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Investigating Biological Processes at the Single Molecule Level Using Luminescent Quantum Dots

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Abstract

In this report we summarize the progress made in the past several years on the use of luminescent QDs to probe biological processes at the single molecule level. We start by providing a quick overview of the basic properties of semiconductor nanocrystals, including synthetic routes, surface-functionalization strategies, along with the main attributes of QDs that are of direct relevance to single molecule studies based on fluorescence detection. We then detail some valuable insights into specific biological processes gained using single QDs. These include progress made in probing biomolecular interactions, tracking of protein receptors both in vitro and in live cells, and single particle resonance energy transfer. We will also discuss the advantages offered and limitations encountered by single QD fluorescence as an investigative tool in biology.

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References

  1. Agrawal, A., Zhang, C.Y. Byassee, T. Tripp, R.A. and Nie, S. Counting single native biomolecules and intact viruses with color-coded nanoparticles. Anal. Chem. 78:1061-1070, 2006. doi:10.1021/ac051801t

    Article  CAS  PubMed  Google Scholar 

  2. N. Anikeeva, T. Lebedeva, A.R. Clapp, E.R. Goldman, M.L. Dustin, H. Mattoussi, and Y. Sykulev, Quantum Dot-peptide-MHC Biosensors Reveal Strong CD8-dependent Cooperation Between Self and Viral Antigens that Augment the T cell Response. Proc. Natl. Acad. Sci. 103:16846-16851, 2006. doi:10.1073/pnas.0607771103

    Article  CAS  PubMed  Google Scholar 

  3. Bats, C., L. Groc, and D. Choquet, “The interaction between stargazin and PSD-95 regulates AMPA receptor surface trafficking”. Neuron 53:719-734, 2007. doi:10.1016/j.neuron.2007.01.030

    Article  CAS  PubMed  Google Scholar 

  4. Bouzigues, C. and M. Dahan, “Transient directed motions of GABA(A) receptors in growth cones detected by a speed correlation index”. Biophys. J. 92:654-660, 2007. doi:10.1529/biophysj.106.094524

    Article  CAS  PubMed  Google Scholar 

  5. Bouzigues, C., M. Morel, A. Triller, et al., “Asymmetric redistribution of GABA receptors during GABA gradient sensing by nerve growth cones analyzed by single quantum dot imaging”. Proceed. Nat. Acad. Sci. 104:11251-11256, 2007. doi:10.1073/pnas.0702536104

    Article  CAS  Google Scholar 

  6. Bruchez, M., Jr., Moronne, M., Gin, P., Weiss, S. & Alivisatos, A. P. Semiconductor nanocrystals as fluorescent biological labels. Science 281:2013-2016, 1998. doi:10.1126/science.281.5385.2013

    Article  CAS  PubMed  Google Scholar 

  7. O. Carion, B. Mahler, T. Pons, B. Dubertret. Synthesis, Encapsulation, Purification and Coupling of Single Quantum Dots in Phospholipid Micelles for their Use in Cellular and In Vivo Imaging. Nat. Protocols 2: 2383-2390, 2007. doi:10.1038/nprot.2007.351

    Article  CAS  Google Scholar 

  8. Charrier, C., M.V. Ehrensperger, M. Dahan, et al., “Cytoskeleton regulation of glycine receptor number at synapses and diffusion in the plasma membrane”. J. Neuroscience 26:8502-8511, 2006. doi:10.1523/JNEUROSCI.1758-06.2006

    Article  CAS  PubMed  Google Scholar 

  9. Chen, H.F., I. Titushkin, M. Stroscio, et al., “Altered membrane dynamics of quantum dot-conjugated integrins during osteogenic differentiation of human bone marrow derived progenitor cells”. Biophys. J. 92:1399-1408, 2007. doi:10.1529/biophysj.106.094896

    Article  CAS  PubMed  Google Scholar 

  10. Y.F. Chen, J. Vela, H. Htoon, J.L. Casson, D.J. Werder, D.A. Bussian, V.I. Klimov, and J.A. Hollingsworth. “Giant” multishell CdSe nanocrystal quantum dots with suppressed blinking. J. Am. Chem. Soc. 130: 5026-5027, 2008. doi:10.1021/ja711379k

    Article  CAS  PubMed  Google Scholar 

  11. Clapp, A.R., I.L. Medintz, and H. Mattoussi. Förster resonance energy transfer investigations using quantum-dot fluorophores. ChemPhysChem. 7:47-57, 2006. doi:10.1002/cphc.200500217

    Article  CAS  PubMed  Google Scholar 

  12. A.R. Clapp, I.L. Medintz, J.M. Mauro, B.R. Fisher, M.G. Bawendi, and H. Mattoussi. Fluorescence resonance energy transfer between quantum dot donors and dye-labeled protein acceptors. J. Am. Chem. Soc.126:301-310, 2004. doi:10.1021/ja037088b

