Advertisement

Time-Gated Luminescence Acquisition for Biochemical Sensing: miRNA Detection

  • Emilio Garcia-FernandezEmail author
  • Salvatore Pernagallo
  • Juan A. González-Vera
  • María J. Ruedas-Rama
  • Juan J. Díaz-Mochón
  • Angel Orte
Chapter
Part of the Springer Series on Fluorescence book series (SS FLUOR, volume 18)

Abstract

Luminescence emission is a multidimensional phenomenon comprising a time-domain layer defined by its excited-state kinetics and corresponding lifetime, which is specific to each luminophore and depends on environmental conditions. This feature allows for the discrimination of luminescence signals from species with a similar spectral profile but different lifetimes by time-gating (TG) the acquisition of luminescence. This approach represents an efficient tool for removing unwanted, usually short-lived, signals from scattered light and fluorescence interferents using luminophores with a long lifetime. Due to the emergence of time-resolved techniques using rapid excitation and acquisition methods (i.e. pulsed lasers and single-photon timing acquisition) and new long-lifetime luminophores (i.e. acridones, lanthanide complexes, nanoparticles, etc.), TG analyses can be easily applied to relevant chemical and biochemical issues. The successful application of TG to important biomedical topics has attracted the attention of the R&D industry due to its potential in the development and patenting of new probes, methods and techniques for drug discovery, immunoassays, biomarker discovery and biomolecular interactions, etc. Here, we review the technological efforts of innovative companies in the application of TG-based techniques.

Among the many currently available biomarkers, circulating microRNAs (miRNAs) have received attention since they are highly specific and sensitive to different pathological stages of numerous diseases and easily accessible from biological fluids. qPCR is a powerful and routine technique used for the detection and quantification of miRNAs, but qPCR may introduce numerous artefacts and low reproducibility during the amplification process, particularly using complex samples. Thus, due to the efficiency of TG in separating short-lived sources of fluorescence common in biological fluids, TG is an ideal approach for the direct detection of miRNAs in liquid biopsies. Recently, great efforts in the use of TG have been achieved. Our contribution is the proposal of a direct detection approach using TG-imaging with single-nucleobase resolution.

Keywords

FLIM Fluorescence Lanthanides Lifetime Luminescence miRNA Time-gated fluorescence Time-gating Time-resolved fluorescence 

Notes

Acknowledgements

The authors acknowledge funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 690866 (miRNA-DisEASY) and grants CTQ2017–85658-R from the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (ERDF).

References

  1. 1.
    Lakowicz JR (2006) Principles of fluorescence spectroscopy3rd edn. Springer, New York.  https://doi.org/10.1007/978-0-387-46312-4 CrossRefGoogle Scholar
  2. 2.
    Valeur B, Berberan-Santos MN (2012) Molecular fluorescence: principles and applications. Wiley, Weinheim.  https://doi.org/10.1002/9783527650002 CrossRefGoogle Scholar
  3. 3.
    Williams RT, Bridges JW (1964) Fluorescence of solutions: a review. J Clin Pathol 17:371–394CrossRefGoogle Scholar
  4. 4.
    Demas JN (1983) Excited state lifetime measurements. Academic, New YorkGoogle Scholar
  5. 5.
    O’Connor DV, Phillips D (1984) Time-correlated single photon counting. Academic, New YorkGoogle Scholar
  6. 6.
    Berezin MY, Achilefu S (2010) Fluorescence lifetime measurements and biological imaging. Chem Rev 110:2641–2684.  https://doi.org/10.1021/cr900343z CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Schneckenburger H (1985) Fluorescence techniques in biotechnology. Trends Biotechnol 3:257–261.  https://doi.org/10.1016/0167-7799(85)90025-3 CrossRefGoogle Scholar
  8. 8.
    Schneckenburger H, Seidlitz HK, Eberz J (1988) New trends in photobiology. J Photochem Photobiol B 2:1–19.  https://doi.org/10.1016/1011-1344(88)85033-4 CrossRefPubMedGoogle Scholar
  9. 9.
    Lehn JM (1978) Cryptates: the chemistry of macropolycyclic inclusion complexes. Acc Chem Res 11:49–57.  https://doi.org/10.1021/ar50122a001 CrossRefGoogle Scholar
  10. 10.
    Nobelprize.org. Nobel Media AB (2014) Jean-Marie Lehn - facts. http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1987/lehn-facts.html. Accessed 28 Dec 2017
  11. 11.
    Sabbatini N, Guardigli M, Lehn J-M (1993) Luminescent lanthanide complexes as photochemical supramolecular devices. Coord Chem Rev 123:201–228.  https://doi.org/10.1016/0010-8545(93)85056-A CrossRefGoogle Scholar
  12. 12.
    Dickson EF, Pollak A, Diamandis EP (1995) Ultrasensitive bioanalytical assays using time-resolved fluorescence detection. Pharmacol Ther 66:207–235.  https://doi.org/10.1016/0163-7258(94)00078-H CrossRefPubMedGoogle Scholar
  13. 13.
    Gudgin Dickson EF, Pollak A, Diamandis EP (1995) Time-resolved detection of lanthanide luminescence for ultrasensitive bioanalytical assays. J Photochem Photobiol B 27:3–19.  https://doi.org/10.1016/1011-1344(94)07086-4 CrossRefGoogle Scholar
  14. 14.
    Mathis G, Lehn JM (1986) Macropolycyclic complexes of rare earth metals and application as fluorescent labels. Patent number: EP0180492 A1Google Scholar
  15. 15.
    Lehn JM, Mathis G, Alpha B, Deschenaux R, Jolu E (1996) Rare earth cryptates, processes for their preparation, synthesis intermediates and application as fluorescent tracers. Patent number: US5534622 AGoogle Scholar
  16. 16.
    Siitari H, Hemmilä I, Soini E, Lövgren T, Koistinen V (1983) Detection of hepatitis B surface antigen using time-resolved fluoroimmunoassay. Nature 301:258–260.  https://doi.org/10.1038/301258a0 CrossRefPubMedGoogle Scholar
  17. 17.
    Pettersson K, Siitari H, Hemmilä I, Soini E, Lövgren T, Hänninen V, Tanner P, Stenman UH (1983) Time-resolved fluoroimmunoassay of human choriogonadotropin. Clin Chem 29:60–64PubMedGoogle Scholar
  18. 18.
    Suonpää MU, Lavi JT, Hemmilä IA, Lövgren TN (1985) A new sensitive assay of human alpha-fetoprotein using time-resolved fluorescence and monoclonal antibodies. Clin Chim Acta 145:341–348.  https://doi.org/10.1016/0009-8981(85)90044-0 CrossRefPubMedGoogle Scholar
  19. 19.
    Lövgren TNE (1987) Time-resolved fluoroimmunoassay of steroid hormones. J Steroid Biochem 27:47–51.  https://doi.org/10.1016/0022-4731(87)90293-7 CrossRefPubMedGoogle Scholar
  20. 20.
    Bertoft E, Eskola JU, Näntö V, Lövgren T (1984) Competitive solid-phase immunoassay of testosterone using time-resolved fluorescence. FEBS Lett 173:213–216.  https://doi.org/10.1016/0014-5793(84)81049-2 CrossRefPubMedGoogle Scholar
  21. 21.
    Beverloo HB, van Schadewijk A, van Gelderen-Boele S, Tanke HJ (1990) Inorganic phosphors as new luminescent labels for immunocytochemistry and time-resolved microscopy. Cytometry 11:784–792.  https://doi.org/10.1002/cyto.990110704 CrossRefPubMedGoogle Scholar
  22. 22.
    Beverloo HB, van Schadewijk A, Bonnet J, van der Geest R, Runia R, Verwoerd NP, Vrolijk J, Ploem JS, Tanke HJ (1992) Preparation and microscopic visualization of multicolor luminescent immunophosphors. Cytometry 13:561–570.  https://doi.org/10.1002/cyto.990130603 CrossRefPubMedGoogle Scholar
  23. 23.
    Marriott G, Clegg RM, Arndt-Jovin DJ, Jovin TM (1991) Time resolved imaging microscopy. Phosphorescence and delayed fluorescence imaging. Biophys J 60:1374–1387.  https://doi.org/10.1016/S0006-3495(91)82175-0 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Marriott G, Heidecker M, Diamandis EP, Yan-Marriott Y (1994) Time-resolved delayed luminescence image microscopy using an europium ion chelate complex. Biophys J 67:957–965.  https://doi.org/10.1016/S0006-3495(94)80597-1 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Cubeddu R, Taroni P, Valentini G, Canti G (1992) Use of time-gated fluorescence imaging for diagnosis in biomedicine. J Photochem Photobiol B 12:109–113.  https://doi.org/10.1016/1011-1344(92)85023-N CrossRefPubMedGoogle Scholar
  26. 26.
    Cubeddu R (1993) Time-gated imaging system for tumor diagnosis. Opt Eng 32:320.  https://doi.org/10.1117/12.60754 CrossRefGoogle Scholar
  27. 27.
    Cubeddu R, Taroni P, Valentini G, Ghetti F, Lenci F (1993) Time-gated fluorescence imaging of Blepharisma red and blue cells. Biochim Biophys Acta 1143:327–331.  https://doi.org/10.1016/0005-2728(93)90204-S CrossRefGoogle Scholar
  28. 28.
    Seveus L, Väisälä M, Syrjänen S, Sandberg M, Kuusisto A, Harju R, Salo J, Hemmilä I, Kojola H, Soini E (1992) Time-resolved fluorescence imaging of europium chelate label in immunohistochemistry and in situ hybridization. Cytometry 13:329–338.  https://doi.org/10.1002/cyto.990130402 CrossRefPubMedGoogle Scholar
  29. 29.
    Schneckenburger H, Feyh J, Götz A, Jocham D, Unsöld E (1986) Time-resolved fluorescence of hematoporphyrin derivative in tumor cells and animal tissues. In: Waidelich W, Kiefhaber P (eds) Laser/optoelectronics in medicine/laser/optoelektronik in der medizin. Springer, Berlin, pp 70–73CrossRefGoogle Scholar
  30. 30.
