Mechanism to Signal Receptor-Ligand Interactions with Luminescent Quantum Dots
Françisco Raymo, Massimiliano Tomasulo and Ibrahim Yildiz
Problem
Organic dyes are traditionally used to image biological samples on the basis of fluorescence microscopy. This technique relies on the injection of a fluorescent organic dye in the sample under analysis, followed by the excitation with light of appropriate wavelength. The incident radiation is absorbed and re-emitted by the fluorescent molecules. Organic dyes, however, have shortcomings such as low absorption coefficients, poor photobleaching resistance, short luminescence lifetimes and lack of flexibility in adjusting the emission wavelength. Therefore, it is highly desirable to introduce novel luminescent probes and sensing methods capable of overcoming the limitations of organic dyes in imaging applications.
Solution
This invention uses quantum dots for biosensing applications by adjusting quantum dots emission properties to environmental conditions and signaling certain analytes. The invention provides luminescent chemosensors able to indicate the presence of target analytes on the basis of molecular recognition events occurring on the surface of semiconductor quantum dots. In particular, it offers the opportunity to signal protein-ligand interactions with significant luminescence enhancements. Some of the benefits of the present invention over the conventional bioimaging methods are:
(1) Increased light absorption coefficients require lower excitation powers and, therefore, the risk of damage to a biological sample is reduced;
(2) High two-photon absorption cross sections allow for simultaneous illumination with two infrared sources, offering improved light penetration and increased spatial resolution;
(3) Longer luminescence lifetimes offer the opportunity to filter the auto-fluorescence of biological samples with time-gated measurements, improving the signal-to-noise ratio;
(4) Narrow and tunable emission bands permit the simultaneous monitoring of multiple parameters in parallel.
Competitive Advantage
The inventions offers several improvements over organic dyes, such as improved light absorption, increased spatial resolution, increased luminescence, and tunable emission bands.
Applications
This invention can be used for biological imaging to outperform conventional fluorescent organic dye imaging methods.
Patent Status
International patent application
WO2008005561
entitled "MECHANISM TO SIGNAL RECEPTOR-LIGAND INTERACTIONS WITH LUMINESCENT QUANTUM DOTS" was published on January 10, 2008.
Licensing Opportunity
We are looking for a commercialization partner with capabilities in product development, sales, and marketing. An exclusive worldwide license is available.
About the Inventors
Françisco M. Raymo received a Laurea in Chemistry from the University of Messina (Italy) in 1992 and a Ph.D. in Chemistry from the University of Birmingham (UK) in 1996. He was a postdoctoral associate at the University of Birmingham (UK) in 1996-1997 and at the University of California, Los Angeles in 1997-1999. He was appointed Assistant Professor of Chemistry at the University of Miami in 2000 and promoted to Associate Professor in 2004. His research interests combine the design, synthesis, and analysis of functional molecule-based materials. Specifically, he is developing electroactive films, fluorescent probes and photochromic glasses for chemical sensing and signal processing applications. He is the author of more than 130 publications in the areas of chemical synthesis, computational chemistry, materials science, and supramolecular chemistry.
Massimiliano Tomasulo received a Laurea in Chemistry from the University of Bologna (Italy) in 1999 and a Ph.D. in Chemistry from the University of Miami in 2005. Currently, he is a postdoctoral associate in the research group of professor Raymo. His research focuses on the design and synthesis of photochromic compounds, the electrochemical, photochemical and photophysical investigation of their behavior in solution, the entrapment of these molecules in rigid matrices, and the analysis of the optical properties of the resulting photochromic materials.
Ibrahim Yildiz received a B.S. in Chemistry from Bogazici University (Turkey) in 2000 and a M.S. in Chemistry from Marmara University (Turkey) in 2003. Currently, he is a graduate student in the research group of professor Raymo. His research focuses on the design and synthesis of hydrophilic organic ligands for semiconductor quantum dots, the electrochemical, photochemical and photophysical investigation of their behavior before and after the adsorption on the surface of the nanoparticles and the implementation of sensing schemes based on the luminescence properties of these nanostructured assemblies.
