PUBLICATIONS

56. K. M. Mayer, F. Hao, S. Lee, P. Nordlander, J. H. Hafner, "A Single Molecule Immunoassay by Localized Surface Plasmon Resonance," Nanotechnology 21, 255503 (2010).

Noble metal nanoparticles exhibit sharp spectral extinction peaks at visible and near-infrared frequencies due to the resonant excitation of their free electrons, termed localized surface plasmon resonance (LSPR). Since the resonant frequency is dependent on the refractive index of the nanoparticle surroundings, LSPR can be the basis for sensing molecular interactions near the nanoparticle surface. However, previous studies have not yet determined whether the LSPR mechanism can reach the ultimate sensing limit: the detection of individual molecules. Here we demonstrate single molecule LSPR detection by monitoring antibody–antigen unbinding events through the scattering spectra of individual gold bipyramids. Both experiments and finite element simulations indicate that the unbinding of single antigen molecules results in small, discrete < 0.5 nm blue-shifts of the plasmon resonance. The unbinding rate is consistent with antibody–antigen binding kinetics determined from previous ensemble experiments. According to these results, the effective refractive index of a single protein is approximately 1.54. LSPR sensing could therefore be a powerful addition to the current toolbox of single molecule detection methods since it probes interactions on long timescales and under relatively natural conditions.

Physorg.com --- Nanowerk.com --- Sciencedaily.com

55. L. J. E. Anderson, K. M. Mayer, R. D. Fraleigh, Y. Yang, S. Lee, J. H. Hafner, "Quantitative measurements of individual gold nanoparticle scattering cross sections," J. Phys. Chem. C. 114, 11127-11132 (2010).

54. L. J. E. Anderson, E. Hansen, E. Y. Lukianova-Hleb, J. H. Hafner, D. O. Lapotko, "Optically Guided Controlled Release from Liposomes with Tunable Plamonic Nanobubbles," Journal of Controlled Release 144, 151 (2010).

A new method of optically guided controlled release was experimentally evaluated with liposomes containing a molecular load and gold nanoparticles (NPs). NPs were exposed to short laser pulses to induce transient vapor bubbles around the NPs, plasmonic nanobubbles, in order to disrupt the liposome and eject its molecular contents. The release efficacy was tuned by varying the lifetime and size of the nanobubble with the fluence of the laser pulse. Optical scattering by nanobubbles correlated to the molecular release and was used to guide the release. The release of two fluorescent proteins from individual liposomes has been directly monitored by fluorescence microscopy, while the generation of the plasmonic nanobubbles was imaged and measured with optical scattering techniques. Plasmonic nanobubble-induced release was found to be a mechanical, nonthermal process that requires a single laser pulse and ejects the liposome contents within a millisecond timescale without damage to the molecular cargo and that can be controlled through the fluence of laser pulse.

53. E. Y. Lukianova-Hleb, J. H. Hafner, D. O. Lapotko, "Generation and detection of plasmonic nanobubbles in zebrafish," Nanotechnology 21, 225102 (2010).

52. E. Y. Lukianova-Hleb, Y. Hu, L. Latterini, L. Tarpani, S. Lee, R. A. Drezek, J. H. Hafner, D. O. Lapotko, "Plasmonic Nanobubbles as Transient Vapor Nanobubbles Generated around Plasmonic Nanoparticles," ACS Nano 4, 2109-2123 (2010).

51. E. Y. Lukianova-Hleb, E. Y. Hanna, J. H. Hafner, D. O. Lapotko, "Tunable plasmonic nanobubbles for cell theranostics," Nanotechnology 21, 085102 (2010).

Combining diagnostic and therapeutic processes into one (theranostics) and improving their selectivity to the cellular level may offer significant benefits in various research and disease systems and currently is not supported with efficient methods and agents. We have developed a novel method based on the gold nanoparticle-generated transient photothermal vapor nanobubbles, that we refer to as plasmonic nanobubbles (PNB). After delivery and clusterization of the gold nanoparticles (NP) to the target cells the intracellular PNBs were optically generated and controlled through the laser fluence. The PNB action was tuned in individual living cells from non-invasive high-sensitive imaging at lower fluence to disruption of the cellular membrane at higher fluence. We have achieved non-invasive 50-fold amplification of the optical scattering amplitude with the PNBs (relative to that of NPs), selective mechanical and fast damage to specific cells with bigger PNBs, and optical guidance of the damage through the damage-specific signals of the bubbles. Thus the PNBs acted as tunable theranostic agents at the cellular level and in one process that have supported diagnosis, therapy and guidance of the therapy.