    Schneckenburger H, Koenig K, Dienersberger T, Hahn R (1994) Time-gated microscopic imaging and spectroscopy. In: Fercher AF, Lewis A, Podbielska H, Schneckenburger H, Wilson T (eds) Microscopy, holography, and interferometry in biomedicine. SPIE, Budapest, p 124CrossRefGoogle Scholar
  31. 31.
    Koenig K (1994) Time-gated microscopic imaging and spectroscopy in medical diagnosis and photobiology [also Erratum 33(11)3828(Nov1994)]. Opt Eng 33:2600.  https://doi.org/10.1117/12.177101 CrossRefGoogle Scholar
  32. 32.
    Kohl M, Neukammer J, Sukowski U, Rinneberg H, Wöhrle D, Sinn HJ, Friedrich EA (1993) Delayed observation of laser-induced fluorescence for imaging of tumors. Appl Phys B Lasers Opt 56:131–138.  https://doi.org/10.1007/BF00332192 CrossRefGoogle Scholar
  33. 33.
    Lakowicz JR, Szmacinski H, Nowaczyk K, Johnson ML (1992) Fluorescence lifetime imaging of free and protein-bound NADH. Proc Natl Acad Sci U S A 89:1271–1275.  https://doi.org/10.1073/pnas.89.4.1271 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Lakowicz JR, Szmacinski H, Nowaczyk K, Berndt KW, Johnson M (1992) Fluorescence lifetime imaging. Anal Biochem 202:316–330.  https://doi.org/10.1016/0003-2697(92)90112-K CrossRefPubMedGoogle Scholar
  35. 35.
    Gadella TWJ, Jovin TM, Clegg RM (1993) Fluorescence lifetime imaging microscopy (FLIM): spatial resolution of microstructures on the nanosecond time scale. Biophys Chem 48:221–239.  https://doi.org/10.1016/0301-4622(93)85012-7 CrossRefGoogle Scholar
  36. 36.
    Becker W (2012) Fluorescence lifetime imaging--techniques and applications. J Microsc 247:119–136.  https://doi.org/10.1111/j.1365-2818.2012.03618.x CrossRefPubMedGoogle Scholar
  37. 37.
    Birks JB, Dyson DJ, Munro IH (1963) ‘Excimer’ fluorescence. II. Lifetime studies of pyrene solutions. Proc R Soc A 275:575–588.  https://doi.org/10.1098/rspa.1963.0187 CrossRefGoogle Scholar
  38. 38.
    Smith JA, West RM, Allen M (2004) Acridones and quinacridones: novel fluorophores for fluorescence lifetime studies. J Fluoresc 14:151–171CrossRefGoogle Scholar
  39. 39.
    Boettcher A, Gradoux N, Lorthiois E, Brandl T, Orain D, Schiering N, Cumin F, Woelcke J, Hassiepen U (2014) Fluorescence lifetime-based competitive binding assays for measuring the binding potency of protease inhibitors in vitro. J Biomol Screen 19:870–877.  https://doi.org/10.1177/1087057114521295 CrossRefPubMedGoogle Scholar
  40. 40.
    Maltman BA, Dunsmore CJ, Couturier SCM, Tirnaveanu AE, Delbederi Z, McMordie RAS, Naredo G, Ramage R, Cotton G (2010) 9-Aminoacridine peptide derivatives as versatile reporter systems for use in fluorescence lifetime assays. Chem Commun 46:6929–6931.  https://doi.org/10.1039/c0cc01901a CrossRefGoogle Scholar
  41. 41.
    Ruedas-Rama MJ, Orte A, Hall EAH, Alvarez-Pez JM, Talavera EM (2012) A chloride ion nanosensor for time-resolved fluorimetry and fluorescence lifetime imaging. Analyst 137:1500–1508.  https://doi.org/10.1039/c2an15851e CrossRefPubMedGoogle Scholar
  42. 42.
    Bora I, Bogh SA, Rosenberg M, Santella M, Sørensen TJ, Laursen BW (2016) Diazaoxatriangulenium: synthesis of reactive derivatives and conjugation to bovine serum albumin. Org Biomol Chem 14:1091–1101.  https://doi.org/10.1039/c5ob02293b CrossRefPubMedGoogle Scholar
  43. 43.
    Sørensen TJ, Thyrhaug E, Szabelski M, Luchowski R, Gryczynski I, Gryczynski Z, Laursen BW (2013) Azadioxatriangulenium: a long fluorescence lifetime fluorophore for large biomolecule binding assay. Methods Appl Fluoresc 1:025001.  https://doi.org/10.1088/2050-6120/1/2/025001 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Wawrzinek R, Ziomkowska J, Heuveling J, Mertens M, Herrmann A, Schneider E, Wessig P (2013) DBD dyes as fluorescence lifetime probes to study conformational changes in proteins. Chemistry 19:17349–17357.  https://doi.org/10.1002/chem.201302368 CrossRefPubMedGoogle Scholar
  45. 45.
    Nau WM, Greiner G, Rau H, Wall J, Olivucci M, Scaiano JC (1999) Fluorescence of 2,3-diazabicyclo[2.2.2]oct-2-ene revisited: solvent-induced quenching of the n,π*-excited state by an aborted hydrogen atom transfer. J Phys Chem A 103:1579–1584.  https://doi.org/10.1021/jp984303f CrossRefGoogle Scholar
  46. 46.
    Petersen KJ, Peterson KC, Muretta JM, Higgins SE, Gillispie GD, Thomas DD (2014) Fluorescence lifetime plate reader: resolution and precision meet high-throughput. Rev Sci Instrum 85:113101.  https://doi.org/10.1063/1.4900727 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Patsenker LD, Tatarets AL, Povrozin YA, Terpetschnig EA (2011) Long-wavelength fluorescence lifetime labels. Bioanal Rev 3:115–137.  https://doi.org/10.1007/s12566-011-0025-2 CrossRefGoogle Scholar
  48. 48.
    Patsenker LD, Yermolenko IG, Fedyunyaeva IA, Obukhova YN, Semenova ON, Terpetschnig EA (2011) Highly water-soluble, cationic luminescent labels. US 2011/0143387A1. https://patents.google.com/patent/US20110143387A1/en?oq=US+2011%2f0143387A1
  49. 49.
    Zhao Q, Huang C, Li F (2011) Phosphorescent heavy-metal complexes for bioimaging. Chem Soc Rev 40:2508–2524.  https://doi.org/10.1039/c0cs00114g CrossRefPubMedGoogle Scholar
  50. 50.
    Ma D-L, He H-Z, Leung K-H, Chan DS-H, Leung C-H (2013) Bioactive luminescent transition-metal complexes for biomedical applications. Angew Chem Int Ed Engl 52:7666–7682.  https://doi.org/10.1002/anie.201208414 CrossRefPubMedGoogle Scholar
  51. 51.
    Browne WR, Coates CG, Brady C, Matousek P, Towrie M, Botchway SW, Parker AW, Vos JG, McGarvey JJ (2003) Isotope effects on the picosecond time-resolved emission spectroscopy of tris(2,2′-bipyridine)ruthenium (II). J Am Chem Soc 125:1706–1707.  https://doi.org/10.1021/ja0289346 CrossRefPubMedGoogle Scholar
  52. 52.
    Terpetschnig E, Dattelbaum JD, Szmacinski H, Lakowicz JR (1997) Synthesis and spectral characterization of a thiol-reactive long-lifetime Ru(II) complex. Anal Biochem 251:241–245.  https://doi.org/10.1006/abio.1997.2253 CrossRefPubMedGoogle Scholar
  53. 53.
    Heffern MC, Matosziuk LM, Meade TJ (2014) Lanthanide probes for bioresponsive imaging. Chem Rev 114:4496–4539.  https://doi.org/10.1021/cr400477t CrossRefPubMedGoogle Scholar
  54. 54.
    Eliseeva SV, Bünzli J-CG (2010) Lanthanide luminescence for functional materials and bio-sciences. Chem Soc Rev 39:189–227.  https://doi.org/10.1039/b905604c CrossRefPubMedGoogle Scholar
  55. 55.
    Silvi S, Credi A (2015) Luminescent sensors based on quantum dot-molecule conjugates. Chem Soc Rev 44:4275–4289.  https://doi.org/10.1039/c4cs00400k CrossRefPubMedGoogle Scholar
  56. 56.
    Wegner KD, Hildebrandt N (2015) Quantum dots: bright and versatile in vitro and in vivo fluorescence imaging biosensors. Chem Soc Rev 44:4792–4834.  https://doi.org/10.1039/c4cs00532e CrossRefPubMedGoogle Scholar
  57. 57.
    Baker SN, Baker GA (2010) Luminescent carbon nanodots: emergent nanolights. Angew Chem Int Ed Engl 49:6726–6744.  https://doi.org/10.1002/anie.200906623 CrossRefPubMedGoogle Scholar
  58. 58.
    Dekaliuk MO, Viagin O, Malyukin YV, Demchenko AP (2014) Fluorescent carbon nanomaterials: “quantum dots” or nanoclusters? Phys Chem Chem Phys 16:16075–16084.  https://doi.org/10.1039/c4cp00138a CrossRefPubMedGoogle Scholar
  59. 59.
    Joo J, Liu X, Kotamraju VR, Ruoslahti E, Nam Y, Sailor MJ (2015) Gated luminescence imaging of silicon nanoparticles. ACS Nano 9:6233–6241.  https://doi.org/10.1021/acsnano.5b01594 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Lavis LD, Raines RT (2008) Bright ideas for chemical biology. ACS Chem Biol 3:142–155.  https://doi.org/10.1021/cb700248m CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Soini AE, Seveus L, Meltola NJ, Papkovsky DB, Soini E (2002) Phosphorescent metalloporphyrins as labels in time-resolved luminescence microscopy: effect of mounting on emission intensity. Microsc Res Tech 58:125–131.  https://doi.org/10.1002/jemt.10129 CrossRefPubMedGoogle Scholar
  62. 62.
