Metal-Transfer-Micromolded Three-Dimensional Microelectrode Arrays for in-vitro Brain-Slice Recordings

We report the development of metal-transfer-micromolded 3-D microelectrode arrays (3-D MEAs) and demonstrate successful electrical characterization, biocompatibility measurements, and electrophysiological recordings from rat hippocampal brain slices with these MEAs. Metal transfer micromolding is introduced as a manufacturing technology for producing nonplanar metallized patterned microelectromechanical-systems devices such as MEAs on polymeric substrates. This technology provides a self-aligned metallization scheme that eliminates the need for complex 3-D lithography. Two techniques, i.e., an intentionally formed nonplanar mold and a shadow mask, are demonstrated for the self-aligned metallization scheme. The MEAs have further been packaged using custom-designed commercial printed circuit boards and insulated using parylene deposition. Recording sites have been defined using two techniques: laser micromachining/reactive ion etching (RIE) of parylene and selective deposition of parylene using a “capping” technique. Electrical (impedance spectroscopy), biocompatibility (2-D planar cultures of neurons), electrophysiological (tissue slice recordings) characterizations of the MEAs are successfully demonstrated in this paper. The impedance of the electrodes was modeled based on a classical equivalent circuit, and high-frequency impedance estimation techniques were studied. We believe this fabrication approach offers an attractive route to disposable and biocompatible 3-D MEAs, utilizable by the neurophysiology and pharmacology communities.