Chip NMR biosensor for molecular analysis of cells

Summary

Principal Investigator: R Weissleder
Affiliation: Harvard University
Country: USA
Abstract: 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.
Funding Period: 2004-09-01 - 2011-08-31
more information: NIH RePORT

Top Publications

  1. ncbi Protamine as an efficient membrane-translocating peptide
    Fred Reynolds
    Center for Molecular Imaging Research, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts 02129, USA
    Bioconjug Chem 16:1240-5. 2005
  2. pmc A multifunctional single-attachment-point reagent for controlled protein biotinylation
    Elisabeth Garanger
    Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Boston, Massachusetts 02129, USA
    Bioconjug Chem 20:170-3. 2009
  3. pmc Electrode chemistry yields a nanoparticle-based NMR sensor for calcium
    Sonia Taktak
    Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA
    Langmuir 24:7596-8. 2008
  4. pmc Sensitive NMR sensors detect antibodies to influenza
    Isaac Koh
    Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Boston, MA 02129, USA
    Angew Chem Int Ed Engl 47:4119-21. 2008
  5. pmc Magnetic nanoparticles for MR imaging: agents, techniques and cardiovascular applications
    David E Sosnovik
    Center for Molecular Imaging Research, Massachusetts General Hospital, 149 13th Street, Charlestown, MA, 02129, USA
    Basic Res Cardiol 103:122-30. 2008
  6. pmc Magnetic microparticle aggregation for viscosity determination by MR
    Rui Hong
    Center for Molecular Imaging Research, Harvard Medical School, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    Magn Reson Med 59:515-20. 2008
  7. ncbi Multiparameter magnetic relaxation switch assays
    Sonia Taktak
    Center for Molecular Imaging Research and Department of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA
    Anal Chem 79:8863-9. 2007
  8. ncbi Molecular magnetic resonance imaging in cardiovascular medicine
    David E Sosnovik
    Center for Molecular Imaging Research, Massachusetts General Hospital, 149 13th St, Charlestown, MA 02129, USA
    Circulation 115:2076-86. 2007
  9. ncbi Cell internalization of magnetic nanoparticles using transfection agents
    Karin Montet-Abou
    Center for Molecular Imaging Research Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Mol Imaging 6:1-9. 2007
  10. ncbi Continuous analyte sensing with magnetic nanoswitches
    Eric Yi Sun
    Center for Molecular Imaging Research, Massachusetts General Hospital, Building 149, 13th St, Room 5410, Charlestown, MA 02129, USA
    Small 2:1144-7. 2006

Scientific Experts

  • David Sosnovik
  • Ralph Weissleder
  • Lee Josephson
  • Sonia Taktak
  • Karin Montet-Abou
  • Rui Hong
  • Elisabeth Garanger
  • Moritz Wildgruber
  • Isaac Koh
  • Michael J Cima
  • Eric Yi Sun
  • Xavier Montet
  • Hushan Yuan
  • Fred Reynolds
  • Tae Jong Yoon
  • Mikael J Pittet
  • Aleksey Chudnovskiy
  • Filip K Swirski
  • Hakho Lee
  • Matthias Nahrendorf
  • Peter Libby
  • Kevin Croce
  • Martin Etzrodt
  • Lewis Cantley
  • Ji Luo

Detail Information

Publications13

  1. ncbi Protamine as an efficient membrane-translocating peptide
    Fred Reynolds
    Center for Molecular Imaging Research, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts 02129, USA
    Bioconjug Chem 16:1240-5. 2005
    ..In addition, the fluorescent protamines developed here might be used to further our understanding of this important pharmaceutical...
  2. pmc A multifunctional single-attachment-point reagent for controlled protein biotinylation
    Elisabeth Garanger
    Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Boston, Massachusetts 02129, USA
    Bioconjug Chem 20:170-3. 2009
    ..The MSAP peptide-scaffold approach allows fluorophores, chromophores, or reactive groups to be combined with biotin and provides a broad approach to obtain multifunctional biotin-based reagents...
  3. pmc Electrode chemistry yields a nanoparticle-based NMR sensor for calcium
    Sonia Taktak
    Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA
    Langmuir 24:7596-8. 2008
    ..Our work suggests that the many chemistries of nonbiological origin, such as those employed for ion-selective electrodes, can be adapted to obtain NMR-based sensors for ions...
  4. pmc Sensitive NMR sensors detect antibodies to influenza
    Isaac Koh
    Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Boston, MA 02129, USA
    Angew Chem Int Ed Engl 47:4119-21. 2008
  5. pmc Magnetic nanoparticles for MR imaging: agents, techniques and cardiovascular applications
    David E Sosnovik
    Center for Molecular Imaging Research, Massachusetts General Hospital, 149 13th Street, Charlestown, MA, 02129, USA
    Basic Res Cardiol 103:122-30. 2008
    ..First generation MNP are already in clinical use and second generation agents, with longer blood half lives, are likely to be approved for routine clinical use in the near future...
  6. pmc Magnetic microparticle aggregation for viscosity determination by MR
    Rui Hong
    Center for Molecular Imaging Research, Harvard Medical School, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    Magn Reson Med 59:515-20. 2008
    ....
  7. ncbi Multiparameter magnetic relaxation switch assays
    Sonia Taktak
    Center for Molecular Imaging Research and Department of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA
    Anal Chem 79:8863-9. 2007
    ..The T1/T2 and T2 replication interrogation methods illustrate how MRSw assays can employ multiple parameters, instead of relying only on T2, to obtain information about the reaction of NPs with molecular targets...
  8. ncbi Molecular magnetic resonance imaging in cardiovascular medicine
    David E Sosnovik
    Center for Molecular Imaging Research, Massachusetts General Hospital, 149 13th St, Charlestown, MA 02129, USA
    Circulation 115:2076-86. 2007
  9. ncbi Cell internalization of magnetic nanoparticles using transfection agents
    Karin Montet-Abou
    Center for Molecular Imaging Research Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Mol Imaging 6:1-9. 2007
    ..Conditions for loading cells with Feridex and a TFA need to be carefully selected to minimize nanoparticle precipitation and dextran adsorption to the cell surface...
  10. ncbi Continuous analyte sensing with magnetic nanoswitches
    Eric Yi Sun
    Center for Molecular Imaging Research, Massachusetts General Hospital, Building 149, 13th St, Room 5410, Charlestown, MA 02129, USA
    Small 2:1144-7. 2006
  11. ncbi Wortmannin-C20 conjugates generate wortmannin
    Hushan Yuan
    Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Med Chem 49:740-7. 2006
    ....
  12. ncbi Transfection agent induced nanoparticle cell loading
    Karin Montet-Abou
    Center for Molecular Imaging Research and Harvard Medical School, Charlestown, MA 02129, USA
    Mol Imaging 4:165-71. 2005
    ..However, we found that the conditions used to label cells with Feridex and transfection agents need to be carefully selected to avoid the problems of surface adsorption and nanoparticle precipitation...
  13. pmc Monocyte subset dynamics in human atherosclerosis can be profiled with magnetic nano-sensors
    Moritz Wildgruber
    Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
    PLoS ONE 4:e5663. 2009
    ....