    Finikova OS, Cheprakov AV, Vinogradov SA (2005) Synthesis and luminescence of soluble meso-unsubstituted tetrabenzo- and tetranaphtho[2,3]porphyrins. J Org Chem 70:9562–9572.  https://doi.org/10.1021/jo051580r CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Papkovsky DB, O’Riordan TC (2005) Emerging applications of phosphorescent metalloporphyrins. J Fluoresc 15:569–584.  https://doi.org/10.1007/s10895-005-2830-x CrossRefPubMedGoogle Scholar
  64. 64.
    Bünzli J-CG (2010) Lanthanide luminescence for biomedical analyses and imaging. Chem Rev 110:2729–2755.  https://doi.org/10.1021/cr900362e CrossRefPubMedGoogle Scholar
  65. 65.
    Moore EG, Samuel APS, Raymond KN (2009) From antenna to assay: lessons learned in lanthanide luminescence. Acc Chem Res 42:542–552.  https://doi.org/10.1021/ar800211j CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Mohamadi A, Miller LW (2016) Brightly luminescent and kinetically inert lanthanide bioprobes based on linear and preorganized chelators. Bioconjug Chem 27(10):2540–2548.  https://doi.org/10.1021/acs.bioconjchem.6b00473 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Bünzli J-CG (2015) On the design of highly luminescent lanthanide complexes. Coord Chem Rev 293–294:19–47.  https://doi.org/10.1016/j.ccr.2014.10.013 CrossRefGoogle Scholar
  68. 68.
    Wang Q, Nchimi Nono K, Syrjänpää M, Charbonnière LJ, Hovinen J, Härmä H (2013) Stable and highly fluorescent europium(III) chelates for time-resolved immunoassays. Inorg Chem 52:8461–8466.  https://doi.org/10.1021/ic400384f CrossRefPubMedGoogle Scholar
  69. 69.
    Sund H, Blomberg K, Meltola N, Takalo H (2017) Design of novel, water soluble and highly luminescent europium labels with potential to enhance immunoassay sensitivities. Molecules 22(10):E1807.  https://doi.org/10.3390/molecules22101807 CrossRefPubMedGoogle Scholar
  70. 70.
    Delbianco M, Sadovnikova V, Bourrier E, Mathis G, Lamarque L, Zwier JM, Parker D (2014) Bright, highly water-soluble triazacyclononane europium complexes to detect ligand binding with time-resolved FRET microscopy. Angew Chem Int Ed Engl 53:10718–10722.  https://doi.org/10.1002/anie.201406632 CrossRefPubMedGoogle Scholar
  71. 71.
    Butler SJ, Delbianco M, Lamarque L, McMahon BK, Neil ER, Pal R, Parker D, Walton JW, Zwier JM (2015) EuroTracker® dyes: design, synthesis, structure and photophysical properties of very bright europium complexes and their use in bioassays and cellular optical imaging. Dalton Trans 44:4791–4803.  https://doi.org/10.1039/c4dt02785j CrossRefPubMedGoogle Scholar
  72. 72.
    Orte A, Alvarez-Pez JM, Ruedas-Rama MJ (2013) Fluorescence lifetime imaging microscopy for the detection of intracellular pH with quantum dot nanosensors. ACS Nano 7:6387–6395.  https://doi.org/10.1021/nn402581q CrossRefPubMedGoogle Scholar
  73. 73.
    Kruss S, Hilmer AJ, Zhang J, Reuel NF, Mu B, Strano MS (2013) Carbon nanotubes as optical biomedical sensors. Adv Drug Deliv Rev 65:1933–1950.  https://doi.org/10.1016/j.addr.2013.07.015 CrossRefPubMedGoogle Scholar
  74. 74.
    Liu J-H, Cao L, LeCroy GE, Wang P, Meziani MJ, Dong Y, Liu Y, Luo PG, Sun Y-P (2015) Carbon “quantum” dots for fluorescence labeling of cells. ACS Appl Mater Interfaces 7:19439–19445.  https://doi.org/10.1021/acsami.5b05665 CrossRefPubMedGoogle Scholar
  75. 75.
    Ortega-Liebana MC, Encabo-Berzosa MM, Ruedas-Rama MJ, Hueso JL (2017) Nitrogen-induced transformation of vitamin C into multifunctional up-converting carbon nanodots in the visible-NIR range. Chemistry 23:3067–3073.  https://doi.org/10.1002/chem.201604216 CrossRefPubMedGoogle Scholar
  76. 76.
    Eda G, Lin Y-Y, Mattevi C, Yamaguchi H, Chen H-A, Chen I-S, Chen C-W, Chhowalla M (2010) Blue photoluminescence from chemically derived graphene oxide. Adv Mater 22:505–509.  https://doi.org/10.1002/adma.200901996 CrossRefPubMedGoogle Scholar
  77. 77.
    Loh KP, Bao Q, Eda G, Chhowalla M (2010) Graphene oxide as a chemically tunable platform for optical applications. Nat Chem 2:1015–1024.  https://doi.org/10.1038/nchem.907 CrossRefPubMedGoogle Scholar
  78. 78.
    Wang F, Gu Z, Lei W, Wang W, Xia X, Hao Q (2014) Graphene quantum dots as a fluorescent sensing platform for highly efficient detection of copper(II) ions. Sensors Actuators B Chem 190:516–522.  https://doi.org/10.1016/j.snb.2013.09.009 CrossRefGoogle Scholar
  79. 79.
    Röding M, Bradley SJ, Nydén M, Nann T (2014) Fluorescence lifetime analysis of graphene quantum dots. J Phys Chem C 118:30282–30290.  https://doi.org/10.1021/jp510436r CrossRefGoogle Scholar
  80. 80.
    Vaijayanthimala V, Cheng P-Y, Yeh S-H, Liu K-K, Hsiao C-H, Chao J-I, Chang H-C (2012) The long-term stability and biocompatibility of fluorescent nanodiamond as an in vivo contrast agent. Biomaterials 33:7794–7802.  https://doi.org/10.1016/j.biomaterials.2012.06.084 CrossRefPubMedGoogle Scholar
  81. 81.
    Faklaris O, Garrot D, Joshi V, Druon F, Boudou J-P, Sauvage T, Georges P, Curmi PA, Treussart F (2008) Detection of single photoluminescent diamond nanoparticles in cells and study of the internalization pathway. Small 4:2236–2239.  https://doi.org/10.1002/smll.200800655 CrossRefPubMedGoogle Scholar
  82. 82.
    Kuo Y, Hsu T-Y, Wu Y-C, Chang H-C (2013) Fluorescent nanodiamond as a probe for the intercellular transport of proteins in vivo. Biomaterials 34:8352–8360.  https://doi.org/10.1016/j.biomaterials.2013.07.043 CrossRefPubMedGoogle Scholar
  83. 83.
    Gu L, Hall DJ, Qin Z, Anglin E, Joo J, Mooney DJ, Howell SB, Sailor MJ (2013) In vivo time-gated fluorescence imaging with biodegradable luminescent porous silicon nanoparticles. Nat Commun 4:2326.  https://doi.org/10.1038/ncomms3326 CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Bryan JD (2005) Doped semiconductor nanocrystals: synthesis, characterization, physical properties, and applications. In: Karlin KD (ed) Progress in inorganic chemistry. Wiley, Hoboken, pp 47–126CrossRefGoogle Scholar
  85. 85.
    Wu P, Yan X-P (2013) Doped quantum dots for chemo/biosensing and bioimaging. Chem Soc Rev 42:5489–5521.  https://doi.org/10.1039/c3cs60017c CrossRefPubMedGoogle Scholar
  86. 86.
    Del Rosal B, Ortgies DH, Fernández N, Sanz-Rodríguez F, Jaque D, Rodríguez EM (2016) Overcoming autofluorescence: long-lifetime infrared nanoparticles for time-gated in vivo imaging. Adv Mater 28:10188–10193.  https://doi.org/10.1002/adma.201603583 CrossRefPubMedGoogle Scholar
  87. 87.
    Tian L, Dai Z, Zhang L, Zhang R, Ye Z, Wu J, Jin D, Yuan J (2012) Preparation and time-gated luminescence bioimaging applications of long wavelength-excited silica-encapsulated europium nanoparticles. Nanoscale 4:3551–3557.  https://doi.org/10.1039/c2nr30233k CrossRefPubMedGoogle Scholar
  88. 88.
    Song C, Ye Z, Wang G, Jin D, Yuan J, Guan Y, Piper J (2009) Preparation and time-gated luminescence bioimaging application of ruthenium complex covalently bound silica nanoparticles. Talanta 79:103–108.  https://doi.org/10.1016/j.talanta.2009.03.018 CrossRefPubMedGoogle Scholar
  89. 89.
    Wessel D, Flügge UI (1984) A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids. Anal Biochem 138:141–143.  https://doi.org/10.1016/0003-2697(84)90782-6 CrossRefPubMedGoogle Scholar
  90. 90.
    Maple PA, Jones CS, Andrews NJ (2001) Time resolved fluorometric immunoassay, using europium labelled antihuman IgG, for the detection of human tetanus antitoxin in serum. J Clin Pathol 54:812–815CrossRefGoogle Scholar
  91. 91.
    Qin Q, Christiansen M, Lövgren T, Nørgaard-Pedersen B, Pettersson K (1997) Dual-label time-resolved immunofluorometric assay for simultaneous determination of pregnancy-associated plasma protein A and free beta-subunit of human chorionic gonadotrophin. J Immunol Methods 205:169–175CrossRefGoogle Scholar
  92. 92.
    Bookout JT, Joaquim TR, Magin KM, Rogan GJ, Lirette RP (2000) Development of a dual-label time-resolved fluorometric immunoassay for the simultaneous detection of two recombinant proteins in potato. J Agric Food Chem 48:5868–5873.  https://doi.org/10.1021/jf000841p CrossRefPubMedGoogle Scholar
  93. 93.
