Aerosol jet printing of biological inks by ultrasonic delivery

Printing is a promising method to reduce the cost of fabricating biomedical devices. While there have been significant advancements in direct-write printing techniques, non-contact printing of biological reagents has been almost exclusively limited to inkjet printing. Motivated by this lacuna, this work investigated aerosol jet printing (AJP) of biological reagents onto a nonfouling polymer brush to fabricate in vitro diagnostic (IVD) assays. The ultrasonication ink delivery process, which had previously been reported to damage DNA molecules, caused no degradation of printed proteins, allowing printing of a streptavidin-biotin binding assay with sub-nanogram ml^-1 analytical sensitivity. Furthermore, a carcinoembryogenic antigen IVD was printed and found to have sensitivities in the clinically relevant range (limit of detection of approximately 0.5 ng ml^-1 and a dynamic range of approximately three orders of magnitude). Finally, the multi-material printing capabilities of the aerosol jet printer were demonstrated by printing silver nanowires and streptavidin as interconnected patterns in the same print job without removal of the substrate from the printer, which will facilitate the fabrication of mixed-material devices. As cost, versatility, and ink usage become more prominent factors in the development of IVDs, this work has shown that AJP should become a more widely considered technique for fabrication.