設計可檢測全血凝血酶原時間之新式床邊檢驗生物晶片

Design of Novel Point-of-care Testing Biochips for Whole-blood Prothrombin Time

床邊檢驗(point- of- ca re testing，POCT)凝血臨原時間(prothrombin time, PT)利於就近檢測，包括正在接受抗凝血劑治療、手術前評估、患有肝臟或腎臟疾病及需要診斷疾病惡化的病患。然而，現有的POCT PT儀器價格昂貴。在過去的報告中，檢測PT儀器包括採用電阻抗法、壓電石英晶體感測、表面聲波、表面電漿共振及光學法等原理，其中，光學法已被運用在檢測血漿樣本的桌上型PT儀器上數年，且可能應用在檢測全血樣本的POCTPT儀器上。在本研究中，設計及製造光學法POCT儀器搭配塑膠材質的PMMA或PET生物晶片來進行全血PT測試。結果顯示，光學法POCT儀器使用PMMA晶片(n=50)檢測全血PT與傳統手工法(r=0.9911，p＜0.0001)及ACL TOP700全自動凝血儀(r=0.9374，p＜0.0001)，或使用PET晶片(n=39)檢測全血PT與傳統手工法(r= 0.9909，p＜0.0001)及ACL TOP700全自動凝血儀r=0.9502，p＜0.0001)皆呈高度相關，本新式設計之生物晶片具有快速、價格低之優點，且光學法儀器原理與醫院中央血液室之凝血儀相容。總結，使用拋棄式PMMA及PET生物晶片在光學法全血凝血檢測具有高靈敏度及準確性，並可能提供一種具低成本之商業潛力的可攜式光學法POCT PT儀器。

Point-of-care testing (POCT) for prothrombin time (PT) benefit nearby patients, including those are undergoing anticoagulant therapy, receiving pre-operation evaluation, suffering from hepatic or renal disorders and needing the diagnosis of severe disease progression. However, the prices of available POCT PT devices are still high. The previously reported PT devices included those based on principles of electric impedance, piezoelectric quartz crystal, surface acoustic wave, surface plasmon resonance and optics. Among them, the optically based methodologies have been reliably exploited in bench-top PT instruments with plasma samples for years, and might be applied in POCT PT devices with whole blood samples. In this study, an optical POCT device in coupled with plastic materials of either polymethylmethacrylate (PMMA) or polyethylene terephthalate (PET) biochip was designed and manufactured for performing whole blood PT testing. As a result, the optical POCT device showed high correlations either using PMMA biochip (n=50) with the manual method (r=0.9911, p＜0.0001) and with ACL TOP 700 automatic coagulation analyzer (r=0.9374, p＜0.0001 ), or using PET biochip (n=39) with the manual method (r=0.9909, p＜0.0001) and with ACL TOP 700 automatic coagulation analyzer (r=0.9502, p＜0.0001). The novel POCT device provided a rapid and low-cost biochip for PT, where the optical-based principle was matched with the coagulant instruments mostly used in hospital central hematology laboratory. In conclusion, the disposal PMMA and PET biochips are highly sensitive and accurate in optic-based whole blood coagulation testing and might provide a commercial potential with low costs in the design of portable optic POCT PT device.