    Article  CAS  PubMed  Google Scholar 

  13. S. Coe, W-K. Woo, M. Bawendi, V. Bulovic. Electroluminescence from single monolayers of nanocrystals in molecular organic devices. Nature 420: 800-803, 2002. doi:10.1038/nature01217

    Article  CAS  PubMed  Google Scholar 

  14. Crut, A., B. Geron-Landre, I. Bonnet, Bonneau, S., Desbiolles, P. and Escude. C., Detection of single DNA molecules by multicolor quantum-dot end-labeling. Nucleic Acids Res., 33:e98, 2005. doi:10.1093/nar/gni097

    Article  CAS  PubMed  Google Scholar 

  15. B.O. Dabbousi, J. Rodriguez-Viejo, F.V. Mikulec, J.R. Heine, H. Mattoussi, R. Ober, K.F. Jensen, and M.G. Bawendi. (CdSe)ZnS Core–Shell Quantum Dots: Synthesis and Characterization of a Size Series of Highly Luminescent Nanocrystallites. J. Phys. Chem. B 101:9463–9475, 1997. doi:10.1021/jp971091y

    Article  CAS  Google Scholar 

  16. M. Dahan, S. Levi, C. Luccardini, P. Rostaing, B. Riveau and A. Triller. Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Science 302:442-445, 2003. doi:10.1126/science.1088525

    Article  CAS  PubMed  Google Scholar 

  17. Deniz, A.A., M. Dahan, J.R. Grunwell, et al., “Single-pair fluorescence resonance energy transfer on freely diffusing molecules: Observation of Förster distance dependence and subpopulations”. Proc. Natl. Acad. Sci.96:3670-3675, 1999. doi:10.1073/pnas.96.7.3670

    Article  CAS  PubMed  Google Scholar 

  18. Deniz, A.A., T.A. Laurence, M. Dahan, et al.,. Ratiometric single-molecule studies of freely diffusing biomolecules. Ann. Rev. Phys. Chem. 52:233-253, 2001. doi:10.1146/annurev.physchem.52.1.233

    Article  CAS  Google Scholar 

  19. H. Du, C. Chen, R. Krishnan, T.D. Krauss, J.M. Harbold, F.W. Wise, M.G. Thomas, and J. Silcox. Optical Properties of Colloidal PbSe Nanocrystals. Nano Lett. 2:1321–1324, 2002. doi:10.1021/nl025785g

    Article  CAS  Google Scholar 

  20. Duan, H. and S. Nie. Cell-Penetrating Quantum Dots Based on Multivalent and Endosome-Disrupting Surface Coatings. J. Am. Chem. Soc., 129: 3333–3338, 2007. doi:10.1021/ja068158s

    Article  CAS  PubMed  Google Scholar 

  21. Dubertret, B.; Skourides, P.; Norris, D. J.; Noireaux, V.; Brivanlou, A. H.; Libchaber, A. “In Vivo Imaging of Quantum Dots Encapsulated in Phospholipid Micelles,” Science 298:1759–1762, 2002. doi:10.1126/science.1077194

    Article  CAS  PubMed  Google Scholar 

  22. Durisic, N., A.I. Bachir, D.L. Kolin, et al., “Detection and correction of blinking bias in image correlation transport measurements of quantum dot tagged macromolecules”. Biophysical Journal 93:1338-1346, 2007. doi:10.1529/biophysj.107.106864

    Article  CAS  PubMed  Google Scholar 

  23. Edgar, R., M. McKinstry, J. Hwang, et al., High-sensitivity bacterial detection using biotin-tagged phage and quantum-dot nanocomplexes. Proc. Natl. Acad. Sci. 103: 4841-4845, 2006. doi:10.1073/pnas.0601211103

    Article  CAS  PubMed  Google Scholar 

  24. Al. L. Efros and M. Rosen. Random Telegraph Signal in the Photoluminescence Intensity of a Single Quantum Dot. Phys. Rev. Lett. 78:1110-1113, 1996.

    Article  Google Scholar 

  25. Ehrensperger, M.V., C. Hanus, C. Vannier, et al., “Multiple association states between glycine receptors and gephyrin identified by SPT analysis”. Biophys. J. 92:3706-3718, 2007. doi:10.1529/biophysj.106.095596

    Article  CAS  PubMed  Google Scholar 

  26. S.A. Empedocles, D.J. Norris, and M.G. Bawendi. Photoluminescence Spectroscopy of Single CdSe Nanocrystallite Quantum Dots. Phys. Rev. Lett. 77:3873, 1996. doi:10.1103/PhysRevLett.77.3873

    Article  CAS  PubMed  Google Scholar 

  27. H. Fan, E. W. Leve, C. Scullin, J. Gabaldon, D. Tallant, S. Bunge, T. Boyle, M.C. Wilson, and C.J. Brinker. Surfactant-Assisted Synthesis of Water-Soluble and Biocompatible Semiconductor Quantum Dot Micelles, Nano Lett. 5:645–648, 2005. doi:10.1021/nl050017l

    Article  CAS  PubMed  Google Scholar 

  28. Gao, X. H.; Cui, Y. Y.; Levenson, R. M.; Chung, L. W. K.; Nie, S. M. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat. Biotechnol. 22: 969-976, 2004. doi:10.1038/nbt994

    Article  CAS  PubMed  Google Scholar 

  29. Gaponenko, S. V., Optical Properties of Semiconductor Nanocrystals, Vol. 23, Cambridge: Cambridge University Press, 1998.

