TWM610718U - Biochip detection device and biosensor platform thereof - Google Patents
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Abstract
本新型提供一種生物晶片檢測裝置及其生物傳感器平台，該生物傳感器平台包括以半導體製造技術生產製成之芯片；該芯片上設有金薄膜電極，該金薄膜電極的表面固定有生物素化接頭以及與該生物素化接頭連接的生物受體，該金薄膜電極具有至少單一金原子的厚度；令待測生物樣本置於該生物傳感器平台上與該生物受體反應形成阻抗訊號，以檢測該待測生物樣本是否受到感染。藉此，改善生物受體的固定性，從而生產出具有優異準確性、穩定性之無標記親和電化學生物傳感器，達到快速檢測病毒及/或微生物類型感染之目的。The present model provides a biological wafer detection device and a biological sensor platform thereof. The biological sensor platform includes a chip produced by semiconductor manufacturing technology; the chip is provided with a gold film electrode, and a biotinylation joint is fixed on the surface of the gold film electrode And a biological receptor connected to the biotinylated connector, the gold film electrode has a thickness of at least a single gold atom; the biological sample to be tested is placed on the biosensor platform to react with the biological receptor to form an impedance signal to detect the Whether the biological sample to be tested is infected. In this way, the immobilization of the bioreceptor is improved, thereby producing a label-free affinity electrochemical biosensor with excellent accuracy and stability, and achieving the purpose of rapid detection of virus and/or microbial infections.
Description
本新型係關於一種電化學生物傳感器；特別關於一種以半導體製造技術製成，以免疫球蛋白自組裝結合於金薄膜電極上所形成之生物晶片檢測裝置及其生物傳感器平台、製法和應用。This new model relates to an electrochemical biosensor; in particular, it relates to a biochip detection device made by semiconductor manufacturing technology and self-assembled with immunoglobulin combined with a gold film electrode, and its biosensor platform, manufacturing method and application.
生物晶片（Biochip）廣義地定義是指固相（玻璃、矽片、塑膠、尼龍膜等材質）上，利用微影或微量固定樣本等方法製成之反應區，生物樣本將與固相上的分子進行反應，以應用於生物檢測及化學分析的產品，因所需樣品量少、反應速度快、平行化檢測等特性，所以能夠在短時間內檢測大量分子，使人們快速地獲取樣品中的資訊。在所有的生物晶片中，生物傳感器（BioSensor）是利用生物要素與物理化學檢測要素組合在一起對被分析物進行檢測的裝置，由於其具有簡易型檢測試片的開發可大幅降低檢測成本、對於檢測目標物具辨識性、可工業化大量生產、操作簡易、靈敏度高而所需樣品量少、分析時間短、可用於現場即時偵測等優點，從而深具市場潛力。The broad definition of Biochip refers to the reaction zone made on the solid phase (glass, silicon wafer, plastic, nylon membrane, etc.) using methods such as photolithography or micro-fixing of the sample. The biological sample will be compared with the solid phase. Molecules are reacted to be used in biological detection and chemical analysis products. Due to the small amount of sample required, fast reaction speed, parallel detection and other characteristics, a large number of molecules can be detected in a short period of time, allowing people to quickly obtain the content of the sample. News. Among all biochips, BioSensor is a device that uses a combination of biological elements and physicochemical detection elements to detect analytes. The development of simple test strips can greatly reduce the cost of detection. The detection target has the advantages of recognizability, industrial mass production, simple operation, high sensitivity, small sample amount required, short analysis time, and real-time detection on site, which has deep market potential.
目前最適合開發成為即時醫療（Point of Care，POC）產品的是一種無標記親和電化學生物傳感器（label-free affinity electrochemical biosensor），該傳感器包括以半導體製造技術生產的電極和生物合成的鏈黴親和素介體（streptavidin mediator）；其中，半導體製造技術能夠增強電極組件的一致性，藉此提高生物傳感器的重現性，無標記親和力檢測（label-free affinity detection）可簡化生產並與廣泛的待測目標（target）直接相互作用，從而擴大了潛在用途並提高了生物傳感器的準確性，進而，鏈黴親和素對生物素鍵結的生物受體表現出強大的結合親和力，且鏈黴親和素可穩定生物受體修飾，從而提高生物傳感器的穩定性；因此，前述無標記親和電化學生物傳感器與其他方法生產的生物傳感器相比，具有更高的重現性、準確性和穩定性。At present, the most suitable point of care (POC) product is a label-free affinity electrochemical biosensor (label-free affinity electrochemical biosensor), which includes electrodes produced by semiconductor manufacturing technology and biosynthetic streptomyces Streptavidin mediator; among them, semiconductor manufacturing technology can enhance the consistency of the electrode assembly, thereby improving the reproducibility of the biosensor, label-free affinity detection (label-free affinity detection) can simplify production and be compatible with a wide range of The target to be tested directly interacts, thereby expanding the potential use and improving the accuracy of the biosensor. Furthermore, streptavidin has a strong binding affinity for biotin-bonded bioreceptors, and streptavidin has affinity It can stabilize the bioreceptor modification, thereby improving the stability of the biosensor; therefore, the aforementioned label-free affinity electrochemical biosensor has higher reproducibility, accuracy and stability than biosensors produced by other methods.
