Design and analysis of microfluidic cell counter using spice simulation

Microfluidic cytometers based on Coulter principle have recently shown a great potential for point of care biosensors for medical diagnostics. In this study, the design and characterization of Coulter-based microfluidic cytometer are investigated through electrical circuit simulations considering an equivalent electrical model for the biological cell. We explore the effects related to microelectrode dimensions, microfluidic detection volume, suspension medium, size/morphology of the target cells, and the impedance of the external readout circuit, on the output response of the sensor. We show that the effect of microelectrodes' surface area and the dielectric properties of the suspension medium should be carefully considered when characterizing the output response of the sensor. In particular, the area of the microelectrodes can have a significant effect on cell's electrical opacity (the ratio of cell impedance at high to low frequency) which is commonly used to distinguish between subpopulations of the target cells (e.g., lymphocytes vs. monocytes when counting white blood cells). Moreover, we highlight that the opacity response versus frequency can significantly vary based upon whether the absolute cell impedance or the differential output impedance is used in its calculation. These insights could provide valuable guidelines for the design and characterization of Coulter-based microfluidic sensors.