Non-contact plotter for precise patterning of proteins on novel microdevices

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Cells in the body respond to mechanical forces, chemical signals, and the protein matrix to which they are adhered. Stem cell engineering strategies attempt to use these signals to guide unspecialized progenitor cells to become functional cells that can be used therapeutically. In order for this approach to work, we need to know the appropriate combination of signals to give the cells to produce the functional cell types we want.     Our interdisciplinary team is developing new technologies to screen combinations of mechanical, chemical, and protein signals for their integrated effects on guiding stem cell differentiation. These microscale devices allow us to test multiple combinations of regulatory factors on many samples simultaneously at a higher rate and lower cost than is possible currently.  Our current devices apply precise mechanical and chemical stimuli to cells, but we have had difficulty creating precise matrix protein patterns to adhere the cells. This is because standard protein printing methods have poor reproducibility and poor pattern uniformity.     In this proposal, we have requested an automated liquid dispenser to print proteins at precise locations on our microdevices. This protein printer prints at high speed, with excellent precision and resolution, and without contacting the microdevices, which is important for preventing damage to the delicate polymer surfaces. Printing is controlled by a robot that can print any pattern desired. The accuracy, reproducibility, and versatility of this printer will enable us to reliably print proteins in well-defined patterns on our microdevices.  This ability is critical to future development of our systems. We anticipate that with further development, our microsystems will speed discovery and innovation in the fields of regenerative medicine and stem cell engineering.     The printer will be housed at the University of Toronto in a new, state-of-the-art facility for biomicrodevice fabrication and characterization. Because the instrument is readily expandable and adaptable for many applications, and will be fully accessible through our nationally-unique fabrication facility, we expect that it will be used extensively by several research groups from our institution and others.