In traditional cell culture, cells distribute randomly in a dish. But suppose you wanted to position cells just so, say to control their spacing, arrangement, or cell-cell interactions? Standard cell culture doesn’t offer that level of control, but a new microfluidic single-cell printing device does.
Designed by Lidong Qin of the Houston Methodist Research Institute, and colleagues, “Block-Cell-Printing” (BloC-Printing) is a modern molecular twist on the ancient art of woodblock printing, in which a relief of the pattern to be printed is inked and pressed to paper, thereby transferring the image.
In BloC-Printing, the “woodblock” is a microfluidic device fabricated from polydimethylsiloxane (PDMS), and the “paper” is a tissue culture dish. Cells pass through a series of parallel microfluidic channels studded with hooks that capture the cells as they pass. Once the cells are trapped, the mold can be placed on a Petri plate or glass slide and then removed, leaving the “inked” cells in their arrayed positions. According to the authors, the technique does little harm to the cells, yielding “close to 100% cell viability.”
Luke Lee, a professor at the University of California, Berkeley, who has also developed single-cell analysis microfluidic tools, called the new approach “a brilliant idea.” He noted, for instance, that previous microfluidic designs had a closed fluidic channel for cell trapping and culturing, which made it difficult to access the cells directly for isolation or chemical perturbation. Qin’s design, in contrast, uses a vacuum to adhere the BloC-mold to a surface temporarily and draw cells into the channels, after which the mold can be removed.
“They really demonstrated a very simple and elegant way to pattern the cells and culture the cells” to drive statistically rigorous quantitative cell biology studies, Lee said.
In particular, Lee said, the technique should make it possible to position and monitor large numbers of cell pairs for studying cell-cell interactions. Other likely applications include tissue engineering and drug discovery, particularly for compounds that alter cell-cell adhesion or communication.
The authors demonstrated the technique by placing individual dye-labeled donor fibroblasts next to unlabeled recipient fibroblasts and detecting dye transfer from donor to recipient through gap junctions. In another experiment, they arrayed primary cortical neurons and maintained them in culture for two weeks.
While it is not yet clear whether this approach will enable applications that are impossible using existing methods, Lee is excited by the possibilities. “We have a microfluidic platform to study gap junctions, but this method is much better,” he said. “I thought, ‘Oh, my God, why didn’t I do this?’”
Zhang, K., et al., “Block-Cell-Printing for live single-cell printing,” PNAS, 111:2948–53, 2014. [DOI:10.1073/pnas.1313661111]