Block-Cell-Printing, or BloC-Printing, is a precise method of printing functional single-cell arrays – and keeping them alive. An adaptation of ancient Chinese woodblock printing techniques, the biomedical printing approach uses microfluidic arrays, hook-shaped traps, to keep cells within designated positions as they're directly transferred onto various substrates.
Researchers in Houston, led by Dr. Lidong Qin, are using this methodology to print living cells – in virtually any shape – onto nearly any surface. The key to the efficacy of the process is that nearly all the cells survive the process. The work was published this week in Proceedings of the National Academy of Sciences.
"Current technologies are inadequate," said Qin, a Nanomedicine expert at the Houston Methodist Research Institute. "Inkjet-based cell printing leaves many of the cells damaged or dead. We wanted to see if we could invent a tool that helps researchers obtain arrays of cells that are alive."
Thus far, Qin and his team have printed out cancer cells, neurons, fibroblasts, and immune cells.
The ability to print single-cell arrays with high precision and efficiency down to a single-cell resolution, to print multiple cell types, and to maintain the viability of cell functions is crucial to creating structures to measure cell function and heterogeneity.
Qin and his team say BloC-Printing may serve as a "rapid and high-throughput cell protrusion characterization tool to measure the invasion and migration capability of cancer cells."
While previous attempts to print cells in two and three dimensions used specialized inkjet printers, they suffered from a cell survival rate of 80 percent. The BloC-Printing technology provides a marked improvement to those numbers.
"We are seeing close to 100 percent of cells in BloC-Printing survive the printing process," Qin, said.
As most animal cells are some 10 to 30 micrometers wide, BloC-Printing outputs the cells within five micrometers of each other.
Back in December of last year, a team using 3D inkjet printers in the UK managed to print out ocular cells. That marked the first time 3DP technology was used successfully to print mature central nervous system cells. Using material made from retinal cells taken from adult rat retinas which were then suspended in a cultural medium, the ganglion cells used in that work demonstrated the use of 3D biomedical printing as a tool to arrange cells in a defined pattern and structure.
"We...started to think of other approaches to prepare a cell pattern," Qin said. "One day, suddenly inspired by the little stamps kids play with, we were struck by the technical mechanism for the kids' stamps. It's essentially the same as the ancient woodblock printing."
Another advantage of the method is that the output will survive on virtually any substrate surface.
"We tried glass and a few plastic surfaces," Qin says. "They all work with BloC-Printing. Many cell printing applications require cells to stay on certain surfaces. If you run electro-physiology measurement, you want cells stay on an electrode array. If you do tissue regeneration, you want cells to stay on scaffold materials."
Qin said he sees a wide variety of research applications for BloC Printing.
"The cell junctions we created may be useful for future neuron signal transduction and axon regeneration studies," Qin said. "Such work could be helpful in understanding Alzheimer's disease and other neurodegenerative diseases. Printing multilayers of cells is still a big challenge for BloC printing,"
Qin's technology is most promising in the area of cancer diagnosis. The technique can be used to arrange metastatic cancer cells in a grid, and the structure of the cells let Qin and his team determine the metastatic potential of those cells.
"The measurement may help to diagnose a cancer's stage," Qin said. "When cancer cells are trapped by the BloC printing hooks, their membrane can be extended along the device channel. The elongated length correlates to cancer cells' migration and invasion capability."
A BloC mold has the added advantage of being far less expensive to produce – at about a dollar each – versus the $10,000 to $200,000 it costs to produce them with the previous inkjet cell printer method.