    Google Scholar 

  30. Gerion, D.; Pinaud, F.; Williams, S. C.; Parak, W. J.; Zanchet, D.; Weiss, S.; Alivisatos, A. P. Synthesis and Properties of Biocompatible Water-Soluble Silica-Coated CdSe/ZnS Semiconductor Quantum Dots. J. Phys. Chem. B 105:8861–8871, 2001. doi:10.1021/jp0105488

    Article  CAS  Google Scholar 

  31. E.R. Goldman, A.R. Clapp, G.P. Anderson, H.T. Uyeda, J.M. Mauro, I.L. Medintz, and H. Mattoussi, “Multiplexed toxin analysis using four colors of quantum dot fluoro-reagents,” Anal. Chem. 76:684-688, 2004. doi:10.1021/ac035083r

    Article  CAS  PubMed  Google Scholar 

  32. Greenham, N. C., X. G. Peng, and A. P. Alivisatos. Charge separation and transport in conjugated-polymer/semiconductor-nanocrystal composites studied by photoluminescence quenching and photoconductivity. Phys. Rev. B 54:17628, 1996. doi:10.1103/PhysRevB.54.17628.

    Google Scholar 

  33. W. Guo, J. Li, Y. A. Wang, X. Peng. Conjugation Chemistry and Bio-Applications of Semiconductor Box-Nanocrystals Prepared via Dendrimer-Bridging. Chem. Mater. 15:3125–3133, 2003. doi:10.1021/cm034341y

    Article  CAS  Google Scholar 

  34. Ha, T., T. Enderle, D.F. Ogletree, et al., “Probing the interaction between two single molecules: fluorescence resonance energy transfer between a single donor and a single acceptor.” Proced. Nat. Acad. Sci 93:6264-6268, 1996. doi:10.1073/pnas.93.13.6264

    Article  CAS  PubMed  Google Scholar 

  35. Haggie, P.M., J.K. Kim, G.L. Lukacs, et al., “Tracking of quantum dot-labeled CFTR shows near immobilization by C-terminal PDZ interactions”. Molecular Biology of the Cell 17:4937-4945, 2006. doi:10.1091/mbc.E06-08-0670

    Article  CAS  PubMed  Google Scholar 

  36. Hahn, M.A., J.S. Tabb, and T.D. Krauss, “Detection of single bacterial pathogens with semiconductor quantum dots”. Anal. Chem. 77: 4861-4869, 2005. doi:10.1021/ac050641i

    Article  CAS  PubMed  Google Scholar 

  37. M. Heine, L. Groc, R. Frischknecht, J-C. Béïque, B. Lounis, G. Rumbaugh, R.L. Huganir, L. Cognet, and D. Choquet. Surface Mobility of Postsynaptic AMPARs Tunes Synaptic Transmission. Science 320:201-205, 2008. doi:10.1126/science.1152089

    Article  CAS  PubMed  Google Scholar 

  38. Henglein, A., “Photodegradation and fluorescence of colloidal cadmium sulfide in aqueous solution,” Ber. Bunsen-Ges. Phys. Chem. 86:301–305, 1982.

    CAS  Google Scholar 

  39. Hines, M. A., and P. Guyot-Sionnest. Synthesis and characterization of strongly luminescing ZnS-capped CdSe nanocrystals. J. Phys. Chem. 100:468–471, 1996.

    Google Scholar 

  40. Ho, Y.P., M.C. Kung, S. Yang, et al., “Multiplexed hybridization detection with multicolor colocalization of quantum dot nanoprobes”. Nano Lett. 5:1693-1697, 2005. doi:10.1021/nl050888v

    Article  CAS  PubMed  Google Scholar 

  41. Hohng, S. and T. Ha, “Single-molecule quantum-dot fluorescence resonance energy transfer”. Chemphyschem. 6: 956-960, 2005. doi:10.1002/cphc.200400557

    Article  CAS  PubMed  Google Scholar 

  42. Hurtley, S. M., and L. Helmuth (Eds.). Special issue on biological imaging. Science 300, 2003.

  43. W.U. Huynh, J.J. Dittmer, A.P. Alivisatos. Hybrid Nanorod-Polymer Solar Cells. Science 295: 2425-2427, 2002. doi:10.1126/science.1069156

    Article  CAS  PubMed  Google Scholar 

  44. Iyer, G., X. Michalet, Y.-P. Chang, F. F. Pinaud, S. E. Matyas, G. Payne, and S. Weiss. High affinity scFv hapten pair as a tool for quantum dot labeling and tracking of single proteins in live cells. Nano Lett. 8:4618–4623, 2008.

