Advantages of Lanthanides   |    Uses of Technology   |    Additional Applications

CORE TECHNOLOGY

Lumiphore's patented lanthanide technology offers key advantages over current fluorescent systems:

 

  • Long lifetimes and high quantum yields give high signal-to-noise ratio results and assay sensitivity significantly better than current fluorophores.
  • Multiple lanthanide fluorophores (four different colors) enable up to four simultaneous assays.
  • A large gap between excitation and emission energies means no self quenching and permits multiple excitation.
  • Resistance to photo bleaching allows archiving of samples for improved quality control and for comparisons between old and new data.

The company has exclusive rights to patents owned by the University of California. These patents cover a proprietary shell around the lanthanide molecule that confers exceptional luminescence, brightness, stability and versatility. The two University of California inventors remain actively involved with Lumiphore. The company intends to pursue a patent strategy so that it will own patented technology for specific conjugation of the lanthanide compounds.

Luminescence

Luminescence describes any process in which energy is emitted from a material at a different wavelength from that at which it is absorbed. It is the preferred detection technology in biology, primarily because luminescent compounds can be manipulated easily in contrast to conventional radioactive labels. This general ease of use has led to the development of a variety of luminescent probe technologies. Light can be detected, quantified and localized with a wide range of established optical methods. The process can be automated with optical scanners, analysis software and well-plate readers. This ease of use has made luminescence the dominant detection platform in biological assays.

Lanthanides as Fluorophores

The most common source of luminescent probes is organic fluorophores, but the excitation of lanthanides (a group of fourteen heavy metals) is superior in several ways. However, since water molecules are very efficient at deactivating the lanthanide metal emission, the lanthanide metal must be protected in order to prevent loss in luminescence signal; this can be done using organic ligands (The figure at the bottom right shows general lanthanide luminescent energy transfer process from the cage to the lanthanide). Several development efforts, including a major program at Perkin Elmer, have attempted to develop such caged ligands.

Building cages that both protect the lanthanide from surrounding water molecules and efficiently deliver light energy to the lanthanide is a significant challenge. Drs. Kenneth Raymond, Stéphane Petoud and Jide Xu at University of California, Berkeley, made a significant breakthrough in designing isophthalamide-lanthanide and salicylamide-lanthanide complexes that combine the stability of organic fluorophores with the superior luminescent properties of lanthanides-a new ligand structure possessing properties required to obtain bright luminescence from the lanthanide ions. (The figure at the top left shows one of these ligands; the lanthanide is in the center of the complex.)

References Citing Lumiphore Technology

1) Jide Xu, Todd M. Corneillie, Evan G. Moore, Ga-Lai Law, Nathaniel G. Butlin, and Kenneth N. Raymond. J. Am. Chem. Soc. 2011, 133, 19900. Octadentate Cages of Tb(III) 2-Hydroxyisophthalamides: A New Standard for Luminescent Lanthanide Labels

2) Ward, R. J.; Pediani, J. D.; Milligan, G. Br. J. Pharmacol. 2011, 162, 1439-1452. Ligand-induced internalization of the orexin OX1 and cannabinoid CB1 receptors assessed via N-terminal SNAP and CLIP-tagging

3) Gaborit, N.; Larbouret, C.; Vallaghe, J.; Peyrusson, F.; Bascoul-Mollevi, C.; Crapez, E.; Azria, D.; Chardès, T.; Poul, M.-A.; Mathis, G.; Bazin, H.; Pèlegrin, A. J. Biol. Chem. 2011, 286, 11337-11345. Time-resolved Fluorescence Resonance Energy Transfer (TR-FRET) to Analyze the Disruption of EGFR/HER2 Dimers

4) Cottet, M.; Faklaris, O.; Zwier, J. M.; Trinquet, E.; Pin, J.-P.; Durroux, T. Pharmaceuticals 2011, 4, 202-214. Original Fluorescent Ligand-Based Assays Open New Perspectives in G-Protein Coupled Receptor Drug Screening

