An electroactive microwell array device to realize simultaneous trapping of single cancer cells and clusters

Abstract

The importance of circulating tumor cells (CTCs) as biomarkers has been greatly increased for early diagnosis and detection of cancer metastases. Along with a single form of CTCs, CTC clusters have recently attracted much attention due to their characteristics, such as suppression of apoptosis and survival from immune responses with high metastatic potential. Thus, it is highly necessary to investigate not only single cells but clustered cells at the same time to perform precise analysis of the current cancer state and develop suitable treatment. However, no cancer marker-free microfluidic devices have been realized to trap single cells and clusters at the same time in a single device yet. In this paper, we introduced a novel microfluidic device utilizing a microwell-on-electrode (MOE) array to realize simultaneous trapping of a single cell and clustered cells at a single cell/cluster level. Cell-sized microwells fabricated on interdigitated electrodes efficiently arrayed single cells with high trapping efficiency and single-cell occupancy (more than 90%) using dielectrophoresis (DEP). This high single cell trapping performance of MOE allows arraying of single clusters by trapping one of the cells that constitute a cluster. The feasibility of the MOE device for simultaneous arraying of single cancer cells and clusters was demonstrated by trapping a mixture of single cancer cells and clusters and measuring the size distribution of trapped clusters, which was almost identical with that of introduced cell population. Our work demonstrated that the developed MOE device can be one of the promising methods for trapping single cancer cells as well as clusters on a single device for cancer diagnosis and performing further analyses at a single cell/cluster level.