    Google Scholar 

  45. Jaiswal, J.K., H. Mattoussi, J.M. Mauro, et al., “Long-term multiple color imaging of live cells using quantum dot bioconjugates”. Nature Biotechnol. 21: 47-51, 2003. doi:10.1038/nbt767

    Article  CAS  PubMed  Google Scholar 

  46. Kim, S., Lim, Y. T., Soltesz, E. G., De Grand, A. M., Lee, J., Nakayama, A., Parker, J. A., Mihaljevic, T., Laurence, R. G., Dor, D. M., Cohn, L. H., Bawendi, M. G. and Frangioni, J. V. (2004) Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat. Biotechnol., 22:93-97, 2004. doi:10.1038/nbt920

    Article  CAS  PubMed  Google Scholar 

  47. Kippeny, T., L. A. Swafford and S. J. Rosenthal. Semiconductor Nanocrystals: A Powerful Visual Aid for Introducing the Particle in a Box. J. Chem. Educ. 79:1094–1100, 2002.

    Article  CAS  Google Scholar 

  48. Kortan, A.R., R. Hull, R.L. Opila, M.G. Bawendi, M.L. Steigerwald, P.J. Carrolla and L.E. Brus. Nucleation and Growth of CdSe on ZnS Quantum Crystallite Seeds, and Vice Versa, in Inverse Micelle Media. J. Am. Chem. Soc.112:1327–1332, 1990. doi:10.1021/ja00160a005

    Article  CAS  Google Scholar 

  49. M. Kuno, D. P. Fromm, H. F. Hamann, A. Gallagher, and D. J. Nesbitt. ‘‘On’’/’’off’’ fluorescence intermittency of single semiconductor quantum dots. 2001, J. Chem. Phys. 115:1028-1040, 2001. doi:10.1063/1.1377883

    Article  CAS  Google Scholar 

  50. M. Kuno, D. P. Fromm, S. T. Johnson, A. Gallagher, and D. J. Nesbitt. Modeling distributed kinetics in isolated semiconductor quantum dots. Phys. Rev. B 67:125304, 2003. doi:10.1103/PhysRevB.67.125304

    Article  CAS  Google Scholar 

  51. D.R. Larson, W.R. Zipfel, R.M. Williams, S.W. Clark, M.P. Bruchez, F.W. Wise, Watt W. Webb, Water-Soluble Quantum Dots for Multiphoton Fluorescence Imaging in Vivo. Science 300:1434- 1436, 2003. doi:10.1126/science.1083780

    Article  CAS  PubMed  Google Scholar 

  52. Leduc, C., F. Ruhnow, J. Howard, and Diez, S. Detection of fractional steps in cargo movement by the collective operation of kinesin-1 motors. Proceed. Nat. Acad. Sci. 104:10847-10852, 2007. doi:10.1073/pnas.0701864104

    Article  CAS  PubMed  Google Scholar 

  53. Levy, M., S. F. Cater, and A. D. Ellington. Quantum-dot aptamer beacons for the detection of proteins. ChemBioChem 6:2163–2166, 2005. doi:10.1002/cbic.200500218

    Google Scholar 

  54. J.J. Li, Y. A. Wang, W. Guo, J.C. Keay, T.D. Mishima, M.B. Johnson, and X. Peng. Large-Scale Synthesis of Nearly Monodisperse CdSe/CdS Core/Shell Nanocrystals Using Air-Stable Reagents via Successive Ion Layer Adsorption and Reaction. J. Am. Chem. Soc. 125:12567-12575, 2003. doi:10.1021/ja0363563

    Article  CAS  PubMed  Google Scholar 

  55. Lidke, D.S., Lidke, K.A., Rieger, B., Jovin, T.M., and Arndt-Jovin, D. “Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors”. Journal of Cell Biology 170:619–626, 2005. doi:10.1083/jcb.200503140

    Article  CAS  PubMed  Google Scholar 

  56. Lidke, D. S., Nagy, P., Heintzmann, R., Arndt-Jovin, D. J., Post, J. N., Grecco, H. E., Jares-Erijman, E. A. and Jovin, T. M. Quantum dot ligands provide new insights into erbB/HER receptor-mediated signal transduction. Nat. Biotechnol. 22: 198-203, 2004. doi:10.1038/nbt929

    Article  CAS  PubMed  Google Scholar 

  57. Lin, C. A. J.; Sperling, R. A.; Li, J. K.; Yang, T. Y.; Li, P. Y.; Zanella, M.; Chang, W. H.; Parak, W. G. Design of an Amphiphilic Polymer for nanoparticle Coating and Functionalization. Small 4: 334-341, 2008. doi:10.1002/smll.200700654

    Article  CAS  PubMed  Google Scholar 

  58. Liu, W.; Howarth, M.; Greytak, A. B.; Zheng, Y.; Nocera, D. G.; Ting, A. Y.; Bawendi, M. G. Compact Biocompatible Quantum Dots Functionalized for Cellular Imaging. J. Am. Chem. Soc. 130:1274-1284, 2008. doi:10.1021/ja076069p