值得注意的是，雖然前述無標記親和電化學生物傳感器已在重現性、準確性和穩定性的性能表現上有所提升，但前述三個指標是POC產品的重要指標，而目前已知許多因素會嚴重影響生物傳感器的重現性、準確性和穩定性，例如，在電極組裝方面，調整半導體製造技術以適應無標籤親和力檢測；這種檢測方法直接在芯片表面上測量電信號的變化，因此準確性在很大程度上取決於電極的製造方法；其中，金屬薄膜的厚度是影響準確性的重要因素之一，且會嚴重影響導電率（conductivity），從而最終影響檢測結果。因此，半導體製造技術的調整能夠有效提高準確性。同時，儘管使用鏈黴親和素生物介體可以提高穩定性，但將生物受體直接固定在介體上會限制其方向並干擾功能，從而限制了準確性，亦有待進一步改進。It is worth noting that although the aforementioned label-free affinity electrochemical biosensors have improved their reproducibility, accuracy, and stability, the aforementioned three indicators are important indicators for POC products, and many are currently known Factors can seriously affect the reproducibility, accuracy and stability of biosensors. For example, in electrode assembly, semiconductor manufacturing technology is adjusted to adapt to label-free affinity detection; this detection method directly measures changes in electrical signals on the chip surface, Therefore, the accuracy largely depends on the manufacturing method of the electrode; among them, the thickness of the metal film is one of the important factors that affect the accuracy, and it will seriously affect the conductivity (conductivity), which ultimately affects the detection result. Therefore, the adjustment of semiconductor manufacturing technology can effectively improve accuracy. At the same time, although the use of a streptavidin biomediator can improve stability, the direct immobilization of the bioreceptor on the mediator will limit its direction and interfere with the function, thereby limiting the accuracy, and further improvement is needed.
綜上，有必要對習知生物傳感器進一步改進，特別是決定電化學生物傳感器之重現性、準確性和穩定性的重要組件：電極和生物介體。In summary, it is necessary to further improve conventional biosensors, especially the important components that determine the reproducibility, accuracy and stability of electrochemical biosensors: electrodes and biological mediators.
本新型之第一目的在於提供一種生物傳感器平台及其製法，透過半導體技術製程的優化實現對該生物傳感器平台上的金薄膜電極厚度進行調整，以及使用鏈黴親和生物介體做為接頭（linker），改善生物受體的固定性，從而生產出適用於即時醫療產品且具有優異準確性、穩定性之無標記親和電化學生物傳感器，達到優化無標記親和力檢測重現性之目的。The first purpose of the present invention is to provide a biosensor platform and its manufacturing method. The thickness of the gold film electrode on the biosensor platform can be adjusted through optimization of the semiconductor technology process, and the use of streptavidin as a linker (linker) ) To improve the immobility of bioreceptors, thereby producing a label-free affinity electrochemical biosensor with excellent accuracy and stability suitable for instant medical products, and achieve the purpose of optimizing the reproducibility of label-free affinity detection.
本新型之另一目的在於提供一種生物晶片檢測裝置，透過將前述生物傳感器平台設置於便攜且一次性使用的芯片模組上並配合檢測主機使用，即可基於免疫球蛋白、核酸探針、化學分子、功能蛋白或其組合的生物受體檢測法的原理進行生物樣本的快速篩檢，大幅度減少篩檢時間。Another object of the present invention is to provide a biological chip detection device, which can be based on immunoglobulin, nucleic acid probes, chemical The principle of the bioreceptor detection method of molecules, functional proteins or their combinations allows rapid screening of biological samples, greatly reducing the screening time.
