Skip to main content

Advertisement

SpringerLink
Log in

Quantum dots for quantitative imaging: from single molecules to tissue

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Since their introduction to biological imaging, quantum dots (QDs) have progressed from a little known, but attractive, technology to one that has gained broad application in many areas of biology. The versatile properties of these fluorescent nanoparticles have allowed investigators to conduct biological studies with extended spatiotemporal capabilities that were previously not possible. In this review, we focus on QD applications that provide enhanced quantitative information concerning protein dynamics and localization, including single particle tracking and immunohistochemistry, and finish by examining the prospects of upcoming applications, such as correlative light and electron microscopy and super-resolution. Advances in single molecule imaging, including multi-color and three-dimensional QD tracking, have provided new insights into the mechanisms of cell signaling and protein trafficking. New forms of QD tracking in vivo have allowed the observation of biological processes at molecular level resolution in the physiological context of the whole animal. Further methodological development of multiplexed QD-based immunohistochemistry assays should enable more quantitative analysis of key proteins in tissue samples. These advances highlight the unique quantitative data sets that QDs can provide to further our understanding of biological and disease processes.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Akhtar RS, Latham CB, Siniscalco D, Fuccio C, Roth KA (2007) Immunohistochemical detection with quantum dots. Methods Mol Biol 374:11–28. doi:10.1385/1-59745-369-2:11

    CAS  PubMed  Google Scholar 

  • Altman RB, Terry DS, Zhou Z, Zheng Q, Geggier P, Kolster RA, Zhao Y, Javitch JA, Warren JD, Blanchard SC (2011) Cyanine fluorophore derivatives with enhanced photostability. Nat Methods 9:68–71. doi:10.1038/nmeth.1774

  • Andrews NL, Lidke KA, Pfeiffer JR, Burns AR, Wilson BS, Oliver JM, Lidke DS (2008) Actin restricts FcepsilonRI diffusion and facilitates antigen-induced receptor immobilization. Nat Cell Biol 10:955–963. doi:10.1038/ncb1755

    PubMed Central  CAS  PubMed  Google Scholar 

  • Arnspang EC, Brewer JR, Lagerholm BC (2012) Multi-color single particle tracking with quantum dots. PLoS One 7:e48521. doi:10.1371/journal.pone.0048521

    PubMed Central  CAS  PubMed  Google Scholar 

  • Au GH, Mejias L, Swami VK, Brooks AD, Shih WY, Shih WH (2014) Quantitative assessment of Tn antigen in breast tissue micro-arrays using CdSe aqueous quantum dots. Biomaterials 35:2971–2980. doi:10.1016/j.biomaterials.2013.12.034

    CAS  PubMed  Google Scholar 

  • Bannai H, Lévi S, Schweizer C, Dahan M, Triller A (2006) Imaging the lateral diffusion of membrane molecules with quantum dots. Nat Protoc 1:2628–2634. doi:10.1038/nprot.2006.429

    CAS  PubMed  Google Scholar 

  • Barrow E, Evans DG, McMahon R, Hill J, Byers R (2011) A comparative study of quantitative immunohistochemistry and quantum dot immunohistochemistry for mutation carrier identification in Lynch syndrome. J Clin Pathol 64:208–214. doi:10.1136/jcp.2010.084418

    PubMed  Google Scholar 

  • Bernardin A, Cazet A, Guyon L, Delannoy P, Vinet F, Bonnaffé D, Texier I (2010) Copper-free click chemistry for highly luminescent quantum dot conjugates: application to in vivo metabolic imaging. Bioconjug Chem 21:583–588. doi:10.1021/bc900564w

    CAS  PubMed  Google Scholar 

  • Blanco-Canosa JB, Wu M, Susumu K, Petryayeva E, Jennings TL, Dawson PE, Algar WR, Medintz IL (2014) Recent progress in the bioconjugation of quantum dots. Coord Chem Rev 263–264:101–137. doi:10.1016/j.ccr.2013.08.030

    Google Scholar 

  • Breger J, Delehanty JB, Medintz IL (2014) Continuing progress toward controlled intracellular delivery of semiconductor quantum dots. Wiley Interdiscip Rev Nanomed Nanobiotechnol. doi:10.1002/wnan.1281

    PubMed Central  PubMed  Google Scholar 

  • Bruchez M, Moronne M, Gin P, Weiss S, Alivisatos AP (1998) Semiconductor nanocrystals as fluorescent biological labels. Science 281:2013–2016. doi:10.1126/science.281.5385.2013

    CAS  PubMed  Google Scholar 

  • Byers RJ, Hitchman ER (2011) Quantum dots brighten biological imaging. Prog Histochem Cytochem 45:201–237. doi:10.1016/j.proghi.2010.11.001

    PubMed  Google Scholar 

  • Caldwell ML, Moffitt RA, Liu J, Parry M, Sharma Y, Wang MD (2008) Simple quantification of multiplexed quantum dot staining in clinical tissue samples. Annu Int Conf IEEE Eng Med Biol Soc 2008:1907–1910. doi:10.1109/IEMBS.2008.4649559

    Google Scholar 

  • Chan W, Nie S (1998) Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281:2016–2018. doi:10.1126/science.281.5385.2016

  • Chang JC, Rosenthal SJ (2012) Visualization of lipid raft membrane compartmentalization in living RN46A neuronal cells using single quantum dot tracking. ACS Chem Neurosci 3:737–743. doi:10.1021/cn3000845

