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US006207392B1
(12) United States Patent ao) Patent No.: us 6,207,392 Bi
Weiss et al. (45) Date of Patent: *Mar. 27,2001
Page 2
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(21) Appl. No.: 09/259,982
(22) Filed: Mar. 1, 1999
Related U.S. Application Data
(63) Continuation-in-part of application No. 08/978,450, filed on Nov. 25, 1997, now Pat. No. 5,990,479.
(51) Int. CI.7 G01J 5/02; G01J 3/30;
F21V 4/16; H01J 65/06; C09K 11/06
(52) U.S. CI 435/7.1; 250/352; 250/459.1;
356/317; 422/82.08; 252/301.17; 378/47;
436/546; 436/6
(58) Field of Search 250/307, 459.1,
250/302; 356/317; 422/82.08; 252/301.17;
378/47; 436/546; 435/6, 7.1
(56) References Cited
U.S. PATENT DOCUMENTS
3,996,345 12/1976 Ullman et al 424/12
4,637,988 1/1987 Hinshaw et al 436/546
4,777,128 10/1988 Lippa 435/5
5,262,357 11/1993 Alivisatos et al. .
5,319,209 6/1994 Miyakawa et al 250/459.1
5,505,928 4/1996 Alivisatos et al. .
5,537,000 * 7/1996 Alivisatos et al 313/506
5,585,640 12/1996 Huston et al 250/483.1
5,674,698 10/1997 Zarling et al 435/7.92
5,736,330 4/1998 Fulton 435/6
5,751,018 5/1998 Alivisatos et al. .
5,990,479 * 11/1999 Weiss et al 250/307
FOREIGN PATENT DOCUMENTS
0 990 903 4/2000 (EP) G01N/33/58
WO 98/04740 2/1998 (WO) C12Q/1/68
WO 99/19515 4/1999 (WO) C12Q/1/68
OTHER PUBLICATIONS
Lacoste, T.D., et al., "Super Resolution Molecular Ruler Using Single Quantum Dots", Biophysical Journal, vol. 78, Jan. 2000, p. 402A, XP-000933548 Abstract. Alivisatos, A. P., "Semiconductor Clusters, Nanocrystals, and Quantum Dots," Science 211 (Feb. 16, 1996) :933-937. Alivisatos, A. P., "Perspectives on the Physical Chemistry of Semiconductor Nanocrystals," /. Phys. Chem. 100 (1996) :13226-13239.
Alivisatos, A. Paul, et al., "Organization of 'Nanocrystal Molecules' Using DNA," Nature 382 (Aug. 15, 1996) :609-611.
Beverloo, H.B., et al., "Preparation and Microscopic Visualization of Multicolor Luminescent Immunophosphors," Chapter 4 of Beverloo, H.B., "Inorganic Crystals as Luminescent Labels: Their Applications in Immunocytochemistry and Time-Resolved Microscopy," Ph.D. dissertation, University of Leiden (The Netherlands), May 13, 1992, pp. 553-573.
Bruchez, Marcel P., Jr., "Luminescent Semiconductor Nanocrystals: Intermittent Behavior and Use as Fluorescent Biological Probes," Ph.D. dissertation, Universtiy of California, Dec. 17, 1998.
(List continued on next page.)
Primary Examiner—John S. Brusca Assistant Examiner—Stephen Siu
(74) Attorney, Agent, or Firm—Paul R. Martin; Kerry S. Taylor; John F. Taylor
(57) ABSTRACT
A semiconductor nanocrystal compound is described which is capable of linking to one or more affinity molecules. The compound comprises (1) one or more semiconductor nanocrystals capable of, in response to exposure to a first energy, providing a second energy, and (2) one or more linking agents, having a first portion linked to the one or more semiconductor nanocrystals and a second portion capable of linking to one or more affinity molecules. One or more of these semiconductor nanocrystal compounds are linked to one or more affinity molecules to form a semiconductor nanocrystal probe capable of bonding with one or more detectable substances in a material being analyzed, and capable of, in response to exposure to a first energy, providing a second energy.
Treatment of a material with the semiconductor nanocrystal probe, and subsequent exposure of this treated material to a first energy, to determine the presence of the detectable substance within the material bonded to the probe, will excite the semiconductor nanocrystal in the probe bonded to the detectable substance, causing the probe to provide a second energy signifying the presence, in the material, of the detectable substance bonded to the semiconductor nanocrystal probe.
Also described are processes for respectively making the semiconductor nanocrystal compound and the semiconductor nanocrystal probe. Processes are also described for treating materials with the probe, for example, to determine the presence of a detectable substance in the material bonded to the probe.
155 Claims, 4 Drawing Sheets
OTHER PUBLICATIONS
Bruchez, Marcel, Jr. et al., "Semiconductor Nanocrystals as Fluorescent Probes for Biology", Cytometry Supp. 9 (1998) :26.