    Mitrunen K, Pettersson K, Piironen T, Björk T, Lilja H, Lövgren T (1995) Dual-label one-step immunoassay for simultaneous measurement of free and total prostate-specific antigen concentrations and ratios in serum. Clin Chem 41:1115–1120PubMedGoogle Scholar
  94. 94.
    Zhu L, Leinonen J, Zhang W-M, Finne P, Stenman U-H (2003) Dual-label immunoassay for simultaneous measurement of prostate-specific antigen (PSA)-alpha1-antichymotrypsin complex together with free or total PSA. Clin Chem 49:97–103.  https://doi.org/10.1373/49.1.97 CrossRefPubMedGoogle Scholar
  95. 95.
    Degorce F, Card A, Soh S, Trinquet E, Knapik GP, Xie B (2009) HTRF: a technology tailored for drug discovery - a review of theoretical aspects and recent applications. Curr Chem Genomics 3:22–32.  https://doi.org/10.2174/1875397300903010022 CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Bazin H, Trinquet E, Mathis G (2002) Time resolved amplification of cryptate emission: a versatile technology to trace biomolecular interactions. J Biotechnol 82:233–250PubMedGoogle Scholar
  97. 97.
    Mabile M, Mathis G, Jolu EJP, Pouyat D, Dumont C (1996) Method of measuring the luminescence emitted in a luminescent assay. Patent number: US5527684 AGoogle Scholar
  98. 98.
    Hildebrandt N, Charbonnière LJ, Beck M, Ziessel RF, Löhmannsröben H-G (2005) Quantum dots as efficient energy acceptors in a time-resolved fluoroimmunoassay. Angew Chem Int Ed Engl 44:7612–7615.  https://doi.org/10.1002/anie.200501552 CrossRefPubMedGoogle Scholar
  99. 99.
    Charbonnière LJ, Hildebrandt N, Ziessel RF, Löhmannsröben H-G (2006) Lanthanides to quantum dots resonance energy transfer in time-resolved fluoro-immunoassays and luminescence microscopy. J Am Chem Soc 128:12800–12809.  https://doi.org/10.1021/ja062693a CrossRefPubMedGoogle Scholar
  100. 100.
    Algar WR, Wegner D, Huston AL, Blanco-Canosa JB, Stewart MH, Armstrong A, Dawson PE, Hildebrandt N, Medintz IL (2012) Quantum dots as simultaneous acceptors and donors in time-gated Förster resonance energy transfer relays: characterization and biosensing. J Am Chem Soc 134:1876–1891.  https://doi.org/10.1021/ja210162f CrossRefPubMedGoogle Scholar
  101. 101.
    Jia Y, Quinn CM, Clabbers A, Talanian R, Xu Y, Wishart N, Allen H (2006) Comparative analysis of various in vitro COT kinase assay formats and their applications in inhibitor identification and characterization. Anal Biochem 350:268–276.  https://doi.org/10.1016/j.ab.2005.11.010 CrossRefPubMedGoogle Scholar
  102. 102.
    Schröter T, Minond D, Weiser A, Dao C, Habel J, Spicer T, Chase P, Baillargeon P, Scampavia L, Schürer S, Chung C, Mader C, Southern M, Tsinoremas N, LoGrasso P, Hodder P (2008) Comparison of miniaturized time-resolved fluorescence resonance energy transfer and enzyme-coupled luciferase high-throughput screening assays to discover inhibitors of Rho-kinase II (ROCK-II). J Biomol Screen 13:17–28.  https://doi.org/10.1177/1087057107310806 CrossRefPubMedGoogle Scholar
  103. 103.
    Gracias V, Ji Z, Akritopoulou-Zanze I, Abad-Zapatero C, Huth JR, Song D, Hajduk PJ, Johnson EF, Glaser KB, Marcotte PA, Pease L, Soni NB, Stewart KD, Davidsen SK, Michaelides MR, Djuric SW (2008) Scaffold oriented synthesis. Part 2: design, synthesis and biological evaluation of pyrimido-diazepines as receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett 18:2691–2695.  https://doi.org/10.1016/j.bmcl.2008.03.021 CrossRefPubMedGoogle Scholar
  104. 104.
    Liu J, Lin TH, Cole AG, Wen R, Zhao L, Brescia M-R, Jacob B, Hussain Z, Appell KC, Henderson I, Webb ML (2008) Identification and characterization of small-molecule inhibitors of Tie2 kinase. FEBS Lett 582:785–791.  https://doi.org/10.1016/j.febslet.2008.02.003 CrossRefPubMedGoogle Scholar
  105. 105.
    Ayoub MA, Trebaux J, Vallaghe J, Charrier-Savournin F, Al-Hosaini K, Gonzalez Moya A, Pin J-P, Pfleger KDG, Trinquet E (2014) Homogeneous time-resolved fluorescence-based assay to monitor extracellular signal-regulated kinase signaling in a high-throughput format. Front Endocrinol (Lausanne) 5:94.  https://doi.org/10.3389/fendo.2014.00094 CrossRefGoogle Scholar
  106. 106.
    Vaasa A, Ligi K, Mohandessi S, Enkvist E, Uri A, Miller LW (2012) Time-gated luminescence microscopy with responsive nonmetal probes for mapping activity of protein kinases in living cells. Chem Commun (Camb) 48:8595–8597.  https://doi.org/10.1039/c2cc33565d CrossRefGoogle Scholar
  107. 107.
    Enkvist E, Vaasa A, Kasari M, Kriisa M, Ivan T, Ligi K, Raidaru G, Uri A (2011) Protein-induced long lifetime luminescence of nonmetal probes. ACS Chem Biol 6:1052–1062.  https://doi.org/10.1021/cb200120v CrossRefPubMedGoogle Scholar
  108. 108.
    Enomoto K, Okamoto H, Numata Y, Takemoto H (2006) A simple and rapid assay for heparanase activity using homogeneous time-resolved fluorescence. J Pharm Biomed Anal 41:912–917.  https://doi.org/10.1016/j.jpba.2006.01.032 CrossRefPubMedGoogle Scholar
  109. 109.
    Aouadi W, Eydoux C, Coutard B, Martin B, Debart F, Vasseur JJ, Contreras JM, Morice C, Quérat G, Jung M-L, Canard B, Guillemot J-C, Decroly E (2017) Toward the identification of viral cap-methyltransferase inhibitors by fluorescence screening assay. Antivir Res 144:330–339.  https://doi.org/10.1016/j.antiviral.2017.06.021 CrossRefPubMedGoogle Scholar
  110. 110.
    Ji J, Lao K, Hu J, Pang T, Jiang Z, Yuan H, Miao J, Chen X, Ning S, Xiang H, Guo Y, Yan M, Zhang L (2014) Discovery of novel aromatase inhibitors using a homogeneous time-resolved fluorescence assay. Acta Pharmacol Sin 35:1082–1092.  https://doi.org/10.1038/aps.2014.53 CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Algar WR, Malanoski AP, Susumu K, Stewart MH, Hildebrandt N, Medintz IL (2012) Multiplexed tracking of protease activity using a single color of quantum dot vector and a time-gated Förster resonance energy transfer relay. Anal Chem 84:10136–10146.  https://doi.org/10.1021/ac3028068 CrossRefPubMedGoogle Scholar
  112. 112.
    Zhang S, Ma Y, Li J, Ma J, Yu B, Xie X (2014) Molecular matchmaking between the popular weight-loss herb Hoodia gordonii and GPR119, a potential drug target for metabolic disorder. Proc Natl Acad Sci U S A 111:14571–14576.  https://doi.org/10.1073/pnas.1324130111 CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    Keppler A, Gendreizig S, Gronemeyer T, Pick H, Vogel H, Johnsson K (2003) A general method for the covalent labeling of fusion proteins with small molecules in vivo. Nat Biotechnol 21:86–89.  https://doi.org/10.1038/nbt765 CrossRefPubMedGoogle Scholar
  114. 114.
    Valencia C, Dujet C, Margathe J-F, Iturrioz X, Roux T, Trinquet E, Villa P, Hibert M, Dupuis E, Llorens-Cortes C, Bonnet D (2017) A time-resolved FRET cell-based binding assay for the apelin receptor. ChemMedChem 12:925–931.  https://doi.org/10.1002/cmdc.201700106 CrossRefPubMedGoogle Scholar
  115. 115.
    Zwier JM, Roux T, Cottet M, Durroux T, Douzon S, Bdioui S, Gregor N, Bourrier E, Oueslati N, Nicolas L, Tinel N, Boisseau C, Yverneau P, Charrier-Savournin F, Fink M, Trinquet E (2010) A fluorescent ligand-binding alternative using Tag-lite® technology. J Biomol Screen 15:1248–1259.  https://doi.org/10.1177/1087057110384611 CrossRefPubMedGoogle Scholar
  116. 116.
    Leyris J-P, Roux T, Trinquet E, Verdié P, Fehrentz J-A, Oueslati N, Douzon S, Bourrier E, Lamarque L, Gagne D, Galleyrand J-C, M’kadmi C, Martinez J, Mary S, Banères J-L, Marie J (2011) Homogeneous time-resolved fluorescence-based assay to screen for ligands targeting the growth hormone secretagogue receptor type 1a. Anal Biochem 408:253–262.  https://doi.org/10.1016/j.ab.2010.09.030 CrossRefPubMedGoogle Scholar
  117. 117.
    Emami-Nemini A, Roux T, Leblay M, Bourrier E, Lamarque L, Trinquet E, Lohse MJ (2013) Time-resolved fluorescence ligand binding for G protein-coupled receptors. Nat Protoc 8:1307–1320.  https://doi.org/10.1038/nprot.2013.073 CrossRefPubMedGoogle Scholar
  118. 118.
