A Plug-and-Play, Drug-on-Pillar Platform for Combination Drug Screening Implemented by Microfluidic Adaptive Printing

Anal Chem. 2018 Dec 4;90(23):13969-13977. doi: 10.1021/acs.analchem.8b03456. Epub 2018 Nov 13.

Abstract

Traditional high-throughput drug combination screening requires automatic pipetting of drugs into high-density microtiter plates. Here, a drug-on-pillar platform is proposed for efficient combination drug screening. Using the proposed approach, combination drug screening can be carried out in a plug-and-play manner, allowing for high-throughput screening of large permutations of drug combinations at various concentrations, such that drug dispensing and cell-based screening can be temporally separated and therefore can potentially be performed at distant laboratories. The dispensing is implemented using our recently developed microfluidic pneumatic printing platform, which features a low-cost disposable cartridge that minimizes cross contamination. Moreover, our previously developed drug nanoformulation method with amphiphilic telodendrimers has been utilized to maintain drug stability in a dry form, allowing for convenient drug storage, shipping, and subsequent rehydration. Combining the features described above, we have implemented a 1260-spot drug combination array to study the effect of paired drugs against MDA-MB-231 triple negative human breast cancer cells. This study supports the feasibility of the drug-on-pillar platform for combination drug screening and has provided valuable insight into drug combination efficacy against breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Combinations
  • Drug Evaluation, Preclinical
  • Drug Screening Assays, Antitumor
  • Humans
  • Microfluidic Analytical Techniques*
  • Printing, Three-Dimensional*
  • Structure-Activity Relationship
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Drug Combinations
  • Doxorubicin