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chang JC, Tomlinson ID, Warnement MR, Ustione A, Carneiro AM, Piston DW, Blakely RD, Rosenthal SJ (2012) Single molecule analysis of serotonin transporter regulation using antagonist-conjugated quantum dots reveals restricted, p38 MAPK-dependent mobilization underlying uptake activation. J Neurosci 32:8919–8929. doi:10.1523/JNEUROSCI. 0048-12.2012

  • Chen C, Peng J, Xia HS, Yang GF, Wu QS, Chen LD, Zeng LB, Zhang ZL, Pang DW, Li Y (2009) Quantum dots-based immunofluorescence technology for the quantitative determination of HER2 expression in breast cancer. Biomaterials 30:2912–2918. doi:10.1016/j.biomaterials.2009.02.010

    CAS  PubMed  Google Scholar 

  • Chen C, Peng J, Xia H, Wu Q, Zeng L, Xu H, Tang H, Zhang Z, Zhu X, Pang D, Li Y (2010) Quantum-dot-based immunofluorescent imaging of HER2 and ER provides new insights into breast cancer heterogeneity. Nanotechnology 21:095101. doi:10.1088/0957-4484/21/9/095101

    PubMed  Google Scholar 

  • Chen C, Peng J, Sun SR, Peng CW, Li Y, Pang DW (2012) Tapping the potential of quantum dots for personalized oncology: current status and future perspectives. Nanomedicine (Lond) 7:411–428. doi:10.2217/nnm.12.9

    CAS  Google Scholar 

  • Chung I, Akita R, Vandlen R, Toomre D, Schlessinger J, Mellman I (2010) Spatial control of EGF receptor activation by reversible dimerization on living cells. Nature 464:783–787. doi:10.1038/nature08827

    CAS  PubMed  Google Scholar 

  • Clarke S, Pinaud F, Beutel O, You C, Piehler J, Dahan M (2010) Covalent monofunctionalization of peptide-coated quantum dots for single-molecule assays. Nano Lett 10:2147–2154. doi:10.1021/nl100825n

    CAS  PubMed  Google Scholar 

  • Clausen MP, Arnspang EC, Ballou B, Bear JE, Lagerholm BC (2014) Simultaneous multi-species tracking in live cells with quantum dot conjugates. PLoS One 9:e97671. doi:10.1371/journal.pone.0097671

    PubMed Central  PubMed  Google Scholar 

  • Cognet L, Leduc C, Lounis B (2014) Advances in live-cell single-particle tracking and dynamic super-resolution imaging. Curr Opin Chem Biol 20:78–85. doi:10.1016/j.cbpa.2014.04.015

    CAS  PubMed  Google Scholar 

  • Courty S, Bouzigues C, Luccardini C, Ehrensperger MV, Bonneau S, Dahan M (2006a) Tracking individual proteins in living cells using single quantum dot imaging. Methods Enzymol 414:211–228. doi:10.1016/S0076-6879(06)14012-4

    CAS  PubMed  Google Scholar 

  • Courty S, Luccardini C, Bellaiche Y, Cappello G, Dahan M (2006b) Tracking individual kinesin motors in living cells using single quantum-dot imaging. Nano Lett 6:1491–1495. doi:10.1021/nl060921t

    CAS  PubMed  Google Scholar 

  • Crane JM, Verkman AS (2008) Long-range nonanomalous diffusion of quantum dot-labeled aquaporin-1 water channels in the cell plasma membrane. Biophys J 94:702–713. doi:10.1529/biophysj.107.115121

    PubMed Central  CAS  PubMed  Google Scholar 

  • Crane JM, Van Hoek AN, Skach WR, Verkman AS (2008) Aquaporin-4 dynamics in orthogonal arrays in live cells visualized by quantum dot single particle tracking. Mol Biol Cell 19:3369–3378. doi:10.1091/mbc.E08-03-0322

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cui B, Wu C, Chen L, Ramirez A, Bearer EL, Li WP, Mobley WC, Chu S (2007) One at a time, live tracking of NGF axonal transport using quantum dots. Proc Natl Acad Sci U S A 104:13666–13671. doi:10.1073/pnas.0706192104

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cutler PJ, Malik MD, Liu S, Byars JM, Lidke DS, Lidke KA (2013) Multi-color quantum dot tracking using a high-speed hyperspectral line-scanning microscope. PLoS One 8:e64320. doi:10.1371/journal.pone.0064320

    PubMed Central  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Deerinck TJ, Giepmans BNG, Smarr BL, Martone ME, Ellisman MH (2007) Light and electron microscopic localization of multiple proteins using quantum dots. Methods Mol Biol 374:43–53. doi:10.1385/1-59745-369-2:43

    CAS  PubMed  Google Scholar 

  • Delehanty JB, Mattoussi H, Medintz IL (2009) Delivering quantum dots into cells: strategies, progress and remaining issues. Anal Bioanal Chem 393:1091–1105. doi:10.1007/s00216-008-2410-4

    CAS  PubMed  Google Scholar 

  • Derfus AM, Chan WCW, Bhatia SN (2004) Intracellular delivery of quantum dots for live cell labeling and organelle tracking. Adv Mater 16:961–966. doi:10.1002/adma.200306111

    CAS  Google Scholar 

  • Dertinger T, Colyer R, Iyer G, Weiss S, Enderlein J (2009) Fast, background-free, 3D super-resolution optical fluctuation imaging (SOFI). Proc Natl Acad Sci U S A 106:22287–22292. doi:10.1073/pnas.0907866106

