整合高解析度讀出電路用於核酸電化學感測與溫度和 pH監控

Abstract

本論文分為兩個部分：高解析度讀出電路用於電化學生物感測器，以及溫度和 pH 監測電路。 使用由合成核酸製成的適體的生物感測器來檢測目標分子的實時存在和濃度。這種檢測不需要試劑，因而適合於長期體內分子感測。本論文開發了一種高解析度類比數位轉換器，作為基於適體的電化學生物感測器的讀出電路，此電化學生物感測器採用方波伏安庫侖法進行電化學適體讀出。與方波伏安法讀出電路相比，SWVC讀出電路可以在不過度消耗功率的情況下將檢測信噪比提高超過100倍。 此類比數位轉換器由三階增量連續時間三角積分調變器實現。它採用切換負電阻來消除第一級積分器和負電阻的1/f噪聲。它還採用四抽頭FIR-DAC來減少切換混疊效應。為了減少補償FIR-DAC的面積，補償FIR-DAC中加入了一個衰減增益電阻。引入衰減增益電阻後，補償FIR-DAC的電阻減少了10倍。該類比數位轉換器在20 kHz頻寬內達到91.2 dB的信噪比，消耗功率為288.5 μW。此類比數位轉換器與8通道基於適體的電化學讀出電路集成。該電化學讀出電路將與256像素多電極陣列整合。 在第二部分中，為了補償適體的信號漂移，此系統內集成了pH和溫度傳感器。溫度傳感器採用基於BJT的方法。溫度誤差範圍在15到50℃之間為-1.24到+1.46℃。pH感測器採用準差分架構，由離子敏感場效應管和參考場效應管組成。兩個電極都塗有20納米的二氧化矽作為感測膜，感測區域僅為20 μm × 20 μm。pH感測器表現出59.6 mV/pH的靈敏度。為了放大溫度和pH傳感器的信號，使用了開關電容放大器。開關電容放大器的運算跨導放大器採用摺疊共源極架構。放大器的增益調節範圍為2到20。

This thesis is divided into two parts: a high-resolution readout circuit for electrochemical biosensor and a temperature and pH monitoring circuit. A biosensor utilizing aptamers made of synthetic nucleic acids is employed to detect the real-time presence and concentration of target molecules. This detection occurs without the requirement for reagents, rendering it well-suited for prolonged in vivo molecular sensing. This thesis develops a high-resolution ADC as the readout circuit of an aptamer-based electrochemical biosensor employing square-wave volt-coulometry (SWVC) for the electrochemical aptamer readout. In comparison to square-wave voltammetry (SWV) readout circuit, the SWVC readout circuit can boost the detection SNR by >100× without excessive power consumption. This ADC is implemented with a 3rd order incremental continuous-time delta-sigma modulator. It employs a chopped negative-resistor (Neg-R) network to remove the 1/f noise of the first stage integrator as well as the Neg-R itself. The modulator also employs a 4-tap FIR-DAC to reduce the aliasing of the chopping ripple. To reduce the area of compensation FIR-DAC, an attenuated gain resistor is added to reduce the area by 10 times. The ADC achieves 91.2-dB SNR in 20 kHz bandwidth and consumes 288.5 μW. This ADC is integrated with an 8-channel aptamer-based electrochemical readout circuit. This electrochemical readout circuit will interface with a 256-pixel multi-electrode array. In the second part, to compensate the aptamer signaling drift, a pH sensor and a temperature sensor are co-integrated in the same chip. The temperature sensor is designed using BJT-based approach. The temperature error ranges for a -1.24 to +1.46 ℃ within temperature range of 15 to 50 ℃. The pH sensor utilizes a pseudo-differential architecture consisting of an ion sensitive FET (ISFET) and a reference FET (REFET). Both electrodes are coated with 20-nm SiO2 as a sensing membrane at a sensing area of 20 μm × 20 μm. The pH sensor exhibits a sensitive 59.6 mV/pH. To amplify the signal of the temperature and pH sensor, a switch capacitor amplifier is employed. The OTA of the switch capacitor amplifier uses a fold cascode architecture. The amplifier gain turning range is 2 to 20.