Cell bioprinting as a potential high-throughput method for fabricating Cell-Based Biosensors (CBBs)

Cell-based biosensors (CBBs) are becoming an important tool for biosecurity applications and rapid diagnostics. For current CBBs technology, cell immobilization and high throughput fabrication are the main challenges. To address these in this study, the feasibility of bioprinting cell-laden hydrogel to fabricate CBBs at high throughput was investigated and cell response was tracked by using lensless charge-coupled device (CCD) technology. This study indicated that (i) a cell-laden collagen printing platform was capable of immobilizing cells (smooth muscle cells) in collagen droplets with precise spatial control and pattern them onto surfaces, (ii) high post-printing cell viability was achieved (>94%) and the immobilized cells proliferated over five days, (iii) the immobilized cells maintain their biological and physiological sensitivity to environmental stimuli (e.g. environmental temperature change and lysis by adding of de-ionized water), as quantified by change in cell spread size (decreasing from ∼3000 μm² at t=0 hour to ∼600 μm² at t=16 hours), and (iv) our developed lensless CCD technology is capable detecting the cell morphology change under environmental stimuli, which is essential for the portability of the CBBs. These results show that printing cells encapsulated inbiocompatible hydrogels could lead to fabrication of CBBs in a high throughput manner. Also, the lensless CCD systems can be used to monitor the morphological cell responses over a wide field of view (as large as 37.25 mm x 25.70 mm).