Utilization of optically induced dielectrophoresis in a microfluidic system for sorting and isolation of cells with varied degree of viability: Demonstration of the sorting and isolation of drug-treated cancer cells with various degrees of anti-cancer drug resistance gene expression

Abstract

The heterogeneity of the drug resistance of cancer cells in a tumor is regarded as an important cause of therapeutic resistance and thus treatment failure. An understanding of the heterogeneity of cancer cells in a tumor in terms of their anti-cancer drug resistance is of great value for clinical applications or fundamental studies. To achieve this goal, a combination of cell-based drug testing and optically induced dielectrophoresis (ODEP)-based cell manipulation for sorting, separation, and isolation of drug-treated cells with various degrees of cell viability is proposed. For the latter, the key working principle is based on the difference in the ODEP force generated on the cells with various degrees of viability. To test the proposed idea, an ODEP microfluidic system was designed and fabricated in which two types of ODEP-based cell manipulation schemes were tested. The results successfully demonstrated that the proof-of-concept and practical application schemes were capable of effectively sorting, separating, and isolating doxorubicin-treated Dx5 (i.e., cells with drug resistance) and MES-SA (i.e., cells without drug resistance) cells that exhibited various degrees of viability and levels of anti-cancer drug resistance gene (i.e., ABCB1) expression. Moreover, the results also demonstrated that the proposed technique was capable of sorting and separating cell of the same type (i.e., drug-treated Dx5 cells) but different degrees of viability and anti-cancer drug resistance gene expression levels. Overall, this study presents a technique that is able to effectively sort, separate, and isolate drug-treated cancer cells with phenotypic heterogeneity for subsequent clinical applications or fundamental studies.