Integrating a Concentration Gradient Generator and a Single-Cell Trapper Array for High-Throughput Screening the Bioeffects of Nanomaterials

Angew Chem Int Ed Engl. 2021 May 25;60(22):12319-12322. doi: 10.1002/anie.202101293. Epub 2021 Apr 26.

Abstract

We herein develop a concentration gradient generator (CGG) on a microfluidic chip for diluting different nanoparticles. Specifically designed compact disk (CD)-shaped microchannels in the CGG module could thoroughly mix the flowing solutions and generate a linear concentration gradient of nanoparticles without aggregation. We combine the CGG with a single-cell trapper array (SCA) on microfluidics to evaluate the concentration-dependent bioeffects of the nanoparticles. The precise control of the spatiotemporal generation of nanoparticle concentration on the CGG module and the single-cell-level monitoring of the cell behaviors on the SCA module by a high-content system in real time, render the CGG-SCA system a highly precise platform, which can exclude the average effect of cell population and reflect the response of individual cells to the gradient concentrations accurately. In addition, the CGG-SCA system provides an automated platform for high-throughput screening of nanomedicines with high precision and low sample consumption.

Keywords: drug screening; microfluidic chips; nanoparticle dilution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • High-Throughput Screening Assays / methods*
  • Humans
  • Lipids / chemistry
  • Microfluidics
  • Nanoparticles / chemistry*
  • Nerve Growth Factor / chemistry
  • Nerve Growth Factor / pharmacology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Single-Cell Analysis

Substances

  • Lipids
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Doxorubicin
  • Nerve Growth Factor