Chan, Warren C.W., et al., "Quantum Dot Bioconjugates for Ultrasensitive Nonisotopic Detection," Science 281 (Sep. 25, 1998) :2016-2018.
Coffer, Jeffrey L., et al., "Characterization of Quantum-Confined CdS Nanocrystallites Stablized by Deoxyribonucleic Acid (DNA)," Nanotechnol. 3 (1992) :69-76.
Cook, Neil D., "Scintillation Proximity Assay: A Versatile High-Throughput Screening Technology," Drug Discovery Today 1 (Jul. 1996) :287-294.
Correa-Duarte, Miguel A., et al., "Stabilization of CdS Semiconductor Nanoparticles Against Photodegradation by a Silica Coating Procedure," Chem. Phys. Lett. 286 (Apr. 17, 1998) :497-501.
Jacoby, Mitch, "Quantum Dots Meet Biomolecules," C&E News 76 (Sep. 28, 1998) :Copied from the Internet as pp. 1-3.
Kagan, C.R., et al, "Electronic Energy Transfer in CdSe Quantum Dot Solids," Phys. Rev. Lett. 76 (Feb. 26, 1996) :1517-1520.
Leff, David N., "Color-Coding Quantum Dots Debut with Promising Careers in Clinical Diagnostics Field," Bioworld Today, Sep. 25, 1998, Copied from the Internet as pp. 1-2. Liz-Marzan, Luis M., et al., "Synthesis of Nanosized Gold-Silica Core-Shell Particles," Langmuir 12 (1996) :4329-4335.
Mahtab, Rahina, et al., "Preferential Adsorption of a 'Kinked' DNA to a Neutral Curved Surface: Comparisons to and Implications for Nonspecific DNA-Protein Interactions," /. Am. Chem. Soc. 118 (1996) :7028-7032.
Mahtab, Rahina, et al., "Protein-Sized Quantum Dot Luminescence Can Distinguish Between 'Straight,' 'Bent,' and 'Kinked' Oligonucleotides," /. Am. Chem. Soc. Ill bx;l(1995) :9099-9100.
Murphy, Catherine J., et al., "Quantum Dots as Inorganic DNA-Binding Proteins," Mat. Res. Soc. Symp. Proc. 452 (1997) :597-600.
Peng, Xiaogang, et al., "Synthesis and Isolation of a Homodimer of Cadmium Selenide Nanocrystals," Angewandte Chemie-International Edition in English, 36 (1997) :145-147.
Service, Robert E, "Semiconductor Beacons Light Up Cell Structures," Science 281 (Sep. 25, 1998) :1930-1931. Shrock, E., et al., "Multicolor Spectral Karyotyping of Human Chromosomes," Science 273 (Jul. 26, 1996) :494-497.
Zhang, Yu-zhong, et al., "Novel Flow Cytometry Compen- sation Standards: Internally Stained Fluorescent Micro- spheres with Matched Emission Spectra and Long-Term Stability," Cytometry 33 (1998) :244-248. Bruchez, Marcel, Jr., et al., "Semiconductor Nanocrystals as Fluorescent Biological Labels", Science, vol. 281, Sep. 25, 1998, pp. 2013-2016.
Dabbousi, B.O., et al., "(CdSe) ZnS Core-Shell Quantum Dots: Synthesis and Characterization of a Size Series of Highly Luminescent Nanocrystal-lites",/ourwa/ of Physical Chemistry B, vol. 101, 1997, pp. 9463-9475. Peng, Xiaogang, et al., "Epitaxial Growth of Highly Lumi- nescent CdSe/CdS Core/Shell Nanocrystals with Photosta- bility and Electronic Accessibility", Journal of the American Chemical Society, vol. 119, No. 30, pp. 7019-7029.
* cited by examiner
LINKING TOGETHER ONE OR MORE SEMICONDUCTOR NANOCRYSTALS CAPABLE OF PROVIDING A DETECTABLE SIGNAL AND
ONE OR MORE LINKING AGENTS CAPABLE OF ALSO LINKING TO ONE OR MORE AFFINITY MOLECULES; AND
LINKING TOGETHER ONE OR MORE AFFINITY
MOLECULES CAPABLE OF SELECTIVELY BONDING WITH ONE OR MORE DETECTABLE SUBSTANCES AND
THE ONE OR MORE LINKING AGENTS LINKED TO THE ONE OR MORE SEMICONDUCTOR NANOCRYSTALS;
TO THEREBY FORM A SEMICONDUCTOR NANOCRYSTAL PROBE CAPABLE OF BONDING TO ONE OR MORE DETECTABLE SUBSTANCES IN A MATERIAL, AND CAPABLE OF PROVIDING A DETECTABLE SIGNAL IN RESPONSE TO EXPOSURE TO ENERGY TO INDICATE THE PRESENCE OF SUCH ONE OR MORE DETECTABLE SUBSTANCES
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