A Microfluidic Platform for Characterizing Single-Cell Intrinsic Bioelectrical Properties With Large Sample Size

Abstract

As the golden instrument of blood-cell phenotyping, hematology analyzers still cannot quantify intrinsic bioelectrical parameters of single cells due to limitations in sensitive structures and models. In this article, a microfluidic impedance platform composed of multiple paralleled double T-type constriction microchannels was developed, where raw impedance of traveling cells can be converted into intrinsic bioelectrical parameters of specific membrane capacitance C-sm, cytoplasmic conductivity sigma(cy), and cell diameter D-c leveraging the newly developed bioelectrical model. In order to solve the problem of channel blockage, pathways for impedance measurement and cellular passing through were decoupled, and thus the microfluidic platform was capable of characterizing 1906 +/- 909 K562 cells/sample (n(sample) = similar to 50) and 2010 +/- 1218 HL-60 cells/sample (n(sample) = similar to 30), effectively meeting the requirements of hematology analyzers (similar to 1000 cells/sample). Based on this microfluidic platform: 1) C-sm, sigma(cy), and D-c from similar to 100 000 K562 and HL-60 cells were quantified, producing a high successful rate of similar to 100% in classifying K562 versus HL-60 cells and 2) C-sm, sigma(cy), and D-c from similar to 1000 cells of granulocytes, lymphocytes, and monocytes were quantified, producing a high successful rate of similar to 80% in classifying these three types. In conclusion, the presented microfluidic platform has the potential to be used as an indispensable sensing unit in hematology analyzers in the future.