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ACS Nano. 2017 Nov 28;11(11):11425-11432. doi: 10.1021/acsnano.7b06074. Epub 2017 Nov 14.

Nanomagnetic System for Rapid Diagnosis of Acute Infection.

Park KS1,2,3,4, Kim H3,4,5, Kim S3,4,5, Lee K1,2, Park S3,4,5, Song J1, Min C1, Khanam F6, Rashu R6, Bhuiyan TR6, Ryan ET7,8,9, Qadri F6, Weissleder R1,2,10, Cheon J3,4,5, Charles RC7,8, Lee H1,2,3,4.

Author information

1
Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School , Boston, Massachusetts 02114, United States.
2
Department of Radiology, Harvard Medical School , Boston, Massachusetts 02114, United States.
3
Center for NanoMedicine, Institute for Basic Science (IBS) , Seoul 03722, Republic of Korea.
4
Yonsei-IBS Institute, Yonsei University , Seoul 03722, Republic of Korea.
5
Department of Chemistry, Yonsei University , Seoul 03722, Republic of Korea.
6
International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) , Dhaka, Bangladesh.
7
Department of Medicine, Harvard Medical School , Boston, Massachusetts 02114, United States.
8
Division of Infectious Diseases, Massachusetts General Hospital , Boston, Massachusetts 02114, United States.
9
Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health , Boston, Massachusetts 02115, United States.
10
Department of Systems Biology, Harvard Medical School , Boston, Massachusetts 02115, United States.

Abstract

Pathogen-activated antibody-secreting cells (ASCs) produce and secrete antigen-specific antibodies. ASCs are detectable in the peripheral blood as early as 3 days after antigen exposure, which makes ASCs a potential biomarker for early disease detection. Here, we present a magnetic capture and detection (MCD) assay for sensitive, on-site detection of ASCs. In this approach, ASCs are enriched through magnetic capture, and secreted antibodies are magnetically detected by a miniaturized nuclear magnetic resonance (μNMR) system. This approach is based entirely on magnetics, which supports high contrast against biological background and simplifies assay procedures. We advanced the MCD system by (i) synthesizing magnetic nanoparticles with high magnetic moments for both cell capture and antibody detection, (ii) developing a miniaturized magnetic device for high-yield cell capture, and (iii) optimizing the μNMR assay for antibody detection. Antibody responses targeting hemolysin E (HlyE) can accurately identify individuals with acute enteric fever. As a proof-of-concept, we applied MCD to detect antibodies produced by HlyE-specific hybridoma cells. The MCD achieved high sensitivity in detecting antibodies secreted from as few as 5 hybridoma cells (50 cells/mL). Importantly, the assay could be performed with whole blood with minimal sample processing.

KEYWORDS:

acute infections; biosensors; enteric fever; host response; magnetic nanoparticles; nuclear magnetic resonance

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