Post-enrichment circulating tumor cell detection and enumeration via deformability impedance cytometry

Abstract

Circulating tumor cells (CTCs) in blood can provide valuable information when detecting, diagnosing, and monitoring cancer. This paper describes a system that consists of a constriction-based microfluidic sensor with embedded electrodes that can detect and enumerate cancer cells in blood. The biosensor measures impedance in terms of magnitude and phase at multiple frequencies as cells transit through the constriction channel. Cancer cells deform as they move through while blood cells remain intact, thus generating differential impedance profiles that can be used for detecting and counting CTCs. Two versions of this device are reported, one where the electrodes are embedded into the disposable microfluidic channel, and the other in which the disposable chip is externally fixed to a reusable substrate housing the electrodes. Both configurations were tested by spiking breast or prostate cancer cells into murine blood, and both detected all tumor cells passing through the narrow channels while being able to differentiate between the two cell lines. The chip in its current format has a throughput of 1 μL/min. While the throughput is scalable by integrating more constriction channels in parallel, the presented assay is intended for post-enrichment label-free enumeration and characterization of CTCs.