Separable Bilayer Microfiltration Device for Viable Label-free Enrichment of Circulating Tumour Cells
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 × 10^3), 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 0.4–0.6 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.
Additional Information© 2014 The Authors. This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Received 17 June 2014. Accepted 20 November 2014. Published 9 December 2014. S.-Y. Zheng thanks the Penn State Materials Research Institute, Nanofabrication laboratory and Microscopy and Cytometry facility, and Penn State Hershey Cancer Institute for their support. This work was partially supported by the Pennsylvania State University start-up fund and the National Cancer Institute of the National Institutes of Health under Award Number DP2CA174508. Additionally, the authors would like to acknowledge research support provided by the Sylvester Comprehensive Cancer Centre at the University of Miami through their Braman Foundation Breast Cancer Developmental Grant. Funding support for A. Williams was provided through a fellowship award from the UNCF-Merck Science Initiative.
Published - srep07392.pdf
Supplemental Material - srep07392-s1.pdf