Separable bilayer microfiltration device for viable label-free enrichment of circulating tumour cells

Ming Da Zhou, Sijie Hao, Anthony J. Williams, Ramdane A. Harouaka, Brett Schrand, Siddarth Rawal, Zheng Ao, Randall Brennaman, Eli Gilboa, Bo Lu, Shuwen Wang, Jiyue Zhu, Ram Datar, Richard Cote, Yu Chong Tai, Si Yang Zheng

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56 Scopus citations

Abstract

The analysis of circulating tumour cells (CTCs) in cancer patients could provide important information for therapeutic management. Enrichment of viable CTCs could permit performance of functional analyses on CTCs to broaden understanding of metastatic disease. However, this has not been widely accomplished. Addressing this challenge, we present a separable bilayer (SB) microfilter for viable size-based CTC capture. Unlike other single-layer CTC microfilters, the precise gap between the two layers and the architecture of pore alignment result in drastic reduction in mechanical stress on CTCs, capturing them viably. Using multiple cancer cell lines spiked in healthy donor blood, the SB microfilter demonstrated high capture efficiency (78-83%), high retention of cell viability (71-74%), high tumour cell enrichment against leukocytes (1.7-2 × 103), and widespread ability to establish cultures post-capture (100% of cell lines tested). In a metastatic mouse model, SB microfilters successfully enriched viable mouse CTCs from 0.4-0.6a mL whole mouse blood samples and established in vitro cultures for further genetic and functional analysis. Our preliminary studies reflect the efficacy of the SB microfilter device to efficiently and reliably enrich viable CTCs in animal model studies, constituting an exciting technology for new insights in cancer research.

Original languageEnglish (US)
Article number7392
JournalScientific reports
Volume4
DOIs
StatePublished - 2014

All Science Journal Classification (ASJC) codes

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    Zhou, M. D., Hao, S., Williams, A. J., Harouaka, R. A., Schrand, B., Rawal, S., Ao, Z., Brennaman, R., Gilboa, E., Lu, B., Wang, S., Zhu, J., Datar, R., Cote, R., Tai, Y. C., & Zheng, S. Y. (2014). Separable bilayer microfiltration device for viable label-free enrichment of circulating tumour cells. Scientific reports, 4, [7392]. https://doi.org/10.1038/srep07392