5) Moscovitch-Lopatin, M.; Weiss, A.; Rosas, H. D.; Ritch, J.; Doros, G.; Kegel, K. B.; Difiglia, M.; Kuhn, R.; Bilbe, G.; Paganetti, P.; Hersch, S. PLoS Curr. 2010, 2. Optimization of an HTRF Assay for the Detection of Soluble Mutant Huntingtin in Human Buffy Coats: A Potential Biomarker in Blood for Huntington Disease

6) Weiss, A.; Grueninger, S.; Abramowski, D.; Giorgio, F. P. D.; Lopatin, M. M.; Rosas, H. D.; Hersch, S.; Paganetti, P. Anal. Biochem. 2011, 410, 304-306. Microtiter plate quantification of mutant and wild-type huntingtin normalized to cell count

7) Monnier, C.; Tu, H.; Bourrier, E.; Vol, C.; Lamarque, L.; Trinquet, E.; Pin, J.-P.; Rondard, P. EMBO J. 2011, 30, 32-42. Trans-activation between 7TM domains: implication in heterodimeric GABAB receptor activation

8) Zwier, J. M.; 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. J. Biomol. Screening 2010, 15, 1248-1259. Technology ® A Fluorescent Ligand-Binding Alternative Using Tag-lite

9) 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. Anal. Biochem. 2011, 408, 253-262. Homogeneous time-resolved fluorescence-based assay to screen for ligands targeting the growth hormone secretagogue receptor type 1a

10) Doumazane, E.; Scholler, P.; Zwier, J. M.; Trinquet, E.; Rondard, P.; Pin, J.-P. The FASEB Journal 2011, 25, 66-77. A new approach to analyze cell surface protein complexes reveals specific heterodimeric metabotropic glutamate receptors

11) Gahlaut, N.; Miller, L. W. Cytometry Part A 2010, 77A, 1113-1125. Time-Resolved Microscopy for Imaging Lanthanide Luminescence in Living Cells

12) Morgner, F.; Geißler, D.; Stufler, S.; Butlin, N. G.; Löhmannsröben, H.-G.; Hildebrandt, N. Angew. Chem. Int. Ed. 2010, 49, 7570-7574. A Quantum-Dot-Based Molecular Ruler for Multiplexed Optical Analysis

13) Rajapakse, H. E.; Gahlaut, N.; Mohandessi, S.; Yu, D.; Turner, J. R.; Miller, L. W. PNAS 2010, 107, 13582-13587. Time-resolved luminescence resonance energy transfer imaging of protein–protein interactions in living cells

14) 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. Nat. Chem. Biol. 2010, 6, 587-594. Time-resolved FRET between GPCR ligands reveals oligomers in native tissues

15) Alvarez-Curto, E.; Ward, R. J.; Pediani, J. D.; Milligan, G. J. Biol. Chem. 2010, 285, 23318-23330.Ligand Regulation of the Quaternary Organization of Cell Surface M3 Muscarinic Acetylcholine Receptors Analyzed by Fluorescence Resonance Energy Transfer (FRET) Imaging and Homogeneous Time-resolved FRET

16) Chiranjib, C.; Hsu, C.-H.; Wen, Z.-H.; Lin, C.-S. Curr. Pharm. Des. 2009, 15, 3552-3570.Recent Advances of Fluorescent Technologies for Drug Discovery and Development

17) Rajapakse, H. E.; Reddy, D. R.; Mohandessi, S.; Butlin, N. G.; Miller, L. W. Angew. Chem. Int. Ed. 2009, 48, 4990-4992. Luminescent Terbium Protein Labels for Time-Resolved Microscopy and Screening

18) Degorce, F.; Card, A.; Soh, S.; Trinquet, E.; Knapik, G. P.; Xie, B. Current Chemical Genomics 2009, 3, 22-32. HTRF: A Technology Tailored for Drug Discovery –A Review of Theoretical Aspects and Recent Applications

19) Moore, E. G.; Samuel, A. P. S.; Raymond, K. N. Acc. Chem. Res. 2009, 42, 542-552. From Antenna to Assay: Lessons Learned in Lanthanide Luminescence

20) Jia, Y. Expert Opin. Drug Discovery 2008, 3, 1461-1474. Current status of HTRF(®) technology in kinase assays

 

Molecule
Molecule

Caged Ligand

Caged Ligand