測器感測螢光， 可精確掌握反應的進程。 1287574 本發明的生物化學反應更明舰係指與溫度相關的 反應，如PCR。 本發明的磁場變鋪置可以為任何會產生磁場變化的裝 置’較佳可為高週波線圈。而磁性物質可以為任何具磁性的物 貝，車义佳可為磁性金屬，更佳係可選自鐵、銘、鎳其中之一。 該磁性金屬形狀並沒有特定的限制，較佳可為粉末狀或顆粒 狀0 7 同週波加熱裝置原理如第一圖所示，在數匝線圈中放置 -磁性體，通人交變電流於線圈中，此時磁性體因感應產生磁 通’於磁性體中產生一與、線圈交變電流方向相反之渦電流，因 磁性體本身之固有姐產生—「職損」；又因磁通對電流之 父變造成磁滯現象，產生-「磁流損」；藉由兩種能量消耗， 磁性體會產生熱，溫度亦隨之上升。本發_姻此原理達成 加熱之目的。 【實施方式】 為了更進一步說明本發明為達成預定目的所採取之技 術、手段及功效，請參閱以下有關本發明之詳細說明，相信本 發明之目的、特徵與特點，當可由此得一深入且具體之了解， 然而下列說明僅提供參考與說明用，並非用來對本發明加以限 制者。 本發明之一實施例請參照第二圖，其為本案用於生物化 學反應之加熱裝置的一示意圖，包含一欲進行PCR反應之檢 體與試劑（8)、一裝承試劑與檢體之試管（9)、一高周波線圈 (6)、一固定試管之固定件（7)。其中試管（9)管壁以塗佈 1287574 方式披覆磁性奈米粉體，且試管（9)與高周波線圈（6)間以 固定件固定其相對位置，當高周波線圈（6)通入線圈交變電 流時’試管（9)管壁所披覆之磁性奈米金屬粉體受高周波感 應，以混合有磁性奈米粉體之管壁為熱源，快速產生熱能，加 熱減管（9)中欲進行PCR反應之檢體與試劑，以進行pcr 之加熱過程。 本發明之另一實施例請參照第三圖，其為本案用於生物 化學反應之加熱裝置的另一示意圖，包含一欲進行PCR反應 • 之檢體及含有磁性奈米粉體之試劑的混合物（11)、一裝承試 劑與檢體之試管（9)、一高周波線圈（6)、一固定試管之固定 件（7)。磁性奈米粉體均勻分散於試劑中，當高周波線圈（6) 通入線圈交變電流時，試劑中包含之磁性奈米金屬粉體受高周 波感應，以混合有磁性奈米粉體之試劑（11)為熱源，快^產 生熱能，加熱試管中欲進行PCR反應之檢體與試劑，以進行 PCR之加熱過程。 本發明更有一實施例請參照第四圖，其為本案用於生物 化學反應之加熱裝置的又一示意圖，包含一欲進行pCR反應 之檢體與試劑（8)、一裝承試劑與檢體之試管（12)、一高^ 波線圈（6)、-固定試管之固定件⑺。其中，奈米粉體=試 管原料均勻混合後射出成形為磁性奈米粉體嵌入試管壁之試 管（12)’當高周波線圈⑷通入線圈交變電流時，試管（& 壁内嵌人之樹生奈米金屬㈣受高周波感應，以嵌入有磁性齐 米粉體之試管（12)為熱源，快迷產生熱能，加熱試管中欲^ 行PCR反應之檢體與试劑’以進行pCR之加熱過程。 ^87574 本發明尚有一實施例係以上各實施例之改良，使用者可 於進打PCR反麟於試射加人縣物質，螢光物質可被適 當波長之光源激發出螢光，方便使用者觀察反應進程。觀察的 方式可以_任何相的觀察；^法，如以顯微鏡觀測或以螢光 偵測器偵測等方式。 雖然本發明已以數個較佳實施例揭露如上，然其 並非用以限定本發明，任何熟習此技藝者，在不脫離 本發明之精神和範圍内，當可作些許之更動與潤飾， 因此本發明之保護範圍當視後附之申請專利範圍所 界定者為準。 【圖式簡單說明】 第一圖··本案高週波加熱原理的示意圖； 第二圖：本案用於生物化學反應之加熱裝置的一實施例之示意 圖； 第三圖：本案用於生物化學反應之加熱裝置的另一實施例之示 意圖；及 第四圖：本案用於生物化學反應之加熱裝置的更一實施例之示 意圖。 【主要元件符號說明】 1 磁通 8 試劑 2 磁性體 9 試管 3 線圈交變電流 10 彼覆金屬的管壁 4 渦電流 11 混合奈米金屬粉的試劑 5 線圈 12 嵌入金屬顆粒的試管 6 高周波線圈 7 固定件 101287574 IX. Description of the Invention: [Technical Field] The present invention relates to a rapid heating device for biochemical reactions, and more particularly to a heating device for a polymerase chain reaction (PCR) . [Prior Art] Due to the invention of PCR technology, humans have made even more significant breakthroughs in molecular biology and biomedicine. By PCR, researchers can easily increase the amount of DNA in a large amount of DNA, which can identify the presence or absence of a specific gene, and detect whether the gene is abnormal. For genetic diseases, bacteria, and viruses. , even the paternity test and the identification of forensic science. The key technology of PCR is in the short time, in the three temperature intervals of Denature, Annealing, and DNA synthesis (generally 〜93~95 C, 30~65°C, 65~) 75 °C) 'Sequential three-stage reaction, repeat about 20~30 times to enlarge the specific DNA sequence, wherein the rise/fall temperature needs to be very fast, if the temperature rise and fall is too slow, or the temperature is not accurate, it is easy to produce non-Tru Non-specific products, which interfere with the test results. There are many heating methods, such as the US 5,475,61 专利 patent, which uses a heated metal block and contacts to transfer heat to the test tube, but because the thermal mass of the metal block is very large, it is difficult to quickly and gently rise and fall. . Another heating method is provided in U.S. Patent No. 5,720,923 and U.S. Patent No. 6,852,986. It uses a heating plate to preheat the fluid, and then heats it by riding or conducting, so that heat energy is transferred to the test tube for heating purposes, but also because the thermal mass of the fluid is large, it is difficult to quickly change the temperature. In addition to conduction and convection methods, there are also non-contact heating methods such as infrared radiation and tungsten lamps, such as TW 564,887 and US Pat. No. 6,833,536, which can selectively cooperate with filters and light mirrors to enhance concentrated heat sources and reduce heating. The volume can increase the heating and cooling rate. However, this heating method is prone to overheating and it is difficult to accurately control the temperature. In addition, contact heating is performed by a metal film resistance heating coil device such as platinum, nickel, chromium, or titanium, such as TW451, 〇52 patent. The heat source is directly transferred to the reaction reagent. The heating device is suitable for use in a microchip. The miniaturization causes the heating volume to be reduced, and the heat capacity thereof is also reduced, thereby increasing the rate of temperature rise, but the wafer manufacturing cost is high. As a result of the job, the inventor, in view of the lack of design of the prior art, was carefully tested and researched, and the spirit