UPI --- Sciencedaily --- Physorg

50. B. C. Rostro-Kohanloo, L. R. Bickford, C. M. Payne, E. S. Day, L. J. E. Anderson, M. Zhong, S. Lee, K. M. Mayer, T. Zal, L. Adam, C. P. N. Dinney, R. A. Drezek, J. L. West, J. H. Hafner, "Stabilization and Targeting of Surfactant-Synthesized Gold Nanorods", Nanotechnology 20, 434005 (2009).

The strong cetyltrimethylammonium bromide (CTAB) surfactant responsible for the synthesis and stability of gold nanorod solutions complicates their biomedical applications. The critical parameter to maintain nanorod stability is the ratio of CTAB to nanorod concentration. The ratio is approximately 740,000 as determined by chloroform extraction of the CTAB from a nanorod solution. A comparison of nanorod stabilization by thiol-terminal poly(ethylene glycol) (PEG) and by anionic polymers reveals that PEGylation results in higher yields and less aggregation upon removal of CTAB. A heterobifunctional PEG yields nanorods with exposed carboxyl groups for covalent conjugation to antibodies with the zero length carbodiimide linker EDC. This conjugation strategy leads to approximately 2 functional antibodies per nanorod according to fluorimetry and ELISA assays. The nanorods specifically targeted cells in vitro, and were visible with both two photon and confocal reflectance microscopies. This covalent strategy should be generally applicable to other biomedical applications of gold nanorods as well as other gold nanoparticles synthesized with CTAB.

49. S. Lee, K. M. Mayer, J. H. Hafner,"Improved Localized Surface Plasmon Resonance Immunoassay with Gold Bipyramid Substrates", Analytical Chemistry 81, 4450-4455 (2009).

Gold nanoparticles bound to substrates exhibit localized surface plasmon resonance (LSPR) in their optical extinction spectra at visible and near-infrared wavelengths. The LSPR wavelength is sensitive to the surrounding refractive index, enabling a simple, label-free immunoassay when capture antibodies are bound to the nanoparticles. Gold bipyramids are nanoparticles with a penta-twinned crystal structure, which have a sharp LSPR due to their high monodispersity. Bipyramid substrates were found to have a refractive index sensitivity ranging from 288 to 381 nm/RIU (-0.62 to -0.68 eV/RIU), increasing with the nanoparticle size and aspect ratio. In an immunoassay, the bipyramid substrates yielded higher sensitivity than nanorods and nanospheres. An immunoassay sensitivity constant which depends on both the optical properties of the nanoparticle and conjugation chemistry was found to be KLSPR = 0.01 nm-m^2 for gold bipyramids.

48. E. Y. Hleb, Y. Hu, R. A. Drezek, J. H. Hafner, D. O. Lapotko, "Photothermal bubbles as optical scattering probes for imaging living cells", Nanomedicine 3, 797-812 (2008).

47. Y. Yang, K. M. Mayer, N. S. Wickremasinghe, J. H. Hafner, "Probing the Lipid Membrane Dipole Potential by Atomic Force Microscopy", Biophysical Journal 95, 5193-5199 (2008).

The electrostatic properties of biological membranes can be described by three parameters: the transmembrane potential, the membrane surface potential, and the membrane dipole potential. The first two are well characterized in terms of their magnitudes and biological effects. The dipole potential, however, is not well characterized. Various methods to measure the membrane dipole potential indirectly yield different values, and there is not even agreement on the source of the membrane dipole moment. This ambiguity impedes investigations into the biological effects of the membrane dipole moment, which should be substantial considering the large interfacial fields with which it is associated. Electrostatic analysis of phosphatidylcholine lipid membranes with the atomic force microscope reveals a repulsive force between the negatively charged probe tips and the zwitterionic lipids. This unexpected interaction has been analyzed quantitatively to reveal that the repulsion is due to a weak external field created by the internal membrane dipole potential. The analysis yields a dipole moment of 1.5 Debye per lipid with a dipole potential of +275 mV for supported phosphatidylcholine membranes. This new ability to quantitatively measure the membrane dipole moment in a noninvasive manner with nanometer scale spatial resolution will be useful in identifying the biological effects of the dipole potential.

