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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL113156-02
Application #
8458935
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Danthi, Narasimhan
Project Start
2012-04-16
Project End
2017-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2013
Total Cost
$414,060
Indirect Cost
$176,060
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Im, Hyungsoon; Pathania, Divya; McFarland, Philip J et al. (2018) Design and clinical validation of a point-of-care device for the diagnosis of lymphoma via contrast-enhanced microholography and machine learning. Nat Biomed Eng 2:666-674
Park, Jongmin; Im, Hyungsoon; Hong, Seonki et al. (2018) Analyses of Intravesicular Exosomal Proteins Using a Nano-Plasmonic System. ACS Photonics 5:487-494
Min, Jouha; Nothing, Maria; Coble, Ben et al. (2018) Integrated Biosensor for Rapid and Point-of-Care Sepsis Diagnosis. ACS Nano 12:3378-3384
Shao, Huilin; Im, Hyungsoon; Castro, Cesar M et al. (2018) New Technologies for Analysis of Extracellular Vesicles. Chem Rev 118:1917-1950
Lin, Hsing-Ying; Huang, Chen-Han; Park, Jongmin et al. (2017) Integrated Magneto-Chemical Sensor For On-Site Food Allergen Detection. ACS Nano 11:10062-10069
Jeong, Sangmoo; Eskandari, Roozbeh; Park, Sun Mi et al. (2017) Real-time quantitative analysis of metabolic flux in live cells using a hyperpolarized micromagnetic resonance spectrometer. Sci Adv 3:e1700341
Im, Hyungsoon; Lee, Kyungheon; Weissleder, Ralph et al. (2017) Novel nanosensing technologies for exosome detection and profiling. Lab Chip 17:2892-2898
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
Park, Yong Il; Kim, Eunha; Huang, Chen-Han et al. (2017) Facile Coating Strategy to Functionalize Inorganic Nanoparticles for Biosensing. Bioconjug Chem 28:33-37
Yang, Katherine S; Im, Hyungsoon; Hong, Seonki et al. (2017) Multiparametric plasma EV profiling facilitates diagnosis of pancreatic malignancy. Sci Transl Med 9:

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