紙質微流道設備和智能手機的應用程序快速並同時定量酪氨酸羥化酶缺乏症之生物標誌物

Abstract

酪氨酸羥化酶（Tyrosine hydroxylase , TH）是一種限速酶，涉及將酪氨酸轉化代謝合成為人體內的左旋多巴以及其他重要神經傳導物質。而酪氨酸羥化酶缺乏症是一種罕見的遺傳代謝疾病，它會影響神經傳導物質在人體中的正常的含量，因為酪氨酸是左旋多巴和其他兒茶酚胺的前驅物。現今研究尚無用於確定疾病的專一性測定法。在這項研究中，我們開發了一種新的測量方法，該方法是使用4,5-多巴雙加氧酶和高碘酸鈉修飾紙基材料的表面，並與智能手機成像互相結合，以通過形成黃色的甜菜醛胺酸衍生物來定量左旋多巴，並且能夠有良好的相關係數以及偵測極限 (0.12 nM)。另外，同時檢查酪氨酸和肌酐在人體中水平以了解酪氨酸和左旋多巴之間的比例。所提出的系統簡單、方便、低成本、高生物相容性，並通過監測智能手機應用程序中的顏色變化而同時針對左旋多巴、酪胺酸、肌酐的濃度進行定量。該方法用於檢測人造尿液和胎牛血清樣品中的左旋多巴、酪氨酸和肌酐。因此，這種基於修飾紙基材料的方式來偵測多種生物標誌物，能應用在居家檢驗的一個快篩檢測並為將來的應用打開了新的策略。

yrosine hydroxylase (TH) enzyme involves in converting the tyrosine to L-DOPA in the human body. The deficiency of TH is a rare genetic metabolic disorder and it affects the neurotransmitters levels because tyrosine is the precursor of L-DOPA and other catecholamines. There is still no specific assay for the determination of the disorder. In this study, we have developed a novel assay using 4,5-DOPA-dioxygenase and sodium periodate to modify the surface of paper and to combine with smartphone imaging for the quantification of L-DOPA through the formation of yellow betalamic acid derivatives in vitro. In addition, the tyrosine and creatinine levels are examined simultaneously to understand the ratio between tyrosine and L-DOPA. The proposed system is simple, convenient, low cost, high biocompatibility, and specific towards L-DOPA, tyrosine, and creatinine through monitoring the color changes in smartphone App. This method was App to the detection of L-DOPA, tyrosine, and creatinine in artificial urine and fetal bovine serum samples. Thereby, this paper-based modified materials can detect various biomarkers and have opened a new strategy for future App.