Skip to main content
SpringerLink
Log in

Molecular Detection of Biomarkers and Cells Using Magnetic Nanoparticles and Diagnostic Magnetic Resonance

  • Protocol
  • First Online:
Biomedical Nanotechnology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 726))

Abstract

The rapid and sensitive detection of molecular targets such as proteins, cells, and pathogens in biological specimens is a major focus of ongoing medical research, as it could promote early disease diagnoses and the development of tailored therapeutic strategies. Magnetic nanoparticles (MNP) are attractive candidates for molecular biosensing applications because most biological samples exhibit negligible magnetic susceptibility, and thus the background against which measurements are made is extremely low. Numerous magnetic detection methods exist, but sensing based on magnetic resonance effects has successfully been developed into a general detection platform termed diagnostic magnetic resonance (DMR). DMR technology encompasses numerous assay configurations and sensing principles, and to date magnetic nanoparticle biosensors have been designed to detect a wide range of targets including DNA/mRNA, proteins, enzymes, drugs, pathogens, and tumor cells with exquisite sensitivity. The core principle behind DMR is the use of MNP as proximity sensors that modulate the transverse relaxation time of neighboring water molecules. This signal can be quantified using MR imagers or NMR relaxometers, including miniaturized NMR detector chips that are capable of performing highly sensitive measurements on microliter sample volumes and in a multiplexed format. The speed, sensitivity, and simplicity of the DMR principle, coupled with further advances in NMR biosensor technology should provide a high-throughput, low-cost, and portable platform for large-scale parallel sensing in clinical and point-of-care settings.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Tamanaha, C. R., Mulvaney, S. P., Rife, J. C., and Whitman, L. J. (2008) Magnetic labeling, detection, and system integration. Biosens. Bioelectron. 24, 1–13.

    Article  CAS  Google Scholar 

  2. Lee, H., Sun, E., Ham, D., and Weissleder, R. (2008) Chip-NMR biosensor for detection and molecular analysis of cells. Nat. Med. 14, 869–874.

    Article  Google Scholar 

  3. Lee, H., Yoon, T. J., Figueiredo, J. L., Swirski, F. K., and Weissleder, R. (2009) Rapid detection and profiling of cancer cells in fine-needle aspirates. Proc. Natl Acad. Sci. USA 106, 12459–12464.

    Article  CAS  Google Scholar 

  4. Perez, J. M., Josephson, L., O’Loughlin, T., Hogemann, D., and Weissleder, R. (2002) Magnetic relaxation switches capable of sensing molecular interactions. Nat. Biotechnol. 20, 816–820.

    CAS  Google Scholar 

  5. Josephson, L., Perez, J. M., and Weissleder, R. (2001) Magnetic nanosensors for the detection of oligonucleotide sequences. Angew. Chem. Int. Ed. Engl. 40, 3204–3206.

    Article  CAS  Google Scholar 

  6. Lee, H., Yoon, T. J., and Weissleder, R. (2009) Ultrasensitive detection of bacteria using core-shell nanoparticles and an NMR-filter system. Angew. Chem. Int. Ed. Engl. 48, 5657–5660.

    Article  CAS  Google Scholar 

  7. Josephson, L., Tung, C. H., Moore, A., and Weissleder, R. (1999) High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates. Bioconjug. Chem. 10, 186–191.

    Article  CAS  Google Scholar 

  8. Lu, A. H., Salabas, E. L., and Schuth, F. (2007) Magnetic nanoparticles: synthesis, protection, functionalization, and application. Angew. Chem. Int. Ed. Engl. 46, 1222–1244.

    Article  CAS  Google Scholar 

  9. Harisinghani, M. G., Barentsz, J., Hahn, P. F., Deserno, W. M., Tabatabaei, S., van de Kaa, C. H., et al. (2003) Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N. Engl. J. Med. 348, 2491–2499.

    Article  Google Scholar 

  10. Lee, J. H., Huh, Y. M., Jun, Y. W., Seo, J. W., Jang, J. T., Song, H. T., et al. (2007) Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging. Nat. Med. 13, 95–99.

    Article  CAS  Google Scholar 

  11. Peng, S., Wang, C., Xie, J., and Sun, S. (2006) Synthesis and stabilization of monodisperse Fe nanoparticles. J. Am. Chem. Soc. 128, 10676–10677.

    Article  CAS  Google Scholar 

  12. Koh, I., Hong, R., Weissleder, R., and Josephson, L. (2008) Sensitive NMR sensors detect antibodies to influenza. Angew. Chem. Int. Ed. Engl. 47, 4119–4121.

    Article  CAS  Google Scholar 

  13. Koh, I., Hong, R., Weissleder, R., and Josephson, L. (2009) Nanoparticle-target interactions parallel antibody-protein interactions. Anal. Chem. 81, 3618–3622.

    Article  CAS  Google Scholar 

  14. Sun, E. Y., Josephson, L., Kelly, K. A., and Weissleder, R. (2006) Development of nanoparticle libraries for biosensing. Bioconjug. Chem. 17, 109–113.

    Article  Google Scholar 

  15. Kolb, H. C., Finn, M. G., and Sharpless, K. B. (2001) Click chemistry: diverse chemical function from a few good reactions. Angew. Chem. Int. Ed. Engl. 40, 2004–2021.

    Article  CAS  Google Scholar 

  16. Rostovtsev, V. V., Green, L. G., Fokin, V. V., and Sharpless, K. B. (2002) A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew. Chem. Int. Ed. Engl. 41, 2596–2599.

    Article  CAS  Google Scholar 

  17. Tornoe, C. W., Christensen, C., and Meldal, M. (2002) Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J. Org. Chem. 67, 3057–3064.

