據互補式金氧半導體晶片發展之多功能調頻光學生物感測器

Abstract

此研究提出一個同時具有生物化學冷光訊號和發色物質偵測定量能力的互補式金氧半導體(CMOS)晶片。此互補式金氧半導體晶片首創被指出可用於多樣式的光學反應偵測，可直接偵測冷光訊號，並於組裝市售發光二極體後，進行發色物質定量。晶片偵測面積為1.28 毫米 × 1.28 毫米，經由0.35毫米半導體標準製程製成。在集成電路中設計的阻抗放大器可放大由化學冷光或發散光源所激發的訊號電流，並可藉調整晶片週期波頻率參數，針對不同強度光訊號設定最適應的掃描頻率。本實驗先以山葵過氧化氫酶 (過氧化氫酶)–胺基苯二醯井–過氧化氫和過氧化氫酶- 4-胺基安替碄-酚-過氧化氫系統為設立實用襙作平台的範例，在待測物氧化反應生成過氧化氫後，連結上述系統而成不同的光學訊號。膽固醇–膽固醇氧化酵素(COD)和葡萄糖-葡萄糖氧化酵素(GOD)氧化反應皆各自與不同過氧化氫光學反應結合，證明其具備冷光物質及發色物質定量能力，極具應用於不同臨床分析的潛力。相較於早期晶片，此晶片具有多項優點，如高靈敏度、少量樣品體積需求、高度辨識範圍，同時也證實，此晶片相較於組裝式商用感光二極體設備，擁有較高單位靈敏度。總結之，創新之互補式金氧半導體集成電路與商用電子元件相結合，可建立出實用且有力的多功能生物光學感測器。

This work presents a complementary metal oxide semiconductor (CMOS) chip with accompanied accessories as a system for the detections and quantifications of both biochemical luminescence and chromogens. The CMOS photosensing chip originality has been reported to detect multiple optical reactions, which detects not only chemiluminescence directly but also chromogen quantification while integrated with a commercial light emitting diode (LED), with a 1.28 mm× 1.28 mm detection area via a 0.35μm standard process. A transimpedance amplifier was designed in integrated circuit (IC) to amplify the signal current induced by luminescence or emitted light. By adjusting the frequency parameter setting of CMOS chip, the optimized scanning frequency can be set to fit different optical reactions. After the detected target is oxidized, hydrogen peroxide occurs. Horseradish peroxidase (HRP)–luminol–H2O2 and HRP-phenol-H2O2 systems were used as examples to constitute the platforms for coupling to produce different optical signals. Cholesterol–cholesterol oxidase (COD) and glucose-glucose oxidase(GOD) reactions were both coupled with different H2O2 production reactions to demonstrate the ability of biological luminescence and chromogen quantification and potential for diverse clinical diagnosis. Compared with the CMOS chip in the early stages, our chip has many advantages, such as high sensitivity, a less sample volume requirement, and high dynamic range. It even possesses higher unit sensitivity compared with the integrated commercial photodiode setup device. In conclusion, the combination of the specifically designed CMOS IC and available electronic devices establishes a useful and powerful multifunctional optical biosensor.