    PubMed Central  CAS  PubMed  Google Scholar 

  • Dertinger T, Pallaoro A, Braun G, Ly S, Laurence TA, Weiss S (2013) Advances in superresolution optical fluctuation imaging (SOFI). Q Rev Biophys 46:210–221. doi:10.1017/S0033583513000036

  • Diagaradjane P, Orenstein-Cardona JM, Colón-Casasnovas NE, Deorukhkar A, Shentu S, Kuno N, Schwartz DL, Gelovani JG, Krishnan S (2008) Imaging epidermal growth factor receptor expression in vivo: pharmacokinetic and biodistribution characterization of a bioconjugated quantum dot nanoprobe. Clin Cancer Res 14:731–741. doi:10.1158/1078-0432.CCR-07-1958

    CAS  PubMed  Google Scholar 

  • Fang M, Peng C-W, Pang D-W, Li Y (2012) Quantum dots for cancer research: current status, remaining issues, and future perspectives. Cancer Biol Med 9:151–163. doi:10.7497/j.issn. 2095-3941.2012.03.001

    PubMed Central  CAS  PubMed  Google Scholar 

  • Faratian D, Christiansen J, Gustavson M, Jones C, Scott C, Um I, Harrison DJ (2011) Heterogeneity mapping of protein expression in tumors using quantitative immunofluorescence. J Vis Exp 56:e3334. doi:10.3791/3334

  • Fichter KM, Flajolet M, Greengard P, Vu TQ (2010) Kinetics of G-protein-coupled receptor endosomal trafficking pathways revealed by single quantum dots. Proc Natl Acad Sci U S A 107:18658–18663. doi:10.1073/pnas.1013763107

    PubMed Central  CAS  PubMed  Google Scholar 

  • Filonov GS, Piatkevich KD, Ting LM, Zhang J, Kim K, Verkhusha VV (2011) Bright and stable near-infrared fluorescent protein for in vivo imaging. Nat Biotechnol 29:757–761. doi:10.1038/nbt.1918

    PubMed Central  CAS  PubMed  Google Scholar 

  • Gao X, Cui Y, Levenson RM, Chung LW, Nie S (2004) In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 22:969–976. doi:10.1038/nbt994

    CAS  PubMed  Google Scholar 

  • Ghosh Y, Mangum BD, Casson JL, Williams DJ, Htoon H, Hollingsworth JA (2012) New insights into the complexities of shell growth and the strong influence of particle volume in nonblinking “giant” core/shell nanocrystal quantum dots. J Am Chem Soc 134:9634–9643. doi:10.1021/ja212032q

    CAS  PubMed  Google Scholar 

  • Giepmans BNG, Adams SR, Ellisman MH, Tsien RY (2006) The fluorescent toolbox for assessing protein location and function. Science 312:217–224. doi:10.1126/science.1124618

    CAS  PubMed  Google Scholar 

  • Gonda K, Watanabe TM, Ohuchi N, Higuchi H (2010) In vivo nano-imaging of membrane dynamics in metastatic tumor cells using quantum dots. J Biol Chem 285:2750–2757. doi:10.1074/jbc.M109.075374

  • Gonda K, Miyashita M, Watanabe M, Takahashi Y, Goda H, Okada H, Nakano Y, Tada H, Amari M, Ohuchi N (2012) Development of a quantitative diagnostic method of estrogen receptor expression levels by immunohistochemistry using organic fluorescent material-assembled nanoparticles. Biochem Biophys Res Commun 426:409–414. doi:10.1016/j.bbrc.2012.08.105

    CAS  PubMed  Google Scholar 

  • Groc L, Lafourcade M, Heine M, Renner M, Racine V, Sibarita JB, Lounis B, Choquet D, Cognet L (2007) Surface trafficking of neurotransmitter receptor: comparison between single-molecule/quantum dot strategies. J Neurosci 27:12433–12437. doi:10.1523/JNEUROSCI. 3349-07.2007

    CAS  PubMed  Google Scholar 

  • Haggie PM, Kim JK, Lukacs GL, Verkman AS (2006) Tracking of quantum dot-labeled CFTR shows near immobilization by C-terminal PDZ interactions. Mol Biol Cell 17:4937–4945. doi:10.1091/mbc.E06-08-0670

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hamada Y, Gonda K, Takeda M, Sato A, Watanabe M, Yambe T, Satomi S, Ohuchi N (2011) In vivo imaging of the molecular distribution of the VEGF receptor during angiogenesis in a mouse model of ischemia. Blood 118:e93–e100. doi:10.1182/blood-2010-12-322842

    CAS  PubMed  Google Scholar 

  • Hammond MEH, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 134:e48–e72

    CAS  PubMed  Google Scholar 

  • Han H-S, Devaraj NK, Lee J, Hilderbrand SA, Weissleder R, Bawendi MG (2010) Development of a bioorthogonal and highly efficient conjugation method for quantum dots using tetrazine-norbornene cycloaddition. J Am Chem Soc 132:7838–7839. doi:10.1021/ja101677r

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hermanson GT (2013) Bioconjugate techniques. Academic Press, Amsterdam

    Google Scholar 

  • Hild WA, Breunig M, Goepferich A (2008) Quantum dots—nano-sized probes for the exploration of cellular and intracellular targeting. Eur J Pharm Biopharm 68:153–168. doi:10.1016/j.ejpb.2007.06.009

