Biology Department Biology Department  


James F. Hainfeld

Brookhaven National Laboratory
From: 1976-2009

Phone: (631) 344-3367
Fax: (631) 344-3407
Currently at Nanoprobes


Research Interests

James Hainfeld develops organometallic cluster compounds to be used as high resolution molecular labels. These heavy metal clusters are covalently attached to peptides, antibodies, other proteins, nucleic acids, carbohydrates or lipids to map sites of macromolecules or complexes for visualization in the Scanning Transmission Electron Microscope (STEM). Such clusters have been useful in studying the proteasome, pyruvate dehydrogenase enzyme complex, actin filaments, viruses, blood clotting components, nuclear proteins, and other structures. Use of clusters in anomalous X-ray scattering or for isomorphous replacements is being investigated also. Gold, platinum, palladium, silver, iridium, and other metal clusters have been synthesized. Recently, gold clusters having Nickel-NTA for binding 6x-His tagged proteins, gold-liposomes, gold-cluster-ATP, and giant platinum clusters have been studied.

He also is co-principal investigator (with Joseph Wall) of the Scanning Transmission Electron Microscope STEM Facility which currently hosts over 50 user projects per year from around the world. These projects focus on use of the STEM for mass measurements of single molecules, or of gold cluster labeling for identifying molecular sites.

The article 'New Ways to Tag, Track Molecules' gives an account of the golden opportunities in metal cluster labeling of molecular complexes. See the Brookhaven Bulletin of April 7, 2000 (Vol 54 No 12), and the BNL Press Release of January 10, 2000.