Selected References
"Signal Processing at the Molecular Level": F. M. Raymo, S. Giordani, J. Am. Chem. Soc., 2001, 123, 4651-4652
"Digital Communication through Intermolecular Fluorescence Modulation": F. M. Raymo, S. Giordani, Org. Lett., 2001, 3, 1833-1836
"Signal Communication between Molecular Switches": F. M. Raymo, S. Giordani, Org. Lett., 2001, 3, 3475-3478
"Multichannel Digital Transmission in an Optical Network of Communicating Molecules": F. M. Raymo, S. Giordani, J. Am. Chem. Soc., 2002, 124, 2004-2007
"All-Optical Processing with Molecular Switches": F. M. Raymo, S. Giordani, Proc. Natl. Acad. Sci. USA, 2002, 99, 4941-4944
"Supramolecular Association of Dopamine with Immobilized Fluorescent Probes": F. M. Raymo, M. A. Cejas, Org. Lett., 2002, 4, 3183-3185
"A Switch in a Cage with a Memory": S. Giordani, F. M. Raymo, Org. Lett., 2003, 5, 3559-3562
"Memory Effects Based on Intermolecular Photoinduced Proton Transfer": F. M. Raymo, R. J. Alvarado, S. Giordani, M. A. Cejas, J. Am. Chem. Soc., 2003, 125, 2361-2364
"Digital Processing with A Three-State Molecular Switch": F. M. Raymo, S. Giordani, A. J. P. White, D. J. Williams, J. Org. Chem., 2003, 68, 4158-4169
"Electron Transport in Self-Assembled Bipyridinium Multilayers": F. M. Raymo, R. J. Alvarado, E. J. Pacsial, D. Alexander, J. Phys. Chem. B, 2004, 108, 8622-8625
"Donor/Acceptor Interactions in Self-Assembled Monolayers and Their Consequences on Interfacial Electron Transfer": E. J. Pacsial, D. Alexander, R. J. Alvarado, M. Tomasulo, F. M. Raymo, J. Phys. Chem. B, 2004, 108, 19307-19313
"A Fast and Stable Photochromic Switch Based on the Opening and Closing of an Oxazine Ring": M. Tomasulo, S. Sortino, F. M. Raymo, Org. Lett., 2005, 7, 1109-1112
"Self-Assembling Bipyridinium Multilayers": R. J. Alvarado, J. Mukherjee, E. J. Pacsial, D. Alexander, F. M. Raymo, J. Phys. Chem. B, 2005, 109, 6164-6173
"Fluorescent Diazapyrenium Films and Their Response to Dopamine": M. A. Cejas, F. M. Raymo, Langmuir, 2005, 21, 5795-5802
"Fluorescence Modulation with Photochromic Switches": F. M. Raymo, M. Tomasulo, J. Phys. Chem. A, 2005, 109, 7343-7352 "Fast and Stable Photochromic Oxazines": M. Tomasulo, S. Sortino, A. J. P. White, F. M. Raymo, J. Org. Chem., 2005, 70, 8180-8189
"Colorimetric Detection of Cyanide with a Chromogenic Oxazine": M. Tomasulo, F. M. Raymo, Org. Lett., 2005, 7, 4633-4636
"Chromogenic Oxazines for Cyanide Detection": M. Tomasulo, S. Sortino, A. J. P. White, F. M. Raymo, J. Org. Chem., 2006, 71, 744-753
"pH-Sensitive Quantum Dots": M. Tomasulo, I. Yildiz, F. M. Raymo, J. Phys. Chem. B, 2006, 110, 3853-3855
"A Mechanism to Signal Receptor-Substrate Interactions with Luminescent Quantum Dots": I. Yildiz, M. Tomasulo, F. M. Raymo, Proc. Natl. Acad. Sci. USA, 2006, 103, 11457-11460
