Stochastic sensors have been the subject of considerable recent interest as a result of their ability for reconfigurable, rapid, multi-analyte detection as well as their potential for sequencing DNA. These sensors are created by placing a nanometre-sized pore in an insulating membrane and measuring the ionic transport through the pore in the presence of the molecules of interest. The magnitude, duration, and rates of occurrence of the resultant current blockades allow rapid determination of analyte concentration as well as discrimination between similar molecular species. The bulk of the work in this nascent field has been focused on biologically-based stochastic sensors using protein pores and lipid membranes, although hybrid and completely non-biological systems are also the subject of active investigation. I review this work as well as recent efforts to extend these systems and translate them into usable laboratory and clinical tools.
We present a microfluidic platform for the formation and electrical measurement of lipid bilayer membranes. Using electrowetting on dielectric (EWOD), two or more aqueous droplets surrounded by a lipid-containing organic phase were manipulated into contact to form a lipid bilayer at their interface. Thin-film Ag/AgCl electrodes integrated into the device enabled electrical measurement of membrane formation and the incorporation of gramicidin channels of two bilayers in parallel.
Membrane permeability assays play an important role in assessing drug transport activities across biological membranes. However, in conventional parallel artificial membrane permeability assays (PAMPA), the membrane model used is dissimilar to biological membranes physically and chemically. Here, we describe a microfluidic passive permeability assay using droplet interface bilayers (DIBs). In a microfluidic network, nanoliter-sized donor and acceptor aqueous droplets are alternately formed in cross-flowing oil containing phospholipids. Subsequently, selective removal of oil through hydrophobic pseudo-porous sidewalls induces the contact of the lipid monolayers, creating arrayed planar DIBs between the donor and acceptor droplets. Permeation of fluorescein from the donor to the acceptor droplets was fluorometrically measured. From the measured data and a simple diffusion model we calculated the effective permeabilities of 5.1 × 10−6 cm s−1, 60.0 × 10−6 cm s−1, and 87.6 × 10−6 cm s−1 with donor droplets at pH values of 7.5, 6.4 and 5.4, respectively. The intrinsic permeabilities of specific monoanionic and neutral fluorescein species were obtained similarly. We also measured the permeation of caffeine in 10 min using UV microspectroscopy, obtaining a permeability of 20.8 × 10−6 cm s−1. With the small solution volumes, short measurement time, and ability to measure a wide range of compounds, this device has considerable potential as a platform for high-throughput drug permeability assays.