MASSACHUSETTS GENERAL HOSPITAL, THE
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.
| AWARD OVERVIEW |
| Award Number |
3R01EB004626-05A1S1 |
Funding Agency |
Department of Health and Human Services |
| Total Award Amount |
$175,968 |
Project Location - City |
Boston |
| Award Date |
08/31/2009 |
Project Location - State |
MA |
| Project Status |
Completed |
Project Location - Zip |
02114-0000
|
| Jobs Reported |
0.00 |
Congressional District |
09 |
| Project Location - Country |
US |
|
|
Recipient Information
(Grants)
| Recipient Information (Grants) |
|
Recipient Name
|
MASSACHUSETTS GENERAL HOSPITAL, THE |
| Recipient DUNS Number |
073130411
|
| Recipient Address |
55 FRUIT ST |
| Recipient City |
BOSTON |
| Recipient State |
Massachusetts |
| Recipient Zip |
02114-2621 |
| Recipient Congressional District |
09 |
| Recipient Country |
USA |
Required to Report Top 5
Highly Compensated Officials |
No |
Projects and Jobs Information
| Projects and Jobs Information |
| Project Title |
CHIP NMR biosensor for molecular analysis of cells |
| Project Status |
Completed |
| Final Project Report Submitted |
Yes |
| Project Activities Description |
General Medical and Surgical Hospitals |
| Quarterly Activities/Project Description |
The transverse relaxivity (r2) is a major determinant of the potency of magnetic nanoparticles (MNPs) as sensing agents for DMR (diagnostic magnetic resonance) and MRI (magnetic resonance imaging). In order to increase r2, we have previously developed various synthetic methods to produce MNPs from highly magnetic materials as well as to enlarge the particle size. By doping ferrite with Mn and making bigger particles, for example, we have achieved r2 = 420 s-1 mM-1 [metal], which is >600% higher than that of conventional MNPs. Further improving r2 in a single-core particle format, however, posed significant difficulties; bigger MNPs tend to be polydisperse and spontaneously flocculate in suspension. Overcoming this challenge, we have recently designed a new MNP construct that not only assumes superb colloidal stability but also achieves r2 relaxivities near the maximum theoretical limit. The new MNP consists of a cluster of individually grown MNPs, embedded in a thin silica shell. The approach provides a facile way to increase the overall size of the magnetic cores; by assembling 12-nm MnFe2O4 MNPs, we could obtain clustered cores with diameter of 70 nm. The silica overcoating also enables the incorporation of other functional materials (e.g., fluorochromes) and protects the particle contents. Due to their large size, the clustered particles fall into the ?static dephasing? regime that sets the maximum r2 for a given magnetic material. Indeed, the measured r2 was ~695 s-1·mM-1 [metal], close to the predicted limit of 759 s-1·mM-1 [metal]. Moreover, by embedding fluorescent molecules during the silica shell formation, the resultant MNPs could function as multimodal imaging agents to improve detection accuracy. We plan to apply these new particles to DMR sensing and MRI. Performance of the particles will be comparatively analyzed with those of single-core MNPs. |
| Jobs Created |
0.00 |
| Description of Jobs Created |
The goal of this administrative supplement (NOT OD-09-056) is to provide additional support for two postdoctoral fellows per year to work in a mentored, multidisciplinary research environment focused on developing next generation miniaturized, chip-based NMR sensors. The research environment is ideally suited for project based training, will result in job creation, newly trained scientists and speed up the science of the NIBIB base project (R01 EB004626). In the base project, we are developing chip-based NMR nanosensors using microfluidic technologies for detecting and profiling of cells from peripheral blood, fine needle aspirates and other sources. The ability to non-invasively detect and profile such cells has far-reaching diagnostic, prognostic, therapeutic, and basic biology implications. Recently, we have developed a chip-based platform dubbed DMR (diagnostic NMR) for multiplexed, quantitative and rapid analysis. Using magnetic particles as a proximity sensor to amplify molecular interactions, the hand-held DMR system can be used to perform measurements on unprocessed biological samples. The capability of the DMR system has been successfully demonstrated by identifying small numbers of cells and molecularly analyzing them in real time, and by measuring a series of protein biomarkers in parallel. This technological advance has important basic science and clinical implications and ultimately could be applied as a point-of-care high-throughput diagnostic device, for characterizing other rare cells (stem cells, immune cells) and for longitudinal follow-up of during personalized therapy. |
Purchaser Information
(Grants)
| Purchaser Information |
| Contracting Office ID |
Not Reported |
| Contracting Office Name |
Not Available |
| Contracting Office Region |
Not Available |
| TAS Major Program |
75-0899 |
| Award Information |
| Award Date |
08/31/2009 |
| Award Number |
3R01EB004626-05A1S1 |
| Order Number |
|
| Award Type |
Grants |
| Funding Agency ID |
75 |
| Funding Agency Name |
Department of Health and Human Services |
| Funding Office Name |
Not Available |
| Awarding Agency ID |
75 |
| Awarding Agency Name |
Department of Health and Human Services |
| Amount of Award |
$175,968 |
| Funds Invoiced/Received |
$175,968 |
| Expenditure Amount |
$175,968 |
| Infrastructure Expenditure Amount |
$0 |
| Infrastructure Purpose and Rationale |
Not Reported |
| Infrastructure Point of Contact Name |
Not Reported |
| Infrastructure Point of Contact Email |
Not Reported |
| Infrastructure Point of Contact Phone |
Not Reported |
| Infrastructure Point of Contact Address |
Not Reported |
| Infrastructure Point of Contact City |
Not Reported |
| Infrastructure Point of Contact State |
Not Reported |
| Infrastructure Point of Contact Zip |
Not Reported |
Product or Service Information
(Grants)
| Product or Service Information |
| Primary Activity Code |
622110 |
| Activity Description |
General Medical and Surgical Hospitals |
| Sub-Awards Information |
| Sub-awards to Organizations |
0 |
| Sub-award Amounts to Organizations |
$0 |
| Sub-Awards to Individuals |
0 |
| Sub-Award Amounts to Individuals |
$0 |
| Number of Sub-awards less than $25,000/award |
0 |
| Amount of Sub-awards less than $25,000/award |
$0 |
| Number of payments to vendors greater than $25,000 |
0 |
| Total Amount of payments to vendors greater than $25,000/award |
$0 |
| Number of payments to vendors less than $25,000/award |
0 |
| Total Amount of payments to vendors less than $25,000/award |
$0 |
| Location Information |
| Latitude, Longitude |
42º 21' 44",
-71º 4' 11" |
| Congressional District |
09 |
| Address 1 |
55 Fruit Street |
| Address 2 |
|
| City |
Boston |
| County |
Suffolk |
| State |
MA |
| Zip |
02114-0000 |
|
 |