title: T2 magnetic resonance enables nanoparticle-mediated rapid detection of candidemia in whole blood.
abstract: Candida spp. cause both local and disseminated infections in immunocompromised patients. Bloodstream infections of Candida spp., known as "candidemia," are associated with a high mortality rate (40%), which is mainly attributed to the long diagnostic time required by blood culture. We introduce a diagnostic platform based on T2 magnetic resonance (T2MR), which is capable of sensitive and rapid detection of fungal targets in whole blood. In our approach, blood-compatible polymerase chain reaction is followed by hybridization of the amplified pathogen DNA to capture probe-decorated nanoparticles. Hybridization yields nanoparticle microclusters that cause large changes in the sample's T2MR signal. With this T2MR-based method, Candida spp. can be detected directly in whole blood, thus eliminating the need for analyte purification. Using a small, portable T2MR detection device, we were able to rapidly, accurately, and reproducibly detect five Candida species within human whole blood with a limit of detection of 1 colony-forming unit/ml and a time to result of <3 hours. Spiked blood samples showed 98% positive agreement and 100% negative agreement between T2MR and blood culture. Additionally, performance of the assay was evaluated on 21 blinded clinical specimens collected serially. This study shows that the nanoparticle- and T2MR-based detection method is rapid and amenable to automation and offers clinicians the opportunity to detect and identify multiple human pathogens within hours of sample collection.
authors.affiliation: T2 Biosystems, Lexington, MA 02421, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Neely
authors.forename: Mark
authors.initials: M
authors.lastname: Audeh
authors.forename: Nu Ai
authors.initials: NA
authors.lastname: Phung
authors.forename: Michael
authors.initials: M
authors.lastname: Min
authors.forename: Adam
authors.initials: A
authors.lastname: Suchocki
authors.forename: Daniella
authors.initials: D
authors.lastname: Plourde
authors.forename: Matthew
authors.initials: M
authors.lastname: Blanco
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Demas
authors.forename: Lynell R
authors.initials: LR
authors.lastname: Skewis
authors.forename: Theodora
authors.initials: T
authors.lastname: Anagnostou
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Coleman
authors.forename: Parris
authors.initials: P
authors.lastname: Wellman
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lowery
mesh_terms: D002175:Candida / Q000472:pathogenicity*; D058387:Candidemia / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D053758:Nanoparticles; D016133:Polymerase Chain Reaction