46. E. Y. Hleb, J. H. Hafner, J. N. Myers, E. Y. Hanna, B. C. Rostro, S. A. Zhdanok, D. O. Lapotko, "LANTCET: elimination of solid tumor cells with photothermal bubbles generated around clusters of gold nanoparticles", Nanomedicine 3, 647-667 (2008).

45. C. L. Nehl, J. H. Hafner, "Shape-dependent Plasmon Resonances of Gold Nanoparticles", Journal of Materials Chemistry 8, 2415-2419 (2008).

Localized surface plasmon resonances in noble metal nanoparticles cause enhanced optical absorption and scattering that is tunable through the visible and near-infrared. Furthermore, these resonances create large local electric field enhancements at the nanoparticle surfaces, essentially focussing light at the nanometer scale. These properties suggest a range of applications, including biomedical imaging, therapeutics, and molecular sensing. Here we review some recent advances regarding shape-dependent optical properties of two specific nanoparticle geometries: gold nanorods and branched gold nanoparticles.

44. K. M. Mayer, S. Lee, H. Liao, B. C. Rostro, A. Fuentes, P. T. Scully, C. L. Nehl, J. H. Hafner, "A Label-Free Immunoassay Based Upon Localized Surface Plasmon Resonance of Gold Nanorods", ACS Nano 2, 687-692 (2008).

43. J. N. Lassiter, J. Aizpurua, L. I. Hernandez, D. W. Brandl, I. Romero, S. Lal, J. H. Hafner, P. Nordlander, N. J. Halas, "Close Encounters between Two Nanoshells", Nano Letters 8, 1212-1218 (2008).

42. F. Hao, C. L. Nehl, J. H. Hafner, P. Nordlander, "Plasmon Resonances of a gold Nanostar, Nano Letters 7, 729-732 (2007).

41. Y. Yang, K. Mayer, J. H. Hafner, "Quantitative membrane electrostatics with the atomic force microscope", Biophysical Journal 92, 1966-1974 (2007).

40. H. Liao, C. L. Nehl, J. H. Hafner, "Biomedical Applications of Plasmon Resonant Metal Nanoparticles", Nanomedicine 1, 201-208 (2006).

39. A. Gulati, H. Liao, J. H. Hafner, "Monitoring Gold Nanorod Synthesis by Localized Surface Plasmon Resonance", Journal of Physical Chemistry B, 110, 22323-22327 (2006).

38. H. Wang, Y. Wu, B. Lassiter, C. L. Nehl, J. H. Hafner, P. Nordlander, N. J. Halas, "Symmetry breaking in individual plasmonic nanoparticles", Proceedings of the National Academy of Science (USA) 103, 10856-10860 (2006).

37. C. L. Nehl, H. Liao, J. H. Hafner, "Plasmon Resonant Molecular Sensing with Single Gold Nanostars", Proceedings of the SPIE 6323 (2006).

36.  C. L. Nehl, H. Liao, J. H. Hafner, "Synthesis and Optical Properties of Star-shaped Gold Nanoparticles", Nano Letters 6, 683-688 (2006).

35. A. Conjusteau, S. A. Ermilov, D. Lapotko, H. Liao, J. H. Hafner, M. Eghtedari, M. Motamedi, N. Kotov, A. A. Oraevsky, "Metallic nanoparticles as optoacoustic contrast agents for medical sensing", Proc. SPIE 6086 (2006).

34. J. H. Hafner, "Plasmonics - Metal Nanoparticles Shaped for Effect", Laser Focus World 4 (2006).

33.  N. Wickremasinghe, J. H. Hafner, "Protein Crystal as Scanned Probes", Nano Letters 5, 2418-2421 (2005).

32.  H. Liao, J. H. Hafner, "Gold Nanorod Bioconjugates", Chemistry of Materials 17, 4636-4641 (2005).

31.  C. L. Nehl, N. K. Grady, G. P. Goodrich, F. Tam, N. J. Halas, J. H. Hafner, "Scattering Spectra of Single Gold Nanoshells", Nano Letters 4, 2355-2359 (2004).

30. H. Liao, J. H. Hafner, "Monitoring Gold Nanorod Growth on Surfaces.", Journal of Physical Chemistry B 108, 19276-19280 (2004).

29. H. Liao, J. H. Hafner, "Low-Temperature Single-Wall Carbon Nanotube Synthesis by Thermal Chemical Vapor Deposition." Journal of Physical Chemistry B 108, 6941-6943 (2004).

