TY - JOUR
T1 - T2 magnetic resonance enables nanoparticle-mediated rapid detection of candidemia in whole blood
AU - Neely, Lori A.
AU - Audeh, Mark
AU - Phung, Nu Ai
AU - Min, Michael
AU - Suchocki, Adam
AU - Plourde, Daniella
AU - Blanco, Matthew
AU - Demas, Vasiliki
AU - Skewis, Lynell R.
AU - Anagnostou, Theodora
AU - Coleman, Jeffrey J.
AU - Wellman, Parris
AU - Mylonakis, Eleftherios
AU - Lowery, Thomas J.
PY - 2013/4/24
Y1 - 2013/4/24
N2 - 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.
AB - 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.
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U2 - 10.1126/scitranslmed.3005377
DO - 10.1126/scitranslmed.3005377
M3 - Article
C2 - 23616121
AN - SCOPUS:84877777940
VL - 5
JO - Science translational medicine
JF - Science translational medicine
SN - 1946-6234
IS - 182
M1 - 182ra54
ER -