利用微流體系統結合電化學阻抗頻譜進行雙心血管疾病標誌物檢測

Abstract

心血管疾病在全球的高死亡率和醫療成本使其成為全球主要健康問題。為了在早期階段預防心血管疾病，需要高靈敏度和多功能生物感測器，以提高診斷的準確性並了解疾病狀態。然而，目前的心血管疾病診斷方法存在操作繁瑣、儀器龐大、成本高昂、靈敏度有限以及訊號讀出時間長的問題。為了解決這些問題，我們提出了一整合高靈敏度的雙重電化學感測器之微流體系統，可在原位即時監測稀釋四倍之血清樣本中兩種高風險心血管疾病特定生物標記: C反應蛋白(CRP)及心肌肌鈣蛋白(cTnI)，並結合輔助開關幫助轉換訊號輸出及輸入，使微流道系統降低人為更換晶片量測導致之錯誤及所需時間，可達成30分鐘內同時檢測出0.01 -100 ng/mL CRP以及0.1 -1000 pg/mL cTnI，此檢測範圍已包含臨床hs-CRP及hs-cTnI所需之靈敏度及動態範圍。上述的結果證明此微流體系統具有應用於定點照護(Point-of-care)的能力，並且可在未來使用微流道進行全血處理並準確量測出血液中CRP及cTnI濃度。

The high mortality rate and healthcare costs associated with cardiovascular diseases make them a major global health concern. To prevent cardiovascular diseases at an early stage, highly sensitive and multifunctional biosensors are needed to improve diagnostic accuracy and understand disease status. However, current diagnostic methods for cardiovascular diseases suffer from cumbersome operation, bulky instrumentation, high costs, limited sensitivity, and long signal readout times. To address the above issues, we propose a highly sensitive dual electrochemical sensor combined with a microfluidic platform. This microfluidic platform can simultaneously monitor two high-risk cardiovascular disease-specific biomarkers (CRP and cTnI) in 450 μL of four-fold diluted serum samples. Additionally, an auxiliary switch is incorporated to perform electrochemical output and input conversion, reducing human errors and operation time associated with manual chip replacement in the microfluidic system. This setup enables the detection of CRP and cTnI in serum within 30 minutes using the embedded sensors in a microfluidic channel. The detection range includes clinical hs-CRP and hs-cTnI, successfully detecting of 0.01 to 111.11 ng/mL of CRP and 0.1 to 1111.1 pg/mL of cTnI. These results demonstrate the potential application of this microfluidic platform for point-of-care diagnostics, and it can be further utilized for whole blood processing and accurate measurement of CRP and cTnI concentrations in the future.