@article{CharbonniereHildebrandt2008,
  author    = {Charbonni{\`e}re, Loic J. and Hildebrandt, Niko},
  title     = {Lanthanide complexes and quantum dots : a bright wedding for resonance energy transfer},
  year      = {2008},
  abstract  = {In this microreview we describe the principle of Forster resonance energy transfer (FRET) occurring between closely spaced energy-donor and -acceptor molecules. The theoretical treatment is depicted in relation with the data extractable from spectroscopic measurements. We present the specific case of semiconductor nanocrystals (or quantum dots QDs) as energy donors in FRET experiments and a particular emphasis is put on the specific advantages of these fluorophores with regard to both their exceptional photophysical properties and their nanoscopic morphology. In a following section, the special attributes of luminescent lanthanide complexes (LLCs) are outlined with illustrations of properties such as their characteristic emission spectra, long-lived luminescence, and large "Stokes shift". Finally, the successful combination of LLCs and QDs in FRET experiments is demonstrated, showing the unrivaled benefits of this singular marriage, opening doors for energy transfer at very large distances and excellent sensitivity of detection within the frame of time-resolved fluoroimmunoassays. ((C) Wiley-VCH Verlag GmbH \& Co. KGaA, 69451 Weinheim, Germany, 2008).},
  language  = {en}
}
@article{CywinskiHammannHuehnetal.2014,
  author    = {Cywinski, Piotr J. and Hammann, Tommy and Huehn, Dominik and Parak, Wolfgang J. and Hildebrandt, Niko and L{\"o}hmannsr{\"o}ben, Hans-Gerd},
  title     = {Europium-quantum dot nanobioconjugates as luminescent probes for time-gated biosensing},
  series = {Journal of biomedical optics},
  volume    = {19},
  journal   = {Journal of biomedical optics},
  number    = {10},
  publisher = {SPIE},
  address   = {Bellingham},
  issn      = {1083-3668},
  doi       = {10.1117/1.JBO.19.10.101506},
  pages     = {8},
  year      = {2014},
  abstract  = {Nanobioconjugates have been synthesized using cadmium selenide quantum dots (QDs), europium complexes (EuCs), and biotin. In those conjugates, long-lived photoluminescence (PL) is provided by the europium complexes, which efficiently transfer energy via Forster resonance energy transfer (FRET) to the QDs in close spatial proximity. As a result, the conjugates have a PL emission spectrum characteristic for QDs combined with the long PL decay time characteristic for EuCs. The nanobioconjugates synthesis strategy and photo-physical properties are described as well as their performance in a time-resolved streptavidin-biotin PL assay. In order to prepare the QD-EuC-biotin conjugates, first an amphiphilic polymer has been functionalized with the EuC and biotin. Then, the polymer has been brought onto the surface of the QDs (either QD655 or QD705) to provide functionality and to make the QDs water dispersible. Due to a short distance between EuC and QD, an efficient FRET can be observed. Additionally, the QD-EuC-biotin conjugates' functionality has been demonstrated in a PL assay yielding good signal discrimination, both from autofluorescence and directly excited QDs. These newly designed QD-EuC-biotin conjugates expand the class of highly sensitive tools for bioanalytical optical detection methods for diagnostic and imaging applications. (C) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE)},
  language  = {en}
}
@article{CywinskiMoroRitscheletal.2011,
  author    = {Cywinski, Piotr J. and Moro, Artur J. and Ritschel, Thomas and Hildebrandt, Niko and L{\"o}hmannsr{\"o}ben, Hans-Gerd},
  title     = {Sensitive and selective fluorescence detection of guanosine nucleotides by nanoparticles conjugated with a naphthyridine receptor},
  series = {Analytical \& bioanalytical chemistry},
  volume    = {399},
  journal   = {Analytical \& bioanalytical chemistry},
  number    = {3},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {1618-2642},
  doi       = {10.1007/s00216-010-4420-2},
  pages     = {1215 -- 1222},
  year      = {2011},
