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基于 MEMS 的双层堆叠塔生物传感器阵列与集成读出电路,用于检测唾液 pH 值作为慢性牙周病的诊断生物标志物。

MEMSbased Double-Stacked Tower Biosensor Array with Integrated Readout Circuitry for Detection of Salivary pH as a Diagnostic Biomarker Applied for Chronic Periodontal Disease.

机构信息

Department of Electrical Engineering, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan 33302, Taiwan.

Department of Trauma and Emergency, Linkou Chang Gung Memorial Hospital, Guishan Dist., Taoyuan 33305, Taiwan.

出版信息

Sensors (Basel). 2022 Nov 9;22(22):8652. doi: 10.3390/s22228652.

Abstract

MEMS based 3D double stacked tower pixel biosensor 10 × 10 array with integration of readout circuit for detection of saliva pH ion is demonstrated. The pixel biosensor comprised a driving electrode, sensing electrode and double stack tower pixel structure. The sensitivity of double stacked tower biosensor can be auxiliary enhanced by proposed lower-jitter low dropout regulator circuit and dual offset cancellation comparator. The double stacked tower sensor is fabricated by MEMS backend-of-line CMOS process, it is compatible with CMOS frontend readout circuits and integrated as a system-on-chip (SoC). The double stacked tower pixel by MEMS process is to obtain a larger volume ratio of charge groups in a pixel of biosensor to enhance the sensitivity and linearity for ion detection. With the double stacked tower structure in biosensor, the sensitivity is improved by 31% than that of single tower structure proved by simulation. A wide-range linearity from pH 2.0 to pH 8.3, high sensitivity of -21 ADC counts/pH (or 212 mV/pH), response time of 5 s, repetition of 98.9%, and drift over time of 0.5 mV are achieved. Furthermore, the proposed biosensor was performed to confirm the artificial saliva from healthy gingiva, chronic gingivitis and chronic periodontitis, the measured ADC counts from proposed biosensor SoC was in consistent of that measured cyclic voltametric (CV) method very well. The proposed 3D double stack tower biosensor and readout circuit can be further integrated with internet-of-thing (IoT) device and NFC for data transmission for continuous pH sensing to facilitate the chronic gingiva disease health care at home.

摘要

MEMS 基 3D 双层堆叠塔像素生物传感器 10×10 阵列与读出电路集成,用于检测唾液 pH 离子。像素生物传感器由驱动电极、传感电极和双层堆叠塔像素结构组成。所提出的低抖动低压降稳压器电路和双失调消除比较器可辅助增强双层堆叠生物传感器的灵敏度。双层堆叠传感器由 MEMS 后端 CMOS 工艺制造,与 CMOS 前端读出电路兼容,并集成到系统级芯片(SoC)中。MEMS 工艺中的双层堆叠像素用于获得生物传感器像素中电荷组的更大体积比,以增强离子检测的灵敏度和线性度。通过在生物传感器中使用双层堆叠结构,灵敏度比模拟证实的单塔结构提高了 31%。实现了从 pH 2.0 到 pH 8.3 的宽线性度、高灵敏度-21 ADC 计数/pH(或 212 mV/pH)、响应时间为 5 s、重复性为 98.9%、以及随时间的漂移为 0.5 mV。此外,所提出的生物传感器用于确认来自健康牙龈、慢性牙龈炎和慢性牙周炎的人工唾液,从提出的生物传感器 SoC 测量的 ADC 计数与通过循环伏安法(CV)测量的非常一致。所提出的 3D 双层堆叠塔生物传感器和读出电路可以进一步与物联网(IoT)设备和 NFC 集成,用于数据传输,以进行连续 pH 感应,从而方便在家中进行慢性牙龈疾病保健。

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