Selected Publications

  • Briñas R.P., Hu M., Qian L., Lymar E.S. and Hainfeld J.F.
    Gold nanoparticle size controlled by polymeric Au(I) thiolate precursor size.
    J Am Chem Soc., 130(3):975-982 (2008).  PubMed
  • Hu M., Qian L., Brinas R.P., Lymar E.S., Kuznetsova L. and Hainfeld J.F.
    Gold nanoparticle-protein arrays improve resolution for cryo-electron microscopy.
    J. Struct. Biol., 161(1):83-91 (2008).  PubMed
  • Hu M., Qian L., Brinas R.P., Lymar E.S. and Hainfeld J.F.
    Assembly of nanoparticle-protein binding complexes: From monomers to ordered arrays.
    Angewandte Chemie, 46(27):5111-5114 (2007).  PubMed
  • Hu M., Zhang Y.-B., Qian L., Brinas R.P., Kuznetsova L. and Hainfeld J.F.
    Three-dimensional structure of human chromatin accessibility complex hCHRAC by electron microscopy.
    Journal of Structural Biology, 164(3):263-269 (December, 2008).  PubMed
  • Powell R.D., Pettay J.D., Powell W.C., Roche P.C., Grogan T.M., Hainfeld J.F. and Tubbs R.R.
    Metallographic in situ hybridization.
    Hum Pathol., 38(8):1145-1159 (2007).  PubMed
  • Hainfeld J.F., Slatkin D.N., Focella T.M. and Smilowitz H.M.
    Gold nanoparticles: a new X-ray contrast agent.
    Br J Radiol., 79(939):248-253 (2006).  PubMed
  • Dilmanian F.A., Qu Y., Liu S., Cool C.D., Gilbert J., Hainfeld J.F., Kruse C.A., Laterra J.S., Lenihan D., Nawrocky M.M., Pappas G., Sze C.-I., Yuasa T., Zhong N., Zhong Z., and McDonald J.W.
    X-ray microbeams: Tumor therapy and central nervous system research.
    Nuc Inst and Meth in Phys Res Section, A548:30-37 (2005). PubMed
  • Downs-Kelly E., Pettay J., Hicks D., Skacel M., Yoder B., Rybicki L., Myles J., Sreenan J., Roche P., 146. Powell R., Hainfeld J., Grogan T. and Tubbs R.
    Analytical validation and interobserver reproducibility of EnzMet GenePro: a second-generation bright-field metallography assay for concomitant detection of HER2 gene status and protein expression in invasive carcinoma of the breast.
    Am J Surg Pathol., 29(11):1505-1511 (2005).
  • Hainfeld J.F. and Powell R.D.
    Gold cluster labels and related technologies in molecular morphology.
    In: Advances in Pathology, Microscopy & Molecular Morphology Series: Molecular Morphology in Human Tissues: Techniques and Applications, Vol. 2, (G.W. Hacker and R.R. Tubbs, Edts), Chapter 4, pp. 81-100, CRC Press, Boca Raton, FL (2005).
  • Möller R., Powell R.D., Hainfeld J.F. and Fritzsche W.
    Enzymatic control of metal deposition as key step for a low-background electrical detection for DNA chips.
    Nano Lett., 5(7):1475-1482 (2005).  PubMed
  • Reddy V., Lymar E., Hu M. and Hainfeld J.F.
    5 nm gold-Ni-NTA binds His tags.
    Microscopy and Microanalysis, 11(S2):1118-1119 (2005). (Extended Abstract).
  • Tubbs R., Pettay J., Powell R., Hicks D.G., Roche P., Powell W., Grogan T. and Hainfeld J.F.
    High-resolution immunophenotyping of subcellular compartments in tissue microarrays by enzyme metallography.
    Appl Immunohistochem Mol Morphol., 13(4):371-375 (2005).  PubMed
  • Tubbs R.R., Pettay J., Skacel M., Downs-Kelly E., Powell R.D., Hicks D.G. and Hainfeld J.F.
    Gold- and silver-facilitated metallographic in situ hybridization procedures for detection of HER2 gene amplification.
    Advances in Pathology, Microscopy & Molecular Morphology Series: Molecular Morphology in Human Tissues: Techniques and Applications, Vol. 2, (G.W. Hacker and R.R. Tubbs, Edts), Chapter 5: 101-106, CRC Press, Boca Raton, FL (2005).
  • Hainfeld J.F., Slatkin D.N. and Smilowitz H.M.
    The use of gold nanoparticles to enhance radiotherapy in mice.
    Phys Med Biol., 49(18):N309-315 (2004).   PubMed
  • Mosesson M.W., DiOrio J.P., Hernandez I., Hainfeld J.F., Wall J.S. and Greininger G.
    The ultrastructure of fibrinogen-420 and the fibrin-420 clot.
    Biophys Chem., 112(2-3):209-214 (2004).   PubMed
  • Tubbs R., Pettay J., Hicks D., Skacel M., Powell R., Gorgan T. and Hainfeld J.
    Novel bright field molecular morphology methods for detection of HER2 gene amplification.
    J Mol Histol., 35(6):589-594 (2004).   PubMed
  • Dilmanian F.A., Morris G.M., Zhong N., Bacarian T., Hainfeld J.F., Kalef-Ezra J., Brewington L., Tammam J. and Rosen E.M.
    Murine EMT-6 carcinoma: high therapeutic efficacy of microbeam radiation therapy.
    Radiat Res., 159:632-641 (2003).   PubMed
  • Xiao Y., Patolsky F., Katz E., Hainfeld J.F. and Willner I.
    "Plugging into Enzymes": nanowiring of redox enzymes by a gold nanoparticle.
    Science, 299:1877-1881 (2003).   PubMed   Full Text
  • Hainfeld J.F. and Powell R.D.
    Silver and gold-based autometallography of Nanogold.
    in: Gold and Silver Staining: Techniques in Molecular Morphology. (Hacker, G.W. and Gu, J. Eds.), CRC Press, Boca Raton, 29-46 (2002).
  • Hainfeld J.F., Powell R.D. and Furuya F.R.
    Microscopic uses of nanogold.
    in: Gold and Silver Staining: Techniques in Molecular Morphology (Hacker, GW and Gu, J Eds.), CRC Press, Boca Raton, 85-106 (2002).
  • Mosesson M.W., Siebenlist K.R., Hernandez I., Wall J.S. and Hainfeld J.F.
    Fibrinogen asembly and crosslinking on a fibrin fragment E template.
    Thromb Haemost., 87:651-658 (2002).   PubMed
  • Powell R.D. and Hainfeld J.F.
    Combined fluorescent and gold probes for microscopic and morphological investigations.
    in: Gold and Silver Staining: Techniques in Molecular Morphology. (Hacker, G.W. and Gu, J. Eds.), CRC Press, Boca Raton, 107-118 (2002).