    Thibon A, Pierre VC (2009) Principles of responsive lanthanide-based luminescent probes for cellular imaging. Anal Bioanal Chem 394:107–120.  https://doi.org/10.1007/s00216-009-2683-2 CrossRefPubMedGoogle Scholar
  119. 119.
    Aulsebrook ML, Graham B, Grace MR, Tuck KL (2017) Lanthanide complexes for luminescence-based sensing of low molecular weight analytes. Coord Chem Rev 375:191–220.  https://doi.org/10.1016/j.ccr.2017.11.018 CrossRefGoogle Scholar
  120. 120.
    Strimbu K, Tavel JA (2010) What are biomarkers? Curr Opin HIV AIDS 5:463–466.  https://doi.org/10.1097/COH.0b013e32833ed177 CrossRefPubMedPubMedCentralGoogle Scholar
  121. 121.
    Detassis S, Grasso M, Del Vescovo V, Denti MA (2017) microRNAs make the call in cancer personalized medicine. Front Cell Dev Biol 5:86.  https://doi.org/10.3389/fcell.2017.00086 CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    Borrebaeck CAK (2017) Precision diagnostics: moving towards protein biomarker signatures of clinical utility in cancer. Nat Rev Cancer 17:199–204.  https://doi.org/10.1038/nrc.2016.153 CrossRefPubMedGoogle Scholar
  123. 123.
    Jeromin A, Bowser R (2017) Biomarkers in neurodegenerative diseases. Adv Neurobiol 15:491–528.  https://doi.org/10.1007/978-3-319-57193-5_20 CrossRefPubMedGoogle Scholar
  124. 124.
    Wang J, Tan G-J, Han L-N, Bai Y-Y, He M, Liu H-B (2017) Novel biomarkers for cardiovascular risk prediction. J Geriatr Cardiol 14:135–150.  https://doi.org/10.11909/j.issn.1671-5411.2017.02.008 CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    Dorcely B, Katz K, Jagannathan R, Chiang SS, Oluwadare B, Goldberg IJ, Bergman M (2017) Novel biomarkers for prediabetes, diabetes, and associated complications. Diabetes Metab Syndr Obes 10:345–361.  https://doi.org/10.2147/DMSO.S100074 CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    Kashani K, Cheungpasitporn W, Ronco C (2017) Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption. Clin Chem Lab Med 55:1074–1089.  https://doi.org/10.1515/cclm-2016-0973 CrossRefPubMedGoogle Scholar
  127. 127.
    Qin Q-P, Christiansen M, Pettersson K (2002) Point-of-care time-resolved immunofluorometric assay for human pregnancy-associated plasma protein A: use in first-trimester screening for Down syndrome. Clin Chem 48:473–483PubMedGoogle Scholar
  128. 128.
    Tsukerman GL, Gusina NB, Cuckle HS (1999) Maternal serum screening for Down syndrome in the first trimester: experience from Belarus. Prenat Diagn 19:499–504.  https://doi.org/10.1002/(SICI)1097-0223(199906)19:6<499::AID-PD555>3.0.CO;2-6 CrossRefPubMedGoogle Scholar
  129. 129.
    Niemimaa M, Suonpää M, Perheentupa A, Seppälä M, Heinonen S, Laitinen P, Ruokonen A, Ryynänen M (2001) Evaluation of first trimester maternal serum and ultrasound screening for Down’s syndrome in Eastern and Northern Finland. Eur J Hum Genet 9:404–408.  https://doi.org/10.1038/sj.ejhg.5200655 CrossRefPubMedGoogle Scholar
  130. 130.
    Prieto B, Llorente E, González-Pinto I, Alvarez FV (2008) Plasma procalcitonin measured by time-resolved amplified cryptate emission (TRACE) in liver transplant patients. A prognosis marker of early infectious and non-infectious postoperative complications. Clin Chem Lab Med 46:660–666CrossRefGoogle Scholar
  131. 131.
    Tousch D, Lajoix A-D, Hosy E, Azay-Milhau J, Ferrare K, Jahannault C, Cros G, Petit P (2008) Chicoric acid, a new compound able to enhance insulin release and glucose uptake. Biochem Biophys Res Commun 377:131–135.  https://doi.org/10.1016/j.bbrc.2008.09.088 CrossRefPubMedGoogle Scholar
  132. 132.
    Wang D-Y, Lu Q, Walsh SL, Payne L, Modha SS, Scott MJ, Sweitzer TD, Ames RS, Krosky DJ, Li H (2008) Development of a high-throughput cell-based assay for 11beta-hydroxysteroid dehydrogenase type 1 using BacMam technology. Mol Biotechnol 39:127–134.  https://doi.org/10.1007/s12033-008-9050-y CrossRefPubMedGoogle Scholar
  133. 133.
    Goedken ER, Gagnon AI, Overmeyer GT, Liu J, Petrillo RA, Burchat AF, Tomlinson MJ (2008) HTRF-based assay for microsomal prostaglandin E2 synthase-1 activity. J Biomol Screen 13:619–625.  https://doi.org/10.1177/1087057108321145 CrossRefPubMedGoogle Scholar
  134. 134.
    Lewis H, Beher D, Cookson N, Oakley A, Piggott M, Morris CM, Jaros E, Perry R, Ince P, Kenny RA, Ballard CG, Shearman MS, Kalaria RN (2006) Quantification of Alzheimer pathology in ageing and dementia: age-related accumulation of amyloid-beta(42) peptide in vascular dementia. Neuropathol Appl Neurobiol 32:103–118.  https://doi.org/10.1111/j.1365-2990.2006.00696.x CrossRefPubMedGoogle Scholar
  135. 135.
    Penas C, Pazos E, Mascareñas JL, Vázquez ME (2013) A folding-based approach for the luminescent detection of a short RNA hairpin. J Am Chem Soc 135:3812–3814.  https://doi.org/10.1021/ja400270a CrossRefPubMedGoogle Scholar
  136. 136.
    Pazos E, Jiménez-Balsa A, Mascareñas JL, Vázquez ME (2011) Sensing coiled-coil proteins through conformational modulation of energy transfer processes—selective detection of the oncogenic transcription factor c-Jun. Chem Sci 2:1984.  https://doi.org/10.1039/c1sc00108f CrossRefGoogle Scholar
  137. 137.
    González-Vera JA, Bouzada D, Bouclier C, Eugenio Vázquez M, Morris MC (2017) Lanthanide-based peptide biosensor to monitor CDK4/cyclin D kinase activity. Chem Commun (Camb) 53:6109–6112.  https://doi.org/10.1039/c6cc09948c CrossRefGoogle Scholar
  138. 138.
    Pazos E, Torrecilla D, Vázquez López M, Castedo L, Mascareñas JL, Vidal A, Vázquez ME (2008) Cyclin A probes by means of intermolecular sensitization of terbium-chelating peptides. J Am Chem Soc 130:9652–9653.  https://doi.org/10.1021/ja803520q CrossRefPubMedGoogle Scholar
  139. 139.
    Newton P, Harrison P, Clulow S (2008) A novel method for determination of the affinity of protein: protein interactions in homogeneous assays. J Biomol Screen 13:674–682.  https://doi.org/10.1177/1087057108321086 CrossRefPubMedGoogle Scholar
  140. 140.
    Maurel D, Comps-Agrar L, Brock C, Rives M-L, Bourrier E, Ayoub MA, Bazin H, Tinel N, Durroux T, Prézeau L, Trinquet E, Pin J-P (2008) Cell-surface protein-protein interaction analysis with time-resolved FRET and snap-tag technologies: application to GPCR oligomerization. Nat Methods 5:561–567.  https://doi.org/10.1038/nmeth.1213 CrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    Vischer HF, Nijmeijer S, Smit MJ, Leurs R (2008) Viral hijacking of human receptors through heterodimerization. Biochem Biophys Res Commun 377:93–97.  https://doi.org/10.1016/j.bbrc.2008.09.082 CrossRefPubMedGoogle Scholar
  142. 142.
    Lakowicz JR (2001) Method and composition for detecting the presence of a nucleic acid sequence in a sample. US6200752B1. https://patents.google.com/patent/US6200752B1/
  143. 143.
    Rajendran M, Miller LW (2015) Evaluating the performance of time-gated live-cell microscopy with lanthanide probes. Biophys J 109:240–248.  https://doi.org/10.1016/j.bpj.2015.06.028 CrossRefPubMedPubMedCentralGoogle Scholar
  144. 144.
    Jin D, Piper JA (2011) Time-gated luminescence microscopy allowing direct visual inspection of lanthanide-stained microorganisms in background-free condition. Anal Chem 83:2294–2300.  https://doi.org/10.1021/ac103207r CrossRefPubMedGoogle Scholar
  145. 145.
    Zhang L, Zheng X, Deng W, Lu Y, Lechevallier S, Ye Z, Goldys EM, Dawes JM, Piper JA, Yuan J, Verelst M, Jin D (2014) Practical implementation, characterization and applications of a multi-colour time-gated luminescence microscope. Sci Rep 4:6597.  https://doi.org/10.1038/srep06597 CrossRefPubMedPubMedCentralGoogle Scholar
  146. 146.
    Soini AE, Kuusisto A, Meltola NJ, Soini E, Seveus L (2003) A new technique for multiparameter imaging microscopy: use of long decay time photoluminescent labels enables multiple color immunocytochemistry with low channel-to-channel crosstalk. Microsc Res Tech 62:396–407.  https://doi.org/10.1002/jemt.10389 CrossRefPubMedGoogle Scholar
  147. 147.
    Grichine A, Haefele A, Pascal S, Duperray A, Michel R, Andraud C, Maury O (2014) Millisecond lifetime imaging with a europium complex using a commercial confocal microscope under one or two-photon excitation. Chem Sci 5:3475–3485.  https://doi.org/10.1039/C4SC00473F CrossRefGoogle Scholar
  148. 148.
