A nanodroplet cell processing platform facilitating drug synergy evaluations for anti-cancer treatments

Sci Rep. 2019 Jul 12;9(1):10120. doi: 10.1038/s41598-019-46502-3.

Abstract

Therapeutic drug synergism intervened in cancer treatments has been demonstrated to be more effective than using a single effector. However, it remains inherently challenging, with a limited cell count from tumor samples, to achieve potent personalized drug cocktails. To address the issue above, we herein present a nanodroplet cell processing platform. The platform incorporates an automatic nanodroplet dispenser with cell array ParaStamp chips, which were fabricated by a new wax stamping approach derived from laser direct writing. Such approach enables not only the on-demand de-wetting with hydrophobic wax films on substrates but also the mask-less fabrication of non-planar microstructures (i.e. no photolithography process). The ParaStamp chip was pre-occupied with anti-cancer drugs and their associate mixtures, enabling for the spatially addressable screening of optimal drug combinations simultaneously. Each droplet with a critical volume of 200 nl containing with 100 cells was utilized. Results revealed that the optimal combination reduces approximate 28-folds of conducted doses compared with single drugs. Tumor inhibition with the optimally selected drug combination was further confirmed by using PC-3 tumor-bearing mouse models. Together, the nanodroplet cell processing platform could therefore offer new opportunities to power the personalized cancer medicine at early-stage drug screening and discovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Dimethylpolysiloxanes
  • Drug Screening Assays, Antitumor / instrumentation*
  • Drug Screening Assays, Antitumor / methods*
  • Drug Synergism
  • Equipment Design
  • High-Throughput Screening Assays / instrumentation
  • High-Throughput Screening Assays / methods
  • Humans
  • Lasers
  • Male
  • Mice, Nude
  • Miniaturization
  • PC-3 Cells
  • Xenograft Model Antitumor Assays

Substances

  • Dimethylpolysiloxanes
  • baysilon