Pérez P, Serrano J A, Martín M E, Daza P, Huertas G, Yúfera A
Instituto de Microelectrónica de Sevilla (IMSE-CSIC), Av. Americo Vespuccio 24, 41092 Sevilla, Spain; Departamento de Tecnología Electrónica, ETSII, Universidad de Sevilla, Av. Reina Mercedes sn, 41012, Sevilla, Spain.
Instituto de Microelectrónica de Sevilla (IMSE-CSIC), Av. Americo Vespuccio 24, 41092 Sevilla, Spain.
Comput Methods Programs Biomed. 2021 Mar;200:105840. doi: 10.1016/j.cmpb.2020.105840. Epub 2020 Nov 12.
The biomedical engineering must frequently develop sensor designs by including information from performance of bio-samples (cell cultures or tissues), technical specifications of transducers, and constrains from electronic circuits. A computer program for real-time cell culture monitoring system design is developed; analyzing, modelling and integrating into the program design flow the electrodes, cell culture and test circuit's influences.
The computer tool, first, generates an equivalent electric circuit model for the cell-electrode bio-systems based on the area covered by cells, which also considers the cell culture dynamics. Second, proposes an Oscillation Based Test (OBT) parameterized circuit, for Electrical Cell-Substrate Sensing (ECIS) measurements of the cell culture system bioimpedance. Third, simulates electrically the full system to define the best system parameter values for the sensor.
Reported experimental results are based on commercial gold electrodes and the AA8 cell line. Characteristics of the cell lines, as time-division or cell size, are incorporated into the program design flow, showing that for a given assay, the optimal OBT circuit parameters can be selected with the help of the computer tool. The electrical simulations of the full system demonstrate that the can be correctly predicted the output frequency and amplitude ranges of the voltage response, obtaining accurate results when cell culture approaches to confluence phase.
It is proposed a computer program for system design of biosensors applied to monitoring cell culture dynamics. The program allows obtaining confident system information by electrical stimulation. All system components (electrodes, cell culture and test circuits) are properly modelled. The employed procedure can be applied to any other 2D electrode layout or alternative circuit technique for ECIS test. Finally, deep insight information on cell size, number, and time-division can be extracted from the comparison with real cell culture assays in the future.
生物医学工程经常需要通过纳入生物样本（细胞培养物或组织）性能信息、传感器技术规格以及电子电路限制来开发传感器设计。开发了一个用于实时细胞培养监测系统设计的计算机程序；分析、建模并将电极、细胞培养和测试电路的影响整合到程序设计流程中。
该计算机工具首先基于细胞覆盖面积生成细胞 - 电极生物系统的等效电路模型，该模型还考虑了细胞培养动态。其次，提出一种基于振荡测试（OBT）的参数化电路，用于细胞培养系统生物阻抗的细胞 - 基质电传感（ECIS）测量。第三，对整个系统进行电模拟以确定传感器的最佳系统参数值。
报告的实验结果基于商业金电极和AA8细胞系。细胞系的特征，如时间划分或细胞大小，被纳入程序设计流程，表明对于给定的检测，借助计算机工具可以选择最佳的OBT电路参数。整个系统的电模拟表明，可以正确预测电压响应的输出频率和幅度范围，当细胞培养接近汇合阶段时可获得准确结果。
提出了一个用于应用于监测细胞培养动态的生物传感器系统设计的计算机程序。该程序允许通过电刺激获得可靠的系统信息。对所有系统组件（电极、细胞培养和测试电路）进行了适当建模。所采用的程序可应用于任何其他用于ECIS测试的二维电极布局或替代电路技术。最后，未来通过与实际细胞培养检测的比较，可以提取有关细胞大小、数量和时间划分的深入洞察信息。
