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Separable Bilayer Microfiltration Device for Viable Label-free Enrichment of Circulating Tumour Cells

Zhou, Ming-Da and Hao, Sijie and Williams, Anthony J. and Harouaka, Ramdane A. and Schrand, Brett and Rawal, Siddharth and Ao, Zheng and Brennaman, Randall and Gilboa, Eli and Wang, Shuwen and Zhu, Jiyue and Datar, Ram and Cote, Richard and Tai, Yu-Chong and Zheng, Si-Yang (2014) Separable Bilayer Microfiltration Device for Viable Label-free Enrichment of Circulating Tumour Cells. Scientific Reports, 4 (12). Art. No. 7392. ISSN 2045-2322. PMCID PMC4260227. https://resolver.caltech.edu/CaltechAUTHORS:20141216-075929841

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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 × 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/srep07392DOIArticle
http://www.nature.com/srep/2014/141209/srep07392/full/srep07392.htmlPublisherArticle
http://www.nature.com/srep/2014/141209/srep07392/extref/srep07392-s1.pdfPublisherSupplementary Information
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260227/PubMed CentralArticle
ORCID:
AuthorORCID
Tai, Yu-Chong0000-0001-8529-106X
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.
Funders:
Funding AgencyGrant Number
Pennsylvania State UniversityUNSPECIFIED
NIHDP2CA174508
University of Miami, Sylvester Comprehensive Cancer CentreUNSPECIFIED
UNCF-Merck Science InitiativeUNSPECIFIED
Subject Keywords:Tumour biomarkers; Biomedical engineering
Issue or Number:12
PubMed Central ID:PMC4260227
Record Number:CaltechAUTHORS:20141216-075929841
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20141216-075929841
Official Citation: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, + et al. Scientific Reports 4, doi:10.1038/srep07392
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52841
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:16 Dec 2014 17:32
Last Modified:03 Oct 2019 07:44

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