The ability to generate protein and cellular patterns on surfaces is important for biosensor technology, tissue engineering, and for basic research in cell biology. Certain bioassays, combinatorial screening, and biosensor fabrication all require the placement of biological ligands at well-defined locations on a substrate. Control over cellular localization is also important for cell-based screens, where repeated visits to individual cells are required to perturb them and monitor their responses. In addition, tissue engineering may also require placing cells in specific locations to create organized structures.
Lithography is the most widely used technique for patterning proteins and cells. For example, photolithography can be used to generate patterns by photoablating proteins pre-adsorbed on silicon or glass surfaces, immobilizing proteins on thiol-terminated siloxane membranes that have been patterned by UV irradiation, and by covalent attachment. Lithography is a high-throughput method that enables large-area surface patterning. Photolithography is the process of transferring geometric patterns from a mask to a substrate by means of ultraviolet light. In the exposed areas, the polymer chains of the photoresist applied to the surface are broken, making them more soluble in chemical solutions called developers. Then, further processing steps will mainly depend on the type of target chemical pattern. To create protein patterns that localize cells, lithography is often combined with self-assembly methods, a bottom-up process.
Fig. 1 Cell and protein patterning using photolithography.
Our soft lithography procedures are capable of producing microstamps for microcontact printing, microtemplates, and polymer channels for microfluidic patterning. We utilize a fully biocompatible process to achieve high-throughput, high-efficiency cell patterning and achieve high-efficiency patterning of adherent and non-adherent cells. Our lithographic approach allows protein patterning and indirect cellular patterning after master molds are fabricated using dead-end microfluidic channels as small as 10 µm in size and with nearly all equipment available in biological laboratories. Furthermore, the patterns we generate on the wafer during the lithography process can generate specific microchannel networks for the flow and deposition of protein solutions in the desired pattern. In our patterning strategy, cells can be deposited with the solution rather than added after the protein pattern is generated.
Our technique enables the patterning of complex shapes and large areas without adverse effects on cell viability. Compared to standard cell culture techniques, our cell patterning technology opens up new avenues for your cell biology research.