    Article  CAS  PubMed  Google Scholar 

  59. B. Mahler, P. Spinicelli, S. Buil, X. Quelin, J.-P. Hermier, and B. Dubertret. Towards Non-Blinking Colloidal Quantum Dots. Nat. Mater. 7: 659-664, 2008. doi:10.1038/nmat2222

    Article  CAS  PubMed  Google Scholar 

  60. Mansson, A., M. Sundberg, M. Balaz, et al., “In vitro sliding of actin filaments labelled with single quantum dots”. Biochemical and Biophysical Research Communication 314:529-534, 2004. doi:10.1016/j.bbrc.2003.12.133

    Article  CAS  PubMed  Google Scholar 

  61. H. Mattoussi, A.W. Cumming, C.B. Murray, M.G. Bawendi, and R. Ober, “Properties of CdSe nanocrystal dispersions in the dilute regime: Structure and interparticle interactions,” Phys. Rev. B 58:7850–7863, 1998. doi:10.1103/PhysRevB.58.7850

    Article  CAS  Google Scholar 

  62. H. Mattoussi, J.M. Mauro, E.R. Goldman, G.P. Anderson, V.C. Sundar, F.V. Mikulec and M.G. Bawendi. Self-assembly of CdSe–ZnS quantum dot bioconjugates using an engineered recombinant protein. J. Am. Chem. Soc. 122, 12142-12150, 2000. doi:10.1021/ja002535y

    Article  CAS  Google Scholar 

  63. H. Mattoussi, L.H. Radzilowski, B.O. Dabbousi, E.L. Thomas, M.G. Bawendi, and M. F. Rubner, “Electroluminescence from heterostructures of organic PPV and inorganic nanocrystals,” J. Appl. Phys. 83:7965-7974, 1998. doi:10.1063/1.367978

    Article  CAS  Google Scholar 

  64. I.L. Medintz, A.R. Clapp, H. Mattoussi, E.R. Goldman, and J.M. Mauro. Nanoscale biosensor assemblies built on quantum dot FRET donors. Nat. Mater. 2:630-638, 2003. doi:10.1038/nmat961

    Article  CAS  PubMed  Google Scholar 

  65. I.L. Medintz, P.E. Dawson, A.R. Clapp, H.T. Uyeda, E.L. Chang, J.R. Deschamps, and H. Mattoussi. Monitoring Protease Activity Using QD–Peptide Conjugates and Energy Transfer. Nat. Mater. 5:581-589, 2006. doi:10.1038/nmat1676

    Article  CAS  PubMed  Google Scholar 

  66. I.L. Medintz, J.H. Konnert, A.R. Clapp, I. Stanish, M.E. Twigg, H. Mattoussi, J.M. Mauro, J.R. Deschamps. A fluorescence resonance energy transfer-derived structure of a quantum dot-protein bioconjugate nanoassembly”. Proc. Natl. Acad. Sci.101:9612-9617, 2004. doi:10.1073/pnas.0403343101

    Article  CAS  PubMed  Google Scholar 

  67. Medintz, I.L., H.T. Uyeda, E.R. Goldman, et al., “Quantum dot bioconjugates for imaging, labelling and sensing”. Nat. Mater. 4: 435-446, 2005. doi:10.1038/nmat1390

    Article  CAS  PubMed  Google Scholar 

  68. B.C. Mei, K. Susumu, I.L. Medintz, J.B. Delehanty, H. Mattoussi, “Modular Poly(ethylene glycol) Ligands for Biocompatible Semiconductor and Gold Nanocrystals with Extended pH and Ionic Stability,” J. Mater. Chem., 18:4949-4958, 2008. doi:10.1039/b810488c

    Article  CAS  Google Scholar 

  69. X. Michalet, F.F. Pinaud, L.A. Bentolila, J.M. Tsay, S. Doose, J.J. Li, G. Sundaresan, A.M. Wu, S.S. Gambhir, S. Weiss. Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307: 538-544, 2005. doi:10.1126/science.1104274

    Article  CAS  PubMed  Google Scholar 

  70. Murray, C. B., C. R. Kagan, and M. G. Bawendi. Synthesis and characterization of monodisperse nanocrystals and close-packed nanocrystal assemblies. Ann. Rev. Mater. Sci. 30:545, 2000. doi:10.1146/annurev.matsci.30.1.545.

    Google Scholar 

  71. Murray, C. B., D. J. Norris, and M. G. Bawendi. Synthesis and characterization of nearly monodisperse CdE (E = sulfur, selenium, tellurium) semiconductor nanocrystallites. J. Am. Chem. Soc. 115:8706–8713, 1993. doi:10.1021/ja00072a025.

    Google Scholar 

  72. Murray, C. B., Sun, S., Gaschler, W.; Doyle, H., Betley, T. A.; Kagan, C. R. Colloidal synthesis of nanocrystals and nanocrystal superlattices. IBM J. Res. Dev., 45: 47–56, 2001.