    Vicidomini G, Moneron G, Han KY, Westphal V, Ta H, Reuss M, Engelhardt J, Eggeling C, Hell SW (2011) Sharper low-power STED nanoscopy by time gating. Nat Methods 8:571–573.  https://doi.org/10.1038/nmeth.1624 CrossRefPubMedGoogle Scholar
  149. 149.
    Lu Y, Xi P, Piper JA, Huo Y, Jin D (2012) Time-gated orthogonal scanning automated microscopy (OSAM) for high-speed cell detection and analysis. Sci Rep 2:837.  https://doi.org/10.1038/srep00837 CrossRefPubMedPubMedCentralGoogle Scholar
  150. 150.
    Ruedas-Rama MJ, Alvarez-Pez JM, Crovetto L, Paredes JM, Orte A (2015) FLIM strategies for intracellular sensing. In: Kapusta P, Wahl M, Erdmann R (eds) Advanced photon counting. Springer, Cham, pp 191–223Google Scholar
  151. 151.
    Dahan M, Laurence T, Pinaud F, Chemla DS, Alivisatos AP, Sauer M, Weiss S (2001) Time-gated biological imaging by use of colloidal quantum dots. Opt Lett 26:825–827CrossRefGoogle Scholar
  152. 152.
    Mandal G, Darragh M, Wang YA, Heyes CD (2013) Cadmium-free quantum dots as time-gated bioimaging probes in highly-autofluorescent human breast cancer cells. Chem Commun (Camb) 49:624–626.  https://doi.org/10.1039/c2cc37529j CrossRefGoogle Scholar
  153. 153.
    Bouccara S, Fragola A, Giovanelli E, Sitbon G, Lequeux N, Pons T, Loriette V (2014) Time-gated cell imaging using long lifetime near-infrared-emitting quantum dots for autofluorescence rejection. J Biomed Opt 19:051208.  https://doi.org/10.1117/1.JBO.19.5.051208 CrossRefPubMedGoogle Scholar
  154. 154.
    Liu M, Ye Z, Xin C, Yuan J (2013) Development of a ratiometric time-resolved luminescence sensor for pH based on lanthanide complexes. Anal Chim Acta 761:149–156.  https://doi.org/10.1016/j.aca.2012.11.025 CrossRefPubMedGoogle Scholar
  155. 155.
    Smith DG, McMahon BK, Pal R, Parker D (2012) Live cell imaging of lysosomal pH changes with pH responsive ratiometric lanthanide probes. Chem Commun (Camb) 48:8520–8522.  https://doi.org/10.1039/c2cc34267g CrossRefGoogle Scholar
  156. 156.
    Liu X, Guo L, Song B, Tang Z, Yuan J (2017) Development of a novel europium complex-based luminescent probe for time-gated luminescence imaging of hypochlorous acid in living samples. Methods Appl Fluoresc 5:014009.  https://doi.org/10.1088/2050-6120/aa61af CrossRefPubMedGoogle Scholar
  157. 157.
    Liu X, Tang Z, Song B, Ma H, Yuan J (2017) A mitochondria-targeting time-gated luminescence probe for hypochlorous acid based on a europium complex. J Mater Chem B 5:2849–2855.  https://doi.org/10.1039/C6TB02991D CrossRefGoogle Scholar
  158. 158.
    Song B, Ye Z, Yang Y, Ma H, Zheng X, Jin D, Yuan J (2015) Background-free in-vivo imaging of vitamin C using time-gateable responsive probe. Sci Rep 5:14194.  https://doi.org/10.1038/srep14194 CrossRefPubMedPubMedCentralGoogle Scholar
  159. 159.
    Dai Z, Tian L, Song B, Ye Z, Liu X, Yuan J (2014) Ratiometric time-gated luminescence probe for hydrogen sulfide based on lanthanide complexes. Anal Chem 86:11883–11889.  https://doi.org/10.1021/ac503611f CrossRefPubMedGoogle Scholar
  160. 160.
    Dai Z, Tian L, Ye Z, Song B, Zhang R, Yuan J (2013) A lanthanide complex-based ratiometric luminescence probe for time-gated luminescence detection of intracellular thiols. Anal Chem 85:11658–11664.  https://doi.org/10.1021/ac403370g CrossRefPubMedGoogle Scholar
  161. 161.
    Sun J, Song B, Ye Z, Yuan J (2015) Mitochondria targetable time-gated luminescence probe for singlet oxygen based on a β-diketonate-europium complex. Inorg Chem 54:11660–11668.  https://doi.org/10.1021/acs.inorgchem.5b02458 CrossRefPubMedGoogle Scholar
  162. 162.
    Afsari HS, Cardoso Dos Santos M, Lindén S, Chen T, Qiu X, van Bergen En Henegouwen PMP, Jennings TL, Susumu K, Medintz IL, Hildebrandt N, Miller LW (2016) Time-gated FRET nanoassemblies for rapid and sensitive intra- and extracellular fluorescence imaging. Sci Adv 2:e1600265.  https://doi.org/10.1126/sciadv.1600265 CrossRefPubMedPubMedCentralGoogle Scholar
  163. 163.
    Tu C-C, Awasthi K, Chen K-P, Lin C-H, Hamada M, Ohta N, Li Y-K (2017) Time-gated imaging on live cancer cells using silicon quantum dot nanoparticles with long-lived fluorescence. ACS Photonics 4:1306–1315.  https://doi.org/10.1021/acsphotonics.7b00188 CrossRefGoogle Scholar
  164. 164.
    Monici M (2005) Cell and tissue autofluorescence research and diagnostic applications. Biotechnol Annu Rev 11:227–256.  https://doi.org/10.1016/S1387-2656(05)11007-2 CrossRefPubMedGoogle Scholar
  165. 165.
    Zipfel WR, Williams RM, Christie R, Nikitin AY, Hyman BT, Webb WW (2003) Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc Natl Acad Sci U S A 100:7075–7080.  https://doi.org/10.1073/pnas.0832308100 CrossRefPubMedPubMedCentralGoogle Scholar
  166. 166.
    Thorson MK, Ung P, Leaver FM, Corbin TS, Tuck KL, Graham B, Barrios AM (2015) Lanthanide complexes as luminogenic probes to measure sulfide levels in industrial samples. Anal Chim Acta 896:160–165.  https://doi.org/10.1016/j.aca.2015.09.024 CrossRefPubMedGoogle Scholar
  167. 167.
    Surender EM, Bradberry SJ, Bright SA, McCoy CP, Williams DC, Gunnlaugsson T (2017) Luminescent lanthanide cyclen-based enzymatic assay capable of diagnosing the onset of catheter-associated urinary tract infections both in solution and within polymeric hydrogels. J Am Chem Soc 139:381–388.  https://doi.org/10.1021/jacs.6b11077 CrossRefPubMedGoogle Scholar
  168. 168.
    Chen X, Wang Y, Chai R, Xu Y, Li H, Liu B (2017) Luminescent lanthanide-based organic/inorganic hybrid materials for discrimination of glutathione in solution and within hydrogels. ACS Appl Mater Interfaces 9:13554–13563.  https://doi.org/10.1021/acsami.7b02679 CrossRefPubMedGoogle Scholar
  169. 169.
    Gorai T, Maitra U (2016) Supramolecular approach to enzyme sensing on paper discs using lanthanide photoluminescence. ACS Sens 1:934–940.  https://doi.org/10.1021/acssensors.6b00341 CrossRefGoogle Scholar
  170. 170.
    Zhang R, Liu S, Wang J, Han G, Yang L, Liu B, Guan G, Zhang Z (2016) Visualization of exhaled hydrogen sulphide on test paper with an ultrasensitive and time-gated luminescent probe. Analyst 141:4919–4925.  https://doi.org/10.1039/c6an00830e CrossRefPubMedGoogle Scholar
  171. 171.
    Hashino K, Ikawa K, Ito M, Hosoya C, Nishioka T, Makiuchi M, Matsumoto K (2007) Application of a fluorescent lanthanide chelate label on a solid support device for detecting DNA variation with ligation-based assay. Anal Biochem 364:89–91.  https://doi.org/10.1016/j.ab.2007.02.004 CrossRefPubMedGoogle Scholar
  172. 172.
    Lövgren T, Meriö L, Mitrunen K, Mäkinen ML, Mäkelä M, Blomberg K, Palenius T, Pettersson K (1996) One-step all-in-one dry reagent immunoassays with fluorescent europium chelate label and time-resolved fluorometry. Clin Chem 42:1196–1201PubMedGoogle Scholar
  173. 173.
    Nagl S, Stich MIJ, Schäferling M, Wolfbeis OS (2009) Method for simultaneous luminescence sensing of two species using optical probes of different decay time, and its application to an enzymatic reaction at varying temperature. Anal Bioanal Chem 393:1199–1207.  https://doi.org/10.1007/s00216-008-2467-0 CrossRefPubMedGoogle Scholar
  174. 174.
    Leblanc V, Delaunay V, Claude Lelong J, Gas F, Mathis G, Grassi J, May E (2002) Homogeneous time-resolved fluorescence assay for identifying p53 interactions with its protein partners, directly in a cellular extract. Anal Biochem 308:247–254CrossRefGoogle Scholar
  175. 175.
    Albizu L, Cottet M, Kralikova M, Stoev S, Seyer R, Brabet I, Roux T, Bazin H, Bourrier E, Lamarque L, Breton C, Rives M-L, Newman A, Javitch J, Trinquet E, Manning M, Pin J-P, Mouillac B, Durroux T (2010) Time-resolved FRET between GPCR ligands reveals oligomers in native tissues. Nat Chem Biol 6:587–594.  https://doi.org/10.1038/nchembio.396 CrossRefPubMedPubMedCentralGoogle Scholar
  176. 176.
    Lu Y, Jin D, Leif RC, Deng W, Piper JA, Yuan J, Duan Y, Huo Y (2011) Automated detection of rare-event pathogens through time-gated luminescence scanning microscopy. Cytometry A 79:349–355.  https://doi.org/10.1002/cyto.a.21045 CrossRefPubMedGoogle Scholar
  177. 177.
