Abstract: A tissue staining method which comprises: staining a tissue with a staining reagent wherein a biosubstance recognition site is bonded to particles carrying multiple fluorescent substances accumulated therein; in the stained tissue, counting fluorescent points or measuring fluorescent brightness; and evaluating the expression level of a biosubstance, which matches the biosubstance recognition site, in the aforesaid tissue on the basis of the number of the fluorescent points or fluorescent brightness that was measured.

Abstract: The present invention provides a nanoparticle containing a hydrophobic fluorescent substance accumulated therein and a thermosetting resin as a matrix, which nanoparticle, when used for labeling of a biological substance such as a protein or nucleic acid, has brightness sufficient for allowing pathological diagnosis using a fluorescence image obtained thereby. The present invention is a phosphor integrated dots nanoparticles wherein a thermosetting resin contains a structural unit formed from a raw material containing a hydrophobic substituent, and wherein a fluorescent substance is accumulated in the nanoparticle at least by hydrophobic interaction, preferably further by stacking interaction, with the hydrophobic substituent of the thermosetting resin.

Abstract: A tissue staining method which comprises: staining a tissue with a staining reagent wherein a biosubstance recognition site is bonded to particles carrying multiple fluorescent substances accumulated therein; in the stained tissue, counting fluorescent points or measuring fluorescent brightness; and evaluating the expression level of a biosubstance, which matches the biosubstance recognition site, in the aforesaid tissue on the basis of the number of the fluorescent points or fluorescent brightness that was measured.

Abstract: The present invention relates to a method for evaluating a drug involved in angiogenesis. The method includes a drug administration step (A) of administering a drug involved in angiogenesis to a subject having a lesion. The method further includes: an imaging step (1) of performing radiography on a subject in a state where metal nanoparticles are present in a blood vessel or an imaging step (2) of performing fluorescence staining and fluorescence imaging using a dimeric protein; and evaluating the drug using an image acquired in the imaging step (1) or (2).

Abstract: A tissue staining method which comprises: staining a tissue with a staining reagent wherein a biosubstance recognition site is bonded to particles carrying multiple fluorescent substances accumulated therein; in the stained tissue, counting fluorescent points or measuring fluorescent brightness; and evaluating the expression level of a biosubstance, which matches the biosubstance recognition site, in the aforesaid tissue on the basis of the number of the fluorescent points or fluorescent brightness that was measured.

Abstract: A tissue staining method which comprises: staining a tissue with a staining reagent wherein a biosubstance recognition site is bonded to particles carrying multiple fluorescent substances accumulated therein; in the stained tissue, counting fluorescent points or measuring fluorescent brightness; and evaluating the expression level of a biosubstance, which matches the biosubstance recognition site, in the aforesaid tissue on the basis of the number of the fluorescent points or fluorescent brightness that was measured.

Abstract: An object of the present invention is to provide a method of detecting a specific tissue or cell in a sample tissue section and accurately specifying both the position(s) and amount of a biological substance of interest that is expressed on the specific tissue or cell.

Abstract: The present invention provides a nanoparticle containing a hydrophobic fluorescent substance accumulated therein and a thermosetting resin as a matrix, which nanoparticle, when used for labeling of a biological substance such as a protein or nucleic acid, has brightness sufficient for allowing pathological diagnosis using a fluorescence image obtained thereby. The present invention is a phosphor integrated dots nanoparticles wherein a thermosetting resin contains a structural unit formed from a raw material containing a hydrophobic substituent, and wherein a fluorescent substance is accumulated in the nanoparticle at least by hydrophobic interaction, preferably further by stacking interaction, with the hydrophobic substituent of the thermosetting resin.

Abstract: An object of the invention is to provide an environmentally-responsive dye-accumulated nanoparticle for grasping an intracellular environment such as pH with respect to each cell. The invention provides an environmentally-responsive dye-accumulated nanoparticle, in which an environmentally-responsive dye is accumulated on the surface of, or inside a thermosetting resin particle, and which has an average particle diameter of 30 to 800 nm, wherein the accumulated amount of the environmentally-responsive dye is 200 to 10,000,000 molecules/particle. The environmentally-responsive dye has dependence on pH, or a Ca ion in terms of fluorescence intensity, and the thermosetting resin is a melamine resin.