    Article  CAS  Google Scholar 

  18. Sun, E. Y., Josephson, L., and Weissleder, R. (2006) “Clickable” nanoparticles for targeted imaging. Mol. Imaging 5, 122–128.

    Google Scholar 

  19. Thorek, D. L., Elias, D. R., and Tsourkas, A. (2009) Comparative analysis of nanoparticle-antibody conjugations: carbodiimide versus click chemistry. Mol. Imaging 8, 221–229.

    CAS  Google Scholar 

  20. Devaraj, N. K., Upadhyay, R., Haun, J. B., Hilderbrand, S. A., and Weissleder, R. (2009) Fast and sensitive pretargeted labeling of cancer cells through a tetrazine/trans-cyclooctene cycloaddition. Angew. Chem. Int. Ed. Engl. 48, 7013–7016.

    Article  CAS  Google Scholar 

  21. Haun, J. B., Devaraj, N. K., Hilderbrand, S. A., Lee, H., and Weissleder, R. (2010) Bioor­thogonal chemistry amplifies nanoparticle binding and enhances the sensitivity of cell detection. Nat. Nanotechnol. 5, 660–665.

    Article  CAS  Google Scholar 

  22. Chan, T. R., Hilgraf, R., Sharpless, K. B., and Fokin, V. V. (2004) Polytriazoles as copper(I)-stabilizing ligands in catalysis. Org. Lett. 6, 2853–2855.

    Article  CAS  Google Scholar 

  23. Reynolds, F., O’Loughlin, T., Weissleder, R., and Josephson, L. (2005) Method of determining nanoparticle core weight. Anal. Chem. 77, 814–817.

    Article  CAS  Google Scholar 

  24. Grimm, J., Perez, J. M., Josephson, L., and Weissleder, R. (2004) Novel nanosensors for rapid analysis of telomerase activity. Cancer Res. 64, 639–643.

    Article  CAS  Google Scholar 

  25. Kim, G. Y., Josephson, L., Langer, R., and Cima, M. J. (2007) Magnetic relaxation switch detection of human chorionic gonadotrophin. Bioconjug. Chem. 18, 2024–2028.

    Article  CAS  Google Scholar 

  26. Perez, J. M., Grimm, J., Josephson, L., and Weissleder, R. (2008) Integrated nanosensors to determine levels and functional activity of human telomerase. Neoplasia 10, 1066–1072.

    CAS  Google Scholar 

  27. Perez, J. M., O’Loughin, T., Simeone, F. J., Weissleder, R., and Josephson, L. (2002) DNA-based magnetic nanoparticle assembly acts as a magnetic relaxation nanoswitch allowing screening of DNA-cleaving agents. J. Am. Chem. Soc. 124, 2856–2857.

    Article  CAS  Google Scholar 

  28. Zhao, M., Josephson, L., Tang, Y., and Weissleder, R. (2003) Magnetic sensors for protease assays. Angew. Chem. Int. Ed. Engl. 42, 1375–1378.

    Article  CAS  Google Scholar 

  29. Perez, J. M., Simeone, F. J., Tsourkas, A., Josephson, L., and Weissleder, R. (2004) Peroxidase substrate nanosensors for MR imaging. Nano Lett. 4, 119–122.

    Article  CAS  Google Scholar 

  30. Tsourkas, A., Hofstetter, O., Hofstetter, H., Weissleder, R., and Josephson, L. (2004) Magnetic relaxation switch immunosensors detect enantiomeric impurities. Angew. Chem. Int. Ed. Engl. 43, 2395–2399.

    Article  CAS  Google Scholar 

  31. Sun, E. Y., Weissleder, R., and Josephson, L. (2006) Continuous analyte sensing with magnetic nanoswitches. Small 2, 1144–1147.

    Article  CAS  Google Scholar 

  32. Atanasijevic, T., Shusteff, M., Fam, P., and Jasanoff, A. (2006) Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin. Proc. Natl Acad. Sci. USA 103, 14707–14712.

    Article  CAS  Google Scholar 

  33. Taktak, S., Weissleder, R., and Josephson, L. (2008) Electrode chemistry yields a nanoparticle-based NMR sensor for calcium. Langmuir 24, 7596–7598.

    Article  CAS  Google Scholar 

  34. Perez, J. M., Simeone, F. J., Saeki, Y., Josephson, L., and Weissleder, R. (2003) Viral-induced self-assembly of magnetic nanoparticles allows the detection of viral particles in biological media. J. Am. Chem. Soc. 125, 10192–10193.

    Article  CAS  Google Scholar 

  35. Kaittanis, C., Naser, S. A., and Perez, J. M. (2007) One-step, nanoparticle-mediated bacterial detection with magnetic relaxation. Nano Lett. 7, 380–383.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Nikolay Sergeyev for technical guidance regarding MNP synthesis and characterization and Dr. Neal K. Devaraj for assistance with click chemistry protocols.

Author information

Authors and Affiliations

  1. Center for Systems Biology, Department of Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Ralph Weissleder

Authors
  1. Jered B. Haun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tae-Jong Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hakho Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ralph Weissleder
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ralph Weissleder .

Editor information

Editors and Affiliations

  1. Center for Nanoscale Materials, Argonne National Laboratory, S. Cass Avenue 9700, Argonne, 60439, Illinois, USA

    Sarah J. Hurst

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Haun, J.B., Yoon, TJ., Lee, H., Weissleder, R. (2011). Molecular Detection of Biomarkers and Cells Using Magnetic Nanoparticles and Diagnostic Magnetic Resonance. In: Hurst, S. (eds) Biomedical Nanotechnology. Methods in Molecular Biology, vol 726. Humana Press. https://doi.org/10.1007/978-1-61779-052-2_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-052-2_3

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-051-5

  • Online ISBN: 978-1-61779-052-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation