title: A gradient-generating microfluidic device for cell biology.
abstract: The fabrication and operation of a gradient-generating microfluidic device for studying cellular behavior is described. A microfluidic platform is an enabling experimental tool, because it can precisely manipulate fluid flows, enable high-throughput experiments, and generate stable soluble concentration gradients. Compared to conventional gradient generators, poly(dimethylsiloxane) (PDMS)-based microfluidic devices can generate stable concentration gradients of growth factors with well-defined profiles. Here, we developed simple gradient-generating microfluidic devices with three separate inlets. Three microchannels combined into one microchannel to generate concentration gradients. The stability and shape of growth factor gradients were confirmed by fluorescein isothyiocyanate (FITC)-dextran with a molecular weight similar to epidermal growth factor (EGF). Using this microfluidic device, we demonstrated that fibroblasts exposed to concentration gradients of EGF migrated toward higher concentrations. The directional orientation of cell migration and motility of migrating cells were quantitatively assessed by cell tracking analysis. Thus, this gradient-generating microfluidic device might be useful for studying and analyzing the behavior of migrating cells.
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Bong Geun
authors.initials: BG
authors.lastname: Chung
authors.forename: Amir
authors.initials: A
authors.lastname: Manbachi
authors.forename: Wajeeh
authors.initials: W
authors.lastname: Saadi
authors.forename: Francis
authors.initials: F
authors.lastname: Lin
authors.forename: Noo Li
authors.initials: NL
authors.lastname: Jeon
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D000818:Animals; D002465:Cell Movement; D002468:Cell Physiological Phenomena; D002477:Cells / Q000187:drug effects / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000494:pharmacology; D004867:Equipment Design; D005347:Fibroblasts / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D008970:Molecular Weight; D009994:Osmolar Concentration
chemical_list: D003911:Dextrans; D036341:Intercellular Signaling Peptides and Proteins; C015219:fluorescein isothiocyanate dextran; D004815:Epidermal Growth Factor; D016650:Fluorescein-5-isothiocyanate