    CAS  PubMed  Google Scholar 

  • Hoyer P, Staudt T, Engelhardt J, Hell SW (2011) Quantum dot blueing and blinking enables fluorescence nanoscopy. Nano Lett 11:245–250. doi:10.1021/nl103639f

    CAS  PubMed  Google Scholar 

  • Ishihama Y, Funatsu T (2009) Single molecule tracking of quantum dot-labeled mRNAs in a cell nucleus. Biochem Biophys Res Commun 381:33–38. doi:10.1016/j.bbrc.2009.02.001

    CAS  PubMed  Google Scholar 

  • Iyer G, Pinaud F, Xu J, Ebenstein Y, Li J, Chang J, Dahan M, Weiss S (2011) Aromatic aldehyde and hydrazine activated peptide coated quantum dots for easy bioconjugation and live cell imaging. Bioconjug Chem 22:1006–1011. doi:10.1021/bc100593m

    PubMed Central  CAS  PubMed  Google Scholar 

  • Izeddin I, El Beheiry M, Andilla J, Ciepielewski D, Darzacq X, Dahan M (2012) PSF shaping using adaptive optics for three-dimensional single-molecule super-resolution imaging and tracking. Opt Express 20:4957–4967. doi:10.1364/OE.20.004957

    CAS  PubMed  Google Scholar 

  • Jacquier V, Prummer M, Segura JM, Pick H, Vogel H (2006) Visualizing odorant receptor trafficking in living cells down to the single-molecule level. Proc Natl Acad Sci U S A 103:14325–14330. doi:10.1073/pnas.0603942103

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jung K-H, Choe YS, Paik J-Y, Lee K-H (2011) 99mTc-Hydrazinonicotinamide epidermal growth factor-polyethylene glycol-quantum dot imaging allows quantification of breast cancer epidermal growth factor receptor expression and monitors receptor downregulation in response to cetuximab therapy. J Nucl Med 52:1457–1464. doi:10.2967/jnumed.111.087619

    CAS  PubMed  Google Scholar 

  • Kairdolf BA, Smith AM, Stokes TH, Wang MD, Young AN, Nie S (2013) Semiconductor quantum dots for bioimaging and biodiagnostic applications. Annu Rev Anal Chem (Palo Alto, Calif) 6:143–162. doi:10.1146/annurev-anchem-060908-155136

    CAS  Google Scholar 

  • Kao HP, Verkman AS (1994) Tracking of single fluorescent particles in three dimensions: use of cylindrical optics to encode particle position. Biophys J 67:1291–1300. doi:10.1016/S0006-3495(94)80601-0

    PubMed Central  CAS  PubMed  Google Scholar 

  • Keller AM, Ghosh Y, DeVore MS, Phipps ME, Stewart MH, Lidke DS, Wilson BS, Hollingsworth JA, Werner JH (2014) Live cell imaging: 3-dimensional tracking of non-blinking “giant” quantum dots in live cells. Adv Funct Mater 24:4795–4795. doi:10.1002/adfm.201470200

    Google Scholar 

  • Keren K, Yam PT, Kinkhabwala A, Mogilner A, Theriot JA (2009) Intracellular fluid flow in rapidly moving cells. Nat Cell Biol 11:1219–1224. doi:10.1038/ncb1965

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kim S, Lim YT, Soltesz EG, De Grand AM, Lee J, Nakayama A, Parker JA, Mihaljevic T, Laurence RG, Dor DM, Cohn LH, Bawendi MG, Frangioni JV (2004) Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol 22:93–97. doi:10.1038/nbt920

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed Engl 40:2004–2021

    CAS  PubMed  Google Scholar 

  • Lagerholm BC, Averett L, Weinreb GE, Jacobson K, Thompson NL (2006) Analysis method for measuring submicroscopic distances with blinking quantum dots. Biophys J 91:3050–3060. doi:10.1529/biophysj.105.079178

    PubMed Central  CAS  PubMed  Google Scholar 

  • Larson DR, Zipfel WR, Williams RM, Clark SW, Bruchez MP, Wise FW, Webb WW (2003) Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science 300(80):1434–1436. doi:10.1126/science.1083780

    CAS  PubMed  Google Scholar 

  • Lessard GA, Goodwin PM, Werner JH (2007) Three-dimensional tracking of individual quantum dots. Appl Phys Lett 91:224106. doi:10.1063/1.2819074

    Google Scholar 

  • Li H, Duan ZW, Xie P, Liu YR, Wang WC, Dou SX, Wang PY (2012) Effects of paclitaxel on EGFR endocytic trafficking revealed using quantum dot tracking in single cells. PLoS One 7:e45465. doi:10.1371/journal.pone.0045465

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lidke DS, Nagy P, Heintzmann R, Arndt-Jovin DJ, Post JN, Grecco HE, Jares-Erijman EA, Jovin TM (2004) Quantum dot ligands provide new insights into erbB/HER receptor-mediated signal transduction. Nat Biotechnol 22:198–203. doi:10.1038/nbt929

    CAS  PubMed  Google Scholar 

  • Lidke DS, Lidke KA, Rieger B, Jovin TM, Arndt-Jovin DJ (2005a) Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors. J Cell Biol 170:619–626. doi:10.1083/jcb.200503140

