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(12)United States Patent Bawendi etal.

(54) BIOLOGICAL APPLICATIONS OF QUANTUM DOTS

(75) Inventors: MoungiG.Bawendi,Boston,MA (US);FrederickV.Mikulec,LaJolla,

CA(US);VikramC.Sundar, Stoneham,MA (US)

(73) Assignee: MassachusettsInstituteof Technology,Cambridge,MA (US)

US 6,326,144B1

Notice:

Subject to any disclaimer, the term of this patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days.

Spanhel, et al., “Photochemistry of Colloidal Semiconduc tors. Surface Modi?cation and Stability of Strong Lumi nescing CdS Particles,” J. Am. Chem. Soc.

109(19):5649—5655, 1987.

Kortan, et al., “Nucleation and GroWth of CdSe on ZnS Quantum Crystallite Seeds, and Vice Versa, in Inverse Micelle Media,” J. Am. Chem. Soc. 112:1327—1332, 1990. Coffer, et al., “Characterization of quantum—con?ned CdS Nanocrystallites stabilized by deoxyribonucleic acid (DNA),” Nanotechnology 3:69—76, 1992.

Murray, et al., “Synthesis and Characterization of Nearly MonodisperseCdE(E=S,Se,Te)SemiconductorNanocrys tallites,”J.Am. Chem. Soc. 115(19):8706—8715, 1993. Whitesell,etal.,“DirectionallyAlignedHelicalPeptideson Surfaces,” Science 261:73—76, Jul. 1993.

Rajh, et al., “Synthesis and Characterization of Surface— Modi?ed Colloidal CdTe Quantum Dots,” J. Phys. Chem. 97:11999—12003, Nov. 1993.

(List continued on neXt page.)

PrimaryExaminer—LongV.be AssistantExaminer—Minh-Quan K. Pham

(74)Attorney,Agent,orFirm—Fish& RichardsonPC.

(57) ABSTRACT

The present invention provides a composition comprising ?uorescent semiconductor nanocrystals associated to a compound, Wherein the nanocrystals have a characteristic spectralemission,Whereinsaidspectralemissionistunable to a desired Wavelength by controlling the size of the nanocrystal, and Wherein said emission provides informa tion about a biological state or event.

72Claims,8DrawingSheets

(21) Appl.No.:09/160,454

(2) Filed:

Sep.24,1998

Related US. Application Data

(60) Provisional application No. 60/100,947, ?led on Sep. 18, 1998, and provisional application No. 60/101,046, ?led on Sep. 18, 1998.

(51)Int.Cl.7..C12Q1/68 (52) US. Cl. ..435/6; 435/7.1; 436/172;

436/546;436/2;250/307;250/302;250/459.1; 356/317;252/301.7;252/301.33;252/301.36; 378/47; 422/8208

(58)FieldofSearch ..436/172,546, 436/2;435/6,7.1;250/307,302,459.1; 356/317;252/301.7,301.33,301.36;378/47;

(56)

References Cited U.S. PATENT DOCUMENTS

5,293,050 3/1994Chapple-Sokoletal.............257/17 5,354,707 10/1994 Chapple-Sokoletal. 437/106 5,422,489 6/1995 Bhargava ......................... 250/488.1 5,505,928 * 4/1996 Alivisatos et al. .

5,525,377 6/1996 Gallagher et al. .................. 427/512 5,751,018 * 5/1998 Alivisatos et al. .

5,985,353 * 11/1999 Lawton et al. .

422/8208

SINGLE-QUANTUM DOT LABELED IMMUNOASSAY

OD LABELED

ANTIBODY

ANTIGEN

ANTIBODY

C310 OD

SUBSTRATE

CZ Ci>

WO 98/04740 98/19963 WO 98/33070

2/1998 (WO). 5/1998 (W0). 7/1998 (WO).

OTHER PUBLICATIONS

CK IFO

US006326144B1

(10)Patent N0.:

(45)Date ofPatent: Dec.4,2001

5,990,479 * 11/1999 Weiss et a1. . FOREIGN PATENT DOCUMENTS

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