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 J Cote, Yu Chong Tai, Si Yang Zheng

Research output: Contribution to journalArticle

47 Citations (Scopus)

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
Article number7392
JournalScientific Reports
Volume4
DOIs
StatePublished - 2014

Fingerprint

Circulating Neoplastic Cells
Equipment and Supplies
Neoplasms
Cell Line
Information Management
Mechanical Stress
Blood Donors
Cell Survival
Leukocytes
Animal Models
Technology

ASJC Scopus subject areas

  • General

Cite this

Separable bilayer microfiltration device for viable label-free enrichment of circulating tumour cells. / Zhou, Ming Da; Hao, Sijie; Williams, Anthony J.; Harouaka, Ramdane A.; Schrand, Brett; Rawal, Siddarth; Ao, Zheng; Brennaman, Randall; Gilboa, Eli; Lu, Bo; Wang, Shuwen; Zhu, Jiyue; Datar, Ram; Cote, Richard J; Tai, Yu Chong; Zheng, Si Yang.

In: Scientific Reports, Vol. 4, 7392, 2014.

Research output: Contribution to journalArticle

Zhou, MD, Hao, S, Williams, AJ, Harouaka, RA, Schrand, B, Rawal, S, Ao, Z, Brennaman, R, Gilboa, E, Lu, B, Wang, S, Zhu, J, Datar, R, Cote, RJ, Tai, YC & Zheng, SY 2014, 'Separable bilayer microfiltration device for viable label-free enrichment of circulating tumour cells', Scientific Reports, vol. 4, 7392. https://doi.org/10.1038/srep07392
Zhou, Ming Da ; Hao, Sijie ; Williams, Anthony J. ; Harouaka, Ramdane A. ; Schrand, Brett ; Rawal, Siddarth ; Ao, Zheng ; Brennaman, Randall ; Gilboa, Eli ; Lu, Bo ; Wang, Shuwen ; Zhu, Jiyue ; Datar, Ram ; Cote, Richard J ; Tai, Yu Chong ; Zheng, Si Yang. / Separable bilayer microfiltration device for viable label-free enrichment of circulating tumour cells. In: Scientific Reports. 2014 ; Vol. 4.
@article{daa2a253763745529eff5283be8181ab,
title = "Separable bilayer microfiltration device for viable label-free enrichment of circulating tumour cells",
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.",
author = "Zhou, {Ming Da} and Sijie Hao and Williams, {Anthony J.} and Harouaka, {Ramdane A.} and Brett Schrand and Siddarth Rawal and Zheng Ao and Randall Brennaman and Eli Gilboa and Bo Lu and Shuwen Wang and Jiyue Zhu and Ram Datar and Cote, {Richard J} and Tai, {Yu Chong} and Zheng, {Si Yang}",
year = "2014",
doi = "10.1038/srep07392",
language = "English",
volume = "4",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Separable bilayer microfiltration device for viable label-free enrichment of circulating tumour cells

AU - Zhou, Ming Da

AU - Hao, Sijie

AU - Williams, Anthony J.

AU - Harouaka, Ramdane A.

AU - Schrand, Brett

AU - Rawal, Siddarth

AU - Ao, Zheng

AU - Brennaman, Randall

AU - Gilboa, Eli

AU - Lu, Bo

AU - Wang, Shuwen

AU - Zhu, Jiyue

AU - Datar, Ram

AU - Cote, Richard J

AU - Tai, Yu Chong

AU - Zheng, Si Yang

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84923238726&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923238726&partnerID=8YFLogxK

U2 - 10.1038/srep07392

DO - 10.1038/srep07392

M3 - Article

C2 - 25487434

AN - SCOPUS:84923238726

VL - 4

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 7392

ER -