Wang Yingying, Wu Haoran, Geng Yulu, Zhang Zhao, Fu Jiaming, Ouyang Jia, Zhu Zhen
School of Integrated Circuits, Southeast University, Wuxi Campus, Zhuangyuan Road 5, Wuxi 214000, China.
College of Chemical Engineering, Nanjing Forestry University, Longpan Road 159, Nanjing 210037, China.
Biosensors (Basel). 2025 Feb 14;15(2):113. doi: 10.3390/bios15020113.
Microfluidics has significantly advanced the field of single-cell analysis, particularly in studies related to cell growth, division, and heterogeneity. Electrical impedance spectroscopy (EIS), a label-free and non-invasive biosensing technique, has been integrated into microfluidic devices for high-throughput and long-term monitoring of single budding yeast cells. Accurate interpretation of EIS measurements of cell growth dynamics necessitates the establishment of theoretical equivalent circuit models for the single-cell sensing system. Here, we report on the development of equivalent circuit models of an in situ EIS sensing system to elucidate cell growth. Firstly, finite element modeling and simulation of an EIS measurement of cell growth in the EIS sensing unit were performed, guiding the fittings of electrical components for an established equivalent circuit model (ECM). From the ECM, we extracted an equivalent volume fraction applicable to various cell and sensing unit geometries to describe the geometry-dependent sensing characteristics corresponding to the electrical response in the model. Then, EIS measurements of an immobilized cell in a microfluidic device were conducted via peripheral circuits. A lumped parameter model for the entire EIS measurement system was established, with electrical components determined by fitting to experimental data. The rationality of the proposed theoretical model was validated through the long-term impedance variation induced by cell growth in experiments, demonstrating its feasibility in linking EIS data with the bio-physics underlying the experimental phenomenon.
微流控技术极大地推动了单细胞分析领域的发展，尤其是在与细胞生长、分裂和异质性相关的研究中。电阻抗光谱法（EIS）是一种无标记且非侵入性的生物传感技术，已被集成到微流控设备中，用于对单个出芽酵母细胞进行高通量和长期监测。要准确解读细胞生长动力学的EIS测量结果，就需要为单细胞传感系统建立理论等效电路模型。在此，我们报告了用于阐明细胞生长的原位EIS传感系统等效电路模型的开发情况。首先，对EIS传感单元中细胞生长的EIS测量进行了有限元建模和模拟，指导为已建立的等效电路模型（ECM）拟合电气元件。从ECM中，我们提取了适用于各种细胞和传感单元几何形状的等效体积分数，以描述与模型中电响应相对应的几何形状相关的传感特性。然后，通过外围电路对微流控设备中固定化细胞进行EIS测量。建立了整个EIS测量系统的集总参数模型，其电气元件通过拟合实验数据来确定。通过实验中细胞生长引起的长期阻抗变化验证了所提出理论模型的合理性，证明了其在将EIS数据与实验现象背后的生物物理联系起来方面的可行性。