of perseverance was used to invent the case "heating device and heating method for biochemical reactions". The following is a brief description of the case. SUMMARY OF THE INVENTION One aspect of the present invention relates to a device for heating a reactant and/or a product in a biochemical reaction, comprising: a container for holding the reactant and/or product; a magnetic substance on the container; and a magnetic field changing device mounted around the container, and the magnetic field changing device causes the magnetic substance to generate thermal energy to heat the reactant and/or product. The magnetic substance may be disposed on the inside of the container in contact with the reactants and/or product and/or on the outside of the container not in contact with the reactants and/or product. The magnetic substance can be placed on the container by means of coating. Generally, the conventional coating method can be applied to the present invention, and the preferred coating method such as strip coating or oblique coating is 0 1287574. It may be disposed in the wall of the container and/or outside the wall of the container, or may be disposed in the wall of the container, and may be mixed with the container material to be injected into a container containing a magnetic substance in the wall. The apparatus as described above may further comprise a fluorescent substance mixed with the reactants and/or products to form a mixture which is excited by the fluorescence of the corresponding light intensity depending on the degree of reaction. Regardless of the position at which the magnetic substance is placed in the container, preferably, after the magnetic substance is placed on the container, the container is still transparent, so that the fluorescent material emits fluorescence through the container. A fluorescent detector can be placed outside the container to sense the fluorescence, so that the progress of the reaction can be accurately grasped. Another aspect of the invention relates to a device for heating a reactant and/or a product in a biochemical reaction, comprising: a container for holding the reactant and/or product; a magnetic substance in the reactant and/or product; and a magnetic field changing device disposed around the container, and the magnetic field changing device causes the magnetic material to generate thermal energy to heat the reactant and/or product. In another aspect of the invention described above, the magnetic material can be dispersed in the reactants and/or products, and after dispersion, the light is still permeable to the mixture of the magnetic material and the reactants and/or products. In another aspect of the invention described above, the apparatus may further comprise a fluorescent substance mixed with the reactant and/or the product to form a mixture, and the mixture may be excited by the corresponding light intensity according to the degree of reaction. . Since the light is allowed to pass through after the magnetic substance is dispersed, the fluorescent light emitted from the dispersed fluorescent material can pass through the container. A fluorescent detector can be set outside the container to sense the fluorescence, so that the progress of the reaction can be accurately grasped. 1287574 The more biochemical reaction of the present invention refers to temperature dependent reactions such as PCR. The magnetic field degrading of the present invention can be any device that produces a change in the magnetic field, preferably a high frequency coil. The magnetic substance may be any magnetic material, and the car may be a magnetic metal, and more preferably one of iron, m, and nickel. The magnetic metal shape is not particularly limited, and may preferably be in the form of powder or granules. The principle of the same-wave heating device is as shown in the first figure. The magnetic body is placed in the coil of the number of turns, and the alternating current is applied to the coil. In this case, the magnetic body generates a magnetic flux in the magnetic body to generate an eddy current in the magnetic body opposite to the direction of the alternating current of the coil, which is caused by the inherent sister of the magnetic body itself, and the magnetic flux is opposite to the current. The father becomes a hysteresis and produces - "magnetic flow loss"; with two energy consumptions, the magnetic body generates heat and the temperature rises. This is the principle of heating. [Embodiment] In order to further illustrate the