组成图示
示意图生成中
传感器类型
场效应晶体管(FET)生物传感器
检测对象
青霉素(penicillin);样品基质:PBS标准溶液、青霉素发酵液(penicillin fermentation broth)
检测原理
青霉素氧化酶(POx)催化青霉素水解生成青霉酸并释放H+。H+与青霉酸被Si3N4离子敏感膜感知,改变Si3N4/SiO2/p-Si界面电荷,使p型硅表面势阱深度随青霉素浓度变化。传感器采用电荷转移(fill and spill)方式,将势阱中对应浓度的电荷经输入二极管、控制栅和转移栅多次转移到浮动扩散区(FD),进行5次信号积分循环。信号电荷在FD中积累,信噪比按√n提高,并经CSENS/CFD电容比和源极跟随器增益放大,最终由VOUT读出。青霉素浓度越高,产生的H+越多,转移电荷量越大,输出信号越强。
检测灵敏度
LOD: 约0.01 mM;线性范围: 0–25 mM;灵敏度: 47.852 mV/mM;R^2 = 0.9961
效应效果
CTTPS在0–25 mM范围内重复测量60次,总非线性误差小于1%,重现性良好。对0.05 M青霉素连续测量RSD为4.9%,传感器间和运行间重现性分别为1.34%和1.21%。4 ℃ PBS保存下,30天内保持初始灵敏度的98%,之后因酶活性下降而缓慢降低,可稳定使用约1个月。与ISFET相比,CTTPS灵敏度约为8倍,线性范围更宽、跨度更大。作者还评估了生物活性分子干扰,并将传感器用于青霉素发酵液等实际样品分析,认为其适用于生物技术过程、食品控制和临床检测。
传感器的构成
- 半导体基底:p型硅衬底(p-type Si substrate),形成势阱并作为电荷存储与换能基础
- 栅氧化层:二氧化硅(SiO2,65 nm),隔离硅衬底与离子敏感膜
- 离子敏感膜:氮化硅(Si3N4,100 nm,LP-CVD沉积),感知青霉酸和H+并改变界面电荷
- 识别元件:青霉素氧化酶(penicillin oxidase, POx),吸附固定于Si3N4表面,催化青霉素水解
- 电荷控制电极:输入二极管(ID)、输入控制栅(ICG)、转移栅(TG),控制电荷注入、保持与转移
- 电荷积累区:浮动扩散区(FD),多次接收并积累与青霉素浓度对应的信号电荷
- 读出电路:复位开关(reset switch)与源极跟随器(source follower circuit),将FD电位转换为输出电压VOUT
中文摘要
本文报道了一种基于电荷转移技术(CTTPS)的高灵敏度青霉素生物传感器的制备与性能验证。该传感器采用电荷积累方式感知青霉酸和氢离子,无需外部放大器即可通过多次电荷积累循环放大传感信号。所制备的CTTPS在青霉素检测中表现出高灵敏度(47.852 mV/mM)、高信噪比、大跨度(1445 mV)、宽线性范围(0–25 mM)、快速响应(<3 s)和良好重现性,检出限约为0.01 mM。在最优条件下,其性能优于常用ISFET青霉素传感器,灵敏度约为ISFET(6.56 mV/mM)的8倍。该传感器系统已用于青霉素发酵液中青霉素浓度的测定。
英文摘要
A highly sensitive penicillin biosensor based on a charge-transfer technique (CTTPS) has been fabricated and demonstrated in this paper. CTTPS comprised a charge accumulation technique for penicilloic acid and H(+) ions perception system. With the proposed CTTPS, it is possible to amplify the sensing signals without external amplifier by using the charge accumulation cycles. The fabricated CTTPS exhibits excellent performance for penicillin detection and exhibit a high-sensitivity (47.852 mV/mM), high signal-to-noise ratio (SNR), large span (1445 mV), wide linear range (0-25 mM), fast response time (<3s), and very good reproducibility. A very lower detection limit of about 0.01 mM was observed from the proposed sensor. Under optimum conditions, the proposed CTTPS outstripped the performance of the widely used ISFET penicillin sensor and exhibited almost eight times greater sensitivity as compared to ISFET (6.56 mV/mM). The sensor system is implemented for the measurement of the penicillin concentration in penicillin fermentation broth.