28. A. S. Johnson, C. L. Nehl, M. G. Mason, J. H. Hafner, "Fluid electric force microscopy for charge density mapping in biological systems", Langmuir 19, 10007-10010 (2003).

27. D. Bozovic, M. Bockrath, J. H. Hafner, C. M. Lieber, H. Park, M. Tinkham, “Plastic deformations in mechanically strained single-wall carbon nanotubes” Physical Review B 67, 033407 (2003).

26. A. Jorio, F. M. Matinaga, A. Righi, M. S. S. Dantas, M. A. Pimenta, A. G. Souza, J. Mendes, J. H. Hafner, C. M. Lieber, R. Saito, G. Dresselhaus, M. S. Dresselhaus, “Resonance Raman scattering: Nondestructive and noninvasive technique for structural and electronic characterization of isolated single-wall carbon nanotubes” Brazilian Journal of Physics 32, 921-924 (2002).

25. A. Jorio, A.G. Souza, G. Dresselhaus, M.S. Dresselhaus, A.K. Swan, M.S. Unlu, B.B. Goldberg, M.A. Pimenta, J.H. Hafner, C.M. Lieber, R. Saito, “G-band resonant Raman study of 62 isolated single-wall carbon nanotubes” Physical Review B 65, 155412 (2002).

24. A. Jorio, A.G Souza, V.W. Brar, A.K. Swan, M.S. Unlu, B.B. Goldberg, A. Righi, J.H. Hafner, C.M. Lieber, R. Saito, G. Dresselhaus, M.S. Dresselhaus, “Polarized resonant Raman study of single-wall carbon nanotubes:  Symmetry selection rules, dipolar and multipolar antenna effects” Physical Review B 65, 121402 (2002).

23. A.G. Souza, A. Jorio, G.G. Samsonidze, G. Dresselhaus, M.S. Dresselhaus, A.K. Swan, M.S. Unlu, B.B. Goldberg, R. Saito, J.H. Hafner, C.M. Lieber, M.A. Pimenta, “Probing the electronic trigonal warping effect in individual single-wall carbon nanotubes using phonon spectra” Chemical Physics Letters 354, 62-68 (2002).

22. A.G. Souza, A. Jorio, A.K. Swan, M.S. Unlu, B.B. Goldberg, R. Saito, J.H. Hafner, C.M. Lieber, M.A. Pimenta, G. Dresselhaus, M.S. Dresselhaus, “Anomalous two-peak G’-band Raman effect in one isolated single-wall carbon nanotube” Physical Review B 65, 085417 (2002).

21. A.G. Souza, A. Jorio, G. Dresselhaus, M.S. Dresselhaus, R. Saito, A.K. Swan, M.S. Unlu, B.B. Goldberg, J.H. Hafner, C.M. Lieber, M.A. Pimenta, “Effect of quantized electronic states on the dispersive Raman features in individual single-wall carbon nanotubes” Physical Review B 65, 035404 (2002).

20. G. R. Schnitzler, C.L. Cheung, J.H. Hafner, A.J. Saurin, R.E. Kingston, C.M. Lieber, "Direct imaging of hSWI/SNF remodeled mono- and polynucleosomes by atomic force microscopy employing carbon nanotube tips", Molecular and Cellular Biology 21, 8504-8511 (2001).

19. M. A. Pimenta, A. Jorio, S. D. M. Brown, A. G. Souza, G. Dresselhaus, J. H. Hafner, C. M. Lieber, R. Saito, M. S. Dresselhaus, "Diameter dependence of the Raman D-band in isolated single-wall carbon nanotubes," Physical Review B 64, 041401 (2001).

18. R. Saito, A. Jorio, J. H. Hafner, C. M. Lieber, M. Hunter, T. McClure, G. Dresselhaus, M. S. Dresselhaus, "Chirality Dependent G-band Raman Intensity of Carbon Nanotubes," Physical Review B 64, 085312 (2001).

17. W. Liang, M. Bockrath, D. Bozovic, J. H. Hafner, M. Tinkham, H. Park, "Fabry-Perot Interference in a Nanotube Electron Waveguide," Nature 411, 665-669 (2001).