    Article  CAS  Google Scholar 

  73. Nann, T. Phase-transfer of CdSe@ZnS quantum dots using amphiphilic hyperbranched polyethylenimine. Chem. Commun., 1735–1736, 2005. doi:10.1039/b414807j.

  74. M. Nirmal, B. O. Dabbousi, M. G. Bawendi, J. J. Macklin, J. K. Trautman, T. D. Harris and L. E. Brus. Fluorescence intermittency in single cadmium selenide nanocrystals. Nature 383: 802-804, 1996. doi:10.1038/383802a0

    Article  CAS  Google Scholar 

  75. D.J. Norris, A. Sacra, C.B. Murray, and M.G. Bawendi. Measurement of the size dependent hole spectrum in CdSe quantum dots. Phys. Rev. Lett. 72:2612,1994. doi:10.1103/PhysRevLett.72.2612

    Article  CAS  PubMed  Google Scholar 

  76. Oh, E., D. Lee, Y. P. Kim, S. Y. Cha, D. B. Oh, H. A. Kang, J. Kim, and H. S. Kim. Nanoparticle-based energy transfer for rapid and simple detection of protein glycosylation. Angew. Chem. Int. Ed. 45:7959, 2006. doi:10.1002/anie.200601948

    Google Scholar 

  77. Park, J., Soon, J.J., Kwon, G., Jang, Y. and Hyeon, T. Synthesis of Monodisperse Spherical Nanocrystals. Angew. Chem. Int. Ed. 46:4630–4660, 2007. doi:10.1002/anie.200603148

    Article  CAS  Google Scholar 

  78. T.Pellegrino, L. Manna, S. Kudera, T. Liedl, D. Koktysh, A.L. Rogach, S. Keller, J. Radler, G. Natile, and W.J. Parak. Hydrophobic Nanocrystals Coated with an Amphiphilic Polymer Shell: A General Route to Water Soluble Nanocrystals. Nano Lett. 4:703–707, 2004. doi:10.1021/nl035172j

    Article  CAS  Google Scholar 

  79. Peng, X. G., Schlamp, M. C., Kadavanich, A. V. and Alivisatos, A. P. Epitaxial Growth of Highly Luminescent CdSe/CdS Core/Shell Nanocrystals with Photostability and Electronic Accessibility. J. Am. Chem. Soc. 119:7019–7029, 1997. doi:10.1021/ja970754m

    Article  CAS  Google Scholar 

  80. Peng, Z. A. and X. Peng, “Formation of High-Quality CdTe, CdSe, and CdS Nanocrystals Using CdO as Precursor,” J. Am. Chem. Soc. 123:183–184, 2001. doi:10.1021/ja003633m

    Article  CAS  PubMed  Google Scholar 

  81. Pinaud, F.; King, D.; Moore, H. P.; Weiss. S. Bioactivation and Cell Targeting of Semiconductor CdSe/ZnS Nanocrystals with Phytochelatin-Related Peptides. J. Am. Chem. Soc. 126: 6115-6123, 2004. doi:10.1021/ja031691c

    Article  CAS  PubMed  Google Scholar 

  82. Pinaud, F., X. Michalet, G. Iyer, E. Margaret, H.-P. Moore, and S. Weiss. Traffic. doi: 10.1111/j.1600-0854.2009.00902.x.

  83. T. Pons, I.L. Medintz, H.T. Uyeda and H. Mattoussi, “Spectrally-Dependent Fluorescence Resonant Energy Transfer Using Quantum Dot Donors: Ensemble and Single Molecule Studies,” Phys. Rev. B 73:245302, 2006. doi:10.1103/PhysRevB.73.245302

    Article  CAS  Google Scholar 

  84. Pons, T., I.L. Medintz, X. Wang, et al., “Solution-Phase Single Quantum Dot Fluorescence Resonance Energy Transfer”. J. Am. Chem. Soc 128:15324-15331, 2006. doi:10.1021/ja0657253

    Article  CAS  PubMed  Google Scholar 

  85. T. Pons, H.T. Uyeda, I.L. Medintz and H. Mattoussi, “Hydrodynamic Dimensions, Electrophoretic Mobility and Stability of Hydrophilic Quantum Dots,” J. Phys. Chem. B 110:20308-20316, 2006. doi:10.1021/jp065041h

    Article  CAS  PubMed  Google Scholar 

  86. Qu, L., Z. A. Peng and X. Peng, “Alternative Routes toward High Quality CdSe Nanocrystals,” Nano Lett., 1:333–337, 2001. doi:10.1021/nl0155532

    Article  CAS  Google Scholar 

  87. S.S. Rajan, H.Y. Liu, and T.Q. Vu. Studying the Molecular Scale Dynamics of Receptor Endocytic Trafficking in Live Cells. ACS Nano 2:1153–1166, 2008. doi:10.1021/nn700399e

