Robust and Flexible Fabrication of Chemical Micropatterns for Tumor Spheroid Preparation

• Published in: ACS applied materials & interfaces Vol. 6; no. 13; pp. 10162 - 10171
• Main Authors: Liu, Tianqing, Yang, Chih-Tsung, Dieguez, Lorena, Denman, John A, Thierry, Benjamin
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 09-07-2014
• Subjects: Dimethylpolysiloxanes - chemistry; Humans; MCF-7 Cells; Photoelectron Spectroscopy; Spheroids, Cellular; multicellular tumor spheroids; plasma polymers; micropatterning; immunotargeting; gold nanoparticles
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/am501390v

A robust and flexible approach is described for the straightforward preparation of multicellular tumor spheroids of controllable dimensions. The approach is based on a one-step plasma polymerization of the monomer allylamine carried out through conformal micropatterning physical masks that is used to deposit amine-rich (PolyAA) micrometer-scale features that promote cellular attachment and initiate the formation of multicellular spheroids. A simple backfilling step of the nonpolymerized poly­(dimethylsiloxane) background with Pluronic F127 significantly reduced background cellular adhesion on the untreated substrate and, in turn, improved the quality of the spheroid formed. Tumor cells grown on the PolyAA/F127 patterned surfaces reliably formed multicellular spheroids within 24–48 h depending on the cell type. The dimension of the spheroids could be readily controlled by the dimension of the amine-rich micropatterns. This simple approach is compatible with the long-term culture of multicellular spheroids and their characterization with high-resolution optical microscopy. These features facilitate the development of on-chip assays, as demonstrated here for the study of the binding of transferrin-functionalized gold nanoparticles to multicellular tumor spheroids.