Microvesicles (MVs) are phospholipid vesicles released into the circulation by cells, which have recently emerged as a new diagnostic biomarker. Elevated level of MVs has been reported in various malignancies, including cardiovascular diseases, diabetes, and inflammation;MVs also appear to play an integral role in the erythrocyte aging process. However, a major barrier to advancing our knowledge of MV biology, and thus fully harnessing their clinical potential, has been the lack of accurate and standardized methods for MV analysis. We have recently developed a new, nanotechnology-based diagnostic platform termed """"""""DMR"""""""" (diagnostic magnetic resonance). By employing principles of nuclear magnetic resonance (NMR), the DMR device measures the transverse relaxation of samples, whereby biological targets are labeled with molecular-specific magnetic nanoparticles (MNPs). By systematically developing optimized MNPs and chip-based miniature NMR systems, the DMR technology has now significantly advanced so as to provide sensitive, point-of-care molecular analyses of cells. Building upon these achievements, the overall goal of this proposal is to adapt and further advance the DMR platform for rapid detection and multiplexed profiling of MVs directly from whole blood. We will specifically focus on the following aims.
In Aim 1, we will synthesize new magnetic nanoagents and assay methods that will allow highly efficient and selective MNP-labeling of MV targets.
In Aim 2, we will implement a miniaturized NMR system integrated with sophisticated microfluidics. This system will be designed to enable MV analysis to be performed entirely on a single chip;it will isolate MVs directly from whole blood, label MVs with MNPs, and perform NMR measurements on the targeted MVs.
In Aim 3, both the optimized nanoagents and device will be applied to the detection and comprehensive profiling of erythrocyte-derived MVs in blood products. This study will advance our understanding of the biology of blood aging, which could lead to improved blood product quality and transfusion safety. We envision a broad diagnostic potential for the proposed DMR-MV technology in both the life sciences and in clinical practice. By facilitating the rapid and quantitative molecular analysis of MVs from different cellular origins, this technology could enable early disease detection and treatment monitoring. In turn, this could expedite advances in creating personalized treatment by providing valuable information on the cellular/molecular signatures of individual patients.

Public Health Relevance

We propose to develop a new, nanotechnology-based platform for highly sensitive medical diagnosis. The research is highly synergistic, integrating advantages of magnetic nanomaterials, novel bioconjugation chemistry technology, and microelectronics. The developed platform will be applied to detect and screen microvesicles in blood, an emergent diagnostic biomarker in vascular diseases and transfusion medicine.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Instrumentation and Systems Development Study Section (ISD)
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Danthi, Narasimhan
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Massachusetts General Hospital
United States
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Im, Hyungsoon; Lee, Kyungheon; Weissleder, Ralph et al. (2017) Novel nanosensing technologies for exosome detection and profiling. Lab Chip 17:2892-2898
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Hong, Seonki; Park, Ki Soo; Weissleder, Ralph et al. (2017) Facile silicification of plastic surface for bioassays. Chem Commun (Camb) 53:2134-2137
Min, Changwook; Park, Jongmin; Mun, Jae Kyoung et al. (2017) Integrated microHall magnetometer to measure the magnetic properties of nanoparticles. Lab Chip 17:4000-4007
Im, Hyungsoon; Park, Yong Il; Pathania, Divya et al. (2016) Digital diffraction detection of protein markers for avian influenza. Lab Chip 16:1340-5
Pathania, Divya; Im, Hyungsoon; Kilcoyne, Aoife et al. (2016) Holographic Assessment of Lymphoma Tissue (HALT) for Global Oncology Field Applications. Theranostics 6:1603-10
Song, Jun; Leon Swisher, Christine; Im, Hyungsoon et al. (2016) Sparsity-Based Pixel Super Resolution for Lens-Free Digital In-line Holography. Sci Rep 6:24681
Park, Ki Soo; Huang, Chen-Han; Lee, Kyungheon et al. (2016) Rapid identification of health care-associated infections with an integrated fluorescence anisotropy system. Sci Adv 2:e1600300
Park, Ki Soo; Chung, Hyun Jung; Khanam, Farhana et al. (2016) A magneto-DNA nanoparticle system for the rapid and sensitive diagnosis of enteric fever. Sci Rep 6:32878
Im, Hyungsoon; Lee, Hakho; Castro, Cesar M (2016) Challenges influencing next generation technologies for precision medicine. Expert Rev Precis Med Drug Dev 1:121-123

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