16. A.G. Souza Filho, A. Jorio, J.H. Hafner, C.M. Lieber, R. Saito, M.A. Pimenta, G. Dresselhaus, M.S. Dresselhaus, "Electronic transition energy Eii for an isolated (n,m) single-wall carbon nanotube obtained by anti-Stokes/Stokes resonant Raman intensity ratio", Physical Review B 63, 241404 (2001).

15. A. Jorio, A.G. Souza Filho, G. Dresselhaus, M.S. Dresselhaus, R. Saito, J.H. Hafner, C.M. Lieber, F.M. Matinage, M.S.S. Dantas, M.A. Pimenta "Joint density of electronic states for one isolated single-walled carbon nanotube studied by resonant Raman scattering", Physical Review B 63, 245416 (2001).

14. D. Bozovic, M. Bockrath, J. H. Hafner, C. M. Lieber, H. Park, M. Tinkham, "Electronic Properties of Mechanically Induced Kinks in Single-Walled Carbon Nanotubes," Applied Physics Letters 78, 3693- (2001).

13. A. Jorio, R. Saito, J. H. Hafner, C. M. Lieber, G. Dresselhaus, M. S. Dresselhaus, "Structural (n,m) determination of isolated single walled carbon nanotubes by resonant Raman scattering," Physical Review Letters 86, 1118-1121 (2001).

12. J. H. Hafner, C.L. Cheung, T. H. Oosterkamp, C. M. Lieber, "High-yield fabrication of individual single-walled nanotube probe tips for atomic force microscopy," Journal of Physical Chemistry B 105, 743-746 (2001).

11. M. Bockrath, W. Liang, D. Bozovic, J. H. Hafner, C. M. Lieber, M. Tinkham, H. Park, "Resonant Electron Scattering by Defects in Single-Walled Carbon Nanotubes," Science 291, 283-285 (2001).

10. C. L. Cheung, J. H. Hafner, T. W. Odom, K. Kim, C. M. Lieber, "Growth and fabrication with single-walled carbon nanotube probe microscopy tips," Applied Physics Letters 76, 3136 (2000).

9. C. L. Cheung, J. H. Hafner, C. M. Lieber, "Carbon nanotube atomic force microscopy tips: Direct growth by chemical vapor deposition and application to high-resolution imaging," Proceedings of the National Academy of Sciences of the United States of America 97, 3809 (2000).

8. J. H. Hafner, C. L. Cheung, and C. M. Lieber, "Direct Growth of Single-Walled Carbon Nanotube Scanning Probe Microscopy Tips," Journal of the American Chemical Society 121, 9750 (1999).

7. J. H. Hafner, C. L. Cheung, and C. M. Lieber, "Growth of Nanotubes as Probe Microscopy Tips," Nature 398, 761 (1999).

6. J. H. Hafner, M. J. Bronikowski, B. R. Azamian, P. Nikolaev, A. G. Rinzler, D. T. Colbert, K. A. Smith, and R. E. Smalley, "Catalytic Growth of Single Wall Carbon Nanotubes from Metal Particles," Chemical Physics Letters 296, 195 (1998).

5. J. Liu, A. G. Rinzler, H. Dai, J. H. Hafner, R. K. Bradley, A. Lu, K. Shelimov, C.B. Huffman, F. Rodriguez-Macias, P. Boul, T. Iverson, D. T. Colbert, and R. E. Smalley, "Fullerene Pipes," Science 280, 1253 (1998).

4. J. Liu, H. Dai, J. H. Hafner, D. T. Colbert, S. J. Tans, C. Dekker, and R. E. Smalley, "Fullerene Crop Circles," Nature 385, 780 (1997).

3. H. Dai, J. H. Hafner, A. G. Rinzler, D. T. Colbert, and R. E. Smalley, "Nanotubes as Nanoprobes in Scanning Probe Microscopy," Nature 384, 147 (1996).

2. A. G .Rinzler, J. H. Hafner, P. Nikolaev, L. Lou, S. G. Kim, D. Tomanek, P. Nordlander, D. T. Colbert, and R. E. Smalley, "Unraveling Nanotubes: Field Emission from an Atomic Wire," Science 269, 1550 (1995).

1. D. T. Colbert, J. Zhang, S. M. McClure, P. Nikolaev, Z. Chen, J. H. Hafner, D. W. Owens, P. G. Kotula, C. B. Carter, J. H. Weaver, A. G. Rinzler, and R. E. Smalley, "Growth and Sintering of Fullerene Nanotubes," Science 266, 1218 (1994).