    Article  CAS  PubMed  Google Scholar 

  88. Rajan, S.S. and T.Q. Vu, “Quantum dots monitor TrkA receptor dynamics in the interior of neural PC12 cells”. Nano Lett. 6, 2049-2059, 2006. doi:10.1021/nl0612650

    Article  CAS  Google Scholar 

  89. Reiss, P., J. Bleuse and A. Pron, “Highly Luminescent CdSe/ZnSe Core/Shell Nanocrystals of Low Size Dispersion,” Nano Lett. 2:781–784, 2002. doi:10.1021/nl025596y

    Article  CAS  Google Scholar 

  90. Rossetti, R., J.E. Ellison, J.M. Gibson and L.E. Brus, “Size effects in the excited electronic states of small colloidal CdS crystallites,” J. Chem. Phys. 80:4464–4469, 1984. doi:10.1063/1.447228

    Article  CAS  Google Scholar 

  91. Saxton, M. and K. Jacobson, “Single-Particle Tracking: Applications to Membrane Dynamics”. Annual Reviews - Biophysics and Biomolecular Structure 26: 373, 1997. doi:10.1146/annurev.biophys.26.1.373

    Article  CAS  PubMed  Google Scholar 

  92. Seitz, A. and T. Surrey, “Processive movement of single kinesins on crowded microtubules visualized using quantum dots”. EMBO Journal 25:267-277, 2006. doi:10.1038/sj.emboj.7600937

    Article  CAS  PubMed  Google Scholar 

  93. L. F. Shi, V. De Paoli, N. Rosenzweig and Z. Rosenzweig. Synthesis and application of quantum dots FRET-based protease sensors. J. Am. Chem. Soc. 128: 10378-10379, 2006. doi:10.1021/ja063509o

    Article  CAS  PubMed  Google Scholar 

  94. Snee, P. T., R. C. Somers, G. Nair, J. P. Zimmer, M. G. Bawendi, and D. G. Nocera. A ratiometric CdSe/ZnS nanocrystal pH sensor. J. Am. Chem. Soc. 128:13320–13321, 2006. doi:10.1021/ja0618999.

    Google Scholar 

  95. Somers, R. C.; Bawendi, M. G.; Nocera. D. G. CdSe nanocrystal based chem-/bio- sensors. Chem. Soc. Rev. 36:579-591, 2007. doi:10.1039/b517613c

    Article  CAS  PubMed  Google Scholar 

  96. Susumu, K., Mei, B.C. and Mattoussi, H. Multifunctional Ligands Based on Dihydrolipoic Acid and Polyethylene Glycol to Promote Biocompatibility of Quantum Dots. Nat. Protocols 4: 424-436, 2009. doi:10.1038/nprot.2008.247

    Article  CAS  Google Scholar 

  97. Susumu, K.; Uyeda, H. T.; Medintz, I. L.; Pons, T.; Delehanty, J. B.; Mattoussi. Enhancing the Biological Stability and Functionalities of Quantum Dots via Compact Multifunctional Surface Ligands. H. J. Am. Chem. Soc. 129:13987-13996, 2007. doi:10.1021/ja0749744

    Article  CAS  PubMed  Google Scholar 

  98. Ueda, M., Y. Sako, T. Tanaka, Devreotes, P., and Yanagida T. Single-Molecule Analysis of Chemotactic Signaling in Dictyostelium Cells. Science 294: 864, 2001. doi:10.1126/science.1063951

    Article  CAS  PubMed  Google Scholar 

  99. Uyeda, H. T.; Medintz, I. L.; Jaiswal, J. K.; Simon, S. M.; Mattoussi, H. Synthesis of Compact Mutidentate Ligands to Prepare Stable Hydrophilic Quantum Dot Fluorophores. J. Am. Chem. Soc. 127:3870–3878, 2005. doi:10.1021/ja044031w

    Article  CAS  PubMed  Google Scholar 

  100. M. Wang, N. Felorzabihi, G. Guerin, J.C. Haley, G.D. Scholes, and M.A. Winnik. Water-Soluble CdSe Quantum Dots Passivated by a Multidentate Diblock Copolymer. Macromolecules 40: 6377–6384, 2007. doi:10.1021/ma070553v

    Article  CAS  Google Scholar 

  101. Wang, Y. A., Li, J. J., Chen, H., Peng, X. Stabilize Inorganic Nanocrystals by Organic Dendrons. J. Am. Chem. Soc. 124:2293-2298, 2002. doi:10.1021/ja016711u

    Article  CAS  PubMed  Google Scholar 

  102. Warshaw, D.M., G.G. Kennedy, S.S. Work, et al., “Differential Labeling of myosin V heads with quantum dots allows direct visualization of hand-over-hand processivity”. Biophysical J. 88:L30-L32, 2005. doi:10.1529/biophysj.105.061903

