Developing a Microfabricated Lab-On-A-Chip Device for Patch-Clamp Applications with Internal Solution Exchange

Abstract

Patch-clamp electrophysiology is a widely utilized technique in both academic and industrial laboratories to assess the function of ion channels. Despite its importance, conventional patch-clamp experiments remain inherently difficult to perform, laborious, and suffer from low data throughput. Automated patch-clamp systems have since been developed to address these issues, but have done so to the detriment of the versatility and affordability of the technique. Here, we have developed a new chip-based patch-clamp system, dubbed the SMPL system, that has been specifically microfabricated to deliver high quality patch-clamp recordings while improving upon the versatility of other chip-based patch-clamp systems. The SMPL chip is compatible with any adherent cell type, and can be used to culture and assess the electrophysiological properties of induced pluripotent stem cell (iPSC)-derived and primary cultures in addition to more conventional, stable-expression cell lines. The chip contains four independent microfluidic channels, each linked to a micropatterned patch-site, that enables for up to four sequential recordings to be taken. These microchannels also serve to allow intracellular solution to be exchanged during the course of an experiment. Since the chip has been fabricated entirely of optically transparent materials, imaging experiments can also be performed in parallel to electrophysiological assessments. The SPML chip connects to any existing patch-clamp amplifier using an affordable universal adapter and switchbox, allowing the user to decide which of the four sites is to be accessed. We are currently evaluating the capabilities of this technology applied to recording lipid bilayers and ion channels reconstituted in lipid vesicles.