免標定電化學阻抗生醫親和力感測系統之研究與開發

Abstract

隨著社會進步、生活水平的提升和醫療科技的發展，人類平均壽命已大幅增加，這也意味者高齡化社會的來臨。老年人的身體機能及代謝能力都較差，所以容易罹患多種慢性病(如高血壓、糖尿病、心血管疾病)或癌症，於是老年人居家照護和健康管理也逐漸有迫切的需求。從醫院走入一般家庭，以定點照護(Point of care)為訴求的生物感測器，陸陸續續地被開發出來，本論文的研究方向在於開發出一免標定式電化學生物感測器，嘗試能夠符合定點照護的需求。 本論文，以團隊開發的創新型導電分子為基礎，配合自己設計的晶片和流道系統，利用電化學阻抗頻譜分析技術，完成一完整的量測系統。由於使用導電性連結分子，大幅提升了傳統電化學阻抗生物感測器的訊雜比(Signal to noise ratio)，降低了後端電路的設計難度和成本。在訊號處理上，使用一張訊號擷取卡，將電訊號數位化後，利用LabVIEW來設計鎖相放大器消除所有環境雜訊，以得到乾淨的阻抗資訊。另外，將泵的驅動電路整合至同一塊電路板上，都從LabVIEW設計的人機介面來進行操縱。使用最基本的微機電製程，做出以玻璃為底，金為工作電極的生物晶片。也對該生物晶片量身打造了對應的流道機構，因此乃能做到快速抽換晶片且小體積的需求。 本研究已成功運用測量C-反應蛋白、S-100蛋白所得成果，來驗證系統的可行性和靈敏度，驗證所得最低檢測極限能達到一般醫院的檢測要求。測試了不同PI值和不同分子量的蛋白分子，發現大分子的CRP比起小分子的s100蛋白有者更大的阻抗變化；在不同PI值之分子CRP和cTnI之間，所得成果並沒有發現顯著的差異。

With the societal advancement, living style improvement, and medical technologies development, the average human life span has increased significantly. These changes also signal the coming of aging society. The body function and metabolism of the elders are known to be weaker than grownups and children. In addition, the elders are prone to many chronic diseases or cancer. All of which indicate that home care and health care services of elders are becoming ever more important. The biosensors developed with a goal to pursue point of care are becoming more widely available. This thesis focuses on developing a label-free electrochemical biosensor that fits the point-of-care application needs. Taking novel conducting linker as the starting point and integrating it into the corresponding chip equipped with microfluidic system developed by the NTU BioMEMS team, this thesis further utilized electrochemical impedance spectroscopy to develop a complete bio-affinity metrology system. With the adoption of the innovative conducting linker developed within the team, the signal to noise ratio of traditional electrochemical bio-affinity sensor was greatly improved such that the difficulty associated with the design and the implementation cost of the interfacing circuits were minimized. In the signal processing part, we used a DAQ card (data acquisition card) to digitize the analog signal. We then employed LabVIEW to establish the lock-in amplifier for noise elimination so as to lead to precise impedance measurement. Besides, we integrated driving circuits of syringe pump into an electro-board, which was controlled by using LabVIEW to design the HMI (Human Machine Interface). Our biochips were made by micro machining process with glass as the substrate and Au as the working electrode. We also designed a locking mechanism to ease the biochips replacement and to reduce the overall system volume. Our study measures C-reactive protein, S-100 protein, successfully. These results verified the feasibility and sensitivity of our system, which was found to meet the lowest detected limits currently required by the hospital. We found that protein with bigger molecular weight may result in bigger ΔRct changes.