Clinical validation of an ultra high-throughput spiral microfluidics for the detection and enrichment of viable circulating tumor cells.

Khoo, BL; Warkiani, ME; Tan, DS-W; Bhagat, AAS; Irwin, D; Lau, DP; Lim, AST; Lim, KH; Krisna, SS; Lim, W-T; Yap, YS; Lee, SC; Soo, RA; Han, J; Lim, CT

Clinical validation of an ultra high-throughput spiral microfluidics for the detection and enrichment of viable circulating tumor cells.

Khoo, BL Warkiani, ME Tan, DS-W Bhagat, AAS Irwin, D Lau, DP Lim, AST Lim, KH Krisna, SS Lim, W-T Yap, YS Lee, SC Soo, RA Han, J Lim, CT

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Publisher:: PUBLIC LIBRARY SCIENCE
Publication Type:: Journal Article
Citation:: PLoS One, 2014, 9, (7), pp. e99409
Issue Date:: 2014

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Field	Value	Language
dc.contributor.author	Khoo, BL
dc.contributor.author	Warkiani, ME
dc.contributor.author	Tan, DS-W
dc.contributor.author	Bhagat, AAS
dc.contributor.author	Irwin, D
dc.contributor.author	Lau, DP
dc.contributor.author	Lim, AST
dc.contributor.author	Lim, KH
dc.contributor.author	Krisna, SS
dc.contributor.author	Lim, W-T
dc.contributor.author	Yap, YS
dc.contributor.author	Lee, SC
dc.contributor.author	Soo, RA
dc.contributor.author	Han, J
dc.contributor.author	Lim, CT
dc.contributor.editor	Wanjin, H
dc.date.accessioned	2023-03-12T23:07:35Z
dc.date.available	2014-05-14
dc.date.available	2023-03-12T23:07:35Z
dc.date.issued	2014
dc.identifier.citation	PLoS One, 2014, 9, (7), pp. e99409
dc.identifier.issn	1932-6203
dc.identifier.issn	1932-6203
dc.identifier.uri	http://hdl.handle.net/10453/167096
dc.description.abstract	BACKGROUND: Circulating tumor cells (CTCs) are cancer cells that can be isolated via liquid biopsy from blood and can be phenotypically and genetically characterized to provide critical information for guiding cancer treatment. Current analysis of CTCs is hindered by the throughput, selectivity and specificity of devices or assays used in CTC detection and isolation. METHODOLOGY/PRINCIPAL FINDINGS: Here, we enriched and characterized putative CTCs from blood samples of patients with both advanced stage metastatic breast and lung cancers using a novel multiplexed spiral microfluidic chip. This system detected putative CTCs under high sensitivity (100%, n = 56) (Breast cancer samples: 12-1275 CTCs/ml; Lung cancer samples: 10-1535 CTCs/ml) rapidly from clinically relevant blood volumes (7.5 ml under 5 min). Blood samples were completely separated into plasma, CTCs and PBMCs components and each fraction were characterized with immunophenotyping (Pan-cytokeratin/CD45, CD44/CD24, EpCAM), fluorescence in-situ hybridization (FISH) (EML4-ALK) or targeted somatic mutation analysis. We used an ultra-sensitive mass spectrometry based system to highlight the presence of an EGFR-activating mutation in both isolated CTCs and plasma cell-free DNA (cf-DNA), and demonstrate concordance with the original tumor-biopsy samples. CONCLUSIONS/SIGNIFICANCE: We have clinically validated our multiplexed microfluidic chip for the ultra high-throughput, low-cost and label-free enrichment of CTCs. Retrieved cells were unlabeled and viable, enabling potential propagation and real-time downstream analysis using next generation sequencing (NGS) or proteomic analysis.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	PUBLIC LIBRARY SCIENCE
dc.relation.ispartof	PLoS One
dc.relation.isbasedon	10.1371/journal.pone.0099409
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	General Science & Technology
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Cell Separation
dc.subject.mesh	Cell-Free System
dc.subject.mesh	ErbB Receptors
dc.subject.mesh	Humans
dc.subject.mesh	Lung Neoplasms
dc.subject.mesh	Microfluidic Analytical Techniques
dc.subject.mesh	Mutation
dc.subject.mesh	Neoplasm Metastasis
dc.subject.mesh	Neoplastic Cells, Circulating
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Cell-Free System
dc.subject.mesh	Humans
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Lung Neoplasms
dc.subject.mesh	Neoplasm Metastasis
dc.subject.mesh	Microfluidic Analytical Techniques
dc.subject.mesh	Cell Separation
dc.subject.mesh	Mutation
dc.subject.mesh	Neoplastic Cells, Circulating
dc.subject.mesh	ErbB Receptors
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Cell Separation
dc.subject.mesh	Cell-Free System
dc.subject.mesh	ErbB Receptors
dc.subject.mesh	Humans
dc.subject.mesh	Lung Neoplasms
dc.subject.mesh	Microfluidic Analytical Techniques
dc.subject.mesh	Mutation
dc.subject.mesh	Neoplasm Metastasis
dc.subject.mesh	Neoplastic Cells, Circulating
dc.title	Clinical validation of an ultra high-throughput spiral microfluidics for the detection and enrichment of viable circulating tumor cells.
dc.type	Journal Article
utslib.citation.volume	9
utslib.location.activity	United States
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2023-03-12T23:07:32Z
pubs.issue	7
pubs.publication-status	Published online
pubs.volume	9
utslib.citation.issue	7

Abstract:

BACKGROUND: Circulating tumor cells (CTCs) are cancer cells that can be isolated via liquid biopsy from blood and can be phenotypically and genetically characterized to provide critical information for guiding cancer treatment. Current analysis of CTCs is hindered by the throughput, selectivity and specificity of devices or assays used in CTC detection and isolation. METHODOLOGY/PRINCIPAL FINDINGS: Here, we enriched and characterized putative CTCs from blood samples of patients with both advanced stage metastatic breast and lung cancers using a novel multiplexed spiral microfluidic chip. This system detected putative CTCs under high sensitivity (100%, n = 56) (Breast cancer samples: 12-1275 CTCs/ml; Lung cancer samples: 10-1535 CTCs/ml) rapidly from clinically relevant blood volumes (7.5 ml under 5 min). Blood samples were completely separated into plasma, CTCs and PBMCs components and each fraction were characterized with immunophenotyping (Pan-cytokeratin/CD45, CD44/CD24, EpCAM), fluorescence in-situ hybridization (FISH) (EML4-ALK) or targeted somatic mutation analysis. We used an ultra-sensitive mass spectrometry based system to highlight the presence of an EGFR-activating mutation in both isolated CTCs and plasma cell-free DNA (cf-DNA), and demonstrate concordance with the original tumor-biopsy samples. CONCLUSIONS/SIGNIFICANCE: We have clinically validated our multiplexed microfluidic chip for the ultra high-throughput, low-cost and label-free enrichment of CTCs. Retrieved cells were unlabeled and viable, enabling potential propagation and real-time downstream analysis using next generation sequencing (NGS) or proteomic analysis.

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http://hdl.handle.net/10453/167096