    Article  CAS  PubMed  Google Scholar 

  103. Wehrenberg, B. L., C. Wang and P. Guyot-Sionnest, “Interband and Intraband Optical Studies of PbSe Colloidal Quantum Dots,” J. Phys. Chem. B 106:10634–10640, 2002. doi:10.1021/jp021187e

    Article  CAS  Google Scholar 

  104. Wu, X.; Liu, H.; Liu, J.; Haley, K. N.; Treadway, J. A.; Larson, J. P.; Ge, N.; Peale, F.; Bruchez, M. P. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat. Biotechnol. 21:41–46, 2003. doi:10.1038/nbt764

    Article  CAS  PubMed  Google Scholar 

  105. Xie R.G., Kolb U., Li J.X., Basche T., Mews A. Synthesis and characterization of highly luminescent CdSe-Core CdS/Zn0.5Cd0.5S/ZnS multi-shell nanocrystals. J. Am. Chem. Soc. 127:7480-7488, 2005. doi:10.1021/ja042939g

    Article  CAS  PubMed  Google Scholar 

  106. Xie, X.S. and J.K. Trautman. Optical Studies of Single Molecules at Room Temperature. Ann. Rev. Phys. Chem. 49:441-480, 1998. doi:10.1146/annurev.physchem.49.1.441

    Article  CAS  Google Scholar 

  107. Yao, J., D.R. Larson, H.D. Vishwasrao, et al., Blinking and nonradiant dark fraction of water-soluble quantum dots in aqueous solution. Proc. Natl. Acad. Sci. 102:14284-14289, 2005. doi:10.1073/pnas.0506523102

    Article  CAS  PubMed  Google Scholar 

  108. Yildiz, J.N. Forkey, S.A. McKinney,T. Ha, Y.E. Goldman, P.R. Selvin. Myosin V walks hand-over-hand: single fluorophore imaging with 1.5-nm localization. Science 300:2061-2065, 2003. doi:10.1126/science.1084398

    Article  CAS  PubMed  Google Scholar 

  109. W. W. Yu, E. Chang, J.C. Falkner, J. Zhang, A.M. Al-Somali, C.M. Sayes, J. Johns, R. Drezek, and V.L. Colvin. Forming Biocompatible and Nonaggregated Nanocrystals in Water Using Amphiphilic Polymers. J. Am. Chem. Soc. 129:2871-2879, 2007. doi:10.1021/ja067184n

    Article  CAS  PubMed  Google Scholar 

  110. William W. Yu, Joshua C. Falkner, Bertram S. Shih, and Vicki L. Colvin. Preparation and Characterization of Monodisperse PbSe Semiconductor Nanocrystals in a Noncoordinating Solvent,” Chem. Mater.16:3318–3322, 2004. doi:10.1021/cm049476y

    Article  CAS  Google Scholar 

  111. Zhang, C.Y. and L.W. Johnson, “Quantum dot-based fluorescence resonance energy transfer with improved FRET efficiency in capillary flows”. Anal. Chem. 78:5532-5537, 2006. doi:10.1021/ac0605389

    Article  CAS  PubMed  Google Scholar 

  112. Zhang C.Y. and Johnson L.W. Microfluidic Control of Fluorescence Resonance Energy Transfer: Breaking the FRET Limit. Angew. Chem. Int. Ed. 46:3482–3485, 2007. doi:10.1002/anie.200604861

    Article  CAS  Google Scholar 

  113. Zhang, C.Y. and L.W. Johnson, “Quantifying RNA-Peptide Interaction by Single-quantum Dot-Based Nanosensor: An Approach for Drug Screening”. Anal. Chem.79:7775-7781, 2007. doi:10.1021/ac071225w

    Article  CAS  PubMed  Google Scholar 

  114. Zhang, C.Y., H.C. Yeh, M.T. Kuroki, et al., Single-quantum-dot-based DNA nanosensor. Nat. Mater., Vol. 4:826-831, 2005. doi:10.1038/nmat1508

    Article  PubMed  Google Scholar 

  115. Q. Zhang, Y. Li, R.W. Tsien. The Dynamic Control of Kiss-And-Run and Vesicular Reuse Probed with Single Nanoparticles. Science 323:1448-1453, 2009. doi:10.1126/science.1167373

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We acknowledge NRL, the Office of Naval Research, Army Research Office and DTRA for financial support. We also thank Dorothy Farrell at NRL for the assistance with TEM image shown in Fig. 1, and Xavier Michalet at UCLA from the fruitful discussions.

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  1. Laboratoire Photons et Matière, CNRS UPR5, ESPCI, 10, rue Vauquelin, 75005, Paris, France

    Thomas Pons

  2. Division of Optical Sciences, US Naval Research Laboratory, Washington, DC, 20375, USA

    Hedi Mattoussi

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  1. Thomas Pons
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Correspondence to Hedi Mattoussi.

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Pons, T., Mattoussi, H. Investigating Biological Processes at the Single Molecule Level Using Luminescent Quantum Dots. Ann Biomed Eng 37, 1934–1959 (2009). https://doi.org/10.1007/s10439-009-9715-0

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