title: Interference-Free Detection of Genetic Biomarkers Using Synthetic Dipole-Facilitated Nanopore Dielectrophoresis.
abstract: The motion of polarizable particles in a nonuniform electric field (i.e., dielectrophoresis) has been extensively used for concentration, separation, sorting, and transport of biological particles from cancer cells and viruses to biomolecules such as DNAs and proteins. However, current approaches to dielectrophoretic manipulation are not sensitive enough to selectively target individual molecular species. Here, we describe the application of the dielectrophoretic principle for selective detection of DNA and RNA molecules using an engineered biological nanopore. The key element of our approach is a synthetic polycationic nanocarrier that selectively binds to the target biomolecules, dramatically increasing their dielectrophoretic response to the electric field gradient generated by the nanopore. The dielectrophoretic capture of the nanocarrier-target complexes is detected as a transient blockade of the nanopore ionic current, while any nontarget nucleic acids are repelled from the nanopore by electrophoresis and thus do not interfere with the signal produced by the target's capture. Strikingly, we show that even modestly charged nanocarriers can be used to capture DNA or RNA molecules of any length or secondary structure and simultaneously detect several molecular targets. Such selective, multiplex molecular detection technology would be highly desirable for real-time analysis of complex clinical samples.
authors.affiliation: Department of Bioengineering and Dalton Cardiovascular Research Center, University of Missouri , Columbia, Missouri 65211, United States.
authors.forename: Kai
authors.identifier: 0000-0002-5543-571X
authors.initials: K
authors.lastname: Tian
authors.affiliation: Department of Physics, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Karl
authors.initials: K
authors.lastname: Decker
authors.affiliation: Department of Physics, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Aleksei
authors.identifier: 0000-0002-6042-8442
authors.initials: A
authors.lastname: Aksimentiev
authors.affiliation: Department of Bioengineering and Dalton Cardiovascular Research Center, University of Missouri , Columbia, Missouri 65211, United States.
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Gu
mesh_terms: D015415:Biomarkers / Q000032:analysis; D002412:Cations / Q000737:chemistry; D004247:DNA / Q000032:analysis* / Q000235:genetics; D004586:Electrophoresis; D056004:Molecular Dynamics Simulation; D058608:Nanopores; D011108:Polymers / Q000737:chemistry; D012313:RNA / Q000032:analysis* / Q000235:genetics
chemical_list: D015415:Biomarkers; D002412:Cations; D011108:Polymers; D012313:RNA; D004247:DNA
keywords: HIV-TAT; microRNA; molecular dynamics simulation; nucleic acids; single-molecule detection; single-nucleotide polymorphism