On the Feasibility of Tracking Multiple Single-Cell Properties with Impedance Spectroscopy.

Electric cell-substrate impedance sensing (ECIS) has been instrumental in tracking collective behavior of confluent cell layers for decades. Toward probing cellular heterogeneity in a population, the single-cell version of ECIS has also been explored, yet its intrinsic capability and limitation remain unclear. In this work, we argue for the fundamental feasibility of impedance spectroscopy to track changes of multiple cellular properties using a noninvasive single-cell approach. While changing individual properties is experimentally prohibitive, we take a simulation approach instead and mimic the corresponding changes using a 3D computational model. From the resultant impedance spectra, we identify the spectroscopic signature characteristic to each property considered herein. Since multiple properties change concurrently in practice, the respective signatures often overlap spectroscopically and become hidden. We further attempt to deconvolve such spectra and reveal the underlying property changes. This work provides the theoretical foundation to inspire experimental validation and adoption of ECIS for multi-property single-cell measurements.