title: Multi-chamber microfluidic platform for high-precision skin permeation testing.
abstract: The established in vitro tool used for testing the absorption and penetration of chemicals through skin in pharmacology, toxicology and cosmetic science is the static Franz diffusion cell. While widespread, Franz cells are relatively costly, low-throughput and results may suffer from poor reproducibility. Microfluidics has the potential to overcome these drawbacks. In this paper, we present a novel microfluidic skin permeation platform and validate it rigorously against the Franz cell by comparing the transport of 3 model chemicals of varying lipophilicity: caffeine, salicylic acid and testosterone. Permeation experiments through silicone membranes show that the chip yields higher sensitivity in permeant cumulative amounts and comparable or lower coefficients of variation. Using a skin organotypic culture, we show that the chip decreases the effect of unstirred water layers that can occur in static Franz cells. The validation reported herein sets the stage for efficient skin permeation and toxicity screening and further development of microfluidic skin-on-chip devices.
authors.affiliation: Singapore Institute of Manufacturing Technology, A*STAR, 2 Fusionopolis Way, Level 10, Innovis, 138634 Singapore. yuri.dancik@imb.a-star.edu.sg zpwang@simtech.a-star.edu.sg.
authors.forename: M
authors.identifier: 0000-0001-9515-4448
authors.initials: M
authors.lastname: Alberti
authors.affiliation: Experimental Dermatology Laboratory, Institute of Medical Biology, A*STAR, 8a Biomedical Grove, #06-06, 138648 Singapore and Clinical Research Unit for Skin, Allergy and Regeneration, Institute of Medical Biology, A*STAR, 8a Biomedical Grove, #06-06, 138648 Singapore.
authors.forename: Y
authors.identifier: 0000-0002-3652-9673
authors.initials: Y
authors.lastname: Dancik
authors.affiliation: Experimental Dermatology Laboratory, Institute of Medical Biology, A*STAR, 8a Biomedical Grove, #06-06, 138648 Singapore.
authors.forename: G
authors.identifier: 0000-0001-8423-5197
authors.initials: G
authors.lastname: Sriram
authors.affiliation: Singapore Institute of Manufacturing Technology, A*STAR, 2 Fusionopolis Way, Level 10, Innovis, 138634 Singapore. yuri.dancik@imb.a-star.edu.sg zpwang@simtech.a-star.edu.sg.
authors.forename: B
authors.initials: B
authors.lastname: Wu
authors.affiliation: Clinical Research Unit for Skin, Allergy and Regeneration, Institute of Medical Biology, A*STAR, 8a Biomedical Grove, #06-06, 138648 Singapore.
authors.forename: Y L
authors.initials: YL
authors.lastname: Teo
authors.affiliation: Singapore Institute of Manufacturing Technology, A*STAR, 2 Fusionopolis Way, Level 10, Innovis, 138634 Singapore. yuri.dancik@imb.a-star.edu.sg zpwang@simtech.a-star.edu.sg.
authors.forename: Z
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Experimental Dermatology Laboratory, Institute of Medical Biology, A*STAR, 8a Biomedical Grove, #06-06, 138648 Singapore and Clinical Research Unit for Skin, Allergy and Regeneration, Institute of Medical Biology, A*STAR, 8a Biomedical Grove, #06-06, 138648 Singapore.
authors.forename: M
authors.initials: M
authors.lastname: Bigliardi-Qi
authors.affiliation: Singapore Institute of Manufacturing Technology, A*STAR, 2 Fusionopolis Way, Level 10, Innovis, 138634 Singapore. yuri.dancik@imb.a-star.edu.sg zpwang@simtech.a-star.edu.sg.
authors.forename: R G
authors.initials: RG
authors.lastname: Wu
authors.affiliation: Singapore Institute of Manufacturing Technology, A*STAR, 2 Fusionopolis Way, Level 10, Innovis, 138634 Singapore. yuri.dancik@imb.a-star.edu.sg zpwang@simtech.a-star.edu.sg.
authors.forename: Z P
authors.initials: ZP
authors.lastname: Wang
authors.affiliation: Experimental Dermatology Laboratory, Institute of Medical Biology, A*STAR, 8a Biomedical Grove, #06-06, 138648 Singapore and Clinical Research Unit for Skin, Allergy and Regeneration, Institute of Medical Biology, A*STAR, 8a Biomedical Grove, #06-06, 138648 Singapore.
authors.forename: P L
authors.initials: PL
authors.lastname: Bigliardi
mesh_terms: D002110:Caffeine / Q000032:analysis / Q000378:metabolism; D002460:Cell Line; D004867:Equipment Design; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods*; D015203:Reproducibility of Results; D020156:Salicylic Acid / Q000032:analysis / Q000378:metabolism; D012867:Skin / Q000737:chemistry / Q000378:metabolism; D012869:Skin Absorption; D013739:Testosterone / Q000032:analysis / Q000378:metabolism
chemical_list: D002110:Caffeine; D013739:Testosterone; D020156:Salicylic Acid