It sounds like a typical “eureka” moment: Why not print proteins to help cultivate cell cultures on large sheets of film instead of putting them on glass or rigid plastic in traditional petri dishes? Imagine sheets coming fresh off the printing press like the daily papers. The advantages are clear: The printing-process would be less expensive and more flexible, it would allow greater throughput and a variety of new applications that are currently too expensive for use on a commercial scale.
Scientists at the Fraunhofer Institut für Biomedizinische Technik partnered with the German printing company Saueressig, which is part of Matthews Europe, to develop a process and brand-new equipment to coat substrates for cell cultures with proteins. The proteins are important in research because cell cultures have been shown to behave differently when grown in quasi-isolation on a petri dish. Thus, researchers add proteins to provide a more natural environment for the cell cultures – or, as one researcher put it, “to make them feel more at home”.
Up to now, applying the proteins has been a challenge, however, and the commonly used processes have been resource-intense, expensive and not well suited for large-scale production. One process, spin-coating, for example, wasted a considerable amount of liquid protein. Another process, micro-contact is more precise but expensive and labor-intensive.
The researchers at the Fraunhofer Institute, the team at Saueressig and two Spanish partners set out to change the status quo in an interdisciplinary project called Bioreel. They envisioned a process that makes applying proteins to the substrate as easy and flexible as printing the daily paper by using a very similar process. Thus, they aimed at developing a roll-to-roll printing plant for applying microstructured protein patterns to large-area film substrates.
The scientists and engineers had to develop a new kind of protein ink as well as innovative roll-to-roll printing equipment that could fulfill the requirements of this intricate process that demands low drying temperatures without solvents as well as very precise application of the proteins in the micrometer range. The film substrate and all other materials used in the process had to be biocompatible. The work was quite challenging – at first, the transparent film with printed proteins showed a structure that was nowhere near the desired pattern. But the learning curve was steep and over time, the results got better and better, recalls Dr. Thomas Velten, Head of Department Biomedical Microsystems at Fraunhofer Institut and lead author of the report describing the project.
After several years of work, the process on the flexo- and gravure roll-to-roll printing equipment was robust enough to produce consistent results. Currently, the maximum film width is 30 centimeters, and the smallest printable structures are in the range of 10 to 20 micrometers. Possible applications are in many areas of the biological and medical sciences that use thin micro-structured films of biomaterials.
Promising areas for this new technology have been identified in pharmaceutical research, in the growing of in-vitro tissue, skin and organs, and in standardizing transplants. The technology can also be used for in-vitro-diagnostics. At the Fraunhofer Institute, the researchers are, among other projects, interested in exploring the process further for optimized wound dressings that could be used for burn victims to regrow skin.
As an additional next step, Velten and his team are exploring how to print conductive structures using the roll-to-roll process and combine them with the protein patterns. They aim at printing complete biosensors. The sensors could be used for evaluating antiviral substances and for measuring a blood-glucose marker on what is known as a lab on a foil.