本新型之再一目的在於提供一種生物晶片檢測裝置之應用，根據所要篩檢對象（病毒及/或微生物類型之感染），透過在裝置的芯片模組的生物晶片上固定選自免疫球蛋白、核酸探針、化學分子、功能蛋白或其組合的生物受體，即可快速應用於不同的感染標的進行篩檢，能夠廣泛應用於生物技術、醫學診斷、藥物及檢疫等領域，極具市場競爭優勢。Another purpose of the present invention is to provide an application of a biochip detection device. According to the object to be screened (virus and/or microbial type infection), the biochip of the chip module of the device is fixed on the biochip selected from immunoglobulin, Nucleic acid probes, chemical molecules, functional proteins or their combination of biological receptors can be quickly applied to different infection targets for screening, and can be widely used in biotechnology, medical diagnosis, medicine and quarantine and other fields, which is extremely competitive in the market. Advantage.
緣是，為達上述目的，本新型所提供一種生物傳感器平台，其包括以半導體製造技術生產製成之芯片；其中：該芯片上設有金薄膜電極，該金薄膜電極的表面固定有生物素化接頭以及與該生物素化接頭連接的生物受體，且該金薄膜電極具有至少單一金原子的厚度；令待測生物樣本置於該生物傳感器平台上與該生物受體反應形成阻抗訊號，以檢測該待測生物樣本是否受到感染。The reason is that, in order to achieve the above purpose, the present invention provides a biosensor platform, which includes a chip produced by semiconductor manufacturing technology; wherein: the chip is provided with a gold film electrode, and biotin is fixed on the surface of the gold film electrode The biotinylated connector and the bioreceptor connected to the biotinylated connector, and the gold film electrode has a thickness of at least a single gold atom; the biological sample to be tested is placed on the biosensor platform to react with the bioreceptor to form an impedance signal, To detect whether the biological sample to be tested is infected.
本新型另提供一種生物傳感器平台之製法，該生物傳感器平台係包括半導體製造技術生產製成之芯片，該芯片上設有金薄膜電極；其中，該製法的步驟包括：The present invention also provides a method for manufacturing a biosensor platform. The biosensor platform includes a chip produced by semiconductor manufacturing technology, and the chip is provided with a gold thin film electrode; wherein the steps of the method include:
步驟1：將該金薄膜電極進行活化反應，以在該金薄膜電極的表面上形成自組裝單層（SAM）結構；Step 1: Perform an activation reaction on the gold film electrode to form a self-assembled monolayer (SAM) structure on the surface of the gold film electrode;
步驟2：對該金薄膜電極進行生物素鍵結，以將生物素化的生物受體添加到生物介體修飾的金薄膜電極表面上；Step 2: Perform biotin bonding on the gold film electrode to add the biotinylated bioreceptor to the surface of the gold film electrode modified by the biomediator;
步驟3：清洗並乾燥該金薄膜電極，製得具有金薄膜電極的生物傳感器平台。Step 3: Wash and dry the gold thin film electrode to prepare a biosensor platform with gold thin film electrode.
本新型再提供一種生物晶片檢測裝置，包括：檢測主機；芯片模組，其內部設有生物晶片，該生物晶片包括基板、設於該基板相對兩端的生物傳感器平台以及傳導電極；其中，該生物晶片的基板上設有金薄膜電極，該金薄膜電極的表面固定有生物素化接頭以及與該生物素化接頭連接的生物受體，且該金薄膜電極具有至少單一金原子的厚度；該傳導電極與該生物傳感器平台的金薄膜電極之間具有導電線連接；令該芯片模組與該檢測主機連接，將待測生物樣本置於該生物傳感器平台上與該生物受體反應形成阻抗訊號，該檢測主機接收處理該阻抗訊號以判斷待測生物樣本是否受到感染。The present model further provides a biological chip detection device, which includes: a detection host; a chip module in which a biological chip is arranged. The biological chip includes a substrate, a biosensor platform arranged on opposite ends of the substrate, and a conductive electrode; wherein, the biological The substrate of the wafer is provided with a gold thin film electrode, the surface of the gold thin film electrode is fixed with a biotinylated joint and a bioreceptor connected to the biotinylated joint, and the gold thin film electrode has a thickness of at least a single gold atom; the conduction There is a conductive wire connection between the electrode and the gold film electrode of the biosensor platform; the chip module is connected to the detection host, and the biological sample to be tested is placed on the biosensor platform to react with the bioreceptor to form an impedance signal, The detection host receives and processes the impedance signal to determine whether the biological sample to be tested is infected.