  • Tubbs R., Pettay J., Skacel M., Powell R., Stoler M., Roche P. and Hainfeld J.
    Gold-facilitated in situ hybridization : A bright-field autometallographic alternative to fluorescence in situ hybridization for detection of HER-2/neu gene amplification.
    Am J Pathol., 160:1589-1595 (2002).
  • Xiao S., Liu F., Rosen A.E., Hainfeld J.F., Seeman N.C., Musier-Forsyth K., and Kiehl R.A.
    Assembly of nanoparticle arrays by DNA scaffolding.
    J Nanoparticle Research, 4:313-317 (2002).
  • Hainfeld J.F., Furuya F.R., Powell R.D. and Liu W.
    DNA Nanowires.
    in: Proc. 59th Ann. Mtg., Micros. Soc. Amer. (Bailey, G.W., Price, R.L., Voelkl, E., and Musselman, I.H. Eds.), Springer-Verlag, New York, NY, 1034-1035 (2001).
  • Linderoth N.A., Simon M.N., Hainfeld J.F. and Sastry S.
    Binding of antigenic peptide to the endoplasmic reticulum-resident protein gp96/GRP94 heat shock chaperone occurs in higher order complexes. Essential role of some aromatic amino acid residues in the peptide binding site.
    J Biol Chem., 276:11049-11054 (2001).   PubMed   Full Text
  • Traxler K.W., Norcum M.T., Hainfeld J.F. and Carlson G.M.
    Direct Visualization of the Calmodulin Subunit of Phosphorylase Kinase via Electron Microscopy Following Subunit Exchange.
    J Struct Biol., 135:231-238 (2001).   PubMed
  • Hainfeld J.F. and Powell R.D.
    New frontiers in gold labeling. (Review)
    J Histochem Cytochem, 48:471-480 (2000).   PubMed   Full Text
  • Hainfeld J.F. and Robinson J.M.
    New frontiers in gold labeling: symposium overview.
    J Histochem Cytochem., 48:459-460 (2000).   PubMed   Full Text
  • Mayer G., Leone R.D., Hainfeld J.F. and Bendayan M.
    Introduction of a novel HRP substrate-Nanogold probe for signal amplification in immunocytochemistry.
    J Histochem Cytochem, 48:461-470 (2000).   PubMed   Full Text
  • Wall J.S., Simon M.N. and Hainfeld J.F.
    The BNL STEM Facility.
    Microscopy and Microanalysis, 3(2):277-278 (2000).
  • Wall J.S., Simon M.N. and Hainfeld J.F.
    Gold Cluster Crystals
    Microscopy and Microanalysis, 6(2):326-327 (2000).
  • Cheng N., Conway J.F., Watts N.R., Hainfeld J.F., Joshi V., Powell R.D., Stahl S.J., Wingfield P.E. and Steven A.C.
    Tetrairidium, a four-atom cluster, is readily visible as a density label in three-dimensional cryo-EM maps of proteins at 10-25 Å resolution.
    J Struct Biol., 127:169-176 (1999).   PubMed
  • Gutierrez E., Powell R.D., Furuya F.R., Hainfeld J.F., Schaaff T.G., Shaffigullin M.N., Stephens P.W. and Wetten R.L.
    Greengold, a giant cluster compound of unusual electronic structure.
    Eur Phys J., D9:647-651 (1999).
  • Hainfeld J.F.
    Editorial:Metal cluster labeling
    J Struct Biol., 127:93 (1999).   PubMed
  • Hainfeld J.F., Furuya F.R. and Powell R.D.
    J Struct Biol., 127:152-160 (1999).   PubMed
  • Hainfeld J.F., Liu W. and Barcena M.
    J Struct Biol., 127:120-134 (1999).   PubMed
  • Hainfeld J.F., Liu W., Halsey C.M.R., Freimuth P. and Powell R.D.
    Ni-NTA-gold clusters target His-tagged proteins.
    J Struct Biol., 127:185-198 (1999).   PubMed
    Cover: Gold clusters with nickel-NTA attached bind to 6x-histidine tagged proteins. These gold clusters are shown bound to the knob protein of adenovirus containing the 6x-histidine tag. Darkfield STEM micrograph, 128 nm full width, pseudocolored.
  • Gregori L., Hainfeld J.F., Simon M.N. and Goldgaber D.
    Binding of amyloid beta protein to the 20 S proteasome.
    J Biol Chem., 272:58-62 (1997).   PubMed   Full Text
  • Hainfeld J.F. and Powell R.D.
    Nanogold technology: new frontiers in gold labeling.
    Cell Vision, 4:408-432 (1997).
  • Powell R.D., Halsey C.M.R., Spector D.L., Kaurin S.L., McCann J. and Hainfeld J.F.
    A covalent fluorescent-gold immunoprobe: simultaneous detection of a pre-mRNA splicing factor by light and electron microscopy.
    J Histochem Cytochem., 45:947-956 (1997).   PubMed   Full Text
  • Hainfeld J.F.
    Labeling with Nanogold and Undecagold: Techniques and Results.
    Scanning Micros Suppl., 1:309-325 (1996). PubMed
  • Hainfeld J.F. and Furuya F.R.
    A 1.4-nm gold cluster covalently attached to antibodies improves immunolabeling.
    J Histochem Cytochem., 40:177-184 (1992).   PubMed
  • Hainfeld J.F., Sprinzl M., Mandiyan V., Tumminia S.J. and Boublik M.
    Localization of a specific nucleotide in yeast tRNA by scanning transmission electron microscopy using an undecagold cluster.
    J Struct Biol., 107:1-5 (1991). PubMed
    Cover: Scanning transmission electron micrograph of a yeast tRNA(phe) molecule (green) labeled with an undecagold cluster (yellow spot). 2-Thiocytidine was enzymatically introduced into the tRNA at position 75 for linking to a maleimide-eleven gold atom cluster. The image was low-pass-filtered and colored according to intensity.
  • Hainfeld J.F.
    A small gold-conjugated antibody label:
    improved resolution for electron microscopy.

    Science, 236:450-453 (1987). PubMed
    Cover: The smallest gold-conjugated antibody label yet developed is demostrated in this pseudocolored electron micrograph. Anti-ferritin Fab' antibody fragments are covalently linked to 11 gold atom clusters (yellow spots, discerned by high pass filtration) and attached to ferritin, which consists of a protein shell surrounding an iron core (red).


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Last Modified: June 16, 2009
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