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.

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“…This system can detect the presence of five important species of Candida. The overall sensitivity and specificity has been reported to be 91.1% and 99.4% respectively in a clinical trial 31,32 .…”

Diagnostic Microbiology: Present Status and Future Prospect

“…The molecular methods involve both genomics and proteomics in concert with bioinformatics. The FDA has now approved NAATs for multiple viruses and bacteria 21 . The presence of these organisms usually indicates diseases because they are not normally found on human body surfaces or tissues.…”

T2 Magnetic Resonance: A Diagnostic Platform for Studying Integrated Hemostasis in Whole Blood—Proof of Concept

“…The instrument consists of a 0.54 T (approximately 23 MHz) permanent magnet assembly, radiofrequency probe, single-board spectrometer, and peripheral electronics within a 37°C temperature-controlled enclosure (10 ). The radiofrequency probe accommodates 10 -40 L samples contained within a standard 0.2-mL polypropylene tube.…”

“…A small, portable T2MR instrument (35 ϫ 15 ϫ 18 cm, 9 kg) was designed to measure the proton T2 relaxation times within blood samples (10 ). The instrument consists of a 0.54 T (approximately 23 MHz) permanent magnet assembly, radiofrequency probe, single-board spectrometer, and peripheral electronics within a 37°C temperature-controlled enclosure (10 ).…”