本新型再提供一種所述生物傳感器平台的應用，該生物傳感器平台用於檢測免疫球蛋白、核酸探針、化學分子、功能蛋白或其組合的生物受體。The present invention further provides an application of the biosensor platform, which is used to detect immunoglobulins, nucleic acid probes, chemical molecules, functional proteins or a combination of biological receptors.
本新型再提供一種所述生物晶片檢測裝置的應用，該生物晶片檢測裝置用於檢測免疫球蛋白、核酸探針、化學分子、功能蛋白或其組合的生物受體。The present model further provides an application of the biological chip detection device, which is used for detecting the biological receptors of immunoglobulin, nucleic acid probe, chemical molecule, functional protein or a combination thereof.
有關於本新型為達成上述目的，所採用之技術、手段及其他功效，茲舉較佳可行實施例並配合圖式詳細說明如後。With regard to the technology, means and other effects adopted by the present invention to achieve the above-mentioned purpose, preferred and feasible embodiments are described in detail below in conjunction with the drawings.
本新型提供的生物傳感器平台是一種半導體製造電化學生物傳感器平台，其係對半導體製造技術製成的電極厚度進行優化，再與鏈黴親和素生物介體相結合以備後續與不同的生物受體結合，從而提供一種適用於即時醫療（POC）的無標記親和電化學生物傳感器。該生物傳感器平台包括芯片及其於其上的薄膜電極，透過對電極的厚度進行調整，達到優化生物傳感器在無標記親和力檢測中的重現性及穩定性；此外，透過向鏈黴親和素生物介體添加了具有理想柔韌性的獨特接頭，達到提高生物傳感器檢測準確性之目的。The biosensor platform provided by the present invention is an electrochemical biosensor platform for semiconductor manufacturing, which optimizes the thickness of electrodes made by semiconductor manufacturing technology, and then combines with streptavidin biomediator to prepare for subsequent exposure to different organisms. In order to provide a label-free affinity electrochemical biosensor suitable for point-of-care (POC). The biosensor platform includes a chip and a thin film electrode on it. The thickness of the electrode is adjusted to optimize the reproducibility and stability of the biosensor in the detection of label-free affinity; in addition, the biosensor can be applied to streptavidin. A unique joint with ideal flexibility is added to the mediator to achieve the purpose of improving the detection accuracy of the biosensor.
如圖1及圖2，顯示本新型生物傳感器平台100的半導體技術製程步驟以及在金薄膜電極15上固定生物受體18的製法流程。本新型生物傳感器平台100是在半導體技術製成之芯片10的金薄膜電極15表面固定生物受體18後形成。本新型透過調整該金薄膜電極15的厚度，使該金薄膜電極15具有至少單一金原子的厚度。藉此，該金薄膜電極15由於厚度調整，使薄膜狀的電極具有更平均的厚度分布，使測到的阻抗值下降，且能測到平均分布的阻抗值，使生物傳感器平台100輸出的阻抗訊號穩定性更高且一致。FIGS. 1 and 2 show the semiconductor technology manufacturing process steps of the
如圖1所示，本新型生物傳感器平台100包括以半導體製造技術生產製成之芯片10，該芯片10上設有金薄膜電極15，該金薄膜電極15的表面固定有生物素化接頭16以及與該生物素化接頭16連接的生物受體18，且該金薄膜電極15具有至少單一金原子的厚度。As shown in FIG. 1, the new type of
