title: Generating nonlinear concentration gradients in microfluidic devices for cell studies.
abstract: We describe a microfluidic device for generating nonlinear (exponential and sigmoidal) concentration gradients, coupled with a microwell array for cell storage and analysis. The device has two inputs for coflowing multiple aqueous solutions, a main coflow channel and an asymmetrical grid of fluidic channels that allows the two solutions to combine at intersection points without fully mixing. Due to this asymmetry and diffusion of the two species in the coflow channel, varying amounts of the two solutions enter each fluidic path. This induces exponential and sigmoidal concentration gradients at low and high flow rates, respectively, making the microfluidic device versatile. A key feature of this design is that it is space-saving, as it does not require multiplexing or a separate array of mixing channels. Furthermore, the gradient structure can be utilized in concert with cell experiments, to expose cells captured in microwells to various concentrations of soluble factors. We demonstrate the utility of this design to assess the viability of fibroblast cells in response to a range of hydrogen peroxide (H(2)O(2)) concentrations.
authors.affiliation: Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.
authors.forename: Šeila
authors.initials: Š
authors.lastname: Selimović
authors.forename: Woo Young
authors.initials: WY
authors.lastname: Sim
authors.forename: Sang Bok
authors.initials: SB
authors.lastname: Kim
authors.forename: Yun Ho
authors.initials: YH
authors.lastname: Jang
authors.forename: Won Gu
authors.initials: WG
authors.lastname: Lee
authors.forename: Masoud
authors.initials: M
authors.lastname: Khabiry
authors.forename: Hojae
authors.initials: H
authors.lastname: Bae
authors.forename: Sachin
authors.initials: S
authors.lastname: Jambovane
authors.forename: Jong Wook
authors.initials: JW
authors.lastname: Hong
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003584:Cytological Techniques / Q000295:instrumentation*; D003603:Cytotoxins / Q000633:toxicity; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D051379:Mice; D046210:Microfluidic Analytical Techniques; D041681:NIH 3T3 Cells; D017711:Nonlinear Dynamics
chemical_list: D003603:Cytotoxins