Label-Free Differential Leukocyte Counts Using a Microfabricated, Single-Cell Impedance Spectrometer

Impedance spectroscopy is a non-invasive technique which allows analysis of the electrical properties of biological cells and other materials. Typically, the electrical properties of a cell suspension are measured using relatively large volumes (>100 mul). This approach suffers from the significant drawback that the measurement is averaged over several million cells, and as such, discrimination of cell sub-population and cell sorting is impossible. We have developed a microfluidic device capable of high-speed impedance analysis of individual cells in rapid succession. In this paper, we outline the theory for impedance analysis of a single cell in a microchip. We show experimentally, the ability of the technology to distinguish, based on impedance alone, the three main leukocyte (white blood cell) sub-populations (monocytes, lymphocytes, neutrophils) in human blood. Fluorescence analysis of the cells is performed simultaneously with impedance measurement, as cells flow through the device. This provides a direct correlation between cell type (based on antibody) and impedance properties. The data shows distinct differences in the impedance properties of leukocyte sub-populations at specific frequencies.