如圖1，顯示本新型生物傳感器平台100上金薄膜電極15的製造流程，其步驟包括(a)提供陶瓷基板11→(b)鍍銅：於該陶瓷基板11表面形成銅鍍層12→(c)電阻塗層：於該銅鍍層12表面形成電阻塗層13→(d)曝光/顯影：利用光源裝置14照射電阻塗層13以進行曝光及顯影程序→(e)電鍍金：於該電阻塗層13去除後形成的空間內電鍍金，以形成金薄膜電極15→(f)蝕刻/去膜：去除剩餘電阻塗層13→(g)製成表面設有金薄膜電極15之芯片10。其中，本新型係經由直接鍍銅（DPC）技術、濺鍍和蝕刻工藝生產了金薄膜電極15，其與半導體製造技術生產的電極具有相同的製造流程。此外，如圖1之 (f)小圖所示，以至少單一金原子的厚度塗佈形成該金薄膜電極15；於本新型實施態樣中，該金薄膜電極15的厚度最大值可分別視實際需要增加至合理範圍。Figure 1 shows the manufacturing process of the gold
如圖2，顯示本新型生物傳感器平台之製法的步驟包括：As shown in Figure 2, the steps of the manufacturing method of the new type of biosensor platform include:
步驟1：透過將芯片10表面的金薄膜電極15浸入活化劑中進行活化反應，以在金薄膜電極15表面上建立自組裝單層（SAM）結構，再以明膠17封閉；Step 1: The
步驟2：為了將生物受體（免疫球蛋白、核酸探針、化學分子、功能蛋白或其組合的生物受體）固定在金薄膜電極15上，進行了生物素鍵結，並將生物素化的生物受體18添加到生物介體（生物素化接頭16）修飾的金薄膜電極15上，使生物受體18與生物素化接頭16鍵結；Step 2: In order to immobilize the biological receptor (immunoglobulin, nucleic acid probe, chemical molecule, functional protein, or a combination of biological receptors) on the
步驟3：最後，將修飾後電極清洗並乾燥，製得金薄膜電極15具有至少單一金原子的厚度之半導體製造電化學生物傳感器平台。Step 3: Finally, the modified electrode is cleaned and dried to obtain a semiconductor manufacturing electrochemical biosensor platform with a gold
其中，該生物受體18為結合分子(binding molecules)，生物受體18具體可選自免疫球蛋白、核酸探針、化學分子、功能蛋白或其組合的生物受體，用以篩檢不同的標的物。Wherein, the
其中，該生物素化接頭16為鏈黴親和素生物介體。具體地，本新型生物傳感器平台所使用之生物介體係由鏈黴親和素序列獨立構建之接頭（linker）。Wherein, the biotinylated
如圖3至圖5及圖6A至圖6B，顯示本新型生物晶片檢測裝置200的整體架構、外觀結構以及檢測顯示結果。FIGS. 3 to 5 and FIGS. 6A to 6B show the overall structure, appearance structure, and inspection and display results of the
如圖3顯示本新型生物晶片檢測裝置200的一種實施例示意圖，該實施例不用於限制本新型的生物晶片檢測裝置200，本新型生物晶片檢測裝置200可根據實際檢測需求進行元件、部件的數量及設置方法、位置之調整。Fig. 3 shows a schematic diagram of an embodiment of the new type of biological
如圖3所示，本新型生物晶片檢測裝置200包括檢測主機20及芯片模組30，其中，該芯片模組30的內部設有生物晶片31，該生物晶片31包括基板311、設於該基板311相對兩端的生物傳感器平台100以及傳導電極312；其中，該生物晶片31的基板311上設有前述金薄膜電極15，該金薄膜電極15的表面固定有生物素化接頭16以及與該生物素化接頭16連接的生物受體18，且該金薄膜電極15具有至少單一金原子的厚度；該傳導電極312與該生物傳感器平台100的金薄膜電極15之間具有導電線313連接；藉此，令該芯片模組30與該檢測主機20連接，將待測生物樣本置於該生物傳感器平台100上與該生物受體18反應形成阻抗訊號，該檢測主機20接收處理該阻抗訊號以判斷待測生物樣本是否受到感染。As shown in FIG. 3, the new type of
於本新型生物晶片檢測裝置200的較佳實施例中，該檢測主機20內部設有電路板21，該電路板21分別與設於該檢測主機20內部的推進器和供電源25以及顯露設於該檢測主機20外部表面的芯片插口26、人機界面27與啟動鍵28連接；該芯片模組30內部設有生物晶片31以及測試液容器；該生物晶片31具有一電極連接頭310形成於該芯片模組30外部表面；令該芯片模組30與該檢測主機20連接，該電極連接頭310與該芯片插口26插接，該推進器與該測試液容器連通，該測試液透過該推進器形成壓力推進而輸出至該生物晶片31。In a preferred embodiment of the new biological
本新型生物晶片檢測裝置200的實施態樣中，該檢測主機20內的推進器用於與該芯片模組30的測試液容器連接以推進測試液輸出至該生物晶片31進行反應形成阻抗訊號；於本新型實施例中，該推進器可以是微幫浦或其他能夠實現將測試液從其容器中輸出的動力源，該芯片模組30內的測試液種類及其容器數量可根據實際檢測需求進行調整，該芯片模組30內的測試液種類較佳為一至三種，但不限於此；該測試液分別容置於對應測試液種類數量的容器中。In the implementation aspect of the
