title: Magnetic barcode assay for genetic detection of pathogens.
abstract: The task of rapidly identifying patients infected with Mycobacterium tuberculosis in resource-constrained environments remains a challenge. A sensitive and robust platform that does not require bacterial isolation or culture is critical in making informed diagnostic and therapeutic decisions. Here we introduce a platform for the detection of nucleic acids based on a magnetic barcoding strategy. PCR-amplified mycobacterial genes are sequence-specifically captured on microspheres, labelled by magnetic nanoprobes and detected by nuclear magnetic resonance. All components are integrated into a single, small fluidic cartridge for streamlined on-chip operation. We use this platform to detect M. tuberculosis and identify drug-resistance strains from mechanically processed sputum samples within 2.5 h. The specificity of the assay is confirmed by detecting a panel of clinically relevant non-M. tuberculosis bacteria, and the clinical utility is demonstrated by the measurements in M. tuberculosis-positive patient specimens. Combined with portable systems, the magnetic barcode assay holds promise to become a sensitive, high-throughput and low-cost platform for point-of-care diagnostics.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Monty
authors.initials: M
authors.lastname: Liong
authors.forename: Anh N
authors.initials: AN
authors.lastname: Hoang
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Chung
authors.forename: Nil
authors.initials: N
authors.lastname: Gural
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Ford
authors.forename: Changwook
authors.initials: C
authors.lastname: Min
authors.forename: Rupal R
authors.initials: RR
authors.lastname: Shah
authors.forename: Rushdy
authors.initials: R
authors.lastname: Ahmad
authors.forename: Marta
authors.initials: M
authors.lastname: Fernandez-Suarez
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Fortune
authors.forename: Mehmet
authors.initials: M
authors.lastname: Toner
authors.forename: Hakho
authors.initials: H
authors.lastname: Lee
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
mesh_terms: D001483:Base Sequence; D058893:DNA Barcoding, Taxonomic / Q000379:methods*; D004269:DNA, Bacterial / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D008280:Magnetics / Q000379:methods*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012680:Sensitivity and Specificity
chemical_list: D004269:DNA, Bacterial