Real-time circulating tumor cells detection via highly sensitive needle-like cytosensor-demonstrated by a blood flow simulation

Biosens Bioelectron. 2018 Sep 30:116:51-59. doi: 10.1016/j.bios.2018.05.035. Epub 2018 May 24.

Abstract

The concept of rapid detection of circulating tumor cells (CTCs) has always been the focal point of modern and future medicine. However, the dispersity and rarity of CTCs in the bloodstream makes it hard to detect metastasis. Herein, our newly designed needle-like cytosensor demonstrates that the capture and analysis of CTCs are a much less laborious process and have more potential than ever. Our aim is to detect and capture CTCs directly in the bloodstream without altering the genetic information; further benefit of current cytosensor is allows for the whole circulation of blood to run through the cytosensor, giving a much better sensitivity and chance of detecting CTCs. Our functionalized needle-like cytosensor has been modified with 3-aminopropyltriethoxysilane, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, N-hydroxysuccinimide and conjugated streptavidin to allow the binding of the biotinylated-antibody of epithelial cell adhesion molecules, which captures targeted colon cancer CTC. The capability of our needle-like cytosensor to detect CTCs spanned from 102 to 106 cells/mL. Beyond this, the needle-like cytosensor avoids the distortion of the cell information. In addition, we constructed a blood flow simulation that mimics human circulating system about 10 mL/min speed; by using cyclic voltammetry we could detect significant signals from captured cancer CTCs more than 21 cells/mL without delay; the fluorescence dye detection was further performed for data confirmation. The future of biosensors begins with this, by providing early monitoring quality care in cancer therapy.

Keywords: Blood flow simulation; Circulating tumor cell (CTC); Label-free; Needle-like cytosensor; Real-time detect.

MeSH terms

  • Antibodies, Immobilized / chemistry
  • Antibodies, Immobilized / immunology
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Biomimetics
  • Biosensing Techniques*
  • Blood Circulation*
  • Cell Line, Tumor
  • Cell Separation / methods*
  • Colonic Neoplasms / blood
  • Colonic Neoplasms / diagnosis
  • Colonic Neoplasms / immunology
  • Epithelial Cell Adhesion Molecule / immunology
  • Ethyldimethylaminopropyl Carbodiimide / chemistry
  • Humans
  • Indoles / chemistry
  • Neoplastic Cells, Circulating / chemistry*
  • Neoplastic Cells, Circulating / immunology
  • Propylamines / chemistry
  • Sensitivity and Specificity
  • Silanes / chemistry
  • Streptavidin / chemistry
  • Succinimides / chemistry

Substances

  • Antibodies, Immobilized
  • Antibodies, Monoclonal
  • Epithelial Cell Adhesion Molecule
  • Indoles
  • Propylamines
  • Silanes
  • Succinimides
  • DAPI
  • Streptavidin
  • amino-propyl-triethoxysilane
  • N-hydroxysuccinimide
  • Ethyldimethylaminopropyl Carbodiimide