In Vivo Imaging of Single Tumor Cells in Fast-Flowing Bloodstream Using Near-Infrared Quantum Dots and Time-Gated Imaging

ACS Nano. 2019 Mar 26;13(3):3125-3131. doi: 10.1021/acsnano.8b08463. Epub 2019 Mar 11.

Abstract

Whereas in vivo fluorescence imaging of cells immobilized within tissues provides a valuable tool to a broad range of biological studies, it still lacks the sensitivity required to visualize isolated cells circulating fast in the bloodstream due, in particular, to the autofluorescence from endogenous fluorophores. Time-gated imaging of near-infrared emitting ZnCuInSe/ZnS quantum dots (QDs) with fluorescence lifetimes in the range of 150-300 ns enables the efficient rejection of fast autofluorescence photons and the selection of QD fluorescence photons, thus significantly increasing sensitivity. We labeled model erythrocytes as well as lymphoma cells using these QDs coated with a stable zwitterionic polymer surface chemistry. After reinjection in the bloodstream, we were able to image and count individual QD-labeled cells circulating at mm·s-1 velocities in blood vessels.

Keywords: circulating tumor cells; in vivo cytometry; in vivo fluorescence imaging; near-infrared; quantum dots; time-gated.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Erythrocytes / cytology
  • Fluorescence
  • Healthy Volunteers
  • Humans
  • Infrared Rays
  • Male
  • Optical Imaging*
  • Quantum Dots / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Single-Cell Analysis*
  • Spectrometry, Fluorescence
  • Surface Properties
  • Time Factors