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lidke KA, Rieger B, Jovin TM, Heintzmann R (2005b) Superresolution by localization of quantum dots using blinking statistics. Opt Express 13:7052. doi:10.1364/OPEX.13.007052

    PubMed  Google Scholar 

  • Liu J, Lau SK, Varma VA, Moffitt RA, Caldwell M, Liu T, Young AN, Petros JA, Osunkoya AO, Krogstad T, Leyland-Jones B, Wang MD, Nie S (2010a) Molecular mapping of tumor heterogeneity on clinical tissue specimens with multiplexed quantum dots. ACS Nano 4:2755–2765. doi:10.1021/nn100213v

    PubMed Central  CAS  PubMed  Google Scholar 

  • Liu J, Lau SK, Varma VA, Kairdolf BA, Nie S (2010b) Multiplexed detection and characterization of rare tumor cells in Hodgkin’s lymphoma with multicolor quantum dots. Anal Chem 82:6237–6243. doi:10.1021/ac101065b

    PubMed Central  CAS  PubMed  Google Scholar 

  • Liu SL, Zhang ZL, Sun EZ, Peng J, Xie M, Tian ZQ, Lin Y, Pang DW (2011) Visualizing the endocytic and exocytic processes of wheat germ agglutinin by quantum dot-based single-particle tracking. Biomaterials 32:7616–7624. doi:10.1016/j.biomaterials.2011.06.046

    CAS  PubMed  Google Scholar 

  • Liu SL, Zhang ZL, Tian ZQ, Zhao HS, Liu H, Sun EZ, Xiao GF, Zhang W, Wang HZ, Pang DW (2012) Effectively and efficiently dissecting the infection of influenza virus by quantum-dot-based single-particle tracking. ACS Nano 6:141–150. doi:10.1021/nn2031353

    CAS  PubMed  Google Scholar 

  • Liu XL, Peng CW, Chen C, Yang XQ, Hu MB, Xia HS, Liu SP, Pang DW, Li Y (2011) Quantum dots-based double-color imaging of HER2 positive breast cancer invasion. Biochem Biophys Res Commun 409:577–582. doi:10.1016/j.bbrc.2011.05.052

    CAS  PubMed  Google Scholar 

  • Lowe AR, Siegel JJ, Kalab P, Siu M, Weis K, Liphardt JT (2010) Selectivity mechanism of the nuclear pore complex characterized by single cargo tracking. Nature 467:600–603. doi:10.1038/nature09285

    PubMed Central  CAS  PubMed  Google Scholar 

  • Low-Nam ST, Lidke KA, Cutler PJ, Roovers RC, Bergen en Henegouwen PM van, Wilson BS, Lidke DS (2011) ErbB1 dimerization is promoted by domain co-confinement and stabilized by ligand binding. Nat Struct Mol Biol 18:1244–1249. doi:10.1038/nsmb.2135

  • Lv X, Lei X, Ji M, Guo XF, Wang J, Dong WG (2013) Clinical significance of EBP50 overexpression assessed by quantum dot analysis in gastric cancer. Oncol Lett 5:1844–1848

    PubMed Central  PubMed  Google Scholar 

  • Matsuno A, Itoh J, Takekoshi S, Nagashima T, Osamura RY (2005) Three-dimensional imaging of the intracellular localization of growth hormone and prolactin and their mRNA using nanocrystal (Quantum dot) and confocal laser scanning microscopy techniques. J Histochem Cytochem 53:833–838. doi:10.1369/jhc.4A6577.2005

    CAS  PubMed  Google Scholar 

  • Matsuno A, Mizutani A, Takekoshi S, Itoh J, Okinaga H, Nishina Y, Takano K, Nagashima T, Osamura RY, Teramoto A (2006) Analyses of the mechanism of intracellular transport and secretion of pituitary hormone, with an insight of the subcellular localization of pituitary hormone and its mRNA. Brain Tumor Pathol 23:1–5. doi:10.1007/s10014-005-0189-y

    CAS  PubMed  Google Scholar 

  • Medintz IL, Uyeda HT, Goldman ER, Mattoussi H (2005) Quantum dot bioconjugates for imaging, labelling and sensing. Nat Mater 4:435–446. doi:10.1038/nmat1390

    CAS  PubMed  Google Scholar 

  • Michalet X, Pinaud FF, Bentolila LA, Tsay JM, Doose S, Li JJ, Sundaresan G, Wu AM, Gambhir SS, Weiss S (2005) Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307:538–544. doi:10.1126/science.1104274

    PubMed Central  CAS  PubMed  Google Scholar 

  • Montón H, Roldán M, Merkoçi A, Rossinyol E, Castell O, Nogués C (2012) The use of quantum dots for immunochemistry applications. Methods Mol Biol 906:185–192. doi:10.1007/978-1-61779-953-2_13

    PubMed  Google Scholar 

  • Nan X, Sims PA, Chen P, Xie XS (2005) Observation of individual microtubule motor steps in living cells with endocytosed quantum dots. J Phys Chem B 109:24220–24224. doi:10.1021/jp056360w

    CAS  PubMed  Google Scholar 

  • Nisman R, Dellaire G, Ren Y, Li R, Bazett-Jones DP (2004) Application of quantum dots as probes for correlative fluorescence, conventional, and energy-filtered transmission electron microscopy. J Histochem Cytochem 52:13–18. doi:10.1177/002215540405200102

