Isolation of Rare Tumor Cells from Blood Cells with Buoyant Immuno-Microbubbles

Guixin Shi, Wenjin Cui, Michael Benchimol, Yu Tsueng Liu, Robert F. Mattrey, Rajesh Mukthavaram, Santosh Kesari, Sadik C. Esener, Dmitri Simberg

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Circulating tumor cells (CTCs) are exfoliated at various stages of cancer, and could provide invaluable information for the diagnosis and prognosis of cancers. There is an urgent need for the development of cost-efficient and scalable technologies for rare CTC enrichment from blood. Here we report a novel method for isolation of rare tumor cells from excess of blood cells using gas-filled buoyant immuno-microbubbles (MBs). MBs were prepared by emulsification of perfluorocarbon gas in phospholipids and decorated with anti-epithelial cell adhesion molecule (EpCAM) antibody. EpCAM-targeted MBs efficiently (85%) and rapidly (within 15 minutes) bound to various epithelial tumor cells suspended in cell medium. EpCAM-targeted MBs efficiently (88%) isolated frequent tumor cells that were spiked at 100,000 cells/ml into plasma-depleted blood. Anti-EpCAM MBs efficiently (>77%) isolated rare mouse breast 4T1, human prostate PC-3 and pancreatic cancer BxPC-3 cells spiked into 1, 3 and 7 ml (respectively) of plasma-depleted blood. Using EpCAM targeted MBs CTCs from metastatic cancer patients were isolated, suggesting that this technique could be developed into a valuable clinical tool for isolation, enumeration and analysis of rare cells.

Original languageEnglish (US)
Article numbere58017
JournalPloS one
Volume8
Issue number3
DOIs
StatePublished - Mar 13 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Shi, G., Cui, W., Benchimol, M., Liu, Y. T., Mattrey, R. F., Mukthavaram, R., Kesari, S., Esener, S. C., & Simberg, D. (2013). Isolation of Rare Tumor Cells from Blood Cells with Buoyant Immuno-Microbubbles. PloS one, 8(3), [e58017]. https://doi.org/10.1371/journal.pone.0058017