如圖3所示，顯示本新型生物晶片檢測裝置200的推進器與測試液容器具體實施例，該生物晶片檢測裝置200的推進器包括第一幫浦23及第二幫浦24與該電路板21電連接，該芯片模組30內部設有清洗液及檢測液兩種測試液並分別容置於清洗液容器33及檢測液容器34中；其中，該第一幫浦23、第二幫浦24為微型幫浦，供輸出氣體至管路中形成氣壓，以推動清洗液容器33、檢測液容器34中的液體流向生物晶片31進行清洗及檢測。As shown in FIG. 3, a specific embodiment of the pusher and test liquid container of the new type of
具體地，該第一幫浦23透過第一輸氣管路231與設於該檢測主機20外部表面的第一管路接口232連通，該第二幫浦24透過第二輸氣管路241與設於該檢測主機20外部表面的第二管路接口242連通；該生物晶片31與該清洗液容器33之間具有第一輸液管路333連通，該生物晶片31與該檢測液容器34之間具有第二輸液管路343連通；該芯片模組30的表面設有第一進氣插頭332及第二進氣插頭342，該第一進氣插頭332與該清洗液容器33之間具有第一氣壓管路331連通，該第二進氣插頭342與該檢測液容器34之間具有第二氣壓管路341連通；藉此，令該芯片模組30與該檢測主機20連接，該第一進氣插頭332及該第二進氣插頭342分別與該第一管路接口232及該第二管路接口242接合密封，使該第一輸氣管路231與該第一氣壓管路331連通形成密封流道，該第二輸氣管路241與該第二氣壓管路341連通形成密封流道；該清洗液容器33及該檢測液容器34內部液體分別受該第一幫浦23及該第二幫浦24於該密封流道中形成的壓力作用而朝向該生物晶片31流動。Specifically, the
如圖3的實施例中，該檢測主機20的第一幫浦23、第二幫浦24為微型幫浦，供輸出氣體至管路中形成氣壓，以推動清洗液容器33、檢測液容器34中的液體流向生物晶片31進行清洗及檢測。該檢測主機20的第一管路接口232、第二管路接口242較佳為母接口，該芯片模組30的第一進氣插頭332、第二進氣插頭342較佳為公接頭，但不限於此，公母可互換。藉此，該檢測主機20與該芯片模組30插接時，該檢測主機20的輸氣管路（231、241）與該芯片模組30的氣壓管路（331、341）之間透過該母接口與該公接頭對接密合，形成完整的流道，供該第一幫浦23及該第二幫浦24輸出氣體時於該流道內形成壓力促使該清洗液容器33、檢測液容器34中的液體流向生物晶片31。In the embodiment shown in FIG. 3, the
進一步地，為確認生物晶片31能夠與測試液充分接觸反應，如圖3所示，本新型生物晶片檢測裝置200的芯片模組30內部還設有液體回收盒35，供回收輸出至生物晶片31的過多測試液；該生物晶片31與該液體回收盒35之間設有回收管路351連通，藉此，當輸出至生物晶片31的測試液多於生物晶片31的吸收量或反應量時，可利用前述密封流道中形成的壓力作用，經由該回收管路351流入該液體回收盒35內集中。Further, in order to confirm that the
此外，如圖3的生物晶片檢測裝置200所示，該檢測主機20還包括集成殼體29，該集成殼體29具有相對的操作端及顯示端，該操作端的表面設有該芯片插口26及該推進器的連接結構；該顯示端的表面設有該人機界面27、該啟動鍵28以及與該電路板21電連接的充電插孔293；該芯片模組30還包括集成外殼32，該生物晶片31的基板311一端及該傳導電極312共同形成該生物晶片31的電極連接頭310，該電極連接頭310凸伸於該集成外殼32外部；該芯片模組30的測試液容器連接結構設於該集成外殼32的表面。In addition, as shown in the biological
於本新型生物晶片檢測裝置200的實施態樣中，如圖3、圖4、圖5所示，該檢測主機20的集成殼體29可以包括主殼體291及樞設於該主殼體291操作端的翻蓋292，該翻蓋292用以封閉或顯露設於該集成殼體29操作端的連接結構，例如：芯片插口26、第一管路接口232、第二管路接口242。如圖3所示，該芯片模組30的集成外殼32表面設有測試液容器連接結構，例如：第一進氣插頭332、第二進氣插頭342。其中，該集成殼體29的翻蓋292為可選擇的部件；具體地，該集成殼體29整體可視實際需求進行結構設置及部件安裝位置安排，不限於圖4、圖5的形式。In the implementation aspect of the novel biological
於本新型生物晶片檢測裝置實施例中，該檢測主機20的電路板21為微控制器（MCU）電路板；該電路板21與該第一幫浦23、該第二幫浦24、該供電源25、該芯片插口26、該人機界面27及該啟動鍵28之間透過電纜線22電連接。該檢測主機20的供電源25為可重覆充電使用之充電電池。In the embodiment of the novel biological chip inspection device, the
於本新型生物晶片檢測裝置實施例中，該芯片模組30的傳導電極312及導電線313係經半導體技術製成之電極圖案。該芯片模組30的集成外殼32對應該清洗液容器33及該檢測液容器34位置開設有注射口（圖未示），供注入清洗液及檢測液至該清洗液容器33及該檢測液容器34中；且該集成外殼32對應該生物晶片31的生物傳感器平台100位置開設有窗口（圖未示），供將待測生物樣本添加到該生物傳感器平台100上。In the embodiment of the novel biological chip inspection device, the
於本新型實施例中，芯片模組30為所有構件整合一個整體的物件，使用時整個芯片模組30被拿取，使用後整個丟棄，為一次性使用物品。In the embodiment of the present invention, the
