One of the major challenges in medicine is the rapid and accurate measurement of protein bio- markers, cells and organisms in different biological samples. During the prior funding period we had developed a broadly applicable, novel, point-of-care diagnostic platform using "magnetic relaxation switches" as a proximity sensor to amplify molecular interactions. We have shown that highly sensitive and selective measurements (e.g. DNA, mRNA, proteins, metabolites, drugs, bacteria, cells) can be obtained on small volume of unprocessed biological samples. One of the critical limitations of the approach however, was the need for bulky and/or complex NMR systems to carry out the measurements. We have now achieved a technological breakthrough by miniaturizing an entire NMR system onto a single, integrated circuit (IC) chip (dubbed DMR for "diagnostic magnetic resonance"). In preliminary feasibility experiments, we have shown that we can already achieve detection sensitivities of 10-12 M surpassing those of many traditional, time consuming assays. The goal of this competing renewal is to further mature DMR into a cutting-edge detection technology and apply it to molecular and cellular sensing and profiling of cells. Using cancer cells as a specific sensing target, we propose three specific aims to refine and further validate the DMR technology: 1) optimize particle constructs for high efficiency detection of cancer cells;2) determine the detection threshold and specificity for cancer cells and 3) develop real time molecular analysis of cells in biological samples. This proposal addresses a number of unmet needs and aims at optimizing, validating and further improving the novel DMR biodetection platform.

Public Health Relevance

We are developing a handheld sensor to quickly assay blood and tissue samples in cancer patients. Based on fundamentally new designs, this technology allows sensing and rapid profiling of cancer cells in blood.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB004626-08
Application #
8286934
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Conroy, Richard
Project Start
2004-09-01
Project End
2013-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
8
Fiscal Year
2012
Total Cost
$378,969
Indirect Cost
$164,862
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Im, Hyungsoon; Shao, Huilin; Park, Yong Il et al. (2014) Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nat Biotechnol 32:490-5
Liong, Monty; Im, Hyungsoon; Majmudar, Maulik D et al. (2014) Magnetic ligation method for quantitative detection of microRNAs. Adv Healthc Mater 3:1015-9
Castro, Cesar M; Ghazani, Arezou A; Chung, Jaehoon et al. (2014) Miniaturized nuclear magnetic resonance platform for detection and profiling of circulating tumor cells. Lab Chip 14:14-23
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