Lab on a chip rare cell isolation platform with dielectrophoretic smart sample focusing, automated whole cell tracking analysis script, and a bioinspired on-chip electroactive polymer micropump

Abstract

Dielectrophoresis (DEP), an electrokinetic force, is the motion of a polarizable particle in a non-uniform electric field. Contactless DEP (cDEP) is a recently developed cell sorting and isolation technique that uses the DEP force by capacitavely coupling the electrodes across the channel. The cDEP platform sorts cells based on intrinsic biophysical properties, is inexpensive, maintains a sterile environment by using disposable chips, is a rapid process with minimal sample preparation, and allows for immediate downstream recovery. This platform is highly competitive compared to other cell sorting techniques and is one of the only platforms to sort cells based on phenotype, allowing for the isolation of unique cell populations not possible in other systems. The original purpose of this work was to determine differences in the bioelectrical fingerprint between several critical cancer types. Results demonstrate a difference between Tumor Initiating Cells, Multiple Drug Resistant Cells, and their bulk populations for experiments conducted on three prostate cancer cell lines and treated and untreated MOSE cells. However, three significant issues confounded these experiments and challenged the use of the cDEP platform. The purpose of this work then became the development of solutions to these barriers and presenting a more commercializable cDEP platform. An improved analysis script was first developed that performs whole cell detection and cell tracking with an accuracy of 93.5%. Second, a loading system for doing smart sample handling, specifically cell focusing, was developed using a new in-house system and validated. Experimental results validated the model and showed that cells were successfully focused into a tight band in the middle of the channel. Finally, a proof of concept for an on-chip micropump is presented and achieved 4.5% in-plane deformation. When bonded over a microchannel, fluid flow was induced and measured. These solutions present a stronger, more versatile cDEP platform and make for a more competitive commercial product. However, these solutions are not just limited to the cDEP platform and may be applicable to multitudes of other microfluidic devices and applications.