Fluorescent labeling reagent

• US 7,842,505 B2
• Filed: 02/26/2007
• Issued: 11/30/2010
• Est. Priority Date: 02/27/2006
• Status: Expired due to Fees

• Current Assignee: KEIO University
• Original Assignee: KEIO University
• Inventors: Ohkubo, Michio, Aizawa, Hideki, Saito, Daisuke, Noda, Kunihiro, Takagi, Tomohiro, Asakura, Ryo, Isobe, Tetsuhiko
• Primary Examiner(s): Warden; Jill
• Assistant Examiner(s): Wecker; Jennifer
• Application Number:
  US11/678,885
• Publication Number:
  US 20080124806A1
• Time in Patent Office: 1,373 Days
• Field of Search: 436/56
• US Class Current: 436/56
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: G01N 33/585 with a particulate label, e.g. coloured latex
• CPC Class Codes: G01N 33/588 with semiconductor nanocrystal label, e.g. quantum dots
• CPC Class Codes: Y10T 436/13 Tracers or tags

Abstract

A fluorescent labeling reagent of the present invention includes an inorganic fluorescent particle and a material (A) having a material (B) of biological origin adsorbed or bound thereto. The inorganic fluorescent particle is integrated with the material (A) so as to form the reagent of the present invention. The inorganic fluorescent particle used in the present invention is capable of emitting light with a wavelength of 650 nm to 1600 nm in the infrared region or the near-infrared region which can be detected by means of Si—CCD or InGaAs—PD and can penetrate an H₂O rich sample when excited by light with a wavelength of 650 nm or longer which has the shortest transparent wavelength of AlInGaP-LD including oxygen adsorption type hemoglobin used for DVDs etc.

Claims

1. A fluorescent labeling reagent comprising:

an inorganic fluorescent particle capable of emitting light with a wavelength of 650 nm to 1600 nm when excited by light with a wavelength of 650 nm or longer; and

a material (A) capable of absorbing or binding to a material (B) of biological origin, the material (A) being integrated with the inorganic fluorescent particle,

wherein the material (A) is a functional bead matrix composed of an inorganic material or a polymer material of which surface is chemically modified to have a molecule capable of absorbing or binding to a specific biomolecule,

wherein the inorganic fluorescent particle is dispersed into the functional bead matrix, whereby the material (A) is integrated with the inorganic fluorescent particle,

wherein the inorganic fluorescent particle comprises one or more rare earth element capable of producing fluorescence as dopants selected from the group consisting of cerium, praseodymium, neodymium, gadolinium, holmium, erbium, thulium, ytterbium, europium, terbium, samarium, and dysprosium, and

wherein the inorganic fluorescent particle has a garnet structure of yttrium, aluminum and oxygen, and the inorganic fluorescent particle is a crystalline particle in which the one or more rare earth element is incorporated into the garnet structure.

2. The fluorescent labeling reagent according to claim 1, wherein the inorganic fluorescent particle has a primary particle size of 1 nm to 5000 nm.

3. The fluorescent labeling reagent according to claim 1, wherein the rare earth element has a fluorescent spectrum in the near-infrared region.

4. The fluorescent labeling reagent according to claim 1,

wherein the functional bead matrix has a diameter of 0.1 μ

m to 100 μ

m,

wherein the functional bead matrix is selected from the group consisting of a polystyrene bead matrix, a polypropylene bead matrix, a cross-linked acrylic bead matrix, a polylactide bead matrix, a magnetic bead matrix, a glass bead matrix, and a metallic bead matrix, and

wherein the surface of the functional bead is chemically modified to have the capability of specifically absorbing or binding to the material of biological origin.

5. The fluorescent labeling reagent according to claim 1,

wherein the material (A) is integrated with the inorganic fluorescent particle by a chemical reaction, via a modification group introduced onto a surface of the inorganic fluorescent particle, such that the inorganic fluorescent particle has the capability of being directly bound to the material of the biological origin.

6. The fluorescent labeling reagent according to claim 1,

wherein the material (A) is integrated with the inorganic fluorescent particle by a silane coupling agent having an amino group, a thiol group, or a carboxyl group so that the amino group, the thiol group, or the carboxyl group is introduced onto a surface of the inorganic fluorescent particle.

7. The fluorescent labeling reagent according to claim 6,

wherein the introduction of amino group is carried out by using aminoalkyl thiol compound and utilizing a binding of the inorganic fluorescent particle and thiol.

8. The fluorescent labeling reagent according to claim 1,

wherein the material (B) is selected from the group consisting of avidin, streptavidin, fusion protein of avidin or streptavidin, biotin, antigen, antibody, DNA, and RNA.