Microfluidic passive permeability assay using nanoliter droplet interface lipid bilayers.

作者: Takasi Nisisako , Shiva A. Portonovo , Jacob J. Schmidt

DOI: 10.1039/C3AN01314F

关键词: MembraneMembrane permeabilityMolecular diffusionMonolayerPermeationSynthetic membraneChromatographyChemistryBiological membraneLipid bilayer

摘要: Membrane permeability assays play an important role in assessing drug transport activities across biological membranes. However, conventional parallel artificial membrane (PAMPA), the model used is dissimilar to membranes physically and chemically. Here, we describe a microfluidic passive assay using droplet interface bilayers (DIBs). In network, nanoliter-sized donor acceptor aqueous droplets are alternately formed cross-flowing oil containing phospholipids. Subsequently, selective removal of through hydrophobic pseudo-porous sidewalls induces contact lipid monolayers, creating arrayed planar DIBs between droplets. Permeation fluorescein from was fluorometrically measured. From measured data simple diffusion calculated effective permeabilities 5.1 × 10−6 cm s−1, 60.0 87.6 s−1 with at pH values 7.5, 6.4 5.4, respectively. The intrinsic specific monoanionic neutral species were obtained similarly. We also permeation caffeine 10 min UV microspectroscopy, obtaining 20.8 s−1. With small solution volumes, short measurement time, ability measure wide range compounds, this device has considerable potential as platform for high-throughput assays.

参考文章(27)
N P Blair, E Shakin, M M Rusin, The effect of pH on the transfer of fluorescein across the blood-retinal barrier. Investigative Ophthalmology & Visual Science. ,vol. 26, pp. 1133- 1139 ,(1985)
David M. Maurice, Saiichi Mishima, Yoichi Ota, Endothelial permeability of the living cornea to fluorescein. Investigative Ophthalmology & Visual Science. ,vol. 13, pp. 945- 949 ,(1974)
Mehran Yazdanian, Susan L. Glynn, James L. Wright, Amale Hawi, Correlating Partitioning and caco-2 Cell Permeability of Structurally Diverse Small Molecular Weight Compounds Pharmaceutical Research. ,vol. 15, pp. 1490- 1494 ,(1998) , 10.1023/A:1011930411574
Melissa J. Simon, Woo Hyeun Kang, Shan Gao, Scott Banta, Barclay Morrison III, TAT is not capable of transcellular delivery across an intact endothelial monolayer in vitro. Annals of Biomedical Engineering. ,vol. 39, pp. 394- 401 ,(2011) , 10.1007/S10439-010-0144-X
Yunpeng Bai, Ximin He, Dingsheng Liu, Santoshkumar N. Patil, Dan Bratton, Ansgar Huebner, Florian Hollfelder, Chris Abell, Wilhelm T. S. Huck, A double droplet trap system for studying mass transport across a droplet-droplet interface Lab on a Chip. ,vol. 10, pp. 1281- 1285 ,(2010) , 10.1039/B925133B
Akihiko Ishida, Chieko Otsuka, Hirofumi Tani, Tamio Kamidate, Fluorescein chemiluminescence method for estimation of membrane permeability of liposomes. Analytical Biochemistry. ,vol. 342, pp. 338- 340 ,(2005) , 10.1016/J.AB.2005.03.042
Gøril Eide Flaten, Anand Babu Dhanikula, Kristina Luthman, Martin Brandl, Drug permeability across a phospholipid vesicle based barrier: A novel approach for studying passive diffusion ☆ European Journal of Pharmaceutical Sciences. ,vol. 27, pp. 80- 90 ,(2006) , 10.1016/J.EJPS.2005.08.007
Sara Aghdaei, Mairi E. Sandison, Michele Zagnoni, Nicolas G. Green, Hywel Morgan, Formation of artificial lipid bilayers using droplet dielectrophoresis. Lab on a Chip. ,vol. 8, pp. 1617- 1620 ,(2008) , 10.1039/B807374K
Gabriel Villar, Andrew J. Heron, Hagan Bayley, Formation of droplet networks that function in aqueous environments Nature Nanotechnology. ,vol. 6, pp. 803- 808 ,(2011) , 10.1038/NNANO.2011.183