Microfabricated Cell-based Biosensor Arrays.

Abstract

Here, we described the fabrication using photolithography of poly(ethylene glycol) (PEG)-based hydrogel microstructures encapsulating viable mammalian cells on glass and silicon substrates. Substrates were treated with 3-(trichlorosilyl) propyl methacrylate to form pendant acrylate group to covalent link the hydrogel microstructure. Cells were encapsulated in arrays of cylindrical hydrogel microstructures 600 and 50 μm in diameter and viability assays demonstrated that encapsulated cells remained viable after photoencapsulation. These microstructures had clearly defined, three-dimensional structure without any residual cells remaining surface and no delamination of hydrogel elements from functionalized substrate occurred in aqueous environment for over a week. By changing spin-coating rates and feature sizes of photomasks, we could create cell-containing microstructures with aspect ratios ranging from 0.12 to 1.4. In case of 50 μm hydrogel microstructure, number of cells could be limited to 1 or 2 cells per element and array consisting of 400 elements could be fabricated in a square of 2 mm2. These cell-containinghydrogel microstructures were also successfully fabricated in poly(dimethylsiloxane) microchannels to create optical biosensor arrays of individually addressable single or multiple cell- containing hydrogel microstructures with potential applications in drug screening or pathogen detection.