    CAS  PubMed  Google Scholar 

  • Peng CW, Liu XL, Chen C, Liu X, Yang XQ, Pang DW, Zhu XB, Li Y (2011) Patterns of cancer invasion revealed by QDs-based quantitative multiplexed imaging of tumor microenvironment. Biomaterials 32:2907–2917. doi:10.1016/j.biomaterials.2010.12.053

  • Petryayeva E, Algar WR, Medintz IL (2013) Quantum dots in bioanalysis: a review of applications across various platforms for fluorescence spectroscopy and imaging. Appl Spectrosc 67:215–252

    CAS  PubMed  Google Scholar 

  • Pierobon P, Achouri S, Courty S, Dunn AR, Spudich JA, Dahan M, Cappello G (2009) Velocity, processivity, and individual steps of single myosin V molecules in live cells. Biophys J 96:4268–4275. doi:10.1016/j.bpj.2009.02.045

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pinaud F, Clarke S, Sittner A, Dahan M (2010) Probing cellular events, one quantum dot at a time. Nat Methods 7:275–285. doi:10.1038/nmeth.1444

    CAS  PubMed  Google Scholar 

  • Pons T, Mattoussi H (2009) Investigating biological processes at the single molecule level using luminescent quantum dots. Ann Biomed Eng 37:1934–1959. doi:10.1007/s10439-009-9715-0

    PubMed  Google Scholar 

  • Prabhat P, Gan Z, Chao J, Ram S, Vaccaro C, Gibbons S, Ober RJ, Ward ES (2007) Elucidation of intracellular recycling pathways leading to exocytosis of the Fc receptor, FcRn, by using multifocal plane microscopy. Proc Natl Acad Sci U S A 104:5889–5894. doi:10.1073/pnas.0700337104

    PubMed Central  CAS  PubMed  Google Scholar 

  • Rajan SS, Liu HY, Vu TQ (2008) Ligand-bound quantum dot probes for studying the molecular scale dynamics of receptor endocytic trafficking in live cells. ACS Nano 2:1153–1166. doi:10.1021/nn700399e

    CAS  PubMed  Google Scholar 

  • Ram S, Prabhat P, Chao J, Ward ES, Ober RJ (2008) High accuracy 3D quantum dot tracking with multifocal plane microscopy for the study of fast intracellular dynamics in live cells. Biophys J 95:6025–6043. doi:10.1529/biophysj.108.140392

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ram S, Kim D, Ober RJ, Ward ES (2012) 3D single molecule tracking with multifocal plane microscopy reveals rapid intercellular transferrin transport at epithelial cell barriers. Biophys J 103:1594–1603. doi:10.1016/j.bpj.2012.08.054

    PubMed Central  CAS  PubMed  Google Scholar 

  • Regoes A, Hehl AB (2005) SNAP-tag mediated live cell labeling as an alternative to GFP in anaerobic organisms. Biotechniques 39:809–812

    CAS  PubMed  Google Scholar 

  • Schieber C, Bestetti A, Lim JP, Ryan AD, Nguyen TL, Eldridge R, White AR, Gleeson PA, Donnelly PS, Williams SJ, Mulvaney P (2012) Conjugation of transferrin to azide-modified CdSe/ZnS core-shell quantum dots using cyclooctyne click chemistry. Angew Chem Int Ed Engl 51:10523–10527. doi:10.1002/anie.201202876

    CAS  PubMed  Google Scholar 

  • Schütz GJ, Axmann M, Schindler H (2001) Imaging single molecules in three dimensions. Single Mol 2:69–74. doi:10.1002/1438-5171(200107)2:2<69::AID-SIMO69>3.0.CO;2-N

    Google Scholar 

  • Schwartz SL, Yan Q, Telmer CA, Lidke KA, Bruchez MP, Lidke DS (2014) Fluorogen activating proteins provide tunable labeling densities for tracking FcεRI independent of IgE. ACS Chem Biol. doi:10.1021/cb5005146

    Google Scholar 

  • Serizawa T, Terui T, Kagemoto T, Mizuno A, Shimozawa T, Kobirumaki F, Ishiwata S, Kurihara S, Fukuda N (2011) Real-time measurement of the length of a single sarcomere in rat ventricular myocytes: a novel analysis with quantum dots. Am J Physiol Cell Physiol 301:C1116–C1127. doi:10.1152/ajpcell.00161.2011

  • Shaner NC, Lambert GG, Chammas A, Ni Y, Cranfill PJ, Baird MA, Sell BR, Allen JR, Day RN, Israelsson M, Davidson MW, Wang J (2013) A bright monomeric green fluorescent protein derived from Branchiostoma lanceolatum. Nat Methods 10:407–409. doi:10.1038/nmeth.2413

    CAS  PubMed  Google Scholar 

  • Shu X, Lev-Ram V, Deerinck TJ, Qi Y, Ramko EB, Davidson MW, Jin Y, Ellisman MH, Tsien RY (2011) A genetically encoded tag for correlated light and electron microscopy of intact cells, tissues, and organisms. PLoS Biol 9:e1001041. doi:10.1371/journal.pbio.1001041

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sjollema KA, Schnell U, Kuipers J, Kalicharan R, Giepmans BN (2012) Correlated light microscopy and electron microscopy. Methods Cell Biol 111:157–173

  • Sosinsky GE, Giepmans BNG, Deerinck TJ, Gaietta GM, Ellisman MH (2007) Markers for correlated light and electron microscopy. Methods Cell Biol 79:575–591. doi:10.1016/S0091-679X(06)79023-9

