Clinical Validation of an Ultra High-Throughput Spiral Microfluidics for the Detection and Enrichment of Viable Circulating Tumor Cells

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Majid Ebrahimi Warkiani
  • Daniel Shao-Weng Tan
  • Ali Asgar S. Bhagat
  • Darryl Irwin
  • Dawn Pingxi Lau
  • Alvin S. T. Lim
  • Kiat Hon Lim
  • Sai Sakktee Krisna
  • Wan-Teck Lim
  • Yoon Sim Yap
  • Soo Chin Lee
  • Ross A. Soo
  • Jongyoon Han
  • Chwee Teck Lim

Detail(s)

Original languageEnglish
Article numbere99409
Journal / PublicationPLoS ONE
Volume9
Issue number7
Online published7 Jul 2014
Publication statusPublished - Jul 2014
Externally publishedYes

Link(s)

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, lowcost and label-free enrichment of CTCs. Retrieved cells were unlabeled and viable, enabling potential propagation and realtime downstream analysis using next generation sequencing (NGS) or proteomic analysis.

Research Area(s)

Citation Format(s)

Clinical Validation of an Ultra High-Throughput Spiral Microfluidics for the Detection and Enrichment of Viable Circulating Tumor Cells. / Khoo, Bee Luan; Warkiani, Majid Ebrahimi; Tan, Daniel Shao-Weng et al.

In: PLoS ONE, Vol. 9, No. 7, e99409, 07.2014.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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