title: Breast on-a-chip: mimicry of the channeling system of the breast for development of theranostics.
abstract: Improved detection and therapy of breast neoplasia might benefit from nanodevices traveling inside mammary ducts. However, the decreasing size of branched mammary ducts prevents access to remote areas of the ductal system using a pressure-driven fluid-based approach. Magnetic field guidance of superparamagnetic submicron particles (SMPs) in a stationary fluid might provide a possible alternative but it is critical to first reproduce the breast ductal system to assess the use of such devices for future therapeutic & diagnostic ("theranostic") purposes. Here we describe the engineering of a portion of a breast ductal system using polydimethylsiloxane (PDMS) microfluidic channels with a total volume of 0.09 μl. A magnet was used to move superparamagnetic/fluorescent SMPs through a static fluid inside the microchannels. Non-neoplastic mammary epithelial S1 cells developed basoapical polarity as a flat monolayer on the PDMS surface when cultured in the presence of laminin 111, and incubation with SMPs did not result in detectable toxicity. Cells could not withstand the fluid pressure if microinjected directly in completed channels. Whereas, they readily covered laminin 111-coated PDMS surfaces when cultured in U-shaped "hemichannels" before completing the channels. This breast-on-chip model represents a critical step towards the mimicry of the tree-like ductal system of the breast for further testing and targeting of SMPs.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907-2026, USA.
authors.forename: Meggie M G
authors.initials: MM
authors.lastname: Grafton
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Vidi
authors.forename: James
authors.initials: J
authors.lastname: Leary
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Lelièvre
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D016764:Cell Polarity / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology; D024141:Collagen Type IV / Q000737:chemistry / Q000494:pharmacology; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D004338:Drug Combinations; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D056656:Lab-On-A-Chip Devices; D007797:Laminin / Q000737:chemistry / Q000494:pharmacology; D008280:Magnetics; D042361:Mammary Glands, Human; D008856:Microscopy, Fluorescence; D008863:Microspheres; D009038:Motion; D011509:Proteoglycans / Q000737:chemistry / Q000494:pharmacology
chemical_list: D024141:Collagen Type IV; D004129:Dimethylpolysiloxanes; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; C013830:baysilon; D003094:Collagen