以上說明了本新型生物晶片檢測裝置的結構，以下說明其操作方法。本新型生物晶片檢測裝置的檢測操作步驟包括：The structure of the novel biological wafer inspection device has been described above, and its operation method will be described below. The detection operation steps of the new biological wafer detection device include:
步驟1，將芯片模組30的電極連接頭***檢測主機20的芯片插口26；Step 1. Insert the electrode connector of the
步驟2，將待測生物樣本添加至該生物晶片31的反應區（即生物傳感器平台100）上；Step 2: Add the biological sample to be tested to the reaction area of the biochip 31 (ie, the biosensor platform 100);
步驟3，驅動第一幫浦23使清洗液容器33中的清洗緩衝液流向生物晶片31的反應區，直到流入液體回收盒35，完成後使生物晶片31的反應區乾燥；Step 3: Drive the
步驟4，等待檢測主機20反應；Step 4. Wait for the response of the
步驟5，再次驅動第一幫浦23使清洗液容器33中的清洗緩衝液流向生物晶片31的反應區，直到流入液體回收盒35，完成後使生物晶片31的反應區乾燥；Step 5. Drive the
步驟6，驅動第二幫浦24使檢測液容器34中的檢測緩衝液流向生物晶片31的反應區，直到流入液體回收盒35，完成後使生物晶片31的反應區乾燥；Step 6, driving the
步驟7，按下檢測主機20的啟動鍵28，開始檢測待測生物樣品；Step 7. Press the
步驟8，等待檢測；Step 8, waiting for detection;
步驟9，檢測主機20的人機界面27顯示檢測結果（圖6A、圖6B）。Step 9. The man-
如圖6A、圖6B，顯示本新型生物晶片檢測裝置200的人機界面27顯示內容。其中，圖6A顯示檢測主機20檢測判斷生物樣本為「未檢出」（N.D.）的畫面，即生物樣本中未檢測出帶有病毒及/或微生物類型之感染；圖6B顯示檢測主機20檢測判斷生物樣本為「感染」（Infection）的畫面，即生物樣本中檢測出帶有病毒或微生物類型之感染。As shown in Fig. 6A and Fig. 6B, the display content of the man-
於本新型生物晶片檢測裝置的應用實施例中，生物晶片檢測裝置200可用於檢測病毒及/或微生物類型之感染，該生物晶片31上的生物受體18為帶有可偵測標記的結合分子；較佳地，適用於檢測病毒及/或微生物類型感染之抗原/抗體的結合分子為IgG抗體及IgM抗體。藉此，當待測生物樣本（例如血樣）已受病毒及/或微生物類型之感染時，生物晶片31上的結合分子會與該待測生物樣本中的病毒及/或微生物類型之感染後產生之免疫球蛋白結合產生生化反應，從而導致測得阻抗值變化，該阻抗值變化經轉換形成相應的電氣訊號後輸出至檢測主機20的電路板21，經該電路板21的感測線路進行匹配、放大訊號等處理後形成可讀反應訊號，最終輸出至人機界面27顯示檢測結果。In the application embodiment of the novel biochip detection device, the
綜上所述，本新型透過建立一個生物傳感器平台，該生物傳感器平台能夠進一步形成便攜的生物晶片檢測裝置。透過優化該生物傳感器平台中以半導體製造技術製成的電極厚度為至少單一金原子的厚度；此外，鏈黴親和素生物介體能夠為固定的生物受體提供理想的柔韌性，使生物傳感器平台的表現效能比以前使用的接頭更好，從而大幅提高生物傳感器的性能，使其重現性、準確性和穩定性都符合POC標準。整體而言，本新型提供的生物傳感器平台可同時實現重現性、準確性和穩定性，並適合集成到各種POC產品中。In summary, the present invention establishes a biosensor platform, which can further form a portable biochip detection device. By optimizing the thickness of the electrode made with semiconductor manufacturing technology in the biosensor platform to at least the thickness of a single gold atom; in addition, the streptavidin biomediator can provide ideal flexibility for the immobilized bioreceptor, making the biosensor platform The performance and performance of the biosensor are better than the previous connectors, which greatly improves the performance of the biosensor, so that its reproducibility, accuracy and stability are in line with the POC standard. On the whole, the biosensor platform provided by the present invention can achieve reproducibility, accuracy and stability at the same time, and is suitable for integration into various POC products.