techniques, means, and effects of the present invention in order to achieve the intended purpose, refer to the following detailed description of the present invention. It is believed that the objects, features and features of the present invention can be The detailed description is to be understood as illustrative and not restrictive. For an embodiment of the present invention, please refer to the second figure, which is a schematic diagram of a heating device for biochemical reaction, comprising a sample and reagent (8) for performing a PCR reaction, a loading reagent and a sample. A test tube (9), a high-frequency coil (6), and a fixing member (7) for fixing the test tube. Wherein the tube (9) wall is coated with magnetic nano-nano powder by coating 1287754, and the relative position between the test tube (9) and the high-frequency coil (6) is fixed by a fixing member, when the high-frequency coil (6) is passed into the coil and alternating At the time of current, the magnetic nano-metal powder coated by the tube of the test tube (9) is subjected to high-frequency induction, and the wall of the magnetic nano-powder is used as a heat source to rapidly generate heat energy, and the heat-reduced tube (9) is to be subjected to PCR. The sample and reagent are reacted to carry out the heating process of pcr. Another embodiment of the present invention refers to the third figure, which is another schematic diagram of a heating device for biochemical reaction, comprising a sample for performing a PCR reaction and a mixture of reagents containing magnetic nano-powder ( 11), a test tube (9) for loading the reagent and the sample, a high-frequency coil (6), and a fixing member (7) for fixing the test tube. The magnetic nano-powder is uniformly dispersed in the reagent. When the high-frequency coil (6) is supplied to the coil alternating current, the magnetic nano-metal powder contained in the reagent is subjected to high-frequency induction to mix the magnetic nano-powder reagent (11). As a heat source, heat is generated quickly, and the sample and reagent to be subjected to the PCR reaction in the test tube are heated to perform a PCR heating process. In another embodiment of the present invention, please refer to the fourth figure, which is still another schematic diagram of a heating device for biochemical reaction, comprising a sample and reagent (8) for preparing a pCR reaction, a loading reagent and a sample. The test tube (12), a high-wave coil (6), and a fixing member (7) for fixing the test tube. Among them, the nano-powder = test tube raw material is uniformly mixed and then injected into a test tube (12) in which the magnetic nano-powder is embedded in the test tube wall. When the high-frequency coil (4) is passed into the coil alternating current, the test tube (& The nano metal (4) is subjected to high-frequency induction, and the test tube (12) in which the magnetic rice powder is embedded is used as a heat source to generate heat energy, and the sample and the reagent to be subjected to the PCR reaction in the test tube are heated to perform the heating process of the pCR. ^87574 There is still an embodiment of the present invention which is an improvement of the above embodiments. The user can perform the PCR reaction to test the material of the county, and the fluorescent substance can be excited by the light source of the appropriate wavelength to facilitate the user to observe. The progress of the reaction can be observed in any way, such as by microscopic observation or by fluorescent detector detection. In order to limit the present invention, those skilled in the art can make some modifications and refinements without departing from the spirit and scope of the present invention. The definitions shall prevail. [Simplified description of the diagram] The first diagram · The schematic diagram of the high-frequency heating principle of this case; The second diagram: The schematic diagram of an embodiment of the heating device for biochemical reaction in this case; The third picture: the case A schematic view of another embodiment of a heating device for a biochemical reaction; and a fourth view: a schematic view of a further embodiment of a heating device for a biochemical reaction in this case. [Explanation of main components] 1 Magnetic flux 8 Reagent 2 Magnetic body 9 Test tube 3 Coil alternating current 10 Metal-coated tube wall 4 Eddy current 11 Reagent for mixing nano metal powder 5 Coil 12 Test tube embedded with metal particles 6 High-frequency coil 7 Fixing member 10