In this chapter, we will discuss our recent approaches for improving the reproducibility and stability of free-standing bilayer lipid membranes (BLMs) by combining with BLM formation and silicon microfabrication techniques. Membrane formation by the painting method on agarose-gel-coated silicon substrate was monitored with infrared absorption spectroscopy in a multiple-internal reflection geometry. It was demonstrated that the appearance of the C=O stretching modes of phospholipid just after the lipid application can be a measure for the successful and reproducible formation of BLMs with gigaohm seal. For preparation of stable BLMs, we have fabricated a tapered aperture with nanometer-scale smoothness. Owing to this structure, the stress on lipid bilayers at the contact with the septum was minimized, leading to improved membrane stability. Tolerance of the present BLMs to repetitive solution exchanges demonstrates high mechanical stability of the membranes. Such reproducible and stable BLMs will open up variety of applications, including a high-throughput drug screening for ion channels.
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