Abstract
Cell patterning platforms support broad research goals, such as construction of predefined in vitro neuronal networks and the exploration of certain central aspects of cellular physiology. To easily combine cell patterning with Multi-Electrode Arrays (MEAs) and silicon-based ‘lab on a chip’ technologies, a microfabrication-compatible protocol is required. We describe a method that utilizes deposition of the polymer parylene-C on SiO2 wafers. Photolithography enables accurate and reliable patterning of parylene-C at micron-level resolution. Subsequent activation by immersion in fetal bovine serum (or another specific activation solution) results in a substrate in which cultured cells adhere to, or are repulsed by, parylene or SiO2 regions respectively. This technique has allowed patterning of a broad range of cell types (including primary murine hippocampal cells, HEK 293 cell line, human neuron-like teratocarcinoma cell line, primary murine cerebellar granule cells, and primary human glioma-derived stem-like cells). Interestingly, however, the platform is not universal; reflecting the importance of cell-specific adhesion molecules. This cell patterning process is cost effective, reliable, and importantly can be incorporated into standard microfabrication (chip manufacturing) protocols, paving the way for integration of microelectronic technology.
Highlights
Understanding mechanisms that dictate cell adhesion and patterning on synthetic materials is important for applications such as tissue engineering, drug discovery, and the fabrication of biosensors[1,2,3]
SiO2 with parylene-C is be patterned in culture
Chip activation in this example was with fetal bovine serum
Summary
Understanding mechanisms that dictate cell adhesion and patterning on synthetic materials is important for applications such as tissue engineering, drug discovery, and the fabrication of biosensors[1,2,3]. Many techniques are available and evolving, each taking advantage of the myriad biological, chemical, and physical factors that influence cell adhesion. We describe a cell-patterning technique that utilizes processes initially developed for microelectronic fabrication purposes. The platform is well-placed to enable downstream integration of microelectronic technologies, such as MEAs, into the patterning platform. Extracellular matrix proteins provide structure and strength and impact upon cell behavior via interactions with cell adhesion receptors. Cells in vitro interact with synthetic substrates via absorbed layers of proteins[4] whilst physico-chemical influences modulate adhesion. A key driver in our work, is to integrate cell patterning with microelectromechanical systems (MEMS)
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