Gapless Chip-in-Carrier Integration and Injectable Ag/AgCl-Epoxy Reference Electrode for Bilayer Lipid Membrane Sensor

There are emerging needs for bilayer lipid membrane (BLM) sensors utilizing the vastly and highly developed molecular recognition ability of membrane proteins, especially those combined with CMOS chips. However, this type of BLM sensor has barely been studied so far mainly because of two problems: (i) the difficulty of their fabrication processes resulting from chip-carrier discontinuity, (ii) a skill-dependent and manual fashion to form BLMs. Here, we introduce a gapless chip-in-carrier integration process utilizing parylene as a gap filler and a microfluidic packaging method with an injectable Ag/AgCl-epoxy reference electrode. These methods allow for subsequent photolithography processes and later microfluidic-based BLM formation where the surface continuity of a microchannel is crucial. As a proof-of-concept device, we fabricated chip-in-carrier assemblies with a dummy chip coupled with a microfluidic system for BLM formation compatible with simultaneous optical observation. With this device, we validated the capability to form BLMs by microfluidic technique and characterized the configuration of a formed BLM through the observation of fluorescent localization. This chip integration and microfluidic packaging scheme can provide a solution for the full implementation of CMOS ICs with BLM sensors and broaden the possibilities of practical applications in the engineering and medical fields.