University of Toronto

Faculty of Applied Science & Engineering

3D Microgels “On-demand” Offer New Potential for Cell Research, the Future of Personalized Medicine

IBBME doctoral graduate Irwin A. Eydelnant
IBBME doctoral graduate Irwin A. Eydelnant (Photo courtesy of Erin Vollick).

February 25, 2014

Stars, diamonds, circles.

Rather than your average bowl of Lucky Charms, these are three-dimensional cell cultures that can be generated by a new digital microfluidics platform from researchers at U of T’s Institute for Biomaterials and Biomedical Engineering (IBBME).

Published this week in Nature Communications, the tool can be used to study cells in cost-efficient, three-dimensional microgels. This may hold the key to personalized medicine applications in the future.

“We already know that the microenvironment can greatly influence cell fate,” said Irwin A. Eydelnant (IBBME PhD 1T3), recent doctoral graduate from IBBME and first author of the publication. “The important part of this study is that we’ve developed a tool that will allow us to investigate the sensitivity of cells to their 3D environment.”

“Everyone wants to do three-dimensional (3D) cell culture,” explained co-author Aaron Wheeler (IBBME), Professor and Canada Research Chair in Bioanalytical Chemistry at IBBME, the Department of Chemistry, and the Donnelly Centre for Cellular and Biomolecular Research (DCCBR) at the University of Toronto.

“Cells grown in this manner share much more in common with living systems than the standard two-dimensional (2D) cell culture format.” But more naturalistic, 3D cell cultures are a challenge to grow.

“The reagents are expensive, the materials are inconvenient for automation, and 3D matrices break down upon repeated handling,” said Wheeler, who was named an Inventor of the Year by the University of Toronto in 2012.

Eydelnant was able to address these difficulties by adapting a digital microfluidics platform first created in the Wheeler lab. Cells, caught up in a hydrogel material, are gently flowed across a small field that, on a screen, looks much like a tiny chessboard.

The cells are strategically manipulated by a small electric field across a cutout shape on the top plate of the system, made from indium in oxide, and they become fixed.

Microgels on demand
Microgels on demand (Image courtesy of Irwin A. Eydelnant).

The tool allows for a greater level of flexibility in both the many number and types of cells, and the shape and size of the microenvironments. Some are whimsical, like the stars; diamonds and circles like those in Lucky Charms, or those designed to mimic living 3D niches. These diverse offerings give researchers a glimpse into how these many factors can affect cell fate decisions.

What’s more, according to Eydelnant, the platform permits researchers to run, “32 experiments at the same time, automatically, and all on something the size of a credit card.”

“[This new] system allows for hands-free assembly of sub-microlitre, three-dimensional microgels,” said Wheeler. “Each gel is individually addressable, fluid exchange is gentler than macro-scale alternatives, and reagent use is reduced more than 100-fold.”

“We believe that this new tool will make 3D cell culture a more attractive and accessible format for cell biology research.”

Although the researchers can foresee numerous possible applications for this platform, the team is “particularly excited” about its potential for personalized medicine.

“We may be able to collect small tissue samples from patients, distribute them into 3D gels on digital microfluidic devices, and screen for conditions to identify individually tailored therapies. This is in the ‘dream’ stages for now,” Wheeler argued, “but we think the methods described here will be useful for these types of applications in the future.”

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