Pfeiffer Norman, Rullkotter Johannes, Hofmann Christian, Errachid Abdelhamid, Heuberger Albert
Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021:7304-7309. doi: 10.1109/EMBC46164.2021.9630764.
Electrochemical impedance spectroscopy (EIS) is a useful approach for modeling the equivalent circuit of biosensors such as field-effect transistor (FET)-based biosensors. During the process of sensor development, laboratory potentiostats are mainly used to realize the EIS. However, those devices are normally not applicable for real use-cases outside the laboratory, so miniaturized and optimized instrumentations are needed. Various integrated circuits (IC) are available that provide EIS, but these make developed systems highly dependent on semiconductor manufacturers, including component availability. In addition, these generally do not meet the instrumentation requirements for FET-based biosensors, thus external circuitry is necessary as well. In this work, an instrumentation is presented that performs EIS between 10 Hz and 100 kHz for FET-based biosensors. The instrumentation includes the generation of the excitation signal, the configuration of the semiconductor and the readout circuit. The readout circuit consists of a transimpedance amplifier with automatic gain adjustment, filter stages, a magnitude and a phase detection circuit. Since magnitude and phase are converted to a DC signal, digitization of the results is trivial without further signal processing steps, minimizing the computational load on the microcontroller. The transmission behavior of the magnitude and phase measurement circuits shows a high linearity for sinusoidal signals. Furthermore, the overall system was tested with resistors, whereby the magnitude measurement error (1.7%) and the phase shift error (1.6°) were determined within the working range of the instrumentation. The functionality of the instrumentation is demonstrated using pH-sensitive field-effect transistors (ISFET) in various solutions.Clinical relevance- Based on the electrochemical impedance spectroscopy of FET-based biosensors such as ImmunoFETs, new point-of-care testing (POCT) devices can be developed that e.g. quantitatively detect the concentration of biomarkers with very low detection limits in body fluids. The instrumentation presented in this work can be part of new generation of diagnostic tools featuring innovative sensor technologies.
电化学阻抗谱(EIS)是一种用于对生物传感器(如基于场效应晶体管(FET)的生物传感器)的等效电路进行建模的有用方法。在传感器开发过程中,实验室恒电位仪主要用于实现EIS。然而,这些设备通常不适用于实验室之外的实际应用场景,因此需要小型化和优化的仪器。有各种可提供EIS的集成电路(IC),但这些会使开发的系统高度依赖半导体制造商,包括组件的可用性。此外,这些通常不符合基于FET的生物传感器的仪器要求,因此还需要外部电路。在这项工作中,展示了一种用于基于FET的生物传感器在10 Hz至100 kHz之间执行EIS的仪器。该仪器包括激励信号的产生、半导体的配置和读出电路。读出电路由具有自动增益调整的跨阻放大器、滤波级、幅度和相位检测电路组成。由于幅度和相位被转换为直流信号,无需进一步的信号处理步骤即可轻松实现结果的数字化,从而将微控制器上的计算负载降至最低。幅度和相位测量电路的传输行为对正弦信号显示出高线性度。此外,整个系统用电阻器进行了测试,从而在仪器的工作范围内确定了幅度测量误差(1.7%)和相移误差(1.6°)。使用pH敏感场效应晶体管(ISFET)在各种溶液中展示了该仪器的功能。临床相关性——基于诸如免疫FET等基于FET的生物传感器的电化学阻抗谱,可以开发新的即时检测(POCT)设备,例如以非常低的检测限定量检测体液中生物标志物的浓度。这项工作中展示的仪器可以成为具有创新传感器技术的新一代诊断工具的一部分。