title: Bioinspired multivalent DNA network for capture and release of cells.
abstract: Capture and isolation of flowing cells and particulates from body fluids has enormous implications in diagnosis, monitoring, and drug testing, yet monovalent adhesion molecules used for this purpose result in inefficient cell capture and difficulty in retrieving the captured cells. Inspired by marine creatures that present long tentacles containing multiple adhesive domains to effectively capture flowing food particulates, we developed a platform approach to capture and isolate cells using a 3D DNA network comprising repeating adhesive aptamer domains that extend over tens of micrometers into the solution. The DNA network was synthesized from a microfluidic surface by rolling circle amplification where critical parameters, including DNA graft density, length, and sequence, could readily be tailored. Using an aptamer that binds to protein tyrosine kinase-7 (PTK7) that is overexpressed on many human cancer cells, we demonstrate that the 3D DNA network significantly enhances the capture efficiency of lymphoblast CCRF-CEM cells over monovalent aptamers and antibodies, yet maintains a high purity of the captured cells. When incorporated in a herringbone microfluidic device, the 3D DNA network not only possessed significantly higher capture efficiency than monovalent aptamers and antibodies, but also outperformed previously reported cell-capture microfluidic devices at high flow rates. This work suggests that 3D DNA networks may have broad implications for detection and isolation of cells and other bioparticles.
authors.affiliation: Center for Regenerative Therapeutics and Department of Medicine, Brigham and Women's Hospital, Cambridge, MA 02139, USA.
authors.forename: Weian
authors.initials: W
authors.lastname: Zhao
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Cui
authors.forename: Suman
authors.initials: S
authors.lastname: Bose
authors.forename: Dagang
authors.initials: D
authors.lastname: Guo
authors.forename: Chong
authors.initials: C
authors.lastname: Shen
authors.forename: Wesley P
authors.initials: WP
authors.lastname: Wong
authors.forename: Ken
authors.initials: K
authors.lastname: Halvorsen
authors.forename: Omid C
authors.initials: OC
authors.lastname: Farokhzad
authors.forename: Grace Sock Leng
authors.initials: GS
authors.lastname: Teo
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Phillips
authors.forename: David M
authors.initials: DM
authors.lastname: Dorfman
authors.forename: Rohit
authors.initials: R
authors.lastname: Karnik
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Karp
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D044085:Microfluidics
chemical_list: D004247:DNA