Magnetic Nanosensors for Probing Molecular Interactions

  • J. Manuel Perez
  • Charalambos Kaittanis
Part of the Fundamental Biomedical Technologies book series (FBMT, volume 102)


Magnetic nanosensors exhibiting high specificity and biocompatibility have been synthesized for the in vitro and in vivo detection of molecular interactions. Upon target-induced nanoassembly formation, a sensitive and dosedependent decrease in the spin-spin relaxation time (T2) of adjacent water molecules was observed. Various molecular targets ranging from DNAoligonucleotides, proteins, small molecules, and even whole viruses have been detected using this technology, with sensitivity in the low femtomole range (0.5–30 fmol). Furthermore, the engymatic activity of restriction endonucleases and proteases, among others, has also been detected using an alternate method, based on the enzyme-induced dispersion of nanoparticles from a pre-formed nanoassembly. Furthermore, this technique was used to monitor disease-associated enzymatic activity, such as up-regulated activity of telomerase, myeloperoxidase and caspase. The observed changes in T2 can be easily detected in water suspension of the magnetic nanosensors by existing magnetic resonance (NMR/MRI) techniques with minimal sample preparation and permitting high-throughput screening. Homogenous and high-throughput assays to selectively detect a variety of molecular targets in solution can be designed using this magnetic nanosensor technology. Finally, the presence of a target in whole blood or turbid media can be performed as the magnetic relaxation signal is independent of the optical properties of the solution.


