February 24, 2014

The Art and Science of Single-Cell Printing

Image of cells in a grid pattern. Rows of single cells trapped in the hook-shaped parts of a mold.Image by the researchers, courtesy of PNAS

Researchers developed and tested a technique for convenient, precise, and fast printing of live single cells. The method, based on traditional woodblock printing techniques, could have many potential medical uses.

The ability to grow and study cells individually is important in understanding various aspects of cell function. Currently available methods, such as inkjet printing of cells, can be expensive and may damage or kill cells.

A team led by Dr. Lidong Qin from Houston Methodist Research Institute set out to develop a new, low-cost technique to print single cells with high precision and efficiency. The work was funded in part by NIH’s National Cancer Institute (NCI) and National Institute on Drug Abuse (NIDA). The study appeared online on February 10, 2014, in Proceedings of the National Academy of Sciences.

For inspiration, the scientists peered back in time more than 1,800 years to the art of woodblock printing. In this process, a pattern is cut into a block of wood. Ink is applied to the block, and then paper is laid on top of the block to transfer the carved pattern from wood to paper.

In a process the researchers termed “Block-Cell-Printing” (BloC-Printing), computer software was used to design a mold containing a network of channels with hook-shaped structures that could trap a single cell. Fluid with cells was injected into the mold channels. Individual cells became caught in the traps in precise patterns.

The researchers then transferred the mold to a Petri dish, where the cells attached. When the reusable mold was removed, a specific pattern of cells remained. The team demonstrated that altering the mold design could generate various cell patterns.

Just as artists can use several colors of ink in woodblock printing, the researchers could “print” with multiple cell types by varying the size of the traps or by injecting cells into a mold from opposite directions. The scientists found that the process could be completed in about 30 minutes and that very few cells died.

The team tested how the technique affected certain cell functions. After 3 hours of growth, the shapes and sizes of 6 types of breast cancer cells correlated with previously reported properties of the cells. The team also showed that the technique could be used to print neurons, potentially giving scientists a new tool with which to study nerve signaling.

One limitation of the technique is that unlike inkjet printing, it can’t print multi-layer structures. However, it could be combined with other techniques such as the nanoscale printing of molecules.

“Cell printing is used in so many different ways now—for drug development and in studies of tissue regeneration, cell function, and cell-cell communication,” Qin says. “BloC-Printing can be combined with molecular printing for many types of drug screening, RNA interference, and molecule-cell interaction studies. We believe the technology has big potential.”

—by Carol Torgan, Ph.D.

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References: Block-Cell-Printing for live single-cell printing. Zhang K, Chou CK, Xia X, Hung MC, Qin L. Proc Natl Acad Sci U S A. 2014 Feb 10. [Epub ahead of print]. PMID: 24516129.

Funding: NIH’s National Cancer Institute (NCI) and National Institute on Drug Abuse (NIDA); Cancer Prevention and Research Institute of Texas; Emily Herman Research Fund; Department of Defense; Alliance of Nanohealth; and the Golfers Against Cancer Foundation