Sensitive and Specific Biomimetic Lipid Coated Microfluidics to Isolate Viable Circulating Tumor Cells and Microemboli for Cancer Detection

PLoS One. 2016 Mar 3;11(3):e0149633. doi: 10.1371/journal.pone.0149633. eCollection 2016.

Abstract

Here we presented a simple and effective membrane mimetic microfluidic device with antibody conjugated supported lipid bilayer (SLB) "smart coating" to capture viable circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) directly from whole blood of all stage clinical cancer patients. The non-covalently bound SLB was able to promote dynamic clustering of lipid-tethered antibodies to CTC antigens and minimized non-specific blood cells retention through its non-fouling nature. A gentle flow further flushed away loosely-bound blood cells to achieve high purity of CTCs, and a stream of air foam injected disintegrate the SLB assemblies to release intact and viable CTCs from the chip. Human blood spiked cancer cell line test showed the ~95% overall efficiency to recover both CTCs and CTMs. Live/dead assay showed that at least 86% of recovered cells maintain viability. By using 2 mL of peripheral blood, the CTCs and CTMs counts of 63 healthy and colorectal cancer donors were positively correlated with the cancer progression. In summary, a simple and effective strategy utilizing biomimetic principle was developed to retrieve viable CTCs for enumeration, molecular analysis, as well as ex vivo culture over weeks. Due to the high sensitivity and specificity, it is the first time to show the high detection rates and quantity of CTCs in non-metastatic cancer patients. This work offers the values in both early cancer detection and prognosis of CTC and provides an accurate non-invasive strategy for routine clinical investigation on CTCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies / immunology
  • Antigens, Neoplasm / blood*
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / isolation & purification
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / immunology
  • Early Detection of Cancer
  • Female
  • HCT116 Cells
  • Humans
  • Lab-On-A-Chip Devices*
  • Lipids / chemistry
  • Male
  • Middle Aged
  • Neoplastic Cells, Circulating / immunology*
  • Neoplastic Cells, Circulating / pathology

Substances

  • Antibodies
  • Antigens, Neoplasm
  • Lipids

Grants and funding

This work was supported by grants from National Science Council (now Ministry of Science and Technology, Taiwan) contract: NSC101-2113-M-001-021-MY2, NSC102-2321-B-001-060, MOST-103-2321-B-001-042, and Summit Program from Academia Sinica, Taiwan under 104-0210-01-09-02. This work was also supported by Taiwan Ministry of Health and Welfare (Welfare Surcharge of tobacco products), No.CMRPG3C1141. J.M. Lai was supported by Academia Sinica Postdoctoral Fellowship 2013-14. J.Y. Chen was supported by MOST-103-2811-B-001-132. The funders had no role in study design, data collection and interpretation, decision of publication, or preparation of the manuscript.