传感器类型
电化学生物传感器
检测对象
蜡样芽孢杆菌(Bacillus cereus, B. cereus)、大肠杆菌(Escherichia coli, E. coli);样品基质:病原菌悬液/液体样品(浓度以 CFU/mL 表示)
检测原理
样品在毛细力作用下流经多孔膜,目标抗原与结合垫上的抗体结合,抗体偶联聚苯胺(PANI)导电纳米线,形成抗原-抗体-PANI复合物。复合物迁移至电极间捕获区,与固定抗体结合,在两个银电极之间形成PANI纳米线桥。病原浓度越高,桥接纳米线越多,电极间电导越大,响应近似对数线性。AND门串联两种抗体,仅当两种病原同时存在时形成完整导电桥;OR门混合抗体,任一病原存在即可形成桥。电导测量受系统噪声和随机结合噪声影响,输入因子图消息传递解码器,利用重复码或非对称AND/OR编码估计病原存在概率,降低检测误差率;非对称编码的非线性耦合还可实现高浓度病原辅助痕量病原的共检测。
检测灵敏度
—
效应效果
仿真中每个病原浓度重复1000次,以0.5为阈值判断病原存在与否。结果显示,病原浓度升高时检测误差率(DER)下降;重复码因冗余度高于无编码方案,DER更低。非对称(6,2)编码在除极低浓度外,DER较重复码降低约5倍,表明其可靠性更优。扩展(10,2)非对称编码进一步降低DER,说明编码规模增大可提升可靠性,但会增加冗余元件和成本。非对称编码还揭示两种病原检测间的非线性耦合,提出共检测协议:先识别高浓度易检病原,再将其加入样品以辅助痕量病原检测。作者认为该框架可作为评估生物传感器编码/解码策略的设计工具。
传感器的构成
- 基底/流道:多孔膜(porous membrane),提供毛细流动通道并承载电极与抗体捕获线
- 换能电极:银电极(Ag electrodes),作为源/漏电极,用于测量电极间电导
- 识别元件:固定抗体(immobilized antibody,如 B. cereus 抗体、E. coli 抗体),捕获抗原并构成 AND/OR 逻辑门
- 信号标记物:聚苯胺导电纳米线(polyaniline nanowires, PANI NWs),与抗体偶联并在电极间形成导电桥
- 侧流组件:样品垫(sample pad)与结合垫(conjugate pad),形成抗原-抗体-PANI 复合物并分配至捕获线
- 逻辑门结构:串联抗体(AND gate)或混合抗体(OR gate),实现双病原逻辑检测
- 读出装置:电导式恒电位仪(conductimetric potentiostat),测量电导并输入解码器
中文摘要
我们此前报道了新型生物分子晶体管的制备与验证,其聚苯胺纳米线通道的电导率受抗原-抗体相互作用控制。本文提出一种用于分析由这些生物分子晶体管构建的生物传感器电路可靠性的仿真框架。该框架的核心是一组电路模型库,能够表征生物分子间随机相互作用,以及环境条件和实验方案变化所引起的变异性。可靠性分析通过因子图解码技术利用多个电路元件之间的概率依赖关系完成。所提出的计算方法可在避免繁琐且耗时实验流程的情况下,快速评估生物传感器前向纠错(FEC)策略。分析结果表明,非对称 FEC 生物传感器编码优于此前用于微阵列技术的重复 FEC 编码。此外,研究还表明该分析方法可导出一种新的“共检测”协议,可用于可靠检测样品中痕量病原体。
英文摘要
We previously reported the fabrication and the verification of novel biomolecular transistors where electrical conductivity of a ldquopolyaniline nanowiresrdquo channel is controlled by antigen-antibody interactions. In this paper, we present a simulation framework for analyzing the reliability of biosensor circuits constructed by using these biomolecular transistors. At the core of the proposed framework is a library of electrical circuit models that capture the stochastic interaction between biomolecules and their variability to environmental conditions and experimental protocols. Reliability analysis is then performed by exploiting probabilistic dependencies between multiple circuit elements by using a factor graph-based decoding technique. The proposed computational approach facilitates rapid evaluation of forward error correction (FEC) strategies for biosensors without resorting to painstaking and time-consuming experimental procedures. The analysis presented in this paper shows that an asymmetric FEC biosensor code outperforms a repetition FEC biosensor code which has been proposed for microarray technology. In addition, we also show that the proposed analysis leads to a novel ldquoco-detectionrdquo protocol that could be used for reliable detection of trace quantities of pathogens.