    U.S. EPA (2005) Method 1623: Cryptosporidium and Giardia in Water by Filtration/IMS/FA. EPA 815-R-05-002Google Scholar
  178. 178.
    Rich RM, Stankowska DL, Maliwal BP, Sørensen TJ, Laursen BW, Krishnamoorthy RR, Gryczynski Z, Borejdo J, Gryczynski I, Fudala R (2013) Elimination of autofluorescence background from fluorescence tissue images by use of time-gated detection and the AzaDiOxaTriAngulenium (ADOTA) fluorophore. Anal Bioanal Chem 405:2065–2075.  https://doi.org/10.1007/s00216-012-6623-1 CrossRefPubMedGoogle Scholar
  179. 179.
    Zhu Z, Song B, Yuan J, Yang C (2016) Enabling the triplet of tetraphenylethene to sensitize the excited state of Europium(III) for protein detection and time-resolved luminescence imaging. Adv Sci 3:1600146.  https://doi.org/10.1002/advs.201600146 CrossRefGoogle Scholar
  180. 180.
    Von Lode P, Rosenberg J, Pettersson K, Takalo H (2003) A europium chelate for quantitative point-of-care immunoassays using direct surface measurement. Anal Chem 75:3193–3201CrossRefGoogle Scholar
  181. 181.
    Jia Y (2008) Current status of HTRF(®) technology in kinase assays. Expert Opin Drug Discov 3:1461–1474.  https://doi.org/10.1517/17460440802518171 CrossRefPubMedGoogle Scholar
  182. 182.
    Cisbio Bioassays, Codolet, France Application Note: HTRF KinEASE: a universal expanded platform to address Serine/Threonine & Tyrosine kinases. https://www.cisbio.com/drug-discovery/htrf-kinease-universal-expanded-platform-address-serinethreonine-tyrosine-kinases. Accessed 29 Jan 2018
  183. 183.
    Harbert C, Marshall J, Soh S, Steger K (2008) Development of a HTRF kinase assay for determination of Syk activity. Curr Chem Genomics 1:20–26.  https://doi.org/10.2174/1875397300801010020 CrossRefPubMedPubMedCentralGoogle Scholar
  184. 184.
    Larson B, Gonzalez-Moya A, Wolff A, Luty W. Application Note: analysis of the effect of aggregated β-amyloid on cellular signaling pathways critical for memory in Alzheimer’s disease. http://www.enzolifesciences.com/about-us/collaborations-at-work/neuroscience/analysis-of-the-effect-of-aggregated-b-amyloid-on-cellular-signaling-pathways-critical-for-memory-in-alzheimer%27s-disease/. Accessed 29 Jan 2018
  185. 185.
    PerkinElmer I (2012) DELFIA assays: flexible and sensitive tools for monoclonal antibody development. Technical note. PerkinElmer, HopkintonGoogle Scholar
  186. 186.
    Allicotti G, Borras E, Pinilla C (2003) A time-resolved fluorescence immunoassay (DELFIA) increases the sensitivity of antigen-driven cytokine detection. J Immunoassay Immunochem 24:345–358.  https://doi.org/10.1081/IAS-120025772 CrossRefPubMedGoogle Scholar
  187. 187.
    Karvinen J, Hurskainen P, Gopalakrishnan S, Burns D, Warrior U, Hemmilä I (2002) Homogeneous time-resolved fluorescence quenching assay (LANCE) for caspase-3. J Biomol Screen 7:223–231.  https://doi.org/10.1177/108705710200700306 CrossRefPubMedGoogle Scholar
  188. 188.
    Ylikoski A, Elomaa A, Ollikka P, Hakala H, Mukkala V-M, Hovinen J, Hemmilä I (2004) Homogeneous time-resolved fluorescence quenching assay (TruPoint) for nucleic acid detection. Clin Chem 50:1943–1947.  https://doi.org/10.1373/clinchem.2004.036616 CrossRefPubMedGoogle Scholar
  189. 189.
    Laitala V, Hemmilä I (2005) Homogeneous assay based on anti-Stokes’ shift time-resolved fluorescence resonance energy-transfer measurement. Anal Chem 77:1483–1487.  https://doi.org/10.1021/ac048414o CrossRefPubMedGoogle Scholar
  190. 190.
    Rickard DJ, Sehon CA, Kasparcova V, Kallal LA, Haile PA, Zeng X, Montoute MN, Poore DD, Li H, Wu Z, Eidam PM, Emery JG, Marquis RW, Gough PJ, Bertin J (2014) Identification of selective small molecule inhibitors of the nucleotide-binding oligomerization domain 1 (NOD1) signaling pathway. PLoS One 9:e96737.  https://doi.org/10.1371/journal.pone.0096737 CrossRefPubMedPubMedCentralGoogle Scholar
  191. 191.
    Gakamsky DM, Dennis RB, Smith SD (2011) Use of fluorescence lifetime technology to provide efficient protection from false hits in screening applications. Anal Biochem 409:89–97.  https://doi.org/10.1016/j.ab.2010.10.017 CrossRefPubMedGoogle Scholar
  192. 192.
    De Witte WEA, Wong YC, Nederpelt I, Heitman LH, Danhof M, van der Graaf PH, Gilissen RAHJ, de Lange ECM (2016) Mechanistic models enable the rational use of in vitro drug-target binding kinetics for better drug effects in patients. Expert Opin Drug Discov 11:45–63.  https://doi.org/10.1517/17460441.2016.1100163 CrossRefPubMedGoogle Scholar
  193. 193.
    Schiele F, Ayaz P, Fernández-Montalván A (2015) A universal homogeneous assay for high-throughput determination of binding kinetics. Anal Biochem 468:42–49.  https://doi.org/10.1016/j.ab.2014.09.007 CrossRefPubMedGoogle Scholar
  194. 194.
    Lipchik AM, Perez M, Bolton S, Dumrongprechachan V, Ouellette SB, Cui W, Parker LL (2015) KINATEST-ID: a pipeline to develop phosphorylation-dependent terbium sensitizing kinase assays. J Am Chem Soc 137:2484–2494.  https://doi.org/10.1021/ja507164a CrossRefPubMedPubMedCentralGoogle Scholar
  195. 195.
    Cui W, Parker LL (2016) Modular, antibody-free time-resolved LRET kinase assay enabled by quantum dots and Tb(3+)-sensitizing peptides. Sci Rep 6:28971.  https://doi.org/10.1038/srep28971 CrossRefPubMedPubMedCentralGoogle Scholar
  196. 196.
    Lipchik AM, Perez M, Cui W, Parker LL (2015) Multicolored, Tb3+-based antibody-free detection of multiple tyrosine kinase activities. Anal Chem 87:7555–7558.  https://doi.org/10.1021/acs.analchem.5b02233 CrossRefPubMedPubMedCentralGoogle Scholar
  197. 197.
    Cui W, Parker LL (2015) A time-resolved luminescence biosensor assay for anaplastic lymphoma kinase (ALK) activity. Chem Commun (Camb) 51:362–365.  https://doi.org/10.1039/c4cc07453j CrossRefGoogle Scholar
  198. 198.
    Pritz S, Meder G, Doering K, Drueckes P, Woelcke J, Mayr LM, Hassiepen U (2011) A fluorescence lifetime-based assay for abelson kinase. J Biomol Screen 16:65–72.  https://doi.org/10.1177/1087057110385817 CrossRefPubMedGoogle Scholar
  199. 199.
    Doering K, Meder G, Hinnenberger M, Woelcke J, Mayr LM, Hassiepen U (2009) A fluorescence lifetime-based assay for protease inhibitor profiling on human kallikrein 7. J Biomol Screen 14:1–9.  https://doi.org/10.1177/1087057108327328 CrossRefPubMedGoogle Scholar
  200. 200.
    Whateley JG (2003) Fluorescence-based methods for measuring enzyme activity. US20030228646A1Google Scholar
  201. 201.
    Whateley JG (2010) Methods for measuring enzyme activity. US7727739B2. https://patents.google.com/patent/US7727739
  202. 202.
    Cohen JD, Li L, Wang Y, Thoburn C, Afsari B, Danilova L, Douville C, Javed AA, Wong F, Mattox A, Hruban RH, Wolfgang CL, Goggins MG, Dal Molin M, Wang T-L, Roden R, Klein AP, Ptak J, Dobbyn L, Schaefer J, Silliman N, Popoli M, Vogelstein JT, Browne JD, Schoen RE, Brand RE, Tie J, Gibbs P, Wong H-L, Mansfield AS, Jen J, Hanash SM, Falconi M, Allen PJ, Zhou S, Bettegowda C, Diaz L, Tomasetti C, Kinzler KW, Vogelstein B, Lennon AM, Papadopoulos N (2018) Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 359(6378):926–930.  https://doi.org/10.1126/science.aar3247 CrossRefPubMedPubMedCentralGoogle Scholar
  203. 203.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297CrossRefGoogle Scholar
  204. 204.
    Kosaka N, Iguchi H, Ochiya T (2010) Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci 101:2087–2092.  https://doi.org/10.1111/j.1349-7006.2010.01650.x CrossRefPubMedGoogle Scholar
  205. 205.
    Zhao H, Shen J, Medico L, Wang D, Ambrosone CB, Liu S (2010) A pilot study of circulating miRNAs as potential biomarkers of early stage breast cancer. PLoS One 5:e13735.  https://doi.org/10.1371/journal.pone.0013735 CrossRefPubMedPubMedCentralGoogle Scholar
  206. 206.
    Hu Z, Chen X, Zhao Y, Tian T, Jin G, Shu Y, Chen Y, Xu L, Zen K, Zhang C, Shen H (2010) Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol 28:1721–1726.  https://doi.org/10.1200/JCO.2009.24.9342 CrossRefPubMedGoogle Scholar
  207. 207.
    Sita-Lumsden A, Dart DA, Waxman J, Bevan CL (2013) Circulating microRNAs as potential new biomarkers for prostate cancer. Br J Cancer 108:1925–1930.  https://doi.org/10.1038/bjc.2013.192 CrossRefPubMedPubMedCentralGoogle Scholar
  208. 208.
