title: Design of a Microfluidic Chip for Magnetic-Activated Sorting of One-Bead-One-Compound Libraries.
abstract: Molecular targeting using ligands specific to disease markers has shown great promise for early detection and directed therapy. Bead-based combinatorial libraries have served as powerful tools for the discovery of novel targeting agents. Screening platforms employing magnetic capture have been used to achieve rapid and efficient identification of high-affinity ligands from one-bead-one-compound (OBOC) libraries. Traditional manual methodologies to isolate magnetized "hit" beads are tedious and lack accuracy, and existing instruments to expedite bead sorting tend to be costly and complex. Here, we describe the design and construction of a simple and inexpensive microfluidic magnetic sorting device using standard photolithography and soft lithography approaches to facilitate high-throughput isolation of magnetized positive hit beads from combinatorial libraries. We have demonstrated that the device is able to sort magnetized beads with superior accuracy compared to conventional manual sorting approaches. This chip offers a very convenient yet inexpensive alternative for screening OBOC libraries.
authors.affiliation: Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Choi-Fong
authors.initials: CF
authors.lastname: Cho
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School , Boston, Massachusetts 02114, United States.
authors.forename: Kyungheon
authors.initials: K
authors.lastname: Lee
authors.affiliation: Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Maria-Carmela
authors.initials: MC
authors.lastname: Speranza
authors.affiliation: Departments of Chemistry and Oncology, University of Western Ontario , London, Ontario N6A 3K7, Canada.
authors.forename: Fernanda C
authors.initials: FC
authors.lastname: Bononi
authors.affiliation: Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Mariano S
authors.initials: MS
authors.lastname: Viapiano
authors.affiliation: Departments of Chemistry and Oncology, University of Western Ontario , London, Ontario N6A 3K7, Canada.
authors.forename: Leonard G
authors.initials: LG
authors.lastname: Luyt
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School , Boston, Massachusetts 02114, United States.
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.affiliation: Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: E Antonio
authors.initials: EA
authors.lastname: Chiocca
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School , Boston, Massachusetts 02114, United States.
authors.forename: Hakho
authors.initials: H
authors.lastname: Lee
authors.affiliation: Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Sean E
authors.initials: SE
authors.lastname: Lawler
mesh_terms: D015415:Biomarkers; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D008024:Ligands; D008280:Magnetics; D044085:Microfluidics / Q000379:methods*; D008863:Microspheres; D054852:Small Molecule Libraries
chemical_list: D015415:Biomarkers; D008024:Ligands; D054852:Small Molecule Libraries
keywords: magnetic-activated sorting; microfluidics; one-bead-one-compound combinatorial library