    CAS  PubMed  Google Scholar 

  • Specht CG, Izeddin I, Rodriguez PC, El Beheiry M, Rostaing P, Darzacq X, Dahan M, Triller A (2013) Quantitative nanoscopy of inhibitory synapses: counting gephyrin molecules and receptor binding sites. Neuron 79:308–321. doi:10.1016/j.neuron.2013.05.013

    CAS  PubMed  Google Scholar 

  • Steinkamp MP, Low-Nam ST, Yang S, Lidke KA, Lidke DS, Wilson BS (2014) erbB3 is an active tyrosine kinase capable of homo- and heterointeractions. Mol Cell Biol 34:965–977. doi:10.1128/MCB. 01605-13

    PubMed Central  PubMed  Google Scholar 

  • Storch KN, Taatjes DJ, Bouffard NA, Locknar S, Bishop NM, Langevin HM (2007) Alpha smooth muscle actin distribution in cytoplasm and nuclear invaginations of connective tissue fibroblasts. Histochem Cell Biol 127:523–530. doi:10.1007/s00418-007-0275-9

    CAS  PubMed  Google Scholar 

  • Sun B, Xie W, Yi G, Chen D, Zhou Y, Cheng J (2001) Microminiaturized immunoassays using quantum dots as fluorescent label by laser confocal scanning fluorescence detection. J Immunol Methods 249:85–89. doi:10.1016/S0022-1759(00)00331-8

    CAS  PubMed  Google Scholar 

  • Sun JZ, Chen C, Jiang G, Tian WQ, Li Y, Sun SR (2014) Quantum dot-based immunofluorescent imaging of Ki67 and identification of prognostic value in HER2-positive (non-luminal) breast cancer. Int J Nanomedicine 9:1339–1346. doi:10.2147/IJN.S58881

    PubMed Central  PubMed  Google Scholar 

  • Szent-Gyorgyi C, Schmidt BF, Creeger Y, Fisher GW, Zakel KL, Adler S, Fitzpatrick JA, Woolford CA, Yan Q, Vasilev KV, Berget PB, Bruchez MP, Jarvik JW, Waggoner A (2008) Fluorogen-activating single-chain antibodies for imaging cell surface proteins. Nat Biotechnol 26:235–240. doi:10.1038/nbt1368

    CAS  PubMed  Google Scholar 

  • Tabatabaei-Panah AS, Jeddi-Tehrani M, Ghods R, Akhondi MM, Mojtabavi N, Mahmoudi AR, Mirzadegan E, Shojaeian S, Zarnani AH (2013) Accurate sensitivity of quantum dots for detection of HER2 expression in breast cancer cells and tissues. J Fluoresc 23:293–302. doi:10.1007/s10895-012-1147-9

  • Tada H, Higuchi H, Wanatabe TM, Ohuchi N (2007) In vivo real-time tracking of single quantum dots conjugated with monoclonal anti-HER2 antibody in tumors of mice. Cancer Res 67:1138–1144. doi:10.1158/0008-5472.CAN-06-1185

    CAS  PubMed  Google Scholar 

  • Torreno-Pina JA, Castro BM, Manzo C, Buschow SI, Cambi A, Garcia-Parajo MF (2014) Enhanced receptor-clathrin interactions induced by N-glycan-mediated membrane micropatterning. Proc Natl Acad Sci U S A 111:11037–11042. doi:10.1073/pnas.1402041111

    PubMed Central  CAS  PubMed  Google Scholar 

  • True LD, Gao X (2007) Quantum dots for molecular pathology: their time has arrived. J Mol Diagn 9:7–11. doi:10.2353/jmoldx.2007.060186

    PubMed Central  CAS  PubMed  Google Scholar 

  • Uematsu M, Adachi E, Nakamura A, Tsuchiya K, Uchihara T (2012) Atomic identification of fluorescent Q-dots on tau-positive fibrils in 3D-reconstructed pick bodies. Am J Pathol 180:1394–1397. doi:10.1016/j.ajpath.2011.12.029

    CAS  PubMed  Google Scholar 

  • Valentine CD, Verkman AS, Haggie PM (2012) Protein trafficking rates assessed by quantum dot quenching with bromocresol green. Traffic 13:25–29. doi:10.1111/j.1600-0854.2011.01287.x

    PubMed Central  CAS  PubMed  Google Scholar 

  • Vermehren-Schmaedick A, Krueger W, Jacob T, Ramunno-Johnson D, Balkowiec A, Lidke KA, Vu TQ (2014) Heterogeneous intracellular trafficking dynamics of brain-derived neurotrophic factor complexes in the neuronal soma revealed by single quantum dot tracking. PLoS One 9:e95113. doi:10.1371/journal.pone.0095113

    PubMed Central  PubMed  Google Scholar 

  • Wang Y, Fruhwirth G, Cai E, Ng T, Selvin PR (2013) 3D super-resolution imaging with blinking quantum dots. Nano Lett 13:5233–5241. doi:10.1021/nl4026665

    CAS  PubMed  Google Scholar 

  • Watanabe TM, Sato T, Gonda K, Higuchi H (2007) Three-dimensional nanometry of vesicle transport in living cells using dual-focus imaging optics. Biochem Biophys Res Commun 359:1–7. doi:10.1016/j.bbrc.2007.04.168