    Guay C, Regazzi R (2013) Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol 9:513–521.  https://doi.org/10.1038/nrendo.2013.86 CrossRefPubMedGoogle Scholar
  209. 209.
    Cattaneo M, Pelosi E, Castelli G, Cerio AM, D’Angiò A, Porretti L, Rebulla P, Pavesi L, Russo G, Giordano A, Turri J, Cicconi L, Lo-Coco F, Testa U, Biunno I (2015) A miRNA signature in human cord blood stem and progenitor cells as potential biomarker of specific acute myeloid leukemia subtypes. J Cell Physiol 230:1770–1780.  https://doi.org/10.1002/jcp.24876 CrossRefPubMedGoogle Scholar
  210. 210.
    Benes V, Castoldi M (2010) Expression profiling of microRNA using real-time quantitative PCR, how to use it and what is available. Methods 50:244–249.  https://doi.org/10.1016/j.ymeth.2010.01.026 CrossRefPubMedGoogle Scholar
  211. 211.
    Zipper H, Brunner H, Bernhagen J, Vitzthum F (2004) Investigations on DNA intercalation and surface binding by SYBR Green I, its structure determination and methodological implications. Nucleic Acids Res 32:e103.  https://doi.org/10.1093/nar/gnh101 CrossRefPubMedPubMedCentralGoogle Scholar
  212. 212.
    Bustin SA (2000) Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol 25:169–193.  https://doi.org/10.1677/jme.0.0250169 CrossRefPubMedGoogle Scholar
  213. 213.
    Okamura Y, Kondo S, Sase I, Suga T, Mise K, Furusawa I, Kawakami S, Watanabe Y (2000) Double-labeled donor probe can enhance the signal of fluorescence resonance energy transfer (FRET) in detection of nucleic acid hybridization. Nucleic Acids Res 28:E107CrossRefGoogle Scholar
  214. 214.
    Tyagi S, Kramer FR (1996) Molecular beacons: probes that fluoresce upon hybridization. Nat Biotechnol 14:303–308.  https://doi.org/10.1038/nbt0396-303 CrossRefPubMedPubMedCentralGoogle Scholar
  215. 215.
    Ng CT, Gilchrist CA, Lane A, Roy S, Haque R, Houpt ER (2005) Multiplex real-time PCR assay using Scorpion probes and DNA capture for genotype-specific detection of Giardia lamblia on fecal samples. J Clin Microbiol 43:1256–1260.  https://doi.org/10.1128/JCM.43.3.1256-1260.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  216. 216.
    Wegman DW, Krylov SN (2011) Direct quantitative analysis of multiple miRNAs (DQAMmiR). Angew Chem Int Ed Engl 50:10335–10339.  https://doi.org/10.1002/anie.201104693 CrossRefPubMedGoogle Scholar
  217. 217.
    Wegman DW, Ghasemi F, Khorshidi A, Yang BB, Liu SK, Yousef GM, Krylov SN (2015) Highly-sensitive amplification-free analysis of multiple miRNAs by capillary electrophoresis. Anal Chem 87:1404–1410.  https://doi.org/10.1021/ac504406s CrossRefPubMedGoogle Scholar
  218. 218.
    Pernagallo S, Ventimiglia G, Cavalluzzo C, Alessi E, Ilyine H, Bradley M, Diaz-Mochon JJ (2012) Novel biochip platform for nucleic acid analysis. Sensors (Basel) 12:8100–8111.  https://doi.org/10.3390/s120608100 CrossRefGoogle Scholar
  219. 219.
    Bowler FR, Reid PA, Boyd AC, Diaz-Mochon JJ, Bradley M (2011) Dynamic chemistry for enzyme-free allele discrimination in genotyping by MALDI-TOF mass spectrometry. Anal Methods 3:1656.  https://doi.org/10.1039/c1ay05176h CrossRefGoogle Scholar
  220. 220.
    Bowler FR, Diaz-Mochon JJ, Swift MD, Bradley M (2010) DNA analysis by dynamic chemistry. Angew Chem Int Ed Engl 49:1809–1812.  https://doi.org/10.1002/anie.200905699 CrossRefPubMedGoogle Scholar
  221. 221.
    Rissin DM, López-Longarela B, Pernagallo S, Ilyine H, Vliegenthart ADB, Dear JW, Díaz-Mochón JJ, Duffy DC (2017) Polymerase-free measurement of microRNA-122 with single base specificity using single molecule arrays: detection of drug-induced liver injury. PLoS One 12:e0179669.  https://doi.org/10.1371/journal.pone.0179669 CrossRefPubMedPubMedCentralGoogle Scholar
  222. 222.
    Venkateswaran S, Luque-González MA, Tabraue-Chávez M, Fara MA, López-Longarela B, Cano-Cortes V, López-Delgado FJ, Sánchez-Martín RM, Ilyine H, Bradley M, Pernagallo S, Díaz-Mochón JJ (2016) Novel bead-based platform for direct detection of unlabelled nucleic acids through Single Nucleobase Labelling. Talanta 161:489–496.  https://doi.org/10.1016/j.talanta.2016.08.072 CrossRefPubMedGoogle Scholar
  223. 223.
    Del Vescovo V, Meier T, Inga A, Denti MA, Borlak J (2013) A cross-platform comparison of affymetrix and Agilent microarrays reveals discordant miRNA expression in lung tumors of c-Raf transgenic mice. PLoS One 8:e78870.  https://doi.org/10.1371/journal.pone.0078870 CrossRefPubMedPubMedCentralGoogle Scholar
  224. 224.
    Jiang L, Duan D, Shen Y, Li J (2012) Direct microRNA detection with universal tagged probe and time-resolved fluorescence technology. Biosens Bioelectron 34:291–295.  https://doi.org/10.1016/j.bios.2012.01.035 CrossRefPubMedGoogle Scholar
  225. 225.
    Hemmilä I, Dakubu S, Mukkala VM, Siitari H, Lövgren T (1984) Europium as a label in time-resolved immunofluorometric assays. Anal Biochem 137:335–343.  https://doi.org/10.1016/0003-2697(84)90095-2 CrossRefPubMedGoogle Scholar
  226. 226.
    Geissler D, Charbonnière LJ, Ziessel RF, Butlin NG, Löhmannsröben H-G, Hildebrandt N (2010) Quantum dot biosensors for ultrasensitive multiplexed diagnostics. Angew Chem Int Ed Engl 49:1396–1401.  https://doi.org/10.1002/anie.200906399 CrossRefPubMedGoogle Scholar
  227. 227.
    Qiu X, Hildebrandt N (2015) Rapid and multiplexed microRNA diagnostic assay using quantum dot-based Förster resonance energy transfer. ACS Nano 9:8449–8457.  https://doi.org/10.1021/acsnano.5b03364 CrossRefPubMedGoogle Scholar
  228. 228.
    Jin Z, Geißler D, Qiu X, Wegner KD, Hildebrandt N (2015) A rapid, amplification-free, and sensitive diagnostic assay for single-step multiplexed fluorescence detection of microRNA. Angew Chem Int Ed Engl 54:10024–10029.  https://doi.org/10.1002/anie.201504887 CrossRefPubMedGoogle Scholar
  229. 229.
    Geißler D, Stufler S, Löhmannsröben H-G, Hildebrandt N (2013) Six-color time-resolved Förster resonance energy transfer for ultrasensitive multiplexed biosensing. J Am Chem Soc 135:1102–1109.  https://doi.org/10.1021/ja310317n CrossRefPubMedGoogle Scholar
  230. 230.
    Zhou S, Zheng W, Chen Z, Tu D, Liu Y, Ma E, Li R, Zhu H, Huang M, Chen X (2014) Dissolution-enhanced luminescent bioassay based on inorganic lanthanide nanoparticles. Angew Chem Int Ed Engl 53:12498–12502.  https://doi.org/10.1002/anie.201405937 CrossRefPubMedGoogle Scholar
  231. 231.
    Lu L, Tu D, Liu Y, Zhou S, Zheng W, Chen X (2018) Ultrasensitive detection of cancer biomarker microRNA by amplification of fluorescence of lanthanide nanoprobes. Nano Res 11:1–10.  https://doi.org/10.1007/s12274-017-1629-9 CrossRefGoogle Scholar
  232. 232.
    DestiNA Genomics Ltd. http://www.destinagenomics.com. Accessed 24 Jan 2018
  233. 233.
    Optoi Microelectronics. http://www.optoi.com/. Accessed 27 Jan 2018
  234. 234.
    miRNA-DisEASY: microRNA biomarkers in an innovative biophotonic sensor kit for high-specific diagnosis. https://optoi.com/en/applications/research-and-development/projects/mirna-diseasy-home-page. Accessed 24 Jan 2018
  235. 235.
    Destina Genomics. In: www.destinagenomics.com; http://www.destinagenomics.com. Accessed 27 Jan 2018
  236. 236.
    Bradley M, Diaz-Mochon JJ (2009) Nucleobase characterisation. WO2009037473A2. https://patents.google.com/patent/WO2009037473A2/

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Emilio Garcia-Fernandez
    • 1
    Email author
  • Salvatore Pernagallo
    • 2
    • 3
  • Juan A. González-Vera
    • 1
  • María J. Ruedas-Rama
    • 1
  • Juan J. Díaz-Mochón
    • 2
    • 4
    • 5
  • Angel Orte
    • 1
  1. 1.Department of Physical Chemistry, Faculty of PharmacyUniversity of GranadaGranadaSpain
  2. 2.DestiNA Genómica S.L.GranadaSpain
  3. 3.DestiNA Genomics Ltd.EdinburghUK
  4. 4.Pfizer-Universidad de Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Parque Tecnológico de Ciencias de la Salud (PTS)GranadaSpain
  5. 5.Faculty of PharmacyUniversity of GranadaGranadaSpain

Personalised recommendations