Electrochemical impedance spectroscopy based microfluidic biosensor for the detection of circulating tumor cells

Abstract

Circulating tumor cells (CTCs) can be detected using newly emerging non-invasive liquid biopsy techniques and they can be used for early diagnosis, for cancer treatment management and treatment efficiency assessment, precision medicine and to better understand the metastasis process. The number of CTCs can be as low as 1 cell/mL of blood thus there is a need for very high detection sensitivity and specificity. In this article we propose a label-free detection method based on a microfluidic device integrated with an electrochemical impedance spectroscopy biosensor capable of capturing and quantifying CTCs. We propose an interdigitated gold electrode functionalized with specific antibodies encapsulated in PDMS. The sensor was functionalized with anti-EpCAM and anti-CD36 antibodies, molecules which are expressed by CTCs and which are absent on normal blood cells. The microfluidic device was tested on MCF-7 breast cancer cells and on blood samples from canines with mammary carcinomas. The device proved to be highly sensitive to the attachment of CTCs, being able to detect the attachment of only 3 MCF-7 cells on the surface of the sensor. Thus, we report that the developed microfluidic device is a promising tool for CTCs detection, quantification and characterization.