使用電性免疫感測晶片檢測肺栓塞與心肌梗塞之生物標誌物

根據WHO世界衛生組織統計2019年全球主要死因第一名為心血管相關疾病，其死亡數約佔總死亡人口數35%，因此對於心血管疾病的臨床治療與檢測日漸重要。其中肺栓塞與心肌梗塞症狀相似且死亡風險高，但治療方式截然不同，因此需要發展快速檢測技術以提高診斷準確率與降低診斷時間。本研究以氧化石墨烯、絲素蛋白與兩種病症之混合抗體修飾二極式電極後，使其具備抓取抗原能力做為量測平台，接著以高精度電源電錶針對血液中不同濃度抗原進行檢測並擬合數據獲得最終結果。在實驗結果中輔以SEM影像可發現，在以高精度電錶量測晶片各改質階段之電性變化說明了晶片改質的成功。將各別與混合抗體線性變化實驗之結果進行比較，可發現各別抗體之檢測線性斜率接近完美的複製到混合抗體實驗上且兩線並無交錯有著良好的線性趨勢，僅在整體線性的基準點有變動，因此可說明將抗體混合孵育並進行檢測的做法是可行且不會造成抗原之間的檢測結果互相干擾。在干擾性實驗中，檢測晶片對於抗原溶液內含干擾物有著強大的抗干擾能力。最後為極限值實驗，免疫晶片對於Factor VIII檢測能力較不足但已含蓋大部分異常值；而對於cTni則有良好的極限表現，在高濃度下仍能夠依照線性預期結果產生電子訊號。綜合以上，即為本研究對於肺栓塞與心肌梗塞之檢測技術能力之貢獻。

關鍵字

肺栓塞；心肌梗塞；線性伏安；氧化石墨烯；電化學生物感測器

並列摘要

According to the statistics of the World Health Organization (WHO), the number one cause of death in the world in 2019 is cardiovascular-related diseases, which account for about 35% of the total number of deaths. Therefore, the clinical treatment and detection of cardiovascular diseases are becoming increasingly important. Among them, pulmonary embolism and myocardial infarction have similar symptoms and a high risk of death, but the treatment methods are completely different. Therefore, rapid detection technology needs to be developed to improve diagnostic accuracy and to reduce the time of diagnosis. In this study, graphene oxide, silk fibroin, and mixed antibodies of the two diseases were used to modify the bipolar electrode, so that it could grab antigens as a measurement platform, and then used a high-precision power meter to measure antigens with different concentrations in blood. Check and fit the data to get the final result. The experimental results are supplemented by SEM images, and it can be found that the electrical changes in each modification stage of the wafer are measured with a high-precision electric meter, indicating the success of the wafer modification. Comparing the results of the linear change experiment of each antibody and the mixed antibody, it can be found that the detection linear slope of each antibody is close to a perfect replication of the mixed antibody experiment, and the two lines are not interlaced. There is a good linear trend, only in the overall linear benchmark The points have changed, so it can be shown that the method of incubating the antibodies together and performing the detection is feasible and will not cause mutual interference between the detection results of the antigens. In the interference experiment, the detection chip has a strong anti-interference ability against the interference substances contained in the antigen solution. The last is the limit value experiment. The immunochip has insufficient detection ability for Factor VIII but covers most of the outliers; while for cTni, it has a good limit performance, and can still generate electronic signals according to the linear expected results at high concentrations. To sum up, this is the contribution of this study to the detection technology of pulmonary embolism and myocardial infarction.