Abstract: The present invention provides a method of producing core/shell-type fluorescent dye-containing nanoparticles for immunohistochemical staining or live cell imaging, the method including: the step 1 of polymerizing monomers for thermoplastic resin synthesis in the presence of a fluorescent dye and thereby preparing core particles composed of a thermoplastic resin containing the fluorescent dye; and the step 2 of coating the core particles each with a shell layer composed of a thermosetting resin. By the method of producing fluorescent dye-containing nanoparticles according to the present invention, fluorescent dye-containing nanoparticles having a high brightness, whose dye does not elutes into water, physiological saline, culture medium and the like, can be produced, and the fluorescent dye-containing nanoparticles can be effectively utilized in immunohistochemical staining and live cell imaging.

Abstract: An object of the present invention is to provide a labeling agent which exhibits excellent binding to a target molecule in a bioassay or histological staining method that relates to a compound containing a nitrogen-containing aromatic ring. The labeling agent according to the present invention is a labeling agent having a structure in which a molecular target drug, which is a compound containing a nitrogen atom-containing aromatic ring, is bound with a label via a divalent linking group, wherein one end of the divalent linking group is bound to a carbon atom of the nitrogen atom-containing aromatic ring. The label is preferably a fluorescent substance-integrated nanoparticle, and the nitrogen atom-containing aromatic ring is preferably a pyridine ring.

Abstract: A tissue staining method which comprises: staining a tissue with a staining reagent wherein a biosubstance recognition site is bonded to particles carrying multiple fluorescent substances accumulated therein; in the stained tissue, counting fluorescent points or measuring fluorescent brightness; and evaluating the expression level of a biosubstance, which matches the biosubstance recognition site, in the aforesaid tissue on the basis of the number of the fluorescent points or fluorescent brightness that was measured.

Abstract: Disclosed is a quantum dot-embedded silica nanoparticle having plural quantum dots embedded within the silica nanoparticle, wherein the number of quantum dots existing in a concentric area within 10% of a radius from a center of the silica nanoparticle accounts for 10 to 70% of the number of total quantum dots embedded in the silica nanoparticle.

Abstract: A silica nanoparticle for diagnostic imaging that may be capable of use for X-ray CT, fluorescent imaging, or the like, and have high emission intensity. A method for producing such a silica nanoparticle for diagnostic imaging is provided. Also, a biosubstance labeling agent using the silica nanoparticle for diagnostic imaging is provided. The silica nanoparticle for diagnostic imaging encapsulates an organic fluorescent dye and a metal complex, wherein a ligand of the metal complex form a covalent bond with constituent molecules of the silica nanoparticle.

Abstract: Disclosed are fluorescent substance-containing silica nanoparticles containing a fluorescent substance therein featured in that the surface of the silica nanoparticles is coated with a material having a bulk refractive index of from 1.60 to 4.00. The invention can provide fluorescent substance-containing silica nanoparticles excellent in long term storage stability and a biosubstance labeling agent employing the same.

Abstract: A tissue staining method which comprises: staining a tissue with a staining reagent wherein a biosubstance recognition site is bonded to particles carrying multiple fluorescent substances accumulated therein; in the stained tissue, counting fluorescent points or measuring fluorescent brightness; and evaluating the expression level of a biosubstance, which matches the biosubstance recognition site, in the aforesaid tissue on the basis of the number of the fluorescent points or fluorescent brightness that was measured.

Abstract: Disclosed are fluorescent substance-containing silica nanoparticles containing a fluorescent substance therein featured in that the surface of the silica nanoparticles is coated with a material having a bulk refractive index of from 1.60 to 4.00. The invention can provide fluorescent substance-containing silica nanoparticles excellent in long term storage stability and a biosubstance labeling agent employing the same.

Abstract: Disclosed is a quantum dot-embedded silica nanoparticle having plural quantum dots embedded within the silica nanoparticle, wherein the number of quantum dots existing in a concentric area within 10% of a radius from a center of the silica nanoparticle accounts for 10 to 70% of the number of total quantum dots embedded in the silica nanoparticle.

Abstract: An inorganic nanoparticle labeling agent having adaptability for being employed as a labeled material in the field of biology and medical science and capable of emitting fluorescence at a stable emission intensity is disclosed, comprising inorganic nanoparticles which were surface-modified with an organic compound, wherein the inorganic nanoparticles exhibit an average particle size of 1 to 10 nm, the organic compound is a compound containing a polyethylene glycol chain, the average particle size D of the inorganic nanoparticle labeling agent is from 8 to 25 nm; and an amount M (mol) of the organic compound per inorganic nanoparticle and a length L (nm) of the organic compound measured from an inorganic nanoparticle surface meet the relationship represented by the following formula (I): (M×1022)×L/D=1.0?4.