  abstract  = {Novel fluorescent nanosensors, based on a naphthyridine receptor, have been developed for the detection of guanosine nucleotides, and both their sensitivity and selectivity to various nucleotides were evaluated. The nanosensors were constructed from polystyrene nanoparticles functionalized by (N-(7-((3-aminophenyl) ethynyl)-1,8-naphthyridin- 2-yl) acetamide) via carbodiimide ester activation. We show that this naphthyridine nanosensor binds guanosine nucleotides preferentially over adenine, cytosine, and thymidine nucleotides. Upon interaction with nucleotides, the fluorescence of the nanosensor is gradually quenched yielding Stern-Volmer constants in the range of 2.1 to 35.9mM(-1). For all the studied quenchers, limits of detection (LOD) and tolerance levels for the nanosensors were also determined. The lowest (3 sigma) LOD was found for guanosine 3',5'-cyclic monophosphate (cGMP) and it was as low as 150 ng/ml. In addition, we demonstrated that the spatial arrangement of bound analytes on the nanosensors' surfaces is what is responsible for their selectivity to different guanosine nucleotides. We found a correlation between the changes of the fluorescence signal and the number of phosphate groups of a nucleotide. Results of molecular modeling and zeta-potential measurements confirm that the arrangement of analytes on the surface provides for the selectivity of the nanosensors. These fluorescent nanosensors have the potential to be applied in multi-analyte, array-based detection platforms, as well as in multiplexed microfluidic systems.},
  language  = {en}
}
@article{GeisslerStuflerLoehmannsroebenetal.2013,
  author    = {Geissler, Daniel and Stufler, Stefan and L{\"o}hmannsr{\"o}ben, Hans-Gerd and Hildebrandt, Niko},
  title     = {Six-color time-resolved forster resonance energy transfer for ultrasensitive multiplexed biosensing},
  series = {Journal of the American Chemical Society},
  volume    = {135},
  journal   = {Journal of the American Chemical Society},
  number    = {3},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {0002-7863},
  doi       = {10.1021/ja310317n},
  pages     = {1102 -- 1109},
  year      = {2013},
  abstract  = {Simultaneous monitoring of multiple molecular interactions and multiplexed detection of several diagnostic biomarkers at very low concentrations have become important issues in advanced biological and chemical sensing. Here we present an optically multiplexed six-color Forster resonance energy transfer (FRET) biosensor for simultaneous monitoring of five different individual binding events. We combined simultaneous FRET from one Tb complex to five different organic dyes measured in a filter-based time-resolved detection format with a sophisticated spectral crosstalk correction, which results in very efficient background suppression. The advantages and robustness of the multiplexed FRET sensor were exemplified by analyzing a 15-component lung cancer immunoassay involving 10 different antibodies and five different tumor markers in a single 50 mu L human serum sample. The multiplexed biosensor offers clinically relevant detection limits in the low picomolar (ng/mL) concentration range for all five markers, thus providing an effective early screening tool for lung cancer with the possibility of distinguishing small-cell from non-small-cell lung carcinoma. This novel technology will open new doors for multiple biomarker diagnostics as well as multiplexed real-time imaging and spectroscopy.},
  language  = {en}
}
@article{GeisslerButlinHilletal.2008,
  author    = {Geißler, Daniel and Butlin, Nathaniel G. and Hill, Diana and L{\"o}hmannsr{\"o}ben, Hans-Gerd and Hildebrandt, Niko},
  title     = {Multiplexed diagnostics and spectroscopic ruler applications with terbium to quantum dots FRET},
  issn      = {1605-7422},
  year      = {2008},
  language  = {en}
}
@article{GeisslerCharbonniereZiesseletal.2010,
  author    = {Geißler, Daniel and Charbonni{\`e}re, Lo{\"i}c J. and Ziessel, Raymond F. and Butlin, Nathaniel G. and L{\"o}hmannsr{\"o}ben, Hans-Gerd and Hildebrandt, Niko},
  title     = {Quantum dot biosensors for ultrasensitive multiplexed diagnostics},
  issn      = {1433-7851},
  doi       = {10.1002/anie.200906399},
  year      = {2010},
  abstract  = {Time- and color-resolved detection of Foerster resonance energy transfer (FRET) from luminescent terbium complexes to different semiconductor quantum dots results in a fivefold multiplexed bioassay with sub-picomolar detection limits for all five bioanalytes (see picture). The detection of up to five biomarkers occurs with a sensitivity that is 40-240-fold higher than one of the best-established single-analyte reference assays.},
  language  = {en}
}
@article{HildebrandtCharbonniereBecketal.2005,
  author    = {Hildebrandt, Niko and Charbonniere, Lo{\"i}c J. and Beck, Michael and Ziessel, Raymond F. and L{\"o}hmannsr{\"o}ben, Hans-Gerd},
  title     = {Quantum dots as efficient energy acceptors in a time-resolved fluoroimmunoassay},
  issn      = {1433-7851},
  year      = {2005},
  language  = {en}
}
@article{HildebrandtGeissler2012,
  author    = {Hildebrandt, Niko and Geissler, Daniel},
