IEEE Trans Biomed Circuits Syst. 2021 Jun;15(3):497-508. doi: 10.1109/TBCAS.2021.3084540. Epub 2021 Aug 12.
Both bacterial viability and concentration are significant metrics for bacterial detection. Existing miniaturized and cost-effective single-mode sensor, pH or optical, can only be skilled at detecting single information viability or concentration. This paper presents an inverter-based CMOS ion-sensitive-field-effect-transistor (ISFET) sensor array, featuring bacterial pH detection which is an indicator of viability. The proposed design realizes pH detection using the native passivation layer of CMOS process as a sensing layer and configuring an inverter-based front-end as a capacitive feedback amplifier. This sensor array is assisted by temperature sensing and optical detection which reveals bacterial concentration. The optical detection is enabled using the leakage current of a reset switch as a response to a light source. While in reset mode, the inverter-based amplifier works as a temperature sensor that could help to reduce temperature influences on pH and optical detection. All the functionalities are realized using one single inverter-based amplifier, resulting in a compact pixel structure and largely relaxed design complexity for the sensor system. Fabricated in 0.18 μm standard CMOS process, the proposed CMOS sensor array system achieves an amplified pH sensitivity of 221 mV/pH, an improved sensor resolution of 0.03 pH through systematic noise optimization, a linear optical response, and a maximum temperature error of 0.69 C. The sensing capabilities of the proposed design are demonstrated through on-chip Escherichia coli (E. coli) detection. This study may be extended to a rapid and cost-effective platform that renders multiple information of bacterial samples.
细菌活力和浓度都是细菌检测的重要指标。现有的小型化和低成本的单模传感器,无论是 pH 传感器还是光学传感器,都只能擅长检测单一信息——活力或浓度。本文提出了一种基于反相器的 CMOS 离子敏感场效应晶体管(ISFET)传感器阵列,用于检测细菌 pH 值,这是细菌活力的一个指标。该设计使用 CMOS 工艺的固有钝化层作为传感层,并配置基于反相器的前端作为电容反馈放大器,实现 pH 值检测。该传感器阵列还辅助以温度传感和光学检测,以揭示细菌浓度。光学检测利用复位开关的漏电流作为对光源的响应来实现。在复位模式下,基于反相器的放大器作为温度传感器工作,有助于降低温度对 pH 值和光学检测的影响。所有功能都使用单个基于反相器的放大器来实现,从而实现了紧凑的像素结构和大大简化的传感器系统设计复杂度。该传感器系统采用 0.18 μm 标准 CMOS 工艺制造,实现了 221 mV/pH 的放大 pH 灵敏度,通过系统噪声优化提高了 0.03 pH 的传感器分辨率,具有线性光学响应,最大温度误差为 0.69°C。通过片上大肠杆菌(E. coli)检测,展示了该设计的传感能力。本研究可扩展到一个快速且具有成本效益的平台,可提供细菌样本的多种信息。