    CAS  PubMed  Google Scholar 

  • Wells NP, Lessard GA, Phipps ME, Goodwin PM, Lidke DS, Wilson BS, Werner JH (2009) Going beyond 2D: following membrane diffusion and topography in the IgE-Fc[epsilon]RI system using 3-dimensional tracking microscopy. Proc SPIE 7185:71850Z1–71850Z13. doi:10.1117/12.809412

  • Welsher K, Yang H (2014) Multi-resolution 3D visualization of the early stages of cellular uptake of peptide-coated nanoparticles. Nat Nanotechnol 9:198–203. doi:10.1038/nnano.2014.12

    CAS  PubMed  Google Scholar 

  • Xing Y, Chaudry Q, Shen C, Kong KY, Zhau HE, Chung LW, Petros JA, O'Regan RM, Yezhelyev MV, Simons JW, Wang MD, Nie S (2007) Bioconjugated quantum dots for multiplexed and quantitative immunohistochemistry. Nat Protoc 2:1152–1165. doi:10.1038/nprot.2007.107

    CAS  PubMed  Google Scholar 

  • Xu J, Teslaa T, Wu TH, Chiou PY, Teitell MA, Weiss S (2012) Nanoblade delivery and incorporation of quantum dot conjugates into tubulin networks in live cells. Nano Lett 12:5669–5672. doi:10.1021/nl302821g

    PubMed Central  CAS  PubMed  Google Scholar 

  • Xu J, Chang J, Yan Q, Dertinger T, Bruchez M, Weiss S (2013) Labeling cytosolic targets in live cells with blinking probes. J Phys Chem Lett 4:2138–2146. doi:10.1021/jz400682m

    PubMed Central  CAS  PubMed  Google Scholar 

  • You C, Wilmes S, Beutel O, Löchte S, Podoplelowa Y, Roder F, Richter C, Seine T, Schaible D, Uzé G, Clarke S, Pinaud F, Dahan M, Piehler J (2010) Self-controlled monofunctionalization of quantum dots for multiplexed protein tracking in live cells. Angew Chem Int Ed Engl 49:4108–4112. doi:10.1002/anie.200907032

    CAS  PubMed  Google Scholar 

  • You C, Richter CP, Löchte S, Wilmes S, Piehler J (2014) Dynamic submicroscopic signaling zones revealed by pair correlation tracking and localization microscopy. Anal Chem 86:8593–8602. doi:10.1021/ac501127r

    CAS  PubMed  Google Scholar 

  • Yu J, Monaco SE, Onisko A, Bhargava R, Dabbs DJ, Cieply KM, Fine JL (2013) A validation study of quantum dot multispectral imaging to evaluate hormone receptor status in ductal carcinoma in situ of the breast. Hum Pathol 44:394–401. doi:10.1016/j.humpath.2012.06.002

    CAS  PubMed  Google Scholar 

  • Zahavy E, Freeman E, Lustig S, Keysary A, Yitzhaki S (2005) Double labeling and simultaneous detection of B- and T cells using fluorescent nano-crystal (q-dots) in paraffin-embedded tissues. J Fluoresc 15:661–665. doi:10.1007/s10895-005-2972-x

    CAS  PubMed  Google Scholar 

  • Zajac AL, Goldman YE, Holzbaur ELF, Ostap EM (2013) Local cytoskeletal and organelle interactions impact molecular-motor-driven early endosomal trafficking. Curr Biol 23:1173–1180. doi:10.1016/j.cub.2013.05.015

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zrazhevskiy P, Gao X (2013) Quantum dot imaging platform for single-cell molecular profiling. Nat Commun 4:1619. doi:10.1038/ncomms2635

    PubMed Central  PubMed  Google Scholar 

  • Zrazhevskiy P, Sena M, Gao X (2010) Designing multifunctional quantum dots for bioimaging, detection, and drug delivery. Chem Soc Rev 39:4326–4354. doi:10.1039/b915139g

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zrazhevskiy P, True LD, Gao X (2013) Multicolor multicycle molecular profiling with quantum dots for single-cell analysis. Nat Protoc 8:1852–1869. doi:10.1038/nprot.2013.112

    PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Tracy George for collaboration in the generation of the QD-IHC samples in Figs. 1, 3.

Author information

Author notes

    Authors and Affiliations

    1. Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, Ore., USA

      Tania Q. Vu & Wai Yan Lam

    2. Department of Pathology and Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, N.M., USA

      Ellen W. Hatch & Diane S. Lidke

    Authors
    1. Tania Q. Vu
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Wai Yan Lam
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Ellen W. Hatch
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Diane S. Lidke
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Tania Q. Vu or Diane S. Lidke.

    Additional information

    Wai Yan Lam and Ellen W. Hatch contributed equally to this work.

    This work was supported by NIH 1RO1NS071116, NIH 1R21NS073113 to T.Q.V., and the OHSU Neuroscience Imaging Center (P30-NS061800); NIH 1R01GM100114 and NSF MCB-0845062 to D.S.L., and the NM Spatiotemporal Modeling Center (NIH P50GM085273). E.W.H. was supported by an NM Cancer Nanotechnology Training Grant.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Vu, T.Q., Lam, W.Y., Hatch, E.W. et al. Quantum dots for quantitative imaging: from single molecules to tissue. Cell Tissue Res 360, 71–86 (2015). https://doi.org/10.1007/s00441-014-2087-2

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00441-014-2087-2

    Keywords

    Search

    Navigation