Magnetic Nanoparticles Magnetic Relaxation Superparamagnetic Iron Oxide Gadolinium Oxide Iron Oxide Core 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Avilion, A.A., Piatyszek, M.A., Gupta, J., Shay, J.W., Bacchetti, S., Greider, C.W., 1996. “Human telomerase RNA and telomerase activity in immortal cell lines and tumor tissues”. Cancer Res 56, 645–650.PubMedGoogle Scholar
  2. Baselt, D.R., Lee, G.U., Natesan, M., Metzger, S.W., Sheehan, P.E., Colton, R.J., 1998. “A biosensor based on magnetoresistance technology”. Biosens Bioelectron 13, 731–739.PubMedCrossRefGoogle Scholar
  3. Brennan, M.L., Penn, M.S., Van Lente, F., Nambi, V., Shishehbor, M.H., Aviles, R.J., Goormastic, M., Pepoy, M.L., McErlean, E.S., Topol, E.J., Nissen, S.E., Hazen, S.L., 2003. “Prognostic value of myeloperoxidase in patients with chest pain”. N Engl J Med 349, 1595–1604.PubMedCrossRefGoogle Scholar
  4. Brooks, R. A., 2002. “T(2)-shortening by strongly magnetized spheres: a chemical exchange model”. Magn Reson Med 47, 388–391.PubMedCrossRefGoogle Scholar
  5. Bulte, J.W., Brooks, R.A., Moskowitz, B.M., Bryant, L.H. Jr., Frank, J.A., 1998. “T1 and T2 relaxometry of monocrystalline iron oxide nanoparticles (MION-46L): theory and experiment”. Acad Radiol 5 Suppl 1, S137–140.PubMedCrossRefGoogle Scholar
  6. Bulte, J.W., Kraitchman, D.L., 2004a. “Iron oxide MR contrast agents for molecular and cellular imaging”. NMR Biomed 17, 484–499.CrossRefGoogle Scholar
  7. Bulte, J.W., Kraitchman, D.L., 2004b. “Monitoring cell therapy using iron oxide MR contrast agents”. Curr Pharm Biotechnol 5, 567–584.CrossRefGoogle Scholar
  8. Chemla, Y.R., Grossman, H.L., Poon, Y., McDermott, R., Stevens, R., Alper, M.D., Clarke, J., 2000. “Ultrasensitive magnetic biosensor for homogeneous immunoassay”. Proc Natl Acad SciUSA97, 14268–14272.CrossRefGoogle Scholar
  9. Edelstein, R.L., Tamanaha, C.R., Sheehan, P.E., Miller, M.M., Baselt, D.R., Whitman, L.J., Colton, R.J., 2000. “The BARC biosensor applied to the detection of biological warfare agents”. Biosens Bioelectron 14, 805–813.PubMedCrossRefGoogle Scholar
  10. Frank, J.A., Miller, B.R., Arbab, A.S., Zywicke, H.A., Jordan, E.K., Lewis, B.K., Bryant, L.H. Jr., Bulte, J.W., 2003. “Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents”. Radiology 228, 480–487.PubMedCrossRefGoogle Scholar
  11. Gillis, P., Moiny, F., Brooks, R.A., 2002. “On T(2)-shortening by strongly magnetized spheres: a partial refocusing model”. Magn Reson Med 47, 257–263.PubMedCrossRefGoogle Scholar
  12. Grimm, J., Perez, J.M., Josephson, L., Weissleder, R., 2004. ” Novel nanosensors for rapid analysis of telomerase activity”. Cancer Res 64, 639–643.PubMedCrossRefGoogle Scholar
  13. Grossman, H.L., Myers, W.R., Vreeland, V.J., Bruehl, R., Alper, M.D., Bertozzi, C.R., Clarke, J., 2004. “Detection of bacteria in suspension by using a superconducting quantum interference device”. Proc Natl Acad SciUSA 101, 129–134.CrossRefGoogle Scholar
  14. Harisinghani, M.G., Barentsz, J., Hahn, P.F., Deserno, W.M., Tabatabaei, S., van de Kaa, C.H., de la Rosette, J., Weissleder, R., 2003. “Noninvasive detection of clinically occult lymph-node metastases in prostate cancer”. N Engl J Med 348, 2491–2499.PubMedCrossRefGoogle Scholar
  15. Harisinghani, M.G., Weissleder, R., 2004. “Sensitive, noninvasive detection of lymph node metastases”. PLoS Med 1, e66, 202–209.Google Scholar
  16. Josephson, L., Perez, J.M., Weissleder, R., 2001. “Magnetic nanosensors for the detection of oligonucleotide sequences”. Angewandte Chemie-International Edition 40, 3204–3206.CrossRefGoogle Scholar
  17. Josephson, L., Tung, C.H., Moore, A., Weissleder, R., 1999. “High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates”. Bioconjug Chem 10, 186–191.PubMedCrossRefGoogle Scholar
  18. Kelly, K., Alencar, H., Funovics, M., Mahmood, U., Weissleder, R., 2004. “Detection of invasive colon cancer using a novel, targeted, library-derived fluorescent peptide”. Cancer Res 64, 6247–6251.PubMedCrossRefGoogle Scholar
  19. Kelly, K.A., Allport, J.R., Tsourkas, A., Shinde-Patil, V.R., Josephson, L., Weissleder, R., 2005. “Detection of vascular adhesion molecule-1 expression using a novel multimodal nanoparticle”. Circ Res 96, 327–336.PubMedCrossRefGoogle Scholar
  20. Kriz, K., Gehrke, J., Kriz, D., 1998. “Advancements toward magneto immunoassays”. Biosens Bioelectron 13, 817–823.PubMedCrossRefGoogle Scholar
  21. McDonald, M.A., Watkin, K.L., 2006. “Investigations into the physicochemical properties of dextran small particulate gadolinium oxide nanoparticles”. Acad Radiol 13, 421–427.PubMedCrossRefGoogle Scholar
  22. Modo, M., Hoehn, M., Bulte, J.W., 2005. “Cellular MR imaging”. Mol Imaging 4, 143–164.PubMedGoogle Scholar
  23. Perez, J.M., Josephson, L., O’Loughlin, T., Hogemann, D., Weissleder, R., 2002a. “Magnetic relaxation switches capable of sensing molecular interactions”. Nat Biotechnol 20, 816–820.Google Scholar
  24. Perez, J.M., O’Loughin, T., Simeone, F.J., Weissleder, R., Josephson, L., 2002b. “DNAbased magnetic nanoparticle assembly acts as a magnetic relaxation nanoswitch allowing screening of DNA-cleaving agents”. J Am Chem Soc 124, 2856–2857.CrossRefGoogle Scholar
  25. Perez, J.M., Simeone, F.J., Saeki, Y., Josephson, L., 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.PubMedCrossRefGoogle Scholar
  26. Perez, J.M., Simeone, F.J., Tsourkas, A., Josephson, L., Weissleder, R., 2004. “Peroxidase substrate nanosensors for MR imaging”. Nano Letters 4, 119–122.CrossRefGoogle Scholar
  27. Shay, J.W., Bacchetti, S., 1997. “A survey of telomerase activity in human cancer”. Eur J Cancer 33, 787–791.PubMedCrossRefGoogle Scholar
  28. Shen, T., Weissleder, R., Papisov, M., Bogdanov, A. Jr., Brady, T.J., 1993. “Monocrystalline iron oxide nanocompounds (MION): physicochemical properties”. Magn Reson Med 29, 599–604.PubMedCrossRefGoogle Scholar
  29. Song, Q., Zhang, Z.J., 2004. “Shape control and associated magnetic properties of spinel cobalt ferrite nanocrystals”. J Am Chem Soc 126, 6164–6168.PubMedCrossRefGoogle Scholar
  30. Song, Q., Zhang, Z.J., 2006. “Correlation between spin-orbital coupling and the super-paramagnetic properties in magnetite and cobalt ferrite spinel nanocrystals”. J Phys Chem B Condens Matter Mater Surf Interfaces Biophys 110, 11205–11209.PubMedGoogle Scholar
  31. Thorek, D.L., Chen, A.K., Czupryna, J., Tsourkas, A., 2006. “Superparamagnetic iron oxide nanoparticle probes for molecular imaging”. Ann Biomed Eng 34, 23–38.PubMedCrossRefGoogle Scholar
  32. Tsourkas, A., Hofstetter, O., Hofstetter, H., Weissleder, R., Josephson, L., 2004. “Magnetic relaxation switch immunosensors detect enantiomeric impurities”. Angewandte Chemie-International Edition 43, 2395–2399.CrossRefGoogle Scholar
  33. Weissleder, R., Kelly, K., Sun, E.Y., Shtatland, T., Josephson, L., 2005. “Cell-specific targeting of nanoparticles by multivalent attachment of small molecules”. Nat Biotechnol 23, 1418–1423.PubMedCrossRefGoogle Scholar
  34. Zhang, R., Brennan, M.L., Fu, X., Aviles, R.J., Pearce, G.L., Penn, M.S., Topol, E.J., Sprecher, D.L., Hazen, S.L., 2001. “Association between myeloperoxidase levels and risk of coronary artery disease”. Jama 286, 2136–2142.PubMedCrossRefGoogle Scholar
  35. Zhao, M., Josephson, L., Tang, Y., Weissleder, R., 2003. “Magnetic sensors for protease assays”. Angewandte Chemie-International Edition 42, 1375–1378.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • J. Manuel Perez
  • Charalambos Kaittanis

There are no affiliations available

Personalised recommendations