Design and Analysis of Microfluidic Cell Counter using Spice Simulation

TL;DR

This paper investigates the design of microfluidic cell counters based on the coulter principle using electrical circuit simulations, focusing on how physical and electrical parameters affect sensor sensitivity and cell differentiation.

Contribution

It provides new insights into how electrode size, medium properties, and impedance measurement methods influence the performance of coulter-based microfluidic cytometers.

Findings

Electrode surface area significantly affects cell impedance opacity.

Dielectric properties of the suspension medium impact sensor response.

Choice of impedance measurement (absolute vs differential) alters opacity calculations.

Abstract

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 of coulter based microfluidic cytometer is investigated by using electrical circuit simulations. We explore the effects of physical dimensions of the microelectrodes, the measurement volume, size/morphology of the targeted cells, electrical properties of the reagents in the measurement volume, and, the impedance of external readout circuit, on the sensitivity of the sensor. We show that the effect of microelectrode's 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 microelectrodes can have significant effect on cells electrical opacity( the ratio of the cell impedance at high to low frequency) which is commonly used to distinguish between sub-population of the target cells( e.g. lymphocytes vs monocytes when counting white blood cells).Moreover, we highlight that the opacity response vs frequency can significantly vary depending upon whether the absolute cell impedance or the differential output impedance is used in the calculation. These insights can provide valuable guidelines for the design and characterization of coulter based microfluidic sensors.