Recent Advances in Microfluidic Impedance Detection: Principle, Design and Applications

Abstract

Under the dual drivers of precision medicine development and health monitoring demands, the development of real-time biosensing technologies has emerged as a key breakthrough in the field of life science analytics. Microfluidic impedance detection technology, achieved through the integration of microscale fluid manipulation and bioimpedance spectrum analysis, has enabled the real-time monitoring of biological samples ranging from single cells to organ-level systems, now standing at the forefront of biological real-time detection research. This review systematically summarizes the core principles of microfluidic impedance detection technology, modeling methods for cell equivalent circuits, system optimization strategies, and recent research advancements in biological detection applications. We first elucidate the fundamental principles of microfluidic impedance detection technologies, followed by a comprehensive analysis of cellular equivalent circuit model construction and microfluidic system design optimization strategies. Subsequently, we categorize applications based on biological sample types, elaborating on respective research progress and existing challenges. This review concludes with prospective insights into future developmental trajectories. We hope this work will provide novel research perspectives for advancing microfluidic impedance detection technology while stimulating interdisciplinary collaboration among researchers in biology, medicine, chemistry, and physics to propel technological innovation collectively.

Keywords: cell equivalent circuits; impedance; microfluidics; single cell.

Figure 2

Equivalent circuit models: (a) an equivalent circuit diagram when measuring the electrical properties of the cell; (b) an equivalent circuit diagram when measuring the mechanical properties of the cell in the constricted channel; (c) corresponding impedance spectra showing the different dispersion dominated by R, C_sm, and σ_i; (d) an equivalent impedance–deformability mapping model of a single cell extruded through the constricted channel; (e) an equivalent circuit model of the background fluid (reprinted with permission from [18], published by AIP Publishing, 2025); (f) an equivalent circuit model at the orifice (reprinted with permission from [19], published by Elsevier, 2023).

Figure 3

Tumor detection: (a) microfluidic impedance flow cytometer featuring xanthan gum pretreatment protocol to mitigate microchannel occlusion in constriction-based cellular interrogation systems (reprinted with permission from [21], published by American Chemical Society, 2024); (b) ultrahigh-throughput single-cell biophysical analyzer employing parallel physics-informed solver architecture for concurrent quantification of specific membrane capacitance and cytoplasmic conductivity (reprinted with permission from [35], published by Springer Nature, 2023); (c) multimodal microfluidic system with integrated electromechanical sensing modules for concurrent mechanoelectrical phenotyping of cellular intrinsic properties (reprinted with permission from [36], published by Wiley-VCH Verlag, 2023); (d) integrated microfluidic impedance cytometer implementing label-free operation mode with single-step analytical process combining cellular characterization and on-chip desalination (reprinted with permission from [40], published by Wiley-VCH Verlag, 2024).

Figure 4

Blood detection: (a) neural network-based decoding of raw impedance data streams enabling extraction of single-cell signatures hidden within overlapping cellular measurements (reprinted with permission from [41], published by Royal Society of Chemistry, 2022); (b) microfluidic chip with unique coplanar electrode configuration achieving concentration-independent sensitivity through elimination of high-concentration dependency (reprinted with permission from [25], published by Elsevier, 2022); (c) portable, wash-free microfluidic platform for multiplex assessment of erythrocyte health, functional characterization and therapeutic efficacy monitoring within 15 min (reprinted with permission from [44], published by Elsevier, 2024); (d) origami-inspired electrochemical microfluidic paper-based device for simultaneous quantitation of three cardiac protein biomarkers in fingerprick whole blood without pretreatment (reprinted with permission from [45], published by American Chemical Society, 2023).

Figure 5

Organ on a chip: (a) a 3D biomimetic model based on matrix gel microchannels for the dynamic monitoring of tumor angiogenesis (reprinted with permission from [49], published by Elsevier, 2022); (b) a brain-on-chip biomimetic microenvironment with interstitial flow regulation and neural network analysis for the dynamic characterization of synaptic connection/disconnection kinetics (reprinted with permission from [50], published by the Royal Society of Chemistry, 2024); (c) a microfluidic platform for the spatiotemporal tracking of renal tubular epithelial barrier formation and pharmacodynamic evaluation (reprinted with permission from [53], published by Elsevier, 2023); (d) a multi-channel microfluidic array for the real-time assessment of epithelial barrier integrity (reprinted with permission from [54], published by the Royal Society of Chemistry, 2022).

Figure 1

Innovative applications of microfluidic impedance detection technology in various fields.

Figure 6

Microbial detection: (a) 3D-architected microfluidic impedance cytometer with dual cylindrical electrodes and embedded microchannels for enhanced cellular interrogation (reprinted with permission from [56], published by Royal Society of Chemistry, 2024); (b) single-bacterium-resolution impedance cytometry platform enabling rapid antimicrobial susceptibility testing via electrophysiological profiling (reprinted with permission from [59], published by Wiley-VCH Verlag, 2024); (c) microfluidic device integrated with convolutional neural network-based deep learning framework for automated interpretation of impedance flow cytometry data to achieve precision bacterial classification (reprinted with permission from [61], published by American Chemical Society, 2024); (d) differential impedance biosensing system implementing phase-sensitive signal demodulation for label-free detection of anti-dengue viral antibodies in low-concentration sera (reprinted with permission from [62], published by Elsevier, 2022).

Figure 7

Conceptual map of prevailing challenges in microfluidic impedance detection technology.