T2 magnetic resonance enables nanoparticle-mediated rapid detection of candidemia in whole blood

Lori A. Neely, Mark Audeh, Nu Ai Phung, Michael Min, Adam Suchocki, Daniella Plourde, Matthew Blanco, Vasiliki Demas, Lynell R. Skewis, Theodora Anagnostou, Jeffrey J. Coleman, Parris Wellman, Eleftherios Mylonakis, Thomas J. Lowery

Research output: Contribution to journalArticlepeer-review

220 Scopus citations

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.

Original languageEnglish (US)
Article number182ra54
JournalScience translational medicine
Volume5
Issue number182
DOIs
StatePublished - Apr 24 2013

ASJC Scopus subject areas

  • Medicine(all)

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