  title     = {Semiconductor quantum dots as FRET acceptors for multiplexed diagnostics and molecular ruler application},
  series = {Advances in Experimental Medicine and Biology},
  volume    = {733},
  journal   = {Advances in Experimental Medicine and Biology},
  editor    = {Zahavy, E and Ordentlich, A and Yitzhaki, S and Shafferman, A},
  publisher = {Springer},
  address   = {Dordrecht},
  isbn      = {978-94-007-2554-6},
  issn      = {0065-2598},
  doi       = {10.1007/978-94-007-2555-3_8},
  pages     = {75 -- 86},
  year      = {2012},
  abstract  = {Applications based on Forster resonance energy transfer (FRET) play an important role for the determination of concentrations and distances within nanometer-scale systems in vitro and in vivo in many fields of biotechnology. Semiconductor nanocrystals (Quantum dots - QDs) possess ideal properties for their application as FRET acceptors when the donors have long excited state lifetimes and when direct excitation of QDs can be efficiently suppressed. Therefore, luminescent terbium complexes (LTCs) with excited state lifetimes of more than 2 ms are ideal FRET donor candidates for QD-acceptors. This chapter will give a short overview of theoretical and practical background of FRET, QDs and LTCs, and present some recent applications of LTC-QD FRET pairs for multiplexed ultra-sensitive in vitro diagnostics and nanometer-resolution molecular distance measurements.},
  language  = {en}
}
@article{KadjaneStarckCamereletal.2009,
  author    = {Kadjane, Pascal and Starck, Matthieu and Camerel, Franck and Hill, Diana and Hildebrandt, Niko and Ziessel, Raymond and Charbonni{\`e}re, Lo{\"i}c J.},
  title     = {Divergent approach to a large variety of versatile luminescent lanthanide complexes},
  issn      = {0020-1669},
  doi       = {10.1021/Ic9001169},
  year      = {2009},
  abstract  = {Using a regioselective strategy for nucleophilic aromatic substitution on polyfluoropyridines, a nonacoordinating precursor was designed that is adequately suited for complexation of lanthanide cations. Further functionalizations afforded numerous applications for near-IR emission, two-photon absorption spectroscopy, or the formation of luminescent gels.},
  language  = {en}
}
@article{KupstatKumkeHildebrandt2011,
  author    = {Kupstat, Annette and Kumke, Michael Uwe and Hildebrandt, Niko},
  title     = {Toward sensitive, quantitative point-of-care testing (POCT) of protein markers miniaturization of a homogeneous time-resolved fluoroimmunoassay for prostate-specific antigen detection},
  series = {The analyst : the analytical journal of the Royal Society of Chemistry},
  volume    = {136},
  journal   = {The analyst : the analytical journal of the Royal Society of Chemistry},
  number    = {5},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {0003-2654},
  doi       = {10.1039/c0an00684j},
  pages     = {1029 -- 1035},
  year      = {2011},
  abstract  = {Point-of-care testing (POCT) systems which allow for a sensitive, quantitative detection of protein markers are extremely useful for the early detection and therapy progress monitoring of cancer. However, currently commercially available POCT devices are mainly limited to the qualitative detection of protein markers. In this study we demonstrate the successive miniaturization of a sensitive and fast assay for the quantitative detection of prostate-specific antigen (PSA) using a well established and clinically approved homogeneous time-resolved fluoroimmunoassay technology (TRACE (R)) on a commercial plate-reader system (KRYPTOR (R)). Regarding the initial requirements for the development of POCT devices we applied a 30-fold assay volume reduction (150 mu L to 5 mu L) to achieve a reasonable lab-on-a-chip volume and a 24-fold and 120-fold excitation pulse energy reduction to achieve reasonable pulse energies for low-cost miniature excitation sources. Due to highly efficient optimization of key POCT parameters our miniaturized PSA assay achieved a 30\% increased sensitivity and a 2-fold improved limit of detection compared to the standard plate-reader method. Our results demonstrate the successful implementation of key parameters for a significant miniaturization and for cost reduction in the clinically approved KRYPTOR (R) platform for protein detection. The technological alterations required are easy-to-implement and can be immediately adapted for more than 30 diagnostic protein markers already available for the KRYPTOR (R) platform. These features strongly recommend our assay format to be utilized in innovative, sensitive, quantitative POCT of protein markers.},
  language  = {en}
}