100:生物傳感器平台 10:芯片 11:陶瓷基板 12:銅鍍層 13:電阻塗層 14:光源裝置 15:金薄膜電極 16:生物素化接頭 17:明膠 18:生物受體 200:生物晶片檢測裝置 20:檢測主機 21:電路板 22:電纜線 23:第一幫浦 231:第一輸氣管路 232:第一管路接口 24:第二幫浦 241:第二輸氣管路 242:第二管路接口 25:供電源 26:芯片插口 27:人機界面 28:啟動鍵 29:集成殼體 291:主殼體 292:翻蓋 293:充電插孔 30:芯片模組 31:生物晶片 310:電極連接頭 311:基板 312:傳導電極 313:導電線 32:集成外殼 33:清洗液容器 331:第一氣壓管路 332:第一進氣插頭 333:第一輸液管路 34:檢測液容器 341:第二氣壓管路 342:第二進氣插頭 343:第二輸液管路 35:液體回收盒 351:回收管路100: Biosensor platform 10: Chip 11: Ceramic substrate 12: Copper plating 13: Resistive coating 14: Light source device 15: Gold thin film electrode 16: Biotinylated adapter 17: Gelatin 18: Biological receptor 200: Biological wafer inspection device 20: detect the host 21: circuit board 22: Cable 23: First Pump 231: The first gas pipeline 232: The first pipeline interface 24: second pump 241: The second gas pipeline 242: second pipeline interface 25: power supply 26: chip socket 27: Human-Machine Interface 28: Start button 29: Integrated housing 291: main shell 292: Clamshell 293: Charging jack 30: Chip module 31: Biochip 310: Electrode connector 311: Substrate 312: Conductive electrode 313: conductive thread 32: Integrated shell 33: Cleaning fluid container 331: The first pneumatic line 332: First intake plug 333: The first infusion line 34: Test fluid container 341: The second pneumatic line 342: second air inlet plug 343: The second infusion line 35: Liquid recovery box 351: recovery line
圖1係本新型生物傳感器平台上的金薄膜電極的製造流程示意圖； 圖2係本新型生物傳感器平台的製造流程示意圖； 圖3係本新型生物晶片檢測裝置的整體架構示意圖； 圖4係本新型生物晶片檢測裝置的檢測主機呈翻蓋閉合的立體外觀示意圖； 圖5係本新型生物晶片檢測裝置的檢測主機呈翻蓋打開的立體外觀示意圖； 圖6A、圖6B係本新型生物晶片檢測裝置的人機界面顯示內容示意圖。 Figure 1 is a schematic diagram of the manufacturing process of the gold thin film electrode on the new biosensor platform; Figure 2 is a schematic diagram of the manufacturing process of the new biosensor platform; Fig. 3 is a schematic diagram of the overall structure of the novel biological chip inspection device; Fig. 4 is a schematic diagram of the three-dimensional appearance of the detection host of the novel biochip detection device with the flip closed; Fig. 5 is a schematic diagram of the stereo appearance of the detection host of the novel biological wafer detection device with the flip open; Fig. 6A and Fig. 6B are schematic diagrams of the display content of the human-machine interface of the novel biological chip detection device.
100:生物傳感器平台 100: Biosensor platform
10:芯片 10: Chip
15:金薄膜電極 15: Gold thin film electrode
16:生物素化接頭 16: Biotinylated adapter
17:明膠 17: Gelatin
18:生物受體 18: Biological receptor
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