Circulating tumor cells (CTCs) are detached from primary solid tumors and carried through the vasculature to potentially seed distant site metastases in the vital organs - the main cause of death by cancer. Formative and iterative assessments of CTCs throughout the cancer treatment process could inform a more effective disease management. The precise counting of CTCs in the blood circulation may constitute a very powerful tool to monitor treatment efficacy in cancer patients, but it also requires the development of highly sensitive, high-throughput, and low-cost separation technology.<br/><br/>This paper reports a biocompatible and label-free cell separation strategy using ferrofluids in microfluidic devices. The separation is based on cell size difference and conducted in a custom-made biocompatible ferrofluid that retains not only short-term viabilities but also normal proliferations of 7 commonly used cancer cell lines. The microfluidic device is designed and optimized specifically to shorten the exposure time of live cells in ferrofluids from hours to seconds, by eliminating time-consuming off-chip sample preparation and extraction steps and integrating them on-chip. This combination of approaches resulted in a live cell separation strategy in ferrofluids. As a proof-of-concept demonstration, a ferrofluid with 0.26% volume fraction was used in a device to separate spiked cancer cells (100 cancer cells/mL) from white blood cells. The separation efficiencies were 80±3%, 81±5%, 82±5%, 82±4%, and 86±6% for A549, H1299, MCF-7, MDA-MB-23, and PC-3 cancer cell lines, respectively. Separated cancer cells purity was on the order of 20%. After separation, captured cancer cells showed excellent viability (93.8±1.5%) and normal proliferation to the confluence. We further demonstrated the technology worked well with clinical samples by successfully enriching CTCs from blood samples of non-small cell lung cancer patients. The analyzed results of CTCs and their mutations have the potential to assist in treatment decisions for patients. This technology can be applied to other areas of cancer biology where an understanding of cancer metastasis requires enrichment and manipulation of CTCs.

Biocompatible and label-free microfluidic separation of cancer cells from blood in ferrofluids

254th National Meeting (2017)

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